Author: "Eric J.G. Sijbrands" - Searchworks@Jio Institute Digital Library Search Results

Your search keyword '"Eric J.G. Sijbrands"' showing total 322 results

Start Over Author "Eric J.G. Sijbrands"

322 results on '"Eric J.G. Sijbrands"'

1. Age- and sex-based heterogeneity in coronary artery plaque presence and burden in familial hypercholesterolemia: A multi-national study

Author: Khurram Nasir, Reed Mszar, Miguel Cainzos-Achirica, Gowtham R. Grandhi, Tycho R. Tromp, Rodrigo Alonso, Márcio S. Bittencourt, Eric Bruckert, José Luis Díaz-Díaz, Antonio Gallo, G. Kees Hovingh, Marcio H. Miname, Ovidio Muñiz-Grijalvo, Jing Pang, Leopoldo Perez de Isla, Eric J.G. Sijbrands, Gerald F. Watts, Pedro Mata, and Raul D. Santos
Subjects: Atherosclerotic cardiovascular disease, Coronary artery calcium, Familial hypercholesterolemia, Low-density lipoprotein cholesterol, Plaque burden, Diseases of the circulatory (Cardiovascular) system, RC666-701, Public aspects of medicine, RA1-1270
Abstract: Objectives: Individuals with familial hypercholesterolemia (FH) are at an increased risk for coronary artery disease (CAD). While prior research has shown variability in coronary artery calcification (CAC) among those with FH, studies with small sample sizes and single-center recruitment have been limited in their ability to characterize CAC and plaque burden in subgroups based on age and sex. Understanding the spectrum of atherosclerosis may result in personalized risk assessment and tailored allocation of costly add-on, non-statin lipid-lowering therapies. We aimed to characterize the presence and burden of CAC and coronary plaque on computed tomography angiography (CTA) across age- and sex-stratified subgroups of individuals with FH who were without CAD at baseline. Methods: We pooled 1,011 patients from six cohorts across Brazil, France, the Netherlands, Spain, and Australia. Our main measures of subclinical atherosclerosis included CAC ranges (i.e., 0, 1–100, 101–400, >400) and CTA-derived plaque burden (i.e., no plaque, non-obstructive CAD, obstructive CAD). Results: Ninety-five percent of individuals with FH (mean age: 48 years; 54% female; treated LDL-C: 154 mg/dL) had a molecular diagnosis and 899 (89%) were on statin therapy. Overall, 423 (42%) had CAC=0, 329 (33%) had CAC 1–100, 160 (16%) had CAC 101–400, and 99 (10%) had CAC >400. Compared to males, female patients were more likely to have CAC=0 (48% [n = 262] vs 35% [n = 161]) and no plaque on CTA (39% [n = 215] vs 26% [n = 120]). Among patients with CAC=0, 85 (20%) had non-obstructive CAD. Females also had a lower prevalence of obstructive CAD in CAC 1–100 (8% [n = 15] vs 18% [n = 26]), CAC 101–400 (32% [n = 22] vs 40% [n = 36]), and CAC >400 (52% [n = 16] vs 65% [n = 44]). Female patients aged 50–59 years were less likely to have obstructive CAD in CAC >400 (55% [n = 6] vs 70% [n = 19]). Conclusion: In this large, multi-national study, we found substantial age- and sex-based heterogeneity in CAC and plaque burden in a cohort of predominantly statin-treated individuals with FH, with evidence for a less pronounced increase in atherosclerosis among female patients. Future studies should examine the predictors of resilience to and long-term implications of the differential burden of subclinical coronary atherosclerosis in this higher risk population.
Published: 2024
Full Text: View/download PDF

2. Transcription factor 7-like 2 gene links increased in vivo insulin synthesis to type 2 diabetes

Author: Sjaam Jainandunsing, H. Rita Koole, Joram N.I. van Miert, Trinet Rietveld, J.L. Darcos Wattimena, Eric J.G. Sijbrands, and Felix W.M. de Rooij
Subjects: Medicine, Medicine (General), R5-920
Abstract: Transcription factor 7-like 2 (TCF7L2) is the main susceptibility gene for type 2 diabetes, primarily through impairing the insulin secretion by pancreatic β cells. However, the exact in vivo mechanisms remain poorly understood. We performed a family study and determined if the T risk allele of the rs7903146 in the TCF7L2 gene increases the risk of type 2 diabetes based on real-time stable isotope measurements of insulin synthesis during an Oral Glucose Tolerance Test. In addition, we performed oral minimal model (OMM) analyses to assess insulin sensitivity and β cell function indices. Compared to unaffected relatives, individuals with type 2 diabetes had lower OMM indices and a higher level of insulin synthesis. We found a T allele-dosage effect on insulin synthesis and on glucose tolerance status, therefore insulin synthesis was higher among T-allele carriers with type 2 diabetes than in wild-type individuals. These results suggest that hyperinsulinemia is not only an adaptation to insulin resistance, but also a direct cause of type 2 diabetes. Keywords: Insulin synthesis, Insulin secretion in vivo, Genetics of type 2 diabetes
Published: 2018
Full Text: View/download PDF

3. The effect of guideline revisions on vascular complications of type 2 diabetes

Author: Ralph Heijmans, Sunny S. Singh, Aloysius G. Lieverse, Eric J.G. Sijbrands, and Mandy van Hoek
Subjects: Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract: Background: The aim of this study was to investigate the impact of implementation and revision of the ‘Diabetes Mellitus type II’ guideline by the Dutch College of General Practitioners (DCGP) on the prevalence and incidence of macrovascular and microvascular complications. Methods: The DiaGene study is a case-control study ( n = 1886 patients of type 2 diabetes) with extensive, retrospectively collected complication data, as well as prospective follow up of complications. The study incorporates all lines of diabetes care. Cases were divided into categories according to the date of onset of diabetes and publication dates of the DCGP. Logistic regression models were used to investigate the associations between guideline version and complications. To investigate a possible trend between guideline version and complications, the ‘guideline category’ was also used as a continuous variable. All models were adjusted for clinical covariables. Results: The 1999 and 2006 guidelines versions were associated with significantly lower risk of retinopathy than the group that started without a guideline [OR 0.32 (95% CI 0.14–0.72, p = 0.006) and 0.31 (95% CI 0.11–0.91, p = 0.034), respectively]. A significant trend in reduction of peripheral artery disease (PAD) over the guideline versions was found, adjusted for age, sex and diabetes duration (odds ratio (OR) 0.70, 95% CI 0.51-0.97, p trend = 0.029) and for retinopathy in all models (OR = 0.52, 95% CI 0.37-0.73, p trend
Published: 2019
Full Text: View/download PDF

4. Hepatic lipase

Author: Hans Jansen, Adrie J.M. Verhoeven, and Eric J.G. Sijbrands
Subjects: coronary heart disease, risk factor, lipoprotein metabolism, lipid homeostasis, liver, hyperlipidemia, Biochemistry, QD415-436
Abstract: Hepatic lipase (HL) plays a role in the metabolism of pro- and anti-atherogenic lipoproteins affecting their plasma level and composition. However, there is controversy regarding whether HL accelerates or retards atherosclerosis. Its effects on different lipoprotein classes show that, potentially, HL may promote as well as decrease atherogenesis. Studies in animals with genetically modulated HL expression show that it depends on the model used whether HL acts pro- or anti-atherogenic. In humans, HL activity seems to correlate inversely with atherosclerosis in (familial) hypercholesterolemia, and positively in hypertriglyceridemia. In normolipidemia, HL activity is weakly associated with coronary artery disease (CAD). Genetically low or absent HL activity is usually associated with increased CAD risk, especially if plasma lipid transport is impaired due to other factors. Since HL promotes the uptake of lipoproteins and lipoprotein-associated lipids, HL may affect intracellular lipid content.We hypothesize that the prime role of HL is to maintain, in concert with other factors (e.g., lipoprotein receptors), intracellular lipid homeostasis. This, and the uncertainties about its impact on human atherosclerosis, makes it difficult to predict whether HL is a suitable target for intervention to lower CAD risk. First, the physiological meaning of changes in HL activity under different conditions should be clarified.
Published: 2002
Full Text: View/download PDF

5. Associations of baseline glycemic status and its transitions with cognitive and physical functioning decline

Author: Kan Wang, Hui Gao, Eric J.G. Sijbrands, Maryam Kavousi, Fariba Ahmadizar, Epidemiology, and Internal Medicine
Subjects: SDG 3 - Good Health and Well-being, Obstetrics and Gynecology, General Biochemistry, Genetics and Molecular Biology
Abstract: Objective: Evidence about the decline of cognition and physical function across glycemic status (normoglycemia, prediabetes, and diabetes) is inconsistent. We evaluated longitudinal changes in cognition and physical function according to glycemic status and also different glycemic transitions. Study design: Population-based cohort study. Methods: 9307 participants (mean age 59.7 years, 53.7 % women) were included from the China Health and Retirement Longitudinal Study (2011–2018). Global cognition (assessed by orientation, memory, and executive function) and physical function (calculated as the sum of impaired basic and instrumental activities of daily living) were assessed in each wave. The glycemic status was assessed in waves 2011 and 2015. Diabetes was defined as fasting blood glucose ≥7.0 mmol/L, HbA1c ≥6.5 %, self-reported diabetes, or glucose-lowering medication use. Prediabetes was defined as fasting blood glucose 5.6–6.9 mmol/L or an HbA1c of 5.7–6.4 %. Results: Compared with normoglycemia, baseline diabetes was associated with a faster decline in orientation (−0.018 SD/year, 95%CI -0.032, −0.004) and a faster increase in physical function score (0.082 /year, 95%CI 0.038, 0.126). We did not observe any effect of prediabetes on the changing rate of cognition and physical function. Progression from normoglycemia to diabetes between waves 2011 and 2015 was associated with a significantly faster decline in global cognition, memory, executive function, and physical function compared with stable normoglycemia. Conclusions: Baseline diabetes was associated with accelerated decline of cognition and physical function. Associations with prediabetes were not observed, suggesting an important short diagnostic window when diabetes presents de novo.
Published: 2023

6. Sphingolipids in Cerebrospinal Fluid and Plasma Lipoproteins of APOE4 Homozygotes and Non-APOE4 Carriers with Mild Cognitive Impairment versus Subjective Cognitive Decline

Author: Sandra den Hoedt, Kristien Y. Dorst-Lagerwerf, Helga E. de Vries, Annemieke J.M. Rozemuller, Philip Scheltens, Jochen Walter, Eric J.G. Sijbrands, Pilar Martinez-Martinez, Adrie J.M. Verhoeven, Charlotte E. Teunissen, Monique T. Mulder, Molecular cell biology and Immunology, ACS - Microcirculation, Amsterdam Neuroscience - Neuroinfection & -inflammation, Amsterdam Neuroscience - Neurovascular Disorders, Pathology, Amsterdam Neuroscience - Neurodegeneration, Neurology, and Neurochemistry Laboratory
Subjects: RISK, ceramides, sphingolipids, CERAMIDE, DEMENTIA, General Neuroscience, Apolipoprotein E4, BETA, ASSOCIATION, Alzheimer's disease, METABOLISM, CEREBRAL AMYLOID ANGIOPATHY, SPHINGOMYELINS, cerebrospinal fluid, APOLIPOPROTEIN-E, lipoproteins, ALZHEIMERS-DISEASE, Psychiatry and Mental health, Clinical Psychology, cognitive dysfunction, amyloid-beta peptides, Geriatrics and Gerontology
Abstract: BACKGROUND: Alzheimer's disease (AD) patients display alterations in cerebrospinal fluid (CSF) and plasma sphingolipids. The APOE4 genotype increases the risk of developing AD.OBJECTIVE: To test the hypothesis that the APOE4 genotype affects common sphingolipids in CSF and in plasma of patients with early stages of AD.METHODS: Patients homozygous for APOE4 and non-APOE4 carriers with mild cognitive impairment (MCI; n = 20 versus 20) were compared to patients with subjective cognitive decline (SCD; n = 18 versus 20). Sphingolipids in CSF and plasma lipoproteins were determined by liquid-chromatography-tandem mass spectrometry. Aβ42 levels in CSF were determined by immunoassay.RESULTS: APOE4 homozygotes displayed lower levels of sphingomyelin (SM; p = 0.042), SM(d18:1/18:0) (p = 0.026), and Aβ42 (p 0.49; p CONCLUSION: The APOE4 genotype affects sphingolipid profiles of CSF and plasma lipoproteins already at early stages of AD. ApoE4 may contribute to the early development of AD through modulation of sphingolipid metabolism.
Published: 2023

7. Breakfast partly restores the anti-inflammatory function of high-density lipoproteins from patients with type 2 diabetes mellitus

Author: Willem A. Dik, Monique T. Mulder, Nikita Martens, Roosmarijn F.H. Lemmers, Adrie J.M. Verhoeven, L. C. van Vark-van der Zee, M. van Hoek, Aloysius G Lieverse, Frank P.J. Leijten, Harm R. Haak, Eric J.G. Sijbrands, A.H. Maas, Pieter J. M. Leenen, C.M. Groot-van Ruijven, Internal Medicine, and Immunology
Subjects: medicine.medical_specialty, medicine.drug_class, High density, Anti-inflammatory, chemistry.chemical_compound, SDG 3 - Good Health and Well-being, Internal medicine, Type 2 diabetes mellitus, Internal Medicine, Medicine, Diseases of the circulatory (Cardiovascular) system, Peg precipitation, Endothelium, Breakfast, VCAM-1, business.industry, Type 2 Diabetes Mellitus, nutritional and metabolic diseases, Retinal, Iodixanol, High-density lipoprotein function, Endocrinology, medicine.anatomical_structure, chemistry, RC666-701, Density gradient ultracentrifugation, lipids (amino acids, peptides, and proteins), Cardiology and Cardiovascular Medicine, business, Density gradient centrifugation, medicine.drug, Artery
Abstract: Background and aims: High-density lipoproteins (HDL) of patients with type 2 diabetes mellitus (T2DM) have impaired anti-inflammatory activities. The anti-inflammatory activity of HDL has been determined ex vivo after isolation by different methods from blood mostly obtained after overnight fasting. We first determined the effect of the HDL isolation method, and subsequently the effect of food intake on the anti-inflammatory function of HDL from T2DM patients. Methods: Blood was collected from healthy controls and T2DM patients after an overnight fast, and from T2DM patients 3 h after breakfast (n = 17 each). HDL was isolated by a two-step density gradient ultracentrifugation in iodixanol (HDLDGUC2), by sequential salt density flotation (HDLSEQ) or by PEG precipitation (HDLPEG). The anti-inflammatory function of HDL was determined by the reduction of the TNFα-induced expression of VCAM-1 in human coronary artery endothelial cells (HCAEC) and retinal endothelial cells (REC). Results: HDL isolated by the three different methods from healthy controls inhibited TNFα-induced VCAM-1 expression in HCAEC. With apoA-I at 0.7 μM, HDLDGUC2 and HDLSEQ were similarly effective (16% versus 14% reduction; n = 3; p > 0.05) but less effective than HDLPEG (28%, p < 0.05). Since ultracentrifugation removes most of the unbound plasma proteins, we used HDLDGUC2 for further experiments. With apoA-I at 3.2 μM, HDL from fasting healthy controls and T2DM patients reduced TNFα-induced VCAM-1 expression in HCAEC by 58 ± 13% and 51 ± 20%, respectively (p = 0.35), and in REC by 42 ± 13% and 25 ± 18%, respectively (p < 0.05). Compared to preprandial HDL, postprandial HDL from T2DM patients reduced VCAM-1 expression by 56 ± 16% (paired test: p < 0.001) in HCAEC and by 34 ± 13% (paired test: p < 0.05) in REC. Conclusions: The ex vivo anti-inflammatory activity of HDL is affected by the HDL isolation method. Two-step ultracentrifugation in an iodixanol gradient is a suitable method for HDL isolation when testing HDL anti-inflammatory function. The anti-inflammatory activity of HDL from overnight fasted T2DM patients is significantly impaired in REC but not in HCAEC. The anti-inflammatory function of HDL is partly restored by food intake.
Published: 2021

8. Lipoprotein(a) is robustly associated with aortic valve calcium

Author: Rutger Verbeek, Yannick Kaiser, Daniel Bos, Meike W. Vernooij, Kang H. Zheng, Yolanda B. de Rijke, Eric J.G. Sijbrands, Maryam Kavousi, S. Matthijs Boekholdt, Sunny S Singh, Sara-Joan Pinto, Erik S.G. Stroes, Graduate School, Vascular Medicine, Cardiology, ACS - Atherosclerosis & ischemic syndromes, Experimental Vascular Medicine, Radiology and Nuclear Medicine, ACS - Heart failure & arrhythmias, Epidemiology, Internal Medicine, Clinical Chemistry, and Radiology & Nuclear Medicine
Subjects: Aortic valve, Male, medicine.medical_specialty, Hyperlipoproteinemias, Population, aortic valve stenosis, multidetector computed tomography, 030204 cardiovascular system & hematology, Time-to-Treatment, Cohort Studies, 03 medical and health sciences, Rotterdam Study, 0302 clinical medicine, Internal medicine, medicine, Prevalence, Outpatient clinic, Humans, 030212 general & internal medicine, education, Correlation of Data, Aged, Netherlands, education.field_of_study, Lipid Regulating Agents, biology, business.industry, Calcinosis, Lipoprotein(a), Middle Aged, medicine.anatomical_structure, Heart Disease Risk Factors, Aortic Valve, Valvular Heart Disease, Cohort, biology.protein, Cardiology, Disease Progression, Female, Cardiology and Cardiovascular Medicine, Agatston score, business, hyperlipidaemias, Blood sampling
Abstract: ObjectivesTo investigate the prevalence and quantity of aortic valve calcium (AVC) in two large cohorts, stratified according to age and lipoprotein(a) (Lp(a)), and to assess the association between Lp(a) and AVC.MethodsWe included 2412 participants from the population-based Rotterdam Study (52% women, mean age=69.6±6.3 years) and 859 apparently healthy individuals from the Amsterdam University Medical Centers (UMC) outpatient clinic (57% women, mean age=45.9±11.6 years). All individuals underwent blood sampling to determine Lp(a) concentration and non-enhanced cardiac CT to assess AVC. Logistic and linear regression analyses were performed to investigate the associations of Lp(a) with the presence and amount of AVC.ResultsThe prevalence of AVC was 33.1% in the Rotterdam Study and 5.4% in the Amsterdam UMC cohort. Higher Lp(a) concentrations were independently associated with presence of AVC in both cohorts (OR per 50 mg/dL increase in Lp(a): 1.54 (95% CI 1.36 to 1.75) in the Rotterdam Study cohort and 2.02 (95% CI 1.19 to 3.44) in the Amsterdam UMC cohort). In the Rotterdam Study cohort, higher Lp(a) concentrations were also associated with increase in aortic valve Agatston score (β 0.19, 95% CI 0.06 to 0.32 per 50 mg/dL increase).ConclusionsLp(a) is robustly associated with presence of AVC in a wide age range of individuals. These results provide further rationale to assess the effect of Lp(a) lowering interventions in individuals with early AVC to prevent end-stage aortic valve stenosis.
Published: 2021

9. Effect of FLAVAnols on bone turnover markers in type 2 diabetes mellitus-post hoc analysis from a 3-month randomized placebo-controlled trial

Author: Komal Waqas, Mardin Rashid, Bram C.J. van der Eerden, Sjoerd A.A. van den Berg, Eric J.G. Sijbrands, Kirsten A. Berk, M. Carola Zillikens, and Internal Medicine
Subjects: Nutrition and Dietetics, SDG 3 - Good Health and Well-being, Medicine (miscellaneous), Biochemistry, Food Science
Abstract: BACKGROUND: Individuals with type 2 diabetes mellitus (T2DM) have increased fracture risk with high bone mineral density, possibly related to advanced glycation end products (AGEs) accumulation in bone. Flavanol supplementation in postmenopausal women reduced AGEs formation and decreased bone resorption markers. However, to date, these effects have not been investigated in T2DM. OBJECTIVE: We used a post hoc secondary analysis to determine the effect of monomeric and oligomeric flavanols supplementation on bone turnover markers (BTMs) in individuals with T2DM. METHODS: Eighty-three individuals with T2DM, aged 40–85 years, with microalbuminuria were enrolled from 4 trial centers in Rotterdam, the Netherlands, into a randomized, double-blind, placebo-controlled trial with renal vascular health as the primary outcome. Participants were randomized (1:1) to receive either a placebo or 200 mg of monomeric and oligomeric flavanols as intervention for three months. Serum alkaline phosphatase (ALP), type I collagen crosslinked beta C-telopeptide (β-CTx), and type I procollagen-N-propeptide (P1NP) were measured at baseline and three months. ANCOVA was performed on rank transformed BTMs at three months as the outcome, adjusting for baseline BTMs, group, age, sex, and BMI. RESULTS: Baseline characteristics did not differ between the two arms. The adjusted mean change in BTMs at three months was not different between the placebo vs. intervention arm: ALP –0.059 (–0.262–0.145) vs. 0.060 (–0.135–0.356), p = 0.41; β-CTx 0.013 (–0.205–0.231) vs. 0.100 (–0.109–0.310), p = 0.53 and P1NP 0.091 (–0.080–0.262) vs. 0.030 (–0.134–0.195), p = 0.61. There was no significant within-group change in BTMs after three months in both study arms. CONCLUSION: Supplementation with daily 200 mg of flavanols during three months, on top of usual care in individuals with T2DM, did not result in changes in BTMs compared to placebo. Future studies are needed to show whether long-term supplementation in higher dosages may positively affect BTMs in individuals with T2DM.
Published: 2022

10. Sharing ICU Patient Data Responsibly Under the Society of Critical Care Medicine/European Society of Intensive Care Medicine Joint Data Science Collaboration

Author: Mihaela van der Schaar, Patrick Thoral, Matthew M. Churpek, Ari Ercole, Armand R. J. Girbes, Eric J.G. Sijbrands, Lewis J. Kaplan, Erwin J. O. Kompanje, Maurizio Cecconi, Ronald H. Driessen, Jan M. Peppink, Gilles Clermont, Heatherlee Bailey, Paul W. G. Elbers, Jozef Kesecioglu, Intensive care medicine, ACS - Diabetes & metabolism, Internal Medicine, and Intensive Care
Subjects: medicine.medical_specialty, Health Information Exchange, Databases, Factual, Privacy laws of the United States, data anonymization, Audit, Critical Care and Intensive Care Medicine, computer.software_genre, Hospitals, University, 03 medical and health sciences, 0302 clinical medicine, big data, Medicine, Humans, Critical Care Outcomes, Intensive care medicine, database, Societies, Medical, Netherlands, Health Insurance Portability and Accountability Act, Data anonymization, Database, business.industry, Online Clinical Investigations, 030208 emergency & critical care medicine, artificial intelligence, Data science, United States, Data sharing, Intensive Care Units, machine learning, 030228 respiratory system, General Data Protection Regulation, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, data science, Privacy law, business, computer, Algorithms, Confidentiality
Abstract: Supplemental Digital Content is available in the text., OBJECTIVES: Critical care medicine is a natural environment for machine learning approaches to improve outcomes for critically ill patients as admissions to ICUs generate vast amounts of data. However, technical, legal, ethical, and privacy concerns have so far limited the critical care medicine community from making these data readily available. The Society of Critical Care Medicine and the European Society of Intensive Care Medicine have identified ICU patient data sharing as one of the priorities under their Joint Data Science Collaboration. To encourage ICUs worldwide to share their patient data responsibly, we now describe the development and release of Amsterdam University Medical Centers Database (AmsterdamUMCdb), the first freely available critical care database in full compliance with privacy laws from both the United States and Europe, as an example of the feasibility of sharing complex critical care data. SETTING: University hospital ICU. SUBJECTS: Data from ICU patients admitted between 2003 and 2016. INTERVENTIONS: We used a risk-based deidentification strategy to maintain data utility while preserving privacy. In addition, we implemented contractual and governance processes, and a communication strategy. Patient organizations, supporting hospitals, and experts on ethics and privacy audited these processes and the database. MEASUREMENTS AND MAIN RESULTS: AmsterdamUMCdb contains approximately 1 billion clinical data points from 23,106 admissions of 20,109 patients. The privacy audit concluded that reidentification is not reasonably likely, and AmsterdamUMCdb can therefore be considered as anonymous information, both in the context of the U.S. Health Insurance Portability and Accountability Act and the European General Data Protection Regulation. The ethics audit concluded that responsible data sharing imposes minimal burden, whereas the potential benefit is tremendous. CONCLUSIONS: Technical, legal, ethical, and privacy challenges related to responsible data sharing can be addressed using a multidisciplinary approach. A risk-based deidentification strategy, that complies with both U.S. and European privacy regulations, should be the preferred approach to releasing ICU patient data. This supports the shared Society of Critical Care Medicine and European Society of Intensive Care Medicine vision to improve critical care outcomes through scientific inquiry of vast and combined ICU datasets.
Published: 2021

11. The Clinical Genome Resource (ClinGen) Familial Hypercholesterolemia Variant Curation Expert Panel consensus guidelines for LDLR variant classification

Author: Joana Rita Chora, Margaret Chen, Lukáš Tichý, Sarah Leigh, Tomáš Freiberger, Michael A. Iacocca, Michal Kramarek, Robert A. Hegele, Hannah Wand, Cinthia E. Jannes, Liam R. Brunham, Heather Zimmermann, ClinGen Familial Hypercholesterolemia Expert Panel, Tami Johnston, Eric J.G. Sijbrands, Steve E. Humphries, Serra Kim, C. Lisa Kurtz, Alexandre C. Pereira, Mafalda Bourbon, Amanda J. Hooper, Jessica Chonis, Jian Wang, Mark Trinder, Joshua W. Knowles, Premysl Soucek, Maggie Williams, Annette Leon, Alain Carrié, and Internal Medicine
Subjects: ClinGen, medicine.medical_specialty, Population, Genomics, Familial hypercholesterolemia, Computational biology, 030204 cardiovascular system & hematology, Genome, Doenças Cardio e Cérebro-vasculares, Hyperlipoproteinemia Type II, 03 medical and health sciences, 0302 clinical medicine, Resource (project management), Hipercolesterolemia Familiar, medicine, Humans, ACMG/AMP, Genetic Testing, Familial Hypercholesterolemia, education, Mendelian disorders, Genetics (clinical), 030304 developmental biology, 0303 health sciences, education.field_of_study, business.industry, Genome, Human, Genetic Variation, medicine.disease, Variant Classification, 3. Good health, LDLR, Medical genetics, business, Colesterol
Abstract: The online version of this article (https://doi.org/10.1016/j. gim.2021.09.012) contains supplementary material, which is available to authorized users. Purpose: In 2015, the American College of Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology (AMP) published consensus standardized guidelines for sequence-level variant classification in Mendelian disorders. To increase accuracy and consistency, the Clinical Genome Resource Familial Hypercholesterolemia (FH) Variant Curation Expert Panel was tasked with optimizing the existing ACMG/AMP framework for disease-specific classification in FH. In this study, we provide consensus recommendations for the most common FH-associated gene, LDLR, where >2300 unique FH-associated variants have been identified. Methods: The multidisciplinary FH Variant Curation Expert Panel met in person and through frequent emails and conference calls to develop LDLR-specific modifications of ACMG/AMP guidelines. Through iteration, pilot testing, debate, and commentary, consensus among experts was reached. Results: The consensus LDLR variant modifications to existing ACMG/AMP guidelines include (1) alteration of population frequency thresholds, (2) delineation of loss-of-function variant types, (3) functional study criteria specifications, (4) cosegregation criteria specifications, and (5) specific use and thresholds for in silico prediction tools, among others. Conclusion: Establishment of these guidelines as the new standard in the clinical laboratory setting will result in a more evidence-based, harmonized method for LDLR variant classification worldwide, thereby improving the care of patients with FH. Clinical Genome Resource (ClinGen) is primarily funded by the National Human Genome Research Institute through the following 3 grants: U41HG006834, U41HG009649, and U41HG009650. ClinGen also receives support for content curation from the Eunice Kennedy Shriver National Institute of Child Health and Human Development through the following 3 grants: U24HD093483, U24HD093486, and U24HD093487. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. J.R.C. acknowledges her PhD fellowship funded by the Science and Technology Foundation (SFRH/BD/108503/2015). L.T. and T.F. are supported by the Ministry of Health of the Czech Republic (grant NU20-02-00261). S.E.H. is an Emeritus British Heart Foundation Professor and is funded by PG08/ 008 and by the National Institute for Health Research University College London Hospitals Biomedical Research Centre. M.T. is supported by a Vanier Canada Graduate Scholarship. L.R.B. is a Michael Smith Foundation for Health Research scholar and a Canada Research Chair in Precision Cardiovascular Disease Prevention. R.A.H. is supported by the Jacob J. Wolfe Distinguished Medical Research Chair, the Edith Schulich Vinet Canada Research Chair in Human Genetics, the Martha G. Blackburn Chair in Cardiovascular Research, and operating grants from the Canadian Institutes of Health Research (Foundation Grant) and the Heart and Stroke Foundation of Ontario (G-18- 0022147). J.W.K. is supported by the National Institutes of Health through grants P30DK116074 (to the Stanford Diabetes Research Center), R01 DK116750, R01 DK120565, and R01 DK106236 and by the American Diabetes Association (grant #1-19-JDF-108). info:eu-repo/semantics/publishedVersion
Published: 2022

12. Health economic evaluation of screening and treating children with familial hypercholesterolemia early in life: Many happy returns on investment?

