Showing papers by "University of Miami published in 2017"
University of Texas Health Science Center at Houston1, University of South Florida2, Washington University in St. Louis3, University of Miami4, Stanford University5, Harvard University6, Yeshiva University7, Vanderbilt University8, City of Hope National Medical Center9, Mayo Clinic10, University of California, Los Angeles11, Loyola University Chicago12, University of Rochester13, Sarah Cannon Research Institute14, Rutgers University15, Cleveland Clinic16, Wayne State University17, University of Iowa18, University of Texas MD Anderson Cancer Center19, Tel Aviv University20, University of California, San Diego21
TL;DR: Patients with refractory large B‐cell lymphoma who received CAR T‐cell therapy with axi‐cel had high levels of durable response, with a safety profile that included myelosuppression, the cytokine release syndrome, and neurologic events.
Abstract: BackgroundIn a phase 1 trial, axicabtagene ciloleucel (axi-cel), an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, showed efficacy in patients with refractory large B-cell lymphoma after the failure of conventional therapy. MethodsIn this multicenter, phase 2 trial, we enrolled 111 patients with diffuse large B-cell lymphoma, primary mediastinal B-cell lymphoma, or transformed follicular lymphoma who had refractory disease despite undergoing recommended prior therapy. Patients received a target dose of 2×106 anti-CD19 CAR T cells per kilogram of body weight after receiving a conditioning regimen of low-dose cyclophosphamide and fludarabine. The primary end point was the rate of objective response (calculated as the combined rates of complete response and partial response). Secondary end points included overall survival, safety, and biomarker assessments. ResultsAmong the 111 patients who were enrolled, axi-cel was successfully manufactured for 110 (99%) and administered to 101 (91%)....
3,363 citations
Imperial College London1, Anglia Ruskin University2, University of New South Wales3, Brien Holden Vision Institute4, International Agency for the Prevention of Blindness5, Moorfields Eye Hospital6, York Hospital7, Heidelberg University8, L V Prasad Eye Institute9, Massachusetts Eye and Ear Infirmary10, Nova Southeastern University11, University of KwaZulu-Natal12, National Health and Medical Research Council13, World Health Organization14, National University of Singapore15, University of Melbourne16, Selçuk University17, University of Miami18, University of Adelaide19, Queen's University Belfast20, Harvard University21, The George Institute for Global Health22, University of Washington23, University of Michigan24, Universiti Tunku Abdul Rahman25, University of Alabama at Birmingham26, National Institutes of Health27, Johns Hopkins University28, University of São Paulo29, Henry Ford Health System30, University College London31, Sankara Nethralaya32, University of Nairobi33, University of Georgia34, University of Utah35, Federal University of São Paulo36, Yale University37, Alberta Children's Hospital38, University of Illinois at Chicago39, Medical College of Wisconsin40, Novartis41, University of Udine42, University of Illinois at Urbana–Champaign43, Royal Children's Hospital44, University of Missouri45, Centers for Disease Control and Prevention46, University of Milan47, Icahn School of Medicine at Mount Sinai48, Mayo Clinic49, Pan American Health Organization50, University of Indonesia51, University of Pennsylvania52, University of Crete53, University of Southern California54, University of Florence55, Capital Medical University56, Leipzig University57
TL;DR: A series of regression models were fitted to estimate the proportion of moderate or severe vision impairment and blindness by cause, age, region, and year, and found that world regions varied markedly in the causes of blindness and vision impairment in this age group.
1,909 citations
Anglia Ruskin University1, University of Oxford2, Heidelberg University3, L V Prasad Eye Institute4, Massachusetts Eye and Ear Infirmary5, Nova Southeastern University6, Brien Holden Vision Institute7, University of KwaZulu-Natal8, Flinders University9, University of New South Wales10, Royal Liverpool University Hospital11, World Health Organization12, National University of Singapore13, University of Melbourne14, Selçuk University15, University of Burgundy16, University of Miami17, University of Adelaide18, Queen's University Belfast19, Harvard University20, The George Institute for Global Health21, University of Washington22, University of Michigan23, Universiti Tunku Abdul Rahman24, University of Alabama25, National Institutes of Health26, Johns Hopkins University27, University of São Paulo28, Henry Ford Health System29, University College London30, University of Nairobi31, University of Georgia32, University of Utah33, Federal University of São Paulo34, Yale University35, Alberta Children's Hospital36, University of Pennsylvania37, Medical College of Wisconsin38, Novartis39, University of Udine40, University of Illinois at Urbana–Champaign41, Royal Children's Hospital42, University of Missouri43, University of Milan44, Centers for Disease Control and Prevention45, Singapore National Eye Center46, Icahn School of Medicine at Mount Sinai47, Mayo Clinic48, Pan American Health Organization49, University of Indonesia50, University of Crete51, Erasmus University Rotterdam52, University of Southern California53, University of Florence54, Stellenbosch University55, Capital Medical University56, Leipzig University57, Moorfields Eye Hospital58
TL;DR: There is an ongoing reduction in the age-standardised prevalence of blindness and visual impairment, yet the growth and ageing of the world's population is causing a substantial increase in number of people affected, highlighting the need to scale up vision impairment alleviation efforts at all levels.
