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Showing papers by "Curtin University published in 2016"


Journal ArticleDOI
Daniel J. Klionsky1, Kotb Abdelmohsen2, Akihisa Abe3, Joynal Abedin4  +2519 moreInstitutions (695)
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


Journal ArticleDOI
Theo Vos1, Christine Allen1, Megha Arora1, Ryan M Barber1  +696 moreInstitutions (260)
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


Journal ArticleDOI
Haidong Wang1, Mohsen Naghavi1, Christine Allen1, Ryan M Barber1  +841 moreInstitutions (293)
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


Journal ArticleDOI
TL;DR: The associations of both overweight and obesity with higher all-cause mortality were broadly consistent in four continents and supports strategies to combat the entire spectrum of excess adiposity in many populations.

1,731 citations


Journal ArticleDOI
Nicholas J Kassebaum1, Megha Arora1, Ryan M Barber1, Zulfiqar A Bhutta2  +679 moreInstitutions (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.

1,533 citations


Journal ArticleDOI
TL;DR: Among patients receiving initial systemic treatment for HR-positive, HER2-negative advanced breast cancer, the duration of progression-free survival was significantly longer among those receiving ribociclib plus letrozole than among those received placebo plus let rozole, with a higher rate of myelosuppression in the ribocIClib group.
Abstract: BackgroundThe inhibition of cyclin-dependent kinases 4 and 6 (CDK4/6) could potentially overcome or delay resistance to endocrine therapy in advanced breast cancer that is positive for hormone receptor (HR) and negative for human epidermal growth factor receptor 2 (HER2). MethodsIn this randomized, placebo-controlled, phase 3 trial, we evaluated the efficacy and safety of the selective CDK4/6 inhibitor ribociclib combined with letrozole for first-line treatment in 668 postmenopausal women with HR-positive, HER2-negative recurrent or metastatic breast cancer who had not received previous systemic therapy for advanced disease. We randomly assigned the patients to receive either ribociclib (600 mg per day on a 3-weeks-on, 1-week-off schedule) plus letrozole (2.5 mg per day) or placebo plus letrozole. The primary end point was investigator-assessed progression-free survival. Secondary end points included overall survival, overall response rate, and safety. A preplanned interim analysis was performed on Januar...

1,232 citations


Journal ArticleDOI
Juanita A. Haagsma1, Nicholas Graetz1, Ian Bolliger1, Mohsen Naghavi1, Hideki Higashi1, Erin C Mullany1, Semaw Ferede Abera2, Jerry Puthenpurakal Abraham3, Koranteng Adofo4, Ubai Alsharif5, Emmanuel A. Ameh6, Walid Ammar, Carl Abelardo T. Antonio7, Lope H Barrero8, Tolesa Bekele9, Dipan Bose10, Alexandra Brazinova, Ferrán Catalá-López, Lalit Dandona1, Rakhi Dandona11, Paul I. Dargan12, Diego De Leo13, Louisa Degenhardt14, Sarah Derrett15, Samath D Dharmaratne16, Tim Driscoll17, Leilei Duan18, Sergey Petrovich Ermakov19, Farshad Farzadfar20, Valery L. Feigin21, Richard C. Franklin22, Belinda J. Gabbe23, Richard A. Gosselin24, Nima Hafezi-Nejad20, Randah R. Hamadeh25, Martha Híjar, Guoqing Hu26, Sudha Jayaraman27, Guohong Jiang, Yousef Khader28, Ejaz Ahmad Khan29, Sanjay Krishnaswami30, Chanda Kulkarni, Fiona Lecky31, Ricky Leung32, Raimundas Lunevicius33, Ronan A Lyons34, Marek Majdan, Amanda J. Mason-Jones35, Richard Matzopoulos36, Peter A. Meaney37, Wubegzier Mekonnen38, Ted R. Miller39, Charles Mock40, Rosana E. Norman41, Ricardo Orozco, Suzanne Polinder, Farshad Pourmalek42, Vafa Rahimi-Movaghar20, Amany H. Refaat43, David Rojas-Rueda, Nobhojit Roy44, David C. Schwebel45, Amira Shaheen46, Saeid Shahraz47, Vegard Skirbekk48, Kjetil Søreide49, Sergey Soshnikov, Dan J. Stein50, Bryan L. Sykes51, Karen M. Tabb52, Awoke Misganaw Temesgen, Eric Y. Tenkorang53, Alice Theadom21, Bach Xuan Tran54, Bach Xuan Tran55, Tommi Vasankari, Monica S. Vavilala40, Vasiliy Victorovich Vlassov56, Solomon Meseret Woldeyohannes57, Paul S. F. Yip58, Naohiro Yonemoto, Mustafa Z. Younis59, Chuanhua Yu60, Christopher J L Murray1, Theo Vos1 
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.

