Showing papers by "University of Kentucky published in 2015"
Michael S. Lawrence1, Carrie Sougnez1, Lee Lichtenstein1, Kristian Cibulskis1 +306 more•Institutions (26)
TL;DR: It is shown that human-papillomavirus-associated tumours are dominated by helical domain mutations of the oncogene PIK3CA, novel alterations involving loss of TRAF3, and amplification of the cell cycle gene E2F1.
Abstract: The Cancer Genome Atlas profiled 279 head and neck squamous cell carcinomas (HNSCCs) to provide a comprehensive landscape of somatic genomic alterations Here we show that human-papillomavirus-associated tumours are dominated by helical domain mutations of the oncogene PIK3CA, novel alterations involving loss of TRAF3, and amplification of the cell cycle gene E2F1 Smoking-related HNSCCs demonstrate near universal loss-of-function TP53 mutations and CDKN2A inactivation with frequent copy number alterations including amplification of 3q26/28 and 11q13/22 A subgroup of oral cavity tumours with favourable clinical outcomes displayed infrequent copy number alterations in conjunction with activating mutations of HRAS or PIK3CA, coupled with inactivating mutations of CASP8, NOTCH1 and TP53 Other distinct subgroups contained loss-of-function alterations of the chromatin modifier NSD1, WNT pathway genes AJUBA and FAT1, and activation of oxidative stress factor NFE2L2, mainly in laryngeal tumours Therapeutic candidate alterations were identified in most HNSCCs
2,997 citations
TL;DR: In a longitudinal study of patients with NAFLD, fibrosis stage, but no other histologic features of steatohepatitis, were associated independently with long-term overall mortality, liver transplantation, and liver-related events.
2,061 citations
TL;DR: The aim was to initiate worldwide surveillance of cancer survival by central analysis of population-based registry data, as a metric of the effectiveness of health systems, and to inform global policy on cancer control.
1,866 citations
University of Zurich1, Hannover Medical School2, University of California, Davis3, Heidelberg University4, Ludwig Maximilian University of Munich5, Charité6, University of Kentucky7, University of Cologne8, Saarland University9, University of Duisburg-Essen10, University of Göttingen11, University of Hamburg12, University of Ulm13, Technische Universität München14, Otto-von-Guericke University Magdeburg15, John Radcliffe Hospital16, Winterthur Museum, Garden and Library17, University of Turku18, Gdańsk Medical University19, University of Warmia and Mazury in Olsztyn20, Medical University of Warsaw21, University of Cambridge22, University of Basel23, Catholic University of the Sacred Heart24, Innsbruck Medical University25, University of Greifswald26, Leiden University27, University of Glasgow28
TL;DR: Patients with takotsubo cardiomyopathy had a higher prevalence of neurologic or psychiatric disorders than did those with an acute coronary syndrome and physical triggers, acute neurologics or psychiatric diseases, high troponin levels, and a low ejection fraction on admission were independent predictors for in-hospital complications.
Abstract: BackgroundThe natural history, management, and outcome of takotsubo (stress) cardiomyopathy are incompletely understood. MethodsThe International Takotsubo Registry, a consortium of 26 centers in Europe and the United States, was established to investigate clinical features, prognostic predictors, and outcome of takotsubo cardiomyopathy. Patients were compared with age- and sex-matched patients who had an acute coronary syndrome. ResultsOf 1750 patients with takotsubo cardiomyopathy, 89.8% were women (mean age, 66.8 years). Emotional triggers were not as common as physical triggers (27.7% vs. 36.0%), and 28.5% of patients had no evident trigger. Among patients with takotsubo cardiomyopathy, as compared with an acute coronary syndrome, rates of neurologic or psychiatric disorders were higher (55.8% vs. 25.7%) and the mean left ventricular ejection fraction was markedly lower (40.7±11.2% vs. 51.5±12.3%) (P<0.001 for both comparisons). Rates of severe in-hospital complications including shock and death were ...
1,721 citations
National Institutes of Health1, University of Toronto2, Martin Luther University of Halle-Wittenberg3, University of Pisa4, Medical College of Wisconsin5, Memorial Sloan Kettering Cancer Center6, Washington University in St. Louis7, University of Siena8, Heidelberg University9, University of Sydney10, University of Kentucky11, University of Naples Federico II12, Institut Gustave Roussy13, Ohio State University14
TL;DR: The revised guidelines are focused primarily on the diagnosis and treatment of patients with sporadic medullary thyroid carcinoma (MTC) and hereditary MTC and developed 67 evidence-based recommendations to assist clinicians in the care of Patients with MTC.
Abstract: Introduction: The American Thyroid Association appointed a Task Force of experts to revise the original Medullary Thyroid Carcinoma: Management Guidelines of the American Thyroid Association. Methods: The Task Force identified relevant articles using a systematic PubMed search, supplemented with additional published materials, and then created evidence-based recommendations, which were set in categories using criteria adapted from the United States Preventive Services Task Force Agency for Healthcare Research and Quality. The original guidelines provided abundant source material and an excellent organizational structure that served as the basis for the current revised document. Results: The revised guidelines are focused primarily on the diagnosis and treatment of patients with sporadic medullary thyroid carcinoma (MTC) and hereditary MTC. Conclusions: The Task Force developed 67 evidence-based recommendations to assist clinicians in the care of patients with MTC. The Task Force considers the recommendati...
