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5. The MSK-Tracker Study (MSK-Tracker)

Author

Pro-Mapp Limited Company number 10152526, Georgina Craig Associates Limited, University of Oxford, and Arthritis Research UK

Published
2021

7. Towards prevention of post-traumatic osteoarthritis: report from an international expert working group on considerations for the design and conduct of interventional studies following acute knee injury

Author

Watt, FE, Corp, N, Kingsbury, SR, Frobell, R, Englund, M, Felson, DT, Levesque, M, Majumdar, S, Wilson, C, Beard, DJ, Lohmander, LS, Kraus, VB, Roemer, F, Conaghan, PG, Mason, DJ, Group, Arthritis Research UK Osteoarthritis and Crystal Disease Clinical Study Group Expert Working, Adams, J, Blank, M, Batt, M, Biggs, P, Busse-Morris, M, Button, K, Calder, J, Cook, J, Edwards, C, Fisheleva, E, Hamilton, DF, Harrison, H, Holt, C, Jones, M, Jones, R, Kluzek, S, Knight, T, Nuki, G, Parekh, S, Peat, G, Pothet, C, Rainer, T, Robinson, N, Sawle, L, Vincent, T, Williams, A, Wise, E, Zhang, W, and Bierma-Zeinstra, S

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Health Sciences, Aging, Clinical Trials and Supportive Activities, Arthritis, Osteoarthritis, Patient Safety, Prevention, Physical Injury - Accidents and Adverse Effects, Clinical Research, Musculoskeletal, Good Health and Well Being, Acute Disease, Clinical Trials as Topic, Evidence-Based Medicine, Humans, Knee Injuries, Osteoarthritis, Knee, Research Design, Treatment Outcome, Injury, Outcome, Clinical trial, Knee, Considerations, Arthritis Research UK Osteoarthritis and Crystal Disease Clinical Study Group Expert Working Group, Biomedical Engineering, Human Movement and Sports Sciences, Arthritis & Rheumatology, Clinical sciences, Sports science and exercise
Abstract

ObjectiveThere are few guidelines for clinical trials of interventions for prevention of post-traumatic osteoarthritis (PTOA), reflecting challenges in this area. An international multi-disciplinary expert group including patients was convened to generate points to consider for the design and conduct of interventional studies following acute knee injury.DesignAn evidence review on acute knee injury interventional studies to prevent PTOA was presented to the group, alongside overviews of challenges in this area, including potential targets, biomarkers and imaging. Working groups considered pre-identified key areas: eligibility criteria and outcomes, biomarkers, injury definition and intervention timing including multi-modality interventions. Consensus agreement within the group on points to consider was generated and is reported here after iterative review by all contributors.ResultsThe evidence review identified 37 studies. Study duration and outcomes varied widely and 70% examined surgical interventions. Considerations were grouped into three areas: justification of inclusion criteria including the classification of injury and participant age (as people over 35 may have pre-existing OA); careful consideration in the selection and timing of outcomes or biomarkers; definition of the intervention(s)/comparator(s) and the appropriate time-window for intervention (considerations may be particular to intervention type). Areas for further research included demonstrating the utility of patient-reported outcomes, biomarkers and imaging outcomes from ancillary/cohort studies in this area, and development of surrogate clinical trial endpoints that shorten the duration of clinical trials and are acceptable to regulatory agencies.ConclusionsThese considerations represent the first international consensus on the conduct of interventional studies following acute knee joint trauma.

Published
2019

9. Understanding Acute Sarcopenia

Author

Dowager Countess Eleanor Peel Trust, University Hospital Birmingham NHS Foundation Trust, and MRC-Arthritis Research UK Centre for Musculoskeletal Ageing Research

Published
2019

26. Modelling physical resilience in ageing mice

Author

European Cooperation in Science and Technology, European Commission, Austrian Science Fund, Arthritis Research UK, Ministerio de Economía y Competitividad (España), Schosserer, Markus, Banks, Gareth, Dogan, Soner, Dungel, Peter, Fernandes, Adelaide, Marolt Presen, Darja, Matheu, Ander, Osuchowski, Marcin, Potter, Paul, Sanfeliu, Coral, Guvenc Tuna, Bilge, Varela-Nieto, Isabel, Bellantuono, Ilaria, European Cooperation in Science and Technology, European Commission, Austrian Science Fund, Arthritis Research UK, Ministerio de Economía y Competitividad (España), Schosserer, Markus, Banks, Gareth, Dogan, Soner, Dungel, Peter, Fernandes, Adelaide, Marolt Presen, Darja, Matheu, Ander, Osuchowski, Marcin, Potter, Paul, Sanfeliu, Coral, Guvenc Tuna, Bilge, Varela-Nieto, Isabel, and Bellantuono, Ilaria

Abstract

Geroprotectors, a class of drugs targeting multiple deficits occurring with age, necessitate the development of new animal models to test their efficacy. The COST Action MouseAGE is a European network whose aim is to reach consensus on the translational path required for geroprotectors, interventions targeting the biology of ageing. In our previous work we identified frailty and loss of resilience as a potential target for geroprotectors. Frailty is the result of an accumulation of deficits, which occurs with age and reduces the ability to respond to adverse events (physical resilience). Modelling frailty and physical resilience in mice is challenging for many reasons. There is no consensus on the precise definition of frailty and resilience in patients or on how best to measure it. This makes it difficult to evaluate available mouse models. In addition, the characterization of those models is poor. Here we review potential models of physical resilience, focusing on those where there is some evidence that the administration of acute stressors requires integrative responses involving multiple tissues and where aged mice showed a delayed recovery or a worse outcome then young mice in response to the stressor. These models include sepsis, trauma, drug- and radiation exposure, kidney and brain ischemia, exposure to noise, heat and cold shock.

Published
2019

27. Towards prevention of post-traumatic osteoarthritis: report from an international expert working group on considerations for the design and conduct of interventional studies following acute knee injury

Author

Watt, FE, Corp, N, Kingsbury, SR, Frobell, R, Englund, M, Felson, DT, Levesque, M, Majumdar, S, Wilson, C, Beard, DJ, Lohmander, LS, Kraus, VB, Roemer, F, Conaghan, PG, Mason, DJ, and Arthritis Research UK Osteoarthritis and Crystal Disease Clinical Study Group Expert Working Group

Subjects
Aging, Clinical Trials and Supportive Activities, Clinical Sciences, 1106 Human Movement and Sports Sciences, Biomedical Engineering, Injury, Knee Injuries, Considerations, 0903 Biomedical Engineering, Clinical Research, Osteoarthritis, Humans, Knee, Outcome, Clinical Trials as Topic, Evidence-Based Medicine, Arthritis, Prevention, 1103 Clinical Sciences, Human Movement and Sports Sciences, Osteoarthritis, Knee, Arthritis Research UK Osteoarthritis and Crystal Disease Clinical Study Group Expert Working Group, Arthritis & Rheumatology, Clinical trial, Good Health and Well Being, Treatment Outcome, Research Design, Musculoskeletal, Acute Disease, Injury (total) Accidents/Adverse Effects, Patient Safety
Abstract

Objective There are few guidelines for clinical trials of interventions for prevention of post-traumatic osteoarthritis (PTOA), reflecting challenges in this area. An international multi-disciplinary expert group including patients was convened to generate points to consider for the design and conduct of interventional studies following acute knee injury. Design An evidence review on acute knee injury interventional studies to prevent PTOA was presented to the group, alongside overviews of challenges in this area, including potential targets, biomarkers and imaging. Working groups considered pre-identified key areas: eligibility criteria and outcomes, biomarkers, injury definition and intervention timing including multi-modality interventions. Consensus agreement within the group on points to consider was generated and is reported here after iterative review by all contributors. Results The evidence review identified 37 studies. Study duration and outcomes varied widely and 70% examined surgical interventions. Considerations were grouped into three areas: justification of inclusion criteria including the classification of injury and participant age (as people over 35 may have pre-existing OA); careful consideration in the selection and timing of outcomes or biomarkers; definition of the intervention(s)/comparator(s) and the appropriate time-window for intervention (considerations may be particular to intervention type). Areas for further research included demonstrating the utility of patient-reported outcomes, biomarkers and imaging outcomes from ancillary/cohort studies in this area, and development of surrogate clinical trial endpoints that shorten the duration of clinical trials and are acceptable to regulatory agencies. Conclusions These considerations represent the first international consensus on the conduct of interventional studies following acute knee joint trauma.

Published
2018

28. Harmonising data collection from osteoarthritis studies to enable stratification: recommendations on core data collection from an Arthritis Research UK clinical studies group

Author

Kingsbury, SR, Corp, N, Watt, F, Felson, DT, O'Neill, TW, Holt, CA, Jones, RK, Conaghan, PG, Arthritis Research UK Osteoarthritis and Crystal Disease Clinical Studies Group working group, and Arden, N

Subjects
osteoarthritis, clinical trials, stratification, prognosis, personalized medicine
Abstract

OBJECTIVE: Treatment of OA by stratifying for commonly used and novel therapies will likely improve the range of effective therapy options and their rational deployment in this undertreated, chronic disease. In order to develop appropriate datasets for conducting post hoc analyses to inform approaches to stratification for OA, our aim was to develop recommendations on the minimum data that should be recorded at baseline in all future OA interventional and observational studies. METHODS: An Arthritis Research UK study group comprised of 32 experts used a Delphi-style approach supported by a literature review of systematic reviews to come to a consensus on core data collection for OA studies. RESULTS: Thirty-five systematic reviews were used as the basis for the consensus group discussion. For studies with a primary structural endpoint, core domains for collection were defined as BMI, age, gender, racial origin, comorbidities, baseline OA pain, pain in other joints and occupation. In addition to the items generalizable to all anatomical sites, joint-specific domains included radiographic measures, surgical history and anatomical factors, including alignment. To demonstrate clinical relevance for symptom studies, the collection of mental health score, self-efficacy and depression scales were advised in addition to the above. CONCLUSIONS: Currently it is not possible to stratify patients with OA into therapeutic groups. A list of core and optional data to be collected in all OA interventional and observational studies was developed, providing a basis for future analyses to identify predictors of progression or response to treatment.

Published
2017

29. Transancestral mapping and genetic load in systemic lupus erythematosus

Author

National Institute for Health Research (UK), Arthritis Research UK, Alliance for Lupus Research, Junta de Andalucía, National Institute of Arthritis and Musculoskeletal and Skin Diseases (US), National Institutes of Health (US), RILITE Foundation, Genentech Foundation, Langefeld, C. D., Ainsworth, H. C., Kelly, J. A., Comeau, M. E., Marion, M. C., Howard, T. D., Ramos, P. S., Croker, J. A., Morris, D. L., Sandling, J. K., Almlöf, J. C., Pons-Estel, Bernardo A., Pope, Janet, Raj, Prithvi, Ramsey-Goldman, Rosalind, Reveille, John D., Russell, Laurie P., Sabio, José Mario, Aguilar-Salinas, Carlos A., Scherbarth, Hugo R., Scorza, Raffaella, Seldin, Michael F., Sjowall, Christopher, Svenungsson, Elisabet, Thompson, Susan D., Toloza, Sergio M. A., Truedsson, Lennart, Tusie-Luna, Teresa, Vasconcelos, C., Vilá, Luis M., Wallace, Daniel J., Weisman, Michael H., Wither, Joan E., Bhangale, Tushar, Oksenberg, Jorge R., Rioux, John D., Gregersen, Peter K., Syvanen, Ann-Christine, Ronnblom, Lars, Criswell, Lindsey A., Jacob, Chaim O., Sivils, Kathy L., Tsao, Betty P., Schanberg, Laura E., Behrens, Timothy W., Silverman, Earl D., Alarcón-Riquelme, M. E., Kimberly, Robert P., Harley, John B., Wakeland, Edward K., Graham, Robert R., Gaffney, P. M., Vyse, Timothy J., Acevedo-Vásquez, E. M., Alarcón, G. S., Babini, A. M., Baca, V., Bengtsson, A. A., Berbotto, G. A., Bij, l. M., Brown, E. E., Brunner, H.I., Cardiel, Mario H., Catoggio, Luis, Cervera, Ricard, Cucho-Venegas, Jorge M., Dahlqvist, Solbritt Rantapaa, D'Alfonso, Sandra, Da Silva, Berta Martins, de la Rua Figueroa, Inigo, Doria, Andrea, Edberg, Jeffrey C., Endreffy, Emoke, Esquivel-Valerio, Jorge A., Fortin, Paul R., Freedman, Barry I., Frostegård, Johan, García, Mercedes A., García de la Torre, Ignacio, Gilkeson, G. S., Gladman, Dafna D., Gunnarsson, Iva, Guthridge, Joel M., Huggins, Jennifer L., James, Judith A., Kallenberg, Cees G. M., Kamen, D. L., Karp, David R., Kaufman, Kenneth M, Kottyan, Leah C., Kovacs, Laszlo, Laustrup, Helle, Lauwerys, Bernard R., Li, Quan-Zhen, Maradiaga-Cecena, Marco A., Martín, J., McCune, Joseph M., McWilliams, David R, Merrill, Joan T, Miranda, Pedro, Moctezuma, Jose F., Nath, Swapan K., Niewold, Timothy B., Orozco, Lorena, Ortego-Centeno, N., Petri, Michelle, Pineau, Christian A., National Institute for Health Research (UK), Arthritis Research UK, Alliance for Lupus Research, Junta de Andalucía, National Institute of Arthritis and Musculoskeletal and Skin Diseases (US), National Institutes of Health (US), RILITE Foundation, Genentech Foundation, Langefeld, C. D., Ainsworth, H. C., Kelly, J. A., Comeau, M. E., Marion, M. C., Howard, T. D., Ramos, P. S., Croker, J. A., Morris, D. L., Sandling, J. K., Almlöf, J. C., Pons-Estel, Bernardo A., Pope, Janet, Raj, Prithvi, Ramsey-Goldman, Rosalind, Reveille, John D., Russell, Laurie P., Sabio, José Mario, Aguilar-Salinas, Carlos A., Scherbarth, Hugo R., Scorza, Raffaella, Seldin, Michael F., Sjowall, Christopher, Svenungsson, Elisabet, Thompson, Susan D., Toloza, Sergio M. A., Truedsson, Lennart, Tusie-Luna, Teresa, Vasconcelos, C., Vilá, Luis M., Wallace, Daniel J., Weisman, Michael H., Wither, Joan E., Bhangale, Tushar, Oksenberg, Jorge R., Rioux, John D., Gregersen, Peter K., Syvanen, Ann-Christine, Ronnblom, Lars, Criswell, Lindsey A., Jacob, Chaim O., Sivils, Kathy L., Tsao, Betty P., Schanberg, Laura E., Behrens, Timothy W., Silverman, Earl D., Alarcón-Riquelme, M. E., Kimberly, Robert P., Harley, John B., Wakeland, Edward K., Graham, Robert R., Gaffney, P. M., Vyse, Timothy J., Acevedo-Vásquez, E. M., Alarcón, G. S., Babini, A. M., Baca, V., Bengtsson, A. A., Berbotto, G. A., Bij, l. M., Brown, E. E., Brunner, H.I., Cardiel, Mario H., Catoggio, Luis, Cervera, Ricard, Cucho-Venegas, Jorge M., Dahlqvist, Solbritt Rantapaa, D'Alfonso, Sandra, Da Silva, Berta Martins, de la Rua Figueroa, Inigo, Doria, Andrea, Edberg, Jeffrey C., Endreffy, Emoke, Esquivel-Valerio, Jorge A., Fortin, Paul R., Freedman, Barry I., Frostegård, Johan, García, Mercedes A., García de la Torre, Ignacio, Gilkeson, G. S., Gladman, Dafna D., Gunnarsson, Iva, Guthridge, Joel M., Huggins, Jennifer L., James, Judith A., Kallenberg, Cees G. M., Kamen, D. L., Karp, David R., Kaufman, Kenneth M, Kottyan, Leah C., Kovacs, Laszlo, Laustrup, Helle, Lauwerys, Bernard R., Li, Quan-Zhen, Maradiaga-Cecena, Marco A., Martín, J., McCune, Joseph M., McWilliams, David R, Merrill, Joan T, Miranda, Pedro, Moctezuma, Jose F., Nath, Swapan K., Niewold, Timothy B., Orozco, Lorena, Ortego-Centeno, N., Petri, Michelle, and Pineau, Christian A.

Abstract

Systemic lupus erythematosus (SLE) is an autoimmune disease with marked gender and ethnic disparities. We report a large transancestral association study of SLE using Immunochip genotype data from 27,574 individuals of European (EA), African (AA) and Hispanic Amerindian (HA) ancestry. We identify 58 distinct non-HLA regions in EA, 9 in AA and 16 in HA (similar to 50% of these regions have multiple independent associations); these include 24 novel SLE regions (P < 5 x 10(-8)), refined association signals in established regions, extended associations to additional ancestries, and a disentangled complex HLA multigenic effect. The risk allele count (genetic load) exhibits an accelerating pattern of SLE risk, leading us to posit a cumulative hit hypothesis for autoimmune disease. Comparing results across the three ancestries identifies both ancestry-dependent and ancestry-independent contributions to SLE risk. Our results are consistent with the unique and complex histories of the populations sampled, and collectively help clarify the genetic architecture and ethnic disparities in SLE.

Published
2017

30. Harmonising collection of data from osteoarthritis studies to enable stratification: Recommendations on core data collection from an Arthritis Research UK clinical studies group

Author

Kingsbury, SR, Corp, N, Watt, FE, Felson, DT, O'Neil, TW, Holt, CA, Jones, RK, Conaghan, PG, Arthritis Research UK working group, and Arden, NK

Abstract

Objective: Treatment of OA by stratifying for commonly used and novel therapies will likely improve the range of effective therapy options and their rational deployment in this undertreated, chronic disease. In order to develop appropriate datasets for conducting post hoc analyses to inform approaches to stratification for OA, our aim was to develop recommendations on the minimum data that should be recorded at baseline in all future OA interventional and observational studies. Methods: An Arthritis Research UK study group comprised of 32 experts used a Delphi-style approach supported by a literature review of systematic reviews to come to a consensus on core data collection for OA studies. Results: Thirty-five systematic reviews were used as the basis for the consensus group discussion. For studies with a primary structural endpoint, core domains for collection were defined as BMI, age, gender, racial origin, comorbidities, baseline OA pain, pain in other joints and occupation. In addition to the items generalizable to all anatomical sites, joint-specific domains included radiographic measures, surgical history and anatomical factors, including alignment. To demonstrate clinical relevance for symptom studies, the collection of mental health score, self-efficacy and depression scales were advised in addition to the above. Conclusions: Currently it is not possible to stratify patients with OA into therapeutic groups. A list of core and optional data to be collected in all OA interventional and observational studies was developed, providing a basis for future analyses to identify predictors of progression or response to treatment.

Published
2016

31. Consequences of cardiovascular disease and osteoarthritis comorbidity on short and long-term physical health change in general practice

Author

Prior, James Andrew and Arthritis Research UK Primary Care Centre

Subjects
mental disorders, R1
Abstract

Comorbidity is defined as experiencing an ‘index’ health condition with one or more other conditions at the same time. The prevalence of comorbidity, in particular chronic disease comorbidity, is set to rise in ageing Western populations and negatively influences patient health and health care services. However, our understanding of how specific comorbid chronic disease combinations (such as cardiovascular disease and osteoarthritis) interact, the subsequent outcomes and how severity influences these remains limited. The aim of this thesis was to investigate the consequences of cardiovascular disease and osteoarthritis comorbidity on short and long-term physical health change in general practice populations.

Published
2013

32. Depression and anxiety coexisting with osteoarthritis in primary care: from recognition to management

Author

Rzewuska, Magdalena, Arthritis Research UK Primary Care Centre, Mallen, CD, Peat, G, and Belcher, J

Subjects
RC0321
Abstract

Osteoarthritis (OA), depression and anxiety are common problems in primary care. OA coexisting with depressive and/or anxiety symptoms has detrimental consequences to the individual. To inform recognition and management of these important problems in primary care a better understanding of their coexistence is needed. \ud A systematic review with meta-analysis was undertaken to determine the prevalence of depression and anxiety in adults with OA/joint pain in the community. Elevated anxiety symptoms were more common (45%) than depression symptoms (24%) in persons with OA joint pain. Sources of between study variance include methods of ascertainment and geographical location. A review of measurement properties of several recommended patient-reported depression and anxiety measures found evidence to support properties in some populations, but some critical properties warrant investigation in adults with OA in the community. \ud A secondary data analysis was conducted for older consecutive primary care patients with musculoskeletal pain recruited to a cohort (n=443) of the PROGnostic Research study. Latent Class Growth Analyses identified clusters of individuals who exhibited different trajectories of anxiety and depression symptoms over a 12-month period: three anxiety and two depression symptom trajectories. In total, 56% and 63% of participants experienced persistent anxiety and depression symptoms respectively for at least 12 months. Pain characteristics and coping strategies were the most prominent risk factors for persistent anxiety and depression symptoms. With the aim of identifying individuals with sub- threshold persistent anxiety and depression symptoms, characteristics predisposing to symptoms persistence may be considered. \ud A medical records review found that only half of all older musculoskeletal patients with persistent anxiety and depression symptoms have their mental health problems detected by their GP. Frequent consulters and those with more severe anxiety were more likely to be detected. This reinforces the need to recognise and manage OA coexisting with depression and/or anxiety by patients and health professionals alike.