883 citations


Journal ArticleDOI
08 Jul 2016-Science
TL;DR: It is shown that extreme warming of a temperate kelp forest off Australia resulted not only in its collapse, but also in a shift in community composition that brought about an increase in herbivorous tropical fishes that prevent the reestablishment of kelp.
Abstract: Ecosystem reconfigurations arising from climate-driven changes in species distributions are expected to have profound ecological, social, and economic implications. Here we reveal a rapid climate-driven regime shift of Australian temperate reef communities, which lost their defining kelp forests and became dominated by persistent seaweed turfs. After decades of ocean warming, extreme marine heat waves forced a 100-kilometer range contraction of extensive kelp forests and saw temperate species replaced by seaweeds, invertebrates, corals, and fishes characteristic of subtropical and tropical waters. This community-wide tropicalization fundamentally altered key ecological processes, suppressing the recovery of kelp forests.

856 citations


Journal ArticleDOI
TL;DR: The size of the ego-depletion effect was small with 95% confidence intervals (CIs) that encompassed zero (d = 0.04, 95% CI [−0.07, 0.15]), and implications of the findings for the psyche depletion effect and the resource depletion model of self-control are discussed.
Abstract: Good self-control has been linked to adaptive outcomes such as better health, cohesive personal relationships, success in the workplace and at school, and less susceptibility to crime and addictions. In contrast, self-control failure is linked to maladaptive outcomes. Understanding the mechanisms by which self-control predicts behavior may assist in promoting better regulation and outcomes. A popular approach to understanding self-control is the strength or resource depletion model. Self-control is conceptualized as a limited resource that becomes depleted after a period of exertion resulting in self-control failure. The model has typically been tested using a sequential-task experimental paradigm, in which people completing an initial self-control task have reduced self-control capacity and poorer performance on a subsequent task, a state known as ego depletion Although a meta-analysis of ego-depletion experiments found a medium-sized effect, subsequent meta-analyses have questioned the size and existence of the effect and identified instances of possible bias. The analyses served as a catalyst for the current Registered Replication Report of the ego-depletion effect. Multiple laboratories (k = 23, total N = 2,141) conducted replications of a standardized ego-depletion protocol based on a sequential-task paradigm by Sripada et al. Meta-analysis of the studies revealed that the size of the ego-depletion effect was small with 95% confidence intervals (CIs) that encompassed zero (d = 0.04, 95% CI [-0.07, 0.15]. We discuss implications of the findings for the ego-depletion effect and the resource depletion model of self-control.

661 citations


Journal ArticleDOI
TL;DR: This research paper develops, explicates, and provides evidence for the utility of a Framework for Evaluation in Design Science (FEDS) together with a process to guide design science researchers in developing a strategy for evaluating the artefacts they develop within a DSR project.
Abstract: Evaluation of design artefacts and design theories is a key activity in Design Science Research (DSR), as it provides feedback for further development and (if done correctly) assures the rigour of the research. However, the extant DSR literature provides insufficient guidance on evaluation to enable Design Science Researchers to effectively design and incorporate evaluation activities into a DSR project that can achieve DSR goals and objectives. To address this research gap, this research paper develops, explicates, and provides evidence for the utility of a Framework for Evaluation in Design Science (FEDS) together with a process to guide design science researchers in developing a strategy for evaluating the artefacts they develop within a DSR project. A FEDS strategy considers why, when, how, and what to evaluate. FEDS includes a two-dimensional characterisation of DSR evaluation episodes (particular evaluations), with one dimension being the functional purpose of the evaluation (formative or summative) and the other dimension being the paradigm of the evaluation (artificial or naturalistic). The FEDS evaluation design process is comprised of four steps: (1) explicate the goals of the evaluation, (2) choose the evaluation strategy or strategies, (3) determine the properties to evaluate, and (4) design the individual evaluation episode(s). The paper illustrates the framework with two examples and provides evidence of its utility via a naturalistic, summative evaluation through its use on an actual DSR project.