1,504 citations
TL;DR: This state-of-the-science manuscript seeks to describe the specific evidence based interventions, tools, programs, and recommendations that have had an impact on the transition of care in patients with HF.
Abstract: The purpose of this feature is to highlight the contributions and the expertise of the members of the American Heart Association’s Council on Cardiovascular and StrokeNursing.Anurse-led scientific statement was recently published in Circulation; this state-of-science manuscript was authored by Albert et al. Dr Albert and her colleagues are representatives of the Council on Cardiovascular and Stroke Nursing. This is a brief review of the manuscript describing the state-of-science related to transitions of care in heart failure (HF). Hospitalization rates for patients with HF have remained stagnant over the past decade, with the current 30-day rehospitalization rate forHFholding steady at 24.7%. Heart failure providers in both the inpatient and outpatient settings have recognized the urgent need for an organized transition of care to improve patient-centered and health systems outcomes. The complexity of HFmanagement burdens the patient, the provider, and the healthcare system. This state-of-the-science manuscript seeks to describe the specific evidence based interventions, tools, programs, andrecommendations that have had an impact on the transition of care in patients with HF. Within the structure of the Affordable Care Act, hospitals that have high 30-day readmission rates are penalized. Identifying modifiable factors that predict and contribute to HF readmission rates has become the standard operating milieu for hospital staff, and regulatory compliance is a fiscal responsibility for hospital administrators. There have been a multitude of interventions identified as having a significant impact on readmission rates. These interventions include individualized patient education, telephone follow-up, medication reconciliation, early assessment postdischarge, inclusion of caregivers, home visits, and a transition of care report to the primary care provider once the patient is discharged. Those patients at highest risk for readmission, the elderly, those with multiple hospitalizations for HF in the previous 6 months, and those with longer length of stays are being targeted to identify high-risk characteristics amenable to individualized or bundled interventions for smooth transition of care.
1,087 citations
TL;DR: In this paper, the authors examined recent research evidence of the health consequences of food insecurity for children, nonsenior adults, and seniors in the United States and found that the literature has consistently found food insecurity to be negatively associated with health.
Abstract: Almost fifty million people are food insecure in the United States, which makes food insecurity one of the nation's leading health and nutrition issues. We examine recent research evidence of the health consequences of food insecurity for children, nonsenior adults, and seniors in the United States. For context, we first provide an overview of how food insecurity is measured in the country, followed by a presentation of recent trends in the prevalence of food insecurity. Then we present a survey of selected recent research that examined the association between food insecurity and health outcomes. We show that the literature has consistently found food insecurity to be negatively associated with health. For example, after confounding risk factors were controlled for, studies found that food-insecure children are at least twice as likely to report being in fair or poor health and at least 1.4 times more likely to have asthma, compared to food-secure children; and food-insecure seniors have limitations in activities of daily living comparable to those of food-secure seniors fourteen years older. The Supplemental Nutrition Assistance Program (SNAP) substantially reduces the prevalence of food insecurity and thus is critical to reducing negative health outcomes.
952 citations
University of Colorado Boulder1, University of Notre Dame2, Commonwealth Scientific and Industrial Research Organisation3, University of Minnesota4, Queensland University of Technology5, Martin Luther University of Halle-Wittenberg6, Iowa State University7, University of Nebraska–Lincoln8, University of Kentucky9, University of California, Berkeley10, Swiss Federal Institute for Forest, Snow and Landscape Research11, Lancaster University12
TL;DR: The results suggest that elevated N and P inputs lead to predictable shifts in the taxonomic and functional traits of soil microbial communities, including increases in the relative abundances of faster-growing, copiotrophic bacterial taxa, with these shifts likely to impact belowground ecosystems worldwide.
Abstract: Soil microorganisms are critical to ecosystem functioning and the maintenance of soil fertility. However, despite global increases in the inputs of nitrogen (N) and phosphorus (P) to ecosystems due to human activities, we lack a predictive understanding of how microbial communities respond to elevated nutrient inputs across environmental gradients. Here we used high-throughput sequencing of marker genes to elucidate the responses of soil fungal, archaeal, and bacterial communities using an N and P addition experiment replicated at 25 globally distributed grassland sites. We also sequenced metagenomes from a subset of the sites to determine how the functional attributes of bacterial communities change in response to elevated nutrients. Despite strong compositional differences across sites, microbial communities shifted in a consistent manner with N or P additions, and the magnitude of these shifts was related to the magnitude of plant community responses to nutrient inputs. Mycorrhizal fungi and methanogenic archaea decreased in relative abundance with nutrient additions, as did the relative abundances of oligotrophic bacterial taxa. The metagenomic data provided additional evidence for this shift in bacterial life history strategies because nutrient additions decreased the average genome sizes of the bacterial community members and elicited changes in the relative abundances of representative functional genes. Our results suggest that elevated N and P inputs lead to predictable shifts in the taxonomic and functional traits of soil microbial communities, including increases in the relative abundances of faster-growing, copiotrophic bacterial taxa, with these shifts likely to impact belowground ecosystems worldwide.
867 citations
TL;DR: Proteins pathogenic in Alzheimer's disease were extracted from neurally derived blood exosomes and quantified to develop biomarkers for the staging of sporadic AD.
