156 research outputs found

    UK-wide evaluation of the Millennium Volunteers Programme

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    The Millennium Volunteers programme is a UK-wide government supported initiative designed to promote sustained volunteering among young people aged 16-24

    The Simple Chordate \u3cem\u3eCiona intestinalis\u3c/em\u3e Has a Reduced Complement of Genes Associated with Fanconi Anemia

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    Fanconi anemia (FA) is a human genetic disease characterized by congenital defects, bone marrow failure, and increased cancer risk. FA is associated with mutation in one of 24 genes. The protein products of these genes function cooperatively in the FA pathway to orchestrate the repair of DNA interstrand cross-links. Few model organisms exist for the study of FA. Seeking a model organism with a simpler version of the FA pathway, we searched the genome of the simple chordate Ciona intestinalis for homologs of the human FA-associated proteins. BLAST searches, sequence alignments, hydropathy comparisons, maximum likelihood phylogenetic analysis, and structural modeling were used to infer the likelihood of homology between C. intestinalis and human FA proteins. Our analysis indicates that C. intestinalis indeed has a simpler and potentially functional FA pathway. The C. intestinalis genome was searched for candidates for homology to 24 human FA and FA-associated proteins. Support was found for the existence of homologs for 13 of these 24 human genes in C. intestinalis. Members of each of the three commonly recognized FA gene functional groups were found. In group I, we identified homologs of FANCE, FANCL, FANCM, and UBE2T/FANCT. Both members of group II, FANCD2 and FANCI, have homologs in C. intestinalis. In group III, we found evidence for homologs of FANCJ, FANCO, FANCQ/ERCC4, FANCR/RAD51, and FANCS/BRCA1, as well as the FA-associated proteins ERCC1 and FAN1. Evidence was very weak for the existence of homologs in C. intestinalis for any other recognized FA genes. This work supports the notion that C. intestinalis, as a close relative of vertebrates, but having a much reduced complement of FA genes, offers a means of studying the function of certain FA proteins in a simpler pathway than that of vertebrate cells

    Utilizing UV and Visible Sensors on Micro Satellites to Demonstrate Target Acquisition and Tracking

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    The Distributed Sensing Experiment (DSE) program is a technology demonstration of target acquisition, tracking, and three-dimensional track development using a constellation of three micro satellites. DSE will demonstrate how micro satellites, working singly and as a group, can observe test-missile boost and ballistic-flight events. The overarching program objective is to demonstrate a means of fusing measurements from multiple sensors into a composite track. To perform this demonstration, each DSE micro satellite will acquire and track a target, determine a two-dimensional direction and movement rate for each, communicate observations to other DSE satellites, determine a three-dimensional target position and velocity, and relay this information to ground systems. A key design parameter of the program is incorporating commercial off-the-shelf (COTS) hardware and software to reduce risk and control costs, while maintaining performance. Having completed a successful Critical Design Review, the program is currently in fabrication, integration, and test phase. The constellation of satellites is scheduled for launch in CY2009. This paper describes the status and capabilities of the UV and visible sensor payloads, as well as the algorithms and software being developed to achieve the DSE mission

    Proteomic responses to elevated ocean temperature in ovaries of the ascidian \u3cem\u3eCiona intestinalis\u3c/em\u3e

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    Ciona intestinalis, a common sea squirt, exhibits lower reproductive success at the upper extreme of the water temperatures it experiences in coastal New England. In order to understand the changes in protein expression associated with elevated temperatures, and possible response to global temperature change, we reared C. intestinalis from embryos to adults at 18°C (a temperature at which they reproduce normally at our collection site in Rhode Island) and 22°C (the upper end of the local temperature range). We then dissected ovaries from animals at each temperature, extracted protein, and measured proteomic levels using shotgun mass spectrometry (LC-MS/MS). 1532 proteins were detected at a 1% false discovery rate present in both temperature groups by our LC-MS/MS method. 62 of those proteins are considered up- or down-regulated according to our statistical criteria. Principal component analysis shows a clear distinction in protein expression pattern between the control (18°C) group and high temperature (22°C) group. Similar to previous studies, cytoskeletal and chaperone proteins are upregulated in the high temperature group. Unexpectedly, we find evidence that proteolysis is downregulated at the higher temperature. We propose a working model for the high temperature response in C. intestinalis ovaries whereby increased temperature induces upregulation of signal transduction pathways involving PTPN11 and CrkL, and activating coordinated changes in the proteome especially in large lipid transport proteins, cellular stress responses, cytoskeleton, and downregulation of energy metabolism

