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Showing papers by "Flinders University published in 2017"


Journal ArticleDOI
TL;DR: The Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016) provides a comprehensive assessment of prevalence, incidence, and years lived with disability (YLDs) for 328 causes in 195 countries and territories from 1990 to 2016.

10,401 citations


Journal ArticleDOI
TL;DR: The rapid increase in the prevalence and disease burden of elevated BMI highlights the need for continued focus on surveillance of BMI and identification, implementation, and evaluation of evidence‐based interventions to address this problem.
Abstract: BACKGROUND Although the rising pandemic of obesity has received major attention in many countries, the effects of this attention on trends and the disease burden of obesity remain uncertain. METHOD ...

4,519 citations


Journal ArticleDOI
TL;DR: The assessment of chronic obstructive pulmonary disease has been refined to separate the spirometric assessment from symptom evaluation, and the concept of deescalation of therapy is introduced in the treatment assessment scheme.
Abstract: This Executive Summary of the Global Strategy for the Diagnosis, Management, and Prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2017 report focuses primarily on the revised and novel parts of the document. The most significant changes include: (1) the assessment of chronic obstructive pulmonary disease has been refined to separate the spirometric assessment from symptom evaluation. ABCD groups are now proposed to be derived exclusively from patient symptoms and their history of exacerbations; (2) for each of the groups A to D, escalation strategies for pharmacologic treatments are proposed; (3) the concept of deescalation of therapy is introduced in the treatment assessment scheme; (4) nonpharmacologic therapies are comprehensively presented; and (5) the importance of comorbid conditions in managing chronic obstructive pulmonary disease is reviewed.

2,547 citations


Journal ArticleDOI
Rupert R A Bourne1, Seth Flaxman2, Tasanee Braithwaite1, Maria V Cicinelli, Aditi Das, Jost B. Jonas3, Jill E Keeffe4, John H Kempen5, Janet L Leasher6, Hans Limburg, Kovin Naidoo7, Kovin Naidoo8, Konrad Pesudovs9, Serge Resnikoff7, Serge Resnikoff10, Alexander J Silvester11, Gretchen A Stevens12, Nina Tahhan7, Nina Tahhan10, Tien Yin Wong13, Hugh R. Taylor14, Rupert R A Bourne1, Peter Ackland, Aries Arditi, Yaniv Barkana, Banu Bozkurt15, Alain M. Bron16, Donald L. Budenz17, Feng Cai, Robert J Casson18, Usha Chakravarthy19, Jaewan Choi, Maria Vittoria Cicinelli, Nathan Congdon19, Reza Dana20, Rakhi Dandona21, Lalit Dandona22, Iva Dekaris, Monte A. Del Monte23, Jenny deva24, Laura Dreer25, Leon B. Ellwein26, Marcela Frazier25, Kevin D. Frick27, David S. Friedman27, João M. Furtado28, H. Gao29, Gus Gazzard30, Ronnie George, Stephen Gichuhi31, Victor H. Gonzalez, Billy R. Hammond32, Mary Elizabeth Hartnett33, Minguang He14, James F. Hejtmancik26, Flavio E. Hirai34, John J Huang35, April D. Ingram36, Jonathan C. Javitt27, Jost B. Jonas3, Charlotte E. Joslin, John H. Kempen37, John H. Kempen20, Moncef Khairallah, Rohit C Khanna4, Judy E. Kim38, George N. Lambrou39, Van C. Lansingh, Paolo Lanzetta40, Jennifer I. Lim41, Kaweh Mansouri, Anu A. Mathew42, Alan R. Morse, Beatriz Munoz27, David C. Musch23, Vinay Nangia, Maria Palaiou20, Maurizio Battaglia Parodi, Fernando Yaacov Pena42, Tunde Peto19, Harry A. Quigley27, Murugesan Raju43, Pradeep Y. Ramulu27, Alan L. Robin27, Luca Rossetti44, Jinan B. Saaddine45, Mya Sandar46, Janet B. Serle47, Tueng T. Shen22, Rajesh K. Shetty48, Pamela C. Sieving26, Juan Carlos Silva49, Rita S. Sitorus50, Dwight Stambolian37, Gretchen Stevens12, Hugh Taylor14, Jaime Tejedor, James M. Tielsch27, Miltiadis K. Tsilimbaris51, Jan C. van Meurs52, Rohit Varma53, Gianni Virgili54, Jimmy Volmink55, Ya Xing Wang, Ningli Wang56, Sheila K. West27, Peter Wiedemann57, Tien Wong13, Richard Wormald58, Yingfeng Zheng46 
Anglia Ruskin University1, University of Oxford2, Heidelberg University3, L V Prasad Eye Institute4, Massachusetts Eye and Ear Infirmary5, Nova Southeastern University6, Brien Holden Vision Institute7, University of KwaZulu-Natal8, Flinders University9, University of New South Wales10, Royal Liverpool University Hospital11, World Health Organization12, National University of Singapore13, University of Melbourne14, Selçuk University15, University of Burgundy16, University of Miami17, University of Adelaide18, Queen's University Belfast19, Harvard University20, The George Institute for Global Health21, University of Washington22, University of Michigan23, Universiti Tunku Abdul Rahman24, University of Alabama25, National Institutes of Health26, Johns Hopkins University27, University of São Paulo28, Henry Ford Health System29, University College London30, University of Nairobi31, University of Georgia32, University of Utah33, Federal University of São Paulo34, Yale University35, Alberta Children's Hospital36, University of Pennsylvania37, Medical College of Wisconsin38, Novartis39, University of Udine40, University of Illinois at Urbana–Champaign41, Royal Children's Hospital42, University of Missouri43, University of Milan44, Centers for Disease Control and Prevention45, Singapore National Eye Center46, Icahn School of Medicine at Mount Sinai47, Mayo Clinic48, Pan American Health Organization49, University of Indonesia50, University of Crete51, Erasmus University Rotterdam52, University of Southern California53, University of Florence54, Stellenbosch University55, Capital Medical University56, Leipzig University57, Moorfields Eye Hospital58
TL;DR: There is an ongoing reduction in the age-standardised prevalence of blindness and visual impairment, yet the growth and ageing of the world's population is causing a substantial increase in number of people affected, highlighting the need to scale up vision impairment alleviation efforts at all levels.

