Showing papers by "Cardiff University published in 2015"
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TL;DR: The 1000 Genomes Project set out to provide a comprehensive description of common human genetic variation by applying whole-genome sequencing to a diverse set of individuals from multiple populations, and has reconstructed the genomes of 2,504 individuals from 26 populations using a combination of low-coverage whole-generation sequencing, deep exome sequencing, and dense microarray genotyping.
Abstract: The 1000 Genomes Project set out to provide a comprehensive description of common human genetic variation by applying whole-genome sequencing to a diverse set of individuals from multiple populations. Here we report completion of the project, having reconstructed the genomes of 2,504 individuals from 26 populations using a combination of low-coverage whole-genome sequencing, deep exome sequencing, and dense microarray genotyping. We characterized a broad spectrum of genetic variation, in total over 88 million variants (84.7 million single nucleotide polymorphisms (SNPs), 3.6 million short insertions/deletions (indels), and 60,000 structural variants), all phased onto high-quality haplotypes. This resource includes >99% of SNP variants with a frequency of >1% for a variety of ancestries. We describe the distribution of genetic variation across the global sample, and discuss the implications for common disease studies.
12,661 citations
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TL;DR: The UK Biobank is described, a large population-based prospective study, established to allow investigation of the genetic and non-genetic determinants of the diseases of middle and old age.
Abstract: Cathie Sudlow and colleagues describe the UK Biobank, a large population-based prospective study, established to allow investigation of the genetic and non-genetic determinants of the diseases of middle and old age.
6,114 citations
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TL;DR: New MRC guidance provides a framework for conducting and reporting process evaluation studies that will help improve the quality of decision-making in the design and testing of complex interventions.
Abstract: Process evaluation is an essential part of designing and testing complex interventions. New MRC guidance provides a framework for conducting and reporting process evaluation studies
3,662 citations
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TL;DR: The effect of IL-6 on innate and adaptive immunity and the possible advantages of various antagonists ofIL-6 are discussed and how the immunobiology of IL -6 may inform clinical decisions is considered.
Abstract: Interleukin 6 (IL-6) has a broad effect on cells of the immune system and those not of the immune system and often displays hormone-like characteristics that affect homeostatic processes. IL-6 has context-dependent pro- and anti-inflammatory properties and is now regarded as a prominent target for clinical intervention. However, the signaling cassette that controls the activity of IL-6 is complicated, and distinct intervention strategies can inhibit this pathway. Clinical experience with antagonists of IL-6 has raised new questions about how and when to block this cytokine to improve disease outcome and patient wellbeing. Here we discuss the effect of IL-6 on innate and adaptive immunity and the possible advantages of various antagonists of IL-6 and consider how the immunobiology of IL-6 may inform clinical decisions.
1,726 citations
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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
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TL;DR: In this paper, the authors review the performance of the LIGO instruments during this epoch, the work done to characterize the detectors and their data, and the effect that transient and continuous noise artefacts have on the sensitivity of the detectors to a variety of astrophysical sources.
Abstract: In 2009–2010, the Laser Interferometer Gravitational-Wave Observatory (LIGO) operated together with international partners Virgo and GEO600 as a network to search for gravitational waves (GWs) of astrophysical origin. The sensitivity of these detectors was limited by a combination of noise sources inherent to the instrumental design and its environment, often localized in time or frequency, that couple into the GW readout. Here we review the performance of the LIGO instruments during this epoch, the work done to characterize the detectors and their data, and the effect that transient and continuous noise artefacts have on the sensitivity of LIGO to a variety of astrophysical sources.
1,266 citations
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TL;DR: Strong evidence for dust and no statistically significant evidence for tensor modes is found and various model variations and extensions are probe, including adding a synchrotron component in combination with lower frequency data, and find that these make little difference to the r constraint.
Abstract: We report the results of a joint analysis of data from BICEP2/Keck Array and Planck. BICEP2 and Keck Array have observed the same approximately 400 deg2 patch of sky centered on RA 0h, Dec. −57.5deg. The combined maps reach a depth of 57 nK deg in Stokes Q and U in a band centered at 150 GHz. Planck has observed the full sky in polarization at seven frequencies from 30 to 353 GHz, but much less deeply in any given region (1.2 μK deg in Q and U at 143 GHz). We detect 150×353 cross-correlation in B-modes at high significance. We fit the single- and cross-frequency power spectra at frequencies above 150 GHz to a lensed-ΛCDM model that includes dust and a possible contribution from inflationary gravitational waves (as parameterized by the tensor-to-scalar ratio r). We probe various model variations and extensions, including adding a synchrotron component in combination with lower frequency data, and find that these make little difference to the r constraint. Finally we present an alternative analysis which is similar to a map-based cleaning of the dust contribution, and show that this gives similar constraints. The final result is expressed as a likelihood curve for r, and yields an upper limit r0.05<0.12 at 95% confidence. Marginalizing over dust and r, lensing B-modes are detected at 7.0σ significance.
