Multimorbidity in bipolar disorder and under-treatment of cardiovascular disease: a cross sectional study

Background: Individuals with serious mental disorders experience poor physical health, especially increased rates of cardiometabolic morbidity and premature morbidity. Recent evidence suggests that individuals with schizophrenia have numerous comorbid physical conditions which may be under-recorded and under-treated but to date very few studies have explored this issue for bipolar disorder. Methods:We conducted a cross-sectional analysis of a dataset of 1,751,841 registered patients within 314 primary-care practices in Scotland, U.K. Bipolar disorder was identified using Read Codes recorded within electronic medical records. Data on 32 common chronic physical conditions were also assessed. Potential prescribing inequalities were evaluated by analyzing prescribing data for coronary heart disease (CHD) and hypertension. Results: Compared to controls, individuals with bipolar disorder were significantly less likely to have no recorded physical conditions (OR 0.59, 95% CI 0.54-0.63) and significantly more likely to have one physical condition (OR 1.27, 95% CI 1.16-1.39), two physical conditions (OR 1.45, 95% CI 1.30-1.62) and three or more physical conditions (OR 1.44, 95% CI 1.30-1.64). People with bipolar disorder also had higher rates of thyroid disorders, chronic kidney disease, chronic pain, chronic obstructive airways disease and diabetes but, surprisingly, lower recorded rates of hypertension and atrial fibrillation. People with bipolar disorder and comorbid CHD or hypertension were significantly more likely to be prescribed no antihypertensive or cholesterol-lowering medications compared to controls, and bipolar individuals with CHD or hypertension were significantly less likely to be on 2 or more antihypertensive agents. Conclusions: Individuals with bipolar disorder are similar to individuals with schizophrenia in having a wide range of comorbid and multiple physical health conditions. They are also less likely than controls to have a primary-care record of cardiovascular conditions such as hypertension and atrial fibrillation. Those with a recorded diagnosis of CHD or hypertension were less likely to be treated with cardiovascular medications and were treated less intensively. This study highlights the high physical healthcare needs of people with bipolar disorder, and provides evidence for a systematic under-recognition and under-treatment of cardiovascular disease in this group

A broad distribution of the alternative oxidase in microsporidian parasites

Microsporidia are a group of obligate intracellular parasitic eukaryotes that were considered to be amitochondriate until the recent discovery of highly reduced mitochondrial organelles called mitosomes. Analysis of the complete genome of Encephalitozoon cuniculi revealed a highly reduced set of proteins in the organelle, mostly related to the assembly of ironsulphur clusters. Oxidative phosphorylation and the Krebs cycle proteins were absent, in keeping with the notion that the microsporidia and their mitosomes are anaerobic, as is the case for other mitosome bearing eukaryotes, such as Giardia. Here we provide evidence opening the possibility that mitosomes in a number of microsporidian lineages are not completely anaerobic. Specifically, we have identified and characterized a gene encoding the alternative oxidase (AOX), a typically mitochondrial terminal oxidase in eukaryotes, in the genomes of several distantly related microsporidian species, even though this gene is absent from the complete genome of E. cuniculi. In order to confirm that these genes encode functional proteins, AOX genes from both A. locustae and T. hominis were over-expressed in E. coli and AOX activity measured spectrophotometrically using ubiquinol-1 (UQ-1) as substrate. Both A. locustae and T. hominis AOX proteins reduced UQ-1 in a cyanide and antimycin-resistant manner that was sensitive to ascofuranone, a potent inhibitor of the trypanosomal AOX. The physiological role of AOX microsporidia may be to reoxidise reducing equivalents produced by glycolysis, in a manner comparable to that observed in trypanosome

MMOG Game-Based Collaborative Learning: An Exploratory Study and its Research Potential

This study aims to theoretically explore whether Massively Multiplayer Online Game (MMOG) is an effective collaborative learning environment, empirically examine the occurrence of knowledge creation in MMOG game-play, and conceptually advocate the research potential of MMOG game-based collaborative learning. Although a growing number of researchers have started to use MMOG as a new generation of educational platform, the study of the theoretical justification for the occurrence of collaborative learning behavior in MMOG are still under-researched. To bridge this gap, this study integrates MMOG and technology-based collaborative learning streams of research to theoretically explore whether MMOG is an effective learning platform based on Alavi’s three attributes of effective technology-mediated collaborative learning environment. In order to examine the occurrence of knowledge creation in the MMOG game-based collaborative learning, we propose definitions of explicit and tacit knowledge in MMOG. Then we conduct an exploratory study using a semi-structural interview approach to collect qualitative data, in order to support our stipulation of the occurrence of four modes of knowledge conversion in MMOG game-play based on the Nonaka’s dynamic theory of organization creation. According to our research findings, this paper advocates research potential of MMOG game-based collaborative learning in future research

Effect of maternal Schistosoma mansoni infection and praziquantel treatment during pregnancy on Schistosoma mansoni infection and immune responsiveness among offspring at age five years.

