Showing papers by "Case Western Reserve University 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
Christina Fitzmaurice1, Christina Fitzmaurice2, Christina Fitzmaurice3, Tomi Akinyemiju4 +177 more•Institutions (102)
TL;DR: In this paper, the authors assess the burden of 29 cancer groups over time to provide a framework for policy discussion, resource allocation, and research focus, and evaluate cancer incidence, mortality, years lived with disability, years of life lost, and disability-adjusted life-years (DALYs) for 195 countries and territories by age and sex using the Global Burden of Disease study estimation methods.
Abstract: Importance The increasing burden due to cancer and other noncommunicable diseases poses a threat to human development, which has resulted in global political commitments reflected in the Sustainable Development Goals as well as the World Health Organization (WHO) Global Action Plan on Non-Communicable Diseases. To determine if these commitments have resulted in improved cancer control, quantitative assessments of the cancer burden are required. Objective To assess the burden for 29 cancer groups over time to provide a framework for policy discussion, resource allocation, and research focus. Evidence Review Cancer incidence, mortality, years lived with disability, years of life lost, and disability-adjusted life-years (DALYs) were evaluated for 195 countries and territories by age and sex using the Global Burden of Disease study estimation methods. Levels and trends were analyzed over time, as well as by the Sociodemographic Index (SDI). Changes in incident cases were categorized by changes due to epidemiological vs demographic transition. Findings In 2016, there were 17.2 million cancer cases worldwide and 8.9 million deaths. Cancer cases increased by 28% between 2006 and 2016. The smallest increase was seen in high SDI countries. Globally, population aging contributed 17%; population growth, 12%; and changes in age-specific rates, −1% to this change. The most common incident cancer globally for men was prostate cancer (1.4 million cases). The leading cause of cancer deaths and DALYs was tracheal, bronchus, and lung cancer (1.2 million deaths and 25.4 million DALYs). For women, the most common incident cancer and the leading cause of cancer deaths and DALYs was breast cancer (1.7 million incident cases, 535 000 deaths, and 14.9 million DALYs). In 2016, cancer caused 213.2 million DALYs globally for both sexes combined. Between 2006 and 2016, the average annual age-standardized incidence rates for all cancers combined increased in 130 of 195 countries or territories, and the average annual age-standardized death rates decreased within that timeframe in 143 of 195 countries or territories. Conclusions and Relevance Large disparities exist between countries in cancer incidence, deaths, and associated disability. Scaling up cancer prevention and ensuring universal access to cancer care are required for health equity and to fulfill the global commitments for noncommunicable disease and cancer control.
4,621 citations
Emory University1, University of Pittsburgh2, Riverside Methodist Hospital3, University of Miami4, Autonomous University of Barcelona5, Centre Hospitalier Universitaire de Toulouse6, Baptist Health7, Case Western Reserve University8, University at Buffalo9, Royal Melbourne Hospital10, Rush University Medical Center11, California Pacific Medical Center12, University Health Network13, University Of Tennessee System14, University of Kansas15, University of Barcelona16, Capital District Health Authority17, Kaiser Permanente18, University of California, Los Angeles19, University of California, San Francisco20
TL;DR: Among patients with acute stroke who had last been known to be well 6 to 24 hours earlier and who had a mismatch between clinical deficit and infarct, outcomes for disability at 90 days were better with thrombectomy plus standard care than with standard care alone.
Abstract: BackgroundThe effect of endovascular thrombectomy that is performed more than 6 hours after the onset of ischemic stroke is uncertain. Patients with a clinical deficit that is disproportionately severe relative to the infarct volume may benefit from late thrombectomy. MethodsWe enrolled patients with occlusion of the intracranial internal carotid artery or proximal middle cerebral artery who had last been known to be well 6 to 24 hours earlier and who had a mismatch between the severity of the clinical deficit and the infarct volume, with mismatch criteria defined according to age (<80 years or ≥80 years). Patients were randomly assigned to thrombectomy plus standard care (the thrombectomy group) or to standard care alone (the control group). The coprimary end points were the mean score for disability on the utility-weighted modified Rankin scale (which ranges from 0 [death] to 10 [no symptoms or disability]) and the rate of functional independence (a score of 0, 1, or 2 on the modified Rankin scale, whic...
3,331 citations
Jeffrey D. Stanaway1, Ashkan Afshin1, Emmanuela Gakidou1, Stephen S Lim1 +1050 more•Institutions (346)
TL;DR: This study estimated levels and trends in exposure, attributable deaths, and attributable disability-adjusted life-years (DALYs) by age group, sex, year, and location for 84 behavioural, environmental and occupational, and metabolic risks or groups of risks from 1990 to 2017 and explored the relationship between development and risk exposure.