Published
2013

33. Statistical analysis of randomised controlled trials: a simulation and empirical study of methods of covariate adjustment

Author

Egbewale, Bolaji Emmanuel and Arthritis Research UK Primary Care Centre

Subjects
R1
Abstract

Randomised controlled trials (RCTs) are widely accepted as the optimum design for comparing two or more medical therapies. Chance baseline imbalance (BI) through randomization opens the estimate of effect to bias. Statistical methods such as change score analysis (CSA) and analysis of covariance (ANCOVA) - are commonly used to deal with BI. However, unadjusted analysis by analysis of variance (ANOVA) is still common.\ud \ud This study examined precision, power, efficiency and bias of estimates of effect associated with ANOVA, CSA and ANCOVA in RCTs with a single post-treatment assessment of a continuous outcome variable. A total of 210 hypothetical trial scenarios were evaluated; each was simulated (1000 iterations per scenario) using combinations of specific levels of treatment effect, covariate-outcome correlation, direction and level of BI. Evaluation was also performed on three empirical trial datasets, which showed different baseline-outcome correlations.\ud \ud Precision and efficiency of CSA were not better than those of ANOVA unless baseline-outcome correlation exceeded 0.5. Depending on the level of baseline-outcome correlation, the sample size required at a given level of nominal power can be reduced by up to 80% using ANCOVA. Conditionally, both ANOVA and CSA are prone to false-negative or false-positive error. When BI exists in the same direction as treatment effect, the conditional power to detect the unbiased effect by ANCOVA falls below the nominal power in most trial scenarios. Also the review of current practices regarding covariate adjustment shows that whereas over 60% adopt appropriate (modelling and stratified analysis) statistical adjustment, the most widely used single analytical approach is change. Overall, minimum covariate-outcome correlation of 0.3 is necessary but not sufficient to consider a covariate for inclusion in the model for adjustment. Appropriateness of CSA depends largely on baseline-outcome correlation and direction of imbalance. ANOVA is reasonable if the prognostic strength of the covariate is low. ANCOVA is the optimum statistical strategy regardless of BI.

Published
2012

34. The 2010 American College of Rheumatology/European League Against Rheumatism classification criteria for rheumatoid arthritis: Phase 2 methodological report

Author

University of Michigan, Ann Arbor, Boston University School of Medicine, Boston, Massachusetts, Medical University of Vienna, Vienna, Austria ; Dr. Aletaha has received consulting fees, speaking fees, and/or honoraria from Abbott, Bristol-Myers Squibb, UCB, Schering-Plough, Wyeth, and Roche (less than $10,000 each)., Arthritis Research UK, Chesterfield, UK, Ministry of Health, Auckland, New Zealand ; Dr. Naden has received consulting fees from the American College of Rheumatology in regard to the methodology of developing weighted scoring systems (more than $10,000)., University of Pittsburgh, Pittsburgh, Pennsylvania, Johns Hopkins University, Baltimore, Maryland ; Dr. Bingham has received consulting fees, speaking fees, and/or honoraria from UCB, Roche, Genentech, Celgene, and Merck Serono (less than $10,000 each); he has received research and/or educational grant support from Bristol-Myers Squibb, Genentech, UCB, Centocor, Abbott, and Amgen., California Pacific Medical Center and University of California, San Francisco ; Dr. Birnbaum has received consulting fees, speaking fees, and/or honoraria from Amgen, Pfizer, Centocor, Abbott, and UCB (less than $10,000 each)., Charit?? Hospital???University Medicine Berlin, Free University and Humboldt University, Berlin, Germany ; Dr. Burmester has received consulting fees, speaking fees, and/or honoraria from Abbott, Bristol-Myers Squibb, Pfizer, UCB, and Roche (less than $10,000 each)., Mount Sinai Hospital and University of Toronto, Toronto, Ontario, Canada ; Dr. Bykerk has received consulting fees, speaking fees, and/or honoraria from Amgen, Wyeth, Abbott, Schering-Plough, Roche, Bristol-Myers Squibb, and UCB (less than $10,000 each); her spouse is employed by Genzyme and owns stock in the company., National Jewish Medical and Research Center, Denver, Colorado ; Dr. Cohen has received consulting fees, speaking fees, and/or honoraria from UCB, Genentech, Bristol-Myers Squibb, and Human Genome Sciences (less than $10,000 each)., Lapeyronie Hospital and Montpellier I University, Montpellier, France ; Dr. Combe has received consulting fees, speaking fees, and/or honoraria from Abbott, Bristol-Myers Squibb, Pfizer, Roche, Schering-Plough, and Merck, Sharpe, and Dohme (less than $10,000 each)., Brigham and Women's Hospital and Harvard University, Boston, Massachusetts, Cochin Hospital, Assistance Publique H??pitaux de Paris, and Paris-Descartes University, Paris, France, University of Leeds and NIHR Leeds Biomedical Research Unit, Leeds, UK ; Dr. Emery has received consulting fees, speaking fees, and/or honoraria from Pfizer, Abbott, Centocor, UCB, Roche, Bristol-Myers Squibb, and Merck, Sharpe, and Dohme (less than $10,000 each)., School of Medicine, Catholic University of the Sacred Heart, Rome, Italy ; Dr. Ferraccioli holds a patent for T cell receptor clonotype analysis (PCT/IB 2008/053152 NP)., Erasmus Medical Center and University of Rotterdam, Rotterdam, The Netherlands, University of Colorado School of Medicine, Denver, Leiden University Medical Center, Leiden, The Netherlands ; Dr. Huizinga has received consulting fees, speaking fees, and/or honoraria from Schering-Plough, Bristol-Myers Squibb, UCB, Biotest AG, Wyeth/Pfizer, Novartis, Roche, Sanofi-Aventis, Abbott, and Axis-Shield (less than $10,000 each)., University of California, San Diego ; Dr. Kavanaugh has conducted clinical research for Amgen, Abbott, Bristol-Myers Squibb, UCB, Roche, Centocor, Genentech, and Sanofi-Aventis., UMassMemorial Medical Center and University of Massachusetts Medical School, Worcester ; Dr. Kay has received consulting fees from Array BioPharma, Bristol-Myers Squibb, Celgene, Centocor, Genentech, Roche, UCB, and Sanofi-Aventis (less than $10,000 each)., David Geffen School of Medicine at University of California, Los Angeles ; Dr. Khanna has received consulting fees, speaking fees, and/or honoraria from UCB and Abbott (less than $10,000 each)., Diakonhjemmet Hospital, Oslo, Norway, Swedish Medical Center and University of Washington, Seattle ; Dr. Mease has received consulting fees, speaking fees, and/or honoraria from Abbott, Amgen, Biogen Idec, Bristol-Myers Squibb, Centocor, Roche, Genentech, UCB, Pfizer, Novartis, and Eli Lilly (less than $10,000 each)., McGill University Health Centre and McGill University, Montreal, Quebec, Canada ; Dr. M??nard has received unrestricted educational and research grants as well as consulting and speaking fees from Abbott, Amgen, Inova, Merck, Pfizer, Roche, Schering-Plough, UCB, and Wyeth (less than $10,000 each) and investigator-initiated research grants from Bristol-Myers Squibb, EuroImmun AG, and Roche (more than $10,000 each); he owns stock or stock options in Merck; and he has a license agreement with EuroImmun AG for an anti-Sa enzyme-linked immunosorbent assay., University of Pittsburgh, Pittsburgh, Pennsylvania ; Dr. Moreland has received consulting fees, speaking fees, and/or honoraria from Biogen Idec, Centocor, Pfizer, Takeda, KaloBios, ChemoCentryx, UCB, Genentech, Incyte, and Eli Lilly (less than $10,000 each)., University of North Carolina, Chapel Hill, New York University Hospital for Joint Diseases, New York, New York ; Dr. Pincus has received consulting fees, speaking fees, and/or honoraria from Amgen, Abbott, Bristol-Myers Squibb, Centocor, UCB, Wyeth, and Genentech (less than $10,000 each) and investigator-initiated research grants from Amgen, Bristol-Myers Squibb, UCB, and Centocor., Seattle Children's Hospital, Seattle, Washington, Medical University of Vienna, Vienna, Austria, Institute of Rheumatology, Warsaw, Poland ; Dr. Stanislawska-Biernat has received speaking fees from Abbott and Pfizer (less than $10,000 each)., University of Manchester, Manchester, UK, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands, UMassMemorial Medical Center and University of Massachusetts Medical School, Worcester, Institute of Rheumatology, Prague, Czech Republic ; Dr. Vencovsk?? has received speaking fees from Pfizer, UCB, Abbott, Roche, and Merck, Sharpe, and Dohme (less than $10,000 each)., National Data Bank for Rheumatic Diseases and University of Kansas, Wichita, Women's College Hospital and University of Toronto, Toronto, Ontario, Canada ; Department of Medicine, Women's College Hospital, 76 Grenville Street, 8th Floor, Room 815, Toronto, Ontario M5S 1B2, Canada, Neogi, Tuhina, Aletaha, Daniel, Silman, Alan J., Naden, Raymond L., Felson, David T., Aggarwal, Rohit, Bingham, Clifton O., Birnbaum, Neal S., Burmester, Gerd R., Bykerk, Vivian P., Cohen, Marc D., Combe, Bernard, Costenbader, Karen H., Dougados, Maxime, Emery, Paul, Ferraccioli, Gianfranco, Hazes, Johanna M. W., Hobbs, Kathryn, Huizinga, Tom W. J., Kavanaugh, Arthur, Kay, Jonathan, Khanna, Dinesh, Kvien, Tore K., Laing, Timothy, Liao, Katherine, Mease, Philip, M??nard, Henri A., Moreland, Larry W., Nair, Raj, Pincus, Theodore, Ringold, Sarah, Smolen, Josef S., Stanislawska-Biernat, Ewa, Symmons, Deborah, Tak, Paul P., Upchurch, Katherine S., Vencovsk??, Jir??, Wolfe, Frederick, Hawker, Gillian, University of Michigan, Ann Arbor, Boston University School of Medicine, Boston, Massachusetts, Medical University of Vienna, Vienna, Austria ; Dr. Aletaha has received consulting fees, speaking fees, and/or honoraria from Abbott, Bristol-Myers Squibb, UCB, Schering-Plough, Wyeth, and Roche (less than $10,000 each)., Arthritis Research UK, Chesterfield, UK, Ministry of Health, Auckland, New Zealand ; Dr. Naden has received consulting fees from the American College of Rheumatology in regard to the methodology of developing weighted scoring systems (more than $10,000)., University of Pittsburgh, Pittsburgh, Pennsylvania, Johns Hopkins University, Baltimore, Maryland ; Dr. Bingham has received consulting fees, speaking fees, and/or honoraria from UCB, Roche, Genentech, Celgene, and Merck Serono (less than $10,000 each); he has received research and/or educational grant support from Bristol-Myers Squibb, Genentech, UCB, Centocor, Abbott, and Amgen., California Pacific Medical Center and University of California, San Francisco ; Dr. Birnbaum has received consulting fees, speaking fees, and/or honoraria from Amgen, Pfizer, Centocor, Abbott, and UCB (less than $10,000 each)., Charit?? Hospital???University Medicine Berlin, Free University and Humboldt University, Berlin, Germany ; Dr. Burmester has received consulting fees, speaking fees, and/or honoraria from Abbott, Bristol-Myers Squibb, Pfizer, UCB, and Roche (less than $10,000 each)., Mount Sinai Hospital and University of Toronto, Toronto, Ontario, Canada ; Dr. Bykerk has received consulting fees, speaking fees, and/or honoraria from Amgen, Wyeth, Abbott, Schering-Plough, Roche, Bristol-Myers Squibb, and UCB (less than $10,000 each); her spouse is employed by Genzyme and owns stock in the company., National Jewish Medical and Research Center, Denver, Colorado ; Dr. Cohen has received consulting fees, speaking fees, and/or honoraria from UCB, Genentech, Bristol-Myers Squibb, and Human Genome Sciences (less than $10,000 each)., Lapeyronie Hospital and Montpellier I University, Montpellier, France ; Dr. Combe has received consulting fees, speaking fees, and/or honoraria from Abbott, Bristol-Myers Squibb, Pfizer, Roche, Schering-Plough, and Merck, Sharpe, and Dohme (less than $10,000 each)., Brigham and Women's Hospital and Harvard University, Boston, Massachusetts, Cochin Hospital, Assistance Publique H??pitaux de Paris, and Paris-Descartes University, Paris, France, University of Leeds and NIHR Leeds Biomedical Research Unit, Leeds, UK ; Dr. Emery has received consulting fees, speaking fees, and/or honoraria from Pfizer, Abbott, Centocor, UCB, Roche, Bristol-Myers Squibb, and Merck, Sharpe, and Dohme (less than $10,000 each)., School of Medicine, Catholic University of the Sacred Heart, Rome, Italy ; Dr. Ferraccioli holds a patent for T cell receptor clonotype analysis (PCT/IB 2008/053152 NP)., Erasmus Medical Center and University of Rotterdam, Rotterdam, The Netherlands, University of Colorado School of Medicine, Denver, Leiden University Medical Center, Leiden, The Netherlands ; Dr. Huizinga has received consulting fees, speaking fees, and/or honoraria from Schering-Plough, Bristol-Myers Squibb, UCB, Biotest AG, Wyeth/Pfizer, Novartis, Roche, Sanofi-Aventis, Abbott, and Axis-Shield (less than $10,000 each)., University of California, San Diego ; Dr. Kavanaugh has conducted clinical research for Amgen, Abbott, Bristol-Myers Squibb, UCB, Roche, Centocor, Genentech, and Sanofi-Aventis., UMassMemorial Medical Center and University of Massachusetts Medical School, Worcester ; Dr. Kay has received consulting fees from Array BioPharma, Bristol-Myers Squibb, Celgene, Centocor, Genentech, Roche, UCB, and Sanofi-Aventis (less than $10,000 each)., David Geffen School of Medicine at University of California, Los Angeles ; Dr. Khanna has received consulting fees, speaking fees, and/or honoraria from UCB and Abbott (less than $10,000 each)., Diakonhjemmet Hospital, Oslo, Norway, Swedish Medical Center and University of Washington, Seattle ; Dr. Mease has received consulting fees, speaking fees, and/or honoraria from Abbott, Amgen, Biogen Idec, Bristol-Myers Squibb, Centocor, Roche, Genentech, UCB, Pfizer, Novartis, and Eli Lilly (less than $10,000 each)., McGill University Health Centre and McGill University, Montreal, Quebec, Canada ; Dr. M??nard has received unrestricted educational and research grants as well as consulting and speaking fees from Abbott, Amgen, Inova, Merck, Pfizer, Roche, Schering-Plough, UCB, and Wyeth (less than $10,000 each) and investigator-initiated research grants from Bristol-Myers Squibb, EuroImmun AG, and Roche (more than $10,000 each); he owns stock or stock options in Merck; and he has a license agreement with EuroImmun AG for an anti-Sa enzyme-linked immunosorbent assay., University of Pittsburgh, Pittsburgh, Pennsylvania ; Dr. Moreland has received consulting fees, speaking fees, and/or honoraria from Biogen Idec, Centocor, Pfizer, Takeda, KaloBios, ChemoCentryx, UCB, Genentech, Incyte, and Eli Lilly (less than $10,000 each)., University of North Carolina, Chapel Hill, New York University Hospital for Joint Diseases, New York, New York ; Dr. Pincus has received consulting fees, speaking fees, and/or honoraria from Amgen, Abbott, Bristol-Myers Squibb, Centocor, UCB, Wyeth, and Genentech (less than $10,000 each) and investigator-initiated research grants from Amgen, Bristol-Myers Squibb, UCB, and Centocor., Seattle Children's Hospital, Seattle, Washington, Medical University of Vienna, Vienna, Austria, Institute of Rheumatology, Warsaw, Poland ; Dr. Stanislawska-Biernat has received speaking fees from Abbott and Pfizer (less than $10,000 each)., University of Manchester, Manchester, UK, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands, UMassMemorial Medical Center and University of Massachusetts Medical School, Worcester, Institute of Rheumatology, Prague, Czech Republic ; Dr. Vencovsk?? has received speaking fees from Pfizer, UCB, Abbott, Roche, and Merck, Sharpe, and Dohme (less than $10,000 each)., National Data Bank for Rheumatic Diseases and University of Kansas, Wichita, Women's College Hospital and University of Toronto, Toronto, Ontario, Canada ; Department of Medicine, Women's College Hospital, 76 Grenville Street, 8th Floor, Room 815, Toronto, Ontario M5S 1B2, Canada, Neogi, Tuhina, Aletaha, Daniel, Silman, Alan J., Naden, Raymond L., Felson, David T., Aggarwal, Rohit, Bingham, Clifton O., Birnbaum, Neal S., Burmester, Gerd R., Bykerk, Vivian P., Cohen, Marc D., Combe, Bernard, Costenbader, Karen H., Dougados, Maxime, Emery, Paul, Ferraccioli, Gianfranco, Hazes, Johanna M. W., Hobbs, Kathryn, Huizinga, Tom W. J., Kavanaugh, Arthur, Kay, Jonathan, Khanna, Dinesh, Kvien, Tore K., Laing, Timothy, Liao, Katherine, Mease, Philip, M??nard, Henri A., Moreland, Larry W., Nair, Raj, Pincus, Theodore, Ringold, Sarah, Smolen, Josef S., Stanislawska-Biernat, Ewa, Symmons, Deborah, Tak, Paul P., Upchurch, Katherine S., Vencovsk??, Jir??, Wolfe, Frederick, and Hawker, Gillian

Abstract

Objective The American College of Rheumatology and the European League Against Rheumatism have developed new classification criteria for rheumatoid arthritis (RA). The aim of Phase 2 of the development process was to achieve expert consensus on the clinical and laboratory variables that should contribute to the final criteria set. Methods Twenty-four expert RA clinicians (12 from Europe and 12 from North America) participated in Phase 2. A consensus-based decision analysis approach was used to identify factors (and their relative weights) that influence the probability of ???developing RA,??? complemented by data from the Phase 1 study. Patient case scenarios were used to identify and reach consensus on factors important in determining the probability of RA development. Decision analytic software was used to derive the relative weights for each of the factors and their categories, using choice-based conjoint analysis. Results The expert panel agreed that the new classification criteria should be applied to individuals with undifferentiated inflammatory arthritis in whom at least 1 joint is deemed by an expert assessor to be swollen, indicating definite synovitis. In this clinical setting, they identified 4 additional criteria as being important: number of joints involved and site of involvement, serologic abnormality, acute-phase response, and duration of symptoms in the involved joints. These criteria were consistent with those identified in the Phase 1 data-driven approach. Conclusion The consensus-based, decision analysis approach used in Phase 2 complemented the Phase 1 efforts. The 4 criteria and their relative weights form the basis of the final criteria set.

Published
2010

35. The effect of oral essential amino acids on incretin hormone production in youth and ageing

Author

Arthritis Research UK, Medical Research Council, Abdulla, Haitham, Bass, Joseph J., Stokes, Tanner, Gorissen, Stefan H.M., McGlory, Chris, Phillips, Bethan E., Phillips, Stuart M., Smith, Kenneth, Idris, Iskandar, Atherton, Philip J., Arthritis Research UK, Medical Research Council, Abdulla, Haitham, Bass, Joseph J., Stokes, Tanner, Gorissen, Stefan H.M., McGlory, Chris, Phillips, Bethan E., Phillips, Stuart M., Smith, Kenneth, Idris, Iskandar, and Atherton, Philip J.