Author: Gerald F. Watts, Brian A. Ference, Sophia Zoungas, Richard Norman, Zanfina Ademi, Albert Wiegman, Eric J.G. Sijbrands, Danny Liew, Jing Pang, Paediatric Metabolic Diseases, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, ACS - Heart failure & arrhythmias, ACS - Diabetes & metabolism, and ACS - Atherosclerosis & ischemic syndromes
Subjects: 0301 basic medicine, Cardiovascular event, Lifetime exposure, Pediatrics, medicine.medical_specialty, Statin, Cost effectiveness, medicine.drug_class, Cost-Benefit Analysis, Familial hypercholesterolemia, 030204 cardiovascular system & hematology, Hyperlipoproteinemia Type II, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Mass Screening, Child, Children, health care economics and organizations, Cost–benefit analysis, business.industry, Australia, Cholesterol, LDL, medicine.disease, Investment (macroeconomics), Markov Chains, Quality-adjusted life year, 030104 developmental biology, Economic evaluation, Life years gained, Cost-effectiveness, Quality-Adjusted Life Years, Cardiology and Cardiovascular Medicine, business
Abstract: Background There are no studies that have specifically investigated the cost-effectiveness of cascade screening of children for heterozygous familial hypercholesterolemia (FH) and treatment of affected individuals with statins to prevent coronary heart disease (CHD). Purpose This study explores the cost-effectiveness of this strategy from the perspective of the Australian public healthcare system. Methods A lifetime Markov model with four health states (Alive without CHD, Alive with CHD, Dead from fatal CHD, and Dead from other causes) was developed to simulate the progression of ten- year-old children screened for FH and treated immediately with statins if found to have FH. The underlying prevalence of FH in this target population was assumed to be 56.8%, and the sensitivity and specificity of testing was 100%. The comparator was usual care, which assumed that subjects started statins spontaneously at a later point or when they experienced a cardiovascular event. The effect of reducing low-density lipoprotein cholesterol (LDL-C) on the risk of a first event at each age assumed that risk was proportional to total lifetime exposure and was implemented using Mendelian randomisation analysis data. Cost and other outcome data were sourced from published sources. Outcome of interests were costs in Australian dollars (AUD), life years gained (LYG) and quality-adjusted life years (QALYs) gained, as well as incremental cost-effectiveness ratios (ICERs) of costs per LYG and per QALY gained. All future costs and outcomes were discounted by 5% annually. Results Undiscounted results showed that compared with usual care, cascade screening of ten year-old children for FH and initiation of treatment of affected individuals saved 7.77 LYG and 7.53 QALYs per person over a lifetime. With 5% annual discounting, there were 0.97 LYG and 1.07 QALYs gained per person, at an additional cost of $3,244. These equated to ICERs of $3334 per LYG and $3023 per QALY gained. The equivalent ICERs in USD would be $5089 per LYG gained and $4615 per QALY gained. Sensitivity analysis showed the results to be robust. Conclusions Compared to usual care, cascade screening of ten year old children for FH and treating affected individuals is likely to be highly cost-effective. Table 1. Granular cost and benefit data Funding Acknowledgement Type of funding source: None
Published: 2020

13. Sex difference in the incidence of microvascular complications in patients with type 2 diabetes mellitus: a prospective cohort study

Author: Eric J.G. Sijbrands, Roosmarijn F.H. Lemmers, Jeanine E. Roeters-van Lennep, Aloysius G Lieverse, Thijs T. W. van Herpt, Sunny S Singh, Mandy van Hoek, and Internal Medicine
Subjects: Male, medicine.medical_specialty, Microvascular complications, Endocrinology, Diabetes and Metabolism, Type 2 diabetes, Cohort Studies, Endocrinology, SDG 3 - Good Health and Well-being, Risk Factors, Internal medicine, Diabetes mellitus, Sex differences, Internal Medicine, medicine, Albuminuria, Humans, Prospective Studies, Retinopathy, Prospective cohort study, Aged, Dyslipidemias, Netherlands, Cause of death, Sex Characteristics, business.industry, Incidence, Microcirculation, Incidence (epidemiology), Type 2 Diabetes Mellitus, General Medicine, Middle Aged, medicine.disease, Neuropathy, Diabetes Mellitus, Type 2, Hypertension, Original Article, Female, Microalbuminuria, business, Diabetic Angiopathies, Dyslipidemia, Follow-Up Studies
Abstract: Aims Type 2 diabetes mellitus is a major cause of death and disability due to its long-term macro- and microvascular diseases. Although women with type 2 diabetes have more macrovascular diseases, it is unclear whether there are sex differences in the occurrence of microvascular disease. The aim of our study was to investigate sex differences in the incidence of microvascular complications in type 2 diabetes. Methods Analyses were performed in the DiaGene study, a prospective cohort study for complications of type 2 diabetes, collected in the city of Eindhoven, the Netherlands (n = 1886, mean follow-up time = 6.93 years). Cox proportional hazard models adjusted for risk factors for complications (age, smoking, hypertension, dyslipidemia, HbA1c and duration of type 2 diabetes) were used to analyze the incidence of microvascular complications in men and women. Results The incidence of microalbuminuria was significantly higher in men (HR microalbuminuria 1.64 [CI 1.21–2.24], p = 0.002). Additionally, men are more likely to develop two or three microvascular complications compared to women (OR 2.42 [CI 1.69–3.45], p Conclusions This study shows that men with type 2 diabetes are more likely to develop microvascular complications, especially microalbuminuria. Furthermore, men seem to have a higher chance of developing multiple microvascular complications. Our results highlight that men and women may not benefit to a similar extent from current treatment approaches to prevent diabetes-related microvascular diseases.
Published: 2020

14. Lipoprotein(a) plasma levels are not associated with incident microvascular complications in type 2 diabetes mellitus

Author: Mandy van Hoek, Yolanda B. de Rijke, M. Rashid, Florian Kronenberg, Sunny S Singh, Monique T. Mulder, Aloysius G Lieverse, Eric J.G. Sijbrands, Claudia Lamina, Internal Medicine, and Clinical Chemistry
Subjects: Male, medicine.medical_specialty, Microvascular complications, Endocrinology, Diabetes and Metabolism, Population, SNP, Type 2 diabetes, rs3798220, Gastroenterology, Polymorphism, Single Nucleotide, Article, Nephropathy, Lp(a), SDG 3 - Good Health and Well-being, Risk Factors, Internal medicine, Internal Medicine, medicine, Humans, Genetic Predisposition to Disease, rs10455872, Prospective Studies, Risk factor, education, Prospective cohort study, Retinopathy, Macrovascular disease, Aged, education.field_of_study, biology, business.industry, Type 2 Diabetes Mellitus, Lipoprotein(a), Middle Aged, medicine.disease, Spline, Neuropathy, LPA, Diabetes Mellitus, Type 2, biology.protein, Female, business
Abstract: Aims/hypothesis Microvascular disease in type 2 diabetes is a significant cause of end-stage renal disease, blindness and peripheral neuropathy. The strict control of known risk factors, e.g. lifestyle, hyperglycaemia, hypertension and dyslipidaemia, reduces the incidence of microvascular complications, but a residual risk remains. Lipoprotein (a) [Lp(a)] is a strong risk factor for macrovascular disease in the general population. We hypothesised that plasma Lp(a) levels and the LPA gene SNPs rs10455872 and rs3798220 are associated with the incident development of microvascular complications in type 2 diabetes. Methods Analyses were performed of data from the DiaGene study, a prospective study for complications of type 2 diabetes, collected in the city of Eindhoven, the Netherlands (n = 1886 individuals with type 2 diabetes, mean follow-up time = 6.97 years). To assess the relationship between plasma Lp(a) levels and the LPA SNPs with each newly developed microvascular complication (retinopathy n = 223, nephropathy n = 246, neuropathy n = 236), Cox proportional hazards models were applied and adjusted for risk factors for microvascular complications (age, sex, mean arterial pressure, non-HDL-cholesterol, HDL-cholesterol, BMI, duration of type 2 diabetes, HbA1c and smoking). Results No significant associations of Lp(a) plasma levels and the LPA SNPs rs10455872 and rs3798220 with prevalent or incident microvascular complications in type 2 diabetes were found. In line with previous observations the LPA SNPs rs10455872 and rs3798220 did influence the plasma Lp(a) levels. Conclusions/interpretation Our data show no association between Lp(a) plasma levels and the LPA SNPs with known effect on Lp(a) plasma levels with the development of microvascular complications in type 2 diabetes. This indicates that Lp(a) does not play a major role in the development of microvascular complications. However, larger studies are needed to exclude minimal effects of Lp(a) on the development of microvascular complications.
Published: 2020

