Showing papers by "University of Rochester published in 2014"
TL;DR: Results of this multistate prevalence survey of health care-associated infections indicate that public health surveillance and prevention activities should continue to address C. difficile infections.
Abstract: Background Currently, no single U.S. surveillance system can provide estimates of the burden of all types of health care–associated infections across acute care patient populations. We conducted a prevalence survey in 10 geographically diverse states to determine the prevalence of health care–associated infections in acute care hospitals and generate updated estimates of the national burden of such infections. Methods We defined health care–associated infections with the use of National Healthcare Safety Network criteria. One-day surveys of randomly selected inpatients were performed in participating hospitals. Hospital personnel collected demographic and limited clinical data. Trained data collectors reviewed medical records retrospectively to identify health care–associated infections active at the time of the survey. Survey data and 2010 Nationwide Inpatient Sample data, stratified according to patient age and length of hospital stay, were used to estimate the total numbers of health care–associated in...
3,010 citations
Johns Hopkins University1, University of Utah2, University of Rochester3, The Royal Marsden NHS Foundation Trust4, National Institutes of Health5, Stanford University6, Washington University in St. Louis7, Ontario Institute for Cancer Research8, University of Sydney9, St. Jude Medical Center10, University of Toronto11, Mayo Clinic12, American Society of Clinical Oncology13, University of Southern California14, North Carolina State University15, Indiana University16, University of Milan17, University of Michigan18
TL;DR: The Update Committee recommends that HER2 status (HER2 negative or positive) be determined in all patients with invasive breast cancer on the basis of one or more HER2 test results (negative, equivocal, or positive).
Abstract: Purpose
To update the American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guideline recommendations for human epidermal growth factor receptor 2 (HER2) testing in breast cancer to improve the accuracy of HER2 testing and its utility as a predictive marker in invasive breast cancer.
2,934 citations
Icahn School of Medicine at Mount Sinai1, Cleveland Clinic2, University of Alabama at Birmingham3, University of Copenhagen4, University College London5, University of Texas Health Science Center at Houston6, New York University7, University of Pennsylvania8, VU University Amsterdam9, National Multiple Sclerosis Society10, Johns Hopkins University11, Vita-Salute San Raffaele University12, University of Ottawa13, University of Rochester14, University of Basel15, University of Düsseldorf16, Pierre-and-Marie-Curie University17, Autonomous University of Barcelona18, University of Toronto19, University of British Columbia20, Sapienza University of Rome21, University of Texas Southwestern Medical Center22, University of California, San Francisco23
TL;DR: Refined descriptors that include consideration of disease activity (based on clinical relapse rate and imaging findings) and disease progression are proposed and strategies for future research to better define phenotypes are outlined.
Abstract: Accurate clinical course descriptions (phenotypes) of multiple sclerosis (MS) are important for communication, prognostication, design and recruitment of clinical trials, and treatment decision-making. Standardized descriptions published in 1996 based on a survey of international MS experts provided purely clinical phenotypes based on data and consensus at that time, but imaging and biological correlates were lacking. Increased understanding of MS and its pathology, coupled with general concern that the original descriptors may not adequately reflect more recently identified clinical aspects of the disease, prompted a re-examination of MS disease phenotypes by the International Advisory Committee on Clinical Trials of MS. While imaging and biological markers that might provide objective criteria for separating clinical phenotypes are lacking, we propose refined descriptors that include consideration of disease activity (based on clinical relapse rate and imaging findings) and disease progression. Strategies for future research to better define phenotypes are also outlined.
2,180 citations
Case Western Reserve University1, Imperial College London2, South Dakota School of Mines and Technology3, University of Maryland, College Park4, Yale University5, Lawrence Livermore National Laboratory6, University of South Dakota7, University of California, Santa Barbara8, Brown University9, University of Coimbra10, University of Edinburgh11, University of Rochester12, Lawrence Berkeley National Laboratory13, University of California, Davis14, University College London15, University of California, Berkeley16, Texas A&M University17, Harvard University18
TL;DR: The first WIMP search data set is reported, taken during the period from April to August 2013, presenting the analysis of 85.3 live days of data, finding that the LUX data are in disagreement with low-mass W IMP signal interpretations of the results from several recent direct detection experiments.
