Showing papers by "Maastricht University published in 2012"
TL;DR: Prevalence and severity of health loss were weakly correlated and age-specific prevalence of YLDs increased with age in all regions and has decreased slightly from 1990 to 2010, but population growth and ageing have increased YLD numbers and crude rates over the past two decades.
7,021 citations
TL;DR: The results for 1990 and 2010 supersede all previously published Global Burden of Disease results and highlight the importance of understanding local burden of disease and setting goals and targets for the post-2015 agenda taking such patterns into account.
6,861 citations
Daniel J. Klionsky1, Fábio Camargo Abdalla2, Hagai Abeliovich3, Robert T. Abraham4 +1284 more•Institutions (463)
TL;DR: These guidelines are presented for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes.
Abstract: In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
4,316 citations
TL;DR: Radiomics--the high-throughput extraction of large amounts of image features from radiographic images--addresses this problem and is one of the approaches that hold great promises but need further validation in multi-centric settings and in the laboratory.
3,411 citations
TL;DR: An integrative conceptual model was developed containing 12 dimensions referring to the knowledge, motivation and competencies of accessing, understanding, appraising and applying health-related information within the healthcare, disease prevention and health promotion setting, respectively.
Abstract: Health literacy concerns the knowledge and competences of persons to meet the complex demands of health in modern society. Although its importance is increasingly recognised, there is no consensus about the definition of health literacy or about its conceptual dimensions, which limits the possibilities for measurement and comparison. The aim of the study is to review definitions and models on health literacy to develop an integrated definition and conceptual model capturing the most comprehensive evidence-based dimensions of health literacy. A systematic literature review was performed to identify definitions and conceptual frameworks of health literacy. A content analysis of the definitions and conceptual frameworks was carried out to identify the central dimensions of health literacy and develop an integrated model. The review resulted in 17 definitions of health literacy and 12 conceptual models. Based on the content analysis, an integrative conceptual model was developed containing 12 dimensions referring to the knowledge, motivation and competencies of accessing, understanding, appraising and applying health-related information within the healthcare, disease prevention and health promotion setting, respectively. Based upon this review, a model is proposed integrating medical and public health views of health literacy. The model can serve as a basis for developing health literacy enhancing interventions and provide a conceptual basis for the development and validation of measurement tools, capturing the different dimensions of health literacy within the healthcare, disease prevention and health promotion settings.
3,290 citations
TL;DR: Beige cells have a gene expression pattern distinct from either white or brown fat and are preferentially sensitive to the polypeptide hormone irisin, providing evidence that previously identified brown fat deposits in adult humans are composed of beige adipocytes.
2,767 citations
Johns Hopkins University1, University of Barcelona2, St George's, University of London3, Taipei Veterans General Hospital4, Maastricht University5, Washington University in St. Louis6, Imperial College London7, University of Virginia8, Virginia Commonwealth University9, Thomas Jefferson University10, Beaumont Hospital11, University of Bordeaux12, Leipzig University13, University of Oklahoma14, University of Michigan15, Royal Melbourne Hospital16, University College Dublin17, Korea University18, University of Birmingham19, University of Münster20, University of Western Ontario21, Cleveland Clinic22, Harvard University23, University of Pennsylvania24, Northwestern University25, Université de Montréal26, Mayo Clinic27, Icahn School of Medicine at Mount Sinai28, University of California, Los Angeles29, National Yang-Ming University30, Loyola University Chicago31
TL;DR: This 2012 Consensus Statement is to provide a state-of-the-art review of the field of catheter and surgical ablation of AF and to report the findings of a Task Force, convened by the Heart Rhythm Society, the European Heart Rhythm Association, and the European Cardiac Arrhythmia Society and charged with defining the indications, techniques, and outcomes of this procedure.
Abstract: During the past decade, catheter ablation of atrial fibrillation (AF) has evolved rapidly from an investigational procedure to its current status as a commonly performed ablation procedure in many major hospitals throughout the world. Surgical ablation of AF, using either standard or minimally invasive techniques, is also performed in many major hospitals throughout the world.
