Showing papers by "University of Ioannina published in 2020"
Public Health Research Institute1, Katholieke Universiteit Leuven2, Leiden University3, John Radcliffe Hospital4, University of Oxford5, Keele University6, Medical University of Vienna7, University Medical Center Utrecht8, University College Cork9, University of Pennsylvania10, University of Cologne11, Manchester Academic Health Science Centre12, University of Aberdeen13, RMIT University14, University of Manchester15, University of Amsterdam16, Imperial College London17, University of Ioannina18, Maastricht University Medical Centre19, Humboldt University of Berlin20
TL;DR: Proposed models for covid-19 are poorly reported, at high risk of bias, and their reported performance is probably optimistic, according to a review of published and preprint reports.
Abstract: Objective To review and appraise the validity and usefulness of published and preprint reports of prediction models for diagnosing coronavirus disease 2019 (covid-19) in patients with suspected infection, for prognosis of patients with covid-19, and for detecting people in the general population at increased risk of covid-19 infection or being admitted to hospital with the disease. Design Living systematic review and critical appraisal by the COVID-PRECISE (Precise Risk Estimation to optimise covid-19 Care for Infected or Suspected patients in diverse sEttings) group. Data sources PubMed and Embase through Ovid, up to 1 July 2020, supplemented with arXiv, medRxiv, and bioRxiv up to 5 May 2020. Study selection Studies that developed or validated a multivariable covid-19 related prediction model. Data extraction At least two authors independently extracted data using the CHARMS (critical appraisal and data extraction for systematic reviews of prediction modelling studies) checklist; risk of bias was assessed using PROBAST (prediction model risk of bias assessment tool). Results 37 421 titles were screened, and 169 studies describing 232 prediction models were included. The review identified seven models for identifying people at risk in the general population; 118 diagnostic models for detecting covid-19 (75 were based on medical imaging, 10 to diagnose disease severity); and 107 prognostic models for predicting mortality risk, progression to severe disease, intensive care unit admission, ventilation, intubation, or length of hospital stay. The most frequent types of predictors included in the covid-19 prediction models are vital signs, age, comorbidities, and image features. Flu-like symptoms are frequently predictive in diagnostic models, while sex, C reactive protein, and lymphocyte counts are frequent prognostic factors. Reported C index estimates from the strongest form of validation available per model ranged from 0.71 to 0.99 in prediction models for the general population, from 0.65 to more than 0.99 in diagnostic models, and from 0.54 to 0.99 in prognostic models. All models were rated at high or unclear risk of bias, mostly because of non-representative selection of control patients, exclusion of patients who had not experienced the event of interest by the end of the study, high risk of model overfitting, and unclear reporting. Many models did not include a description of the target population (n=27, 12%) or care setting (n=75, 32%), and only 11 (5%) were externally validated by a calibration plot. The Jehi diagnostic model and the 4C mortality score were identified as promising models. Conclusion Prediction models for covid-19 are quickly entering the academic literature to support medical decision making at a time when they are urgently needed. This review indicates that almost all pubished prediction models are poorly reported, and at high risk of bias such that their reported predictive performance is probably optimistic. However, we have identified two (one diagnostic and one prognostic) promising models that should soon be validated in multiple cohorts, preferably through collaborative efforts and data sharing to also allow an investigation of the stability and heterogeneity in their performance across populations and settings. Details on all reviewed models are publicly available at https://www.covprecise.org/. Methodological guidance as provided in this paper should be followed because unreliable predictions could cause more harm than benefit in guiding clinical decisions. Finally, prediction model authors should adhere to the TRIPOD (transparent reporting of a multivariable prediction model for individual prognosis or diagnosis) reporting guideline. Systematic review registration Protocol https://osf.io/ehc47/, registration https://osf.io/wy245. Readers’ note This article is a living systematic review that will be updated to reflect emerging evidence. Updates may occur for up to two years from the date of original publication. This version is update 3 of the original article published on 7 April 2020 (BMJ 2020;369:m1328). Previous updates can be found as data supplements (https://www.bmj.com/content/369/bmj.m1328/related#datasupp). When citing this paper please consider adding the update number and date of access for clarity.
2,183 citations
National and Kapodistrian University of Athens1, Athens Regional Medical Center2, Aristotle University of Thessaloniki3, Democritus University of Thrace4, University of Ioannina5, Alexandra Hospital6, University of Patras7, Instituto Politécnico Nacional8, Yale University9, Icahn School of Medicine at Mount Sinai10
TL;DR: A role for colchicine in the treatment of patients with coronavirus disease 2019 is suggested, with results suggesting a smaller increase in dimerized plasma fragment D compared with patients in the control group.
Abstract: Importance Severe acute respiratory syndrome coronavirus 2 infection has evolved into a global pandemic Low-dose colchicine combines anti-inflammatory action with a favorable safety profile Objective To evaluate the effect of treatment with colchicine on cardiac and inflammatory biomarkers and clinical outcomes in patients hospitalized with coronavirus disease 2019 (COVID-19) Design, Setting, and Participants In this prospective, open-label, randomized clinical trial (the Greek Study in the Effects of Colchicine in COVID-19 Complications Prevention), 105 patients hospitalized with COVID-19 were randomized in a 1:1 allocation from April 3 to April 27, 2020, to either standard medical treatment or colchicine with standard medical treatment The study took place in 16 tertiary hospitals in Greece Intervention Colchicine administration (15-mg loading dose followed by 05 mg after 60 min and maintenance doses of 05 mg twice daily) with standard medical treatment for as long as 3 weeks Main Outcomes and Measures Primary end points were (1) maximum high-sensitivity cardiac troponin level; (2) time for C-reactive protein to reach more than 3 times the upper reference limit; and (3) time to deterioration by 2 points on a 7-grade clinical status scale, ranging from able to resume normal activities to death Secondary end points were (1) the percentage of participants requiring mechanical ventilation, (2) all-cause mortality, and (3) number, type, severity, and seriousness of adverse events The primary efficacy analysis was performed on an intention-to-treat basis Results A total of 105 patients were evaluated (61 [581%] men; median [interquartile range] age, 64 [54-76] years) with 50 (476%) randomized to the control group and 55 (524%) to the colchicine group Median (interquartile range) peak high-sensitivity cardiac troponin values were 00112 (00043-00093) ng/mL in the control group and 0008 (0004-00135) ng/mL in the colchicine group (P = 34) Median (interquartile range) maximum C-reactive protein levels were 45 (14-89) mg/dL vs 31 (08-98) mg/dL (P = 73), respectively The clinical primary end point rate was 140% in the control group (7 of 50 patients) and 18% in the colchicine group (1 of 55 patients) (odds ratio, 011; 95% CI, 001-096;P = 02) Mean (SD) event-free survival time was 186 (083) days the in the control group vs 207 (031) in the colchicine group (log rankP = 03) Adverse events were similar in the 2 groups, except for diarrhea, which was more frequent with colchicine group than the control group (25 patients [455%] vs 9 patients [180%];P = 003) Conclusions and Relevance In this randomized clinical trial, participants who received colchicine had statistically significantly improved time to clinical deterioration There were no significant differences in high-sensitivity cardiac troponin or C-reactive protein levels These findings should be interpreted with caution Trial Registration ClinicalTrialsgov Identifier:NCT04326790
345 citations
TL;DR: In this exploratory analysis, low levels of national preparedness, scale of testing and population characteristics were associated with increased national case load and overall mortality.