Abstract

peer-reviewed, The effect of substantive doses of essential amino acids (EAA) on incretin and insulin production, and the impact of age upon this effect, is ill‐defined. Methods: A 15‐g oral EAA drink was administered to young (N = 8; 26 ± 4.4 years) and older (N = 8; 69 ± 3.8 years) healthy volunteers. Another group of younger volunteers (N = 9; 21 ± 1.9 years) was given IV infusions to achieve equivalent plasma amino acids (AA) profiles. Plasma AA, insulin, glucagon‐like peptide‐1 (GLP‐1) and glucose‐dependent insulinotropic peptide (GIP) were quantified over 2 hours. Results: In younger recruits, EAA‐induced rapid insulinaemia and aminoacidaemia with total amino acids(AA), EAA and branched chain amino acids (BCAA) matched between oral and IV groups. Insulin peaked at 39 ± 29 pmol L−1 at 30 minutes following oral feeding compared to 22 ± 9 pmol L−1 at 60 minutes following IV feeding (P: NS). EAA peaked at 3395 μmol L−1 at 45 minutes during IV infusion compared to 2892 μmol L−1 following oral intake (Feeding effect: P < 0.0001. Oral vs IV feeding: P: NS). There was an 11% greater increase in insulin levels in the 120 minutes duration of the study in response to oral EAA as opposed to IV EAA. GIP increased following oral EAA (452 pmol L−1 vs 232 pmol L−1, P < 0.05). Age did not impact insulin or incretins production. Conclusion: Postprandial rises in EAA levels lead to rapid insulinaemia which is higher with oral compared with IV EAA, that is attributed more to GIP and unaffected by age. This finding supports EAA, on their own or as part of high‐protein meal, as nutritive therapeutics in impaired glycaemia and ageing.

36. Loss of adenylyl cyclase 6 in leptin receptor-expressing stromal cells attenuates loading-induced endosteal bone formation

Author

SFI, IRC, ERC, Biotechnology and Biological Sciences Research Council, Arthritis Research UK, European Union (EU), ERDF, Riffault, Mathieu, Johnson, Gillian P., Owen, Madeline M., Javaheri, Behzad, Pitsillides, Andrew A., Hoey, David A., SFI, IRC, ERC, Biotechnology and Biological Sciences Research Council, Arthritis Research UK, European Union (EU), ERDF, Riffault, Mathieu, Johnson, Gillian P., Owen, Madeline M., Javaheri, Behzad, Pitsillides, Andrew A., and Hoey, David A.

Abstract

peer-reviewed, Bone marrow stromal/stem cells represent a quiescent cell population that replenish the osteoblast bone-forming cell pool with age and in response to injury, maintaining bone mass and repair. A potent mediator of stromal/stem cell differentiation in vitro and bone formation in vivo is physical loading, yet it still remains unclear whether loading-induced bone formation requires the osteogenic differentiation of these resident stromal/stem cells. Therefore, in this study, we utilized the leptin receptor (LepR) to identify and trace the contribution of bone marrow stromal cells to mechanoadaptation of bone in vivo. Twelve-week-old Lepr-cre;tdTomato mice were subjected to compressive tibia loading with an 11 N peak load for 40 cycles, every other day for 2 weeks. Histological analysis revealed that Lepr-cre;tdTomato+ cells arise perinatally around blood vessels and populate bone surfaces as lining cells or osteoblasts before a percentage undergo osteocytogenesis. Lepr-cre;tdTomato+ stromal cells within the marrow increase in abundance with age, but not following the application of tibial compressive loading. Mechanical loading induces an increase in bone mass and bone formation parameters, yet does not evoke an increase in Lepr-cre;tdTomato+ osteoblasts or osteocytes. To investigate whether adenylyl cyclase-6 (AC6) in LepR cells contributes to this mechanoadaptive response, Lepr-cre;tdTomato mice were further crossed with AC6fl/fl mice to generate a LepR+ cell-specific knockout of AC6. These Lepr-cre;tdTomato;AC6fl/fl animals have an attenuated response to compressive tibia loading, characterized by a deficient load-induced osteogenic response on the endosteal bone surface. This, therefore, shows that Lepr-cre;tdTomato+ cells contribute to short-term bone mechanoadaptation. © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

37. Global, regional, and national disability-adjusted life years (DALYs) for 306 diseases and injuries and healthy life expectancy (HALE) for 188 countries, 1990-2013

