Showing papers by "University of New South Wales published in 2016"
TL;DR: This is the first direct detection of gravitational waves and the first observation of a binary black hole merger, and these observations demonstrate the existence of binary stellar-mass black hole systems.
Abstract: On September 14, 2015 at 09:50:45 UTC the two detectors of the Laser Interferometer Gravitational-Wave Observatory simultaneously observed a transient gravitational-wave signal. The signal sweeps upwards in frequency from 35 to 250 Hz with a peak gravitational-wave strain of $1.0 \times 10^{-21}$. It matches the waveform predicted by general relativity for the inspiral and merger of a pair of black holes and the ringdown of the resulting single black hole. The signal was observed with a matched-filter signal-to-noise ratio of 24 and a false alarm rate estimated to be less than 1 event per 203 000 years, equivalent to a significance greater than 5.1 {\sigma}. The source lies at a luminosity distance of $410^{+160}_{-180}$ Mpc corresponding to a redshift $z = 0.09^{+0.03}_{-0.04}$. In the source frame, the initial black hole masses are $36^{+5}_{-4} M_\odot$ and $29^{+4}_{-4} M_\odot$, and the final black hole mass is $62^{+4}_{-4} M_\odot$, with $3.0^{+0.5}_{-0.5} M_\odot c^2$ radiated in gravitational waves. All uncertainties define 90% credible intervals.These observations demonstrate the existence of binary stellar-mass black hole systems. This is the first direct detection of gravitational waves and the first observation of a binary black hole merger.
9,596 citations
TL;DR: In this paper, the authors present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macro-autophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes.
Abstract: In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes.
For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure flux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy.
Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation, it is imperative to target by gene knockout or RNA interference more than one autophagy-related protein. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways implying that not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular assays, we hope to encourage technical innovation in the field.
5,187 citations
TL;DR: It is anticipated that this review can stimulate a new research doorway to facilitate the next generation of g-C3N4-based photocatalysts with ameliorated performances by harnessing the outstanding structural, electronic, and optical properties for the development of a sustainable future without environmental detriment.
Abstract: As a fascinating conjugated polymer, graphitic carbon nitride (g-C3N4) has become a new research hotspot and drawn broad interdisciplinary attention as a metal-free and visible-light-responsive photocatalyst in the arena of solar energy conversion and environmental remediation. This is due to its appealing electronic band structure, high physicochemical stability, and “earth-abundant” nature. This critical review summarizes a panorama of the latest progress related to the design and construction of pristine g-C3N4 and g-C3N4-based nanocomposites, including (1) nanoarchitecture design of bare g-C3N4, such as hard and soft templating approaches, supramolecular preorganization assembly, exfoliation, and template-free synthesis routes, (2) functionalization of g-C3N4 at an atomic level (elemental doping) and molecular level (copolymerization), and (3) modification of g-C3N4 with well-matched energy levels of another semiconductor or a metal as a cocatalyst to form heterojunction nanostructures. The constructi...
5,054 citations
TL;DR: The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 (GBD 2015) as discussed by the authors was used to estimate the incidence, prevalence, and years lived with disability for diseases and injuries at the global, regional, and national scale over the period of 1990 to 2015.
5,050 citations
TL;DR: The Global Burden of Disease 2015 Study provides a comprehensive assessment of all-cause and cause-specific mortality for 249 causes in 195 countries and territories from 1980 to 2015, finding several countries in sub-Saharan Africa had very large gains in life expectancy, rebounding from an era of exceedingly high loss of life due to HIV/AIDS.
4,804 citations
TL;DR: The fundamental role of the biofilm matrix is considered, describing how the characteristic features of biofilms — such as social cooperation, resource capture and enhanced survival of exposure to antimicrobials — all rely on the structural and functional properties of the matrix.