300 citations
National Institute for Health Research1, Harvard University2, Montreal Heart Institute3, University of North Carolina at Chapel Hill4, Wellcome Trust Sanger Institute5, VA Boston Healthcare System6, Osaka University7, Icahn School of Medicine at Mount Sinai8, University of Wisconsin–Milwaukee9, Kyushu University10, University of Washington11, University of Bristol12, University of Copenhagen13, Erasmus University Medical Center14, National Institutes of Health15, Veterans Health Administration16, Kaiser Permanente17, International Agency for Research on Cancer18, Wake Forest University19, Imperial College London20, Broad Institute21, Greifswald University Hospital22, University of Pennsylvania23, British Heart Foundation24, Fred Hutchinson Cancer Research Center25, Chinese National Human Genome Center26, Technische Universität München27, University of Tampere28, University of Tokyo29, University of Ioannina30, University of Colorado Denver31, Duke University32, University of Virginia33, University of Minnesota34, Turku University Hospital35, Los Angeles Biomedical Research Institute36, Stanford University37, Mashhad University of Medical Sciences38, NHS Blood and Transplant39, Brigham and Women's Hospital40, University of Oxford41, University of Liège42, European Bioinformatics Institute43, John Radcliffe Hospital44
TL;DR: The results show the power of large-scale blood cell trait GWAS to interrogate clinically meaningful variants across a wide allelic spectrum of human variation.
284 citations
TL;DR: The addition of a polygenic risk score for CAD to pooled cohort equations was associated with a statistically significant, yet modest, improvement in the predictive accuracy for incident CAD and improved risk stratification for only a small proportion of individuals.
Abstract: Importance The incremental value of polygenic risk scores in addition to well-established risk prediction models for coronary artery disease (CAD) is uncertain. Objective To examine whether a polygenic risk score for CAD improves risk prediction beyond pooled cohort equations. Design, Setting, and Participants Observational study of UK Biobank participants enrolled from 2006 to 2010. A case-control sample of 15 947 prevalent CAD cases and equal number of age and sex frequency–matched controls was used to optimize the predictive performance of a polygenic risk score for CAD based on summary statistics from published genome-wide association studies. A separate cohort of 352 660 individuals (with follow-up to 2017) was used to evaluate the predictive accuracy of the polygenic risk score, pooled cohort equations, and both combined for incident CAD. Exposures Polygenic risk score for CAD, pooled cohort equations, and both combined. Main Outcomes and Measures CAD (myocardial infarction and its related sequelae). Discrimination, calibration, and reclassification using a risk threshold of 7.5% were assessed. Results In the cohort of 352 660 participants (mean age, 55.9 years; 205 297 women [58.2%]) used to evaluate the predictive accuracy of the examined models, there were 6272 incident CAD events over a median of 8 years of follow-up. CAD discrimination for polygenic risk score, pooled cohort equations, and both combined resulted in C statistics of 0.61 (95% CI, 0.60 to 0.62), 0.76 (95% CI, 0.75 to 0.77), and 0.78 (95% CI, 0.77 to 0.79), respectively. The change in C statistic between the latter 2 models was 0.02 (95% CI, 0.01 to 0.03). Calibration of the models showed overestimation of risk by pooled cohort equations, which was corrected after recalibration. Using a risk threshold of 7.5%, addition of the polygenic risk score to pooled cohort equations resulted in a net reclassification improvement of 4.4% (95% CI, 3.5% to 5.3%) for cases and −0.4% (95% CI, −0.5% to −0.4%) for noncases (overall net reclassification improvement, 4.0% [95% CI, 3.1% to 4.9%]). Conclusions and Relevance The addition of a polygenic risk score for CAD to pooled cohort equations was associated with a statistically significant, yet modest, improvement in the predictive accuracy for incident CAD and improved risk stratification for only a small proportion of individuals. The use of genetic information over the pooled cohort equations model warrants further investigation before clinical implementation.
266 citations
TL;DR: For the first time, predictions from pythia8 obtained with tunes based on NLO or NNLO PDFs are shown to reliably describe minimum-bias and underlying-event data with a similar level of agreement to predictions from tunes using LO PDF sets.
Abstract: New sets of CMS underlying-event parameters (“tunes”) are presented for the pythia8 event generator. These tunes use the NNPDF3.1 parton distribution functions (PDFs) at leading (LO), next-to-leading (NLO), or next-to-next-to-leading (NNLO) orders in perturbative quantum chromodynamics, and the strong coupling evolution at LO or NLO. Measurements of charged-particle multiplicity and transverse momentum densities at various hadron collision energies are fit simultaneously to determine the parameters of the tunes. Comparisons of the predictions of the new tunes are provided for observables sensitive to the event shapes at LEP, global underlying event, soft multiparton interactions, and double-parton scattering contributions. In addition, comparisons are made for observables measured in various specific processes, such as multijet, Drell–Yan, and top quark-antiquark pair production including jet substructure observables. The simulation of the underlying event provided by the new tunes is interfaced to a higher-order matrix-element calculation. For the first time, predictions from pythia8 obtained with tunes based on NLO or NNLO PDFs are shown to reliably describe minimum-bias and underlying-event data with a similar level of agreement to predictions from tunes using LO PDF sets.
