Vru (Sub0144) controls expression of proven and putative virulence determinants and alters the ability of Streptococcus uberis to cause disease in dairy cattle

The regulation and control of gene expression in response to differing environmental stimuli is crucial for successful pathogen adaptation and persistence. The regulatory gene vru of Streptococcus uberis encodes a stand-alone response regulator with similarity to the Mga of group A Streptococcus. Mga controls expression of a number of important virulence determinants. Experimental intramammary challenge of dairy cattle with a mutant of S. uberis carrying an inactivating lesion in vru showed reduced ability to colonize the mammary gland and an inability to induce clinical signs of mastitis compared with the wild-type strain. Analysis of transcriptional differences of gene expression in the mutant, determined by microarray analysis, identified a number of coding sequences with altered expression in the absence of Vru. These consisted of known and putative virulence determinants, including Lbp (Sub0145), SclB (Sub1095), PauA (Sub1785) and hasA (Sub1696)

Territorial Tactics: The Socio-spatial Significance of Private Policing Strategies in Cape Town

This paper analyses the policing strategies of private security companies operating in urban space. An existing literature has considered the variety of ways that territory becomes of fundamental importance in the work of public police forces. However, this paper examines territory in the context of private security companies. Drawing on empirical research in Cape Town, it examines how demarcated territories become key subjects in private policing. Private security companies are responsible for a relatively small section of the city, while in contrast the public police ultimately have to see city space as a whole. Hence, private policing strategy becomes one of displacement, especially of so-called undesirables yielding a patchworked public space associated with private enclaves of consumption. The conclusions signal the historical resonances and comparative implications of these political-legal-security dynamics. © 2013 Urban Studies Journal Limited

Mental health in UK Biobank - development, implementation and results from an online questionnaire completed by 157 366 participants: a reanalysis

Background UK Biobank is a well-characterised cohort of over 500 000 participants including genetics, environmental data and imaging. An online mental health questionnaire was designed for UK Biobank participants to expand its potential. Aims Describe the development, implementation and results of this questionnaire. Method An expert working group designed the questionnaire, using established measures where possible, and consulting a patient group. Operational criteria were agreed for defining likely disorder and risk states, including lifetime depression, mania/hypomania, generalised anxiety disorder, unusual experiences and self-harm, and current post-traumatic stress and hazardous/harmful alcohol use. Results A total of 157 366 completed online questionnaires were available by August 2017. Participants were aged 45–82 (53% were ≥65 years) and 57% women. Comparison of self-reported diagnosed mental disorder with a contemporary study shows a similar prevalence, despite respondents being of higher average socioeconomic status. Lifetime depression was a common finding, with 24% (37 434) of participants meeting criteria and current hazardous/harmful alcohol use criteria were met by 21% (32 602), whereas other criteria were met by less than 8% of the participants. There was extensive comorbidity among the syndromes. Mental disorders were associated with a high neuroticism score, adverse life events and long-term illness; addiction and bipolar affective disorder in particular were associated with measures of deprivation. Conclusions The UK Biobank questionnaire represents a very large mental health survey in itself, and the results presented here show high face validity, although caution is needed because of selection bias. Built into UK Biobank, these data intersect with other health data to offer unparalleled potential for crosscutting biomedical research involving mental health

D-Brane Dynamics and NS5 Rings

We consider the classical motion of a probe D-brane moving in the background geometry of a ring of NS5 branes, assuming that the latter are non-dynamical. We analyse the solutions to the Dirac-Born-Infield (DBI) action governing the approximate dynamics of the system. In the near horizon (throat) approximation we find several exact solutions for the probe brane motion. These are compared to numerical solutions obtained in more general cases. One solution of particular interest is when the probe undergoes oscillatory motion through the centre of the ring (and perpendicular to it). By taking the ring radius sufficiently large, this solution should remain stable to any stringy corrections coming from open-strings stretching between the probe and the NS5-branes along the ring.Comment: 17 pages, Latex, 8 figures; References adde

Cannabis use and risk of schizophrenia: a Mendelian randomization study.

Cannabis use is observationally associated with an increased risk of schizophrenia, but whether the relationship is causal is not known. Using a genetic approach, we took 10 independent genetic variants previously identified to associate with cannabis use in 32 330 individuals to determine the nature of the association between cannabis use and risk of schizophrenia. Genetic variants were employed as instruments to recapitulate a randomized controlled trial involving two groups (cannabis users vs nonusers) to estimate the causal effect of cannabis use on risk of schizophrenia in 34 241 cases and 45 604 controls from predominantly European descent. Genetically-derived estimates were compared with a meta-analysis of observational studies reporting ever use of cannabis and risk of schizophrenia or related disorders. Based on the genetic approach, use of cannabis was associated with increased risk of schizophrenia (odds ratio (OR) of schizophrenia for users vs nonusers of cannabis: 1.37; 95% confidence interval (CI), 1.09-1.67; P-value=0.007). The corresponding estimate from observational analysis was 1.43 (95% CI, 1.19-1.67; P-value for heterogeneity =0.76). The genetic markers did not show evidence of pleiotropic effects and accounting for tobacco exposure did not alter the association (OR of schizophrenia for users vs nonusers of cannabis, adjusted for ever vs never smoker: 1.41; 95% CI, 1.09-1.83). This adds to the substantial evidence base that has previously identified cannabis use to associate with increased risk of schizophrenia, by suggesting that the relationship is causal. Such robust evidence may inform public health messages about cannabis use, especially regarding its potential mental health consequences

Exploring the equity of GP practice prescribing rates for selected coronary heart disease drugs: a multiple regression analysis with proxies of healthcare need

