Showing papers by "University of Ottawa published in 2015"
TL;DR: In the Global Burden of Disease Study 2013 (GBD 2013) as discussed by the authors, the authors used the GBD 2010 methods with some refinements to improve accuracy applied to an updated database of vital registration, survey, and census data.
5,792 citations
Mohammad H. Forouzanfar1, Lily Alexander, H. Ross Anderson, Victoria F Bachman1 +733 more•Institutions (289)
TL;DR: The Global Burden of Disease, Injuries, and Risk Factor study 2013 (GBD 2013) as discussed by the authors provides a timely opportunity to update the comparative risk assessment with new data for exposure, relative risks, and evidence on the appropriate counterfactual risk distribution.
5,668 citations
TL;DR: In this paper, the authors evaluated rapid endovascular treatment in addition to standard care in patients with acute ischemic stroke with a small infarct core, a proximal intracranial arterial occlusion, and moderate-to-good collateral circulation.
Abstract: Among patients with a proximal vessel occlusion in the anterior circulation, 60 to 80% of patients die within 90 days after stroke onset or do not regain functional independence despite alteplase treatment. We evaluated rapid endovascular treatment in addition to standard care in patients with acute ischemic stroke with a small infarct core, a proximal intracranial arterial occlusion, and moderate-to-good collateral circulation. Methods We randomly assigned participants to receive standard care (control group) or standard care plus endovascular treatment with the use of available thrombectomy devices (intervention group). Patients with a proximal intracranial occlusion in the anterior circulation were included up to 12 hours after symptom onset. Patients with a large infarct core or poor collateral circulation on computed tomography (CT) and CT angiography were excluded. Workflow times were measured against predetermined targets. The primary outcome was the score on the modified Rankin scale (range, 0 [no symptoms] to 6 [death]) at 90 days. A proportional odds model was used to calculate the common odds ratio as a measure of the likelihood that the intervention would lead to lower scores on the modified Rankin scale than would control care (shift analysis). Results The trial was stopped early because of efficacy. At 22 centers worldwide, 316 participants were enrolled, of whom 238 received intravenous alteplase (120 in the intervention group and 118 in the control group). In the intervention group, the median time from study CT of the head to first reperfusion was 84 minutes. The rate of functional independence (90-day modified Rankin score of 0 to 2) was increased with the intervention (53.0%, vs. 29.3% in the control group; P<0.001). The primary outcome favored the intervention (common odds ratio, 2.6; 95% confidence interval, 1.7 to 3.8; P<0.001), and the intervention was associated with reduced mortality (10.4%, vs. 19.0% in the control group; P = 0.04). Symptomatic intracerebral hemorrhage occurred in 3.6% of participants in intervention group and 2.7% of participants in control group (P = 0.75). Conclusions Among patients with acute ischemic stroke with a proximal vessel occlusion, a small infarct core, and moderate-to-good collateral circulation, rapid endovascular treatment improved functional outcomes and reduced mortality. (Funded by Covidien and others; ESCAPE ClinicalTrials.gov number, NCT01778335.)
4,739 citations
TL;DR: In the Global Burden of Disease Study 2013 (GBD 2013) as mentioned in this paper, the authors estimated the quantities for acute and chronic diseases and injuries for 188 countries between 1990 and 2013.
4,510 citations
TL;DR: The process of developing specific advice for the reporting of systematic reviews that incorporate network meta-analyses is described, and the guidance generated from this process is presented.
Abstract: The PRISMA statement is a reporting guideline designed to improve the completeness of reporting of systematic reviews and meta-analyses. Authors have used this guideline worldwide to prepare their reviews for publication. In the past, these reports typically compared 2 treatment alternatives. With the evolution of systematic reviews that compare multiple treatments, some of them only indirectly, authors face novel challenges for conducting and reporting their reviews. This extension of the PRISMA (Preferred Reporting Items for Systematic Reviews and Metaanalyses) statement was developed specifically to improve the reporting of systematic reviews incorporating network meta-analyses.
