Showing papers by "Louisiana State University published in 2015"
TL;DR: The 1000 Genomes Project set out to provide a comprehensive description of common human genetic variation by applying whole-genome sequencing to a diverse set of individuals from multiple populations, and has reconstructed the genomes of 2,504 individuals from 26 populations using a combination of low-coverage whole-generation sequencing, deep exome sequencing, and dense microarray genotyping.
Abstract: The 1000 Genomes Project set out to provide a comprehensive description of common human genetic variation by applying whole-genome sequencing to a diverse set of individuals from multiple populations. Here we report completion of the project, having reconstructed the genomes of 2,504 individuals from 26 populations using a combination of low-coverage whole-genome sequencing, deep exome sequencing, and dense microarray genotyping. We characterized a broad spectrum of genetic variation, in total over 88 million variants (84.7 million single nucleotide polymorphisms (SNPs), 3.6 million short insertions/deletions (indels), and 60,000 structural variants), all phased onto high-quality haplotypes. This resource includes >99% of SNP variants with a frequency of >1% for a variety of ancestries. We describe the distribution of genetic variation across the global sample, and discuss the implications for common disease studies.
12,661 citations
University Hospital Bonn1, University of California, Riverside2, Harvard University3, Case Western Reserve University4, University of Illinois at Chicago5, European Institute6, VA Palo Alto Healthcare System7, Stanford University8, Spanish National Research Council9, Cleveland Clinic Lerner Research Institute10, Hong Kong University of Science and Technology11, University of California, Los Angeles12, University of Southern Denmark13, University of Cambridge14, University of Manchester15, Ikerbasque16, University of the Basque Country17, RIKEN Brain Science Institute18, University of Eastern Finland19, University of Bonn20, University of Massachusetts Medical School21, Center of Advanced European Studies and Research22, University of Southern California23, University of South Florida24, Duke University25, Southampton General Hospital26, University of Southampton27, Moorgreen Hospital28, Louisiana State University29, Imperial College London30, Centre national de la recherche scientifique31, Karolinska Institutet32, Max Planck Society33, University of Tübingen34, University of Groningen35, University of Colorado Denver36, Douglas Mental Health University Institute37
TL;DR: Genome-wide analysis suggests that several genes that increase the risk for sporadic Alzheimer's disease encode factors that regulate glial clearance of misfolded proteins and the inflammatory reaction.
Abstract: Increasing evidence suggests that Alzheimer's disease pathogenesis is not restricted to the neuronal compartment, but includes strong interactions with immunological mechanisms in the brain. Misfolded and aggregated proteins bind to pattern recognition receptors on microglia and astroglia, and trigger an innate immune response characterised by release of inflammatory mediators, which contribute to disease progression and severity. Genome-wide analysis suggests that several genes that increase the risk for sporadic Alzheimer's disease encode factors that regulate glial clearance of misfolded proteins and the inflammatory reaction. External factors, including systemic inflammation and obesity, are likely to interfere with immunological processes of the brain and further promote disease progression. Modulation of risk factors and targeting of these immune mechanisms could lead to future therapeutic or preventive strategies for Alzheimer's disease.
3,947 citations
University of Washington1, University of Maryland, Baltimore2, Harvard University3, Broad Institute4, Mayo Clinic5, Yale University6, Washington University in St. Louis7, University of Michigan8, University of Texas Health Science Center at Houston9, Louisiana State University10, University of North Carolina at Charlotte11, Wellcome Trust12, University of Texas MD Anderson Cancer Center13, Boston College14, Yeshiva University15, Bilkent University16, University of California, San Diego17, National Institutes of Health18, Leiden University19, Baylor College of Medicine20, Cornell University21, University of Oxford22, Utrecht University23, Icahn School of Medicine at Mount Sinai24, Kyoto University25, Virginia Commonwealth University26, Heidelberg University27, Ewha Womans University28
TL;DR: In this paper, the authors describe an integrated set of eight structural variant classes comprising both balanced and unbalanced variants, which are constructed using short-read DNA sequencing data and statistically phased onto haplotype blocks in 26 human populations.
Abstract: Structural variants are implicated in numerous diseases and make up the majority of varying nucleotides among human genomes. Here we describe an integrated set of eight structural variant classes comprising both balanced and unbalanced variants, which we constructed using short-read DNA sequencing data and statistically phased onto haplotype blocks in 26 human populations. Analysing this set, we identify numerous gene-intersecting structural variants exhibiting population stratification and describe naturally occurring homozygous gene knockouts that suggest the dispensability of a variety of human genes. We demonstrate that structural variants are enriched on haplotypes identified by genome-wide association studies and exhibit enrichment for expression quantitative trait loci. Additionally, we uncover appreciable levels of structural variant complexity at different scales, including genic loci subject to clusters of repeated rearrangement and complex structural variants with multiple breakpoints likely to have formed through individual mutational events. Our catalogue will enhance future studies into structural variant demography, functional impact and disease association.
1,971 citations
TL;DR: In this paper, the authors review the performance of the LIGO instruments during this epoch, the work done to characterize the detectors and their data, and the effect that transient and continuous noise artefacts have on the sensitivity of the detectors to a variety of astrophysical sources.
Abstract: In 2009–2010, the Laser Interferometer Gravitational-Wave Observatory (LIGO) operated together with international partners Virgo and GEO600 as a network to search for gravitational waves (GWs) of astrophysical origin. The sensitivity of these detectors was limited by a combination of noise sources inherent to the instrumental design and its environment, often localized in time or frequency, that couple into the GW readout. Here we review the performance of the LIGO instruments during this epoch, the work done to characterize the detectors and their data, and the effect that transient and continuous noise artefacts have on the sensitivity of LIGO to a variety of astrophysical sources.