265 citations
University of Barcelona1, University of Liverpool2, Vita-Salute San Raffaele University3, University of Tübingen4, Medical University of Vienna5, Charles University in Prague6, Freeman Hospital7, Autonomous University of Barcelona8, Royal Free London NHS Foundation Trust9, Netherlands Cancer Institute10, Heidelberg University11, University of Patras12, Leeds Teaching Hospitals NHS Trust13, University of Ioannina14, University of Modena and Reggio Emilia15, Zhejiang University16, Radboud University Nijmegen17, Umeå University18, University of Paris19, Istanbul Medipol University20, University of Basel21, Erasmus University Rotterdam22, Praxis23, Innsbruck Medical University24, University of St. Gallen25, Ghent University Hospital26, St. George's University27, University College London Hospitals NHS Foundation Trust28, European Association of Urology29, University of Sheffield30, Katholieke Universiteit Leuven31, Dresden University of Technology32, University of Copenhagen33, University of Aberdeen34
TL;DR: It is hoped that the revised recommendations will assist urologist surgeons across the globe to guide the management of urological conditions during the current COVID-19 pandemic.
249 citations
University of North Carolina at Chapel Hill1, Montreal Heart Institute2, Osaka University3, VA Boston Healthcare System4, Icahn School of Medicine at Mount Sinai5, Queen Mary University of London6, University of Cambridge7, National Institute for Health Research8, Wellcome Trust Sanger Institute9, Harvard University10, Vanderbilt University11, University of Wisconsin–Milwaukee12, Université de Montréal13, University of Southern California14, Kyushu University15, University of Washington16, University of Bristol17, University of Copenhagen18, Erasmus University Medical Center19, National Institutes of Health20, Brigham and Women's Hospital21, Kaiser Permanente22, University of Mississippi Medical Center23, International Agency for Research on Cancer24, Wake Forest University25, Imperial College London26, Broad Institute27, University of Pennsylvania28, Greifswald University Hospital29, Fred Hutchinson Cancer Research Center30, Chinese National Human Genome Center31, Technische Universität München32, University of Tampere33, University of Tokyo34, University of Ioannina35, University of Colorado Denver36, Duke University37, University of Virginia38, NHS Blood and Transplant39, University of Minnesota40, Turku University Hospital41, Los Angeles Biomedical Research Institute42, Stanford University43, King's College London44, Mashhad University of Medical Sciences45, Veterans Health Administration46
TL;DR: The clinical significance and predictive value of trans-ethnic variants in multiple populations are explored, genetic architecture and the effect of natural selection on these blood phenotypes between populations are compared and the value of a more global representation of populations in genetic studies is highlighted.
233 citations
Fudan University Shanghai Medical College1, Qingdao University2, University of Toulouse3, University of Cambridge4, University of Ioannina5, Huazhong University of Science and Technology6, Harvard University7, Capital Medical University8, National University of Singapore9, Third Military Medical University10, The Chinese University of Hong Kong11, Fudan University12, McGill University13, University of Southern California14
TL;DR: In this paper, a systematic review and meta-analysis of current evidence with prospective designs to propose evidence-based suggestions on AD prevention was conducted, and twenty-one suggestions are proposed based on the consolidated evidence, with Class I suggestions targeting 19 factors: education, cognitive activity, high body mass index in latelife, hyperhomocysteinaemia, depression, stress, diabetes, head trauma, hypertension in midlife and orthostatic hypotension.
Abstract: Background Evidence on preventing Alzheimer’s disease (AD) is challenging to interpret due to varying study designs with heterogeneous endpoints and credibility. We completed a systematic review and meta-analysis of current evidence with prospective designs to propose evidence-based suggestions on AD prevention. Methods Electronic databases and relevant websites were searched from inception to 1 March 2019. Both observational prospective studies (OPSs) and randomised controlled trials (RCTs) were included. The multivariable-adjusted effect estimates were pooled by random-effects models, with credibility assessment according to its risk of bias, inconsistency and imprecision. Levels of evidence and classes of suggestions were summarised. Results A total of 44 676 reports were identified, and 243 OPSs and 153 RCTs were eligible for analysis after exclusion based on pre-decided criteria, from which 104 modifiable factors and 11 interventions were included in the meta-analyses. Twenty-one suggestions are proposed based on the consolidated evidence, with Class I suggestions targeting 19 factors: 10 with Level A strong evidence (education, cognitive activity, high body mass index in latelife, hyperhomocysteinaemia, depression, stress, diabetes, head trauma, hypertension in midlife and orthostatic hypotension) and 9 with Level B weaker evidence (obesity in midlife, weight loss in late life, physical exercise, smoking, sleep, cerebrovascular disease, frailty, atrial fibrillation and vitamin C). In contrast, two interventions are not recommended: oestrogen replacement therapy (Level A2) and acetylcholinesterase inhibitors (Level B). Interpretation Evidence-based suggestions are proposed, offering clinicians and stakeholders current guidance for the prevention of AD.
210 citations
European Institute of Oncology1, The Royal Marsden NHS Foundation Trust2, Carlos III Health Institute3, University of Valencia4, University of Milan5, University of Alcalá6, Curie Institute7, Claude Bernard University Lyon 18, Netherlands Cancer Institute9, Heidelberg University10, Leipzig University11, Cliniques Universitaires Saint-Luc12, University of Lausanne13, Hebron University14, University of Ioannina15, University of Geneva16, Université Paris-Saclay17, Harvard University18, Duke University19, National University of Singapore20, Université libre de Bruxelles21, Lund University22, Institut Gustave Roussy23, Vita-Salute San Raffaele University24
TL;DR: An international consortium to develop expert consensus statements related to cancer management during the severe acute respiratory syndrome coronavirus 2-related disease (COVID-19) pandemic agreed on 28 consensus statements that can be used to overcome many of the clinical and technical areas of uncertainty.