Author

Meghan D. Mooney, Ken Takahashi, Andrea Stewart, Jonathan C Brown, Shireen Sindi, Amany H Refaat, Ruben Castro, Sara Sheikhbahaei, Kyle R. Heuton, Gillian M. Hansen, Chante Karimkhani, Bryan K. Phillips, Ibrahim Abubakar, Yohannes Kinfu, Victoria F Bachman, Konstantinos Stroumpoulis, Megan Coggeshall, Lucía Cuevas-Nasu, Yichong Li, Vineet K. Chadha, Andrew G. M. Bulloch, Takayoshi Ohkubo, Don C. Des Jarlais, Giancarlo Logroscino, Francis Apolinary Mhimbira, Jefferson G Fernandes, Cheng Huang, Ejaz Ahmad Khan, Fortuné Gbètoho Gankpé, Roderick J Hay, Itamar S. Santos, Zanfina Ademi, Fiona J Charlson, Norlinah Mohamed Ibrahim, Anwar Rafay, Andrew L. Thorne-Lyman, Juanita A. Haagsma, Emmanuel A. Ameh, John J. McGrath, Massimo Cirillo, Wubegzier Mekonnen, Holly Hagan, Naohiro Yonemoto, Frida Namnyak Ngalesoni, Dietrich Plass, Matias Trillini, David Phillips, Braden Te Ao, Wanqing Chen, Yun Jin Kim, David Rojas-Rueda, Christina Papachristou, Andrew E. Moran, Richard A. Gosselin, Maziar Moradi-Lakeh, Soraya Seedat, Janet L Leasher, Belinda K Lloyd, Lorenzo Monasta, Bruno F. Sunguya, Eun-Kee Park, Eduardo A. Undurraga, Mohammad A. AlMazroa, Mohammad H. Forouzanfar, Young-Ho Khang, Vasiliki Stathopoulou, Dima M. Qato, James Scott, Ileana Heredia-Pi, Luca Ronfani, Haidong Kan, Tasara T. Mazorodze, Murugesan Raju, Saeid Shahraz, Taavi Tillmann, Wang Wenzhi, Neil Pearce, Eric Y. Tenkorang, Aliya Naheed, Ferrán Catalá-López, Sudan Prasad Neupane, Emily Dansereau, Michael McKee, Derrick A Bennett, Mazeda Hossain, Paul S. F. Yip, Grant Nguyen, Norberto Perico, Miguel Angel Alegretti, Babak Eshrati, Boris Bikbov, Palwasha Anwari, Guoqing Hu, Amelia Bertozzi-Villa, Peter A. Meaney, Farshad Farzadfar, Svetlana Popova, Tara Templin, Hmwe H Kyu, Uche S. Uchendu, Kebede Deribe, Sergey Soshnikov, Nobhojit Roy, Daniel Kim, Ilana N. Ackerman, Homie Razavi, Leslie T. Cooper, Sandra Nolte, David T. Felson, John J Huang, Yang Liu, Fiorella Cavalleri, Adrian Davis, Héctor Gómez Dantés, Klara Dokova, Yuantao Hao, Catalina Medina, Austin E Schumacher, Stan Biryukov, Jane Rowley, Arindam Basu, Jose C. Adsuar, Rosana E. Norman, Yousef Khader, Rafael Alfonso-Cristancho, Sukanta Saha, Simón Barquera, Diego Gonzalez-Medina, Philip B. Mitchell, Lars Barregard, Haidong Wang, Yongmei Li, Ami R. Moore, Marie Ng, Raghib Ali, Peter T. Serina, Lijing L Yan, Ayse Abbasoglu Ozgoren, Ricky Leung, Michelle L. Bell, Tim Driscoll, Azmeraw T. Amare, Farshad Pourmalek, Tea Lallukka, Benjamin O Anderson, Raimundas Lunevicius, Corine Karema, Robert G. Weintraub, Erin C Mullany, Anders Larsson, Glen Mola, Paulo A. Lotufo, Luke Nyakarahuka, Sayed Saidul Alam, Louisa Degenhardt, Hugh R. Taylor, E. Ray Dorsey, Suzanne Polinder, Hilton Lam, Urbano Fra Paleo, David Zonies, Rahman Shiri, Marco A Avila, Alicia Elena Beatriz Lawrynowicz, Katya Anne Shackelford, Lynne Gaffikin, Konstantin Kazanjan, Mark T Mackay, Jasvinder A. Singh, Bryan L. Sykes, Sadaf G. Sepanlou, Chantal Huynh, Rakhi Dandona, Logan Sandar, Lavanya Singh, Dietrich Rothenbacher, Theo Vos, Steven E. Lipshultz, Coen H. Van Gool, Peggy P. Chiang, Mark G. Shrime, Christopher J L Murray, Scott Weichenthal, Jae-Hyun Park, Samia Alhabib, Philimon Gona, Christian Kieling, Yuichiro Yano, Ronny Westerman, Thomas Truelsen, Rajeev Gupta, Megan Bohensky, Abdullatif Husseini, Qing Lan, Luke D. Knibbs, Yousef M. Elshrek, H. Ross Anderson, Guohong Jiang, Madeline L. Moyer, Vinod K. Paul, Wim H. van Brakel, Emin Murat Tuzcu, Kara Estep, Lalit Dandona, Uchechukwu K.A. Sampson, Mohammad Tavakkoli, Ying Jiang, Joseph A Wagner, Mitsuru Mukaigawara, In-Hwan Oh, Siyi Shangguan, Noela M. Prasad, Charles D.A. Wolfe, Borja del Pozo-Cruz, Gokalp Kadri Yentur, Hilda L Harb, Elena Alvarez, Carlos A Castañeda-Orjuela, Mustafa Z. Younis, Herbert C. Duber, Erica Leigh Slepak, George A. Mensah, Knud Juel, Graeme J. Hankey, Natan M. Bornstein, Martha Híjar, Johan Ärnlöv, Mohamed Hsairi, Katherine T. Lofgren, Murray B. Stein, Renata Micha, Luigi Naldi, Margreet ten Have, Bolajoko O. Olusanya, Kyle J Foreman, Kenji Shibuya, F. Gerry R. Fowkes, Abdullah Sulieman Terkawi, Rana J. Asghar, Karen M. Tabb, Kovin Naidoo, Rogelio Pérez-Padilla, Honglei Chen, Antônio Luiz Pinho Ribeiro, Rasmus Havmoeller, Yukito Shinohara, Bongani M. Mayosi, Ernst J Kuipers, Konrad Pesudovs, Mouhanad Hammami, Lee Richardson, Rintaro Mori, Thomas D. Fleming, Pouria Heydarpour, Stephen G. Waller, Nicholas Graetz, Chanda Kulkarni, Peter Brooks, Gulfaraz Khan, Marcel Tanner, Van C. Lansingh, François Alla, Jamie Hancock, Yohannes Adama Melaku, Neeraj Bedi, Anthony D. Woolf, Tariku Jibat Beyene, Amanda W Pain, Eric L. Ding, Narayanaswamy Venketasubramanian, Semaw Ferede Abera, Devina Nand, Odgerel Chimed-Ochir, George D Thurston, Victor Aboyans, Alanur Çavlin, Jefferson Traebert, Michael R. Phillips, Yingfeng Zheng, Baffour Awuah, Carlo Irwin A. Panelo, Selen Begüm Uzun, Muhammad Imran Nisar, Samir Soneji, Veena S. Kulkarni, Mukesh Dherani, Stephen S Lim, Andre Keren, Kingsley N. Ukwaja, Sajjad Ur Rahman, Giuseppe Remuzzi, Kjetil Søreide, Blake Thomson, Samath D Dharmaratne, Christopher D. Blosser, David H. Rothstein, Amanda G. Thrift, Fabrizio Tediosi, Andrew H. Kemp, H. Dean Hosgood, Yoshihiro Kokubo, Miia Kivipelto, Amitava Banerjee, Edgar P. Simard, Reza Malekzadeh, Maggie Lind, Robert P. Dellavalle, Emerito Jose A. Faraon, Lydia S. Atkins, Tom Achoki, Aslam Pervaiz, Peter Scarborough, Hans W. Hoek, Ettore Beghi, Emilie Agardh, Abraham D. Flaxman, Dariush Mozaffarian, Juan R. Sanabria, Muluken Dessalegn, David C. Schwebel, Caitlyn Steiner, Ubai Alsharif, Richard C. Franklin, Gail Davey, Gelin Xu, Reyna A Gutiérrez, Joannie Lortet-Tieulent, Ashish Bhalla, Jost B. Jonas, Paul N. Jensen, Simon I. Hay, Xiaonong Zou, Andre Pascal Kengne, Tolesa Bekele, Brittany Wurtz, Jung-Chen Chang, Joseph Murray, Luciano A. Sposato, Stefan Ma, Summer Lockett Ohno, Charles R. Newton, Bradford D. Gessner, JianLi Wang, Scott B. Patten, Thomas Fürst, Carol Brayne, Christina Fitzmaurice, Peilin Shi, Ted R. Miller, Kinnari S. Murthy, Habib Benzian, Peter W. Gething, Cesar Diaz-Torne, Burcu Kucuk Bicer, Bo Norrving, Carly E Levitz, Adam D M Briggs, Sungroul Kim, Isabela M. Benseñor, John A. Crump, Sergey Petrovich Ermakov, Kalpana Balakrishnan, Awoke Misganaw Temesgen, Marcella Montico, Sanjay Krishnaswami, Kim Moesgaard Iburg, Ann Kristin Knudsen, Sun Ha Jee, Valery L. Feigin, Christine M. Budke, Anne Bulchis, Anand Dayama, Jonathan R. Carapetis, Cyrus Cooper, Teresa Shamah Levy, Ismael R. Campos-Nonato, Nataliya A. Foigt, Beth E. Ebel, Max Petzold, Heresh Amini, Ole Frithjof Norheim, Zulfiqar A Bhutta, Dan Poenaru, Jim van Os, Michele E. Murdoch, Samantha M. Colquhoun, Michael H. Criqui, Giorgia Giussani, Man Mohan Mehndiratta, Thomas N. Williams, Chandrashekhar T Sreeramareddy, Chuanhua Yu, Luis M. Coppola, Thomas J. Montine, Alaa Badawi, Eduardo Bernabé, Melvin Barrientos Marzan, James Leigh, Frédéric B. Piel, Ratilal Lalloo, Panniyammakal Jeemon, Maheswar Satpathy, Hélène Carabin, Corina Benjet, Seyed-Mohammad Fereshtehnejad, Ryan M Barber, Fotis Topouzis, Bin Li, Serge Resnikoff, Taavi Lai, Rachelle Buchbinder, Randah R. Hamadeh, Valeria Caso, Holly E. Erskine, Dragos Virgil Davitoiu, Miltiadis K. Tsilimbaris, Rachel L. Pullan, Ben Schöttker, Rafael Lozano, Damian G Hoy, Fiona M. Blyth, Belinda J. Gabbe, Hebe N. Gouda, Farhad Islami, Atte Meretoja, Christopher Margono, Marissa Iannarone, Ronan A Lyons, Wilkister N. Moturi, Donald H. Silberberg, Alexandra Brazinova, Monica Cortinovis, Deena Alasfoor, Richard Matzopoulos, Jerry Abraham, Francesco Saverio Violante, Monika Sawhney, Dorairaj Prabhakaran, Valentina Colistro, Derek F J Fay, Mamta Swaroop, Nima Hafezi-Nejad, John Nelson Opio, Hanne Christensen, Jun She, Soewarta Kosen, Atsushi Goto, Costas A. Christophi, Jeyaraj D. Pandian, Peter J. Hotez, K. Srinath Reddy, Al Artaman, Peter Allebeck, Jonas Minet Kinge, Graham S Cooke, Dan J. Stein, Kawkab Shishani, Laith J. Abu-Raddad, Katrina F Ortblad, Deborah Jarvis, Arsène Kouablan Adou, Barthelemy Kuate Defo, Alan D. Lopez, G Anil Kumar, K.M. Venkat Narayan, Yong Zhao, Rajiv Chowdhury, Hadi Danawi, George C Patton, Vasiliy Victorovich Vlassov, André Karch, Tommi J. Vasankari, Matthias Endres, Ione Jayce Ceola Schneider, Nelson Alvis-Guzman, Charles N Mock, Katharine J Looker, Bach Xuan Tran, Fernando Perez-Ruiz, Harish Chander Gugnani, Reza Assadi, Hannah Hamavid, Rosario Cárdenas, Mohammed I. Albittar, Sarah Derrett, Mohammad Yahya Saeedi, Traolach S. Brugha, Jan Hendrik Richardus, Alireza Esteghamati, Seok Jun Yoon, Josep Maria Haro, Michael Brainin, Ziad A. Memish, Rupert R A Bourne, Katherine B Gibney, David M. Pereira, Kathryn H. Jacobsen, Luc E. Coffeng, Joshua A. Salomon, Xia Wan, Ian Bolliger, Boris I. Pavlin, Karen Sliwa, Tati S. Warouw, Geoffrey Buckle, Chakib Nejjari, Diego De Leo, Ashkan Afshin, Vinay Nangia, Daniel Pope, Johanna M. Geleijnse, Nikhil Tandon, Kelly Bienhoff, Jed D. Blore, Walid Ammar, D. Allen Roberts, Elisabete Weiderpass, Gregory A. Roth, Manami Inoue, James D. Wilkinson, Hideaki Toyoshima, Soufiane Boufous, Ivy Shiue, Edward J Mills, Leilei Duan, Matthew M Coates, Ganesan Karthikeyan, Alberto Ortiz, Steven van de Vijver, David Carpenter, Suzanne Lyn Barker-Collo, Antony Stevens, Sanjay Basu, Maria Cecilia Bahit, Kaire Innos, Lindsay N. Boyers, Nicholas J K Breitborde, Alize J. Ferrari, Timothy M. Wolock, Simerjot K. Jassal, Mohammad Ali Sahraian, Joanna Moschandreas, Howard J. Hoffman, Hideki Higashi, George M. Ruhago, Karzan Abdulmuhsin Mohammad, Mohammed Basulaiman, D. Alex Quistberg, Justin Beardsley, Marcello Tonelli, Maurice Giroud, Karen Edmond, Norito Kawakami, Mohammad T Mashal, Neeraj Bhala, Carl Abelardo T. Antonio, David Tanne, Abhishek Singh, Kazem Rahimi, Vivekanand Jha, Wagner Marcenes, David J. Margolis, Yara A. Halasa, Zewdie Aderaw Alemu, Carrie Beth Peterson, Edson Serván-Mori, Anil Kaul, Foad Abd-Allah, Marek Majdan, Rahul Gupta, Robyn M. Lucas, Sarah Wulf, Lars Jacob Stovner, Mohsen Naghavi, Vegard Skirbekk, Ulrich Otto Mueller, Pengpeng Ye, Ali H. Mokdad, Dipan Bose, Saleem M Rana, Jeffrey D Stanaway, Abigail Mclain, Timothy J. Steiner, Amira Shaheen, Stein Emil Vollset, Andrea Werdecker, Michele Meltzer, Richie G Poulton, Joseph R. Masci, Inga Dora Sigfusdottir, Daniel Dicker, Maysaa El Sayed Zaki, Shiwei Liu, Julio C. Montañez Hernandez, Valentina Arsić Arsenijević, William Msemburi, Lope H Barrero, Linhong Wang, Soumya Swaminathan, Harvey Whiteford, Michael F. Macintyre, Berrak Bora Basara, Gregory R. Wagner, Paul I. Dargan, Hermann Brenner, Carolyn C. Gotay, Niveen M E Abu-Rmeileh, Nicholas J Kassebaum, Shams Eldin Ali Hassan Khalifa, Neil McGill, Murray, Christopher J. L, Barber, Ryan M., Foreman, Kyle J., Ozgoren, Ayse Abbasoglu, Abd-Allah, Foad, Abera, Semaw F., Aboyans, Victor, Abraham, Jerry P., Abubakar, Ibrahim, Abu-Raddad, Laith J., Abu-Rmeileh, Niveen M., Achoki, Tom, Ackerman, Ilana N., Ademi, Zanfina, Adou, Arsène K., Adsuar, José C., Afshin, Ashkan, Agardh, Emilie E., Alam, Sayed Saidul, Alasfoor, Deena, Albittar, Mohammed I., Alegretti, Miguel A., Alemu, Zewdie A., Alfonso-Cristancho, Rafael, Alhabib, Samia, Ali, Raghib, Alla, Françoi, Allebeck, Peter, Almazroa, Mohammad A., Alsharif, Ubai, Alvarez, Elena, Alvis-Guzman, Nelson, Amare, Azmeraw T., Ameh, Emmanuel A., Amini, Heresh, Ammar, Walid, Anderson, H. Ro, Anderson, Benjamin O., Antonio, Carl Abelardo T., Anwari, Palwasha, Arnlöv, Johan, Arsenijevic, Valentina S. Arsic, Artaman, Al, Asghar, Rana J., Assadi, Reza, Atkins, Lydia S., Avila, Marco A., Awuah, Baffour, Bachman, Victoria F., Badawi, Alaa, Bahit, Maria C., Balakrishnan, Kalpana, Banerjee, Amitava, Barker-Collo, Suzanne L., Barquera, Simon, Barregard, Lar, Barrero, Lope H., Basu, Arindam, Basu, Sanjay, Basulaiman, Mohammed O., Beardsley, Justin, Bedi, Neeraj, Beghi, Ettore, Bekele, Tolesa, Bell, Michelle L., Benjet, Corina, Bennett, Derrick A., Bensenor, Isabela M., Benzian, Habib, Bernabé, Eduardo, Bertozzi-Villa, Amelia, Beyene, Tariku J., Bhala, Neeraj, Bhalla, Ashish, Bhutta, Zulfiqar A., Bienhoff, Kelly, Bikbov, Bori, Biryukov, Stan, Blore, Jed D., Blosser, Christopher D., Blyth, Fiona M., Bohensky, Megan A., Bolliger, Ian W., Başara, Berrak Bora, Bornstein, Natan M., Bose, Dipan, Boufous, Soufiane, Bourne, Rupert R. A., Boyers, Lindsay N., Brainin, Michael, Brayne, Carol E., Brazinova, Alexandra, Breitborde, Nicholas J. K., Brenner, Hermann, Briggs, Adam D., Brooks, Peter M., Brown, Jonathan C., Brugha, Traolach S., Buchbinder, Rachelle, Buckle, Geoffrey C., Budke, Christine M., Bulchis, Anne, Bulloch, Andrew G., Campos-Nonato, Ismael R., Carabin, Hélène, Carapetis, Jonathan R., Cárdenas, Rosario, Carpenter, David O., Caso, Valeria, Castañeda-Orjuela, Carlos A., Castro, Ruben E., Catalá-López, Ferrán, Cavalleri, Fiorella, Çavlin, Alanur, Chadha, Vineet K., Chang, Jung-Chen, Charlson, Fiona J., Chen, Honglei, Chen, Wanqing, Chiang, Peggy P., Chimed-Ochir, Odgerel, Chowdhury, Rajiv, Christensen, Hanne, Christophi, Costas A., Cirillo, Massimo, Coates, Matthew M., Coffeng, Luc E., Coggeshall, Megan S., Colistro, Valentina, Colquhoun, Samantha M., Cooke, Graham S., Cooper, Cyru, Cooper, Leslie T., Coppola, Luis M., Cortinovis, Monica, Criqui, Michael H., Crump, John A., Cuevas-Nasu, Lucia, Danawi, Hadi, Dandona, Lalit, Dandona, Rakhi, Dansereau, Emily, Dargan, Paul I., Davey, Gail, Davis, Adrian, Davitoiu, Dragos V., Dayama, Anand, De Leo, Diego, Degenhardt, Louisa, Del Pozo-Cruz, Borja, Dellavalle, Robert P., Deribe, Kebede, Derrett, Sarah, Des Jarlais, Don C., Dessalegn, Muluken, Dharmaratne, Samath D., Dherani, Mukesh K., Diaz-Torné, Cesar, Dicker, Daniel, Ding, Eric L., Dokova, Klara, Dorsey, E Ray, Driscoll, Tim R., Duan, Leilei, Duber, Herbert C., Ebel, Beth E., Edmond, Karen M., Elshrek, Yousef M., Endres, Matthia, Ermakov, Sergey P., Erskine, Holly E., Eshrati, Babak, Esteghamati, Alireza, Estep, Kara, Faraon, Emerito Jose A., Farzadfar, Farshad, Fay, Derek F., Feigin, Valery L., Felson, David T., Fereshtehnejad, Seyed-Mohammad, Fernandes, Jefferson G., Ferrari, Alize J., Fitzmaurice, Christina, Flaxman, Abraham D., Fleming, Thomas D., Foigt, Nataliya, Forouzanfar, Mohammad H., Fowkes, F Gerry R., Paleo, Urbano Fra., Franklin, Richard C., Fürst, Thoma, Gabbe, Belinda, Gaffikin, Lynne, Gankpé, Fortuné G., Geleijnse, Johanna M., Gessner, Bradford D., Gething, Peter, Gibney, Katherine B., Giroud, Maurice, Giussani, Giorgia, Dantes, Hector Gomez, Gona, Philimon, González-Medina, Diego, Gosselin, Richard A., Gotay, Carolyn C., Goto, Atsushi, Gouda, Hebe N., Graetz, Nichola, Gugnani, Harish C., Gupta, Rahul, Gupta, Rajeev, Gutiérrez, Reyna A., Haagsma, Juanita, Hafezi-Nejad, Nima, Hagan, Holly, Halasa, Yara A., Hamadeh, Randah R., Hamavid, Hannah, Hammami, Mouhanad, Hancock, Jamie, Hankey, Graeme J., Hansen, Gillian M., Hao, Yuantao, Harb, Hilda L., Haro, Josep Maria, Havmoeller, Rasmu, Hay, Simon I., Hay, Roderick J., Heredia-Pi, Ileana B., Heuton, Kyle R., Heydarpour, Pouria, Higashi, Hideki, Hijar, Martha, Hoek, Hans W., Hoffman, Howard J., Hosgood, H Dean, Hossain, Mazeda, Hotez, Peter J., Hoy, Damian G., Hsairi, Mohamed, Hu, Guoqing, Huang, Cheng, Huang, John J., Husseini, Abdullatif, Huynh, Chantal, Iannarone, Marissa L., Iburg, Kim M., Innos, Kaire, Inoue, Manami, Islami, Farhad, Jacobsen, Kathryn H., Jarvis, Deborah L., Jassal, Simerjot K., Jee, Sun Ha, Jeemon, Panniyammakal, Jensen, Paul N., Jha, Vivekanand, Jiang, Guohong, Jiang, Ying, Jonas, Jost B., Juel, Knud, Kan, Haidong, Karch, André, Karema, Corine K., Karimkhani, Chante, Karthikeyan, Ganesan, Kassebaum, Nicholas J., Kaul, Anil, Kawakami, Norito, Kazanjan, Konstantin, Kemp, Andrew H., Kengne, Andre P., Keren, Andre, Khader, Yousef S., Khalifa, Shams Eldin A., Khan, Ejaz A., Khan, Gulfaraz, Khang, Young-Ho, Kieling, Christian, Kim, Daniel, Kim, Sungroul, Kim, Yunjin, Kinfu, Yohanne, Kinge, Jonas M., Kivipelto, Miia, Knibbs, Luke D., Knudsen, Ann Kristin, Kokubo, Yoshihiro, Kosen, Soewarta, Krishnaswami, Sanjay, Defo, Barthelemy Kuate, Bicer, Burcu Kucuk, Kuipers, Ernst J., Kulkarni, Chanda, Kulkarni, Veena S., Kumar, G Anil, Kyu, Hmwe H., Lai, Taavi, Lalloo, Ratilal, Lallukka, Tea, Lam, Hilton, Lan, Qing, Lansingh, Van C., Larsson, Ander, Lawrynowicz, Alicia E. B., Leasher, Janet L., Leigh, Jame, Leung, Ricky, Levitz, Carly E., Li, Bin, Li, Yichong, Li, Yongmei, Lim, Stephen S., Lind, Maggie, Lipshultz, Steven E., Liu, Shiwei, Liu, Yang, Lloyd, Belinda K., Lofgren, Katherine T., Logroscino, Giancarlo, Looker, Katharine J., Lortet-Tieulent, Joannie, Lotufo, Paulo A., Lozano, Rafael, Lucas, Robyn M., Lunevicius, Raimunda, Lyons, Ronan A., Ma, Stefan, Macintyre, Michael F., Mackay, Mark T., Majdan, Marek, Malekzadeh, Reza, Marcenes, Wagner, Margolis, David J., Margono, Christopher, Marzan, Melvin B., Masci, Joseph R., Mashal, Mohammad T., Matzopoulos, Richard, Mayosi, Bongani M., Mazorodze, Tasara T., Mcgill, Neil W., Mcgrath, John J., Mckee, Martin, Mclain, Abigail, Meaney, Peter A., Medina, Catalina, Mehndiratta, Man Mohan, Mekonnen, Wubegzier, Melaku, Yohannes A., Meltzer, Michele, Memish, Ziad A., Mensah, George A., Meretoja, Atte, Mhimbira, Francis A., Micha, Renata, Miller, Ted R., Mills, Edward J., Mitchell, Philip B., Mock, Charles N., Ibrahim, Norlinah Mohamed, Mohammad, Karzan A., Mokdad, Ali H., Mola, Glen L. D., Monasta, Lorenzo, Hernandez, Julio C. Montañez, Montico, Marcella, Montine, Thomas J., Mooney, Meghan D., Moore, Ami R., Moradi-Lakeh, Maziar, Moran, Andrew E., Mori, Rintaro, Moschandreas, Joanna, Moturi, Wilkister N., Moyer, Madeline L., Mozaffarian, Dariush, Msemburi, William T., Mueller, Ulrich O., Mukaigawara, Mitsuru, Mullany, Erin C., Murdoch, Michele E., Murray, Joseph, Murthy, Kinnari S., Naghavi, Mohsen, Naheed, Aliya, Naidoo, Kovin S., Naldi, Luigi, Nand, Devina, Nangia, Vinay, Narayan, K M. Venkat, Nejjari, Chakib, Neupane, Sudan P., Newton, Charles R., Ng, Marie, Ngalesoni, Frida N., Nguyen, Grant, Nisar, Muhammad I., Nolte, Sandra, Norheim, Ole F., Norman, Rosana E., Norrving, Bo, Nyakarahuka, Luke, Oh, In-Hwan, Ohkubo, Takayoshi, Ohno, Summer L., Olusanya, Bolajoko O., Opio, John Nelson, Ortblad, Katrina, Ortiz, Alberto, Pain, Amanda W., Pandian, Jeyaraj D., Panelo, Carlo Irwin A., Papachristou, Christina, Park, Eun-Kee, Park, Jae-Hyun, Patten, Scott B., Patton, George C., Paul, Vinod K., Pavlin, Boris I., Pearce, Neil, Pereira, David M., Perez-Padilla, Rogelio, Perez-Ruiz, Fernando, Perico, Norberto, Pervaiz, Aslam, Pesudovs, Konrad, Peterson, Carrie B., Petzold, Max, Phillips, Michael R., Phillips, Bryan K., Phillips, David E., Piel, Frédéric B., Plass, Dietrich, Poenaru, Dan, Polinder, Suzanne, Pope, Daniel, Popova, Svetlana, Poulton, Richie G., Pourmalek, Farshad, Prabhakaran, Dorairaj, Prasad, Noela M., Pullan, Rachel L., Qato, Dima M., Quistberg, D Alex, Rafay, Anwar, Rahimi, Kazem, Rahman, Sajjad U., Raju, Murugesan, Rana, Saleem M., Razavi, Homie, Reddy, K Srinath, Refaat, Amany, Remuzzi, Giuseppe, Resnikoff, Serge, Ribeiro, Antonio L., Richardson, Lee, Richardus, Jan Hendrik, Roberts, D Allen, Rojas-Rueda, David, Ronfani, Luca, Roth, Gregory A., Rothenbacher, Dietrich, Rothstein, David H., Rowley, Jane T., Roy, Nobhojit, Ruhago, George M., Saeedi, Mohammad Y., Saha, Sukanta, Sahraian, Mohammad Ali, Sampson, Uchechukwu K. A., Sanabria, Juan R., Sandar, Logan, Santos, Itamar S., Satpathy, Maheswar, Sawhney, Monika, Scarborough, Peter, Schneider, Ione J., Schöttker, Ben, Schumacher, Austin E., Schwebel, David C., Scott, James G., Seedat, Soraya, Sepanlou, Sadaf G., Serina, Peter T., Servan-Mori, Edson E., Shackelford, Katya A., Shaheen, Amira, Shahraz, Saeid, Levy, Teresa Shamah, Shangguan, Siyi, She, Jun, Sheikhbahaei, Sara, Shi, Peilin, Shibuya, Kenji, Shinohara, Yukito, Shiri, Rahman, Shishani, Kawkab, Shiue, Ivy, Shrime, Mark G., Sigfusdottir, Inga D., Silberberg, Donald H., Simard, Edgar P., Sindi, Shireen, Singh, Abhishek, Singh, Jasvinder A., Singh, Lavanya, Skirbekk, Vegard, Slepak, Erica Leigh, Sliwa, Karen, Soneji, Samir, Søreide, Kjetil, Soshnikov, Sergey, Sposato, Luciano A., Sreeramareddy, Chandrashekhar T., Stanaway, Jeffrey D., Stathopoulou, Vasiliki, Stein, Dan J., Stein, Murray B., Steiner, Caitlyn, Steiner, Timothy J., Stevens, Antony, Stewart, Andrea, Stovner, Lars J., Stroumpoulis, Konstantino, Sunguya, Bruno F., Swaminathan, Soumya, Swaroop, Mamta, Sykes, Bryan L., Tabb, Karen M., Takahashi, Ken, Tandon, Nikhil, Tanne, David, Tanner, Marcel, Tavakkoli, Mohammad, Taylor, Hugh R., Te Ao, Braden J., Tediosi, Fabrizio, Temesgen, Awoke M., Templin, Tara, Ten Have, Margreet, Tenkorang, Eric Y., Terkawi, Abdullah S., Thomson, Blake, Thorne-Lyman, Andrew L., Thrift, Amanda G., Thurston, George D., Tillmann, Taavi, Tonelli, Marcello, Topouzis, Foti, Toyoshima, Hideaki, Traebert, Jefferson, Tran, Bach X., Trillini, Matia, Truelsen, Thoma, Tsilimbaris, Miltiadi, Tuzcu, Emin M., Uchendu, Uche S., Ukwaja, Kingsley N., Undurraga, Eduardo A., Uzun, Selen B., Van Brakel, Wim H., Van De Vijver, Steven, Van Gool, Coen H., Van Os, Jim, Vasankari, Tommi J., Venketasubramanian, N, Violante, Francesco S., Vlassov, Vasiliy V., Vollset, Stein Emil, Wagner, Gregory R., Wagner, Joseph, Waller, Stephen G., Wan, Xia, Wang, Haidong, Wang, Jianli, Wang, Linhong, Warouw, Tati S., Weichenthal, Scott, Weiderpass, Elisabete, Weintraub, Robert G., Wenzhi, Wang, Werdecker, Andrea, Westerman, Ronny, Whiteford, Harvey A., Wilkinson, James D., Williams, Thomas N., Wolfe, Charles D., Wolock, Timothy M., Woolf, Anthony D., Wulf, Sarah, Wurtz, Brittany, Xu, Gelin, Yan, Lijing L., Yano, Yuichiro, Ye, Pengpeng, Yentür, Gökalp K., Yip, Paul, Yonemoto, Naohiro, Yoon, Seok-Jun, Younis, Mustafa Z., Yu, Chuanhua, Zaki, Maysaa E., Zhao, Yong, Zheng, Yingfeng, Zonies, David, Zou, Xiaonong, Salomon, Joshua A., Lopez, Alan D., Vos, Theo, Medische Sociologie, MUMC+: Hersen en Zenuw Centrum (3), MUMC+: MA Psychiatrie (3), Psychiatrie & Neuropsychologie, Barber, Ryan M, Foreman, Kyle J, Abd Allah, Foad, Abera, Semaw F, Abraham, Jerry P, Abu Raddad, Laith J, Abu Rmeileh, Niveen M, Ackerman, Ilana N, Adou, Arsène K, Adsuar, José C, Agardh, Emilie E, Albittar, Mohammed I, Alegretti, Miguel A, Alemu, Zewdie A, Alfonso Cristancho, Rafael, Almazroa, Mohammad A, Alvis Guzman, Nelson, Amare, Azmeraw T, Ameh, Emmanuel A, Anderson, Benjamin O, Antonio, Carl Abelardo T, Asghar, Rana J, Atkins, Lydia S, Avila, Marco A, Bachman, Victoria F, Bahit, Maria C, Barker Collo, Suzanne L, Barrero, Lope H, Basulaiman, Mohammed O, Bell, Michelle L, Bennett, Derrick A, Bensenor, Isabela M, Bertozzi Villa, Amelia, Beyene, Tariku J, Bhutta, Zulfiqar A, Blore, Jed D, Blosser, Christopher D, Blyth, Fiona M, Bohensky, Megan A, Bolliger, Ian W, Bornstein, Natan M, Bourne, Rupert R. A, Boyers, Lindsay N, Brayne, Carol E, Breitborde, Nicholas J. K, Briggs, Adam D, Brooks, Peter M, Brown, Jonathan C, Brugha, Traolach S, Buckle, Geoffrey C, Budke, Christine M, Bulloch, Andrew G, Campos Nonato, Ismael R, Carapetis, Jonathan R, Carpenter, David O, Castañeda Orjuela, Carlos A, Castro, Ruben E, Catalá López, Ferrán, Chadha, Vineet K, Chang, Jung Chen, Charlson, Fiona J, Chiang, Peggy P, Chimed Ochir, Odgerel, Christophi, Costas A, Coates, Matthew M, Coffeng, Luc E, Coggeshall, Megan S, Colquhoun, Samantha M, Cooke, Graham S, Cooper, Leslie T, Coppola, Luis M, Criqui, Michael H, Crump, John A, Cuevas Nasu, Lucia, Dargan, Paul I, Davitoiu, Dragos V, Del Pozo Cruz, Borja, Dellavalle, Robert P, Jarlais, Don C. De, Dharmaratne, Samath D, Dherani, Mukesh K, Diaz Torné, Cesar, Ding, Eric L, Dorsey, E. 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Dean, Hotez, Peter J, Hoy, Damian G, Huang, John J, Iannarone, Marissa L, Iburg, Kim M, Jacobsen, Kathryn H, Jarvis, Deborah L, Jassal, Simerjot K, Jensen, Paul N, Jonas, Jost B, Karema, Corine K, Kassebaum, Nicholas J, Kemp, Andrew H, Kengne, Andre P, Khader, Yousef S, Khalifa, Shams Eldin A, Khan, Ejaz A, Khang, Young Ho, Kinge, Jonas M, Knibbs, Luke D, Kuipers, Ernst J, Kulkarni, Veena S, Kumar, G. Anil, Kyu, Hmwe H, Lansingh, Van C, Lawrynowicz, Alicia E. B, Leasher, Janet L, Levitz, Carly E, Lim, Stephen S, Lipshultz, Steven E, Lloyd, Belinda K, Lofgren, Katherine T, Looker, Katharine J, Lortet Tieulent, Joannie, Lotufo, Paulo A, Lucas, Robyn M, Lyons, Ronan A, Macintyre, Michael F, Mackay, Mark T, Margolis, David J, Marzan, Melvin B, Masci, Joseph R, Mashal, Mohammad T, Mayosi, Bongani M, Mazorodze, Tasara T, Mcgill, Neil W, Mcgrath, John J, Meaney, Peter A, Melaku, Yohannes A, Memish, Ziad A, Mensah, George A, Mhimbira, Francis A, Miller, Ted R, Mills, Edward J, Mitchell, Philip B, Mock, Charles N, Mohammad, Karzan A, Mokdad, Ali H, Mola, Glen L. D, Montine, Thomas J, Mooney, Meghan D, Moore, Ami R, Moradi Lakeh, Maziar, Moran, Andrew E, Moturi, Wilkister N, Moyer, Madeline L, Msemburi, William T, Mueller, Ulrich O, Mullany, Erin C, Murdoch, Michele E, Murthy, Kinnari S, Naidoo, Kovin S, Narayan, K. M. Venkat, Neupane, Sudan P, Newton, Charles R, Ngalesoni, Frida N, Nisar, Muhammad I, Norheim, Ole F, Norman, Rosana E, Oh, In Hwan, Ohno, Summer L, Olusanya, Bolajoko O, Pain, Amanda W, Pandian, Jeyaraj D, Panelo, Carlo Irwin A, Park, Eun Kee, Park, Jae Hyun, Patten, Scott B, Patton, George C, Paul, Vinod K, Pavlin, Boris I, Pereira, David M, Perez Padilla, Rogelio, Perez Ruiz, Fernando, Peterson, Carrie B, Phillips, Michael R, Phillips, Bryan K, Phillips, David E, Piel, Frédéric B, Poulton, Richie G, Prasad, Noela M, Pullan, Rachel L, Qato, Dima M, Quistberg, D. Alex, Rahman, Sajjad U, Rana, Saleem M, Reddy, K. Srinath, Ribeiro, Antonio L, Roberts, D. Allen, Rojas Rueda, David, Roth, Gregory A, Rothstein, David H, Rowley, Jane T, Ruhago, George M, Saeedi, Mohammad Y, Sampson, Uchechukwu K. A, Sanabria, Juan R, Santos, Itamar S, Schneider, Ione J, Schumacher, Austin E, Schwebel, David C, Scott, James G, Sepanlou, Sadaf G, Serina, Peter T, Servan Mori, Edson E, Shackelford, Katya A, Shrime, Mark G, Sigfusdottir, Inga D, Silberberg, Donald H, Simard, Edgar P, Singh, Jasvinder A, Sposato, Luciano A, Sreeramareddy, Chandrashekhar T, Stanaway, Jeffrey D, Stein, Dan J, Stein, Murray B, Steiner, Timothy J, Stovner, Lars J, Sunguya, Bruno F, Sykes, Bryan L, Tabb, Karen M, Taylor, Hugh R, Ao, Braden J. Te, Temesgen, Awoke M, Tenkorang, Eric Y, Terkawi, Abdullah S, Thorne Lyman, Andrew L, Thrift, Amanda G, Thurston, George D, Tran, Bach X, Tuzcu, Emin M, Uchendu, Uche S, Ukwaja, Kingsley N, Undurraga, Eduardo A, Uzun, Selen B, Van Brakel, Wim H, van Gool, Coen H, Vasankari, Tommi J, Violante, Francesco S, Vlassov, Vasiliy V, Wagner, Gregory R, Waller, Stephen G, Warouw, Tati S, Weintraub, Robert G, Whiteford, Harvey A, Wilkinson, James D, Williams, Thomas N, Wolfe, Charles D, Wolock, Timothy M, Woolf, Anthony D, Yan, Lijing L, Yentür, Gökalp K, Yoon, Seok Jun, Younis, Mustafa Z, Zaki, Maysaa E, Salomon, Joshua A, Lopez, Alan D, Computational Science and Engineering Department [Daresbury] ( STFC ), Science & Technologie Facilities Council, Neuroépidémiologie Tropicale ( NET ), CHU Limoges-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut Génomique, Environnement, Immunité, Santé, Thérapeutique ( GEIST ), Université de Limoges ( UNILIM ) -Université de Limoges ( UNILIM ), Service de Chirurgie Thoracique et Vasculaire - Médecine vasculaire [CHU Limoges], CHU Limoges, Weill Cornell Medical College - Qatar, Qatar Foundation - Education City, Doha, Maladies chroniques, santé perçue, et processus d'adaptation ( APEMAC ), Université Paris Descartes - Paris 5 ( UPD5 ) -Université de Lorraine ( UL ), Centre d'Investigation Clinique - Epidemiologie Clinique/essais Cliniques Nancy, Cancéropôle du Grand Est-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Karolinska Institute, karolinska institute, Centro de Estudios Avanzados en Zonas Aridas ( CEAZA ), Ecole Polytechnique Fédérale de Lausanne ( EPFL ), Wisconsin Division of Public Health, Regional Genetic Service, St Mary's Hospital, Manchester, Laboratoire d'Ingénierie des Matériaux ( LIM ), Centre National de la Recherche Scientifique ( CNRS ), Computer Science Department [Bristol], University of Bristol [Bristol], Lawrence Berkeley National Laboratory [Berkeley] ( LBNL ), Samsung Research &Development Institute India - Bangalore (Groupe Samsung) ( SRI-B ), Multimedia Research Center ( MRC ), University of Alberta [Edmonton], Division of Biostatistics ( Biostat - MINNEAPOLIS ), University of Minnesota [Minneapolis], Laboratory of Neurologic Diseases, Mario Negri Institute, Milan, University of Southampton [Southampton], Imperial College London, Neurology Department, Ichilov Medical Center, Department of Public Health and Primary Care, Cambridge University, Interactions, transferts, ruptures artistiques et culturels - EA 6301 ( InTRu ), Université de Tours, Institut Jacques Monod ( IJM ), Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ), Institute of Parasitology, STAR laboratory, Stanford University [Stanford], Unité de recherche Virologie et Immunologie Moléculaires ( VIM ), Institut National de la Recherche Agronomique ( INRA ), Tennent Institute of Ophthalmology, National University of Singapore ( NUS ), Multidisciplinary Nanotechnology Centre, Swansea University, Department of Computer Sciences [Scheffield], University of Sheffield [Sheffield], Cyprus International Institute for the Environment and Public Health, Harvard School of Public Health, Glasgow Centre for Physical Organic Chemistry, University of Glasgow, King‘s College London, Université Panthéon-Sorbonne - UFR Science Politique ( UP1 UFR11 ), Université Panthéon-Sorbonne ( UP1 ), National Diagnostics Centre ( NDC ), National University of Ireland [Galway] ( NUI Galway ), Arthritis Research UK Epidemiology Unit ( MANCHESTER - Arthritis Research ), University of Manchester [Manchester], CEGOT - Porto, Universidade do Porto [Porto], Advanced Laboratories on Embedded Systems [Roma] ( ALES ), Department of Biology [Miami], University of Miami [Coral Gables], Division of Human Nutrition, Wageningen University and Research Centre [Wageningen] ( WUR ), Spatial Ecology and Epidemiology Group, University of Oxford [Oxford], Department of Civil Engineering [Hamirpur], National Institute of Technology [Hamirpur], GEMMA — Environmental Engineering and Microbiology Research Group, Department of Hydraulic, Maritime and Environmental Engineering, Universitat Politècnica de Catalunya [Barcelona] ( UPC ), Institut National de Recherche et d'Analyse Physico-Chimique ( INRAP ), Institut National de Recherche et d'Analyse Physico-chimique (INRAP-Tunisie), University of Connecticut ( UCONN ), Norwegian Institute for Air Research ( NILU ), Franche-Comté Électronique Mécanique, Thermique et Optique - Sciences et Technologies (UMR 6174) ( FEMTO-ST ), Université de Franche-Comté ( UFC ) -Centre National de la Recherche Scientifique ( CNRS ) -Ecole Nationale Supérieure de Mécanique et des Microtechniques ( ENSMM ) -Université de Technologie de Belfort-Montbeliard ( UTBM ), Tehran University, Friedrich-Alexander Universität Erlangen-Nürnberg ( FAU ), Secretariat of the Pacific Community, Public Health Division, Sociétés, Acteurs, Gouvernement en Europe ( SAGE ), Université de Strasbourg ( UNISTRA ) -Centre National de la Recherche Scientifique ( CNRS ), School of Physics and Astronomy, Washington State University ( WSU ), Laboratoire de Physique de l'ENS Lyon ( Phys-ENS ), École normale supérieure - Lyon ( ENS Lyon ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique ( CNRS ), Institut de recherche en informatique de Toulouse ( IRIT ), Institut National Polytechnique [Toulouse] ( INP ) -Université Toulouse 1 Capitole ( UT1 ) -Université Toulouse - Jean Jaurès ( UT2J ) -Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique ( CNRS ), School of Computer Science - China University of Geosciences (China University of Geosciences (East Area)), Université Catholique de Louvain ( UCL ), Div Cyclotron & Radiopharmaceut Sci ( DRDO, INMAS ), Univ New Delhi, University of St Andrews [Scotland], University of Cape Town, Department of Neuroscience, Karolinska Institutet [Stockholm], Institut de Physique Nucléaire d'Orsay ( IPNO ), Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de Physique Nucléaire et de Physique des Particules du CNRS ( IN2P3 ) -Centre National de la Recherche Scientifique ( CNRS ), Department of Computer Science and Engineering [Daejeon] (Chungnam National University), Lawrence University, Gastroenterology & Hepatology, Tata Research Development and Design Center ( TRDDC ), TCS Innovation Labs, Laboratoire MOLTECH-Anjou [Angers] ( MOLTECH ANJOU ), Université d'Angers ( UA ) -Centre National de la Recherche Scientifique ( CNRS ), University of Helsinki [Helsinki], Google Inc [Mountain View], Research at Google, Swedish Defense Research Agency ( FOI ), Centre de Recherche en Information Biomédicale sino-français ( CRIBS ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Southeast University [Jiangsu]-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Laboratory of Image Science and Technology [Nanjing] ( LIST ), Southeast University [Jiangsu]-School of Computer Science and Engineering, Laboratoire de glaciologie et géophysique de l'environnement ( LGGE ), Observatoire des Sciences de l'Univers de Grenoble ( OSUG ), Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut national des sciences de l'Univers ( INSU - CNRS ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ) -Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut national des sciences de l'Univers ( INSU - CNRS ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ) -Centre National de la Recherche Scientifique ( CNRS ), School of Business and Informatics, University of Boras, Department of Mechanical and Automation Engineering ( CAD Laboratory ), The Chinese University of Hong Kong [Hong Kong], Università degli studi di Bari, Heuristique et Diagnostic des Systèmes Complexes [Compiègne] ( Heudiasyc ), Université de Technologie de Compiègne ( UTC ) -Centre National de la Recherche Scientifique ( CNRS ), Department of plant pathology and microbiology - centre for sustainable pest and disease management, Rothamsted Research, RGU, Department of Rheumatology and Connective Tissue Diseases, Medical University of Lublin, Barts and The London School of Medicine and Dentistry, Queen Mary University of London ( QMUL ), Centre d'économie de la Sorbonne ( CES ), Université Panthéon-Sorbonne ( UP1 ) -Centre National de la Recherche Scientifique ( CNRS ), Paris School of Economics ( PSE ), Istituto Dalle Molle di Studi sull'Intelligenza Artificiale ( IDSIA ), Università della Svizzera italiana ( USI ) -Scuola universitaria professionale della Svizzera italiana [Manno] ( SUPSI ), Anaesthetics, Southampton University Hospital, Department of Mathematics, University of Iowa [Iowa City], College of Medicine, Alfaisal University, Saudi Ministry of Health, Institut national des recherches agricoles du Bénin, Centre de Recherches agricoles du Sud, Departments of Epidemiology and Nutrition, Unit of Human Nutrition, Agricultural University of Athens, Department of Animal Science, PennState University [Pennsylvania] ( PSU ), University of Virginia, University of Virginia [Charlottesville], Epidemiology and Biostatistics Unit, Institute for Maternal and Child Health - IRCCS ‘‘Burlo Garofolo', Jet Propulsion Laboratory ( JPL ), NASA-California Institute of Technology ( CALTECH ), Division of Cardiovascular Medicine and Channing Division of Network Medicine, Brigham and Women's Hospital [Boston], Division of Gastroenterology and Hepatology, Department of Immunology, Mayo Clinic, Department of Chemistry, Scientific Computing Research Unit, Department of dermatology, Milano University-Azienda Ospedaleria Ospedali Riuniti di Bergamo, Department of epidemiology and Public Health, Faculty of Medicine, Hong Kong Baptist University ( HKBU ), Département Optique ( OPT ), Université européenne de Bretagne ( UEB ) -Télécom Bretagne-Institut Mines-Télécom [Paris], Department of Neurology Lunds University Hospital Lund, Services répartis, Architectures, MOdélisation, Validation, Administration des Réseaux ( SAMOVAR ), Institut Mines-Télécom [Paris]-Télécom SudParis ( TSP ) -Centre National de la Recherche Scientifique ( CNRS ), Département Réseaux et Services Multimédia Mobiles ( RS2M ), Institut Mines-Télécom [Paris]-Télécom SudParis ( TSP ), Electrical Engineering and Computer Science Department - Case Western Reserve University, Case Western Reserve University [Cleveland], Institut Lumière Matière [Villeurbanne] ( ILM ), Université Claude Bernard Lyon 1 ( UCBL ), World Health Organization, Nordic School of Public Health, The James Hutton Institute, Sero, Sero consulting, Evolutionary Ecology of Infectious Disease Group, Department of Zoology, Horia Hulubei National Institute for Physics and Nuclear Engineering, Dunedin School of Medicine, University of Otago, Department of Physics, Clarendon Laboratory, Center for TeleInFrastruktur ( CTIF ), Aalborg University [Denmark] ( AAU ), Physikalisches Institut [Freiburg], Albert-Ludwigs-Universität Freiburg, Savoirs, Textes, Langage (STL) - UMR 8163 ( STL ), Université de Lille-Centre National de la Recherche Scientifique ( CNRS ), Dept.of Computer Science, Indian Institute of Technology Madras ( IIT Madras ), Istituto Mario Negri Bergamo, Centro Ricerche e Trapianti Villa Camozzi, Universidade Estadual Paulista Júlio de Mesquita ( UNESP ), Department of Public Health, Erasmus MC-University Medical Center Rotterdam, Université Grenoble Alpes - UFR Médecine ( UGA UFRM ), Université Grenoble Alpes ( UGA ), Clinical Epidemiology and Aging Research, German Cancer Research Center, Institut Cochin ( UM3 (UMR 8104 / U1016) ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Symantec, European Microsoft Innovation Center ( EMIC ), Microsoft Corporation [Redmond, Wash.], Laboratoire de Mécanique, Physique et Géosciences ( LMPG ), Université Le Havre Normandie ( ULH ), Normandie Université ( NU ) -Normandie Université ( NU ), Novartis institute for tropical diseases, Institut de Génétique et de Biologie Moléculaire et Cellulaire ( IGBMC ), Université de Strasbourg ( UNISTRA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Departments of Anatomy and Cell Biology, Wayne State University School of Medicine, Departments of Ophthalmology, Departments of Applied Physics [New Haven], Yale University [New Haven], Center for Mathematical Modeling ( CMM ), Universidad de Santiago de Chile [Santiago] ( USACH ), Laboratory for Atmospheric and Space Physics [Boulder] ( LASP ), University of Colorado Boulder [Boulder], University of Occupational and Environmental Health [Kitakyushu] ( UEOH ), Department of Computer Science and Engineering [New Delhi], Indian Institute of Technology Delhi ( IIT Delhi ), Institut de Recherche sur les Phénomènes Hors Equilibre ( IRPHE ), Aix Marseille Université ( AMU ) -Ecole Centrale de Marseille ( ECM ) -Centre National de la Recherche Scientifique ( CNRS ), GlaxoSmithKline, Imperial College London-Clinical Imaging Center, Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, Yale School of Medicine-Yale School of Medicine-Yale Stem Cell Center, Maclean Building, Benson Lane, Crowmarsh Gifford, Centre for Ecology and Hydrology, Nanoscience Institute ( NEST ), Dipartimento di Fisica, Università di Pisa, Aristotle University of Thessaloniki, Laboratory Of Immune Cell Biology ( LICB ), National Institutes of Health ( NIH ), Institute of Human Genetics, Bonn Universität [Bonn], Occupational Health Unit, Bologna University Hospital-Sant'Orsola-Malpighi Polyclinic, Royal Institute of Technology [Stockholm] ( KTH ), Institut für Informatik [München/Munich] ( LMU ), Ludwig-Maximilians-Universität München, NICTA [Eveleigh], National ICT Australia [Sydney] ( NICTA ), Manchester Academic Health Sciences Centre, Institut d'Histoire et de Philosophie des Sciences et des Techniques ( IHPST ), Université Panthéon-Sorbonne ( UP1 ) -Département d'Etudes Cognitives - ENS Paris ( DEC ), École normale supérieure - Paris ( ENS Paris ) -École normale supérieure - Paris ( ENS Paris ) -Centre National de la Recherche Scientifique ( CNRS ), Ghent University [Belgium] ( UGENT ), German Research Centre for Geosciences - Helmholtz-Centre Potsdam ( GFZ ), Laboratoire de recherche en Hydrodynamique, Énergétique et Environnement Atmosphérique ( LHEEA ), École Centrale de Nantes ( ECN ) -Centre National de la Recherche Scientifique ( CNRS ), Institut de Recherche en Génie Civil et Mécanique ( GeM ), Université de Nantes ( UN ) -École Centrale de Nantes ( ECN ) -Centre National de la Recherche Scientifique ( CNRS ), Neurorestoration Group, King‘s College London-Wolfson Centre for Age-related Diseases, Department of Computer Science [KAIST] ( CS ), Korea Advanced Institute of Science and Technology ( KAIST ), Laboratoire de l'Accélérateur Linéaire ( LAL ), Natl Engn Res Ctr Vegetables, Key Lab Biol & Genet Improvement Hort Crops N Chi, Beijing Acad Agr & Forestry Sci, University Hospital Puerta de Hierro, Madrid, Computational Science and Engineering Department [Daresbury] (STFC), Neuroépidémiologie Tropicale (NET), CHU Limoges-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), Weill Cornell Medicine [Qatar], Maladies chroniques, santé perçue, et processus d'adaptation (APEMAC), Université Paris Descartes - Paris 5 (UPD5)-Université de Lorraine (UL), Cancéropôle du Grand Est-Institut National de la Santé et de la Recherche Médicale (INSERM), Centro de Estudios Avanzados en Zonas Aridas (CEAZA), Ecole Polytechnique Fédérale de Lausanne (EPFL), Laboratoire d'Ingénierie des Matériaux (LIM), Centre National de la Recherche Scientifique (CNRS), Lawrence Berkeley National Laboratory [Berkeley] (LBNL), Samsung Research &Development Institute India - Bangalore (Groupe Samsung) (SRI-B), Multimedia Research Center (MRC), University of Alberta, Division of Biostatistics (Biostat - MINNEAPOLIS), University of Minnesota [Twin Cities] (UMN), University of Minnesota System-University of Minnesota System, University of Southampton, University of Cambridge [UK] (CAM), Interactions, transferts, ruptures artistiques et culturels - EA 6301 (InTRu), Université de Tours (UT), Institut Jacques Monod (IJM (UMR_7592)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Stanford University, Unité de recherche Virologie et Immunologie Moléculaires (VIM (UR 0892)), Institut National de la Recherche Agronomique (INRA), National University of Singapore (NUS), Université Paris 1 Panthéon-Sorbonne - UFR Science Politique (UP1 UFR11), Université Paris 1 Panthéon-Sorbonne (UP1), National Diagnostics Centre (NDC), National University of Ireland [Galway] (NUI Galway), Arthritis Research UK Epidemiology Unit (MANCHESTER - Arthritis Research), Universidade do Porto = University of Porto, Advanced Laboratories on Embedded Systems [Roma] (ALES), Wageningen University and Research [Wageningen] (WUR), University of Oxford, Universitat Politècnica de Catalunya [Barcelona] (UPC), Institut National de Recherche et d'Analyse Physico-Chimique (INRAP), University of Connecticut (UCONN), Norwegian Institute for Air Research (NILU), Franche-Comté Électronique Mécanique, Thermique et Optique - Sciences et Technologies (UMR 6174) (FEMTO-ST), Université de Technologie de Belfort-Montbeliard (UTBM)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), University of Tehran, Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), Sociétés, Acteurs, Gouvernement en Europe (SAGE), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), The George Washington University (GW), Washington State University (WSU), Laboratoire de Physique de l'ENS Lyon (Phys-ENS), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Institut de recherche en informatique de Toulouse (IRIT), Université Toulouse Capitole (UT Capitole), Université de Toulouse (UT)-Université de Toulouse (UT)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Toulouse Mind & Brain Institut (TMBI), Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Université Catholique de Louvain = Catholic University of Louvain (UCL), Div Cyclotron & Radiopharmaceut Sci (DRDO, INMAS), School of Physics and Astronomy [St Andrews], Tata Research Development and Design Center (TRDDC), MOLTECH-Anjou, Université d'Angers (UA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Swedish Defense Research Agency (FOI), Centre de Recherche en Information Biomédicale sino-français (CRIBS), Université de Rennes (UR)-Southeast University [Jiangsu]-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratory of Image Science and Technology [Nanjing] (LIST), Laboratoire de glaciologie et géophysique de l'environnement (LGGE), Observatoire des Sciences de l'Univers de Grenoble (OSUG), Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut national des sciences de l'Univers (INSU - CNRS)-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut national des sciences de l'Univers (INSU - CNRS)-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Department of Mechanical and Automation Engineering (CAD Laboratory), Università degli studi di Bari Aldo Moro = University of Bari Aldo Moro (UNIBA), Heuristique et Diagnostic des Systèmes Complexes [Compiègne] (Heudiasyc), Université de Technologie de Compiègne (UTC)-Centre National de la Recherche Scientifique (CNRS), Biotechnology and Biological Sciences Research Council (BBSRC)-Biotechnology and Biological Sciences Research Council (BBSRC), Queen Mary University of London (QMUL), Centre d'économie de la Sorbonne (CES), Université Paris 1 Panthéon-Sorbonne (UP1)-Centre National de la Recherche Scientifique (CNRS), Paris School of Economics (PSE), Université Paris 1 Panthéon-Sorbonne (UP1)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École des hautes études en sciences sociales (EHESS)-École des Ponts ParisTech (ENPC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Istituto Dalle Molle di Studi sull'Intelligenza Artificiale (IDSIA), Università della Svizzera italiana = University of Italian Switzerland (USI)-Scuola universitaria professionale della Svizzera italiana = University of Applied Sciences and Arts of Southern Switzerland [Manno] (SUPSI), Pennsylvania State University (Penn State), Penn State System-Penn State System, Jet Propulsion Laboratory (JPL), NASA-California Institute of Technology (CALTECH), Hong Kong Baptist University (HKBU), Département Optique (OPT), Université européenne de Bretagne - European University of Brittany (UEB)-Télécom Bretagne-Institut Mines-Télécom [Paris] (IMT), Services répartis, Architectures, MOdélisation, Validation, Administration des Réseaux (SAMOVAR), Institut Mines-Télécom [Paris] (IMT)-Télécom SudParis (TSP), Département Réseaux et Services Multimédia Mobiles (TSP - RS2M), University of Melbourne, Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), University of Otago [Dunedin, Nouvelle-Zélande], Center for TeleInFrastruktur (CTIF), Aalborg University [Denmark] (AAU), Savoirs, Textes, Langage (STL) - UMR 8163 (STL), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Indian Institute of Technology Madras (IIT Madras), Universidade Estadual Paulista Júlio de Mesquita Filho = São Paulo State University (UNESP), Erasmus University Medical Center [Rotterdam] (Erasmus MC), Université Grenoble Alpes - UFR Médecine (UGA UFRM), Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), European Microsoft Innovation Center (EMIC), Laboratoire de Mécanique, Physique et Géosciences (LMPG), Université Le Havre Normandie (ULH), Normandie Université (NU)-Normandie Université (NU), Novartis Institute for Tropical Diseases (NITD), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Center for Mathematical Modeling (CMM), Universidad de Chile = University of Chile [Santiago] (UCHILE), Laboratory for Atmospheric and Space Physics [Boulder] (LASP), University of Colorado [Boulder], University of Occupational and Environmental Health [Kitakyushu] (UEOH), Indian Institute of Technology Delhi (IIT Delhi), Institut de Recherche sur les Phénomènes Hors Equilibre (IRPHE), Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Centre National de la Recherche Scientifique (CNRS), Yale University [New Haven]-Yale School of Medicine [New Haven, Connecticut] (YSM), Nanoscience Institute (NEST), University of Pisa - Università di Pisa, Laboratory Of Immune Cell Biology (LICB), National Institutes of Health [Bethesda] (NIH), Rheinische Friedrich-Wilhelms-Universität Bonn, Royal Institute of Technology [Stockholm] (KTH ), Institut für Informatik [München/Munich] (LMU), Ludwig-Maximilians-Universität München (LMU), National ICT Australia [Sydney] (NICTA), Institut d'Histoire et de Philosophie des Sciences et des Techniques (IHPST), Université Paris 1 Panthéon-Sorbonne (UP1)-Département d'Etudes Cognitives - ENS Paris (DEC), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), Universiteit Gent = Ghent University (UGENT), German Research Centre for Geosciences - Helmholtz-Centre Potsdam (GFZ), Laboratoire de recherche en Hydrodynamique, Énergétique et Environnement Atmosphérique (LHEEA), École Centrale de Nantes (ECN)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche en Génie Civil et Mécanique (GeM), Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Université de Nantes (UN)-École Centrale de Nantes (ECN)-Centre National de la Recherche Scientifique (CNRS), Department of Computer Science [KAIST] (CS), Korea Advanced Institute of Science and Technology (KAIST), Kardiyoloji, Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-CHU Limoges-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Minnesota [Twin Cities], Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Unité de recherche Virologie et Immunologie Moléculaires (VIM), Université Panthéon-Sorbonne - UFR Science Politique (UP1 UFR11), Université Panthéon-Sorbonne (UP1), Wageningen University and Research Centre [Wageningen] (WUR), Institut National de Recherche et d'Analyse Physico-chimique (Ariana, Tunisie) (INRAP), Université de Franche-Comté (UFC)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Université de Technologie de Belfort-Montbeliard (UTBM), George Washington University (GW), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université Toulouse 1 Capitole (UT1)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées, Université Catholique de Louvain (UCL), MOLTECH-ANJOU (MOLTECH-ANJOU), Université d'Angers (UA)-Centre National de la Recherche Scientifique (CNRS), University of Helsinki, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Southeast University [Jiangsu]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Centre National de la Recherche Scientifique (CNRS), Université Panthéon-Sorbonne (UP1)-Centre National de la Recherche Scientifique (CNRS), Università della Svizzera italiana (USI)-Scuola universitaria professionale della Svizzera italiana [Manno] (SUPSI), California Institute of Technology (CALTECH)-NASA, Institut Mines-Télécom [Paris] (IMT)-Télécom SudParis (TSP)-Centre National de la Recherche Scientifique (CNRS), Département Réseaux et Services Multimédia Mobiles (RS2M), Universidade Estadual Paulista Júlio de Mesquita Filho [São José do Rio Preto] (UNESP), Université Grenoble Alpes (UGA), Universidad de Santiago de Chile [Santiago] (USACH), Yale University [New Haven]-Yale University School of Medicine, Université Panthéon-Sorbonne (UP1)-Centre National de la Recherche Scientifique (CNRS)-Département d'Etudes Cognitives - ENS Paris (DEC), École normale supérieure - Paris (ENS Paris)-École normale supérieure - Paris (ENS Paris), Ghent University [Belgium] (UGENT), Université de Nantes - Faculté des Sciences et des Techniques, Grelier, Elisabeth, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Toulouse Mind & Brain Institut (TMBI), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Universidade do Porto, Université de Technologie de Belfort-Montbeliard (UTBM)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS), École normale supérieure - Lyon (ENS Lyon)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Université Toulouse 1 Capitole (UT1), Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire des Sciences de l'Univers de Grenoble (OSUG), Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry]), Università degli studi di Bari Aldo Moro (UNIBA), École des Ponts ParisTech (ENPC)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris 1 Panthéon-Sorbonne (UP1)-Centre National de la Recherche Scientifique (CNRS)-École des hautes études en sciences sociales (EHESS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Università della Svizzera italiana = University of Italian Switzerland (USI)-Scuola universitaria professionale della Svizzera italiana [Manno] (SUPSI), Institut Mines-Télécom [Paris] (IMT)-Télécom Bretagne-Université européenne de Bretagne - European University of Brittany (UEB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Universiteit Gent = Ghent University [Belgium] (UGENT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-CHU Limoges-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Centre National de la Recherche Scientifique (CNRS)-Université de Technologie de Belfort-Montbeliard (UTBM), Institut de Chimie du CNRS (INC)-Université d'Angers (UA)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS)-École Centrale de Nantes (ECN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut national des sciences de l'Univers (INSU - CNRS)-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS), Wolfson Centre for Age-related Diseases-King‘s College London, Cell biology, Public Health, Epidemiology, Health Technology Assessment (HTA), Erasmus MC other, Pathology, and Cardiothoracic Surgery