3,932 citations
University of Washington1, Institute for Health Metrics and Evaluation2, Iran University of Medical Sciences3, King's College London4, Arabian Gulf University5, University of North Texas6, Auckland University of Technology7, Alaska Native Tribal Health Consortium8, Columbia University9, Wuhan University10, Imperial College London11, University of Alabama at Birmingham12, University at Albany, SUNY13, City University of New York14, University of California, San Francisco15, Griffith University16, Environment Agency17, New York University18, Southern University College19, Emory University20, University of Ottawa21, Kosin University22, University of Toronto23, University of British Columbia24, United Arab Emirates University25, Albert Einstein College of Medicine26, University of São Paulo27, Nova Southeastern University28, University of Sydney29, Heidelberg University30, Case Western Reserve University31, Cancer Treatment Centers of America32, University of Oxford33, George Mason University34, James Cook University35, University of Trieste36, University of Calgary37, Wageningen University and Research Centre38, University of the Witwatersrand39, University of Gothenburg40, Harvard University41, Jackson State University42, University of Arizona43, University of Hong Kong44, Tehran University of Medical Sciences45, University of Western Australia46, Aintree University Hospitals NHS Foundation Trust47, Veterans Health Administration48, University of Colorado Denver49, Royal Children's Hospital50, University of Melbourne51, Australian National University52, University of Marburg53, Charité54, Health Canada55, College of Health Sciences, Bahrain56, Karolinska Institutet57, Northumbria University58, University of Edinburgh59, National Research University – Higher School of Economics60, Queen Mary University of London61, Addis Ababa University62, Northwestern University63, Northeastern University64, Mario Negri Institute for Pharmacological Research65, Arak University of Medical Sciences66, University of Nottingham67, University of Tokyo68, Public Health Foundation of India69, University of Groningen70, University of the Philippines Manila71, University of Bologna72, Kyung Hee University73, Brighton and Sussex Medical School74, University of Bergen75, Stavanger University Hospital76, University of Queensland77, National Centre for Disease Control78, University of Sheffield79, Universidad Autónoma Metropolitana80, University College London81, Genentech82, Universiti Tunku Abdul Rahman83, Norwegian Institute of Public Health84
TL;DR: To estimate mortality, incidence, years lived with disability, years of life lost, and disability-adjusted life-years for 28 cancers in 188 countries by sex from 1990 to 2013, the general methodology of the Global Burden of Disease 2013 study was used.
Abstract: Importance Cancer is among the leading causes of death worldwide. Current estimates of cancer burden in individual countries and regions are necessary to inform local cancer control strategies. Objective To estimate mortality, incidence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs) for 28 cancers in 188 countries by sex from 1990 to 2013. Evidence Review The general methodology of the Global Burden of Disease (GBD) 2013 study was used. Cancer registries were the source for cancer incidence data as well as mortality incidence (MI) ratios. Sources for cause of death data include vital registration system data, verbal autopsy studies, and other sources. The MI ratios were used to transform incidence data to mortality estimates and cause of death estimates to incidence estimates. Cancer prevalence was estimated using MI ratios as surrogates for survival data; YLDs were calculated by multiplying prevalence estimates with disability weights, which were derived from population-based surveys; YLLs were computed by multiplying the number of estimated cancer deaths at each age with a reference life expectancy; and DALYs were calculated as the sum of YLDs and YLLs. Findings In 2013 there were 14.9 million incident cancer cases, 8.2 million deaths, and 196.3 million DALYs. Prostate cancer was the leading cause for cancer incidence (1.4 million) for men and breast cancer for women (1.8 million). Tracheal, bronchus, and lung (TBL) cancer was the leading cause for cancer death in men and women, with 1.6 million deaths. For men, TBL cancer was the leading cause of DALYs (24.9 million). For women, breast cancer was the leading cause of DALYs (13.1 million). Age-standardized incidence rates (ASIRs) per 100 000 and age-standardized death rates (ASDRs) per 100 000 for both sexes in 2013 were higher in developing vs developed countries for stomach cancer (ASIR, 17 vs 14; ASDR, 15 vs 11), liver cancer (ASIR, 15 vs 7; ASDR, 16 vs 7), esophageal cancer (ASIR, 9 vs 4; ASDR, 9 vs 4), cervical cancer (ASIR, 8 vs 5; ASDR, 4 vs 2), lip and oral cavity cancer (ASIR, 7 vs 6; ASDR, 2 vs 2), and nasopharyngeal cancer (ASIR, 1.5 vs 0.4; ASDR, 1.2 vs 0.3). Between 1990 and 2013, ASIRs for all cancers combined (except nonmelanoma skin cancer and Kaposi sarcoma) increased by more than 10% in 113 countries and decreased by more than 10% in 12 of 188 countries. Conclusions and Relevance Cancer poses a major threat to public health worldwide, and incidence rates have increased in most countries since 1990. The trend is a particular threat to developing nations with health systems that are ill-equipped to deal with complex and expensive cancer treatments. The annual update on the Global Burden of Cancer will provide all stakeholders with timely estimates to guide policy efforts in cancer prevention, screening, treatment, and palliation.
