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Showing papers by "University of Kentucky published in 2016"


Journal ArticleDOI
Daniel J. Klionsky1, Kotb Abdelmohsen2, Akihisa Abe3, Joynal Abedin4  +2519 moreInstitutions (695)
TL;DR: In this paper, the authors present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macro-autophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes.
Abstract: In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure flux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation, it is imperative to target by gene knockout or RNA interference more than one autophagy-related protein. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways implying that not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular assays, we hope to encourage technical innovation in the field.

5,187 citations


Journal ArticleDOI
TL;DR: A comprehensive taxonomy of the various energy harvesting sources that can be used by WSNs is presented and some of the challenges still need to be addressed to develop cost-effective, efficient, and reliable energy harvesting systems for the WSN environment are identified.
Abstract: Recently, Wireless Sensor Networks (WSNs) have attracted lot of attention due to their pervasive nature and their wide deployment in Internet of Things, Cyber Physical Systems, and other emerging areas. The limited energy associated with WSNs is a major bottleneck of WSN technologies. To overcome this major limitation, the design and development of efficient and high performance energy harvesting systems for WSN environments are being explored. We present a comprehensive taxonomy of the various energy harvesting sources that can be used by WSNs. We also discuss various recently proposed energy prediction models that have the potential to maximize the energy harvested in WSNs. Finally, we identify some of the challenges that still need to be addressed to develop cost-effective, efficient, and reliable energy harvesting systems for the WSN environment.

914 citations



Journal ArticleDOI
TL;DR: Imaging results suggest that intra-brain vascular dysregulation is an early pathological event during disease development, suggesting early memory deficit associated with the primary disease factors.
Abstract: Multifactorial mechanisms underlying late-onset Alzheimer's disease (LOAD) are poorly characterized from an integrative perspective. Here spatiotemporal alterations in brain amyloid-β deposition, metabolism, vascular, functional activity at rest, structural properties, cognitive integrity and peripheral proteins levels are characterized in relation to LOAD progression. We analyse over 7,700 brain images and tens of plasma and cerebrospinal fluid biomarkers from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Through a multifactorial data-driven analysis, we obtain dynamic LOAD-abnormality indices for all biomarkers, and a tentative temporal ordering of disease progression. Imaging results suggest that intra-brain vascular dysregulation is an early pathological event during disease development. Cognitive decline is noticeable from initial LOAD stages, suggesting early memory deficit associated with the primary disease factors. High abnormality levels are also observed for specific proteins associated with the vascular system's integrity. Although still subjected to the sensitivity of the algorithms and biomarkers employed, our results might contribute to the development of preventive therapeutic interventions.

786 citations


Journal ArticleDOI
TL;DR: This position paper outlines the Academy's, DC, and ACSM's stance on nutrition factors that have been determined to influence athletic performance and emerging trends in the field of sports nutrition.