1,266 citations
Memorial Sloan Kettering Cancer Center1, Louisiana State University2, Fred Hutchinson Cancer Research Center3, Harvard University4, University of Texas MD Anderson Cancer Center5, University of California, San Francisco6, University of Minnesota7, Emory University8, University of Virginia9, American Cancer Society10
TL;DR: The updated ACS guidelines for breast cancer screening for women at average risk of breast cancer provide evidence-based recommendations and should be considered by physicians and women in discussions about breast cancer Screening.
Abstract: Importance Breast cancer is a leading cause of premature mortality among US women. Early detection has been shown to be associated with reduced breast cancer morbidity and mortality. Objective To update the American Cancer Society (ACS) 2003 breast cancer screening guideline for women at average risk for breast cancer. Process The ACS commissioned a systematic evidence review of the breast cancer screening literature to inform the update and a supplemental analysis of mammography registry data to address questions related to the screening interval. Formulation of recommendations was based on the quality of the evidence and judgment (incorporating values and preferences) about the balance of benefits and harms. Evidence Synthesis Screening mammography in women aged 40 to 69 years is associated with a reduction in breast cancer deaths across a range of study designs, and inferential evidence supports breast cancer screening for women 70 years and older who are in good health. Estimates of the cumulative lifetime risk of false-positive examination results are greater if screening begins at younger ages because of the greater number of mammograms, as well as the higher recall rate in younger women. The quality of the evidence for overdiagnosis is not sufficient to estimate a lifetime risk with confidence. Analysis examining the screening interval demonstrates more favorable tumor characteristics when premenopausal women are screened annually vs biennially. Evidence does not support routine clinical breast examination as a screening method for women at average risk. Recommendations The ACS recommends that women with an average risk of breast cancer should undergo regular screening mammography starting at age 45 years (strong recommendation). Women aged 45 to 54 years should be screened annually (qualified recommendation). Women 55 years and older should transition to biennial screening or have the opportunity to continue screening annually (qualified recommendation). Women should have the opportunity to begin annual screening between the ages of 40 and 44 years (qualified recommendation). Women should continue screening mammography as long as their overall health is good and they have a life expectancy of 10 years or longer (qualified recommendation). The ACS does not recommend clinical breast examination for breast cancer screening among average-risk women at any age (qualified recommendation). Conclusions and Relevance These updated ACS guidelines provide evidence-based recommendations for breast cancer screening for women at average risk of breast cancer. These recommendations should be considered by physicians and women in discussions about breast cancer screening.
1,244 citations
TL;DR: The authors highlights the critical role of social capital and networks in disaster survival and recovery and lays out recent literature and evidence on the topic, concluding with concrete policy recommendations for disaster managers, government decision makers, and no...
Abstract: Despite the ubiquity of disaster and the increasing toll in human lives and financial costs, much research and policy remain focused on physical infrastructure–centered approaches to such events. Governmental organizations such as the Department of Homeland Security, United States Federal Emergency Management Agency, United States Agency for International Development, and United Kingdom’s Department for International Development continue to spend heavily on hardening levees, raising existing homes, and repairing damaged facilities despite evidence that social, not physical, infrastructure drives resilience. This article highlights the critical role of social capital and networks in disaster survival and recovery and lays out recent literature and evidence on the topic. We look at definitions of social capital, measurement and proxies, types of social capital, and mechanisms and application. The article concludes with concrete policy recommendations for disaster managers, government decision makers, and no...
1,096 citations
Iwate Medical University1, University of Pittsburgh2, Louisiana State University3, Toho University4, Mayo Clinic5, Royal Brisbane and Women's Hospital6, Tokyo Medical and Dental University7, Beaumont Hospital8, Ghent University9, University Hospital Southampton NHS Foundation Trust10, Sungkyunkwan University11, University of Oslo12, Yonsei University13, Vita-Salute San Raffaele University14, Zhejiang University15, University of Toronto16, Memorial Hospital of South Bend17, Fujita Health University18, Pamela Youde Nethersole Eastern Hospital19, University of São Paulo20, Hospital Italiano de Buenos Aires21, Huazhong University of Science and Technology22, South University23, Memorial Sloan Kettering Cancer Center24, University of Queensland25, Lilavati Hospital and Research Centre26, University of Hong Kong27, University of Zurich28, McGill University29, Washington University in St. Louis30
TL;DR: The Second International Consensus Conference on Laparoscopic Liver Resections (LLR) was held in Morioka, Japan, from October 4 to 6, 2014 to evaluate the current status of laparoscopic liver surgery and to provide recommendations to aid its future development.
Abstract: The use of laparoscopy for liver surgery is increasing rapidly. The Second International Consensus Conference on Laparoscopic Liver Resections (LLR) was held in Morioka, Japan, from October 4 to 6, 2014 to evaluate the current status of laparoscopic liver surgery and to provide recommendations to aid its future development. Seventeen questions were addressed. The first 7 questions focused on outcomes that reflect the benefits and risks of LLR. These questions were addressed using the Zurich-Danish consensus conference model in which the literature and expert opinion were weighed by a 9-member jury, who evaluated LLR outcomes using GRADE and a list of comparators. The jury also graded LLRs by the Balliol Classification of IDEAL. The jury concluded that MINOR LLRs had become standard practice (IDEAL 3) and that MAJOR liver resections were still innovative procedures in the exploration phase (IDEAL 2b). Continued cautious introduction of MAJOR LLRs was recommended. All of the evidence available for scrutiny was of LOW quality by GRADE, which prompted the recommendation for higher quality evaluative studies. The last 10 questions focused on technical questions and the recommendations were based on literature review and expert panel opinion. Recommendations were made regarding preoperative evaluation, bleeding controls, transection methods, anatomic approaches, and equipment. Both experts and jury recognized the need for a formal structure of education for those interested in performing major laparoscopic LLR because of the steep learning curve.
