Showing papers by "University of Rochester published in 2018"
Clotilde Théry1, Kenneth W. Witwer2, Elena Aikawa3, María José Alcaraz4 +414 more•Institutions (209)
TL;DR: The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities, and a checklist is provided with summaries of key points.
Abstract: The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines for the field in 2014. We now update these “MISEV2014” guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points.
5,988 citations
Gregory A. Roth1, Gregory A. Roth2, Degu Abate3, Kalkidan Hassen Abate4 +1025 more•Institutions (333)
TL;DR: Non-communicable diseases comprised the greatest fraction of deaths, contributing to 73·4% (95% uncertainty interval [UI] 72·5–74·1) of total deaths in 2017, while communicable, maternal, neonatal, and nutritional causes accounted for 18·6% (17·9–19·6), and injuries 8·0% (7·7–8·2).
5,211 citations
18 Jun 2018
TL;DR: This paper proposes residual dense block (RDB) to extract abundant local features via dense connected convolutional layers and uses global feature fusion in RDB to jointly and adaptively learn global hierarchical features in a holistic way.
Abstract: A very deep convolutional neural network (CNN) has recently achieved great success for image super-resolution (SR) and offered hierarchical features as well. However, most deep CNN based SR models do not make full use of the hierarchical features from the original low-resolution (LR) images, thereby achieving relatively-low performance. In this paper, we propose a novel residual dense network (RDN) to address this problem in image SR. We fully exploit the hierarchical features from all the convolutional layers. Specifically, we propose residual dense block (RDB) to extract abundant local features via dense connected convolutional layers. RDB further allows direct connections from the state of preceding RDB to all the layers of current RDB, leading to a contiguous memory (CM) mechanism. Local feature fusion in RDB is then used to adaptively learn more effective features from preceding and current local features and stabilizes the training of wider network. After fully obtaining dense local features, we use global feature fusion to jointly and adaptively learn global hierarchical features in a holistic way. Experiments on benchmark datasets with different degradation models show that our RDN achieves favorable performance against state-of-the-art methods.
2,860 citations
University of Rochester1, French Institute of Health and Medical Research2, Institute for Health Metrics and Evaluation3, Cairo University4, University of Extremadura5, Debre Berhan University6, University of Cambridge7, Seoul National University Hospital8, Autonomous University of Chile9, University of Pennsylvania10, Haramaya University11, Humboldt University of Berlin12, McGill University13, Karolinska Institutet14, Imperial College London15, University of Western Australia16, West Virginia University17, Hawassa University18, Tehran University of Medical Sciences19, Jordan University of Science and Technology20, Seoul National University21, Xiamen University22, University of Bari23, University of Porto24, National University of Malaysia25, University of Sydney26, Baqiyatallah University of Medical Sciences27, Iran University of Medical Sciences28, Mekelle University29, University of Western Sydney30, University of Ibadan31, La Trobe University32, Deakin University33, Ahvaz Jundishapur University of Medical Sciences34, University of Maragheh35, Utkal University36, University of North Carolina at Charlotte37, New York University38
TL;DR: Over the past generation, the global burden of Parkinson's disease has more than doubled as a result of increasing numbers of older people, with potential contributions from longer disease duration and environmental factors.
Abstract: Summary Background Neurological disorders are now the leading source of disability globally, and ageing is increasing the burden of neurodegenerative disorders, including Parkinson's disease. We aimed to determine the global burden of Parkinson's disease between 1990 and 2016 to identify trends and to enable appropriate public health, medical, and scientific responses. Methods Through a systematic analysis of epidemiological studies, we estimated global, regional, and country-specific prevalence and years of life lived with disability for Parkinson's disease from 1990 to 2016. We estimated the proportion of mild, moderate, and severe Parkinson's disease on the basis of studies that used the Hoehn and Yahr scale and assigned disability weights to each level. We jointly modelled prevalence and excess mortality risk in a natural history model to derive estimates of deaths due to Parkinson's disease. Death counts were multiplied by values from the Global Burden of Disease study's standard life expectancy to compute years of life lost. Disability-adjusted life-years (DALYs) were computed as the sum of years lived with disability and years of life lost. We also analysed results based on the Socio-demographic Index, a compound measure of income per capita, education, and fertility. Findings In 2016, 6·1 million (95% uncertainty interval [UI] 5·0–7·3) individuals had Parkinson's disease globally, compared with 2·5 million (2·0–3·0) in 1990. This increase was not solely due to increasing numbers of older people, because age-standardised prevalence rates increased by 21·7% (95% UI 18·1–25·3) over the same period (compared with an increase of 74·3%, 95% UI 69·2–79·6, for crude prevalence rates). Parkinson's disease caused 3·2 million (95% UI 2·6–4·0) DALYs and 211 296 deaths (95% UI 167 771–265 160) in 2016. The male-to-female ratios of age-standardised prevalence rates were similar in 2016 (1·40, 95% UI 1·36–1·43) and 1990 (1·37, 1·34–1·40). From 1990 to 2016, age-standardised prevalence, DALY rates, and death rates increased for all global burden of disease regions except for southern Latin America, eastern Europe, and Oceania. In addition, age-standardised DALY rates generally increased across the Socio-demographic Index. Interpretation Over the past generation, the global burden of Parkinson's disease has more than doubled as a result of increasing numbers of older people, with potential contributions from longer disease duration and environmental factors. Demographic and potentially other factors are poised to increase the future burden of Parkinson's disease substantially. Funding Bill & Melinda Gates Foundation.
1,388 citations
Brookhaven National Laboratory1, Columbia University2, University of Texas at Austin3, Utah State University4, University of Rochester5, Pacific Northwest National Laboratory6, Texas A&M University7, Yale University8, Northwestern University9, Pennsylvania State University10, Arizona State University11, National Renewable Energy Laboratory12, Cornell University13, Washington State University14, University of Notre Dame15, Massachusetts Institute of Technology16
TL;DR: Research prospects for more sustainable routes to nitrogen commodity chemicals are reviewed, considering developments in enzymatic, homogeneous, and heterogeneous catalysis, as well as electrochemical, photochemical, and plasma-based approaches.