In 2007, an initial Consensus Statement on Catheter and Surgical AF Ablation was developed as a joint effort of the Heart Rhythm Society, the European Heart Rhythm Association, and the European Cardiac Arrhythmia Society.1 The 2007 document was also developed in collaboration with the Society of Thoracic Surgeons and the American College of Cardiology. Since the publication of the 2007 document, there has been much learned about AF ablation, and the indications for these procedures have changed. Therefore the purpose of this 2012 Consensus Statement is to provide a state-of-the-art review of the field of catheter and surgical ablation of AF and to report the findings of a Task Force, convened by the Heart Rhythm Society, the European Heart Rhythm Association, and the European Cardiac Arrhythmia Society and charged with defining the indications, techniques, and outcomes of this procedure. Included within this document are recommendations pertinent to the design of clinical trials in the field of AF ablation, including definitions relevant to this topic.
This statement summarizes the opinion of the Task Force members based on an extensive literature review as well as their own experience. It is directed to all health care professionals who are involved in the care of patients with AF, particularly those who are undergoing, or are being considered for, catheter or surgical ablation procedures for AF. This statement is not intended to recommend or promote catheter ablation of AF. Rather the ultimate judgment regarding care of a particular patient …
2,754 citations
TL;DR: In this paper, a conceptual model of an ideal-typical transdisciplinary research process is synthesized and structures such a set of principles from various strands of the literature and empirical experiences, looking at challenges and coping strategies as experienced in transdisciplinary sustainability projects in Europe, North America, South America, Africa, and Asia.
Abstract: There is emerging agreement that sustainability challenges require new ways of knowledge production and decision-making. One key aspect of sustainability science, therefore, is the involvement of actors from outside academia into the research process in order to integrate the best available knowledge, reconcile values and preferences, as well as create ownership for problems and solution options. Transdisciplinary, community-based, interactive, or participatory research approaches are often suggested as appropriate means to meet both the requirements posed by real-world problems as well as the goals of sustainability science as a transformational scientific field. Dispersed literature on these approaches and a variety of empirical projects applying them make it difficult for interested researchers and practitioners to review and become familiar with key components and design principles of how to do transdisciplinary sustainability research. Starting from a conceptual model of an ideal–typical transdisciplinary research process, this article synthesizes and structures such a set of principles from various strands of the literature and empirical experiences. We then elaborate on them, looking at challenges and some coping strategies as experienced in transdisciplinary sustainability projects in Europe, North America, South America, Africa, and Asia. The article concludes with future research needed in order to further enhance the practice of transdisciplinary sustainability research.
1,927 citations
TL;DR: It is shown that childhood adversity is strongly associated with increased risk for psychosis and population attributable risk was 33% (16%–47%).
Abstract: Evidence suggests that adverse experiences in childhood are associated with psychosis. To examine the association between childhood adversity and trauma (sexual abuse, physical abuse, emotional/psychological abuse, neglect, parental death, and bullying) and psychosis outcome, MEDLINE, EMBASE, PsychINFO, and Web of Science were searched from January 1980 through November 2011. We included prospective cohort studies, large-scale cross-sectional studies investigating the association between childhood adversity and psychotic symptoms or illness, case-control studies comparing the prevalence of adverse events between psychotic patients and controls using dichotomous or continuous measures, and case-control studies comparing the prevalence of psychotic symptoms between exposed and nonexposed subjects using dichotomous or continuous measures of adversity and psychosis. The analysis included 18 case-control studies (n = 2048 psychotic patients and 1856 nonpsychiatric controls), 10 prospective and quasi-prospective studies (n = 41 803) and 8 population-based cross-sectional studies (n = 35 546). There were significant associations between adversity and psychosis across all research designs, with an overall effect of OR = 2.78 (95% CI = 2.34–3.31). The integration of the case-control studies indicated that patients with psychosis were 2.72 times more likely to have been exposed to childhood adversity than controls (95% CI = 1.90–3.88). The association between childhood adversity and psychosis was also significant in population-based cross-sectional studies (OR = 2.99 [95% CI = 2.12–4.20]) as well as in prospective and quasi-prospective studies (OR = 2.75 [95% CI = 2.17–3.47]). The estimated population attributable risk was 33% (16%–47%). These findings indicate that childhood adversity is strongly associated with increased risk for psychosis.