Subjects
Gerontology, Male, CHANGING RELATION, Nutrition and Disease, MESH : Life Expectancy, MESH : Aged, ECONOMIC-DEVELOPMENT, Poison control, MESH: Global Health, Global Health, Socioeconomic Factor, Communicable Disease, MESH : Chronic Disease, Health Transition, Voeding en Ziekte, Quality-Adjusted Life Year, SELF-RATED HEALTH, MESH : Socioeconomic Factors, Medicine, MESH : Female, MESH: Mortality, Premature, 2. Zero hunger, MESH: Aged, education.field_of_study, MESH: Middle Aged, Mortality rate, Medicine (all), GBD2013 diseases, [ SDV.SPEE ] Life Sciences [q-bio]/Santé publique et épidémiologie, General Medicine, Middle Aged, 3. Good health, MESH : Wounds and Injuries, Epidemiological transition, MESH: Quality-Adjusted Life Years, MESH: Communicable Diseases, NONCOMMUNICABLE DISEASES, Female, Quality-Adjusted Life Years, MESH: Life Expectancy, MESH: Health Transition, Human, MESH: Socioeconomic Factors, ACUTE MYOCARDIAL-INFARCTION, MESH : Male, MORTALITY TRENDS, Population, MESH : Health Transition, Communicable Diseases, Article, Life Expectancy, EUROPEAN-UNION, SDG 3 - Good Health and Well-being, General & Internal Medicine, SYSTEMATIC ANALYSIS, Disability-adjusted life year, Humans, Life Science, MESH : Middle Aged, Mortality, education, Premature, MESH : Mortality, Premature, VLAG, Aged, MESH: Humans, business.industry, Mortality, Premature, MESH: Chronic Disease, MESH : Communicable Diseases, Wounds and Injurie, MESH : Humans, MESH : Quality-Adjusted Life Years, Non-communicable disease, Chronic Disease, Socioeconomic Factors, Wounds and Injuries, medicine.disease, MESH: Male, LOW SOCIOECONOMIC-STATUS, Years of potential life lost, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, MESH: Wounds and Injuries, Life expectancy, RISK-FACTORS, MESH : Global Health, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, MESH: Female, Demography
Abstract