Abstract: The Large Underground Xenon (LUX) experiment is a dual-phase xenon time-projection chamber operating at the Sanford Underground Research Facility (Lead, South Dakota). The LUX cryostat was filled for the first time in the underground laboratory in February 2013. We report results of the first WIMP search data set, taken during the period from April to August 2013, presenting the analysis of 85.3 live days of data with a fiducial volume of 118 kg. A profile-likelihood analysis technique shows our data to be consistent with the background-only hypothesis, allowing 90% confidence limits to be set on spin-independent WIMP-nucleon elastic scattering with a minimum upper limit on the cross section of 7.6 × 10(-46) cm(2) at a WIMP mass of 33 GeV/c(2). We find that the LUX data are in disagreement with low-mass WIMP signal interpretations of the results from several recent direct detection experiments.
1,962 citations
TL;DR: Bapineuzumab did not improve clinical outcomes in patients with Alzheimer's disease, despite treatment differences in biomarkers observed in APOE ε4 carriers.
Abstract: Background Bapineuzumab, a humanized anti-amyloid-beta monoclonal antibody, is in clinical development for the treatment of Alzheimer's disease. Methods We conducted two double-blind, randomized, placebo-controlled, phase 3 trials involving patients with mild-to-moderate Alzheimer's disease--one involving 1121 carriers of the apolipoprotein E (APOE) e4 allele and the other involving 1331 noncarriers. Bapineuzumab or placebo, with doses varying by study, was administered by intravenous infusion every 13 weeks for 78 weeks. The primary outcome measures were scores on the 11-item cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-cog11, with scores ranging from 0 to 70 and higher scores indicating greater impairment) and the Disability Assessment for Dementia (DAD, with scores ranging from 0 to 100 and higher scores indicating less impairment). A total of 1090 carriers and 1114 noncarriers were included in the efficacy analysis. Secondary outcome measures included findings on positron-emission tomographic amyloid imaging with the use of Pittsburgh compound B (PIB-PET) and cerebrospinal fluid phosphorylated tau (phospho-tau) concentrations. Results There were no significant between-group differences in the primary outcomes. At week 78, the between-group differences in the change from baseline in the ADAS-cog11 and DAD scores (bapineuzumab group minus placebo group) were -0.2 (P=0.80) and -1.2 (P=0.34), respectively, in the carrier study; the corresponding differences in the noncarrier study were -0.3 (P=0.64) and 2.8 (P=0.07) with the 0.5-mg-per-kilogram dose of bapineuzumab and 0.4 (P=0.62) and 0.9 (P=0.55) with the 1.0-mg-per-kilogram dose. The major safety finding was amyloid-related imaging abnormalities with edema among patients receiving bapineuzumab, which increased with bapineuzumab dose and APOE e4 allele number and which led to discontinuation of the 2.0-mg-per-kilogram dose. Between-group differences were observed with respect to PIB-PET and cerebrospinal fluid phospho-tau concentrations in APOE e4 allele carriers but not in noncarriers. Conclusions Bapineuzumab did not improve clinical outcomes in patients with Alzheimer's disease, despite treatment differences in biomarkers observed in APOE e4 carriers. (Funded by Janssen Alzheimer Immunotherapy and Pfizer; Bapineuzumab 301 and 302 ClinicalTrials.gov numbers, NCT00575055 and NCT00574132, and EudraCT number, 2009-012748-17.).
1,579 citations
04 Mar 2014
TL;DR: The largest-scale study of video engagement to date is presented, using data from 6.9 million video watching sessions across four courses on the edX MOOC platform, finding that shorter videos are much more engaging, that informal talking-head videos are more engage, and that Khan-style tablet drawings are more engaging.
Abstract: Videos are a widely-used kind of resource for online learning. This paper presents an empirical study of how video production decisions affect student engagement in online educational videos. To our knowledge, ours is the largest-scale study of video engagement to date, using data from 6.9 million video watching sessions across four courses on the edX MOOC platform. We measure engagement by how long students are watching each video, and whether they attempt to answer post-video assessment problems.Our main findings are that shorter videos are much more engaging, that informal talking-head videos are more engaging, that Khan-style tablet drawings are more engaging, that even high-quality pre-recorded classroom lectures might not make for engaging online videos, and that students engage differently with lecture and tutorial videos.Based upon these quantitative findings and qualitative insights from interviews with edX staff, we developed a set of recommendations to help instructors and video producers take better advantage of the online video format. Finally, to enable researchers to reproduce and build upon our findings, we have made our anonymized video watching data set and analysis scripts public. To our knowledge, ours is one of the first public data sets on MOOC resource usage.
1,473 citations
TL;DR: Solanezumab, a humanized monoclonal antibody that binds amyloid, failed to improve cognition or functional ability in patients with mild Alzheimer's disease.