684 citations


Journal ArticleDOI
TL;DR: Patients with locally advanced pancreatic cancer treated with FOLFIRINOX had a median overall survival of 24·2 months-longer than that reported with gemcitabine (6-13 months).
Abstract: Summary Background 35% of patients with pancreatic cancer have unresectable locally advanced disease at diagnosis. Several studies have examined systemic chemotherapy with FOLFIRINOX (leucovorin and fluorouracil plus irinotecan and oxaliplatin) in patients with locally advanced pancreatic cancer. We aimed to assess the effectiveness of FOLFIRINOX as first-line treatment in this patient population. Methods We systematically searched Embase, MEDLINE (OvidSP), Web of Science, Scopus, PubMed Publisher, Cochrane, and Google Scholar from July 1, 1994, to July 2, 2015, for studies of treatment-naive patients of any age who received FOLFIRINOX as first-line treatment of locally advanced pancreatic cancer. Our primary outcome was overall survival. Secondary outcomes were progression-free survival; rates of grade 3 or 4 adverse events; and the proportion of patients who underwent radiotherapy or chemoradiotherapy, surgical resection after FOLFIRINOX, and R0 resection. We evaluated survival outcomes with the Kaplan–Meier method with patient-level data. Grade 3 or 4 adverse events, and the proportion of patients who underwent subsequent radiotherapy or chemoradiotherapy or resection, were pooled in a random-effects model. Findings We included 13 studies comprising 689 patients, of whom 355 (52%) patients had locally advanced pancreatic cancer. 11 studies, comprising 315 patients with locally advanced disease, reported survival outcomes and were eligible for patient-level meta-analysis. Median overall survival from the start of FOLFIRINOX ranged from 10·0 months (95% CI 4·0–16·0) to 32·7 months (23·1–42·3) across studies with a pooled patient-level median overall survival of 24·2 months (95% CI 21·7–26·8). Median progression-free survival ranged from 3·0 months (95% CI not calculable) to 20·4 months (6·5–34·3) across studies with a patient-level median progression-free survival of 15·0 months (95% 13·8–16·2). In ten studies comprising 490 patients, 296 grade 3 or 4 adverse events were reported (60·4 events per 100 patients). No deaths were attributed to FOLFIRINOX toxicity. The proportion of patients who underwent radiotherapy or chemoradiotherapy ranged from 31% to 100% across studies. In eight studies, 154 (57%) of 271 patients received radiotherapy or chemoradiotherapy after FOLFIRINOX. The pooled proportion of patients who received any radiotherapy treatment was 63·5% (95% CI 43·3–81·6, I 2 90%). The proportion of patients who underwent surgical resection for locally advanced pancreatic cancer ranged from 0% to 43%. The proportion of patients who had R0 resection of those who underwent resection ranged from 50% to 100% across studies. In 12 studies, 91 (28%) of 325 patients underwent resection after FOLFIRINOX. The pooled proportion of patients who had resection was 25·9% (95% CI 20·2–31·9, I 2 24%). R0 resection was reported in 60 (74%) of 81 patients. The pooled proportion of patients who had R0 resection was 78·4% (95% CI 60·2–92·2, I 2 64%). Interpretation Patients with locally advanced pancreatic cancer treated with FOLFIRINOX had a median overall survival of 24·2 months—longer than that reported with gemcitabine (6–13 months). Future research should assess these promising results in a randomised controlled trial, and should establish which patients might benefit from radiotherapy or chemoradiotherapy or resection after FOLFIRINOX. Funding None.

674 citations


Journal ArticleDOI
TL;DR: It is explained how a package of culturally evolved religious beliefs and practices characterized by increasingly potent, moralizing, supernatural agents, credible displays of faith, and other psychologically active elements conducive to social solidarity promoted high fertility rates and large-scale cooperation with co-religionists, often contributing to success in intergroup competition and conflict.
Abstract: We develop a cultural evolutionary theory of the origins of prosocial religions and apply it to resolve two puzzles in human psychology and cultural history: (1) the rise of large-scale cooperation among strangers and, simultaneously, (2) the spread of prosocial religions in the last 10-12 millennia. We argue that these two developments were importantly linked and mutually energizing. We explain how a package of culturally evolved religious beliefs and practices characterized by increasingly potent, moralizing, supernatural agents, credible displays of faith, and other psychologically active elements conducive to social solidarity promoted high fertility rates and large-scale cooperation with co-religionists, often contributing to success in intergroup competition and conflict. In turn, prosocial religious beliefs and practices spread and aggregated as these successful groups expanded, or were copied by less successful groups. This synthesis is grounded in the idea that although religious beliefs and practices originally arose as nonadaptive by-products of innate cognitive functions, particular cultural variants were then selected for their prosocial effects in a long-term, cultural evolutionary process. This framework (1) reconciles key aspects of the adaptationist and by-product approaches to the origins of religion, (2) explains a variety of empirical observations that have not received adequate attention, and (3) generates novel predictions. Converging lines of evidence drawn from diverse disciplines provide empirical support while at the same time encouraging new research directions and opening up new questions for exploration and debate.

628 citations


Journal ArticleDOI
TL;DR: Mindfulness research activity is surging within organizational science as discussed by the authors, and emerging evidence across multiple fields suggests that mindfulness is fundamentally connected to many aspects of workplace functioning, but this knowledge base has not been systematically integrated to date.