1,064 citations
TL;DR: An update on the latest advances in the clinical development of treatment strategies targeting cancer stem cells with rational combinations of agents to inhibit possible compensatory escape mechanisms is provided.
Abstract: During the past decade, cancer stem cells (CSCs) have been increasingly identified in many malignancies Although the origin and plasticity of these cells remain controversial, tumour heterogeneity and the presence of small populations of cells with stem-like characteristics is established in most malignancies CSCs display many features of embryonic or tissue stem cells, and typically demonstrate persistent activation of one or more highly conserved signal transduction pathways involved in development and tissue homeostasis, including the Notch, Hedgehog (HH), and Wnt pathways CSCs generally have slow growth rates and are resistant to chemotherapy and/or radiotherapy Thus, new treatment strategies targeting these pathways to control stem-cell replication, survival and differentiation are under development Herein, we provide an update on the latest advances in the clinical development of such approaches, and discuss strategies for overcoming CSC-associated primary or acquired resistance to cancer treatment Given the crosstalk between the different embryonic developmental signalling pathways, as well as other pathways, designing clinical trials that target CSCs with rational combinations of agents to inhibit possible compensatory escape mechanisms could be of particular importance We also share our views on the future directions for targeting CSCs to advance the clinical development of these classes of agents
976 citations
TL;DR: The possibility that multiple ROS sources contribute to reperfusion injury in most tissues is supported by evidence demonstrating that redox-signaling enables ROS produced by one enzymatic source to activate and enhance ROS production by a second source.
Abstract: Reperfusion injury, the paradoxical tissue response that is manifested by blood flow-deprived and oxygen-starved organs following the restoration of blood flow and tissue oxygenation, has been a focus of basic and clinical research for over 4-decades. While a variety of molecular mechanisms have been proposed to explain this phenomenon, excess production of reactive oxygen species (ROS) continues to receive much attention as a critical factor in the genesis of reperfusion injury. As a consequence, considerable effort has been devoted to identifying the dominant cellular and enzymatic sources of excess ROS production following ischemia-reperfusion (I/R). Of the potential ROS sources described to date, xanthine oxidase, NADPH oxidase (Nox), mitochondria, and uncoupled nitric oxide synthase have gained a status as the most likely contributors to reperfusion-induced oxidative stress and represent priority targets for therapeutic intervention against reperfusion-induced organ dysfunction and tissue damage. Although all four enzymatic sources are present in most tissues and are likely to play some role in reperfusion injury, priority and emphasis has been given to specific ROS sources that are enriched in certain tissues, such as xanthine oxidase in the gastrointestinal tract and mitochondria in the metabolically active heart and brain. The possibility that multiple ROS sources contribute to reperfusion injury in most tissues is supported by evidence demonstrating that redox-signaling enables ROS produced by one enzymatic source (e.g., Nox) to activate and enhance ROS production by a second source (e.g., mitochondria). This review provides a synopsis of the evidence implicating ROS in reperfusion injury, the clinical implications of this phenomenon, and summarizes current understanding of the four most frequently invoked enzymatic sources of ROS production in post-ischemic tissue.
910 citations
Paris Descartes University1, Institut Gustave Roussy2, Mount Sinai Hospital3, University of Texas Southwestern Medical Center4, University of Kiel5, Thomas Jefferson University6, Seconda Università degli Studi di Napoli7, University of Toronto8, University of Massachusetts Medical School9, Louisiana State University10, Flanders Institute for Biotechnology11, Ghent University12, Cancer Research UK13, Queen Mary University of London14, Roswell Park Cancer Institute15, Karolinska Institutet16, University of Freiburg17, University of California, San Francisco18, Buck Institute for Research on Aging19, French Institute of Health and Medical Research20, Université Paris-Saclay21, University College London22, University of Rome Tor Vergata23, Northwestern University24, Memorial Sloan Kettering Cancer Center25, National Institutes of Health26, Technion – Israel Institute of Technology27, Johns Hopkins University28, University of Chieti-Pescara29, University of Ulm30, Genentech31, New York University32, Pennsylvania State University33, University of Salento34, Yale University35, Goethe University Frankfurt36, University of Burgundy37, Pasteur Institute38, University of Strasbourg39, University of Zurich40, University of Tokyo41, Technische Universität München42, University of Bern43, University of Michigan44, Medical Research Council45, University of Adelaide46, University of South Australia47, Medical University of South Carolina48, Howard Hughes Medical Institute49, University of Texas at Dallas50, St. John's University51, University of Oviedo52, University of Graz53, Istituto Superiore di Sanità54, Katholieke Universiteit Leuven55, Trinity College, Dublin56, University of Geneva57, University of Amsterdam58, Stony Brook University59, University of Washington60, University of Ferrara61, Royal College of Surgeons in Ireland62, La Trobe University63, University of Buenos Aires64, University of Virginia65, University of Padua66, University of Lisbon67, University of Cambridge68, University of Würzburg69, Soochow University (Suzhou)70, Columbia University71, University of Glasgow72, University of Crete73, Foundation for Research & Technology – Hellas74, Innsbruck Medical University75, Carlos III Health Institute76, Rutgers University77, University of Minnesota78, Harvard University79, City University of New York80, Moscow State University81
TL;DR: The Nomenclature Committee on Cell Death formulates a set of recommendations to help scientists and researchers to discriminate between essential and accessory aspects of cell death.