1,893 citations
TL;DR: "Radiomics" refers to the extraction and analysis of large amounts of advanced quantitative imaging features with high throughput from medical images obtained with computed tomography, positron emission tomography or magnetic resonance imaging, leading to a very large potential subject pool.
1,608 citations
University of Pennsylvania1, Johns Hopkins University2, Mayo Clinic3, University of Barcelona4, St George's, University of London5, Maastricht University6, Cleveland Clinic7, University of Virginia8, Baylor University9, Virginia Commonwealth University10, Thomas Jefferson University11, Beaumont Hospital12, University of Bordeaux13, Leipzig University14, University of Oklahoma15, University of Michigan16, Royal Melbourne Hospital17, University College Dublin18, Korea University19, University of Birmingham20, University of Münster21, University of Western Ontario22, Imperial College London23, Harvard University24, Northwestern University25, National Yang-Ming University26, Washington University in St. Louis27, Université de Montréal28, Icahn School of Medicine at Mount Sinai29, University of California, Los Angeles30, Loyola University Chicago31
TL;DR: A report of the Heart Rhythm Society (HRS) Task Force on Catheter and Surgical Ablation of Atrial Fibrillation, developed in partnership with the European Heart Rhythm Association (EHRA), a registered branch of the European Society of Cardiology and the European Cardiac Arrhythmia Society (ECAS), was published in this paper.
TL;DR: Goldstein et al. as discussed by the authors used induced pluripotent stem (iPS) cells to study phenotypes that are relevant to familial and sporadic Alzheimer's disease, including elevated amyloid- secretion.
Abstract: Induced pluripotent stem (iPS) cell cultures are being used as models for various genetic diseases, including Parkinson's disease and diabetes. Alzheimer's disease seems an unlikely candidate for such a technique, because it can take decades for the disease to manifest in patients. But here, Lawrence Goldstein and colleagues provide evidence that iPS cell technology can be used to study phenotypes that are relevant to familial and sporadic Alzheimer's disease. Patient-derived fibroblasts were reprogrammed as iPS cells and differentiated into neurons expressing various biochemical markers of Alzheimer's disease, including elevated amyloid- secretion. Treatment of neurons with a -secretase inhibitor, a type of drug considered a candidate for Alzheimer's therapy, significantly reduced both amyloid- and phospho-tau levels.
University of Cambridge1, Medical Research Council2, University of Glasgow3, Pasteur Institute4, University of Groningen5, The Heart Research Institute6, University of California, San Diego7, Boston University8, University of Gothenburg9, German Cancer Research Center10, University College London11, University of Oxford12, Ludwig Maximilian University of Munich13, University of Vermont14, University of Bristol15, VU University Amsterdam16, Lund University17, University of Minnesota18, University of Edinburgh19, Cardiff University20, Harvard University21, Istituto Superiore di Sanità22, Centers for Disease Control and Prevention23, Erasmus University Rotterdam24, Memorial Hospital of South Bend25, Karolinska Institutet26, Osaka University27, University of Copenhagen28, Innsbruck Medical University29, Kyushu University30, University of Ulm31, Wageningen University and Research Centre32, University of Pittsburgh33, University of London34, National Institute for Health and Welfare35, Istanbul University36, Harokopio University37, University of Washington38, University of Hawaii at Manoa39, University of Eastern Finland40, Analytical Services41, Columbia University42, Maastricht University43, University of Oulu44, Merck & Co.45, Yeshiva University46, Umeå University47, Leiden University48, St George's, University of London49, University of Sydney50, University of Iceland51
TL;DR: It is estimated that under current treatment guidelines, assessment of the CRP or fibrinogen level in people at intermediate risk for a cardiovascular event could help prevent one additional event over a period of 10 years for every 400 to 500 people screened.
