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Background Atrial fibrillation (AF), which affects 1% to 4% of the general population, is an important risk factor for stroke. New technologies for AF screening are now available, but their real-world application in clinical settings has not yet been thoroughly investigated. The aim of this project was to describe the introduction and feasibility of a mobile electrocardiogram (ECG) device for AF screening in a large-scale, undifferentiated population. Methods A total of 184 Canadian primary care physicians were provided with a KardiaMobile ECG device (AliveCor) for 3 months. Physicians were asked to obtain a single 30-second ECG recording of all patients seen in their daily practice who were ≥65 years old and not previously diagnosed with AF. Evaluation of the Kardia device by physicians was measured using a Likert scale–based questionnaire. Results One hundred thirty-three physicians (72%) reported their findings and completed the survey. A total of 7585 patients were screened (42% of eligible patients). AF was detected in 471 patients (6.2%). Anticoagulation therapy was initiated in 270 patients (57%). Physicians generally reported a high perceived clinical value (94%) and ease of integration (89%) of the device. Conclusions Previously undiagnosed AF is common in older individuals attending primary care clinics. The KardiaMobile ECG device appears to be an effective screening tool for AF with high physician acceptability. More research on the feasibility of such novel technologies is warranted for future consideration of integration in population-based screening programs.

Background Compelling evidence showing a link between atrial fibrillation (AF) and cognitive decline and dementia is accumulating. Methods Blinded Randomized Trial of Anticoagulation to Prevent Ischemic Stroke and Neurocognitive Impairment in Atrial Fibrillation (BRAIN-AF) is a prospective, multicentric, double-blind, randomized-controlled trial, recruiting patients with nonvalvular AF and a low risk of stroke. Patients with a high risk of bleeding will be excluded from the study. Participants will be randomized to receive either rivaroxaban (15 mg daily) or standard of care (placebo in patients without vascular disease or acetylsalicylic acid 100 mg daily in patients with vascular disease). Results The primary outcome is the composite of stroke, transient ischemic attack, and cognitive decline (defined by a decrease in the Montreal Cognitive Assessment score ≥ 3 at any follow-up visit after baseline). Approximately 3250 patients will be enrolled in approximately 130 clinical sites until 609 adjudicated primary outcome events have occurred. Conclusions BRAIN-AF determines whether oral anticoagulation therapy with rivaroxaban compared with standard of care reduces the risk of stroke, transient ischemic attack, or cognitive decline in patients with nonvalvular AF and a low risk of stroke.

Supply chains are dependent on Information Technology (IT) and cyberspace processes. Yet, despite the advantages of its increased connectivity and systems integration with suppliers and customers, this also opens the door to new risks from and to supply chain partners. Literature in this nascent research area is limited, with few frameworks available to complement traditional risk management methods. This paper shows the current results of a literature review on the field of supply chain cyber risk management (SCCRM), with the aim of gathering and structuring its extant literature and proposing a taxonomy that will give a better overview of the approaches found in the scientific literature. This taxonomy is then used to propose a novel SCCRM framework. Finally, a novel Impact-Wave analogy is presented to provide a graphical understanding of the application of this framework.

