Showing papers by "University of North Carolina at Chapel Hill published in 2008"
Roger E. McLendon1, Allan H. Friedman1, Darrell D. Bigner1, Erwin G. Van Meir2 +230 more•Institutions (23)
TL;DR: The interim integrative analysis of DNA copy number, gene expression and DNA methylation aberrations in 206 glioblastomas reveals a link between MGMT promoter methylation and a hypermutator phenotype consequent to mismatch repair deficiency in treated gliobeasts, demonstrating that it can rapidly expand knowledge of the molecular basis of cancer.
Abstract: Human cancer cells typically harbour multiple chromosomal aberrations, nucleotide substitutions and epigenetic modifications that drive malignant transformation. The Cancer Genome Atlas ( TCGA) pilot project aims to assess the value of large- scale multi- dimensional analysis of these molecular characteristics in human cancer and to provide the data rapidly to the research community. Here we report the interim integrative analysis of DNA copy number, gene expression and DNA methylation aberrations in 206 glioblastomas - the most common type of primary adult brain cancer - and nucleotide sequence aberrations in 91 of the 206 glioblastomas. This analysis provides new insights into the roles of ERBB2, NF1 and TP53, uncovers frequent mutations of the phosphatidylinositol- 3- OH kinase regulatory subunit gene PIK3R1, and provides a network view of the pathways altered in the development of glioblastoma. Furthermore, integration of mutation, DNA methylation and clinical treatment data reveals a link between MGMT promoter methylation and a hypermutator phenotype consequent to mismatch repair deficiency in treated glioblastomas, an observation with potential clinical implications. Together, these findings establish the feasibility and power of TCGA, demonstrating that it can rapidly expand knowledge of the molecular basis of cancer.
6,761 citations
TL;DR: In this paper, the authors investigated whether intensive therapy to target normal glycated hemoglobin levels would reduce cardiovascular events in patients with type 2 diabetes who had either established cardiovascular disease or additional cardiovascular risk factors.
Abstract: BACKGROUND Epidemiologic studies have shown a relationship between glycated hemoglobin levels and cardiovascular events in patients with type 2 diabetes. We investigated whether intensive therapy to target normal glycated hemoglobin levels would reduce cardiovascular events in patients with type 2 diabetes who had either established cardiovascular disease or additional cardiovascular risk factors. METHODS In this randomized study, 10,251 patients (mean age, 62.2 years) with a median glycated hemoglobin level of 8.1% were assigned to receive intensive therapy (targeting a glycated hemoglobin level below 6.0%) or standard therapy (targeting a level from 7.0 to 7.9%). Of these patients, 38% were women, and 35% had had a previous cardiovascular event. The primary outcome was a composite of nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes. The finding of higher mortality in the intensive-therapy group led to a discontinuation of intensive therapy after a mean of 3.5 years of follow-up. RESULTS At 1 year, stable median glycated hemoglobin levels of 6.4% and 7.5% were achieved in the intensive-therapy group and the standard-therapy group, respectively. During follow-up, the primary outcome occurred in 352 patients in the intensive-therapy group, as compared with 371 in the standard-therapy group (hazard ratio, 0.90; 95% confidence interval [CI], 0.78 to 1.04; P=0.16). At the same time, 257 patients in the intensive-therapy group died, as compared with 203 patients in the standard-therapy group (hazard ratio, 1.22; 95% CI, 1.01 to 1.46; P=0.04). Hypoglycemia requiring assistance and weight gain of more than 10 kg were more frequent in the intensive-therapy group (P<0.001). CONCLUSIONS As compared with standard therapy, the use of intensive therapy to target normal glycated hemoglobin levels for 3.5 years increased mortality and did not significantly reduce major cardiovascular events. These findings identify a previously unrecognized harm of intensive glucose lowering in high-risk patients with type 2 diabetes. (ClinicalTrials.gov number, NCT00000620.)
6,621 citations
State Street Corporation1, University of California, Santa Barbara2, University of Hawaii at Manoa3, Stanford University4, Arizona State University5, Wildlife Conservation Society6, University of North Carolina at Chapel Hill7, National Oceanic and Atmospheric Administration8, Environmental Defense Fund9, Ocean Conservancy10, The Nature Conservancy11, University of Maine12, University of British Columbia13
TL;DR: This article developed an ecosystem-specific, multiscale spatial model to synthesize 17 global data sets of anthropogenic drivers of ecological change for 20 marine ecosystems and found that no area is unaffected by human influence and that a large fraction (41%) is strongly affected by multiple drivers.
