127 research outputs found
Role of the QBO in modulating the influence of the 11 year solar cycle on the atmosphere using constant forcings
We present a set of six 20 year experiments made with a state-of-the-art chemistry-climate model that incorporates the atmosphere from the surface to the lower thermosphere. The response of the middle atmosphere to the 11 year solar cycle, its impact on the troposphere, and especially the role of an externally prescribed stratospheric quasi-biennial oscillation (QBO) is investigated with NCAR's Whole Atmosphere Community Climate Model (WACCM3). The model experiments use either fixed solar cycle inputs or fixed solar cycle together with prescribed QBO phase. The annual mean solar response in temperature and ozone in the upper stratosphere is in qualitative agreement with other modeling and observational studies and does not depend on the presence of the imposed QBO. However, the solar response in the middle to lower stratosphere differs significantly for the two QBO phases. During solar maxima a weaker Brewer-Dobson circulation with relative downwelling, warming, and enhanced ozone occurs in the tropical lower stratosphere during QBO east conditions, while a stronger circulation, cooling, and decreased ozone exists during QBO west conditions. The net ozone increase during QBO east is the combined result of production and advection, whereas during QBO west the effects cancel each other and result in little net ozone changes. Especially during Southern Hemisphere late winter to early spring, the solar response at polar latitudes switches sign between the two QBO phases and qualitatively confirms observations and other recent model studies. During a poleward downward modulation of the polar night jet and a corresponding modulation of the Brewer-Dobson circulation in time, solar signals are detected all the way down to the extratropical troposphere. Possible limitations of the model experiments with respect to the fixed solar cycle conditions or the prescribed QBO phases, as well as the constant sea surface temperatures, are discussed
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Summary of research for FY-1995: Progress report
The object of this proposal is to study the reduction in mid-latitude stratospheric ozone and to estimate the budget of tropospheric ozone. The product of this proposal include: (1) the estimation of dilution of air masses processed by polar stratospheric clouds inside the polar vortex during winter; and (2) the destruction of ozone via heterogeneous reactions on the surface of aerosol particles which are present at all latitudes, especially after large volcanic eruptions such as Mt. Pinatubo; (3) to quantify photochemical production and destruction of O{sub 3} in the free troposphere; (4) to quantify export of ozone from polluted to remote regions, and (5) to quantify cross-tropopause exchanges of O{sub 3} and other species. The approach of this proposal is to use and to improve the two-dimensional and three-dimensional global chemical/dynamical models
The current provision of community-based teaching in UK medical schools: an online survey and systematic review
Objective: To evaluate the current provision and outcome of community-based education (CBE) in UK medical schools.
Design and data sources: An online survey of UK medical school websites and course prospectuses and a systematic review of articles from PubMed and Web of Science were conducted. Articles in the systematic review were assessed using Rossi, Lipsey and Freeman’s approach to programme evaluation.
Study selection: Publications from November 1998 to 2013 containing information related to community teaching in undergraduate medical courses were included.
Results: Out of the 32 undergraduate UK medical schools, one was excluded due to the lack of course specifications available online. Analysis of the remaining 31 medical schools showed that a variety of CBE models are utilised in medical schools across the UK. Twenty-eight medical schools (90.3%) provide CBE in some form by the end of the first year of undergraduate training, and 29 medical schools (93.5%) by the end of the second year. From the 1378 references identified, 29 papers met the inclusion criteria for assessment. It was found that CBE mostly provided advantages to students as well as other participants, including GP tutors and patients. However, there were a few concerns regarding the lack of GP tutors’ knowledge in specialty areas, the negative impact that CBE may have on the delivery of health service in education settings and the cost of CBE.
Conclusions: Despite the wide variations in implementation, community teaching was found to be mostly beneficial. To ensure the relevance of CBE for ‘Tomorrow’s Doctors’, a national framework should be established, and solutions sought to reduce the impact of the challenges within CBE.
