619 research outputs found

    The effect of cannabis use and cognitive reserve on age at onset and psychosis outcomes in first-episode schizophrenia

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    Cannabis use is associated with a younger age at onset of psychosis, an indicator of poor prognosis, but better cognitive function, a positive prognostic indicator. We aimed to clarify the role of age at onset and cognition on outcomes in cannabis users with first-episode schizophrenia as well as the effect of cannabis dose and cessation of use

    Expression and DNA methylation of TNF, IFNG and FOXP3 in colorectal cancer and their prognostic significance.

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    BACKGROUND: Colorectal cancer (CRC) progression is associated with suppression of host cell-mediated immunity and local immune escape mechanisms. Our aim was to assess the immune function in terms of expression of TNF, IFNG and FOXP3 in CRC. METHODS: Sixty patients with CRC and 15 matched controls were recruited. TaqMan quantitative PCR and methylation-specific PCR was performed for expression and DNA methylation analysis of TNF, IFNG and FOXP3. Survival analysis was performed over a median follow-up of 48 months. RESULTS: TNF was suppressed in tumour and IFNG was suppressed in peripheral blood mononuclear cells (PBMCs) of patients with CRC. Tumours showed enhanced expression of FOXP3 and was significantly higher when tumour size was >38 mm (median tumour size; P=0.006, Mann-Whitney U-test). Peripheral blood mononuclear cell IFNG was suppressed in recurrent CRC (P=0.01). Methylated TNFpromoter (P=0.003) and TNFexon1 (P=0.001) were associated with significant suppression of TNF in tumours. Methylated FOXP3cpg was associated with significant suppression of FOXP3 in both PBMC (P=0.018) and tumours (P=0.010). Reduced PBMC FOXP3 expression was associated with significantly worse overall survival (HR=8.319, P=0.019). CONCLUSIONS: We have detected changes in the expression of immunomodulatory genes that could act as biomarkers for prognosis and future immunotherapeutic strategies

    Adult meningitis in a setting of high HIV and TB prevalence: findings from 4961 suspected cases

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    BACKGROUND: The presentation and causes of adult meningitis in South Africa have changed substantially as a result of HIV. Knowledge of aetiology and laboratory findings in patients presenting with meningitis are important in guiding management. We performed a retrospective study to determine these findings in a setting of high HIV and TB prevalence in Cape Town. METHODS: Patients undergoing lumbar punctures between 1st January 2006 and 31st December 2008 at a public sector referral hospital were studied. Cases were classified by microbiological diagnosis, or in the absence of definitive microbiology as 1) normal CSF (neutrophils or =1.5 mmol/L), 2) minor abnormalities (neutrophils 2-5, lymphocytes 6-20, protein 0.51-1.0, glucose 1.0-1.49) or 3) markedly abnormal (neutrophils>5, lymphocytes>20, protein>1.0, glucose<1.0). RESULTS: 5578 LPs were performed on 4549 patients, representing 4961 clinical episodes. Of these, 2293 had normal CSF and 931 had minor abnormalities and no aetiology identified. Of the remaining 1737, microbiological diagnoses were obtained in 820 (47%). Cryptococcus accounted for 63% (514) of microbiological diagnoses, TB for 28% (227), bacterial meningitis for 8% (68). Of the remaining 917 who had marked abnormalities, the majority (59%) had a sterile lymphocytic CSF. Of note 16% (81) patients with confirmed Cryptococcus, 5% (12) with TB and 4% (3) with bacterial meningitis had normal CSF cell-counts and biochemistry. CONCLUSIONS: Cryptococcal and tuberculous meningitis are now the commonest causes of adult meningitis in this setting. TB meningitis is probably underdiagnosed by laboratory investigation, as evidence by the large numbers presenting with sterile lymphocytic markedly abnormal CSFs