203 citations
11 Feb 2020
TL;DR: This review focuses exactly on the function of S. cerevisiae in food, beverage -especially wine- and biofuel production industries, alone or in conjunction with other useful microorganisms involved in these processes.
Abstract: Saccharomyces cerevisiae is the best studied eukaryote and a valuable tool for most aspects of basic research on eukaryotic organisms. This is due to its unicellular nature, which often simplifies matters, offering the combination of the facts that nearly all biological functions found in eukaryotes are also present and well conserved in S. cerevisiae. In addition, it is also easily amenable to genetic manipulation. Moreover, unlike other model organisms, S. cerevisiae is concomitantly of great importance for various biotechnological applications, some of which date back to several thousands of years. S. cerevisiae's biotechnological usefulness resides in its unique biological characteristics, i.e., its fermentation capacity, accompanied by the production of alcohol and CO2 and its resilience to adverse conditions of osmolarity and low pH. Among the most prominent applications involving the use of S. cerevisiae are the ones in food, beverage -especially wine- and biofuel production industries. This review focuses exactly on the function of S. cerevisiae in these applications, alone or in conjunction with other useful microorganisms involved in these processes. Furthermore, various aspects of the potential of the reservoir of wild, environmental, S. cerevisiae isolates are examined under the perspective of their use for such applications.
Royal Botanic Gardens1, University of Ioannina2, University of León3, National University of Ireland, Galway4, University of Coimbra5, Royal Botanic Garden Edinburgh6, University of Vienna7, University of São Paulo8, University of Yaoundé I9, University of Sydney10, University of Minnesota11, Botanic Gardens Conservation International12, Royal Holloway, University of London13, Universidade Federal de Pelotas14, Universidade Federal do Rio Grande do Sul15, Federal University of Paraná16, University of Gothenburg17
TL;DR: Although the NLR and TAN hold clinical promise in their association with poor cancer prognosis, further research is required to provide robust evidence, assess causality and test clinical utility.
Abstract: Although neutrophils have been linked to the progression of cancer, uncertainty exists around their association with cancer outcomes, depending on the site, outcome and treatments considered. We aimed to evaluate the strength and validity of evidence on the association between either the neutrophil to lymphocyte ratio (NLR) or tumour-associated neutrophils (TAN) and cancer prognosis. We searched MEDLINE, Embase and Cochrane Database of Systematic Reviews from inception to 29 May 2020 for systematic reviews and meta-analyses of observational studies on neutrophil counts (here NLR or TAN) and specific cancer outcomes related to disease progression or survival. The available evidence was graded as strong, highly suggestive, suggestive, weak or uncertain through the application of pre-set GRADE criteria. A total of 204 meta-analyses from 86 studies investigating the association between either NLR or TAN and cancer outcomes met the criteria for inclusion. All but one meta-analyses found a hazard ratio (HR) which increased risk (HR > 1). We did not find sufficient meta-analyses to evaluate TAN and cancer outcomes (N = 9). When assessed for magnitude of effect, significance and bias related to heterogeneity and small study effects, 18 (9%) associations between NLR and outcomes in composite cancer endpoints (combined analysis), cancers treated with immunotherapy and some site specific cancers (urinary, nasopharyngeal, gastric, breast, endometrial, soft tissue sarcoma and hepatocellular cancers) were supported by strong evidence. In total, 60 (29%) meta-analyses presented strong or highly suggestive evidence. Although the NLR and TAN hold clinical promise in their association with poor cancer prognosis, further research is required to provide robust evidence, assess causality and test clinical utility. PROSPERO CRD42017069131
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National Institute for Health Research1, Wellcome Trust Sanger Institute2, Broad Institute3, Boston Children's Hospital4, Montreal Heart Institute5, British Heart Foundation6, University of North Carolina at Chapel Hill7, VA Boston Healthcare System8, NHS Blood and Transplant9, University of Cambridge10, Osaka University11, Icahn School of Medicine at Mount Sinai12, University of Wisconsin–Milwaukee13, Kyushu University14, University of Washington15, University of Bristol16, University of Copenhagen17, Hasso Plattner Institute18, Erasmus University Medical Center19, National Institutes of Health20, Brigham and Women's Hospital21, Harvard University22, Kaiser Permanente23, University of Mississippi Medical Center24, University of Ioannina25, International Agency for Research on Cancer26, Wake Forest University27, Greifswald University Hospital28, University of Pennsylvania29, Fred Hutchinson Cancer Research Center30, Chinese National Human Genome Center31, Technische Universität München32, University of Tampere33, University of Tokyo34, University of Colorado Denver35, Frederiksberg Hospital36, Duke University37, University of Virginia38, University of Minnesota39, University of Turku40, Turku University Hospital41, Los Angeles Biomedical Research Institute42, Stanford University43, Université de Montréal44, Veterans Health Administration45, University of Oxford46, University of Liège47, European Bioinformatics Institute48, Imperial College London49, John Radcliffe Hospital50, Churchill Hospital51
TL;DR: These results show the power of large-scale blood cell GWAS to interrogate clinically meaningful variants across the full allelic spectrum of human variation.
Abstract: Blood cells play essential roles in human health, underpinning physiological processes such as immunity, oxygen transport, and clotting, which when perturbed cause a significant health burden. Here we integrate data from UK Biobank and a large-scale international collaborative effort, including 563,946 European ancestry participants, and discover 5,106 new genetic variants independently associated with 29 blood cell phenotypes covering the full allele frequency spectrum of variation impacting hematopoiesis. We holistically characterize the genetic architecture of hematopoiesis, assess the relevance of the omnigenic model to blood cell phenotypes, delineate relevant hematopoietic cell states influenced by regulatory genetic variants and gene networks, identify novel splice-altering variants mediating the associations, and assess the polygenic prediction potential for blood cell traits and clinical disorders at the interface of complex and Mendelian genetics. These results show the power of large-scale blood cell GWAS to interrogate clinically meaningful variants across the full allelic spectrum of human variation.