Abstract: BACKGROUND The invention of the Haber-Bosch (H-B) process in the early 1900s to produce ammonia industrially from nitrogen and hydrogen revolutionized the manufacture of fertilizer and led to fundamental changes in the way food is produced. Its impact is underscored by the fact that about 50% of the nitrogen atoms in humans today originate from this single industrial process. In the century after the H-B process was invented, the chemistry of carbon moved to center stage, resulting in remarkable discoveries and a vast array of products including plastics and pharmaceuticals. In contrast, little has changed in industrial nitrogen chemistry. This scenario reflects both the inherent efficiency of the H-B process and the particular challenge of breaking the strong dinitrogen bond. Nonetheless, the reliance of the H-B process on fossil fuels and its associated high CO 2 emissions have spurred recent interest in finding more sustainable and environmentally benign alternatives. Nitrogen in its more oxidized forms is also industrially, biologically, and environmentally important, and synergies in new combinations of oxidative and reductive transformations across the nitrogen cycle could lead to improved efficiencies. ADVANCES Major effort has been devoted to developing alternative and environmentally friendly processes that would allow NH 3 production at distributed sources under more benign conditions, rather than through the large-scale centralized H-B process. Hydrocarbons (particularly methane) and water are the only two sources of hydrogen atoms that can sustain long-term, large-scale NH 3 production. The use of water as the hydrogen source for NH 3 production requires substantially more energy than using methane, but it is also more environmentally benign, does not contribute to the accumulation of greenhouse gases, and does not compete for valuable and limited hydrocarbon resources. Microbes living in all major ecosystems are able to reduce N 2 to NH 3 by using the enzyme nitrogenase. A deeper understanding of this enzyme could lead to more efficient catalysts for nitrogen reduction under ambient conditions. Model molecular catalysts have been designed that mimic some of the functions of the active site of nitrogenase. Some modest success has also been achieved in designing electrocatalysts for dinitrogen reduction. Electrochemistry avoids the expense and environmental damage of steam reforming of methane (which accounts for most of the cost of the H-B process), and it may provide a means for distributed production of ammonia. On the oxidative side, nitric acid is the principal commodity chemical containing oxidized nitrogen. Nearly all nitric acid is manufactured by oxidation of NH 3 through the Ostwald process, but a more direct reaction of N 2 with O 2 might be practically feasible through further development of nonthermal plasma technology. Heterogeneous NH 3 oxidation with O 2 is at the heart of the Ostwald process and is practiced in a variety of environmental protection applications as well. Precious metals remain the workhorse catalysts, and opportunities therefore exist to develop lower-cost materials with equivalent or better activity and selectivity. Nitrogen oxides are also environmentally hazardous pollutants generated by industrial and transportation activities, and extensive research has gone into developing and applying reduction catalysts. Three-way catalytic converters are operating on hundreds of millions of vehicles worldwide. However, increasingly stringent emissions regulations, coupled with the low exhaust temperatures of high-efficiency engines, present challenges for future combustion emissions control. Bacterial denitrification is the natural analog of this chemistry and another source of study and inspiration for catalyst design. OUTLOOK Demands for greater energy efficiency, smaller-scale and more flexible processes, and environmental protection provide growing impetus for expanding the scope of nitrogen chemistry. Nitrogenase, as well as nitrifying and denitrifying enzymes, will eventually be understood in sufficient detail that robust molecular catalytic mimics will emerge. Electrochemical and photochemical methods also demand more study. Other intriguing areas of research that have provided tantalizing results include chemical looping and plasma-driven processes. The grand challenge in the field of nitrogen chemistry is the development of catalysts and processes that provide simple, low-energy routes to the manipulation of the redox states of nitrogen.
1,153 citations
Monash University1, National Health and Medical Research Council2, University of New South Wales3, University of Pennsylvania4, Erasmus University Rotterdam5, Oulu University Hospital6, University of Adelaide7, Odense University Hospital8, State University of New York System9, Australian Catholic University10, University Medical Center Utrecht11, Sanjay Gandhi Post Graduate Institute of Medical Sciences12, University of Chile13, university of lille14, Utrecht University15, Imperial College London16, University of Western Australia17, Karolinska Institutet18, University of Rochester19, Pennsylvania State University20, Peking University21, Cornell University22, Royal College of Surgeons in Ireland23, University of Hong Kong24, Columbia University Medical Center25, Pennington Biomedical Research Center26, Agostino Gemelli University Polyclinic27, Deakin University28, Universidade Federal do Rio Grande do Sul29, Victoria University, Australia30, University of Helsinki31, Queen Mary University of London32, Taipei Medical University Hospital33, University of Cape Town34, Norwegian University of Science and Technology35, Children's Hospital of Philadelphia36, University of Colombo37, University of Pittsburgh38, Boston Children's Hospital39, Hacettepe University40
TL;DR: The international guideline for the assessment and management of PCOS provides clinicians with clear advice on best practice based on the best available evidence, expert multidisciplinary input and consumer preferences to promote consistent, evidence-based care and improve the experience and health outcomes of women with PCOS.
Abstract: Study Question What is the recommended assessment and management of women with polycystic ovary syndrome (PCOS), based on the best available evidence, clinical expertise, and consumer preference? Summary Answer International evidence-based guidelines including 166 recommendations and practice points, addressed prioritized questions to promote consistent, evidence-based care and improve the experience and health outcomes of women with PCOS. What Is Known Already Previous guidelines either lacked rigorous evidence-based processes, did not engage consumer and international multidisciplinary perspectives, or were outdated. Diagnosis of PCOS remains controversial and assessment and management are inconsistent. The needs of women with PCOS are not being adequately met and evidence practice gaps persist. Study Design, Size, Duration International evidence-based guideline development engaged professional societies and consumer organizations with multidisciplinary experts and women with PCOS directly involved at all stages. Appraisal of Guidelines for Research and Evaluation (AGREE) II-compliant processes were followed, with extensive evidence synthesis. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework was applied across evidence quality, feasibility, acceptability, cost, implementation and ultimately recommendation strength. Participants/Materials, Setting, Methods Governance included a six continent international advisory and a project board, five guideline development groups, and consumer and translation committees. Extensive health professional and consumer engagement informed guideline scope and priorities. Engaged international society-nominated panels included pediatrics, endocrinology, gynecology, primary care, reproductive endocrinology, obstetrics, psychiatry, psychology, dietetics, exercise physiology, public health and other experts, alongside consumers, project management, evidence synthesis, and translation experts. Thirty-seven societies and organizations covering 71 countries engaged in the process. Twenty face-to-face meetings over 15 months addressed 60 prioritized clinical questions involving 40 systematic and 20 narrative reviews. Evidence-based recommendations were developed and approved via consensus voting within the five guideline panels, modified based on international feedback and peer review, with final recommendations approved across all panels. Main Results and the Role of Chance The evidence in the assessment and management of PCOS is generally of low to moderate quality. The guideline provides 31 evidence based recommendations, 59 clinical consensus recommendations and 76 clinical practice points all related to assessment and management of PCOS. Key changes in this guideline include: i) considerable refinement of individual diagnostic criteria with a focus on improving accuracy of diagnosis; ii) reducing unnecessary testing; iii) increasing focus on education, lifestyle modification, emotional wellbeing and quality of life; and iv) emphasizing evidence based medical therapy and cheaper and safer fertility management. Limitations, Reasons for Caution Overall evidence is generally low to moderate quality, requiring significantly greater research in this neglected, yet common condition, especially around refining specific diagnostic features in PCOS. Regional health system variation is acknowledged and a process for guideline and translation resource adaptation is provided. Wider Implications of the Findings The international guideline for the assessment and management of PCOS provides clinicians with clear advice on best practice based on the best available evidence, expert multidisciplinary input and consumer preferences. Research recommendations have been generated and a comprehensive multifaceted dissemination and translation program supports the guideline with an integrated evaluation program. Study Funding/Competing Interest(S) The guideline was primarily funded by the Australian National Health and Medical Research Council of Australia (NHMRC) supported by a partnership with ESHRE and the American Society for Reproductive Medicine. Guideline development group members did not receive payment. Travel expenses were covered by the sponsoring organizations. Disclosures of conflicts of interest were declared at the outset and updated throughout the guideline process, aligned with NHMRC guideline processes. Full details of conflicts declared across the guideline development groups are available at https://www.monash.edu/medicine/sphpm/mchri/pcos/guideline in the Register of disclosures of interest. Of named authors, Dr Costello has declared shares in Virtus Health and past sponsorship from Merck Serono for conference presentations. Prof. Laven declared grants from Ferring, Euroscreen and personal fees from Ferring, Euroscreen, Danone and Titus Healthcare. Prof. Norman has declared a minor shareholder interest in an IVF unit. The remaining authors have no conflicts of interest to declare. The guideline was peer reviewed by special interest groups across our partner and collaborating societies and consumer organizations, was independently assessed against AGREEII criteria and underwent methodological review. This guideline was approved by all members of the guideline development groups and was submitted for final approval by the NHMRC.