Abstract: Cells exposed to extreme physicochemical or mechanical stimuli die in an uncontrollable manner, as a result of their immediate structural breakdown. Such an unavoidable variant of cellular demise is generally referred to as ‘accidental cell death’ (ACD). In most settings, however, cell death is initiated by a genetically encoded apparatus, correlating with the fact that its course can be altered by pharmacologic or genetic interventions. ‘Regulated cell death’ (RCD) can occur as part of physiologic programs or can be activated once adaptive responses to perturbations of the extracellular or intracellular microenvironment fail. The biochemical phenomena that accompany RCD may be harnessed to classify it into a few subtypes, which often (but not always) exhibit stereotyped morphologic features. Nonetheless, efficiently inhibiting the processes that are commonly thought to cause RCD, such as the activation of executioner caspases in the course of apoptosis, does not exert true cytoprotective effects in the mammalian system, but simply alters the kinetics of cellular demise as it shifts its morphologic and biochemical correlates. Conversely, bona fide cytoprotection can be achieved by inhibiting the transduction of lethal signals in the early phases of the process, when adaptive responses are still operational. Thus, the mechanisms that truly execute RCD may be less understood, less inhibitable and perhaps more homogeneous than previously thought. Here, the Nomenclature Committee on Cell Death formulates a set of recommendations to help scientists and researchers to discriminate between essential and accessory aspects of cell death.
809 citations
University of Illinois at Urbana–Champaign1, United States Department of Agriculture2, University of California, Los Angeles3, Centre national de la recherche scientifique4, University of Oregon5, Washington University in St. Louis6, Max Planck Society7, VU University Amsterdam8, Cornell University9, University of Cambridge10, Arizona State University11, Louisiana State University12, Lawrence Berkeley National Laboratory13, University of California, Berkeley14, Rothamsted Research15, Georgia Institute of Technology16, ExxonMobil17, Iowa State University18, Australian National University19, University of Düsseldorf20, Texas A&M University21
TL;DR: This work explores an array of prospective redesigns of plant systems at various scales aimed at increasing crop yields through improved photosynthetic efficiency and performance, and suggests some proposed redesigns are certain to face obstacles that will require alternate routes.
Abstract: The world’s crop productivity is stagnating whereas population growth, rising affluence, and mandates for biofuels put increasing demands on agriculture. Meanwhile, demand for increasing cropland competes with equally crucial global sustainability and environmental protection needs. Addressing this looming agricultural crisis will be one of our greatest scientific challenges in the coming decades, and success will require substantial improvements at many levels. We assert that increasing the efficiency and productivity of photosynthesis in crop plants will be essential if this grand challenge is to be met. Here, we explore an array of prospective redesigns of plant systems at various scales, all aimed at increasing crop yields through improved photosynthetic efficiency and performance. Prospects range from straightforward alterations, already supported by preliminary evidence of feasibility, to substantial redesigns that are currently only conceptual, but that may be enabled by new developments in synthetic biology. Although some proposed redesigns are certain to face obstacles that will require alternate routes, the efforts should lead to new discoveries and technical advances with important impacts on the global problem of crop productivity and bioenergy production.
TL;DR: A complete understanding of the function of NOX is important to direct the role of this enzyme towards host defense and tissue repair or increase resistance to stress in a timely and disease-specific manner.
Abstract: Oxygen-derived free radicals, collectively termed reactive oxygen species (ROS), play important roles in immunity, cell growth, and cell signaling. In excess, however, ROS are lethal to cells, and the overproduction of these molecules leads to a myriad of devastating diseases. The key producers of ROS in many cells are the NOX family of NADPH oxidases, of which there are seven members, with various tissue distributions and activation mechanisms. NADPH oxidase is a multisubunit enzyme comprising membrane and cytosolic components, which actively communicate during the host responses to a wide variety of stimuli, including viral and bacterial infections. This enzymatic complex has been implicated in many functions ranging from host defense to cellular signaling and the regulation of gene expression. NOX deficiency might lead to immunosuppression, while the intracellular accumulation of ROS results in the inhibition of viral propagation and apoptosis. However, excess ROS production causes cellular stress, leading to various lethal diseases, including autoimmune diseases and cancer. During the later stages of injury, NOX promotes tissue repair through the induction of angiogenesis and cell proliferation. Therefore, a complete understanding of the function of NOX is important to direct the role of this enzyme towards host defense and tissue repair or increase resistance to stress in a timely and disease-specific manner.
The American College of Financial Services1, Icahn School of Medicine at Mount Sinai2, Wayne State University3, Emory University4, Cleveland Clinic5, University of California, San Diego6, Ochsner Medical Center7, Louisiana State University8, University of Tennessee Health Science Center9, University of Texas at Dallas10, American Association of Clinical Endocrinologists11, Harvard University12, Baylor College of Medicine13, University of Alabama at Birmingham14, Veterans Health Administration15, University of Washington16, Mayo Clinic17, University of Miami18, University of California, Santa Barbara19, SUNY Downstate Medical Center20, University of Arizona21, Washington University in St. Louis22, University of Southern California23, University of California, Los Angeles24, University of California, Irvine25, Eastern Virginia Medical School26, Cornell University27
TL;DR: These guidelines are a working document that reflects the state of the field at the time of publication and any decision by practitioners to apply these guidelines must be made in light of local resources and individual patient circumstances.