15. Apolipoprotein B, Residual Cardiovascular Risk After Acute Coronary Syndrome, and Effects of Alirocumab

Author: Emil Hagström, P. Gabriel Steg, Michael Szarek, Deepak L. Bhatt, Vera A. Bittner, Nicolas Danchin, Rafael Diaz, Shaun G. Goodman, Robert A. Harrington, J. Wouter Jukema, Evangelos Liberopoulos, Nikolaus Marx, Jennifer McGinniss, Garen Manvelian, Robert Pordy, Michel Scemama, Harvey D. White, Andreas M. Zeiher, Gregory G. Schwartz, Pierluigi Tricoci, Matthew T. Roe, Kenneth W. Mahaffey, Jay M. Edelberg, Corinne Hanotin, Guillaume Lecorps, Angèle Moryusef, William J. Sasiela, Jean-François Tamby, Philip E Aylward, Heinz Drexel, Peter Sinnaeve, Mirza Dilic, Renato D. Lopes, Nina N Gotcheva, Juan-Carlos Prieto, Huo Yong, Patricio López-Jaramillo, Ivan Pećin, Zeljko Reiner, Petr Ostadal, Steen Hvitfeldt Poulsen, Margus Viigimaa, Markku S Nieminen, Vakhtang Chumburidze, Pablo Carlos, Montenegro Valdovinos, Hung-Fat Tse, Robert Gabor Kiss, Denis Xavier, Doron Zahger, Marco Valgimigli, Takeshi Kimura, Hyo Soo Kim, Sang-Hyun Kim, Andrejs Erglis, Aleksandras Laucevicius, Sasko Kedev, Khalid Yusoff, Gabriel Arturo Ramos López, Marco Alings, Sigrun Halvorsen, Roger M Correa Flores, Rody G. Sy, Andrzej Budaj, Joao Morais, Maria Dorobantu, Yuri Karpov, Arsen D. Ristic, Terrance Chua, Jan Murin, Zlatko Fras, Anthony J Dalby, José Tuñón, H. Asita de Silva, Ulf Landmesser, Christian Müller, Chern-En Chiang, Piyamitr Sritara, Sema Guneri, Alexander Parkhomenko, Kausik K. Ray, Patrick M. Moriarty, Robert Vogel, Bernard Chaitman, Sheryl F. Kelsey, Anders G. Olsson, Jean-Lucien Rouleau, Maarten L. Simoons, Karen Alexander, Chiara Meloni, Robert Rosenson, Eric J.G. Sijbrands, John H. Alexander, Luciana Armaganijan, Akshay Bagai, Maria Cecilia Bahit, J. Matthew Brennan, Shaun Clifton, Adam D. DeVore, Shalonda Deloatch, Sheila Dickey, Keith Dombrowski, Grégory Ducrocq, Zubin Eapen, Patricia Endsley, Arleen Eppinger, Robert W. Harrison, Connie Ng Hess, Mark A. Hlatky, Joseph Dedrick Jordan, Joshua W. Knowles, Bradley J. Kolls, David F. Kong, Sergio Leonardi, Linda Lillis, David J. Maron, Jill Marcus, Robin Mathews, Rajendra H. Mehta, Robert J. Mentz, Humberto Graner Moreira, Chetan B. Patel, Sabrina Bernardez Pereira, Lynn Perkins, Thomas J. Povsic, Etienne Puymirat, William Schuyler Jones, Bimal R. Shah, Matthew W. Sherwood, Kenya Stringfellow, Darin Sujjavanich, Mustafa Toma, Charlene Trotter, Sean F.P. van Diepen, Matthew D. Wilson, Andrew Tze-Kay Yan, Lilia B Schiavi, Marcelo Garrido, Andrés F Alvarisqueta, Sonia A Sassone, Anselmo P Bordonava, Alberto E Alves De Lima, Jorge M Schmidberg, Ernesto A Duronto, Orlando C Caruso, Leonardo P Novaretto, Miguel Angel Hominal, Oscar R Montaña, Alberto Caccavo, Oscar A Gomez Vilamajo, Alberto J Lorenzatti, Luis R Cartasegna, Gustavo A Paterlini, Ignacio J Mackinnon, Guillermo D Caime, Marcos Amuchastegui, Oscar Salomone, Oscar R Codutti, Horacio O Jure, Julio OE Bono, Adrian D Hrabar, Julio A Vallejos, Rodolfo A Ahuad Guerrero, Federico Novoa, Cristian A Patocchi, Cesar J Zaidman, Maria E Giuliano, Ricardo D Dran, Marisa L Vico, Gabriela S Carnero, Pablo N Guzman, Juan C Medrano Allende, Daniela F Garcia Brasca, Miguel H Bustamante Labarta, Sebastian Nani, Eduardo DS Blumberg, Hugo R Colombo, Alberto Liberman, Victorino Fuentealba, Hector L Luciardi, Gabriel D Waisman, Mario A Berli, Ruben O Garcia Duran, Horacio G Cestari, Hugo A Luquez, Jorge A Giordano, Silvia S Saavedra, Gerardo Zapata, Osvaldo Costamagna, Susana Llois, Jonathon H Waites, Nicholas Collins, Allan Soward, Chris LS Hii, James Shaw, Margaret A Arstall, John Horowitz, Daniel Ninio, James F Rogers, David Colquhoun, Romulo E Oqueli Flores, Philip Roberts-Thomson, Owen Raffel, Sam J Lehman, Constantine Aroney, Steven GM Coverdale, Paul J Garrahy, Gregory Starmer, Mark Sader, Patrick A Carroll, Ronald Dick, Robert Zweiker, Uta Hoppe, Kurt Huber, Rudolf Berger, Georg Delle-Karth, Bernhard Frey, Franz Weidinger, Dirk Faes, Kurt Hermans, Bruno Pirenne, Attilio Leone, Etienne Hoffer, Mathias CM Vrolix, Luc De Wolf, Bart Wollaert, Marc Castadot, Karl Dujardin, Christophe Beauloye, Geert Vervoort, Harry Striekwold, Carl Convens, John Roosen, Emanuele Barbato, Marc Claeys, Frank Cools, Ibrahim Terzic, Fahir Barakovic, Zlatko Midzic, Belma Pojskic, Emir Fazlibegovic, Azra Durak-Nalbantic, Mehmed Kulić, Dusko Vulic, Adis Muslibegovic, Boris Goronja, Gilmar Reis, Luciano Sousa, Jose C Nicolau, Flavio E Giorgeto, Ricardo P Silva, Lilia Nigro Maia, Rafael Rech, Paulo RF Rossi, Maria José AG Cerqueira, Norberto Duda, Renato Kalil, Adrian Kormann, José Antonio M Abrantes, Pedro Pimentel Filho, Ana Priscila Soggia, Mayler ON de Santos, Fernando Neuenschwander, Luiz C Bodanese, Yorghos L Michalaros, Freddy G Eliaschewitz, Maria H Vidotti, Paulo E Leaes, Roberto V Botelho, Sergio Kaiser, Euler Roberto F Fernandes Manenti, Dalton B Precoma, Jose C Moura Jorge, Pedro Silva, Jose A Silveira, Wladmir Saporito, Jose A Marin Neto, Gilson S Feitosa, Luiz Eduardo F Ritt, Juliana A de Souza, Fernando Costa, Weimar KSB Souza, Helder JL Reis, Leandro Machado, José Carlos Aidar Ayoub, Georgi V Todorov, Fedya P Nikolov, Elena S Velcheva, Maria L Tzekova, Haralambi O Benov, Stanislav L Petranov, Haralin S Tumbev, Nina S Shehova-Yankova, Dimitar T Markov, Dimitar H Raev, Mihail N Mollov, Kostadin N Kichukov, Katya A Ilieva- Pandeva, Raya Ivanova, Maryana Gospodinov, Valentina M Mincheva, Petar V Lazov, Bojidar I Dimov, Manohara Senaratne, James Stone, Jan Kornder, Stephen Pearce, Danielle Dion, Daniel Savard, Yves Pesant, Amritanshu Pandey, Simon Robinson, Gilbert Gosselin, Saul Vizel, Gordon Hoag, Ronald Bourgeois, Anne Morisset, Eric Sabbah, Bruce Sussex, Simon Kouz, Paul MacDonald, Ariel Diaz, Nicolas Michaud, David Fell, Raymond Leung, Tycho Vuurmans, Christopher Lai, Frank Nigro, Richard Davies, Gustavo Nogareda, Ram Vijayaraghavan, John Ducas, Serge Lepage, Shamir Mehta, James Cha, Robert Dupuis, Peter Fong, Sohrab Lutchmedial, Josep Rodes-Cabau, Hussein Fadlallah, David Cleveland, Thao Huynh, Iqbal Bata, Adnan Hameed, Cristian Pincetti, Sergio Potthoff, Juan C Prieto, Monica Acevedo, Arnoldo Aguirre, Margarita Vejar, Mario Yañez, Guillermo Araneda, Mauricio Fernandez, Luis Perez, Paola Varleta, Fernando Florenzano, Laura Huidobro, Carlos A Raffo, Claudia Olivares, Leonardo Nahuelpan, Humberto Montecinos, Jiyan Chen, Yugang Dong, Weijian Huang, Jianzhong Wang, Shi’An Huang, Zhuhua Yao, Xiang Li, Lan Cui, Wenhua Lin, Yuemin Sun, Jingfeng Wang, Jianping Li, Xuelian Zhang, Hong Zhu, Dandan Chen, Lan Huang, Shaohong Dong, Guohai Su, Biao Xu, Xi Su, Xiaoshu Cheng, Jinxiu Lin, Wenxia Zong, Huanming Li, Yi Feng, Dingli Xu, Xinchun Yang, Yuannan Ke, Xuefeng Lin, Zheng Zhang, Zeqi Zheng, Zhurong Luo, Yundai Chen, Chunhua Ding, Yi Zhong, Yang Zheng, Xiaodong Li, Daoquan Peng, Shuiping Zhao, Ying Li, Xuebo Liu, Meng Wei, Shaowen Liu, Yihua Yu, Baiming Qu, Weihong Jiang, Yujie Zhou, Xingsheng Zhao, Zuyi Yuan, Ying Guo, Xiping Xu, Xubo Shi, Junbo Ge, Guosheng Fu, Feng Bai, Weiyi Fang, Xiling Shou, Xiangjun Yang, Jian’An Wang, Meixiang Xiang, Yingxian Sun, Qinghua Lu, Ruiyan Zhang, Jianhua Zhu, Yizhou Xu, Zhongcai Fan, Tianchang Li, Chun Wu, Nicolas Jaramillo, Gregorio Sanchez Vallejo, Diana C Luna Botia, Rodrigo Botero Lopez, Dora I Molina De Salazar, Alberto J Cadena Bonfanti, Carlos Cotes Aroca, Juan Diego Higuera, Marco Blanquicett, Sandra I Barrera Silva, Henry J Garcia Lozada, Julian A Coronel Arroyo, Jose L Accini Mendoza, Ricardo L Fernandez Ruiz, Alvaro M. Quintero Ossa, Fernando G Manzur Jatin, Aristides Sotomayor Herazo, Jeffrey Castellanos Parada, Rafael Suarez Arambula, Miguel A Urina Triana, Angela M Fernandez Trujillo, Maja Strozzi, Siniša Car, Davor Miličić, Martina Lovrić Benčić, Hrvoje Pintarić, Đeiti Prvulović, Jozica Šikić, Viktor Peršić, Dean Mileta, Kresimir Štambuk, Zdravko Babić, Vjekoslav Tomulic, Josip Lukenda, Stanka Mejic-Krstulovic, Boris Starcevic, Jindrich Spinar, David Horak, Zdenek Velicka, David Alan, Vilma Machova, Ales Linhart, Vojtech Novotny, Vladimir Kaucak, Richard Rokyta, Robert Naplava, Zdenek Coufal, Vera Adamkova, Ivo Podpera, Jiri Zizka, Zuzana Motovska, Ivana Marusincova, Petr Heinc, Jiri Kuchar, Petr Povolny, Jiri Matuska, Steen H Poulsen, Bent Raungaard, Peter Clemmensen, Lia E Bang, Ole May, Morten Bøttcher, Jens D Hove, Lars Frost, Gunnar Gislason, John Larsen, Peter Betton Johansen, Flemming Hald, Peter Johansen, Jørgen Jeppesen, Tonny Nielsen, Kjeld S Kristensen, Piotr Maria Walichiewicz, Jens D Lomholdt, Ib C Klausen, Peter Kaiser Nielsen, Flemming Davidsen, Lars Videbaek, Mai Soots, Veiko Vahula, Anu Hedman, Üllar Soopõld, Kaja Märtsin, Tiina Jurgenson, Arved Kristjan, Saila Vikman, Heikki Huikuri, Juhani Airaksinen, Pierre Coste, Emile Ferrari, Olivier Morel, Gilles Montalescot, Jacques Machecourt, Gilles Barone-Rochette, Jacques Mansourati, Yves Cottin, Ph. Gabriel Steg, Florence Leclercq, Abdelkader Belhassane, Nicolas Delarche, Franck Boccara, Franck Paganelli, Jérôme Clerc, Francois Schiele, Victor Aboyans, Vincent Probst, Jacques Berland, Thierry Lefèvre, Irakli Khintibidze, Tamaz Shaburishvili, Zurab Pagava, Ramaz Ghlonti, Zaza Lominadze, George Khabeishvili, Rayyan Hemetsberger, Kemala Edward, Ursula Rauch-Kröhnert, Matthias Stratmann, Karl-Friedrich Appel, Ekkehard Schmidt, Heyder Omran, Christoph Stellbrink, Thomas Dorsel, Emmanouil Lianopoulos, Hans Friedrich Vöhringer, Roger Marx, Andreas Zirlik, Detlev Schellenberg, Thomas Heitzer, Ulrich Laufs, Christian Werner, Stephan Gielen, Sebastian Nuding, Bernhard Winkelmann, Steffen Behrens, Karsten Sydow, Mahir Karakas, Gregor Simonis, Thomas Muenzel, Nikos Werner, Stefan Leggewie, Dirk Böcker, Rüdiger Braun- Dullaeus, Nicole Toursarkissian, Michael Jeserich, Matthias Weißbrodt, Tim Schaeufele, Joachim Weil, Heinz Völler, Johannes Waltenberger, Mohammed Natour, Susanne Schmitt, Dirk Müller-Wieland, Stephan Steiner, Lothar Heidenreich, Elmar Offers, Uwe Gremmler, Holger Killat, Werner Rieker, Sotiris Patsilinakos, Athanasios Kartalis, Athanassios Manolis, Dimitrios Sionis, Geargios Chachalis, Ioannis Skoumas, Vasilios Athyros, Panagiotis Vardas, Frangkiskos Parthenakis, Georgios Hahalis, John Lekakis, Apostolos Hatzitolios, Sergio R Fausto Ovando, Pablo Carlos Montenegro Valdovinos, Juan L Arango Benecke, Edgar R Rodriguez De Leon, Bryan PY Yan, David CW Siu, Tibor Turi, Bela Merkely, Imre Ungi, Geza Lupkovics, Lajos Nagy, András Katona, István Édes, Gábor Müller, Iván Horvath, Tibor Kapin, Zsolt Szigeti, József Faluközy, Mukund Kumbla, Manjinder Sandhu, Sharath Annam, Naveen Reddy Proddutur, Reddy Regella, Rajendra K Premchand, Ajaykumar Mahajan, Sudhir Pawar, Atul D Abhyanakar, Prafulla Kerkar, Ravishankar A Govinda, Abraham Oomman, Dhurjati Sinha, Sachin N Patil, Dhiman Kahali, Jitendra Sawhney, Abhijeet B Joshi, Sanjeev Chaudhary, Pankaj Harkut, Santanu Guha, Sanjay Porwal, Srimannarayana Jujjuru, Ramesh B Pothineni, Minguel R Monteiro, Aziz Khan, Shamanna S Iyengar, Jasprakash Singh Grewal, Manoj Chopda, Mahesh C Fulwani, Dr. Aparna Patange, Patil Sachin, Vijay K Chopra, Naresh K Goyal, Rituparna Shinde, Gajendra V Manakshe, Nitin Patki, Sumeet Sethi, Vengatesh Munusamy, Sunil Karnaand Sunil Thanvi, Srilakshmi Adhyapak, Chandrakant Patil, Ulhas Pandurangi, Rishabh Mathur, Jugal Gupta, Suhas Kalashetti, Ajit Bhagwat, Bagirath Raghuraman, Shiv Kumar Yerra, Prasant Bhansali, Rohidas Borse, Patil Rahul, Srihari Das, Vinay Kumar, Jabir Abdullakutty, Shireesh Saathe, Priya Palimkar, Jabir Abdullkutty, Shireesh Sathe, Shaul Atar, Michael Shechter, Morris Mosseri, Yaron Arbel, Chorin Ehud, Havakuk Ofer, Chaim Lotan, Uri Rosenschein, Amos Katz, Yaakov Henkin, Adi Francis, Marc Klutstein, Eugenia Nikolsky, Robert Zukermann, Yoav Turgeman, Majdi Halabi, Alon Marmor, Ran Kornowski, Michael Jonas, Offer Amir, Yonathan Hasin, Yoseph Rozenman, Shmuel Fuchs, Vered Zvi, Osamah Hussein, Dov Gavish, Zvi Vered, Yoseph Caraco, Mazen Elias, Naveh Tov, Efrat Wolfovitz, Michael Lishner, Nizar Elias, Giancarlo Piovaccari, Annamaria De Pellegrin, Raffaella Garbelotto, Gabriele Guardigli, Valgimigli Marco, Giovanni Licciardello, Carla Auguadro, Filippo Scalise, Claudio Cuccia, Alessandro Salvioni, Giuseppe Musumeci, Michelle Senni, Paolo Calabrò, Salvatore Novo, Pompilio Faggiano, Marco Metra, Nicoletta B De Cesare, Sergio Berti, Enrico Puccioni, Marcello Galvani, Maurizio Tespili, Piermarco Piatti, Michela Palvarini, Giuseppe De Luca, Roberto Violini, Alessandro De Leo, Zoran Olivari, Pasquale Perrone Filardi, Maurizio Ferratini, Vittorio Racca, Kazuoki Dai, Yuji Shimatani, Haruo Kamiya, Kenji Ando, Yoshihiro Takeda, Yoshihiro Morino, Yoshiki Hata, Kazuo Kimura, Koichi Kishi, Ichiro Michishita, Hiroki Uehara, Toshinori Higashikata, Atsushi Hirayama, Keiji Hirooka, Yasuji Doi, Satoru Sakagami, Shuichi Taguchi, Akihiro Koike, Hiroyuki Fujinaga, Shinji Koba, Ken Kozuma, Tomohiro Kawasaki, Yujiro Ono, Masatoshi Shimizu, Yousuke Katsuda, Atsuyuki Wada, Toshiro Shinke, Junya Ako, Kenshi Fujii, Toshiyuki Takahashi, Koichi Nakao, Yutaka Furukawa, Hiroshi Sugino, Ritsu Tamura, Toshiaki Mano, Masaaki Uematsu, Noriaki Utsu, Kashima Ito, Takuya Haraguchi, Katsuhiko Sato, Yasunori Ueda, Akira Nishibe, Kazuteru Fujimoto, Motomaru Masutani, Jung Han Yoon, Hack-Lyoung Kim, Hun Sik Park, In-Ho Chae, Moo Hyun Kim, Myung Ho Jeong, Seungwoon Rha, Chongjin Kim, Hyo-Soo Kim, Hae Young Kim, Taekjong Hong, Seung-Jea Tahk, Youngkwon Kim, Arija Busmane, Natalija Pontaga, Aldis Strelnieks, Iveta Mintale, Iveta Sime, Zaneta Petrulioniene, Roma Kavaliauskiene, Ruta Jurgaitiene, Gintare Sakalyte, Rimvydas Slapikas, Sigute Norkiene, Nerijus Misonis, Aleksandras Kibarskis, Raimondas Kubilius, Stojko Bojovski, Nensi Lozance, Aleksandar Kjovkaroski, Snezana Doncovska, Tiong Kiam Ong, Sazzli Kasim, Oteh Maskon, Balachandran Kandasamy, Houng B Liew, Wan Mohd Izani Wan Mohamed, Armando García Castillo, Jorge Carrillo Calvillo, Pedro Fajardo Campos, Juan Carlos Núñez Fragoso, Edmundo Alfredo Bayram Llamas, Marco Antonio Alcocer Gamba, Jaime Carranza Madrigal, Luis Gerardo González Salas, Enrique López Rosas, Belinda González Díaz, Eduardo Salcido Vázquez, Alfredo Nacoud Ackar, Guillermo Antonio Llamas Esperón, Carlos Rodolfo Martínez Sánchez, María Guerrero De Leon, Rodrigo Suarez Otero, Guillermo Fanghänel Salmón, Jesús Antonio Pérez Ríos, José Angel Garza Ruíz, Robert W Breedveld, Margriet Feenema-Aardema, Alida Borger-Van Der Burg, Pieter AM Hoogslag, Harry Suryapranata, Antonius Oomen, Paulus Van Haelst, Margriet Feenema-Aradema, Jacobijne J Wiersma, Dirk Basart, Ruud MA Van Der Wal, Peter Zwart, Pascalle Monraats, Henricus Van Kesteren, Ioannis Karalis, Johan Jukema, Gerardus JE Verdel, Bart RG Brueren, Roland PTh Troquay, Eric P Viergever, Nadea YY Al-Windy, Gerard L Bartels, Jan H Cornel, Walter RM Hermans, Johannes PR Herrman, Robert J Bos, Reginald GEJ Groutars, Coenraad C Van Der Zwaan, Refik Kaplan, Eelko Ronner, Bjorn E Groenemeijer, Patrick NA Bronzwaer, Anho AH Liem, Bernard JWM Rensing, Marcel JJA Bokern, Remco Nijmeijer, Ferry MRJ Hersbach, Frank F Willems, Antonius TM Gosselink, Saman Rasoul, John Elliott, Gerard Wilkins, Raewyn Fisher, Douglas Scott, Hamish Hart, Ralph Stewart, Scott Harding, Ian Ternouth, Nicholas Fisher, Samuel Wilson, Denise Aitken, Russell Anscombe, Laura Davidson, Tadeusz Tomala, Ottar Nygård, Jon Arne Sparby, Kjell Andersen, Lars Gullestad, Jarle Jortveit, Peter S Munk, Erlend gyllensten Singsaas, Ulf Hurtig, Jorge R Calderon Ticona, Julio R Durand Velasquez, Sandra A Negron Miguel, Enrique S Sanabria Perez, Jesus M Carrion Chambilla, Carlos A Chavez Ayala, Reynaldo P Castillo Leon, Rolando J Vargas GonzalesC, Jose D Hernandez Zuniga, Luis A Camacho Cosavalente, Jorge E Bravo Mannucci, Javier Heredia Landeo, Nassip C Llerena Navarro, Yudy M Roldan Concha, Víctor E Rodriguez Chavez, Henry A Anchante Hernandez, Carlos A Zea Nunez, Walter Mogrovejo Ramos, Arthur Ferrolino, Rosa Allyn G Sy, Louie Tirador, Generoso Matiga, Raul Martin Coching, Alisa Bernan, Gregorio Rogelio, Dante D. Morales, Edgar Tan, Dennis Jose Sulit, Adrian Wlodarczak, Grzegorz Skonieczny, Lidia Pawlowicz, Pawel Wojewoda, Benita Busz-Papiez, Janusz Bednarski, Aleksander Goch, Pawel Staneta, Elzbieta Dulak, Krzysztof Saminski, Wlodzimierz Krasowski, Wanda Sudnik, Aleksander Zurakowski, Marcin Skorski, Roman Lysek, Beata Miklaszewicz, Jan Andrzej Lipko, Edyta Kostarska-Srokosz, Marek Piepiorka, Anna Drzewiecka, Arkadiusz Stasiewski, Tomasz Blicharski, Leszek Bystryk, Michal Szpajer, Marek Korol, Tomasz Czerski, Jacek Gniot, Andrzej Lubinski, Jerzy Gorny, Edward Franek, Grzegorz Raczak, Hanna Szwed, Pedro Monteiro, Jose Mesquita Bastos, Helder H Pereira, Filipe Seixo, Carlos Mendonça, Ana Botelho, Francisca Caetano, Bogdan Minescu, Octavian Istratoaie, Dan N Tesloianu, Gabriel Cristian, Silviu Dumitrescu, Cristian GC Podoleanu, Mircea CA Constantinescu, Cristina M Bengus, Constantin Militaru, Doina Rosu, Irinel R Parepa, Adrian V Matei, Tom M Alexandru, Mihaela Malis, Ioan Coman, Yury Shvarts, Olga Orlikova, Zhanna Kobalava, Olga L Barbarash, Valentin Markov, Nadezhda Lyamina, Alexander Gordienko, Konstantin Zrazhevsky, Alexander Y Vishnevsky, Victor Gurevich, Raisa Stryuk, Nikita V Lomakin, Igor Bokarev, Tatiana Khlevchuk, Sergey Shalaev, Larisa Khaisheva, Petr Chizhov, Inna Viktorova, Natalya Osokina, Vladimir Shchekotov, Evgenia Akatova, Galina Chumakova, Igor Libov, Mikhail I Voevoda, Tatyana V Tretyakova, Evgeny Baranov, Sergey Shustov, Sergey Yakushin, Ivan Gordeev, Niiaz Khasanov, Olga Reshetko, Tatiana Sotnikova, Olga Molchanova, Konstantin Nikolaev, Liudmila Gapon, Elena Baranova, Elena Kosmachova, Yuriy Karpov, Anton Povzun, Liudmila Egorova, Vadim V Tyrenko, Igor G Ivanov, Masterov Ilya, Sergey Kanorsky, Dragan Simic, Nikola Ivanovic, Goran Davidovic, Nebojsa Tasic, Milika R. Asanin, Stevo Stojic, Svetlana R. Apostolovic, Stevan Ilic, Biljana Putnikovic Tosic, Aleksandar Stankovic, Aleksandra Arandjelovic, Slavica Radovanovic, Branislava Todic, Jovan Balinovac, Dragan V. Dincic, Petar Seferovic, Ana Karadzic, Slobodan Dodic, Sinisa Dimkovic, Tamara Jakimov, Kian-Keong Poh, Hean Yee Ong, Justin Tang I-Shing, Karol Micko, Jan Nociar, Daniel Pella, Peter Fulop, Marian Hranai, Juraj Palka, Juraj Mazur, Ivan Majercák, Andrej Dzupina, František Fazekas, Jozef Gonsorcik, Viliam Bugan, Juraj Selecky, Gabriel Kamensky, Jaroslava Strbova, Rudolf Smik, Andrej Dukat, Peter Olexa, Ivan Žuran, Janez Poklukar, Nataša Černič Šuligoj, Matija Cevc, Henry P Cyster, Naresh Ranjith, Clive Corbett, Junaid Bayat, Ellen Makoali Makotoko, Hendrik du Toit Theron, Ilse E Kapp, Matthys M de V Basson, Hanlie Lottering, Dina Van Aswegen, Louis J Van Zyl, Peter J Sebastian, Thayabran Pillay, Jan A Saaiman, Patrick J Commerford, Soraya Cassimjee, Garda Riaz, Iftikhar O Ebrahim, Mahomed Sarvan, Joseph H Mynhardt, Helmuth Reuter, Rajendran Moodley, Manuel Vida, Angel R. Cequier Fillat, Vicente Bodí Peris, Francisco Fuentes Jimenez, Francisco Marín, Jose M Cruz Fernández, Rafael Jesus Hidalgo Urbano, Blas Gil-Extremera, Pablo Toledo, Fernando Worner Diz, David Garcia-Dorado, Andres Iñiguez, Jose R Gonzalez-Juanatey, Javier Fernandez Portales, Fernando Civeira Murillo, Laia Matas Pericas, Jose Luis Zamorano, Manuel De Mora Martin, Jordi Bruguera Cortada, Joaquin J Alonso Martin, Jose Maria Serrano Antolin, José R De Berrazueta Fernández, José Antonio Vázquez de Prada, Jose Francisco Díaz Fernández, José Alberto García Lledó, Juan Cosín Sales, Javier Botas Rodriguez, Gabriel Gusi Tragant, Amparo Benedicto, Carlos Gonzalez-Juanatey, Mercedes Camprubí Potau, Ignacio Plaza Perez, César Morís De La Tassa, Pablo Loma-Osorio Rincon, Javier Balaguer Recena, Juan M Escudier, Antonio Coca Payeras, Norberto Alonso Orcajo, Godwin Constantine, Ruvaiz Haniffa, Nirmali Tissera, Stanley Amarasekera, Chandrike Ponnamperuma, Nimali Fernando, Kaputella Fernando, Jayanthimala Jayawardena, Santharaj Wijeyasingam, Gotabhaya Ranasinghe, Ruvan Ekanayaka, Sepalika Mendis, Vajira Senaratne, Gnanamoorthy Mayurathan, Ajantha Rajapaksha, Thilak Sirisena, Jagath I Herath, Naomali Amarasena, Stefan Berglund, Gundars Rasmanis, Ola Vedin, Nils Witt, Georgios Mourtzinis, Peter Nicol, Ole Hansen, Stefano Romeo, Steen Agergaard Jensen, Ingemar Torstensson, Ulf Ahremark, Torbjörn Sundelin, Tiziano Moccetti, Francois Mach, Ronald Binde, Oliver Gämperli, Wei- Chuan Tsai, Kwo-Chang Ueng, Wen-Ter Lai, Ming-En Liu, Juey- Jen Hwang, Wei-Hsian Yin, I-Chang Hsieh, Ming-Jer Hsieh, Wei Hsiang Lin, Jen-Yuan Kuo, Tsuei-Yuan Huang, Chih-Yuan Fang, Pinij Kaewsuwanna, Wasant Soonfuang, Woravut Jintapakorn, Apichard Sukonthasarn, Nattawut Wongpraparut, Krisada Sastravaha, Nakarin Sansanayudh, Wirash Kehasukcharoen, Dilok Piyayotai, Paiboon Chotnoparatpat, Ahmet Camsari, Hakan Kultursay, Bulent Mutlu, Murat Ersanli, Mustafa Demirtas, Cevat Kirma, Ertan Ural, Lale Koldas, Oleksandr Karpenko, Alexander Prokhorov, Ihor Vakaluyk, Halyna Myshanych, Dmytro Reshotko, Valeriy Batushkin, Leonid Rudenko, Ihor Kovalskyi, Mykola Kushnir, Vira Tseluyko, Yuriy Mostovoy, Mykola Stanislavchuk, Yulian Kyiak, Yuriy Karpenko, Yaroslav Malynovsky, Andriy Klantsa, Oles Kutniy, Ekaterina Amosova, Viktor Tashchuk, Oleh Leshchuk, Mykola Rishko, Mykola Kopytsya, Andriy Yagensky, Mykola Vatutin, Andriy Bagriy, Olga M Barna, Olexiy Ushakov, Georgiy Dzyak, Borys Goloborodko, Anatolii Rudenko, Volodymyr Zheleznyy, Jasper Trevelyan, Azfar Zaman, Kaeng Lee, Andrew Moriarty, Rajesh K Aggarwal, Piers Clifford, Yuk- Ki Wong, Syed MR Iqbal, Eduardas Subkovas, Denise Braganza, David Sarkar, Robert Storey, Huw Griffiths, Sam Mcclure, Rangasamy Muthusamy, Simon Smith, John Kurian, Terry Levy, Craig Barr, Honer Kadr, Robert Gerber, Audrius Simaitis, Handrean Soran, Adrian Brodison, Mohammad Ayaz, Muhammad Cheema, Richard Oliver, Simon Thackray, Telal Mudawi, Gohar Rahma, Ayyaz Sultan, Timothy Reynolds, David Sharman, david Spriging, Rob Butler, Peter Wilkinson, Gregory YH Lip, Nicholas Ossei-Gerning, Gil Vardi, Duccio Baldari, David Brabham, Charles Treasure II, Charles Dahl, Bruce Palmer, Alan Wiseman, Abul Khan, Sanjeev Puri, Ann Elizabeth Mohart, Carlos Ince, Enrique Flores, Scott Wright, Shi-Chi Cheng, Michael Rosenberg, William Rogers, Edward Kosinski, Les Forgosh, Jonathan Waltman, Mohammad Shoukfeh, Georges Dagher, Patrick Cambier, Ira Lieber, Priya Kumar, Cara East, Perry Krichmar, Mian Hasan, Lindsey White, Thomas Knickelbine, Thomas Haldis, Eve Gillespie, Thomas Amidon, David Suh, Imran Arif, mouhamad Abdallah, Faiq Akhter, Eric Carlson, Michael D’Urso, Fadi El- Ahdab, William Nelson, Katie Moriarty, Barry Harris, Steven Cohen, Luther Carter, Daniel Doty, Kenneth Sabatino, Tariq Haddad, Sunder Rao, Angel Mulkay, Ion Jovin, Kim Klancke, Vinay Malhotra, Sai K Devarapalli, Michael Koren, Harish Chandna, George Dodds III, Tauqir Goraya, James Bengston, Matthew Janik, Joseph Moran, Andrew Sumner, John Kobayashi, William Davis, Shahram Yazdani, John Pasquini, Maitreya Thakkar, Amarnath Vedere, Wayne Leimbach, James Rider, Sarah fenton, Narendra Singh, Anil V Shah, Denise Janosik, Carl Pepine, Brett Berman, Joseph Gelormini, Christopher Daniels, Kerensky Richard, Friederike Keating, Nicholas I Kondo, Sanjay Shetty, Howard Levite, Winfried Waider, Theodore Takata, Mazen Abu-Fadel, Vipul Shah, Rahul Aggarwal, Anil Kumar, Brack Hattler, Rose Do, Chad Link, Anna Bortnick, George Kinzfogl III, Arnold Ghitis, John Larry, Edward Teufel, Peter Kuhlman, Brent Mclaurin, Wenwu Zhang, Stephen Thew, Jalal Abbas, Matthew White, Othman Islam, Sumeet Subherwal, Nandkishore Ranadive, Babak Vakili, Christian Gring, David Henderson, Timothy Schuchard, Naim Farhat, Geoffrey Kline, Sharan Mahal, Jack Whitaker, Shawn Speirs, Rolf Andersen, Nizar Daboul, Phillip Horwitz, Firas Zahr, George Ponce, Zubair Jafar, Joseph Mcgarvey, Vipul Panchal, Stephen Voyce, Thomas Blok, William Sheldon, Masoud M Azizad, Carsten Schmalfuss, Mark Picone, Robert Pederson, William Herzog, Keith Friedman, Jason Lindsey, Eichenlaub Timothy, Parilak Leonard, Norman Lepor, Mahfouz El Shahawy, Howard Weintraub, Anand Irimpen, Alvaro Alonso, Wade May, Daniels Christopher, Thomas Galski, Alan Chu, Freny Mody, Ebrahimi Ramin, Zachary Hodes, Joseph Rossi, Gregory Rose, James Fairlamb, Charles Lambert, Ajit Raisinghani, Antonio Abbate, George Vetrovec, Marilyn King, Charles Carey, Jaime Gerber, Liwa Younis, Hyeun (Tom) Park, Mladen Vidovich, Thomas Knutson, Dennis Friedman, Fred Chaleff, Arthur Loussararian, Phillip Rozeman, Carey Kimmelstiel, Jeffrey Kuvin, Kevin Silver, Malcolm Foster, Glen Tonnessen, Andrey Espinoza, Mohamadali Amlani, Andreas Wali, Christopher Malozzi, Geert T Jong, Clara Massey, Keattiyoat Wattanakit, Philip J. O’Donnell, Dinesh Singal, Naseem Jaffrani, Sridhar Banuru, Daniel Fisher, Mark Xenakis, Neal Perlmutter, Ravi Bhagwat, James Strader, Ronald Blonder, Ayim Akyea-Djamson, Ajay Labroo, Kwan Lee, H. John Marais, Edmund Claxton, Robert Weiss, Rohr Kathryn, Martin Berk, Peter Rossi, Parag Joshi, Amit Khera, Ajit S Khaira, Greg Kumkumian, Steven Lupovitch, Joshua Purow, Stephen Welka, David Hoffman, Stuart Fischer, Eugene Soroka, Donald Eagerton, Samir Pancholy, Michael Ray, Norman Erenrich, Michael Farrar, Stewart Pollock, William J French, Steve Diamantis, Douglas Guy, Lawrence Gimple, Mark Neustel, Steven Schwartz, Edward Pereira, Seals Albert, Douglas Spriggs, Janet Strain, Suneet Mittal, Anthony Vo, Majed Chane, Jason Hall, Nampalli Vijay, Kapildeo Lotun, F. Martin Lester, Ahed Nahhas, Theodore Pope, Paul Nager, Rakesh Vohra, Mukesh Sharma, Riyaz Bashir, Hinan Ahmed, Michael Berlowitz, Robert Fishberg, Robert Barrucco, Eric Yang, Michael Radin, Daniel Sporn, Dwight Stapleton, Steven Eisenberg, Joel Landzberg, Martin Mcgough, Samir Turk, Michael Schwartz, P. Sandy Sundram, Diwakar Jain, Mark Zainea, Carlos Bayron, Ronald Karlsberg, Suhail Dohad, Henry Lui, William Keen, Donald Westerhausen, Sandeep Khurana, Himanshu Agarwal, Jessica Birchem, William Penny, Mark Chang, Sherrill Murphy, John Henry, Branislav Schifferdecker, John M Gilbert, Gopal Chalavarya, Charles Eaton, John F Schmedtje, Stuart Christenson, Imran Dotani, Douglas Denham, Alexander Macdonell, Paul Gibson, Aref Rahman, Tammam Al Joundi, Nizar Assi, Gary Conrad, Purushotham Kotha, Michael Love, Gregory Giesler, Howard Rubenstein, Dawood Gamil, Laura Akright, Justine Krawczyk, Joanne Cobler, Terry Wells, James Welker, Robert Foster, Richard Gilmore, Jay Anderson, Douglas Jacoby, Bill Harris, Geraldine Gardner, Ramprasad Dandillaya, Kishor Vora, John Kostis, John Hunter, David Laxson, Eric Ball, Flavia Egydio, Anelise Kawakami, Janaina Oliveira, Julianna Wozniak, Alexander Matthews, Caroline Ratky, Janine Valiris, Lisa Berdan, Anita Hepditch, Kirby Quintero, Tyrus Rorick, Melissa Westbrook, Madeleine Bezault, Elodie Drouet, Tabassome Simon, Caroline Alsweiler, Anne Luyten, Julie Butters, Liddy Griffith, Michelle Shaw, Lena Grunberg, Shahidul Islam, Marie-France Brégeault, Nathalie Bougon, Douglas Faustino, Sylvie Fontecave, Judith Murphy, Jean- Francois Tamby, Melanie Verrier, Veronique Agnetti, Dorthe Andersen, Emmy Badreddine, Mhamed Bekkouche, Cecile Bouancheau, Imane Brigui, Maddy Brocklehurst, Joseph Cianciarulo, Dawn Devaul, Szilvia Domokos, Cecile Gache, Caroline Gobillot, Severine Guillou, Jan Healy, Megan Heath, Gayatri Jaiwal, Carine Javierre, Julien Labeirie, Myriam Monier, Ulises Morales, Asmaa Mrabti, Bicky Mthombeni, Betim Okan, Lucile Smith, Jennifer Sheller, Sebastien Sopena, Valerie Pellan, Fadela Benbernou, Nafissa Bengrait, Maud Lamoureux, Katarina Kralova, Raphael Bejuit, Anthony Coulange, Christelle Berthou, Jérôme Repincay, Christelle Lorenzato, Alexis Etienne, Valerie Gouet, Virginie Loizeau, Mickael Normand, Anne Ourliac, Christelle Rondel, Antony Adamo, Pascale Beltran, Pauline Barraud, Helene Dubois-Gache, Benjamin Halle, Lamia Metwally, Maxime Mourgues, Marc Sotty, Marion Vincendet, Raluca Cotruta, Zhu Chengyue, Dominique Fournie-Lloret, Christine Morrello, Aurelie Perthuis, Patrick Picault, Isabelle Zobouyan, Helen M. Colhoun, Michael A. Dempsey, Mark A. McClanahan, Roe, Matthew T., Blicharski, Tomasz, Bystryk, Leszek, Szpajer, Michal, Korol, Marek, Czerski, Tomasz, Gniot, Jacek, Lubinski, Andrzej, Gorny, Jerzy, Franek, Edward, Raczak, Grzegorz, Vogel, Robert, Szwed, Hanna, Monteiro, Pedro, Mesquita Bastos, Jose, Pereira, Helder H., Morais, Joao, Seixo, Filipe, Mendonça, Carlos, Botelho, Ana, Caetano, Francisca, Minescu, Bogdan, Chaitman, Bernard, Istratoaie, Octavian, Tesloianu, Dan N., Dorobantu, Maria, Cristian, Gabriel, Dumitrescu, Silviu, Podoleanu, Cristian Gc, Constantinescu, Mircea Ca, Bengus, Cristina M., Militaru, Constantin, Rosu, Doina, Kelsey, Sheryl F., Parepa, Irinel R., Matei, Adrian V., Alexandru, Tom M., Malis, Mihaela, Coman, Ioan, Shvarts, Yury, Orlikova, Olga, Kobalava, Zhanna, Barbarash, Olga L., Markov, Valentin, Olsson, Anders G., Lyamina, Nadezhda, Gordienko, Alexander, Zrazhevsky, Konstantin, Vishnevsky, Alexander Y., Gurevich, Victor, Stryuk, Raisa, Lomakin, Nikita V., Bokarev, Igor, Khlevchuk, Tatiana, Shalaev, Sergey, Rouleau, Jean-Lucien, Khaisheva, Larisa, Chizhov, Petr, Viktorova, Inna, Osokina, Natalya, Shchekotov, Vladimir, Akatova, Evgenia, Chumakova, Galina, Libov, Igor, Voevoda, Mikhail I., Tretyakova, Tatyana V., Simoons, Maarten L., Baranov, Evgeny, Shustov, Sergey, Yakushin, Sergey, Gordeev, Ivan, Khasanov, Niiaz, Reshetko, Olga, Sotnikova, Tatiana, Molchanova, Olga, Nikolaev, Konstantin, Gapon, Liudmila, Alexander, Karen, Baranova, Elena, Kosmachova, Elena, Karpov, Yuriy, Karpov, Yuri, Povzun, Anton, Egorova, Liudmila, Tyrenko, Vadim V., Ivanov, Igor G., Ilya, Masterov, Kanorsky, Sergey, Meloni, Chiara, Simic, Dragan, Ivanovic, Nikola, Davidovic, Goran, Tasic, Nebojsa, Asanin, Milika R., Stojic, Stevo, Apostolovic, Svetlana R., Ilic, Stevan, Tosic, Biljana Putnikovic, Stankovic, Aleksandar, Rosenson, Robert, Arandjelovic, Aleksandra, Radovanovic, Slavica, Todic, Branislava, Ristic, Arsen D., Balinovac, Jovan, Dincic, Dragan V., Seferovic, Petar, Karadzic, Ana, Dodic, Slobodan, Dimkovic, Sinisa, Sijbrands, Eric J. G., Jakimov, Tamara, Poh, Kian-Keong, Yee Ong, Hean, Tang I-Shing, Justin, Micko, Karol, Nociar, Jan, Pella, Daniel, Fulop, Peter, Hranai, Marian, Palka, Juraj, Tricoci, Pierluigi, Mazur, Juraj, Majercák, Ivan, Dzupina, Andrej, Fazekas, František, Gonsorcik, Jozef, Bugan, Viliam, Murin, Jan, Selecky, Juraj, Kamensky, Gabriel, Strbova, Jaroslava, Alexander, John H., Smik, Rudolf, Dukat, Andrej, Olexa, Peter, Žuran, Ivan, Poklukar, Janez, Šuligoj, Nataša Černič, Cevc, Matija, Fras, Zlatko, Cyster, Henry P., Ranjith, Naresh, Armaganijan, Luciana, Corbett, Clive, Bayat, Junaid, Makoali Makotoko, Ellen, du Toit Theron, Hendrik, Kapp, Ilse E., de V Basson, Matthys M., Lottering, Hanlie, Van Aswegen, Dina, Van Zyl, Louis J., Sebastian, Peter J., Bagai, Akshay, Pillay, Thayabran, Saaiman, Jan A., Commerford, Patrick J., Cassimjee, Soraya, Riaz, Garda, Ebrahim, Iftikhar O., Sarvan, Mahomed, Mynhardt, Joseph H., Dalby, Anthony J., Reuter, Helmuth, Bahit, Maria Cecilia, Moodley, Rajendran, Vida, Manuel, Fillat, Angel R. Cequier, Peris, Vicente Bodí, Jimenez, Francisco Fuentes, Marín, Francisco, Cruz Fernández, Jose M., Hidalgo Urbano, Rafael Jesus, Gil-Extremera, Blas, Toledo, Pablo, Brennan, J. Matthew, Worner Diz, Fernando, Garcia-Dorado, David, Iñiguez, Andres, Gonzalez-Juanatey, Jose R., Portales, Javier Fernandez, Murillo, Fernando Civeira, Pericas, Laia Matas, Zamorano, Jose Luis, De Mora Martin, Manuel, Cortada, Jordi Bruguera, Clifton, Shaun, Alonso Martin, Joaquin J., Serrano Antolin, Jose Maria, De Berrazueta Fernández, José R., Vázquez de Prada, José Antonio, Díaz Fernández, Jose Francisco, García Lledó, José Alberto, Cosín Sales, Juan, Rodriguez, Javier Botas, Tragant, Gabriel Gusi, Benedicto, Amparo, DeVore, Adam D., Gonzalez-Juanatey, Carlos, Camprubí Potau, Mercedes, Perez, Ignacio Plaza, De La Tassa, César Morís, Rincon, Pablo Loma-Osorio, Recena, Javier Balaguer, Escudier, Juan M., Payeras, Antonio Coca, Orcajo, Norberto Alonso, Constantine, Godwin, Deloatch, Shalonda, Haniffa, Ruvaiz, Tissera, Nirmali, Amarasekera, Stanley, Ponnamperuma, Chandrike, Fernando, Nimali, Fernando, Kaputella, Jayawardena, Jayanthimala, Wijeyasingam, Santharaj, Ranasinghe, Gotabhaya, Ekanayaka, Ruvan, Dickey, Sheila, Mendis, Sepalika, Senaratne, Vajira, Mayurathan, Gnanamoorthy, Rajapaksha, Ajantha, Sirisena, Thilak, Herath, Jagath I., Amarasena, Naomali, Berglund, Stefan, Rasmanis, Gundars, Hagström, Emil, Dombrowski, Keith, Vedin, Ola, Witt, Nils, Mourtzinis, Georgios, Nicol, Peter, Hansen, Ole, Romeo, Stefano, Jensen, Steen Agergaard, Torstensson, Ingemar, Ahremark, Ulf, Sundelin, Torbjörn, Ducrocq, Grégory, Moccetti, Tiziano, Müller, Christian, Mach, Francois, Binde, Ronald, Landmesser, Ulf, Gämperli, Oliver, Chiang, Chern-En, Tsai, Wei-Chuan, Ueng, Kwo-Chang, Lai, Wen-Ter, Eapen, Zubin, Liu, Ming-En, Hwang, Juey-Jen, Yin, Wei-Hsian, Hsieh, I.-Chang, Hsieh, Ming-Jer, Hsiang Lin, Wei, Kuo, Jen-Yuan, Huang, Tsuei-Yuan, Fang, Chih-Yuan, Kaewsuwanna, Pinij, Endsley, Patricia, Soonfuang, Wasant, Jintapakorn, Woravut, Sukonthasarn, Apichard, Sritara, Piyamitr, Wongpraparut, Nattawut, Sastravaha, Krisada, Sansanayudh, Nakarin, Kehasukcharoen, Wirash, Piyayotai, Dilok, Chotnoparatpat, Paiboon, Eppinger, Arleen, Camsari, Ahmet, Kultursay, Hakan, Guneri, Sema, Mutlu, Bulent, Ersanli, Murat, Demirtas, Mustafa, Kirma, Cevat, Ural, Ertan, Koldas, Lale, Karpenko, Oleksandr, Harrison, Robert W., Prokhorov, Alexander, Vakaluyk, Ihor, Myshanych, Halyna, Reshotko, Dmytro, Batushkin, Valeriy, Rudenko, Leonid, Kovalskyi, Ihor, Kushnir, Mykola, Tseluyko, Vira, Mostovoy, Yuriy, Hess, Connie Ng, Stanislavchuk, Mykola, Kyiak, Yulian, Karpenko, Yuriy, Malynovsky, Yaroslav, Klantsa, Andriy, Kutniy, Oles, Amosova, Ekaterina, Tashchuk, Viktor, Leshchuk, Oleh, Parkhomenko, Alexander, Hlatky, Mark A., Rishko, Mykola, Kopytsya, Mykola, Yagensky, Andriy, Vatutin, Mykola, Bagriy, Andriy, Barna, Olga M., Ushakov, Olexiy, Dzyak, Georgiy, Goloborodko, Borys, Rudenko, Anatolii, Jordan, Joseph Dedrick, Zheleznyy, Volodymyr, Trevelyan, Jasper, Zaman, Azfar, Lee, Kaeng, Moriarty, Andrew, Aggarwal, Rajesh K., Clifford, Piers, Wong, Yuk-ki, Iqbal, Syed Mr, Subkovas, Eduardas, Knowles, Joshua W., Braganza, Denise, Sarkar, David, Storey, Robert, Griffiths, Huw, Mcclure, Sam, Muthusamy, Rangasamy, Smith, Simon, Kurian, John, Levy, Terry, Barr, Craig, Kolls, Bradley J., Kadr, Honer, Gerber, Robert, Simaitis, Audrius, Soran, Handrean, Brodison, Adrian, Ayaz, Mohammad, Cheema, Muhammad, Oliver, Richard, Thackray, Simon, Mudawi, Telal, Kong, David F., Rahma, Gohar, Sultan, Ayyaz, Reynolds, Timothy, Sharman, David, Spriging, David, Butler, Rob, Wilkinson, Peter, Lip, Gregory Yh, Ossei-Gerning, Nicholas, Vardi, Gil, Leonardi, Sergio, Baldari, Duccio, Brabham, David, Treasure Ii, Charles, Dahl, Charles, Palmer, Bruce, Wiseman, Alan, Khan, Abul, Puri, Sanjeev, Mohart, Ann Elizabeth, Ince, Carlos, Lillis, Linda, Flores, Enrique, Wright, Scott, Cheng, Shi-Chi, Rosenberg, Michael, Rogers, William, Kosinski, Edward, Forgosh, Les, Waltman, Jonathan, Shoukfeh, Mohammad, Dagher, Georges, Lopes, Renato D., Cambier, Patrick, Lieber, Ira, Kumar, Priya, East, Cara, Krichmar, Perry, Hasan, Mian, White, Lindsey, Knickelbine, Thomas, Haldis, Thomas, Gillespie, Eve, Maron, David J., Amidon, Thomas, Suh, David, Arif, Imran, Abdallah, Mouhamad, Akhter, Faiq, Carlson, Eric, D'Urso, Michael, El-Ahdab, Fadi, Nelson, William, Moriarty, Katie, Mahaffey, Kenneth W., Harris, Barry, Cohen, Steven, Carter, Luther, Doty, Daniel, Sabatino, Kenneth, Haddad, Tariq, Rao, Sunder, Mulkay, Angel, Jovin, Ion, Klancke, Kim, Marcus, Jill, Malhotra, Vinay, Devarapalli, Sai K., Koren, Michael, Chandna, Harish, Dodds Iii, George, Goraya, Tauqir, Bengston, James, Janik, Matthew, Moran, Joseph, Sumner, Andrew, Mathews, Robin, Kobayashi, John, Davis, William, Yazdani, Shahram, Pasquini, John, Thakkar, Maitreya, Vedere, Amarnath, Leimbach, Wayne, Rider, James, Fenton, Sarah, Singh, Narendra, Mehta, Rajendra H., Shah, Anil V., Moriarty, Patrick M., Janosik, Denise, Pepine, Carl, Berman, Brett, Gelormini, Joseph, Daniels, Christopher, Richard, Kerensky, Keating, Friederike, Kondo, Nicholas I., Mentz, Robert J., Shetty, Sanjay, Levite, Howard, Waider, Winfried, Takata, Theodore, Abu-Fadel, Mazen, Shah, Vipul, Aggarwal, Rahul, Kumar, Anil, Hattler, Brack, Do, Rose, Moreira, Humberto Graner, Link, Chad, Bortnick, Anna, Kinzfogl Iii, George, Ghitis, Arnold, Larry, John, Teufel, Edward, Kuhlman, Peter, Mclaurin, Brent, Zhang, Wenwu, Thew, Stephen, Patel, Chetan B., Abbas, Jalal, White, Matthew, Islam, Othman, Subherwal, Sumeet, Ranadive, Nandkishore, Vakili, Babak, Gring, Christian, Henderson, David, Schuchard, Timothy, Farhat, Naim, Pereira, Sabrina Bernardez, Kline, Geoffrey, Mahal, Sharan, Whitaker, Jack, Speirs, Shawn, Andersen, Rolf, Daboul, Nizar, Horwitz, Phillip, Zahr, Firas, Ponce, George, Jafar, Zubair, Perkins, Lynn, Mcgarvey, Joseph, Panchal, Vipul, Voyce, Stephen, Blok, Thomas, Sheldon, William, Azizad, Masoud M., Schmalfuss, Carsten, Picone, Mark, Pederson, Robert, Herzog, William, Povsic, Thomas J., Friedman, Keith, Lindsey, Jason, Timothy, Eichenlaub, Leonard, Parilak, Lepor, Norman, El Shahawy, Mahfouz, Weintraub, Howard, Irimpen, Anand, Alonso, Alvaro, May, Wade, Puymirat, Etienne, Christopher, Daniels, Galski, Thomas, Chu, Alan, Mody, Freny, Ramin, Ebrahimi, Hodes, Zachary, Rossi, Joseph, Rose, Gregory, Fairlamb, James, Lambert, Charles, Raisinghani, Ajit, Abbate, Antonio, Vetrovec, George, King, Marilyn, Carey, Charles, Gerber, Jaime, Younis, Liwa, Park, Hyeun Tom, Vidovich, Mladen, Knutson, Thomas, Jones, William Schuyler, Friedman, Dennis, Chaleff, Fred, Loussararian, Arthur, Rozeman, Phillip, Kimmelstiel, Carey, Kuvin, Jeffrey, Silver, Kevin, Foster, Malcolm, Tonnessen, Glen, Espinoza, Andrey, Shah, Bimal R., Amlani, Mohamadali, Wali, Andreas, Malozzi, Christopher, Jong, Geert T., Massey, Clara, Wattanakit, Keattiyoat, O'Donnell, Philip J., Singal, Dinesh, Jaffrani, Naseem, Banuru, Sridhar, Sherwood, Matthew W., Fisher, Daniel, Xenakis, Mark, Perlmutter, Neal, Bhagwat, Ravi, Strader, James, Blonder, Ronald, Akyea-Djamson, Ayim, Labroo, Ajay, Lee, Kwan, Marais, H. John, Stringfellow, Kenya, Claxton, Edmund, Weiss, Robert, Kathryn, Rohr, Berk, Martin, Rossi, Peter, Joshi, Parag, Khera, Amit, Khaira, Ajit S., Kumkumian, Greg, Lupovitch, Steven, Sujjavanich, Darin, Purow, Joshua, Welka, Stephen, Hoffman, David, Fischer, Stuart, Soroka, Eugene, Eagerton, Donald, Pancholy, Samir, Ray, Michael, Erenrich, Norman, Farrar, Michael, Toma, Mustafa, Pollock, Stewart, French, William J., Diamantis, Steve, Guy, Douglas, Gimple, Lawrence, Neustel, Mark, Schwartz, Steven, Pereira, Edward, Albert, Seals, Spriggs, Douglas, Trotter, Charlene, Strain, Janet, Mittal, Suneet, Vo, Anthony, Chane, Majed, Hall, Jason, Vijay, Nampalli, Lotun, Kapildeo, Lester, F. Martin, Nahhas, Ahed, Pope, Theodore, van Diepen, Sean F. P., Nager, Paul, Vohra, Rakesh, Sharma, Mukesh, Bashir, Riyaz, Ahmed, Hinan, Berlowitz, Michael, Fishberg, Robert, Barrucco, Robert, Yang, Eric, Radin, Michael, Wilson, Matthew D., Sporn, Daniel, Stapleton, Dwight, Eisenberg, Steven, Landzberg, Joel, Mcgough, Martin, Turk, Samir, Schwartz, Michael, Sundram, P. Sandy, Jain, Diwakar, Zainea, Mark, Tze-Kay Yan, Andrew, Bayron, Carlos, Karlsberg, Ronald, Dohad, Suhail, Lui, Henry, Keen, William, Westerhausen, Donald, Khurana, Sandeep, Agarwal, Himanshu, Birchem, Jessica, Penny, William, Schiavi, Lilia B., Chang, Mark, Murphy, Sherrill, Henry, John, Schifferdecker, Branislav, Gilbert, John M., Chalavarya, Gopal, Eaton, Charles, Schmedtje, John F., Christenson, Stuart, Dotani, Imran, Garrido, Marcelo, Denham, Douglas, Macdonell, Alexander, Gibson, Paul, Rahman, Aref, Al Joundi, Tammam, Assi, Nizar, Conrad, Gary, Kotha, Purushotham, Love, Michael, Giesler, Gregory, Alvarisqueta, Andrés F., Rubenstein, Howard, Gamil, Dawood, Akright, Laura, Krawczyk, Justine, Cobler, Joanne, Wells, Terry, Welker, James, Foster, Robert, Gilmore, Richard, Anderson, Jay, Sassone, Sonia A., Jacoby, Douglas, Harris, Bill, Gardner, Geraldine, Dandillaya, Ramprasad, Vora, Kishor, Kostis, John, Hunter, John, Laxson, David, Ball, Eric, Bordonava, Anselmo P., Egydio, Flavia, Kawakami, Anelise, Oliveira, Janaina, Goodman, Shaun G., Wozniak, Julianna, Alves De Lima, Alberto E., Matthews, Alexander, Ratky, Caroline, Valiris, Janine, Berdan, Lisa, Hepditch, Anita, Quintero, Kirby, Rorick, Tyrus, Westbrook, Melissa, Danchin, Nicolas, Schmidberg, Jorge M., Bezault, Madeleine, Drouet, Elodie, Simon, Tabassome, White, Harvey D., Alsweiler, Caroline, Sinnaeve, Peter, Luyten, Anne, Aylward, Philip E., Butters, Julie, Griffith, Liddy, Duronto, Ernesto A., Shaw, Michelle, Grunberg, Lena, Szarek, Michael, Islam, Shahidul, Brégeault, Marie-France, Bougon, Nathalie, Faustino, Douglas, Fontecave, Sylvie, Murphy, Judith, Caruso, Orlando C., Tamby, Jean-Francois, Verrier, Melanie, Agnetti, Veronique, Andersen, Dorthe, Badreddine, Emmy, Bekkouche, Mhamed, Bouancheau, Cecile, Brigui, Imane, Brocklehurst, Maddy, Cianciarulo, Joseph, Novaretto, Leonardo P., Devaul, Dawn, Domokos, Szilvia, Gache, Cecile, Gobillot, Caroline, Guillou, Severine, Healy, Jan, Heath, Megan, Jaiwal, Gayatri, Javierre, Carine, Labeirie, Julien, Hominal, Miguel Angel, Monier, Myriam, Morales, Ulises, Mrabti, Asmaa, Mthombeni, Bicky, Okan, Betim, Smith, Lucile, Sheller, Jennifer, Sopena, Sebastien, Pellan, Valerie, Benbernou, Fadela, Montaña, Oscar R., Bengrait, Nafissa, Lamoureux, Maud, Kralova, Katarina, Scemama, Michel, Bejuit, Raphael, Coulange, Anthony, Berthou, Christelle, Repincay, Jérôme, Lorenzato, Christelle, Etienne, Alexis, Caccavo, Alberto, Gouet, Valerie, Lecorps, Guillaume, Loizeau, Virginie, Normand, Mickael, Ourliac, Anne, Rondel, Christelle, Adamo, Antony, Beltran, Pascale, Barraud, Pauline, Dubois-Gache, Helene, Gomez Vilamajo, Oscar A., Halle, Benjamin, Metwally, Lamia, Mourgues, Maxime, Sotty, Marc, Vincendet, Marion, Cotruta, Raluca, Chengyue, Zhu, Fournie-Lloret, Dominique, Morrello, Christine, Perthuis, Aurelie, Lorenzatti, Alberto J., Picault, Patrick, Zobouyan, Isabelle, Colhoun, Helen M., Dempsey, Michael A., McClanahan, Mark A., Cartasegna, Luis R., Paterlini, Gustavo A., Mackinnon, Ignacio J., Caime, Guillermo D., Amuchastegui, Marcos, Salomone, Oscar, Codutti, Oscar R., Jure, Horacio O., Bono, Julio Oe, Hrabar, Adrian D., Vallejos, Julio A., Ahuad Guerrero, Rodolfo A., Novoa, Federico, Patocchi, Cristian A., Zaidman, Cesar J., Giuliano, Maria E., Schwartz, Gregory G., Dran, Ricardo D., Vico, Marisa L., Carnero, Gabriela S., Guzman, Pablo N., Medrano Allende, Juan C., Garcia Brasca, Daniela F., Bustamante Labarta, Miguel H., Nani, Sebastian, Blumberg, Eduardo Ds, Colombo, Hugo R., Bhatt, Deepak L., Liberman, Alberto, Fuentealba, Victorino, Luciardi, Hector L., Waisman, Gabriel D., Berli, Mario A., Garcia Duran, Ruben O., Cestari, Horacio G., Luquez, Hugo A., Giordano, Jorge A., Saavedra, Silvia S., Bittner, Vera A., Zapata, Gerardo, Costamagna, Osvaldo, Llois, Susana, Waites, Jonathon H., Collins, Nicholas, Soward, Allan, Hii, Chris Ls, Shaw, James, Diaz, Rafael, Arstall, Margaret A., Horowitz, John, Ninio, Daniel, Rogers, James F., Colquhoun, David, Oqueli Flores, Romulo E., Roberts-Thomson, Philip, Raffel, Owen, Lehman, Sam J., Aroney, Constantine, Coverdale, Steven Gm, Garrahy, Paul J., Starmer, Gregory, Sader, Mark, Carroll, Patrick A., Dick, Ronald, Zweiker, Robert, Hoppe, Uta, Drexel, Heinz, Huber, Kurt, Harrington, Robert A., Berger, Rudolf, Delle-Karth, Georg, Frey, Bernhard, Weidinger, Franz, Faes, Dirk, Hermans, Kurt, Pirenne, Bruno, Leone, Attilio, Hoffer, Etienne, Jukema, J. Wouter, Vrolix, Mathias Cm, De Wolf, Luc, Wollaert, Bart, Castadot, Marc, Dujardin, Karl, Beauloye, Christophe, Vervoort, Geert, Striekwold, Harry, Convens, Carl, Roosen, John, Barbato, Emanuele, Claeys, Marc, Cools, Frank, Terzic, Ibrahim, Barakovic, Fahir, Midzic, Zlatko, Pojskic, Belma, Fazlibegovic, Emir, Dilic, Mirza, Durak-Nalbantic, Azra, Kulić, Mehmed, Vulic, Dusko, Muslibegovic, Adis, Goronja, Boris, Reis, Gilmar, Sousa, Luciano, Nicolau, Jose C., Giorgeto, Flavio E., Silva, Ricardo P., Maia, Lilia Nigro, Zeiher, Andreas M., Rech, Rafael, Rossi, Paulo Rf, Cerqueira, Maria José Ag, Duda, Norberto, Kalil, Renato, Kormann, Adrian, Abrantes, José Antonio M., Filho, Pedro Pimentel, Soggia, Ana Priscila, de Santos, Mayler On, Neuenschwander, Fernando, Bodanese, Luiz C., Michalaros, Yorghos L., Eliaschewitz, Freddy G., Vidotti, Maria H., Leaes, Paulo E., Botelho, Roberto V., Kaiser, Sergio, Manenti, Euler Roberto F. Fernandes, Precoma, Dalton B., Moura Jorge, Jose C., Silva, Pedro, Silveira, Jose A., Saporito, Wladmir, Neto, Jose A. Marin, Feitosa, Gilson S., Ritt, Luiz Eduardo F., de Souza, Juliana A., Costa, Fernando, Souza, Weimar Ksb, Reis, Helder Jl, Machado, Leandro, Aidar Ayoub, José Carlos, Todorov, Georgi V., Nikolov, Fedya P., Velcheva, Elena S., Tzekova, Maria L., Benov, Haralambi O., Petranov, Stanislav L., Edelberg, Jay M., Tumbev, Haralin S., Shehova-Yankova, Nina S., Markov, Dimitar T., Raev, Dimitar H., Mollov, Mihail N., Kichukov, Kostadin N., Ilieva-Pandeva, Katya A., Gotcheva, Nina N., Ivanova, Raya, Gospodinov, Maryana, Hanotin, Corinne, Mincheva, Valentina M., Lazov, Petar V., Dimov, Bojidar I., Senaratne, Manohara, Stone, James, Kornder, Jan, Pearce, Stephen, Dion, Danielle, Savard, Daniel, Pesant, Yves, Pandey, Amritanshu, Robinson, Simon, Gosselin, Gilbert, Vizel, Saul, Hoag, Gordon, Bourgeois, Ronald, Morisset, Anne, Sabbah, Eric, Sussex, Bruce, Kouz, Simon, Moryusef, Angèle, MacDonald, Paul, Diaz, Ariel, Michaud, Nicolas, Fell, David, Leung, Raymond, Vuurmans, Tycho, Lai, Christopher, Nigro, Frank, Davies, Richard, Nogareda, Gustavo, Pordy, Robert, Vijayaraghavan, Ram, Ducas, John, Lepage, Serge, Mehta, Shamir, Cha, James, Dupuis, Robert, Fong, Peter, Lutchmedial, Sohrab, Rodes-Cabau, Josep, Fadlallah, Hussein, Sasiela, William J., Cleveland, David, Huynh, Thao, Bata, Iqbal, Hameed, Adnan, Pincetti, Cristian, Potthoff, Sergio, Prieto, Juan C., Acevedo, Monica, Aguirre, Arnoldo, Vejar, Margarita, Tamby, Jean-François, Yañez, Mario, Araneda, Guillermo, Fernandez, Mauricio, Perez, Luis, Varleta, Paola, Florenzano, Fernando, Huidobro, Laura, Raffo, Carlos A., Olivares, Claudia, Nahuelpan, Leonardo, Montecinos, Humberto, Chen, Jiyan, Dong, Yugang, Huang, Weijian, Wang, Jianzhong, Huang, Shi'An, Yao, Zhuhua, Li, Xiang, Cui, Lan, Lin, Wenhua, Sun, Yuemin, Wang, Jingfeng, Li, Jianping, Zhang, Xuelian, Zhu, Hong, Chen, Dandan, Huang, Lan, Dong, Shaohong, Su, Guohai, Xu, Biao, Su, Xi, Cheng, Xiaoshu, Lin, Jinxiu, Zong, Wenxia, Li, Huanming, Feng, Yi, Xu, Dingli, Yang, Xinchun, Ke, Yuannan, Lin, Xuefeng, Zhang, Zheng, Zheng, Zeqi, Luo, Zhurong, Chen, Yundai, Ding, Chunhua, Zhong, Yi, Zheng, Yang, Li, Xiaodong, Peng, Daoquan, Zhao, Shuiping, Li, Ying, Liu, Xuebo, Wei, Meng, Liu, Shaowen, Yu, Yihua, Qu, Baiming, Jiang, Weihong, Zhou, Yujie, Zhao, Xingsheng, Yuan, Zuyi, Guo, Ying, Xu, Xiping, Shi, Xubo, Ge, Junbo, Fu, Guosheng, Bai, Feng, Fang, Weiyi, Shou, Xiling, Yang, Xiangjun, Wang, Jian'An, Xiang, Meixiang, Sun, Yingxian, Lu, Qinghua, Zhang, Ruiyan, Zhu, Jianhua, Xu, Yizhou, Fan, Zhongcai, Li, Tianchang, Wu, Chun, Jaramillo, Nicolas, Vallejo, Gregorio Sanchez, Luna Botia, Diana C., Lopez, Rodrigo Botero, De Salazar, Dora I. Molina, Bonfanti, Alberto J. Cadena, Aroca, Carlos Cotes, Higuera, Juan Diego, Blanquicett, Marco, Barrera Silva, Sandra I., Garcia Lozada, Henry J., Prieto, Juan-Carlos, Coronel Arroyo, Julian A., Accini Mendoza, Jose L., Fernandez Ruiz, Ricardo L., Quintero Ossa, Alvaro M., Manzur Jatin, Fernando G., Sotomayor Herazo, Aristides, Parada, Jeffrey Castellanos, Arambula, Rafael Suarez, Urina Triana, Miguel A., Trujillo, Angela M. Fernandez, Yong, Huo, Strozzi, Maja, Car, Siniša, Miličić, Davor, Lovrić Benčić, Martina, Pintarić, Hrvoje, Prvulović, Đeiti, Šikić, Jozica, Peršić, Viktor, Mileta, Dean, Štambuk, Kresimir, López-Jaramillo, Patricio, Babić, Zdravko, Tomulic, Vjekoslav, Lukenda, Josip, Mejic-Krstulovic, Stanka, Starcevic, Boris, Spinar, Jindrich, Horak, David, Velicka, Zdenek, Alan, David, Machova, Vilma, Pećin, Ivan, Linhart, Ales, Novotny, Vojtech, Kaucak, Vladimir, Rokyta, Richard, Naplava, Robert, Coufal, Zdenek, Adamkova, Vera, Podpera, Ivo, Zizka, Jiri, Motovska, Zuzana, Reiner, Zeljko, Marusincova, Ivana, Ostadal, Petr, Heinc, Petr, Kuchar, Jiri, Povolny, Petr, Matuska, Jiri, Poulsen, Steen H., Raungaard, Bent, Clemmensen, Peter, Bang, Lia E., May, Ole, Bøttcher, Morten, Hove, Jens D., Frost, Lars, Gislason, Gunnar, Larsen, John, Johansen, Peter Betton, Hald, Flemming, Johansen, Peter, Jeppesen, Jørgen, Poulsen, Steen Hvitfeldt, Nielsen, Tonny, Kristensen, Kjeld S., Walichiewicz, Piotr Maria, Lomholdt, Jens D., Klausen, Ib C., Nielsen, Peter Kaiser, Davidsen, Flemming, Videbaek, Lars, Viigimaa, Margus, Soots, Mai, Vahula, Veiko, Hedman, Anu, Soopõld, Üllar, Märtsin, Kaja, Jurgenson, Tiina, Kristjan, Arved, Nieminen, Markku S., Vikman, Saila, Huikuri, Heikki, Airaksinen, Juhani, Coste, Pierre, Ferrari, Emile, Morel, Olivier, Montalescot, Gilles, Machecourt, Jacques, Barone-Rochette, Gilles, Mansourati, Jacques, Cottin, Yves, Steg, Ph Gabriel, Leclercq, Florence, Belhassane, Abdelkader, Delarche, Nicolas, Boccara, Franck, Paganelli, Franck, Clerc, Jérôme, Schiele, Francois, Aboyans, Victor, Probst, Vincent, Berland, Jacques, Chumburidze, Vakhtang, Lefèvre, Thierry, Khintibidze, Irakli, Shaburishvili, Tamaz, Pagava, Zurab, Ghlonti, Ramaz, Lominadze, Zaza, Khabeishvili, George, Hemetsberger, Rayyan, Edward, Kemala, Marx, Nikolaus, Rauch-Kröhnert, Ursula, Stratmann, Matthias, Appel, Karl-Friedrich, Schmidt, Ekkehard, Omran, Heyder, Stellbrink, Christoph, Dorsel, Thomas, Lianopoulos, Emmanouil, Vöhringer, Hans Friedrich, Marx, Roger, Liberopoulos, Evangelos, Zirlik, Andreas, Schellenberg, Detlev, Heitzer, Thomas, Laufs, Ulrich, Werner, Christian, Gielen, Stephan, Nuding, Sebastian, Winkelmann, Bernhard, Behrens, Steffen, Carlos, Pablo, Sydow, Karsten, Karakas, Mahir, Simonis, Gregor, Muenzel, Thomas, Werner, Nikos, Leggewie, Stefan, Böcker, Dirk, Braun-Dullaeus, Rüdiger, Toursarkissian, Nicole, Jeserich, Michael, Valdovinos, Montenegro, Weißbrodt, Matthias, Schaeufele, Tim, Weil, Joachim, Völler, Heinz, Waltenberger, Johannes, Natour, Mohammed, Schmitt, Susanne, Müller-Wieland, Dirk, Steiner, Stephan, Heidenreich, Lothar, Tse, Hung-Fat, Offers, Elmar, Gremmler, Uwe, Killat, Holger, Rieker, Werner, Patsilinakos, Sotiris, Kartalis, Athanasios, Manolis, Athanassios, Sionis, Dimitrios, Chachalis, Geargios, Kiss, Robert Gabor, Skoumas, Ioannis, Athyros, Vasilios, Vardas, Panagiotis, Parthenakis, Frangkiskos, Hahalis, Georgios, Lekakis, John, Hatzitolios, Apostolos, Fausto Ovando, Sergio R., Montenegro Valdovinos, Pablo Carlos, Arango Benecke, Juan L., Xavier, Denis, Rodriguez De Leon, Edgar R., Yan, Bryan Py, Siu, David Cw, Turi, Tibor, Merkely, Bela, Gabor Kiss, Robert, Ungi, Imre, Lupkovics, Geza, Nagy, Lajos, Katona, András, Zahger, Doron, Édes, István, Müller, Gábor, Horvath, Iván, Kapin, Tibor, Szigeti, Zsolt, Faluközy, József, Kumbla, Mukund, Sandhu, Manjinder, Annam, Sharath, Reddy Proddutur, Naveen, Valgimigli, Marco, Regella, Reddy, Premchand, Rajendra K., Mahajan, Ajaykumar, Pawar, Sudhir, Abhyanakar, Atul D., Kerkar, Prafulla, Govinda, Ravishankar A., Oomman, Abraham, Sinha, Dhurjati, Patil, Sachin N., Kimura, Takeshi, Kahali, Dhiman, Sawhney, Jitendra, Joshi, Abhijeet B., Chaudhary, Sanjeev, Harkut, Pankaj, Guha, Santanu, Porwal, Sanjay, Jujjuru, Srimannarayana, Pothineni, Ramesh B., Monteiro, Minguel R., Kim, Hyo Soo, Khan, Aziz, Iyengar, Shamanna S., Grewal, Jasprakash Singh, Chopda, Manoj, Fulwani, Mahesh C., Patange, Dr Aparna, Sachin, Patil, Chopra, Vijay K., Goyal, Naresh K., Shinde, Rituparna, Kim, Sang-Hyun, Manakshe, Gajendra V., Patki, Nitin, Sethi, Sumeet, Munusamy, Vengatesh, Sunil Thanvi, Sunil Karnaand, Adhyapak, Srilakshmi, Patil, Chandrakant, Pandurangi, Ulhas, Mathur, Rishabh, Gupta, Jugal, Erglis, Andrejs, Kalashetti, Suhas, Bhagwat, Ajit, Raghuraman, Bagirath, Kumar Yerra, Shiv, Bhansali, Prasant, Borse, Rohidas, Rahul, Patil, Das, Srihari, Kumar, Vinay, Abdullakutty, Jabir, Laucevicius, Aleksandras, Saathe, Shireesh, Palimkar, Priya, Abdullkutty, Jabir, Sathe, Shireesh, Atar, Shaul, Shechter, Michael, Mosseri, Morris, Arbel, Yaron, Ehud, Chorin, Ofer, Havakuk, Kedev, Sasko, Lotan, Chaim, Rosenschein, Uri, Katz, Amos, Henkin, Yaakov, Francis, Adi, Klutstein, Marc, Nikolsky, Eugenia, Zukermann, Robert, Turgeman, Yoav, Halabi, Majdi, Yusoff, Khalid, Marmor, Alon, Kornowski, Ran, Jonas, Michael, Amir, Offer, Hasin, Yonathan, Rozenman, Yoseph, Fuchs, Shmuel, Zvi, Vered, Hussein, Osamah, Gavish, Dov, Ramos López, Gabriel Arturo, Vered, Zvi, Caraco, Yoseph, Elias, Mazen, Tov, Naveh, Wolfovitz, Efrat, Lishner, Michael, Elias, Nizar, Piovaccari, Giancarlo, De Pellegrin, Annamaria, Garbelotto, Raffaella, Alings, Marco, Guardigli, Gabriele, Marco, Valgimigli, Licciardello, Giovanni, Auguadro, Carla, Scalise, Filippo, Cuccia, Claudio, Salvioni, Alessandro, Musumeci, Giuseppe, Senni, Michelle, Calabrò, Paolo, Novo, Salvatore, Faggiano, Pompilio, Metra, Marco, De Cesare, Nicoletta B., Berti, Sergio, Puccioni, Enrico, Galvani, Marcello, Tespili, Maurizio, Piatti, PierMarco, Palvarini, Michela, Halvorsen, Sigrun, De Luca, Giuseppe, Violini, Roberto, De Leo, Alessandro, Olivari, Zoran, Filardi, Pasquale Perrone, Ferratini, Maurizio, Racca, Vittorio, Dai, Kazuoki, Shimatani, Yuji, Kamiya, Haruo, Correa Flores, Roger M., Ando, Kenji, Takeda, Yoshihiro, Morino, Yoshihiro, Hata, Yoshiki, Kimura, Kazuo, Kishi, Koichi, Michishita, Ichiro, Uehara, Hiroki, Higashikata, Toshinori, Hirayama, Atsushi, Sy, Rody G., Hirooka, Keiji, Doi, Yasuji, Sakagami, Satoru, Taguchi, Shuichi, Koike, Akihiro, Fujinaga, Hiroyuki, Koba, Shinji, Kozuma, Ken, Kawasaki, Tomohiro, Ono, Yujiro, Budaj, Andrzej, Shimizu, Masatoshi, Katsuda, Yousuke, Wada, Atsuyuki, Shinke, Toshiro, Ako, Junya, Fujii, Kenshi, Takahashi, Toshiyuki, Nakao, Koichi, Furukawa, Yutaka, Sugino, Hiroshi, Tamura, Ritsu, Mano, Toshiaki, Uematsu, Masaaki, Utsu, Noriaki, Ito, Kashima, Haraguchi, Takuya, Sato, Katsuhiko, Ueda, Yasunori, Nishibe, Akira, Fujimoto, Kazuteru, Masutani, Motomaru, Yoon, Jung Han, Kim, Hack-Lyoung, Sik Park, Hun, Chae, In-Ho, Kim, Moo Hyun, Jeong, Myung Ho, Rha, Seungwoon, Kim, Chongjin, Kim, Hyo-Soo, Kim, Hae Young, Hong, Taekjong, Tahk, Seung-Jea, Kim, Youngkwon, Busmane, Arija, Pontaga, Natalija, Strelnieks, Aldis, Mintale, Iveta, Sime, Iveta, Petrulioniene, Zaneta, Kavaliauskiene, Roma, Jurgaitiene, Ruta, Sakalyte, Gintare, Slapikas, Rimvydas, Norkiene, Sigute, Misonis, Nerijus, Chua, Terrance, Kibarskis, Aleksandras, Kubilius, Raimondas, Bojovski, Stojko, Lozance, Nensi, Kjovkaroski, Aleksandar, Doncovska, Snezana, Ong, Tiong Kiam, Kasim, Sazzli, Maskon, Oteh, Kandasamy, Balachandran, Liew, Houng B., Wan Mohamed, Wan Mohd Izani, Castillo, Armando García, Calvillo, Jorge Carrillo, Campos, Pedro Fajardo, Núñez Fragoso, Juan Carlos, Bayram Llamas, Edmundo Alfredo, Alcocer Gamba, Marco Antonio, Madrigal, Jaime Carranza, González Salas, Luis Gerardo, Rosas, Enrique López, González Díaz, Belinda, Vázquez, Eduardo Salcido, Nacoud Ackar, Alfredo, Llamas Esperón, Guillermo Antonio, Martínez Sánchez, Carlos Rodolfo, De Leon, María Guerrero, Suarez Otero, Rodrigo, Salmón, Guillermo Fanghänel, Pérez Ríos, Jesús Antonio, Garza Ruíz, José Angel, Breedveld, Robert W., Feenema-Aardema, Margriet, Borger-Van Der Burg, Alida, Hoogslag, Pieter Am, Suryapranata, Harry, Tuñón, José, Oomen, Antonius, Van Haelst, Paulus, Feenema-Aradema, Margriet, Wiersma, Jacobijne J., Basart, Dirk, Van Der Wal, Ruud Ma, Zwart, Peter, Monraats, Pascalle, Van Kesteren, Henricus, Karalis, Ioannis, de Silva, H. Asita, Jukema, Johan, Verdel, Gerardus Je, Brueren, Bart Rg, Troquay, Roland P. Th, Viergever, Eric P., Al-Windy, Nadea Yy, Bartels, Gerard L., Cornel, Jan H., Hermans, Walter Rm, Herrman, Johannes Pr, Bos, Robert J., Groutars, Reginald Gej, Van Der Zwaan, Coenraad C., Kaplan, Refik, Ronner, Eelko, Groenemeijer, Bjorn E., Bronzwaer, Patrick Na, Liem, Anho Ah, Rensing, Bernard Jwm, Bokern, Marcel Jja, Nijmeijer, Remco, Hersbach, Ferry Mrj, Willems, Frank F., Gosselink, Antonius Tm, Rasoul, Saman, Elliott, John, Wilkins, Gerard, Fisher, Raewyn, Scott, Douglas, Hart, Hamish, Stewart, Ralph, Harding, Scott, Ternouth, Ian, Fisher, Nicholas, Wilson, Samuel, Aitken, Denise, Anscombe, Russell, Davidson, Laura, Tomala, Tadeusz, Nygård, Ottar, Sparby, Jon Arne, Andersen, Kjell, Gullestad, Lars, Jortveit, Jarle, Munk, Peter S., Singsaas, Erlend Gyllensten, Hurtig, Ulf, Calderon Ticona, Jorge R., Durand Velasquez, Julio R., Negron Miguel, Sandra A., Sanabria Perez, Enrique S., Carrion Chambilla, Jesus M., Chavez Ayala, Carlos A., Castillo Leon, Reynaldo P., Vargas GonzalesC, Rolando J., Hernandez Zuniga, Jose D., Camacho Cosavalente, Luis A., Bravo Mannucci, Jorge E., Landeo, Javier Heredia, Llerena Navarro, Nassip C., Roldan Concha, Yudy M., Rodriguez Chavez, Víctor E., Anchante Hernandez, Henry A., Zea Nunez, Carlos A., Ramos, Walter Mogrovejo, Ferrolino, Arthur, Sy, Rosa Allyn G., Tirador, Louie, Matiga, Generoso, Coching, Raul Martin, Bernan, Alisa, Rogelio, Gregorio, Morales, Dante D., Tan, Edgar, Sulit, Dennis Jose, Wlodarczak, Adrian, Skonieczny, Grzegorz, Ray, Kausik K., Pawlowicz, Lidia, Wojewoda, Pawel, Busz-Papiez, Benita, Bednarski, Janusz, Goch, Aleksander, Staneta, Pawel, Dulak, Elzbieta, Saminski, Krzysztof, Krasowski, Wlodzimierz, Sudnik, Wanda, Zurakowski, Aleksander, Skorski, Marcin, Lysek, Roman, Miklaszewicz, Beata, Lipko, Jan Andrzej, Kostarska-Srokosz, Edyta, Piepiorka, Marek, Drzewiecka, Anna, Stasiewski, Arkadiusz, Bhatt, Deepak L, Bittner, Vera A, Goodman, Shaun G, Harrington, Robert A, Jukema, J Wouter, White, Harvey D, Zeiher, Andreas M, Roe, Matthew T, Mahaffey, Kenneth W, Edelberg, Jay M, Sasiela, William J, Aylward, Philip E, Lopes, Renato D, Gotcheva, Nina N, Nieminen, Markku S, Laucevičius, Aleksandras, Correa Flores, Roger M, Sy, Rody G, Ristic, Arsen D, Dalby, Anthony J, de Silva, H Asita, Ray, Kausik K, Moriarty, Patrick M, Kelsey, Sheryl F, Olsson, Anders G, Simoons, Maarten L, Sijbrands, Eric J G, Alexander, John H, Brennan, J Matthew, DeVore, Adam D, Harrison, Robert W, Hlatky, Mark A, Knowles, Joshua W, Kolls, Bradley J, Kong, David F, Maron, David J, Mehta, Rajendra H, Mentz, Robert J, Patel, Chetan B, Povsic, Thomas J, Shah, Bimal R, Sherwood, Matthew W, van Diepen, Sean F P, Wilson, Matthew D, Schiavi, Lilia B, Alvarisqueta, Andrés F, Sassone, Sonia A, Bordonava, Anselmo P, Alves De Lima, Alberto E, Schmidberg, Jorge M, Duronto, Ernesto A, Caruso, Orlando C, Novaretto, Leonardo P, Montaña, Oscar R, Gomez Vilamajo, Oscar A, Lorenzatti, Alberto J, Cartasegna, Luis R, Paterlini, Gustavo A, Mackinnon, Ignacio J, Caime, Guillermo D, Codutti, Oscar R, Jure, Horacio O, Hrabar, Adrian D, Vallejos, Julio A, Ahuad Guerrero, Rodolfo A, Patocchi, Cristian A, Zaidman, Cesar J, Giuliano, Maria E, Dran, Ricardo D, Vico, Marisa L, Carnero, Gabriela S, Guzman, Pablo N, Medrano Allende, Juan C, Garcia Brasca, Daniela F, Bustamante Labarta, Miguel H, Colombo, Hugo R, Luciardi, Hector L, Waisman, Gabriel D, Berli, Mario A, Garcia Duran, Ruben O, Cestari, Horacio G, Luquez, Hugo A, Giordano, Jorge A, Saavedra, Silvia S, Waites, Jonathon H, Arstall, Margaret A, Rogers, James F, Oqueli Flores, Romulo E, Lehman, Sam J, Garrahy, Paul J, Carroll, Patrick A, Wolf, Luc De, Nicolau, Jose C, Giorgeto, Flavio E, Silva, Ricardo P, Abrantes, José Antonio M, Bodanese, Luiz C, Michalaros, Yorghos L, Eliaschewitz, Freddy G, Vidotti, Maria H, Leaes, Paulo E, Botelho, Roberto V, Manenti, Euler Roberto F Fernandes, Precoma, Dalton B, Moura Jorge, Jose C, Silveira, Jose A, Neto, Jose A Marin, Feitosa, Gilson S, Ritt, Luiz Eduardo F, de Souza, Juliana A, Todorov, Georgi V, Nikolov, Fedya P, Velcheva, Elena S, Tzekova, Maria L, Benov, Haralambi O, Petranov, Stanislav L, Tumbev, Haralin S, Shehova-Yankova, Nina S, Markov, Dimitar T, Raev, Dimitar H, Mollov, Mihail N, Kichukov, Kostadin N, Ilieva-Pandeva, Katya A, Mincheva, Valentina M, Lazov, Petar V, Dimov, Bojidar I, Prieto, Juan C, Raffo, Carlos A, Luna Botia, Diana C, De Salazar, Dora I Molina, Bonfanti, Alberto J Cadena, Barrera Silva, Sandra I, Garcia Lozada, Henry J, Coronel Arroyo, Julian A, Accini Mendoza, Jose L, Fernandez Ruiz, Ricardo L, Quintero Ossa, Alvaro M, Manzur Jatin, Fernando G, Urina Triana, Miguel A, Trujillo, Angela M Fernandez, Poulsen, Steen H, Bang, Lia E, Hove, Jens D, Kristensen, Kjeld S, Lomholdt, Jens D, Klausen, Ib C, Fausto Ovando, Sergio R, Arango Benecke, Juan L, Rodriguez De Leon, Edgar R, Premchand, Rajendra K, Abhyanakar, Atul D, Govinda, Ravishankar A, Patil, Sachin N, Joshi, Abhijeet B, Pothineni, Ramesh B, Monteiro, Minguel R, Iyengar, Shamanna S, Fulwani, Mahesh C, Chopra, Vijay K, Goyal, Naresh K, Manakshe, Gajendra V, Pellegrin, Annamaria De, De Cesare, Nicoletta B, Piatti, Piermarco, Luca, Giuseppe De, Leo, Alessandro De, Petrulionienė, Žaneta, Šakalytė, Gintarė, Šlapikas, Rimvydas, Liew, Houng B, Breedveld, Robert W, Wiersma, Jacobijne J, Troquay, Roland PTh, Viergever, Eric P, Bartels, Gerard L, Cornel, Jan H, Bos, Robert J, Van Der Zwaan, Coenraad C, Groenemeijer, Bjorn E, Willems, Frank F, Munk, Peter S, Calderon Ticona, Jorge R, Durand Velasquez, Julio R, Negron Miguel, Sandra A, Sanabria Perez, Enrique S, Carrion Chambilla, Jesus M, Chavez Ayala, Carlos A, Castillo Leon, Reynaldo P, Vargas GonzalesC, Rolando J, Hernandez Zuniga, Jose D, Camacho Cosavalente, Luis A, Bravo Mannucci, Jorge E, Llerena Navarro, Nassip C, Roldan Concha, Yudy M, Rodriguez Chavez, Víctor E, Anchante Hernandez, Henry A, Zea Nunez, Carlos A, Sy, Rosa Allyn G, Morales, Dante D, Pereira, Helder H, Tesloianu, Dan N, Bengus, Cristina M, Parepa, Irinel R, Matei, Adrian V, Alexandru, Tom M, Barbarash, Olga L, Vishnevsky, Alexander Y, Lomakin, Nikita V, Voevoda, Mikhail I, Tretyakova, Tatyana V, Tyrenko, Vadim V, Ivanov, Igor G, Asanin, Milika R, Apostolovic, Svetlana R, Dincic, Dragan V, Cyster, Henry P, Kapp, Ilse E, de V Basson, Matthys M, Aswegen, Dina Van, Van Zyl, Louis J, Sebastian, Peter J, Saaiman, Jan A, Commerford, Patrick J, Ebrahim, Iftikhar O, Mynhardt, Joseph H, Fillat, Angel R Cequier, Cruz Fernández, Jose M, Gonzalez-Juanatey, Jose R, Alonso Martin, Joaquin J, De Berrazueta Fernández, José R, Escudier, Juan M, Herath, Jagath I, Hsieh, I-Chang, Barna, Olga M, Aggarwal, Rajesh K, Wong, Yuk-Ki, Devarapalli, Sai K, Shah, Anil V, Kondo, Nicholas I, Azizad, Masoud M, Jong, Geert T, O'Donnell, Philip J, Marais, H John, Khaira, Ajit S, French, William J, Lester, F Martin, Sundram, P Sandy, Gilbert, John M, Schmedtje, John F, Colhoun, Helen M, Dempsey, Michael A, and McClanahan, Mark A
Subjects: Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use, Anticholesteremic Agents/adverse effects, Vascular damage Radboud Institute for Health Sciences [Radboudumc 16], prevention & control, heart disease risk factors, diagnosis [Cardiovascular Diseases], Antibodies, Monoclonal, Humanized, PCSK9 inhibitors, acute coronary syndrome, apolipoproteins B, LDL cholesterol, Antibodies, acute coronary syndrome, LDL, drug therapy [Atherosclerosis], Risk Factors, Physiology (medical), therapeutic use [Hydroxymethylglutaryl-CoA Reductase Inhibitors], Monoclonal, Humans, Cardiac and Cardiovascular Systems, Humanized, Cardiovascular Diseases/diagnosis, Apolipoproteins B, Kardiologi, diagnosis [Acute Coronary Syndrome], Anticholesteremic Agents, PCSK9 inhibitors, apolipoproteins B, cholesterol, LDL, cholesterol, Atherosclerosis/drug therapy, Cholesterol, LDL, Atherosclerosis, Acute Coronary Syndrome/diagnosis, drug therapy, Cholesterol, Treatment Outcome, Cardiovascular Diseases, Heart Disease Risk Factors, epidemiology, adverse effects [Anticholesteremic Agents], Hydroxymethylglutaryl-CoA Reductase Inhibitors, Cardiology and Cardiovascular Medicine
Abstract: Circulation : an official journal of the American Heart Association / ed.-in-chief Ephraim Donosco 146(9), 657-672 (2022). doi:10.1161/CIRCULATIONAHA.121.057807, Published by Ovid, [Erscheinungsort nicht ermittelbar]
Published: 2022