Abstract: Background There is debate about the value of assessing levels of C-reactive protein (CRP) and other biomarkers of inflammation for the prediction of first cardiovascular events. Methods We analyzed data from 52 prospective studies that included 246,669 participants without a history of cardiovascular disease to investigate the value of adding CRP or fibrinogen levels to conventional risk factors for the prediction of cardiovascular risk. We calculated measures of discrimination and reclassification during follow-up and modeled the clinical implications of initiation of statin therapy after the assessment of CRP or fibrinogen. Results The addition of information on high-density lipoprotein cholesterol to a prognostic model for cardiovascular disease that included age, sex, smoking status, blood pressure, history of diabetes, and total cholesterol level increased the C-index, a measure of risk discrimination, by 0.0050. The further addition to this model of information on CRP or fibrinogen increased the C-index by 0.0039 and 0.0027, respectively (P = 20%) (P = 20% and for those with certain other risk factors, such as diabetes, irrespective of their 10-year predicted risk), additional targeted assessment of CRP or fibrinogen levels in the 13,199 remaining participants at intermediate risk could help prevent approximately 30 additional cardiovascular events over the course of 10 years. Conclusions In a study of people without known cardiovascular disease, we estimated that under current treatment guidelines, assessment of the CRP or fibrinogen level in people at intermediate risk for a cardiovascular event could help prevent one additional event over a period of 10 years for every 400 to 500 people screened. (Funded by the British Heart Foundation and others.)
TL;DR: The metabolic and cardiovascular risks of various antipsychotic medications in adults and children are outlined, the disparities in health care are defined, and recommendations for screening and monitoring of patients taking these agents are made.
Abstract: Antipsychotic medications can induce cardiovascular and metabolic abnormalities (such as obesity, hyperglycemia, dyslipidemia and the metabolic syndrome) that are associated with an increased risk of type 2 diabetes mellitus and cardiovascular disease. Controversy remains about the contribution of individual antipsychotic drugs to this increased risk and whether they cause sudden cardiac death through prolongation of the corrected QT interval. Although some drug receptor-binding affinities correlate with specific cardiovascular and metabolic abnormalities, the exact pharmacological mechanisms underlying these associations remain unclear. Antipsychotic agents with prominent metabolic adverse effects might cause abnormalities in glucose and lipid metabolism via both obesity-related and obesity-unrelated molecular mechanisms. Despite existing guidelines and recommendations, many antipsychotic-drug-treated patients are not assessed for even the most easily measurable metabolic and cardiac risk factors, such as obesity and blood pressure. Subsequently, concerns have been raised over the use of these medications, especially pronounced in vulnerable pediatric patients, among whom their use has increased markedly in the past decade and seems to have especially orexigenic effects. This Review outlines the metabolic and cardiovascular risks of various antipsychotic medications in adults and children, defines the disparities in health care and finally makes recommendations for screening and monitoring of patients taking these agents.
University of Cambridge1, University of Kiel2, University of East Anglia3, University of Copenhagen4, University of Manchester5, Karolinska Institutet6, Maastricht University7, Wellcome Trust Sanger Institute8, Trinity College, Dublin9, University of Paris10, University of Birmingham11, Charles University in Prague12, University College London13, University of Parma14, University of Jena15, Lund University16, University of Glasgow17, Imperial College London18, GlaxoSmithKline19, Linköping University20, Ruhr University Bochum21, Medical University of Vienna22, University of Erlangen-Nuremberg23
TL;DR: This study confirms that the pathogenesis of ANCA-associated vasculitis has a genetic component, shows genetic distinctions between granulomatosis with polyang iitis and microscopic polyangiitis that are associated with ANCA specificity, and suggests that the response against the autoantigen proteinase 3 is a central pathogenic feature ofproteinase 3 ANCA -associated vasulitis.