Abstract: Bacterial biofilms are formed by communities that are embedded in a self-produced matrix of extracellular polymeric substances (EPS). Importantly, bacteria in biofilms exhibit a set of 'emergent properties' that differ substantially from free-living bacterial cells. In this Review, we consider the fundamental role of the biofilm matrix in establishing the emergent properties of biofilms, describing how the characteristic features of biofilms - such as social cooperation, resource capture and enhanced survival of exposure to antimicrobials - all rely on the structural and functional properties of the matrix. Finally, we highlight the value of an ecological perspective in the study of the emergent properties of biofilms, which enables an appreciation of the ecological success of biofilms as habitat formers and, more generally, as a bacterial lifestyle.
3,277 citations
TL;DR: In this article, the authors used a Bayesian hierarchical model to estimate trends in diabetes prevalence, defined as fasting plasma glucose of 7.0 mmol/L or higher, or history of diagnosis with diabetes, or use of insulin or oral hypoglycaemic drugs in 200 countries and territories in 21 regions, by sex and from 1980 to 2014.
2,782 citations
University of Queensland1, University of Glasgow2, QIMR Berghofer Medical Research Institute3, Garvan Institute of Medical Research4, Baylor College of Medicine5, University of Utah6, South Australia Pathology7, University of Adelaide8, Harvard University9, Campbelltown Hospital10, St. Vincent's Health System11, University of New South Wales12, University of Newcastle13, Royal North Shore Hospital14, University of Sydney15, Royal Prince Alfred Hospital16, Fiona Stanley Hospital17, Royal Adelaide Hospital18, Princess Alexandra Hospital19, University of Western Australia20, Beatson West of Scotland Cancer Centre21, Southern General Hospital22, Dresden University of Technology23, University of Texas MD Anderson Cancer Center24, Memorial Sloan Kettering Cancer Center25, Johns Hopkins University School of Medicine26, University of Verona27, Mayo Clinic28, University of Melbourne29
TL;DR: Detailed genomic analysis of 456 pancreatic ductal adenocarcinomas identified 32 recurrently mutated genes that aggregate into 10 pathways: KRAS, TGF-β, WNT, NOTCH, ROBO/SLIT signalling, G1/S transition, SWI-SNF, chromatin modification, DNA repair and RNA processing.
Abstract: Integrated genomic analysis of 456 pancreatic ductal adenocarcinomas identified 32 recurrently mutated genes that aggregate into 10 pathways: KRAS, TGF-β, WNT, NOTCH, ROBO/SLIT signalling, G1/S transition, SWI-SNF, chromatin modification, DNA repair and RNA processing. Expression analysis defined 4 subtypes: (1) squamous; (2) pancreatic progenitor; (3) immunogenic; and (4) aberrantly differentiated endocrine exocrine (ADEX) that correlate with histopathological characteristics. Squamous tumours are enriched for TP53 and KDM6A mutations, upregulation of the TP63∆N transcriptional network, hypermethylation of pancreatic endodermal cell-fate determining genes and have a poor prognosis. Pancreatic progenitor tumours preferentially express genes involved in early pancreatic development (FOXA2/3, PDX1 and MNX1). ADEX tumours displayed upregulation of genes that regulate networks involved in KRAS activation, exocrine (NR5A2 and RBPJL), and endocrine differentiation (NEUROD1 and NKX2-2). Immunogenic tumours contained upregulated immune networks including pathways involved in acquired immune suppression. These data infer differences in the molecular evolution of pancreatic cancer subtypes and identify opportunities for therapeutic development.
2,443 citations
TL;DR: Myopia and high myopia estimates from 2000 to 2050 suggest significant increases in prevalences globally, with implications for planning services, including managing and preventing myopia-related ocular complications and vision loss among almost 1 billion people with highMyopia.
2,345 citations
TL;DR: This paper proposes a 3-D CNN-based FE model with combined regularization to extract effective spectral-spatial features of hyperspectral imagery and reveals that the proposed models with sparse constraints provide competitive results to state-of-the-art methods.