1,473 citations
TL;DR: Although screening for rarer atypical forms of diabetic neuropathy may be warranted, DSPN and autonomic neuropathy are the most common forms encountered in practice and the strongest available evidence regarding treatment pertains to these forms.
Abstract: Diabetic neuropathies are the most prevalent chronic complications of diabetes. This heterogeneous group of conditions affects different parts of the nervous system and presents with diverse clinical manifestations. The early recognition and appropriate management of neuropathy in the patient with diabetes is important for a number of reasons:
1. Diabetic neuropathy is a diagnosis of exclusion. Nondiabetic neuropathies may be present in patients with diabetes and may be treatable by specific measures.
2. A number of treatment options exist for symptomatic diabetic neuropathy.
3. Up to 50% of diabetic peripheral neuropathies may be asymptomatic. If not recognized and if preventive foot care is not implemented, patients are at risk for injuries to their insensate feet.
4. Recognition and treatment of autonomic neuropathy may improve symptoms, reduce sequelae, and improve quality of life.
Among the various forms of diabetic neuropathy, distal symmetric polyneuropathy (DSPN) and diabetic autonomic neuropathies, particularly cardiovascular autonomic neuropathy (CAN), are by far the most studied (1–4). There are several atypical forms of diabetic neuropathy as well (1–4). Patients with prediabetes may also develop neuropathies that are similar to diabetic neuropathies (5–10). Table 1 provides a comprehensive classification scheme for the diabetic neuropathies.
View this table:
Table 1
Classification for diabetic neuropathies
Due to a lack of treatments that target the underlying nerve damage, prevention is the key component of diabetes care. Screening for symptoms and signs of diabetic neuropathy is also critical in clinical practice, as it may detect the earliest stages of neuropathy, enabling early intervention. Although screening for rarer atypical forms of diabetic neuropathy may be warranted, DSPN and autonomic neuropathy are the most common forms encountered in practice. The strongest available evidence regarding treatment pertains to these forms.
This Position Statement is based on several recent technical reviews, to which the reader is referred for detailed discussion …
1,306 citations
University of California, San Francisco1, University of Basel2, University of British Columbia3, McGill University4, Vita-Salute San Raffaele University5, Queen Mary University of London6, University of Düsseldorf7, Icahn School of Medicine at Mount Sinai8, University of Miami9, Hoffmann-La Roche10, Genentech11, Baylor College of Medicine12
TL;DR: Among patients with primary progressive multiple sclerosis, ocrelizumab was associated with lower rates of clinical and MRI progression than placebo; there was no clinically significant difference between groups in the rates of serious adverse events and serious infections.
Abstract: BackgroundAn evolving understanding of the immunopathogenesis of multiple sclerosis suggests that depleting B cells could be useful for treatment. We studied ocrelizumab, a humanized monoclonal antibody that selectively depletes CD20-expressing B cells, in the primary progressive form of the disease. MethodsIn this phase 3 trial, we randomly assigned 732 patients with primary progressive multiple sclerosis in a 2:1 ratio to receive intravenous ocrelizumab (600 mg) or placebo every 24 weeks for at least 120 weeks and until a prespecified number of confirmed disability progression events had occurred. The primary end point was the percentage of patients with disability progression confirmed at 12 weeks in a time-to-event analysis. ResultsThe percentage of patients with 12-week confirmed disability progression was 32.9% with ocrelizumab versus 39.3% with placebo (hazard ratio, 0.76; 95% confidence interval [CI], 0.59 to 0.98; P=0.03). The percentage of patients with 24-week confirmed disability progression w...
1,220 citations
Memorial Sloan Kettering Cancer Center1, Cornell University2, University of Texas MD Anderson Cancer Center3, University of Colorado Denver4, Harvard University5, NewYork–Presbyterian Hospital6, Northwestern University7, Sarah Cannon Research Institute8, University of Texas Southwestern Medical Center9, City of Hope National Medical Center10, Cleveland Clinic11, University of Miami12, Stanford University13, Université Paris-Saclay14, Institut Gustave Roussy15, University of Oxford16, Celgene17, Agios Pharmaceuticals18
TL;DR: Inducing differentiation of myeloblasts, not cytotoxicity, seems to drive the clinical efficacy of enasidenib, a first-in-class, oral, selective inhibitor of mutant-IDH2 enzymes.
