250 research outputs found

    What's Gender Got to Do with It? Incivility in the Federal Courts

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    Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72366/1/j.1747-4469.2002.tb00804.x.pd

    Amisulpride augmentation in clozapine-unresponsive schizophrenia: A double-blind, placebo-controlled, randomised trial of clinical and cost-effectiveness.

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    BACKGROUND: When treatment-refractory schizophrenia shows an insufficient response to a trial of clozapine, clinicians commonly add a second antipsychotic, despite the lack of robust evidence to justify this practice. OBJECTIVES: The main objectives of the study were to establish the clinical effectiveness and cost-effectiveness of augmentation of clozapine medication with a second antipsychotic, amisulpride, for the management of treatment-resistant schizophrenia. DESIGN: The study was a multicentre, double-blind, individually randomised, placebo-controlled trial with follow-up at 12 weeks. SETTINGS: The study was set in NHS multidisciplinary teams in adult psychiatry. PARTICIPANTS: Eligible participants were people aged 18-65 years with treatment-resistant schizophrenia unresponsive, at a criterion level of persistent symptom severity and impaired social function, to an adequate trial of clozapine monotherapy. INTERVENTIONS: Interventions comprised clozapine augmentation over 12 weeks with amisulpride or placebo. Participants received 400 mg of amisulpride or two matching placebo capsules for the first 4 weeks, after which there was a clinical option to titrate the dosage of amisulpride up to 800 mg or four matching placebo capsules for the remaining 8 weeks. MAIN OUTCOME MEASURES: The primary outcome measure was the proportion of 'responders', using a criterion response threshold of a 20% reduction in total score on the Positive and Negative Syndrome Scale. RESULTS: A total of 68 participants were randomised. Compared with the participants assigned to placebo, those receiving amisulpride had a greater chance of being a responder by the 12-week follow-up (odds ratio 1.17, 95% confidence interval 0.40 to 3.42) and a greater improvement in negative symptoms, although neither finding had been present at 6-week follow-up and neither was statistically significant. Amisulpride was associated with a greater side effect burden, including cardiac side effects. Economic analyses indicated that amisulpride augmentation has the potential to be cost-effective in the short term [net saving of between £329 and £2011; no difference in quality-adjusted life-years (QALYs)] and possibly in the longer term. LIMITATIONS: The trial under-recruited and, therefore, the power of statistical analysis to detect significant differences between the active and placebo groups was limited. The economic analyses indicated high uncertainty because of the short duration and relatively small number of participants. CONCLUSIONS: The risk-benefit of amisulpride augmentation of clozapine for schizophrenia that has shown an insufficient response to a trial of clozapine monotherapy is worthy of further investigation in larger studies. The size and extent of the side effect burden identified for the amisulpride-clozapine combination may partly reflect the comprehensive assessment of side effects in this study. The design of future trials of such a treatment strategy should take into account that a clinical response may be not be evident within the 4- to 6-week follow-up period usually considered adequate in studies of antipsychotic treatment of acute psychotic episodes. Economic evaluation indicated the need for larger, longer-term studies to address uncertainty about the extent of savings because of amisulpride and impact on QALYs. The extent and nature of the side effect burden identified for the amisulpride-clozapine combination has implications for the nature and frequency of safety and tolerability monitoring of clozapine augmentation with a second antipsychotic in both clinical and research settings. TRIAL REGISTRATION: EudraCT number 2010-018963-40 and Current Controlled Trials ISRCTN68824876. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 21, No. 49. See the NIHR Journals Library website for further project information

    School Toileting Environment, Bullying, and Lower Urinary Tract Symptoms in a Population of Adolescent and Young Adult Girls:Preventing Lower Urinary Tract Symptoms Consortium Analysis of Avon Longitudinal Study of Parents and Children

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    AIM: Little is known about the association of the school toilet environment with voiding behaviors and lower urinary tract symptoms (LUTS) in adolescents. The purpose of the present longitudinal, secondary data analysis is to examine whether the school toilet environment at age 13, including bullying, is associated with LUTS at ages 13 and 19. METHODS: The sample comprised 3962 female participants from the Avon Longitudinal Study of Parents and Children (ALSPAC). At age 13, participants reported on 7 school toilet environment characteristics and a range of LUTS items. At age 19, participants completed the Bristol Female Lower Urinary Tract Symptoms (ICIQ-BFLUTS) questionnaire. RESULTS: All toilet environmental factors were associated with at least one LUTS outcome at age 13. Holding behavior was associated with all school toilet environmental factors, with odds ratios (ORs) ranging from 1.36 (95% CI: 1.05, 1.76) for dirty toilets to 2.38 (95% CI: 1.60, 3.52) for feeling bullied at toilets. Bullying was associated with all LUTS symptoms; ORs ranged from 1.60 (95% CI: 1.04, 2.07) for nocturia to 2.90 (95% CI: 1.77, 4.75) for urgency. Associations between age 13 school toilets and age 19 LUTS were in the same direction as age 13 LUTS. CONCLUSION: This is the first examination of associations between school toilets and LUTS. Toileting environments were cross-sectionally associated with LUTS in adolescent girls. While further work is needed to determine whether these associations are causal, school toilet environments are modifiable and thus a promising target for LUTS prevention

    Spatio-temporal trends in normal-fault segmentation recorded by low-temperature thermochronology: Livingstone fault scarp, Malawi Rift, East African Rift System

