Showing papers by "Research Triangle Park published in 2011"
TL;DR: The Cochrane Collaboration’s tool for assessing risk of bias aims to make the process clearer and more accurate.
Abstract: Flaws in the design, conduct, analysis, and reporting of randomised trials can cause the effect of an intervention to be underestimated or overestimated. The Cochrane Collaboration’s tool for assessing risk of bias aims to make the process clearer and more accurate
22,227 citations
TL;DR: Low health literacy was consistently associated with more hospitalizations; greater use of emergency care; lower receipt of mammography screening and influenza vaccine; poorer ability to demonstrate taking medications appropriately; poorer able to interpret labels and health messages; and, among elderly persons, poorer overall health status and higher mortality rates.
Abstract: Health literacy has been associated with health-related knowledge and patient comprehension. This systematic review updates a 2004 review and found 96 eligible studies that suggest that low health ...
3,457 citations
United States Department of Agriculture1, French Institute of Health and Medical Research2, Research Triangle Park3, Boston University4, Saint Louis University5, University of Pittsburgh6, University of Erlangen-Nuremberg7, Nestlé8, Uppsala University9, Merck & Co.10, Sapienza University of Rome11, National Institutes of Health12, Novartis13, University of Verona14
TL;DR: Sarcopenia should be considered in all older patients who present with observed declines in physical function, strength, or overall health, and patients who meet these criteria should further undergo body composition assessment using dual energy x-ray absorptiometry with sarcopenia being defined using currently validated definitions.
2,378 citations
TL;DR: Although the checklist should not be interpreted as endorsing any specific methodological approach to conjoint analysis, it can facilitate future training activities and discussions of good research practices for the application of conjoint-analysis methods in health care studies.
1,365 citations
TL;DR: Prader-Willi syndrome is characterized by severe infantile hypotonia with poor suck and failure to thrive; hypogonadism causing genital hypoplasia and pubertal insufficiency; characteristic facial features; early-childhood onset obesity and hyperphagia; developmental delay/mild intellectual disability; short stature; and a distinctive behavioral phenotype.
1,353 citations
TL;DR: It is demonstrated that microbiota have a strong effect on energy homeostasis in the colon compared to other tissues and this tissue specificity is due to colonocytes utilizing bacterially produced butyrate as their primary energy source.
1,328 citations
TL;DR: The utility of these compounds seems to ensure their continued use in one form or another for the foreseeable future, presenting a long-term challenge to scientists, industry leaders, and public health officials worldwide.
Abstract: Interest and concern about polyfluorinated compounds (PFCs), such as perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), and an increasing number of other related compounds is growing as more is learned about these ubiquitous anthropogenic substances. Many of these compounds can be toxic, and they are regularly found in the blood of animals and humans worldwide. A great deal of research has been conducted in this area, but a surprising amount remains unknown about their distribution in the environment and how people ultimately become exposed. The utility of these compounds seems to ensure theircontinueduseinoneformoranotherfortheforeseeablefuture,presentingalong-termchallengetoscientists,industryleaders, and public health officials worldwide.
1,149 citations
TL;DR: The mode of action of arsenic for its disease endpoints is currently under study, and two key areas are the interaction of trivalent arsenicals with sulfur in proteins and the ability of arsenic to generate oxidative stress.
1,007 citations
National Center for Atmospheric Research1, University of Tsukuba2, San Jose State University3, Research Triangle Park4, King's College London5, Arizona State University6, China Meteorological Administration7, Portland State University8, Sun Yat-sen University9, National Natural Science Foundation of China10
TL;DR: The authors developed an integrated urban modelling system coupled to the weather research and forecasting (WRF) model as a community tool to address urban environmental issues, which can capture urban heat islands, complex boundary-layer structures aloft, and urban plume T&D for several major metropolitan regions.