1,084 citations
University of East Anglia1, University of Exeter2, Max Planck Society3, Commonwealth Scientific and Industrial Research Organisation4, Stanford University5, Oak Ridge National Laboratory6, National Oceanic and Atmospheric Administration7, Cooperative Institute for Marine and Atmospheric Studies8, Atlantic Oceanographic and Meteorological Laboratory9, Geophysical Institute, University of Bergen10, Bjerknes Centre for Climate Research11, Met Office12, École Normale Supérieure13, Centre national de la recherche scientifique14, University of Maryland, College Park15, National Institute of Water and Atmospheric Research16, International Institute for Applied Systems Analysis17, Alfred Wegener Institute for Polar and Marine Research18, Woods Hole Oceanographic Institution19, University of New Hampshire20, University of Illinois at Urbana–Champaign21, Karlsruhe Institute of Technology22, University of California, San Diego23, Netherlands Environmental Assessment Agency24, Utrecht University25, Leibniz Institute of Marine Sciences26, University of Paris27, Hobart Corporation28, Cooperative Research Centre29, Oeschger Centre for Climate Change Research30, University of Bern31, National Center for Atmospheric Research32, University of Miami33, Council of Scientific and Industrial Research34, Institute of Arctic and Alpine Research35, National Institute for Environmental Studies36, Spanish National Research Council37, Montana State University38, Goddard Space Flight Center39, Leibniz Institute for Baltic Sea Research40, University of Delaware41, Auburn University42, Food and Agriculture Organization43, Wageningen University and Research Centre44, VU University Amsterdam45, University of Groningen46
TL;DR: In this paper, the authors quantify the five major components of the global carbon budget and their uncertainties, and the resulting carbon budget imbalance (BIM) is a measure of imperfect data and understanding of the contemporary carbon cycle.
Abstract: Accurate assessment of anthropogenic carbon dioxide (CO2) emissions and their redistribution among the atmosphere, ocean, and terrestrial biosphere – the "global carbon budget" – is important to better understand the global carbon cycle, support the development of climate policies, and project future climate change. Here we describe data sets and methodology to quantify the five major components of the global carbon budget and their uncertainties. CO2 emissions from fossil fuels and industry (EFF) are based on energy statistics and cement production data, respectively, while emissions from land-use change (ELUC), mainly deforestation, are based on land-cover change data and bookkeeping models. The global atmospheric CO2 concentration is measured directly and its rate of growth (GATM) is computed from the annual changes in concentration. The ocean CO2 sink (SOCEAN) and terrestrial CO2 sink (SLAND) are estimated with global process models constrained by observations. The resulting carbon budget imbalance (BIM), the difference between the estimated total emissions and the estimated changes in the atmosphere, ocean, and terrestrial biosphere, is a measure of imperfect data and understanding of the contemporary carbon cycle. All uncertainties are reported as ±1σ. For the last decade available (2007–2016), EFF was 9.4 ± 0.5 GtC yr−1, ELUC 1.3 ± 0.7 GtC yr−1, GATM 4.7 ± 0.1 GtC yr−1, SOCEAN 2.4 ± 0.5 GtC yr−1, and SLAND 3.0 ± 0.8 GtC yr−1, with a budget imbalance BIM of 0.6 GtC yr−1 indicating overestimated emissions and/or underestimated sinks. For year 2016 alone, the growth in EFF was approximately zero and emissions remained at 9.9 ± 0.5 GtC yr−1. Also for 2016, ELUC was 1.3 ± 0.7 GtC yr−1, GATM was 6.1 ± 0.2 GtC yr−1, SOCEAN was 2.6 ± 0.5 GtC yr−1, and SLAND was 2.7 ± 1.0 GtC yr−1, with a small BIM of −0.3 GtC. GATM continued to be higher in 2016 compared to the past decade (2007–2016), reflecting in part the high fossil emissions and the small SLAND consistent with El Nino conditions. The global atmospheric CO2 concentration reached 402.8 ± 0.1 ppm averaged over 2016. For 2017, preliminary data for the first 6–9 months indicate a renewed growth in EFF of +2.0 % (range of 0.8 to 3.0 %) based on national emissions projections for China, USA, and India, and projections of gross domestic product (GDP) corrected for recent changes in the carbon intensity of the economy for the rest of the world. This living data update documents changes in the methods and data sets used in this new global carbon budget compared with previous publications of this data set (Le Quere et al., 2016, 2015b, a, 2014, 2013). All results presented here can be downloaded from https://doi.org/10.18160/GCP-2017 (GCP, 2017).
884 citations
University of Miami1, University of California, Irvine2, Icahn School of Medicine at Mount Sinai3, Tulane University4, Baylor College of Medicine5, Oakland University6, University of California, San Diego7, University of Alabama8, The Ohio State University Wexner Medical Center9, Foundation for Biomedical Research10, Oregon Health & Science University11, University of Chicago12
TL;DR: This CPG is a practical tool that endocrinologists, other health care professionals, health-related organizations, and regulatory bodies can use to reduce the risks and consequences of dyslipidemia.
834 citations
TL;DR: It is shown that cytoplasmic chromatin activates the innate immunity cytosolic DNA-sensing cGAS–STING (cyclic GMP–AMP synthase linked to stimulator of interferon genes) pathway, leading both to short-term inflammation to restrain activated oncogenes and to chronic inflammation that associates with tissue destruction and cancer.