Summary Background The Global Burden of Disease Study 2013 (GBD 2013) aims to bring together all available epidemiological data using a coherent measurement framework, standardised estimation methods, and transparent data sources to enable comparisons of health loss over time and across causes, age–sex groups, and countries. The GBD can be used to generate summary measures such as disability-adjusted life-years (DALYs) and healthy life expectancy (HALE) that make possible comparative assessments of broad epidemiological patterns across countries and time. These summary measures can also be used to quantify the component of variation in epidemiology that is related to sociodemographic development. Methods We used the published GBD 2013 data for age-specific mortality, years of life lost due to premature mortality (YLLs), and years lived with disability (YLDs) to calculate DALYs and HALE for 1990, 1995, 2000, 2005, 2010, and 2013 for 188 countries. We calculated HALE using the Sullivan method; 95% uncertainty intervals (UIs) represent uncertainty in age-specific death rates and YLDs per person for each country, age, sex, and year. We estimated DALYs for 306 causes for each country as the sum of YLLs and YLDs; 95% UIs represent uncertainty in YLL and YLD rates. We quantified patterns of the epidemiological transition with a composite indicator of sociodemographic status, which we constructed from income per person, average years of schooling after age 15 years, and the total fertility rate and mean age of the population. We applied hierarchical regression to DALY rates by cause across countries to decompose variance related to the sociodemographic status variable, country, and time. Findings Worldwide, from 1990 to 2013, life expectancy at birth rose by 6·2 years (95% UI 5·6–6·6), from 65·3 years (65·0–65·6) in 1990 to 71·5 years (71·0–71·9) in 2013, HALE at birth rose by 5·4 years (4·9–5·8), from 56·9 years (54·5–59·1) to 62·3 years (59·7–64·8), total DALYs fell by 3·6% (0·3–7·4), and age-standardised DALY rates per 100 000 people fell by 26·7% (24·6–29·1). For communicable, maternal, neonatal, and nutritional disorders, global DALY numbers, crude rates, and age-standardised rates have all declined between 1990 and 2013, whereas for non–communicable diseases, global DALYs have been increasing, DALY rates have remained nearly constant, and age-standardised DALY rates declined during the same period. From 2005 to 2013, the number of DALYs increased for most specific non-communicable diseases, including cardiovascular diseases and neoplasms, in addition to dengue, food-borne trematodes, and leishmaniasis; DALYs decreased for nearly all other causes. By 2013, the five leading causes of DALYs were ischaemic heart disease, lower respiratory infections, cerebrovascular disease, low back and neck pain, and road injuries. Sociodemographic status explained more than 50% of the variance between countries and over time for diarrhoea, lower respiratory infections, and other common infectious diseases; maternal disorders; neonatal disorders; nutritional deficiencies; other communicable, maternal, neonatal, and nutritional diseases; musculoskeletal disorders; and other non-communicable diseases. However, sociodemographic status explained less than 10% of the variance in DALY rates for cardiovascular diseases; chronic respiratory diseases; cirrhosis; diabetes, urogenital, blood, and endocrine diseases; unintentional injuries; and self-harm and interpersonal violence. Predictably, increased sociodemographic status was associated with a shift in burden from YLLs to YLDs, driven by declines in YLLs and increases in YLDs from musculoskeletal disorders, neurological disorders, and mental and substance use disorders. In most country-specific estimates, the increase in life expectancy was greater than that in HALE. Leading causes of DALYs are highly variable across countries. Interpretation Global health is improving. Population growth and ageing have driven up numbers of DALYs, but crude rates have remained relatively constant, showing that progress in health does not mean fewer demands on health systems. The notion of an epidemiological transition—in which increasing sociodemographic status brings structured change in disease burden—is useful, but there is tremendous variation in burden of disease that is not associated with sociodemographic status. This further underscores the need for country-specific assessments of DALYs and HALE to appropriately inform health policy decisions and attendant actions. Funding Bill & Melinda Gates Foundation. BACKGROUND: The Global Burden of Disease Study 2013 (GBD 2013) aims to bring together all available epidemiological data using a coherent measurement framework, standardised estimation methods, and transparent data sources to enable comparisons of health loss over time and across causes, age-sex groups, and countries. The GBD can be used to generate summary measures such as disability-adjusted life-years (DALYs) and healthy life expectancy (HALE) that make possible comparative assessments of broad epidemiological patterns across countries and time. These summary measures can also be used to quantify the component of variation in epidemiology that is related to sociodemographic development. METHODS: We used the published GBD 2013 data for age-specific mortality, years of life lost due to premature mortality (YLLs), and years lived with disability (YLDs) to calculate DALYs and HALE for 1990, 1995, 2000, 2005, 2010, and 2013 for 188 countries. We calculated HALE using the Sullivan method; 95% uncertainty intervals (UIs) represent uncertainty in age-specific death rates and YLDs per person for each country, age, sex, and year. We estimated DALYs for 306 causes for each country as the sum of YLLs and YLDs; 95% UIs represent uncertainty in YLL and YLD rates. We quantified patterns of the epidemiological transition with a composite indicator of sociodemographic status, which we constructed from income per person, average years of schooling after age 15 years, and the total fertility rate and mean age of the population. We applied hierarchical regression to DALY rates by cause across countries to decompose variance related to the sociodemographic status variable, country, and time. FINDINGS: Worldwide, from 1990 to 2013, life expectancy at birth rose by 6·2 years (95% UI 5·6-6·6), from 65·3 years (65·0-65·6) in 1990 to 71·5 years (71·0-71·9) in 2013, HALE at birth rose by 5·4 years (4·9-5·8), from 56·9 years (54·5-59·1) to 62·3 years (59·7-64·8), total DALYs fell by 3·6% (0·3-7·4), and age-standardised DALY rates per 100 000 people fell by 26·7% (24·6-29·1). For communicable, maternal, neonatal, and nutritional disorders, global DALY numbers, crude rates, and age-standardised rates have all declined between 1990 and 2013, whereas for non-communicable diseases, global DALYs have been increasing, DALY rates have remained nearly constant, and age-standardised DALY rates declined during the same period. From 2005 to 2013, the number of DALYs increased for most specific non-communicable diseases, including cardiovascular diseases and neoplasms, in addition to dengue, food-borne trematodes, and leishmaniasis; DALYs decreased for nearly all other causes. By 2013, the five leading causes of DALYs were ischaemic heart disease, lower respiratory infections, cerebrovascular disease, low back and neck pain, and road injuries. Sociodemographic status explained more than 50% of the variance between countries and over time for diarrhoea, lower respiratory infections, and other common infectious diseases; maternal disorders; neonatal disorders; nutritional deficiencies; other communicable, maternal, neonatal, and nutritional diseases; musculoskeletal disorders; and other non-communicable diseases. However, sociodemographic status explained less than 10% of the variance in DALY rates for cardiovascular diseases; chronic respiratory diseases; cirrhosis; diabetes, urogenital, blood, and endocrine diseases; unintentional injuries; and self-harm and interpersonal violence. Predictably, increased sociodemographic status was associated with a shift in burden from YLLs to YLDs, driven by declines in YLLs and increases in YLDs from musculoskeletal disorders, neurological disorders, and mental and substance use disorders. In most country-specific estimates, the increase in life expectancy was greater than that in HALE. Leading causes of DALYs are highly variable across countries. INTERPRETATION: Global health is improving. Population growth and ageing have driven up numbers of DALYs, but crude rates have remained relatively constant, showing that progress in health does not mean fewer demands on health systems. The notion of an epidemiological transition-in which increasing sociodemographic status brings structured change in disease burden-is useful, but there is tremendous variation in burden of disease that is not associated with sociodemographic status. This further underscores the need for country-specific assessments of DALYs and HALE to appropriately inform health policy decisions and attendant actions. FUNDING: Bill & Melinda Gates Foundation.

Published
2015

39. Serum Lipid Levels and Risk Of Hand Osteoarthritis: the Chingford Prospective Cohort Study

Author

Nigel K Arden, Sanchez-Santos, Carlen Reyes, Maria García-Gil, Tim D. Spector, Rafel Ramos, Deborah J. Hart, Daniel Prieto-Alhambra, [Garcia-Gil M] Unitat de Suport a la Recerca Girona, Institut Universitari d'Investigació en Atenció Primària Jordi Gol (IDIAP Jordi Gol), Girona, Spain. Grup d’Investigació Translab, Departament de Ciències Mèdiques, Facultat de Medicina, Universitat de Girona, Girona, Spain. [Reyes C] Grup d’Investigació GREMPAL, Institut Universitari d'Investigació en Atenció Primària Jordi Gol (IDIAP Jordi Gol), Barcelona, Spain. CIBERFes, Universitat Autònoma de Barcelona and Instituto de Salud Carlos III, Barcelona, Spain. [Ramos R] Unitat de Suport a la Recerca-Girona, Institut Universitari d'Investigació en Atenció Primària Jordi Gol (IDIAP Jordi Gol), Girona, Spain. Centres d’Atenció Primària, Institut Català de la Salut, Girona, Spain. [Sanchez-Santos MT] Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, United Kingdom. Arthritis Research UK Sports Exercise and Osteoarthritis Centre of Excellence, University of Oxford, Oxford, United Kingdom. [Prieto-Alhambra D] Grup d’Investigació GREMPAL, Institut Universitari d'Investigació en Atenció Primària Jordi Gol (IDIAP Jordi Gol), Barcelona, Spain. CIBERFes, Universitat Autònoma de Barcelona and Instituto de Salud Carlos III, Barcelona, Spain. Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, United Kingdom. Arthritis Research UK Sports Exercise and Osteoarthritis Centre of Excellence, University of Oxford, Oxford, United Kingdom. [Spector TD, Hart DJ] Department of Twin Research & Genetic Epidemiology, King’s College London, Oxford, United Kingdom. [Arden NK] Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, United Kingdom. Arthritis Research UK Sports Exercise and Osteoarthritis Centre of Excellence, University of Oxford, Oxford, United Kingdom. MRC Lifecourse Epidemiology Unit, University of Southampton, Oxford, United Kingdom, and IDIAP Jordi Gol

Subjects
Blood Glucose, 0301 basic medicine, Other subheadings::Other subheadings::Other subheadings::/blood [Other subheadings], RHOA, Lipids [CHEMICALS AND DRUGS], Lípids de la sang, Gastroenterology, lípidos [COMPUESTOS QUÍMICOS Y DROGAS], chemistry.chemical_compound, 0302 clinical medicine, Odds Ratio, Prospective Studies, Prospective cohort study, education.field_of_study, Multidisciplinary, medicine.diagnostic_test, biology, Incidence (epidemiology), Musculoskeletal Diseases::Joint Diseases::Arthritis::Osteoarthritis [DISEASES], Middle Aged, Prognosis, Cohort, Medicine, Female, lipids (amino acids, peptides, and proteins), Raonament basat en casos, Otros calificadores::Otros calificadores::Otros calificadores::/sangre [Otros calificadores], Risk, medicine.medical_specialty, Science, Population, Hyperlipidemias, Article, 03 medical and health sciences, enfermedades musculoesqueléticas::artropatías::artritis::osteoartritis [ENFERMEDADES], Internal medicine, Osteoarthritis, medicine, Humans, epidemiología y bioestadística::epidemiología::estudios epidemiológicos::epidemiología analítica::estudios observacionales como asunto::estudios de cohortes [SALUD PÚBLICA], education, Triglycerides, 030203 arthritis & rheumatology, Artritis, business.industry, Cholesterol, Cholesterol, HDL, Epidemiology and Biostatistics::Epidemiology::Epidemiologic Studies::Analytical Epidemiology::Observational Studies as Topic::Cohort Studies [PUBLIC HEALTH], Cholesterol, LDL, Odds ratio, Hand, Surgery, Radiography, Logistic Models, 030104 developmental biology, chemistry, biology.protein, Lipid profile, business
Abstract

Serum Lipid Levels; Osteoarthritis; Cohort Studies Nivells de lípids sèrics; Osteoartritis; Estudis de cohorts Niveles de lípidos séricos; Osteoartritis; Estudios de cohortes The development of hand osteoarthritis (HOA) could be linked to hyperlipidaemia. No longitudinal studies have addressed the relationship between serum lipid profile and HOA. The study aim was to determine the association between serum lipid profile and the incidence of radiographic hand osteoarthritis (RHOA). All women in a prospective population-based cohort from the Chingford study with available baseline lipid measurements and without RHOA on a baseline were included. Study outcome was the incidence of RHOA in year 11 of follow-up. Serum lipid profile variables were analysed as continuous variables and categorised into quartiles. The association between serum lipid profile and RHOA was modeled using multivariable logistic regression. Overall RHOA incidence was 51.6% (45.7-57.4%). An inverse association between HDL cholesterol levels and the incidence of RHOA was observed by quartile: OR of 0.36 [95%CI 0.17-0.75], 0.52 [95%CI 0.26-1.06], and 0.48 [95%CI 0.22-1.03]. Triglycerides levels showed a significant trend. No relationship was found with total or LDL cholesterol. Higher levels of HDL cholesterol appear to protect against RHOA after 11 years of follow-up. More research is needed to elucidate HOA risk factors, the mechanisms related to the lipid pathway, and the effects of lipid-lowering agents on reducing the incidence of OA.