1,255 citations
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University of Mississippi1, University of Lisbon2, Institut d'Astrophysique de Paris3, Perimeter Institute for Theoretical Physics4, Sapienza University of Rome5, California Institute of Technology6, University of Cambridge7, Cornell University8, Max Planck Society9, Princeton University10, Montana State University11, University of Oxford12, McMaster University13, University of Aveiro14, University of Tübingen15, Naresuan University16, Rochester Institute of Technology17, University of Oldenburg18, Georgia Institute of Technology19, University of Florida20, University of Wisconsin–Milwaukee21, University of Illinois at Urbana–Champaign22, The Chinese University of Hong Kong23, Northwestern University24, Case Western Reserve University25, Sao Paulo State University26, Cardiff University27, Imperial College London28, Grand Valley State University29, Kyoto University30
TL;DR: In this article, a catalog of modified theories of gravity for which strong-field predictions have been computed and contrasted to Einstein's theory is presented, and the current understanding of the structure and dynamics of compact objects in these theories is summarized.
Abstract: One century after its formulation, Einstein's general relativity (GR) has made remarkable predictions and turned out to be compatible with all experimental tests. Most of these tests probe the theory in the weak-field regime, and there are theoretical and experimental reasons to believe that GR should be modified when gravitational fields are strong and spacetime curvature is large. The best astrophysical laboratories to probe strong-field gravity are black holes and neutron stars, whether isolated or in binary systems. We review the motivations to consider extensions of GR. We present a (necessarily incomplete) catalog of modified theories of gravity for which strong-field predictions have been computed and contrasted to Einstein's theory, and we summarize our current understanding of the structure and dynamics of compact objects in these theories. We discuss current bounds on modified gravity from binary pulsar and cosmological observations, and we highlight the potential of future gravitational wave measurements to inform us on the behavior of gravity in the strong-field regime.
1,066 citations
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University of Melbourne1, University of Oxford2, Cornell University3, United States Army Medical Research Institute of Infectious Diseases4, Cardiff University5, University Health System6, Erasmus University Medical Center7, Pasteur Institute8, University of California, San Francisco9, University of Queensland10, University of Amsterdam11, Airlangga University12, Mahosot Hospital13, Wellcome Trust14, University of London15
TL;DR: The DNA sequence of K. pneumoniae isolates from around the world is determined and it is shown that there is a wide spectrum of diversity, including variation within shared sequences and gain and loss of whole genes, and there is an unrecognized association between the possession of specific gene profiles associated with virulence and antibiotic resistance.
Abstract: Klebsiella pneumoniae is now recognized as an urgent threat to human health because of the emergence of multidrug-resistant strains associated with hospital outbreaks and hypervirulent strains associated with severe community-acquired infections. K. pneumoniae is ubiquitous in the environment and can colonize and infect both plants and animals. However, little is known about the population structure of K. pneumoniae, so it is difficult to recognize or understand the emergence of clinically important clones within this highly genetically diverse species. Here we present a detailed genomic framework for K. pneumoniae based on whole-genome sequencing of more than 300 human and animal isolates spanning four continents. Our data provide genome-wide support for the splitting of K. pneumoniae into three distinct species, KpI (K. pneumoniae), KpII (K. quasipneumoniae), and KpIII (K. variicola). Further, for K. pneumoniae (KpI), the entity most frequently associated with human infection, we show the existence of >150 deeply branching lineages including numerous multidrug-resistant or hypervirulent clones. We show K. pneumoniae has a large accessory genome approaching 30,000 protein-coding genes, including a number of virulence functions that are significantly associated with invasive community-acquired disease in humans. In our dataset, antimicrobial resistance genes were common among human carriage isolates and hospital-acquired infections, which generally lacked the genes associated with invasive disease. The convergence of virulence and resistance genes potentially could lead to the emergence of untreatable invasive K. pneumoniae infections; our data provide the whole-genome framework against which to track the emergence of such threats.
879 citations
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TL;DR: This editorial aims to propose clear definitions of each of these terms such as microbiome, microbiota, metabolomic, and meetagenome and metagenomics among others, and to implore scientists in the field to adopt and perfect them.