    Drama-based education to motivate participation in substance abuse prevention

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    BACKGROUND: The substance abuse prevention goal of the theatre production "TUNNELS" was to provide community education on substance abuse to an audience in Durham, NC and surrounding communities. The education effort intended to increase awareness and understanding of the risk and protective factors associated with alcohol and other drug use, and to promote pro-active behaviors in substance abuse prevention within the adult community. It was hypothesized that community-based education via drama would change attitudes toward alcohol and substance abuse, and increase participation in family and community activities aimed at substance abuse prevention. METHODS: A focus group comprised of educators, substance abuse researchers and local substance abuse counselors developed "life stories" of users of alcohol and other drugs and a local playwright incorporated these and other experiences into a series of six vignettes. The production was publicized throughout the Durham area, and 700 adults attending the play signed a consent form and completed the pre-play survey. The participant pool was restricted to those adults who completed both the time-1 and time-2 surveys and resided within Durham and surrounding communities. Paired comparisons of mean responses were analyzed using a paired sample two-tailed t-test. A telephone survey three months after the play assessed attitudes toward substance abuse as a disease, and whether the respondents had increased their participation in prevention activities including discussions of the play with others. RESULTS: Viewing the play increased the knowledge base of participants regarding substance abuse as a disease, even though the audience demonstrated an appreciation of risk and protective factors prior to attending the performance. In the pre-play survey, participants indicated a strong opinion that parental involvement in teen life was important, and therefore this was not increased as a result of viewing the play. It was found that the drama increased intent to participate in substance abuse prevention activities at home and in the community. Follow-up surveys performed three months after the performance indicated that participants had discussed the play with others and had increased their participation in substance abuse prevention activities, particularly regarding donations of money. CONCLUSION: Drama incorporates a component of emotional response to the informational content, and the combination of emotion and information works together to promote individual intentions to become more involved in family and community prevention activities. This study demonstrates the efficacy of drama as a mechanism to educate and motivate. Support for this mechanism is warranted at the level of state, local community, school district, and faith-based and community organizations

    The Short-Term Impact of Ontario's Generic Pricing Reforms

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    Background: Canadians pay amongst the highest generic drug prices in the world. In July 2010, the province of Ontario enacted a policy that halved reimbursement for generic drugs from the public drug plan, and substantially lowered prices for private purchases. We quantified the impact of this policy on overall generic drug expenditures in the province, and projected the impact in other provinces had they mimicked this pricing change. Methods: We used quarterly prescription generic drug dispensing data from the IMS-Brogan CompuScript Audit. We used the price per unit in both the pre- and post-policy period and two economics price indexes to estimate the expenditure reduction in Ontario. Further, we used the post-policy Ontario prices to estimate the potential reduction in other provinces. Results: We estimate that total expenditure on generic drugs in Ontario during the second half of 2010 was between 181and181 and 194 million below what would be expected if prices had remained at pre-policy level. Over half of the reduction in spending was due to savings on just 10 generic ingredients. If other provinces had matched Ontario’s prices, their expenditures over during the latter half of 2010 would have been 445millionlower.Discussion:WefoundthatifOntariospricingschemewereadoptednationally,overallspendingongenericdrugsinCanadawoulddropatleast445 million lower. Discussion: We found that if Ontario’s pricing scheme were adopted nationally, overall spending on generic drugs in Canada would drop at least 1.28 billion annually—a 5 % decrease in total prescription drug expenditure. Other provinces should seriously consider both changes to their generic drug prices and the use of more competitive bulk purchasing policies

    Attention Deficit Hyperactivity Disorder and Risk of Posttraumatic Stress and Related Disorders: A Prospective Longitudinal Evaluation in U.S. Army Soldiers