Introdução: A hipertensão arterial é uma doença complexa, multifatorial, controlada por fatores genéticos e ambientais. Objetivo: Avaliar a susceptibilidade genética no aparecimento de hipertensão arterial e sua associação com os fatores de risco tradicionais na eclosão desta patologia. Material e Métodos: Estudo caso-controlo com 1712 indivíduos, idade média de 51,0 ± 7,9 anos (860 hipertensos e 852 controlos). Avaliaram-se os fatores tradicionais, bioquímicos e as variantes genéticas: ACE I/D rs4340, ACE A2350G rs4343, AGT T174M rs4762, AGT M235T rs699 AGTR1 A1166C rs5186, CYP11B2 -344 C/T rs1799998, ADRB1 R389G rs1801253, ADRB2 R16G rs1042713, ADD1 G460W rs4961, SCNN1G G173A rs5718, GNB3 C825T rs5443, ATP2B1 A/G rs2681472, CYP17A1 T/C rs11191548, SLC4A2 C/T rs2303934. Calculámos o risco de cada gene para a hipertensão, pelos modelos dominante, recessivo, co-dominante e multiplicativo. Através da regressão logística, avaliámos as variáveis associadas à hipertensão. Elaboraram-se curvas ROC com os fatores tradicionais e posteriormente adicionando as variantes genéticas associadas com hipertensão. Analisámos os dados através do SPSS for Windows 19.0 e MedCalc v. 13.3.3.0. Resultados: As variantes genéticas ADD1 G460W, GNB3 C825T, ACE I/D e ACE A2350G associaram-se à hipertensão. A curva ROC com os factores de risco tradicionais e estas variantes mostrou um incremento na capacidade preditiva de hipertensão (p = 0,018). Discussão: Segundo os resultados do nosso estudo as variantes genéticas que após análise univariada se associaram à hipertensão arterial foram a ACE I/D rs4340, ACE A2350G rs4343, ADD1 G460W rs4961, GNB3 C825T rs5443. As duas primeiras variantes relacionam-se com a hipertensão arterial por interferirem no sistema renina-angiotensina-aldosterona, que tem um importante papel na regulação da pressão arterial. Salienta-se o facto dos genes que codificam os componentes do sistema renina-angiotensinaaldosterona serem candidatos naturais ao desenvolvimento e progressão da hipertensão arterial. Também na nossa população os polimorfismos da alfa-aducina (ADD1 G460W rs4961), associaram-se à hipertensão arterial. Nesta população portuguesa, conhecida por ter elevado consumo de sal, faz sentido que estes polimorfismos, sejam relevantes na gestão do sal e da água e consequentemente, no aparecimento de hipertensão arterial. A variante genética GNB3 C825T rs5443 que interfere na sinalização intracelular também constituiu uma forte candidata à hipertensão arterial. Com a elaboração da curva ROC e cálculo das AUC inicialmente só com os fatores de risco tradicionais e posteriormente adicionando as variantes ADD1 G460W, GNB3 C825T, ACE I/D e ACE A2350G aos fatores de risco tradicionais, verificámos ter havido um incremento no risco preditivo de hipertensão arterial, relativamente ao existente só com os fatores de risco tradicionais, com significado estatístico (p = 0,018). Isto sugere que a hipertensão arterial é uma doença multifatorial, que resulta da interação de fatores ambientais, genéticos e estilos de vida que interagem entre si e levam ao aparecimento desta importante patologia. Conclusão: No nosso estudo os polimorfismos associados à hipertensão, estão ligados ao eixo renina-angiotensina-aldosterona (ACE I/D, ACE A2350G), bem como à gestão de sal e água (ADD1 G460W, GNB3 C825T). Através de uma análise multivariada, concluiuse que estas duas últimas variantes genéticas conjuntamente com quatro dos fatores tradicionais (tabagismo, hábitos alcoólicos, obesidade e diabetes) se associam de forma significativa e independente à hipertensão arterial essencial. Num modelo preditivo de hipertensão arterial, a introdução das variantes genéticas aumenta ligeiramente o valor preditivo do modelo. Introduction: Arterial hypertension is a complex, multifactorial disease, controlled by genetic and environmental factors. Objective: Evaluate the genetic susceptibility for developing arterial hypertension and its association with the traditional risk factors in the outbreak of this pathology. Material and Methods: Case-control study with 1712 individuals, mean age of 51.0 ± 7.9 years (860 hypertensive patients and 852 controls). Biochemical and traditional risk factors, and genetic variants were evaluated: ACE I/D rs4340, ACE A2350G rs4343, AGT T174M rs4762, AGT M235T rs699 AGTR1 A1166C rs5186, CYP11B2 -344 C/T rs1799998, ADRB1 R389G rs1801253, ADRB2 R16G rs1042713, ADD1 G460W rs4961, SCNN1G G173A rs5718, GNB3 C825T rs5443, ATP2B1 A/G rs2681472, CYP17A1 T/C rs11191548, SLC4A2 C/T rs2303934. The risk of each gene for hypertension was estimated by the dominant, recessive, co-dominant and multiplicative models. By logistic regression, variables associated with hypertension were evaluated. ROC curves were first performed with traditional risk factors and then adding the genetic variants associated with hypertension. Data were analyzed by SPSS for Windows 19.0 and MedCalc v. 13.3.3.0. Results: The genetic variants ADD1 G460W, GNB3 C825T, ACE I/D, ACE A2350G were associated with hypertension. ROC curve with traditional risk factors and these variants showed an increase in the predictive capacity of hypertension (p = 0.018). Discussion: According to the results of our study, the genetic variants found to be associated with hypertension were: ACE I/D rs4340, ACE A2350G rs4343, ADD1 G460W rs4961 and GNB3 C825T rs5443. The first two variants are associated with hypertension by interfering with the renin-angiotensin-aldosterone system, which plays an important role in regulating blood pressure. It should be noted that genes encoding the components of renin-angiotensin-aldosterone system are natural candidates for the development and progression of hypertension. In our population alpha-aducin polymorphism (ADD1 G460W rs4961) was also associated with hypertension. In a Portuguese population, known to have high salt intake, it makes sense that this polymorphism which is relevant in salt and water management may consequently be relevant in the onset of hypertension. The genetic variant GNB3 C825T rs5443 that affects intracellular signalling was also found to be a strong risk candidate for hypertension. Initially, with the elaboration of the ROC curve and calculation of the AUC using only with traditional risk factors and later by adding the variants ADD1 G460W, GNB3 C825T, ACE I/D and ACE A2350G to the traditional risk factors, we verified that genetic polymorphisms increased the predictive risk of hypertension, when compared to the risk given only by traditional risk factors, with statistical significance (p = 0.018). This suggests that hypertension is a multifactorial disease that results from the interaction of environmental, genetic and lifestyle factors that interact with each other and lead to the advent of this important pathology. Conclusion: In our study, the hypertension-associated polymorphisms are linked to the renin-angiotensin-aldosterone axis (ACE I/D, ACE A2350G), as well as to salt and water management (ADD1 G460W, GNB3 C825T). Through a multivariate analysis, it was concluded that these two last genetic variants together with four of the traditional risk factors (smoking, alcohol consumption, obesity and diabetes) are associated in a significant and independent way with essential hypertension. In a predictive model of hypertension, the introduction of genetic variants slightly increases the predictive value of the model. info:eu-repo/semantics/publishedVersion

Sensor-Based Navigation and CRT ImplantationIntroduction Cardiac resynchronization therapy (CRT) implant procedures are often complex and prolonged, resulting in substantial ionizing radiation (IR) exposure to the patient and operator. We assessed the impact of lower-dose fluoroscopy settings and a sensor-based electromagnetic tracking system (MediGuide™, MDG) on reducing IR exposure during CRT implantation. Methods A single-center 2-group cohort study was conducted on 348 consecutive patients, age 66.4 ± 11.0 years, 80.4% male, with CRT implant procedures from 2013 to 2015. Patients were arbitrarily assigned to MDG (N = 239) versus no MDG (N = 109) guidance. Lower-dose fluoroscopy settings were adopted in January 2015 (3 instead of 6 fps; 23 instead of 40 nGy/pulse; N = 101). Results Overall, MDG was associated with an 82.1% reduction in IR exposure (393 μGray·m2 vs. 2191 μGray·m2, P < 0.001). Lower-dose fluoroscopy resulted in a 59.5% reduction in IR-exposure without MDG (1055 μGray·m2 vs. 2608 μGray·m2, P < 0.001) and 81.8% reduction with MDG (108 μGray·m2 vs. 595 μGray·m2, P < 0.001). Low-dose fluoroscopy combined with MDG was associated with a 95.9% lower exposure to IR when compared to standard fluoroscopy without MDG (108 μGray·m2 vs. 2608 μGray·m2, P < 0.001). Procedures with MDG were shorter (96 minutes vs. 123 minutes, P < 0.001) and associated with a trend towards a higher success rate (94.6% vs. 89.0%, P = 0.062), with fewer coronary sinus cannulation failures (2.1% vs. 6.4%, P = 0.040). Conclusion Low-dose fluoroscopy settings are highly effective (>50%) in reducing IR exposure during CRT implant procedures. When combined with MDG, >95% reduction in IR exposure is achieved. Moreover, MDG shortens procedural duration and may improve acute procedural outcomes.