Abstract: Background Proteins pathogenic in Alzheimer's disease (AD) were extracted from neurally derived blood exosomes and quantified to develop biomarkers for the staging of sporadic AD. Methods Blood exosomes obtained at one time-point from patients with AD (n = 57) or frontotemporal dementia (FTD) (n = 16), and at two time-points from others (n = 24) when cognitively normal and 1 to 10 years later when diagnosed with AD were enriched for neural sources by immunoabsorption. AD-pathogenic exosomal proteins were extracted and quantified by enzyme-linked immunosorbent assays. Results Mean exosomal levels of total tau, P-T181-tau, P-S396-tau, and amyloid β 1–42 (Aβ1–42) for AD and levels of P-T181-tau and Aβ1–42 for FTD were significantly higher than for case-controls. Step-wise discriminant modeling incorporated P-T181-tau, P-S396-tau, and Aβ1–42 in AD, but only P-T181-tau in FTD. Classification of 96.4% of AD patients and 87.5% of FTD patients was correct. In 24 AD patients, exosomal levels of P-S396-tau, P-T181-tau, and Aβ1–42 were significantly higher than for controls both 1 to 10 years before and when diagnosed with AD. Conclusions Levels of P-S396-tau, P-T181-tau, and Aβ1–42 in extracts of neurally derived blood exosomes predict the development of AD up to 10 years before clinical onset.
632 citations
TL;DR: This work proposes a CPPA scheme for VANETs that does not use bilinear paring and demonstrates that it could supports both the mutual authentication and the privacy protection simultaneously and yields a better performance in terms of computation cost and communication cost.
Abstract: By broadcasting messages about traffic status to vehicles wirelessly, a vehicular ad hoc network (VANET) can improve traffic safety and efficiency. To guarantee secure communication in VANETs, security and privacy issues must be addressed before their deployment. The conditional privacy-preserving authentication (CPPA) scheme is suitable for solving security and privacy-preserving problems in VANETs, because it supports both mutual authentication and privacy protection simultaneously. Many identity-based CPPA schemes for VANETs using bilinear pairings have been proposed over the last few years to enhance security or to improve performance. However, it is well known that the bilinear pairing operation is one of the most complex operations in modern cryptography. To achieve better performance and reduce computational complexity of information processing in VANET, the design of a CPPA scheme for the VANET environment that does not use bilinear paring becomes a challenge. To address this challenge, we propose a CPPA scheme for VANETs that does not use bilinear paring and we demonstrate that it could supports both the mutual authentication and the privacy protection simultaneously. Our proposed CPPA scheme retains most of the benefits obtained with the previously proposed CPPA schemes. Moreover, the proposed CPPA scheme yields a better performance in terms of computation cost and communication cost making it be suitable for use by the VANET safety-related applications.
625 citations
Brigham and Women's Hospital1, Harvard University2, East Jefferson General Hospital3, University of Kentucky4, Florida Hospital Orlando5, Holmes Regional Medical Center6, St. John's University7, Holy Name Medical Center8, Hartford Hospital9, Memorial Medical Center10, Memorial Hospital of South Bend11, Montefiore Medical Center12, Christiana Care Health System13, Overlook Medical Center14, Cardiovascular Institute of the South15, Miriam Hospital16, Stanford University17, Fred Hutchinson Cancer Research Center18
TL;DR: Ultrasound-facilitated, catheter-directed, low-dose fibrinolysis decreased RV dilation, reduced pulmonary hypertension, decreased anatomic thrombus burden, and minimized intracranial hemorrhage in patients with acute massive and submassive PE.
Abstract: Objectives This study conducted a prospective, single-arm, multicenter trial to evaluate the safety and efficacy of ultrasound-facilitated, catheter-directed, low-dose fibrinolysis, using the EkoSonic Endovascular System (EKOS, Bothell, Washington). Background Systemic fibrinolysis for acute pulmonary embolism (PE) reduces cardiovascular collapse but causes hemorrhagic stroke at a rate exceeding 2%. Methods Eligible patients had a proximal PE and a right ventricular (RV)-to-left ventricular (LV) diameter ratio ≥0.9 on chest computed tomography (CT). We included 150 patients with acute massive (n = 31) or submassive (n = 119) PE. We used 24 mg of tissue-plasminogen activator (t-PA) administered either as 1 mg/h for 24 h with a unilateral catheter or 1 mg/h/catheter for 12 h with bilateral catheters. The primary safety outcome was major bleeding within 72 h of procedure initiation. The primary efficacy outcome was the change in the chest CT–measured RV/LV diameter ratio within 48 h of procedure initiation. Results Mean RV/LV diameter ratio decreased from baseline to 48 h post-procedure (1.55 vs. 1.13; mean difference, −0.42; p Conclusions Ultrasound-facilitated, catheter-directed, low-dose fibrinolysis decreased RV dilation, reduced pulmonary hypertension, decreased anatomic thrombus burden, and minimized intracranial hemorrhage in patients with acute massive and submassive PE. (A Prospective, Single-arm, Multi-center Trial of EkoSonic® Endovascular System and Activase for Treatment of Acute Pulmonary Embolism (PE) [SEATTLE II]; NCT01513759 )
TL;DR: The cellular demands of nucleotide biosynthesis, their metabolic pathways and mechanisms of regulation during the cell cycle are reviewed and how this may lead to potential new approaches to drug development in diseases such as cancer is discussed.