Abstract: The management and conservation of the world's oceans require synthesis of spatial data on the distribution and intensity of human activities and the overlap of their impacts on marine ecosystems. We developed an ecosystem-specific, multiscale spatial model to synthesize 17 global data sets of anthropogenic drivers of ecological change for 20 marine ecosystems. Our analysis indicates that no area is unaffected by human influence and that a large fraction (41%) is strongly affected by multiple drivers. However, large areas of relatively little human impact remain, particularly near the poles. The analytical process and resulting maps provide flexible tools for regional and global efforts to allocate conservation resources; to implement ecosystem-based management; and to inform marine spatial planning, education, and basic research.
5,365 citations
TL;DR: This report provides the best available prevalence estimates for the US for osteoarthritis, polymyalgia rheumatica, gout, fibromyalgia, and carpal tunnel syndrome as well as the symptoms of neck and back pain.
Abstract: Objective
To provide a single source for the best available estimates of the US prevalence of and number of individuals affected by osteoarthritis, polymyalgia rheumatica and giant cell arteritis, gout, fibromyalgia, and carpal tunnel syndrome, as well as the symptoms of neck and back pain. A companion article (part I) addresses additional conditions.
4,813 citations
Federal University of Bahia1, McMaster University2, University of Amsterdam3, National Institutes of Health4, Charité5, Catholic University of Cordoba6, University of Genoa7, Radboud University Nijmegen8, Transilvania University of Brașov9, Ghent University10, University of Tennessee Health Science Center11, University of Naples Federico II12, Laval University13, Universidade Federal de Minas Gerais14, University of Oslo15, University of Manchester16, Aarhus University17, Imperial College London18, Erasmus University Rotterdam19, George Washington University20, Seoul National University21, Medical University of Łódź22, Hai phong University Of Medicine and Pharmacy23, Université de Montréal24, Guangzhou Medical University25, University of South Florida26, University of California, San Diego27, University of California28, University of Chicago29, Monash University30, Teikyo University31, National and Kapodistrian University of Athens32, Nippon Medical School33, Sofia Medical University34, Leiden University35, Leiden University Medical Center36, University College London37, University of Manitoba38, University of Helsinki39, Finnish Institute of Occupational Health40, National University of Singapore41, Karolinska Institutet42, University of Minnesota43, Celal Bayar University44, University of Cape Town45, Pierre-and-Marie-Curie University46, Tunis University47, University of Ghana48, University of Wisconsin-Madison49, University of British Columbia50, Georgia Regents University51, Vilnius University52, University of Washington53, University of Dundee54, University of Poitiers55, University of Mississippi56, Federal University of São Paulo57, German Red Cross58, Jagiellonian University Medical College59, Chiba University60, American Pharmacists Association61, University of Aberdeen62, University of Nevada, Reno63, University of North Carolina at Chapel Hill64
TL;DR: The ARIA guidelines for the management of allergic rhinitis and asthma are similar in both the 1999 ARIA workshop report and the 2008 Update as discussed by the authors, but the GRADE approach is not yet available.
Abstract: Allergic rhinitis is a symptomatic disorder of the nose induced after allergen exposure by an IgE-mediated inflammation of the membranes lining the nose. It is a global health problem that causes major illness and disability worldwide. Over 600 million patients from all countries, all ethnic groups and of all ages suffer from allergic rhinitis. It affects social life, sleep, school and work and its economic impact is substantial. Risk factors for allergic rhinitis are well identified. Indoor and outdoor allergens as well as occupational agents cause rhinitis and other allergic diseases. The role of indoor and outdoor pollution is probably very important, but has yet to be fully understood both for the occurrence of the disease and its manifestations.
In 1999, during the Allergic Rhinitis and its Impact on Asthma (ARIA) WHO workshop, the expert panel proposed a new classification for allergic rhinitis which was subdivided into 'intermittent' or 'persistent' disease.
This classification is now validated. The diagnosis of allergic rhinitis is often quite easy, but in some cases it may cause problems and many patients are still under-diagnosed, often because they do not perceive the symptoms of rhinitis as a disease impairing their social life, school and work.
The management of allergic rhinitis is well established and the ARIA expert panel based its recommendations on evidence using an extensive review of the literature available up to December 1999. The statements of evidence for the development of these guidelines followed WHO rules and were based on those of Shekelle et al. A large number of papers have been published since 2000 and are extensively reviewed in the 2008 Update using the same evidence-based system. Recommendations for the management of allergic rhinitis are similar in both the ARIA workshop report and the 2008 Update. In the future, the GRADE approach will be used, but is not yet available.