While radiation exposure related to natural sources plays a minor role, medicine-related exposure, represents, to date, a major exposure source. Within this exposure interventional electrophysiology is a relevant contributor. Unfortunately, no safe dose in radioprotection exists, the negative acute and long-term effects of radiological exposure may emerge at any radiation exposure dose. For this reason, patients and physicians should be aware of the risk of radiation exposure and the benefits of the imaging/procedure balanced by the required radiation exposure. Given this, performing a near to zero X-rays transcatheter ablation procedure should therefore represent an aim for all electrophysiological lab. Fortunately, the introduction of electroanatomic mapping systems, have provided the possibility to perform simple and complex electrophysiological procedures avoiding, or at least, limiting the use of radiations. The present review summarizes state of the art of feasibility and safety of the near to zero approach for the main electrophysiological procedures, highlighting the potential health benefits.

ECG and Cardiovascular Outcomes in AFBackground The association between standard parameters from a simple 12-lead ECG (i.e., QRS duration and PR, JT, and QT intervals) and adverse cardiovascular outcomes (cardiovascular mortality, all-cause mortality, arrhythmic mortality, and hospitalizations) in patients with a history of atrial fibrillation (AF) has not been previously studied. Methods and Results A pooled analysis of patient-level data was conducted on 5,436 patients, age 68.2 ± 8.3 years, 34.8% female, with a history of non-permanent AF randomized in AFFIRM and AF-CHF trials. The predictive value of ECG parameters was assessed in AF and sinus rhythm in multivariate Cox regression models. During a follow-up of 40.8 ± 16.3 months, QRS duration >120 milliseconds was independently associated with all-cause mortality (hazard ratio [HR] 1.46, 95% confidence interval [CI; 1.21–1.76] in AF, P 200 milliseconds) was independently associated with cardiovascular (HR 1.56, 95% CI [1.11–2.21], P = 0.010) and arrhythmic (HR 1.91, 95% CI [1.14–3.18], P = 0.004) mortality. The JT and QTc intervals were not predictive of mortality. Conclusions Simple parameters from standard ECGs are significantly and independently associated with adverse cardiovascular outcomes in patients with a history of AF.

We describe the development and validation of a new instrument to measure the non-academic impact of education abroad, the Global Engagement Measurement Scale (GEMS). Based on a review of the extant literature, we developed a 37-item instrument containing scales for four specific constructs of interest: a) cultural engagement; b) ambiguity tolerance; c) knowledge of the host site; and d) diversity openness. The measure was piloted with 263 education abroad students before and after a 5- week education abroad program. We examined the scales’ underlying factor structure, reliability, and sensitivity to education abroad program effects. Results indicate strong reliability and statistically significant increases across all scales following education abroad experiences. The GEMS instrument is brief and easy to administer, publically available, and includes important constructs for assessing the impact of education abroad. Additionally, the GEMS could be used to assess campus internationalization efforts with domestic and international students.

Treatment Failures in AF-CHF Introduction Rate and rhythm control strategies for atrial fibrillation (AF) are not always effective or well tolerated in patients with congestive heart failure (CHF). We assessed reasons for treatment failure, associated characteristics, and effects on survival. Methods and Results A total of 1,376 patients enrolled in the AF-CHF trial were followed for 37 ± 19 months, 206 (15.0%) of whom failed initial therapy leading to crossover. Rhythm control was abandoned more frequently than rate control (21.0% vs. 9.1%, P < 0.0001). Crossovers from rhythm to rate control were driven by inefficacy, whereas worsening heart failure was the most common reason to crossover from rate to rhythm control. In multivariate analyses, failure of rhythm control was associated with female sex, higher serum creatinine, functional class III or IV symptoms, lack of digoxin, and oral anticoagulation. Factors independently associated with failure of rate control were paroxysmal (vs. persistent) AF, statin therapy, and presence of an implantable cardioverter–defibrillator. Crossovers were not associated with cardiovascular mortality (hazard ratio [HR] 1.11 from rhythm to rate control; 95% confidence interval [95% CI, 0.73–1.73]; P = 0.6069; HR 1.29 from rate to rhythm control; 95% CI, 0.73–2.25; P = 0.3793) or all-cause mortality (HR 1.16 from rhythm to rate control, 95% CI [0.79–1.72], P = 0.4444; HR 1.15 from rate to rhythm control, 95% [0.69, 1.91], P = 0.5873). Conclusions Rhythm control is abandoned more frequently than rate control in patients with AF and CHF. The most common reasons for treatment failure are inefficacy for rhythm control and worsening heart failure for rate control. Changing strategies does not impact survival.