Abstract: The advancement of DNA/RNA, proteins, and metabolite analytical platforms, combined with increased computing technologies, has transformed the field of microbial community analysis. This transformation is evident by the exponential increase in the number of publications describing the composition and structure, and sometimes function, of the microbial communities inhabiting the human body. This rapid evolution of the field has been accompanied by confusion in the vocabulary used to describe different aspects of these communities and their environments. The misuse of terms such as microbiome, microbiota, metabolomic, and metagenome and metagenomics among others has contributed to misunderstanding of many study results by the scientific community and the general public alike. A few review articles have previously defined those terms, but mainly as sidebars, and no clear definitions or use cases have been published. In this editorial, we aim to propose clear definitions of each of these terms, which we would implore scientists in the field to adopt and perfect.
735 citations
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TL;DR: It is reported that rapid evolution of enhancers is a universal feature of mammalian genomes and most of the recently evolved enhancers arise from ancestral DNA exaptation, rather than lineage-specific expansions of repeat elements.
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TL;DR: It is indicated that risk variants for psychiatric disorders aggregate in particular biological pathways and that these pathways are frequently shared between disorders.
Abstract: Genome-wide association studies (GWAS) of psychiatric disorders have identified multiple genetic associations with such disorders, but better methods are needed to derive the underlying biological mechanisms that these signals indicate. We sought to identify biological pathways in GWAS data from over 60,000 participants from the Psychiatric Genomics Consortium. We developed an analysis framework to rank pathways that requires only summary statistics. We combined this score across disorders to find common pathways across three adult psychiatric disorders: schizophrenia, major depression and bipolar disorder. Histone methylation processes showed the strongest association, and we also found statistically significant evidence for associations with multiple immune and neuronal signaling pathways and with the postsynaptic density. Our study indicates that risk variants for psychiatric disorders aggregate in particular biological pathways and that these pathways are frequently shared between disorders. Our results confirm known mechanisms and suggest several novel insights into the etiology of psychiatric disorders.
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TL;DR: In this article, the binding energies of RuO2, RuCl3, Ru(NO)(NO3)3 and Ru(AcAc)3 were investigated using X-ray photoelectron spectroscopy (XPS).
Abstract: X-ray photoelectron spectroscopy (XPS) utilising monochromatic Al Kα radiation has been employed to study metallic ruthenium and the catalytically and technologically important ruthenium compounds RuO2, RuCl3, Ru(NO)(NO3)3 and Ru(AcAc)3. The results improve on the accuracy of already published Ru(3d) binding energies, expand known Ru(3p) binding energies and also report spin-orbit splitting for the core levels. For RuO2, the difference between anhydrous and hydrated samples is explored, and the effect on curve fitting such spectra is discussed. Analysis of RuCl3 has allowed, for the first time, the positive identification of Ru(OH)3 by XPS. Copyright © 2015 John Wiley & Sons, Ltd.
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TL;DR: In this article, the authors conducted a survey with 84 respondents from 70 higher education institutions and found that academic leadership's commitment was a leading cause for signing a declaration, charter, or initiative, and implementing sustainable development.
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TL;DR: Evidence showing that unconventional T cells are an abundant component of the human immune system is reviewed and the immunotherapeutic potential of these cells and their antigenic targets are discussed.
Abstract: While most studies of T lymphocytes have focused on T cells reactive to complexes of peptide and major histocompatibility complex (MHC) proteins, many other types of T cells do not fit this paradigm. These include CD1-restricted T cells, MR1-restricted mucosal associated invariant T cells (MAIT cells), MHC class Ib-reactive T cells, and γδ T cells. Collectively, these T cells are considered 'unconventional', in part because they can recognize lipids, small-molecule metabolites and specially modified peptides. Unlike MHC-reactive T cells, these apparently disparate T cell types generally show simplified patterns of T cell antigen receptor (TCR) expression, rapid effector responses and 'public' antigen specificities. Here we review evidence showing that unconventional T cells are an abundant component of the human immune system and discuss the immunotherapeutic potential of these cells and their antigenic targets.