Another important aspect of the ARIA guidelines was to consider co-morbidities. Both allergic rhinitis and asthma are systemic inflammatory conditions and often co-exist in the same patients. In the 2008 Update, these links have been confirmed.
The ARIA document is not intended to be a standard-of-care document for individual countries. It is provided as a basis for physicians, health care professionals and organizations involved in the treatment of allergic rhinitis and asthma in various countries to facilitate the development of relevant local standard-of-care documents for patients.
3,769 citations
TL;DR: It is concluded that damage suffered in early life leads to permanent impairment, and might also affect future generations, as undernutrition is associated with lower human capital and its prevention will probably bring about important health, educational, and economic benefits.
3,341 citations
01 Jan 2008
3,298 citations
TL;DR: These findings suggest that HeLa cells readily internalize nonspherical particles with dimensions as large as 3 μm by using several different mechanisms of endocytosis, and it was found that rod-like particles enjoy an appreciable advantage when it comes to internalization rates.
Abstract: The interaction of particles with cells is known to be strongly influenced by particle size, but little is known about the interdependent role that size, shape, and surface chemistry have on cellular internalization and intracellular trafficking. We report on the internalization of specially designed, monodisperse hydrogel particles into HeLa cells as a function of size, shape, and surface charge. We employ a top-down particle fabrication technique called PRINT that is able to generate uniform populations of organic micro- and nanoparticles with complete control of size, shape, and surface chemistry. Evidence of particle internalization was obtained by using conventional biological techniques and transmission electron microscopy. These findings suggest that HeLa cells readily internalize nonspherical particles with dimensions as large as 3 μm by using several different mechanisms of endocytosis. Moreover, it was found that rod-like particles enjoy an appreciable advantage when it comes to internalization rates, reminiscent of the advantage that many rod-like bacteria have for internalization in nonphagocytic cells.
2,617 citations
TL;DR: A facile and scalable preparation of aqueous solutions of isolated, sparingly sulfonated graphene is reported, and NMR and FTIR spectra indicate that the bulk of the oxygen-containing functional groups was removed from graphene oxide.
Abstract: A facile and scalable preparation of aqueous solutions of isolated, sparingly sulfonated graphene is reported. 13C NMR and FTIR spectra indicate that the bulk of the oxygen-containing functional groups was removed from graphene oxide. The electrical conductivity of thin evaporated films of graphene (1250 S/m) relative to similarly prepared graphite (6120 S/m) implies that an extended conjugated sp2 network is restored in the water soluble graphene.
2,577 citations
Harvard University1, University of California, Santa Cruz2, University of British Columbia3, University of Oxford4, University of Washington5, University of California, San Diego6, Oak Ridge National Laboratory7, Arizona State University8, Brown University9, Case Western Reserve University10, Boston University11, University of North Carolina at Chapel Hill12, North Carolina State University13, National Institutes of Health14
TL;DR: A nanopore-based device provides single-molecule detection and analytical capabilities that are achieved by electrophoretically driving molecules in solution through a nano-scale pore, a unique analytical capability that makes inexpensive, rapid DNA sequencing a possibility.
Abstract: A nanopore-based device provides single-molecule detection and analytical capabilities that are achieved by electrophoretically driving molecules in solution through a nano-scale pore. The nanopore provides a highly confined space within which single nucleic acid polymers can be analyzed at high throughput by one of a variety of means, and the perfect processivity that can be enforced in a narrow pore ensures that the native order of the nucleobases in a polynucleotide is reflected in the sequence of signals that is detected. Kilobase length polymers (single-stranded genomic DNA or RNA) or small molecules (e.g., nucleosides) can be identified and characterized without amplification or labeling, a unique analytical capability that makes inexpensive, rapid DNA sequencing a possibility. Further research and development to overcome current challenges to nanopore identification of each successive nucleotide in a DNA strand offers the prospect of 'third generation' instruments that will sequence a diploid mammalian genome for ∼$1,000 in ∼24 h.
2,512 citations
University of Zurich1, Icahn School of Medicine at Mount Sinai2, University of North Carolina at Chapel Hill3, Monash University4, University Hospital of Lausanne5, University of California, San Diego6, Radboud University Nijmegen7, University of Buenos Aires8, Cornell University9, University of Amsterdam10, University of Alabama at Birmingham11, Johns Hopkins University School of Medicine12, University of California, San Francisco13
TL;DR: This report provides guidelines for when to initiate antiretroviral therapy, selection of appropriate initial regimens, patient monitoring, when to change therapy, and what regimens to use when changing.