Abstract: Chromatin is traditionally viewed as a nuclear entity that regulates gene expression and silencing. However, we recently discovered the presence of cytoplasmic chromatin fragments that pinch off from intact nuclei of primary cells during senescence, a form of terminal cell-cycle arrest associated with pro-inflammatory responses. The functional significance of chromatin in the cytoplasm is unclear. Here we show that cytoplasmic chromatin activates the innate immunity cytosolic DNA-sensing cGAS-STING (cyclic GMP-AMP synthase linked to stimulator of interferon genes) pathway, leading both to short-term inflammation to restrain activated oncogenes and to chronic inflammation that associates with tissue destruction and cancer. The cytoplasmic chromatin-cGAS-STING pathway promotes the senescence-associated secretory phenotype in primary human cells and in mice. Mice deficient in STING show impaired immuno-surveillance of oncogenic RAS and reduced tissue inflammation upon ionizing radiation. Furthermore, this pathway is activated in cancer cells, and correlates with pro-inflammatory gene expression in human cancers. Overall, our findings indicate that genomic DNA serves as a reservoir to initiate a pro-inflammatory pathway in the cytoplasm in senescence and cancer. Targeting the cytoplasmic chromatin-mediated pathway may hold promise in treating inflammation-related disorders.
741 citations
TL;DR: Three new genome-wide significant nonsynonymous variants associated with Alzheimer's disease are observed, providing additional evidence that the microglia-mediated innate immune response contributes directly to the development of Alzheimer's Disease.
Abstract: We identified rare coding variants associated with Alzheimer's disease in a three-stage case–control study of 85,133 subjects. In stage 1, we genotyped 34,174 samples using a whole-exome microarray. In stage 2, we tested associated variants (P < 1 × 10−4) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, we used an additional 14,997 samples to test the most significant stage 2 associations (P < 5 × 10−8) using imputed genotypes. We observed three new genome-wide significant nonsynonymous variants associated with Alzheimer's disease: a protective variant in PLCG2 (rs72824905: p.Pro522Arg, P = 5.38 × 10−10, odds ratio (OR) = 0.68, minor allele frequency (MAF)cases = 0.0059, MAFcontrols = 0.0093), a risk variant in ABI3 (rs616338: p.Ser209Phe, P = 4.56 × 10−10, OR = 1.43, MAFcases = 0.011, MAFcontrols = 0.008), and a new genome-wide significant variant in TREM2 (rs143332484: p.Arg62His, P = 1.55 × 10−14, OR = 1.67, MAFcases = 0.0143, MAFcontrols = 0.0089), a known susceptibility gene for Alzheimer's disease. These protein-altering changes are in genes highly expressed in microglia and highlight an immune-related protein–protein interaction network enriched for previously identified risk genes in Alzheimer's disease. These genetic findings provide additional evidence that the microglia-mediated innate immune response contributes directly to the development of Alzheimer's disease.
730 citations
Mayo Clinic1, Yale University2, Case Western Reserve University3, Children's National Medical Center4, University of California, San Diego5, University of Miami6, Virginia Commonwealth University7, University of Calgary8, Cleveland Clinic9, University of Gothenburg10, University of British Columbia11, Saint Louis University12, Johns Hopkins University13, Dartmouth College14, University of Washington15, University of Texas MD Anderson Cancer Center16, Veterans Health Administration17, Royal Melbourne Hospital18, Cedars-Sinai Medical Center19, University of Colorado Denver20
TL;DR: Fred M. Kusumoto,MD, FHRS, FACC, Chair, Mark H. Schoenfeld, MD, F hrs, F ACC, FAHA, CCDS, Vice-Chair, Bruce L. Wilkoff, MD; Ulrika M. Birgersdotter-Green, MD.
TL;DR: The aim of this study was to provide evidence that palliative care and pain relief research should be considered as a continuum of treatment for patients with life-threatening illnesses.
Charité1, Oregon Health & Science University2, French Institute of Health and Medical Research3, University of Western Australia4, King Edward Memorial Hospital5, Sanford Health6, Children's Hospital of Eastern Ontario7, University of Toronto8, University of Cambridge9, University College London10, Cold Spring Harbor Laboratory11, Queen Mary University of London12, Radboud University Nijmegen13, Wellcome Trust Sanger Institute14, Katholieke Universiteit Leuven15, Johns Hopkins University School of Medicine16, University of Kiel17, University of Pennsylvania18, University of Luxembourg19, Medical College of Wisconsin20, Newcastle University21, Tohoku University22, Manchester Royal Eye Hospital23, John Radcliffe Hospital24, University of Sydney25, University of Miami26, Garvan Institute of Medical Research27, Lawrence Berkeley National Laboratory28, University of Connecticut29
TL;DR: The progress of the HPO project is reviewed, including specific areas of expansion such as common (complex) disease, new algorithms for phenotype driven genomic discovery and diagnostics, integration of cross-species mapping efforts with the Mammalian Phenotype Ontology, an improved quality control pipeline, and the addition of patient-friendly terminology.