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University of Cambridge1, Utrecht University2, University of Glasgow3, University of Oslo4, Howard University5, Copenhagen University Hospital6, University of Washington7, University of Western Australia8, Medical University of South Carolina9, University of Eastern Finland10, Analytical Services11, University of Pittsburgh12, University of New South Wales13, University of California, San Diego14, Norwegian Institute of Public Health15, Portland State University16, University of Hawaii17, National Institutes of Health18, Uppsala University19, University Medical Center Groningen20, University of Gothenburg21, University of Iowa22, German Cancer Research Center23, Pasteur Institute24, Baker IDI Heart and Diabetes Institute25, Osaka University26, Istanbul University27, City College of New York28, Boston University29, University of Oxford30, University of Southampton31, Erasmus University Rotterdam32, French Institute of Health and Medical Research33, Paris Diderot University34, Harvard University35, Columbia University Medical Center36, MedStar Health37, Greifswald University Hospital38, VU University Amsterdam39, Maastricht University Medical Centre40, Istituto Superiore di Sanità41, Wageningen University and Research Centre42, University of Edinburgh43, University of London44, University of Padua45, University of Bristol46, Cardiff University47, Ludwig Maximilian University of Munich48, Leiden University Medical Center49, University of Sydney50, University College London51, Medical Research Council52, University of North Carolina at Chapel Hill53, University of Tromsø54, Lund University55, Albert Einstein College of Medicine56, Johns Hopkins University57
TL;DR: Because any combination of these conditions was associated with multiplicative mortality risk, life expectancy was substantially lower in people with multimorbidity.
Abstract: IMPORTANCE: The prevalence of cardiometabolic multimorbidity is increasing. OBJECTIVE: To estimate reductions in life expectancy associated with cardiometabolic multimorbidity. DESIGN, SETTING, AND PARTICIPANTS: Age- and sex-adjusted mortality rates and hazard ratios (HRs) were calculated using individual participant data from the Emerging Risk Factors Collaboration (689,300 participants; 91 cohorts; years of baseline surveys: 1960-2007; latest mortality follow-up: April 2013; 128,843 deaths). The HRs from the Emerging Risk Factors Collaboration were compared with those from the UK Biobank (499,808 participants; years of baseline surveys: 2006-2010; latest mortality follow-up: November 2013; 7995 deaths). Cumulative survival was estimated by applying calculated age-specific HRs for mortality to contemporary US age-specific death rates. EXPOSURES: A history of 2 or more of the following: diabetes mellitus, stroke, myocardial infarction (MI). MAIN OUTCOMES AND MEASURES: All-cause mortality and estimated reductions in life expectancy. RESULTS: In participants in the Emerging Risk Factors Collaboration without a history of diabetes, stroke, or MI at baseline (reference group), the all-cause mortality rate adjusted to the age of 60 years was 6.8 per 1000 person-years. Mortality rates per 1000 person-years were 15.6 in participants with a history of diabetes, 16.1 in those with stroke, 16.8 in those with MI, 32.0 in those with both diabetes and MI, 32.5 in those with both diabetes and stroke, 32.8 in those with both stroke and MI, and 59.5 in those with diabetes, stroke, and MI. Compared with the reference group, the HRs for all-cause mortality were 1.9 (95% CI, 1.8-2.0) in participants with a history of diabetes, 2.1 (95% CI, 2.0-2.2) in those with stroke, 2.0 (95% CI, 1.9-2.2) in those with MI, 3.7 (95% CI, 3.3-4.1) in those with both diabetes and MI, 3.8 (95% CI, 3.5-4.2) in those with both diabetes and stroke, 3.5 (95% CI, 3.1-4.0) in those with both stroke and MI, and 6.9 (95% CI, 5.7-8.3) in those with diabetes, stroke, and MI. The HRs from the Emerging Risk Factors Collaboration were similar to those from the more recently recruited UK Biobank. The HRs were little changed after further adjustment for markers of established intermediate pathways (eg, levels of lipids and blood pressure) and lifestyle factors (eg, smoking, diet). At the age of 60 years, a history of any 2 of these conditions was associated with 12 years of reduced life expectancy and a history of all 3 of these conditions was associated with 15 years of reduced life expectancy. CONCLUSIONS AND RELEVANCE: Mortality associated with a history of diabetes, stroke, or MI was similar for each condition. Because any combination of these conditions was associated with multiplicative mortality risk, life expectancy was substantially lower in people with multimorbidity.
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Innlandet Hospital Trust1, University of Giessen2, University of Zaragoza3, Hedmark University College4, Université libre de Bruxelles5, University of Copenhagen6, University of Szeged7, University of Padua8, Leiden University9, University of Oslo10, Stavanger University Hospital11, Wrocław Medical University12, Cardiff University13
TL;DR: The association with depression and anxiety was highest for patients with psoriasis, atopic dermatitis, hand eczema, and leg ulcers, and only patients with Psoriasis had significant association with suicidal ideation.