University of Alabama at Birmingham1, University of Texas Southwestern Medical Center2, Carolinas Medical Center3, Johns Hopkins University4, University of Pittsburgh5, University of California, Irvine6, University of Washington7, University of South Alabama8, University of Arkansas for Medical Sciences9, University of Colorado Denver10, University of Rochester11, Medical University of South Carolina12, University of South Florida13, Washington University in St. Louis14, George Washington University15, University of Minnesota16, University of Mississippi17, State University of New York Upstate Medical University18, Louisiana State University19, Brown University20, Bristol Royal Hospital for Children21, University College London22, Stanford University23, Vanderbilt University24, University of Southern California25, Emory University26, St George’s University Hospitals NHS Foundation Trust27, University of Nebraska Medical Center28, University of Louisville29
TL;DR: Treating symptomatic congenital CMV disease with valganciclovir for 6 months, as compared with 6 weeks, did not improve hearing in the short term but appeared to improve hearing and developmental outcomes modestly in the longer term.
Abstract: BackgroundThe treatment of symptomatic congenital cytomegalovirus (CMV) disease with intravenous ganciclovir for 6 weeks has been shown to improve audiologic outcomes at 6 months, but the benefits wane over time. MethodsWe conducted a randomized, placebo-controlled trial of valganciclovir therapy in neonates with symptomatic congenital CMV disease, comparing 6 months of therapy with 6 weeks of therapy. The primary end point was the change in hearing in the better ear (“best-ear” hearing) from baseline to 6 months. Secondary end points included the change in hearing from baseline to follow-up at 12 and 24 months and neurodevelopmental outcomes, with each end point adjusted for central nervous system involvement at baseline. ResultsA total of 96 neonates underwent randomization, of whom 86 had follow-up data at 6 months that could be evaluated. Best-ear hearing at 6 months was similar in the 6-month group and the 6-week group (2 and 3 participants, respectively, had improvement; 36 and 37 had no change; and...
TL;DR: Data from epidemiological and ET studies in the primary and secondary prevention of cardiovascular diseases, particularly coronary heart disease and heart failure, strongly support the routine prescription of ET to all patients and referrals for patients with cardiovascular diseases to specific cardiac rehabilitation and ET programs.
Abstract: Substantial evidence has established the value of high levels of physical activity, exercise training (ET), and overall cardiorespiratory fitness in the prevention and treatment of cardiovascular diseases. This article reviews some basics of exercise physiology and the acute and chronic responses of ET, as well as the effect of physical activity and cardiorespiratory fitness on cardiovascular diseases. This review also surveys data from epidemiological and ET studies in the primary and secondary prevention of cardiovascular diseases, particularly coronary heart disease and heart failure. These data strongly support the routine prescription of ET to all patients and referrals for patients with cardiovascular diseases, especially coronary heart disease and heart failure, to specific cardiac rehabilitation and ET programs.
Johns Hopkins University1, Stanford University2, Baylor College of Medicine3, California Pacific Medical Center4, Cleveland Clinic5, Columbia University6, Dartmouth College7, Emory University8, George Washington University9, Henry Ford Health System10, Indiana University11, Louisiana State University12, Harvard University13, Mayo Clinic14, Georgia Regents University15, Medical University of South Carolina16, Boston Children's Hospital17, Oregon Health & Science University18, Rush University Medical Center19, Thomas Jefferson University20, University of Florida21, University of Rochester22, University of Southern California23, University of Texas Southwestern Medical Center24, University of Virginia25, University of Wisconsin-Madison26, Comprehensive Epilepsy Center27, Wake Forest University28, Cornell University29, Yale University30
TL;DR: This study provides Class IV evidence that for adults with medically refractory partial onset seizures, responsive direct cortical stimulation reduces seizures and improves quality of life over a mean follow-up of 5.4 years.
Abstract: Objective: The long-term efficacy and safety of responsive direct neurostimulation was assessed in adults with medically refractory partial onset seizures. Methods: All participants were treated with a cranially implanted responsive neurostimulator that delivers stimulation to 1 or 2 seizure foci via chronically implanted electrodes when specific electrocorticographic patterns are detected (RNS System). Participants had completed a 2-year primarily open-label safety study (n = 65) or a 2-year randomized blinded controlled safety and efficacy study (n = 191); 230 participants transitioned into an ongoing 7-year study to assess safety and efficacy. Results: The average participant was 34 (±11.4) years old with epilepsy for 19.6 (±11.4) years. The median preimplant frequency of disabling partial or generalized tonic-clonic seizures was 10.2 seizures a month. The median percent seizure reduction in the randomized blinded controlled trial was 44% at 1 year and 53% at 2 years ( p p Conclusions: The RNS System is the first direct brain responsive neurostimulator. Acute and sustained efficacy and safety were demonstrated in adults with medically refractory partial onset seizures arising from 1 or 2 foci over a mean follow-up of 5.4 years. This experience supports the RNS System as a treatment option for refractory partial seizures. Classification of evidence: This study provides Class IV evidence that for adults with medically refractory partial onset seizures, responsive direct cortical stimulation reduces seizures and improves quality of life over a mean follow-up of 5.4 years.
TL;DR: It is shown that biotic migrations across the Isthmus of Panama began several million years earlier than commonly assumed, indicating that the dramatic biotic turnover associated with the Great American Biotic Interchange was a long and complex process that began as early as the Oligocene–Miocene transition.