Abstract: Deep phenotyping has been defined as the precise and comprehensive analysis of phenotypic abnormalities in which the individual components of the phenotype are observed and described. The three components of the Human Phenotype Ontology (HPO; www.human-phenotype-ontology.org) project are the phenotype vocabulary, disease-phenotype annotations and the algorithms that operate on these. These components are being used for computational deep phenotyping and precision medicine as well as integration of clinical data into translational research. The HPO is being increasingly adopted as a standard for phenotypic abnormalities by diverse groups such as international rare disease organizations, registries, clinical labs, biomedical resources, and clinical software tools and will thereby contribute toward nascent efforts at global data exchange for identifying disease etiologies. This update article reviews the progress of the HPO project since the debut Nucleic Acids Research database article in 2014, including specific areas of expansion such as common (complex) disease, new algorithms for phenotype driven genomic discovery and diagnostics, integration of cross-species mapping efforts with the Mammalian Phenotype Ontology, an improved quality control pipeline, and the addition of patient-friendly terminology.
TL;DR: The methods used to create OCTA images, the practical applications of OCTA in light of invasive dye‐imaging studies (e.g. fluorescein angiography) and clinical studies demonstrating the utility of OCT a for research and clinical practice are discussed.
TL;DR: A concise summary of known structural and functional features of the human insular cortex with a focus on lesion case studies and recent neuroimaging evidence for considerable functional heterogeneity of this brain region is provided.
Abstract: The insular cortex, or "Island of Reil," is hidden deep within the lateral sulcus of the brain. Subdivisions within the insula have been identified on the basis of cytoarchitectonics, sulcal landmarks, and connectivity. Depending on the parcellation technique used, the insula can be divided into anywhere between 2 and 13 distinct subdivisions. The insula subserves a wide variety of functions in humans ranging from sensory and affective processing to high-level cognition. Here, we provide a concise summary of known structural and functional features of the human insular cortex with a focus on lesion case studies and recent neuroimaging evidence for considerable functional heterogeneity of this brain region.
University of North Florida1, Georgia Regents University2, Medical University of South Carolina3, East Carolina University4, Universidade Federal do Rio Grande do Sul5, Baptist Health6, University of the West Indies7, University of Miami8, University of Illinois at Chicago9, University of São Paulo10, State University of Campinas11, Virginia Commonwealth University12
TL;DR: In patients with Sickle cell disease, crizanlizumab therapy resulted in a significantly lower rate of sickle cell–related pain crises than placebo and was associated with a low incidence of adverse events.
Abstract: BackgroundThe up-regulation of P-selectin in endothelial cells and platelets contributes to the cell–cell interactions that are involved in the pathogenesis of vaso-occlusion and sickle cell–related pain crises. The safety and efficacy of crizanlizumab, an antibody against the adhesion molecule P-selectin, were evaluated in patients with sickle cell disease. MethodsIn this double-blind, randomized, placebo-controlled, phase 2 trial, we assigned patients to receive low-dose crizanlizumab (2.5 mg per kilogram of body weight), high-dose crizanlizumab (5.0 mg per kilogram), or placebo, administered intravenously 14 times over a period of 52 weeks. Patients who were receiving concomitant hydroxyurea as well as those not receiving hydroxyurea were included in the study. The primary end point was the annual rate of sickle cell–related pain crises with high-dose crizanlizumab versus placebo. The annual rate of days hospitalized, the times to first and second crises, annual rates of uncomplicated crises (defined a...
University of Western Ontario1, University of Edinburgh2, King's College London3, California Pacific Medical Center4, University of Manchester5, University of East Anglia6, Northwestern University7, University of Miami8, University of Debrecen9, Loma Linda University10, University of Milan11, University of Sheffield12, University of Oxford13
TL;DR: These revised consensus criteria expand upon those of 2009 and embrace the concept of the frontotemporal spectrum disorder of ALS (ALS-FTSD), which is a re-conceptualisation that neuropsychological deficits in ALS fall along a spectrum.
Abstract: This article presents the revised consensus criteria for the diagnosis of frontotemporal dysfunction in amyotrophic lateral sclerosis (ALS) based on an international research workshop on frontotemporal dementia (FTD) and ALS held in London, Canada in June 2015. Since the publication of the Strong criteria, there have been considerable advances in the understanding of the neuropsychological profile of patients with ALS. Not only is the breadth and depth of neuropsychological findings broader than previously recognised –– including deficits in social cognition and language – but mixed deficits may also occur. Evidence now shows that the neuropsychological deficits in ALS are extremely heterogeneous, affecting over 50% of persons with ALS. When present, these deficits significantly and adversely impact patient survival. It is the recognition of this clinical heterogeneity in association with neuroimaging, genetic and neuropathological advances that has led to the current re-conceptualisation that neu...