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University College London1, University of Glasgow2, University of Cambridge3, Utrecht University4, University of Groningen5, University of Pennsylvania6, University of London7, University of Edinburgh8, Imperial College London9, Jackson State University10, Lithuanian University of Health Sciences11, Jagiellonian University12, Russian Academy13, University of Milan14, Karolinska Institutet15, Translational Genomics Research Institute16, Leiden University17, Memorial Hospital of Rhode Island18, University of Iowa19, University of Oslo20, University of Texas at San Antonio21, Veterans Health Administration22, Cornell University23, University of Sydney24, University of Paris25, Harvard University26, St George's, University of London27, University of Minnesota28, University of Texas Health Science Center at Houston29, University of Washington30, University of Vermont31, GlaxoSmithKline32, Broad Institute33, Children's Hospital Oakland Research Institute34, University of North Carolina at Chapel Hill35, University of Bristol36, Johns Hopkins University37, Cardiff University38, University of Mississippi39, Fred Hutchinson Cancer Research Center40
TL;DR: The increased risk of type 2 diabetes noted with statins is at least partially explained by HMGCR inhibition.
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TL;DR: The clinical problems and how, through better dialogue between basic researchers and clinicians, the current knowledge may be extended to enable the development of novel potential therapeutic treatments are described.
Abstract: A considerable understanding of the fundamental cellular and molecular mechanisms underpinning healthy acute wound healing has been gleaned from studying various animal models, and we are now unravelling the mechanisms that lead to chronic wounds and pathological healing including fibrosis. A small cut will normally heal in days through tight orchestration of cell migration and appropriate levels of inflammation, innervation and angiogenesis. Major surgeries may take several weeks to heal and leave behind a noticeable scar. At the extreme end, chronic wounds – defined as a barrier defect that has not healed in 3 months – have become a major therapeutic challenge throughout the Western world and will only increase as our populations advance in age, and with the increasing incidence of diabetes, obesity and vascular disorders. Here we describe the clinical problems and how, through better dialogue between basic researchers and clinicians, we may extend our current knowledge to enable the development of novel potential therapeutic treatments.
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TL;DR: An introduction to IGA applied to simple analysis problems and the related computer implementation aspects is presented, and implementation of the extended IGA which incorporates enrichment functions through the partition of unity method (PUM) is presented.
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TL;DR: Two new feature selection methods are proposed based on joint mutual information, namely JMIM and NJMIM, which alleviates the problem of overestimation of the feature significance as demonstrated both theoretically and experimentally.
Abstract: Two new feature selection methods are proposed based on joint mutual information.The methods use joint mutual information with maximum of the minimum criterion.The methods address the problem of selection of redundant and irrelevant features.The methods are evaluated using eleven public data sets and five competing methods.The proposed JMIM method outperforms five competing methods in terms of accuracy. Feature selection is used in many application areas relevant to expert and intelligent systems, such as data mining and machine learning, image processing, anomaly detection, bioinformatics and natural language processing. Feature selection based on information theory is a popular approach due its computational efficiency, scalability in terms of the dataset dimensionality, and independence from the classifier. Common drawbacks of this approach are the lack of information about the interaction between the features and the classifier, and the selection of redundant and irrelevant features. The latter is due to the limitations of the employed goal functions leading to overestimation of the feature significance.To address this problem, this article introduces two new nonlinear feature selection methods, namely Joint Mutual Information Maximisation (JMIM) and Normalised Joint Mutual Information Maximisation (NJMIM); both these methods use mutual information and the 'maximum of the minimum' criterion, which alleviates the problem of overestimation of the feature significance as demonstrated both theoretically and experimentally. The proposed methods are compared using eleven publically available datasets with five competing methods. The results demonstrate that the JMIM method outperforms the other methods on most tested public datasets, reducing the relative average classification error by almost 6% in comparison to the next best performing method. The statistical significance of the results is confirmed by the ANOVA test. Moreover, this method produces the best trade-off between accuracy and stability.
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TL;DR: The current state of knowledge about the three-dimensional stromal architecture at the microscopic level is described, and about the control mechanisms at the nanoscopic level that lead to optical transparency are described.
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TL;DR: In this paper, the authors conduct a structured literature review and aim at mapping the use of theories in sustainable supply chain management (SSCM) and propose possible future avenues for the field to develop.
Abstract: Purpose – The purpose of this paper is to investigate theoretical perspectives in sustainable supply
chain management (SSCM) and contributes to understanding the current state of research in the field
and its future development.
Design/methodology/approach – This paper conducts a structured literature review and aims at
mapping the use of theories in the field. The authors assess the current state of research, looking in
more details at popular theories, and propose possible future avenues for the field to develop.