Abstract: The linking of North and South America by the Isthmus of Panama had major impacts on global climate, oceanic and atmospheric currents, and biodiversity, yet the timing of this critical event remains contentious. The Isthmus is traditionally understood to have fully closed by ca. 3.5 million years ago (Ma), and this date has been used as a benchmark for oceanographic, climatic, and evolutionary research, but recent evidence suggests a more complex geological formation. Here, we analyze both molecular and fossil data to evaluate the tempo of biotic exchange across the Americas in light of geological evidence. We demonstrate significant waves of dispersal of terrestrial organisms at approximately ca. 20 and 6 Ma and corresponding events separating marine organisms in the Atlantic and Pacific oceans at ca. 23 and 7 Ma. The direction of dispersal and their rates were symmetrical until the last ca. 6 Ma, when northern migration of South American lineages increased significantly. Variability among taxa in their timing of dispersal or vicariance across the Isthmus is not explained by the ecological factors tested in these analyses, including biome type, dispersal ability, and elevation preference. Migration was therefore not generally regulated by intrinsic traits but more likely reflects the presence of emergent terrain several millions of years earlier than commonly assumed. These results indicate that the dramatic biotic turnover associated with the Great American Biotic Interchange was a long and complex process that began as early as the Oligocene–Miocene transition.
TL;DR: The basic aspects of the physics of proton therapy are reviewed, including proton interaction mechanisms, proton transport calculations, the determination of dose from therapeutic and stray radiations, and shielding design.
Abstract: The physics of proton therapy has advanced considerably since it was proposed in 1946. Today analytical equations and numerical simulation methods are available to predict and characterize many aspects of proton therapy. This article reviews the basic aspects of the physics of proton therapy, including proton interaction mechanisms, proton transport calculations, the determination of dose from therapeutic and stray radiations, and shielding design. The article discusses underlying processes as well as selected practical experimental and theoretical methods. We conclude by briefly speculating on possible future areas of research of relevance to the physics of proton therapy.
Henry Ford Health System1, University of Utah2, Johns Hopkins University3, Virginia Mason Medical Center4, University of Chicago5, Veterans Health Administration6, Saint Louis University7, Pomona College8, Eastern Virginia Medical School9, Cincinnati Children's Hospital Medical Center10, Wayne State University11, Georgetown University12, Wake Forest Baptist Medical Center13, Morehouse School of Medicine14, Florida Atlantic University15, Louisiana State University16
TL;DR: This clinical practice guideline was undertaken to optimize the care of patients with AR by addressing quality improvement opportunities through an evaluation of the available evidence and an assessment of the harm-benefit balance of various diagnostic and management options.
Abstract: Objective. Allergic rhinitis (AR) is one of the most common diseases affecting adults. It is the most common chronic disease in children in the United States today and the fifth most common chronic disease in the United States overall. AR is estimated to affect nearly 1 in every 6 Americans and generates $2 to $5 billion in direct health expenditures annually. It can impair quality of life and, through loss of work and school attendance, is responsible for as much as $2 to $4 billion in lost productivity annually. Not surprisingly, myriad diagnostic tests and treatments are used in managing this disorder, yet there is considerable variation in their use. This clinical practice guideline was undertaken to optimize the care of patients with AR by addressing quality improvement opportunities through an evaluation of the available evidence and an assessment of the harm-benefit balance of various diagnostic and management options. Purpose. The primary purpose of this guideline is to address quality improvement opportunities for all clinicians, in any setting, who are likely to manage patients with AR as well as to optimize patient care, promote effective diagnosis and therapy, and reduce harmful or unnecessary variations in care. The guideline is intended to be applicable for both pediatric and adult patients with AR. Children under the age of 2 years were excluded from the clinical practice guideline because rhinitis in this population may be different than in older patients and is not informed by the same evidence base. The guideline is intended to focus on a limited number of quality improvement opportunities deemed most important by the working group and is not intended to be a comprehensive reference for diagnosing and managing AR. The recommendations outlined in the guideline are not intended to represent the standard of care for patient management, nor are the recommendations intended to limit treatment or care provided to individual patients. Action Statements. The development group made a strong recommendation that clinicians recommend intranasal steroids for patients with a clinical diagnosis of AR whose symptoms affect their quality of life. The development group also made a strong recommendation that clinicians recommend oral second-generation/less sedating antihistamines for patients with AR and primary complaints of sneezing and itching. The panel made the following recommendations: (1) Clinicians should make the clinical diagnosis of AR when patients present with a history and physical examination consistent with an allergic cause and 1 or more of the following symptoms: nasal congestion, runny nose, itchy nose, or sneezing. Findings of AR consistent with an allergic cause include, but are not limited to, clear rhinorrhea, nasal congestion, pale discoloration of the nasal mucosa, and red and watery eyes. (2) Clinicians should perform and interpret, or refer to a clinician who can perform and interpret, specific IgE (skin or blood) allergy testing for patients with a clinical diagnosis of AR who do not respond to empiric treatment, or when the diagnosis is uncertain, or when knowledge of the specific causative allergen is needed to target therapy. (3) Clinicians should assess patients with a clinical diagnosis of AR for, and document in the medical record, the presence of associated conditions such as asthma, atopic dermatitis, sleep-disordered breathing, conjunctivitis, rhinosinusitis, and otitis media. (4) Clinicians should offer, or refer to a clinician who can offer, immunotherapy (sublingual or subcutaneous) for patients with AR who have inadequate response to symptoms with pharmacologic therapy with or without environmental controls.
University of Colorado Denver1, Brown University2, American University3, University at Buffalo4, Sanford-Burnham Institute for Medical Research5, National Institutes of Health6, Rutgers University7, University of Florida8, Pennsylvania State University9, Columbia University10, University of Minnesota11, Louisiana State University12
TL;DR: A working group of experts in integrative physiology and behavioral psychology was convened with the goal of merging their perspectives regarding the barriers to scientific progress and the development of novel ways to improve long‐term outcomes in obesity therapeutics.