16. Cross-Laboratory Standardization of Preclinical Lipidomics Using Differential Mobility Spectrometry and Multiple Reaction Monitoring

Author: Jacqueline Lovett, Baolong Su, Kenneth Nazir, Rebekah Sayers, Vidya Velagapudi, Mina Mirzaian, Michael Snyder, Yassene Mohammed, Daniel Hornburg, Ruin Moaddel, Mathew Ellenberger, Oleg A. Mayboroda, Eric J.G. Sijbrands, Christie L. Hunter, Christina M. Jones, Baljit K. Ubhi, Kevin J. Williams, John A. Bowden, M. Ghorasaini, Mackenzie J. Pearson, Matías Cabruja, Daniel Raftery, Kévin Contrepois, Theo Klein, Mark Haid, Luigi Ferrucci, Bharat Gajera, Jerzy Adamski, Martin Giera, Lisa F. Bettcher, Yolanda B. de Rijke, Fabien Riols, Clinical Chemistry, and Internal Medicine
Subjects: Standardization, Computational biology, Mass spectrometry, 01 natural sciences, Article, Analytical Chemistry, Cohort Studies, 03 medical and health sciences, Metabolomics, SDG 3 - Good Health and Well-being, Lipidomics, Humans, 030304 developmental biology, 0303 health sciences, Chemistry, Spectrum Analysis, 010401 analytical chemistry, Selected reaction monitoring, Reference Standards, 3. Good health, 0104 chemical sciences, Biomarker (cell), Informatics, NIST, Laboratories
Abstract: Modern biomarker and translational research as well as personalized health care studies rely heavily on powerful omics' technologies, including metabolomics and lipidomics. However, to translate metabolomics and lipidomics discoveries into a high-throughput clinical setting, standardization is of utmost importance. Here, we compared and benchmarked a quantitative lipidomics platform. The employed Lipidyzer platform is based on lipid class separation by means of differential mobility spectrometry with subsequent multiple reaction monitoring. Quantitation is achieved by the use of 54 deuterated internal standards and an automated informatics approach. We investigated the platform performance across nine laboratories using NIST SRM 1950-Metabolites in Frozen Human Plasma, and three NIST Candidate Reference Materials 8231-Frozen Human Plasma Suite for Metabolomics (high triglyceride, diabetic, and African-American plasma). In addition, we comparatively analyzed 59 plasma samples from individuals with familial hypercholesterolemia from a clinical cohort study. We provide evidence that the more practical methyl-tert-butyl ether extraction outperforms the classic Bligh and Dyer approach and compare our results with two previously published ring trials. In summary, we present standardized lipidomics protocols, allowing for the highly reproducible analysis of several hundred human plasma lipids, and present detailed molecular information for potentially disease relevant and ethnicity-related materials.
Published: 2021

17. The effect of monomeric and oligomeric FLAVAnols in patients with type 2 diabetes and microalbuminuria (FLAVA-trial): A double-blind randomized controlled trial

Author: Yvonne van Beek-Nieuwland, Willem A. Dik, Behiye Özcan, Monique T. Mulder, Eric J.G. Sijbrands, Reinier Timman, Adrie J.M. Verhoeven, Lei M. Chow, Roel J.J.M. van de Laar, Mardin Rashid, Kirsten A. Berk, Internal Medicine, Psychiatry, and Immunology
Subjects: Male, medicine.medical_specialty, Flavonols, Type 2 diabetes, Critical Care and Intensive Care Medicine, Placebo, law.invention, Double-Blind Method, Randomized controlled trial, SDG 3 - Good Health and Well-being, law, Internal medicine, medicine, Clinical endpoint, Albuminuria, Humans, Endothelial dysfunction, Aged, Nutrition and Dietetics, business.industry, Middle Aged, medicine.disease, Clinical trial, Treatment Outcome, Diabetes Mellitus, Type 2, Dietary Supplements, Female, Microalbuminuria, Endothelium, Vascular, medicine.symptom, business, Biomarkers
Abstract: Summary Background & aims Microalbuminuria is an early sign of vascular complications of type 2 diabetes and predicts cardiovascular disease and mortality. Monomeric and oligomeric flavanols (MOFs) are linked to improved vascular health. The aim of this study was to assess the effect of 3 months MOFs on albuminuria and endothelial function markers in patients with type 2 diabetes and microalbuminuria. Methods We conducted a double-blind, placebo-controlled trial among patients with type 2 diabetes and microalbuminuria. Patients with type 2 diabetes received either 200 mg MOFs or placebo daily on top of their habitual diet and medication. The primary endpoint was the between-group difference of the change in 24-h Albumin Excretion Rate (AER) over three months. Secondary endpoints were the between-group differences of the change in plasma levels of different markers of endothelial dysfunction. Mixed-modelling was applied for the longitudinal analyses. Results Participants (n = 97) were 63.0 ± 9.5 years old; diabetes-duration was 15.7 ± 8.5 years. Median baseline AER was 60 (IQR 20–120) mg/24 h. There was no within-group difference in median change of AER from baseline to 3 months in the intervention (0 (-35-21) mg/24 h, p = 0.41) or the control group (0 (-20-10) mg/24 h, p = 0.91). There was no between-group difference in the course of AER over three months (log-transformed data: β = −0.02 (95%CI -0.23-0.20), p = 0.88), nor in the plasma levels of the endothelial dysfunction markers. Conclusion Daily 200 mg MOFs for three months on top of habitual diet and usual care did not reduce AER and plasma markers of endothelial dysfunction compared to placebo, in patients with long-term type 2 diabetes and microalbuminuria. Clinical trials registration NTR4669, www.trialregister.nl .
Published: 2021