Norwich Research Park1, Institut national de la recherche agronomique2, French Institute for Research in Computer Science and Automation3, Institut national des sciences Appliquées de Lyon4, University of Montpellier5, University of East Anglia6, University of Rennes7, University of Miami8, Pompeu Fabra University9, Rothamsted Research10, Simplot11, University of Cambridge12, Université Paris-Saclay13, Boyce Thompson Institute for Plant Research14
TL;DR: It is shown that the generalist aphid pest M. persicae is able to colonise diverse host plant species in the absence of genetic specialisation through rapid transcriptional plasticity of genes that have duplicated during aphid evolution.
Abstract: The prevailing paradigm of host-parasite evolution is that arms races lead to increasing specialisation via genetic adaptation. Insect herbivores are no exception and the majority have evolved to colonise a small number of closely related host species. Remarkably, the green peach aphid, Myzus persicae, colonises plant species across 40 families and single M. persicae clonal lineages can colonise distantly related plants. This remarkable ability makes M. persicae a highly destructive pest of many important crop species. To investigate the exceptional phenotypic plasticity of M. persicae, we sequenced the M. persicae genome and assessed how one clonal lineage responds to host plant species of different families. We show that genetically identical individuals are able to colonise distantly related host species through the differential regulation of genes belonging to aphid-expanded gene families. Multigene clusters collectively upregulate in single aphids within two days upon host switch. Furthermore, we demonstrate the functional significance of this rapid transcriptional change using RNA interference (RNAi)-mediated knock-down of genes belonging to the cathepsin B gene family. Knock-down of cathepsin B genes reduced aphid fitness, but only on the host that induced upregulation of these genes. Previous research has focused on the role of genetic adaptation of parasites to their hosts. Here we show that the generalist aphid pest M. persicae is able to colonise diverse host plant species in the absence of genetic specialisation. This is achieved through rapid transcriptional plasticity of genes that have duplicated during aphid evolution.
TL;DR: In this article, the variation of anti-corruption and anti-elite saliency in party positioning across Europe was studied. And it was shown that while anticorruption salience is primarily related to the (regional) context in which a party operates, anti-ELite salience was primarily a function of party ideology, and extreme left and extreme conservative (TAN) parties are significantly more likely to emphasize antielite views.
Abstract: This article addresses the variation of anti-corruption and anti-elite salience in party positioning across Europe. It demonstrates that while anti-corruption salience is primarily related to the (regional) context in which a party operates, anti-elite salience is primarily a function of party ideology. Extreme left and extreme conservative (TAN) parties are significantly more likely to emphasize anti-elite views. Through its use of the new 2014 Chapel Hill Expert Survey wave, this article also introduces the dataset.
TL;DR: Overall effect size (ES) and moderator effects were assessed using multilevel modeling to address ES dependency that is common, but typically not modeled, in meta-analyses, and only youth-focused behavioral therapies showed similar and robust effects across youth, parent, and teacher reports.
Abstract: Across 5 decades, hundreds of randomized trials have tested psychological therapies for youth internalizing (anxiety, depression) and externalizing (misconduct, attention deficit and hyperactivity disorder) disorders and problems. Since the last broad-based youth meta-analysis in 1995, the number of trials has almost tripled and data-analytic methods have been refined. We applied these methods to the expanded study pool (447 studies; 30,431 youths), synthesizing 50 years of findings and identifying implications for research and practice. We assessed overall effect size (ES) and moderator effects using multilevel modeling to address ES dependency that is common, but typically not modeled, in meta-analyses. Mean posttreatment ES was 0.46; the probability that a youth in the treatment condition would fare better than a youth in the control condition was 63%. Effects varied according to multiple moderators, including the problem targeted in treatment: Mean ES at posttreatment was strongest for anxiety (0.61), weakest for depression (0.29), and nonsignificant for multiproblem treatment (0.15). ESs differed across control conditions, with "usual care" emerging as a potent comparison condition, and across informants, highlighting the need to obtain and integrate multiple perspectives on outcome. Effects of therapy type varied by informant; only youth-focused behavioral therapies (including cognitive-behavioral therapy) showed similar and robust effects across youth, parent, and teacher reports. Effects did not differ for Caucasian versus minority samples, but more diverse samples are needed. The findings underscore the benefits of psychological treatments as well as the need for improved therapies and more representative, informative, and rigorous intervention science. (PsycINFO Database Record
TL;DR: In this article, a review summarizes the relationship between obesity and breast cancer development and outcomes in premenopausal and postmenopausal women and in those with hormone receptor-positive and -negative disease.
