Showing papers by "University of Kentucky published in 2017"
University of South Florida1, University of Kentucky2, Cedars-Sinai Medical Center3, University of Texas MD Anderson Cancer Center4, Stanford University5, Harvard University6, University of Iowa7, Royal Free Hospital8, Mayo Clinic9, Katholieke Universiteit Leuven10, Northwestern University11, University of Cambridge12, Charité13, University of Barcelona14, Vanderbilt University15, Uppsala University16, Erasmus University Rotterdam17
TL;DR: Treatment with lutetium‐177 (177Lu)–Dotatate resulted in markedly longer progression‐free survival and a significantly higher response rate than high‐dose octreotide LAR among patients with advanced midgut neuroendocrine tumors.
Abstract: BackgroundPatients with advanced midgut neuroendocrine tumors who have had disease progression during first-line somatostatin analogue therapy have limited therapeutic options. This randomized, controlled trial evaluated the efficacy and safety of lutetium-177 (177Lu)–Dotatate in patients with advanced, progressive, somatostatin-receptor–positive midgut neuroendocrine tumors. MethodsWe randomly assigned 229 patients who had well-differentiated, metastatic midgut neuroendocrine tumors to receive either 177Lu-Dotatate (116 patients) at a dose of 7.4 GBq every 8 weeks (four intravenous infusions, plus best supportive care including octreotide long-acting repeatable [LAR] administered intramuscularly at a dose of 30 mg) (177Lu-Dotatate group) or octreotide LAR alone (113 patients) administered intramuscularly at a dose of 60 mg every 4 weeks (control group). The primary end point was progression-free survival. Secondary end points included the objective response rate, overall survival, safety, and the side-ef...
1,975 citations
TL;DR: A comprehensive review on Industry 4.0 is conducted and presents an overview of the content, scope, and findings by examining the existing literatures in all of the databases within the Web of Science.
1,906 citations
Stony Brook University1, University of Minnesota2, University of Notre Dame3, University of Vermont4, University of Toronto5, Boston University6, University of Maryland, Baltimore7, Duke University8, University of Kansas9, King's College London10, Columbia University11, Broad Institute12, Purdue University13, University of Iowa14, University of Georgia15, Texas A&M University16, Oklahoma State University–Stillwater17, University of Groningen18, Florida State University19, Uniformed Services University of the Health Sciences20, Bryn Mawr College21, University of North Texas22, University of Otago23, University at Buffalo24, University of Arizona25, University of New South Wales26, Northwestern University27, Emory University28, University of Kentucky29, University of Pittsburgh30, Brown University31
TL;DR: The HiTOP promises to improve research and clinical practice by addressing the aforementioned shortcomings of traditional nosologies and provides an effective way to summarize and convey information on risk factors, etiology, pathophysiology, phenomenology, illness course, and treatment response.
Abstract: The reliability and validity of traditional taxonomies are limited by arbitrary boundaries between psychopathology and normality, often unclear boundaries between disorders, frequent disorder co-occurrence, heterogeneity within disorders, and diagnostic instability. These taxonomies went beyond evidence available on the structure of psychopathology and were shaped by a variety of other considerations, which may explain the aforementioned shortcomings. The Hierarchical Taxonomy Of Psychopathology (HiTOP) model has emerged as a research effort to address these problems. It constructs psychopathological syndromes and their components/subtypes based on the observed covariation of symptoms, grouping related symptoms together and thus reducing heterogeneity. It also combines co-occurring syndromes into spectra, thereby mapping out comorbidity. Moreover, it characterizes these phenomena dimensionally, which addresses boundary problems and diagnostic instability. Here, we review the development of the HiTOP and the relevant evidence. The new classification already covers most forms of psychopathology. Dimensional measures have been developed to assess many of the identified components, syndromes, and spectra. Several domains of this model are ready for clinical and research applications. The HiTOP promises to improve research and clinical practice by addressing the aforementioned shortcomings of traditional nosologies. It also provides an effective way to summarize and convey information on risk factors, etiology, pathophysiology, phenomenology, illness course, and treatment response. This can greatly improve the utility of the diagnosis of mental disorders. The new classification remains a work in progress. However, it is developing rapidly and is poised to advance mental health research and care significantly as the relevant science matures. (PsycINFO Database Record
1,635 citations
Michael R. Blanton1, Matthew A. Bershady2, Bela Abolfathi3, Franco D. Albareti4 +412 more•Institutions (91)
TL;DR: SDSS-IV as mentioned in this paper is a project encompassing three major spectroscopic programs: the Mapping Nearby Galaxies at Apache Point Observatory (MaNGA), the Extended Baryon Oscillation Spectroscopic Survey (eBOSS), and the Time Domain Spectroscopy Survey (TDSS).