Objective To investigate whether nailfold videocapillaroscopy (NVC), an increasingly worldwide used non-invasive tool to reliably evaluate the peripheral microcirculation, may be an outcome measure in future screening algorithms for systemic sclerosis related interstitial lung disease (SSc-ILD). Methods A systematic review to identify original research papers documenting an association between NVC and SSc-ILD was performed in 3 electronic databases according to the PRISMA guidelines. Subsequently, NVC parameters were subdivided according to the consented standardised capillaroscopic definitions of the EULAR Study Group on Microcirculation in Rheumatic Diseases / Scleroderma Clinical Trials Consortium on Capillaroscopy, into quantitative (capillary density, capillary dimension, capillary morphology and haemorrhages) and qualitative assessment (NVC pattern). Results The systematic search identified 310 unique search results, of which 2 cross-sectional and 1 longitudinal study were retained. In both cross-sectional studies, the presence of SSc-ILD was found to be inversely associated with capillary density (p = .008 and p = .005). The presence of a severe (active/late) NVC pattern was evaluated and associated with the presence of SSc-ILD in one of the cross-sectional studies. In the longitudinal study, incident SSc-ILD was associated with progressive capillary loss (p = .03) and the conversion to a worse (active/late) NVC pattern (p = .001/p = .003). Conclusions This first systematic literature review investigating the role of NVC in SSc-ILD using standardised capillaroscopic definitions uncovered associations between NVC and (incident) SSc-ILD. If large prospective studies further corroborate and elucidate these findings, NVC might possibly be a candidate outcome measure to be integrated in screening algorithms for incident/progressive SSc-ILD.

Pregnant women are known as high-risk populations to infectious disease including foodborne illnesses. To protect pregnant women and their fetus from serious consequences of foodborne illness, food safety education is critical. The objective of this study was to measure pregnant women's confidence and perceptions on food safety practices in preparing their own meals at home. Two hundred and twenty-two pregnant women in and around urban area in Louisiana were recruited to complete the survey. Participants indicated high confidence in knowing how to keep foods safe for consumption as well as safe food handling skills. Thermometer using skills, however, were rated lowest, which indicated a gap in food safety education.

Nowadays, the use of wild and culture harvest seaweed in food industry is a booming productive sector. In this context, a radiological characterization of five globally common seaweed species that were collected in arrival on Gran Canaria coast was carried out. The studied algae species were Cymopolia barbata, Lobophora variegata, Sargassum vulgare, Dictyota dichotoma and Haliptilon virgatum. Radionuclides analysed by alpha and gamma spectrometry were 238U, 234U, 235U, 210Po, 234Th, 226Ra, 210Pb, 228Th, 224Ra, 40K and 7Be. Activity concentrations, ratios, and concentration factors (CF) were determined for all samples collected. The CF in algae was higher for reactive-particle radionuclides (210Po, 234Th, 228Th and 210Pb) than for conservative ones (40K and the uranium isotopes). 210Po, 228Th and 234Th CF were one or two orders of magnitude higher than those recommended by the IAEA. L. variegata, C. barbata and S. vulgare showed a clear preference for 210Pb and 210Po, for uranium radioisotopes, and for 40K and 234Th, respectively. A dosimetry assessment due to seaweed ingestion showed considerable values of annual committed effective dose for H. virgatum (605 ± 19 μSv/y), L. variegata (574 ± 17 μSv/y) and D. dichotoma (540 ± 30 μSv/y). Hence, this study suggests that an algae radiological characterization is recommended as part of the product valorising process.

Knowledge of coastal sedimentary dynamics is an essential tool in the sustainable management of high-value natural places, such as beaches, which play an important role in human life. With this aim, spatio-temporal variations of activity concentrations of the main natural radionuclides in intertidal sand samples were measured in order to analyse their role as tracers of different sedimentary processes on a beach with wide and diversified sedimentary dynamics (Las Canteras beach at Gran Canaria Island). The radionuclides studied were 226Ra, 232Th, 40K and 210Pbex. A cluster analysis and a principal component analysis performed by using stationary averages of the studied radionuclides activity concentrations and other quantities, such as grain size and or bulk density, were developed. These analyses divided the beach into three zones of sediment distribution related to one of the main geomorphological characteristics of the beach. Finally, annual variations in 226Ra/228Ra ratios were used to study erosion and accretion periods on the beach.

Atrial fibrillation (AF) is the most frequent arrhythmia worldwide. While mostly seen in elderly, it can also affect young adults (≤ 45 years of age), older adolescent, and children. Areas covered: The aim of this review is to provide an overview of the current management of AF in young patients. Specific issues arise over diagnostic workup as well as antiarrhythmic and anticoagulation therapies. The future management and diagnostic strategies are also discussed. Expert commentary: Management of AF in the young adult is largely extrapolated from adult studies and guidelines. In this population, AF could reveal a genetic pathology (e.g. Brugada, Long QT or Short QT syndromes) or be the initial presentation of a cardiomyopathy. Therefore, thorough workup in the young population to eliminate potential malignant pathology.

Objectives:Cryoablation is an effective alternative treatment for cardiac arrhythmias offering shortened recovery and reduced side effects. As the use of cryoablation increases, the need for new devices and procedures has emerged. This has been driven by technological limitations including lengthy periods to generate a single lesion (3–5 min), uncertain transmurality, and differential efficacy. Furthermore, due to limited ablation capacity under high heat loads, cryo has had limited success in the treatment of ventricular arrhythmias. To this end, in this study we evaluated a new cryoablation catheter, ICEolate, for the targeted ablation of cardiac tissue.Methods:Performance assessment included calorimetry, freeze zone isothermal distribution characterization and catheter ablation capacity in a submerged, circulating, heat-loaded ex vivo tissue model. A pilot in vivo study was also conducted to assess ablative capacity of the cryocatheter in a fully beating heart.Results:Ex vivo studies demonstrated ice formation at the tip of a cryocatheter within 5 s and a tip temperature of ~−150°C within 10 s. The device repeatedly generated freeze zones of 2 cm × 3 cm in less than 2 min. Tissue model studies revealed the generation of a full thickness (5–10 mm) cryogenic lesion within 1 min with an opposite (transmural) surface temperature of Conclusion:These studies suggest that the supercritical nitrogen cryodevice and ICEolate cryocatheter may provide for rapid, effective, controllable freezing of targeted tissue. The ablative power, speed, and directional freeze characteristics also offer the potential of improved safety via a reduction in procedural time compared to current cryoablation devices. These technological developments may open new avenues for the application of cryo to treat other cardiac arrhythmogenic disorders.