2,375 citations
University of Amsterdam1, Utrecht University2, University of Virginia3, Brown University4, Bond University5, University of Sydney6, University of Ottawa7, Ottawa Hospital Research Institute8, University of California, San Francisco9, VU University Medical Center10, Beth Israel Deaconess Medical Center11, Boston Children's Hospital12, Northwestern University13, University of Oxford14, Paris Descartes University15
TL;DR: STARD 2015 is presented, an updated list of 30 essential items that should be included in every report of a diagnostic accuracy study, which incorporates recent evidence about sources of bias and variability in diagnostic accuracy.
Abstract: Incomplete reporting has been identified as a major source of avoidable waste in biomedical research. Essential information is often not provided in study reports, impeding the identification, critical appraisal, and replication of studies. To improve the quality of reporting of diagnostic accuracy studies, the Standards for Reporting Diagnostic Accuracy (STARD) statement was developed. Here we present STARD 2015, an updated list of 30 essential items that should be included in every report of a diagnostic accuracy study. This update incorporates recent evidence about sources of bias and variability in diagnostic accuracy and is intended to facilitate the use of STARD. As such, STARD 2015 may help to improve completeness and transparency in reporting of diagnostic accuracy studies.
2,116 citations
TL;DR: This article conducted a meta-analysis of coronary artery disease (CAD) cases and controls, interrogating 6.7 million common (minor allele frequency (MAF) > 0.05) and 2.7 millions low-frequency (0.005 < MAF < 0.5) variants.
Abstract: Existing knowledge of genetic variants affecting risk of coronary artery disease (CAD) is largely based on genome-wide association study (GWAS) analysis of common SNPs. Leveraging phased haplotypes from the 1000 Genomes Project, we report a GWAS meta-analysis of ∼185,000 CAD cases and controls, interrogating 6.7 million common (minor allele frequency (MAF) > 0.05) and 2.7 million low-frequency (0.005 < MAF < 0.05) variants. In addition to confirming most known CAD-associated loci, we identified ten new loci (eight additive and two recessive) that contain candidate causal genes newly implicating biological processes in vessel walls. We observed intralocus allelic heterogeneity but little evidence of low-frequency variants with larger effects and no evidence of synthetic association. Our analysis provides a comprehensive survey of the fine genetic architecture of CAD, showing that genetic susceptibility to this common disease is largely determined by common SNPs of small effect size.
1,839 citations
Mohammad H. Forouzanfar1, Lily Alexander1, H. Ross Anderson2, Victoria F Bachman1 +718 more•Institutions (295)
TL;DR: The Global Burden of Disease, Injuries, and Risk Factor study 2013 (GBD 2013) as mentioned in this paper provides a timely opportunity to update the comparative risk assessment with new data for exposure, relative risks, and evidence on the appropriate counterfactual risk distribution.
1,656 citations
Harvard University1, Broad Institute2, Cardiff University3, Icahn School of Medicine at Mount Sinai4, University of Michigan5, University of Cambridge6, Karolinska Institutet7, University of Eastern Finland8, University of Oxford9, Cedars-Sinai Medical Center10, University of Ottawa11, University of Helsinki12, University of Pennsylvania13, University of North Carolina at Chapel Hill14, University of Mississippi Medical Center15
TL;DR: The aggregation and analysis of high-quality exome (protein-coding region) sequence data for 60,706 individuals of diverse ethnicities generated as part of the Exome Aggregation Consortium (ExAC) provides direct evidence for the presence of widespread mutational recurrence.
Abstract: Large-scale reference data sets of human genetic variation are critical for the medical and functional interpretation of DNA sequence changes. Here we describe the aggregation and analysis of high-quality exome (protein-coding region) sequence data for 60,706 individuals of diverse ethnicities. The resulting catalogue of human genetic diversity has unprecedented resolution, with an average of one variant every eight bases of coding sequence and the presence of widespread mutational recurrence. The deep catalogue of variation provided by the Exome Aggregation Consortium (ExAC) can be used to calculate objective metrics of pathogenicity for sequence variants, and to identify genes subject to strong selection against various classes of mutation; we identify 3,230 genes with near-complete depletion of truncating variants, 79% of which have no currently established human disease phenotype. Finally, we show that these data can be used for the efficient filtering of candidate disease-causing variants, and for the discovery of human knockout variants in protein-coding genes.
1,552 citations
TL;DR: A typology of review types is developed and descriptive insight into the most common reviews found in top IS journals is provided to encourage researchers who start a review to use the typology to position their contribution.
TL;DR: This review article summarizes the last few decades of research on nickel hydroxide, an important material in physics and chemistry, that has many applications in engineering including, significantly, batteries.