Abstract: Nucleotides are required for a wide variety of biological processes and are constantly synthesized de novo in all cells. When cells proliferate, increased nucleotide synthesis is necessary for DNA replication and for RNA production to support protein synthesis at different stages of the cell cycle, during which these events are regulated at multiple levels. Therefore the synthesis of the precursor nucleotides is also strongly regulated at multiple levels. Nucleotide synthesis is an energy intensive process that uses multiple metabolic pathways across different cell compartments and several sources of carbon and nitrogen. The processes are regulated at the transcription level by a set of master transcription factors but also at the enzyme level by allosteric regulation and feedback inhibition. Here we review the cellular demands of nucleotide biosynthesis, their metabolic pathways and mechanisms of regulation during the cell cycle. The use of stable isotope tracers for delineating the biosynthetic routes of the multiple intersecting pathways and how these are quantitatively controlled under different conditions is also highlighted. Moreover, the importance of nucleotide synthesis for cell viability is discussed and how this may lead to potential new approaches to drug development in diseases such as cancer.
TL;DR: Readmissions after surgery were associated with new postdischarge complications related to the procedure and not exacerbation of prior index hospitalization complications, suggesting that readmission after surgery are a measure of postdis discharge complications.
Abstract: Importance Financial penalties for readmission have been expanded beyond medical conditions to include surgical procedures. Hospitals are working to reduce readmissions; however, little is known about the reasons for surgical readmission. Objective To characterize the reasons, timing, and factors associated with unplanned postoperative readmissions. Design, Setting, and Participants Patients undergoing surgery at one of 346 continuously enrolled US hospitals participating in the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) between January 1, 2012, and December 31, 2012, had clinically abstracted information examined. Readmission rates and reasons (ascertained by clinical data abstractors at each hospital) were assessed for all surgical procedures and for 6 representative operations: bariatric procedures, colectomy or proctectomy, hysterectomy, total hip or knee arthroplasty, ventral hernia repair, and lower extremity vascular bypass. Main Outcomes and Measures Unplanned 30-day readmission and reason for readmission. Results The unplanned readmission rate for the 498 875 operations was 5.7%. For the individual procedures, the readmission rate ranged from 3.8% for hysterectomy to 14.9% for lower extremity vascular bypass. The most common reason for unplanned readmission was surgical site infection (SSI) overall (19.5%) and also after colectomy or proctectomy (25.8%), ventral hernia repair (26.5%), hysterectomy (28.8%), arthroplasty (18.8%), and lower extremity vascular bypass (36.4%). Obstruction or ileus was the most common reason for readmission after bariatric surgery (24.5%) and the second most common reason overall (10.3%), after colectomy or proctectomy (18.1%), ventral hernia repair (16.7%), and hysterectomy (13.4%). Only 2.3% of patients were readmitted for the same complication they had experienced during their index hospitalization. Only 3.3% of patients readmitted for SSIs had experienced an SSI during their index hospitalization. There was no time pattern for readmission, and early (≤7 days postdischarge) and late (>7 days postdischarge) readmissions were associated with the same 3 most common reasons: SSI, ileus or obstruction, and bleeding. Patient comorbidities, index surgical admission complications, non-home discharge (hazard ratio [HR], 1.40 [95% CI, 1.35-1.46]), teaching hospital status (HR, 1.14 [95% CI 1.07-1.21]), and higher surgical volume (HR, 1.15 [95% CI, 1.07-1.25]) were associated with a higher risk of hospital readmission. Conclusions and Relevance Readmissions after surgery were associated with new postdischarge complications related to the procedure and not exacerbation of prior index hospitalization complications, suggesting that readmissions after surgery are a measure of postdischarge complications. These data should be considered when developing quality indicators and any policies penalizing hospitals for surgical readmission.
TL;DR: In this paper, the authors identified and summarized longitudinal studies that, supporting the association of nonalcoholic fatty liver disease with either type 2 diabetes mellitus or metabolic syndrome, suggest that non-ALTL disease precedes the development of both conditions.
Centers for Disease Control and Prevention1, University of Hawaii2, University of Iowa3, University of Southern California4, LSU Health Sciences Center New Orleans5, University of Florida6, Michigan Department of Community Health7, University of Kentucky8, Florida Department of Health9, Battelle Memorial Institute10
TL;DR: In the United States, current vaccines will reduce most HPV-associated cancers; a smaller additional reduction would be contributed by the new 9-valent vaccine.
Abstract: Background: This study sought to determine the prevaccine type-specific prevalence of human papillomavirus (HPV)– associated cancers in the United States to evaluate the potential impact of the HPV types in the current and newly approved 9-valent HPV vaccines. Methods: The Centers for Disease Control and Prevention partnered with seven US population-based cancer registries to obtain archival tissue for cancers diagnosed from 1993 to 2005. HPV testing was performed on 2670 case patients that were fairly representative of all participating cancer registry cases by age and sex. Demographic and clinical data were evaluated by anatomic site and HPV status. Current US cancer registry data and the detection of HPV types were used to estimate the number of cancers potentially preventable through vaccination. Results: HPV DNA was detected in 90.6% of cervical, 91.1% of anal, 75.0% of vaginal, 70.1% of oropharyngeal, 68.8% of vulvar, 63.3% of penile, 32.0% of oral cavity, and 20.9% of laryngeal cancers, as well as in 98.8% of cervical cancer in situ (CCIS). A vaccine targeting HPV 16/18 potentially prevents the majority of invasive cervical (66.2%), anal (79.4%), oropharyngeal (60.2%), and vaginal (55.1%) cancers, as well as many penile (47.9%), vulvar (48.6%) cancers: 24 858 cases annually. The 9-valent vaccine also targeting HPV 31/33/45/52/58 may prevent an additional 4.2% to 18.3% of cancers: 3944 cases annually. For most cancers, younger age at diagnosis was associated with higher HPV 16/18 prevalence. With the exception of oropharyngeal cancers and CCIS, HPV 16/18 prevalence was similar across racial/ethnic groups.