572 citations


Journal ArticleDOI
TL;DR: It is demonstrated that the discotic nematic phase of graphene oxide (GO) can be shear aligned to form highly ordered, continuous, thin films of multi-layered GO on a support membrane by an industrially adaptable method to produce large-area membranes.
Abstract: Graphene-based membranes demonstrating ultrafast water transport, precise molecular sieving of gas and solvated molecules shows great promise as novel separation platforms; however, scale-up of these membranes to large-areas remains an unresolved problem. Here we demonstrate that the discotic nematic phase of graphene oxide (GO) can be shear aligned to form highly ordered, continuous, thin films of multi-layered GO on a support membrane by an industrially adaptable method to produce large-area membranes (13 × 14 cm(2)) in 90%) for charged and uncharged organic probe molecules with a hydrated radius above 5 A as well as modest (30-40%) retention of monovalent and divalent salts. The highly ordered graphene sheets in the plane of the membrane make organized channels and enhance the permeability (71 ± 5 l m(-2) hr(-1) bar(-1) for 150 ± 15 nm thick membranes).

548 citations


Journal ArticleDOI
TL;DR: This guideline provides timely, evidence-based reversal strategies to assist practitioners in the care of patients with antithrombotic-associated intracranial hemorrhage.
Abstract: The use of antithrombotic agents, including anticoagulants, antiplatelet agents, and thrombolytics has increased over the last decade and is expected to continue to rise. Although antithrombotic-associated intracranial hemorrhage can be devastating, rapid reversal of coagulopathy may help limit hematoma expansion and improve outcomes. The Neurocritical Care Society, in conjunction with the Society of Critical Care Medicine, organized an international, multi-institutional committee with expertise in neurocritical care, neurology, neurosurgery, stroke, hematology, hemato-pathology, emergency medicine, pharmacy, nursing, and guideline development to evaluate the literature and develop an evidence-based practice guideline. Formalized literature searches were conducted, and studies meeting the criteria established by the committee were evaluated. Utilizing the GRADE methodology, the committee developed recommendations for reversal of vitamin K antagonists, direct factor Xa antagonists, direct thrombin inhibitors, unfractionated heparin, low-molecular weight heparin, heparinoids, pentasaccharides, thrombolytics, and antiplatelet agents in the setting of intracranial hemorrhage. This guideline provides timely, evidence-based reversal strategies to assist practitioners in the care of patients with antithrombotic-associated intracranial hemorrhage.

524 citations


Journal ArticleDOI
TL;DR: A definition of compassion is proposed and a systematic review of self- and observer-rated measures of this construct is offered and if supported, the development of a measure of compassion based on this operational definition is developed which demonstrates adequate psychometric properties.

Journal ArticleDOI
TL;DR: The proinflammatory enzyme myeloperoxidase induces both oxidative modification and nitrosylation of specific residues on plasma and arterial apolipoprotein A-I to render HDL dysfunctional, which results in impaired ABCA1 macrophage transport, the activation of inflammatory pathways, and an increased risk of coronary artery disease.
Abstract: High-density lipoproteins (HDLs) protect against atherosclerosis by removing excess cholesterol from macrophages through the ATP-binding cassette transporter A1 (ABCA1) and ATP-binding cassette transporter G1 (ABCG1) pathways involved in reverse cholesterol transport. Factors that impair the availability of functional apolipoproteins or the activities of ABCA1 and ABCG1 could, therefore, strongly influence atherogenesis. HDL also inhibits lipid oxidation, restores endothelial function, exerts anti-inflammatory and antiapoptotic actions, and exerts anti-inflammatory actions in animal models. Such properties could contribute considerably to the capacity of HDL to inhibit atherosclerosis. Systemic and vascular inflammation has been proposed to convert HDL to a dysfunctional form that has impaired antiatherogenic effects. A loss of anti-inflammatory and antioxidative proteins, perhaps in combination with a gain of proinflammatory proteins, might be another important component in rendering HDL dysfunctional. The proinflammatory enzyme myeloperoxidase induces both oxidative modification and nitrosylation of specific residues on plasma and arterial apolipoprotein A-I to render HDL dysfunctional, which results in impaired ABCA1 macrophage transport, the activation of inflammatory pathways, and an increased risk of coronary artery disease. Understanding the features of dysfunctional HDL or apolipoprotein A-I in clinical practice might lead to new diagnostic and therapeutic approaches to atherosclerosis.