Findings – Theory-building efforts in SSCM remain scarce, with the predominance of a few popular
imported macro theories (resource-based view (RBV), stakeholder theory and institutional theory)
having implications on the conceptualisation of SSCM and the topics researched to date. More
theoretical contributions can potentially emerge from the adoption of original methodologies, the
investigation of under-explored aspects of SSCM and the testing of recently developed frameworks.
Research limitations/implications – Drawing on the analysis the authors propose an overarching
map of popular theories in SSCM and define potential avenues towards the maturation of the discipline.
A number of propositions are offered to guide future research. This study constitutes a first step
towards understanding how theories in SSCM are developing and how SSCM has been conceptualised.
Originality/value – The originality of this paper lies in its analytical focus on theories in SSCM,
which have not been mapped to date.
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TL;DR: This review evaluates evidence on whether the population prevalence of child and adolescent mental health problems has changed and how cross-cohort comparisons can provide valuable complementary information on the aetiology of mental illness.
Abstract: Background
Child and adolescent mental health problems are common, associated with wide-ranging functional impairments, and show substantial continuities into adult life. It is therefore important to understand the extent to which the prevalence of mental health problems has changed over time, and to identify reasons behind any trends in mental health.
Scope and Methodology
This review evaluates evidence on whether the population prevalence of child and adolescent mental health problems has changed. The primary focus of the review is on epidemiological cross-cohort comparisons identified by a systematic search of the literature (using the Web of Knowledge database).
Findings
Clinical diagnosis and treatment of child and adolescent psychiatric disorders increased over recent decades. Epidemiological comparisons of unselected population cohorts using equivalent assessments of mental health have found little evidence of an increased rate of ADHD, but cross-cohort comparisons of rates of ASD are lacking at this time. Findings do suggest substantial secular change in emotional problems and antisocial behaviour in high-income countries, including periods of increase and decrease in symptom prevalence. Evidence from low- and middle-income countries is very limited. Possible explanations for trends in child and adolescent mental health are discussed. The review also addresses how cross-cohort comparisons can provide valuable complementary information on the aetiology of mental illness.
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Uppsala University1, University of Porto2, Cardiff University3, Katholieke Universiteit Leuven4, University of Groningen5, ETH Zurich6, University of Guelph7, Stockholm University8, Durham University9, University of British Columbia10, University of Tübingen11, Aalborg University12, University of Zurich13, Colorado State University14, Swedish University of Agricultural Sciences15, Karlstad University16, Radboud University Nijmegen17, University of Warsaw18, University of Turku19, University of Hawaii at Manoa20, Instituto Gulbenkian de Ciência21, University of Graz22, United States Department of Agriculture23, University of Freiburg24, University of Eastern Finland25, Wageningen University and Research Centre26, Spanish National Research Council27, Jagiellonian University28
TL;DR: Before the real-world conservation potential of genomic research can be realized, current infrastructures need to be modified, methods must mature, analytical pipelines need to been developed, and successful case studies must be disseminated to practitioners.
Abstract: The global loss of biodiversity continues at an alarming rate. Genomic approaches have been suggested as a promising tool for conservation practice as scaling up to genome-wide data can improve traditional conservation genetic inferences and provide qualitatively novel insights. However, the generation of genomic data and subsequent analyses and interpretations remain challenging and largely confined to academic research in ecology and evolution. This generates a gap between basic research and applicable solutions for conservation managers faced with multifaceted problems. Before the real-world conservation potential of genomic research can be realized, we suggest that current infrastructures need to be modified, methods must mature, analytical pipelines need to be developed, and successful case studies must be disseminated to practitioners.
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University of Paris-Sud1, Paris Diderot University2, Centre national de la recherche scientifique3, National Research Council4, University of Victoria5, Cardiff University6, INAF7, University of Toulouse8, Hoffmann-La Roche9, University of Central Lancashire10, University of Toronto11, Institut d'Astrophysique de Paris12, European Space Research and Technology Centre13, Max Planck Society14, Rutherford Appleton Laboratory15, Open University16
TL;DR: In this article, the results of the Herschel Gould Belt survey (HGBS) observations in an ~11 deg2 area of the Aquila molecular cloud complex at d ~ 260 pc, imaged with the SPIRE and PACS photometric cameras in parallel mode from 70 μm to 500 μm.