646 citations


Journal ArticleDOI
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.

Journal ArticleDOI
TL;DR: Treatment with rosuvastatin at a dose of 10 mg per day resulted in a significantly lower risk of cardiovascular events than placebo in an intermediate-risk, ethnically diverse population without cardiovascular disease.
Abstract: BackgroundPrevious trials have shown that the use of statins to lower cholesterol reduces the risk of cardiovascular events among persons without cardiovascular disease. Those trials have involved persons with elevated lipid levels or inflammatory markers and involved mainly white persons. It is unclear whether the benefits of statins can be extended to an intermediate-risk, ethnically diverse population without cardiovascular disease. MethodsIn one comparison from a 2-by-2 factorial trial, we randomly assigned 12,705 participants in 21 countries who did not have cardiovascular disease and were at intermediate risk to receive rosuvastatin at a dose of 10 mg per day or placebo. The first coprimary outcome was the composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke, and the second coprimary outcome additionally included revascularization, heart failure, and resuscitated cardiac arrest. The median follow-up was 5.6 years. ResultsThe overall mean low-density lipop...

Journal ArticleDOI
TL;DR: This paper examined the social and legal conditions in which many transgender people (often called trans people) live, and the medical perspectives that frame the provision of health care for transgender people across much of the world.

Journal ArticleDOI
Haidong Wang1, Zulfiqar A Bhutta2, Zulfiqar A Bhutta3, Matthew M Coates1  +610 moreInstitutions (263)
TL;DR: The Global Burden of Disease 2015 Study provides an analytical framework to comprehensively assess trends for under-5 mortality, age-specific and cause-specific mortality among children under 5 years, and stillbirths by geography over time and decomposed the changes in under- 5 mortality to changes in SDI at the global level.

Journal ArticleDOI
TL;DR: In this paper, the standard atomic weights of four elements have been revised based on recent determinations of isotopic abundances in natural terrestrial materials: cadmium to 112.414(4) from 112.411(8), molybdenum to 95.95(1) from 95.96(2), selenium to 78.971(8) from 78.96
Abstract: The biennial review of atomic-weight determinations and other cognate data has resulted in changes for the standard atomic weights of 19 elements. The standard atomic weights of four elements have been revised based on recent determinations of isotopic abundances in natural terrestrial materials: cadmium to 112.414(4) from 112.411(8), molybdenum to 95.95(1) from 95.96(2), selenium to 78.971(8) from 78.96(3), and thorium to 232.0377(4) from 232.038 06(2).

Journal ArticleDOI
TL;DR: In this article, a simple and effective strategy for enhancing ORR and OER electrocatalytic activity in alkaline solution by introducing A-site cation deficiency in LaFeO3 perovskite was reported.
Abstract: Development of cost-effective and efficient electrocatalysts for oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) is of prime importance to emerging renewable energy technologies. Here, we report a simple and effective strategy for enhancing ORR and OER electrocatalytic activity in alkaline solution by introducing A-site cation deficiency in LaFeO3 perovskite; the enhancement effect is more pronounced for the OER than the ORR. Among the A-site cation deficient perovskites studied, La0.95FeO3-δ (L0.95F) demonstrates the highest ORR and OER activity and, hence, the best bifunctionality. The dramatic enhancement is attributed to the creation of surface oxygen vacancies and a small amount of Fe4+ species. This work highlights the importance of tuning cation deficiency in perovskites as an effective strategy for enhancing ORR and OER activity for applications in various oxygen-based energy storage and conversion processes.

Journal ArticleDOI
TL;DR: In this paper, a systematic review shows that 3-D printing technology, after years of evolution, can be used to print large-scale architectural models and buildings, however, the potential of the technology is limited by the lack of large scale implementation, the development of building information modeling, the requirements of mass customization, and the life cycle cost of the printed projects.