Abstract: To bridge the gaps between traditional mesoscale modelling and microscale modelling, the National Center for Atmospheric Research, in collaboration with other agencies and research groups, has developed an integrated urban modelling system coupled to the weather research and forecasting (WRF) model as a community tool to address urban environmental issues. The core of this WRF/urban modelling system consists of the following: (1) three methods with different degrees of freedom to parameterize urban surface processes, ranging from a simple bulk parameterization to a sophisticated multi-layer urban canopy model with an indoor–outdoor exchange sub-model that directly interacts with the atmospheric boundary layer, (2) coupling to fine-scale computational fluid dynamic Reynolds-averaged Navier–Stokes and Large-Eddy simulation models for transport and dispersion (TD addresses the daunting challenges of initializing the coupled WRF/urban model and of specifying the potentially vast number of parameters required to execute the WRF/urban model; explores the model sensitivity to these urban parameters; and evaluates the ability of WRF/urban to capture urban heat islands, complex boundary-layer structures aloft, and urban plume T&D for several major metropolitan regions. Recent applications of this modelling system illustrate its promising utility, as a regional climate-modelling tool, to investigate impacts of future urbanization on regional meteorological conditions and on air quality under future climate change scenarios. Copyright © 2010 Royal Meteorological Society
867 citations
TL;DR: The GSK solvent selection guide has been further enhanced by as discussed by the authors, with more than doubling the number of solvents in the guide, to a total of 110 from the initial 47.
842 citations
TL;DR: An international DILI Expert Working Group of clinicians and scientists reviewed current DILi terminology and diagnostic criteria so as to develop more uniform criteria that would define and characterize the spectrum of clinical syndromes that constitute D ILI.
Abstract: Drug-induced liver injury (DILI) is the most frequent reason cited for the withdrawal of approved drugs from the market and accounts for up to 15% of the cases of acute liver failure. Investigators around the globe have begun to identify and study patients with DILI; several large registries and tissue banks are being established. In order to gain the maximum scientific benefit from these efforts, the definitions and terminology related to the clinical phenotypes of DILI must be harmonized. For this purpose, an international DILI Expert Working Group of clinicians and scientists reviewed current DILI terminology and diagnostic criteria so as to develop more uniform criteria that would define and characterize the spectrum of clinical syndromes that constitute DILI. Consensus was established with respect to the threshold criteria for definition of a case as being DILI, the pattern of liver injury, causality assessment, severity, and chronicity. Consensus was also reached on approaches to characterizing DILI in the setting of chronic liver diseases, including autoimmune hepatitis (AIH).
TL;DR: The Consort 2010 Statement as mentioned in this paper has been used worldwide to improve the reporting of randomised controlled trials and has been updated by Schulz et al. in 2010, based on new methodological evidence and accumulating experience.
TL;DR: A large maize SNP array taken from more than 800,000 SNPs was established and its use for diversity analysis and high density linkage mapping and independent validation of the B73 sequence assembly was reported.
Abstract: SNP genotyping arrays have been useful for many applications that require a large number of molecular markers such as high-density genetic mapping, genome-wide association studies (GWAS), and genomic selection. We report the establishment of a large maize SNP array and its use for diversity analysis and high density linkage mapping. The markers, taken from more than 800,000 SNPs, were selected to be preferentially located in genes and evenly distributed across the genome. The array was tested with a set of maize germplasm including North American and European inbred lines, parent/F1 combinations, and distantly related teosinte material. A total of 49,585 markers, including 33,417 within 17,520 different genes and 16,168 outside genes, were of good quality for genotyping, with an average failure rate of 4% and rates up to 8% in specific germplasm. To demonstrate this array's use in genetic mapping and for the independent validation of the B73 sequence assembly, two intermated maize recombinant inbred line populations – IBM (B73×Mo17) and LHRF (F2×F252) – were genotyped to establish two high density linkage maps with 20,913 and 14,524 markers respectively. 172 mapped markers were absent in the current B73 assembly and their placement can be used for future improvements of the B73 reference sequence. Colinearity of the genetic and physical maps was mostly conserved with some exceptions that suggest errors in the B73 assembly. Five major regions containing non-colinearities were identified on chromosomes 2, 3, 6, 7 and 9, and are supported by both independent genetic maps. Four additional non-colinear regions were found on the LHRF map only; they may be due to a lower density of IBM markers in those regions or to true structural rearrangements between lines. Given the array's high quality, it will be a valuable resource for maize genetics and many aspects of maize breeding.