Abstract: We present and discuss the results of the Herschel Gould Belt survey (HGBS) observations in an ~11 deg2 area of the Aquila molecular cloud complex at d ~ 260 pc, imaged with the SPIRE and PACS photometric cameras in parallel mode from 70 μm to 500 μm. Using the multi-scale, multi-wavelength source extraction algorithm getsources, we identify a complete sample of starless dense cores and embedded (Class 0-I) protostars in this region, and analyze their global properties and spatial distributions. We find a total of 651 starless cores, ~60% ± 10% of which are gravitationally bound prestellar cores, and they will likely form stars inthe future. We also detect 58 protostellar cores. The core mass function (CMF) derived for the large population of prestellar cores is very similar in shape to the stellar initial mass function (IMF), confirming earlier findings on a much stronger statistical basis and supporting the view that there is a close physical link between the stellar IMF and the prestellar CMF. The global shift in mass scale observed between the CMF and the IMF is consistent with a typical star formation efficiency of ~40% at the level of an individual core. By comparing the numbers of starless cores in various density bins to the number of young stellar objects (YSOs), we estimate that the lifetime of prestellar cores is ~1 Myr, which is typically ~4 times longer than the core free-fall time, and that it decreases with average core density. We find a strong correlation between the spatial distribution of prestellar cores and the densest filaments observed in the Aquila complex. About 90% of the Herschel-identified prestellar cores are located above a background column density corresponding to AV ~ 7, and ~75% of them lie within filamentary structures with supercritical masses per unit length ≳16 M⊙/pc. These findings support a picture wherein the cores making up the peak of the CMF (and probably responsible for the base of the IMF) result primarily from the gravitational fragmentation of marginally supercritical filaments. Given that filaments appear to dominate the mass budget of dense gas at AV> 7, our findings also suggest that the physics of prestellar core formation within filaments is responsible for a characteristic “efficiency” for the star formation process in dense gas.
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TL;DR: While urban pollinator assemblages were more homogeneous across space than those in farmland or nature reserves, there was no significant difference in the numbers of rarer species between the three landscapes.
Abstract: Insect pollinators provide a crucial ecosystem service, but are under threat. Urban areas could be important for pollinators, though their value relative to other habitats is poorly known. We compared pollinator communities using quantified flower-visitation networks in 36 sites (each 1 km2) in three landscapes: urban, farmland and nature reserves. Overall, flower-visitor abundance and species richness did not differ significantly between the three landscape types. Bee abundance did not differ between landscapes, but bee species richness was higher in urban areas than farmland. Hoverfly abundance was higher in farmland and nature reserves than urban sites, but species richness did not differ significantly. While urban pollinator assemblages were more homogeneous across space than those in farmland or nature reserves, there was no significant difference in the numbers of rarer species between the three landscapes. Network-level specialization was higher in farmland than urban sites. Relative to other habitats, urban visitors foraged from a greater number of plant species (higher generality) but also visited a lower proportion of available plant species (higher specialization), both possibly driven by higher urban plant richness. Urban areas are growing, and improving their value for pollinators should be part of any national strategy to conserve and restore pollinators.
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TL;DR: It is shown that vaginal microbiome composition dramatically changes postpartum to become less Lactobacillus spp.
Abstract: The composition and structure of the pregnancy vaginal microbiome may influence susceptibility to adverse pregnancy outcomes. Studies on the pregnant vaginal microbiome have largely been limited to Northern American populations. Using MiSeq sequencing of 16S rRNA gene amplicons, we characterised the vaginal microbiota of a mixed British cohort of women (n = 42) who experienced uncomplicated term delivery and who were sampled longitudinally throughout pregnancy (8–12, 20–22, 28–30 and 34–36 weeks gestation) and 6 weeks postpartum. We show that vaginal microbiome composition dramatically changes postpartum to become less Lactobacillus spp. dominant with increased alpha-diversity irrespective of the community structure during pregnancy and independent of ethnicity. While the pregnancy vaginal microbiome was characteristically dominated by Lactobacillus spp. and low alpha-diversity, unlike Northern American populations, a significant number of pregnant women this British population had a L. jensenii-dominated microbiome characterised by low alpha-diversity. L. jensenii was predominantly observed in women of Asian and Caucasian ethnicity whereas L. gasseri was absent in samples from Black women. This study reveals new insights into biogeographical and ethnic effects upon the pregnancy and postpartum vaginal microbiome and has important implications for future studies exploring relationships between the vaginal microbiome, host health and pregnancy outcomes.