Abstract: We describe the Sloan Digital Sky Survey IV (SDSS-IV), a project encompassing three major spectroscopic programs. The Apache Point Observatory Galactic Evolution Experiment 2 (APOGEE-2) is observing hundreds of thousands of Milky Way stars at high resolution and high signal-to-noise ratios in the near-infrared. The Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey is obtaining spatially resolved spectroscopy for thousands of nearby galaxies (median $z\sim 0.03$). The extended Baryon Oscillation Spectroscopic Survey (eBOSS) is mapping the galaxy, quasar, and neutral gas distributions between $z\sim 0.6$ and 3.5 to constrain cosmology using baryon acoustic oscillations, redshift space distortions, and the shape of the power spectrum. Within eBOSS, we are conducting two major subprograms: the SPectroscopic IDentification of eROSITA Sources (SPIDERS), investigating X-ray AGNs and galaxies in X-ray clusters, and the Time Domain Spectroscopic Survey (TDSS), obtaining spectra of variable sources. All programs use the 2.5 m Sloan Foundation Telescope at the Apache Point Observatory; observations there began in Summer 2014. APOGEE-2 also operates a second near-infrared spectrograph at the 2.5 m du Pont Telescope at Las Campanas Observatory, with observations beginning in early 2017. Observations at both facilities are scheduled to continue through 2020. In keeping with previous SDSS policy, SDSS-IV provides regularly scheduled public data releases; the first one, Data Release 13, was made available in 2016 July.
1,200 citations
Monash University1, Kyoto University2, Kindai University3, United States Department of Energy4, Kobe University5, National Institute of Genetics6, Austrian Academy of Sciences7, Nara Institute of Science and Technology8, University of Osnabrück9, Universidad Veracruzana10, University of Cambridge11, CINVESTAV12, University of Oxford13, University of Tennessee14, Plant & Food Research15, Uppsala University16, Institut de recherche pour le développement17, University of Zurich18, University of Tokyo19, Nagoya University20, Okayama University21, National Institutes of Natural Sciences, Japan22, Tohoku University23, University of Kentucky24, Gregor Mendel Institute25, Tokyo University of Agriculture26, National Taiwan University27, Cold Spring Harbor Laboratory28, Autonomous University of Madrid29, University of Arizona30, Max Planck Society31, Tokyo Metropolitan University32, University of Minnesota33, Kumamoto University34, University of Ulm35, Saitama University36
TL;DR: Compared with other sequenced land plants, M. polymorpha exhibits low genetic redundancy in most regulatory pathways, with this portion of its genome resembling that predicted for the ancestral land plant.
774 citations
TL;DR: Three new genome-wide significant nonsynonymous variants associated with Alzheimer's disease are observed, providing additional evidence that the microglia-mediated innate immune response contributes directly to the development of Alzheimer's Disease.
Abstract: We identified rare coding variants associated with Alzheimer's disease in a three-stage case–control study of 85,133 subjects. In stage 1, we genotyped 34,174 samples using a whole-exome microarray. In stage 2, we tested associated variants (P < 1 × 10−4) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, we used an additional 14,997 samples to test the most significant stage 2 associations (P < 5 × 10−8) using imputed genotypes. We observed three new genome-wide significant nonsynonymous variants associated with Alzheimer's disease: a protective variant in PLCG2 (rs72824905: p.Pro522Arg, P = 5.38 × 10−10, odds ratio (OR) = 0.68, minor allele frequency (MAF)cases = 0.0059, MAFcontrols = 0.0093), a risk variant in ABI3 (rs616338: p.Ser209Phe, P = 4.56 × 10−10, OR = 1.43, MAFcases = 0.011, MAFcontrols = 0.008), and a new genome-wide significant variant in TREM2 (rs143332484: p.Arg62His, P = 1.55 × 10−14, OR = 1.67, MAFcases = 0.0143, MAFcontrols = 0.0089), a known susceptibility gene for Alzheimer's disease. These protein-altering changes are in genes highly expressed in microglia and highlight an immune-related protein–protein interaction network enriched for previously identified risk genes in Alzheimer's disease. These genetic findings provide additional evidence that the microglia-mediated innate immune response contributes directly to the development of Alzheimer's disease.
730 citations
International Agency for Research on Cancer1, University of Bristol2, University Hospitals Bristol NHS Foundation Trust3, Vanderbilt University Medical Center4, University of Kentucky5, University of Copenhagen6, Lund University7, Technische Universität München8, Fred Hutchinson Cancer Research Center9, Harvard University10, Dartmouth College11, University of Liverpool12, Umeå University13, National Institute of Occupational Health14, New Generation University College15, Radboud University Nijmegen16, BC Cancer Agency17, Washington State University18, University of Hawaii19, Ontario Institute for Cancer Research20, University of Southern California21, Technion – Israel Institute of Technology22, University of Salzburg23, Curie Institute24, Nofer Institute of Occupational Medicine25, University of Ostrava26, Charles University in Prague27, Nanjing Medical University28, University of Oviedo29, University of Sheffield30, University of Texas MD Anderson Cancer Center31, University of Pittsburgh32, Lunenfeld-Tanenbaum Research Institute33
TL;DR: The results are consistent with a causal role of fasting insulin and low-density lipoprotein cholesterol in lung cancer etiology, as well as for BMI in squamous cell and small cell carcinoma, and the latter relation may be mediated by a previously unrecognized effect of obesity on smoking behavior.
Abstract: Background: Assessing the relationship between lung cancer and metabolic conditions is challenging because of the confounding effect of tobacco. Mendelian randomization (MR), or the use of genetic ...