1,088 citations
University of Rochester1, University of California, San Francisco2, University of Gothenburg3, University of Birmingham4, University of Bonn5, University of Michigan6, University of Texas Health Science Center at San Antonio7, Columbia University8, Complutense University of Madrid9, University of Hong Kong10
TL;DR: An overview for the new classification of periodontal and peri-implant diseases and conditions is presented, along with a condensed scheme for each of four workgroup sections, but readers are directed to the pertinent consensus reports and review papers for a thorough discussion of the rationale, criteria, and interpretation of the proposed classification.
Abstract: A classification scheme for periodontal and peri-implant diseases and conditions is necessary for clinicians to properly diagnose and treat patients as well as for scientists to investigate etiology, pathogenesis, natural history, and treatment of the diseases and conditions. This paper summarizes the proceedings of the World Workshop on the Classification of Periodontal and Peri-implant Diseases and Conditions. The workshop was co-sponsored by the American Academy of Periodontology (AAP) and the European Federation of Periodontology (EFP) and included expert participants from all over the world. Planning for the conference, which was held in Chicago on November 9 to 11, 2017, began in early 2015. An organizing committee from the AAP and EFP commissioned 19 review papers and four consensus reports covering relevant areas in periodontology and implant dentistry. The authors were charged with updating the 1999 classification of periodontal diseases and conditions and developing a similar scheme for peri-implant diseases and conditions. Reviewers and workgroups were also asked to establish pertinent case definitions and to provide diagnostic criteria to aid clinicians in the use of the new classification. All findings and recommendations of the workshop were agreed to by consensus. This introductory paper presents an overview for the new classification of periodontal and peri-implant diseases and conditions, along with a condensed scheme for each of four workgroup sections, but readers are directed to the pertinent consensus reports and review papers for a thorough discussion of the rationale, criteria, and interpretation of the proposed classification. Changes to the 1999 classification are highlighted and discussed. Although the intent of the workshop was to base classification on the strongest available scientific evidence, lower level evidence and expert opinion were inevitably used whenever sufficient research data were unavailable. The scope of this workshop was to align and update the classification scheme to the current understanding of periodontal and peri-implant diseases and conditions. This introductory overview presents the schematic tables for the new classification of periodontal and peri-implant diseases and conditions and briefly highlights changes made to the 1999 classification. It cannot present the wealth of information included in the reviews, case definition papers, and consensus reports that has guided the development of the new classification, and reference to the consensus and case definition papers is necessary to provide a thorough understanding of its use for either case management or scientific investigation. Therefore, it is strongly recommended that the reader use this overview as an introduction to these subjects. Accessing this publication online will allow the reader to use the links in this overview and the tables to view the source papers (Table 1).
1,066 citations
TL;DR: In patients with MCI, exercise training (6 months) is likely to improve cognitive measures and cognitive training may improve cognitive Measures, and no high-quality evidence exists to support pharmacologic treatments for MCI.
Abstract: Objective To update the 2001 American Academy of Neurology (AAN) guideline on mild cognitive impairment (MCI). Methods The guideline panel systematically reviewed MCI prevalence, prognosis, and treatment articles according to AAN evidence classification criteria, and based recommendations on evidence and modified Delphi consensus. Results MCI prevalence was 6.7% for ages 60–64, 8.4% for 65–69, 10.1% for 70–74, 14.8% for 75–79, and 25.2% for 80–84. Cumulative dementia incidence was 14.9% in individuals with MCI older than age 65 years followed for 2 years. No high-quality evidence exists to support pharmacologic treatments for MCI. In patients with MCI, exercise training (6 months) is likely to improve cognitive measures and cognitive training may improve cognitive measures. Major recommendations Clinicians should assess for MCI with validated tools in appropriate scenarios (Level B). Clinicians should evaluate patients with MCI for modifiable risk factors, assess for functional impairment, and assess for and treat behavioral/neuropsychiatric symptoms (Level B). Clinicians should monitor cognitive status of patients with MCI over time (Level B). Cognitively impairing medications should be discontinued where possible and behavioral symptoms treated (Level B). Clinicians may choose not to offer cholinesterase inhibitors (Level B); if offering, they must first discuss lack of evidence (Level A). Clinicians should recommend regular exercise (Level B). Clinicians may recommend cognitive training (Level C). Clinicians should discuss diagnosis, prognosis, long-term planning, and the lack of effective medicine options (Level B), and may discuss biomarker research with patients with MCI and families (Level C).
1,064 citations
TL;DR: Geriatric assessment (GA) should be used to identify vulnerabilities that are not routinely captured in oncology assessments and clinicians should take into account GA results when recommending chemotherapy.