Abstract: BACKGROUND Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis is a severe condition encompassing two major syndromes: granulomatosis with polyangiitis (formerly known as Wegener's granulomatosis) and microscopic polyangiitis. Its cause is unknown, and there is debate about whether it is a single disease entity and what role ANCA plays in its pathogenesis. We investigated its genetic basis. METHODS A genomewide association study was performed in a discovery cohort of 1233 U. K. patients with ANCA-associated vasculitis and 5884 controls and was replicated in 1454 Northern European case patients and 1666 controls. Quality control, population stratification, and statistical analyses were performed according to standard criteria. RESULTS We found both major-histocompatibility-complex (MHC) and non-MHC associations with ANCA-associated vasculitis and also that granulomatosis with polyangiitis and microscopic polyangiitis were genetically distinct. The strongest genetic associations were with the antigenic specificity of ANCA, not with the clinical syndrome. Anti-proteinase 3 ANCA was associated with HLA-DP and the genes encoding alpha(1)-antitrypsin (SERPINA1) and proteinase 3 (PRTN3) (P = 6.2x10(-89), P = 5.6x10(-12), and P = 2.6x10(-7), respectively). Anti-myeloperoxidase ANCA was associated with HLA-DQ (P = 2.1x10(-8)). CONCLUSIONS This study confirms that the pathogenesis of ANCA-associated vasculitis has a genetic component, shows genetic distinctions between granulomatosis with polyangiitis and microscopic polyangiitis that are associated with ANCA specificity, and suggests that the response against the autoantigen proteinase 3 is a central pathogenic feature of proteinase 3 ANCA-associated vasculitis. These data provide preliminary support for the concept that proteinase 3 ANCA-associated vasculitis and myeloperoxidase ANCA-associated vasculitis are distinct autoimmune syndromes. (Funded by the British Heart Foundation and others.)
TL;DR: Although many clinicians feel they already use shared decision making, research shows a perception-reality gap and A M Stiggelbout and colleagues discuss why it is important and highlight some best practices.
Abstract: Although many clinicians feel they already use shared decision making, research shows a perception-reality gap. A M Stiggelbout and colleagues discuss why it is important and highlight some best practices
TL;DR: The effects of menarche and menopause on breast cancer risk might not be acting merely by lengthening women's total number of reproductive years, and endogenous ovarian hormones are more relevant for oestrogen receptor-positive disease than for ostrogens receptor-negative disease and for lobular than for ductal tumours.
Abstract: BACKGROUND:Menarche and menopause mark the onset and cessation, respectively, of ovarian activity associated with reproduction, and affect breast cancer risk. Our aim was to assess the strengths of their effects and determine whether they depend on characteristics of the tumours or the affected women.METHODS:Individual data from 117 epidemiological studies, including 118 964 women with invasive breast cancer and 306 091 without the disease, none of whom had used menopausal hormone therapy, were included in the analyses. We calculated adjusted relative risks (RRs) associated with menarche and menopause for breast cancer overall, and by tumour histology and by oestrogen receptor expression.FINDINGS:Breast cancer risk increased by a factor of 1·050 (95% CI 1·044-1·057; p<0·0001) for every year younger at menarche, and independently by a smaller amount (1·029, 1·025-1·032; p<0·0001), for every year older at menopause. Premenopausal women had a greater risk of breast cancer than postmenopausal women of an identical age (RR at age 45-54 years 1·43, 1·33-1·52, p<0·001). All three of these associations were attenuated by increasing adiposity among postmenopausal women, but did not vary materially by women's year of birth, ethnic origin, childbearing history, smoking, alcohol consumption, or hormonal contraceptive use. All three associations were stronger for lobular than for ductal tumours (p<0·006 for each comparison). The effect of menopause in women of an identical age and trends by age at menopause were stronger for oestrogen receptor-positive disease than for oestrogen receptor-negative disease (p<0·01 for both comparisons).INTERPRETATION:The effects of menarche and menopause on breast cancer risk might not be acting merely by lengthening women's total number of reproductive years. Endogenous ovarian hormones are more relevant for oestrogen receptor-positive disease than for oestrogen receptor-negative disease and for lobular than for ductal tumours.
TL;DR: It is argued that the next generation of the FA model needs to more explicitly adopt a motivational perspective, one that is built around the organizing powers of goals and self-regulatory processes.
Abstract: Objective: The fear-avoidance (FA) model of chronic pain describes how individuals experiencing acute pain may become trapped into a vicious circle of chronic disability and suffering. We propose to extend the FA model by adopting a motivational perspective on chronic pain and disability. Methods: A narrative review. Results: There is ample evidence to support the validity of the FA model as originally formulated. There are, however, some key challenges that call for a next generation of the FA model. First, the FA model has its roots in psychopathology, and investigators will have to find a way to account for findings that do not easily fit within such framework. Second, the FA model needs to address the dynamics and complexities of disability and functional recovery. Third, the FA model should incorporate the idea that pain-related fear and avoidance occurs in a context of multiple and often competing personal goals. Discussion: To address these 3 key challenges, we argue that the next generation of the FA model needs to more explicitly adopt a motivational perspective, one that is built around the organizing powers of goals and self-regulatory processes. Using this framework, the FA model is recast as capturing the persistent but futile attempts to solve pain-related problems to protect and restore life goals.