653 citations
TL;DR: It is established that a genetic network controlling the phosphate stress response influences the structure of the root microbiome community, even under non-stress phosphate conditions, and that the master transcriptional regulators of phosphate Stress Response in Arabidopsis thaliana directly repress defence, consistent with plant prioritization of nutritional stress over defence.
Abstract: Plants live in biogeochemically diverse soils with diverse microbiota. Plant organs associate intimately with a subset of these microbes, and the structure of the microbial community can be altered by soil nutrient content. Plant-associated microbes can compete with the plant and with each other for nutrients, but may also carry traits that increase the productivity of the plant. It is unknown how the plant immune system coordinates microbial recognition with nutritional cues during microbiome assembly. Here we establish that a genetic network controlling the phosphate stress response influences the structure of the root microbiome community, even under non-stress phosphate conditions. We define a molecular mechanism regulating coordination between nutrition and defence in the presence of a synthetic bacterial community. We further demonstrate that the master transcriptional regulators of phosphate stress response in Arabidopsis thaliana also directly repress defence, consistent with plant prioritization of nutritional stress over defence. Our work will further efforts to define and deploy useful microbes to enhance plant performance.
557 citations
Franco D. Albareti1, Franco D. Albareti2, Carlos Allende Prieto1, Carlos Allende Prieto3 +397 more•Institutions (95)
TL;DR: Data Release 13 (DR13) as discussed by the authors provides the first 1390 spatially resolved integral field unit observations of nearby galaxies from the Apache Point Observatory Galactic Evolution Experiment 2 (APOGEE-2), Mapping Nearby Galaxies at APO (MaNGA), and the Extended Baryon Oscillation Spectroscopic Survey (eBOSS).
Abstract: The fourth generation of the Sloan Digital Sky Survey (SDSS-IV) began observations in 2014 July. It pursues three core programs: the Apache Point Observatory Galactic Evolution Experiment 2 (APOGEE-2), Mapping Nearby Galaxies at APO (MaNGA), and the Extended Baryon Oscillation Spectroscopic Survey (eBOSS). As well as its core program, eBOSS contains two major subprograms: the Time Domain Spectroscopic Survey (TDSS) and the SPectroscopic IDentification of ERosita Sources (SPIDERS). This paper describes the first data release from SDSS-IV, Data Release 13 (DR13). DR13 makes publicly available the first 1390 spatially resolved integral field unit observations of nearby galaxies from MaNGA. It includes new observations from eBOSS, completing the Sloan Extended QUasar, Emission-line galaxy, Luminous red galaxy Survey (SEQUELS), which also targeted variability-selected objects and X-ray-selected objects. DR13 includes new reductions of the SDSS-III BOSS data, improving the spectrophotometric calibration and redshift classification, and new reductions of the SDSS-III APOGEE-1 data, improving stellar parameters for dwarf stars and cooler stars. DR13 provides more robust and precise photometric calibrations. Value-added target catalogs relevant for eBOSS, TDSS, and SPIDERS and an updated red-clump catalog for APOGEE are also available. This paper describes the location and format of the data and provides references to important technical papers. The SDSS web site, http://www.sdss.org, provides links to the data, tutorials, examples of data access, and extensive documentation of the reduction and analysis procedures. DR13 is the first of a scheduled set that will contain new data and analyses from the planned ∼6 yr operations of SDSS-IV.
532 citations
Posted Content•
TL;DR: The white paper summarizes the workshop "U.S. Cosmic Visions: New Ideas in Dark Matter" held at University of Maryland on March 23-25, 2017.
Abstract: This white paper summarizes the workshop "U.S. Cosmic Visions: New Ideas in Dark Matter" held at University of Maryland on March 23-25, 2017.
464 citations
University of Arizona1, South China Agricultural University2, Qingdao Agricultural University3, University of Greenwich4, Chinese Academy of Sciences5, Institute of Insect Sciences, Zhejiang University6, Yangzhou University7, Henan Agricultural University8, University of Rhode Island9, Hubei University10, United States Department of Agriculture11, University of Kentucky12
TL;DR: These MED/Q genomic resources lay a foundation for future ‘pan-genomic’ comparisons of invasive vs. noninvasive, invasive versus.
Abstract: National Natural Science Foundation of China [31420103919, 31672032]; Chinese Academy of Agricultural Sciences (CAAS-ASTIP-IVFCAAS) the China Agriculture Research System [CARS-26-10]; Beijing Training Project for the Leading Talents in S T [LJRC201412]; Beijing Key Laboratory for Pest Control and Sustainable Cultivation of Vegetables; Beijing Nova Program [Z171100001117039]
AGH University of Science and Technology1, University of Kentucky2, Joint Institute for Nuclear Research3, Panjab University, Chandigarh4, Variable Energy Cyclotron Centre5, Stony Brook University6, Texas A&M University7, University of Tsukuba8, Brookhaven National Laboratory9, Tsinghua University10, Central China Normal University11, National Institute of Science Education and Research12, University of Houston13, University of Jammu14, University of Texas at Austin15, Czech Technical University in Prague16, Academy of Sciences of the Czech Republic17, Kent State University18, Rice University19, National Research Nuclear University MEPhI20, Lehigh University21, Yale University22, University of California, Davis23, Ohio State University24, University of Science and Technology of China25, Chinese Academy of Sciences26, Creighton University27, Lawrence Berkeley National Laboratory28, University of California, Berkeley29, Shandong University30, Pennsylvania State University31, Lamar University32, University of California, Los Angeles33, Wayne State University34, University of Illinois at Chicago35, Southern Connecticut State University36, Purdue University37
TL;DR: In this article, the authors present measurements of bulk properties of the matter produced in Au+Au collisions at sNN=7.7,11.5,19.6,27, and 39 GeV using identified hadrons from the STAR experiment in the Beam Energy Scan (BES) Program at the Relativistic Heavy Ion Collider (RHIC).