    Single Parenting and Child Behavior Problems in Kindergarten

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    Two waves of data from a sample of 89 poor and near-poor single black mothers and their preschool children were used to study the influences of parenting stress, physical discipline practices, and nonresident fathers’ relations with their children on behavior problems in kindergarten. The results indicate that higher levels of parent stress, more frequent spanking, and less frequent father–child contact at time 1 were associated with increased teacher-reported behavior problems at time 2. In addition, more frequent contact between nonresident biological fathers and their children moderated the negative effect of harsh discipline by mothers on subsequent child behavior problems. Specifically, when contact with the father was low, maternal spanking resulted in elevated levels of behavior problems; with average contact, this negative effect of spanking was muted; and with high contact, spanking was not associated with increased behavior problems in kindergarten. The implications of these findings for future research and policy are discussed

    Prevalence of physical frailty, including risk factors, up to 1 year after hospitalisation for COVID-19 in the UK: a multicentre, longitudinal cohort study.

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    BACKGROUND: The scale of COVID-19 and its well documented long-term sequelae support a need to understand long-term outcomes including frailty. METHODS: This prospective cohort study recruited adults who had survived hospitalisation with clinically diagnosed COVID-19 across 35 sites in the UK (PHOSP-COVID). The burden of frailty was objectively measured using Fried's Frailty Phenotype (FFP). The primary outcome was the prevalence of each FFP group-robust (no FFP criteria), pre-frail (one or two FFP criteria) and frail (three or more FFP criteria)-at 5 months and 1 year after discharge from hospital. For inclusion in the primary analysis, participants required complete outcome data for three of the five FFP criteria. Longitudinal changes across frailty domains are reported at 5 months and 1 year post-hospitalisation, along with risk factors for frailty status. Patient-perceived recovery and health-related quality of life (HRQoL) were retrospectively rated for pre-COVID-19 and prospectively rated at the 5 month and 1 year visits. This study is registered with ISRCTN, number ISRCTN10980107. FINDINGS: Between March 5, 2020, and March 31, 2021, 2419 participants were enrolled with FFP data. Mean age was 57.9 (SD 12.6) years, 933 (38.6%) were female, and 429 (17.7%) had received invasive mechanical ventilation. 1785 had measures at both timepoints, of which 240 (13.4%), 1138 (63.8%) and 407 (22.8%) were frail, pre-frail and robust, respectively, at 5 months compared with 123 (6.9%), 1046 (58.6%) and 616 (34.5%) at 1 year. Factors associated with pre-frailty or frailty were invasive mechanical ventilation, older age, female sex, and greater social deprivation. Frail participants had a larger reduction in HRQoL compared with before their COVID-19 illness and were less likely to describe themselves as recovered. INTERPRETATION: Physical frailty and pre-frailty are common following hospitalisation with COVID-19. Improvement in frailty was seen between 5 and 12 months although two-thirds of the population remained pre-frail or frail. This suggests comprehensive assessment and interventions targeting pre-frailty and frailty beyond the initial illness are required. FUNDING: UK Research and Innovation and National Institute for Health Research

    Jet energy measurement with the ATLAS detector in proton-proton collisions at root s=7 TeV