Abstract: Purpose To provide guidance regarding the practical assessment and management of vulnerabilities in older patients undergoing chemotherapy. Methods An Expert Panel was convened to develop clinical practice guideline recommendations based on a systematic review of the medical literature. Results A total of 68 studies met eligibility criteria and form the evidentiary basis for the recommendations. Recommendations In patients ≥ 65 years receiving chemotherapy, geriatric assessment (GA) should be used to identify vulnerabilities that are not routinely captured in oncology assessments. Evidence supports, at a minimum, assessment of function, comorbidity, falls, depression, cognition, and nutrition. The Panel recommends instrumental activities of daily living to assess for function, a thorough history or validated tool to assess comorbidity, a single question for falls, the Geriatric Depression Scale to screen for depression, the Mini-Cog or the Blessed Orientation-Memory-Concentration test to screen for cognitive impairment, and an assessment of unintentional weight loss to evaluate nutrition. Either the CARG (Cancer and Aging Research Group) or CRASH (Chemotherapy Risk Assessment Scale for High-Age Patients) tools are recommended to obtain estimates of chemotherapy toxicity risk; the Geriatric-8 or Vulnerable Elders Survey-13 can help to predict mortality. Clinicians should use a validated tool listed at ePrognosis to estimate noncancer-based life expectancy ≥ 4 years. GA results should be applied to develop an integrated and individualized plan that informs cancer management and to identify nononcologic problems amenable to intervention. Collaborating with caregivers is essential to implementing GA-guided interventions. The Panel suggests that clinicians take into account GA results when recommending chemotherapy and that the information be provided to patients and caregivers to guide treatment decision making. Clinicians should implement targeted, GA-guided interventions to manage nononcologic problems. Additional information is available at www.asco.org/supportive-care-guidelines .
835 citations
McGill University1, Johns Hopkins University School of Medicine2, Massachusetts Institute of Technology3, University of Rochester4, Cold Spring Harbor Laboratory5, University of Cambridge6, Max Delbrück Center for Molecular Medicine7, National Institutes of Health8, University of British Columbia9, Cornell University10
TL;DR: The fundamental properties of TEs and their complex interactions with their cellular environment are introduced, which are crucial to understanding their impact and manifold consequences for organismal biology.
Abstract: Transposable elements (TEs) are major components of eukaryotic genomes. However, the extent of their impact on genome evolution, function, and disease remain a matter of intense interrogation. The rise of genomics and large-scale functional assays has shed new light on the multi-faceted activities of TEs and implies that they should no longer be marginalized. Here, we introduce the fundamental properties of TEs and their complex interactions with their cellular environment, which are crucial to understanding their impact and manifold consequences for organismal biology. While we draw examples primarily from mammalian systems, the core concepts outlined here are relevant to a broad range of organisms.
691 citations
Case Western Reserve University1, Newcastle University2, Research Triangle Park3, Seattle Children's4, Boston Children's Hospital5, Duke University6, University of Pittsburgh7, Children's Hospital of Eastern Ontario8, University of Rochester9, Centers for Disease Control and Prevention10, Children's Hospital of Philadelphia11, Johns Hopkins University12, University of Rochester Medical Center13
TL;DR: Care considerations for diagnosis of DMD and neuromuscular, rehabilitation, endocrine (growth, puberty, and adrenal insufficiency), and gastrointestinal (including nutrition and dysphagia) management are presented.
Abstract: Since the publication of the Duchenne muscular dystrophy (DMD) care considerations in 2010, multidisciplinary care of this severe, progressive neuromuscular disease has evolved. In conjunction with improved patient survival, a shift to more anticipatory diagnostic and therapeutic strategies has occurred, with a renewed focus on patient quality of life. In 2014, a steering committee of experts from a wide range of disciplines was established to update the 2010 DMD care considerations, with the goal of improving patient care. The new care considerations aim to address the needs of patients with prolonged survival, to provide guidance on advances in assessments and interventions, and to consider the implications of emerging genetic and molecular therapies for DMD. The committee identified 11 topics to be included in the update, eight of which were addressed in the original care considerations. The three new topics are primary care and emergency management, endocrine management, and transitions of care across the lifespan. In part 1 of this three-part update, we present care considerations for diagnosis of DMD and neuromuscular, rehabilitation, endocrine (growth, puberty, and adrenal insufficiency), and gastrointestinal (including nutrition and dysphagia) management.
TL;DR: This survey reviews the approaches developed to reproduce various mobility patterns, with the main focus on recent developments, and organizes the subject by differentiating between individual and population mobility and also between short-range and long-range mobility.
University of South Florida1, Washington University in St. Louis2, University of Texas MD Anderson Cancer Center3, Oregon Health & Science University4, University of Kansas5, Cornell University6, Medical University of South Carolina7, Vanderbilt University8, Northside Hospital9, Harvard University10, University of Michigan11, University of California, Los Angeles12, University of California, San Diego13, University of Rochester14, Fred Hutchinson Cancer Research Center15, Stanford University16
TL;DR: CPX-351 treatment is associated with significantly longer survival compared with conventional 7+3 in older adults with newly diagnosed sAML, and improved outcomes were observed across age-groups and AML subtypes.
Abstract: Purpose CPX-351 is a dual-drug liposomal encapsulation of cytarabine and daunorubicin that delivers a synergistic 5:1 drug ratio into leukemia cells to a greater extent than normal bone marrow cells Prior clinical studies demonstrated a sustained drug ratio and exposure in vivo and prolonged survival versus standard-of-care cytarabine plus daunorubicin chemotherapy (7+3 regimen) in older patients with newly diagnosed secondary acute myeloid leukemia (sAML) Patients and Methods In this open-label, randomized, phase III trial, 309 patients age 60 to 75 years with newly diagnosed high-risk/sAML received one to two induction cycles of CPX-351 or 7+3 followed by consolidation therapy with a similar regimen The primary end point was overall survival Results CPX-351 significantly improved median overall survival versus 7+3 (956 v 595 months; hazard ratio, 069; 95% CI, 052 to 090; one-sided P = 003) Overall remission rate was also significantly higher with CPX-351 versus 7+3 (477% v 333%; two-sided P = 016) Improved outcomes were observed across age-groups and AML subtypes The incidences of nonhematologic adverse events were comparable between arms, despite a longer treatment phase and prolonged time to neutrophil and platelet count recovery with CPX-351 Early mortality rates with CPX-351 and 7+3 were 59% and 106% (two-sided P = 149) through day 30 and 137% and 212% (two-sided P = 097) through day 60 Conclusion CPX-351 treatment is associated with significantly longer survival compared with conventional 7+3 in older adults with newly diagnosed sAML The safety profile of CPX-351 was similar to that of conventional 7+3 therapy
Ohio State University1, Washington University in St. Louis2, Duke University3, University of Rochester4, Stanford University5, City of Hope National Medical Center6, Dana Corporation7, University of Chicago8, University of Calgary9, Harvard University10, National Institutes of Health11, Loyola University Chicago12
TL;DR: Among older patients with untreated CLL, treatment with ibrutinib was superior to treatment with bendamustine plus rituximab with regard to progression‐free survival, and there was no significant difference among the three treatment groups with respect to overall survival.