Abstract: © 2017 American Physical Society. We present measurements of bulk properties of the matter produced in Au+Au collisions at sNN=7.7,11.5,19.6,27, and 39 GeV using identified hadrons (π±, K±, p, and p) from the STAR experiment in the Beam Energy Scan (BES) Program at the Relativistic Heavy Ion Collider (RHIC). Midrapidity (|y| < 0.1) results for multiplicity densities dN/dy, average transverse momenta (pT), and particle ratios are presented. The chemical and kinetic freeze-out dynamics at these energies are discussed and presented as a function of collision centrality and energy. These results constitute the systematic measurements of bulk properties of matter formed in heavy-ion collisions over a broad range of energy (or baryon chemical potential) at RHIC.
TL;DR: Aguirre, Matias Ezequiel Aguirre et al. this article, this article presented the Consejo Nacional de Investigaciones Cientificas and Tecnicas Centro Cientícios Tecnologico Conicet -Mar del Plata Instituto de Investigación Fisicas de Mar del PlATA.
Abstract: Fil: Aguirre, Matias Ezequiel Consejo Nacional de Investigaciones Cientificas y Tecnicas Centro Cientifico Tecnologico Conicet - Mar del Plata Instituto de Investigaciones Fisicas de Mar del Plata Universidad Nacional de Mar del Plata Facultad de Csexactas y Naturales Instituto de Investigaciones Fisicas de Mar del Plata; Argentina
International Agency for Research on Cancer1, Lunenfeld-Tanenbaum Research Institute2, Dartmouth College3, Harvard University4, National Institutes of Health5, University of Cambridge6, University of Copenhagen7, Copenhagen University Hospital8, Gentofte Hospital9, University of Texas MD Anderson Cancer Center10, University of Hawaii11, University of Göttingen12, Vanderbilt University Medical Center13, Case Western Reserve University14, University of Oviedo15, Technion – Israel Institute of Technology16, University of Sheffield17, University of Liverpool18, Radboud University Nijmegen19, Washington State University Spokane20, National Institute of Occupational Health21, BC Cancer Agency22, Nanjing Medical University23, New Generation University College24, University of Pittsburgh25, University of Milan26, Princess Margaret Cancer Centre27, University of Southern California28, Sejong University29, Lund University30, Imperial College London31, Aarhus University32, Prevention Institute33, Fred Hutchinson Cancer Research Center34, Technische Universität München35, Ludwig Maximilian University of Munich36, University Hospital Heidelberg37, Umeå University38, University of Kentucky39, Charles University in Prague40, University of Ostrava41, University of Belgrade42, Nofer Institute of Occupational Medicine43, University of Bergen44, National University of Singapore45, Institute of Cancer Research46, American Cancer Society47, Merck & Co.48, University of British Columbia49, University Medical Center Groningen50, University of Leicester51, National Institute for Health Research52, Amgen53, Research Triangle Park54, Washington University in St. Louis55, Baylor College of Medicine56, Anschutz Medical Campus57, University of Washington58, University of Toronto59, Centre for Addiction and Mental Health60, QIMR Berghofer Medical Research Institute61, Laval University62
TL;DR: 18 susceptibility loci achieving genome-wide significance are identified, including 10 new loci linked with lung cancer overall and six loci associated with lung adenocarcinoma, highlighting the striking heterogeneity in genetic susceptibility across the histological subtypes of lung cancer.
Abstract: Although several lung cancer susceptibility loci have been identified, much of the heritability for lung cancer remains unexplained. Here 14,803 cases and 12,262 controls of European descent were genotyped on the OncoArray and combined with existing data for an aggregated genome-wide association study (GWAS) analysis of lung cancer in 29,266 cases and 56,450 controls. We identified 18 susceptibility loci achieving genome-wide significance, including 10 new loci. The new loci highlight the striking heterogeneity in genetic susceptibility across the histological subtypes of lung cancer, with four loci associated with lung cancer overall and six loci associated with lung adenocarcinoma. Gene expression quantitative trait locus (eQTL) analysis in 1,425 normal lung tissue samples highlights RNASET2, SECISBP2L and NRG1 as candidate genes. Other loci include genes such as a cholinergic nicotinic receptor, CHRNA2, and the telomere-related genes OFBC1 and RTEL1. Further exploration of the target genes will continue to provide new insights into the etiology of lung cancer.
TL;DR: Neonatal AKI is a common and independent risk factor for mortality and longer hospital stay, and data suggest that neonates may be impacted by AKI in a manner similar to pediatric and adult patients.