2,910 citations
Tufts Medical Center1, Northeastern University2, McGill University3, Johns Hopkins University4, Utrecht University5, Vanderbilt University Medical Center6, Brigham and Women's Hospital7, New York University8, McMaster University9, Ohio State University10, Radboud University Nijmegen11, University of Western Ontario12, London Health Sciences Centre13, University of Montpellier14, RMIT University15, University of Poitiers16, Maine Medical Center17, University of Washington18, University of Chicago19, Intermountain Healthcare20, Deakin University21, Johns Hopkins University School of Medicine22, Yale University23, University of Grenoble24, University of California, San Francisco25, Monash University26, Case Western Reserve University27, New York Medical College28, University of Toronto29, Stanford University30
TL;DR: Substantial agreement was found among a large, interdisciplinary cohort of international experts regarding evidence supporting recommendations, and the remaining literature gaps in the assessment, prevention, and treatment of Pain, Agitation/sedation, Delirium, Immobility (mobilization/rehabilitation), and Sleep (disruption) in critically ill adults.
Abstract: Objective:To update and expand the 2013 Clinical Practice Guidelines for the Management of Pain, Agitation, and Delirium in Adult Patients in the ICU.Design:Thirty-two international experts, four methodologists, and four critical illness survivors met virtually at least monthly. All section groups g
1,935 citations
TL;DR: A genome-wide association meta-analysis of individuals with clinically assessed or self-reported depression identifies 44 independent and significant loci and finds important relationships of genetic risk for major depression with educational attainment, body mass, and schizophrenia.
Abstract: Major depressive disorder (MDD) is a common illness accompanied by considerable morbidity, mortality, costs, and heightened risk of suicide. We conducted a genome-wide association meta-analysis based in 135,458 cases and 344,901 controls and identified 44 independent and significant loci. The genetic findings were associated with clinical features of major depression and implicated brain regions exhibiting anatomical differences in cases. Targets of antidepressant medications and genes involved in gene splicing were enriched for smaller association signal. We found important relationships of genetic risk for major depression with educational attainment, body mass, and schizophrenia: lower educational attainment and higher body mass were putatively causal, whereas major depression and schizophrenia reflected a partly shared biological etiology. All humans carry lesser or greater numbers of genetic risk factors for major depression. These findings help refine the basis of major depression and imply that a continuous measure of risk underlies the clinical phenotype.
1,898 citations
University of Texas Southwestern Medical Center1, Stanford University2, University of Southern California3, University of California, Los Angeles4, West Virginia University5, Harvard University6, University of Colorado Boulder7, Vanderbilt University8, Case Western Reserve University9, Cincinnati Children's Hospital Medical Center10, Cleveland Clinic11, Fox Chase Cancer Center12, University of Pennsylvania13, University of Washington14, Seattle Children's15, University of Texas MD Anderson Cancer Center16, Nemours Foundation17, Oregon Health & Science University18, International University, Cambodia19
TL;DR: Larotrectinib had marked and durable antitumor activity in patients with TRK fusion–positive cancer, regardless of the age of the patient or of the tumor type.
Abstract: Background Fusions involving one of three tropomyosin receptor kinases (TRK) occur in diverse cancers in children and adults. We evaluated the efficacy and safety of larotrectinib, a highly selective TRK inhibitor, in adults and children who had tumors with these fusions. Methods We enrolled patients with consecutively and prospectively identified TRK fusion–positive cancers, detected by molecular profiling as routinely performed at each site, into one of three protocols: a phase 1 study involving adults, a phase 1–2 study involving children, or a phase 2 study involving adolescents and adults. The primary end point for the combined analysis was the overall response rate according to independent review. Secondary end points included duration of response, progression-free survival, and safety. Results A total of 55 patients, ranging in age from 4 months to 76 years, were enrolled and treated. Patients had 17 unique TRK fusion–positive tumor types. The overall response rate was 75% (95% confidence ...
1,773 citations
University of Alabama at Birmingham1, University of South Florida2, Vanderbilt University3, City of Hope National Medical Center4, Fox Chase Cancer Center5, University Of Tennessee System6, Brigham and Women's Hospital7, Seattle Cancer Care Alliance8, Case Western Reserve University9, Roswell Park Cancer Institute10, Northwestern University11, Harvard University12, University of Nebraska Medical Center13, University of Utah14, Memorial Sloan Kettering Cancer Center15
TL;DR: This manuscript focuses on the NCCN Guidelines Panel recommendations for the workup, primary treatment, risk reduction strategies, and surveillance specific to DCIS.