Research Triangle Park1, RTI International2, National Institutes of Health3, Johns Hopkins University4, Boston University5, Harvard University6, University of Pittsburgh7, Tufts University8, University of Southern California9, University of Texas MD Anderson Cancer Center10, University of Washington11, Vanderbilt University12
TL;DR: The PhenX Toolkit provides the research community with a core set of high-quality, well-established, low-burden measures intended for use in large-scale genomic studies and includes links to standards and resources in an effort to facilitate data harmonization to legacy data.
Abstract: The potential for genome-wide association studies to relate phenotypes to specific genetic variation is greatly increased when data can be combined or compared across multiple studies. To facilitate replication and validation across studies, RTI International (Research Triangle Park, North Carolina) and the National Human Genome Research Institute (Bethesda, Maryland) are collaborating on the consensus measures for Phenotypes and eXposures (PhenX) project. The goal of PhenX is to identify 15 high-priority, well-established, and broadly applicable measures for each of 21 research domains. PhenX measures are selected by working groups of domain experts using a consensus process that includes input from the scientific community. The selected measures are then made freely available to the scientific community via the PhenX Toolkit. Thus, the PhenX Toolkit provides the research community with a core set of high-quality, well-established, low-burden measures intended for use in large-scale genomic studies. PhenX measures will have the most impact when included at the experimental design stage. The PhenX Toolkit also includes links to standards and resources in an effort to facilitate data harmonization to legacy data. Broad acceptance and use of PhenX measures will promote cross-study comparisons to increase statistical power for identifying and replicating variants associated with complex diseases and with gene-gene and gene-environment interactions.
TL;DR: The American Chemical Society Green Chemistry Institute's Pharmaceutical Roundtable has chosen process mass intensity (PMI) as the key, high-level metric for evaluating and benchmarking progress towards more sustainable manufacturing as mentioned in this paper.
TL;DR: The damage estimates provide a crucial but previously missing component of cost-benefit analyses to evaluate policies and management options intended to reduce species introductions and could be similarly employed to estimate damages in other countries or natural resource sectors.
Abstract: Reliable estimates of the impacts and costs of biological invasions are critical to developing credible management, trade and regulatory policies. Worldwide, forests and urban trees provide important ecosystem services as well as economic and social benefits, but are threatened by non-native insects. More than 450 non-native forest insects are established in the United States but estimates of broad-scale economic impacts associated with these species are largely unavailable. We developed a novel modeling approach that maximizes the use of available data, accounts for multiple sources of uncertainty, and provides cost estimates for three major feeding guilds of non-native forest insects. For each guild, we calculated the economic damages for five cost categories and we estimated the probability of future introductions of damaging pests. We found that costs are largely borne by homeowners and municipal governments. Wood- and phloemboring insects are anticipated to cause the largest economic impacts by annually inducing nearly $1.7 billion in local government expenditures and approximately $830 million in lost residential property values. Given observations of new species, there is a 32% chance that another highly destructive borer species will invade the U.S. in the next 10 years. Our damage estimates provide a crucial but previously missing component of cost-benefit analyses to evaluate policies and management options intended to reduce species introductions. The modeling approach we developed is highly flexible and could be similarly employed to estimate damages in other countries or natural resource sectors.
TL;DR: Seven-transmembrane receptors are pleiotropic with respect to the signaling protein to which they couple in a cell, and many conformations of the receptor can be formed, leading to systems where ligands can stabilize unique conformations that go on to selectively activate signaling pathways.
Abstract: With the emergence of information describing functional selectivity and biased agonists and antagonists has come a lack of confidence in "one size fits all" assays for detection of agonism. Seven-transmembrane receptors are pleiotropic with respect to the signaling protein to which they couple in a cell, and many conformations of the receptor can be formed; this leads to systems where ligands can stabilize unique conformations that go on to selectively activate signaling pathways. Thus, such "biased" ligands can produce cell-specific agonism that may require targeted assays to detect and quantify. It also predicts that ligands can have many different efficacies for the many behaviors that the receptor can exhibit (referred to as "pluridimensional efficacy"), leading to a breakdown in the common classifications of agonist and antagonist. This all poses unique challenges to the pharmacologic nomenclature of drugs, the detection and optimization of new drugs, and the association of phenotypic clinical profiles with pharmacological properties of drugs.
TL;DR: Compared with ABC-3TC, TDF-FTC-treated participants had significantly greater decreases in spine and hip BMD, whereas ATV/r led to more significant losses in spine, but not hip, BMD than EFV.