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    Crossâ sectional associations between attention deficit hyperactivity disorder (ADHD) and posttraumatic stress disorder (PTSD) have been observed, but longitudinal studies assessing this association are lacking. This prospective study evaluated the association between predeployment ADHD and postdeployment PTSD among U.S. Army soldiers. Soldiers who deployed to Afghanistan were surveyed before deployment (T0) and approximately 1 month (T1), 3 months (T2), and 9 months (T3) after their return. Logistic regression was performed to estimate the association between predeployment ADHD and postdeployment (T2 or T3) PTSD among 4,612 soldiers with data at all waves and no record of stimulant medication treatment during the study. To evaluate specificity of the ADHDâ PTSD association, we examined associations among predeployment ADHD, postdeployment major depressive episode (MDE), generalized anxiety disorder (GAD), and suicidal ideation. Weighted prevalence of ADHD predeployment was 6.1% (SE = 0.4%). Adjusting for other risk factors, predeployment ADHD was associated with risk of postdeployment PTSD, adjusted odds ratio (AOR) = 2.13, 95% CI [1.51, 3.00], p < .001, including incidence among soldiers with no predeployment history of PTSD, AOR = 2.50, 95% CI [1.69, 3.69], p < .001. ADHD was associated with postdeployment MDE, AOR = 2.80, 95% CI [2.01, 3.91], p < .001, and GAD, AOR = 3.04, 95% CI [2.10, 4.42], p < .001, but not suicidal ideation. Recognition of associations between predeployment ADHD and postdeployment PTSD, MDE, and GAD may inform targeted prevention efforts. Future research should examine whether treatment of ADHD is protective against PTSD and related disorders in traumaâ exposed individuals.ResumenSpanish Abstracts by Asociación Chilena de Estrés Traumático (ACET)El trastorno de déficit atencional con hiperactividad y el riesgo del trastorno de estrés postraumático y trastornos relacionados: Una evaluación longitudinal prospectiva en soldados del ejército estadounidenseTDAH Y RIESGO DE TEPT EN SOLDADOS DEL EJà RCITO DE EE.UU.Se han observado asociaciones transversales entre el trastorno por déficit de atención con hiperactividad (TDAH) y el trastorno por estrés postraumático (TEPT), pero faltan estudios longitudinales que evalúen esta asociación. Este estudio prospectivo evaluó la asociación entre el TDAH previo al despliegue y el TEPT posterior al despliegue entre los soldados del Ejército de Estados Unidos. Los soldados desplegados en Afganistán fueron encuestados antes del despliegue (T0) y aproximadamente 1 mes (T1), 3 meses (T2), y 9 meses (T3) después de su regreso del despliegue. Se realizó una regresión logística para estimar la asociación entre el TDAH previo al despliegue y el TEPT posterior al despliegue (T2 o T3) en 4.612 soldados con datos en todas las etapas y sin registro de tratamiento con medicamentos estimulantes durante el estudio. Para evaluar la especificidad de la asociación TDAHâ TEPT, examinamos las asociaciones entre el TDAH previo al despliegue, el episodio depresivo mayor posterior al despliegue (EDM), el trastorno de ansiedad generalizada (TAG), y la ideación suicida. La prevalencia ponderada del TDAH previo al despliegue fue de 6.1% (SE = 0.4%). Al controlar los otros factores de riesgo, el TDAH previo al despliegue se asoció con el riesgo de TEPT posterior al despliegue, odds ratio ajustado (AOR en su sigla en inglés) = 2.13, IC del 95% [1.51, 3.00], p <.001, incluida la incidencia entre soldados sin historial previo al despliegue de TEPT, AOR = 2.50, IC del 95% [1.69, 3.69], p <.001. El TDAH se asoció con el EDM posterior al despliegue, AOR = 2.80, IC del 95% [2.01, 3.91], p <.001, y TAG, AOR = 3.04, IC del 95% [2.10, 4.42], p <.001, pero no con ideación suicida. El reconocimiento de las asociaciones entre el TDAH previo al despliegue y el TEPT, el EDM, y el TAG posterior al despliegue puede informar los esfuerzos de prevención específicos. Las investigaciones futuras deberían examinar si el tratamiento del TDAH protege contra el TEPT y los trastornos relacionados en personas expuestas a trauma.