1,473 citations


Journal ArticleDOI
TL;DR: The assessment of COPD has been refined to separate the spirometric assessment from symptom evaluation, and the concept of de-escalation of therapy is introduced in the treatment assessment scheme.
Abstract: This Executive Summary of the Global Strategy for the Diagnosis, Management, and Prevention of COPD (GOLD) 2017 Report focuses primarily on the revised and novel parts of the document. The most significant changes include: 1) the assessment of COPD has been refined to separate the spirometric assessment from symptom evaluation. ABCD groups are now proposed to be derived exclusively from patient symptoms and their history of exacerbations; 2) for each of the groups A to D, escalation strategies for pharmacological treatments are proposed; 3) the concept of de-escalation of therapy is introduced in the treatment assessment scheme; 4) nonpharmacologic therapies are comprehensively presented and; 5) the importance of comorbid conditions in managing COPD is reviewed.

818 citations


Journal ArticleDOI
TL;DR: The assessment of chronic obstructive pulmonary disease has been refined to separate the spirometric assessment from symptom evaluation, and the concept of de‐escalation of therapy is introduced in the treatment assessment scheme.
Abstract: This Executive Summary of the Global Strategy for the Diagnosis, Management and Prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2017 Report focuses primarily on the revised and novel parts of the document. The most significant changes include: (i) the assessment of chronic obstructive pulmonary disease has been refined to separate the spirometric assessment from symptom evaluation. ABCD groups are now proposed to be derived exclusively from patient symptoms and their history of exacerbations; (ii) for each of the groups A to D, escalation strategies for pharmacological treatments are proposed; (iii) the concept of de-escalation of therapy is introduced in the treatment assessment scheme; (iv)non-pharmacological therapies are comprehensively presented and (v) the importance of co-morbid conditions in managing COPD is reviewed.

683 citations


Journal ArticleDOI
06 Mar 2017-ACS Nano
TL;DR: This free-standing, adhesive, tough, and biocompatible hydrogel may be more convenient for surgical applications than adhesives that involve in situ gelation and extra agents.
Abstract: Adhesive hydrogels are attractive biomaterials for various applications, such as electronic skin, wound dressing, and wearable devices. However, fabricating a hydrogel with both adequate adhesiveness and excellent mechanical properties remains a challenge. Inspired by the adhesion mechanism of mussels, we used a two-step process to develop an adhesive and tough polydopamine-clay-polyacrylamide (PDA-clay-PAM) hydrogel. Dopamine was intercalated into clay nanosheets and limitedly oxidized between the layers, resulting in PDA-intercalated clay nanosheets containing free catechol groups. Acrylamide monomers were then added and in situ polymerized to form the hydrogel. Unlike previous single-use adhesive hydrogels, our hydrogel showed repeatable and durable adhesiveness. It adhered directly on human skin without causing an inflammatory response and was easily removed without causing damage. The adhesiveness of this hydrogel was attributed to the presence of enough free catechol groups in the hydrogel, which we...

676 citations


Journal ArticleDOI
TL;DR: Coronary revascularization guided by iFR was noninferior to revascularizations guided by FFR with respect to the risk of major adverse cardiac events at 1 year.
Abstract: BackgroundCoronary revascularization guided by fractional flow reserve (FFR) is associated with better patient outcomes after the procedure than revascularization guided by angiography alone. It is unknown whether the instantaneous wave-free ratio (iFR), an alternative measure that does not require the administration of adenosine, will offer benefits similar to those of FFR. MethodsWe randomly assigned 2492 patients with coronary artery disease, in a 1:1 ratio, to undergo either iFR-guided or FFR-guided coronary revascularization. The primary end point was the 1-year risk of major adverse cardiac events, which were a composite of death from any cause, nonfatal myocardial infarction, or unplanned revascularization. The trial was designed to show the noninferiority of iFR to FFR, with a margin of 3.4 percentage points for the difference in risk. ResultsAt 1 year, the primary end point had occurred in 78 of 1148 patients (6.8%) in the iFR group and in 83 of 1182 patients (7.0%) in the FFR group (difference i...