Abstract: Ductal carcinoma in situ (DCIS) of the breast represents a heterogeneous group of neoplastic lesions in the breast ducts. The goal for management of DCIS is to prevent the development of invasive breast cancer. This manuscript focuses on the NCCN Guidelines Panel recommendations for the workup, primary treatment, risk reduction strategies, and surveillance specific to DCIS.
1,545 citations
TL;DR: In insights into the role of alcohol consumption in the genetic architecture of hypertension, a large two-stage investigation incorporating joint testing of main genetic effects and single nucleotide variant (SNV)-alcohol consumption interactions is conducted.
Abstract: Heavy alcohol consumption is an established risk factor for hypertension; the mechanism by which alcohol consumption impact blood pressure (BP) regulation remains unknown. We hypothesized that a genome-wide association study accounting for gene-alcohol consumption interaction for BP might identify additional BP loci and contribute to the understanding of alcohol-related BP regulation. We conducted a large two-stage investigation incorporating joint testing of main genetic effects and single nucleotide variant (SNV)-alcohol consumption interactions. In Stage 1, genome-wide discovery meta-analyses in ≈131K individuals across several ancestry groups yielded 3,514 SNVs (245 loci) with suggestive evidence of association (P < 1.0 x 10-5). In Stage 2, these SNVs were tested for independent external replication in ≈440K individuals across multiple ancestries. We identified and replicated (at Bonferroni correction threshold) five novel BP loci (380 SNVs in 21 genes) and 49 previously reported BP loci (2,159 SNVs in 109 genes) in European ancestry, and in multi-ancestry meta-analyses (P < 5.0 x 10-8). For African ancestry samples, we detected 18 potentially novel BP loci (P < 5.0 x 10-8) in Stage 1 that warrant further replication. Additionally, correlated meta-analysis identified eight novel BP loci (11 genes). Several genes in these loci (e.g., PINX1, GATA4, BLK, FTO and GABBR2) have been previously reported to be associated with alcohol consumption. These findings provide insights into the role of alcohol consumption in the genetic architecture of hypertension.
1,218 citations
TL;DR: This study assesses the state-of-the-art machine learning methods used for brain tumor image analysis in mpMRI scans, during the last seven instances of the International Brain Tumor Segmentation (BraTS) challenge, i.e., 2012-2018, and investigates the challenge of identifying the best ML algorithms for each of these tasks.
Abstract: Gliomas are the most common primary brain malignancies, with different degrees of aggressiveness, variable prognosis and various heterogeneous histologic sub-regions, i.e., peritumoral edematous/invaded tissue, necrotic core, active and non-enhancing core. This intrinsic heterogeneity is also portrayed in their radio-phenotype, as their sub-regions are depicted by varying intensity profiles disseminated across multi-parametric magnetic resonance imaging (mpMRI) scans, reflecting varying biological properties. Their heterogeneous shape, extent, and location are some of the factors that make these tumors difficult to resect, and in some cases inoperable. The amount of resected tumoris a factor also considered in longitudinal scans, when evaluating the apparent tumor for potential diagnosis of progression. Furthermore, there is mounting evidence that accurate segmentation of the various tumor sub-regions can offer the basis for quantitative image analysis towards prediction of patient overall survival. This study assesses thestate-of-the-art machine learning (ML) methods used for brain tumor image analysis in mpMRI scans, during the last seven instances of the International Brain Tumor Segmentation (BraTS) challenge, i.e., 2012-2018. Specifically, we focus on i) evaluating segmentations of the various glioma sub-regions in pre-operative mpMRI scans, ii) assessing potential tumor progression by virtue of longitudinal growth of tumor sub-regions, beyond use of the RECIST/RANO criteria, and iii) predicting the overall survival from pre-operative mpMRI scans of patients that underwent gross tota lresection. Finally, we investigate the challenge of identifying the best ML algorithms for each of these tasks, considering that apart from being diverse on each instance of the challenge, the multi-institutional mpMRI BraTS dataset has also been a continuously evolving/growing dataset.
TL;DR: A comprehensive survey of commonly used deep learning algorithms and discusses their applications toward making manufacturing “smart”, including computational methods based on deep learning that aim to improve system performance in manufacturing.
Bela Abolfathi1, D. S. Aguado2, Gabriela Aguilar3, Carlos Allende Prieto2 +361 more•Institutions (94)
TL;DR: SDSS-IV is the fourth generation of the Sloan Digital Sky Survey and has been in operation since 2014 July. as discussed by the authors describes the second data release from this phase, and the 14th from SDSS overall (making this Data Release Fourteen or DR14).