Abstract: (See the editorial commentary by Yin and Overton, on pages 1705–7.) Background. Long-term effects of abacavir (ABC)–lamivudine (3TC), compared with tenofovir (TDF)–emtricitabine (FTC) with efavirenz (EFV) or atazanavir plus ritonavir (ATV/r), on bone mineral density (BMD) have not been analyzed. Methods. A5224s was a substudy of A5202, in which HIV-infected treatment-naive participants were randomized and blinded to receive ABC-3TC or TDF-FTC with open-label EFV or ATV/r. Primary bone end points included Dual-emission X-ray absorbtiometry (DXA)-measured percent changes in spine and hip BMD at week 96. Primary analyses were intentto-treat. Statistical tests used the factorial design and included linear regression, 2-samplet, log-rank, and Fisher’s exact tests. Results. Two hundred sixty-nine persons randomized to 4 arms of ABC-3TC or TDF-FTC with EFV or ATV/r. At baseline, 85% were male, and 47% were white non-Hispanic; the median HIV-1 RNA load was 4.6 log10 copies/ mL, the median age was 38 years, the median weight was 76 kg, and the median CD4 cell count was 233 cells/lL. At week 96, the mean percentage changes from baseline in spine and hip BMD for ABC-3TC versus TDF-FTC were -1.3% and -3.3% (P 5 .004) and -2.6% and -4.0% (P 5 .024), respectively; and for EFV versus ATV/r were -1.7% and -3.1% (P 5 .035) and -3.1% and -3.4% (P 5 .61), respectively. Bone fracture was observed in 5.6% of participants. The probability of bone fractures and time to first fracture were not different across components. Conclusions. Compared with ABC-3TC, TDF-FTC–treated participants had significantly greater decreases in spine and hip BMD, whereas ATV/r led to more significant losses in spine, but not hip, BMD than EFV. Clinical Trials Registration. NCT00118898.
TL;DR: A clinical problem with use of zirconia-based components is the difficulty in achieving suitable adhesion with intended synthetic substrates or natural tissues, and several technologies are being utilized clinically to address this problem.
TL;DR: The observed increased performance and sex-ratio bias of infected whiteflies are sufficient to explain the spread of Rickettsia across the southwestern United States.
Abstract: Maternally inherited bacterial symbionts of arthropods are common, yet symbiont invasions of host populations have rarely been observed. Here, we show that Rickettsia sp. nr. bellii swept into a population of an invasive agricultural pest, the sweet potato whitefly, Bemisia tabaci, in just 6 years. Compared with uninfected whiteflies, Rickettsia-infected whiteflies produced more offspring, had higher survival to adulthood, developed faster, and produced a higher proportion of daughters. The symbiont thus functions as both mutualist and reproductive manipulator. The observed increased performance and sex-ratio bias of infected whiteflies are sufficient to explain the spread of Rickettsia across the southwestern United States. Symbiont invasions such as this represent a sudden evolutionary shift for the host, with potentially large impacts on its ecology and invasiveness.
United States Forest Service1, Cornell University2, Syracuse University3, University of California, Riverside4, United States Geological Survey5, University of Colorado Boulder6, United States Environmental Protection Agency7, Marshall University8, Research Triangle Park9, Arizona State University10, University of Michigan11, Institute of Ecosystem Studies12
TL;DR: In this article, the authors synthesize current research relating atmospheric N deposition to effects on terrestrial and freshwater ecosystems in the United States, and to estimate associated empirical N critical loads, defined as the input of a pollutant below which no detrimental ecological effects occur over the long-term according to present knowledge.