Abstract: BackgroundAlzheimer's disease is characterized by amyloid-beta plaques, neurofibrillary tangles, gliosis, and neuronal loss. Solanezumab, a humanized monoclonal antibody, preferentially binds soluble forms of amyloid and in preclinical studies promoted its clearance from the brain. MethodsIn two phase 3, double-blind trials (EXPEDITION 1 and EXPEDITION 2), we randomly assigned 1012 and 1040 patients, respectively, with mild-to-moderate Alzheimer's disease to receive placebo or solanezumab (administered intravenously at a dose of 400 mg) every 4 weeks for 18 months. The primary outcomes were the changes from baseline to week 80 in scores on the 11-item cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-cog11; range, 0 to 70, with higher scores indicating greater cognitive impairment) and the Alzheimer's Disease Cooperative Study–Activities of Daily Living scale (ADCS-ADL; range, 0 to 78, with lower scores indicating worse functioning). After analysis of data from EXPEDITION 1, the primary...
1,388 citations
Ohio State University1, Harvard University2, University of Texas MD Anderson Cancer Center3, Hofstra University4, Mayo Clinic5, Vanderbilt University6, Stanford University7, St. Vincent's Health System8, Royal North Shore Hospital9, Medical University of Vienna10, University of Cambridge11, University of Rochester12, NewYork–Presbyterian Hospital13, University of California, San Diego14, East Kent Hospitals University Nhs Foundation Trust15, Beaumont Hospital16, Vita-Salute San Raffaele University17, Medical University of Łódź18, University of Barcelona19, University of Pennsylvania20, University of California, Los Angeles21, Princess Alexandra Hospital22, The Royal Marsden NHS Foundation Trust23, Autonomous University of Barcelona24, Leeds Teaching Hospitals NHS Trust25
TL;DR: Ibrutinib, as compared with ofatumumab, significantly improved progression-free survival, overall survival, and response rate among patients with previously treated CLL or SLL.
Abstract: Background In patients with chronic lymphoid leukemia (CLL) or small lymphocytic lymphoma (SLL), a short duration of response to therapy or adverse cytogenetic abnormalities are associated with a poor outcome. We evaluated the efficacy of ibrutinib, a covalent inhibitor of Bruton’s tyrosine kinase, in patients at risk for a poor outcome. Methods In this multicenter, open-label, phase 3 study, we randomly assigned 391 patients with relapsed or refractory CLL or SLL to receive daily ibrutinib or the anti-CD20 antibody ofatumumab. The primary end point was the duration of progression-free survival, with the duration of overall survival and the overall response rate as secondary end points. Results At a median follow-up of 9.4 months, ibrutinib significantly improved progressionfree survival; the median duration was not reached in the ibrutinib group (with a rate of progression-free survival of 88% at 6 months), as compared with a median of 8.1 months in the ofatumumab group (hazard ratio for progression or death in the ibrutinib group, 0.22; P<0.001). Ibrutinib also significantly improved overall survival (hazard ratio for death, 0.43; P = 0.005). At 12 months, the overall survival rate was 90% in the ibrutinib group and 81% in the ofatumumab group. The overall response rate was significantly higher in the ibrutinib group than in the ofatumumab group (42.6% vs. 4.1%, P<0.001). An additional 20% of ibrutinib-treated patients had a partial response with lymphocytosis. Similar effects were observed regardless of whether patients had a chromosome 17p13.1 deletion or resistance to purine analogues. The most frequent nonhematologic adverse events were diarrhea, fatigue, pyrexia, and nausea in the ibrutinib group and fatigue, infusion-related reactions, and cough in the ofatumumab group. Conclusions Ibrutinib, as compared with ofatumumab, significantly improved progression-free survival, overall survival, and response rate among patients with previously treated CLL or SLL. (Funded by Pharmacyclics and Janssen; RESONATE ClinicalTrials.gov number, NCT01578707.)
1,343 citations
Katholieke Universiteit Leuven1, University of Toronto2, Charles University in Prague3, Maastricht University4, University of South Florida5, Lyon College6, University of Chicago7, Curie Institute8, Catholic University of the Sacred Heart9, University of São Paulo10, University of Liverpool11, University of Rochester12, Drug Abuse Resistance Education13
TL;DR: There is mounting data regarding the utility of GA in oncology practice; however, additional research is needed to continue to strengthen the evidence base.