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    The jet energy scale and its systematic uncertainty are determined for jets measured with the ATLAS detector at the LHC in proton-proton collision data at a centre-of-mass energy of √s = 7TeV corresponding to an integrated luminosity of 38 pb-1. Jets are reconstructed with the anti-kt algorithm with distance parameters R=0. 4 or R=0. 6. Jet energy and angle corrections are determined from Monte Carlo simulations to calibrate jets with transverse momenta pT≥20 GeV and pseudorapidities {pipe}η{pipe}<4. 5. The jet energy systematic uncertainty is estimated using the single isolated hadron response measured in situ and in test-beams, exploiting the transverse momentum balance between central and forward jets in events with dijet topologies and studying systematic variations in Monte Carlo simulations. The jet energy uncertainty is less than 2. 5 % in the central calorimeter region ({pipe}η{pipe}<0. 8) for jets with 60≤pT<800 GeV, and is maximally 14 % for pT<30 GeV in the most forward region 3. 2≤{pipe}η{pipe}<4. 5. The jet energy is validated for jet transverse momenta up to 1 TeV to the level of a few percent using several in situ techniques by comparing a well-known reference such as the recoiling photon pT, the sum of the transverse momenta of tracks associated to the jet, or a system of low-pT jets recoiling against a high-pT jet. More sophisticated jet calibration schemes are presented based on calorimeter cell energy density weighting or hadronic properties of jets, aiming for an improved jet energy resolution and a reduced flavour dependence of the jet response. The systematic uncertainty of the jet energy determined from a combination of in situ techniques is consistent with the one derived from single hadron response measurements over a wide kinematic range. The nominal corrections and uncertainties are derived for isolated jets in an inclusive sample of high-pT jets. Special cases such as event topologies with close-by jets, or selections of samples with an enhanced content of jets originating from light quarks, heavy quarks or gluons are also discussed and the corresponding uncertainties are determined. © 2013 CERN for the benefit of the ATLAS collaboration

    Prevalence of swallow, communication, voice and cognitive compromise following hospitalisation for COVID-19: the PHOSP-COVID analysis

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    Objective: Identify prevalence of self-reported swallow, communication, voice and cognitive compromise following hospitalisation for COVID-19. Design: Multicentre prospective observational cohort study using questionnaire data at visit 1 (2–7 months post discharge) and visit 2 (10–14 months post discharge) from hospitalised patients in the UK. Lasso logistic regression analysis was undertaken to identify associations. Setting: 64 UK acute hospital Trusts. Participants: Adults aged >18 years, discharged from an admissions unit or ward at a UK hospital with COVID-19. Main outcome measures: Self-reported swallow, communication, voice and cognitive compromise. Results: Compromised swallowing post intensive care unit (post-ICU) admission was reported in 20% (188/955); 60% with swallow problems received invasive mechanical ventilation and were more likely to have undergone proning (p=0.039). Voice problems were reported in 34% (319/946) post-ICU admission who were more likely to have received invasive (p<0.001) or non-invasive ventilation (p=0.001) and to have been proned (p<0.001). Communication compromise was reported in 23% (527/2275) univariable analysis identified associations with younger age (p<0.001), female sex (p<0.001), social deprivation (p<0.001) and being a healthcare worker (p=0.010). Cognitive issues were reported by 70% (1598/2275), consistent at both visits, at visit 1 respondents were more likely to have higher baseline comorbidities and at visit 2 were associated with greater social deprivation (p<0.001). Conclusion: Swallow, communication, voice and cognitive problems were prevalent post hospitalisation for COVID-19, alongside whole system compromise including reduced mobility and overall health scores. Research and testing of rehabilitation interventions are required at pace to explore these issues

    Barriers to asymptomatic screening and other STD services for adolescents and young adults: focus group discussions

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    BACKGROUND: Sexually transmitted diseases (STDs) are a major public health problem among young people and can lead to the spread of HIV. Previous studies have primarily addressed barriers to STD care for symptomatic patients. The purpose of our study was to identify perceptions about existing barriers to and ideal services for STDs, especially asymptomatic screening, among young people in a southeastern community. METHODS: Eight focus group discussions including 53 White, African American, and Latino youth (age 14–24) were conducted. RESULTS: Perceived barriers to care included lack of knowledge of STDs and available services, cost, shame associated with seeking services, long clinic waiting times, discrimination, and urethral specimen collection methods. Perceived features of ideal STD services included locations close to familiar places, extended hours, and urine-based screening. Television was perceived as the most effective route of disseminating STD information. CONCLUSIONS: Further research is warranted to evaluate improving convenience, efficiency, and privacy of existing services; adding urine-based screening and new services closer to neighborhoods; and using mass media to disseminate STD information as strategies to increase STD screening
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