Journal ArticleDOI
TL;DR: In this article, the authors sequenced the genome of spotted gar (Lepisosteus oculatus), whose lineage diverged from teleosts before teleost genome duplication (TGD).
Abstract: To connect human biology to fish biomedical models, we sequenced the genome of spotted gar (Lepisosteus oculatus), whose lineage diverged from teleosts before teleost genome duplication (TGD). The slowly evolving gar genome has conserved in content and size many entire chromosomes from bony vertebrate ancestors. Gar bridges teleosts to tetrapods by illuminating the evolution of immunity, mineralization and development (mediated, for example, by Hox, ParaHox and microRNA genes). Numerous conserved noncoding elements (CNEs; often cis regulatory) undetectable in direct human-teleost comparisons become apparent using gar: functional studies uncovered conserved roles for such cryptic CNEs, facilitating annotation of sequences identified in human genome-wide association studies. Transcriptomic analyses showed that the sums of expression domains and expression levels for duplicated teleost genes often approximate the patterns and levels of expression for gar genes, consistent with subfunctionalization. The gar genome provides a resource for understanding evolution after genome duplication, the origin of vertebrate genomes and the function of human regulatory sequences.

Journal ArticleDOI
TL;DR: The Metabolicomics Workbench provides data from the Common Fund's Metabolomics Resource Cores, metabolite standards, and analysis tools to the wider metabolomics community and seeks data depositions from metabolomics researchers across the world.
Abstract: The Metabolomics Workbench, available at www.metabolomicsworkbench.org, is a public repository for metabolomics metadata and experimental data spanning various species and experimental platforms, metabolite standards, metabolite structures, protocols, tutorials, and training material and other educational resources. It provides a computational platform to integrate, analyze, track, deposit and disseminate large volumes of heterogeneous data from a wide variety of metabolomics studies including mass spectrometry (MS) and nuclear magnetic resonance spectrometry (NMR) data spanning over 20 different species covering all the major taxonomic categories including humans and other mammals, plants, insects, invertebrates and microorganisms. Additionally, a number of protocols are provided for a range of metabolite classes, sample types, and both MS and NMR-based studies, along with a metabolite structure database. The metabolites characterized in the studies available on the Metabolomics Workbench are linked to chemical structures in the metabolite structure database to facilitate comparative analysis across studies. The Metabolomics Workbench, part of the data coordinating effort of the National Institute of Health (NIH) Common Fund's Metabolomics Program, provides data from the Common Fund's Metabolomics Resource Cores, metabolite standards, and analysis tools to the wider metabolomics community and seeks data depositions from metabolomics researchers across the world.

Journal ArticleDOI
TL;DR: This work focuses on how state-of-the-art routing algorithms can achieve intelligent D2D communication in the IoT, and presents an overview of how such communication can be achieved.
Abstract: Analogous to the way humans use the Internet, devices will be the main users in the Internet of Things (IoT) ecosystem. Therefore, device-to-device (D2D) communication is expected to be an intrinsic part of the IoT. Devices will communicate with each other autonomously without any centralized control and collaborate to gather, share, and forward information in a multihop manner. The ability to gather relevant information in real time is key to leveraging the value of the IoT as such information will be transformed into intelligence, which will facilitate the creation of an intelligent environment. Ultimately, the quality of the information gathered depends on how smart the devices are. In addition, these communicating devices will operate with different networking standards, may experience intermittent connectivity with each other, and many of them will be resource constrained. These characteristics open up several networking challenges that traditional routing protocols cannot solve. Consequently, devices will require intelligent routing protocols in order to achieve intelligent D2D communication. We present an overview of how intelligent D2D communication can be achieved in the IoT ecosystem. In particular, we focus on how state-of-the-art routing algorithms can achieve intelligent D2D communication in the IoT.