Abstract: Objectives
The National Institutes of Health, led by the National Heart, Lung, and Blood Institute, organized a working group of experts to discuss the problem of weight regain after weight loss. A number of experts in integrative physiology and behavioral psychology were convened with the goal of merging their perspectives regarding the barriers to scientific progress and the development of novel ways to improve long-term outcomes in obesity therapeutics. The specific objectives of this working group were to: (1) identify the challenges that make maintaining a reduced weight so difficult; (2) review strategies that have been used to improve success in previous studies; and (3) recommend novel solutions that could be examined in future studies of long-term weight control.
Results
Specific barriers to successful weight loss maintenance include poor adherence to behavioral regimens and physiological adaptations that promote weight regain. A better understanding of how these behavioral and physiological barriers are related, how they vary between individuals, and how they can be overcome will lead to the development of novel strategies with improved outcomes.
Conclusions
Greater collaboration and cross-talk between physiological and behavioral researchers is needed to advance the science and develop better strategies for weight loss maintenance.
TL;DR: Results show that social media recommendations improve levels of media trust, and also make people want to follow more news from that particular media outlet in the future.
Abstract: Polls show a strong decline in public trust of traditional news outlets; however, social media offers new avenues for receiving news content. This experiment used the Facebook API to manipulate whether a news story appeared to have been posted on Facebook by one of the respondent's real-life Facebook friends. Results show that social media recommendations improve levels of media trust, and also make people want to follow more news from that particular media outlet in the future. Moreover, these effects are amplified when the real-life friend sharing the story on social media is perceived as an opinion leader. Implications for democracy and the news business are discussed.
Louisiana State University1, Aarhus University Hospital2, University of California, Los Angeles3, Saarland University4, Haukeland University Hospital5, Helsinki University Central Hospital6, Wills Eye Institute7, University of Pittsburgh8, Yonsei University9, University of Kansas10, Vision Institute11, Tufts University12, Kyoto Prefectural University of Medicine13, University of Mainz14
TL;DR: This revision of the IC3D classification includes an updated anatomic classification of corneal dystrophy more accurately classifying TGFBI dystrophies that affect multiple layers rather than are confined to one cornean layer.
Abstract: Purpose:To update the 2008 International Classification of Corneal Dystrophies (IC3D) incorporating new clinical, histopathologic, and genetic information.Methods:The IC3D reviewed worldwide peer-reviewed articles for new information on corneal dystrophies published between 2008 and 2014. Using this
TL;DR: The findings can be utilized to improve the understanding of the mechanisms that produce air pollution, enhance the forecast accuracy of the air pollution under different meteorological conditions, and provide effective measures for mitigating the pollution.
TL;DR: Categorize the applications of the POCT diagnostic systems according to the analyte types such as proteins, cells, nucleic acids, and metabolites, and advantages and disadvantages of POCT systems are reviewed and discussed along with future prospects.
TL;DR: The authors identified the North American Coastal Plain (NACP) as a global hotspot based on the classic definition, a region with > 1500 endemic plant species and > 70% habitat loss.
Abstract: Biodiversity hotspots are conservation priorities. We identify the North American Coastal Plain (NACP) as a global hotspot based on the classic definition, a region with > 1500 endemic plant species and > 70% habitat loss. This region has been bypassed in prior designations due to misconceptions and myths about its ecology and history. These fallacies include: (1) young age of the NACP, climatic instability over time and submergence during high sea-level stands; (2) climatic and environmental homogeneity; (3) closed forest as the climax vegetation; and (4) fire regimes that are mostly anthropogenic. We show that the NACP is older and more climatically stable than usually assumed, spatially heterogeneous and extremely rich in species and endemics for its range of latitude, especially within pine savannas and other mostly herbaceous and fire-dependent communities. We suspect systematic biases and misconceptions, in addition to missing information, obscure the existence of similarly biologically significant regions world-wide. Potential solutions to this problem include (1) increased field biological surveys and taxonomic determinations, especially within grassy biomes and regions with low soil fertility, which tend to have much overlooked biodiversity; (2) more research on the climatic refugium role of hotspots, given that regions of high endemism often coincide with regions with low velocity of climate change; (3) in low-lying coastal regions, consideration of the heterogeneity in land area generated by historically fluctuating sea levels, which likely enhanced opportunities for evolution of endemic species; and (4) immediate actions to establish new protected areas and implement science-based management to restore evolutionary environmental conditions in newly recognized hotspots.
TL;DR: The new-generation polymer-based materials tested in this study exhibited significantly higher flexural strength and modulus of resilience, along with lower flexural modulus values compared with the tested ceramic or hybrid materials.
Abstract: Statement of problem The recent development of polymer-based computer-aided design and computer-aided manufactured (CAD/CAM) milling blocks and the limited availability of independent studies on these materials make it pertinent to evaluate their properties and identify potential strengths and limitations. Purpose The purpose of this in vitro study was to determine and compare mechanical properties (flexural strength, flexural modulus, modulus of resilience) and compare the margin edge quality of recently introduced polymer-based CAD/CAM materials with some of their commercially available composite resin and ceramic counterparts. Material and methods The materials studied were Lava Ultimate Restorative (LVU; 3M ESPE), Enamic (ENA; Vita Zahnfabrik), Cerasmart (CES; GC Dental Products), IPS Empress CAD (EMP; Ivoclar Vivadent AG), Vitablocs Mark II (VM2; Vita Zahnfabrik), and Paradigm MZ100 Block (MZ1; 3M ESPE). Polished 4×1×13.5 mm bars (n=25) were prepared from standard-sized milling blocks of each tested material. The bars were subjected to a 3-point flexural test on a 10-mm span with a crosshead speed of 0.5 mm/min. In addition, 42 conventional monolithic crowns (7 per material) were milled. Margin edge quality was observed by means of macrophotography and optical microscopy, providing a qualitative visual assessment and a measurement of existing roughness. The results were analyzed by ANOVA followed by the Tukey HSD test (α=.05). Results The mean flexural strength of the tested materials ranged from 105 ±9 MPa (VM2) to 219 ±20 MPa (CES). The mean flexural modulus ranged from 8 ±0.25 GPa (CES) to 32 ±1.9 GPa (EMP). The mean modulus of resilience ranged from 0.21 ±0.02 MPa (VM2) to 3.07 ±0.45 MPa (CES). The qualitative assessment of margin edge roughness revealed visible differences among the tested materials, with mean roughness measurements ranging from 60 ±16 μm (CES) to 190 ±15 μm (EMP). The material factor had a significant effect on the mean flexural strength ( P P P P Conclusions The new-generation polymer-based materials tested in this study exhibited significantly higher flexural strength and modulus of resilience, along with lower flexural modulus values compared with the tested ceramic or hybrid materials. Crowns milled from the new resin-based blocks seemed to exhibit visibly smoother margins compared with the ceramic materials studied.