Journal ArticleDOI
TL;DR: The cellular and molecular origins and significance of ROS production, the molecular targets and responses describing how oxidative stress affects cell function including mechanisms of insulin secretion and action are reviewed from the point of view of possible application of novel diabetic therapies based on redox regulation.
Abstract: Oxidative stress and chronic inflammation are known to be associated with the development of metabolic diseases, including diabetes. Oxidative stress, an imbalance between oxidative and antioxidative systems of cells and tissues, is a result of over production of oxidative-free radicals and associated reactive oxygen species (ROS). One outcome of excessive levels of ROS is the modification of the structure and function of cellular proteins and lipids, leading to cellular dysfunction including impaired energy metabolism, altered cell signalling and cell cycle control, impaired cell transport mechanisms and overall dysfunctional biological activity, immune activation and inflammation. Nutritional stress, such as that caused by excess high-fat and/or carbohydrate diets, promotes oxidative stress as evident by increased lipid peroxidation products, protein carbonylation and decreased antioxidant status. In obesity, chronic oxidative stress and associated inflammation are the underlying factors that lead to the development of pathologies such as insulin resistance, dysregulated pathways of metabolism, diabetes and cardiovascular disease through impaired signalling and metabolism resulting in dysfunction to insulin secretion, insulin action and immune responses. However, exercise may counter excessive levels of oxidative stress and thus improve metabolic and inflammatory outcomes. In the present article, we review the cellular and molecular origins and significance of ROS production, the molecular targets and responses describing how oxidative stress affects cell function including mechanisms of insulin secretion and action, from the point of view of possible application of novel diabetic therapies based on redox regulation.

Journal ArticleDOI
TL;DR: In this article, the peroxymonosulfate (PMS) activation was investigated on different carbocatalysts with varying carbon-conjugation structures and functional groups, and density functional theory (DFT) calculations were employed to explore the adsorption and O O O bond activation on the different carbon configurations.
Abstract: Metal-free activation of superoxides provides an efficient and environmentally benign strategy for heterogeneous catalytic oxidation. In this study, nanocarbons with varying carbon-conjugation structures and functional groups were investigated for peroxymonosulfate (PMS) activation. It was discovered that radical and nonradical oxidations could occur on different carbocatalysts depending on the carbon structure. Radical oxidation occurs exclusively on MWCNTs and CMK-3, similar to a metal oxide, MnO2. Both radical and nonradical oxidations are very pronounced in nanodiamond (AND-900)/PMS whilst nonradical oxidation is dominated in reduced graphene oxide (rGO-900)/PMS. Density functional theory (DFT) calculations were employed to explore the PMS adsorption and O O bond activation on the different carbon configurations for an in-depth probe of the activation mechanism. The intact sp2-conjugated π system in MWCNTs and electron-rich ketonic groups (as Lewis basic sites) in CMK-3 can stimulate PMS dissociation to generate SO4 − and OH, similar to metal-based catalysts. However, the defective edges at the boundary of carbon network are able to facilitate the organic degradation without generation of the reactive radicals, which is well supported by both experiments and the DFT calculation. The emerging nonradical oxidation induced by the carbocatalysis is superior to the radical oxidation on most metal oxides for effective degradation of various organics. The influences of solution pH, various anions (H2PO42−, HCO3− and Cl−) and background organic matters (humic acid) on the nonradical oxidation were further evaluated. The nonradical oxidation on carbocatalysts can be utilized as a green and effective oxidation strategy for aqueous environmental remediation and nonaqueous phase oxidation.

Journal ArticleDOI
TL;DR: The Table of Isotopic Compositions of the Elements (TICE) was updated in 2013 by the International Union of Pure and Applied Chemistry (IUPAC) as mentioned in this paper.
Abstract: The Commission on Isotopic Abundances and Atomic Weights (ciaaw.org) of the International Union of Pure and Applied Chemistry (iupac.org) has revised the Table of Isotopic Compositions of the Elements (TICE). The update involved a critical evaluation of the recent published literature. The new TICE 2013 includes evaluated data from the "best measurement" of the isotopic abundances in a single sample, along with a set of representative isotopic abundances and uncertainties that accommodate known varia- tions in normal terrestrial materials.