Abstract: Context New trial data and drug regimens that have become available in the last 2 years warrant an update to guidelines for antiretroviral therapy (ART) in human immunodeficiency virus (HIV)–infected adults in resource-rich settings. Objective To provide current recommendations for the treatment of adult HIV infection with ART and use of laboratory-monitoring tools. Guidelines include when to start therapy and with what drugs, monitoring for response and toxic effects, special considerations in therapy, and managing antiretroviral failure. Data Sources, Study Selection, and Data Extraction Data that had been published or presented in abstract form at scientific conferences in the past 2 years were systematically searched and reviewed by an International Antiviral Society–USA panel. The panel reviewed available evidence and formed recommendations by full panel consensus. Data Synthesis Treatment is recommended for all adults with HIV infection; the strength of the recommendation and the quality of the evidence increase with decreasing CD4 cell count and the presence of certain concurrent conditions. Recommended initial regimens include 2 nucleoside reverse transcriptase inhibitors (tenofovir/emtricitabine or abacavir/lamivudine) plus a nonnucleoside reverse transcriptase inhibitor (efavirenz), a ritonavir-boosted protease inhibitor (atazanavir or darunavir), or an integrase strand transfer inhibitor (raltegravir). Alternatives in each class are recommended for patients with or at risk of certain concurrent conditions. CD4 cell count and HIV-1 RNA level should be monitored, as should engagement in care, ART adherence, HIV drug resistance, and quality-of-care indicators. Reasons for regimen switching include virologic, immunologic, or clinical failure and drug toxicity or intolerance. Confirmed treatment failure should be addressed promptly and multiple factors considered. Conclusion New recommendations for HIV patient care include offering ART to all patients regardless of CD4 cell count, changes in therapeutic options, and modifications in the timing and choice of ART in the setting of opportunistic illnesses such as cryptococcal disease and tuberculosis.
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TL;DR: A link exists between global warming and the worldwide proliferation of harmful cyanobacterial blooms as discussed by the authors, and it has been shown that global warming can be linked with the proliferation of these blooms.
Abstract: A link exists between global warming and the worldwide proliferation of harmful cyanobacterial blooms.
TL;DR: It is suggested that the two accelerometers can be used to distinguish differing levels of physical activity intensity as well as inactivity among children 5 to 8 years of age.
Abstract: A calibration study was conducted to determine the threshold counts for two commonly used accelerometers, the ActiGraph and the Actical, to classify activities by intensity in children 5 to 8 years of age. Thirty-three children wore both accelerometers and a COSMED portable metabolic system during 15 min of rest and then performed up to nine different activities for 7 min each, on two separate days in the laboratory. Oxygen consumption was measured on a breath-by-breath basis, and accelerometer data were collected in 15-s epochs. Using receiver operating characteristic curve (ROC) analysis, cutpoints that maximised both sensitivity and specificity were determined for sedentary, moderate and vigorous activities. For both accelerometers, discrimination of sedentary behaviour was almost perfect, with the area under the ROC curve at or exceeding 0.98. For both the ActiGraph and Actical, the discrimination of moderate (0.85 and 0.86, respectively) and vigorous activity (0.83 and 0.86, respectively) was acceptable, but not as precise as for sedentary behaviour. This calibration study, using indirect calorimetry, suggests that the two accelerometers can be used to distinguish differing levels of physical activity intensity as well as inactivity among children 5 to 8 years of age.
TL;DR: The average bias associated with defects in the conduct of randomised trials varies with the type of outcome, andSystematic reviewers should routinely assess the risk of bias in the results of trials, and should report meta-analyses restricted to trials at low risk of biases.
Abstract: OBJECTIVE: To examine whether the association of inadequate or unclear allocation concealment and lack of blinding with biased estimates of intervention effects varies with the nature of the intervention or outcome. DESIGN: Combined analysis of data from three meta-epidemiological studies based on collections of meta-analyses. DATA SOURCES: 146 meta-analyses including 1346 trials examining a wide range of interventions and outcomes. MAIN OUTCOME MEASURES: Ratios of odds ratios quantifying the degree of bias associated with inadequate or unclear allocation concealment, and lack of blinding, for trials with different types of intervention and outcome. A ratio of odds ratios <1 implies that inadequately concealed or non-blinded trials exaggerate intervention effect estimates. RESULTS: In trials with subjective outcomes effect estimates were exaggerated when there was inadequate or unclear allocation concealment (ratio of odds ratios 0.69 (95% CI 0.59 to 0.82)) or lack of blinding (0.75 (0.61 to 0.93)). In contrast, there was little evidence of bias in trials with objective outcomes: ratios of odds ratios 0.91 (0.80 to 1.03) for inadequate or unclear allocation concealment and 1.01 (0.92 to 1.10) for lack of blinding. There was little evidence for a difference between trials of drug and non-drug interventions. Except for trials with all cause mortality as the outcome, the magnitude of bias varied between meta-analyses. CONCLUSIONS: The average bias associated with defects in the conduct of randomised trials varies with the type of outcome. Systematic reviewers should routinely assess the risk of bias in the results of trials, and should report meta-analyses restricted to trials at low risk of bias either as the primary analysis or in conjunction with less restrictive analyses.