Abstract: This review article summarizes the last few decades of research on nickel hydroxide, an important material in physics and chemistry, that has many applications in engineering including, significantly, batteries. First, the structures of the two known polymorphs, denoted as α-Ni(OH)2 and β-Ni(OH)2, are described. The various types of disorder, which are frequently present in nickel hydroxide materials, are discussed including hydration, stacking fault disorder, mechanical stresses and the incorporation of ionic impurities. Several related materials are discussed, including intercalated α-derivatives and basic nickel salts. Next, a number of methods to prepare, or synthesize, nickel hydroxides are summarized, including chemical precipitation, electrochemical precipitation, sol-gel synthesis, chemical ageing, hydrothermal and solvothermal synthesis, electrochemical oxidation, microwave-assisted synthesis, and sonochemical methods. Finally, the known physical properties of the nickel hydroxides are reviewed, including their magnetic, vibrational, optical, electrical and mechanical properties. The last section in this paper is intended to serve as a summary of both the potentially useful properties of these materials and the methods for the identification and characterization of 'unknown' nickel hydroxide-based samples.
Harvard University1, University of South Florida2, University of Washington3, University of British Columbia4, University of Ottawa5, Boston Children's Hospital6, Christiana Care Health System7, University of Minnesota8, University of Vermont9, Washington University in St. Louis10, Food and Drug Administration11, Wayne State University12, University of Pennsylvania13, Englewood Hospital and Medical Center14, Yale University15, Canadian Blood Services16, University of Massachusetts Medical School17, University of Texas Southwestern Medical Center18, Johns Hopkins University19, Children's National Medical Center20
TL;DR: These guidelines were designed to provide pragmatic recommendations, based on the best available published evidence, about when platelet transfusion may be appropriate in adult patients, and provide advice for adult patients who are candidates for platelets transfusion.
Abstract: Platelet transfusions are administered to prevent or treat bleeding in patients with quantitative or qualitative platelet disorders The AABB (formerly, the American Association of Blood Banks) dev
TL;DR: This paper provided an inside view of a first project, making connections between theory and practice, highlighting the value of reflexivity both during and after a study, and may help to demystify the research process for those new to the field.
Abstract: Learning how to conduct qualitative research may seem daunting for those new to the task, especially given the paradigm’s emphasis on complexity and emergent design. Although there are guidelines in the literature, each project is unique and ultimately the individual researcher must determine how best to proceed. Reflexivity is thus considered essential, potentially facilitating understanding of both the phenomenon under study and the research process itself. Drawing upon the contents of a reflective journal, the author provides an inside view of a first project, making connections between theory and practice. This personal narrative highlights the value of reflexivity both during and after a study, and may help to demystify the research process for those new to the field. Key Words: Reflexivity, Research Journal, Qualitative Methodology, and Student Researchers
University of Amsterdam1, Utrecht University2, University of Virginia3, Brown University4, Bond University5, University of Sydney6, Ottawa Hospital Research Institute7, University of Ottawa8, University of California, San Francisco9, VU University Amsterdam10, Harvard University11, Northwestern University12, University of Oxford13, Pierre-and-Marie-Curie University14
TL;DR: An updated list of 30 essential items that should be included in every report of a diagnostic accuracy study is presented, which incorporates recent evidence about sources of bias and variability in diagnostic accuracy and is intended to facilitate the use of STARD.
Abstract: Incomplete reporting has been identified as a major source of avoidable waste in biomedical research. Essential information is often not provided in study reports, impeding the identification, critical appraisal, and replication of studies. To improve the quality of reporting of diagnostic accuracy studies, the Standards for Reporting of Diagnostic Accuracy Studies (STARD) statement was developed. Here we present STARD 2015, an updated list of 30 essential items that should be included in every report of a diagnostic accuracy study. This update incorporates recent evidence about sources of bias and variability in diagnostic accuracy and is intended to facilitate the use of STARD. As such, STARD 2015 may help to improve completeness and transparency in reporting of diagnostic accuracy studies.
TL;DR: It is found that solid-state high harmonics are perturbed by fields so weak that they are present in conventional electronic circuits, thus opening a route to integrate electronics with attosecond and high-harmonic technology.
Abstract: When intense light interacts with an atomic gas, recollision between an ionizing electron and its parent ion creates high-order harmonics of the fundamental laser frequency. This sub-cycle effect generates coherent soft X-rays and attosecond pulses, and provides a means to image molecular orbitals. Recently, high harmonics have been generated from bulk crystals, but what mechanism dominates the emission remains uncertain. To resolve this issue, we adapt measurement methods from gas-phase research to solid zinc oxide driven by mid-infrared laser fields of 0.25 volts per angstrom. We find that when we alter the generation process with a second-harmonic beam, the modified harmonic spectrum bears the signature of a generalized recollision between an electron and its associated hole. In addition, we find that solid-state high harmonics are perturbed by fields so weak that they are present in conventional electronic circuits, thus opening a route to integrate electronics with attosecond and high-harmonic technology. Future experiments will permit the band structure of a solid to be tomographically reconstructed.