Journal ArticleDOI
10 Jun 2016-Science
TL;DR: This study demonstrates for the first time the permanent disposal of CO2 as environmentally benign carbonate minerals in basaltic rocks and demonstrates that the safe long-term storage of anthropogenic CO2 emissions through mineralization can be far faster than previously postulated.
Abstract: Carbon capture and storage (CCS) provides a solution toward decarbonization of the global economy. The success of this solution depends on the ability to safely and permanently store CO2. This study demonstrates for the first time the permanent disposal of CO2 as environmentally benign carbonate minerals in basaltic rocks. We find that over 95% of the CO2 injected into the CarbFix site in Iceland was mineralized to carbonate minerals in less than 2 years. This result contrasts with the common view that the immobilization of CO2 as carbonate minerals within geologic reservoirs takes several hundreds to thousands of years. Our results, therefore, demonstrate that the safe long-term storage of anthropogenic CO2 emissions through mineralization can be far faster than previously postulated.

Journal ArticleDOI
Haidong Wang1, Timothy M. Wolock1, Austin Carter1, Grant Nguyen1  +497 moreInstitutions (214)
TL;DR: This report provides national estimates of levels and trends of HIV/AIDS incidence, prevalence, coverage of antiretroviral therapy (ART), and mortality for 195 countries and territories from 1980 to 2015.

Journal ArticleDOI
TL;DR: Therapy with candesartan at a dose of 16 mg per day plus hydrochlorothiazide at a doses of 12.5mg per day was not associated with a lower rate of major cardiovascular events than placebo among persons at intermediate risk who did not have cardiovascular disease.
Abstract: BackgroundAntihypertensive therapy reduces the risk of cardiovascular events among high-risk persons and among those with a systolic blood pressure of 160 mm Hg or higher, but its role in persons at intermediate risk and with lower blood pressure is unclear. MethodsIn one comparison from a 2-by-2 factorial trial, we randomly assigned 12,705 participants at intermediate risk who did not have cardiovascular disease to receive either candesartan at a dose of 16 mg per day plus hydrochlorothiazide at a dose of 12.5 mg per day or placebo. The first coprimary outcome was the composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke; the second coprimary outcome additionally included resuscitated cardiac arrest, heart failure, and revascularization. The median follow-up was 5.6 years. ResultsThe mean blood pressure of the participants at baseline was 138.1/81.9 mm Hg; the decrease in blood pressure was 6.0/3.0 mm Hg greater in the active-treatment group than in the placebo...

Journal ArticleDOI
TL;DR: The objective of this paper is to outline this problem space in more detail and to create a valuable source of information that can help to define the starting position for future research.
Abstract: Within education, concepts such as distance learning, and open universities, are now becoming more widely used for teaching and learning. However, due to the nature of the subject domain, the teaching of Science, Technology, and Engineering are still relatively behind when using new technological approaches (particularly for online distance learning). The reason for this discrepancy lies in the fact that these fields often require laboratory exercises to provide effective skill acquisition and hands-on experience. Often it is difficult to make these laboratories accessible for online access. Either the real lab needs to be enabled for remote access or it needs to be replicated as a fully software-based virtual lab. We argue for the latter concept since it offers some advantages over remotely controlled real labs, which will be elaborated further in this paper.We are now seeing new emerging technologies that can overcome some of the potential difficulties in this area. These include: computer graphics, augmented reality, computational dynamics, and virtual worlds. This paper summarizes the state of the art in virtual laboratories and virtual worlds in the fields of science, technology, and engineering. The main research activity in these fields is discussed but special emphasis is put on the field of robotics due to the maturity of this area within the virtual-education community. This is not a coincidence; starting from its widely multidisciplinary character, robotics is a perfect example where all the other fields of engineering and physics can contribute. Thus, the use of virtual labs for other scientific and non-robotic engineering uses can be seen to share many of the same learning processes. This can include supporting the introduction of new concepts as part of learning about science and technology, and introducing more general engineering knowledge, through to supporting more constructive (and collaborative) education and training activities in a more complex engineering topic such as robotics. The objective of this paper is to outline this problem space in more detail and to create a valuable source of information that can help to define the starting position for future research. State of the art in dynamics-based virtual laboratories.Defining the criteria for critical evaluation of existing technologies.State of the art in virtual worlds.Future advances in the field of virtual-world based laboratories.