672 citations


Journal ArticleDOI
01 Jan 2017-Small
TL;DR: A graphene oxide conductive hydrogel is reported that simultaneously possesses high toughness, self-healability, and self-adhesiveness and can be used asSelf-adhesive bioelectronics, such as electrical stimulators to regulate cell activity and implantable electrodes for recording in vivo signals.
Abstract: A graphene oxide conductive hydrogel is reported that simultaneously possesses high toughness, self-healability, and self-adhesiveness. Inspired by the adhesion behaviors of mussels, our conductive hydrogel shows self-adhesiveness on various surfaces and soft tissues. The hydrogel can be used as self-adhesive bioelectronics, such as electrical stimulators to regulate cell activity and implantable electrodes for recording in vivo signals.

509 citations


Journal ArticleDOI
29 Jun 2017-Cell
TL;DR: C cultured intestinal organoids are exploited together with single-cell measurements to elucidate intrinsic biophysical, pharmacological, and genetic properties of EC cells, showing that EC cells express specific chemosensory receptors, are electrically excitable, and modulate serotonin-sensitive primary afferent nerve fibers via synaptic connections, enabling them to detect and transduce environmental, metabolic, and homeostatic information from the gut directly to the nervous system.

509 citations



Journal ArticleDOI
TL;DR: The assessment of chronic obstructive pulmonary disease has been refined to separate the spirometric assessment from symptom evaluation, and the importance of comorbid conditions in managing COPD is reviewed.
Abstract: This Executive Summary of the Global Strategy for the Diagnosis, Management, and Prevention of COPD (GOLD) 2017 Report focuses primarily on the revised and novel parts of the document. The most significant changes include: 1) the assessment of chronic obstructive pulmonary disease has been refined to separate the spirometric assessment from symptom evaluation. ABCD groups are now proposed to be derived exclusively from patient symptoms and their history of exacerbations; 2) for each of the groups A to D, escalation strategies for pharmacological treatments are proposed; 3) the concept of de-escalation of therapy is introduced in the treatment assessment scheme; 4) nonpharmacologic therapies are comprehensively presented and; 5) the importance of comorbid conditions in managing COPD is reviewed.

Journal ArticleDOI
Ryan M Barber1, Nancy Fullman1, Reed J D Sorensen1, Thomas J. Bollyky  +757 moreInstitutions (314)
TL;DR: In this paper, the authors use the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) to improve and expand the quantification of personal health-care access and quality for 195 countries and territories from 1990 to 2015.

Journal ArticleDOI
TL;DR: A self-healing, super-resilient hydrogel that can accelerate skin regeneration has been made using an adhesive mechanism inspired by mussels using a process that preserves PDA's catechols – substances that impart mussels with high adhesiveness – when embedded in an elastic polymer matrix.
Abstract: An ideal hydrogel for biomedical engineering should mimic the intrinsic properties of natural tissue, especially high toughness and self-healing ability, in order to withstand cyclic loading and repair skin and muscle damage. In addition, excellent cell affinity and tissue adhesiveness enable integration with the surrounding tissue after implantation. Inspired by the natural mussel adhesive mechanism, we designed a polydopamine–polyacrylamide (PDA–PAM) single network hydrogel by preventing the overoxidation of dopamine to maintain enough free catechol groups in the hydrogel. Therefore, the hydrogel possesses super stretchability, high toughness, stimuli-free self-healing ability, cell affinity and tissue adhesiveness. More remarkably, the current hydrogel can repeatedly be adhered on/stripped from a variety of surfaces for many cycles without loss of adhesion strength. Furthermore, the hydrogel can serve as an excellent platform to host various nano-building blocks, in which multiple functionalities are integrated to achieve versatile potential applications, such as magnetic and electrical therapies. A self-healing, super-resilient hydrogel that can accelerate skin regeneration has been made using an adhesive mechanism inspired by mussels. Hydrogels have similar structures to soft biological tissues and have great potential for tissue engineering applications. However, most are too fragile for use in the body and lack the ability to self-heal and adhere to tissue. Now, Xiong Lu from China's Southwest Jiaotong University and co-workers have synthesized a self-healing, super-resilient hydrogel using a process that preserves PDA's catechols – substances that impart mussels with high adhesiveness – when embedded in an elastic polymer matrix. The numerous non-covalent bonds between PDA catechols enable the hydrogel to perfectly re-form after being sliced open and help it stretch over 30 times its initial length without breaking. The material could also carry magnetic or conductive nanoparticles for future integrated healthcare applications. Inspired by mussel chemistry, a novel polydopamine–polyacrymide hydrogel simultaneously possesses super stretchability, stimuli-free self-healing properties, cell affinity and tissue adhesiveness. The current hydrogel lasts its adhesiveness for a long term, and can be repeatedly adhered on/stripped from a variety of substrates. The hydrogel can host various nano-building blocks and be tuned to magnetic and conductive hydrogels with above-mentioned properties.