TL;DR: The authors examined whether application of International Accounting Standards (IAS) is associated with higher accounting quality and found that firms applying IAS from 21 countries generally evidence less earnings management, more timely loss recognition, and more value relevance of accounting amounts than do matched sample firms applying non-U.S. domestic standards.
Abstract: We examine whether application of International Accounting Standards (IAS) is associated with higher accounting quality. The application of IAS reflects combined effects of features of the financial reporting system, including standards, their interpretation, enforcement, and litigation. We find that firms applying IAS from 21 countries generally evidence less earnings management, more timely loss recognition, and more value relevance of accounting amounts than do matched sample firms applying non-U.S. domestic standards. Differences in accounting quality between the two groups of firms in the period before the IAS firms adopt IAS do not account for the postadoption differences. Firms applying IAS generally evidence an improvement in accounting quality between the pre- and postadoption periods. Although we cannot be sure our findings are attributable to the change in the financial reporting system rather than to changes in firms' incentives and the economic environment, we include research design features to mitigate effects of both.
TL;DR: Discussion centers on how positive emotions are the mechanism of change for the type of mind-training practice studied here and how loving-kindness meditation is an intervention strategy that produces positive emotions in a way that outpaces the hedonic treadmill effect.
Abstract: B. L. Fredrickson's (1998, 2001) broaden-and-build theory of positive emotions asserts that people's daily experiences of positive emotions compound over time to build a variety of consequential personal resources. The authors tested this build hypothesis in a field experiment with working adults (n = 139), half of whom were randomly-assigned to begin a practice of loving-kindness meditation. Results showed that this meditation practice produced increases over time in daily experiences of positive emotions, which, in turn, produced increases in a wide range of personal resources (e.g., increased mindfulness, purpose in life, social support, decreased illness symptoms). In turn, these increments in personal resources predicted increased life satisfaction and reduced depressive symptoms. Discussion centers on how positive emotions are the mechanism of change for the type of mind-training practice studied here and how loving-kindness meditation is an intervention strategy that produces positive emotions in a way that outpaces the hedonic treadmill effect.
Los Alamos National Laboratory1, University of Massachusetts Amherst2, University of North Carolina at Chapel Hill3, Duke University4, University of Maryland, College Park5, University of California, San Francisco6, University of Rochester7, University of Cape Town8, Santa Fe Institute9, University of Alabama at Birmingham10
TL;DR: A mathematical model of random viral evolution and phylogenetic tree construction is developed and used to analyze 3,449 complete env sequences derived by single genome amplification from 102 subjects with acute HIV-1 (clade B) infection, suggesting a finite window of potential vulnerability of HIV- 1 to vaccine-elicited immune responses, although phenotypic properties of transmitted Envs pose a formidable defense.
Abstract: The precise identification of the HIV-1 envelope glycoprotein (Env) responsible for productive clinical infection could be instrumental in elucidating the molecular basis of HIV-1 transmission and in designing effective vaccines. Here, we developed a mathematical model of random viral evolution and, together with phylogenetic tree construction, used it to analyze 3,449 complete env sequences derived by single genome amplification from 102 subjects with acute HIV-1 (clade B) infection. Viral env genes evolving from individual transmitted or founder viruses generally exhibited a Poisson distribution of mutations and star-like phylogeny, which coalesced to an inferred consensus sequence at or near the estimated time of virus transmission. Overall, 78 of 102 subjects had evidence of productive clinical infection by a single virus, and 24 others had evidence of productive clinical infection by a minimum of two to five viruses. Phenotypic analysis of transmitted or early founder Envs revealed a consistent pattern of CCR5 dependence, masking of coreceptor binding regions, and equivalent or modestly enhanced resistance to the fusion inhibitor T1249 and broadly neutralizing antibodies compared with Envs from chronically infected subjects. Low multiplicity infection and limited viral evolution preceding peak viremia suggest a finite window of potential vulnerability of HIV-1 to vaccine-elicited immune responses, although phenotypic properties of transmitted Envs pose a formidable defense.