Abstract: Background Ibrutinib has been approved by the Food and Drug Administration for the treatment of patients with untreated chronic lymphocytic leukemia (CLL) since 2016 but has not been compared with chemoimmunotherapy. We conducted a phase 3 trial to evaluate the efficacy of ibrutinib, either alone or in combination with rituximab, relative to chemoimmunotherapy. Methods Patients 65 years of age or older who had untreated CLL were randomly assigned to receive bendamustine plus rituximab, ibrutinib, or ibrutinib plus rituximab. The primary end point was progression-free survival. The Alliance Data and Safety Monitoring Board made the decision to release the data after the protocol-specified efficacy threshold had been met. Results A total of 183 patients were assigned to receive bendamustine plus rituximab, 182 to receive ibrutinib, and 182 to receive ibrutinib plus rituximab. Median progression-free survival was reached only with bendamustine plus rituximab. The estimated percentage of patients wit...
Fredrick R. Schumacher1, Ali Amin Al Olama2, Sonja I. Berndt3, Sara Benlloch2 +204 more•Institutions (79)
TL;DR: A large meta-analysis combining genome-wide and custom high-density genotyping array data identifies 63 new susceptibility loci for prostate cancer, enhancing fine-mapping efforts and providing insights into the underlying biology of PrCa1.
Abstract: Genome-wide association studies (GWAS) and fine-mapping efforts to date have identified more than 100 prostate cancer (PrCa)-susceptibility loci. We meta-analyzed genotype data from a custom high-density array of 46,939 PrCa cases and 27,910 controls of European ancestry with previously genotyped data of 32,255 PrCa cases and 33,202 controls of European ancestry. Our analysis identified 62 novel loci associated (P C, p.Pro1054Arg) in ATM and rs2066827 (OR = 1.06; P = 2.3 × 10−9; T>G, p.Val109Gly) in CDKN1B. The combination of all loci captured 28.4% of the PrCa familial relative risk, and a polygenic risk score conferred an elevated PrCa risk for men in the ninetieth to ninety-ninth percentiles (relative risk = 2.69; 95% confidence interval (CI): 2.55–2.82) and first percentile (relative risk = 5.71; 95% CI: 5.04–6.48) risk stratum compared with the population average. These findings improve risk prediction, enhance fine-mapping, and provide insight into the underlying biology of PrCa1. A large meta-analysis combining genome-wide and custom high-density genotyping array data identifies 63 new susceptibility loci for prostate cancer, enhancing fine-mapping efforts and providing insights into the underlying biology.
TL;DR: In this paper, the authors highlight the progress in three leading material platforms: diamond, silicon carbide and atomically thin semiconductors, with a focus on applications in quantum networks.
Abstract: A central goal in quantum optics and quantum information science is the development of quantum networks to generate entanglement between distributed quantum memories. Experimental progress relies on the quality and efficiency of the light–matter quantum interface connecting the quantum states of photons to internal states of quantum emitters. Quantum emitters in solids, which have properties resembling those of atoms and ions, offer an opportunity for realizing light–matter quantum interfaces in scalable and compact hardware. These quantum emitters require a material platform that enables stable spin and optical properties, as well as a robust manufacturing of quantum photonic circuits. Because no emitter system is yet perfect and different applications may require different properties, several light–matter quantum interfaces are being developed in various platforms. This Review highlights the progress in three leading material platforms: diamond, silicon carbide and atomically thin semiconductors. Atom-like quantum emitters in solids have emerged as promising building blocks for quantum information processing. In this Review, recent advances in three leading material platforms—diamond, silicon carbide and atomically thin semiconductors—are summarized, with a focus on applications in quantum networks
TL;DR: The current knowledge on osteoblast–osteoclast communication is summarized and drugs could be developed by enhancing or restricting some of these interactions.
Abstract: Bone homeostasis depends on the resorption of bones by osteoclasts and formation of bones by the osteoblasts. Imbalance of this tightly coupled process can cause diseases such as osteoporosis. Thus, the mechanisms that regulate communication between osteoclasts and osteoblasts are critical to bone cell biology. It has been shown that osteoblasts and osteoclasts can communicate with each other through direct cell-cell contact, cytokines, and extracellular matrix interaction. Osteoblasts can affect osteoclast formation, differentiation, or apoptosis through several pathways, such as OPG/RANKL/RANK, RANKL/LGR4/RANK, Ephrin2/ephB4, and Fas/FasL pathways. Conversely, osteoclasts also influence formation of bones by osteoblasts via the d2 isoform of the vacuolar (H+) ATPase (v-ATPase) V0 domain (Atp6v0d2), complement component 3a, semaphorin 4D or microRNAs. In addition, cytokines released from the resorbed bone matrix, such as TGF-β and IGF-1, also affect the activity of osteoblasts. Drugs could be developed by enhancing or restricting some of these interactions. Several reviews have been performed on the osteoblast-osteoclast communication. However, few reviews have shown the research advances in the recent years. In this review, we summarized the current knowledge on osteoblast-osteoclast communication.
TL;DR: CSF flow speeds match the instantaneous speeds of the pulsing artery walls that form the inner boundaries of the PVSs, suggesting arterial wall motion is the principal driving mechanism, via a process known as perivascular pumping.
Abstract: Flow of cerebrospinal fluid (CSF) through perivascular spaces (PVSs) in the brain is important for clearance of metabolic waste. Arterial pulsations are thought to drive flow, but this has never been quantitatively shown. We used particle tracking to quantify CSF flow velocities in PVSs of live mice. CSF flow is pulsatile and driven primarily by the cardiac cycle. The speed of the arterial wall matches that of the CSF, suggesting arterial wall motion is the principal driving mechanism, via a process known as perivascular pumping. Increasing blood pressure leaves the artery diameter unchanged but changes the pulsations of the arterial wall, increasing backflow and thereby reducing net flow in the PVS. Perfusion-fixation alters the normal flow direction and causes a 10-fold reduction in PVS size. We conclude that particle tracking velocimetry enables the study of CSF flow in unprecedented detail and that studying the PVS in vivo avoids fixation artifacts.
TL;DR: In this paper, the discriminating variables and the algorithms used for heavy-flavour jet identification during the first years of operation of the CMS experiment in proton-proton collisions at a centre-of-mass energy of 13 TeV, are presented.