Katholieke Universiteit Leuven1, Maastricht University2, Semmelweis University3, Hannover Medical School4, Corvinus University of Budapest5, University of Pavia6, University of Wisconsin-Madison7, Cleveland Clinic8, National Health Service9, Praxis10, University of Edinburgh11, University of Copenhagen12, University of Bern13, University of Milan14
TL;DR: In this paper, a prospective, multi-centre, questionnaire-based survey measured costs and quality of life in ambulatory care and in 12 tertiary care centres in 10 countries.
Abstract: methods: A prospective, multi-centre, questionnaire-based survey measured costs and quality of life in ambulatory care and in 12 tertiary care centres in 10 countries. The study enrolled women with a diagnosis of endometriosis and with at least one centre-specific contact related to endometriosis-associated symptoms in 2008. The main outcome measures were health care costs, costs of productivity loss, total costs and quality-adjusted life years. Predictors of costs were identified using regression analysis. results: Data analysis of 909 women demonstrated that the average annual total cost per woman was E9579 (95% confidence interval E8559–E10 599). Costs of productivity loss of E6298 per woman were double the health care costs of E3113 per woman. Health care costs were mainly due to surgery (29%), monitoring tests (19%) and hospitalization (18%) and physician visits (16%). Endometriosis-associated symptoms generated 0.809 quality-adjusted life years per woman. Decreased quality of life was the most important predictor of direct health care and total costs. Costs were greater with increasing severity of endometriosis, presence of pelvic pain, presence of infertility and a higher number of years since diagnosis. conclusions: Our study invited women to report resource use based on endometriosis-associated symptoms only, rather than drawing on a control population of women without endometriosis. Our study showed that the economic burden associated with endometriosis treated in referral centres is high and is similar to other chronic diseases (diabetes, Crohn’s disease, rheumatoid arthritis). It arises predominantly from productivity loss, and is predicted by decreased quality of life.
University of Barcelona1, Research Triangle Park2, University of Nebraska Medical Center3, University of Edinburgh4, GlaxoSmithKline5, University of Manchester6, University of Copenhagen7, University of Cambridge8, University of Liverpool9, Maastricht University10, Brigham and Women's Hospital11, University of British Columbia12, University of Bergen13
TL;DR: Overall, the results identify a novel systemic inflammatory COPD phenotype that may be the target of specific research and treatment and show associations but do not prove causality.
Abstract: Background: Because chronic obstructive pulmonary disease (COPD) is a heterogeneous condition, the identification of specific clinical phenotypes is key to developing more effective therapies. To explore if the persistence of systemic inflammation is associated with poor clinical outcomes in COPD we assessed patients recruited to the well-characterized ECLIPSE cohort (NCT00292552). Methods and Findings: Six inflammatory biomarkers in peripheral blood (white blood cells (WBC) count and CRP, IL-6, IL-8, fibrinogen and TNF-a levels) were quantified in 1,755 COPD patients, 297 smokers with normal spirometry and 202 nonsmoker controls that were followed-up for three years. We found that, at baseline, 30% of COPD patients did not show evidence of systemic inflammation whereas 16% had persistent systemic inflammation. Even though pulmonary abnormalities were similar in these two groups, persistently inflamed patients during follow-up had significantly increased all-cause mortality (13% vs. 2%, p,0.001) and exacerbation frequency (1.5 (1.5) vs. 0.9 (1.1) per year, p,0.001) compared to non-inflamed ones. As a descriptive study our results show associations but do not prove causality. Besides this, the inflammatory response is complex and we studied only a limited panel of biomarkers, albeit they are those investigated by the majority of previous studies and are often and easily measured in clinical practice. Conclusions: Overall, these results identify a novel systemic inflammatory COPD phenotype that may be the target of specific research and treatment.