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Cardiff University1, National Cancer Research Institute2, University of Michigan3, Royal Adelaide Hospital4, University of Naples Federico II5, University of Nebraska Medical Center6, Purdue University7, University of Miami8, Nara Medical University9, National Technical University of Athens10, University of Florence11, United Arab Emirates University12, University of Illinois at Urbana–Champaign13, Creighton University14, University of Rome Tor Vergata15, Wayne State University16, University of Glasgow17, New York Medical College18, Mayo Clinic19, Università Campus Bio-Medico20
TL;DR: This review lists the disruption of E-cadherin and tight junctions, key signaling pathways, including urokinase type plasminogen activator (uPA), phosphatidylinositol 3-kinase/v-akt murine thymoma viral oncogene (PI3K/AKT), focal adhesion kinase (FAK), β-catenin/zinc finger E-box binding homeobox 1 (ZEB
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TL;DR: A chemotherapy-free ATRA and arsenic trioxide treatment regimen with the standard chemotherapy-based regimen (ATRA and idarubicin) in both high-risk and low-risk patients with acute promyelocytic leukaemia is compared.
Abstract: Summary Background Acute promyelocytic leukaemia is a chemotherapy-sensitive subgroup of acute myeloid leukaemia characterised by the presence of the PML–RARA fusion transcript. The present standard of care, chemotherapy and all- trans retinoic acid (ATRA), results in a high proportion of patients being cured. In this study, we compare a chemotherapy-free ATRA and arsenic trioxide treatment regimen with the standard chemotherapy-based regimen (ATRA and idarubicin) in both high-risk and low-risk patients with acute promyelocytic leukaemia. Methods In the randomised, controlled, multicentre, AML17 trial, eligible patients (aged ≥16 years) with acute promyelocytic leukaemia, confirmed by the presence of the PML–RARA transcript and without significant cardiac or pulmonary comorbidities or active malignancy, and who were not pregnant or breastfeeding, were enrolled from 81 UK hospitals and randomised 1:1 to receive treatment with ATRA and arsenic trioxide or ATRA and idarubicin. ATRA was given to participants in both groups in a daily divided oral dose of 45 mg/m 2 until remission, or until day 60, and then in a 2 weeks on–2 weeks off schedule. In the ATRA and idarubicin group, idarubicin was given intravenously at 12 mg/m 2 on days 2, 4, 6, and 8 of course 1, and then at 5 mg/m 2 on days 1–4 of course 2; mitoxantrone at 10 mg/m 2 on days 1–4 of course 3, and idarubicin at 12 mg/m 2 on day 1 of the final (fourth) course. In the ATRA and arsenic trioxide group, arsenic trioxide was given intravenously at 0·3 mg/kg on days 1–5 of each course, and at 0·25 mg/kg twice weekly in weeks 2–8 of course 1 and weeks 2–4 of courses 2–5. High-risk patients (those presenting with a white blood cell count >10 × 10 9 cells per L) could receive an initial dose of the immunoconjugate gemtuzumab ozogamicin (6 mg/m 2 intravenously). Neither maintenance treatment nor CNS prophylaxis was given to patients in either group. All patients were monitored by real-time quantitative PCR. Allocation was by central computer minimisation, stratified by age, performance status, and de-novo versus secondary disease. The primary endpoint was quality of life on the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 global health status. All analyses are by intention to treat. This trial is registered with the ISRCTN registry, number ISRCTN55675535. Findings Between May 8, 2009, and Oct 3, 2013, 235 patients were enrolled and randomly assigned to ATRA and idarubicin (n=119) or ATRA and arsenic trioxide (n=116). Participants had a median age of 47 years (range 16–77; IQR 33–58) and included 57 high-risk patients. Quality of life did not differ significantly between the treatment groups (EORTC QLQ-C30 global functioning effect size 2·17 [95% CI −2·79 to 7·12; p=0·39]). Overall, 57 patients in the ATRA and idarubicin group and 40 patients in the ATRA and arsenic trioxide group reported grade 3–4 toxicities. After course 1 of treatment, grade 3–4 alopecia was reported in 23 (23%) of 98 patients in the ATRA and idarubicin group versus 5 (5%) of 95 in the ATRA and arsenic trioxide group, raised liver alanine transaminase in 11 (10%) of 108 versus 27 (25%) of 109, oral toxicity in 22 (19%) of 115 versus one (1%) of 109. After course 2 of treatment, grade 3–4 alopecia was reported in 25 (28%) of 89 patients in the ATRA and idarubicin group versus 2 (3%) of 77 in the ATRA and arsenic trioxide group; no other toxicities reached the 10% level. Patients in the ATRA and arsenic trioxide group had significantly less requirement for most aspects of supportive care than did those in the ATRA and idarubicin group. Interpretation ATRA and arsenic trioxide is a feasible treatment in low-risk and high-risk patients with acute promyelocytic leukaemia, with a high cure rate and less relapse than, and survival not different to, ATRA and idarubicin, with a low incidence of liver toxicity. However, no improvement in quality of life was seen. Funding Cancer Research UK.