Abstract: Due to the advantages of deep learning, in this paper, a regularized deep feature extraction (FE) method is presented for hyperspectral image (HSI) classification using a convolutional neural network (CNN). The proposed approach employs several convolutional and pooling layers to extract deep features from HSIs, which are nonlinear, discriminant, and invariant. These features are useful for image classification and target detection. Furthermore, in order to address the common issue of imbalance between high dimensionality and limited availability of training samples for the classification of HSI, a few strategies such as L2 regularization and dropout are investigated to avoid overfitting in class data modeling. More importantly, we propose a 3-D CNN-based FE model with combined regularization to extract effective spectral-spatial features of hyperspectral imagery. Finally, in order to further improve the performance, a virtual sample enhanced method is proposed. The proposed approaches are carried out on three widely used hyperspectral data sets: Indian Pines, University of Pavia, and Kennedy Space Center. The obtained results reveal that the proposed models with sparse constraints provide competitive results to state-of-the-art methods. In addition, the proposed deep FE opens a new window for further research.
2,059 citations
National University of Cordoba1, Max Planck Society2, VU University Amsterdam3, Macquarie University4, University of Grenoble5, University of Lyon6, Industrial University of Santander7, Leipzig University8, University of Oldenburg9, Imperial College London10, University of Montpellier11, Forschungszentrum Jülich12, University of Western Sydney13, University of Minnesota14, University of New South Wales15, Royal Botanic Gardens16, Missouri Botanical Garden17, George Washington University18, Paul Sabatier University19, Smithsonian Tropical Research Institute20, Komarov Botanical Institute21, Institut national de la recherche agronomique22, University of Bordeaux23, Florida International University24, University of Insubria25, University of Milan26, Université de Sherbrooke27, Centro Agronómico Tropical de Investigación y Enseñanza28
TL;DR: Analysis of worldwide variation in six major traits critical to growth, survival and reproduction within the largest sample of vascular plant species ever compiled found that occupancy of six-dimensional trait space is strongly concentrated, indicating coordination and trade-offs.
Abstract: The authors found that the key elements of plant form and function, analysed at global scale, are largely concentrated into a two-dimensional plane indexed by the size of whole plants and organs on the one hand, and the construction costs for photosynthetic leaf area, on the other.
Nicholas J Kassebaum1, Megha Arora1, Ryan M Barber1, Zulfiqar A Bhutta2 +679 more•Institutions (268)
TL;DR: In this paper, the authors used the Global Burden of Diseases, Injuries, and Risk Factors Study 2015 (GBD 2015) for all-cause mortality, cause-specific mortality, and non-fatal disease burden to derive HALE and DALYs by sex for 195 countries and territories from 1990 to 2015.
TL;DR: The evidence for and against the ceRNA hypothesis are critically evaluated to assess the impact of endogenous miRNA-sponge interactions and to propose an alternative function for messenger RNAs.
Abstract: The competitive endogenous RNA (ceRNA) hypothesis proposes that transcripts with shared microRNA (miRNA) binding sites compete for post-transcriptional control. This hypothesis has gained substantial attention as a unifying function for long non-coding RNAs, pseudogene transcripts and circular RNAs, as well as an alternative function for messenger RNAs. Empirical evidence supporting the hypothesis is accumulating but not without attracting scepticism. Recent studies that model transcriptome-wide binding-site abundance suggest that physiological changes in expression of most individual transcripts will not compromise miRNA activity. In this Review, we critically evaluate the evidence for and against the ceRNA hypothesis to assess the impact of endogenous miRNA-sponge interactions.