Journal ArticleDOI
Claudio L. Afonso1, Gaya K. Amarasinghe2, Krisztián Bányai3, Yīmíng Bào4, Christopher F. Basler5, Sina Bavari6, Nicolás Bejerman, Kim R. Blasdell7, François Xavier Briand, Thomas Briese8, Alexander Bukreyev9, Charles H. Calisher10, Kartik Chandran11, Jiāsēn Chéng12, Anna N. Clawson4, Peter L. Collins4, Ralf G. Dietzgen13, Olga Dolnik14, Leslie L. Domier15, Ralf Dürrwald, John M. Dye6, Andrew J. Easton16, Hideki Ebihara4, Szilvia L. Farkas3, Juliana Freitas-Astúa17, Pierre Formenty18, Ron A. M. Fouchier19, Yanping Fu12, Elodie Ghedin20, Michael M. Goodin21, Roger Hewson22, Masayuki Horie23, Timothy H. Hyndman24, Dàohóng Jiāng12, E. W. Kitajima25, Gary P. Kobinger26, Hideki Kondo27, Gael Kurath28, Robert A. Lamb29, Sergio Lenardon, Eric M. Leroy, C. Li, Xian Dan Lin30, Lìjiāng Liú12, Ben Longdon31, Szilvia Marton3, Andrea Maisner14, Elke Mühlberger32, Sergey V. Netesov33, Norbert Nowotny34, Norbert Nowotny35, Jean L. Patterson36, Susan Payne37, Janusz T. Paweska, Richard E. Randall38, Bertus K. Rima39, Paul A. Rota30, Dennis Rubbenstroth40, Martin Schwemmle40, Mang Shi41, Sophie J. Smither42, Mark D. Stenglein10, David M. Stone, Ayato Takada43, Calogero Terregino, Robert B. Tesh9, Jun Hua Tian30, Keizo Tomonaga44, Noël Tordo45, Jonathan S. Towner30, Nikos Vasilakis9, Martin Verbeek46, Viktor E. Volchkov47, Victoria Wahl-Jensen, John A. Walsh16, Peter J. Walker7, David Wang2, Lin-Fa Wang48, Thierry Wetzel, Anna E. Whitfield49, Jiǎtāo Xiè12, Kwok-Yung Yuen50, Yong-Zhen Zhang41, Jens H. Kuhn4 
United States Department of Agriculture1, Washington University in St. Louis2, Hungarian Academy of Sciences3, National Institutes of Health4, Georgia State University5, United States Army Medical Research Institute of Infectious Diseases6, Commonwealth Scientific and Industrial Research Organisation7, Columbia University8, University of Texas Medical Branch9, Colorado State University10, Yeshiva University11, Huazhong Agricultural University12, University of Queensland13, University of Marburg14, University of Illinois at Urbana–Champaign15, University of Warwick16, Empresa Brasileira de Pesquisa Agropecuária17, World Health Organization18, Erasmus University Rotterdam19, New York University20, University of Kentucky21, Public Health England22, Kagoshima University23, Murdoch University24, University of São Paulo25, Public Health Agency of Canada26, Okayama University27, United States Geological Survey28, Northwestern University29, Centers for Disease Control and Prevention30, University of Cambridge31, Boston University32, Novosibirsk State University33, University of Veterinary Medicine Vienna34, University of Medicine and Health Sciences35, Texas Biomedical Research Institute36, Texas A&M University37, University of St Andrews38, Queen's University Belfast39, University of Freiburg40, Chinese Center for Disease Control and Prevention41, Defence Science and Technology Laboratory42, Hokkaido University43, Kyoto University44, Pasteur Institute45, Wageningen University and Research Centre46, University of Lyon47, National University of Singapore48, Kansas State University49, University of Hong Kong50
TL;DR: The updated taxonomy of the order Mononegavirales is presented as now accepted by the International Committee on Taxonomy of Viruses (ICTV).
Abstract: In 2016, the order Mononegavirales was emended through the addition of two new families (Mymonaviridae and Sunviridae), the elevation of the paramyxoviral subfamily Pneumovirinae to family status (Pneumoviridae), the addition of five free-floating genera (Anphevirus, Arlivirus, Chengtivirus, Crustavirus, and Wastrivirus), and several other changes at the genus and species levels. This article presents the updated taxonomy of the order Mononegavirales as now accepted by the International Committee on Taxonomy of Viruses (ICTV).

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TL;DR: This comprehensive review summarizes and review current knowledge and understanding of matrix metalloproteinases in the brain and at the blood–brain barrier in neuroinflammation, multiple sclerosis, cerebral aneurysms, stroke, epilepsy, Alzheimer's disease, Parkinson’s disease, and brain cancer.
Abstract: Matrix metalloproteinases are versatile endopeptidases with many different functions in the body in health and disease. In the brain, matrix metalloproteinases are critical for tissue formation, neuronal network remodeling, and blood-brain barrier integrity. Many reviews have been published on matrix metalloproteinases before, most of which focus on the two best studied matrix metalloproteinases, the gelatinases MMP-2 and MMP-9, and their role in one or two diseases. In this review, we provide a broad overview of the role various matrix metalloproteinases play in brain disorders. We summarize and review current knowledge and understanding of matrix metalloproteinases in the brain and at the blood-brain barrier in neuroinflammation, multiple sclerosis, cerebral aneurysms, stroke, epilepsy, Alzheimer's disease, Parkinson's disease, and brain cancer. We discuss the detrimental effects matrix metalloproteinases can have in these conditions, contributing to blood-brain barrier leakage, neuroinflammation, neurotoxicity, demyelination, tumor angiogenesis, and cancer metastasis. We also discuss the beneficial role matrix metalloproteinases can play in neuroprotection and anti-inflammation. Finally, we address matrix metalloproteinases as potential therapeutic targets. Together, in this comprehensive review, we summarize current understanding and knowledge of matrix metalloproteinases in the brain and at the blood-brain barrier in brain disorders.