Abstract: The fourth generation of the Sloan Digital Sky Survey (SDSS-IV) has been in operation since 2014 July. This paper describes the second data release from this phase, and the 14th from SDSS overall (making this Data Release Fourteen or DR14). This release makes the data taken by SDSS-IV in its first two years of operation (2014-2016 July) public. Like all previous SDSS releases, DR14 is cumulative, including the most recent reductions and calibrations of all data taken by SDSS since the first phase began operations in 2000. New in DR14 is the first public release of data from the extended Baryon Oscillation Spectroscopic Survey; the first data from the second phase of the Apache Point Observatory (APO) Galactic Evolution Experiment (APOGEE-2), including stellar parameter estimates from an innovative data-driven machine-learning algorithm known as "The Cannon"; and almost twice as many data cubes from the Mapping Nearby Galaxies at APO (MaNGA) survey as were in the previous release (N = 2812 in total). This paper describes the location and format of the publicly available data from the SDSS-IV surveys. We provide references to the important technical papers describing how these data have been taken (both targeting and observation details) and processed for scientific use. The SDSS web site (www.sdss.org) has been updated for this release and provides links to data downloads, as well as tutorials and examples of data use. SDSS-IV is planning to continue to collect astronomical data until 2020 and will be followed by SDSS-V.
Institute for Health Metrics and Evaluation1, University of Louisville2, Karolinska Institutet3, Kermanshah University of Medical Sciences4, University of Queensland5, Centre for Mental Health6, Tehran University of Medical Sciences7, University of KwaZulu-Natal8, South African Medical Research Council9, University of Colorado Boulder10, University of California, Irvine11, Fred Hutchinson Cancer Research Center12, Montefiore Medical Center13, Northeastern University14, University of Alabama at Birmingham15, Brown University16, San Diego State University17, University of Melbourne18, Albert Einstein College of Medicine19, Cambridge Health Alliance20, University of Cape Town21, University of Pittsburgh22, Johns Hopkins University23, Case Western Reserve University24, Marshall University25, University of London26, University of Illinois at Urbana–Champaign27, National Drug and Alcohol Research Centre28, Harvard University29, University of California, San Diego30, Yale University31, Georgetown University32, Veterans Health Administration33, Jackson State University34, University of Massachusetts Boston35, State University of New York System36, Simmons College37, Charles R. Drew University of Medicine and Science38, University of California, Los Angeles39, University of Oxford40, Norwegian Institute of Public Health41, Curtin University42, Pacific Institute43, Heidelberg University44, Jimma University45, Northwestern University46, Washington University in St. Louis47, Howard University48, University of New Mexico49, University at Buffalo50, University of Washington51, University of South Florida52, Tufts University53, University of Rochester Medical Center54, Kosin University55, Central South University56, Michigan State University57, Ball State University58, Nova Southeastern University59, Dalhousie University60, Mayo Clinic61, University of British Columbia62, Ohio State University63, Baylor University64, Jagiellonian University Medical College65, Wrocław Medical University66, Dartmouth College67, University of Western Ontario68, Oregon Health & Science University69, Virginia Commonwealth University70, Columbia University71, University of Canberra72, Aga Khan University73
TL;DR: There are wide differences in the burden of disease at the state level and specific diseases and risk factors, such as drug use disorders, high BMI, poor diet, high fasting plasma glucose level, and alcohol use disorders are increasing and warrant increased attention.