Wellcome Trust Centre for Human Genetics1, University of Michigan2, University of Oxford3, Brigham and Women's Hospital4, Harvard University5, Massachusetts Institute of Technology6, Lund University7, Steno Diabetes Center8, University of Southern California9, National Institutes of Health10, Health Science University11, Novartis12, Ninewells Hospital13, University of Exeter14, University of Düsseldorf15, Queen Mary University of London16, Glostrup Hospital17, deCODE genetics18, University of Eastern Finland19, University of Cambridge20, Aarhus University21, University of North Carolina at Chapel Hill22, Norwegian University of Science and Technology23, Wellcome Trust Sanger Institute24, University of Bristol25, University of Helsinki26, Newcastle University27
TL;DR: The results illustrate the value of large discovery and follow-up samples for gaining further insights into the inherited basis of T2D, and detect at least six previously unknown loci with robust evidence for association.
Abstract: Genome-wide association (GWA) studies have identified multiple loci at which common variants modestly but reproducibly influence risk of type 2 diabetes (T2D). Established associations to common and rare variants explain only a small proportion of the heritability of T2D. As previously published analyses had limited power to identify variants with modest effects, we carried out meta-analysis of three T2D GWA scans comprising 10,128 individuals of European descent and approximately 2.2 million SNPs (directly genotyped and imputed), followed by replication testing in an independent sample with an effective sample size of up to 53,975. We detected at least six previously unknown loci with robust evidence for association, including the JAZF1 (P = 5.0 x 10(-14)), CDC123-CAMK1D (P = 1.2 x 10(-10)), TSPAN8-LGR5 (P = 1.1 x 10(-9)), THADA (P = 1.1 x 10(-9)), ADAMTS9 (P = 1.2 x 10(-8)) and NOTCH2 (P = 4.1 x 10(-8)) gene regions. Our results illustrate the value of large discovery and follow-up samples for gaining further insights into the inherited basis of T2D.
TL;DR: The results suggest that multiple, individually rare mutations altering genes in neurodevelopmental pathways contribute to schizophrenia, and disrupted genes disproportionately from signaling networks controlling neurodevelopment, including neuregulin and glutamate pathways.
Abstract: Schizophrenia is a devastating neurodevelopmental disorder whose genetic influences remain elusive. We hypothesize that individually rare structural variants contribute to the illness. Microdeletions and microduplications >100 kilobases were identified by microarray comparative genomic hybridization of genomic DNA from 150 individuals with schizophrenia and 268 ancestry-matched controls. All variants were validated by high-resolution platforms. Novel deletions and duplications of genes were present in 5% of controls versus 15% of cases and 20% of young-onset cases, both highly significant differences. The association was independently replicated in patients with childhood-onset schizophrenia as compared with their parents. Mutations in cases disrupted genes disproportionately from signaling networks controlling neurodevelopment, including neuregulin and glutamate pathways. These results suggest that multiple, individually rare mutations altering genes in neurodevelopmental pathways contribute to schizophrenia.
TL;DR: Altered microbial composition and function in inflammatory bowel diseases result in increased immune stimulation, epithelial dysfunction, or enhanced mucosal permeability, which should lead to selective targeted interventions that correct underlying abnormalities and induce sustained and predictable therapeutic responses.
TL;DR: Analysis of prekindergarten programs in 11 states suggests that policies, program development, and professional development efforts that improve teacher-child interactions can facilitate children's school readiness.
Abstract: This study examined development of academic, language, and social skills among 4-year-olds in publicly supported prekindergarten (pre-K) programs in relation to 3 methods of measuring pre-K quality, which are as follows: (a) adherence to 9 standards of quality related to program infrastructure and design, (b) observations of the overall quality of classroom environments, and (c) observations of teachers’ emotional and instructional interactions with children in classrooms. Participants were 2,439 children enrolled in 671 pre-K classrooms in 11 states. Adjusting for prior skill levels, child and family characteristics, program characteristics, and state, teachers’ instructional interactions predicted academic and language skills and teachers’ emotional interactions predicted teacher-reported social skills. Findings suggest that policies, program development, and professional development efforts that improve teacher–child interactions can facilitate children’s school readiness.
University of Alberta1, Harvard University2, Johns Hopkins University3, Mayo Clinic4, University of São Paulo5, University of Maryland, Baltimore6, Vanderbilt University7, University of Manitoba8, University of Paris9, Wake Forest University10, Katholieke Universiteit Leuven11, National Institutes of Health12, University of Basel13, Westmead Hospital14, University of North Carolina at Chapel Hill15, University of Pittsburgh16, University of Vienna17, University of Oxford18, University of Padua19
TL;DR: Emerging research data led to the establishment of collaborative working groups addressing issues like isolated ‘v’ lesion and incorporation of omics‐technologies, paving the way for future combination of graft biopsy and molecular parameters within the Banff process.