Abstract: Purpose To update the International Society of Geriatric Oncology (SIOG) 2005 recommendations on geriatric assessment (GA) in older patients with cancer. Methods SIOG composed a panel with expertise in geriatric oncology to develop consensus statements after literature review of key evidence on the following topics: rationale for performing GA; findings from a GA performed in geriatric oncology patients; ability of GA to predict oncology treatment–related complications; association between GA findings and overall survival (OS); impact of GA findings on oncology treatment decisions; composition of a GA, including domains and tools; and methods for implementing GA in clinical care. Results GA can be valuable in oncology practice for following reasons: detection of impairment not identified in routine history or physical examination, ability to predict severe treatment-related toxicity, ability to predict OS in a variety of tumors and treatment settings, and ability to influence treatment choice and intensit...
1,266 citations
TL;DR: The multiple possible activation states microglia can be polarized to are examined and particular attention is given to utilizing M2 microglial polarization as a potential therapeutic option in treating diseases.
Abstract: The concept of multiple macrophage activation states is not new. However, extending this idea to resident tissue macrophages, like microglia, has gained increased interest in recent years. Unfortunately, the research on peripheral macrophage polarization does not necessarily translate accurately to their central nervous system (CNS) counterparts. Even though pro- and anti-inflammatory cytokines can polarize microglia to distinct activation states, the specific functions of these states is still an area of intense debate. This review examines the multiple possible activation states microglia can be polarized to. This is followed by a detailed description of microglial polarization and the functional relevance of this process in both acute and chronic CNS disease models described in the literature. Particular attention is given to utilizing M2 microglial polarization as a potential therapeutic option in treating diseases.
1,257 citations
University of Rochester1, University of Texas Southwestern Medical Center2, University of North Carolina at Chapel Hill3, Thomas Jefferson University4, University of Colorado Denver5, University of Virginia6, University of Miami7, Johns Hopkins University8, University of Florida9, Harvard University10, Duke University11, Cincinnati Children's Hospital Medical Center12, Mayo Clinic13, National Institutes of Health14, Food and Drug Administration15, American Institutes for Research16
TL;DR: Hydxyurea and transfusion therapy are strongly recommended for many individuals with SCD and many other recommendations are based on quality of evidence that is less than high due to the paucity of clinical trials regarding screening, management, and monitoring for individuals withSCD.
Abstract: Importance Sickle cell disease (SCD) is a life-threatening genetic disorder affecting nearly 100 000 individuals in the United States and is associated with many acute and chronic complications requiring immediate medical attention. Two disease-modifying therapies, hydroxyurea and long-term blood transfusions, are available but underused. Objective To support and expand the number of health professionals able and willing to provide care for persons with SCD. Evidence Review Databases of MEDLINE (including in-process and other nonindexed citations), EMBASE, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, CINAHL, TOXLINE, and Scopus were searched using prespecified search terms and keywords to identify randomized clinical trials, nonrandomized intervention studies, and observational studies. Literature searches of English-language publications from 1980 with updates through April 1, 2014, addressed key questions developed by the expert panel members and methodologists. Findings Strong recommendations for preventive services include daily oral prophylactic penicillin up to the age of 5 years, annual transcranial Doppler examinations from the ages of 2 to 16 years in those with sickle cell anemia, and long-term transfusion therapy to prevent stroke in those children with abnormal transcranial Doppler velocity (≥200 cm/s). Strong recommendations addressing acute complications include rapid initiation of opioids for treatment of severe pain associated with a vasoocclusive crisis, and use of incentive spirometry in patients hospitalized for a vasoocclusive crisis. Strong recommendations for chronic complications include use of analgesics and physical therapy for treatment of avascular necrosis, and use of angiotensin-converting enzyme inhibitor therapy for microalbuminuria in adults with SCD. Strong recommendations for children and adults with proliferative sickle cell retinopathy include referral to expert specialists for consideration of laser photocoagulation and for echocardiography to evaluate signs of pulmonary hypertension. Hydroxyurea therapy is strongly recommended for adults with 3 or more severe vasoocclusive crises during any 12-month period, with SCD pain or chronic anemia interfering with daily activities, or with severe or recurrent episodes of acute chest syndrome. A recommendation of moderate strength suggests offering treatment with hydroxyurea without regard to the presence of symptoms for infants, children, and adolescents. In persons with sickle cell anemia, preoperative transfusion therapy to increase hemoglobin levels to 10 g/dL is strongly recommended with a moderate strength recommendation to maintain sickle hemoglobin levels of less than 30% prior to the next transfusion during long-term transfusion therapy. A strong recommendation to assess iron overload is accompanied by a moderate strength recommendation to begin iron chelation therapy when indicated. Conclusions and Relevance Hydroxyurea and transfusion therapy are strongly recommended for many individuals with SCD. Many other recommendations are based on quality of evidence that is less than high due to the paucity of clinical trials regarding screening, management, and monitoring for individuals with SCD.