Abstract: Introduction Several studies have measured health outcomes in the United States, but none have provided a comprehensive assessment of patterns of health by state. Objective To use the results of the Global Burden of Disease Study (GBD) to report trends in the burden of diseases, injuries, and risk factors at the state level from 1990 to 2016. Design and Setting A systematic analysis of published studies and available data sources estimates the burden of disease by age, sex, geography, and year. Main Outcomes and Measures Prevalence, incidence, mortality, life expectancy, healthy life expectancy (HALE), years of life lost (YLLs) due to premature mortality, years lived with disability (YLDs), and disability-adjusted life-years (DALYs) for 333 causes and 84 risk factors with 95% uncertainty intervals (UIs) were computed. Results Between 1990 and 2016, overall death rates in the United States declined from 745.2 (95% UI, 740.6 to 749.8) per 100 000 persons to 578.0 (95% UI, 569.4 to 587.1) per 100 000 persons. The probability of death among adults aged 20 to 55 years declined in 31 states and Washington, DC from 1990 to 2016. In 2016, Hawaii had the highest life expectancy at birth (81.3 years) and Mississippi had the lowest (74.7 years), a 6.6-year difference. Minnesota had the highest HALE at birth (70.3 years), and West Virginia had the lowest (63.8 years), a 6.5-year difference. The leading causes of DALYs in the United States for 1990 and 2016 were ischemic heart disease and lung cancer, while the third leading cause in 1990 was low back pain, and the third leading cause in 2016 was chronic obstructive pulmonary disease. Opioid use disorders moved from the 11th leading cause of DALYs in 1990 to the 7th leading cause in 2016, representing a 74.5% (95% UI, 42.8% to 93.9%) change. In 2016, each of the following 6 risks individually accounted for more than 5% of risk-attributable DALYs: tobacco consumption, high body mass index (BMI), poor diet, alcohol and drug use, high fasting plasma glucose, and high blood pressure. Across all US states, the top risk factors in terms of attributable DALYs were due to 1 of the 3 following causes: tobacco consumption (32 states), high BMI (10 states), or alcohol and drug use (8 states). Conclusions and Relevance There are wide differences in the burden of disease at the state level. Specific diseases and risk factors, such as drug use disorders, high BMI, poor diet, high fasting plasma glucose level, and alcohol use disorders are increasing and warrant increased attention. These data can be used to inform national health priorities for research, clinical care, and policy.
University of British Columbia1, University of Toronto2, University of Michigan3, University of Minnesota4, McMaster University5, University of Western Ontario6, McGill University7, Dalhousie University8, University of Calgary9, Queen's University10, Kyushu University11, University of São Paulo12, Stanford University13, Case Western Reserve University14, University of Barcelona15, University of Sydney16, George Washington University17, Deakin University18
TL;DR: These 2018 CANMAT and ISBD Bipolar Treatment Guidelines represent the significant advances in the field since the last full edition was published in 2005, including updates to diagnosis and management as well as new research into pharmacological and psychological treatments.
Abstract: The Canadian Network for Mood and Anxiety Treatments (CANMAT) previously published treatment guidelines for bipolar disorder in 2005, along with international commentaries and subsequent updates in 2007, 2009, and 2013. The last two updates were published in collaboration with the International Society for Bipolar Disorders (ISBD). These 2018 CANMAT and ISBD Bipolar Treatment Guidelines represent the significant advances in the field since the last full edition was published in 2005, including updates to diagnosis and management as well as new research into pharmacological and psychological treatments. These advances have been translated into clear and easy to use recommendations for first, second, and third- line treatments, with consideration given to levels of evidence for efficacy, clinical support based on experience, and consensus ratings of safety, tolerability, and treatment-emergent switch risk. New to these guidelines, hierarchical rankings were created for first and second- line treatments recommended for acute mania, acute depression, and maintenance treatment in bipolar I disorder. Created by considering the impact of each treatment across all phases of illness, this hierarchy will further assist clinicians in making evidence-based treatment decisions. Lithium, quetiapine, divalproex, asenapine, aripiprazole, paliperidone, risperidone, and cariprazine alone or in combination are recommended as first-line treatments for acute mania. First-line options for bipolar I depression include quetiapine, lurasidone plus lithium or divalproex, lithium, lamotrigine, lurasidone, or adjunctive lamotrigine. While medications that have been shown to be effective for the acute phase should generally be continued for the maintenance phase in bipolar I disorder, there are some exceptions (such as with antidepressants); and available data suggest that lithium, quetiapine, divalproex, lamotrigine, asenapine, and aripiprazole monotherapy or combination treatments should be considered first-line for those initiating or switching treatment during the maintenance phase. In addition to addressing issues in bipolar I disorder, these guidelines also provide an overview of, and recommendations for, clinical management of bipolar II disorder, as well as advice on specific populations, such as women at various stages of the reproductive cycle, children and adolescents, and older adults. There are also discussions on the impact of specific psychiatric and medical comorbidities such as substance use, anxiety, and metabolic disorders. Finally, an overview of issues related to safety and monitoring is provided. The CANMAT and ISBD groups hope that these guidelines become a valuable tool for practitioners across the globe.
Christina Fitzmaurice1, Christina Fitzmaurice2, Tomi Akinyemiju3, Faris Lami4 +172 more•Institutions (95)
01 Jul 2018
TL;DR: A review of the state of the art and scientific needs for heterogeneous electrocatalysts for electrochemical reduction of dinitrogen to ammonia can be found in this article, with a particular focus on how mechanistic understanding informs catalyst design.