The utility of genetic risk scores (GRS) as independent risk predictors remains inconclusive. Here, we evaluate the additive value of a multi-locus GRS to the Framingham risk score (FRS) in coronary artery disease (CAD) risk prediction. A total of 2888 individuals (1566 coronary patients and 1322 controls) were divided into three subgroups according to FRS. Multiplicative GRS was determined for 32 genetic variants associated to CAD. Logistic Regression and Area Under the Curve (AUC) were determined first, using the TRF for each FRS subgroup, and secondly, adding GRS. Different models (TRF, TRF+GRS) were used to classify the subjects into risk categories for the FRS 10-year predicted risk. The improvement offered by GRS was expressed as Net Reclassification Index and Integrated Discrimination Improvement. Multivariate analysis showed that GRS was an independent predictor for CAD (OR = 1.87; p

The original version of this article contained an error in the spelling of the author Christian A.M. Wilson, which was incorrectly given as Christian M.A. Wilson. This has now been corrected in both the PDF and HTML versions of the article.

Serotonin 2C receptors (5HT2C) are involved in serotonin-driven dynamic equilibrium adjustments responsible for homeostatic stability in brain structures that modulate behavior and emotions. Single nucleotide polymorphisms (SNPs) from the serotonin 2C receptor gene (HTR2C) have been associated with several neurological and mental disorders, including abnormalities in cognitive and emotional processes. The aim of this study was to evaluate the association between the rs6318 SNP of the HTR2C gene and behavioral characteristics exhibited by children and adolescents based on the Child Behavior Checklist (CBCL/6-18) inventory. Eighty-five psychiatric outpatients between 8 and 18 years of age underwent genotyping of the rs6318 SNP. The CBCL/6-18 scale was administered to their caregivers. The chi-squared test was used to assess differences in the frequency of C and G alleles of the rs6318 SNP relative to the grouped CBCL/6-18 scores; significance level was 5%. The presence of the G allele of rs6318 was found to be associated with characteristics of aggressive behavior and social problems, and aggressive behavior was found to be associated with heterozygosis in females. These findings contribute to the identification of mental and behavioral phenotypes associated with gene expression.

Blood Pressure and Atrial Fibrillation Background Hypertension is an established risk factor for new-onset atrial fibrillation (AF). However, the relationship between blood pressure and recurrent AF is less well understood. Methods and Results A pooled analysis of patient-level data from AFFIRM and AF-CHF trials was conducted on all 2,715 patients with paroxysmal or persistent AF, 68 ± 8 years, 66% male, randomized to rhythm control and followed for 40.6 ± 16.5 months. We assessed the impact of a baseline systolic blood pressure (SBP; 140 mmHg [N = 777]) on recurrent AF and proportion of time spent in AF. In patients with LVEF >40% (N = 1,719), SBP was not associated with recurrent AF in multivariate regression analyses (P = 0.752). In contrast, in patients with LVEF ≤40% (N = 996), the AF recurrence rate was higher in those with an SBP >140 mmHg compared to 120–140 mmHg (hazard ratio 1.47; 95% CI [1.12–1.93], P = 0.005). The rate of recurrent AF was similar in patients with SBP 40% (P = 0.645). However, in patients with LVEF ≤40%, the adjusted mean proportion of time spent in AF was 17.2% if SBP was 140 mmHg (P = 0.025). Conclusion Systolic blood pressure is an important determinant of recurrent AF and overall AF burden in patients with left ventricular dysfunction (LVEF≤40%) but not in those with preserved ventricular function.

Background Electrophysiological predictors of atrioventricular (AV) block after transcatheter aortic valve replacement (TAVR) are unknown. Objective We sought to assess the value of electrophysiology study before and after TAVR. Methods Seventy-five consecutive pacemaker-free patients undergoing TAVR at the Montreal Heart Institute were prospectively studied. Results Eleven patients (14.7%) developed AV block during the index hospitalization and 3 (4.0%) after hospital discharge over a median follow-up of 1.4 years (interquartile range 0.6–2.1 years). AV block developed in 5 of 6 patients with preprocedural right bundle branch block (83.3%), 8 of 30 patients with new-onset left bundle branch block (LBBB; 26.7%), and 1 of 7 patients with preexisting LBBB (14.3%). In multivariate analysis that considered all patients, the delta-HV interval (HV interval after TAVR minus HV interval before TAVR) was the only factor independently associated with AV block. In the subgroup of patients with new-onset LBBB, the postprocedural HV interval was strongly associated with AV block. By receiver operating characteristic analysis, a delta-HV interval of ≥13 ms predicted AV block with 100.0% sensitivity and 84.4% specificity and an HV interval of ≥65 ms predicted AV block with 83.3% sensitivity and 81.6% specificity. In multivariate analysis, the HV interval after TAVR (hazard ratio 1.073 per ms; 95% confidence interval 1.029–1.119; P = .001) was also independently associated with all-cause mortality. Conclusion A prolonged delta-HV interval (≥13 ms) is strongly associated with AV block after TAVR. In patients with new-onset LBBB after TAVR, a postprocedural HV interval of ≥65 ms is likewise predictive of AV block.