Abstract: Answer questions and earn CME/CNE
Recent decades have seen an unprecedented rise in obesity, and the health impact thereof is increasingly evident. In 2014, worldwide, more than 1.9 billion adults were overweight (body mass index [BMI], 25-29.9 kg/m2), and of these, over 600 million were obese (BMI ≥30 kg/m2). Although the association between obesity and the risk of diabetes and coronary artery disease is widely known, the impact of obesity on cancer incidence, morbidity, and mortality is not fully appreciated. Obesity is associated both with a higher risk of developing breast cancer, particularly in postmenopausal women, and with worse disease outcome for women of all ages. The first part of this review summarizes the relationships between obesity and breast cancer development and outcomes in premenopausal and postmenopausal women and in those with hormone receptor-positive and -negative disease. The second part of this review addresses hypothesized molecular mechanistic insights that may underlie the effects of obesity to increase local and circulating proinflammatory cytokines, promote tumor angiogenesis and stimulate the most malignant cancer stem cell population to drive cancer growth, invasion, and metastasis. Finally, a review of observational studies demonstrates that increased physical activity is associated with lower breast cancer risk and better outcomes. The effects of recent lifestyle interventions to decrease sex steroids, insulin/insulin-like growth factor-1 pathway activation, and inflammatory biomarkers associated with worse breast cancer outcomes in obesity also are discussed. Although many observational studies indicate that exercise with weight loss is associated with improved breast cancer outcome, further prospective studies are needed to determine whether weight reduction will lead to improved patient outcomes. It is hoped that several ongoing lifestyle intervention trials, which are reviewed herein, will support the systematic incorporation of weight loss intervention strategies into care for patients with breast cancer. CA Cancer J Clin 2017;67:378–397. © 2017 The Authors. CA A Cancer Journal for Clinicians published by Wiley Periodicals, Inc. on behalf of American Cancer Society. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
TL;DR: The techniques required for human islet isolation, in vitro culture before the transplant and clinical islet transplantation are outlined and the potential risks, long-term outcomes and advances in treatment after the transplant are discussed to further move this treatment towards becoming a more widely available option for patients with type 1 diabetes mellitus and eventually a potential cure.
Abstract: Islet transplantation has become a realistic treatment option for a subset of patients with type 1 diabetes mellitus. This Review outlines the techniques involved in the procedure, as well as the risks, long-term outcomes and advances in the care of patients after they have received an islet transplant.
TL;DR: A major upgrade to the Stata (and R) rdrobust package, which provides a wide array of estimation, inference, and falsification methods for the analysis and interpretation of regression-discontinuity designs, has superior performance because of several numerical and implementation improvements.
Abstract: We describe a major upgrade to the Stata (and R) rdrobust package, which provides a wide array of estimation, inference, and falsification methods for the analysis and interpretation of regression-...
TL;DR: TET-mediated DNA oxidation induced by vitamin C treatment in leukemia cells enhances their sensitivity to PARP inhibition and could provide a safe and effective combination strategy to selectively target TET deficiency in cancer.
TL;DR: A critical review of existing studies on the effects of using sea-sand and/or seawater as raw materials of concrete on the properties of the resulting concrete, including its workability, short and long-term strength as well as durability is presented in this paper.
TL;DR: The current focus of this review is resveratrol’s in vivo and in vitro effects in a variety of cancers, and intracellular molecular targets modulated by this polyphenol.
Abstract: Natural product compounds have recently attracted significant attention from the scientific community for their potent effects against inflammation-driven diseases, including cancer. A significant amount of research, including preclinical, clinical, and epidemiological studies, has indicated that dietary consumption of polyphenols, found at high levels in cereals, pulses, vegetables, and fruits, may prevent the evolution of an array of diseases, including cancer. Cancer development is a carefully orchestrated progression where normal cells acquires mutations in their genetic makeup, which cause the cells to continuously grow, colonize, and metastasize to other organs such as the liver, lungs, colon, and brain. Compounds that modulate these oncogenic processes can be considered as potential anti-cancer agents that may ultimately make it to clinical application. Resveratrol, a natural stilbene and a non-flavonoid polyphenol, is a phytoestrogen that possesses anti-oxidant, anti-inflammatory, cardioprotective, and anti-cancer properties. It has been reported that resveratrol can reverse multidrug resistance in cancer cells, and, when used in combination with clinically used drugs, it can sensitize cancer cells to standard chemotherapeutic agents. Several novel analogs of resveratrol have been developed with improved anti-cancer activity, bioavailability, and pharmacokinetic profile. The current focus of this review is resveratrol's in vivo and in vitro effects in a variety of cancers, and intracellular molecular targets modulated by this polyphenol. This is also accompanied by a comprehensive update of the various clinical trials that have demonstrated it to be a promising therapeutic and chemopreventive agent.
TL;DR: A significant genetic correlation with schizophrenia and association of ASD with several neurodevelopmental-related genes such as EXT1, ASTN2, MACROD2, and HDAC4 is identified and identified.
Abstract: Background: Over the past decade genome-wide association studies (GWAS) have been applied to aid in the
understanding of the biology of traits. The success of this approach is governed by the underlying effect sizes carried
by the true risk variants and the corresponding statistical power to observe such effects given the study design and
sample size under investigation. Previous ASD GWAS have identified genome-wide significant (GWS) risk loci; however,
these studies were of only of low statistical power to identify GWS loci at the lower effect sizes (odds ratio (OR) <1.15).