Journal ArticleDOI
Philip C Haycock1, Stephen Burgess2, Aayah Nounu1, Jie Zheng1  +194 moreInstitutions (88)
TL;DR: It is likely that longer telomeres increase risk for several cancers but reduce risk for some non-neoplastic diseases, including cardiovascular diseases, as well as single nucleotide polymorphisms (SNPs) that are strongly associated with telomere length in the general population.
Abstract: IMPORTANCE: The causal direction and magnitude of the association between telomere length and incidence of cancer and non-neoplastic diseases is uncertain owing to the susceptibility of observational studies to confounding and reverse causation. OBJECTIVE: To conduct a Mendelian randomization study, using germline genetic variants as instrumental variables, to appraise the causal relevance of telomere length for risk of cancer and non-neoplastic diseases. DATA SOURCES: Genomewide association studies (GWAS) published up to January 15, 2015. STUDY SELECTION: GWAS of noncommunicable diseases that assayed germline genetic variation and did not select cohort or control participants on the basis of preexisting diseases. Of 163 GWAS of noncommunicable diseases identified, summary data from 103 were available. DATA EXTRACTION AND SYNTHESIS: Summary association statistics for single nucleotide polymorphisms (SNPs) that are strongly associated with telomere length in the general population. MAIN OUTCOMES AND MEASURES: Odds ratios (ORs) and 95% confidence intervals (CIs) for disease per standard deviation (SD) higher telomere length due to germline genetic variation. RESULTS: Summary data were available for 35 cancers and 48 non-neoplastic diseases, corresponding to 420 081 cases (median cases, 2526 per disease) and 1 093 105 controls (median, 6789 per disease). Increased telomere length due to germline genetic variation was generally associated with increased risk for site-specific cancers. The strongest associations (ORs [95% CIs] per 1-SD change in genetically increased telomere length) were observed for glioma, 5.27 (3.15-8.81); serous low-malignant-potential ovarian cancer, 4.35 (2.39-7.94); lung adenocarcinoma, 3.19 (2.40-4.22); neuroblastoma, 2.98 (1.92-4.62); bladder cancer, 2.19 (1.32-3.66); melanoma, 1.87 (1.55-2.26); testicular cancer, 1.76 (1.02-3.04); kidney cancer, 1.55 (1.08-2.23); and endometrial cancer, 1.31 (1.07-1.61). Associations were stronger for rarer cancers and at tissue sites with lower rates of stem cell division. There was generally little evidence of association between genetically increased telomere length and risk of psychiatric, autoimmune, inflammatory, diabetic, and other non-neoplastic diseases, except for coronary heart disease (OR, 0.78 [95% CI, 0.67-0.90]), abdominal aortic aneurysm (OR, 0.63 [95% CI, 0.49-0.81]), celiac disease (OR, 0.42 [95% CI, 0.28-0.61]) and interstitial lung disease (OR, 0.09 [95% CI, 0.05-0.15]). CONCLUSIONS AND RELEVANCE: It is likely that longer telomeres increase risk for several cancers but reduce risk for some non-neoplastic diseases, including cardiovascular diseases.

Journal ArticleDOI
TL;DR: Progresses in multi-step continuous-flow systems have improved the syntheses of active pharmaceutical ingredients, natural products, and commodity chemicals while highlighting the rapid progress, benefits, and diversification of this expanding field.
Abstract: Organic chemistry is continually evolving to improve the syntheses of value added and bioactive compounds. Through this progression, a concomitant advancement in laboratory technology has occurred. Many researchers now choose to mediate transformations in continuous-flow systems given the many benefits over round bottom flasks. Furthermore, reaction scale up is often less problematic as this is addressed at the inception of the science. Although single-step transformations in continuous-flow systems are common, multi-step transformations are more valuable. In these systems, molecular complexity is accrued through sequential transformations to a mobile scaffold, much like an in vitro version of Nature's polyketide synthases. Utilizing this methodology, multi-step continuous-flow systems have improved the syntheses of active pharmaceutical ingredients (APIs), natural products, and commodity chemicals. This Review details these advancements while highlighting the rapid progress, benefits, and diversification of this expanding field.

Journal ArticleDOI
TL;DR: In this article, the authors provide a contextual framework for interpreting the results of recent studies, key clinical messages, and suggestions for future sleep and cardiovascular research, which include further consideration of individual risk factors, use of existing and new multimodality therapies that also address adherence, and implementation of trials that are sufficiently powered to target end points and to support subgroup analyses.
Abstract: Emerging research highlights the complex interrelationships between sleep-disordered breathing and cardiovascular disease, presenting clinical and research opportunities as well as challenges. Patients presenting to cardiology clinics have a high prevalence of obstructive and central sleep apnea associated with Cheyne-Stokes respiration. Multiple mechanisms have been identified by which sleep disturbances adversely affect cardiovascular structure and function. Epidemiological research indicates that obstructive sleep apnea is associated with increases in the incidence and progression of coronary heart disease, heart failure, stroke, and atrial fibrillation. Central sleep apnea associated with Cheyne-Stokes respiration predicts incident heart failure and atrial fibrillation; among patients with heart failure, it strongly predicts mortality. Thus, a strong literature provides the mechanistic and empirical bases for considering obstructive sleep apnea and central sleep apnea associated with Cheyne-Stokes respiration as potentially modifiable risk factors for cardiovascular disease. Data from small trials provide evidence that treatment of obstructive sleep apnea with continuous positive airway pressure improves not only patient-reported outcomes such as sleepiness, quality of life, and mood but also intermediate cardiovascular end points such as blood pressure, cardiac ejection fraction, vascular parameters, and arrhythmias. However, data from large-scale randomized controlled trials do not currently support a role for positive pressure therapies for reducing cardiovascular mortality. The results of 2 recent large randomized controlled trials, published in 2015 and 2016, raise questions about the effectiveness of pressure therapies in reducing clinical end points, although 1 trial supported the beneficial effect of continuous positive airway pressure on quality of life, mood, and work absenteeism. This review provides a contextual framework for interpreting the results of recent studies, key clinical messages, and suggestions for future sleep and cardiovascular research, which include further consideration of individual risk factors, use of existing and new multimodality therapies that also address adherence, and implementation of trials that are sufficiently powered to target end points and to support subgroup analyses. These goals may best be addressed through strengthening collaboration among the cardiology, sleep medicine, and clinical trial communities.