James Bentham1, Mariachiara Di Cesare1, Mariachiara Di Cesare2, Gretchen A Stevens3 +787 more•Institutions (246)
TL;DR: The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
Abstract: Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.5–22.7) and 16.5 cm (13.3–19.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8–144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
Karolinska University Hospital1, Karolinska Institutet2, Pasteur Institute3, University of Toulouse4, Wolfson Centre for Age-Related Diseases5, University of Cambridge6, University of New South Wales7, Pierre-and-Marie-Curie University8, La Trobe University9, Umeå University10, University of British Columbia11, University of Geneva12, Douglas Mental Health University Institute13, Alzheimer Europe14, German Center for Neurodegenerative Diseases15, University of Cologne16, London School of Economics and Political Science17, Radboud University Nijmegen18, Rockefeller University19, VU University Medical Center20, University of Southern California21, Brigham and Women's Hospital22, University of Copenhagen23, UCL Institute of Neurology24, University of Gothenburg25
TL;DR: This poster aims to demonstrate the efforts towards in-situ applicability of EMMARM, which aims to provide real-time information about the physical and cognitive properties of Alzheimer's disease and other dementias.
Abstract: Defeating Alzheimer's disease and other dementias : a priority for European science and society
TL;DR: A basic standard acoustic parameter set for various areas of automatic voice analysis, such as paralinguistic or clinical speech analysis, is proposed and intended to provide a common baseline for evaluation of future research and eliminate differences caused by varying parameter sets or even different implementations of the same parameters.
Abstract: Work on voice sciences over recent decades has led to a proliferation of acoustic parameters that are used quite selectively and are not always extracted in a similar fashion. With many independent teams working in different research areas, shared standards become an essential safeguard to ensure compliance with state-of-the-art methods allowing appropriate comparison of results across studies and potential integration and combination of extraction and recognition systems. In this paper we propose a basic standard acoustic parameter set for various areas of automatic voice analysis, such as paralinguistic or clinical speech analysis. In contrast to a large brute-force parameter set, we present a minimalistic set of voice parameters here. These were selected based on a) their potential to index affective physiological changes in voice production, b) their proven value in former studies as well as their automatic extractability, and c) their theoretical significance. The set is intended to provide a common baseline for evaluation of future research and eliminate differences caused by varying parameter sets or even different implementations of the same parameters. Our implementation is publicly available with the openSMILE toolkit. Comparative evaluations of the proposed feature set and large baseline feature sets of INTERSPEECH challenges show a high performance of the proposed set in relation to its size.
TL;DR: This paper presents an in-depth analysis of four major categories of anomaly detection techniques which include classification, statistical, information theory and clustering and evaluates effectiveness of different categories of techniques.
TL;DR: In this paper, extreme precipitation over land has increased over the wettest and driest regions and is likely to keep intensifying over the twenty-first century and this has key implications for dry regions, which may be unprepared for the potential related flooding.
Abstract: Extreme precipitation over land has increased over the wettest and driest regions and is likely to keep intensifying over the twenty-first century. This has key implications for dry regions, which may be unprepared for the potential related flooding.
Institute for Health Metrics and Evaluation1, College of Health Sciences, Bahrain2, Harvard University3, Kwame Nkrumah University of Science and Technology4, Charité5, Ahmadu Bello University6, University of the Philippines Manila7, Pontifical Xavierian University8, Madawalabu University9, World Bank10, Public Health Foundation of India11, Guy's and St Thomas' NHS Foundation Trust12, Griffith University13, University of New South Wales14, Massey University15, University of Peradeniya16, University of Sydney17, Chinese Center for Disease Control and Prevention18, Russian Academy of Sciences19, Tehran University of Medical Sciences20, Auckland University of Technology21, James Cook University22, Monash University23, University of California, San Francisco24, Arabian Gulf University25, Central South University26, Virginia Commonwealth University27, Jordan University of Science and Technology28, Health Services Academy29, Oregon Health & Science University30, University of Sheffield31, University at Albany, SUNY32, Aintree University Hospitals NHS Foundation Trust33, Swansea University34, University of York35, South African Medical Research Council36, Children's Hospital of Philadelphia37, Addis Ababa University38, Curtin University39, University of Washington40, Queensland University of Technology41, University of British Columbia42, Suez Canal University43, Karolinska Institutet44, University of Alabama at Birmingham45, An-Najah National University46, Tufts Medical Center47, Norwegian Institute of Public Health48, Stavanger University Hospital49, University of Cape Town50, University of California, Irvine51, University of Illinois at Urbana–Champaign52, St. John's University53, Hanoi Medical University54, Johns Hopkins University55, National Research University – Higher School of Economics56, University of Gondar57, University of Hong Kong58, Jackson State University59, Wuhan University60
TL;DR: An overview of injury estimates from the 2013 update of GBD is provided, with detailed information on incidence, mortality, DALYs and rates of change from 1990 to 2013 for 26 causes of injury, globally, by region and by country.