18. Effects of Sex, Age, and Apolipoprotein E Genotype on Brain Ceramides and Sphingosine-1-Phosphate in Alzheimer's Disease and Control Mice

Author: Jochen Walter, Mina Mirzaian, Simone M. Crivelli, Jo Stevens, Pilar Martinez-Martinez, Johannes M. F. G. Aerts, Frank P.J. Leijten, Sandra den Hoedt, Marina Mané-Damas, Helga E. de Vries, Monique T. Mulder, Mario Losen, Adrie J.M. Verhoeven, Eric J.G. Sijbrands, RS: MHeNs - R3 - Neuroscience, Psychiatrie & Neuropsychologie, Internal Medicine, Clinical Chemistry, Molecular cell biology and Immunology, ACS - Microcirculation, Amsterdam Neuroscience - Neuroinfection & -inflammation, and Amsterdam Neuroscience - Neurovascular Disorders
Subjects: Apolipoprotein E, sex differences, medicine.medical_specialty, Ceramide, Cerebellum, Cognitive Neuroscience, Hippocampus, Neurosciences. Biological psychiatry. Neuropsychiatry, Neuropathology, S1P, chemistry.chemical_compound, SDG 3 - Good Health and Well-being, SPHINGOSINE 1-PHOSPHATE, CEREBROSPINAL-FLUID, Internal medicine, Cortex (anatomy), medicine, Sphingosine-1-phosphate, ceramide, TRANSGENIC MOUSE MODEL, OXIDATIVE STRESS, CHOLESTEROL-METABOLISM, Original Research, TYPE-4 ALLELE, RISK, SPHINGOLIPID METABOLISM, business.industry, aging, apolipoprotein E4, Alzheimer's disease, Sphingolipid, DEPENDENT CHANGES, medicine.anatomical_structure, Endocrinology, chemistry, lipids (amino acids, peptides, and proteins), business, PLASMA CERAMIDES, Alzheimer’s disease, RC321-571, Neuroscience
Abstract: Apolipoprotein ε4 (APOE)4 is a strong risk factor for the development of Alzheimer’s disease (AD) and aberrant sphingolipid levels have been implicated in AD. We tested the hypothesis that the APOE4 genotype affects brain sphingolipid levels in AD. Seven ceramides and sphingosine-1-phosphate (S1P) were quantified by LC-MSMS in hippocampus, cortex, cerebellum, and plasma of 5 months old human APOE3 and APOE4-targeted replacement mice with or without the familial AD (FAD) background of both sexes (145 animals). APOE4 mice had higher Cer(d18:1/24:0) levels in the cortex (1.7-fold, p = 0.002) than APOE3 mice. Mice with AD background showed higher levels of Cer(d18:1/24:1) in the cortex than mice without (1.4-fold, p = 0.003). S1P levels were higher in all three brain regions of older mice than of young mice (1.7-1.8-fold, all p ≤ 0.001). In female mice, S1P levels in hippocampus (r = −0.54 [−0.70, −0.35], p < 0.001) and in cortex correlated with those in plasma (r = −0.53 [−0.71, −0.32], p < 0.001). Ceramide levels were lower in the hippocampus (3.7–10.7-fold, all p < 0.001), but higher in the cortex (2.3–12.8-fold, p < 0.001) of female than male mice. In cerebellum and plasma, sex effects on individual ceramides depended on acyl chain length (9.5-fold lower to 11.5-fold higher, p ≤ 0.001). In conclusion, sex is a stronger determinant of brain ceramide levels in mice than APOE genotype, AD background, or age. Whether these differences impact AD neuropathology in men and women remains to be investigated.
Published: 2021

19. Plasma protein N-glycosylation is associated with cardiovascular disease, nephropathy, and retinopathy in type 2 diabetes

Author: Amber A. van der Heijden, Manfred Wuhrer, Giel Nijpels, Leen M 't Hart, Elham Memarian, Viktoria Dotz, Aloysius G Lieverse, Mandy van Hoek, Emma Schoep, Roosmarijn F L Lemmers, Eric J.G. Sijbrands, Femke Rutters, Roderick C. Slieker, Internal Medicine, Epidemiology and Data Science, APH - Health Behaviors & Chronic Diseases, APH - Aging & Later Life, General practice, APH - Methodology, and ACS - Diabetes & metabolism
Subjects: medicine.medical_specialty, Glycosylation, glycosylation, Endocrinology, Diabetes and Metabolism, Disease, Type 2 diabetes, Gastroenterology, Diseases of the endocrine glands. Clinical endocrinology, Nephropathy, Plasma, chemistry.chemical_compound, Retinal Diseases, N-linked glycosylation, SDG 3 - Good Health and Well-being, Internal medicine, Diabetes mellitus, medicine, Humans, Fucosylation, business.industry, Proportional hazards model, biomarkers, diabetes complications, Genetics/Genomes/Proteomics/Metabolomics, Blood Proteins, RC648-665, medicine.disease, Diabetes Mellitus, Type 2, chemistry, Cardiovascular Diseases, business
Abstract: IntroductionAlthough associations of total plasma N-glycome (TPNG) with type 2 diabetes have been reported, little is known on the role of TPNG in type 2 diabetes complications, a major cause of type 2 diabetes-related morbidity and mortality. Here, we assessed TPNG in relation to type 2 diabetes complications in subsamples of two Dutch cohorts using mass spectrometry (n=1815 in DiaGene and n=1518 in Hoorn Diabetes Care System).Research design and methodsBlood plasma samples and technical replicates were pipetted into 96-well plates in a randomized manner. Peptide:N-glycosidase F (PNGase F) was used to release N-glycans, whereafter sialic acids were derivatized for stabilization and linkage differentiation. After total area normalization, 68 individual glycan compositions were quantified in total and were used to calculate 45 derived traits which reflect structural features of glycosylation. Associations of glycan features with prevalent and incident microvascular or macrovascular complications were tested in logistic and Cox regression in both independent cohorts and the results were meta-analyzed.ResultsOur results demonstrated similarities between incident and prevalent complications. The strongest association for prevalent cardiovascular disease was a high level of bisection on a group of diantennary glycans (A2FS0B; OR=1.38, p=1.34×10−11), while for prevalent nephropathy the increase in 2,6-sialylation on triantennary glycans was most pronounced (A3E; OR=1.28, p=9.70×10−6). Several other TPNG features, including fucosylation, galactosylation, and sialylation, firmly demonstrated associations with prevalent and incident complications of type 2 diabetes.ConclusionsThese findings may provide a glance on how TPNG patterns change before complications emerge, paving the way for future studies on prediction biomarkers and potentially disease mechanisms.
Published: 2021

20. Lipoprotein(a) is associated with incidence but not progression of aortic valve calcium

Author: Erik S.G. Stroes, S.M. Boekholdt, Yannick Kaiser, J.E. Van Der Toorn, Daniel Bos, Eric J.G. Sijbrands, Meike W. Vernooij, Y B de Rijke, Maryam Kavousi, and Kang H. Zheng
Subjects: medicine.medical_specialty, biology, business.industry, Incidence (epidemiology), Internal medicine, biology.protein, Cardiology, medicine, Lipoprotein(a), Aortic calcification, Cardiology and Cardiovascular Medicine, business
Abstract: Background Lipoprotein(a) [Lp(a)] has been implicated in the etiology of aortic valve stenosis. Although Lp(a) is strongly associated with the presence of aortic valve calcium (AVC), there are no data evaluating the relationship of Lp(a) with AVC incidence and AVC progression. Purpose To assess whether high Lp(a) levels are associated with AVC incidence and progression. Methods In 922 individuals from the population-based Rotterdam Study (mean age 66.0±4.2 years, 47.7% men) for whom Lp(a) measurements were available, non-enhanced cardiac CT imaging was performed at baseline and after a median follow-up of 14.0 [13.9–14.2] years. AVC incidence was defined as an AVC score >0 on the second scan, in absence of AVC on the first scan. We performed logistic regression analyses to evaluate the relationship of Lp(a) with AVC incidence and linear regression analyses to assess the relationship between Lp(a) and AVC progression. All analyses were corrected for age, sex, body mass index, smoking, non-high-density lipoprotein cholesterol, use of lipid-lowering medication, and hypertension. Additionally, we analyzed the progression conditional on the baseline AVC-score. Results Of the 702 (76.1%) individuals without AVC at baseline, 415 (59.1%) showed incident AVC at follow-up. The 220 (23.9%) individuals with AVC on baseline had a median AVC score of 52 [15–131], with a median yearly progression of 13 [5–38]. Lp(a) concentration was independently associated with AVC incidence (OR 1.32 for each 105 nmol/L Lp(a) increase; 95% CI: 1.03–1.68), but not with AVC progression (β −4.3 AU/year for each 105 nmol/L Lp(a) increase; 95% CI: −12.3–3.7). Conclusions Lp(a) is associated with AVC incidence but not AVC progression, suggesting that Lp(a)-lowering interventions may be futile after AVC has been established. Future studies should focus on whether Lp(a) lowering interventions can prevent the development of AVC in high-risk individuals. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): The Rotterdam Study is supported by Erasmus MC and Erasmus University Rotterdam and the Netherlands Organization for Scientific Research
Published: 2021

21. Lipoprotein(a) and Benefit of PCSK9 Inhibition in Patients With Nominally Controlled LDL Cholesterol

Author: Gregory G. Schwartz, Michael Szarek, Vera A. Bittner, Rafael Diaz, Shaun G. Goodman, J. Wouter Jukema, Ulf Landmesser, Patricio López-Jaramillo, Garen Manvelian, Robert Pordy, Michel Scemama, Peter R. Sinnaeve, Harvey D. White, Ph Gabriel Steg, P.h. Gabriel Steg, Deepak L. Bhatt, Robert A. Harrington, Andreas M. Zeiher, Pierluigi Tricoci, Matthew T. Roe, Kenneth W. Mahaffey, Jay M. Edelberg, Corinne Hanotin, Guillaume Lecorps, Angèle Moryusef, William J. Sasiela, Jean-François Tamby, Philip E. Aylward, Heinz Drexel, Peter Sinnaeve, Mirza Dilic, Renato D. Lopes, Nina N. Gotcheva, Juan-Carlos Prieto, Huo Yong, Ivan Pećin, Zeljko Reiner, Petr Ostadal, Steen Hvitfeldt Poulsen, Margus Viigimaa, Markku S. Nieminen, Nicolas Danchin, Vakhtang Chumburidze, Nikolaus Marx, Evangelos Liberopoulos, Pablo Carlos Montenegro Valdovinos, Hung-Fat Tse, Robert Gabor Kiss, Denis Xavier, Doron Zahger, Marco Valgimigli, Takeshi Kimura, Hyo Soo Kim, Sang-Hyun Kim, Andrejs Erglis, Aleksandras Laucevicius, Sasko Kedev, Khalid Yusoff, Gabriel Arturo Ramos López, Marco Alings, Sigrun Halvorsen, Roger M. Correa Flores, Rody G. Sy, Andrzej Budaj, Joao Morais, Maria Dorobantu, Yuri Karpov, Arsen D. Ristic, Terrance Chua, Jan Murin, Zlatko Fras, Anthony J. Dalby, José Tuñón, H. Asita de Silva, Emil Hagström, Christian Müller, Chern-En Chiang, Piyamitr Sritara, Sema Guneri, Alexander Parkhomenko, Kausik K. Ray, Patrick M. Moriarty, Robert Vogel, Bernard Chaitman, Sheryl F. Kelsey, Anders G. Olsson, Jean-Lucien Rouleau, Maarten L. Simoons, Karen Alexander, Chiara Meloni, Robert Rosenson, Eric J.G. Sijbrands, John H. Alexander, Luciana Armaganijan, Akshay Bagai, Maria Cecilia Bahit, J. Matthew Brennan, Shaun Clifton, Adam D. DeVore, Shalonda Deloatch, Sheila Dickey, Keith Dombrowski, Grégory Ducrocq, Zubin Eapen, Patricia Endsley, Arleen Eppinger, Robert W. Harrison, Connie Ng Hess, Mark A. Hlatky, Joseph Dedrick Jordan, Joshua W. Knowles, Bradley J. Kolls, David F. Kong, Sergio Leonardi, Linda Lillis, David J. Maron, Jill Marcus, Robin Mathews, Rajendra H. Mehta, Robert J. Mentz, Humberto Graner Moreira, Chetan B. Patel, Sabrina Bernardez Pereira, Lynn Perkins, Thomas J. Povsic, Etienne Puymirat, William Schuyler Jones, Bimal R. Shah, Matthew W. Sherwood, Kenya Stringfellow, Darin Sujjavanich, Mustafa Toma, Charlene Trotter, Sean F.P. van Diepen, Matthew D. Wilson, Andrew Tze-Kay Yan, Lilia B. Schiavi, Marcelo Garrido, Andrés F. Alvarisqueta, Sonia A. Sassone, Anselmo P. Bordonava, Alberto E. Alves De Lima, Jorge M. Schmidberg, Ernesto A. Duronto, Orlando C. Caruso, Leonardo P. Novaretto, Miguel Angel Hominal, Oscar R. Montaña, Alberto Caccavo, Oscar A. Gomez Vilamajo, Alberto J. Lorenzatti, Luis R. Cartasegna, Gustavo A. Paterlini, Ignacio J. Mackinnon, Guillermo D. Caime, Marcos Amuchastegui, Oscar Salomone, Oscar R. Codutti, Horacio O. Jure, Julio O.E. Bono, Adrian D. Hrabar, Julio A. Vallejos, Rodolfo A. Ahuad Guerrero, Federico Novoa, Cristian A. Patocchi, Cesar J. Zaidman, Maria E. Giuliano, Ricardo D. Dran, Marisa L. Vico, Gabriela S. Carnero, Pablo N. Guzman, Juan C. Medrano Allende, Daniela F. Garcia Brasca, Miguel H. Bustamante Labarta, Sebastian Nani, Eduardo D.S. Blumberg, Hugo R. Colombo, Alberto Liberman, Victorino Fuentealba, Hector L. Luciardi, Gabriel D. Waisman, Mario A. Berli, Ruben O. Garcia Duran, Horacio G. Cestari, Hugo A. Luquez, Jorge A. Giordano, Silvia S. Saavedra, Gerardo Zapata, Osvaldo Costamagna, Susana Llois, Jonathon H. Waites, Nicholas Collins, Allan Soward, Chris L.S. Hii, James Shaw, Margaret A. Arstall, John Horowitz, Daniel Ninio, James F. Rogers, David Colquhoun, Romulo E. Oqueli Flores, Philip Roberts-Thomson, Owen Raffel, Sam J. Lehman, Constantine Aroney, Steven G.M. Coverdale, Paul J. Garrahy, Gregory Starmer, Mark Sader, Patrick A. Carroll, Ronald Dick, Robert Zweiker, Uta Hoppe, Kurt Huber, Rudolf Berger, Georg Delle-Karth, Bernhard Frey, Dirk Faes, Kurt Hermans, Bruno Pirenne, Attilio Leone, Etienne Hoffer, Mathias C.M. Vrolix, Luc De Wolf, Bart Wollaert, Marc Castadot, Karl Dujardin, Christophe Beauloye, Geert Vervoort, Harry Striekwold, Carl Convens, John Roosen, Emanuele Barbato, Marc Claeys, Frank Cools, Ibrahim Terzic, Fahir Barakovic, Zlatko Midzic, Belma Pojskic, Emir Fazlibegovic, Azra Durak-Nalbantic, Mehmed Kulić, Dusko Vulic, Adis Muslibegovic, Boris Goronja, Gilmar Reis, Luciano Sousa, Jose C. Nicolau, Flavio E. Giorgeto, Ricardo P. Silva, Lilia Nigro Maia, Rafael Rech, Paulo R.F. Rossi, Maria José A.G. Cerqueira, Norberto Duda, Renato Kalil, Adrian Kormann, José Antonio M. Abrantes, Pedro Pimentel Filho, Ana Priscila Soggia, Mayler O.N. de Santos, Fernando Neuenschwander, Luiz C. Bodanese, Yorghos L. Michalaros, Freddy G. Eliaschewitz, Maria H. Vidotti, Paulo E. Leaes, Roberto V. Botelho, Sergio Kaiser, Euler Roberto F. Fernandes Manenti, Dalton B. Precoma, Jose C. Moura Jorge, Pedro Silva, Jose A. Silveira, Wladmir Saporito, Jose A. Marin Neto, Gilson S. Feitosa, Luiz Eduardo F. Ritt, Juliana A. de Souza, Fernando Costa, Weimar K.S.B. Souza, Helder J.L. Reis, Leandro Machado, José Carlos Aidar Ayoub, Georgi V. Todorov, Fedya P. Nikolov, Elena S. Velcheva, Maria L. Tzekova, Haralambi O. Benov, Stanislav L. Petranov, Haralin S. Tumbev, Nina S. Shehova-Yankova, Dimitar T. Markov, Dimitar H. Raev, Mihail N. Mollov, Kostadin N. Kichukov, Katya A. Ilieva-Pandeva, Raya Ivanova, Maryana Gospodinov, Valentina M. Mincheva, Petar V. Lazov, Bojidar I. Dimov, Manohara Senaratne, James Stone, Jan Kornder, Stephen Pearce, Danielle Dion, Daniel Savard, Yves Pesant, Amritanshu Pandey, Simon Robinson, Gilbert Gosselin, Saul Vizel, Gordon Hoag, Ronald Bourgeois, Anne Morisset, Eric Sabbah, Bruce Sussex, Simon Kouz, Paul MacDonald, Ariel Diaz, Nicolas Michaud, David Fell, Raymond Leung, Tycho Vuurmans, Christopher Lai, Frank Nigro, Richard Davies, Gustavo Nogareda, Ram Vijayaraghavan, John Ducas, Serge Lepage, Shamir Mehta, James Cha, Robert Dupuis, Peter Fong, Sohrab Lutchmedial, Josep Rodes-Cabau, Hussein Fadlallah, David Cleveland, Thao Huynh, Iqbal Bata, Adnan Hameed, Cristian Pincetti, Sergio Potthoff, Juan C. Prieto, Monica Acevedo, Arnoldo Aguirre, Margarita Vejar, Mario Yañez, Guillermo Araneda, Mauricio Fernandez, Luis Perez, Paola Varleta, Fernando Florenzano, Laura Huidobro, Carlos A. Raffo, Claudia Olivares, Leonardo Nahuelpan, Humberto Montecinos, Jiyan Chen, Yugang Dong, Weijian Huang, Jianzhong Wang, Shi'An Huang, Zhuhua Yao, Xiang Li, Lan Cui, Wenhua Lin, Yuemin Sun, Jingfeng Wang, Jianping Li, Xuelian Zhang, Hong Zhu, Dandan Chen, Lan Huang, Shaohong Dong, Guohai Su, Biao Xu, Xi Su, Xiaoshu Cheng, Jinxiu Lin, Wenxia Zong, Huanming Li, Yi Feng, Dingli Xu, Xinchun Yang, Yuannan Ke, Xuefeng Lin, Zheng Zhang, Zeqi Zheng, Zhurong Luo, Yundai Chen, Chunhua Ding, Yi Zhong, Yang Zheng, Xiaodong Li, Daoquan Peng, Shuiping Zhao, Ying Li, Xuebo Liu, Meng Wei, Shaowen Liu, Yihua Yu, Baiming Qu, Weihong Jiang, Yujie Zhou, Xingsheng Zhao, Zuyi Yuan, Ying Guo, Xiping Xu, Xubo Shi, Junbo Ge, Guosheng Fu, Feng Bai, Weiyi Fang, Xiling Shou, Xiangjun Yang, Jian'An Wang, Meixiang Xiang, Yingxian Sun, Qinghua Lu, Ruiyan Zhang, Jianhua Zhu, Yizhou Xu, Zhongcai Fan, Tianchang Li, Chun Wu, Nicolas Jaramillo, Gregorio Sanchez Vallejo, Diana C. Luna Botia, Rodrigo Botero Lopez, Dora I. Molina De Salazar, Alberto J. Cadena Bonfanti, Carlos Cotes Aroca, Juan Diego Higuera, Marco Blanquicett, Sandra I. Barrera Silva, Henry J. Garcia Lozada, Julian A. Coronel Arroyo, Jose L. Accini Mendoza, Ricardo L. Fernandez Ruiz, Alvaro M. Quintero Ossa, Fernando G. Manzur Jatin, Aristides Sotomayor Herazo, Jeffrey Castellanos Parada, Rafael Suarez Arambula, Miguel A. Urina Triana, Angela M. Fernandez Trujillo, Maja Strozzi, Siniša Car, Melita Jerić, Davor Miličić, Martina Lovrić Benčić, Hrvoje Pintarić, Đeiti Prvulović, Jozica Šikić, Viktor Peršić, Dean Mileta, Kresimir Štambuk, Zdravko Babić, Vjekoslav Tomulic, Josip Lukenda, Stanka Mejic-Krstulovic, Boris Starcevic, Jindrich Spinar, David Horak, Zdenek Velicka, Josef Stasek, David Alan, Vilma Machova, Ales Linhart, Vojtech Novotny, Vladimir Kaucak, Richard Rokyta, Robert Naplava, Zdenek Coufal, Vera Adamkova, Ivo Podpera, Jiri Zizka, Zuzana Motovska, Ivana Marusincova, Premysl Svab, Petr Heinc, Jiri Kuchar, Petr Povolny, Jiri Matuska, Steen H. Poulsen, Bent Raungaard, Peter Clemmensen, Lia E. Bang, Ole May, Morten Bøttcher, Jens D. Hove, Lars Frost, Gunnar Gislason, John Larsen, Peter Betton Johansen, Flemming Hald, Peter Johansen, Jørgen Jeppesen, Tonny Nielsen, Kjeld S. Kristensen, Piotr Maria Walichiewicz, Jens D. Lomholdt, Ib C. Klausen, Peter Kaiser Nielsen, Flemming Davidsen, Lars Videbaek, Mai Soots, Veiko Vahula, Anu Hedman, Üllar Soopõld, Kaja Märtsin, Tiina Jurgenson, Arved Kristjan, Heikki Huikuri, Juhani Airaksinen Pierre Coste, Emile Ferrari, Olivier Morel, Gilles Montalescot, Jacques Machecourt, Gilles Barone-Rochette, Jacques Mansourati, Yves Cottin, Florence Leclercq, Abdelkader Belhassane, Nicolas Delarche, Franck Boccara, Franck Paganelli, Jérôme Clerc, Francois Schiele, Victor Aboyans, Vincent Probst, Jacques Berland, Thierry Lefèvre, Bernard Citron, Irakli Khintibidze, Tamaz Shaburishvili, Zurab Pagava, Ramaz Ghlonti, Zaza Lominadze, George Khabeishvili, Rayyan Hemetsberger, Kemala Edward, Ursula Rauch-Kröhnert, Matthias Stratmann, Karl-Friedrich Appel, Ekkehard Schmidt, Heyder Omran, Christoph Stellbrink, Thomas Dorsel, Emmanouil Lianopoulos, Hans Friedrich Vöhringer, Roger Marx, Andreas Zirlik, Detlev Schellenberg, Thomas Heitzer, Ulrich Laufs, Christian Werner, Stephan Gielen, Sebastian Nuding, Bernhard Winkelmann, Steffen Behrens, Karsten Sydow, Mahir Karakas, Gregor Simonis, Thomas Muenzel, Nikos Werner, Stefan Leggewie, Dirk Böcker, Rüdiger Braun-Dullaeus, Nicole Toursarkissian, Michael Jeserich, Matthias Weißbrodt, Tim Schaeufele, Joachim Weil, Heinz Völler, Johannes Waltenberger, Mohammed Natour, Susanne Schmitt, Dirk Müller-Wieland, Stephan Steiner, Lothar Heidenreich, Elmar Offers, Uwe Gremmler, Holger Killat, Werner Rieker, Sotiris Patsilinakos, Athanasios Kartalis, Athanassios Manolis, Dimitrios Sionis, Geargios Chachalis, Ioannis Skoumas, Vasilios Athyros, Panagiotis Vardas, Frangkiskos Parthenakis, John Lekakis, Apostolos Hatzitolios, Sergio R. Fausto Ovando, Juan L. Arango Benecke, Edgar R. Rodriguez De Leon, Bryan P.Y. Yan, David C.W. Siu, Tibor Turi, Bela Merkely, Imre Ungi, Geza Lupkovics, Lajos Nagy, András Katona, István Édes, Gábor Müller, Iván Horvath, Tibor Kapin, Zsolt Szigeti, József Faluközy, Mukund Kumbla, Manjinder Sandhu, Sharath Annam, Naveen Reddy Proddutur, Reddy Regella, Rajendra K. Premchand, Ajaykumar Mahajan, Sudhir Pawar, Atul D. Abhyanakar, Prafulla Kerkar, Ravishankar A. Govinda, Abraham Oomman, Dhurjati Sinha, Sachin N. Patil, Dhiman Kahali, Jitendra Sawhney, Abhijeet B. Joshi, Sanjeev Chaudhary, Pankaj Harkut, Santanu Guha, Sanjay Porwal, Srimannarayana Jujjuru, Ramesh B. Pothineni, Minguel R. Monteiro, Aziz Khan, Shamanna S. Iyengar, Jasprakash Singh Grewal, Manoj Chopda, Mahesh C. Fulwani, Aparna Patange, Patil Sachin, Vijay K. Chopra, Naresh K. Goyal, Rituparna Shinde, Gajendra V. Manakshe, Nitin Patki, Sumeet Sethi, Vengatesh Munusamy, Sunil Karnaand Sunil Thanvi, Srilakshmi Adhyapak, Chandrakant Patil, Ulhas Pandurangi, Rishabh Mathur, Jugal Gupta, Suhas Kalashetti, Ajit Bhagwat, Bagirath Raghuraman, Shiv Kumar Yerra, Prasant Bhansali, Rohidas Borse, Patil Rahul, Srihari Das, Vinay Kumar, Jabir Abdullakutty, Shireesh Saathe, Priya Palimkar, Jabir Abdullkutty, Shireesh Sathe, Shaul Atar, Michael Shechter, Morris Mosseri, Yaron Arbel, Chorin Ehud, Havakuk Ofer, Chaim Lotan, Uri Rosenschein, Amos Katz, Yaakov Henkin, Adi Francis, Marc Klutstein, Eugenia Nikolsky, Robert Zukermann, Yoav Turgeman, Majdi Halabi, Alon Marmor, Ran Kornowski, Michael Jonas, Offer Amir, Yonathan Hasin, Yoseph Rozenman, Shmuel Fuchs, Vered Zvi, Osamah Hussein, Dov Gavish, Zvi Vered, Yoseph Caraco, Mazen Elias, Naveh Tov, Efrat Wolfovitz, Michael Lishner, Nizar Elias, Giancarlo Piovaccari, Annamaria De Pellegrin, Raffaella Garbelotto, Gabriele Guardigli, Valgimigli Marco, Giovanni Licciardello, Carla Auguadro, Filippo Scalise, Claudio Cuccia, Alessandro Salvioni, Giuseppe Musumeci, Michelle Senni, Paolo Calabrò, Salvatore Novo, Pompilio Faggiano, Marco Metra, Nicoletta B. De Cesare, Sergio Berti, Claudio Cavallini, Enrico Puccioni, Marcello Galvani, Maurizio Tespili, Piermarco Piatti, Michela Palvarini, Giuseppe De Luca, Roberto Violini, Alessandro De Leo, Zoran Olivari, Pasquale Perrone Filardi, Maurizio Ferratini, Vittorio Racca, Kazuoki Dai, Yuji Shimatani, Haruo Kamiya, Kenji Ando, Yoshihiro Takeda, Yoshihiro Morino, Yoshiki Hata, Kazuo Kimura, Koichi Kishi, Ichiro Michishita, Hiroki Uehara, Toshinori Higashikata, Atsushi Hirayama, Keiji Hirooka, Yasuji Doi, Satoru Sakagami, Shuichi Taguchi, Akihiro Koike, Hiroyuki Fujinaga, Shinji Koba, Ken Kozuma, Tomohiro Kawasaki, Yujiro Ono, Masatoshi Shimizu, Yousuke Katsuda, Atsuyuki Wada, Toshiro Shinke, Junya Ako, Kenshi Fujii, Toshiyuki Takahashi, Tomohiro Sakamoto, Koichi Nakao, Yutaka Furukawa, Hiroshi Sugino, Ritsu Tamura, Toshiaki Mano, Masaaki Uematsu, Noriaki Utsu, Kashima Ito, Takuya Haraguchi, Katsuhiko Sato, Yasunori Ueda, Akira Nishibe, Kazuteru Fujimoto, Motomaru Masutani, Jung Han Yoon, Hack-Lyoung Kim, Hun Sik Park, In-Ho Chae, Moo Hyun Kim, Myung Ho Jeong, Seungwoon Rha, Chongjin Kim, Hae Young Kim, Taekjong Hong, Seung-Jea Tahk, Youngkwon Kim, Arija Busmane, Natalija Pontaga, Aldis Strelnieks, Iveta Mintale, Iveta Sime, Zaneta Petrulioniene, Roma Kavaliauskiene, Ruta Jurgaitiene, Gintare Sakalyte, Rimvydas Slapikas, Sigute Norkiene, Nerijus Misonis, Aleksandras Kibarskis, Raimondas Kubilius, Stojko Bojovski, Nensi Lozance, Aleksandar Kjovkaroski, Snezana Doncovska, Tiong Kiam Ong, Sazzli Kasim, Oteh Maskon, Balachandran Kandasamy, Houng B. Liew, Wan Mohd Izani Wan Mohamed, Armando García Castillo, Jorge Carrillo Calvillo, Pedro Fajardo Campos, Juan Carlos Núñez Fragoso, Edmundo Alfredo Bayram Llamas, Marco Antonio Alcocer Gamba, Jaime Carranza Madrigal, Luis Gerardo González Salas, Enrique López Rosas, Belinda González Díaz, Eduardo Salcido Vázquez, Alfredo Nacoud Ackar, Guillermo Antonio Llamas Esperón, Carlos Rodolfo Martínez Sánchez, María Guerrero De Leon, Rodrigo Suarez Otero, Guillermo Fanghänel Salmón, Jesús Antonio Pérez Ríos, José Angel Garza Ruíz, Robert W. Breedveld, Margriet Feenema-Aardema, Alida Borger-Van Der Burg, Pieter A.M. Hoogslag, Harry Suryapranata, Antonius Oomen, Paulus Van Haelst, Margriet Feenema-Aradema, Jacobijne J. Wiersma, Dirk Basart, Ruud M.A. Van Der Wal, Peter Zwart, Pascalle Monraats, Henricus Van Kesteren, Ioannis Karalis, Johan Jukema, Gerardus J.E. Verdel, Bart R.G. Brueren, Roland PTh Troquay, Eric P. Viergever, Nadea Y.Y. Al-Windy, Gerard L. Bartels, Jan H. Cornel, Walter R.M. Hermans, Johannes P.R. Herrman, Robert J. Bos, Reginald G.E.J. Groutars, Coenraad C. Van Der Zwaan, Refik Kaplan, Raymond Lionarons, Eelko Ronner, Bjorn E. Groenemeijer, Patrick N.A. Bronzwaer, Anho A.H. Liem, Bernard J.W.M. Rensing, Marcel J.J.A. Bokern, Remco Nijmeijer, Ferry M.R.J. Hersbach, Frank F. Willems, Antonius T.M. Gosselink, Saman Rasoul, John Elliott, Gerard Wilkins, Raewyn Fisher, Douglas Scott, Hamish Hart, Ralph Stewart, Scott Harding, Ian Ternouth, Nicholas Fisher, Samuel Wilson, Denise Aitken, Russell Anscombe, Laura Davidson, Tadeusz Tomala, Ottar Nygård, Jon Arne Sparby, Kjell Andersen, Lars Gullestad, Jarle Jortveit, Peter S. Munk, Erlend gyllensten Singsaas, Ulf Hurtig, Jorge R. Calderon Ticona, Julio R. Durand Velasquez, Sandra A. Negron Miguel, Enrique S. Sanabria Perez, Jesus M. Carrion Chambilla, Carlos A. Chavez Ayala, Reynaldo P. Castillo Leon, Rolando J. Vargas Gonzales, Jose D. Hernandez Zuniga, Luis A. Camacho Cosavalente, Jorge E. Bravo Mannucci, Javier Heredia Landeo, Nassip C. Llerena Navarro, Yudy M. Roldan Concha, Víctor E. Rodriguez Chavez, Henry A. Anchante Hernandez, Carlos A. Zea Nunez, Walter Mogrovejo Ramos, Arthur Ferrolino, Rosa Allyn G. Sy, Louie Tirador, Generoso Matiga, Raul Martin Coching, Alisa Bernan, Gregorio Rogelio, Dante D. Morales, Edgar Tan, Dennis Jose Sulit, Adrian Wlodarczak, Krystyna Jaworska, Grzegorz Skonieczny, Lidia Pawlowicz, Pawel Wojewoda, Benita Busz-Papiez, Janusz Bednarski, Aleksander Goch, Pawel Staneta, Elzbieta Dulak, Krzysztof Saminski, Wlodzimierz Krasowski, Wanda Sudnik, Aleksander Zurakowski, Marcin Skorski, Roman Lysek, Beata Miklaszewicz, Jacek Kubica, Jan Andrzej Lipko, Edyta Kostarska-Srokosz, Marek Piepiorka, Anna Drzewiecka, Ryszard Sciborski, Arkadiusz Stasiewski, Tomasz Blicharski, Leszek Bystryk, Michal Szpajer, Marek Korol, Tomasz Czerski, Ewa Mirek-Bryniarska, Jacek Gniot, Andrzej Lubinski, Jerzy Gorny, Edward Franek, Grzegorz Raczak, Hanna Szwed, Pedro Monteiro, Jose Mesquita Bastos, Helder H. Pereira, Dinis Martins, Filipe Seixo, Carlos Mendonça, Ana Botelho, Francisca Caetano, Bogdan Minescu, Octavian Istratoaie, Dan N. Tesloianu, Gabriel Cristian, Silviu Dumitrescu, Cristian G.C. Podoleanu, Mircea C.A. Constantinescu, Cristina M. Bengus, Constantin Militaru, Doina Rosu, Irinel R. Parepa, Adrian V. Matei, Tom M. Alexandru, Mihaela Malis, Ioan Coman, Rodica Stanescu-Cioranu, Doina Dimulescu, Yury Shvarts, Olga Orlikova, Zhanna Kobalava, Olga L. Barbarash, Valentin Markov, Nadezhda Lyamina, Alexander Gordienko, Konstantin Zrazhevsky, Alexander Y. Vishnevsky, Victor Gurevich, Raisa Stryuk, Nikita V. Lomakin, Igor Bokarev, Tatiana Khlevchuk, Sergey Shalaev, Larisa Khaisheva, Petr Chizhov, Inna Viktorova, Natalya Osokina, Vladimir Shchekotov, Evgenia Akatova, Galina Chumakova, Igor Libov, Mikhail I. Voevoda, Tatyana V. Tretyakova, Evgeny Baranov, Sergey Shustov, Sergey Yakushin, Ivan Gordeev, Niiaz Khasanov, Olga Reshetko, Tatiana Sotnikova, Olga Molchanova, Konstantin Nikolaev, Liudmila Gapon, Elena Baranova, Zaur Shogenov, Elena Kosmachova, Yuriy Karpov, Anton Povzun, Liudmila Egorova, Vadim V. Tyrenko, Igor G. Ivanov, Masterov Ilya, Sergey Kanorsky, Dragan Simic, Nikola Ivanovic, Goran Davidovic, Nebojsa Tasic, Milika R. Asanin, Stevo Stojic, Svetlana R. Apostolovic, Stevan Ilic, Biljana Putnikovic Tosic, Aleksandar Stankovic, Aleksandra Arandjelovic, Slavica Radovanovic, Branislava Todic, Jovan Balinovac, Dragan V. Dincic, Petar Seferovic, Ana Karadzic, Slobodan Dodic, Sinisa Dimkovic, Tamara Jakimov, Kian-Keong Poh, Hean Yee Ong, Justin Tang I-Shing, Karol Micko, Jan Nociar, Daniel Pella, Peter Fulop, Marian Hranai, Juraj Palka, Juraj Mazur, Ivan Majercák, Andrej Dzupina, František Fazekas, Jozef Gonsorcik, Viliam Bugan, Juraj Selecky, Gabriel Kamensky, Jaroslava Strbova, Rudolf Smik, Andrej Dukat, Peter Olexa, Ivan Žuran, Janez Poklukar, Nataša Černič Šuligoj, Matija Cevc, Henry P. Cyster, Naresh Ranjith, Clive Corbett, Junaid Bayat, Ellen Makoali Makotoko, Hendrik du Toit Theron, Ilse E. Kapp, Matthys M. de V Basson, Hanlie Lottering, Dina Van Aswegen, Louis J. Van Zyl, Peter J. Sebastian, Thayabran Pillay, Jan A. Saaiman, Patrick J. Commerford, Soraya Cassimjee, Garda Riaz, Iftikhar O. Ebrahim, Mahomed Sarvan, Joseph H. Mynhardt, Helmuth Reuter, Rajendran Moodley, Manuel Vida, Angel R. Cequier Fillat, Vicente Bodí Peris, Francisco Fuentes Jimenez, Francisco Marín, Jose M. Cruz Fernández, Rafael Jesus Hidalgo Urbano, Blas Gil-Extremera, Pablo Toledo, Fernando Worner Diz, David Garcia-Dorado, Andres Iñiguez, José Tuñón Fernández, Jose R. Gonzalez-Juanatey, Javier Fernandez Portales, Fernando Civeira Murillo, Laia Matas Pericas, Jose Luis Zamorano, Manuel De Mora Martin, Jordi Bruguera Cortada, Joaquin J. Alonso Martin, Jose Maria Serrano Antolin, José R. De Berrazueta Fernández, José Antonio Vázquez de Prada, Jose Francisco Díaz Fernández, José Alberto García Lledó, Juan Cosín Sales, Javier Botas Rodriguez, Gabriel Gusi Tragant, Amparo Benedicto, Carlos Gonzalez-Juanatey, Mercedes Camprubí Potau, Ignacio Plaza Perez, César Morís De La Tassa, Pablo Loma-Osorio Rincon, Javier Balaguer Recena, Juan M. Escudier, Antonio Coca Payeras, Norberto Alonso Orcajo, Pedro Valdivielso, Godwin Constantine, Ruvaiz Haniffa, Nirmali Tissera, Stanley Amarasekera, Chandrike Ponnamperuma, Nimali Fernando, Kaputella Fernando, Jayanthimala Jayawardena, Santharaj Wijeyasingam, Gotabhaya Ranasinghe, Ruvan Ekanayaka, Sepalika Mendis, Vajira Senaratne, Gnanamoorthy Mayurathan, Ajantha Rajapaksha, Thilak Sirisena, Jagath I. Herath, Naomali Amarasena, Stefan Berglund, Gundars Rasmanis, Ola Vedin, Nils Witt, Georgios Mourtzinis, Peter Nicol, Ole Hansen, Stefano Romeo, Steen Agergaard Jensen, Ingemar Torstensson, Ulf Ahremark, Torbjörn Sundelin, Tiziano Moccetti, Francois Mach, Ronald Binde, Oliver Gämperli, Wei-Chuan Tsai, Kwo-Chang Ueng, Wen-Ter Lai, Ming-En Liu, Juey-Jen Hwang, Wei-Hsian Yin, I-Chang Hsieh, Ming-Jer Hsieh, Wei Hsiang Lin, Jen-Yuan Kuo, Tsuei-Yuan Huang, Chih-Yuan Fang, Pinij Kaewsuwanna, Wasant Soonfuang, Woravut Jintapakorn, Apichard Sukonthasarn, Nattawut Wongpraparut, Krisada Sastravaha, Nakarin Sansanayudh, Wirash Kehasukcharoen, Dilok Piyayotai, Paiboon Chotnoparatpat, Ahmet Camsari, Hakan Kultursay, Bulent Mutlu, Murat Ersanli, Mustafa Demirtas, Cevat Kirma, Ertan Ural, Lale Koldas, Oleksandr Karpenko, Alexander Prokhorov, Ihor Vakaluyk, Halyna Myshanych, Dmytro Reshotko, Valeriy Batushkin, Leonid Rudenko, Ihor Kovalskyi, Mykola Kushnir, Vira Tseluyko, Yuriy Mostovoy, Mykola Stanislavchuk, Yulian Kyiak, Yuriy Karpenko, Yaroslav Malynovsky, Andriy Klantsa, Oles Kutniy, Ekaterina Amosova, Viktor Tashchuk, Oleh Leshchuk, Mykola Rishko, Mykola Kopytsya, Andriy Yagensky, Mykola Vatutin, Andriy Bagriy, Olga M. Barna, Olexiy Ushakov, Georgiy Dzyak, Borys Goloborodko, Anatolii Rudenko, Volodymyr Zheleznyy, Jasper Trevelyan, Azfar Zaman, Kaeng Lee, Andrew Moriarty, Rajesh K. Aggarwal, Piers Clifford, Yuk-Ki Wong, Syed M.R. Iqbal, Eduardas Subkovas, Denise Braganza, David Sarkar, Robert Storey, Huw Griffiths, Sam Mcclure, Rangasamy Muthusamy, Simon Smith, John Kurian, Terry Levy, Craig Barr, Honer Kadr, Robert Gerber, Audrius Simaitis, Handrean Soran, Anthony Mathur, Adrian Brodison, Mohammad Ayaz, Muhammad Cheema, Richard Oliver, Simon Thackray, Telal Mudawi, Gohar Rahman, Ayyaz Sultan, Timothy Reynolds, David Sharman, null david Sprigings, Rob Butler, Peter Wilkinson, Gregory Y.H. Lip, Julian Halcox, Sean Gallagher, Nicholas Ossei-Gerning, Gil Vardi, Duccio Baldari, David Brabham, Charles Treasure, Charles Dahl, Bruce Palmer, Alan Wiseman, Abul Khan, Sanjeev Puri, Ann Elizabeth Mohart, Carlos Ince, Enrique Flores, Scott Wright, Shi-Chi Cheng, Michael Rosenberg, William Rogers, Edward Kosinski, Les Forgosh, Jonathan Waltman, Misal Khan, Mohammad Shoukfeh, Georges Dagher, Patrick Cambier, Ira Lieber, Priya Kumar, Cara East, Perry Krichmar, Mian Hasan, Lindsey White, Thomas Knickelbine, Thomas Haldis, Eve Gillespie, Thomas Amidon, David Suh, Imran Arif, Mouhamad Abdallah, Faiq Akhter, Eric Carlson, Michael D'Urso, Fadi El-Ahdab, William Nelson, Katie Moriarty, Barry Harris, Steven Cohen, Luther Carter, Daniel Doty, Kenneth Sabatino, Tariq Haddad, Amir Malik, Sunder Rao, Angel Mulkay, Ion Jovin, Kim Klancke, Vinay Malhotra, Sai K. Devarapalli, Michael Koren, Harish Chandna, George Dodds, Tauqir Goraya, James Bengston, Matthew Janik, Joseph Moran, Andrew Sumner, John Kobayashi, William Davis, Shahram Yazdani, John Pasquini, Maitreya Thakkar, Amarnath Vedere, Wayne Leimbach, James Rider, Sarah fenton, Narendra Singh, Anil V. Shah, Denise Janosik, Carl Pepine, Brett Berman, Joseph Gelormini, Christopher Daniels, Kerensky Richard, Friederike Keating, Nicholas I. Kondo, Sanjay Shetty, Howard Levite, Winfried Waider, Theodore Takata, Mazen Abu-Fadel, Vipul Shah, Rahul Aggarwal, Mark Izzo, Anil Kumar, Brack Hattler, Rose Do, Chad Link, Anna Bortnick, George Kinzfogl, Arnold Ghitis, John Larry, Edward Teufel, Peter Kuhlman, Brent Mclaurin, Wenwu Zhang, Stephen Thew, Jalal Abbas, Matthew White, Othman Islam, Sumeet Subherwal, Nandkishore Ranadive, Babak Vakili, Christian Gring, David Henderson, Timothy Schuchard, Naim Farhat, Geoffrey Kline, Sharan Mahal, Jack Whitaker, Shawn Speirs, Rolf Andersen, Nizar Daboul, Phillip Horwitz, Firas Zahr, George Ponce, Zubair Jafar, Joseph Mcgarvey, Vipul Panchal, Stephen Voyce, Thomas Blok, William Sheldon, Masoud M. Azizad, Carsten Schmalfuss, Mark Picone, Robert Pederson, William Herzog, Keith Friedman, Jason Lindsey, Rosemary Nowins, Eichenlaub Timothy, Parilak Leonard, Norman Lepor, Mahfouz El Shahawy, Howard Weintraub, Anand Irimpen, Alvaro Alonso, Wade May, Daniels Christopher, Thomas Galski, Alan Chu, Freny Mody, Ebrahimi Ramin, Zachary Hodes, Joseph Rossi, Gregory Rose, James Fairlamb, Charles Lambert, Ajit Raisinghani, Antonio Abbate, George Vetrovec, Marilyn King, Charles Carey, Jaime Gerber, Liwa Younis, Hyeun Park, Mladen Vidovich, Thomas Knutson, Dennis Friedman, Fred Chaleff, Arthur Loussararian, Phillip Rozeman, Carey Kimmelstiel, Jeffrey Kuvin, Kevin Silver, Malcolm Foster, Glen Tonnessen, Andrey Espinoza, Mohamadali Amlani, Andreas Wali, Christopher Malozzi, Geert T. Jong, Clara Massey, Keattiyoat Wattanakit, Philip J. O'Donnell, Dinesh Singal, Naseem Jaffrani, Sridhar Banuru, Daniel Fisher, Mark Xenakis, Neal Perlmutter, Ravi Bhagwat, James Strader, Ronald Blonder, Ayim Akyea-Djamson, Ajay Labroo, Kwan Lee, H. John Marais, Edmund Claxton, Robert Weiss, Rohr Kathryn, Martin Berk, Peter Rossi, Parag Joshi, Amit Khera, Ajit S. Khaira, Greg Kumkumian, Steven Lupovitch, Joshua Purow, Stephen Welka, David Hoffman, Stuart Fischer, Eugene Soroka, Donald Eagerton, Samir Pancholy, Michael Ray, Norman Erenrich, Michael Farrar, Stewart Pollock, William J. French, Steve Diamantis, Douglas Guy, Lawrence Gimple, Mark Neustel, Steven Schwartz, Edward Pereira, Seals Albert, Douglas Spriggs, Janet Strain, Suneet Mittal, Anthony Vo, Majed Chane, Jason Hall, Nampalli Vijay, Kapildeo Lotun, F. Martin Lester, Ahed Nahhas, Theodore Pope, Paul Nager, Rakesh Vohra, Mukesh Sharma, Riyaz Bashir, Hinan Ahmed, Michael Berlowitz, Robert Fishberg, Robert Barrucco, Eric Yang, Michael Radin, Daniel Sporn, Dwight Stapleton, Steven Eisenberg, Joel Landzberg, Martin Mcgough, Samir Turk, Michael Schwartz, P. Sandy Sundram, Diwakar Jain, Mark Zainea, Carlos Bayron, Ronald Karlsberg, Suhail Dohad, Henry Lui, William Keen, Donald Westerhausen, Sandeep Khurana, Himanshu Agarwal, Jessica Birchem, William Penny, Mark Chang, Sherrill Murphy, John Henry, Branislav Schifferdecker, John M Gilbert, Gopal Chalavarya, Charles Eaton, John F. Schmedtje, Stuart Christenson, Imran Dotani, Douglas Denham, Alexander Macdonell, Paul Gibson, Aref Rahman, Tammam Al Joundi, Nizar Assi, Gary Conrad, Purushotham Kotha, Michael Love, Gregory Giesler, Howard Rubenstein, Dawood Gamil, Laura Akright, Justine Krawczyk, Joanne Cobler, Terry Wells, James Welker, Robert Foster, Richard Gilmore, Jay Anderson, Douglas Jacoby, Bill Harris, Geraldine Gardner, Ramprasad Dandillaya, Kishor Vora, John Kostis, John Hunter, David Laxson, Eric Ball, Flavia Egydio, Anelise Kawakami, Janaina Oliveira, Julianna Wozniak, Alexander Matthews, Caroline Ratky, Janine Valiris, Lisa Berdan, Anita Hepditch, Kirby Quintero, Tyrus Rorick, Melissa Westbrook, Andrea Pascual, Carla Rovito, Madeleine Bezault, Elodie Drouet, Tabassome Simon, Caroline Alsweiler, Anne Luyten, Julie Butters, Liddy Griffith, Michelle Shaw, Lena Grunberg, Shahidul Islam, Marie-France Brégeault, Nathalie Bougon, Douglas Faustino, Sylvie Fontecave, Judith Murphy, Melanie Verrier, null Veronique Agnetti, Dorthe Andersen, Emmy Badreddine, Mhamed Bekkouche, Cecile Bouancheau, Imane Brigui, Maddy Brocklehurst, Joseph Cianciarulo, Dawn Devaul, Szilvia Domokos, Cecile Gache, Caroline Gobillot, Severine Guillou, Jan Healy, Megan Heath, Gayatri Jaiwal, Carine Javierre, Julien Labeirie, Myriam Monier, Ulises Morales, Asmaa Mrabti, Bicky Mthombeni, Betim Okan, Lucile Smith, Jennifer Sheller, Sebastien Sopena, Valerie Pellan, Fadela Benbernou, Nafissa Bengrait, Maud Lamoureux, Katarina Kralova, Raphael Bejuit, Anthony Coulange, Christelle Berthou, Jérôme Repincay, Christelle Lorenzato, Alexis Etienne, Valerie Gouet, Virginie Loizeau, Mickael Normand, Anne Ourliac, Christelle Rondel, Antony Adamo, Pascale Beltran, Pauline Barraud, Helene Dubois-Gache, Benjamin Halle, Lamia Metwally, Maxime Mourgues, Marc Sotty, Marion Vincendet, Raluca Cotruta, Zhu Chengyue, Dominique Fournie-Lloret, Christine Morrello, Aurelie Perthuis, Patrick Picault, Isabelle Zobouyan, Helen M. Colhoun, Michael A. Dempsey, Mark A. McClanahan, Masira, and Laucevičius, Aleksandras
Subjects: Male, Acute coronary syndrome, medicine.medical_specialty, Cardiac & Cardiovascular Systems, Randomization, PCSK9 inhibitor, LOW-DENSITY-LIPOPROTEIN, Antibodies, Monoclonal, Humanized, acute coronary syndrom, Placebo, Gastroenterology, lipoprotein(a), Internal medicine, medicine, Humans, Low-density lipoprotein cholesterol, Aged, Alirocumab, RISK, low-density lipoprotein cholesterol, Science & Technology, biology, business.industry, PCSK9, PCSK9 Inhibitors, Hazard ratio, ALIROCUMAB, acute coronary syndrome, Cholesterol, LDL, Lipoprotein(a), Middle Aged, EFFICACY, medicine.disease, Cardiovascular Diseases, CARDIOVASCULAR-DISEASE, SAFETY, Cardiovascular System & Cardiology, biology.protein, Female, lipids (amino acids, peptides, and proteins), STATIN, low-density lipoprotein, cholesterol PCSK9 inhibitor, CORONARY, Cardiology and Cardiovascular Medicine, business, Life Sciences & Biomedicine, Mace
Abstract: Digital, Background Guidelines recommend nonstatin lipid-lowering agents in patients at very high risk for major adverse cardiovascular events (MACE) if low-density lipoprotein cholesterol (LDL-C) remains ≥70 mg/dL on maximum tolerated statin treatment. It is uncertain if this approach benefits patients with LDL-C near 70 mg/dL. Lipoprotein(a) levels may influence residual risk. Objectives In a post hoc analysis of the ODYSSEY Outcomes (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) trial, the authors evaluated the benefit of adding the proprotein subtilisin/kexin type 9 inhibitor alirocumab to optimized statin treatment in patients with LDL-C levels near 70 mg/dL. Effects were evaluated according to concurrent lipoprotein(a) levels. Methods ODYSSEY Outcomes compared alirocumab with placebo in 18,924 patients with recent acute coronary syndromes receiving optimized statin treatment. In 4,351 patients (23.0%), screening or randomization LDL-C was 13.7 mg/dL or ≤13.7 mg/dL; corresponding adjusted treatment hazard ratios were 0.82 (95% CI: 0.72-0.92) and 0.89 (95% CI: 0.75-1.06), with Pinteraction = 0.43. Conclusions In patients with recent acute coronary syndromes and LDL-C near 70 mg/dL on optimized statin therapy, proprotein subtilisin/kexin type 9 inhibition provides incremental clinical benefit only when lipoprotein(a) concentration is at least mildly elevated. (ODYSSEY Outcomes: Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab; NCT01663402), Ciencias Médicas y de la Salud
Published: 2021