Abstract: Many measurements and searches for physics beyond the standard model at the LHC rely on the efficient identification of heavy-flavour jets, i.e. jets originating from bottom or charm quarks. In this paper, the discriminating variables and the algorithms used for heavy-flavour jet identification during the first years of operation of the CMS experiment in proton-proton collisions at a centre-of-mass energy of 13 TeV, are presented. Heavy-flavour jet identification algorithms have been improved compared to those used previously at centre-of-mass energies of 7 and 8 TeV. For jets with transverse momenta in the range expected in simulated events, these new developments result in an efficiency of 68% for the correct identification of a b jet for a probability of 1% of misidentifying a light-flavour jet. The improvement in relative efficiency at this misidentification probability is about 15%, compared to previous CMS algorithms. In addition, for the first time algorithms have been developed to identify jets containing two b hadrons in Lorentz-boosted event topologies, as well as to tag c jets. The large data sample recorded in 2016 at a centre-of-mass energy of 13 TeV has also allowed the development of new methods to measure the efficiency and misidentification probability of heavy-flavour jet identification algorithms. The b jet identification efficiency is measured with a precision of a few per cent at moderate jet transverse momenta (between 30 and 300 GeV) and about 5% at the highest jet transverse momenta (between 500 and 1000 GeV).
TL;DR: A contamination versus hit rate analysis is presented and demonstrates that BANYAN {\Sigma} achieves a better classification performance than other moving group classification tools, especially in terms of cross-contamination between young associations.
Abstract: BANYAN {\Sigma} is a new Bayesian algorithm to identify members of young stellar associations within 150 pc of the Sun. It includes 27 young associations with ages in the range ~1-800 Myr, modelled with multivariate Gaussians in 6-dimensional XYZUVW space. It is the first such multi-associations classification tool to include the nearest sub-groups of the Sco-Cen OB star-forming region, the IC 2602, IC 2391, Pleiades and Platais 8 clusters, and the {\rho} Ophiuci, Corona Australis, and Taurus star-formation regions. A model of field stars is built from a mixture of multivariate Gaussians based on the Besan\c{c}on Galactic model. The algorithm can derive membership probabilities for objects with only sky coordinates and proper motion, but can also include parallax and radial velocity measurements, as well as spectrophotometric distance constraints from sequences in color-magnitude or spectral type-magnitude diagrams. BANYAN {\Sigma} benefits from an analytical solution to the Bayesian marginalization integrals that makes it more accurate and significantly faster than its predecessor BANYAN II. A contamination versus hit rate analysis is presented and demonstrates that BANYAN {\Sigma} achieves a better classification performance than other moving group classification tools, especially in terms of cross-contamination between young associations. An updated list of bona fide members in the 27 young associations, augmented by the Gaia-DR1 release, are presented. This new tool will make it possible to analyze large data sets such as the upcoming Gaia-DR2 to identify new young stars. IDL and Python versions of BANYAN {\Sigma} are made available with this publication. (shortened)
TL;DR: It is shown that a PLQY up to 79% and linewidth of 20 nm can be reached by controlling crystal rigidity and electron–phonon interactions, and that molecular motion is slowest, and rigidity greatest, in the brightest emitter.
Abstract: Low-dimensional perovskites have—in view of their high radiative recombination rates—shown great promise in achieving high luminescence brightness and colour saturation. Here we investigate the effect of electron–phonon interactions on the luminescence of single crystals of two-dimensional perovskites, showing that reducing these interactions can lead to bright blue emission in two-dimensional perovskites. Resonance Raman spectra and deformation potential analysis show that strong electron–phonon interactions result in fast non-radiative decay, and that this lowers the photoluminescence quantum yield (PLQY). Neutron scattering, solid-state NMR measurements of spin–lattice relaxation, density functional theory simulations and experimental atomic displacement measurements reveal that molecular motion is slowest, and rigidity greatest, in the brightest emitter. By varying the molecular configuration of the ligands, we show that a PLQY up to 79% and linewidth of 20 nm can be reached by controlling crystal rigidity and electron–phonon interactions. Designing crystal structures with electron–phonon interactions in mind offers a previously underexplored avenue to improve optoelectronic materials' performance. Films of exfoliated crystals of two-dimensional hybrid metal halide perovskites with phenyl groups as organic cations show increased molecular rigidity, reduced electron–phonon interactions and blue emission with photoluminescence quantum yield approaching 80%.
TL;DR: Evidence supports the use of ketamine for chronic pain, but the level of evidence varies by condition and dose range; larger studies are needed to better quantify efficacy, improve patient selection, refine the therapeutic dose range, determine the effectiveness of nonintravenous ketamine alternatives, and develop a greater understanding of the long-term risks of repeated treatments.
TL;DR: This study presents extended follow-up of an earlier analysis of environmental lead exposure to all-cause mortality, cardiovascular disease mortality, and ischaemic heart disease mortality in the USA, which found an increase in the concentration of lead in blood from 1·0 μg/dL to 6·7 μg/DL, which represents the tenth to 90th percentiles was associated with all- Cause mortality.
Abstract: Summary Background Lead exposure is a risk factor for cardiovascular disease mortality, but the number of deaths in the USA attributable to lead exposure is poorly defined. We aimed to quantify the relative contribution of environmental lead exposure to all-cause mortality, cardiovascular disease mortality, and ischaemic heart disease mortality. Methods Our study population comprised a nationally representative sample of adults aged 20 years or older who were enrolled in the Third National Health and Nutrition Examination Survey (NHANES-III) between 1988 and 1994 and followed up to Dec 31, 2011. Participants had completed a medical examination and home interview and had results for concentrations of lead in blood, cadmium in urine, and other relevant covariates. Individuals were linked with the National Death Index. This study presents extended follow-up of an earlier analysis. Findings We included 14 289 adults in our study. The geometric mean concentration of lead in blood was 2·71 μg/dL (geometric SE 1·31). 3632 (20%) participants had a concentration of lead in blood of at least 5 μg/dL (≥0·24 μmol/L). During median follow-up of 19·3 years (IQR 17·6–21·0), 4422 people died, 1801 (38%) from cardiovascular disease and 988 (22%) from ischaemic heart disease. An increase in the concentration of lead in blood from 1·0 μg/dL to 6·7 μg/dL (0·048 μmol/L to 0·324 μmol/L), which represents the tenth to 90th percentiles, was associated with all-cause mortality (hazard ratio 1·37, 95% CI 1·17–1·60), cardiovascular disease mortality (1·70, 1·30–2·22), and ischaemic heart disease mortality (2·08, 1·52–2·85). The population attributable fraction of the concentration of lead in blood for all-cause mortality was 18·0% (95% CI 10·9–26·1), which is equivalent to 412 000 deaths annually. Respective fractions were 28·7% (15·5–39·5) for cardiovascular disease mortality and 37·4% (23·4–48·6) for ischaemic heart disease mortality, which correspond to 256 000 deaths a year from cardiovascular disease and 185 000 deaths a year from ischaemic heart disease. Interpretation Low-level environmental lead exposure is an important, but largely overlooked, risk factor for cardiovascular disease mortality in the USA. A comprehensive strategy to prevent deaths from cardiovascular disease should include efforts to reduce lead exposure. Funding The Artemis Fund and Simon Fraser University.