æ ½è±¡Traditional and Simplified Chinese Abstracts by the Asian Society for Traumatic Stress Studies (AsianSTSS)ç°¡é« å ç¹ é« ä¸­æ æ ®è¦ ç ±äº æ´²å µå ·å¿ ç ç  ç©¶å­¸æ 翻譯Attention Deficit Hyperactivity Disorder and Risk of Posttraumatic Stress and Related Disorders: A Prospective Longitudinal Evaluation in US Army SoldiersTraditional Chineseæ¨ é¡ : å° æ³¨å ä¸ è¶³æ é åº¦æ´»èº ç è æ £å µå ·å¾ å£ å ç å ç ¸é ç ¾ç ç é¢¨é ª:å° ç¾ å è» äººé ²è¡ ç å ç »ç¸±è²«ç  ç©¶æ ®è¦ : é å¾ ä¸ ç ´æ ç  ç©¶æª¢è¦ å° æ³¨å ä¸ è¶³æ é åº¦æ´»èº ç (ADHD)è å µå ·å¾ å£ å ç (PTSD)ä¹ é ç æ©«æ ·æ §é é £, å ¯æ ¯, æ å ä» æ¬ ç¼ºæª¢è¦ å ©è é é £ç ç¸±è²«ç  ç©¶ã æ ¬å ç »ç  ç©¶æ ¨å ¨é é ç¾ è» æ¨£æ ¬, è© ä¼°æ å½¹å ADHDè· æ å½¹å¾ PTSDç é é £ã æ¨£æ ¬ç ºå å¾ é ¿å¯ æ± æ å½¹ç è» äºº, å ¨æ å½¹å (T0)å å® æ æ å½¹å¾ ç´ 1å æ (T1)ã 3å æ (T2)å 9å æ (T3)æ ¥å èª¿æ ¥ã æ å 以é 輯迴歸å æ å æ æ 波段ç æ ¸æ , ä¼°è¨ 4,612å è» äººæ å½¹å ADHDè· æ å½¹å¾ (T2 æ T3)PTSDç é é £ã ç  ç©¶ä¸­, æ¨£æ ¬ä¸¦ç ¡æ ç ¨è å¥®è ¥ç ©ã ç ºäº è§£ADHDâ PTSDç ç ¹æ® é é £, æ å æª¢è¦ ä»¥ä¸ é  ç ®ä¹ é ç é é £:æ å½¹å ADHDã å® æ æ å½¹å¾ ç å ´é æ é¬±ç¯ æ®µ(MDE)ã å»£æ³ æ §ç ¦æ ®ç (GAD)ã è ªæ®ºæ 念ã æ å½¹å ADHDæ ®é åº¦ç º6.1% (SE = 0.4%)ã å° å ¶ä» é¢¨é ªå  ç´ ä½ èª¿ç¯ å¾ , æ å½¹å ADHDè· æ å½¹å¾ æ £PTSDç é¢¨é ªæ æ é é £(å·²èª¿ç¯ å ç® æ¯ (AOR) = 2.13, 95% CI [1.51, 3.00], p < .001), ç ¶ä¸­å æ ¬æ å½¹å ä¸¦ç ¡PTSDç è» äºº(AOR = 2.50, 95% CI [1.69, 3.69], p < .001)ã ADHDè· å® æ æ å½¹å¾ æ £MDEç (AOR = 2.80, 95% CI [2.01, 3.91], p < .001)å GAD(AOR = 3.04, 95% CI [2.10, 4.42] p < .001)é ½æ é , ä½ è· è ªæ®ºæ å¿µç ¡é ã äº è§£æ å½¹å ADHDè· æ å½¹å¾ PTSDã MDEå GADç é é £, å ¯è ½æ å ©ç ¼å± é å° æ §ç é  é ²å·¥ä½ ã æ ªä¾ ç  ç©¶æ æª¢è¦ å° å å µäººå£«æ ä¾ ADHDæ²»ç , æ ¯å ¦å° å ¶PTSDå ç ¸é ç ¾ç æ ä¿ è­·æ æ ã Simplified Chineseæ  é¢ : ä¸ æ³¨å ä¸ è¶³æ è¿ åº¦æ´»è· ç ä¸ æ £å 伤å å å ç å ç ¸å ³ç ¾ç ç é£ é ©:å¯¹ç¾ å ½å äººè¿ è¡ ç å ç »çºµè´¯ç  ç©¶æ ®è¦ : è¿ å¾ ä¸ ç ´æ ç  ç©¶æ£ è§ ä¸ æ³¨å ä¸ è¶³æ è¿ åº¦æ´»è· ç (ADHD)ä¸ å 伤å å å ç (PTSD)ä¹ é ´ç æ¨ªæ ­æ §å ³è¿ , å ¯æ ¯, æ ä»¬ä» æ¬ ç¼ºæ£ è§ ä¸¤è å ³è¿ ç çºµè´¯ç  ç©¶ã æ ¬å ç »ç  ç©¶æ ¨å ¨é è¿ ç¾ å æ ·æ ¬, è¯ ä¼°æ å½¹å ADHDè· æ å½¹å PTSDç å ³è¿ ã æ ·æ ¬ä¸ºå å¾ é ¿å¯ æ± æ å½¹ç å 人, å ¨æ å½¹å (T0)å å® æ æ å½¹å 约1个æ (T1)ã 3个æ (T2)å 9个æ (T3)æ ¥å è° æ ¥ã æ ä»¬ä»¥é »è¾ å å½ å æ å æ æ 波段ç æ °æ ®, 估计4,612å å 人æ å½¹å ADHDè· æ å½¹å (T2 æ T3)PTSDç å ³è¿ ã ç  ç©¶ä¸­, æ ·æ ¬å¹¶æ  æ ç ¨å ´å¥ è ¯ç ©ã ä¸ºäº è§£ADHDâ PTSDç ç ¹æ® å ³è¿ , æ ä»¬æ£ è§ ä»¥ä¸ é¡¹ç ®ä¹ é ´ç å ³è¿ :æ å½¹å ADHDã å® æ æ å½¹å ç 严é æ é è 段(MDE)ã å¹¿æ³ æ §ç ¦è ç (GAD)ã è ªæ æ 念ã æ å½¹å ADHDæ ®é 度为6.1% (SE = 0.4%)ã å¯¹å ¶ä» é£ é ©å  ç´ ä½ è° è å , æ å½¹å ADHDè· æ å½¹å æ £PTSDç é£ é ©æ æ å ³è¿ (å·²è° è è ç® æ¯ (AOR) = 2.13, 95% CI [1.51, 3.00], p < .001), å½ ä¸­å æ ¬æ å½¹å å¹¶æ  PTSDç å 人(AOR = 2.50, 95% CI [1.69, 3.69], p < .001)ã ADHDè· å® æ æ å½¹å æ £MDEç (AOR = 2.80, 95% CI [2.01, 3.91], p < .001)å GAD(AOR = 3.04, 95% CI [2.10, 4.42] p < .001)é ½æ å ³, ä½ è· è ªæ æ å¿µæ  å ³ã äº è§£æ å½¹å ADHDè· æ å½¹å PTSDã MDEå GADç å ³è¿ , å ¯è ½æ å ©å å± é å¯¹æ §ç é¢ é ²å·¥ä½ ã æ ªæ ¥ç  ç©¶åº æ£ è§ å¯¹å å 人士æ ä¾ ADHDæ²»ç , æ ¯å ¦å¯¹å ¶PTSDå ç ¸å ³ç ¾ç æ ä¿ æ ¤æ åº ãPeer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146971/1/jts22347_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146971/2/jts22347.pd