Journal ArticleDOI
TL;DR: In this paper, the advantages and disadvantages of several commonly studied anode materials including carbon, alloys, transition metal oxides and silicon along with lithium intercalation are reviewed.
Abstract: As the most commonly used potential energy conversion and storage devices, lithium-ion batteries (LIBs) have been extensively investigated for a wide range of fields including information technology, electric and hybrid vehicles, aerospace, etc. Endowed with attractive properties such as high energy density, long cycle life, small size, low weight, few memory effects and low pollution, LIBs have been recognized as the most likely approach to be used to store electrical power in the future. This review will start with a brief introduction to charge–discharge principles and performance assessment indices. The advantages and disadvantages of several commonly studied anode materials including carbon, alloys, transition metal oxides and silicon along with lithium intercalation will be reviewed. The mechanism and synthesis methods, followed by strategies to enhance battery performance by virtue of interesting structural designs will be examined. Finally, a few issues needing further exploration will be discussed followed by a brief outline of the prospects and outlook for the LIB field.

Journal ArticleDOI
11 Jul 2017-JAMA
TL;DR: The use of PAP, compared with no treatment or sham, was not associated with reduced risks of cardiovascular outcomes or death for patients with sleep apnea, and these findings do not support treatment with PAP with a goal of prevention of these outcomes.
Abstract: Importance Sleep apnea (obstructive and central) is associated with adverse cardiovascular risk factors and increased risks of cardiovascular disease. Positive airway pressure (PAP) provides symptomatic relief, whether delivered continuously (CPAP) or as adaptive servo-ventilation (ASV), but the associations with cardiovascular outcomes and death are unclear. Objective To assess the association of PAP vs control with cardiovascular events and death in patients with sleep apnea. Data Sources and Study Selection MEDLINE, EMBASE, and the Cochrane Library were systematically searched from inception date to March 2017 for randomized clinical trials that included reporting of major adverse cardiovascular events or deaths. Data Extraction and Synthesis Two authors independently extracted data using standardized forms. Summary relative risks (RRs), risk differences (RDs) and 95% CIs were obtained using random-effects meta-analysis. Main Outcomes and Measures The main outcomes were a composite of acute coronary syndrome (ACS) events, stroke, or vascular death (major adverse cardiovascular events); cause-specific vascular events; and death. Results The analyses included data from 10 trials (9 CPAP; 1 ASV) of patients with sleep apnea (N = 7266; mean age, 60.9 [range, 51.5 to 71.1] years; 5847 [80.5%] men; mean [SD] body mass index, 30.0 [5.2]. Among 356 major adverse cardiovascular events and 613 deaths recorded, there was no significant association of PAP with major adverse cardiovascular events (RR, 0.77 [95% CI, 0.53 to 1.13]; P = .19 and RD, −0.01 [95% CI, −0.03 to 0.01]; P = .23), cardiovascular death (RR, 1.15 [95% CI, 0.88 to 1.50]; P = .30 and RD −0.00 [95% CI, −0.02 to 0.02]; P = .87), or all-cause death (RR, 1.13 [95% CI, 0.99 to 1.29]; P = .08 and RD, 0.00 [95% CI, −0.01 to 0.01]; P = .51). The same was true for ACS, stroke, and heart failure. There was no evidence of different associations for CPAP vs ASV (all P value homogeneity >.24), and meta-regressions identified no associations of PAP with outcomes for different levels of apnea severity, follow-up duration, or adherence to PAP (all P values > .13). Conclusions and Relevance The use of PAP, compared with no treatment or sham, was not associated with reduced risks of cardiovascular outcomes or death for patients with sleep apnea. Although there are other benefits of treatment with PAP for sleep apnea, these findings do not support treatment with PAP with a goal of prevention of these outcomes.

Journal ArticleDOI
15 Feb 2017-Heart
TL;DR: A recent Cochrane review demonstrated that both non-invasive telemonitoring and structured telephone support offer statistically and clinically meaningful benefits to people with heart failure.
Abstract: Heart failure is a common and growing problem, worldwide, often leading to repeated hospitalisations, reduced quality of life, disability, loss of independence and shortened life expectancy. Managing heart failure is costly and complex for individual patients, their families and healthcare systems. A range of pharmacological agents, devices and disease management programmes have proven to be effective but are not available to all patients. Non-invasive telemonitoring and structured telephone support for patients with heart failure have been researched for almost two decades; however the jury still appears to be out for the use of this intervention in clinical practice.1 The effectiveness of structured telephone support and non-invasive telemonitoring to reduce hospitalisations and mortality in patients with heart failure was assessed by a recent Cochrane review.2 This review was undertaken as an update to a previously published version. Randomised controlled trials (RCTs) that compared structured telephone support or non-invasive telemonitoring to standard practice were included. Studies were excluded if the telemonitoring intervention included other interventions such as home visits or frequent clinic visits or implanted monitoring devices. Compared with the previously published Cochrane review, 17 new studies were identified and 24 had been included in the previous review (total of 41 studies). Two studies were multiarm and included both structured telephone support and telemonitoring; hence there were 43 comparisons in the review. The primary outcomes included all-cause mortality and all-cause and heart failure related hospitalisations which were analysed using fixed-effects models. The review demonstrated that both non-invasive telemonitoring and structured telephone support offer statistically and clinically meaningful benefits to people with heart failure.2 For non-invasive telemonitoring, a 20% reduction in the risk of all-cause mortality was observed (Relative Risk (RR) 0.80, 95% Confidence Interval (CI) 0.68 to 0.94; participants=3740; studies=17; I2=24%; Grading of Recommendations Assessment, Development and …