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TL;DR: An ASCO-convened expert panel conducted a systematic literature search of studies investigating chronic pain management in cancer survivors to provide evidence-based guidance on the optimum management of chronic pain in adult cancer survivors.
Abstract: PurposeTo provide evidence-based guidance on the optimum management of chronic pain in adult cancer survivors.MethodsAn ASCO-convened expert panel conducted a systematic literature search of studies investigating chronic pain management in cancer survivors. Outcomes of interest included symptom relief, pain intensity, quality of life, functional outcomes, adverse events, misuse or diversion, and risk assessment or mitigation.ResultsA total of 63 studies met eligibility criteria and compose the evidentiary basis for the recommendations. Studies tended to be heterogeneous in terms of quality, size, and populations. Primary outcomes also varied across the studies, and in most cases, were not directly comparable because of different outcomes, measurements, and instruments used at different time points. Because of a paucity of high-quality evidence, many recommendations are based on expert consensus.RecommendationsClinicians should screen for pain at each encounter. Recurrent disease, second malignancy, or lat...

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TL;DR: This study aimed to establish the frequency and clinical significance of sarcopenia, sarcopenic obesity and myosteatosis in cirrhotic patients.
Abstract: Background and aims Obesity is frequently associated with cirrhosis, and cirrhotic patients may develop simultaneous loss of skeletal muscle and gain of adipose tissue, culminating in the condition of sarcopenic obesity Additionally, muscle depletion is characterized by both a reduction in muscle size and increased proportion of muscular fat, termed myosteatosis In this study, we aimed to establish the frequency and clinical significance of sarcopenia, sarcopenic obesity and myosteatosis in cirrhotic patients

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TL;DR: Inflammatory signals and Foxp3 balance mTORC1 signaling and glucose metabolism to control the proliferation and suppressive function of Treg cells.
Abstract: T cells undergo metabolic reprogramming after they are activated. Rathmell and colleagues show that inflammatory Toll-like receptor signals induce glycolysis and impair the suppression of regulatory T cells, but Foxp3 can promote a switch to oxidative phosphorylation and suppression.

Journal ArticleDOI
Abstract: Pathological accumulation of abnormally phosphorylated tau protein in astrocytes is a frequent, but poorly characterized feature of the aging brain. Its etiology is uncertain, but its presence is sufficiently ubiquitous to merit further characterization and classification, which may stimulate clinicopathological studies and research into its pathobiology. This paper aims to harmonize evaluation and nomenclature of aging-related tau astrogliopathy (ARTAG), a term that refers to a morphological spectrum of astroglial pathology detected by tau immunohistochemistry, especially with phosphorylation-dependent and 4R isoform-specific antibodies. ARTAG occurs mainly, but not exclusively, in individuals over 60 years of age. Tau-immunoreactive astrocytes in ARTAG include thorn-shaped astrocytes at the glia limitans and in white matter, as well as solitary or clustered astrocytes with perinuclear cytoplasmic tau immunoreactivity that extends into the astroglial processes as fine fibrillar or granular immunopositivity, typically in gray matter. Various forms of ARTAG may coexist in the same brain and might reflect different pathogenic processes. Based on morphology and anatomical distribution, ARTAG can be distinguished from primary tauopathies, but may be concurrent with primary tauopathies or other disorders. We recommend four steps for evaluation of ARTAG: (1) identification of five types based on the location of either morphologies of tau astrogliopathy: subpial, subependymal, perivascular, white matter, gray matter; (2) documentation of the regional involvement: medial temporal lobe, lobar (frontal, parietal, occipital, lateral temporal), subcortical, brainstem; (3) documentation of the severity of tau astrogliopathy; and (4) description of subregional involvement. Some types of ARTAG may underlie neurological symptoms; however, the clinical significance of ARTAG is currently uncertain and awaits further studies. The goal of this proposal is to raise awareness of astroglial tau pathology in the aged brain, facilitating communication among neuropathologists and researchers, and informing interpretation of clinical biomarkers and imaging studies that focus on tau-related indicators.