TL;DR: This work proposes that selective synchronization renders relevant input effective, thereby modulating effective connectivity in neuronal networks, and uses two stimuli to demonstrate this effect.
Utrecht University1, University of Calgary2, University College London3, VU University Amsterdam4, Lund University5, Wake Forest University6, Radboud University Nijmegen7, University of Malaya8, Erasmus University Rotterdam9, Osaka University10, McMaster University11, Goethe University Frankfurt12, University of Tromsø13, Tufts University14, University of Edinburgh15, University of Virginia16, University of Miami17, Analytical Services18, Maastricht University19
TL;DR: The addition of common CIMT measurements to the Framingham Risk Score was associated with small improvement in 10-year risk prediction of first-time myocardial infarction or stroke, but this improvement is unlikely to be of clinical importance.
Abstract: Context: The evidence that measurement of the common carotid intima-media thickness (CIMT) improves the risk scores in prediction of the absolute risk of cardiovascular events is inconsistent. Objective: To determine whether common CIMT has added value in 10-year risk prediction of first-time myocardial infarctions or strokes, above that of the Framingham Risk Score. Data Sources: Relevant studies were identified through literature searches of databases (PubMed from 1950 to June 2012 and EMBASE from 1980 to June 2012) and expert opinion. Study Selection: Studies were included if participants were drawn from the general population, common CIMT was measured at baseline, and individuals were followed up for first-time myocardial infarction or stroke. Data Extraction: Individual data were combined into 1 data set and an individual participant data meta-analysis was performed on individuals without existing cardiovascular disease. Results: We included 14 population-based cohorts contributing data for 45 828 individuals. During a median follow-up of 11 years, 4007 first-time myocardial infarctions or strokes occurred. We first refitted the risk factors of the Framingham Risk Score and then extended the model with common CIMT measurements to estimate the absolute 10-year risks to develop a first-time myocardial infarction or stroke in both models. The C statistic of both models was similar (0.757; 95% CI, 0.749-0.764; and 0.759; 95% CI, 0.752-0.766). The net reclassification improvement with the addition of common CIMT was small (0.8%; 95% CI, 0.1%-1.6%). In those at intermediate risk, the net reclassification improvement was 3.6% in all individuals (95% CI, 2.7%-4.6%) and no differences between men and women. Conclusion: The addition of common CIMT measurements to the Framingham Risk Score was associated with small improvement in 10-year risk prediction of first-time myocardial infarction or stroke, but this improvement is unlikely to be of clinical importance.
TL;DR: A model for programmatic assessment in action is proposed, which simultaneously optimises assessment for learning and assessment for decision making about learner progress and enables assessment to move, beyond the dominant psychometric discourse with its focus on individual instruments, towards a systems approach to assessment design underpinned by empirical research.
Abstract: We propose a model for programmatic assessment in action, which simultaneously optimises assessment for learning and assessment for decision making about learner progress. This model is based on a set of assessment principles that are interpreted from empirical research. It specifies cycles of training, assessment and learner support activities that are complemented by intermediate and final moments of evaluation on aggregated assessment data points. A key principle is that individual data points are maximised for learning and feedback value, whereas high-stake decisions are based on the aggregation of many data points. Expert judgement plays an important role in the programme. Fundamental is the notion of sampling and bias reduction to deal with the inevitable subjectivity of this type of judgement. Bias reduction is further sought in procedural assessment strategies derived from criteria for qualitative research. We discuss a number of challenges and opportunities around the proposed model. One of its prime virtues is that it enables assessment to move, beyond the dominant psychometric discourse with its focus on individual instruments, towards a systems approach to assessment design underpinned by empirically grounded theory.
TL;DR: To assess whether the community curation experiment can be considered successful, here the relation between use and contribution is analyzed, which gives results in line with other wiki projects.