BACKGROUND Cardiac resynchronization therapy (CRT) implant procedures are often complex and prolonged, resulting in significant ionizing radiation (IR) exposure to the patient and operator. We report our early experience working with a novel sensor-based electromagnetic tracking system (MediGuide™, MDG, St. Jude Medical Inc., St. Paul, MN, USA), in terms of procedural IR exposure reduction. METHODS AND RESULTS Information regarding patient demographics, procedural details, procedural duration, and IR exposure were prospectively collected on 130 consecutive CRT procedures performed between January 2013 and January 2014. Sixty procedures were performed with MDG guidance, and 70 were performed without MDG guidance. Despite a nonsignificant trend toward shorter procedure duration with the use of MDG (120 minutes vs 138 minutes with non-MDG, P = 0.088), a 66% reduction in total IR exposure (median 769 μGray · m(2) vs 2,608 μGray · m(2), P 90% reduction in IR dose required to cannulate the coronary sinus (median 80 μGray · m(2) vs 922 μGray · m(2), P < 0.001), and to a lesser extent from a reduction in IR dose required for LV lead placement (median 330 μGray·m(2) vs 737 μGray · m(2), P = 0.059). In addition, a significant learning curve effect was observed with a significantly shorter procedural duration for the last 15 cases compared to the first 15 cases (median 98 minutes vs 175 minutes, P < 0.001). CONCLUSION The nonfluoroscopic MDG positioning system is associated with a dramatic reduction in exposure to IR during CRT implant procedures, with a 90% decrease in the IR dose required to cannulate the coronary sinus. A steep learning curve was quantified.

Aims To investigate the association between baseline systolic blood pressure levels and mortality in patients with AF with or without LV dysfunction. Hypertension leads to cardiovascular disease but, in specific groups, low blood pressure has been associated with a paradoxical increase in mortality. In patients with AF and heart failure, the relationship between blood pressure and death remains largely unknown. Methods and results We conducted a post-hoc combined analysis on pooled data from AFFIRM and AF-CHF trials and assessed the relationship between baseline systolic blood pressure (SBP) and mortality and hospitalizations. Patients were classified according to LVEF (>40%, ≤40%) and baseline SBP ( 140 mmHg). A total of 5436 patients with non-permanent AF were followed for 41 ± 16 months. In patients with LVEF >40%, baseline SBP was not related to mortality using multivariate Cox regression analyses to adjust for baseline differences (P = 0.563). In contrast, in patients with LVEF ≤40% (n = 1980), SBP 140 mmHg were both associated with a significant increase in total mortality compared with SBP 120–140 mmHg [hazard ratio (HR) 1.75, 95% confidence interval (CI) 1.41–2.17; and HR 1.40, 95% CI 1.04–1.90, respectively]. Hospitalizations were unrelated to SBP regardless of LVEF. Conclusions Mortality is modulated by baseline SBP levels in patients with AF and depressed EF but not in patients with normal EF. Targeted therapy of AF patients based on SBP merits further prospective investigation.

Amiodarone for Atrial Fibrillation Introduction Despite amiodarone's established safety profile in the setting of heart failure, it is unknown whether its impact on cardiovascular outcomes in patients with atrial fibrillation is modulated by left ventricular function. Methods and Results A pooled analysis of 3,307 patients (age 68.0 ± 0.2 years; 31.1% female) enrolled in AFFIRM and AF-CHF trials was conducted to assess the effect of rhythm control with amiodarone on cardiovascular outcomes, according to left ventricular systolic function. In amiodarone-treated patients (N = 1,107), freedom from recurrent atrial fibrillation was 84% and 45% at 1 and 5 years, respectively, with no differences according to left ventricular function (P = 0.8754). Similarly, the adjusted proportion of time spent in atrial fibrillation (15.0 ± 1.8%) did not vary according to ventricular function (P = 0.6094). Over 40.0 ± 0.3 months of follow-up, 1,963 (59.4%) patients required at least one hospitalization, 1,401 (42.6%) of whom had cardiovascular-related hospitalizations. Adjusted all-cause and cardiovascular hospitalization rates were similar with amiodarone versus rate control in all patients and in subgroups with and without severe left ventricular dysfunction. A total of 729 (22.0%) patients died, 498 (15.1%) from cardiovascular causes. Adjusted all-cause and cardiovascular mortality rates were similar with amiodarone versus rate control overall and in subgroups with and without severe left ventricular dysfunction. Conclusion Amiodarone's efficacy in maintaining sinus rhythm and reducing the burden of atrial fibrillation is similar in the presence or absence of severe left ventricular dysfunction. Rhythm control with amiodarone is associated with comparable hospitalization and mortality rates to rate control in patients with and without left ventricular dysfunction.

NKX2-5 is a homeobox transcription factor that is required for the formation of the heart and vessels during development, with significant postnatal down-regulation and reactivation in disease states, characterized by vascular remodeling. The purpose of this study was to investigate mechanisms that activate NKX2-5 expression in diseased vessels, such as systemic sclerosis (scleroderma; SSc)-associated pulmonary hypertension (PH), and to identify genetic variability that potentially underlies susceptibility to specific vascular complications.We explored NKX2-5 expression in biopsy samples from patients with SSc-associated PH and in pulmonary artery smooth muscle cells (PASMCs) from patients with scleroderma. Disease-associated putative functional single-nucleotide polymorphisms (SNPs) at the NKX2-5 locus were cloned and studied in reporter gene assays. SNP function was further examined through protein-DNA binding assays, chromatin immunoprecipitation assays, and RNA silencing analyses.Increased NKX2-5 expression in biopsy samples from patients with SSc-associated PH was localized to remodeled vessels and PASMCs. Meta-analysis of 2 independent scleroderma cohorts revealed an association of rs3131917 with scleroderma (P = 0.029). We demonstrated that disease-associated SNPs are located in a novel functional enhancer, which increases NKX2-5 transcriptional activity through the binding of GATA-6, c-Jun, and myocyte-specific enhancer factor 2C. We also characterized an activator/coactivator transcription-enhancer factor domain 1 (TEAD1)/Yes-associated protein 1 (YAP1) complex, which was bound at rs3095870, another functional SNP, with TEAD1 binding the risk allele and activating the transcription of NKX2-5.NKX2-5 is genetically associated with scleroderma, pulmonary hypertension, and fibrosis. Functional evidence revealed a regulatory mechanism that results in NKX2-5 transcriptional activation in PASMCs through the interaction of an upstream promoter and a novel downstream enhancer. This mechanism can act as a model for NKX2-5 activation in cardiovascular disease characterized by vascular remodeling.