Methods: We conducted a large-scale coordinated international collaboration to combine independent genotyping
data to improve the statistical power and aid in robust discovery of GWS loci. This study uses genome-wide
genotyping data from a discovery sample (7387 ASD cases and 8567 controls) followed by meta-analysis of summary
statistics from two replication sets (7783 ASD cases and 11359 controls; and 1369 ASD cases and 137308 controls).
Results: We observe a GWS locus at 10q24.32 that overlaps several genes including PITX3, which encodes a transcription
factor identified as playing a role in neuronal differentiation and CUEDC2 previously reported to be associated with social
skills in an independent population cohort. We also observe overlap with regions previously implicated in schizophrenia
which was further supported by a strong genetic correlation between these disorders (Rg = 0.23; P=9 ×10−6). We further
combined these Psychiatric Genomics Consortium (PGC) ASD GWAS data with the recent PGC schizophrenia GWAS to
identify additional regions which may be important in a common neurodevelopmental phenotype and identified 12
novel GWS loci. These include loci previously implicated in ASD such as FOXP1 at 3p13, ATP2B2 at 3p25.3, and a
‘neurodevelopmental hub’ on chromosome 8p11.23.
Conclusions: This study is an important step in the ongoing endeavour to identify the loci which underpin the common
variant signal in ASD. In addition to novel GWS loci, we have identified a significant genetic correlation with schizophrenia
and association of ASD with several neurodevelopmental-related genes such as EXT1, ASTN2, MACROD2, and HDAC4.
University of Miami1, University of Chicago2, Dresden University of Technology3, American Diabetes Association4, Anschutz Medical Campus5, Lund University6, Baker IDI Heart and Diabetes Institute7, University of Helsinki8, JDRF9, Katholieke Universiteit Leuven10, University of Washington11, University of Florida12, University of Liverpool13
TL;DR: A structure for data stratification to define the phenotypes and genotypes of subtypes of diabetes that will facilitate individualized treatment is recommended.
Abstract: The American Diabetes Association, JDRF, the European Association for the Study of Diabetes, and the American Association of Clinical Endocrinologists convened a research symposium, “The Differentiation of Diabetes by Pathophysiology, Natural History and Prognosis” on 10–12 October 2015. International experts in genetics, immunology, metabolism, endocrinology, and systems biology discussed genetic and environmental determinants of type 1 and type 2 diabetes risk and progression, as well as complications. The participants debated how to determine appropriate therapeutic approaches based on disease pathophysiology and stage and defined remaining research gaps hindering a personalized medical approach for diabetes to drive the field to address these gaps. The authors recommend a structure for data stratification to define the phenotypes and genotypes of subtypes of diabetes that will facilitate individualized treatment.
University of British Columbia1, Mayo Clinic2, Howard Hughes Medical Institute3, Simon Fraser University4, University of Texas Southwestern Medical Center5, University of Toronto6, Northwestern University7, University of Pittsburgh8, University of Chicago9, University of Miami10, University of Western Ontario11, Drexel University12, Thomas Jefferson University13
TL;DR: The identification of TIA1 mutations in ALS/FTD reinforces the importance of RNA metabolism and SG dynamics in ALS-FTD pathogenesis.
Henry Ford Health System1, Northwestern University2, Ottawa Hospital Research Institute3, Cedars-Sinai Medical Center4, Baylor College of Medicine5, Royal Prince Alfred Hospital6, Icahn School of Medicine at Mount Sinai7, Hannover Medical School8, University of Washington9, Beth Israel Deaconess Medical Center10, University of Miami11, University of Pennsylvania12
TL;DR: Sofosbuvir‐velpatasvir‐voxilaprevir taken for 12 weeks provided high rates of sustained virologic response among patients across HCV genotypes in whom treatment with a DAA regimen had previously failed.
Abstract: BackgroundPatients who are chronically infected with hepatitis C virus (HCV) and who do not have a sustained virologic response after treatment with regimens containing direct-acting antiviral agents (DAAs) have limited retreatment options MethodsWe conducted two phase 3 trials involving patients who had been previously treated with a DAA-containing regimen In POLARIS-1, patients with HCV genotype 1 infection who had previously received a regimen containing an NS5A inhibitor were randomly assigned in a 1:1 ratio to receive either the nucleotide polymerase inhibitor sofosbuvir, the NS5A inhibitor velpatasvir, and the protease inhibitor voxilaprevir (150 patients) or matching placebo (150 patients) once daily for 12 weeks Patients who were infected with HCV of other genotypes (114 patients) were enrolled in the sofosbuvir–velpatasvir–voxilaprevir group In POLARIS-4, patients with HCV genotype 1, 2, or 3 infection who had previously received a DAA regimen but not an NS5A inhibitor were randomly assigned