Abstract: Background The Global Burden of Diseases (GBD), Injuries, and Risk Factors study used the disability-adjusted life year (DALY) to quantify the burden of diseases, injuries, and risk factors. This paper provides an overview of injury estimates from the 2013 update of GBD, with detailed information on incidence, mortality, DALYs and rates of change from 1990 to 2013 for 26 causes of injury, globally, by region and by country.
Methods Injury mortality was estimated using the extensive GBD mortality database, corrections for ill-defined cause of death and the cause of death ensemble modelling tool. Morbidity estimation was based on inpatient and outpatient data sets, 26 cause-of-injury and 47 nature-of-injury categories, and seven follow-up studies with patient-reported long-term outcome measures.
Results In 2013, 973 million (uncertainty interval (UI) 942 to 993) people sustained injuries that warranted some type of healthcare and 4.8 million (UI 4.5 to 5.1) people died from injuries. Between 1990 and 2013 the global age-standardised injury DALY rate decreased by 31% (UI 26% to 35%). The rate of decline in DALY rates was significant for 22 cause-of-injury categories, including all the major injuries.
Conclusions Injuries continue to be an important cause of morbidity and mortality in the developed and developing world. The decline in rates for almost all injuries is so prominent that it warrants a general statement that the world is becoming a safer place to live in. However, the patterns vary widely by cause, age, sex, region and time and there are still large improvements that need to be made.
TL;DR: The data strongly support the claim that exercise is an evidence-based treatment for depression, and previous meta-analyses may have underestimated the benefits of exercise due to publication bias.
City College of New York1, Mackenzie Presbyterian University2, University of São Paulo3, New York University4, Beth Israel Deaconess Medical Center5, University Medical Center Freiburg6, University of Minnesota7, University of Pennsylvania8, University of Michigan9, Air Force Research Laboratory10, University of Calgary11, Albert Einstein College of Medicine12, University of Göttingen13, University of New South Wales14, University of Freiburg15, University of South Carolina16, MedStar National Rehabilitation Hospital17, University of Florida18
TL;DR: Evidence from relevant animal models indicates that brain injury by Direct Current Stimulation (DCS) occurs at predicted brain current densities that are over an order of magnitude above those produced by conventional tDCS.
Hobart Corporation1, University of New South Wales2, Marine Biological Association of the United Kingdom3, University of Western Australia4, University of Tasmania5, Australian Institute of Marine Science6, Scottish Association for Marine Science7, Commonwealth Scientific and Industrial Research Organisation8, Aberystwyth University9, University of Washington10, Pacific Marine Environmental Laboratory11
TL;DR: In this article, a hierarchy of metrics that allow for different data sets to be used in identifying MHWs is proposed, which can be described by its duration, intensity, rate of evolution, and spatial extent.
TL;DR: The EPIC array is a significant improvement over the HM450 array, with increased genome coverage of regulatory regions and high reproducibility and reliability, providing a valuable tool for high-throughput human methylome analyses from diverse clinical samples.