Expert societies recently published strong recommendations to reduce the exposure of patients and staff to ionizing radiation (IR) during interventional and electrophysiology (EP) procedures. However, adherence to these guidelines remains difficult and the impact of implementing such recommendations is poorly characterized.We conducted a single-center cohort study to quantify radiation exposure over time in three EP laboratories at the Montreal Heart Institute during 5,546 consecutive procedures from 2012 to 2015 by 11 primary operators. Overall, 2,618 (47.2%) procedures were catheter-based and 2,928 (52.8%) were device interventions. Interventions to reduce radiation exposure included educational initiatives to raise awareness (i.e., limiting cine acquisition, patient position, table height), slower frame rate, lower radiation dose per pulse, collimation, and integration with 3-D mapping systems and/or MediGuide technology. An 85% reduction in IR exposure was observed from 2012 to 2015, with the mean dose-area-product (DAP) decreasing from 7.65 ± 0.05 Gy·cmEnforcing good clinical practices with simple measures and low-dose fluoroscopy settings are highly effective in reducing IR exposure in the EP lab. These promising results should encourage other EP labs to adopt similar protective measures.

Essential hypertension (EH) is a complex disease in which physiological, environmental, and genetic factors are involved in its genesis. The genetic variant of the alpha-adducin gene (ADD1) has been described as a risk factor for EH, but with controversial results.The objective of this study was to evaluate the association of ADD1 (Gly460Trp) gene polymorphism with the EH risk in a population from Madeira Island.A case-control study with 1614 individuals of Caucasian origin was performed, including 817 individuals with EH and 797 controls. Cases and controls were matched for sex and age, by frequency-matching method. All participants collected blood for biochemical and genotypic analysis for the Gly460Trp polymorphism. We further investigated which variables were independently associated to EH, and, consequently, analyzed their interactions.In our study, we found a significant association between the ADD1 gene polymorphism and EH (odds ratio 2.484, P = .01). This association remained statistically significant after the multivariate analysis (odds ratio 2.548, P = .02).The ADD1 Gly460Trp gene polymorphism is significantly and independently associated with EH risk in our population. The knowledge of genetic polymorphisms associated with EH is of paramount importance because it leads to a better understanding of the etiology and pathophysiology of this pathology. info:eu-repo/semantics/publishedVersion

Several genetic risk scores (GRS) have been associated with cardiovascular disease; their role, however, in survival from proven coronary artery disease (CAD) have yielded conflicting results. Objective: The objective of this study was to evaluate long- term cardiovascular mortality according to the genetic risk score in a Southern European population with CAD. Methods: A cohort of 1464 CAD patients with angiographic proven CAD were followed up prospectively for up to 58.3 (interquartile range: 25.8- 88.1) months. Genotyping of 32 single- nucleotide polymorphisms previously associated with CAD was performed using oligonucleotides probes marked with fluorescence for each allele. GRS was constructed according to the additive model assuming codominance and categorised using the median (=26). Cox Regression analysis was performed to determine independent multivariate predictors of cardiovascular mortality. Kaplan- Meier survival curves compared high vs low GRS using log- rank test. C- index was done for our population, as a measure of discrimination in survival analysis model. Results: During a mean follow- up of 58.3 months, 156 patients (10.7%) died, 107 (7.3%) of CV causes. High GRS (≥26) was associated with reduced cardiovascular survival. Survival analysis with Cox regression model adjusted for 8 variables showed that high GRS, dyslipidemia, diabetes and 3- vessel disease were independent risk factors for cardiovascular mortality (HR=1.53, P=.037; HR=3.64, P=.012; HR=1.75, P=.004; HR=2.97, P

Recent publications have shown that active RNA polymerase (RNAP) from Mycobacterium tuberculosis (MtbRNAP) can be produced by expressing all four subunits in a single recombinant Escherichia coli strain [1-3]. By reducing the number of plasmids and changing the codon usage of the Mtb genes in the co-expression system published by Banerjee et al. [1], we present a simplified, detailed and reproducible protocol for the purification of recombinant MtbRNAP containing the omega subunit. Moreover, we describe the formation of ternary elongation complexes (TECs) with a short fluorescence-labeled RNA primer and DNA oligonucleotides, suitable for transcription elongation studies. The purification of milligram quantities of the pure and highly active holoenzyme omits ammonium sulfate or polyethylene imine precipitation steps [4] and requires only 5 g of wet cells. Our results indicate that subunit assemblies other than alpha2betabeta'omega.sigma(A) can be separated by ion-exchange chromatography on Mono Q column and that assemblies with the wrong RNAP subunit stoichiometry lack transcriptional activity. We show that MtbRNAP TECs can be stalled by NTP substrate deprivation and chased upon the addition of missing NTP(s) without the need of any accessory proteins. Finally, we demonstrate the ability of the purified MtbRNAP to initiate transcription from a promoter and establish that its open promoter complexes are stabilized by the M. tuberculosis protein CarD.

Purpose – The purpose of this paper is to use data from the 2008 and 2012 US Senate elections to examine the relationship between candidate size (obese, overweight, normal weight) and candidate selection and election outcomes. Design/methodology/approach – Using pictures captured from candidate web sites, participants rated the size of candidates in the primary and general US Senate elections. χ2 analyses, t-tests and hierarchical multiple regressions were used to test for evidence of bias against overweight and obese candidates and whether gender and election information moderate that relationship. Findings – Obese candidates were largely absent from the pool of candidates in both the primary and general elections. Overweight women, but not overweight men, were also underrepresented. Supporting our hypothesis that there is bias against overweight candidates, heavier candidates tended to receive lower vote share than their thinner counterparts, and the larger the size difference between the candidates, the larger the vote share discrepancy. The paper did not find a moderating effect for gender or high-information high vs low-information elections on the relationship between candidate size and vote share. Research limitations/implications – Further research is needed to understand the process by which obese candidates are culled from the candidate pool and the cognitions underlying the biases against overweight candidates. Social implications – Because of the bias against obese political candidates, as much as one-third of the adult US population are likely to be excluded or being elected to a major political office. Originality value – This study is the first to use election data to examine whether bias based on size extends to the electoral process.