Journal ArticleDOI
Hmwe H Kyu1, Christine Pinho1, Joseph Wagner1, Jonathan C Brown1  +199 moreInstitutions (118)
TL;DR: Understanding the levels and trends of the leading causes of death and disability among children and adolescents is critical to guide investment and inform policies and give guidance to policy makers in countries where more attention is needed.
Abstract: Importance The literature focuses on mortality among children younger than 5 years. Comparable information on nonfatal health outcomes among these children and the fatal and nonfatal burden of diseases and injuries among older children and adolescents is scarce. Objective To determine levels and trends in the fatal and nonfatal burden of diseases and injuries among younger children (aged Evidence Review Data from vital registration, verbal autopsy studies, maternal and child death surveillance, and other sources covering 14 244 site-years (ie, years of cause of death data by geography) from 1980 through 2013 were used to estimate cause-specific mortality. Data from 35 620 epidemiological sources were used to estimate the prevalence of the diseases and sequelae in the GBD 2013 study. Cause-specific mortality for most causes was estimated using the Cause of Death Ensemble Model strategy. For some infectious diseases (eg, HIV infection/AIDS, measles, hepatitis B) where the disease process is complex or the cause of death data were insufficient or unavailable, we used natural history models. For most nonfatal health outcomes, DisMod-MR 2.0, a Bayesian metaregression tool, was used to meta-analyze the epidemiological data to generate prevalence estimates. Findings Of the 7.7 (95% uncertainty interval [UI], 7.4-8.1) million deaths among children and adolescents globally in 2013, 6.28 million occurred among younger children, 0.48 million among older children, and 0.97 million among adolescents. In 2013, the leading causes of death were lower respiratory tract infections among younger children (905 059 deaths; 95% UI, 810 304-998 125), diarrheal diseases among older children (38 325 deaths; 95% UI, 30 365-47 678), and road injuries among adolescents (115 186 deaths; 95% UI, 105 185-124 870). Iron deficiency anemia was the leading cause of years lived with disability among children and adolescents, affecting 619 (95% UI, 618-621) million in 2013. Large between-country variations exist in mortality from leading causes among children and adolescents. Countries with rapid declines in all-cause mortality between 1990 and 2013 also experienced large declines in most leading causes of death, whereas countries with the slowest declines had stagnant or increasing trends in the leading causes of death. In 2013, Nigeria had a 12% global share of deaths from lower respiratory tract infections and a 38% global share of deaths from malaria. India had 33% of the world’s deaths from neonatal encephalopathy. Half of the world’s diarrheal deaths among children and adolescents occurred in just 5 countries: India, Democratic Republic of the Congo, Pakistan, Nigeria, and Ethiopia. Conclusions and Relevance Understanding the levels and trends of the leading causes of death and disability among children and adolescents is critical to guide investment and inform policies. Monitoring these trends over time is also key to understanding where interventions are having an impact. Proven interventions exist to prevent or treat the leading causes of unnecessary death and disability among children and adolescents. The findings presented here show that these are underused and give guidance to policy makers in countries where more attention is needed.