INTRODUCTION: Offspring of Schistosoma mansoni-infected women in schistosomiasis-endemic areas may be sensitised in-utero. This may influence their immune responsiveness to schistosome infection and schistosomiasis-associated morbidity. Effects of praziquantel treatment of S. mansoni during pregnancy on risk of S. mansoni infection among offspring, and on their immune responsiveness when they become exposed to S. mansoni, are unknown. Here we examined effects of praziquantel treatment of S. mansoni during pregnancy on prevalence of S. mansoni and immune responsiveness among offspring at age five years. METHODS: In a trial in Uganda (ISRCTN32849447, http://www.controlled-trials.com/ISRCTN32849447/elliott), offspring of women treated with praziquantel or placebo during pregnancy were examined for S. mansoni infection and for cytokine and antibody responses to SWA and SEA, as well as for T cell expression of FoxP3, at age five years. RESULTS: Of the 1343 children examined, 32 (2.4%) had S. mansoni infection at age five years based on a single stool sample. Infection prevalence did not differ between children of treated or untreated mothers. Cytokine (IFNγ, IL-5, IL-10 and IL-13) and antibody (IgG1, Ig4 and IgE) responses to SWA and SEA, and FoxP3 expression, were higher among infected than uninfected children. Praziquantel treatment of S. mansoni during pregnancy had no effect on immune responses, with the exception of IL-10 responses to SWA, which was higher in offspring of women that received praziquantel during pregnancy than those who did not. CONCLUSION: We found no evidence that maternal S. mansoni infection and its treatment during pregnancy influence prevalence and intensity of S. mansoni infection or effector immune response to S. mansoni infection among offspring at age five years, but the observed effects on IL-10 responses to SWA suggest that maternal S. mansoni and its treatment during pregnancy may affect immunoregulatory responsiveness in childhood schistosomiasis. This might have implications for pathogenesis of the disease

Targeted hepatitis C antibody testing interventions: a systematic review and meta-analysis

Testing for hepatitis C virus (HCV) infection may reduce the risk of liver-related morbidity, by facilitating earlier access to treatment and care. This review investigated the effectiveness of targeted testing interventions on HCV case detection, treatment uptake, and prevention of liver-related morbidity. A literature search identified studies published up to 2013 that compared a targeted HCV testing intervention (targeting individuals or groups at increased risk of HCV) with no targeted intervention, and results were synthesised using meta-analysis. Exposure to a targeted testing intervention, compared to no targeted intervention, was associated with increased cases detected [number of studies (n) = 14; pooled relative risk (RR) 1.7, 95 % CI 1.3, 2.2] and patients commencing therapy (n = 4; RR 3.3, 95 % CI 1.1, 10.0). Practitioner-based interventions increased test uptake and cases detected (n = 12; RR 3.5, 95 % CI 2.5, 4.8; and n = 10; RR 2.2, 95 % CI 1.4, 3.5, respectively), whereas media/information-based interventions were less effective (n = 4; RR 1.5, 95 % CI 0.7, 3.0; and n = 4; RR 1.3, 95 % CI 1.0, 1.6, respectively). This meta-analysis provides for the first time a quantitative assessment of targeted HCV testing interventions, demonstrating that these strategies were effective in diagnosing cases and increasing treatment uptake. Strategies involving practitioner-based interventions yielded the most favourable outcomes. It is recommended that testing should be targeted at and offered to individuals who are part of a population with high HCV prevalence, or who have a history of HCV risk behaviour