Published
2017

40. The effect on treatment response of fibromyalgic symptoms in early rheumatoid arthritis patients: results from the ESPOIR cohort

Author

Jingbo Niu, Nathalie Rincheval, Bernard Combe, Josefina Durán, David T. Felson, Cécile Gaujoux-Viala, Clinical Epidemiology Research and Training Unit ( BOSTON - Clin Epid Research ), Boston University School, Rheumatology Department ( Rheum Dep - SANTIAGO ), Pontificia Universidad Catolica del Chile, Département de Rhumatologie[Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ) -Hôpital Lapeyronie, Institut de Génétique Moléculaire de Montpellier ( IGMM ), Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS ), Department of rheumatology, University of Nimes, Arthritis Research UK Epidemiology Unit ( MANCHESTER - Arthritis Research ), University of Manchester [Manchester], Centre d'Investigation Clinique INSERM 1412 ( CIC 1412 - BREST ), Centre Hospitalier Régional Universitaire de Brest ( CHRU Brest ), CHRU Brest - Service de Rhumatologie ( CHU - BREST - Rhumato ), Lymphocyte B et Auto-immunité ( LBAI ), Université de Brest ( UBO ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Clinical Epidemiology Research and Training Unit (BOSTON - Clin Epid Research), Boston University School of Medicine (BUSM), Boston University [Boston] (BU)-Boston University [Boston] (BU), Rheumatology Department (Rheum Dep - SANTIAGO), Pontificia Universidad Católica de Chile (UC), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie, Institut de Génétique Moléculaire de Montpellier (IGMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Aide à la Décision pour une Médecine Personnalisé - Laboratoire de Biostatistique, Epidémiologie et Recherche Clinique - EA 2415 (AIDMP), Université Montpellier 1 (UM1)-Université de Montpellier (UM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Arthritis Research UK Epidemiology Unit (MANCHESTER - Arthritis Research), Centre d'Investigation Clinique (CIC - Brest), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHRU Brest - Service de Rhumatologie (CHU - BREST - Rhumato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Service de rhumatologie [CHU Pitié Salpêtrière] (GRC-08 EEMOIS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Boston University [Boston] (BU), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), CIC Brest, Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital de la Cavale Blanche, and Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)

Subjects
Male, rheumatoid arthritis, MESH: Remission Induction, MESH: Antirheumatic Agents, MESH : Fibromyalgia, [SDV]Life Sciences [q-bio], early rheumatoid arthritis, MESH : Aged, Arthritis, Severity of Illness Index, DMARDs, Arthritis, Rheumatoid, Cohort Studies, fibromyalgic RA, 0302 clinical medicine, Fibromyalgia, MESH : Female, Pharmacology (medical), 030212 general & internal medicine, Prospective cohort study, skin and connective tissue diseases, MESH: Cohort Studies, ComputingMilieux_MISCELLANEOUS, MESH: Treatment Outcome, MESH: Aged, MESH: Arthritis, Rheumatoid, MESH: Middle Aged, Remission Induction, MESH: Follow-Up Studies, Middle Aged, Clinical Science, MESH : Adult, Corrigenda, MESH : Antirheumatic Agents, Treatment Outcome, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, MESH: Young Adult, Antirheumatic Agents, Rheumatoid arthritis, Cohort, Female, fibromyalgia, MESH : Severity of Illness Index, Adult, musculoskeletal diseases, medicine.medical_specialty, Adolescent, MESH : Male, MESH : Young Adult, MESH : Cohort Studies, MESH : Treatment Outcome, [ SDV.MHEP.RSOA ] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Young Adult, outcome measures, 03 medical and health sciences, Rheumatology, Internal medicine, MESH: Severity of Illness Index, disease activity scores, MESH : Adolescent, [ SDV.MHEP ] Life Sciences [q-bio]/Human health and pathology, medicine, Humans, MESH : Middle Aged, Aged, MESH: Adolescent, 030203 arthritis & rheumatology, therapy, MESH : Remission Induction, MESH: Fibromyalgia, MESH: Humans, DASS, [ SDV ] Life Sciences [q-bio], Surrogate endpoint, business.industry, MESH : Humans, MESH: Adult, MESH : Follow-Up Studies, medicine.disease, Crohn's Disease Activity Index, MESH: Male, MESH : Arthritis, Rheumatoid, Physical therapy, business, treat to target, MESH: Female, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Follow-Up Studies
Abstract

International audience; OBJECTIVE:To evaluate whether patients with RA who belong to the spectrum of fibromyalgic RA (FRA) have an impaired response to treatment measured by traditional activity scores.METHODS:Patients from the ESPOIR cohort were analysed. This prospective cohort included 813 patients with early arthritis not initially receiving DMARDs. Among the 697 patients who met RA classification criteria, we studied two groups, one with and the other without FRA. The following endpoints were compared at 6, 12 and 18 months using a mixed linear regression model: 28-joint DAS (DAS28), Simple Disease Activity Index (SDAI), Clinical Disease Activity Index (CDAI) and HAQ. In addition, attainment of low disease activity (LDA; DAS28

Published
2017

41. The systemic lupus erythematosus IRF5 risk haplotype is associated with systemic sclerosis

Author

F David Carmona, Jose-Ezequiel Martin, Lorenzo Beretta, Carmen P Simeón, Patricia E Carreira, José Luis Callejas, Mónica Fernández-Castro, Luis Sáez-Comet, Emma Beltrán, María Teresa Camps, María Victoria Egurbide, Spanish Scleroderma Group, Paolo Airó, Raffaella Scorza, Claudio Lunardi, Nicolas Hunzelmann, Gabriela Riemekasten, Torsten Witte, Alexander Kreuter, Jörg H W Distler, Rajan Madhok, Paul Shiels, Jacob M van Laar, Carmen Fonseca, Christopher Denton, Ariane Herrick, Jane Worthington, Annemie J Schuerwegh, Madelon C Vonk, Alexandre E Voskuyl, Timothy R D J Radstake, Javier Martín, Rheumatology, CCA - Disease profiling, The Spanish Scleroderma Group, [Carmona,FD, Martín JE] Instituto de Parasitología y Biomedicina López-Neyra, CSIC, Granada, Spain. [ Beretta,L, Scorza,R] Referral Center for Systemic Autoimmune Diseases, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico di Milano, University of Milan, Italy. [ Carmen,P S] Department of Internal Medicine, Hospital Vall d’Hebron, Barcelona, Spain. [Carreira,P E] Department of Rheumatology, Hospital 12 de Octubre, Madrid, Spain. [Callejas,J.L. ] Department of Internal Medicine, Hospital Clínico San Cecilio, Granada, Spain. [Fernández-Castro,M.] Department of Rheumatology, Hospital Puerta de Hierro Majadahonda, Madrid, Spain. [Sáez-Comet,L] Department of Internal Medicine, Hospital Universitario Miguel Servet, Zaragoza, Spain. [Beltran,E.] Department of Rheumatology, Hospital General Universitario de Valencia, Spain. [Camps,MT.] Department of Internal Medicine, Hospital Carlos Haya, Málaga, Spain. [Egurbide,M.V.] Department of Internal Medicine, Hospital de Cruces, Barakaldo, Spain. [Airo,P.] Servizio di Reumatologia ed Immunologia Clinica Spedali Civili, Brescia, Italy. [Lunardi,C] Department of Medicine, Universita` degli Studi di Verona, Verona, Italy. [Hunzelmann, N] Department of Dermatology, University of Cologne, Cologne, Germany. [Riemekasten,G] Department of Rheumatology and Clinical Immunology, Charite´ University Hospital, Berlin, Germany. [Witte,T] Hannover Medical School, Hannover, Germany. [Kreuter,A] Ruhr University of Bochum, Germany. [Distler,JHW] Department of Internal Medicine 3, Institute for Clinical Immunology, University of Erlangen-Nuremberg, Erlangen, Germany. [Madhok,R, Shiels,P] Centre for Rheumatic Diseases, Glasgow Royal Infirmary, University of Glasgow, United Kingdom. [Van Laar,JM] Institute of Cellular Medicine, Newcastle University, Newcastle, United Kingdom. [Fonseca,C, Denton,C] Centre for Rheumatology, Royal Free and University College Medical School, London, United Kingdom. [Herrick,A, Worthington, J] Arthritis Research UK Epidemiology Unit, University of Manchester, Manchester Academic Health Science Centre, Manchester, United Kingdom. [Schuerwegh,AJ] Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands. [Vonk,MC, Radstake,T.R.D] Department of Rheumatology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands. [Voskuyl,AE] Department of Rheumatology, VU University Medical Center, Amsterdam, The Netherlands. [Radstake,T.R.D] Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, The Netherland., and 17552, Arthritis Research UK, United Kingdom

Subjects
Male, Linkage disequilibrium, Phenomena and Processes::Genetic Phenomena::Phenotype [Medical Subject Headings], Polimorfismo de nucleótido simple, SLE, lcsh:Medicine, Autoimmunity, Genome-wide association study, Linkage Disequilibrium, Scleroderma, Phenomena and Processes::Genetic Phenomena::Genotype::Haplotypes [Medical Subject Headings], Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Gene Frequency, Named Groups::Persons::Population Groups::Continental Population Groups::European Continental Ancestry Group [Medical Subject Headings], Risk Factors, IRF5, Genetics of the Immune System, Lupus Erythematosus, Systemic, Diseases::Skin and Connective Tissue Diseases::Skin Diseases::Scleroderma, Systemic [Medical Subject Headings], skin and connective tissue diseases, lcsh:Science, Multidisciplinary, Diseases::Immune System Diseases::Autoimmune Diseases::Lupus Erythematosus, Systemic [Medical Subject Headings], Predisposición genética a la enfermedad, Phenomena and Processes::Genetic Phenomena::Genetic Linkage::Linkage Disequilibrium [Medical Subject Headings], Phenomena and Processes::Genetic Phenomena::Genotype::Genetic Predisposition to Disease [Medical Subject Headings], Phenotype, Interferon Regulatory Factors, SYSTEMIC SCLEROSIS, Medicine, Evaluation of complex medical interventions Auto-immunity, transplantation and immunotherapy [NCEBP 2], Female, TYPE I INTERFERON, Haplotipos, Research Article, Factores de riesgo, Immunology, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Peptides::Intracellular Signaling Peptides and Proteins::Adaptor Proteins, Signal Transducing::Interferon Regulatory Factors [Medical Subject Headings], Check Tags::Male [Medical Subject Headings], Health Care::Environment and Public Health::Public Health::Epidemiologic Factors::Causality::Risk Factors [Medical Subject Headings], Single-nucleotide polymorphism, Human leukocyte antigen, Biology, Polymorphism, Single Nucleotide, White People, Autoimmune Diseases, Rheumatology, Lupus eritematoso sistémico, Genetics, Humans, Genetic Predisposition to Disease, Grupo de ascendencia continental europea, Allele, Allele frequency, Alleles, Genetic Association Studies, Phenomena and Processes::Genetic Phenomena::Genetic Structures::Genome::Genome Components::Genes::Alleles [Medical Subject Headings], Scleroderma, Systemic, Haplotype, lcsh:R, Phenomena and Processes::Genetic Phenomena::Genetic Structures::Genome::Genome Components::Genetic Loci [Medical Subject Headings], Human Genetics, Phenomena and Processes::Genetic Phenomena::Genetic Variation::Polymorphism, Genetic [Medical Subject Headings], Factores reguladores del interferón, Haplotypes, Desequilibrio de ligamiento, Check Tags::Female [Medical Subject Headings], Genetic Loci, Genetics of Disease, Genetic Polymorphism, Clinical Immunology, lcsh:Q, Phenomena and Processes::Genetic Phenomena::Gene Frequency [Medical Subject Headings], Population Genetics
Abstract

Systemic sclerosis (SSc) is a fibrotic autoimmune disease in which the genetic component plays an important role. One of the strongest SSc association signals outside the human leukocyte antigen (HLA) region corresponds to interferon (IFN) regulatory factor 5 (IRF5), a major regulator of the type I IFN pathway. In this study we aimed to evaluate whether three different haplotypic blocks within this locus, which have been shown to alter the protein function influencing systemic lupus erythematosus (SLE) susceptibility, are involved in SSc susceptibility and clinical phenotypes. For that purpose, we genotyped one representative single-nucleotide polymorphism (SNP) of each block (rs10488631, rs2004640, and rs4728142) in a total of 3,361 SSc patients and 4,012 unaffected controls of Caucasian origin from Spain, Germany, The Netherlands, Italy and United Kingdom. A meta-analysis of the allele frequencies was performed to analyse the overall effect of these IRF5 genetic variants on SSc. Allelic combination and dependency tests were also carried out. The three SNPs showed strong associations with the global disease (rs4728142: P = 1.34×10-8, OR = 1.22, CI 95% = 1.14-1.30; rs2004640: P = 4.60×10-7, OR = 0.84, CI 95% = 0.78-0.90; rs10488631: P = 7.53×10-20, OR = 1.63, CI 95% = 1.47-1.81). However, the association of rs2004640 with SSc was not independent of rs4728142 (conditioned P = 0.598). The haplotype containing the risk alleles (rs4728142*A-rs2004640*T-rs10488631*C: P = 9.04×10-22, OR = 1.75, CI 95% = 1.56-1.97) better explained the observed association (likelihood P-value = 1.48×10-4), suggesting an additive effect of the three haplotypic blocks. No statistical significance was observed in the comparisons amongst SSc patients with and without the main clinical characteristics. Our data clearly indicate that the SLE risk haplotype also influences SSc predisposition, and that this association is not sub-phenotype-specific. © 2013 Carmona et al.

Published
2013

42. Comorbidities in the UK Primary Sjögren’s Syndrome Registry

Author

Jessica Tarn, Dennis Lendrem, Michael Barnes, John Casement, Wan-Fai Ng, Newcastle University [Newcastle], Projet NECESSITY (PN), Hôpitaux Universitaires Paris Sud [AP-HP] (HUPS)-Immunologie des maladies virales, auto-immunes, hématologiques et bactériennes (IMVA-HB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Queen Mary University of London (QMUL), Newcastle Upon Tyne Hospitals NHS Foundation Trust, This work was supported by Foundation of Research in Rheumatology (FOREUM): (grant number: 022). This work received infrastructure support from the National Institute for Health Research (NIHR) Newcastle Biomedical Research Centre and the NIHR Clinical Research Facility, based at Newcastle upon Tyne Hospitals NHS Foundation Trust and Newcastle University, and from the Arthritis Research UK and Versus Arthritis Newcastle upon Tyne Experimental Arthritis Treatment Centre. The UKPSSR received grant support from the UK Medical Research Council (grant number G0800629 to W-FN, SJB, BG) and British Sjögren’s Syndrome Association. This work was supported, in part, by the National Institute for Health Research: NIHR202635 - Artificial Intelligence Multimorbidity Development Award and the Innovative Medicines Initiative 2 Joint Undertaking (JU) (NECESSITY grant agreement No 806975) receiving support from the European Union’s Horizon 2020 research and innovation program and EFPIA., European Project: 806975,NECESSITY, European Project: (grant No 116060),IMPRiND, Piatrova, Alena, NEw Clinical Endpoints in primary Sjögren’s Syndrome: an Interventional Trial based on stratifYing patients - NECESSITY - 0000-00-00 - 0000-00-00 - 806975 - VALID, and EU/EFPIA/Innovative Medicines Initiative 2 Joint Undertaking. - IMPRiND - (grant No 116060) - INCOMING

Subjects
[SDV]Life Sciences [q-bio], Immunology, stratified medicine, Pain, crossectional analysis, United Kingdom, [SDV] Life Sciences [q-bio], comorbidity, Sjogren's syndrome, Humans, Immunology and Allergy, Registries, polypharmacy, Fatigue
Abstract

IntroductionPrimary Sjögren’s Syndrome (PSS) is a chronic disease characterised by symptoms of oral and ocular dryness, pain, fatigue, anxiety and depression. PSS patients can be subclassified by the pattern of severity of these five key symptoms using the Newcastle Sjögren’s Stratification Tool (NSST). Although PSS is often associated with one or more comorbidities, the relationship between comorbidities, polypharmacy, and PSS symptom burden is unclear. Using data from the UK Primary Sjögren’s Syndrome Registry (UKPSSR) we describe the landscape of polypharmacy and comorbidities in PSS.MethodsThe UKPSSR is research biobank of clinically well-defined PSS patients where clinical, demographic, comorbidities and concomitant medications data are recorded. Patients were subclassified into the four NSST subgroups: Low Symptom Burden (LSB), High Symptom Burden (HSB), Dryness Dominated Fatigue (DDF) and Pain Dominated Fatigue (PDF). Group analyses of comorbid conditions and polypharmacy scores were performed. Comorbidity and Polypharmacy Scores (CPS) were modelled as a function of age, sex, symptom duration, body mass index (BMI), current immunosuppressant and hydroxychloroquine prescriptions and NSST subgroup.ResultsThere were marked differences in the number and the nature of comorbidities associated with the NSST subgroups. LSB and DDF patients were characterized by fewer comorbidities and medications. In contrast, HSB and PDF patients were associated with more comorbidities and were more likely to be prescribed multiple medications. Group analysis shows that HSB patients are more closely associated with peripheral vascular disease and infection whereas the PDF patients were associated with cardiovascular disease and gastrointestinal comorbidities. Comorbidity and polypharmacy scores increase with age and BMI regardless of symptom subgroup and symptom duration. In addition, the longer the reported symptom duration the higher the associated comorbidities and polypharmacy scores.ConclusionComorbid conditions are more prevalent in some subgroups of the PSS cohort but increase with age and BMI across the entire cohort. It is unclear from these data whether specific comorbid conditions are a consequence of PSS or represent shared aetiology or pathogenetic susceptibility. Regardless, these findings may have implications for disease management and clinical trial design.