TL;DR: In this article, an interdiffusion method was proposed to fabricate pinhole free perovskite films using a low temperature solution process, achieving an efficiency of 15.4% with a fill factor of ∼80%.
Abstract: We report on an interdiffusion method to fabricate pin-hole free perovskite films using a low temperature (<105 °C) solution process. A high efficiency of 15.4%, with a fill factor of ∼80%, was achieved for the devices under one sun illumination. The interdiffusion method results in high device yield, with an efficiency of above 14.5% for more than 85% of the devices.
TL;DR: A brief overview of deep learning is provided, and current research efforts and the challenges to big data, as well as the future trends are highlighted.
Abstract: Deep learning is currently an extremely active research area in machine learning and pattern recognition society. It has gained huge successes in a broad area of applications such as speech recognition, computer vision, and natural language processing. With the sheer size of data available today, big data brings big opportunities and transformative potential for various sectors; on the other hand, it also presents unprecedented challenges to harnessing data and information. As the data keeps getting bigger, deep learning is coming to play a key role in providing big data predictive analytics solutions. In this paper, we provide a brief overview of deep learning, and highlight current research efforts and the challenges to big data, as well as the future trends.
Columbia University1, American Society of Clinical Oncology2, University of Rochester3, University of Michigan4, University of Milan5, University of Milano-Bicocca6, Ohio State University7, Northwestern University8, Indiana University – Purdue University Indianapolis9, Johns Hopkins University10, Sanford Health11, Washington University in St. Louis12, Mayo Clinic13
TL;DR: Although the CIPN trials are inconclusive regarding tricyclic antidepressants (such as nortriptyline), gabapentin, and a compounded topical gel containing baclofen, amitriptylines HCL, and ketamine, these agents may be offered on the basis of data supporting their utility in other neuropathic pain conditions given the limited other CIPn treatment options.
Abstract: Purpose To provide evidence-based guidance on the optimum prevention and treatment approaches in the management of chemotherapy-induced peripheral neuropathies (CIPN) in adult cancer survivors. Methods A systematic literature search identified relevant, randomized controlled trials (RCTs) for the treatment of CIPN. Primary outcomes included incidence and severity of neuropathy as measured by neurophysiologic changes, patient-reported outcomes, and quality of life. Results A total of 48 RCTs met eligibility criteria and comprise the evidentiary basis for the recommendations. Trials tended to be small and heterogeneous, many with insufficient sample sizes to detect clinically important differences in outcomes. Primary outcomes varied across the trials, and in most cases, studies were not directly comparable because of different outcomes, measurements, and instruments used at different time points. The strength of the recommendations is based on the quality, amount, and consistency of the evidence and the ba...
SUNY Downstate Medical Center1, McGill University2, University of Connecticut3, Cornell University4, Umeå University5, Wayne State University6, University of Iowa7, University of Miami8, University of Pennsylvania9, Mayo Clinic10, University of Sydney11, University of Buenos Aires12, University of Chicago13, Shanghai Jiao Tong University14, North-West University15, University of Rochester16, University of Glasgow17, Virginia Commonwealth University18, University of Melbourne19
TL;DR: Clinical Practice Guidelines for the Management of Hypertension in the Community as mentioned in this paper A Statement by the American Society of hypertension and the International Society of Hyperpharmension (ISH).
Abstract: Clinical Practice Guidelines for the Management of Hypertension in the Community A Statement by the American Society of Hypertension and the International Society of Hypertension
TL;DR: This work discovered and validated a set of ten lipids from peripheral blood that predicted phenoconversion to either amnestic mild cognitive impairment or Alzheimer's disease within a 2–3 year timeframe with over 90% accuracy and may be sensitive to early neurodegeneration of preclinical Alzheimer’s disease.