22. Genetic susceptibility, obesity and lifetime risk of type 2 diabetes

Author: Alanna C. Morrison, James S. Pankow, M. Arfan Ikram, Abbas Dehghan, Maarten J.G. Leening, Symen Ligthart, Natalie R Hasbani, Eric J.G. Sijbrands, Paul S. de Vries, Maryam Kavousi, André G. Uitterlinden, Elizabeth Selvin, Eric Boerwinkle, Fariba Ahmadizar, Thijs T. W. van Herpt, Intensive Care, Epidemiology, Internal Medicine, and Cardiology
Subjects: Male, Risk, Multifactorial Inheritance, Endocrinology, Diabetes and Metabolism, Population, Type 2 diabetes, Article, White People, Rotterdam Study, Endocrinology, SDG 3 - Good Health and Well-being, Diabetes mellitus, Internal Medicine, medicine, Genetic predisposition, Humans, Genetic Predisposition to Disease, Obesity, education, Aric study, Life Style, Aged, education.field_of_study, business.industry, Genetic Variation, Middle Aged, medicine.disease, Diabetes Mellitus, Type 2, Lifetime risk, Female, business, Demography
Abstract: Aims: Both lifestyle factors and genetic background contribute to the development of type 2 diabetes. Estimation of the lifetime risk of diabetes based on genetic information has not been presented, and the extent to which a normal body weight can offset a high lifetime genetic risk is unknown. Methods: We used data from 15,671 diabetes-free participants of European ancestry aged 45 years and older from the prospective population-based ARIC study and Rotterdam Study (RS). We quantified the remaining lifetime risk of diabetes stratified by genetic risk and quantified the effect of normal weight in terms of relative and lifetime risks in low, intermediate and high genetic risk. Results: At age 45 years, the lifetime risk of type 2 diabetes in ARIC in the low, intermediate and high genetic risk category was 33.2%, 41.3% and 47.2%, and in RS 22.8%, 30.6% and 35.5% respectively. The absolute lifetime risk for individuals with normal weight compared to individuals with obesity was 24% lower in ARIC and 8.6% lower in RS in the low genetic risk group, 36.3% lower in ARIC and 31.3% lower in RS in the intermediate genetic risk group, and 25.0% lower in ARIC and 29.4% lower in RS in the high genetic risk group. Conclusions: Genetic variants for type 2 diabetes have value in estimating the lifetime risk of type 2 diabetes. Normal weight mitigates partly the deleterious effect of high genetic risk.
Published: 2021

23. Novel metabolic indices and incident type 2 diabetes among women and men: the Rotterdam Study

Author: Adela Brahimaj, Eric J.G. Sijbrands, Taulant Muka, Oscar H. Franco, Maryam Kavousi, Abbas Dehghan, Fernando Rivadeneira, General Practice, Internal Medicine, and Epidemiology
Subjects: 0301 basic medicine, Male, Epidemiology, Endocrinology, Diabetes and Metabolism, Type 2 diabetes, Body Mass Index, Rotterdam Study, 0302 clinical medicine, Absorptiometry, Photon, Risk Factors, 610 Medicine & health, Adiposity, DXA, Anthropometry, Middle Aged, Obesity, Abdominal, Android fat, Female, Android fat distribution, TyG, 360 Social problems & social services, medicine.medical_specialty, Diabetes risk, 030209 endocrinology & metabolism, Intra-Abdominal Fat, Article, 03 medical and health sciences, BMI, SDG 3 - Good Health and Well-being, Diabetes mellitus, Internal medicine, Internal Medicine, medicine, Humans, Aged, Proportional Hazards Models, Proportional hazards model, business.industry, medicine.disease, VAI, 030104 developmental biology, Diabetes Mellitus, Type 2, Gynoid fat, LAP, Combined indices, business
Abstract: Aims/hypothesis Both visceral and truncal fat have been associated with metabolic disturbances. We aimed to investigate the associations of several novel metabolic indices, combining anthropometric and lipid measures, and dual-energy x-ray absorptiometry (DXA) measurements of body fat, with incident type 2 diabetes among women and men from the large population-based Rotterdam Study. Methods Cox proportional hazards models were used to investigate associations of visceral adiposity index (VAI), lipid accumulation product (LAP), the product of triacylglycerol and glucose (TyG), their formula components and DXA measures with incident type 2 diabetes. Associations were adjusted for traditional diabetes risk factors. Results Among 5576 women and 3988 men free of diabetes, 511 women and 388 men developed type 2 diabetes during a median follow-up of 6.5 years. In adjusted models, the three metabolic indices VAI (per 1 SD naturally log-transformed HR; 95% CI) (1.49; 1.36, 1.65 in women; 1.37; 1.22, 1.53 in men), LAP (1.35; 1.16, 1.56 in women; 1.19; 1.01, 1.42 in men) and TyG (1.73; 1.52, 1.98 in women; 1.43; 1.26, 1.62 in men), gynoid fat mass (0.63; 0.45, 0.89) and android to gynoid fat ratio (1.51; 1.16, 1.97) in women were associated with incident type 2 diabetes. BMI (1.45; 1.28, 1.65) was the strongest predictor of type 2 diabetes in men. Conclusions/interpretation Among women, novel combined metabolic indices were stronger risk markers for type 2 diabetes than the traditional anthropometric and laboratory measures and were comparable with DXA measures. Neither combined metabolic indices nor DXA measures were superior to traditional anthropometric and lipid measures in association with type 2 diabetes among men. Electronic supplementary material The online version of this article (10.1007/s00125-019-4921-2) contains peer-reviewed but unedited supplementary material, which is available to authorised users.
Published: 2019

24. Characteristics associated with polypharmacy in people with type 2 diabetes

Author: Bianca Silvius, Coen D.A. Stehouwer, Behiye Özcan, M. M. van der Klauw, Petra J. M. Elders, S. van Oort, Marielle A Schroijen, Ingrid M. Jazet, Miranda T. Schram, Bruce H. R. Wolffenbuttel, A. J. van Ballegooijen, Joline W. J. Beulens, Sarah E. Siegelaar, M. F. Warle-van Herwaarden, J. H. DeVries, Femke Rutters, C.J.J. Tack, Cornelis Kramers, H. W. de Valk, Eric J.G. Sijbrands, Evertine J. Abbink, Internal Medicine, Endocrinology, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, ACS - Amsterdam Cardiovascular Sciences, APH - Health Behaviors & Chronic Diseases, MUMC+: HVC Pieken Maastricht Studie (9), RS: Carim - V01 Vascular complications of diabetes and metabolic syndrome, Interne Geneeskunde, MUMC+: MA Interne Geneeskunde (3), MUMC+: Centrum voor Chronische Zieken (3), MUMC+: MA Med Staf Artsass Interne Geneeskunde (9), MUMC+: MA Endocrinologie (9), MUMC+: MA Maag Darm Lever (9), MUMC+: MA Hematologie (9), MUMC+: MA Medische Oncologie (9), MUMC+: MA Nefrologie (9), MUMC+: MA Reumatologie (9), Epidemiology and Data Science, Nephrology, ACS - Diabetes & metabolism, ACS - Heart failure & arrhythmias, General practice, APH - Aging & Later Life, Center for Liver, Digestive and Metabolic Diseases (CLDM), and Life Course Epidemiology (LCE)
Subjects: Male, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, MEDLINE, 030209 endocrinology & metabolism, Type 2 diabetes, Primary care, Disease, Healthcare improvement science Radboud Institute for Health Sciences [Radboudumc 18], Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, SDG 3 - Good Health and Well-being, MEDICATION USE, Diabetes mellitus, Internal medicine, Internal Medicine, Prevalence, Medicine, Humans, 030212 general & internal medicine, Aged, Netherlands, Polypharmacy, Aged, 80 and over, OLDER, OUTCOMES, business.industry, Metabolic Disorders Radboud Institute for Molecular Life Sciences [Radboudumc 6], ADULTS, Middle Aged, medicine.disease, Comorbidity, Diabetes Mellitus, Type 2, Socioeconomic Factors, Cardiovascular Diseases, Cohort, Female, business, COMORBIDITY, Research: Epidemiology
Abstract: Contains fulltext : 232027.pdf (Publisher’s version ) (Open Access) AIM: To describe the prevalence and characteristics of polypharmacy in a Dutch cohort of individuals with type 2 diabetes. METHODS: We included people with type 2 diabetes from the Diabetes Pearl cohort, of whom 3886 were treated in primary care and 2873 in academic care (secondary/tertiary). With multivariable multinomial logistic regression analyses stratified for line of care, we assessed which sociodemographic, lifestyle and cardiometabolic characteristics were associated with moderate (5-9 medications) and severe polypharmacy (≥10 medications) compared with no polypharmacy (0-4 medications). RESULTS: Mean age was 63 ± 10 years, and 40% were women. The median number of daily medications was 5 (IQR 3-7) in primary care and 7 (IQR 5-10) in academic care. The prevalence of moderate and severe polypharmacy was 44% and 10% in primary care, and 53% and 29% in academic care respectively. Glucose-lowering and lipid-modifying medications were most prevalent. People with severe polypharmacy used a relatively large amount of other (i.e. non-cardiovascular and non-glucose-lowering) medication. Moderate and severe polypharmacy across all lines of care were associated with higher age, low educational level, more smoking, longer diabetes duration, higher BMI and more cardiovascular disease. CONCLUSIONS: Severe and moderate polypharmacy are prevalent in over half of people with type 2 diabetes in primary care, and even more in academic care. People with polypharmacy are characterized by poorer cardiometabolic status. These results highlight the significance of polypharmacy in type 2 diabetes.
Published: 2021

25. The Clinical Genome Resource (ClinGen) Familial Hypercholesterolemia Variant Curation Expert Panel consensus guidelines for LDLR variant classification

Author: Tomáš Freiberger, Heather Zimmermann, Michael A. Iacocca, Lukas Tichy, Cinthia E. Jannes, Robert A. Hegele, Michal Kramarek, Alain Carrié, Alexandre C. Pereira, Sarah Leigh, Joana Rita Chora, Eric J.G. Sijbrands, Margaret Chen, Hannah Wand, Serra Kim, C. Lisa Kurtz, Tami Johnston, Amanda J. Hooper, Steve E. Humphries, Mark Trinder, Liam R. Brunham, Mafalda Bourbon, Jessica Chonis, Jian Wang, Joshua W. Knowles, Premysl Soucek, Maggie Williams, and Annette Leon
Subjects: 0303 health sciences, education.field_of_study, medicine.medical_specialty, business.industry, Population, Genomics, Familial hypercholesterolemia, Computational biology, 030204 cardiovascular system & hematology, medicine.disease, Genome, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, Resource (project management), medicine, Medical genetics, education, business, Mendelian disorders, 030304 developmental biology
Abstract: PurposeIn 2015, the American College of Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology (AMP) published consensus standardized guidelines for variant classification in Mendelian disorders. To increase accuracy and consistency, the Clinical Genome Resource (ClinGen) Familial Hypercholesterolemia (FH) Variant Curation Expert Panel (VCEP) was tasked with optimizing the existing ACMG/AMP framework for disease-specific classification in FH. Here, we provide consensus recommendations for the most common FH-causing gene, LDLR, where >2,300 unique FH-associated variants have been identified.MethodsThe multidisciplinary FH VCEP met in person and through frequent emails and conference calls to develop LDLR-specific modifications of ACMG/AMP guidelines. Through iteration, pilot testing, debate and commentary, consensus among experts was reached.ResultsThe consensus LDLR variant modifications to existing ACMG/AMP guidelines include: 1) alteration of population frequency thresholds; 2) delineation of loss-of-function variant types; 3) functional study criteria specifications; 4) co-segregation criteria specifications; and 5) specific use and thresholds for in silico prediction tools, among others.ConclusionEstablishment of these guidelines as the new standard in the clinical laboratory setting will result in a more evidence-based, harmonized method for LDLR variant classification worldwide, thereby improving the care of FH patients.
Published: 2021

26. Lipoprotein(a) is a strong risk factor for Aortic Valve Calcium

Author: Kang H. Zheng, Erik S.G. Stroes, Rutger Verbeek, Sara-Joan Pinto-Sietsma, Eric J.G. Sijbrands, S.M. Boekholdt, Maryam Kavousi, Daniel Bos, Yannick Kaiser, Y B de Rijke, and Sunny S Singh
Subjects: medicine.medical_specialty, biology, business.industry, Internal medicine, medicine, biology.protein, Cardiology, Aortic calcification, Lipoprotein(a), Risk factor, Cardiology and Cardiovascular Medicine, business
Abstract: Background Aortic valve calcium (AVC) is an important hallmark of aortic valve stenosis, which is the most common valvular heart disease in the Western world. Studies suggesting an important role for lipoprotein(a) [Lp(a)] in the etiology of AVC are accumulating, yet population-based evidence is scarce. Therefore, we investigated the association of Lp(a) with the presence of AVC in two large cohorts. Methods A total of 2412 participants from the population-based Rotterdam Study (52% women, mean age=69.6±6.3), and 859 asymptomatic persons from the Amsterdam Medical Center outpatient clinic for familial premature (non-valvular) atherosclerosis (57%women, mean age=45.9±11.6) underwent blood sampling to determine serum Lp(a) and non-enhanced cardiac CT-scan to assess AVC. We combined both cohorts and investigated the association of Lp(a) with the presence and amount of AVC using logistic and linear regression models, adjusting for age, sex, smoking, body mass index, non-high density lipoprotein cholesterol and use of antihypertensive medication. Results Out of a total of 3271 subjects with an average age of 63.4±7.98, AVC was present in 844 (25.8%) individuals. Higher levels of Lp(a) were associated with the presence of AVC, independent of age, sex and cardiovascular risk factors [Odds ratio (OR) per 1-SD increase in Lp(a): 1.39 (95% CI:1.27; 1.51). In persons with AVC, a higher level of Lp(a) was also related to larger volume of AVC [β per 1-SD increase in Lp(a): 0.76 (95% CI:1.27; 1.51)]. All findings were similar across both cohorts. Conclusion Lp(a) is a prominent and independent marker of the presence and amount of AVC in the general population. Future studies investigating the effect of Lp(a) lowering on the progression of AVC are warranted. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): NESTOR program for geriatric research, the Netherlands Heart Foundation, the Netherlands Organization for Scientific Research, the Health Research and Development Council (28-2975 and 97-1-364), and the Municipality of Rotterdam
Published: 2020