TL;DR: A proof-of-principle experiment that indicates the feasibility of high-dimensional QKD based on the transverse structure of the light field allowing for the transfer of more than 1 bit per photon and demonstrates that, in addition to having an increased information capacity, multilevel QK D systems based on spatial-mode encoding can be more resilient against intercept-resend eavesdropping attacks.
Abstract: Quantum key distribution (QKD) systems often rely on polarization of light for encoding, thus limiting the amount of information that can be sent per photon and placing tight bounds on the error rates that such a system can tolerate. Here we describe a proof-of-principle experiment that indicates the feasibility of high-dimensional QKD based on the transverse structure of the light field allowing for the transfer of more than 1 bit per photon. Our implementation uses the orbital angular momentum (OAM) of photons and the corresponding mutually unbiased basis of angular position (ANG). Our experiment uses a digital micro-mirror device for the rapid generation of OAM and ANG modes at 4 kHz, and a mode sorter capable of sorting single photons based on their OAM and ANG content with a separation efficiency of 93%. Through the use of a seven-dimensional alphabet encoded in the OAM and ANG bases, we achieve a channel capacity of 2.05 bits per sifted photon. Our experiment demonstrates that, in addition to having an increased information capacity, multilevel QKD systems based on spatial-mode encoding can be more resilient against intercept-resend eavesdropping attacks.
University of Ottawa1, University of Calgary2, York University3, University of Reading4, University of Mons5, Helmholtz Centre for Environmental Research - UFZ6, Wildlife Preservation Canada7, University of Vermont8, University of Connecticut9, American Museum of Natural History10, University of Alaska Fairbanks11, United States Department of Agriculture12
TL;DR: Using long-term observations across Europe and North America over 110 years, testing for climate change–related range shifts in bumblebee species across the full extents of their latitudinal and thermal limits and movements along elevation gradients found cross-continentally consistent trends in failures to track warming through time at species’ northern range limits.
Abstract: For many species, geographical ranges are expanding toward the poles in response to climate change, while remaining stable along range edges nearest the equator. Using long-term observations across Europe and North America over 110 years, we tested for climate change–related range shifts in bumblebee species across the full extents of their latitudinal and thermal limits and movements along elevation gradients. We found cross-continentally consistent trends in failures to track warming through time at species’ northern range limits, range losses from southern range limits, and shifts to higher elevations among southern species. These effects are independent of changing land uses or pesticide applications and underscore the need to test for climate impacts at both leading and trailing latitudinal and thermal limits for species.
McGill University1, Université de Montréal2, Hôpital Maisonneuve-Rosemont3, McGill University Health Centre4, Laval University5, University of Toronto6, University Health Network7, University of Ottawa8, University of Western Ontario9, Tufts University10, Lahey Hospital & Medical Center11, Sunnybrook Health Sciences Centre12
TL;DR: It is recommended that SN evaluation with IHC be further evaluated before being included in future guidelines on the use of SNB after NAC in this setting, and a low SNB FNR (8.4%) can be achieved with mandatory use of IHC.
Abstract: Purpose An increasing proportion of patients (> 30%) with node-positive breast cancer will obtain an axillary pathologic complete response after neoadjuvant chemotherapy (NAC) If sentinel node (SN) biopsy (SNB) is accurate in this setting, completion node dissection (CND) morbidity could be avoided Patients and Methods In the prospective multicentric SN FNAC study, patients with biopsy-proven node-positive breast cancer (T0-3, N1-2) underwent both SNB and CND Immunohistochemistry (IHC) use was mandatory, and SN metastases of any size, including isolated tumor cells (ypN0[i+], ≤ 02 mm), were considered positive The optimal SNB identification rate (IR) ≥ 90% and false-negative rate (FNR) ≤ 10% were predetermined Results From March 2009 to December 2012, 153 patients were accrued to the study The SNB IR was 876% (127 of 145; 95% CI, 822% to 930%), and the FNR was 84% (seven of 83; 95% CI, 24% to 144%) If SN ypN0(i+)s had been considered negative, the FNR would have increased to 133% (11 of 83;
TL;DR: In providing the first experimental demonstration of conformity in a wild non-primate, and of cultural norms in foraging techniques in any wild animal, the results suggest a much broader taxonomic occurrence of such an apparently complex cultural behaviour.