Abstract: The production of synthetic ammonia remains dependent on the energy- and capital-intensive Haber–Bosch process. Extensive research in molecular catalysis has demonstrated ammonia production from dinitrogen, albeit at low production rates. Mechanistic understanding of dinitrogen reduction to ammonia continues to be delineated through study of molecular catalyst structure, as well as through understanding the naturally occurring nitrogenase enzyme. The transition to Haber–Bosch alternatives through robust, heterogeneous catalyst surfaces remains an unsolved research challenge. Catalysts for electrochemical reduction of dinitrogen to ammonia are a specific focus of research, due to the potential to compete with the Haber–Bosch process and reduce associated carbon dioxide emissions. However, limited progress has been made to date, as most electrocatalyst surfaces lack specificity towards nitrogen fixation. In this Review, we discuss the progress of the field in developing a mechanistic understanding of nitrogenase-promoted and molecular catalyst-promoted ammonia synthesis and provide a review of the state of the art and scientific needs for heterogeneous electrocatalysts. The artificial synthesis of ammonia remains one of the most important catalytic processes worldwide, over 100 years after its development. In this Review, recent developments in enzymatic, homogeneous and heterogeneous catalysis towards the conversion of nitrogen to ammonia are discussed, with a particular focus on how mechanistic understanding informs catalyst design.
TL;DR: In this article, the authors provide a brief discussion about additive manufacturing and also the most employed additive manufacturing technologies for polymers, specifically, properties under different loading types such as tensile, bending, compressive, fatigue, impact and others.
Abstract: 3D printing, more formally known as Additive Manufacturing (AM), is already being adopted for rapid prototyping and soon rapid manufacturing. This review provides a brief discussion about AM and also the most employed AM technologies for polymers. The commonly-used ASTM and ISO mechanical test standards which have been used by various research groups to test the strength of the 3D-printed parts have been reported. Also, a summary of an exhaustive amount of literature regarding the mechanical properties of 3D-printed parts is included, specifically, properties under different loading types such as tensile, bending, compressive, fatigue, impact and others. Properties at low temperatures have also been discussed. Further, the effects of fillers as well as post-processing on the mechanical properties have also been discussed. Lastly, several important questions to consider in the standardization of mechanical test methods have been raised.
TL;DR: The rational design and synthesis of a new class of Co@N-C materials (C-MOF-C2-T) from a pair of enantiotopic chiral 3D MOFs by pyrolysis at temperature T is reported, exhibiting higher electrocatalytic activities for oxygen reduction and oxygen evolution reactions than that of commercial Pt/C and RuO2.
Abstract: Metal-organic frameworks (MOFs) and MOF-derived materials have recently attracted considerable interest as alternatives to noble-metal electrocatalysts. Herein, the rational design and synthesis of a new class of Co@N-C materials (C-MOF-C2-T) from a pair of enantiotopic chiral 3D MOFs by pyrolysis at temperature T is reported. The newly developed C-MOF-C2-900 with a unique 3D hierarchical rodlike structure, consisting of homogeneously distributed cobalt nanoparticles encapsulated by partially graphitized N-doped carbon rings along the rod length, exhibits higher electrocatalytic activities for oxygen reduction and oxygen evolution reactions (ORR and OER) than that of commercial Pt/C and RuO2 , respectively. Primary Zn-air batteries based on C-MOF-900 for the oxygen reduction reaction (ORR) operated at a discharge potential of 1.30 V with a specific capacity of 741 mA h gZn-1 under 10 mA cm-2 . Rechargeable Zn-air batteries based on C-MOF-C2-900 as an ORR and OER bifunctional catalyst exhibit initial charge and discharge potentials at 1.81 and 1.28 V (2 mA cm-2 ), along with an excellent cycling stability with no increase in polarization even after 120 h - outperform their counterparts based on noble-metal-based air electrodes. The resultant rechargeable Zn-air batteries are used to efficiently power electrochemical water-splitting systems, demonstrating promising potential as integrated green energy systems for practical applications.
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.
Northwestern University1, University of California, San Francisco2, University of Michigan3, University of California, San Diego4, City of Hope National Medical Center5, Vanderbilt University6, Seattle Cancer Care Alliance7, Fox Chase Cancer Center8, University of Wisconsin-Madison9, Mayo Clinic10, Yale University11, University of South Florida12, Washington University in St. Louis13, University of Alabama at Birmingham14, Stanford University15, Case Western Reserve University16, University of Colorado Boulder17, Harvard University18, Roswell Park Cancer Institute19, Memorial Sloan Kettering Cancer Center20, University of Utah21, University of Tennessee Health Science Center22, University of Texas MD Anderson Cancer Center23, Johns Hopkins University24, Duke University25, Ohio State University26
TL;DR: The NCCN Clinical Practice Guidelines in Oncology for Rectal Cancer address diagnosis, staging, surgical management, perioperative treatment, management of recurrent and metastatic disease, disease surveillance, and survivorship in patients with rectal cancer.