Abstract: Here, we describe the development of WikiPathways (http://www.wikipathways.org), a public wiki for pathway curation, since it was first published in 2008. New features are discussed, as well as developments in the community of contributors. New features include a zoomable pathway viewer, support for pathway ontology annotations, the ability to mark pathways as private for a limited time and the availability of stable hyperlinks to pathways and the elements therein. WikiPathways content is freely available in a variety of formats such as the BioPAX standard, and the content is increasingly adopted by external databases and tools, including Wikipedia. A recent development is the use of WikiPathways as a staging ground for centrally curated databases such as Reactome. WikiPathways is seeing steady growth in the number of users, page views and edits for each pathway. To assess whether the community curation experiment can be considered successful, here we analyze the relation between use and contribution, which gives results in line with other wiki projects. The novel use of pathway pages as supplementary material to publications, as well as the addition of tailored content for research domains, is expected to stimulate growth further.
TL;DR: In this paper, the authors analyze the extent to which the use of gas and electricity is determined by the technical specifications of the dwelling as compared to the demographic characteristics of the residents, and they find that even absent price increases for residential energy, the aging of the population and their increasing wealth will roughly offset improvements in the building stock resulting from policy interventions and natural revitalization.
TL;DR: M1 and M2 macrophage populations are present throughout atherogenesis and these subsets display disparity when it comes to their prevalence in morphological compartments of the vessel wall, warranting continued investigation into the functional implications of polarization populations in human atherosclerosis.
University of Tromsø1, Edinburgh Royal Infirmary2, Maastricht University3, McGill University Health Centre4, Universidade Federal de Mato Grosso5, University Hospital of Lausanne6, National Institute for Health Research7, Università telematica San Raffaele8, Örebro University9, Karolinska Institutet10
TL;DR: An international working group constructed within the Enhanced Recovery After Surgery (ERAS®) Society constructed a comprehensive and evidence-based framework for best perioperative care for pancreaticoduodenectomy patients.
TL;DR: A framework for envisioning how point-of-care testing can be applied to infectious diseases in low- and middle-income countries is discussed.
Abstract: Madhukar Pai and colleagues discuss a framework for envisioning how point-of-care testing can be applied to infectious diseases in low- and middle-income countries.
University of Paris1, Pierre-and-Marie-Curie University2, Leeds Teaching Hospitals NHS Trust3, Leiden University4, University College Dublin5, Medical University of Vienna6, University of Crete7, Ruhr University Bochum8, Charité9, University of Barcelona10, Rikshospitalet–Radiumhospitalet11, Katholieke Universiteit Leuven12, University of Leeds13, University of California, San Diego14, Maastricht University15, University of Münster16, Royal National Hospital for Rheumatic Diseases17, University of Glasgow18, University of Rochester19, University of Amsterdam20, Sapienza University of Rome21, Oregon Health & Science University22
TL;DR: These recommendations are intended to provide rheumatologists, patients and other stakeholders with a consensus on the pharmacological treatment of PsA and strategies to reach optimal outcomes, based on combining evidence and expert opinion.
Abstract: Background Psoriatic arthritis (PsA) is a clinically heterogeneous disease. Clear consensual treatment guidance focused on the musculoskeletal manifestations of PsA would be advantageous. The authors present European League Against Rheumatism (EULAR) recommendations for the treatment of PsA with systemic or local (non-topical) symptomatic and disease-modifying antirheumatic drugs (DMARD). Methods The recommendations are based on evidence from systematic literature reviews performed for non-steroidal anti-infl ammatory drugs (NSAID), glucocorticoids, synthetic DMARD and biological DMARD. This evidence was discussed, summarised and recommendations were formulated by a task force comprising 35 representatives, and providing levels of evidence, strength of recommendations and levels of agreement. Results Ten recommendations were developed for treatment from NSAID through synthetic DMARD to biological agents, accounting for articular and extraarticular manifestations of PsA. Five overarching principles and a research agenda were defi ned. Conclusion These recommendations are intended to provide rheumatologists, patients and other stakeholders with a consensus on the pharmacological treatment of PsA and strategies to reach optimal outcomes, based on combining evidence and expert opinion. The research agenda informs directions within EULAR and other communities interested in PsA.
TL;DR: C culturing meat may provide opportunities for production of novel and healthier products and should be efficiently produced and should mimic meat in all of its physical sensations, such as visual appearance, smell, texture and of course, taste.