Abstract: In human societies, cultural norms arise when behaviours are transmitted through social networks via high-fidelity social learning. However, a paucity of experimental studies has meant that there is no comparable understanding of the process by which socially transmitted behaviours might spread and persist in animal populations. Here we show experimental evidence of the establishment of foraging traditions in a wild bird population. We introduced alternative novel foraging techniques into replicated wild sub-populations of great tits (Parus major) and used automated tracking to map the diffusion, establishment and long-term persistence of the seeded innovations. Furthermore, we used social network analysis to examine the social factors that influenced diffusion dynamics. From only two trained birds in each sub-population, the information spread rapidly through social network ties, to reach an average of 75% of individuals, with a total of 414 knowledgeable individuals performing 57,909 solutions over all replicates. The sub-populations were heavily biased towards using the technique that was originally introduced, resulting in established local traditions that were stable over two generations, despite a high population turnover. Finally, we demonstrate a strong effect of social conformity, with individuals disproportionately adopting the most frequent local variant when first acquiring an innovation, and continuing to favour social information over personal information. Cultural conformity is thought to be a key factor in the evolution of complex culture in humans. In providing the first experimental demonstration of conformity in a wild non-primate, and of cultural norms in foraging techniques in any wild animal, our results suggest a much broader taxonomic occurrence of such an apparently complex cultural behaviour.
TL;DR: This work concludes that during recent interglacial periods, small increases in global mean temperature and just a few degrees of polar warming relative to the preindustrial period resulted in ≥6 m of GMSL rise, which is currently not possible to make a precise estimate of peak G MSL during the Pliocene.
Abstract: BACKGROUND:Although thermal expansion of seawater and melting of mountain glaciers have dominated global mean sea level (GMSL) rise over the last century, mass loss from the Greenland and Antarctic ice sheets is expected to exceed other contributions to GMSL rise under future warming. To better constrain polarice-sheetresponse to warmer temperatures, we draw on evidence from in- terglacial periods in the geologic record that ex- perienced warmer polar temperatures and higher GMSLs than present. Coastal records of sea level from these previous warm periods dem- onstrate geographic variability because of the influence of several geophysical processes that operate across a range of magnitudes and time scales. Inferring GMSL and ice- volume changes from these reconstructions is nontrivial and generally requires the use of geophysical models. ADVANCES: Interdisciplinary studies of geo- logic archives have ushered in a new era of deciphering magnitudes, rates, and sources of sea-level rise. Advances in our understanding of polar ice-sheet response to warmer climates have been made through an increase in the number and geographic distribution of sea- level reconstructions, better ice-sheet constraints, and the recognition that several geophysical processes cause spatially complex patterns in sea level. In particular, accounting for glacial isostatic processes helps to decipher spatial variability in coastal sea-level records and has reconciled a number of site-specific sea-level reconstructions for warm periods that have oc- curred within the past several hundred thou- sand years. This enables us to infer that during recent interglacial periods, small increases in
Harvard University1, Broad Institute2, Washington University in St. Louis3, University of Copenhagen4, University of Milan5, University of Oxford6, University of North Carolina at Chapel Hill7, Fred Hutchinson Cancer Research Center8, University of Verona9, University of Ottawa10, University of Cambridge11, Memorial Hospital of South Bend12, University of Amsterdam13, University of Leicester14, Technische Universität München15, University of Lübeck16, Duke University17, University of Western Ontario18, Synlab Group19, Medical University of Graz20, Heidelberg University21, National Institutes of Health22, University of Pennsylvania23, University of Alabama at Birmingham24, University of Minnesota25, Wake Forest University26, Stanford University27, University of Mississippi28, Karolinska Institutet29, Merck & Co.30, Group Health Cooperative31, University of Washington32, University of Virginia33, University of Vermont34, Boston University35, University of Missouri–Kansas City36, University of Southern California37, Cleveland Clinic38, Ohio State University39, University of Texas Health Science Center at Houston40, University of Michigan41
TL;DR: Kathiresan et al. as mentioned in this paper used exome sequencing of nearly 10,000 people to identify alleles associated with early-onset myocardial infarction; mutations in low-density lipoprotein receptor (LDLR) or apolipoprotein A-V (APOA5) were associated with disease risk.