Abstract: Alzheimer's disease causes a progressive dementia that currently affects over 35 million individuals worldwide and is expected to affect 115 million by 2050 (ref. 1). There are no cures or disease-modifying therapies, and this may be due to our inability to detect the disease before it has progressed to produce evident memory loss and functional decline. Biomarkers of preclinical disease will be critical to the development of disease-modifying or even preventative therapies. Unfortunately, current biomarkers for early disease, including cerebrospinal fluid tau and amyloid-β levels, structural and functional magnetic resonance imaging and the recent use of brain amyloid imaging or inflammaging, are limited because they are either invasive, time-consuming or expensive. Blood-based biomarkers may be a more attractive option, but none can currently detect preclinical Alzheimer's disease with the required sensitivity and specificity. Herein, we describe our lipidomic approach to detecting preclinical Alzheimer's disease in a group of cognitively normal older adults. We discovered and validated a set of ten lipids from peripheral blood that predicted phenoconversion to either amnestic mild cognitive impairment or Alzheimer's disease within a 2-3 year timeframe with over 90% accuracy. This biomarker panel, reflecting cell membrane integrity, may be sensitive to early neurodegeneration of preclinical Alzheimer's disease.
TL;DR: This document updates “Strategies to Prevent Surgical Site Infections in Acute Care Hospitals,” published in 2008, with practical recommendations in a concise format designed to assist acute care hospitals in implementing and prioritizing their surgical site infection prevention efforts.
Abstract: Previously published guidelines are available that provide comprehensive recommendations for detecting and preventing healthcare-associated infections (HAIs). The intent of this document is to highlight practical recommendations in a concise format designed to assist acute care hospitals in implementing and prioritizing their surgical site infection (SSI) prevention efforts. This document updates “Strategies to Prevent Surgical Site Infections in Acute Care Hospitals,” published in 2008. This expert guidance document is sponsored by the Society for Healthcare Epidemiology of America (SHEA) and is the product of a collaborative effort led by SHEA, the Infectious Diseases Society of America (IDSA), the American Hospital Association (AHA), the Association for Professionals in Infection Control and Epidemiology (APIC), and The Joint Commission, with major contributions from representatives of a number of organizations and societies with content expertise. The list of endorsing and supporting organizations is presented in the introduction to the 2014 updates.
TL;DR: Evaluating the efficiency of CSF–ISF exchange and interstitial solute clearance is impaired in the aging brain found that bulk flow drainage via the glymphatic system is driven by cerebrovascular pulsation, and is dependent on astroglial water channels that line paravascular CSF pathways.
Abstract: Objective: In the brain, protein waste removal is partly performed by paravascular pathways that facilitate convective exchange of water and soluble contents between cerebrospinal fluid (CSF) and interstitial fluid (ISF). Several lines of evidence suggest that bulk flow drainage via the glymphatic system is driven by cerebrovascular pulsation, and is dependent on astroglial water channels that line paravascular CSF pathways. The objective of this study was to evaluate whether the efficiency of CSF–ISF exchange and interstitial solute clearance is impaired in the aging brain. Methods: CSF–ISF exchange was evaluated by in vivo and ex vivo fluorescence microscopy and interstitial solute clearance was evaluated by radiotracer clearance assays in young (2–3 months), middle-aged (10–12 months), and old (18–20 months) wild-type mice. The relationship between age-related changes in the expression of the astrocytic water channel aquaporin-4 (AQP4) and changes in glymphatic pathway function was evaluated by immunofluorescence. Results: Advancing age was associated with a dramatic decline in the efficiency of exchange between the subarachnoid CSF and the brain parenchyma. Relative to the young, clearance of intraparenchymally injected amyloid-b was impaired by 40% in the old mice. A 27% reduction in the vessel wall pulsatility of intracortical arterioles and widespread loss of perivascular AQP4 polarization along the penetrating arteries accompanied the decline in CSF–ISF exchange. Interpretation: We propose that impaired glymphatic clearance contributes to cognitive decline among the elderly and may represent a novel therapeutic target for the treatment of neurodegenerative diseases associated with accumulation of misfolded protein aggregates. ANN NEUROL 2014;76:845–861
TL;DR: In this paper, the authors estimate the global burden of rheumatoid arthritis (RA), as part of the Global Burden of Disease 2010 study of 291 conditions and how the burden of RA compares with other conditions.