TL;DR: This meta-analytic review of 148 studies on child and adolescent direct and indirect aggression examined the magnitude of gender differences, intercorrelations between forms, and associations with maladjustment.
Abstract: This meta-analytic review of 148 studies on child and adolescent direct and indirect aggression examined the magnitude of gender differences, intercorrelations between forms, and associations with maladjustment. Results confirmed prior findings of gender differences (favoring boys) in direct aggression and trivial gender differences in indirect aggression. Results also indicated a substantial intercorrelation (r = .76) between these forms. Despite this high intercorrelation, the 2 forms showed unique associations with maladjustment: Direct aggression is more strongly related to externalizing problems, poor peer relations, and low prosocial behavior, and indirect aggression is related to internalizing problems and higher prosocial behavior. Moderation of these effect sizes by method of assessment, age, gender, and several additional variables were systematically investigated.
University of Michigan1, National Institutes of Health2, University of Oxford3, University of Bristol4, National Research Council5, University of Maryland, Baltimore6, French Institute of Health and Medical Research7, University of Paris8, National Institute for Health and Welfare9, University of Southern California10, University of London11, University of Helsinki12, University of North Carolina at Chapel Hill13
TL;DR: In this paper, the authors used genotype imputation and meta-analysis to identify genetic variants influencing plasma lipid concentrations, using three genome-wide scans totaling 8,816 individuals and comprising 6,068 individuals specific to their study.
Abstract: To identify genetic variants influencing plasma lipid concentrations, we first used genotype imputation and meta-analysis to combine three genome-wide scans totaling 8,816 individuals and comprising 6,068 individuals specific to our study (1,874 individuals from the FUSION study of type 2 diabetes and 4,184 individuals from the SardiNIA study of aging-associated variables) and 2,758 individuals from the Diabetes Genetics Initiative, reported in a companion study in this issue. We subsequently examined promising signals in 11,569 additional individuals. Overall, we identify strongly associated variants in eleven loci previously implicated in lipid metabolism (ABCA1, the APOA5-APOA4-APOC3-APOA1 and APOE-APOC clusters, APOB, CETP, GCKR, LDLR, LPL, LIPC, LIPG and PCSK9) and also in several newly identified loci (near MVK-MMAB and GALNT2, with variants primarily associated with high-density lipoprotein (HDL) cholesterol; near SORT1, with variants primarily associated with low-density lipoprotein (LDL) cholesterol; near TRIB1, MLXIPL and ANGPTL3, with variants primarily associated with triglycerides; and a locus encompassing several genes near NCAN, with variants strongly associated with both triglycerides and LDL cholesterol). Notably, the 11 independent variants associated with increased LDL cholesterol concentrations in our study also showed increased frequency in a sample of coronary artery disease cases versus controls.
TL;DR: It is reported that Th17 cell differentiation in the lamina propria of the small intestine requires specific commensal microbiota and is inhibited by treating mice with selective antibiotics, suggesting composition of intestinal microbiota regulates the Th17:Treg balance in the LP and may thus influence intestinal immunity, tolerance, and susceptibility to inflammatory bowel diseases.
TL;DR: In this paper, the authors develop a framework designed to generalize across specific manifestations of proactivity, describing the nature, dimensions, situational antecedents, psychological mechanisms, dispositional moderators, and consequences of proactive behavior.
University of Utah1, Cleveland Clinic2, United States Department of Veterans Affairs3, University of Alabama at Birmingham4, Loyola University Chicago5, National Institutes of Health6, University of Texas Southwestern Medical Center7, University of Michigan8, University of North Carolina at Chapel Hill9, Duke University10, Centers for Disease Control and Prevention11
TL;DR: A cross-sectional analysis of 1961 nonpregnant women who participated in the 2005-2006 National Health and Nutrition Examination Survey, a nationally representative survey of the US noninstitutionalized population, found no differences in prevalence by racial/ethnic group.