Abstract: Exome sequence analysis of nearly 10,000 people was carried out to identify alleles associated with early-onset myocardial infarction; mutations in low-density lipoprotein receptor (LDLR) or apolipoprotein A-V (APOA5) were associated with disease risk, identifying the key roles of low-density lipoprotein cholesterol and metabolism of triglyceride-rich lipoproteins. Sekar Kathiresan and colleagues use exome sequencing of nearly 10,000 people to probe the contribution of multiple rare mutations within a gene to risk for myocardial infarction at a population level. They find that mutations in low-density lipoprotein receptor (LDLR) or apolipoprotein A-V (APOA5) are associated with disease risk. When compared with non-carriers, LDLR mutation carriers had higher plasma levels of LDL cholesterol, whereas APOA5 mutation carriers had higher plasma levels of triglycerides. As well as confirming that APOA5 is a myocardial infarction gene, this work informs the design and conduct of rare-variant association studies for complex diseases. Myocardial infarction (MI), a leading cause of death around the world, displays a complex pattern of inheritance1,2. When MI occurs early in life, genetic inheritance is a major component to risk1. Previously, rare mutations in low-density lipoprotein (LDL) genes have been shown to contribute to MI risk in individual families3,4,5,6,7,8, whereas common variants at more than 45 loci have been associated with MI risk in the population9,10,11,12,13,14,15. Here we evaluate how rare mutations contribute to early-onset MI risk in the population. We sequenced the protein-coding regions of 9,793 genomes from patients with MI at an early age (≤50 years in males and ≤60 years in females) along with MI-free controls. We identified two genes in which rare coding-sequence mutations were more frequent in MI cases versus controls at exome-wide significance. At low-density lipoprotein receptor (LDLR), carriers of rare non-synonymous mutations were at 4.2-fold increased risk for MI; carriers of null alleles at LDLR were at even higher risk (13-fold difference). Approximately 2% of early MI cases harbour a rare, damaging mutation in LDLR; this estimate is similar to one made more than 40 years ago using an analysis of total cholesterol16. Among controls, about 1 in 217 carried an LDLR coding-sequence mutation and had plasma LDL cholesterol > 190 mg dl−1. At apolipoprotein A-V (APOA5), carriers of rare non-synonymous mutations were at 2.2-fold increased risk for MI. When compared with non-carriers, LDLR mutation carriers had higher plasma LDL cholesterol, whereas APOA5 mutation carriers had higher plasma triglycerides. Recent evidence has connected MI risk with coding-sequence mutations at two genes functionally related to APOA5, namely lipoprotein lipase15,17 and apolipoprotein C-III (refs 18, 19). Combined, these observations suggest that, as well as LDL cholesterol, disordered metabolism of triglyceride-rich lipoproteins contributes to MI risk.
TL;DR: A robust grading system incorporating the independent prognostic significance of both BMI and %WL was developed and was observed within specific cancers, stages, ages, and performance status and in an independent validation sample.
Abstract: Purpose Existing definitions of clinically important weight loss (WL) in patients with cancer are unclear and heterogeneous and do not consider current trends toward obesity. Methods Canadian and European patients with cancer (n = 8,160) formed a population-based data set. Body mass index (BMI) and percent WL (%WL) were recorded, and patients were observed prospectively until death. Data were entered into a multivariable analysis controlling for age, sex, cancer site, stage, and performance status. Relationships for BMI and %WL to overall survival were examined to develop a grading system. Results Mean overall %WL was −9.7% ± 8.4% and BMI was 24.4 ± 5.1 kg/m2, and both %WL and BMI independently predicted survival (P < .01). Differences in survival were observed across five categories of BMI (< 20.0, 20.0 to 21.9, 22.0 to 24.9, 25.0 to 27.9, and ≥ 28.0 kg/m2; P < .001) and five categories of %WL (−2.5% to −5.9%, −6.0% to −10.9%, −11.0% to −14.9%, ≥ −15.0%, and weight stable (± 2.4%); P < .001). A 5 × 5 mat...
TL;DR: In this article, the authors report on recent developments of optics with light carrying transverse spin, and also highlight new capabilities and future applications emerging from this young yet already advanced field of research.
Abstract: This Progress Article details the latest achievements and underlying principles of light carrying transverse spin.The capabilities and future applications of this young yet already advanced field are highlighted. Scientists have known for more than a century that light possesses both linear and angular momenta along the direction of propagation. However, only recent advances in optics have led to the notion of spinning electromagnetic fields capable of carrying angular momenta transverse to the direction of motion. Such fields enable numerous applications in nano-optics, biosensing and near-field microscopy, including three-dimensional control over atoms, molecules and nanostructures, and allowing for the realization of chiral nanophotonic interfaces and plasmonic devices. Here, we report on recent developments of optics with light carrying transverse spin. We present both the underlying principles and the latest achievements, and also highlight new capabilities and future applications emerging from this young yet already advanced field of research.
TL;DR: A meta‐analysis to investigate the fitness costs associated with single mutational events that confer resistance found that several drug classes and species of bacteria on average did not show a cost.
Abstract: Antibiotic resistance is increasing in pathogenic microbial populations and is thus a major threat to public health. The fate of a resistance mutation in pathogen populations is determined in part by its fitness. Mutations that suffer little or no fitness cost are more likely to persist in the absence of antibiotic treatment. In this review, we performed a meta-analysis to investigate the fitness costs associated with single mutational events that confer resistance. Generally, these mutations were costly, although several drug classes and species of bacteria on average did not show a cost. Further investigations into the rate and fitness values of compensatory mutations that alleviate the costs of resistance will help us to better understand both the emergence and management of antibiotic resistance in clinical settings.