Background There is a small, but growing body of literature highlighting inequities in GP practice prescribing rates for many drug therapies. The aim of this paper is to further explore the equity of prescribing for five major CHD drug groups and to explain the amount of variation in GP practice prescribing rates that can be explained by a range of healthcare needs indicators (HCNIs). Methods The study involved a cross-sectional secondary analysis in four primary care trusts (PCTs 1–4) in the North West of England, including 132 GP practices. Prescribing rates (average daily quantities per registered patient aged over 35 years) and HCNIs were developed for all GP practices. Analysis was undertaken using multiple linear regression. Results Between 22–25% of the variation in prescribing rates for statins, beta-blockers and bendrofluazide was explained in the multiple regression models. Slightly more variation was explained for ACE inhibitors (31.6%) and considerably more for aspirin (51.2%). Prescribing rates were positively associated with CHD hospital diagnoses and procedures for all drug groups other than ACE inhibitors. The proportion of patients aged 55–74 years was positively related to all prescribing rates other than aspirin, where they were positively related to the proportion of patients aged >75 years. However, prescribing rates for statins and ACE inhibitors were negatively associated with the proportion of patients aged >75 years in addition to the proportion of patients from minority ethnic groups. Prescribing rates for aspirin, bendrofluazide and all CHD drugs combined were negatively associated with deprivation. Conclusion Although around 25–50% of the variation in prescribing rates was explained by HCNIs, this varied markedly between PCTs and drug groups. Prescribing rates were generally characterised by both positive and negative associations with HCNIs, suggesting possible inequities in prescribing rates on the basis of ethnicity, deprivation and the proportion of patients aged over 75 years (for statins and ACE inhibitors, but not for aspirin)

The diurnal and semidiurnal tides over Ascension Island (° S, 14° W) and their interaction with the stratospheric quasi-biennial oscillation:Studies with meteor radar, eCMAM and WACCM

Horizontal winds in the mesosphere have been measured over Ascension Island (8° S, 14° W) in the tropical mid-Atlantic region throughout the years 2002–2011. The observations were made by a very high frequency (VHF) meteor radar. The observations reveal the presence of atmospheric tides of large amplitude. The observations are analysed to characterise the seasonal and interannual variability of the diurnal and semidiurnal tides. Monthly-mean diurnal tidal amplitudes are found to reach values as large as 48 m s−1 in the meridional component and 41 m s−1 in the zonal. A semiannual seasonal variation is found in diurnal tidal amplitudes with amplitude maxima at the equinoxes and amplitude minima at the solstices. Diurnal tidal meridional vertical wavelengths are generally in the range 24–30 km. The diurnal zonal vertical wavelengths are similar to the meridional, except for the winter months when the zonal vertical wavelengths are much longer, occasionally exceeding 100 km. Semidiurnal amplitudes are observed to be significantly smaller than diurnal amplitudes. Semidiurnal vertical wavelengths range from 20 to more than 100 km. Our observations of tidal amplitudes and phases are compared with the predictions of the extended Canadian Middle Atmosphere Model (eCMAM) and the Whole Atmosphere Community Climate Model (WACCM). Both eCMAM and WACCM reproduce the trend for greater diurnal amplitudes in the meridional component than the zonal. However, eCMAM tends to overestimate meridional amplitudes, while WACCM underestimates both zonal and meridional amplitudes. Vertical wavelength predictions are generally good for both models; however, eCMAM predicts shorter diurnal zonal vertical wavelengths than are observed in winter, while WACCM predicts longer zonal vertical wavelengths than observed for the semidiurnal tide for most months. Semidiurnal amplitude predictions are generally good for both models. It is found that larger-than-average diurnal and semidiurnal tidal amplitudes occur when the stratospheric quasi-biennial oscillation (QBO) at 10 hPa is eastwards, and smaller-than-average amplitudes occur when it is westwards. Correlations between the amplitude perturbations and the El Niño Southern Oscillation are also found. The precise mechanism for these correlations remains unclear

Clinical predictors of rectal lymphogranuloma venereum infection: results from a multicentre case-control study in the UK

Objective: Since 2003, over 2000 cases of lymphogranuloma venereum (LGV) have been diagnosed in the UK in men who have sex with men (MSM). Most cases present with proctitis, but there are limited data on how to differentiate clinically between LGV and other pathology. We analysed the clinical presentations of rectal LGV in MSM to identify clinical characteristics predictive of LGV proctitis and produced a clinical prediction model. Design: A prospective multicentre case–control study was conducted at six UK hospitals from 2008 to 2010. Cases of rectal LGV were compared with controls with rectal symptoms but without LGV. Methods: Data from 98 LGV cases and 81 controls were collected from patients and clinicians using computer-assisted self-interviews and clinical report forms. Univariate and multivariate logistic regression was used to compare symptoms and signs. Clinical prediction models for LGV were compared using receiver operating curves. Results: Tenesmus, constipation, anal discharge and weight loss were significantly more common in cases than controls. In multivariate analysis, tenesmus and constipation alone were suggestive of LGV (OR 2.98, 95% CI 0.99 to 8.98 and 2.87, 95% CI 1.01 to 8.15, respectively) and that tenesmus alone or in combination with constipation was a significant predictor of LGV (OR 6.97, 95% CI 2.71 to 17.92). The best clinical prediction was having one or more of tenesmus, constipation and exudate on proctoscopy, with a sensitivity of 77% and specificity of 65%. Conclusions: This study indicates that tenesmus alone or in combination with constipation makes a diagnosis of LGV in MSM presenting with rectal symptoms more likely