TL;DR: The findings provide benchmarks for gauging future policies and practices designed to motivate completion of advance directives, particularly among those people most likely to benefit from having these documents on record.
Abstract: Efforts to promote the completion of advance directives implicitly assume that completion rates of these documents, which help ensure care consistent with people’s preferences in the event of incapacity, are undesirably low. However, data regarding completion of advance directives in the United States are inconsistent and of variable quality. We systematically reviewed studies published in the period 2011–16 to determine the proportion of US adults with a completed living will, health care power of attorney, or both. Among the 795,909 people in the 150 studies we analyzed, 36.7 percent had completed an advance directive, including 29.3 percent with living wills. These proportions were similar across the years reviewed. Similar proportions of patients with chronic illnesses (38.2 percent) and healthy adults (32.7 percent) had completed advance directives. The findings provide benchmarks for gauging future policies and practices designed to motivate completion of advance directives, particularly among those...
TL;DR: A new anonymous authentication scheme for WBANs is proposed and it is proved that it is provably secure and overcomes the security weaknesses in previous schemes but also has the same computation costs at a client side.
Abstract: Advances in wireless communications, embedded systems, and integrated circuit technologies have enabled the wireless body area network (WBAN) to become a promising networking paradigm. Over the last decade, as an important part of the Internet of Things, we have witnessed WBANs playing an increasing role in modern medical systems because of its capabilities to collect real-time biomedical data through intelligent medical sensors in or around the patients’ body and send the collected data to remote medical personnel for clinical diagnostics. WBANs not only bring us conveniences but also bring along the challenge of keeping data’s confidentiality and preserving patients’ privacy. In the past few years, several anonymous authentication (AA) schemes for WBANs were proposed to enhance security by protecting patients’ identities and by encrypting medical data. However, many of these schemes are not secure enough. First, we review the most recent AA scheme for WBANs and point out that it is not secure for medical applications by proposing an impersonation attack. After that, we propose a new AA scheme for WBANs and prove that it is provably secure. Our detailed analysis results demonstrate that our proposed AA scheme not only overcomes the security weaknesses in previous schemes but also has the same computation costs at a client side.
TL;DR: The purpose of this chapter is to advance theory in a world where literacy has become deictic and suggests that a dual-level theory of New Literacies is a useful approach to theory building in a World where the nature of literacy continuously changes.
Abstract: This chapter suggests that a dual-level theory of new literacies is a useful approach to theory building in a world where the nature of literacy continuously changes. It begins by making a central point: Social contexts have always shaped both the function and form of literate practices and been shaped by them in return. The chapter discusses the social context of the current period and explain how this has produced new information and communication technologies, and the new literacies that the technologies demand. It explores several lowercase new literacies perspectives that are emerging. The chapter argues that a dual-level New Literacies theory is essential to take full advantage of this important and diverse work. It presents one lowercase theory of new literacies, the new literacies of online research and comprehension, to illustrate how a dual-level theory of new literacies can inform new literacies research that takes related but different theoretical perspectives.
TL;DR: Cerebral neurofibrillary tangles burden, in addition to α-synuclein pathology and amyloid plaque pathology, are the strongest pathological predictors of a shorter interval between onset of motor and dementia symptoms and survival.
Abstract: Summary Background Great heterogeneity exists in survival and the interval between onset of motor symptoms and dementia symptoms across synucleinopathies. We aimed to identify genetic and pathological markers that have the strongest association with these features of clinical heterogeneity in synucleinopathies. Methods In this retrospective study, we examined symptom onset, and genetic and neuropathological data from a cohort of patients with Lewy body disorders with autopsy-confirmed α synucleinopathy (as of Oct 1, 2015) who were previously included in other studies from five academic institutions in five cities in the USA. We used histopathology techniques and markers to assess the burden of tau neurofibrillary tangles, neuritic plaques, α-synuclein inclusions, and other pathological changes in cortical regions. These samples were graded on an ordinal scale and genotyped for variants associated with synucleinopathies. We assessed the interval from onset of motor symptoms to onset of dementia, and overall survival in groups with varying levels of comorbid Alzheimer's disease pathology according to US National Institute on Aging–Alzheimer's Association neuropathological criteria, and used multivariate regression to control for age at death and sex. Findings On the basis of data from 213 patients who had been followed up to autopsy and met inclusion criteria of Lewy body disorder with autopsy-confirmed α synucleinopathy, we identified 49 (23%) patients with no Alzheimer's disease neuropathology, 56 (26%) with low-level Alzheimer's disease neuropathology, 45 (21%) with intermediate-level Alzheimer's disease neuropathology, and 63 (30%) with high-level Alzheimer's disease neuropathology. As levels of Alzheimer's disease neuropathology increased, cerebral α-synuclein scores were higher, and the interval between onset of motor and dementia symptoms and disease duration was shorter (p 2 0·22, p MAPT haplotype, and APOE genotype as covariates. Interpretation Alzheimer's disease neuropathology is common in synucleinopathies and confers a worse prognosis for each increasing level of neuropathological change. Cerebral neurofibrillary tangles burden, in addition to α-synuclein pathology and amyloid plaque pathology, are the strongest pathological predictors of a shorter interval between onset of motor and dementia symptoms and survival. Diagnostic criteria based on reliable biomarkers for Alzheimer's disease neuropathology in synucleinopathies should help to identify the most appropriate patients for clinical trials of emerging therapies targeting tau, amyloid-β or α synuclein, and to stratify them by level of Alzheimer's disease neuropathology. Funding US National Institutes of Health (National Institute on Aging and National Institute of Neurological Disorders and Stroke).