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TL;DR: The authors' data illustrate the complexity of CR in the context of aging, with a clear separation of outcomes related to health and survival, highlighting complexities of translation of CR into human interventions.

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01 Sep 2016-Nature
TL;DR: In this paper, the authors show that plant species diversity decreased when a greater number of limiting nutrients were added across 45 grassland sites from a multi-continent experimental network, even after controlling for effects of plant biomass, and even where biomass production was not nutrient-limited.
Abstract: Niche dimensionality provides a general theoretical explanation for biodiversity-more niches, defined by more limiting factors, allow for more ways that species can coexist. Because plant species compete for the same set of limiting resources, theory predicts that addition of a limiting resource eliminates potential trade-offs, reducing the number of species that can coexist. Multiple nutrient limitation of plant production is common and therefore fertilization may reduce diversity by reducing the number or dimensionality of belowground limiting factors. At the same time, nutrient addition, by increasing biomass, should ultimately shift competition from belowground nutrients towards a one-dimensional competitive trade-off for light. Here we show that plant species diversity decreased when a greater number of limiting nutrients were added across 45 grassland sites from a multi-continent experimental network. The number of added nutrients predicted diversity loss, even after controlling for effects of plant biomass, and even where biomass production was not nutrient-limited. We found that elevated resource supply reduced niche dimensionality and diversity and increased both productivity and compositional turnover. Our results point to the importance of understanding dimensionality in ecological systems that are undergoing diversity loss in response to multiple global change factors.

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TL;DR: By far the most widespread mechanism of resistance to AGs is the inactivation of these antibiotics by AG-modifying enzymes, and an overview of these mechanisms is provided.
Abstract: Aminoglycoside (AG) antibiotics are used to treat many Gram-negative and some Gram-positive infections and, importantly, multidrug-resistant tuberculosis. Among various bacterial species, resistance to AGs arises through a variety of intrinsic and acquired mechanisms. The bacterial cell wall serves as a natural barrier for small molecules such as AGs and may be further fortified via acquired mutations. Efflux pumps work to expel AGs from bacterial cells, and modifications here too may cause further resistance to AGs. Mutations in the ribosomal target of AGs, while rare, also contribute to resistance. Of growing clinical prominence is resistance caused by ribosome methyltransferases. By far the most widespread mechanism of resistance to AGs is the inactivation of these antibiotics by AG-modifying enzymes. We provide here an overview of these mechanisms by which bacteria become resistant to AGs and discuss their prevalence and potential for clinical relevance.

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TL;DR: The present review discusses the involvements of lipid and protein oxidation in meat quality, nutrition, safety, and organoleptic properties; animal production and meat processing strategies which incorporate natural antioxidants to enhance the nutritional and health benefits of meat; and the application of mixed or purified natural antioxidant to eliminate or minimize the formation of carcinogens for chemical safety of cooked and processed meats.

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TL;DR: In this paper, the authors describe the MaNGA Data Reduction Pipeline algorithms and centralized metadata framework that produce sky-subtracted spectrophotometrically calibrated spectra and rectified three-dimensional data cubes that combine individual dithered observations.
Abstract: Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) is an optical fiber-bundle integral-field unit (IFU) spectroscopic survey that is one of three core programs in the fourth-generation Sloan Digital Sky Survey (SDSS-IV). With a spectral coverage of 3622–10354 A and an average footprint of ~500 arcsec2 per IFU the scientific data products derived from MaNGA will permit exploration of the internal structure of a statistically large sample of 10,000 low-redshift galaxies in unprecedented detail. Comprising 174 individually pluggable science and calibration IFUs with a near-constant data stream, MaNGA is expected to obtain ~100 million raw-frame spectra and ~10 million reduced galaxy spectra over the six-year lifetime of the survey. In this contribution, we describe the MaNGA Data Reduction Pipeline algorithms and centralized metadata framework that produce sky-subtracted spectrophotometrically calibrated spectra and rectified three-dimensional data cubes that combine individual dithered observations. For the 1390 galaxy data cubes released in Summer 2016 as part of SDSS-IV Data Release 13, we demonstrate that the MaNGA data have nearly Poisson-limited sky subtraction shortward of ~8500 A and reach a typical 10σ limiting continuum surface brightness μ = 23.5 AB arcsec-2 in a five-arcsecond-diameter aperture in the g-band. The wavelength calibration of the MaNGA data is accurate to 5 km s-1 rms, with a median spatial resolution of 2.54 arcsec FWHM (1.8 kpc at the median redshift of 0.037) and a median spectral resolution of σ = 72 km s-1.