TL;DR: It is concur that CSF influx is higher in wild-type mice than in four different Aqp4 KO lines and in one line that lacks perivascular AQP4 (Snta1 KO), and it is reported that intrastriatal injections suppress glymphatic function.
Abstract: The glymphatic system is a brain-wide clearance pathway; its impairment contributes to the accumulation of amyloid-β. Influx of cerebrospinal fluid (CSF) depends upon the expression and perivascular localization of the astroglial water channel aquaporin-4 (AQP4). Prompted by a recent failure to find an effect of Aqp4 knock-out (KO) on CSF and interstitial fluid (ISF) tracer transport, five groups re-examined the importance of AQP4 in glymphatic transport. We concur that CSF influx is higher in wild-type mice than in four different Aqp4 KO lines and in one line that lacks perivascular AQP4 (Snta1 KO). Meta-analysis of all studies demonstrated a significant decrease in tracer transport in KO mice and rats compared to controls. Meta-regression indicated that anesthesia, age, and tracer delivery explain the opposing results. We also report that intrastriatal injections suppress glymphatic function. This validates the role of AQP4 and shows that glymphatic studies must avoid the use of invasive procedures.
TL;DR: A large-scale cohort comparison study found that the Safety Planning Intervention was associated with a reduction in suicidal behavior and increased treatment engagement among suicidal patients following ED discharge and may be a valuable clinical tool in health care settings.
Abstract: Importance Suicidal behavior is a major public health problem in the United States. The suicide rate has steadily increased over the past 2 decades; middle-aged men and military veterans are at particularly high risk. There is a dearth of empirically supported brief intervention strategies to address this problem in health care settings generally and particularly in emergency departments (EDs), where many suicidal patients present for care. Objective To determine whether the Safety Planning Intervention (SPI), administered in EDs with follow-up contact for suicidal patients, was associated with reduced suicidal behavior and improved outpatient treatment engagement in the 6 months following discharge, an established high-risk period. Design, Setting, and Participants Cohort comparison design with 6-month follow-up at 9 EDs (5 intervention sites and 4 control sites) in Veterans Health Administration hospital EDs. Patients were eligible for the study if they were 18 years or older, had an ED visit for a suicide-related concern, had inpatient hospitalization not clinically indicated, and were able to read English. Data were collected between 2010 and 2015; data were analyzed between 2016 and 2018. Interventions The intervention combines SPI and telephone follow-up. The SPI was defined as a brief clinical intervention that combined evidence-based strategies to reduce suicidal behavior through a prioritized list of coping skills and strategies. In telephone follow-up, patients were contacted at least 2 times to monitor suicide risk, review and revise the SPI, and support treatment engagement. Main Outcomes and Measures Suicidal behavior and behavioral health outpatient services extracted from medical records for 6 months following ED discharge. Results Of the 1640 total patients, 1186 were in the intervention group and 454 were in the comparison group. Patients in the intervention group had a mean (SD) age of 47.15 (14.89) years and 88.5% were men (n = 1050); patients in the comparison group had a mean (SD) age of 49.38 (14.47) years and 88.1% were men (n = 400). Patients in the SPI+ condition were less likely to engage in suicidal behavior (n = 36 of 1186; 3.03%) than those receiving usual care (n = 24 of 454; 5.29%) during the 6-month follow-up period. The SPI+ was associated with 45% fewer suicidal behaviors, approximately halving the odds of suicidal behavior over 6 months (odds ratio, 0.56; 95% CI, 0.33-0.95,P = .03). Intervention patients had more than double the odds of attending at least 1 outpatient mental health visit (odds ratio, 2.06; 95% CI, 1.57-2.71;P Conclusions and Relevance This large-scale cohort comparison study found that SPI+ was associated with a reduction in suicidal behavior and increased treatment engagement among suicidal patients following ED discharge and may be a valuable clinical tool in health care settings.
22 Feb 2018
TL;DR: The VizWiz dataset as discussed by the authors consists of over 31,000 visual questions originating from blind people who each took a picture using a mobile phone and recorded a spoken question about it, together with 10 crowdsourced answers per visual question.
Abstract: The study of algorithms to automatically answer visual questions currently is motivated by visual question answering (VQA) datasets constructed in artificial VQA settings. We propose VizWiz, the first goal-oriented VQA dataset arising from a natural VQA setting. VizWiz consists of over 31,000 visual questions originating from blind people who each took a picture using a mobile phone and recorded a spoken question about it, together with 10 crowdsourced answers per visual question. VizWiz differs from the many existing VQA datasets because (1) images are captured by blind photographers and so are often poor quality, (2) questions are spoken and so are more conversational, and (3) often visual questions cannot be answered. Evaluation of modern algorithms for answering visual questions and deciding if a visual question is answerable reveals that VizWiz is a challenging dataset. We introduce this dataset to encourage a larger community to develop more generalized algorithms that can assist blind people.
TL;DR: There is much work to be done to better understand suicidal thoughts and behaviors among youth, and future research is strongly encouraged to improve the scientific approach, knowledge base, and ultimately prevention of suicidal thought and behaviors in youth.
Abstract: Background
Suicide is a leading cause of death and a complex clinical outcome. Here, we summarize the current state of research pertaining to suicidal thoughts and behaviors in youth. We review their definitions/measurement and phenomenology, epidemiology, potential etiological mechanisms, and psychological treatment and prevention efforts.
Results
We identify key patterns and gaps in knowledge that should guide future work. Regarding epidemiology, the prevalence of suicidal thoughts and behaviors among youth varies across countries and sociodemographic populations. Despite this, studies are rarely conducted cross-nationally and do not uniformly account for high-risk populations. Regarding etiology, the majority of risk factors have been identified within the realm of environmental and psychological factors (notably negative affect-related processes), and most frequently using self-report measures. Little research has spanned across additional units of analyses including behavior, physiology, molecules, cells, and genes. Finally, there has been growing evidence in support of select psychotherapeutic treatment and prevention strategies, and preliminary evidence for technology-based interventions.