27. Sex differences in cardiometabolic risk factors, pharmacological treatment and risk factor control in type 2 diabetes: Findings from the Dutch Diabetes Pearl cohort

Author: Eric J.G. Sijbrands, Sanne A.E. Peters, Cees J. Tack, Bruce H. R. Wolffenbuttel, Evertine J. Abbink, Behiye Özcan, Femke Rutters, Marieke J. Oskam, Ingrid M. Jazet, J. Hans DeVries, Miranda T. Schram, Simone J S Sep, Petra J. M. Elders, Sarah E. Siegelaar, Marielle A Schroijen, Coen D.A. Stehouwer, Harold W. de Valk, Marit de Jong, Endocrinology, ACS - Amsterdam Cardiovascular Sciences, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, APH - Health Behaviors & Chronic Diseases, Internal Medicine, Interne Geneeskunde, MUMC+: MA Med Staf Artsass Interne Geneeskunde (9), RS: Carim - V01 Vascular complications of diabetes and metabolic syndrome, MUMC+: MA Reumatologie (9), MUMC+: MA Nefrologie (9), MUMC+: MA Medische Oncologie (9), MUMC+: MA Hematologie (9), MUMC+: MA Maag Darm Lever (9), MUMC+: MA Endocrinologie (9), MUMC+: HVC Pieken Maastricht Studie (9), MUMC+: MA Interne Geneeskunde (3), Epidemiology and Data Science, ACS - Diabetes & metabolism, APH - Aging & Later Life, General practice, Lifestyle Medicine (LM), and Center for Liver, Digestive and Metabolic Diseases (CLDM)
Subjects: Male, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Population, Type 2 diabetes, Diseases of the endocrine glands. Clinical endocrinology, MELLITUS, All institutes and research themes of the Radboud University Medical Center, SDG 3 - Good Health and Well-being, DISPARITIES, Risk Factors, Internal medicine, Diabetes mellitus, medicine, Humans, CORONARY-HEART-DISEASE, Risk factor, education, METAANALYSIS, education.field_of_study, COMPLICATIONS, Sex Characteristics, business.industry, MORTALITY, WOMEN, Cardiometabolic Risk Factors, Metabolic Disorders Radboud Institute for Molecular Life Sciences [Radboudumc 6], MEN, medicine.disease, RC648-665, healthcare disparities, INDIVIDUALS, Hemoglobin A, Cross-Sectional Studies, Diabetes Mellitus, Type 2, type 2, CARDIOVASCULAR-DISEASE, Cardiovascular Diseases, Relative risk, Cohort, diabetes mellitus, Epidemiology/Health services research, Female, epidemiology, business, Body mass index
Abstract: IntroductionSex differences in cardiometabolic risk factors and their management in type 2 diabetes (T2D) have not been fully identified. Therefore, we aimed to examine differences in cardiometabolic risk factor levels, pharmacological treatment and achievement of risk factor control between women and men with T2D.Research design and methodsCross-sectional data from the Dutch Diabetes Pearl cohort were used (n=6637, 40% women). Linear and Poisson regression analyses were used to examine sex differences in cardiometabolic risk factor levels, treatment, and control.ResultsCompared with men, women had a significantly higher body mass index (BMI) (mean difference 1.79 kg/m2 (95% CI 1.49 to 2.08)), while no differences were found in hemoglobin A1c (HbA1c) and systolic blood pressure (SBP). Women had lower diastolic blood pressure (−1.94 mm Hg (95% CI −2.44 to −1.43)), higher total cholesterol (TC) (0.44 mmol/L (95% CI 0.38 to 0.51)), low-density lipoprotein cholesterol (LDL-c) (0.26 mmol/L (95% CI 0.22 to 0.31)), and high-density lipoprotein cholesterol (HDL-c) sex-standardized (0.02 mmol/L (95% CI 0.00 to 0.04)), and lower TC:HDL ratio (−0.29 (95% CI −0.36 to −0.23)) and triglycerides (geometric mean ratio 0.91 (95% CI 0.85 to 0.98)). Women had a 16% higher probability of being treated with antihypertensive medication in the presence of high cardiovascular disease (CVD) risk and elevated SBP than men (relative risk 0.84 (95% CI 0.73 to 0.98)), whereas no sex differences were found for glucose-lowering medication and lipid-modifying medication. Among those treated, women were less likely to achieve treatment targets of HbA1c (0.92 (95% CI 0.87 to 0.98)) and LDL-c (0.89 (95% CI 0.85 to 0.92)) than men, while no differences for SBP were found.ConclusionsIn this Dutch T2D population, women had a slightly different cardiometabolic risk profile compared with men and a substantially higher BMI. Women had a higher probability of being treated with antihypertensive medication in the presence of high CVD risk and elevated SBP than men, and were less likely than men to achieve treatment targets for HbA1c and LDL levels.
Published: 2020

28. Specification of ACMG/AMP guidelines for standardized variant interpretation in familial hypercholesterolemia: On behalf of the ClinGen FH Variant Curation Expert Panel

Author: Annette Leon, Marina Cuchel, Eric J.G. Sijbrands, Heather Zimmermann, Liam R. Brunham, M. Bourbon, Jian Wang, Alain Carrié, Steve E. Humphries, A.C. Alves, Maggie Williams, Pedro Mata, Robert A. Hegele, Josh Knowles, Joep C. Defesche, Iftikhar J. Kullo, Joana Rita Chora, Raul D. Santos, Hannah Wand, C.L. Kurtz, Lukas Tichy, Michael A. Iacocca, and Tomáš Freiberger
Subjects: business.industry, Interpretation (philosophy), medicine, lipids (amino acids, peptides, and proteins), Familial hypercholesterolemia, Familial Hypercholesterolemia, Guidelines, Cardiology and Cardiovascular Medicine, Bioinformatics, medicine.disease, business, Doenças Cardio e Cérebro-vasculares
Abstract: Familial Hypercholesterolemia (FH): Lipid metabolism autosomal dominant condition; Patients present elevated low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TC) values since childhood → increased risk of atherosclerotic cardiovascular disease; High heterozygote prevalence (1/250); Homozygous rare (1/1 000 000); Caused by pathogenic variants in LDLR (>90%), APOB (5-10%) and PCSK9 (1-3%) genes. N/A
Published: 2020

29. Trajectories of BMI Before Diagnosis of Type 2 Diabetes: The Rotterdam Study

Author: Eralda Asllanaj, Jana Nano, Abbas Dehghan, Eric J.G. Sijbrands, Taulant Muka, M. Arfan Ikram, Oscar H. Franco, Klodian Dhana, Epidemiology, and Internal Medicine
Subjects: Adult, Male, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Medicine (miscellaneous), 030209 endocrinology & metabolism, 610 Medicine & health, Type 2 diabetes, Overweight, Weight Gain, Body Mass Index, Cohort Studies, 03 medical and health sciences, Rotterdam Study, 0302 clinical medicine, Endocrinology, Insulin resistance, SDG 3 - Good Health and Well-being, Weight loss, Risk Factors, 360 Social problems & social services, Internal medicine, Diabetes mellitus, Weight Loss, medicine, Humans, 030212 general & internal medicine, Obesity, Aged, Netherlands, Nutrition and Dietetics, business.industry, Epidemiology/Genetics, Original Articles, Middle Aged, medicine.disease, Diabetes Mellitus, Type 2, Latent Class Analysis, Female, Original Article, medicine.symptom, business, Body mass index
Abstract: Obesity published by Wiley Periodicals LLC on behalf of The Obesity Society (TOS) Objective: People with diabetes show great variability in weight gain and duration of obesity at the time of diagnosis. BMI trajectories and other cardiometabolic risk factors prior to type 2 diabetes were investigated. Methods: A total of 6,223 participants from the Rotterdam Study cohort were included. BMI patterns before diagnosis of diabetes were identified through latent class trajectories. Results: During a mean follow-up of 13.7 years, 565 participants developed type 2 diabetes. Three distinct trajectories of BMIwere identified, including the “progressive overweight” group (n = 481, 85.1%), “progressive weight loss” group (n = 59, 10.4%), and “persistently high BMI” group (n = 25, 4.4%). The majority, the progressive overweight group, was characterized by a steady increase of BMI in the overweight range 10 years before diabetes diagnosis. The progressive weight lossgroup had fluctuations of glucose and marked beta cell function loss. The persistently high BMI group was characterized by a slight increase in insulin levels and sharp increase of insulin resistance accompanied by a rapid decrease of beta cell function. Conclusions : Heterogeneity of BMI changes prior to type 2 diabetes was found in a middle-aged and elderly white population. Prevention strategies should be tailored rather than focusing only on high-risk individuals.
Published: 2020

30. Anxiety and depression in diabetes care: longitudinal associations with health-related quality of life

Author: Suzanne Polinder, Eric J.G. Sijbrands, Laura Boogaard, Vicki Erasmus, Juanita A. Haagsma, Johan P. Mackenbach, Hanneke Buijks, Xiaona Liu, Public Health, Internal Medicine, and Psychiatry
Subjects: Adult, Male, Time Factors, Epidemiology, lcsh:Medicine, Early detection, 030209 endocrinology & metabolism, Anxiety, Structural equation modeling, Article, Diabetes Complications, 03 medical and health sciences, 0302 clinical medicine, Quality of life, SDG 3 - Good Health and Well-being, Diabetes mellitus, medicine, Prevalence, Humans, 030212 general & internal medicine, Longitudinal Studies, Prospective Studies, lcsh:Science, Depression (differential diagnoses), Aged, Netherlands, Health related quality of life, Preventive medicine, Aged, 80 and over, Multidisciplinary, Models, Statistical, business.industry, Depression, lcsh:R, Confounding, Middle Aged, medicine.disease, Health Surveys, humanities, Outcomes research, Preclinical research, Quality of Life, lcsh:Q, Female, medicine.symptom, business, Clinical psychology
Abstract: Anxiety and depression are commonly found in patients with diabetes, but little is known about how the anxiety and depression symptoms of diabetes patients and the health-related quality of life (HRQoL) over time influence each other. Therefore, we conducted a survey among patients with diabetes (T1) and repeated the survey after 3 months (T2). Linear regression models and cross-lagged structural equation models were used to analyze the associations between anxiety and depression symptoms and HRQoL within and across time intervals. Correcting for baseline index and potential confounders, the HRQoL index at T2 reflected the change in anxiety/depression between T1 and T2 more than anxiety/depression at T1 (P P 2/df = 1.102, P = 0.256; CFI = 1.000, RMSEA = 0.030). Our findings support early detection of anxiety and depression, as well as comprehensive efforts improving HRQoL for patients with diabetes.
Published: 2020

31. High prevalence of impaired awareness of hypoglycemia and severe hypoglycemia among people with insulin-treated type 2 diabetes:The Dutch Diabetes Pearl Cohort

Author: Femke Rutters, Femmie de Vegt, Nicolaas C. Schaper, Coen D.A. Stehouwer, Harold W. de Valk, Bianca Silvius, Melanie M. van der Klauw, Sarah E. Siegelaar, Bastiaan E. de Galan, Bruce H. R. Wolffenbuttel, C.J.J. Tack, Evertine J. Abbink, Behiye Özcan, Eric J.G. Sijbrands, Petra J. M. Elders, Lian A. van Meijel, J. Hans DeVries, Miranda T. Schram, Endocrinology, ACS - Amsterdam Cardiovascular Sciences, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, AGEM - Endocrinology, metabolism and nutrition, APH - Health Behaviors & Chronic Diseases, Epidemiology and Data Science, General practice, APH - Aging & Later Life, ACS - Diabetes & metabolism, Life Course Epidemiology (LCE), Lifestyle Medicine (LM), Center for Liver, Digestive and Metabolic Diseases (CLDM), Internal Medicine, MUMC+: HVC Pieken Maastricht Studie (9), RS: Carim - V01 Vascular complications of diabetes and metabolic syndrome, Interne Geneeskunde, RS: CAPHRI - R2 - Creating Value-Based Health Care, RS: Carim - V02 Hypertension and target organ damage, MUMC+: MA Endocrinologie (9), MUMC+: Centrum voor Chronische Zieken (3), MUMC+: MA Med Staf Artsass Interne Geneeskunde (9), and MUMC+: MA Interne Geneeskunde (3)
Subjects: Male, Pediatrics, SYMPTOMS, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Type 2 diabetes, Severity of Illness Index, Cohort Studies, 0302 clinical medicine, Surveys and Questionnaires, Ethnicity, Prevalence, Insulin, 030212 general & internal medicine, Netherlands, RISK, Metabolic Disorders Radboud Institute for Molecular Life Sciences [Radboudumc 6], ASSOCIATION, Awareness, Middle Aged, Metformin, Treatment Outcome, Cohort, Female, epidemiology, type 2 diabetes, medicine.drug, medicine.medical_specialty, Recurrent hypoglycemia, 030209 endocrinology & metabolism, Hypoglycemia, FREQUENCY, Diseases of the endocrine glands. Clinical endocrinology, EVENTS, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Diabetes mellitus, medicine, Humans, Hypoglycemic Agents, Epidemiology/Health Services Research, Aged, Glycated Hemoglobin, IDENTIFICATION, business.industry, MORTALITY, Other Research Radboud Institute for Health Sciences [Radboudumc 0], ADULTS, hypoglycemia unawareness, RC648-665, medicine.disease, hypoglycemia, Diabetes Mellitus, Type 2, business, Body mass index
Abstract: ObjectivePeople with type 2 diabetes on insulin are at risk for hypoglycemia. Recurrent hypoglycemia can cause impaired awareness of hypoglycemia (IAH), and increase the risk for severe hypoglycemia. The aim of this study was to assess the prevalence and determinants of self-reported IAH and severe hypoglycemia in a Dutch nationwide cohort of people with insulin-treated type 2 diabetes.Research design and methodsObservational study of The Dutch Diabetes Pearl, a cohort of people with type 2 diabetes treated in primary, secondary and tertiary diabetes care centers. The presence of IAH and the occurrence of severe hypoglycemia in the past year, defined as an event requiring external help to recover, were assessed using the validated Dutch version of the Clarke questionnaire. In addition, clinical variables were collected including age, diabetes duration, hemoglobin A1c, ethnicity and education.Results2350 people with type 2 diabetes on insulin were included: 59.1% men, mean age 61.1±10.4 years, mean diabetes duration 14.8±9.2 years and 79.5% on basal-bolus therapy. A total of 229 patients (9.7%) were classified as having IAH and 742 patients (31.6%) reported severe hypoglycemia. Increased odds for IAH were found with complex insulin regimens and lower odds with having a partner and body mass index ≥30 kg/m2. Severe hypoglycemia was associated with complex insulin regimens, non-Caucasian ethnicity and use of psychoactive drugs, and inversely with metformin use.ConclusionsIn this nationwide cohort, almost one out of ten people with type 2 diabetes on insulin had IAH and >30% had a history of severe hypoglycemia in the past year.
Published: 2020

32. Interpreting the Benefit of Simvastatin-Ezetimibe in Patients 75 Years or Older

Author: Eric J.G. Sijbrands, Dieter Lütjohann, Oliver Weingärtner, and Internal Medicine
Subjects: medicine.medical_specialty, Simvastatin, business.industry, Anticholesteremic Agents, Ezetimibe, Simvastatin Drug Combination, Ezetimibe, Article, Text mining, Internal medicine, Medicine, Humans, In patient, Acute Coronary Syndrome, Cardiology and Cardiovascular Medicine, business, medicine.drug
Published: 2020

33. Reducing the Clinical and Public Health Burden of Familial Hypercholesterolemia: A Global Call to Action

Author: Claudia Stefanutti, Myra Tilney, Mutaz Alkhnifsawi, Carlos A. Aguilar-Salinas, Jean-Luc Eiselé, Raul D. Santos, Pedro Mata, Gloria Hastings, Gerald F. Watts, Inge Schalkers, Sarah D. de Ferranti, Francesco Fuggetta, Daniel Soffer, Brian Tomlinson, Rodrigo Alonso, Tania Leme da Rocha Martinez, Rody G. Sy, Maria Cristina de Oliveira Izar, Atsushi Nohara, Ákos G Gesztes, Laura Schreier, Nanette K. Wenger, Aram Zegerius, Leiv Ose, Letrillart Marion, David Marais, André R. Miserez, Lina Badimon, Ian Hamilton-Craig, Martin Prøven Bogsrud, Roopa Mehta, Stephen J. Nicholls, Lale Tokgozoglu, Samuel S. Gidding, Amy L. Peterson, Mariko Harada-Shiba, Sue Koob, Jules Payne, Emanuela Folco, Raman Puri, Meral Kayıkçıoğlu, Martha L. Tamayo, Michael D. Shapiro, David S. Wald, Børge G. Nordestgaard, Inese Maurina, Kristyna Cillíková, Antonio J. Vallejo-Vaz, Gerardo Elikir, Masahiro Koseki, Diana Maxwell, Ashraf Reda, Gunnar N Karlsson, Jasmine Patel, Lynne T. Braun, Greizy López, Jing Pang, Marcos M. Lima-Martínez, Urh Groselj, G. Kees Hovingh, Kausik K. Ray, Stacey R. Lane, Eric J.G. Sijbrands, Darien Wood, I.M. Gaspar, Pablo Corral, Alberico L. Catapano, Alejandra Vázquez-Cárdenas, Khalid Al-Rasadi, Luz M Bernal, Allison Jamison, Wael Almahmeed, Catherine D. Ahmed, Joep C. Defesche, Olivier S. Descamps, Tomáš Freiberger, Athanasios Pallidis, Dermot Neely, Gabriele Hanauer-Mader, Tiziana Sampietro, Liam R. Brunham, Patrícia Vieira de Luca, Mario Stoll, Michaela Wolf, Monica P Popescu, Regina Cuevas, Thomas A. Gaziano, George A. Mensah, Katherine Wilemon, Internal Medicine, and Ege Üniversitesi
Subjects: medicine.medical_specialty, Population, Specialty, Public policy, Familial hypercholesterolemia, 030204 cardiovascular system & hematology, Global Health, Hyperlipoproteinemia Type II, 03 medical and health sciences, 0302 clinical medicine, SDG 3 - Good Health and Well-being, Cost of Illness, medicine, Global health, Humans, 030212 general & internal medicine, education, education.field_of_study, Government, business.industry, Public health, medicine.disease, Call to action, cost of illness, global health, humans, hyperlipoproteinemia type II, practice guidelines as topic, public health, Family medicine, Practice Guidelines as Topic, Public Health, Cardiology and Cardiovascular Medicine, business
Abstract: ImportanceFamilial hypercholesterolemia (FH) is an underdiagnosed and undertreated genetic disorder that leads to premature morbidity and mortality due to atherosclerotic cardiovascular disease. Familial hypercholesterolemia affects 1 in 200 to 250 people around the world of every race and ethnicity. the lack of general awareness of FH among the public and medical community has resulted in only 10% of the FH population being diagnosed and adequately treated. the World Health Organization recognized FH as a public health priority in 1998 during a consultation meeting in Geneva, Switzerland. the World Health Organization report highlighted 11 recommendations to address FH worldwide, from diagnosis and treatment to family screening and education. Research since the 1998 report has increased understanding and awareness of FH, particularly in specialty areas, such as cardiology and lipidology. However, in the past 20 years, there has been little progress in implementing the 11 recommendations to prevent premature atherosclerotic cardiovascular disease in an entire generation of families with FH. ObservationsIn 2018, the Familial Hypercholesterolemia Foundation and the World Heart Federation convened the international FH community to update the 11 recommendations. Two meetings were held: one at the 2018 FH Foundation Global Summit and the other during the 2018 World Congress of Cardiology and Cardiovascular Health. Each meeting served as a platform for the FH community to examine the original recommendations, assess the gaps, and provide commentary on the revised recommendations. the Global Call to Action on Familial Hypercholesterolemia thus represents individuals with FH, advocacy leaders, scientific experts, policy makers, and the original authors of the 1998 World Health Organization report. Attendees from 40 countries brought perspectives on FH from low-, middle-, and high-income regions. Tables listing country-specific government support for FH care, existing country-specific and international FH scientific statements and guidelines, country-specific and international FH registries, and known FH advocacy organizations around the world were created. Conclusions and RelevanceBy adopting the 9 updated public policy recommendations created for this document, covering awareness; advocacy; screening, testing, and diagnosis; treatment; family-based care; registries; research; and cost and value, individual countries have the opportunity to prevent atherosclerotic heart disease in their citizens carrying a gene associated with FH and, likely, all those with severe hypercholesterolemia as well. This guideline presents updated recommendations for management of familial hypercholesterolemia. (c) 2020 American Medical Association. All rights reserved., AmgenAmgen; Sanofi Regeneron Pharmaceuticals, Funding to support the 2 international meetings to achieve consensus was provided by Amgen and Sanofi Regeneron Pharmaceuticals.
Published: 2020

34. Association of the IgG N-glycome with the course of kidney function in type 2 diabetes

Author: Ralph Heijmans, Gordan Lauc, Sunny S Singh, Aloysius G Lieverse, Olga Gornik, Claudia K E Meulen, Mandy van Hoek, Eric J.G. Sijbrands, and Internal Medicine
Subjects: Glycosylation, Endocrinology, Diabetes and Metabolism, Renal function, Type 2 diabetes, N-glycosylation, 030204 cardiovascular system & hematology, Kidney, Diseases of the endocrine glands. Clinical endocrinology, Immunoglobulin G, Nephropathy, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, SDG 3 - Good Health and Well-being, Diabetes mellitus, medicine, Humans, Prospective Studies, Pathophysiology/Complications, kidney function, Fucosylation, 030304 developmental biology, 0303 health sciences, biology, diabetes type 2, business.industry, RC648-665, medicine.disease, Glycome, chemistry, Diabetes Mellitus, Type 2, IgG N-glycans, nephropathy, Case-Control Studies, Immunology, biology.protein, business
Abstract: IntroductionInflammatory processes are thought to be involved in kidney function decline in individuals with type 2 diabetes. Glycosylation of immunoglobulin G (IgG) is an important post-translation process affecting the inflammatory potential of IgG. We investigated the prospective relationship between IgG N-glycosylation patterns and kidney function in type 2 diabetes.Research design and methodsIn the DiaGene study, an all-lines-of-care case–control study (n=1886) with mean prospective follow-up of 7.0 years, the association between 58 IgG N-glycan profiles and estimated glomerular filtration rate (eGFR) and albumin-to-creatinine ratio (ACR) per year and during total follow-up was analyzed. Models were adjusted for clinical variables and multiple comparisons.ResultsEleven traits were significantly associated with eGFR change per year. Bisecting GlcNAc in fucosylated and fucosylated disialylated structures and monosialylation of fucosylated digalactosylated structures were associated with a faster decrease of eGFR. Fucosylation of neutral and monogalactosylated structures was associated with less eGFR decline per year. No significant associations between IgG glycans and ACR were found.ConclusionsIn type 2 diabetes, we found IgG N-glycosylation patterns associated with a faster decline of kidney function, reflecting a pro-inflammatory state of IgG. eGFR, but not ACR, was associated with IgG glycans, which suggests these associations may represent renal macroangiopathy rather than microvascular disease.
Published: 2020

35. Lifetime risk to progress from pre-diabetes to type 2 diabetes among women and men: Comparison between American Diabetes Association and World Health Organization diagnostic criteria

Author: Symen Ligthart, Abbas Dehghan, Thijs T. W. van Herpt, Eric J.G. Sijbrands, Maryam Kavousi, Aloysius G Lieverse, Mandy van Hoek, Maarten J.G. Leening, M. Arfan Ikram, Epidemiology, Internal Medicine, Cardiology, Neurology, and Radiology & Nuclear Medicine
Subjects: Research design, pre-diabetic state, Male, diagnosis, Endocrinology, Diabetes and Metabolism, Population, Type 2 diabetes, World Health Organization, lcsh:Diseases of the endocrine glands. Clinical endocrinology, Prediabetic State, Rotterdam Study, SDG 3 - Good Health and Well-being, Diabetes mellitus, medicine, Humans, Prospective Studies, education, Glycemic, Netherlands, education.field_of_study, lcsh:RC648-665, business.industry, risk assessment, Glucose Tolerance Test, Middle Aged, medicine.disease, United States, type 2, Diabetes Mellitus, Type 2, diabetes mellitus, Lifetime risk, Female, Clinical care/Education/Nutrition, business, Risk assessment, Demography
Abstract: IntroductionPre-diabetes, a status conferring high risk of overt diabetes, is defined differently by the American Diabetes Association (ADA) and the WHO. We investigated the impact of applying definitions of pre-diabetes on lifetime risk of diabetes in women and men from the general population.Research design and methodsWe used data from 8844 women without diabetes and men aged ≥45 years from the prospective population-based Rotterdam Study in the Netherlands. In both gender groups, we calculated pre-diabetes prevalence according to ADA and WHO criteria and estimated the 10-year and lifetime risk to progress to overt diabetes with adjustment for competing risk of death.ResultsOut of 8844 individuals, pre-diabetes was identified in 3492 individuals (prevalence 40%, 95% CI 38% to 41%) according to ADA and 1382 individuals (prevalence 16%, 95% CI 15% to 16%) according to WHO criteria. In both women and men and each age category, ADA prevalence estimates doubled WHO-defined pre-diabetes. For women and men aged 45 years having ADA-defined pre-diabetes, the 10-year risk of diabetes was 14.2% (95% CI 6.0% to 22.5%) and 9.2% (95% CI 3.4% to 15.0%) compared with 23.2% (95% CI 6.8% to 39.6%) and 24.6% (95% CI 8.4% to 40.8%) in women and men with WHO-defined pre-diabetes. At age 45 years, the remaining lifetime risk to progress to overt diabetes was 57.5% (95% CI 51.8% to 63.2%) vs 80.2% (95% CI 74.1% to 86.3%) in women and 46.1% (95% CI 40.8% to 51.4%) vs 68.4% (95% CI 58.3% to 78.5%) in men with pre-diabetes according to ADA and WHO definitions, respectively.ConclusionPrevalence of pre-diabetes differed considerably in both women and men when applying ADA and WHO pre-diabetes definitions. Women with pre-diabetes had higher lifetime risk to progress to diabetes. The lifetime risk of diabetes was lower in women and men with ADA-defined pre-diabetes as compared with WHO. Improvement of pre-diabetes definition considering appropriate sex-specific and age-specific glycemic thresholds may lead to better identification of individuals at high risk of diabetes.
Published: 2020

36. Short-term vascular hemodynamic responses to isometric exercise in young adults and in the elderly

Author: Giacomo Pucci, Francesco U.S. Mattace-Raso, Davide Bolignano, Renee Hartog, Eric J.G. Sijbrands, and Internal Medicine
Subjects: Adult, Male, medicine.medical_specialty, pulse wave velocity, Pulsatile flow, Hemodynamics, Isometric exercise, 030204 cardiovascular system & hematology, Pulse Wave Analysis, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Vascular Stiffness, Heart Rate, medicine.artery, Internal medicine, isometric stress, medicine, Humans, Brachial artery, Young adult, Pulse wave velocity, Exercise, Original Research, Aged, Hand Strength, business.industry, RC952-954.6, blood pressure, General Medicine, Middle Aged, Blood pressure, Carotid Arteries, vascular aging, Geriatrics, Clinical Interventions in Aging, cardiovascular system, Cardiology, Aortic stiffness, Female, Geriatrics and Gerontology, business, 030217 neurology & neurosurgery, Isometric stress, Vascular aging, Blood Pressure, circulatory and respiratory physiology
Abstract: Renee Hartog,1,* Davide Bolignano,1,2,* Eric Sijbrands,1 Giacomo Pucci,3,4 Francesco Mattace-Raso1 1Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands; 2Institute of Clinical Physiology, Italian National Council of Research, Reggio Calabria, Italy; 3Department of Medicine, University of Perugia, Perugia, Italy; 4Unit of Internal Medicine, Terni University Hospital, Terni, Italy *These authors contributed equally to this work Background: Vascular aging is known to induce progressive stiffening of the large elastic arteries, altering vascular hemodynamics under both rest and stress conditions. In this study, we aimed to investigate changes in vascular hemodynamics in response to isometric handgrip exercise across ages.Participants and methods: We included 62 participants, who were divided into three age categories: 20–40 (n=22), 41–60 (n=20), and 61–80 (n=20)years. Vascular hemodynamics were measured using the Mobil-o-Graph® based on the pulsatile pressure changes in the brachial artery. One-way ANOVA test was performed to analyze the changes induced by isometric handgrip exercise.Results: After isometric handgrip exercise, aortic pulse wave velocity (PWV) increased by 0.10m/s in the youngest, 0.06m/s in the middle-age, and 0.02m/s in the oldest age category. Changes in PWV strongly correlated with those in central systolic blood pressure (cSBP) (r=0.878, P
Published: 2018

37. Group cognitive behavioural therapy and weight regain after diet in type 2 diabetes: results from the randomised controlled POWER trial

Author: Monique T. Mulder, Jan J. Busschbach, Adriaan van 't Spijker, Eric J.G. Sijbrands, Adrie J.M. Verhoeven, Hanneke Buijks, Behiye Özcan, Reinier Timman, Kirsten A. Berk, Internal Medicine, and Psychiatry
Subjects: Adult, Male, medicine.medical_specialty, Time Factors, Endocrinology, Diabetes and Metabolism, food.diet, medicine.medical_treatment, 030209 endocrinology & metabolism, Cognitive behavioural therapy, Type 2 diabetes, Overweight, Weight Gain, Very low calorie diet, Article, Group psychotherapy, 03 medical and health sciences, 0302 clinical medicine, food, Cognition, Diabetes mellitus type 2, SDG 3 - Good Health and Well-being, Weight loss, Risk Factors, Psychological intervention, Internal medicine, Internal Medicine, medicine, Humans, 030212 general & internal medicine, Obesity, Aged, Weight maintenance, Cognitive Behavioral Therapy, business.industry, Body Weight, Middle Aged, medicine.disease, Diet, Treatment Outcome, Diabetes Mellitus, Type 2, Psychotherapy, Group, Female, medicine.symptom, business, Weight gain, Dieting
Abstract: Aims/hypothesis Weight-loss programmes for adults with type 2 diabetes are less effective in the long term owing to regain of weight. Our aim was to determine the 2 year effectiveness of a cognitive behavioural group therapy (group-CBT) programme in weight maintenance after diet-induced weight loss in overweight and obese adults with type 2 diabetes, using a randomised, parallel, non-blinded, pragmatic study design. Methods We included 158 obese adults (median BMI 36.3 [IQR 32.5–40.0] kg/m2) with type 2 diabetes from the outpatient diabetes clinic of Erasmus MC, the Netherlands, who achieved ≥5% weight loss on an 8 week very low calorie diet. Participants were randomised (stratified by weight loss) to usual care or usual care plus group-CBT (17 group sessions). The primary outcomes were the between-group differences after 2 years in: (1) body weight; and (2) weight regain. Secondary outcomes were HbA1c levels, insulin dose, plasma lipid levels, depression, anxiety, self-esteem, quality of life, fatigue, physical activity, eating disorders and related cognitions. Data were analysed using linear mixed modelling. Results During the initial 8 week dieting phase, the control group (n = 75) lost a mean of 10.0 (95% CI 9.1, 10.9) kg and the intervention group (n = 83) lost 9.2 (95% CI 8.4, 10.0) kg (p = 0.206 for the between-group difference). During 2 years of follow-up, mean weight regain was 4.7 (95% CI 3.0, 6.3) kg for the control group and 4.0 (95% CI 2.3, 5.6) kg for the intervention group, with a between-group difference of −0.7 (95% CI −3.1, 1.6) kg (p = 0.6). The mean difference in body weight at 2 years was −1.2 (95% CI −7.7, 5.3) kg (p = 0.7). None of the secondary outcomes differed between the two groups. Conclusions/interpretation Despite increased treatment contact, a group-CBT programme for long-term weight maintenance after an initial ≥5% weight loss from dieting in obese individuals with type 2 diabetes was not superior to usual care alone. Trial registration Trialregister.nl NTR2264 Funding The study was funded by the Erasmus MC funding programme ‘Zorgonderzoek’ (grant 2008-8303). Electronic supplementary material The online version of this article (10.1007/s00125-017-4531-9) contains peer-reviewed but unedited supplementary material, which is available to authorised users.
Published: 2018