East Carolina University1, University of Alabama at Birmingham2, Duke University3, Louisiana State University4, University of California, Irvine5, Sanford-Burnham Institute for Medical Research6, University of Missouri7, Anschutz Medical Campus8, Harvard University9, National Institutes of Health10, McGill University11, University of Florida12, University of California, Davis13, University of Pittsburgh14
TL;DR: Identification of the mechanisms that underlie the link between PA and improved health holds extraordinary promise for discovery of novel therapeutic targets and development of personalized exercise medicine.
TL;DR: In this paper, the structure-morphology-rheology relationship for cellulose nanoparticles, including cellulose nanofibers (CNFs) and cellulose Nanocrystals (CNCs), was investigated.
Abstract: The present study aims to investigate the structure–morphology–rheology relationships for cellulose nanoparticles (CNPs), including cellulose nanofibers (CNFs) and cellulose nanocrystals (CNCs). CNCs were extracted from never dried CNFs using sulfuric acid with controlled hydrolysis time. The crystalline structure, surface charge, morphology, and rheological behavior of the CNPs were measured and contrasted. The CNF suspensions exhibited rigid solid-like viscoelastic behavior even at a low concentration due to the formation of a highly entangled network. Upon acid hydrolysis, the network of rigid, long, and highly entangled nanofibers was eliminated, resulting in a significant loss of viscoelastic properties. Both steady-state and dynamic rheological measurements showed that the rheological behavior of the CNC suspensions was strongly dependent on the concentration and acid hydrolysis time. The CNC suspensions exhibited elastic gel-like rheological behavior at high concentrations but viscous liquid-like r...
TL;DR: It is demonstrated that E-cig exposure elicits impaired pulmonary anti-microbial defenses and must be rigorously tested in users for their effects on immune response and susceptibility to bacterial and viral infections.
Abstract: Electronic cigarettes (E-cigs) have experienced sharp increases in popularity over the past five years due to many factors, including aggressive marketing, increased restrictions on conventional cigarettes, and a perception that E-cigs are healthy alternatives to cigarettes. Despite this perception, studies on health effects in humans are extremely limited and in vivo animal models have not been generated. Presently, we determined that E-cig vapor contains 7x1011 free radicals per puff. To determine whether E-cig exposure impacts pulmonary responses in mice, we developed an inhalation chamber for E-cig exposure. Mice that were exposed to E-cig vapor contained serum cotinine concentrations that are comparable to human E-cig users. E-cig exposure for 2 weeks produced a significant increase in oxidative stress and moderate macrophage-mediated inflammation. Since, COPD patients are susceptible to bacterial and viral infections, we tested effects of E-cigs on immune response. Mice that were exposed to E-cig vapor showed significantly impaired pulmonary bacterial clearance, compared to air-exposed mice, following an intranasal infection with Streptococcus pneumonia. This defective bacterial clearance was partially due to reduced phagocytosis by alveolar macrophages from E-cig exposed mice. In response to Influenza A virus infection, E-cig exposed mice displayed increased lung viral titers and enhanced virus-induced illness and mortality. In summary, this study reports a murine model of E-cig exposure and demonstrates that E-cig exposure elicits impaired pulmonary anti-microbial defenses. Hence, E-cig exposure as an alternative to cigarette smoking must be rigorously tested in users for their effects on immune response and susceptibility to bacterial and viral infections.
TL;DR: It is shown that mean Yangtze River water discharge of the first decade after the closing of the Three Gorges Dam (TGD) (2003–2012) was 67 km3/yr (7%) lower than that of the previous 50 years (1950–2002), and 126km3 /yr less compared to the relatively wet period of pre-TGD decade (1993–2002).
Abstract: The increasing impact of both climatic change and human activities on global river systems necessitates an increasing need to identify and quantify the various drivers and their impacts on fluvial water and sediment discharge. Here we show that mean Yangtze River water discharge of the first decade after the closing of the Three Gorges Dam (TGD) (2003–2012) was 67 km3/yr (7%) lower than that of the previous 50 years (1950–2002) and 126 km3/yr less compared to the relatively wet period of pre-TGD decade (1993–2002). Most (60–70%) of the decline can be attributed to decreased precipitation, the remainder resulting from construction of reservoirs, improved water-soil conservation and increased water consumption. Mean sediment flux decreased by 71% between 1950–1968 and the post-TGD decade, about half of which occurred prior to the pre-TGD decade. Approximately 30% of the total decline and 65% of the decline since 2003 can be attributed to the TGD, 5% and 14% of these declines to precipitation change and the remaining to other dams and soil conservation within the drainage basin. These findings highlight the degree to which changes in riverine water and sediment discharge can be related with multiple environmental and anthropogenic factors.