Abstract: In recent years the Illumina HumanMethylation450 (HM450) BeadChip has provided a user-friendly platform to profile DNA methylation in human samples. However, HM450 lacked coverage of distal regulatory elements. Illumina have now released the MethylationEPIC (EPIC) BeadChip, with new content specifically designed to target these regions. We have used HM450 and whole-genome bisulphite sequencing (WGBS) to perform a critical evaluation of the new EPIC array platform. EPIC covers over 850,000 CpG sites, including >90 % of the CpGs from the HM450 and an additional 413,743 CpGs. Even though the additional probes improve the coverage of regulatory elements, including 58 % of FANTOM5 enhancers, only 7 % distal and 27 % proximal ENCODE regulatory elements are represented. Detailed comparisons of regulatory elements from EPIC and WGBS show that a single EPIC probe is not always informative for those distal regulatory elements showing variable methylation across the region. However, overall data from the EPIC array at single loci are highly reproducible across technical and biological replicates and demonstrate high correlation with HM450 and WGBS data. We show that the HM450 and EPIC arrays distinguish differentially methylated probes, but the absolute agreement depends on the threshold set for each platform. Finally, we provide an annotated list of probes whose signal could be affected by cross-hybridisation or underlying genetic variation. The EPIC array is a significant improvement over the HM450 array, with increased genome coverage of regulatory regions and high reproducibility and reliability, providing a valuable tool for high-throughput human methylome analyses from diverse clinical samples.
University of Manchester1, University of New South Wales2, University College London3, Cardiff University4, University College Hospital5, James Cook University Hospital6, Belfast City Hospital7, Qatar Airways8, Medical Research Council9, Bangor University10, Hamad Medical Corporation11, Royal Derby Hospital12, Derriford Hospital13, Royal Free Hospital14, St. Michael's GAA, Sligo15, St Bartholomew's Hospital16, Harvard University17, St Mary's Hospital18, University Hospital of Wales19, National Health Service20, Public Health England21, Nottingham City Hospital22, Queen Alexandra Hospital23, Brighton and Sussex Medical School24, London School of Economics and Political Science25
TL;DR: Although the mortality reduction was not significant in the primary analysis, it was noted a significant mortality reduction with MMS when prevalent cases were excluded, and encouraging evidence of a mortality reduction in years 7–14 was noted.
TL;DR: In this open-label, randomized trial involving patients with locally advanced pancreatic cancer with disease controlled after 4 months of induction chemotherapy, there was no significant difference in overall survival with chemoradiotherapy compared with chemotherapy alone and there wasno significant difference with gem citabine compared with gemcitabine plus erlotinib used as maintenance therapy.
Abstract: Importance In locally advanced pancreatic cancer, the role of chemoradiotherapy is controversial and the efficacy of erlotinib is unknown. Objectives To assess whether chemoradiotherapy improves overall survival of patients with locally advanced pancreatic cancer controlled after 4 months of gemcitabine-based induction chemotherapy and to assess the effect of erlotinib on survival. Design, Setting, and Participants In LAP07, an international, open-label, phase 3 randomized trial, 449 patients were enrolled between 2008 and 2011. Follow-up ended in February 2013. Interventions In the first randomization, 223 patients received 1000 mg/m 2 weekly of gemcitabine alone and 219 patients received 1000 mg/m 2 of gemcitabine plus 100 mg/d of erlotinib. In the second randomization involving patients with progression-free disease after 4 months, 136 patients received 2 months of the same chemotherapy and 133 underwent chemoradiotherapy (54 Gy plus capecitabine). Main Outcomes and Measures The primary outcome was overall survival from the date of the first randomization. Secondary outcomes were the effect of erlotinib and quality assurance of radiotherapy on overall survival, progression-free survival of gemcitabine-erlotinib and erlotinib maintenance with gemcitabine alone at the second randomization, and toxic effects. Results A total of 442 of the 449 patients (232 men; median age, 63.3 years) enrolled underwent the first randomization. Of these, 269 underwent the second randomization. Interim analysis was performed when 221 patients died (109 in the chemoradiotherapy group and 112 in the chemotherapy group), reaching the early stopping boundaries for futility. With a median follow-up of 36.7 months, the median overall survival from the date of the first randomization was not significantly different between chemotherapy at 16.5 months (95% CI, 14.5-18.5 months) and chemoradiotherapy at 15.2 months (95% CI, 13.9-17.3 months; hazard ratio [HR], 1.03; 95% CI, 0.79-1.34; P = .83). Median overall survival from the date of the first randomization for the 223 patients receiving gemcitabine was 13.6 months (95% CI, 12.3-15.3 months) and was 11.9 months (95% CI, 10.4-13.5 months) for the 219 patients receiving gemcitabine plus erlotinib (HR, 1.19; 95% CI, 0.97-1.45; P = .09; 188 deaths vs 191 deaths). Chemoradiotherapy was associated with decreased local progression (32% vs 46%, P = .03) and no increase in grade 3 to 4 toxicity, except for nausea. Conclusions and Relevance In this open-label, randomized trial involving patients with locally advanced pancreatic cancer with disease controlled after 4 months of induction chemotherapy, there was no significant difference in overall survival with chemoradiotherapy compared with chemotherapy alone and there was no significant difference in overall survival with gemcitabine compared with gemcitabine plus erlotinib used as maintenance therapy. Trial Registration clinicaltrials.gov Identifier:NCT00634725