Published
2022

43. Activation and Contraction of Human 'Vascular' Smooth Muscle Cells Grown From Circulating Blood Progenitors

Author

Isra Marei, Hime Gashaw, Ryota Kawai, Fisnik Shala, Nura A. Mohamed, Jake Samuel, Annabelle Vandenheste, Blerina Ahmetaj-Shala, Charis Pericleous, Kalliopi Bokea, Jane A. Mitchell, Nicholas S. Kirkby, Stephen Rothery, Arthritis Research UK, and British Heart Foundation

Subjects
Cell type, Vascular smooth muscle, Contraction (grammar), QH301-705.5, chemistry.chemical_element, Calcium, Calcium in biology, Cell and Developmental Biology, Tissue engineering, blood vessel, medicine, Progenitor cell, Biology (General), smooth muscle progenitor cells, calcium, contraction, Cell Biology, personalized medicine, Brief Research Report, musculoskeletal system, Cell biology, medicine.anatomical_structure, chemistry, cardiovascular system, tissues, Developmental Biology, Blood vessel
Abstract

Blood outgrowth smooth muscle cells offer the means to study vascular cells without the requirement for surgery providing opportunities for drug discovery, tissue engineering and personalised medicine. However, little is known about these cells which has meant their therapeutic potential remains unexplored. Our objective was to investigate for the first time the ability of blood outgrowth smooth muscle cells and vessel derived smooth muscle cells to sense the thromboxane mimetic U46619 by measuring intracellular calcium elevation and contraction. U46619 (10 26 -6 M) increased cytosolic calcium in blood outgrowth smooth muscle cells fibroblasts. Increased calcium signal peaked between 10-20 seconds after U46619 in both smooth muscle cell types. Importantly, U46619 (10-9 to 10-6 M) induced concentration-dependent contractions of both blood outgrowth smooth muscle cells and vascular smooth muscle cells but not in fibroblasts. In summary, we show that functional responses of blood outgrowth smooth muscle cells are in line with vascular smooth muscle cells providing critical evidence of their application in biomedical research.

Published
2021

44. Validation of ACR/EULAR definition of remission in rheumatoid arthritis from RA practice: the ESPOIR cohort

Author

Nathalie Rincheval, Bernard Combe, Bin Zhang, David T. Felson, Clinical Epidemiology Research and Training Unit (BOSTON - Clin Epid Research), Boston University School of Medicine (BUSM), Boston University [Boston] (BU)-Boston University [Boston] (BU), Institut de Génétique Moléculaire de Montpellier (IGMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Département de Rhumatologie[Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie, Arthritis Research UK Epidemiology Unit (MANCHESTER - Arthritis Research), University of Manchester [Manchester], Clinical Epidemiology Research and Training Unit ( BOSTON - Clin Epid Research ), Boston University School, Institut de Génétique Moléculaire de Montpellier ( IGMM ), Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS ), Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ) -Hôpital Lapeyronie, Arthritis Research UK Epidemiology Unit ( MANCHESTER - Arthritis Research ), Immunologie et Pathologie ( EA2216 ), Université de Brest ( UBO ) -IFR148, Centre d'Investigation Clinique ( CIC - Brest ), and Université de Brest ( UBO ) -Institut National de la Santé et de la Recherche Médicale ( INSERM )

Subjects
Male, MESH: Remission Induction, [SDV]Life Sciences [q-bio], MESH : Aged, Arthritis, Cohort Studies, Arthritis, Rheumatoid, 0302 clinical medicine, Medicine, Immunology and Allergy, MESH : Female, 030212 general & internal medicine, skin and connective tissue diseases, MESH: Cohort Studies, MESH: Aged, MESH: Arthritis, Rheumatoid, Clinical Trials as Topic, MESH: Middle Aged, Remission Induction, MESH : Adult, Middle Aged, MESH: Predictive Value of Tests, 3. Good health, Editorial, MESH: Young Adult, Rheumatoid arthritis, Cohort, Female, Cohort study, Research Article, Adult, musculoskeletal diseases, medicine.medical_specialty, MESH: Clinical Trials as Topic, Adolescent, MESH : Male, Immunology, MESH : Young Adult, MESH : Cohort Studies, 03 medical and health sciences, Young Adult, Rheumatology, Predictive Value of Tests, Internal medicine, MESH : Adolescent, MESH: Rheumatology, Humans, MESH : Middle Aged, MESH : Predictive Value of Tests, MESH : Rheumatology, Aged, 030203 arthritis & rheumatology, MESH: Adolescent, MESH : Remission Induction, MESH: Humans, [ SDV ] Life Sciences [q-bio], business.industry, MESH : Humans, MESH: Adult, medicine.disease, MESH: Male, Clinical trial, MESH : Clinical Trials as Topic, MESH : Arthritis, Rheumatoid, Physical therapy, Observational study, business, MESH: Female, Rheumatism
Abstract

International audience; INTRODUCTION: In development of the American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) rheumatoid arthritis (RA) remission definitions using clinical trials data, one criterion used to compare different remission definitions was whether, compared with those not in remission, those in remission had evidence of later disease stability defined by x-ray and functional status. Validation of the RA remission criteria using observational study data is necessary before recommending their use in practice. METHODS: Using data from those who met RA criteria in the ESPOIR cohort, we matched each person in remission with a person not in remission and then carried out analyses comparing later stability of x-ray and health assessment questionnaire (HAQ) between the two groups. We compared the predictive validity of the same candidate definitions of remission evaluated in the ACR/EULAR process. To minimize potential bias and produce more stable results, we used a bootstrap resampling approach to select those not in remission, repeating the sample matching analysis process 500 times. RESULTS: Results were similar to those of clinical trials analyzed for the ACR/EULAR remission criteria. Specifically, the ACR/EULAR remission definitions using either an simple disease activity index (SDAI) ≤ 3.3, clinical disease activity index (CDAI) ≤ 2.8 or a definition of remission requiring tender joint count, swollen joint count, patient global assessment all ≤ 1 performed as well or better than other candidate definitions of remission in terms of predicting later x-ray and function stability. CONCLUSIONS: ACR/EULAR definitions of remission developed for trials are similarly valid in observational studies in RA and could be used in practice.

Published
2012

45. Understanding the impact of lumbar disc degeneration and chronic low back pain: A cross-sectional electromyographic analysis of postural strategy during predicted and unpredicted postural perturbations

Author

Adrian Lim, Paul H. Strutton, Alison H. McGregor, JA Deane, Macaluso, Andrea, and Arthritis Research UK

Subjects
Male, myalgia, Muscle Physiology, Physiology, medicine.medical_treatment, Rectus Abdominis, Intervertebral Disc Degeneration, Electromyography, Medicine and Health Sciences, Biomechanics, Postural Balance, Musculoskeletal System, Multidisciplinary, Rehabilitation, medicine.diagnostic_test, Middle Aged, Magnetic Resonance Imaging, Multidisciplinary Sciences, medicine.anatomical_structure, Neuropathic pain, Science & Technology - Other Topics, Legs, Medicine, Female, Anatomy, medicine.symptom, Research Article, Adult, medicine.medical_specialty, General Science & Technology, Cognitive Neuroscience, Science, Lower Back Pain, Pain, Asymptomatic, Pelvis, Motor Reactions, Signs and Symptoms, Physical medicine and rehabilitation, medicine, Humans, General, Skeleton, Science & Technology, Hip, business.industry, Ankles, Biology and Life Sciences, Myalgia, Trunk, Sagittal plane, Postural Control, Cross-Sectional Studies, Body Limbs, Cognitive Science, Clinical Medicine, Ankle, Musculoskeletal Mechanics, business, Low Back Pain, Neuroscience
Abstract

People with chronic low back pain (LBP) exhibit changes in postural control. Stereotypical muscle activations resulting from external perturbations include anticipatory (APAs) and compensatory (CPAs) postural adjustments. The aim and objective of this study was to determine differences in postural control strategies (peak amplitude, APAs and CPAs) between symptomatic and asymptomatic adults with and without Lumbar Disc Degeneration (LDD) using surface electromyography during forward postural perturbation. Ninety-seven subjects participated in the study (mean age 50 years (SD 12)). 3T MRI was used to acquire T2 weighted images (L1-S1). LDD was determined using Pfirrmann grading. A bespoke translational platform was designed to deliver horizontal perturbations in sagittal and frontal planes. Electromyographic activity was analysed bilaterally from 8 trunk and lower limb muscles during four established APA and CPA epochs. A Kruskal-Wallis H test with Bonferroni correction for multiple comparisons was conducted. Four groups were identified: no LDD no pain (n = 19), LDD no pain (n = 38), LDD pain (n = 35) and no LDD pain (n = 5). There were no significant differences in age or gender between groups. The most significant difference between groups was observed during forward perturbation. In the APA and CPA phases of predictable forward perturbation there were significant differences ankle strategy between groups (p = 0.007–0.008); lateral gastrocnemius and tibialis anterior activity was higher in the LDD pain than the LDD no pain group. There were no significant differences in the unpredictable condition (p>0.05). These findings were different from the remaining groups, where significant differences in hip strategy were observed during both perturbation conditions (p = 0.004–0.006). Symptomatic LDD patients exhibit different electromyographic strategies to asymptomatic LDD controls. Future LBP electromyographic research should benefit from considering assessment of both lower limbs in addition to the spine. This approach could prevent underestimation of postural control deficits and guide targeted rehabilitation.

Published
2021

46. In vivo biomolecular imaging of zebrafish embryos using confocal Raman spectroscopy

Author

Qu Chen, Timothy J. Keane, Molly M. Stevens, Mads Sylvest Bergholt, Håkon Høgset, Margaret J. Dallman, James P. K. Armstrong, Conor C. Horgan, Vincenzo Torraca, Serge Mostowy, Laurence Bugeon, Commission of the European Communities, Medical Research Council (MRC), Wellcome Trust, and Arthritis Research UK

Subjects
DYNAMICS, 0301 basic medicine, Embryo, Nonmammalian, General Physics and Astronomy, GENERATION MICROSCOPY, Spectrum Analysis, Raman, Imaging, Animals, Genetically Modified, 0302 clinical medicine, INFECTION, Zebrafish, Multidisciplinary, biology, Chemistry, CANCER, Molecular Imaging, Cell biology, Multidisciplinary Sciences, Raman spectroscopy, embryonic structures, Science & Technology - Other Topics, GROWTH, animal structures, Science, Confocal, Mycobacterium Infections, Nontuberculous, macromolecular substances, Time-Lapse Imaging, Article, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, In vivo, Wound response, Animals, Mycobacterium marinum, Wound Healing, Science & Technology, IDENTIFICATION, fungi, technology, industry, and agriculture, General Chemistry, biology.organism_classification, 030104 developmental biology, CELLS, Multivariate Analysis, Zebrafish embryo, Molecular imaging, Confocal raman spectroscopy, 030217 neurology & neurosurgery
Abstract

Zebrafish embryos provide a unique opportunity to visualize complex biological processes, yet conventional imaging modalities are unable to access intricate biomolecular information without compromising the integrity of the embryos. Here, we report the use of confocal Raman spectroscopic imaging for the visualization and multivariate analysis of biomolecular information extracted from unlabeled zebrafish embryos. We outline broad applications of this method in: (i) visualizing the biomolecular distribution of whole embryos in three dimensions, (ii) resolving anatomical features at subcellular spatial resolution, (iii) biomolecular profiling and discrimination of wild type and ΔRD1 mutant Mycobacterium marinum strains in a zebrafish embryo model of tuberculosis and (iv) in vivo temporal monitoring of the wound response in living zebrafish embryos. Overall, this study demonstrates the application of confocal Raman spectroscopic imaging for the comparative bimolecular analysis of fully intact and living zebrafish embryos., Raman spectroscopic imaging (RSI) can provide information on the chemical composition of a sample, but application to living organisms has lacked sufficient spatial resolution and signal strength. Here the authors apply confocal RSI to whole-mount zebrafish embryos to distinguish different infectious bacteria and to living zebrafish embryos to monitor the wound healing process.

Published
2020

47. A Blueprint for Translational Regenerative Medicine

Author

Stuart J. Forbes, Molly M. Stevens, P. Stephen Patrick, Daniel J. Stuckey, Venkat Pisupati, Roger A. Barker, Wei-Li Kuan, James P. K. Armstrong, Richard O.C. Oreffo, Anne C. Roques, Fiona M. Watt, Timothy J. Keane, Claire M. Mooney, Commission of the European Communities, Medical Research Council (MRC), Wellcome Trust, Arthritis Research UK, and Medical Research Council

Subjects
0303 health sciences, Engineering, Modalities, business.industry, regenerative medicine, translation, General Medicine, 06 Biological Sciences, Regenerative Medicine, Regenerative medicine, Article, 3. Good health, Translational Research, Biomedical, 03 medical and health sciences, 0302 clinical medicine, Blueprint, tissue engineering, 030220 oncology & carcinogenesis, cells, Engineering ethics, business, 11 Medical and Health Sciences, biomaterials, 030304 developmental biology
Abstract

The last few decades have produced a large number of proof-of-concept studies in regenerative medicine. However, the route to clinical adoption is fraught with technical and translational obstacles that frequently consign promising academic solutions to the so-called “valley of death.” This review is intended to serve as a blueprint for translational regenerative medicine: we suggest principles to help guide cell and material selection, present key in vivo imaging modalities and argue that the host immune response should be considered throughout therapeutic development. Finally, we suggest a pathway to navigate the often complex regulatory and manufacturing landscape of translational regenerative medicine.

Published
2020

48. Reliability and minimal detectable change of the ‘Imperial Spine’ marker set for the evaluation of spinal and lower limb kinematics in adults

Author

Alison H. McGregor, JA Deane, Enrica Papi, Andrew N. Phillips, Arthritis Research UK, and Versus Arthritis

Subjects
Adult, 030506 rehabilitation, medicine.medical_specialty, Kinematics, Bioinformatics, Intraclass correlation, lcsh:Medicine, 0601 Biochemistry and Cell Biology, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, 0302 clinical medicine, Gait (human), Physical medicine and rehabilitation, Sit to stand, Three dimensional motion capture, Marker set, Minimal detectable change, medicine, Humans, Low back pain, Bland–Altman plot, lcsh:Science (General), lcsh:QH301-705.5, Gait, Reliability (statistics), Motion technology, business.industry, lcsh:R, Reproducibility of Results, General Medicine, Reliability, Spine, Sagittal plane, Biomechanical Phenomena, Research Note, Standard error, medicine.anatomical_structure, lcsh:Biology (General), Lower Extremity, Sample size determination, medicine.symptom, 0305 other medical science, business, 030217 neurology & neurosurgery, lcsh:Q1-390, 1199 Other Medical and Health Sciences
Abstract

Objectives As a step towards the comprehensive evaluation of movement in patients with low back pain, the aim of this study is to design a marker set (three rigid segment spine, pelvic and lower limb model) and evaluate the reliability and minimal detectable change (MDC) of this marker set in healthy adults during gait and sit to stand (STS) tasks using three dimensional motion capture. Results The ‘Imperial Spine’ marker set was used to assess relative peak angles during gait and STS tasks using the minimum recommended sample size (n = 10) for reliability studies with minimum Intraclass Correlation Coefficient (ICC) of 0.70, optimum ICC 0.90 and 9 trials replicated per subject per task. Intra- and inter-tester reliability between an experienced and inexperienced user was examined. ICC, mean, standard error (SEM), Bland Altman 95% limits of agreement (LOA) and MDC were computed. ICC values demonstrated excellent intra- and inter-tester reliability in both tasks, particularly in the sagittal plane (majority ICCs > 0.80). SEM measurements were lower in gait (0.8–5.5°) than STS tasks (1°-12.6°) as were MDC values. LOA demonstrated good agreement. The ‘Imperial Spine’ marker set is reliable for use in healthy adults during functional tasks. Future evaluation in patients is required.

Published
2020

49. Loss of Adenylyl Cyclase 6 in Leptin Receptor‐Expressing Stromal Cells Attenuates Loading‐Induced Endosteal Bone Formation

Author

Madeline M Owen, Andrew A. Pitsillides, Gillian P. Johnson, Behzad Javaheri, Mathieu Riffault, David A. Hoey, SFI, IRC, ERC, Biotechnology and Biological Sciences Research Council, Arthritis Research UK, European Union (EU), and ERDF

Subjects
ADENYLYL CYCLASE 6, Stromal cell, Endocrinology, Diabetes and Metabolism, Cellular differentiation, Population, Cell, 030209 endocrinology & metabolism, Diseases of the musculoskeletal system, in vivo mechanical loading, 03 medical and health sciences, 0302 clinical medicine, adenylyl cyclase 6, medicine, Orthopedics and Sports Medicine, education, BONE ADAPTATION, 030304 developmental biology, Orthopedic surgery, 0303 health sciences, education.field_of_study, Leptin receptor, Chemistry, Osteoblast, Original Articles, bone adaptation, MECHANOBIOLOGY, Cell biology, medicine.anatomical_structure, RC925-935, IN VIVO MECHANICAL LOADING, Original Article, Bone marrow, Stem cell, RD701-811, STEM CELLS
Abstract

peer-reviewed Bone marrow stromal/stem cells represent a quiescent cell population that replenish the osteoblast bone-forming cell pool with age and in response to injury, maintaining bone mass and repair. A potent mediator of stromal/stem cell differentiation in vitro and bone formation in vivo is physical loading, yet it still remains unclear whether loading-induced bone formation requires the osteogenic differentiation of these resident stromal/stem cells. Therefore, in this study, we utilized the leptin receptor (LepR) to identify and trace the contribution of bone marrow stromal cells to mechanoadaptation of bone in vivo. Twelve-week-old Lepr-cre;tdTomato mice were subjected to compressive tibia loading with an 11 N peak load for 40 cycles, every other day for 2 weeks. Histological analysis revealed that Lepr-cre;tdTomato+ cells arise perinatally around blood vessels and populate bone surfaces as lining cells or osteoblasts before a percentage undergo osteocytogenesis. Lepr-cre;tdTomato+ stromal cells within the marrow increase in abundance with age, but not following the application of tibial compressive loading. Mechanical loading induces an increase in bone mass and bone formation parameters, yet does not evoke an increase in Lepr-cre;tdTomato+ osteoblasts or osteocytes. To investigate whether adenylyl cyclase-6 (AC6) in LepR cells contributes to this mechanoadaptive response, Lepr-cre;tdTomato mice were further crossed with AC6fl/fl mice to generate a LepR+ cell-specific knockout of AC6. These Lepr-cre;tdTomato;AC6fl/fl animals have an attenuated response to compressive tibia loading, characterized by a deficient load-induced osteogenic response on the endosteal bone surface. This, therefore, shows that Lepr-cre;tdTomato+ cells contribute to short-term bone mechanoadaptation. © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Published
2020

50. Size-Tunable Nanoneedle Arrays for Influencing Stem Cell Morphology, Gene Expression, and Nuclear Membrane Curvature

Author

Michele Becce, Molly M. Stevens, Hyejeong Seong, Julia E. Sero, Stuart G. Higgins, Spencer W. Crowder, A.C. Moore, Jelle Penders, James P. K. Armstrong, Commission of the European Communities, Medical Research Council (MRC), Wellcome Trust, Arthritis Research UK, and Engineering & Physical Science Research Council (EPSRC)

Subjects
Silicon, Materials science, Nuclear Envelope, cell−material interactions, General Physics and Astronomy, Gene Expression, Biointerface, 02 engineering and technology, 010402 general chemistry, Cell morphology, 01 natural sciences, Focused ion beam, Article, biointerface, medicine, Humans, General Materials Science, Nuclear membrane, Nanoscience & Nanotechnology, Nanoneedle, microfabrication, chemistry.chemical_classification, deep reactive ion etching (DRIE), Biomolecule, Stem Cells, General Engineering, 021001 nanoscience & nanotechnology, 0104 chemical sciences, Nanostructures, medicine.anatomical_structure, chemistry, high aspect ratio, Biophysics, Nuclear lamina, nanoneedles, 0210 nano-technology, cell-material interactions, Microfabrication
Abstract

High-aspect-ratio nanostructures have emerged as versatile platforms for intracellular sensing and biomolecule delivery. Here, we present a microfabrication approach in which a combination of reactive ion etching protocols were used to produce high-aspect-ratio, nondegradable silicon nanoneedle arrays with tip diameters that could be finely tuned between 20 and 700 nm. We used these arrays to guide the long-term culture of human mesenchymal stem cells (hMSCs). Notably, we used changes in the nanoneedle tip diameter to control the morphology, nuclear size, and F-actin alignment of interfaced hMSCs and to regulate the expression of nuclear lamina genes, Yes-associated protein (YAP) target genes, and focal adhesion genes. These topography-driven changes were attributed to signaling by Rho-family GTPase pathways, differences in the effective stiffness of the nanoneedle arrays, and the degree of nuclear membrane impingement, with the latter clearly visualized using focused ion beam scanning electron microscopy (FIB-SEM). Our approach to design high-aspect-ratio nanostructures will be broadly applicable to design biomaterials and biomedical devices used for long-term cell stimulation and monitoring.

Published
2020

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