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    The evolution of through-going normal-fault arrays from initial nucleation to growth and subsequent interaction and mechanical linkage is well documented in many extensional provinces. Over time, these processes lead to predictable spatial and temporal variations in the amount and rate of displacement accumulated along strike of individual fault segments, which should be manifested in the patterns of footwall exhumation. Here, we investigate the along-strike and vertical distribution of low-temperature apatite (U–Th)/He (AHe) cooling ages along the bounding fault system, the Livingstone fault, of the Karonga Basin of the northern Malawi Rift. The fault evolution and linkage from rift initiation to the present day has been previously constrained through investigations of the hanging wall basin fill. The new cooling ages from the footwall of the Livingstone fault can be related to the adjacent depocentre evolution and across a relay zone between two palaeo-fault segments. Our data are complimented by published apatite fission-track (AFT) data and reveal significant variation in rock cooling history along-strike: the centre of the footwall yields younger cooling ages than the former tips of earlier fault segments that are now linked. This suggests that low-temperature thermochronology can detect fault interactions along strike. That these former segment boundaries are preserved within exhumed footwall rocks is a function of the relatively recent linkage of the system. Our study highlights that changes in AHe (and potentially AFT) ages associated with the along-strike displacement profile can occur over relatively short horizontal distances (of a few kilometres). This is fundamentally important in the assessment of the vertical cooling history of footwalls in extensional systems: temporal differences in the rate of tectonically driven exhumation at a given location along fault strike may be of greater importance in controlling changes in rates of vertical exhumation than commonly invoked climatic fluctuations

    Fan du Cinéma: Imitation, Europe and The Trip to Italy (2014)

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    his essay considers the role of imitation in Michael Winterbottom’s film The Trip to Italy, with reference to the performances of mimicry by its two protagonists (Steve Coogan and Rob Brydon), but also on the part of the film itself, both as a sequel to The Trip (2010) and through its inter-textual links to earlier works of European and English film, and American-Italian co-production. As I will discuss, this preoccupation with reproduction, situated within a travelogue format, brings into focus a series of related issues concerning the meaning of contemporary film, especially in terms of European cinema in a ‘post-cinematic’ age, as well as the place of cinematic travel in constructing an idea of Europe

    Improving Outcomes in Infants of HIV-Infected Women in a Developing Country Setting

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    Since 1999 GHESKIO, a large voluntary counseling and HIV testing center in Port-au-Prince, Haiti, has had an ongoing collaboration with the Haitian Ministry of Health to reduce the rate of mother to child HIV transmission. There are limited data on the ability to administer complex regimens for reducing mother to child transmission and on risk factors for continued transmission and infant mortality within programmatic settings in developing countries.We analyzed data from 551 infants born to HIV-infected mothers seen at GHESKIO, between 1999 and 2005. HIV-infected mothers and their infants were given "short-course" monotherapy with antiretrovirals for prophylaxis; and, since 2003, highly active antiretroviral therapy (HAART) when clinical or laboratory indications were met. Infected women seen in the pre-treatment era had 27% transmission rates, falling to 10% in this cohort of 551 infants, and to only 1.9% in infants of women on HAART. Mortality rate after HAART introduction (0.12 per year of follow-up [0.08-0.16]) was significantly lower than the period before the availability of such therapy (0.23 [0.16-0.30], P<0.0001). The effects of maternal health, infant feeding, completeness of prophylaxis, and birth weight on mortality and transmission were determined using univariate and multivariate analysis. Infant HIV-1 infection and low birth weight were associated with infant mortality in less than 15 month olds in multivariate analysis.Our findings demonstrate success in prevention of mother-to-child HIV transmission and mortality in a highly resource constrained setting. Elements contributing to programmatic success include provision of HAART in the context of a comprehensive program with pre and postnatal care for both mother and infant

    Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

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    BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

    Population Structure of a Hybrid Clonal Group of Methicillin-Resistant Staphylococcus aureus, ST239-MRSA-III

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    The methicillin-resistant Staphylococcus aureus (MRSA) clonal group known as ST239-MRSA-III is notable for its hybrid origin and for causing sustained hospital epidemics worldwide since the late 1970s. We studied the population structure of this MRSA clonal group using a sample of 111 isolates that were collected over 34 years from 29 countries. Genetic variation was assessed using typing methods and novel ascertainment methods, resulting in approximately 15 kb of sequence from 32 loci for all isolates. A single most parsimonious tree, free of homoplasy, partitioned 28 haplotypes into geographically-associated clades, including prominent European, Asian, and South American clades. The rate of evolution was estimated to be approximately 100× faster than standard estimates for bacteria, and dated the most recent common ancestor of these isolates to the mid-20th century. Associations were discovered between the ST239 phylogeny and the ccrB and dru loci of the methicillin resistance genetic element, SCCmec type III, but not with the accessory components of the element that are targeted by multiplex PCR subtyping tools. In summary, the evolutionary history of ST239 can be characterized by rapid clonal diversification that has left strong evidence of geographic and temporal population structure. SCCmec type III has remained linked to the ST239 chromosome during clonal diversification, but it has undergone homoplasious losses of accessory components. These results provide a population genetics framework for the precise identification of emerging ST239 variants, and invite a re-evaluation of the markers used for subtyping SCCmec
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