Jewish General Hospital1, McGill University2, Public Health Research Institute3, University of York4, Stanford University5, Concordia University6, University of Calgary7, Johns Hopkins University School of Medicine8, Makerere University9, University of Auckland10, Bar-Ilan University11, Iran University of Medical Sciences12, University of Washington13, Australian National University14, University of Newcastle15, University of São Paulo16, The Chinese University of Hong Kong17, University of North Carolina at Chapel Hill18, University of Rochester Medical Center19, Utrecht University20, Charité21, Singapore Ministry of Health22, Harvard University23, University of Pittsburgh24, University of Macau25, University of Hamburg26, Goethe University Frankfurt27, University of Queensland28, University of Ioannina29, Shimane University30, University of New South Wales31, Tan Tock Seng Hospital32, National University of Singapore33, Mahidol University34, Saint Joseph's College35, Universiti Putra Malaysia36, Universidade Federal de Pelotas37, Niigata Seiryo University38, Katholieke Universiteit Leuven39, University Medical Center Freiburg40, Royal Edinburgh Hospital41, Universiti Sains Malaysia42, Allina Health43, Royal Women's Hospital44, University of Amsterdam45, Monash University46, University of California, San Francisco47, King's College London48
TL;DR: Sensitivity may be minimally reduced with the PHQ-8, but specificity is similar, and bivariate random-effects models to assess diagnostic accuracy were similar.
Abstract: BACKGROUND: Item 9 of the Patient Health Questionnaire-9 (PHQ-9) queries about thoughts of death and self-harm, but not suicidality. Although it is sometimes used to assess suicide risk, most positive responses are not associated with suicidality. The PHQ-8, which omits Item 9, is thus increasingly used in research. We assessed equivalency of total score correlations and the diagnostic accuracy to detect major depression of the PHQ-8 and PHQ-9. METHODS: We conducted an individual patient data meta-analysis. We fit bivariate random-effects models to assess diagnostic accuracy. RESULTS: 16 742 participants (2097 major depression cases) from 54 studies were included. The correlation between PHQ-8 and PHQ-9 scores was 0.996 (95% confidence interval 0.996 to 0.996). The standard cutoff score of 10 for the PHQ-9 maximized sensitivity + specificity for the PHQ-8 among studies that used a semi-structured diagnostic interview reference standard (N = 27). At cutoff 10, the PHQ-8 was less sensitive by 0.02 (-0.06 to 0.00) and more specific by 0.01 (0.00 to 0.01) among those studies (N = 27), with similar results for studies that used other types of interviews (N = 27). For all 54 primary studies combined, across all cutoffs, the PHQ-8 was less sensitive than the PHQ-9 by 0.00 to 0.05 (0.03 at cutoff 10), and specificity was within 0.01 for all cutoffs (0.00 to 0.01). CONCLUSIONS: PHQ-8 and PHQ-9 total scores were similar. Sensitivity may be minimally reduced with the PHQ-8, but specificity is similar.
19 Mar 2020
TL;DR: The type of oleaginous microorganisms and their expertise in the field of biodiesel or omega-3 fatty acids, advances in metabolic engineering tools for enhanced lipid accumulation, upstream and downstream processing of lipids, including purification of biod diesel and concentration of omega- 3 fatty acids are reviewed.
Abstract: Microorganisms are known to be natural oil producers in their cellular compartments. Microorganisms that accumulate more than 20% w/w of lipids on a cell dry weight basis are considered as oleaginous microorganisms. These are capable of synthesizing vast majority of fatty acids from short hydrocarbonated chain (C6) to long hydrocarbonated chain (C36), which may be saturated (SFA), monounsaturated (MUFA), or polyunsaturated fatty acids (PUFA), depending on the presence and number of double bonds in hydrocarbonated chains. Depending on the fatty acid profile, the oils obtained from oleaginous microorganisms are utilized as feedstock for either biodiesel production or as nutraceuticals. Mainly microalgae, bacteria, and yeasts are involved in the production of biodiesel, whereas thraustochytrids, fungi, and some of the microalgae are well known to be producers of very long-chain PUFA (omega-3 fatty acids). In this review article, the type of oleaginous microorganisms and their expertise in the field of biodiesel or omega-3 fatty acids, advances in metabolic engineering tools for enhanced lipid accumulation, upstream and downstream processing of lipids, including purification of biodiesel and concentration of omega-3 fatty acids are reviewed.
International Agency for Research on Cancer1, University of Milan2, North-West University3, British Heart Foundation4, University of Cambridge5, Imperial College London6, Université Paris-Saclay7, National and Kapodistrian University of Athens8, German Cancer Research Center9, Aarhus University10, University of Barcelona11, Andalusian School of Public Health12, Cancer Epidemiology Unit13, University of Ioannina14, Prevention Institute15, Centre for Health Protection16, Utrecht University17, Umeå University18, Lund University19
TL;DR: Pre-diagnostic healthy lifestyle behaviours were strongly inversely associated with the risk of cancer and cardiometabolic diseases, and with the prognosis of these diseases by reducing risk of multimorbidity.
Abstract: Although lifestyle factors have been studied in relation to individual non-communicable diseases (NCDs), their association with development of a subsequent NCD, defined as multimorbidity, has been scarcely investigated. The aim of this study was to investigate associations between five lifestyle factors and incident multimorbidity of cancer and cardiometabolic diseases. In this prospective cohort study, 291,778 participants (64% women) from seven European countries, mostly aged 43 to 58 years and free of cancer, cardiovascular disease (CVD), and type 2 diabetes (T2D) at recruitment, were included. Incident multimorbidity of cancer and cardiometabolic diseases was defined as developing subsequently two diseases including first cancer at any site, CVD, and T2D in an individual. Multi-state modelling based on Cox regression was used to compute hazard ratios (HR) and 95% confidence intervals (95% CI) of developing cancer, CVD, or T2D, and subsequent transitions to multimorbidity, in relation to body mass index (BMI), smoking status, alcohol intake, physical activity, adherence to the Mediterranean diet, and their combination as a healthy lifestyle index (HLI) score. Cumulative incidence functions (CIFs) were estimated to compute 10-year absolute risks for transitions from healthy to cancer at any site, CVD (both fatal and non-fatal), or T2D, and to subsequent multimorbidity after each of the three NCDs. During a median follow-up of 11 years, 1910 men and 1334 women developed multimorbidity of cancer and cardiometabolic diseases. A higher HLI, reflecting healthy lifestyles, was strongly inversely associated with multimorbidity, with hazard ratios per 3-unit increment of 0.75 (95% CI, 0.71 to 0.81), 0.84 (0.79 to 0.90), and 0.82 (0.77 to 0.88) after cancer, CVD, and T2D, respectively. After T2D, the 10-year absolute risks of multimorbidity were 40% and 25% for men and women, respectively, with unhealthy lifestyle, and 30% and 18% for men and women with healthy lifestyles. Pre-diagnostic healthy lifestyle behaviours were strongly inversely associated with the risk of cancer and cardiometabolic diseases, and with the prognosis of these diseases by reducing risk of multimorbidity.