38. HDL associates with insulin resistance and beta-cell dysfunction in South Asian families at risk of type 2 diabetes

Author: A. Touw, F W M de Rooij, L. van der Zee, R. Yahya, Adrie J.M. Verhoeven, Eric J.G. Sijbrands, Monique T. Mulder, M. Rashid, Sjaam Jainandunsing, and Internal Medicine
Subjects: Blood Glucose, medicine.medical_specialty, endocrine system diseases, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Type 2 diabetes, Endocrinology, Insulin resistance, Asian People, SDG 3 - Good Health and Well-being, Insulin-Secreting Cells, Internal medicine, Diabetes mellitus, Glucose Intolerance, Internal Medicine, medicine, Humans, Insulin, Prediabetes, First-degree relatives, business.industry, Cholesterol, HDL, nutritional and metabolic diseases, medicine.disease, Diabetes Mellitus, Type 2, Density gradient ultracentrifugation, Insulin Resistance, business, Dyslipidemia
Abstract: Objective: Dyslipidemia precedes type 2 diabetes (T2D) and worsens with increasing glucose intolerance. First degree relatives of T2D patients have an increased risk to develop dyslipidemia and glucose intolerance. The aim of the present study was to assess the relation between the development of dyslipidemia and glucose intolerance in first-degree relatives of T2D patients. Research design and methods: Fasting lipoprotein profiles were determined by density gradient ultracentrifugation in T2D patients and their first-degree relatives (42 Caucasians and 33 South Asians), and in 29 normoglycemic controls from non-T2D families. Glucose tolerance, insulin sensitivity index (ISI) and insulin disposition index (DI) were assessed by an extended, frequently sampled oral glucose tolerance test (OGTT), and fractional insulin synthesis rate (FSR) was measured by 13C-leucine enrichment in urinary C-peptide during the OGTT. Results: Of the first-degree relatives, 40, 16 and 19 had NGT, prediabetes and T2D, respectively. NGT family members had lower plasma HDL-cholesterol (HDL[sbnd]C) (1.34 ± 0.07 vs 1.58 ± 0.06 mmol/L; p = 0.015), HDL2-C (0.41 ± 0.05 vs 0.57 ± 0.05 mmol/L; p = 0.021) and HDL3-C (0.62 ± 0.03 vs 0.72 ± 0.02 mmol/L; p = 0.043) than controls. HDL2-C levels tended to decrease with increasing glucose intolerance state. In South Asians, buoyant LDL-C levels decreased with increasing glucose intolerance state (p = 0.006). In South Asian families, HDL-C correlated with both ISI and DI (β 0.42; p = 0.04 and β 0.53; p = 0.01, respectively), whereas HDL2-C and HDL3-C levels correlated with DI (β 0.64; p = 0.002 and β 0.57; p = 0.005, respectively). HDL2-C and plasma triglyceride correlated with FSR (β 0.48; p = 0.033 and β −0.50; p = 0.029, respectively). Conclusions: Low HDL2-C and HDL3-C levels are present in NGT first-degree relatives of T2D patients, and HDL2-C tend to decrease further with increasing glucose intolerance. In South Asian families HDL2-C and HDL3-C levels linked predominantly to deteriorating beta cell function.
Published: 2021

39. PRESENCE AND BURDEN OF CORONARY ATHEROSCLEROSIS IN HETEROZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA

Author: Eric Bruckert, José Luis Díaz-Díaz, Khurram Nasir, Ovidio Muñiz-Grijalvo, Miguel Cainzos-Achirica, Marcio H. Miname, Gerald F. Watts, Eric J.G. Sijbrands, Antonio Gallo, Raul D. Santos, Pedro Mata, Tycho R Tromp, Jing Pang, Rodrigo Alonso Karlezi, G. Kees Hovingh, Leopoldo Pérez de Isla, Gowtham R. Grandhi, Reed Mszar, and Márcio Sommer Bittencourt
Subjects: medicine.medical_specialty, business.industry, Internal medicine, Cardiology, medicine, Familial hypercholesterolemia, Cardiology and Cardiovascular Medicine, business, medicine.disease, Coronary atherosclerosis
Published: 2021

40. Proprotein convertase subtilisin/kexin 9 inhibition in patients with familial hypercholesterolemia: Initial clinical experience

Author: Jeanine E. Roeters van Lennep, Mattie J. Lenzen, Eric J.G. Sijbrands, Annette J. Galema-Boers, Internal Medicine, and Cardiology
Subjects: Male, medicine.medical_specialty, Statin, medicine.drug_class, Endocrinology, Diabetes and Metabolism, Familial hypercholesterolemia, 030204 cardiovascular system & hematology, Medication Adherence, law.invention, Hyperlipoproteinemia Type II, 03 medical and health sciences, 0302 clinical medicine, Ezetimibe, Randomized controlled trial, law, Internal medicine, Injection site reaction, Internal Medicine, Humans, Medicine, Protease Inhibitors, 030212 general & internal medicine, Nutrition and Dietetics, business.industry, PCSK9, PCSK9 Inhibitors, Middle Aged, medicine.disease, Clinical trial, Endocrinology, Kexin, Female, lipids (amino acids, peptides, and proteins), Cardiology and Cardiovascular Medicine, business, medicine.drug
Abstract: Background Despite optimal lipid-lowering therapy, a minority of patients with familial hypercholesterolemia (FH) reach low-density lipoprotein cholesterol (LDL-c) target goals. In randomized trials, proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitors led to impressive LDL-c reductions and a favorable safety profile. However, data about the efficacy and safety outside clinical trials are not available yet. Objective The purpose of the study is to describe efficacy and side effects of PCSK9 inhibitors in FH patients in clinical practice. Methods Registry of all consecutive FH patients who started with a PCSK9 inhibitor at a lipid clinic of a university hospital. Results We analyzed 83 FH patients (79 heterozygous FH [heFH]—65 with a genetically confirmed heFH and 14 with clinical heFH—and 4 homozygous FH [hoFH]), with a mean age of 55.1 ± 11.6 years. Treatment with a PCSK9 inhibitor resulted in an additional reduction of 55% ± 21% in mean LDL-c levels. Patients with heFH had more LDL-c decrease than those with hoFH (56% vs 38%). Patients using ezetimibe monotherapy because of statin intolerance (n = 24, 29%) had less LDL-c decrease compared with patients who concurrently used statin therapy (47% and 58%, P = .03). Side effects of PCSK9 inhibitors were reported by 32 patients (39%). Flu-like symptoms (n = 12) and injection site reactions (n = 11) were most frequent. Seven patients (8%) discontinued treatment, 5 because of side effects and 2 because of nonresponse. Conclusion Our initial experience of PCSK9 inhibition in FH patients in a clinical setting showed comparable reduction in LDL-c levels but more side effects compared with clinical trials.
Published: 2017

41. Novel protein biomarkers associated with coronary artery disease in statin-treated patients with familial hypercholesterolemia

Author: Natalie C. Ward, Sven Bos, Adrie J.M. Verhoeven, Michael Phillips, Gerald F. Watts, Eric J.G. Sijbrands, and Internal Medicine
Subjects: Adult, Male, Proteomics, Risk, 0301 basic medicine, medicine.medical_specialty, Statin, medicine.drug_class, Endocrinology, Diabetes and Metabolism, Coronary Artery Disease, Familial hypercholesterolemia, 030204 cardiovascular system & hematology, Gastroenterology, Asymptomatic, Hyperlipoproteinemia Type II, Coronary artery disease, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Internal Medicine, Humans, Medicine, Coronary atherosclerosis, Aged, Nutrition and Dietetics, business.industry, Incidence (epidemiology), Proteins, Middle Aged, medicine.disease, 030104 developmental biology, Endocrinology, LRG1, Monocyte differentiation, Female, Hydroxymethylglutaryl-CoA Reductase Inhibitors, medicine.symptom, Cardiology and Cardiovascular Medicine, business, Biomarkers
Abstract: Background Familial hypercholesterolemia (FH) is the most common and serious monogenic disorder of lipid metabolism. The incidence of coronary artery disease (CAD) varies among both treated and untreated FH patients. Objective The aim of the study was to utilize proteomics to identify novel protein biomarkers that differentiate genetically confirmed heterozygous patients with FH at high CAD risk from those at low CAD risk. Methods Sixty genetically confirmed FH patients were recruited and stratified into (1) asymptomatic FH with low atherosclerotic burden (FH, n = 20); (2) asymptomatic FH with high atherosclerotic burden (FH + Ca, n = 20); and (3) FH with previously confirmed symptomatic CAD (FH + CAD, n = 20). Results Six new potential proteins were identified; leucine-rich alpha-2-glycoprotein (LRG1), inter-alpha-trypsin inhibitor heavy chain H3, complement C4-B (C4B), complement C1q subcomponent subunit B (C1QB), monocyte differentiation antigen (CD14), and histidine-rich glycoprotein (HRG). There were significant associations between gender and C4B ( Z = 2.31, P = .021), C1QB ( Z = 2.49, P = .013), CD14 ( Z = 2.17, P = .03), and HRG ( Z = 2.14, P = .033). There were significant associations between smoking and LRG1 (χ 2 2 = 6.59, P = .037), CB4 (χ 2 2 = 7.85, P = .02), and HRG (χ 2 2 = 6.11, P = .047). All the peptides were significantly associated with advanced CAD stages, independently of age and smoking. However, the absence of the proteins was the strongest marker. The most accurate association with CAD was HRG (area under the receiver operating characteristic curve = 0.922), whereas LRG1, C4B, and C1QB were also associated with CAD (area under the receiver operating characteristic curve >0.9). For either coronary atherosclerosis or CAD, LRG1, C4B, C1QB, and HRG were relatively well associated. Conclusions The present study has identified 6 novel protein biomarkers that are associated with more advanced stages of atherosclerotic disease and subsequent coronary events in patients with heterozygous FH.
Published: 2017

42. Low-density lipoprotein receptor negative compound heterozygous familial hypercholesterolemia: Two lifetime journeys of lipid-lowering therapy

Author: Monique Williams, Monique T. Mulder, R. Yahya, Jeanine E. Roeters van Lennep, Eric J.G. Sijbrands, Internal Medicine, and Pediatrics
Subjects: Adult, Male, medicine.medical_specialty, Heterozygote, Endocrinology, Diabetes and Metabolism, Mipomersen, Familial hypercholesterolemia, 030204 cardiovascular system & hematology, Compound heterozygosity, Hyperlipoproteinemia Type II, 03 medical and health sciences, chemistry.chemical_compound, Young Adult, 0302 clinical medicine, Ezetimibe, Internal medicine, Internal Medicine, medicine, Humans, 030212 general & internal medicine, Hypolipidemic Agents, Nutrition and Dietetics, business.industry, medicine.disease, Lomitapide, Endocrinology, chemistry, Receptors, LDL, LDL receptor, lipids (amino acids, peptides, and proteins), Female, Cardiology and Cardiovascular Medicine, business, Laropiprant, medicine.drug, Lipoprotein
Abstract: We present the case history of 2 patients with low-density lipoprotein receptor-negative compound heterozygous familial hypercholesterolemia who did not receive lipoprotein apheresis. We describe the subsequent effect of all lipid-lowering medications during their life course including resins, statins, ezetimibe, nicotinic acid/laropiprant, mipomersen, and lomitapide. These cases tell the story of siblings affected with this rare disease, who are free of symptoms but still are at a very high cardiovascular disease risk, and their treatment from childhood.
Published: 2017

43. Carotid artery plaques and intima medial thickness in familial hypercholesteraemic patients on long-term statin therapy: A case control study

Author: Jeanine E. Roeters van Lennep, Sven Bos, Koen Nieman, Arend F.L. Schinkel, Gerald F. Watts, Adrie J.M. Verhoeven, Martijne H C Duvekot, Gert Jan R ten Kate, Monique T. Mulder, Eric J.G. Sijbrands, Internal Medicine, Cardiology, and Radiology & Nuclear Medicine
Subjects: Adult, Carotid Artery Diseases, Male, Heterozygote, medicine.medical_specialty, Time Factors, Computed Tomography Angiography, Coronary Artery Disease, Familial hypercholesterolemia, 030204 cardiovascular system & hematology, Coronary Angiography, Carotid Intima-Media Thickness, Asymptomatic, Hyperlipoproteinemia Type II, 03 medical and health sciences, 0302 clinical medicine, Predictive Value of Tests, Risk Factors, Internal medicine, medicine, Humans, Genetic Predisposition to Disease, cardiovascular diseases, 030212 general & internal medicine, Vascular Calcification, Coronary atherosclerosis, Subclinical infection, business.industry, Case-control study, Carotid ultrasonography, Middle Aged, medicine.disease, Plaque, Atherosclerotic, Carotid Arteries, Phenotype, Treatment Outcome, Intima-media thickness, Case-Control Studies, Asymptomatic Diseases, cardiovascular system, Cardiology, Female, Statin therapy, Hydroxymethylglutaryl-CoA Reductase Inhibitors, medicine.symptom, Cardiology and Cardiovascular Medicine, business
Abstract: Background and aims Statins reduce subclinical atherosclerosis and premature atherosclerotic cardiovascular disease (ASCVD) in patients with familial hypercholesterolemia (FH). However, some FH patients still develop ASCVD despite statin therapy. We compared subclinical atherosclerosis assessed by carotid plaque presence and intima media thickness (C-IMT), in long-term statin-treated FH patients and healthy controls. Furthermore, we analysed whether carotid ultrasonography findings associated with subclinical coronary atherosclerosis. Methods We assessed the presence of carotid plaques and C-IMT in 221 asymptomatic heterozygous FH patients (48% men; 46 ± 15 years) on long-term (10.0 ± 7.8 years) statin treatment and 103 controls (32% men, 47 ± 16 years). Results The frequency of carotid plaques and C-IMT did not differ significantly between the FH patients and controls (69 (31%) versus 24 (23%), p = 0.1 and 0.58 ± 0.13 versus 0.58 ± 0.12 mm, p = 0.9, respectively). In a subgroup of 49 FH patients who underwent cardiac computed tomography, coronary artery calcification correlated with carotid plaque presence (R = 0.47; p = 0.001), but not with C-IMT (R = 0.20; p = 0.2). Conclusions Carotid plaques and C-IMT did not differ between long-term statin-treated heterozygous FH patients and healthy controls. This shows that long-term statin treatment in these FH patients reduces carotid atherosclerosis to a degree of a healthy population. These findings strongly suggests that sonography of the carotid arteries during follow-up of statin-treated FH patients has limited value.
Published: 2017

44. IgG glycan patterns are associated with type 2 diabetes in independent European populations

Author: Caroline Hayward, Mirna Šimurina, Felix Agakov, Harry Campbell, James F. Wilson, Olga Gornik, Eric J.G. Sijbrands, Igor Rudan, Marija Vilaj, Roosmarijn F.H. Lemmers, Aloysius G Lieverse, Lucija Klaric, Daniel Urda, Mandy van Hoek, Gordan Lauc, and Internal Medicine
Subjects: 0301 basic medicine, Male, Glycan, Glycosylation, IgG Glycosylation Type 2 diabetes Prediction Inflammation Ageing, Population, Biophysics, Type 2 diabetes, Biochemistry, 03 medical and health sciences, chemistry.chemical_compound, symbols.namesake, 0302 clinical medicine, SDG 3 - Good Health and Well-being, Journal Article, medicine, Humans, education, Molecular Biology, Aged, education.field_of_study, biology, Galactose, Middle Aged, medicine.disease, Pathophysiology, N-Acetylneuraminic Acid, 030104 developmental biology, Bonferroni correction, chemistry, Diabetes Mellitus, Type 2, Ageing, 030220 oncology & carcinogenesis, Area Under Curve, Immunoglobulin G, Immunology, biology.protein, symbols, Biomarker (medicine), Female
Abstract: BACKGROUND: Type 2 diabetes results from interplay between genetic and acquired factors. Glycans on proteins reflect genetic, metabolic and environmental factors. However, associations of IgG glycans with type 2 diabetes have not been described. We compared IgG N-glycan patterns in type 2 diabetes with healthy subjects.METHODS: In the DiaGene study, a population-based case-control study, (1886 cases and 854 controls) 58 IgG glycan traits were analyzed. Findings were replicated in the population-based CROATIA-Korcula-CROATIA-Vis-ORCADES studies (162 cases and 3162 controls), and meta-analyzed. AUCs of ROC-curves were calculated using 10-fold cross-validation for clinical characteristics, IgG glycans and their combination.RESULTS: After correction for extensive clinical covariates, 5 IgG glycans and 13 derived traits significantly associated with type 2 diabetes in meta-analysis (after Bonferroni correction). Adding IgG glycans to age and sex increased the AUC from 0.542 to 0.734. Adding them to the extensive model did not substantially improve the AUC. The AUC for IgG glycans alone was 0.729.CONCLUSIONS: Several IgG glycans and traits firmly associate with type 2 diabetes, reflecting a pro-inflammatory and biologically-aged state. IgG glycans showed limited improvement of AUCs. However, IgG glycans showed good prediction alone, indicating they may capture information of combined covariates. The associations found may yield insights in type 2 diabetes pathophysiology.GENERAL SIGNIFICANCE: This work shows that IgG glycomic changes have biomarker potential and may yield important insights into pathophysiology of complex public health diseases, illustrated here for the first time in type 2 diabetes.
Published: 2017

45. Soluble LR11 associates with aortic root calcification in asymptomatic treated male patients with familial hypercholesterolemia

Author: Meizi Jiang, Adrie J.M. Verhoeven, Sven Bos, Jeanine E. Roeters van Lennep, Ranitha Vongpromek, Gert-Jan R. ten Kate, Koen Nieman, Hideaki Bujo, Wolfgang J. Schneider, Eric J.G. Sijbrands, Monique T. Mulder, Internal Medicine, Cardiology, and Radiology & Nuclear Medicine
Subjects: 0301 basic medicine, Aortic valve, Adult, Male, medicine.medical_specialty, Aortic Diseases, Familial hypercholesterolemia, Coronary Artery Disease, 030204 cardiovascular system & hematology, Asymptomatic, Coronary artery disease, Hyperlipoproteinemia Type II, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Humans, Risk factor, Vascular Calcification, LDL-Receptor Related Proteins, Aged, business.industry, Membrane Transport Proteins, Odds ratio, Middle Aged, medicine.disease, 030104 developmental biology, medicine.anatomical_structure, Aortic Valve, Asymptomatic Diseases, Cardiology, medicine.symptom, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Cardiology and Cardiovascular Medicine, business, Calcification, Lipoprotein
Abstract: Background and aims Despite statin treatment, a high prevalence of severe vascular calcification is found in patients with familial hypercholesterolemia (FH). We assessed the relation between the circulating soluble form of low-density lipoprotein receptor relative with 11 ligand-binding repeats (sLR11), a risk factor for cardiovascular disease, and vascular calcification in asymptomatic statin-treated heterozygous FH patients. Methods In 123 asymptomatic heterozygous FH patients (age 40–69 years), aortic root (ARC), aortic valve (AVC) and coronary artery calcification (CAC) were determined with CT-based calcium scoring expressed in Agatston units. Plasma sLR11 levels were measured by sandwich ELISA. Results Seventy-three patients displayed ARC, 48 had AVC and 96 CAC. Plasma sLR11 levels were positively correlated with the presence of ARC (r = 0.2, p = 0.03), but not with AVC or CAC. The correlation between sLR11 levels and ARC was restricted to male FH patients (r = 0.31, p = 0.006). Multivariate logistic analyses showed that the association of plasma sLR11 with the presence of ARC was independent of other determinants (Adjusted Odds Ratio, 2.01 (95% CI = 1.28–3.16) p = 0.002). Conclusions Plasma sLR11 is associated with ARC in male FH patients and may be mechanistically involved in the differential distribution of atherosclerotic lesions in the vasculature.
Published: 2017

46. Letter by Weingärtner et al Regarding Article, 'Ezetimibe Lipid-Lowering Trial on Prevention of Atherosclerotic Cardiovascular Disease in 75 or Older (EWTOPIA 75): A Randomized, Controlled Trial'

Author: Oliver Weingärtner, Dieter Lütjohann, Eric J.G. Sijbrands, and Internal Medicine
Subjects: medicine.medical_specialty, Atherosclerotic cardiovascular disease, business.industry, Anticholesteremic Agents, MEDLINE, Atherosclerosis, Ezetimibe, Lipids, law.invention, Randomized controlled trial, SDG 3 - Good Health and Well-being, Cardiovascular Diseases, law, Physiology (medical), Internal medicine, Humans, Medicine, Lipid lowering, Cardiology and Cardiovascular Medicine, business, medicine.drug
Published: 2020

47. Dietary antioxidant capacity and risk of type 2 diabetes mellitus, prediabetes and insulin resistance: the Rotterdam Study

Author: Jana Nano, Oscar H. Franco, Trudy Voortman, Niels van der Schaft, Jessica C. Kiefte-de Jong, Josje D. Schoufour, Taulant Muka, Eric J.G. Sijbrands, M. Arfan Ikram, Epidemiology, and Internal Medicine
Subjects: Adult, Male, medicine.medical_specialty, Epidemiology, Population, 610 Medicine & health, Type 2 diabetes, 030204 cardiovascular system & hematology, Lower risk, Dietary antioxidant capacity, Antioxidants, Prediabetic State, 03 medical and health sciences, Rotterdam Study, 0302 clinical medicine, Insulin resistance, SDG 3 - Good Health and Well-being, Risk Factors, 360 Social problems & social services, Internal medicine, Diabetes Mellitus, Humans, Medicine, 030212 general & internal medicine, Prediabetes, education, Aged, education.field_of_study, business.industry, Type 2 Diabetes Mellitus, Middle Aged, medicine.disease, Ferric reducing ability of plasma, Diet, Oxidative Stress, Nutrition Assessment, Diabetes Mellitus, Type 2, Fruit, Female, Type 2 Diabetes, Dietary Antioxidant Capacity, Insulin Resistance, business
Abstract: Intake of individual antioxidants has been related to a lower risk of type 2 diabetes. However, the overall diet may contain many antioxidants with additive or synergistic effects. Therefore, we aimed to determine associations between total dietary antioxidant capacity and risk of type 2 diabetes, prediabetes and insulin resistance. We estimated the dietary antioxidant capacity for 5796 participants of the Rotterdam Study using a ferric reducing ability of plasma (FRAP) score. Of these participants, 4957 had normoglycaemia and 839 had prediabetes at baseline. We used covariate-adjusted proportional hazards models to estimate associations between FRAP and risk of type 2 diabetes, risk of type 2 diabetes among participants with prediabetes, and risk of prediabetes. We used linear regression models to determine the association between FRAP score and insulin resistance (HOMA-IR). We observed 532 cases of incident type 2 diabetes, of which 259 among participants with prediabetes, and 794 cases of incident prediabetes during up to 15 years of follow-up. A higher FRAP score was associated with a lower risk of type 2 diabetes among the total population (HR per SD FRAP 0.84, 95% CI 0.75; 0.95) and among participants with prediabetes (HR 0.85, 95% CI 0.73; 0.99), but was not associated with risk of prediabetes. Dietary FRAP was also inversely associated with HOMA-IR (β − 0.04, 95% CI − 0.06; − 0.03). Effect estimates were generally similar between sexes. The findings of this population-based study emphasize the putative beneficial effects of a diet rich in antioxidants on insulin resistance and risk of type 2 diabetes. Electronic supplementary material The online version of this article (10.1007/s10654-019-00548-9) contains supplementary material, which is available to authorized users.
Published: 2019

48. The effect of guideline revisions on vascular complications of type 2 diabetes

Author: Aloysius G Lieverse, Sunny S Singh, Mandy van Hoek, Eric J.G. Sijbrands, Ralph Heijmans, and Internal Medicine
Subjects: microvascular complications, medicine.medical_specialty, lcsh:RC648-665, business.industry, Endocrinology, Diabetes and Metabolism, Incidence (epidemiology), Type 2 diabetes, Guideline, Diabetic retinopathy, Odds ratio, medicine.disease, Lower risk, lcsh:Diseases of the endocrine glands. Clinical endocrinology, diabetic retinopathy, macrovascular complications, SDG 3 - Good Health and Well-being, Internal medicine, Diabetes mellitus, Medicine, type 2 diabetes, business, guideline, diabetes care, Original Research, Retinopathy
Abstract: Background: The aim of this study was to investigate the impact of implementation and revision of the ‘Diabetes Mellitus type II’ guideline by the Dutch College of General Practitioners (DCGP) on the prevalence and incidence of macrovascular and microvascular complications. Methods: The DiaGene study is a case-control study ( n = 1886 patients of type 2 diabetes) with extensive, retrospectively collected complication data, as well as prospective follow up of complications. The study incorporates all lines of diabetes care. Cases were divided into categories according to the date of onset of diabetes and publication dates of the DCGP. Logistic regression models were used to investigate the associations between guideline version and complications. To investigate a possible trend between guideline version and complications, the ‘guideline category’ was also used as a continuous variable. All models were adjusted for clinical covariables. Results: The 1999 and 2006 guidelines versions were associated with significantly lower risk of retinopathy than the group that started without a guideline [OR 0.32 (95% CI 0.14–0.72, p = 0.006) and 0.31 (95% CI 0.11–0.91, p = 0.034), respectively]. A significant trend in reduction of peripheral artery disease (PAD) over the guideline versions was found, adjusted for age, sex and diabetes duration (odds ratio (OR) 0.70, 95% CI 0.51-0.97, p trend = 0.029) and for retinopathy in all models (OR = 0.52, 95% CI 0.37-0.73, p trend Conclusions: The introduction of the first diabetes guideline and subsequent revisions have reduced the risk of macrovascular and microvascular complications of type 2 diabetes, most strongly in diabetic retinopathy. This indicates that real-time diabetes care has improved over time.
Published: 2019

49. An integrative cross-omics analysis of DNA methylation sites of glucose and insulin homeostasis

Author: Jennifer A. Smith, Andrea A. Baccarelli, Jordana T. Bell, James B. Meigs, James S. Pankow, Jun Liu, Ayse Demirkan, Marjolein J. Peters, Jerome I. Rotter, Elias Salfati, Bertha Hidalgo, Audrey Y. Chu, André G. Uitterlinden, Luigi Ferrucci, Pooja R. Mandaviya, Nona Sotoodehnia, Eric A. Whitsel, Liesbeth Duijts, Marie-France Hivert, Elena Carnero-Montoro, Eric J.G. Sijbrands, Ann Zenobia Moore, Janine F. Felix, Jenny van Dongen, Najaf Amin, Tim D. Spector, Oscar H. Franco, Harald Grallert, Tiphaine Martin, Ivana Nedeljkovic, Josée Dupuis, Aaron Isaacs, Themistocles L. Assimes, Pei-Chien Tsai, Cornelia M. van Duijn, Lifang Hou, Daniel Levy, Ko Willems van Dijk, Rahul Gondalia, Samantha Lent, Abbas Dehghan, Rozenn N. Lemaitre, Jan Bressler, Christian Herder, Min A. Jhun, Symen Ligthart, Dorret I. Boomsma, Gonneke Willemsen, Toshiko Tanaka, Rick Jansen, Joyce B. J. van Meurs, Shih-Jen Hwang, Vincent W. V. Jaddoe, Donna K. Arnett, Eco J. C. de Geus, Henning Tiemeier, Stefania Bandinelli, Pediatric surgery, Epidemiology and Data Science, Biological Psychology, APH - Mental Health, APH - Personalized Medicine, APH - Methodology, Epidemiology, Internal Medicine, Pediatrics, Erasmus MC other, Child and Adolescent Psychiatry / Psychology, RS: CARIM - R1 - Thrombosis and haemostasis, RS: FHML MaCSBio, Biochemie, and RS: Carim - B01 Blood proteins & engineering
Subjects: 0301 basic medicine, Epigenomics, Male, Netherlands Twin Register (NTR), medicine.medical_treatment, General Physics and Astronomy, 02 engineering and technology, Type 2 diabetes, UP-REGULATION, Epigenesis, Genetic, Glucose homeostasis, Homeostasis, Insulin, lcsh:Science, Genetics, Aged, 80 and over, Multidisciplinary, Middle Aged, 021001 nanoscience & nanotechnology, 3. Good health, Multidisciplinary Sciences, DNA methylation, Science & Technology - Other Topics, Epigenetics, Female, 0210 nano-technology, WAIST CIRCUMFERENCE, Metabolic Networks and Pathways, Adult, EXPRESSION, Science, 610 Medicine & health, Biology, Polymorphism, Single Nucleotide, Article, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Young Adult, TYPE-2, SDG 3 - Good Health and Well-being, 360 Social problems & social services, Diabetes mellitus, medicine, GLYCEMIC TRAITS, Humans, Computer Simulation, Obesity, Transcriptomics, Aged, EPIGENOME-WIDE ASSOCIATION, Science & Technology, Gene Expression Profiling, DIABETES-MELLITUS, General Chemistry, DNA Methylation, medicine.disease, GENE, IRS2, BODY-MASS INDEX, 030104 developmental biology, Glucose, Diabetes Mellitus, Type 2, Gene Expression Regulation, lcsh:Q, CpG Islands, Genome-Wide Association Study, FASTING GLUCOSE
Abstract: Despite existing reports on differential DNA methylation in type 2 diabetes (T2D) and obesity, our understanding of its functional relevance remains limited. Here we show the effect of differential methylation in the early phases of T2D pathology by a blood-based epigenome-wide association study of 4808 non-diabetic Europeans in the discovery phase and 11,750 individuals in the replication. We identify CpGs in LETM1, RBM20, IRS2, MAN2A2 and the 1q25.3 region associated with fasting insulin, and in FCRL6, SLAMF1, APOBEC3H and the 15q26.1 region with fasting glucose. In silico cross-omics analyses highlight the role of differential methylation in the crosstalk between the adaptive immune system and glucose homeostasis. The differential methylation explains at least 16.9% of the association between obesity and insulin. Our study sheds light on the biological interactions between genetic variants driving differential methylation and gene expression in the early pathogenesis of T2D., Our understanding of the functional link between differential DNA methylation and type 2 diabetes and obesity remains limited. Here the authors present a blood-based EWAS of fasting glucose and insulin among 4808 non-diabetic Europeans and identify nine CpGs not previously implicated in glucose, insulin homeostasis and diabetes.
Published: 2019

50. Dietary Sargassum fusiforme improves memory and reduces amyloid plaque load in an Alzheimer's disease mouse model

Author: Dicky Struik, Niels Hellings, Anja Kerksiek, Melissa Schepers, Ilse Dewachter, Frank P.J. Leijten, Johan W. Jonker, Yupyn Chintapakorn, Thiti Suttiyut, Monique T. Mulder, Hong-Bing Liu, Tim Vanmierlo, Eric J.G. Sijbrands, Jochen Walter, Surachai Pornpakakul, Jeroen F. J. Bogie, Dieter Lütjohann, Assia Tiane, Bart Staels, Ann Cuypers, Albert K. Groen, Jerome J. A. Hendriks, Cindy Hoeks, Pilar Martinez-Martinez, Experimental Vascular Medicine, ACS - Atherosclerosis & ischemic syndromes, ACS - Diabetes & metabolism, AGEM - Endocrinology, metabolism and nutrition, Promovendi MHN, Psychiatrie & Neuropsychologie, RS: MHeNs - R3 - Neuroscience, Internal Medicine, Center for Liver, Digestive and Metabolic Diseases (CLDM), and Lifestyle Medicine (LM)
Subjects: 0301 basic medicine, Male, lcsh:Medicine, Plaque, Amyloid, Pharmacology, Hippocampus, ACTIVATION, chemistry.chemical_compound, 0302 clinical medicine, Cognition, Genes, Reporter, Lipid droplet, BRAIN, lcsh:Science, Luciferases, Liver X Receptors, Multidisciplinary, beta-Sitosterol, Aniline Compounds, Microglia, Chemistry, LIVER-X RECEPTORS, BETA-SITOSTEROL, LXR AGONIST TO901317, 3. Good health, medicine.anatomical_structure, Memory, Short-Term, Neuroprotective Agents, lipids (amino acids, peptides, and proteins), Signal transduction, Signal Transduction, Stigmasterol, Mice, Transgenic, HUMAN SERUM-ALBUMIN, METABOLISM, Article, 03 medical and health sciences, Alzheimer Disease, medicine, Animals, Humans, Liver X receptor, Amyloid beta-Peptides, PLANT STEROLS, Activator (genetics), lcsh:R, Hypertriglyceridemia, Sargassum, medicine.disease, Peptide Fragments, Disease Models, Animal, Thiazoles, MICE, 030104 developmental biology, Gene Expression Regulation, CHOLESTEROL HOMEOSTASIS, Astrocytes, Culture Media, Conditioned, lcsh:Q, Steatosis, 030217 neurology & neurosurgery
Abstract: Activation of liver X receptors (LXRs) by synthetic agonists was found to improve cognition in Alzheimer’s disease (AD) mice. However, these LXR agonists induce hypertriglyceridemia and hepatic steatosis, hampering their use in the clinic. We hypothesized that phytosterols as LXR agonists enhance cognition in AD without affecting plasma and hepatic triglycerides. Phytosterols previously reported to activate LXRs were tested in a luciferase-based LXR reporter assay. Using this assay, we found that phytosterols commonly present in a Western type diet in physiological concentrations do not activate LXRs. However, a lipid extract of the 24(S)-Saringosterol-containing seaweed Sargassum fusiforme did potently activate LXRβ. Dietary supplementation of crude Sargassum fusiforme or a Sargassum fusiforme-derived lipid extract to AD mice significantly improved short-term memory and reduced hippocampal Aβ plaque load by 81%. Notably, none of the side effects typically induced by full synthetic LXR agonists were observed. In contrast, administration of the synthetic LXRα activator, AZ876, did not improve cognition and resulted in the accumulation of lipid droplets in the liver. Administration of Sargassum fusiforme-derived 24(S)-Saringosterol to cultured neurons reduced the secretion of Aβ42. Moreover, conditioned medium from 24(S)-Saringosterol-treated astrocytes added to microglia increased phagocytosis of Aβ. Our data show that Sargassum fusiforme improves cognition and alleviates AD pathology. This may be explained at least partly by 24(S)-Saringosterol-mediated LXRβ activation. This work was supported by the Internationale Stichting Alzheimer Onderzoek (ISAO)/Alzheimer Nederland (AN), Scientific Research-Flanders (FWO), Fondation Vaincre Alzheimer (LECMA), and Alzheimer Forschung Initiative (AFI). The authors like to thank Joke Vanhoof for excellent technical assistance and AstraZeneca for providing the AZ876 compound through the AstraZeneca Open Innovation program. We sincerely thank Patric Delhanty for editing the paper and Kenneth Vanbrabant for performing the GC-MS analysis.
Published: 2019

Catalog

Books, media, physical & digital resources

See catalog results

Searchworks

Select search scope, currently: Articles Catalog books, media & more in Jio Institute collections Articles journal articles & other e-resources

Search

Search Constraints

Refine your results

Search Limiters

Topic

Publication Year Range

Language

Publication Type

Journal

Database

Publisher

322 results on '"Eric J.G. Sijbrands"'

Search Results

Catalog

Select search scope, currently: Articles

Catalog

books, media & more in Jio Institute collections

Articles

journal articles & other e-resources