Abstract: Results The weighted prevalence of at least 1 pelvic floor disorder was 23.7% (95% confidence interval [CI], 21.2%-26.2%), with 15.7% of women (95% CI, 13.2%18.2%) experiencing urinary incontinence, 9.0% of women (95% CI, 7.3%-10.7%) experiencing fecal incontinence, and 2.9% of women (95% CI, 2.1%-3.7%) experiencing pelvic organ prolapse. The proportion of women reporting at least 1 disorder increased incrementally with age, ranging from 9.7% (95% CI, 7.8%-11.7%) in women between ages 20 and 39 years to 49.7% (95% CI, 40.3%-59.1%) in those aged 80 years or older (P.001), and parity (12.8% [95% CI, 9.0%-16.6%], 18.4% [95% CI, 12.9%-23.9%], 24.6% [95% CI, 19.5%-29.8%], and 32.4% [95% CI, 27.8%37.1%] for 0, 1, 2, and 3 or more deliveries, respectively; P.001). Overweight and obese women were more likely to report at least 1 pelvic floor disorder than normal weight women (26.3% [95% CI, 21.7%-30.9%], 30.4% [95% CI, 25.8%-35.0%], and 15.1% [95% CI, 11.6%-18.7%], respectively; P.001). We detected no differences in prevalence by racial/ethnic group.
Harvard University1, Broad Institute2, Massachusetts Institute of Technology3, Cardiff University4, University College London5, University of Edinburgh6, Trinity College, Dublin7, Uppsala University8, Karolinska Institutet9, University of Southern California10, University of Aberdeen11, University of North Carolina at Chapel Hill12, QIMR Berghofer Medical Research Institute13, Royal College of Surgeons in Ireland14, National Health Service15, University of Oxford16, Queen Mary University of London17, State University of New York System18, University of Coimbra19
TL;DR: A genome-wide survey of rare CNVs in 3,391 patients with schizophrenia and 3,181 ancestrally matched controls provides strong support for a model of schizophrenia pathogenesis that includes the effects of multiple rare structural variants, both genome- wide and at specific loci.
Abstract: Schizophrenia is a severe mental disorder marked by hallucinations, delusions, cognitive deficits and apathy, with a heritability estimated at 73 - 90% ( ref. 1). Inheritance patterns are complex, and the number and type of genetic variants involved are not understood. Copy number variants ( CNVs) have been identified in individual patients with schizophrenia(2-7) and also in neurodevelopmental disorders(8-11), but large- scale genome- wide surveys have not been performed. Here we report a genome- wide survey of rare CNVs in 3,391 patients with schizophrenia and 3,181 ancestrally matched controls, using high- density microarrays. For CNVs that were observed in less than 1% of the sample and were more than 100 kilobases in length, the total burden is increased 1.15- fold in patients with schizophrenia in comparison with controls. This effect was more pronounced for rarer, single- occurrence CNVs and for those that involved genes as opposed to those that did not. As expected, deletions were found within the region critical for velo- cardio- facial syndrome, which includes psychotic symptoms in 30% of patients(12). Associations with schizophrenia were also found for large deletions on chromosome 15q13.3 and 1q21.1. These associations have not previously been reported, and they remained significant after genome- wide correction. Our results provide strong support for a model of schizophrenia pathogenesis that includes the effects of multiple rare structural variants, both genome- wide and at specific loci.
19 May 2008
TL;DR: This paper applies the "Reciprocal Velocity Obstacle" concept to navigation of hundreds of agents in densely populated environments containing both static and moving obstacles, and shows that real-time and scalable performance is achieved in such challenging scenarios.
Abstract: In this paper, we propose a new concept - the "Reciprocal Velocity Obstacle"- for real-time multi-agent navigation. We consider the case in which each agent navigates independently without explicit communication with other agents. Our formulation is an extension of the Velocity Obstacle concept [3], which was introduced for navigation among (passively) moving obstacles. Our approach takes into account the reactive behavior of the other agents by implicitly assuming that the other agents make a similar collision-avoidance reasoning. We show that this method guarantees safe and oscillation- free motions for each of the agents. We apply our concept to navigation of hundreds of agents in densely populated environments containing both static and moving obstacles, and we show that real-time and scalable performance is achieved in such challenging scenarios.
TL;DR: The crystal structure of the thiolate gold nanoparticle [TOA+][Au25(SCH2CH2Ph)18-], where TOA+ = N(C8H17)4+.
Abstract: We report the crystal structure of the thiolate gold nanoparticle [TOA+][Au25(SCH2CH2Ph)18-], where TOA+ = N(C8H17)4+. The crystal structure reveals three types of gold atoms: (a) one central gold atom whose coordination number is 12 (12 bonds to gold atoms); (b) 12 gold atoms that form the vertices of an icosahedron around the central atom, whose coordination number is 6 (five bonds to gold atoms and one to a sulfur atom), and (c) 12 gold atoms that are stellated on 12 of the 20 faces of the Au13 icosahedron. The arrangement of the latter gold atoms may be influenced by aurophilic bonding. Together they form six orthogonal semirings, or staples, of −Au2(SCH2CH2Ph)3− in an octahedral arrangement around the Au13 core.