Journal ArticleDOI
16 Aug 2017-Polymers
TL;DR: This review considers bioreceptors to be immobilized on hydrogel based biosensors, their advantages and disadvantages, and immobilization techniques, and identifies the hydrogels that are most favored for this type of biosensor, as well as the predominant transduction strategies.
Abstract: Biosensors that detect and convert biological reactions to a measurable signal have gained much attention in recent years. Between 1950 and 2017, more than 150,000 papers have been published addressing the applications of biosensors in different industries, but to the best of our knowledge and through careful screening, critical reviews that describe hydrogel based biosensors for biomedical applications are rare. This review discusses the biomedical application of hydrogel based biosensors, based on a search performed through Web of Science Core, PubMed (NLM), and Science Direct online databases for the years 2000⁻2017. In this review, we consider bioreceptors to be immobilized on hydrogel based biosensors, their advantages and disadvantages, and immobilization techniques. We identify the hydrogels that are most favored for this type of biosensor, as well as the predominant transduction strategies. We explain biomedical applications of hydrogel based biosensors including cell metabolite and pathogen detection, tissue engineering, wound healing, and cancer monitoring, and strategies for small biomolecules such as glucose, lactate, urea, and cholesterol detection are identified.

Journal ArticleDOI
TL;DR: In this paper, the authors evaluate the feasibility of a 100% renewable electricity system using four objective criteria: (1) consistency with mainstream energy-demand forecasts; (2) simulating supply to meet demand reliably at hourly, half-hourly, and five-minute timescales, with resilience to extreme climate events; (3) identifying necessary transmission and distribution requirements; and (4) maintaining the provision of essential ancillary services.
Abstract: An effective response to climate change demands rapid replacement of fossil carbon energy sources. This must occur concurrently with an ongoing rise in total global energy consumption. While many modelled scenarios have been published claiming to show that a 100% renewable electricity system is achievable, there is no empirical or historical evidence that demonstrates that such systems are in fact feasible. Of the studies published to date, 24 have forecast regional, national or global energy requirements at sufficient detail to be considered potentially credible. We critically review these studies using four novel feasibility criteria for reliable electricity systems needed to meet electricity demand this century. These criteria are: (1) consistency with mainstream energy-demand forecasts; (2) simulating supply to meet demand reliably at hourly, half-hourly, and five-minute timescales, with resilience to extreme climate events; (3) identifying necessary transmission and distribution requirements; and (4) maintaining the provision of essential ancillary services. Evaluated against these objective criteria, none of the 24 studies provides convincing evidence that these basic feasibility criteria can be met. Of a maximum possible unweighted feasibility score of seven, the highest score for any one study was four. Eight of 24 scenarios (33%) provided no form of system simulation. Twelve (50%) relied on unrealistic forecasts of energy demand. While four studies (17%; all regional) articulated transmission requirements, only two scenarios—drawn from the same study—addressed ancillary-service requirements. In addition to feasibility issues, the heavy reliance on exploitation of hydroelectricity and biomass raises concerns regarding environmental sustainability and social justice. Strong empirical evidence of feasibility must be demonstrated for any study that attempts to construct or model a low-carbon energy future based on any combination of low-carbon technology. On the basis of this review, efforts to date seem to have substantially underestimated the challenge and delayed the identification and implementation of effective and comprehensive decarbonization pathways.

Journal ArticleDOI
TL;DR: Evidence is provided for these primary mutations in RAD51C and RAD51D in conferring PARPi sensitivity and secondary mutations as a mechanism of acquired PARPi resistance underpins the need for early delivery of PARPi therapy and for combination strategies.
Abstract: High-grade epithelial ovarian carcinomas containing mutated BRCA1 or BRCA2 (BRCA1/2) homologous recombination (HR) genes are sensitive to platinum-based chemotherapy and PARP inhibitors (PARPi), while restoration of HR function due to secondary mutations in BRCA1/2 has been recognized as an important resistance mechanism. We sequenced core HR pathway genes in 12 pairs of pretreatment and postprogression tumor biopsy samples collected from patients in ARIEL2 Part 1, a phase II study of the PARPi rucaparib as treatment for platinum-sensitive, relapsed ovarian carcinoma. In 6 of 12 pretreatment biopsies, a truncation mutation in BRCA1, RAD51C, or RAD51D was identified. In five of six paired postprogression biopsies, one or more secondary mutations restored the open reading frame. Four distinct secondary mutations and spatial heterogeneity were observed for RAD51CIn vitro complementation assays and a patient-derived xenograft, as well as predictive molecular modeling, confirmed that resistance to rucaparib was associated with secondary mutations.Significance: Analyses of primary and secondary mutations in RAD51C and RAD51D provide evidence for these primary mutations in conferring PARPi sensitivity and secondary mutations as a mechanism of acquired PARPi resistance. PARPi resistance due to secondary mutations underpins the need for early delivery of PARPi therapy and for combination strategies. Cancer Discov; 7(9); 984-98. ©2017 AACR.See related commentary by Domchek, p. 937See related article by Quigley et al., p. 999See related article by Goodall et al., p. 1006This article is highlighted in the In This Issue feature, p. 920.