Journal ArticleDOI
TL;DR: A strong relationship exists between painful musculoskeletal conditions and a reduced capacity to engage in physical activity resulting in functional decline, frailty, reduced well-being, and loss of independence.
Abstract: Persistent pain, impaired mobility and function, and reduced quality of life and mental well-being are the most common experiences associated with musculoskeletal conditions, of which there are more than 150 types. The prevalence and impact of musculoskeletal conditions increase with aging. A profound burden of musculoskeletal disease exists in developed and developing nations. Notably, this burden far exceeds service capacity. Population growth, aging, and sedentary lifestyles, particularly in developing countries, will create a crisis for population health that requires a multisystem response with musculoskeletal health services as a critical component. Globally, there is an emphasis on maintaining an active lifestyle to reduce the impacts of obesity, cardiovascular conditions, cancer, osteoporosis, and diabetes in older people. Painful musculoskeletal conditions, however, profoundly limit the ability of people to make these lifestyle changes. A strong relationship exists between painful musculoskeletal conditions and a reduced capacity to engage in physical activity resulting in functional decline, frailty, reduced well-being, and loss of independence. Multilevel strategies and approaches to care that adopt a whole person approach are needed to address the impact of impaired musculoskeletal health and its sequelae. Effective strategies are available to address the impact of musculoskeletal conditions; some are of low cost (e.g., primary care-based interventions) but others are expensive and, as such, are usually only feasible for developed nations. In developing nations, it is crucial that any reform or development initiatives, including research, must adhere to the principles of development effectiveness to avoid doing harm to the health systems in these settings.

Journal ArticleDOI
Joris P. W. Verbiest1, Joris P. W. Verbiest2, L. Lentati, George Hobbs3, R. van Haasteren4, Paul Demorest5, Gemma H. Janssen, J. B. Wang6, Gregory Desvignes1, R. N. Caballero1, Michael Keith, D. J. Champion1, Zaven Arzoumanian7, Stanislav Babak8, C. G. Bassa9, N. D. R. Bhat10, A. Brazier11, P. Brem8, M. Burgay12, Sarah Burke-Spolaor5, S. J. Chamberlin13, Sourav Chatterjee11, B. Christy14, Ismaël Cognard15, Ismaël Cognard16, James M. Cordes11, Shi Dai3, Shi Dai17, Timothy Dolch18, Timothy Dolch11, Justin A. Ellis4, Robert D. Ferdman, Emmanuel Fonseca19, Jonathan R. Gair20, N. Garver-Daniels21, Peter A. Gentile21, Marjorie Gonzalez22, E. Graikou1, Lucas Guillemot15, Lucas Guillemot16, Jason W. T. Hessels23, Jason W. T. Hessels9, Glenn Jones24, Ramesh Karuppusamy, Matthew Kerr3, Michael Kramer, Michael T. Lam11, Paul D. Lasky25, A. Lassus1, P. Lazarus1, T. J. W. Lazio4, Kejia Lee17, Lina Levin26, Lina Levin21, Kang Liu1, R. S. Lynch5, Andrew Lyne, J. W. McKee26, Maura McLaughlin21, Sean T. McWilliams21, D. R. Madison5, Richard N. Manchester3, Chiara M. F. Mingarelli4, Chiara M. F. Mingarelli1, David J. Nice27, Stefan Oslowski2, Stefan Oslowski1, Nipuni Palliyaguru28, Timothy T. Pennucci29, Benetge Perera, Delphine Perrodin12, A. Possenti12, Antoine Petiteau30, Scott M. Ransom5, Daniel J. Reardon25, Daniel J. Reardon3, Pablo Rosado31, S. A. Sanidas23, Alberto Sesana32, G. Shaifullah2, G. Shaifullah1, Ryan Shannon10, Ryan Shannon3, X. Siemens33, Joseph Simon33, R. Smits, Renée Spiewak33, Ingrid H. Stairs19, Benjamin Stappers, Daniel R. Stinebring34, Kevin Stovall35, J. K. Swiggum21, Stephen Taylor4, Gilles Theureau16, Gilles Theureau15, Gilles Theureau30, Caterina Tiburzi2, Caterina Tiburzi1, L. Toomey3, Michele Vallisneri4, W. van Straten31, Alberto Vecchio32, Yue-Fei Wang36, Linqing Wen37, X. P. You38, Weiwei Zhu1, Xing-Jiang Zhu37 
TL;DR: In this article, the first joint analysis of the data from the three regional pulsar timing arrays (IPTA) is presented, i.e. of the first IPTA data set, and the approach presently followed for its combination and suggest improvements for future PTA research.
Abstract: The highly stable spin of neutron stars can be exploited for a variety of (astro)physical investigations. In particular, arrays of pulsars with rotational periods of the order of milliseconds can be used to detect correlated signals such as those caused by gravitational waves. Three such 'pulsar timing arrays' (PTAs) have been set up around the world over the past decades and collectively form the 'International' PTA (IPTA). In this paper, we describe the first joint analysis of the data from the three regional PTAs, i.e. of the first IPTA data set. We describe the available PTA data, the approach presently followed for its combination and suggest improvements for future PTA research. Particular attention is paid to subtle details (such as underestimation of measurement uncertainty and long-period noise) that have often been ignored but which become important in this unprecedentedly large and inhomogeneous data set. We identify and describe in detail several factors that complicate IPTA research and provide recommendations for future pulsar timing efforts. The first IPTA data release presented here (and available on-line) is used to demonstrate the IPTA's potential of improving upon gravitational-wave limits