TL;DR: In this article, a measurement of the mass of the Higgs boson in the diphoton decay channel is presented, based on 35.9 fb − 1 of proton-proton collision data collected during the 2016 LHC running period, with the CMS detector at a centre-of-mass energy of 13TeV.
TL;DR: In this article, the best fit value of the CMB power spectrum is degenerate with a constant equation-of-state parameter $w, in accordance with the approximate effective linear equation ${H}_{0}+30.47=0$.
Abstract: Phantom dark energy ($wl\ensuremath{-}1$) can produce amplified cosmic acceleration at late times, thus increasing the value of ${H}_{0}$ favored by CMB data and releasing the tension with local measurements of ${H}_{0}$. We show that the best fit value of ${H}_{0}$ in the context of the CMB power spectrum is degenerate with a constant equation-of-state parameter $w$, in accordance with the approximate effective linear equation ${H}_{0}+30.93w\ensuremath{-}36.47=0$ (${H}_{0}$ in $\mathrm{km}\text{ }{\mathrm{sec}}^{\ensuremath{-}1}\text{ }{\mathrm{Mpc}}^{\ensuremath{-}1}$). This equation is derived by assuming that both ${\mathrm{\ensuremath{\Omega}}}_{0m}{h}^{2}$ and ${d}_{A}={\ensuremath{\int}}_{0}^{{z}_{\mathrm{rec}}}\frac{dz}{H(z)}$ remain constant (for an invariant CMB spectrum) and equal to their best fit Planck/$\mathrm{\ensuremath{\Lambda}}\mathrm{CDM}$ values as ${H}_{0}$, ${\mathrm{\ensuremath{\Omega}}}_{0m}$, and $w$ vary. For $w=\ensuremath{-}1$, this linear degeneracy equation leads to the best fit ${H}_{0}=67.4\text{ }\text{ }\mathrm{km}\text{ }{\mathrm{sec}}^{\ensuremath{-}1}\text{ }{\mathrm{Mpc}}^{\ensuremath{-}1}$ as expected. For $w=\ensuremath{-}1.22$, the corresponding predicted CMB best fit Hubble constant is ${H}_{0}=74\text{ }\text{ }\mathrm{km}\text{ }{\mathrm{sec}}^{\ensuremath{-}1}\text{ }{\mathrm{Mpc}}^{\ensuremath{-}1}$, which is identical with the value obtained by local-distance ladder measurements, while the best fit matter density parameter is predicted to decrease, since ${\mathrm{\ensuremath{\Omega}}}_{0m}{h}^{2}$ is fixed. We verify the above ${H}_{0}\ensuremath{-}w$ degeneracy equation by fitting a $w\mathrm{CDM}$ model with fixed values of $w$ to the Planck TT spectrum, showing also that the quality of fit (${\ensuremath{\chi}}^{2}$) is similar to that of $\mathrm{\ensuremath{\Lambda}}\mathrm{CDM}$. However, when including SnIa, baryon acoustic oscillation, or growth data, the quality of fit becomes worse than $\mathrm{\ensuremath{\Lambda}}\mathrm{CDM}$ when $wl\ensuremath{-}1$. Finally, we generalize the ${H}_{0}\ensuremath{-}w(z)$ degeneracy equation for the parametrization $w(z)={w}_{0}+{w}_{1}z/(1+z)$ and identify analytically the full ${w}_{0}\ensuremath{-}{w}_{1}$ parameter region (straight line) that leads to a best fit ${H}_{0}=74\text{ }\text{ }\mathrm{km}\text{ }{\mathrm{sec}}^{\ensuremath{-}1}\text{ }{\mathrm{Mpc}}^{\ensuremath{-}1}$ in the context of the Planck CMB spectrum. This exploitation of ${H}_{0}\ensuremath{-}w(z)$ degeneracy can lead to immediate identification of all parameter values of a given $w(z)$ parametrization that can potentially resolve the ${H}_{0}$ tension.
TL;DR: The GRECCO-19 trial aims to identify whether colchicine may positively intervene in the clinical course of COVID-19 and results will be disseminated through peer-reviewed publications and conference presentations.
National Health Research Institutes1, Kaohsiung Medical University2, National Cheng Kung University3, Seconda Università degli Studi di Napoli4, National Taiwan University5, University of Ioannina6, Samsung Medical Center7, University of Malaya8, Fudan University9, Gandhi Medical College10, University of Ulsan11, University of Valencia12, Memorial Hospital of South Bend13, National Yang-Ming University14, Taipei Veterans General Hospital15, Hebron University16, Taipei Medical University17
TL;DR: These guidelines represent the consensus opinions reached by experts in the treatment of patients with intermediate and advanced/relapsed HCC representing the oncology societies of Taiwan (TOS), China (CSCO), India (ISMPO), Japan (JSMO), Korea (KSMO), Malaysia (MOS) and Singapore (SSO).
TL;DR: This study illustrates how population-based cardiac and aortic imaging phenotypes can be used to better define cardiovascular disease risks as well as heart–brain health interactions, highlighting new opportunities for studying disease mechanisms and developing image-based biomarkers.