Journal ArticleDOI
TL;DR: A conceptual framework for personality-dependent spatial ecology is proposed that links expectations derived from the movement ecology paradigm with behavioural reaction-norms to offer specific predictions on the interactions between environmental factors, such as resource distribution or landscape structure, and intrinsic behavioural variation.
Abstract: Recent studies have established the ecological and evolutionary importance of animal personalities. Individual differences in movement and space-use, fundamental to many personality traits (e.g. activity, boldness and exploratory behaviour) have been documented across many species and contexts, for instance personality-dependent dispersal syndromes. Yet, insights from the concurrently developing movement ecology paradigm are rarely considered and recent evidence for other personality-dependent movements and space-use lack a general unifying framework. We propose a conceptual framework for personality-dependent spatial ecology. We link expectations derived from the movement ecology paradigm with behavioural reaction-norms to offer specific predictions on the interactions between environmental factors, such as resource distribution or landscape structure, and intrinsic behavioural variation. We consider how environmental heterogeneity and individual consistency in movements that carry-over across spatial scales can lead to personality-dependent: (1) foraging search performance; (2) habitat preference; (3) home range utilization patterns; (4) social network structure and (5) emergence of assortative population structure with spatial clusters of personalities. We support our conceptual model with spatially explicit simulations of behavioural variation in space-use, demonstrating the emergence of complex population-level patterns from differences in simple individual-level behaviours. Consideration of consistent individual variation in space-use will facilitate mechanistic understanding of processes that drive social, spatial, ecological and evolutionary dynamics in heterogeneous environments.

Journal ArticleDOI
TL;DR: In this paper, the authors focused on determining whether malnutrition diagnosed by validated nutrition assessment tools such as the Subjective Global Assessment (SGA) or Mini Nutritional Assessment (MNA) is independently associated with poorer clinical outcomes in the ICU and if the use of nutrition screening tools demonstrate a similar association.
Abstract: Malnutrition is associated with poor clinical outcomes among hospitalized patients. However, studies linking malnutrition with poor clinical outcomes in the intensive care unit (ICU) often have conflicting findings due in part to the inappropriate diagnosis of malnutrition. We primarily aimed to determine whether malnutrition diagnosed by validated nutrition assessment tools such as the Subjective Global Assessment (SGA) or Mini Nutritional Assessment (MNA) is independently associated with poorer clinical outcomes in the ICU and if the use of nutrition screening tools demonstrate a similar association. PubMed, CINAHL, Scopus, and Cochrane Library were systematically searched for eligible studies. Search terms included were synonyms of malnutrition, nutritional status, screening, assessment, and intensive care unit. Eligible studies were case-control or cohort studies that recruited adults in the ICU; conducted the SGA, MNA, or used nutrition screening tools before or within 48 hours of ICU admission; and ...

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TL;DR: Early flowering provides a promising strategy for the production of advanced drought-adapted wheat cultivars and can be high both in well-watered and drought-affected field trials, where an efficient strategy of DE was associated with quick growth, yield potential and water use efficiency.
Abstract: Drought escape is a classical adaptive mechanism which involves rapid plant development to enable the completion of the full life-cycle prior to a coming drought event. This strategy is widely used in populations of native plants, and is also applicable to cereal crops such as wheat. Early flowering time and a shorter vegetative phase can be very important for wheat production in conditions of terminal drought since this can minimise exposure to dehydration during the sensitive flowering and post-anthesis grain filling periods. A gradual shift towards early flowering has been observed over the last century of wheat breeding in countries with a Mediterranean-type climate and frequent terminal drought. This trend is predicted to continue for wheat production in the coming years in response to global climate warming. The advantage of early flowering wheat is apparent under conditions of impending terminal drought. Under favourable conditions, a short vegetative phase can result in reduced plant biomass which will limit nutrients and assimilates for high grain yield in the absence of stress. However, where the early flowering trait exists in combination with other drought tolerance mechanisms and high yield potential have been reported, early flowering provides a promising strategy for the production of advanced drought-adapted wheat cultivars.

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TL;DR: Los cambios mas destacados incluyen: a) se ha diferenciado entre la exploracion espirometrica y the de los sintomas para evaluar la enfermedad pulmonar obstructiva cronica (EPOC) and b) se introduce el concepto de reduccion escalonada of the terapia en el esquema de evaluacion del tratamiento.
Abstract: Resumen Este resumen ejecutivo del Informe de 2017 de la Global Strategy for the Diagnosis, Management, and Prevention of COPD (GOLD) se basa principalmente en las modificaciones y novedades del documento anterior. Los cambios mas destacados incluyen: a) se ha diferenciado entre la exploracion espirometrica y la de los sintomas para evaluar la enfermedad pulmonar obstructiva cronica (EPOC). En la propuesta actual, los grupos ABCD se refieren exclusivamente a sintomas y antecedentes de exacerbaciones de los pacientes; b) para cada uno de los grupos, se proponen estrategias de intensificacion de los tratamientos farmacologicos; c) se introduce el concepto de reduccion escalonada de la terapia en el esquema de evaluacion del tratamiento; d) se detalla mas extensamente el tratamiento no farmacologico; y, f) se revisa la importancia de las diferentes co-morbilidades en lo que respecta al tratamiento de la EPOC.