Abstract: Objectives To estimate the global burden of rheumatoid arthritis (RA), as part of the Global Burden of Disease 2010 study of 291 conditions and how the burden of RA compares with other conditions. Methods The optimum case definition of RA for the study was the American College of Rheumatology 1987 criteria. A series of systematic reviews were conducted to gather age-sex-specific epidemiological data for RA prevalence, incidence and mortality. Cause-specific mortality data were also included. Data were entered into DisMod-MR, a tool to pool available data, making use of study-level covariates to adjust for country, region and super-region random effects to estimate prevalence for every country and over time. The epidemiological data, in addition to disability weights, were used to calculate years of life lived with disability (YLDs). YLDs were added to the years of life lost due to premature mortality to estimate the overall burden (disability-adjusted life years (DALYs)) for RA for the years 1990, 2005 and 2010. Results The global prevalence of RA was 0.24% (95% CI 0.23% to 0.25%), with no discernible change from 1990 to 2010. DALYs increased from 3.3 million (M) (95% CI 2.6 M to 4.1 M) in 1990 to 4.8 M (95% CI 3.7 M to 6.1 M) in 2010. This increase was due to a growth in population and increase in aging. Globally, of the 291 conditions studied, RA was ranked as the 42nd highest contributor to global disability, just below malaria and just above iodine deficiency (measured in YLDs). Conclusions RA continues to cause modest global disability, with severe consequences in the individuals affected.
TL;DR: This work reports increased dendritic spine density with reduced developmental spine pruning in layer V pyramidal neurons in postmortem ASD temporal lobe and suggests that mTOR-regulated autophagy is required for developmental spinePruning, and activation of neuronal Autophagy corrects synaptic pathology and social behavior deficits in ASD models with hyperactivated mTOR.
TL;DR: It is suggested that intrinsic timescales reflect areal specialization for task-relevant computations over multiple temporal ranges.
Abstract: Specialization and hierarchy are organizing principles for primate cortex, yet there is little direct evidence for how cortical areas are specialized in the temporal domain. We measured timescales of intrinsic fluctuations in spiking activity across areas and found a hierarchical ordering, with sensory and prefrontal areas exhibiting shorter and longer timescales, respectively. On the basis of our findings, we suggest that intrinsic timescales reflect areal specialization for task-relevant computations over multiple temporal ranges.
TL;DR: Karimi et al. as mentioned in this paper showed that a plasmonic metasurface comprising an array of nano-antennas can couple spin-to-orbital angular momentum at thickness much smaller than the wavelength of the light with an efficiency of around 3%.
Abstract: Visible, circularly polarised light can be transformed into light-carrying orbital angular momentum by a plasmonic metasurface. That is the finding of Ebrahim Karimi and co-workers at the University of Ottawa in Canada and the University of Rochester in the United States. Light with orbital angular momentum (owing to a twisted phase front) is traditionally generated using specially designed optical elements such as spatial light modulator, cylindrical lens mode converters and q-plate. The researchers have now shown that a plasmonic metasurface comprising an array of nano-antennas can couple spin-to-orbital angular momentum at thickness much smaller than the wavelength of the light with an efficiency of around 3%. The conversion takes place due to the birefringence present in the nanostructure array. This approach could yield ultrathin generators of visible light with orbital angular momentum, for potential applications in spectroscopy, imaging, sensing and quantum information.
University of Connecticut1, University of Adelaide2, Winthrop-University Hospital3, University of Texas MD Anderson Cancer Center4, City of Hope National Medical Center5, Virginia Commonwealth University6, University of Tennessee Health Science Center7, National and Kapodistrian University of Athens8, Brigham and Women's Hospital9, University of Rochester10
TL;DR: This study demonstrates optimization of material parameters for 3D printed calcium phosphate scaffolds and enhancement of material properties by volumetric collagen incorporation via inkjet printing.
TL;DR: This guideline update reflects emerging data on duration of tamoxifen treatment and suggests women who have hormone receptor-positive breast cancer and are pre- or perimenopausal and have received 5 years of adjuvant tamoxIFen should be offered 10 years total duration ofTamoxifens.
Abstract: Purpose To update the ASCO clinical practice guideline on adjuvant endocrine therapy on the basis of emerging data on the optimal duration of treatment, particularly adjuvant tamoxifen. Methods ASCO convened the Update Committee and conducted a systematic review of randomized clinical trials from January 2009 to June 2013 and analyzed three historical trials. Guideline recommendations were based on the Update Committee’s review of the evidence. Outcomes of interest included survival, disease recurrence, and adverse events. Results This guideline update reflects emerging data on duration of tamoxifen treatment. There have been five studies of tamoxifen treatment beyond 5 years of therapy. The two largest studies with longest reported follow-up show a breast cancer survival advantage with 10-year durations of tamoxifen use. In addition to modest gains in survival, extended therapy with tamoxifen for 10 years compared with 5 years was associated with lower risks of breast cancer recurrence and contralateral breast cancer.