Conclusions
There is much work to be done to better understand suicidal thoughts and behaviors among youth. We strongly encourage future research to: (1) continue improving the conceptualization and operationalization of suicidal thoughts and behaviors; (2) improve etiological understanding by focusing on individual (preferably malleable) mechanisms; (3) improve etiological understanding also by integrating findings across multiple units of analyses and developing short-term prediction models; (4) demonstrate greater developmental sensitivity overall; and (5) account for diverse high-risk populations via sampling and reporting of sample characteristics. These serve as initial steps to improve the scientific approach, knowledge base, and ultimately prevention of suicidal thoughts and behaviors among youth.
TL;DR: In the largest reported series on ibrutinib- treated chronic lymphocytic leukemia patients, it is shown that 41% of patients discontinued ibrUTinib, the most common reason for discontinuation in all settings.
Abstract: Clinical trials that led to ibrutinib’s approval for the treatment of chronic lymphocytic leukemia showed that its side effects differ from those of traditional chemotherapy. Reasons for discontinuation in clinical practice have not been adequately studied. We conducted a retrospective analysis of chronic lymphocytic leukemia patients treated with ibrutinib either commercially or on clinical trials. We aimed to compare the type and frequency of toxicities reported in either setting, assess discontinuation rates, and evaluate outcomes. This multicenter, retrospective analysis included ibrutinib-treated chronic lymphocytic leukemia patients at nine United States cancer centers or from the Connect® Chronic Lymphocytic Leukemia Registry. We examined demographics, dosing, discontinuation rates and reasons, toxicities, and outcomes. The primary endpoint was progression-free survival. Six hundred sixteen ibrutinib-treated patients were identified. A total of 546 (88%) patients were treated with the commercial drug. Clinical trial patients were younger (mean age 58 versus 61 years, P=0.01) and had a similar time from diagnosis to treatment with ibrutinib (mean 85 versus 87 months, P=0.8). With a median follow-up of 17 months, an estimated 41% of patients discontinued ibrutinib (median time to ibrutinib discontinuation was 7 months). Notably, ibrutinib toxicity was the most common reason for discontinuation in all settings. The median progression-free survival and overall survival for the entire cohort were 35 months and not reached (median follow-up 17 months), respectively. In the largest reported series on ibrutinib- treated chronic lymphocytic leukemia patients, we show that 41% of patients discontinued ibrutinib. Intolerance as opposed to chronic lymphocytic leukemia progression was the most common reason for discontinuation. Outcomes remain excellent and were not affected by line of therapy or whether patients were treated on clinical studies or commercially. These data strongly argue in favor of finding strategies to minimize ibrutinib intolerance so that efficacy can be further maximized. Future clinical trials should consider time-limited therapy approaches, particularly in patients achieving a complete response, in order to minimize ibrutinib exposure.
University of Basel1, University Hospital of Basel2, University of Paris3, Pierre-and-Marie-Curie University4, Aarhus University Hospital5, Hochschule Hannover6, Universidade Federal de Minas Gerais7, Shanghai Jiao Tong University8, Université Paris-Saclay9, University of Rochester10, University of Liège11, University of Groningen12, Utrecht University13, Cardiovascular Institute of the South14, University of Modena and Reggio Emilia15, China-Japan Friendship Hospital16, Monash University17, University of Copenhagen18, Copenhagen University Hospital19, Medisch Spectrum Twente20, Vanderbilt University Medical Center21, McMaster University22
TL;DR: Widespread implementation of procalcitonin protocols in patients with acute respiratory infections has the potential to improve antibiotic management with positive effects on clinical outcomes and on the current threat of increasing antibiotic multiresistance.
Abstract: Summary Background In February, 2017, the US Food and Drug Administration approved the blood infection marker procalcitonin for guiding antibiotic therapy in patients with acute respiratory infections. This meta-analysis of patient data from 26 randomised controlled trials was designed to assess safety of procalcitonin-guided treatment in patients with acute respiratory infections from different clinical settings. Methods Based on a prespecified Cochrane protocol, we did a systematic literature search on the Cochrane Central Register of Controlled Trials, MEDLINE, and Embase, and pooled individual patient data from trials in which patients with respiratory infections were randomly assigned to receive antibiotics based on procalcitonin concentrations (procalcitonin-guided group) or control. The coprimary endpoints were 30-day mortality and setting-specific treatment failure. Secondary endpoints were antibiotic use, length of stay, and antibiotic side-effects. Findings We identified 990 records from the literature search, of which 71 articles were assessed for eligibility after exclusion of 919 records. We collected data on 6708 patients from 26 eligible trials in 12 countries. Mortality at 30 days was significantly lower in procalcitonin-guided patients than in control patients (286 [9%] deaths in 3336 procalcitonin-guided patients vs 336 [10%] in 3372 controls; adjusted odds ratio [OR] 0·83 [95% CI 0·70 to 0·99], p=0·037). This mortality benefit was similar across subgroups by setting and type of infection (p interactions >0·05), although mortality was very low in primary care and in patients with acute bronchitis. Procalcitonin guidance was also associated with a 2·4-day reduction in antibiotic exposure (5·7 vs 8·1 days [95% CI −2·71 to −2·15], p vs 22%, adjusted OR 0·68 [95% CI 0·57 to 0·82], p Interpretation Use of procalcitonin to guide antibiotic treatment in patients with acute respiratory infections reduces antibiotic exposure and side-effects, and improves survival. Widespread implementation of procalcitonin protocols in patients with acute respiratory infections thus has the potential to improve antibiotic management with positive effects on clinical outcomes and on the current threat of increasing antibiotic multiresistance. Funding National Institute for Health Research.
Albert M. Sirunyan1, Robin Erbacher2, C. A. Carrillo Montoya3, Wagner Carvalho4 +2355 more•Institutions (153)
TL;DR: In this paper, the performance of the modified system is studied using proton-proton collision data at center-of-mass energy √s=13 TeV, collected at the LHC in 2015 and 2016.
Abstract: The CMS muon detector system, muon reconstruction software, and high-level trigger underwent significant changes in 2013–2014 in preparation for running at higher LHC collision energy and instantaneous luminosity. The performance of the modified system is studied using proton-proton collision data at center-of-mass energy √s=13 TeV, collected at the LHC in 2015 and 2016. The measured performance parameters, including spatial resolution, efficiency, and timing, are found to meet all design specifications and are well reproduced by simulation. Despite the more challenging running conditions, the modified muon system is found to perform as well as, and in many aspects better than, previously. We dedicate this paper to the memory of Prof. Alberto Benvenuti, whose work was fundamental for the CMS muon detector.