Abstract: Human activity in the last century has led to a significant increase in nitrogen (N) emissions and atmospheric deposition. This N deposition has reached a level that has caused or is likely to cause alterations to the structure and function of many ecosystems across the United States. One approach for quantifying the deposition of pollution that would be harmful to ecosystems is the determination of critical loads. A critical load is defined as the input of a pollutant below which no detrimental ecological effects occur over the long-term according to present knowledge. The objectives of this project were to synthesize current research relating atmospheric N deposition to effects on terrestrial and freshwater ecosystems in the United States, and to estimate associated empirical N critical loads. The receptors considered included freshwater diatoms, mycorrhizal fungi, lichens, bryophytes, herbaceous plants, shrubs, and trees. Ecosystem impacts included: (1) biogeochemical responses and (2) individual species, population, and community responses. Biogeochemical responses included increased N mineralization and nitrification (and N availability for plant and microbial uptake), increased gaseous N losses (ammonia volatilization, nitric and nitrous oxide from nitrification and denitrification), and increased N leaching. Individual species, population, and community responses included increased tissue N, physiological and nutrient imbalances, increased growth, altered root : shoot ratios, increased susceptibility to secondary stresses, altered fire regime, shifts in competitive interactions and community composition, changes in species richness and other measures of biodiversity, and increases in invasive species.
TL;DR: Multiple interventions show promise for mitigating the effects of low health literacy and could be considered for use in clinical practice.
Abstract: The US Department of Health and Human Services recently called for action on health literacy An important first step is defining the current state of the literature about interventions designed to mitigate the effects of low health literacy We performed an updated systematic review examining the effects of interventions that authors reported were specifically designed to mitigate the effects of low health literacy We searched MEDLINE®, The Cumulative Index to Nursing and Allied Health Literature (CINAHL), PsycINFO, Educational Resources Information Center (ERIC), and the Cochrane Library databases (2003 forward for health literacy; 1966 forward for numeracy) Two reviewers independently reviewed titles, abstracts, and full-text articles for inclusion and included studies that examined outcomes by health literacy level and met other pre-specified criteria One reviewer abstracted article information into evidence tables; a second checked accuracy Two reviewers independently rated study quality using predefined criteria Among 38 included studies, we found multiple discrete design features that improved comprehension in one or a few studies (eg, presenting essential information by itself or first, presenting information so that the higher number is better, adding icon arrays to numerical information, adding video to verbal narratives) In a few studies, we also found consistent, direct, fair or good-quality evidence that intensive self-management interventions reduced emergency department visits and hospitalizations; and intensive self- and disease-management interventions reduced disease severity Evidence for the effects of interventions on other outcomes was either limited or mixed Multiple interventions show promise for mitigating the effects of low health literacy and could be considered for use in clinical practice
TL;DR: Findings demonstrate that S/GSK1349572 would be classified as a next-generation drug in the integrase inhibitor class, with a resistance profile markedly different from that of first-generation integrase inhibitors.
Abstract: S/GSK1349572 is a next-generation HIV integrase (IN) inhibitor designed to deliver potent antiviral activity with a low-milligram once-daily dose requiring no pharmacokinetic (PK) booster. In addition, S/GSK1349572 demonstrates activity against clinically relevant IN mutant viruses and has potential for a high genetic barrier to resistance. S/GSK1349572 is a two-metal-binding HIV integrase strand transfer inhibitor whose mechanism of action was established through in vitro integrase enzyme assays, resistance passage experiments, activity against viral strains resistant to other classes of anti-HIV agents, and mechanistic cellular assays. In a variety of cellular antiviral assays, S/GSK1349572 inhibited HIV replication with low-nanomolar or subnanomolar potency and with a selectivity index of 9,400. The protein-adjusted half-maximal effective concentration (PA-EC(50)) extrapolated to 100% human serum was 38 nM. When virus was passaged in the presence of S/GSK1349572, highly resistant mutants were not selected, but mutations that effected a low fold change (FC) in the EC(50) (up to 4.1 fold) were identified in the vicinity of the integrase active site. S/GSK1349572 demonstrated activity against site-directed molecular clones containing the raltegravir-resistant signature mutations Y143R, Q148K, N155H, and G140S/Q148H (FCs, 1.4, 1.1, 1.2, and 2.6, respectively), while these mutants led to a high FC in the EC(50) of raltegravir (11- to >130-fold). Either additive or synergistic effects were observed when S/GSK1349572 was tested in combination with representative approved antiretroviral agents; no antagonistic effects were seen. These findings demonstrate that S/GSK1349572 would be classified as a next-generation drug in the integrase inhibitor class, with a resistance profile markedly different from that of first-generation integrase inhibitors.
TL;DR: The American Chemical Society (ACS) Green Chemistry Institute (GCI) and global pharmaceutical companies established the ACS GCI Pharmaceutical Roundtable to encourage the integration of green chemistry and engineering into the pharmaceutical industry as mentioned in this paper.