Strengths and limitations of this study: This is the first study to review how community-based education is currently provided throughout Medical Schools in the UK. The use of Rossi, Lipsey and Freeman’s method of programme evaluation means that the literature was analysed in a consistent and comprehensive way. However, a weakness is that data from the online survey was obtained from online medical school prospectuses. This means the data may be incomplete or out of date. Data in the literature review may also be skewed by publication bias
Considering the Definition of Addiction
The definition of addiction is explored. Elements of addiction derived from a literature search that uncovered 52 studies include: (a) engagement in the behavior to achieve appetitive effects, (b) preoccupation with the behavior, (c) temporary satiation, (d) loss of control, and (e) suffering negative consequences. Differences from compulsions are suggested. While there is some debate on what is intended by the elements of addictive behavior, we conclude that these five constituents provide a reasonable understanding of what is intended by the concept. Conceptual challenges for future research are mentioned
Rare and Common Variants Conferring Risk of Tooth Agenesis
We present association results from a large genome-wide association study of tooth agenesis (TA) as well as selective TA, including 1,944 subjects with congenitally missing teeth, excluding third molars, and 338,554 controls, all of European ancestry. We also tested the association of previously identified risk variants, for timing of tooth eruption and orofacial clefts, with TA. We report associations between TA and 9 novel risk variants. Five of these variants associate with selective TA, including a variant conferring risk of orofacial clefts. These results contribute to a deeper understanding of the genetic architecture of tooth development and disease. The few variants previously associated with TA were uncovered through candidate gene studies guided by mouse knockouts. Knowing the etiology and clinical features of TA is important for planning oral rehabilitation that often involves an interdisciplinary approach
Ultra-brief intervention for problem drinkers: research protocol
Background: Helping the large number of problem drinkers who will never seek treatment is a challenging issue. Public health initiatives employing educational materials or mass media campaigns
have met with mixed success. However, clinical research has developed effective brief interventions to help problem drinkers. This project will employ an intervention that has been validated in clinical settings and then modified into an ultra-brief format suitable for use as a public health intervention. The major objective of this study is to conduct a randomized controlled trial to establish the effectiveness of an ultra-brief, personalized feedback intervention for problem drinkers.
Methods/design: Problem drinkers recruited on a baseline population telephone survey conducted in a major metropolitan city in Canada will be randomized to one of three conditions -
a personalized feedback pamphlet condition, a control pamphlet condition, or a no intervention control condition. In the week after the baseline survey, households in the two pamphlet conditions will be sent their respective pamphlets. Changes in drinking will be assessed post intervention at three-month and six-month follow-ups. Drinking outcomes will be compared between
experimental conditions using Structural Equation Modeling. The primary hypothesis is that problem drinkers from households who receive the personalized feedback pamphlet intervention will display significantly improved drinking outcomes at three and six-month follow-ups as compared to problem drinkers from households in the no intervention control condition. Secondary hypotheses will test the impact of the intervention on help seeking, and explore the mediating or moderating role of perceived drinking norms, perceived alcohol risks and the problem drinker's social reasons for drinking.
Discussion: This trial will provide information on the effectiveness of a pamphlet-based personalized feedback intervention for problem drinkers in a community setting.
Trial registration: ClinicalTrials.gov registration #NCT00688584.This study is funded by the National Institute on Alcohol Abuse and Alcoholism (NIAAA). Grant #R01 AA015680-01A2
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Genome-wide Association Analysis Identifies 14 New Risk Loci for Schizophrenia
Schizophrenia is a heritable disorder with substantial public health impact. We conducted a multi-stage genome-wide association study (GWAS) for schizophrenia beginning with a Swedish national sample (5,001 cases, 6,243 controls) followed by meta-analysis with prior schizophrenia GWAS (8,832 cases, 12,067 controls) and finally by replication of SNPs in 168 genomic regions in independent samples (7,413 cases, 19,762 controls, and 581 trios). In total, 22 regions met genome-wide significance (14 novel and one previously implicated in bipolar disorder). The results strongly implicate calcium signaling in the etiology of schizophrenia, and include genome-wide significant results for CACNA1C and CACNB2 whose protein products interact. We estimate that ∼8,300 independent and predominantly common SNPs contribute to risk for schizophrenia and that these collectively account for most of its heritability. Common genetic variation plays an important role in the etiology of schizophrenia, and larger studies will allow more detailed understanding of this devastating disorder
MAP1B mutations cause intellectual disability and extensive white matter deficit
Publisher's version (útgefin grein).