TL;DR: This review compares and contrast the healing and inflammatory responses between spinal cord injuries and tissues that undergo complete wound resolution and identifies key macrophage phenotypes that are inaptly triggered or absent after spinal cord injury and discusses spinal cord stimuli that contribute to this maladaptive response.
Commonwealth Scientific and Industrial Research Organisation1, Cooperative Institute for Research in Environmental Sciences2, University of Minnesota3, Queensland University of Technology4, Utah State University5, University of Washington6, University of California, San Diego7, United States Geological Survey8, University of KwaZulu-Natal9, University of Oxford10, Iowa State University11, University of Nebraska–Lincoln12, University of California, Berkeley13, University of Guelph14, University of Kentucky15, University of North Carolina at Chapel Hill16, Swiss Federal Institute for Forest, Snow and Landscape Research17, Lancaster University18
TL;DR: In this paper, the authors compared the diversity of plant, bacterial, archaeal and fungal communities in one hundred and forty-five 1 m 2 plots across 25 temperate grassland sites from four continents.
Abstract: Aboveground–belowground interactions exert critical controls on the composition and function of terrestrial ecosystems, yet the fundamental relationships between plant diversity and soil microbial diversity remain elusive. Theory predicts predominantly positive associations but tests within single sites have shown variable relationships, and associations between plant and microbial diversity across broad spatial scales remain largely unexplored. We compared the diversity of plant, bacterial, archaeal and fungal communities in one hundred and forty-five 1 m 2 plots across 25 temperate grassland sites from four continents. Across sites, the plant alpha diversity patterns were poorly related to those observed for any soil microbial group. However, plant beta diversity (compositional dissimilarity between sites) was significantly correlated with the beta diversity of bacterial and fungal communities, even after controlling for environmental factors. Thus, across a global range of temperate grasslands, plant diversity can predict patterns in the composition of soil microbial communities, but not patterns in alpha diversity.
Alzheimer's Association1, National Institutes of Health2, Wake Forest University3, University of North Carolina at Chapel Hill4, Harvard University5, Mayo Clinic6, Cleveland Clinic7, University of Washington8, Cornell University9, Rush University Medical Center10, University of British Columbia11, University of Kentucky12, Washington University in St. Louis13, University of Southern California14
TL;DR: A summary of the meeting and the resultant discussion of how vascular factors contribute to Alzheimer's disease and related dementia is summarized, including an outline of next steps needed to move this area of research forward.
Abstract: Scientific evidence continues to demonstrate the linkage of vascular contributions to cognitive impairment and dementia such as Alzheimer's disease. In December, 2013, the Alzheimer's Association, with scientific input from the National Institute of Neurological Disorders and Stroke and the National Heart, Lung and Blood Institute from the National Institutes of Health, convened scientific experts to discuss the research gaps in our understanding of how vascular factors contribute to Alzheimer's disease and related dementia. This manuscript summarizes the meeting and the resultant discussion, including an outline of next steps needed to move this area of research forward.
TL;DR: Although many mycoviruses do not have marked effects on their hosts, those that reduce the virulence of their phytopathogenic fungal hosts are of considerable interest for development of novel biocontrol strategies.
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TL;DR: In this paper, the authors argue that the critique of the smart city in its historical and geographical context should be paid to the actually existing smart city, rather than the exceptional or paradigmatic smart cities of Songdo, Masdar and Living PlanIT Valley.
Abstract: This paper grounds the critique of the ‘smart city’ in its historical and geographical context. Adapting Brenner and Theodore’s notion of ‘actually existing neoliberalism’, we suggest a greater attention be paid to the ‘actually existing smart city’, rather than the exceptional or paradigmatic smart cities of Songdo, Masdar and Living PlanIT Valley. Through a closer analysis of cases in Louisville and Philadelphia, we demonstrate the utility of understanding the material effects of these policies in actual cities around the world, with a particular focus on how and from where these policies have arisen, and how they have unevenly impacted the places that have adopted them.
Agricultural Research Service1, Commonwealth Scientific and Industrial Research Organisation2, University of Nebraska–Lincoln3, University of Washington4, University of Minnesota5, University of Guelph6, Utah State University7, Trinity College, Dublin8, Lanzhou University9, University of California, Los Angeles10, University of New Mexico11, University of Colorado Boulder12, University of Illinois at Urbana–Champaign13, Queensland University of Technology14, University of Maryland, College Park15, University of KwaZulu-Natal16, Utrecht University17, University of North Carolina at Chapel Hill18, Colorado State University19, Chinese Academy of Sciences20, University of Kentucky21, Monash University22, La Trobe University23, Swiss Federal Institute for Forest, Snow and Landscape Research24, Lancaster University25, University of California, Davis26
TL;DR: It is suggested that multiple-nutrient constraints must be considered when assessing the ecosystem-scale consequences of nutrient enrichment, and significant variations in the type and degree of nutrient limitation are pointed to.