University of Amsterdam1, Utrecht University2, University of Virginia3, Brown University4, Bond University5, University of Sydney6, Ottawa Hospital Research Institute7, University of Ottawa8, University of California, San Francisco9, VU University Medical Center10, Beth Israel Deaconess Medical Center11, Boston Children's Hospital12, Northwestern University13, University of Oxford14, Paris Descartes University15
TL;DR: An updated list of 30 essential items that should be included in every report of a diagnostic accuracy study is presented, which incorporates recent evidence about sources of bias and variability in diagnostic accuracy and is intended to facilitate the use of STARD.
Abstract: Incomplete reporting has been identified as a major source of avoidable waste in biomedical research. Essential information is often not provided in study reports, impeding the identification, critical appraisal, and replication of studies. To improve the quality of reporting of diagnostic accuracy studies, the Standards for Reporting of Diagnostic Accuracy Studies (STARD) statement was developed. Here we present STARD 2015, an updated list of 30 essential items that should be included in every report of a diagnostic accuracy study. This update incorporates recent evidence about sources of bias and variability in diagnostic accuracy and is intended to facilitate the use of STARD. As such, STARD 2015 may help to improve completeness and transparency in reporting of diagnostic accuracy studies.
TL;DR: Standard-dose and high-dose biological drugs (with or without traditional DMARDs) are associated with an increase in serious infections in rheumatoid arthritis compared with traditionalDMARDs, although low- dose biological drugs are not.
TL;DR: It is explored why it might be that early peer victimization does not have the same impact on all young people by considering factors that place individuals at greater risk or appear to protect them from more lasting harm.
Abstract: The study of peer victimization has drawn together researchers, parents, teachers, and health professionals around the world in an effort to make change. Research attention has focused on the question of whether peer victimization in childhood and adolescence leads to lasting and serious negative ramifications in the lives of young people. We consider the wealth of information documenting the troubling adjustment that follows peer victimization within childhood and adolescence. Findings from prospective studies tracking children and adolescents into young adulthood are presented and synthesized. Using the construct of "multifinality" as our framework, we explore why it might be that early peer victimization does not have the same impact on all young people by considering factors that place individuals at greater risk or appear to protect them from more lasting harm. In addition to a need for carefully planned prospective studies, the field would benefit from the use of qualitative studies aimed at elucidating possible causal, concurrent, and resultant mechanisms involved with victimization.
TL;DR: The role of theimmune system in cardiovascular disease is summarized, focusing on the idea that the immune system evolved to promote tissue homeostasis following injury and/or infection, and that the inherent cost of this evolutionary development is unwanted inflammatory damage.
Abstract: Despite the advances that have been made in developing new therapeutics, cardiovascular disease remains the leading cause of worldwide mortality. Therefore, understanding the mechanisms underlying cardiovascular tissue injury and repair is of prime importance. Following cardiac tissue injury, the immune system has an important and complex role in driving both the acute inflammatory response and the regenerative response. This Review summarizes the role of the immune system in cardiovascular disease - focusing on the idea that the immune system evolved to promote tissue homeostasis following injury and/or infection, and that the inherent cost of this evolutionary development is unwanted inflammatory damage.
TL;DR: The goal of this review is to comprehensively summarize the current knowledge on satellite cell characteristics, functions, and behavior in muscle regeneration and in pathological conditions.
Abstract: Skeletal muscles are essential for vital functions such as movement, postural support, breathing, and thermogenesis. Muscle tissue is largely composed of long, postmitotic multinucleated fibers. The life-long maintenance of muscle tissue is mediated by satellite cells, lying in close proximity to the muscle fibers. Muscle satellite cells are a heterogeneous population with a small subset of muscle stem cells, termed satellite stem cells. Under homeostatic conditions all satellite cells are poised for activation by stimuli such as physical trauma or growth signals. After activation, satellite stem cells undergo symmetric divisions to expand their number or asymmetric divisions to give rise to cohorts of committed satellite cells and thus progenitors. Myogenic progenitors proliferate, and eventually differentiate through fusion with each other or to damaged fibers to reconstitute fiber integrity and function. In the recent years, research has begun to unravel the intrinsic and extrinsic mechanisms controlling satellite cell behavior. Nonetheless, an understanding of the complex cellular and molecular interactions of satellite cells with their dynamic microenvironment remains a major challenge, especially in pathological conditions. The goal of this review is to comprehensively summarize the current knowledge on satellite cell characteristics, functions, and behavior in muscle regeneration and in pathological conditions.