Abstract: The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Rectal Cancer address diagnosis, staging, surgical management, perioperative treatment, management of recurrent and metastatic disease, disease surveillance, and survivorship in patients with rectal cancer This portion of the guidelines focuses on the management of localized disease, which involves careful patient selection for curative-intent treatment options that sequence multimodality therapy usually comprised of chemotherapy, radiation, and surgical resection
Northwestern University1, University of California, San Francisco2, University of Michigan3, University of California, San Diego4, City of Hope National Medical Center5, Vanderbilt University6, Seattle Cancer Care Alliance7, Fox Chase Cancer Center8, University of Wisconsin-Madison9, University of Utah10, Mayo Clinic11, Yale Cancer Center12, University of South Florida13, Washington University in St. Louis14, University of Alabama at Birmingham15, Stanford University16, Case Western Reserve University17, University of Colorado Boulder18, Brigham and Women's Hospital19, Ohio State University20, Roswell Park Cancer Institute21, Memorial Sloan Kettering Cancer Center22, University of Tennessee Health Science Center23, University of Texas MD Anderson Cancer Center24, Johns Hopkins University25, Duke University26, National Comprehensive Cancer Network27
TL;DR: The NCCN Colon Cancer Panel discussions for the 2018 update of the guidelines regarding risk stratification and adjuvant treatment for patients with stage III colon cancer, and treatment of BRAF V600E mutation-positive metastatic colorectal cancer with regimens containing vemurafenib are summarized.
Abstract: The NCCN Guidelines for Colon Cancer provide recommendations regarding diagnosis, pathologic staging, surgical management, perioperative treatment, surveillance, management of recurrent and metastatic disease, and survivorship. These NCCN Guidelines Insights summarize the NCCN Colon Cancer Panel discussions for the 2018 update of the guidelines regarding risk stratification and adjuvant treatment for patients with stage III colon cancer, and treatment of BRAF V600E mutation-positive metastatic colorectal cancer with regimens containing vemurafenib.
TL;DR: In this paper, the conceptual similarities and differences of entrepreneurial ecosystems relative to, for instance, clusters, knowledge clusters, regional systems of innovation, and "innovative milieus" remain unclear.
Abstract: Research Summary: Entrepreneurial ecosystems command increasing attention from policy makers, academics, and practitioners, yet the phenomenon itself remains under‐theorized. Specifically, the conceptual similarities and differences of entrepreneurial ecosystems relative to, for instance, clusters, “knowledge clusters,” regional systems of innovation, and “innovative milieus” remain unclear. Drawing on research on industrial districts and agglomerations, clusters, and systems of innovation, we suggest that entrepreneurial ecosystems differ from traditional clusters by their emphasis on the exploitation of digital affordances; by their organization around entrepreneurial opportunity discovery and pursuit; by their emphasis on business model innovation; by voluntary horizontal knowledge spillovers; and by cluster‐external locus of entrepreneurial opportunities. We highlight how these distinctive characteristics set entrepreneurial ecosystems apart from other cluster types, propose a structural model of entrepreneurial ecosystems, summarize the articles in this special issue, and suggest promising avenues for future research.
Case Western Reserve University1, Newcastle University2, Research Triangle Park3, Duke University4, Seattle Children's5, Nationwide Children's Hospital6, Children's Hospital of Eastern Ontario7, State University of New York System8, Centers for Disease Control and Prevention9, University of Rochester Medical Center10
TL;DR: The new care considerations acknowledge the effects of long-term glucocorticoid use on the natural history of DMD, and the need for care guidance across the lifespan as patients live longer.
Abstract: A coordinated, multidisciplinary approach to care is essential for optimum management of the primary manifestations and secondary complications of Duchenne muscular dystrophy (DMD). Contemporary care has been shaped by the availability of more sensitive diagnostic techniques and the earlier use of therapeutic interventions, which have the potential to improve patients' duration and quality of life. In part 2 of this update of the DMD care considerations, we present the latest recommendations for respiratory, cardiac, bone health and osteoporosis, and orthopaedic and surgical management for boys and men with DMD. Additionally, we provide guidance on cardiac management for female carriers of a disease-causing mutation. The new care considerations acknowledge the effects of long-term glucocorticoid use on the natural history of DMD, and the need for care guidance across the lifespan as patients live longer. The management of DMD looks set to change substantially as new genetic and molecular therapies become available.