Cincinnati Children's Hospital Medical Center1, University of Michigan2, University of Rochester Medical Center3, Rafael Advanced Defense Systems4, Rutgers University5, University of British Columbia6, University of California, San Diego7, University of Colorado Denver8, University of Kentucky9, Northwestern University10, Central DuPage Hospital11, University of Arkansas for Medical Sciences12, University of Padua13, University of Missouri–Kansas City14, Icahn School of Medicine at Mount Sinai15, Boston Children's Hospital16, University of Washington17, University of Pennsylvania18, Ohio State University19, Harvard University20
TL;DR: The addendum guidelines provide the background, rationale, and strength of evidence for each recommendation for early introduction of peanut‐containing foods into the diets of infants at various risk levels for peanut allergy.
Abstract: Background Food allergy is an important public health problem because it affects children and adults, can be severe and even life-threatening, and may be increasing in prevalence. Beginning in 2008, the National Institute of Allergy and Infectious Diseases, working with other organizations and advocacy groups, led the development of the first clinical guidelines for the diagnosis and management of food allergy. A recent landmark clinical trial and other emerging data suggest that peanut allergy can be prevented through introduction of peanut-containing foods beginning in infancy. Objectives Prompted by these findings, along with 25 professional organizations, federal agencies, and patient advocacy groups, the National Institute of Allergy and Infectious Diseases facilitated development of addendum guidelines to specifically address the prevention of peanut allergy. Results The addendum provides 3 separate guidelines for infants at various risk levels for the development of peanut allergy and is intended for use by a wide variety of health care providers. Topics addressed include the definition of risk categories, appropriate use of testing (specific IgE measurement, skin prick tests, and oral food challenges), and the timing and approaches for introduction of peanut-containing foods in the health care provider's office or at home. The addendum guidelines provide the background, rationale, and strength of evidence for each recommendation. Conclusions Guidelines have been developed for early introduction of peanut-containing foods into the diets of infants at various risk levels for peanut allergy.
TL;DR: This guideline summarizes the current recommendations developed by the SIS task force on the treatment of patients who have IAI regarding risk assessment in individual patients; source control; the timing, selection, and duration of antimicrobial therapy; and suggested approaches to patients who fail initial therapy.
Abstract: Background: Previous evidence-based guidelines on the management of intra-abdominal infection (IAI) were published by the Surgical Infection Society (SIS) in 1992, 2002, and 2010. At the t...
TL;DR: In this article, milk-derived exosomes have been investigated for oral delivery of the chemotherapeutic drug paclitaxel (PAC) as an alternative to conventional i.p. therapy for improved efficacy and reduced toxicity.
Journal Article•
University of Louisville1, University of the Pacific (United States)2, University of Illinois at Chicago3, University of Texas Health Science Center at Houston4, University of Kentucky5, LSU Health Sciences Center New Orleans6, Florida State University7, New York University8, Hofstra University9, Lenox Hill Hospital10, NorthShore University HealthSystem11, University of Illinois at Urbana–Champaign12, Wright State University13, Illinois State University14, Icahn School of Medicine at Mount Sinai15, West Virginia University16, Geisinger Medical Center17, University of Oklahoma18, Stanford University19, University of Texas MD Anderson Cancer Center20, University of Wisconsin-Madison21, Harvard University22, University of Texas Medical Branch23, Johns Hopkins University24, Illinois Wesleyan University25, Mary Greeley Medical Center26
TL;DR: These guidelines are intended to provide a systematic and standardized approach to this complex and difficult arena of practice, while recognizing that every clinical situation is unique.