Abstract: Terrestrial ecosystem productivity is widely accepted to be nutrient limited(1). Although nitrogen (N) is deemed a key determinant of aboveground net primary production (ANPP) 2,3, the prevalence of co-limitation by N and phosphorus (P) is increasingly recognized(4-8). However, the extent to which terrestrial productivity is co-limited by nutrients other than N and P has remained unclear. Here, we report results from a standardized factorial nutrient addition experiment, in which we added N, P and potassium (K) combined with a selection of micronutrients (K+mu), alone or in concert, to 42 grassland sites spanning five continents, and monitored ANPP. Nutrient availability limited productivity at 31 of the 42 grassland sites. And pairwise combinations of N, P, and K+mu co-limited ANPP at 29 of the sites. Nitrogen limitation peaked in cool, high latitude sites. Our findings highlight the importance of less studied nutrients, such as K and micronutrients, for grassland productivity, and point to significant variations in the type and degree of nutrient limitation. We suggest that multiple-nutrient constraints must be considered when assessing the ecosystem-scale consequences of nutrient enrichment.
Thomas Jefferson University1, University of Ioannina2, Brown University3, Wills Eye Institute4, University of Texas Southwestern Medical Center5, University of Nebraska Medical Center6, University of North Carolina at Chapel Hill7, Baylor College of Medicine8, University of Kentucky9, University of Genoa10, University of Texas MD Anderson Cancer Center11, Garvan Institute of Medical Research12, University of New South Wales13
TL;DR: The findings suggest that the repertoire of human miRNAs is far more extensive than currently represented by public repositories and that there is a significant number of lineage- and/or tissue-specific mi RNAs that are uncharacterized.
Abstract: Two decades after the discovery of the first animal microRNA (miRNA), the number of miRNAs in animal genomes remains a vexing question. Here, we report findings from analyzing 1,323 short RNA sequencing samples (RNA-seq) from 13 different human tissue types. Using stringent thresholding criteria, we identified 3,707 statistically significant novel mature miRNAs at a false discovery rate of ≤0.05 arising from 3,494 novel precursors; 91.5% of these novel miRNAs were identified independently in 10 or more of the processed samples. Analysis of these novel miRNAs revealed tissue-specific dependencies and a commensurate low Jaccard similarity index in intertissue comparisons. Of these novel miRNAs, 1,657 (45%) were identified in 43 datasets that were generated by cross-linking followed by Argonaute immunoprecipitation and sequencing (Ago CLIP-seq) and represented 3 of the 13 tissues, indicating that these miRNAs are active in the RNA interference pathway. Moreover, experimental investigation through stem-loop PCR of a random collection of newly discovered miRNAs in 12 cell lines representing 5 tissues confirmed their presence and tissue dependence. Among the newly identified miRNAs are many novel miRNA clusters, new members of known miRNA clusters, previously unreported products from uncharacterized arms of miRNA precursors, and previously unrecognized paralogues of functionally important miRNA families (e.g., miR-15/107). Examination of the sequence conservation across vertebrate and invertebrate organisms showed 56.7% of the newly discovered miRNAs to be human-specific whereas the majority (94.4%) are primate lineage-specific. Our findings suggest that the repertoire of human miRNAs is far more extensive than currently represented by public repositories and that there is a significant number of lineage- and/or tissue-specific miRNAs that are uncharacterized.
TL;DR: This article presents and discusses some of the integration challenges that must be addressed to enable an intelligent transportation system to address issues facing the transportation sector such as high fuel prices, high levels of CO2 emissions, increasing traffic congestion, and improved road safety.
Abstract: Transportation is a necessary infrastructure for our modern society. The performance of transportation systems is of crucial importance for individual mobility, commerce, and for the economic growth of all nations. In recent years modern society has been facing more traffic jams, higher fuel prices, and an increase in CO2 emissions. It is imperative to improve the safety and efficiency of transportation. Developing a sustainable intelligent transportation system requires the seamless integration and interoperability with emerging technologies such as connected vehicles, cloud computing, and the Internet of Things. In this article we present and discuss some of the integration challenges that must be addressed to enable an intelligent transportation system to address issues facing the transportation sector such as high fuel prices, high levels of CO2 emissions, increasing traffic congestion, and improved road safety.
TL;DR: In this paper, the authors describe the design, manufacture, and performance of bare-fiber integral field units (IFUs) for the SDSS-IV survey Mapping Nearby Galaxies at Apache Point Observatory (MaNGA).