Stony Brook University1, University of Balamand2, Harvard University3, University of Washington4, University of Pennsylvania5, University of Cape Town6, Pompeu Fabra University7, Moi University8, Ulster University9, Katholieke Universiteit Leuven10, Universidade Nova de Lisboa11, University College Hospital, Ibadan12, Peking University13, Paris Diderot University14, University of Tokyo15, Paris Descartes University16, University of Otago17, New York University18, University of New South Wales19, Utrecht University20, Center for Excellence in Education21, Universidade Federal do Espírito Santo22
TL;DR: Exposure to interpersonal violence had the strongest associations with subsequent traumatic events, and limited resources may best be dedicated to those that are more likely to be further exposed such as victims of interpersonal violence.
Abstract: BACKGROUND: Considerable research has documented that exposure to traumatic events has negative effects on physical and mental health. Much less research has examined the predictors of traumatic event exposure. Increased understanding of risk factors for exposure to traumatic events could be of considerable value in targeting preventive interventions and anticipating service needs. METHOD: General population surveys in 24 countries with a combined sample of 68 894 adult respondents across six continents assessed exposure to 29 traumatic event types. Differences in prevalence were examined with cross-tabulations. Exploratory factor analysis was conducted to determine whether traumatic event types clustered into interpretable factors. Survival analysis was carried out to examine associations of sociodemographic characteristics and prior traumatic events with subsequent exposure. RESULTS: Over 70% of respondents reported a traumatic event; 30.5% were exposed to four or more. Five types - witnessing death or serious injury, the unexpected death of a loved one, being mugged, being in a life-threatening automobile accident, and experiencing a life-threatening illness or injury - accounted for over half of all exposures. Exposure varied by country, sociodemographics and history of prior traumatic events. Being married was the most consistent protective factor. Exposure to interpersonal violence had the strongest associations with subsequent traumatic events. CONCLUSIONS: Given the near ubiquity of exposure, limited resources may best be dedicated to those that are more likely to be further exposed such as victims of interpersonal violence. Identifying mechanisms that account for the associations of prior interpersonal violence with subsequent trauma is critical to develop interventions to prevent revictimization. Language: en
TL;DR: This review discusses the fundamental kinematics of particles in microchannels to familiarise readers with the mechanisms and underlying physics in inertial microfluidic systems and presents a comprehensive review of recent developments and key applications of inertialMicrofluidics systems according to their microchannel structures.
Abstract: In the last decade, inertial microfluidics has attracted significant attention and a wide variety of channel designs that focus, concentrate and separate particles and fluids have been demonstrated. In contrast to conventional microfluidic technologies, where fluid inertia is negligible and flow remains almost within the Stokes flow region with very low Reynolds number (Re ≪ 1), inertial microfluidics works in the intermediate Reynolds number range (~1 < Re < ~100) between Stokes and turbulent regimes. In this intermediate range, both inertia and fluid viscosity are finite and bring about several intriguing effects that form the basis of inertial microfluidics including (i) inertial migration and (ii) secondary flow. Due to the superior features of high-throughput, simplicity, precise manipulation and low cost, inertial microfluidics is a very promising candidate for cellular sample processing, especially for samples with low abundant targets. In this review, we first discuss the fundamental kinematics of particles in microchannels to familiarise readers with the mechanisms and underlying physics in inertial microfluidic systems. We then present a comprehensive review of recent developments and key applications of inertial microfluidic systems according to their microchannel structures. Finally, we discuss the perspective of employing fluid inertia in microfluidics for particle manipulation. Due to the superior benefits of inertial microfluidics, this promising technology will still be an attractive topic in the near future, with more novel designs and further applications in biology, medicine and industry on the horizon.