Firearm-related homicides, suicides, and unintentional injuries continue to undermine the wellbeing and safety of children and adolescents. According to 2010 statistics, homicide and suicide are the second and third leading causes of death, respectively, among youth ages 10 to 19 years. Firearms are involved in a substantial proportion of youth homicides and suicides. Despite the protective benefits of storing guns and ammunition safely, few gun-owning families do so. Health and mental health care providers in pediatric settings can play an important role in educating families about gun safety and in preventing youth involvement in gun violence. This article reviews developmental risk factors for involvement in youth gun violence, as well as evidencebased community programs to prevent gun violence. We then discuss ways in which health and mental health care providers can prevent youth gun violence and promote safety.

The standard 4-minute application time for transcatheter cryoablation was determined in the 1990s when the system employed less potent chlorofluorocarbon refrigerants. The current refrigerant, nitrous oxide, generates substantially colder temperatures, with a faster cooling rate.We conducted a preclinical study on 32 mongrel dogs with stratified randomization of right atrial, right ventricular, and left ventricular chambers to 2-minute versus 4-minute application times using 8-mm electrode tip cryocatheters (Freezor Max, Medtronic CryoCath LP, Montreal, Canada). Animals were sacrificed one month after the procedure. Three-dimensional morphometric analyses were conducted in a blinded fashion. A total of 193 identified ablation lesions were processed for histological analyses, 102 with 2-minute applications and 91 with 4-minute applications. Ablation lesion surface area (167.8 ± 21.6 mmSingle 2-minute and 4-minute application times result in catheter ablation lesions of similar size using the modern cryoablation system with nitrous oxide as a refrigerant. While these findings suggest the potential to reduce the standard 4-minute application time, further studies are required to compare clinical efficacy.

Extended molecular characterization of HLA genes in the IHWG reference B-lymphoblastoid cell lines (B-LCLs) was one of the major goals for the 17(th) International HLA and Immunogenetics Workshop (IHIW). Although reference B-LCLs have been examined extensively in previous workshops complete high-resolution typing was not completed for all the classical class I and class II HLA genes. To address this, we conducted a single-blind study where select panels of B-LCL genomic DNA samples were distributed to multiple laboratories for HLA genotyping by next-generation sequencing methods. Identical cell panels comprised of 24 and 346 samples were distributed and typed by at least four laboratories in order to derive accurate consensus HLA genotypes. Overall concordance rates calculated at both 2- and 4-field allele-level resolutions ranged from 90.4% to 100%. Concordance for the class I genes ranged from 91.7 to 100%, whereas concordance for class II genes was variable; the lowest observed at HLA-DRB3 (84.2%). At the maximum allele-resolution 78 B-LCLs were defined as homozygous for all 11 loci. We identified 11 novel exon polymorphisms in the entire cell panel. A comparison of the B-LCLs NGS HLA genotypes with the HLA genotypes catalogued in the IPD-IMGT/HLA Database Cell Repository, revealed an overall allele match at 68.4%. Typing discrepancies between the two datasets were mostly due to the lower-resolution historical typing methods resulting in incomplete HLA genotypes for some samples listed in the IPD-IMGT/HLA Database Cell Repository. Our approach of multiple-laboratory NGS HLA typing of the B-LCLs has provided accurate genotyping data. The data generated by the tremendous collaborative efforts of the 17(th) IHIW participants is useful for updating the current cell and sequence databases and will be a valuable resource for future studies.

The aim of the present study was to evaluate the effects of the inclusion of mixed (animal and vegetable sources) semi-purified glycerin (MSPG) in broiler diets on performance, litter moisture, serum glycerol concentration, carcass and parts yields, meat quality, and the fatty acid profile. In total, 576 1-day-old male Cobb 500 broiler chicks were distributed in a completely randomised design into four treatments (0%, 2.5%, 5.0% and 7.5% dietary inclusion levels of MSPG, as-fed basis), with six replicate pens of 24 birds each. The apparent metabolisable energy corrected for nitrogen balance and energy metabolisability coefficient values of the MSPG were 12.33 MJ/kg DM and 81.61% respectively. There was no significant (P > 0.05) effect of the MSPG concentration on the performance, and carcass and parts yields or broiler meat-quality variables, except for thigh meat colour, in which the yellowness value (b*) decreased linearly (P < 0.05) with an increasing inclusion level of MSPG. Litter moisture and serum glycerol increased linearly (P < 0.05) and the lipid profile of the thigh and drumstick meat of broilers at 42 days of age was slightly altered (P < 0.05) with an increasing MSPG. Mixed semi-purified glycerin can be used at up to 7.5% in broiler diets without impairing performance, meat quality, carcass and parts yields from 1 to 42 days of age. However, special attention should be paid to litter moisture.

This paper reports on the development and piloting of the Madres a Madres (Mothers to Mothers) program, a new, community-based parent training program designed for immigrant Latina mothers and their children. Promotoras, or female community health workers of Latina background, delivered the program in a home visitation format. A total of 194 mothers and 194 focal children (87 male, 107 female) ages 7-12 were randomized to the intervention (113 mother-child dyads) or wait-list control condition (81 mother-child dyads) over the study period. Outcomes of interest were mother-reported parenting skills, broad family functioning, and child externalizing and internalizing behaviors. Data collection occurred at pretest, 3-month posttest, and 9-month follow-up periods. Multilevel growth models revealed increases in intervention mothers' reported parenting skills, family support, and family organization, and reductions in child internalizing behavior from pretest to follow-up, relative to the control condition. Outcomes did not vary by focal child age, gender, nativity status, or mother acculturative status (years in the United States). Findings are discussed in the context of future directions for research on the Madres a Madres program and on the implementation and dissemination of empirically-supported parent training practices to culturally diverse families.