State University of New York System1, McGill University2, University of Connecticut3, Cornell University4, Umeå University5, Wayne State University6, University of Iowa7, University of Miami8, University of Pennsylvania9, Mayo Clinic10, University of Sydney11, University of Buenos Aires12, University of Chicago13, Shanghai Jiao Tong University14, North-West University15, University of Rochester16, University of Glasgow17, Virginia Commonwealth University18, University of Melbourne19
TL;DR: Clinical practice guidelines for the management of hypertension in the community a statement by the American Society of Hypertension and the International Society of hypertension as mentioned in this paper, which is based on guidelines from the National Institute of Neurological Disorders and Strochastic Hemorrhage.
Abstract: Clinical practice guidelines for the management of hypertension in the community a statement by the American society of hypertension and the International society of hypertension
Northwestern University1, University of British Columbia2, Harvard University3, City of Hope National Medical Center4, Memorial Sloan Kettering Cancer Center5, University of Texas MD Anderson Cancer Center6, University of Michigan7, Roswell Park Cancer Institute8, Fox Chase Cancer Center9, University of Rochester10
TL;DR: The NCCN-IPI is easy to apply and more powerful than the IPI for predicting survival in the rituximab era and demonstrated enhanced discrimination for both low- and high-risk patients.
TL;DR: The authors found that increases in firm CSR ratings are associated with negative future stock returns and declines in firm ROA, suggesting that any benefits to stakeholders from social responsibility come at the direct expense of firm value.
TL;DR: In this brief, a memristor-only logic family, i.e., memristar-aided logic (MAGIC), is presented, and in each MAGIC logic gate, memristors serve as an input with previously stored data, and an additional Memristor serves as an output.
Abstract: Memristors are passive components with a varying resistance that depends on the previous voltage applied across the device. While memristors are naturally used as memory, memristors can also be used for other applications, including logic circuits. In this brief, a memristor-only logic family, i.e., memristor-aided logic (MAGIC), is presented. In each MAGIC logic gate, memristors serve as an input with previously stored data, and an additional memristor serves as an output. The topology of a MAGIC nor gate is similar to the structure of a common memristor-based crossbar memory array. A MAGIC nor gate can therefore be placed within memory, providing opportunities for novel non-von Neumann computer architectures. Other MAGIC gates also exist (e.g., and , or , not , and nand ) and are described in this brief.
TL;DR: Among persons 65 years of age or older, IIV3-HD induced significantly higher antibody responses and provided better protection against laboratory-confirmed influenza illness than did IIV3-SD.
Abstract: BACKGROUND As compared with a standard-dose vaccine, a high-dose, trivalent, inactivated influenza vaccine (IIV3-HD) improves antibody responses to influenza among adults 65 years of age or older. This study evaluated whether IIV3-HD also improves protection against laboratory-confirmed influenza illness. METHODS We conducted a phase IIIb–IV, multicenter, randomized, double-blind, active-controlled trial to compare IIV3-HD (60 μg of hemagglutinin per strain) with standarddose trivalent, inactivated influenza vaccine (IIV3-SD [15 μg of hemagglutinin per strain]) in adults 65 years of age or older. Assessments of relative efficacy, effectiveness, safety (serious adverse events), and immunogenicity (hemagglutinationinhibition [HAI] titers) were performed during the 2011–2012 (year 1) and the 2012–2013 (year 2) northern-hemisphere influenza seasons. RESULTS A total of 31,989 participants were enrolled from 126 research centers in the United States and Canada (15,991 were randomly assigned to receive IIV3-HD, and 15,998 to receive IIV3-SD). In the intention-to-treat analysis, 228 participants in the IIV3HD group (1.4%) and 301 participants in the IIV3-SD group (1.9%) had laboratoryconfirmed influenza caused by any viral type or subtype associated with a protocol-defined influenza-like illness (relative efficacy, 24.2%; 95% confidence interval [CI], 9.7 to 36.5). At least one serious adverse event during the safety surveillance period was reported by 1323 (8.3%) of the participants in the IIV3-HD group, as compared with 1442 (9.0%) of the participants in the IIV3-SD group (relative risk, 0.92; 95% CI, 0.85 to 0.99). After vaccination, HAI titers and seroprotection rates (the percentage of participants with HAI titers ≥1:40) were significantly higher in the IIV3-HD group. CONCLUSIONS Among persons 65 years of age or older, IIV3-HD induced significantly higher antibody responses and provided better protection against laboratory-confirmed influenza illness than did IIV3-SD. (Funded by Sanofi Pasteur; ClinicalTrials.gov number, NCT01427309.)