Abstract: Differences in cardiac and aortic structure and function are associated with cardiovascular diseases and a wide range of other types of disease. Here we analyzed cardiovascular magnetic resonance images from a population-based study, the UK Biobank, using an automated machine-learning-based analysis pipeline. We report a comprehensive range of structural and functional phenotypes for the heart and aorta across 26,893 participants, and explore how these phenotypes vary according to sex, age and major cardiovascular risk factors. We extended this analysis with a phenome-wide association study, in which we tested for correlations of a wide range of non-imaging phenotypes of the participants with imaging phenotypes. We further explored the associations of imaging phenotypes with early-life factors, mental health and cognitive function using both observational analysis and Mendelian randomization. Our study illustrates how population-based cardiac and aortic imaging phenotypes can be used to better define cardiovascular disease risks as well as heart-brain health interactions, highlighting new opportunities for studying disease mechanisms and developing image-based biomarkers.
Maria Teresa Landi1, D. Timothy Bishop2, Stuart MacGregor3, Mitchell J. Machiela1 +180 more•Institutions (57)
TL;DR: Analysis of risk estimates across geographical regions and host factors suggests the acral melanoma subtype is uniquely unrelated to pigmentation, and analysis combining nevus count and hair color GWAS results provide insights into the genetic architecture of melanoma.
Abstract: Most genetic susceptibility to cutaneous melanoma remains to be discovered. Meta-analysis genome-wide association study (GWAS) of 36,760 cases of melanoma (67% newly genotyped) and 375,188 controls identified 54 significant (P < 5 × 10-8) loci with 68 independent single nucleotide polymorphisms. Analysis of risk estimates across geographical regions and host factors suggests the acral melanoma subtype is uniquely unrelated to pigmentation. Combining this meta-analysis with GWAS of nevus count and hair color, and transcriptome association approaches, uncovered 31 potential secondary loci for a total of 85 cutaneous melanoma susceptibility loci. These findings provide insights into cutaneous melanoma genetic architecture, reinforcing the importance of nevogenesis, pigmentation and telomere maintenance, together with identifying potential new pathways for cutaneous melanoma pathogenesis.
TL;DR: The study identifies a previously undescribed mechanism of insecticide resistance that is likely to be highly relevant to malaria control efforts, and shows that expression of a sensory appendage protein (SAP2), which is enriched in the legs, confers pyrethroid resistance to Anopheles gambiae.
Abstract: Pyrethroid-impregnated bed nets have driven considerable reductions in malaria-associated morbidity and mortality in Africa since the beginning of the century1. The intense selection pressure exerted by bed nets has precipitated widespread and escalating resistance to pyrethroids in African Anopheles populations, threatening to reverse the gains that been made by malaria control2. Here we show that expression of a sensory appendage protein (SAP2), which is enriched in the legs, confers pyrethroid resistance to Anopheles gambiae. Expression of SAP2 is increased in insecticide-resistant populations and is further induced after the mosquito comes into contact with pyrethroids. SAP2 silencing fully restores mortality of the mosquitoes, whereas SAP2 overexpression results in increased resistance, probably owing to high-affinity binding of SAP2 to pyrethroid insecticides. Mining of genome sequence data reveals a selective sweep near the SAP2 locus in the mosquito populations of three West African countries (Cameroon, Guinea and Burkina Faso) with the observed increase in haplotype-associated single-nucleotide polymorphisms mirroring the increasing resistance of mosquitoes to pyrethroids reported in Burkina Faso. Our study identifies a previously undescribed mechanism of insecticide resistance that is likely to be highly relevant to malaria control efforts. The leg-enriched sensory appendage protein, SAP2, confers pyrethroid resistance to Anopheles gambiae, through high-affinity binding of pyrethroid insecticides; an observed selective sweep in field mosquitoes mirrors the increasing resistance reported in Africa.
TL;DR: The evidence linking diet and nutrition to cancer risk is described, concluding that obesity and alcohol are the most important factors.
Abstract: Timothy J Key and colleagues describe the evidence linking diet and nutrition to cancer risk, concluding that obesity and alcohol are the most important factors
TL;DR: The standard model (SM) production of four top quarks in proton-proton collisions is studied by the CMS Collaboration, with limits set on the production of a heavy scalar or pseudoscalar boson in Type-II two-Higgs-doublet and simplified dark matter models.
Abstract: The standard model (SM) production of four top quarks ($\text {t} {}{\overline{\text {t}}} \text {t} {}{\overline{\text {t}}} $) in proton–proton collisions is studied by the CMS Collaboration. The data sample, collected during the 2016–2018 data taking of the LHC, corresponds to an integrated luminosity of 137$\,\text {fb}^{-1}$ at a center-of-mass energy of 13$\,\text {TeV}$. The events are required to contain two same-sign charged leptons (electrons or muons) or at least three leptons, and jets. The observed and expected significances for the $\text {t} {}{\overline{\text {t}}} \text {t} {}{\overline{\text {t}}} $ signal are respectively 2.6 and 2.7 standard deviations, and the $\text {t} {}{\overline{\text {t}}} \text {t} {}{\overline{\text {t}}} $ cross section is measured to be $12.6^{+5.8}_{-5.2}\,\text {fb} $. The results are used to constrain the Yukawa coupling of the top quark to the Higgs boson, $y_{\text {t}}$, yielding a limit of $|y_{\text {t}}/y_{\text {t}}^{\mathrm {SM}} | < 1.7$ at $95\%$ confidence level, where $y_{\text {t}}^{\mathrm {SM}}$ is the SM value of $y_{\text {t}}$. They are also used to constrain the oblique parameter of the Higgs boson in an effective field theory framework, $\hat{H}<0.12$. Limits are set on the production of a heavy scalar or pseudoscalar boson in Type-II two-Higgs-doublet and simplified dark matter models, with exclusion limits reaching 350–470$\,\text {GeV}$ and 350–550$\,\text {GeV}$ for scalar and pseudoscalar bosons, respectively. Upper bounds are also set on couplings of the top quark to new light particles.
TL;DR: This present review aims to summarize the trends in the synthesis of FDCA-based copolymers and to investigate the effectiveness of this approach in transforming them to a more versatile class of materials that could potentially be appropriate for a number of high-end and conventional applications.