TL;DR: A computational approach based on deep learning to predict the overall survival of patients diagnosed with brain tumors from microscopic images of tissue biopsies and genomic biomarkers, which surpasses the prognostic accuracy of human experts using the current clinical standard for classifying brain tumors.
Abstract: Cancer histology reflects underlying molecular processes and disease progression and contains rich phenotypic information that is predictive of patient outcomes. In this study, we show a computational approach for learning patient outcomes from digital pathology images using deep learning to combine the power of adaptive machine learning algorithms with traditional survival models. We illustrate how these survival convolutional neural networks (SCNNs) can integrate information from both histology images and genomic biomarkers into a single unified framework to predict time-to-event outcomes and show prediction accuracy that surpasses the current clinical paradigm for predicting the overall survival of patients diagnosed with glioma. We use statistical sampling techniques to address challenges in learning survival from histology images, including tumor heterogeneity and the need for large training cohorts. We also provide insights into the prediction mechanisms of SCNNs, using heat map visualization to show that SCNNs recognize important structures, like microvascular proliferation, that are related to prognosis and that are used by pathologists in grading. These results highlight the emerging role of deep learning in precision medicine and suggest an expanding utility for computational analysis of histology in the future practice of pathology.
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.
Yale University1, Pennsylvania State University2, SUNY Downstate Medical Center3, Allen Institute for Brain Science4, National Research Foundation of South Africa5, University of California, San Francisco6, Chung-Ang University7, Boston University8, Stony Brook University9, University of North Carolina at Chapel Hill10, VU University Amsterdam11, Cardiff University12, Cleveland Clinic13, Case Western Reserve University14, Michigan State University15, Children's Hospital Los Angeles16, University of Southern California17, Johns Hopkins University18, University of California, Los Angeles19
TL;DR: The generation and analysis of a variety of genomic data modalities at the tissue and single-cell levels, including transcriptome, DNA methylation, and histone modifications across multiple brain regions ranging in age from embryonic development through adulthood, reveal insights into neurodevelopment and the genomic basis of neuropsychiatric risks.
Abstract: To broaden our understanding of human neurodevelopment, we profiled transcriptomic and epigenomic landscapes across brain regions and/or cell types for the entire span of prenatal and postnatal development. Integrative analysis revealed temporal, regional, sex, and cell type-specific dynamics. We observed a global transcriptomic cup-shaped pattern, characterized by a late fetal transition associated with sharply decreased regional differences and changes in cellular composition and maturation, followed by a reversal in childhood-adolescence, and accompanied by epigenomic reorganizations. Analysis of gene coexpression modules revealed relationships with epigenomic regulation and neurodevelopmental processes. Genes with genetic associations to brain-based traits and neuropsychiatric disorders (including MEF2C, SATB2, SOX5, TCF4, and TSHZ3) converged in a small number of modules and distinct cell types, revealing insights into neurodevelopment and the genomic basis of neuropsychiatric risks.
TL;DR: Overall effects were weak, but some results supported specific tenets of the theory, namely, that students with low socioeconomic status or who are academically at risk might benefit from mind-set interventions.
Abstract: Mind-sets (aka implicit theories) are beliefs about the nature of human attributes (e.g., intelligence). The theory holds that individuals with growth mind-sets (beliefs that attributes are malleable with effort) enjoy many positive outcomes-including higher academic achievement-while their peers who have fixed mind-sets experience negative outcomes. Given this relationship, interventions designed to increase students' growth mind-sets-thereby increasing their academic achievement-have been implemented in schools around the world. In our first meta-analysis ( k = 273, N = 365,915), we examined the strength of the relationship between mind-set and academic achievement and potential moderating factors. In our second meta-analysis ( k = 43, N = 57,155), we examined the effectiveness of mind-set interventions on academic achievement and potential moderating factors. Overall effects were weak for both meta-analyses. However, some results supported specific tenets of the theory, namely, that students with low socioeconomic status or who are academically at risk might benefit from mind-set interventions.
TL;DR: The American Gastroenterological Association Institute Guideline on Initial Management of Acute Pancreatitis provides a guide for the initial management of acute pancreatic cancer patients.
TL;DR: In this article, the authors determine the association between non-communicable illnesses and HIV-related deaths in people with HIV and cardiovascular diseases, and show that most deaths in persons with HIV are now attributable to noncommunicable diseases, especially cardiovascular diseases.
Abstract: Background: With advances in antiretroviral therapy, most deaths in people with HIV are now attributable to noncommunicable illnesses, especially cardiovascular disease. We determine the associatio...