    Disease Modelling of Cognitive Outcomes and Biomarkers in the European Prevention of Alzheimer’s Dementia Longitudinal Cohort

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    A key challenge for the secondary prevention of Alzheimer’s dementia is the need to identify individuals early on in the disease process through sensitive cognitive tests and biomarkers. The European Prevention of Alzheimer’s Dementia (EPAD) consortium recruited participants into a longitudinal cohort study with the aim of building a readiness cohort for a proof-of-concept clinical trial and also to generate a rich longitudinal data-set for disease modelling. Data have been collected on a wide range of measurements including cognitive outcomes, neuroimaging, cerebrospinal fluid biomarkers, genetics and other clinical and environmental risk factors, and are available for 1,828 eligible participants at baseline, 1,567 at 6 months, 1,188 at one-year follow-up, 383 at 2 years, and 89 participants at three-year follow-up visit. We novelly apply state-of-the-art longitudinal modelling and risk stratification approaches to these data in order to characterise disease progression and biological heterogeneity within the cohort. Specifically, we use longitudinal class-specific mixed effects models to characterise the different clinical disease trajectories and a semi-supervised Bayesian clustering approach to explore whether participants can be stratified into homogeneous subgroups that have different patterns of cognitive functioning evolution, while also having subgroup-specific profiles in terms of baseline biomarkers and longitudinal rate of change in biomarkers

    Designing stakeholder learning dialogues for effective global governance

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    A growing scholarship on multistakeholder learning dialogues suggests the importance of closely managing learning processes to help stakeholders anticipate which policies are likely to be effective. Much less work has focused on how to manage effective transnational multistakeholder learning dialogues, many of which aim to help address critical global environmental and social problems such as climate change or biodiversity loss. They face three central challenges. First, they rarely shape policies and behaviors directly, but work to ‘nudge’ or ‘tip the scales’ in domestic settings. Second, they run the risk of generating ‘compromise’ approaches incapable of ameliorating the original problem definition for which the dialogue was created. Third, they run the risk of being overly influenced, or captured, by powerful interests whose rationale for participating is to shift problem definitions or narrow instrument choices to those innocuous to their organizational or individual interests. Drawing on policy learning scholarship, we identify a six-stage learning process for anticipating effectiveness designed to minimize these risks while simultaneously fostering innovative approaches for meaningful and longlasting problem solving: Problem definition assessments; Problem framing; Developing coalition membership; Causal framework development; Scoping exercises; Knowledge institutionalization. We also identify six management techniques within each process for engaging transnational dialogues around problem solving. We show that doing so almost always requires anticipating multiple-step causal pathways through which influence of transnational and/or international actors and institutions might occur
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