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TL;DR: Perovskite oxides are demonstrated for the first time as efficient electrocatalysts for the hydrogen evolution reaction (HER) in alkaline solutions with improved HER performance originates from the modified surface electronic structures and properties of Pr0.5BSCF induced by the Pr-doping.
Abstract: Perovskite oxides are demonstrated for the first time as efficient electrocatalysts for the hydrogen evolution reaction (HER) in alkaline solutions. A-site praseodymium-doped Pr0.5 (Ba0.5 Sr0.5 )0.5 Co0.8 Fe0.2 O3- δ (Pr0.5BSCF) exhibits dramatically enhanced HER activity and stability compared to Ba0.5 Sr0.5 Co0.8 Fe0.2 O3- δ (BSCF), superior to many well-developed bulk/nanosized nonprecious electrocatalysts. The improved HER performance originates from the modified surface electronic structures and properties of Pr0.5BSCF induced by the Pr-doping.

Journal ArticleDOI
TL;DR: It is found that low-volume alcohol consumption has no net mortality benefit compared with lifetime abstention or occasional drinking, and estimates of mortality risk from alcohol are significantly altered by study design and characteristics.
Abstract: Objective:Previous meta-analyses of cohort studies indicate a J-shaped relationship between alcohol consumption and all-cause mortality, with reduced risk for low-volume drinkers. However, low-volume drinkers may appear healthy only because the “abstainers” with whom they are compared are biased toward ill health. The purpose of this study was to determine whether misclassifying former and occasional drinkers as abstainers and other potentially confounding study characteristics underlie observed positive health outcomes for low-volume drinkers in prospective studies of all-cause mortality.Method:A systematic review and meta-regression analysis of studies investigating alcohol use and mortality risk after controlling for quality-related study characteristics was conducted in a population of 3,998,626 individuals, among whom 367,103 deaths were recorded.Results:Without adjustment, meta-analysis of all 87 included studies replicated the classic J-shaped curve, with low-volume drinkers (1.3–24.9 g ethanol per...

Journal ArticleDOI
TL;DR: In this paper, a metal-free activation of persulfate (PS) on annealed nanodiamonds (ANDs) was investigated, which demonstrated superior performances in decomposition of various pollutants to conventional metal-based catalysis.
Abstract: Production of radicals by metal-free catalysis is expected to offer a promising oxidative reaction for remediation of emerging contaminants. In this study, novel metal-free activation of persulfate (PS) on annealed nanodiamonds (ANDs) was investigated, which demonstrated superior performances in decomposition of various pollutants to conventional metal-based catalysis. Comprehensive investigations on the effects of reaction parameters, such as solution pH, reaction temperature, initial phenol concentration, catalyst loading, PS usage, the presence of chlorine ions and humic acid, on phenol degradation were carried out. In addition, nanodiamond (ND) material optimization and reusability were also studied. Electron paramagnetic resonance (EPR) and selective organic degradation unraveled that the PS/AND system may produce both hydroxyl radicals ( OH) and sulfate radicals (SO4 −), initialized from oxidizing water molecules on the nanodiamond surface. The carbocatalysts served as an excellent electron tunnel to facilitate the charge transfer from water or hydroxide ions to PS, and the oxidized intermediates may play a crucial role in PS activation. Electrochemical analyses in PS oxidant solution and oxygen reduction reaction (ORR) were carried out to understand O O bond activation by the metal-free catalysis. This study provides an environmentally benign and highly efficient oxidative reaction system with reactive radicals along with insights into the metal-free PS activation process.