TL;DR: In this paper, the stability issues of perovskite solar cells are discussed, highlighting the need to view the device as a whole system, due to the interdependent relationships between the layers.
University of Utah1, University of Colorado Boulder2, Stanford University3, Oregon Health & Science University4, University of Chicago5, Rush University Medical Center6, University of Barcelona7, Harvard University8, Vanderbilt University9, University of Arizona10, University of Texas Health Science Center at Houston11, University of Pennsylvania12, Emory University13, Université de Montréal14, Samsung Medical Center15, University of Auckland16, University of Pittsburgh17, University of Amsterdam18, University of Ioannina19, University of California, San Francisco20, Eastern Virginia Medical School21, University of New South Wales22, Katholieke Universiteit Leuven23, Guy's and St Thomas' NHS Foundation Trust24, University of Lorraine25, University of British Columbia26, Northwestern University27, Georgia Regents University28, Johns Hopkins University29, New York University30, Korea University31, University of Texas at Austin32, Uniformed Services University of the Health Sciences33, Jikei University School of Medicine34, University of Washington35, University of Siena36, Medical College of Wisconsin37, University of Adelaide38, West Virginia University39, Innsbruck Medical University40, Pusan National University41, University of Calgary42, Medical University of South Carolina43, University of North Carolina at Chapel Hill44, Cleveland Clinic45, Loyola University Chicago46, Cornell University47, Temple University48, University of São Paulo49, National University of Singapore50, San Antonio Military Medical Center51, University of Alabama at Birmingham52, University of Alberta53, Capital Medical University54
TL;DR: This dissertation aims to provide a history of Chinese medical practice in the United States from 1989 to 2002, a period chosen in order to explore its roots as well as specific cases up to and including the year in which descriptions of “modern China” began to circulate.
Abstract: Background The body of knowledge regarding rhinosinusitis(RS) continues to expand, with rapid growth in number of publications, yet substantial variability in the quality of those presentations. In an effort to both consolidate and critically appraise this information, rhinologic experts from around the world have produced the International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR:RS). Methods Evidence-based reviews with recommendations(EBRRs) were developed for scores of topics, using previously reported methodology. Where existing evidence was insufficient for an EBRR, an evidence-based review (EBR)was produced. The sections were then synthesized and the entire manuscript was then reviewed by all authors for consensus. Results The resulting ICAR:RS document addresses multiple topics in RS, including acute RS (ARS), chronic RS (CRS)with and without nasal polyps (CRSwNP and CRSsNP), recurrent acute RS (RARS), acute exacerbation of CRS (AECRS), and pediatric RS. Conclusion As a critical review of the RS literature, ICAR:RS provides a thorough review of pathophysiology and evidence-based recommendations for medical and surgical treatment. It also demonstrates the significant gaps in our understanding of the pathophysiology and optimal management of RS. Too often the foundation upon which these recommendations are based is comprised of lower level evidence. It is our hope that this summary of the evidence in RS will point out where additional research efforts may be directed.
Nicholas J Kassebaum1, Ryan M Barber1, Zulfiqar A Bhutta2, Zulfiqar A Bhutta3 +613 more•Institutions (272)
TL;DR: In this article, the authors quantified maternal mortality throughout the world by underlying cause and age from 1990 to 2015 for ages 10-54 years by systematically compiling and processing all available data sources from 186 of 195 countries and territories.