Publisher's note: Springer Nature remains neutral with regard to jurisdictional claims in
published maps and institutional affiliations.Discovery of coding variants in genes that confer risk of neurodevelopmental disorders is an
important step towards understanding the pathophysiology of these disorders. Wholegenome sequencing of 31,463 Icelanders uncovers a frameshift variant (E712KfsTer10) in
microtubule-associated protein 1B (MAP1B) that associates with ID/low IQ in a large pedigree
(genome-wide corrected P = 0.022). Additional stop-gain variants in MAP1B (E1032Ter and
R1664Ter) validate the association with ID and IQ. Carriers have 24% less white matter
(WM) volume (β = −2.1SD, P = 5.1 × 10−8), 47% less corpus callosum (CC) volume (β =
−2.4SD, P = 5.5 × 10−10) and lower brain-wide fractional anisotropy (P = 6.7 × 10−4). In
summary, we show that loss of MAP1B function affects general cognitive ability through a
profound, brain-wide WM deficit with likely disordered or compromised axons.We are grateful to the participants and we thank the psychologists, nurses and staff, in
particular Berglind Eiriksdottir, at the Research Recruitment Center and technicians and
staff at Röntgen Domus. We also thank the staff at deCODE genetics core facilities and
all our colleagues for their important contribution to this work. L.J. received support
from the Swedish Society of Medicine, the Swedish Brain Foundation and Swedish
Society for Medical Research. The research leading to these results has received support
from the Innovative Medicines Initiative Joint Undertaking under grant agreements’ no.
115008 (NEWMEDS) and no. 115300 (EUAIMS) of which resources are composed of
EFPIA in-kind contribution and financial contribution from the European Union’s
Seventh Framework Programme (EU-FP7/2007-2013), EU-FP7 funded grant no. 602450
(IMAGEMEND) and EU funded FP7-People-2011-IAPP grant agreement no. 286213
(PsychDPC).Peer Reviewe
A large genome-wide association study of age-related macular degeneration highlights contributions of rare and common variants.
This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/ng.3448Advanced age-related macular degeneration (AMD) is the leading cause of blindness in the elderly, with limited therapeutic options. Here we report on a study of >12 million variants, including 163,714 directly genotyped, mostly rare, protein-altering variants. Analyzing 16,144 patients and 17,832 controls, we identify 52 independently associated common and rare variants (P < 5 × 10(-8)) distributed across 34 loci. Although wet and dry AMD subtypes exhibit predominantly shared genetics, we identify the first genetic association signal specific to wet AMD, near MMP9 (difference P value = 4.1 × 10(-10)). Very rare coding variants (frequency <0.1%) in CFH, CFI and TIMP3 suggest causal roles for these genes, as does a splice variant in SLC16A8. Our results support the hypothesis that rare coding variants can pinpoint causal genes within known genetic loci and illustrate that applying the approach systematically to detect new loci requires extremely large sample sizes.We thank all participants of all the studies included for enabling this research by their participation in these studies. Computer resources for this project have been provided by the high-performance computing centers of the University of Michigan and the University of Regensburg. Group-specific acknowledgments can be found in the Supplementary Note. The Center for Inherited Diseases Research (CIDR) Program contract number is HHSN268201200008I. This and the main consortium work were predominantly funded by 1X01HG006934-01 to G.R.A. and R01 EY022310 to J.L.H
Identification of common genetic risk variants for autism spectrum disorder
Autism spectrum disorder (ASD) is a highly heritable and heterogeneous group of neurodevelopmental phenotypes diagnosed in more than 1% of children. Common genetic variants contribute substantially to ASD susceptibility, but to date no individual variants have been robustly associated with ASD. With a marked sample-size increase from a unique Danish population resource, we report a genome-wide association meta-analysis of 18,381 individuals with ASD and 27,969 controls that identified five genome-wide-significant loci. Leveraging GWAS results from three phenotypes with significantly overlapping genetic architectures (schizophrenia, major depression, and educational attainment), we identified seven additional loci shared with other traits at equally strict significance levels. Dissecting the polygenic architecture, we found both quantitative and qualitative polygenic heterogeneity across ASD subtypes. These results highlight biological insights, particularly relating to neuronal function and corticogenesis, and establish that GWAS performed at scale will be much more productive in the near term in ASD
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