Abstract: Polyesters based on 2,5-furandicarboxylic acid (FDCA) are a new class of biobased polymers with enormous interest, both from a scientific and industrial perspective. The commercialization of these polymers is imminent as the pressure for a sustainable economy grows, and extensive worldwide research currently takes place on developing cost-competitive, renewable plastics. The most prevalent method for imparting these polymers with new properties is copolymerization, as many studies have been published over the last few years. This present review aims to summarize the trends in the synthesis of FDCA-based copolymers and to investigate the effectiveness of this approach in transforming them to a more versatile class of materials that could potentially be appropriate for a number of high-end and conventional applications.
International Agency for Research on Cancer1, Imperial College London2, University of Ioannina3, Fred Hutchinson Cancer Research Center4, University Hospitals Bristol NHS Foundation Trust5, University of Bristol6, National Institutes of Health7, University of Leeds8, German Cancer Research Center9, Royal Melbourne Hospital10, University of Melbourne11, American Cancer Society12, University of Barcelona13, Harvard University14, University of Hamburg15, University of Southern California16, Cedars-Sinai Medical Center17, University of Toronto18, Cancer Council Victoria19, Dresden University of Technology20, Ohio State University21, Umeå University22, Seoul National University23, University of Washington24, University of North Carolina at Chapel Hill25, University of Milan26, University of Virginia27, Karolinska Institutet28, Karolinska University Hospital29, Mayo Clinic30, The Heart Research Institute31, Case Western Reserve University32, Prevention Institute33, Utrecht University34, Memorial Sloan Kettering Cancer Center35, Cornell University36, Institut Gustave Roussy37, Paris Descartes University38, Université Paris-Saclay39, University of Cambridge40, Johns Hopkins University41, Rappaport Faculty of Medicine42, Andalusian School of Public Health43, University of South Florida44, University of Pittsburgh45, University of Utah46, University of Oxford47, Huntsman Cancer Institute48, Wageningen University and Research Centre49, Academy of Sciences of the Czech Republic50, Charles University in Prague51, First Faculty of Medicine, Charles University in Prague52, Memorial University of Newfoundland53
TL;DR: Two-sample Mendelian randomisation analyses using summary genetic data from the UK Biobank and GWA consortia found that a one standard deviation increment in average acceleration was associated with lower risks of breast cancer and colorectal cancer.
Abstract: Physical activity has been associated with lower risks of breast and colorectal cancer in epidemiological studies; however, it is unknown if these associations are causal or confounded. In two-sample Mendelian randomisation analyses, using summary genetic data from the UK Biobank and GWA consortia, we found that a one standard deviation increment in average acceleration was associated with lower risks of breast cancer (odds ratio [OR]: 0.51, 95% confidence interval [CI]: 0.27 to 0.98, P-value = 0.04) and colorectal cancer (OR: 0.66, 95% CI: 0.48 to 0.90, P-value = 0.01). We found similar magnitude inverse associations for estrogen positive (ER+ve) breast cancer and for colon cancer. Our results support a potentially causal relationship between higher physical activity levels and lower risks of breast cancer and colorectal cancer. Based on these data, the promotion of physical activity is probably an effective strategy in the primary prevention of these commonly diagnosed cancers.
TL;DR: In this article, a search for narrow and broad resonances with masses greater than 1.8 TeV decaying to a pair of jets is presented, and the results show that no significant evidence for the production of new particles is observed.
Abstract: A search for narrow and broad resonances with masses greater than 1.8 TeV decaying to a pair of jets is presented. The search uses proton-proton collision data at $ \sqrt{s} $ = 13 TeV collected at the LHC, corresponding to an integrated luminosity of 137 fb$^{−1}$. The background arising from standard model processes is predicted with the fit method used in previous publications and with a new method. The dijet invariant mass spectrum is well described by both data-driven methods, and no significant evidence for the production of new particles is observed. Model independent upper limits are reported on the production cross sections of narrow resonances, and broad resonances with widths up to 55% of the resonance mass. Limits are presented on the masses of narrow resonances from various models: string resonances, scalar diquarks, axigluons, colorons, excited quarks, color-octet scalars, W′ and Z′ bosons, Randall-Sundrum gravitons, and dark matter mediators. The limits on narrow resonances are improved by 200 to 800 GeV relative to those reported in previous CMS dijet resonance searches. The limits on dark matter mediators are presented as a function of the resonance mass and width, and on the associated coupling strength as a function of the mediator mass. These limits exclude at 95% confidence level a dark matter mediator with a mass of 1.8 TeV and width 1% of its mass or higher, up to one with a mass of 4.8 TeV and a width 45% of its mass or higher.[graphic not available: see fulltext]
TL;DR: There is triangulate evidence linking male sex, lower educational attainment and non-White ethnicity with the risk of COVID-19, and the elucidation of the joint and independent effects of these factors is a high-priority area for further research.
Abstract: BACKGROUND: The recent COVID-19 outbreak has generated an unprecedented public health crisis, with millions of infections and hundreds of thousands of deaths worldwide. Using hospital-based or mortality data, several COVID-19 risk factors have been identified, but these may be confounded or biased. METHODS: Using SARS-CoV-2 infection test data (n = 4509 tests; 1325 positive) from Public Health England, linked to the UK Biobank study, we explored the contribution of demographic, social, health risk, medical and environmental factors to COVID-19 risk. We used multivariable and penalized logistic regression models for the risk of (i) being tested, (ii) testing positive/negative in the study population and, adopting a test negative design, (iii) the risk of testing positive within the tested population. RESULTS: In the fully adjusted model, variables independently associated with the risk of being tested for COVID-19 with odds ratio >1.05 were: male sex; Black ethnicity; social disadvantage (as measured by education, housing and income); occupation (healthcare worker, retired, unemployed); ever smoker; severely obese; comorbidities; and greater exposure to particulate matter (PM) 2.5 absorbance. Of these, only male sex, non-White ethnicity and lower educational attainment, and none of the comorbidities or health risk factors, were associated with testing positive among tested individuals. CONCLUSIONS: We adopted a careful and exhaustive approach within a large population-based cohort, which enabled us to triangulate evidence linking male sex, lower educational attainment and non-White ethnicity with the risk of COVID-19. The elucidation of the joint and independent effects of these factors is a high-priority area for further research to inform on the natural history of COVID-19.