Abstract: Background Opioid use, abuse, and adverse consequences, including death, have escalated at an alarming rate since the 1990s. In an attempt to control opioid abuse, numerous regulations and guidelines for responsible opioid prescribing have been developed by various organizations. However, the US opioid epidemic is continuing and drug dose deaths tripled during 1999 to 2015. Recent data show a continuing increase in deaths due to natural and semisynthetic opioids, a decline in methadone deaths, and an explosive increase in the rates of deaths involving other opioids, specifically heroin and illicit synthetic fentanyl. Contrary to scientific evidence of efficacy and negative recommendations, a significant proportion of physicians and patients (92%) believe that opioids reduce pain and a smaller proportion (57%) report better quality of life. In preparation of the current guidelines, we have focused on the means to reduce the abuse and diversion of opioids without jeopardizing access for those patients suffering from non-cancer pain who have an appropriate medical indication for opioid use. Objectives To provide guidance for the prescription of opioids for the management of chronic non-cancer pain, to develop a consistent philosophy among the many diverse groups with an interest in opioid use as to how appropriately prescribe opioids, to improve the treatment of chronic non-cancer pain and to reduce the likelihood of drug abuse and diversion. These guidelines are intended to provide a systematic and standardized approach to this complex and difficult arena of practice, while recognizing that every clinical situation is unique. Methods The methodology utilized included the development of objectives and key questions. The methodology also utilized trustworthy standards, appropriate disclosures of conflicts of interest, as well as a panel of experts from various specialties and groups. The literature pertaining to opioid use, abuse, effectiveness, and adverse consequences was reviewed, with a best evidence synthesis of the available literature, and utilized grading for recommendation as described by the Agency for Healthcare Research and Quality (AHRQ).Summary of Recommendations:i. Initial Steps of Opioid Therapy 1. Comprehensive assessment and documentation. (Evidence: Level I; Strength of Recommendation: Strong) 2. Screening for opioid abuse to identify opioid abusers. (Evidence: Level II-III; Strength of Recommendation: Moderate) 3. Utilization of prescription drug monitoring programs (PDMPs). (Evidence: Level I-II; Strength of Recommendation: Moderate to strong) 4. Utilization of urine drug testing (UDT). (Evidence: Level II; Strength of Recommendation: Moderate) 5. Establish appropriate physical diagnosis and psychological diagnosis if available. (Evidence: Level I; Strength of Recommendation: Strong) 6. Consider appropriate imaging, physical diagnosis, and psychological status to collaborate with subjective complaints. (Evidence: Level III; Strength of Recommendation: Moderate) 7. Establish medical necessity based on average moderate to severe (≥ 4 on a scale of 0 - 10) pain and/or disability. (Evidence: Level II; Strength of Recommendation: Moderate) 8. Stratify patients based on risk. (Evidence: Level I-II; Strength of Recommendation: Moderate) 9. Establish treatment goals of opioid therapy with regard to pain relief and improvement in function. (Evidence: Level I-II; Strength of Recommendation: Moderate) 10. Obtain a robust opioid agreement, which is followed by all parties. (Evidence: Level III; Strength of Recommendation: Moderate)ii. Assessment of Effectiveness of Long-Term Opioid Therapy 11. Initiate opioid therapy with low dose, short-acting drugs, with appropriate monitoring. (Evidence: Level II; Strength of Recommendation: Moderate) 12. Consider up to 40 morphine milligram equivalent (MME) as low dose, 41 to 90 MME as a moderate dose, and greater than 91 MME as high dose. (Evidence: Level II; Strength of Recommendation: Moderate) 13. Avoid long-acting opioids for the initiation of opioid therapy. (Evidence: Level I; Strength of Recommendation: Strong) 14. Recommend methadone only for use after failure of other opioid therapy and only by clinicians with specific training in its risks and uses, within FDA recommended doses. (Evidence: Level I; Strength of Recommendation: Strong) 15. Understand and educate the patients of the effectiveness and adverse consequences. (Evidence: Level I; Strength of Recommendation: Strong) 16. Similar effectiveness for long-acting and short-acting opioids with increased adverse consequences of long-acting opioids. (Evidence: Level I-II; Strength of recommendation: Moderate to strong) 17. Periodically assess pain relief and/or functional status improvement of ≥ 30% without adverse consequences. (Evidence: Level II; Strength of recommendation: Moderate) 18. Recommend long-acting or high dose opioids only in specific circumstances with severe intractable pain. (Evidence: Level I; Strength of Recommendation: Strong)iii. Monitoring for Adherence and Side Effects 19. Monitor for adherence, abuse, and noncompliance by UDT and PDMPs. (Evidence: Level I-II; Strength of Recommendation: Moderate to strong) 20. Monitor patients on methadone with an electrocardiogram periodically. (Evidence: Level I; Strength of Recommendation: Strong). 21. Monitor for side effects including constipation and manage them appropriately, including discontinuation of opioids when indicated. (Evidence: Level I; Strength of Recommendation: Strong)iv. Final Phase 22. May continue with monitoring with continued medical necessity, with appropriate outcomes. (Evidence: Level I-II; Strength of Recommendation: Moderate) 23. Discontinue opioid therapy for lack of response, adverse consequences, and abuse with rehabilitation. (Evidence: Level III; Strength of Recommendation: Moderate) CONCLUSIONS: These guidelines were developed based on comprehensive review of the literature, consensus among the panelists, in consonance with patient preferences, shared decision-making, and practice patterns with limited evidence, based on randomized controlled trials (RCTs) to improve pain and function in chronic non-cancer pain on a long-term basis. Consequently, chronic opioid therapy should be provided only to patients with proven medical necessity and stability with improvement in pain and function, independently or in conjunction with other modalities of treatments in low doses with appropriate adherence monitoring and understanding of adverse events.Key words: Chronic pain, persistent pain, non-cancer pain, controlled substances, substance abuse, prescription drug abuse, dependency, opioids, prescription monitoring, drug testing, adherence monitoring, diversionDisclaimer: The guidelines are based on the best available evidence and do not constitute inflexible treatment recommendations. Due to the changing body of evidence, this document is not intended to be a "standard of care."
TL;DR: In this article, a meta-analysis examines the link between self-control and measures of crime and deviance, taking stock of the empirical status of self control theory and focusing on work published between 2000 and 2010.