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TL;DR: In this article, the authors examine the challenge in the context of an emerging class of polymers made from elemental sulfur and present a forward looking assessment of the opportunities for using sulfur polymers in Green Chemistry.

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TL;DR: A review of cardiometabolic diseases risk (CMD-R) genes and 24 potential pleiotropic genes that are likely to be shared between mood disorders and CMD-Rs provides insights into the shared biological mechanisms of Mood disorders and cardiometric diseases.
Abstract: Meta-analyses of genome-wide association studies (meta-GWASs) and candidate gene studies have identified genetic variants associated with cardiovascular diseases, metabolic diseases and mood disorders. Although previous efforts were successful for individual disease conditions (single disease), limited information exists on shared genetic risk between these disorders. This article presents a detailed review and analysis of cardiometabolic diseases risk (CMD-R) genes that are also associated with mood disorders. First, we reviewed meta-GWASs published until January 2016, for the diseases ‘type 2 diabetes, coronary artery disease, hypertension’ and/or for the risk factors ‘blood pressure, obesity, plasma lipid levels, insulin and glucose related traits’. We then searched the literature for published associations of these CMD-R genes with mood disorders. We considered studies that reported a significant association of at least one of the CMD-R genes and ‘depression’ or ‘depressive disorder’ or ‘depressive symptoms’ or ‘bipolar disorder’ or ‘lithium treatment response in bipolar disorder’, or ‘serotonin reuptake inhibitors treatment response in major depression’. Our review revealed 24 potential pleiotropic genes that are likely to be shared between mood disorders and CMD-Rs. These genes include MTHFR, CACNA1D, CACNB2, GNAS, ADRB1, NCAN, REST, FTO, POMC, BDNF, CREB, ITIH4, LEP, GSK3B, SLC18A1, TLR4, PPP1R1B, APOE, CRY2, HTR1A, ADRA2A, TCF7L2, MTNR1B and IGF1. A pathway analysis of these genes revealed significant pathways: corticotrophin-releasing hormone signaling, AMPK signaling, cAMP-mediated or G-protein coupled receptor signaling, axonal guidance signaling, serotonin or dopamine receptors signaling, dopamine-DARPP32 feedback in cAMP signaling, circadian rhythm signaling and leptin signaling. Our review provides insights into the shared biological mechanisms of mood disorders and cardiometabolic diseases.

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TL;DR: In patients receiving palliative care, individualized management ofdelirium precipitants and supportive strategies result in lower scores and shorter duration of target distressing delirium symptoms than when risperidone or haloperidol are added.
Abstract: Importance Antipsychotics are widely used for distressing symptoms of delirium, but efficacy has not been established in placebo-controlled trials in palliative care. Objective To determine efficacy of risperidone or haloperidol relative to placebo in relieving target symptoms of delirium associated with distress among patients receiving palliative care. Design, Setting, and Participants A double-blind, parallel-arm, dose-titrated randomized clinical trial was conducted at 11 Australian inpatient hospice or hospital palliative care services between August 13, 2008, and April 2, 2014, among participants with life-limiting illness, delirium, and a delirium symptoms score (sum of Nursing Delirium Screening Scale behavioral, communication, and perceptual items) of 1 or more. Interventions Age-adjusted titrated doses of oral risperidone, haloperidol, or placebo solution were administered every 12 hours for 72 hours, based on symptoms of delirium. Patients also received supportive care, individualized treatment of delirium precipitants, and subcutaneous midazolam hydrochloride as required for severe distress or safety. Main Outcome and Measures Improvement in mean group difference of delirium symptom score (severity range, 0-6) between baseline and day 3. Five a priori secondary outcomes: delirium severity, midazolam use, extrapyramidal effects, sedation, and survival. Results Two hundred forty-seven participants (mean [SD] age, 74.9 [9.8] years; 85 women [34.4%]; 218 with cancer [88.3%]) were included in intention-to-treat analysis (82 receiving risperidone, 81 receiving haloperidol, and 84 receiving placebo). In the primary intention-to-treat analysis, participants in the risperidone arm had delirium symptom scores that were significantly higher than those among participants in the placebo arm (on average 0.48 Units higher; 95% CI, 0.09-0.86;P = .02) at study end. Similarly, for those in the haloperidol arm, delirium symptom scores were on average 0.24 Units higher (95% CI, 0.06-0.42;P = .009) than in the placebo arm. Compared with placebo, patients in both active arms had more extrapyramidal effects (risperidone, 0.73; 95% CI, 0.09-1.37;P = .03; and haloperidol, 0.79; 95% CI, 0.17-1.41;P = .01). Participants in the placebo group had better overall survival than those receiving haloperidol (hazard ratio, 1.73; 95% CI, 1.20-2.50;P = .003), but this was not significant for placebo vs risperidone (hazard ratio, 1.29; 95% CI, 0.91-1.84;P = .14). Conclusions and Relevance In patients receiving palliative care, individualized management of delirium precipitants and supportive strategies result in lower scores and shorter duration of target distressing delirium symptoms than when risperidone or haloperidol are added. Trial Registration anzctr.org.au Identifier:ACTRN12607000562471.