TL;DR: The origin and molecular properties of the GR isoforms and their contribution to the sensitivity and specificity of the glucocorticoid response are discussed.
TL;DR: Mepolizumab, an antibody against IL-5, reduces esophageal eosinophilic inflammation in these patients and an analysis to evaluate predictors of response associated a higher mean baseline esophAGEal intraepithelial eOSinophil count with a greater reduction in mean count.
TL;DR: Most protein research focuses on those known before the human genome was mapped, but work on the slew discovered since, urge Aled M. Edwards and his colleagues.
Abstract: Most protein research focuses on those known before the human genome was mapped. Work on the slew discovered since, urge Aled M. Edwards and his colleagues.
TL;DR: Current clinical trial data indicate that fat-free mass parameters are responsive to physical activity/nutritional treatment modalities over short time periods, but pharmacological trials of sarcopenia have yet to show significant efficacy.
Abstract: Sarcopenia is the age-related involuntary loss of skeletal muscle mass and functionality that can lead to the development of disability, frailty and increased health care costs. The development of interventions aimed at preventing and/or treating sarcopenia is complex, requiring the adoption of assumptions and standards that are not well established scientifically or clinically. A number of investigators and clinicians (both from academia and industry) met in Rome (Italy) in 2009 to develop a consensus definition of sarcopenia. Subsequently, in Albuquerque (New Mexico, USA) in 2010, the same group met again to consider the complex issues necessary for designing Phase II clinical trials for sarcopenia. Current clinical trial data indicate that fat-free mass (FFM) parameters are responsive to physical activity/nutritional treatment modalities over short time periods, but pharmacological trials of sarcopenia have yet to show significant efficacy. In order to conduct a clinical trial within a reasonable time frame, groups that model or display accelerated aging and loss of FFM are necessary. Few studies have used acceptable designs for testing treatment effects, sample sizes or primary outcomes that could provide interpretable findings or effects across studies. Dual energy x-ray absorptiometry (DXA) is the measure of choice for assessing FFM, but sufficient time is needed for changes to be detected accurately and reliably. A tool set that would allow clinical, basic and epidemiological research on sarcopenia to advance rapidly toward diagnosis and treatment phases should be those reflecting function and strength.
TL;DR: Nlrx1(-/-) mice exhibited increased expression of antiviral signaling molecules IFN-β, STAT2, OAS1, and IL-6 after influenza virus infection and an inhibitory function is identified for NLRX1 during LPS activation of macrophages where the MAVS-RIG-I pathway was not involved.
TL;DR: This is the first study to demonstrate both respiratory and cardiac effects after brief exposure to peat wildfire smoke in rural counties with sparse air-quality monitoring.
Abstract: Background: In June 2008, burning peat deposits produced haze and air pollution far in excess of National Ambient Air Quality Standards, encroaching on rural communities of eastern North Carolina. Although the association of mortality and morbidity with exposure to urban air pollution is well established, the health effects associated with exposure to wildfire emissions are less well understood.
Objective: We investigated the effects of exposure on cardiorespiratory outcomes in the population affected by the fire.
Methods: We performed a population-based study using emergency department (ED) visits reported through the syndromic surveillance program NC DETECT (North Carolina Disease Event Tracking and Epidemiologic Collection Tool). We used aerosol optical depth measured by a satellite to determine a high-exposure window and distinguish counties most impacted by the dense smoke plume from surrounding referent counties. Poisson log-linear regression with a 5-day distributed lag was used to estimate changes in the cumulative relative risk (RR).
Results: In the exposed counties, significant increases in cumulative RR for asthma [1.65 (95% confidence interval, 1.25–2.1)], chronic obstructive pulmonary disease [1.73 (1.06–2.83)], and pneumonia and acute bronchitis [1.59 (1.07–2.34)] were observed. ED visits associated with cardiopulmonary symptoms [1.23 (1.06–1.43)] and heart failure [1.37 (1.01–1.85)] were also significantly increased.
Conclusions: Satellite data and syndromic surveillance were combined to assess the health impacts of wildfire smoke in rural counties with sparse air-quality monitoring. This is the first study to demonstrate both respiratory and cardiac effects after brief exposure to peat wildfire smoke.