TL;DR: This work explores and discusses how the various enabling technologies can be efficiently deployed to achieve a green IoT environment, and identifies some of the emerging challenges that need to be addressed in the future to enable agreen IoT.
Abstract: Recent technological advances have led to an increase in the carbon footprint. Energy efficiency in the Internet of Things (IoT) has been attracting a lot of attention from researchers and designers over the last couple of years, paving the way for an emerging area called green IoT. There are various aspects (such as key enablers, communications, services, and applications) of IoT, where efficient utilization of energy is needed to enable a green IoT environment. We explore and discuss how the various enabling technologies (such as the Internet, smart objects, sensors, etc.) can be efficiently deployed to achieve a green IoT. Furthermore, we also review various IoT applications, projects and standardization efforts that are currently under way. Finally, we identify some of the emerging challenges that need to be addressed in the future to enable a green IoT.
Journal Article•
TL;DR: The 2017 version of Cloudy as mentioned in this paper is the most recent version of the spectral synthesis code, which has made many improvements to the scope and accuracy of the physics which have been made since the previous release.
Abstract: We describe the 2017 release of the spectral synthesis code Cloudy , summa- rizing the many improvements to the scope and accuracy of the physics which have been made since the previous release. Exporting the atomic data into external data files has enabled many new large datasets to be incorporated into the code. The use of the complete datasets is not realistic for most calculations, so we describe the lim- ited subset of data used by default, which predicts significantly more lines than the previous release of Cloudy . This version is nevertheless faster than the previous release, as a result of code optimizations. We give examples of the accuracy limits using small models, and the performance requirements of large complete models. We summarize several advances in the H- and He-like iso-electronic sequences and use our complete collisional-radiative models to establish the densities where the coronal and local thermodynamic equilibrium approximations work.
TL;DR: Evidence for and against several major theories trying to explain refractory epilepsy are summarized, including the pharmacokinetic hypothesis, neural network hypothesis, intrinsic severity hypothesis, gene variant hypothesis, target hypothesis, and transporter hypothesis.
Abstract: Epilepsy is a common neurological disorder that affects over 70 million people worldwide. Despite the recent introduction of new antiseizure drugs (ASDs), about one-third of patients with epilepsy have seizures refractory to pharmacotherapy. Early identification of patients who will become refractory to ASDs could help direct such patients to appropriate non-pharmacological treatment, but the complexity in the temporal patterns of epilepsy could make such identification difficult. The target hypothesis and transporter hypothesis are the most cited theories trying to explain refractory epilepsy, but neither theory alone fully explains the neurobiological basis of pharmacoresistance. This review summarizes evidence for and against several major theories, including the pharmacokinetic hypothesis, neural network hypothesis, intrinsic severity hypothesis, gene variant hypothesis, target hypothesis, and transporter hypothesis. The discussion is mainly focused on the transporter hypothesis, where clinical and experimental data are discussed on multidrug transporter overexpression, substrate profiles of ASDs, mechanism of transporter upregulation, polymorphisms of transporters, and the use of transporter inhibitors. Finally, future perspectives are presented for the improvement of current hypotheses and the development of treatment strategies as guided by the current understanding of refractory epilepsy.
TL;DR: It is shown that MPCs interact with interstitial fibrogenic cells to ensure proper ECM deposition and optimal muscle remodeling in response to hypertrophic stimuli, providing insights into how skeletal stem and progenitor cells interact with other cell types to actively regulate their extracellular environments for tissue maintenance and adaptation.
TL;DR: This work presents a lightweight and secure user authentication protocol based on the Rabin cryptosystem, which has the characteristic of computational asymmetry and presents a comprehensive heuristic security analysis to show that the protocol is secure against all the possible attacks and provides the desired security features.
Abstract: Wireless sensor networks (WSNs) will be integrated into the future Internet as one of the components of the Internet of Things, and will become globally addressable by any entity connected to the Internet. Despite the great potential of this integration, it also brings new threats, such as the exposure of sensor nodes to attacks originating from the Internet. In this context, lightweight authentication and key agreement protocols must be in place to enable end-to-end secure communication. Recently, Amin et al. proposed a three-factor mutual authentication protocol for WSNs. However, we identified several flaws in their protocol. We found that their protocol suffers from smart card loss attack where the user identity and password can be guessed using offline brute force techniques. Moreover, the protocol suffers from known session-specific temporary information attack, which leads to the disclosure of session keys in other sessions. Furthermore, the protocol is vulnerable to tracking attack and fails to fulfill user untraceability. To address these deficiencies, we present a lightweight and secure user authentication protocol based on the Rabin cryptosystem, which has the characteristic of computational asymmetry. We conduct a formal verification of our proposed protocol using ProVerif in order to demonstrate that our scheme fulfills the required security properties. We also present a comprehensive heuristic security analysis to show that our protocol is secure against all the possible attacks and provides the desired security features. The results we obtained show that our new protocol is a secure and lightweight solution for authentication and key agreement for Internet-integrated WSNs.
TL;DR: In this article, the electrochemical properties and related mechanism of SiO x are reviewed, and the current research progress to enhance SiOx electrochemical performance by nanostructuring and the effect of other battery components such as binders, electrolyte, and prelithiation on its performance is also discussed.