Abstract: We describe the design, manufacture, and performance of bare-fiber integral field units (IFUs) for the SDSS-IV survey Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) on the the Sloan 2.5 m telescope at Apache Point Observatory. MaNGA is a luminosity-selected integral-field spectroscopic survey of 104 local galaxies covering 360–1030 nm at R ~ 2200. The IFUs have hexagonal dense packing of fibers with packing regularity of 3 μm (rms), and throughput of 96 ± 0.5% from 350 nm to 1 μm in the lab. Their sizes range from 19 to 127 fibers (3–7 hexagonal layers) using Polymicro FBP 120:132:150 μm core:clad:buffer fibers to reach a fill fraction of 56%. High throughput (and low focal-ratio degradation (FRD)) is achieved by maintaining the fiber cladding and buffer intact, ensuring excellent surface polish, and applying a multi-layer anti-reflection (AR) coating of the input and output surfaces. In operations on-sky, the IFUs show only an additional 2.3% FRD-related variability in throughput despite repeated mechanical stressing during plate plugging (however other losses are present). The IFUs achieve on-sky throughput 5% above the single-fiber feeds used in SDSS-III/BOSS, attributable to equivalent performance compared to single fibers and additional gains from the AR coating. The manufacturing process is geared toward mass-production of high-multiplex systems. The low-stress process involves a precision ferrule with a hexagonal inner shape designed to lead inserted fibers to settle in a dense hexagonal pattern. The ferrule ID is tapered at progressively shallower angles toward its tip and the final 2 mm are straight and only a few microns larger than necessary to hold the desired number of fibers. Our IFU manufacturing process scales easily to accommodate other fiber sizes and can produce IFUs with substantially larger fiber counts. To assure quality, automated testing in a simple and inexpensive system enables complete characterization of throughput and fiber metrology. Future applications include larger IFUs, higher fill factors with stripped buffer, de-cladding, and lenslet coupling.
TL;DR: It is suggested that lifelong reduction of satellite cells neither accelerated nor exacerbated sarcopenia and that satellite cells did not contribute to the maintenance of muscle size or fiber type composition during aging, but that their loss may contribute to age-related muscle fibrosis.
Abstract: A key determinant of geriatric frailty is sarcopenia, the age-associated loss of skeletal muscle mass and strength. Although the etiology of sarcopenia is unknown, the correlation during aging between the loss of activity of satellite cells, which are endogenous muscle stem cells, and impaired muscle regenerative capacity has led to the hypothesis that the loss of satellite cell activity is also a cause of sarcopenia. We tested this hypothesis in male sedentary mice by experimentally depleting satellite cells in young adult animals to a degree sufficient to impair regeneration throughout the rest of their lives. A detailed analysis of multiple muscles harvested at various time points during aging in different cohorts of these mice showed that the muscles were of normal size, despite low regenerative capacity, but did have increased fibrosis. These results suggest that lifelong reduction of satellite cells neither accelerated nor exacerbated sarcopenia and that satellite cells did not contribute to the maintenance of muscle size or fiber type composition during aging, but that their loss may contribute to age-related muscle fibrosis.
University of Colorado Denver1, Veterans Health Administration2, University of Michigan3, Columbia University Medical Center4, Pierre-and-Marie-Curie University5, Heidelberg University6, University of Alabama at Birmingham7, Brigham and Women's Hospital8, Los Angeles Biomedical Research Institute9, University of California, San Diego10, University of Edinburgh11, Johns Hopkins University12, Temple University13, Chungnam National University14, St. Marianna University School of Medicine15, Duke University16, HealthPartners17, University of Kentucky18
TL;DR: Current smoking was associated with more respiratory symptoms, but former smokers had greater emphysema and gas trapping, and individuals with respiratory impairments were more likely to use respiratory medications, and the use of these medications was associatedWith worse disease.
Abstract: Importance Airflow obstruction on spirometry is universally used to define chronic obstructive pulmonary disease (COPD), and current or former smokers without airflow obstruction may assume that they are disease free. Objective To identify clinical and radiologic evidence of smoking-related disease in a cohort of current and former smokers who did not meet spirometric criteria for COPD, for whom we adopted the discarded label of Global Initiative for Obstructive Lung Disease (GOLD) 0. Design, Setting, and Participants Individuals from the Genetic Epidemiology of COPD (COPDGene) cross-sectional observational study completed spirometry, chest computed tomography (CT) scans, a 6-minute walk, and questionnaires. Participants were recruited from local communities at 21 sites across the United States. The GOLD 0 group (n = 4388) (ratio of forced expiratory volume in the first second of expiration [FEV 1 ] to forced vital capacity >0.7 and FEV 1 ≥80% predicted) from the COPDGene study was compared with a GOLD 1 group (n = 794), COPD groups (n = 3690), and a group of never smokers (n = 108). Recruitment began in January 2008 and ended in July 2011. Main Outcomes and Measures Physical function impairments, respiratory symptoms, CT abnormalities, use of respiratory medications, and reduced respiratory-specific quality of life. Results One or more respiratory-related impairments were found in 54.1% (2375 of 4388) of the GOLD 0 group. The GOLD 0 group had worse quality of life (mean [SD] St George’s Respiratory Questionnaire total score, 17.0 [18.0] vs 3.8 [6.8] for the never smokers; P 1 percent predicted distribution and mean for the GOLD 0 group were lower but still within the normal range for the population. Current smoking was associated with more respiratory symptoms, but former smokers had greater emphysema and gas trapping. Advancing age was associated with smoking cessation and with more CT findings of disease. Individuals with respiratory impairments were more likely to use respiratory medications, and the use of these medications was associated with worse disease. Conclusions and Relevance Lung disease and impairments were common in smokers without spirometric COPD. Based on these results, we project that there are 35 million current and former smokers older than 55 years in the United States who may have unrecognized disease or impairment. The effect of chronic smoking on the lungs and the individual is substantially underestimated when using spirometry alone.
TL;DR: Levels of autolysosomal proteins in neurally derived blood exosomes distinguish patients with AD from case controls and appear to reflect the pathology of AD up to 10 years before clinical onset.