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TL;DR: In this article, the principles of sustainable manufacturing are presented as the basis, and the technological elements to ensure the creation of a circular economy are identified and shown as essential ingredients for achieving economic growth, environmental protection and societal benefits.

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TL;DR: Using a large hierarchical and longitudinal data set comprised of student and school records, the authors examined the impact of student suspension rates on racial differences in reading and math achievement and found that exclusionary school punishment hinders academic growth and contributes to racial disparities in achievement.
Abstract: While scholars have studied the racial “achievement gap” for several decades, the mechanisms that produce this gap remain unclear. In this article, we propose that school discipline is a crucial, but under-examined, factor in achievement differences by race. Using a large hierarchical and longitudinal data set comprised of student and school records, we examine the impact of student suspension rates on racial differences in reading and math achievement. This analysis—the first of its kind—reveals that school suspensions account for approximately one-fifth of black-white differences in school performance. The findings suggest that exclusionary school punishment hinders academic growth and contributes to racial disparities in achievement. We conclude by discussing the implications for racial inequality in education. Mientras que los eruditos han estudiado la "brecha racial educativa" desde hace varias decadas, los mecanismos que producen este vacio no estan claros. En este trabajo, proponemos que la disciplina escolar es muy importante, pero poco examinada en el factor en las diferencias de rendimiento segun la raza. Utilizando un conjunto de datos de jerarquica y datos longitudinales compuestos por registros escolares de estudiantes, examinamos el impacto de los tipos de suspension de los estudiantes y las diferencias raciales en la lectura y el rendimiento en matematicas. Este analisis es primero de su tipo y revela que las suspensiones escolares representan aproximadamente una quinta parte de las diferencias entre el rendimiento escolar entre negros-blancos. Los hallazgos sugieren que el castigo de la escuela de exclusion dificulta el crecimiento academico y contribuye a las disparidades raciales en el rendimiento academico. Concluimos con una discusion de las implicaciones para la desigualdad racial en la educacion.

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TL;DR: Impacts of NO3-BVOC chemistry on air quality and climate are outlined, and critical research needs to better constrain this interaction to improve the predictive capabilities of atmospheric models.
Abstract: . Oxidation of biogenic volatile organic compounds (BVOC) by the nitrate radical (NO3) represents one of the important interactions between anthropogenic emissions related to combustion and natural emissions from the biosphere. This interaction has been recognized for more than 3 decades, during which time a large body of research has emerged from laboratory, field, and modeling studies. NO3-BVOC reactions influence air quality, climate and visibility through regional and global budgets for reactive nitrogen (particularly organic nitrates), ozone, and organic aerosol. Despite its long history of research and the significance of this topic in atmospheric chemistry, a number of important uncertainties remain. These include an incomplete understanding of the rates, mechanisms, and organic aerosol yields for NO3-BVOC reactions, lack of constraints on the role of heterogeneous oxidative processes associated with the NO3 radical, the difficulty of characterizing the spatial distributions of BVOC and NO3 within the poorly mixed nocturnal atmosphere, and the challenge of constructing appropriate boundary layer schemes and non-photochemical mechanisms for use in state-of-the-art chemical transport and chemistry–climate models. This review is the result of a workshop of the same title held at the Georgia Institute of Technology in June 2015. The first half of the review summarizes the current literature on NO3-BVOC chemistry, with a particular focus on recent advances in instrumentation and models, and in organic nitrate and secondary organic aerosol (SOA) formation chemistry. Building on this current understanding, the second half of the review outlines impacts of NO3-BVOC chemistry on air quality and climate, and suggests critical research needs to better constrain this interaction to improve the predictive capabilities of atmospheric models.