Abstract: Objective: Diverse autolysosomal proteins were quantified in neurally derived blood exosomes from patients with Alzheimer disease (AD) and controls to investigate disordered neuronal autophagy. Methods: Blood exosomes obtained once from patients with AD (n = 26) or frontotemporal dementia (n = 16), other patients with AD (n = 20) both when cognitively normal and 1 to 10 years later when diagnosed, and case controls were enriched for neural sources by anti-human L1CAM antibody immunoabsorption. Extracted exosomal proteins were quantified by ELISAs and normalized with the CD81 exosomal marker. Results: Mean exosomal levels of cathepsin D, lysosome-associated membrane protein 1 (LAMP-1), and ubiquitinylated proteins were significantly higher and of heat-shock protein 70 significantly lower for AD than controls in cross-sectional studies ( p ≤ 0.0005). Levels of cathepsin D, LAMP-1, and ubiquitinylated protein also were significantly higher for patients with AD than for patients with frontotemporal dementia ( p ≤ 0.006). Step-wise discriminant modeling of the protein levels correctly classified 100% of patients with AD. Exosomal levels of all proteins were similarly significantly different from those of matched controls in 20 patients 1 to 10 years before and at diagnosis of AD ( p ≤ 0.0003). Conclusions: Levels of autolysosomal proteins in neurally derived blood exosomes distinguish patients with AD from case controls and appear to reflect the pathology of AD up to 10 years before clinical onset. These preliminary results confirm in living patients with AD the early appearance of neuronal lysosomal dysfunction and suggest that these proteins may be useful biomarkers in large prospective studies.
TL;DR: In this article, the number of active galactic nuclei (AGN) candidates at z = 4-6 is estimated by using a relatively novel criterion based on the galaxy rest-frame UV flux, which is defined as the probability of spurious detections of 2 x 10−4 in the deep X-ray 4 Ms Chandra image.
Abstract: Context. Establishing the number of faint active galactic nuclei (AGNs) at z = 4-6 is crucial to understanding their cosmological importance as main contributors to the reionization of the Universe. Aims. In order to derive the AGN contribution to the cosmological ionizing emissivity we have selected faint AGN candidates at z \textgreater 4 in the CANDELS GOODS-South field, which is one of the deepest fields with extensive multiwavelength coverage from Chandra, HST, Spitzer, and various ground-based telescopes. Methods. We have adopted a relatively novel criterion. As a first step, high redshift galaxies are selected in the NIR H band down to very faint levels (H \textless= 27) using reliable photometric redshifts. At z \textgreater 4 this corresponds to a selection criterion based on the galaxy rest-frame UV flux. AGN candidates are then picked up from this parent sample if they show X-ray fluxes above a threshold of F-X similar to 1.5 x 10(-17) erg cm(-2) s(-1) (0.5-2 keV), corresponding to a probability of spurious detections of 2 x 10(-4) in the deep X-ray 4 Ms Chandra image. Results. We have found 22 AGN candidates at z \textgreater 4 and we have derived the first estimate of the UV luminosity function in the redshift interval 4 \textless z \textless 6.5 and absolute magnitude interval -22.5 less than or similar to M-1450 less than or similar to -18.5 typical of local Seyfert galaxies. The faint end of the derived luminosity function is about two to four magnitudes fainter at z similar to 4-6 than that derived from previous UV surveys. We estimated ionizing emissivities and hydrogen photoionization rates in the same redshift interval under reasonable assumptions and after discussion of possible caveats, the most important being the large uncertainties involved in the estimate of photometric redshift for sources with featureless, almost power-law SEDs and/or low average escape fraction of ionizing photons from the AGN host galaxies. Both effects could, in principle, significantly reduce the estimated average volume densities and/or ionizing emissivities, especially at the highest redshifts. Conclusions. At z = 4-6.5 we argue that, under reasonable evaluations of possible biases, the probed AGN population can produce photoionization rates consistent with that required to keep the intergalactic medium observed in the Lyman-alpha forest of high redshift QSO spectra highly ionized, providing an important contribution to the cosmic reionization.
TL;DR: In this article, the inverted capacitive deionization (i-CDI) system was proposed to improve the performance stability of the CDI system by using an anode with net negative surface charges and a cathode with positive surface charges.
Abstract: Unsustainable and inefficient capacitive deionization (CDI) performance has been observed through CDI operation with carbon xerogel (CX) electrodes for 50 hours using a constant-voltage charging method. This behavior is primarily accounted for by changes in the surface chemistry for the studied material via oxidation of the carbon electrodes in an aqueous solution. In order to improve performance stability, we have developed a novel CDI system using an anode with net negative surface charges and a cathode with net positive surface charges. As a result, salt separation in this system is achieved in an opposing manner to the conventional CDI system, e.g., when the system is charged using a power source, cations and anions are desorbed at the anode and cathode, respectively. This system is named the inverted capacitive deionization (i-CDI) system. Most importantly, salt separation in the i-CDI system was maintained for over 600 hours, which is approximately an increase of 530% in lifetime compared to a CDI system operated under similar conditions. This enhanced performance stability is attributed to the use of oxidized anodes in the i-CDI system, which limits the possibility for loss in separation performance due to carbon oxidation in an aqueous solution.
TL;DR: More research is needed into cyberbullying, but available data suggest a serious problem whose consequences are real and should not be dismissed as a "virtual" by-product of an increasingly digitalized childhood and adolescence.