Audit Committee Financial Experts: A Closer Examination Using Firm Designations

The Sarbanes-Oxley Act (SOX) requires the disclosure of whether the audit committee has a financial expert. We examine disclosures related to audit committee financial experts (ACFEs) in the first year that this disclosure requirement is in effect. We find that virtually all companies disclose whether an ACFE is on the audit committee, although the transparency of the disclosure regarding the ACFE’s background is limited. We also find that most ACFEs do not have a background in accounting or finance, although there are notable differences between stock exchanges on this dimension. In addition, we find that companies designate ACFEs who would not have been identified using extant research methods, and companies fail to voluntarily designate many individuals who appear to qualify as an ACFE, particularly if another audit committee member is already designated as an ACFE. Thus, some companies appear to be extremely conservative in designating directors as ACFEs, possibly due to concerns about the legal liability faced by designated ACFEs. Finally, we identify certain company characteristics that are associated with the designation or type of financial expert on the audit committee

Measurement of the inclusive and dijet cross-sections of b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector

The inclusive and dijet production cross-sections have been measured for jets containing b-hadrons (b-jets) in proton-proton collisions at a centre-of-mass energy of sqrt(s) = 7 TeV, using the ATLAS detector at the LHC. The measurements use data corresponding to an integrated luminosity of 34 pb^-1. The b-jets are identified using either a lifetime-based method, where secondary decay vertices of b-hadrons in jets are reconstructed using information from the tracking detectors, or a muon-based method where the presence of a muon is used to identify semileptonic decays of b-hadrons inside jets. The inclusive b-jet cross-section is measured as a function of transverse momentum in the range 20 < pT < 400 GeV and rapidity in the range |y| < 2.1. The bbbar-dijet cross-section is measured as a function of the dijet invariant mass in the range 110 < m_jj < 760 GeV, the azimuthal angle difference between the two jets and the angular variable chi in two dijet mass regions. The results are compared with next-to-leading-order QCD predictions. Good agreement is observed between the measured cross-sections and the predictions obtained using POWHEG + Pythia. MC@NLO + Herwig shows good agreement with the measured bbbar-dijet cross-section. However, it does not reproduce the measured inclusive cross-section well, particularly for central b-jets with large transverse momenta.Comment: 10 pages plus author list (21 pages total), 8 figures, 1 table, final version published in European Physical Journal

CT694 and pgp3 as Serological Tools for Monitoring Trachoma Programs.

Defining endpoints for trachoma programs can be a challenge as clinical signs of infection may persist in the absence of detectable bacteria. Antibody-based tests may provide an alternative testing strategy for surveillance during terminal phases of the program. Antibody-based assays, in particular ELISAs, have been shown to be useful to document C. trachomatis genital infections, but have not been explored extensively for ocular C. trachomatis infections. An antibody-based multiplex assay was used to test two C. trachomatis antigens, pgp3 and CT694, for detection of trachoma antibodies in bloodspots from Tanzanian children (n = 160) collected after multiple rounds of mass azithromycin treatment. Using samples from C. trachomatis-positive (by PCR) children from Tanzania (n = 11) and control sera from a non-endemic group of U.S. children (n = 122), IgG responses to both pgp3 and CT694 were determined to be 91% sensitive and 98% specific. Antibody responses of Tanzanian children were analyzed with regard to clinical trachoma, PCR positivity, and age. In general, children with more intense ocular pathology (TF/TI = 2 or most severe) had a higher median antibody response to pgp3 (p = 0.0041) and CT694 (p = 0.0282) than those with normal exams (TF/TI = 0). However, 44% of children with no ocular pathology tested positive for antibody, suggesting prior infection. The median titer of antibody responses for children less than three years of age was significantly lower than those of older children. (p<0.0001 for both antigens). The antibody-based multiplex assay is a sensitive and specific additional tool for evaluating trachoma transmission. The assay can also be expanded to include antigens representing different diseases, allowing for a robust assay for monitoring across NTD programs

Regulation of mammary gland branching morphogenesis by the extracellular matrix and its remodeling enzymes.

A considerable body of research indicates that mammary gland branching morphogenesis is dependent, in part, on the extracellular matrix (ECM), ECM-receptors, such as integrins and other ECM receptors, and ECM-degrading enzymes, including matrix metalloproteinases (MMPs) and their inhibitors, tissue inhibitors of metalloproteinases (TIMPs). There is some evidence that these ECM cues affect one or more of the following processes: cell survival, polarity, proliferation, differentiation, adhesion, and migration. Both three-dimensional culture models and genetic manipulations of the mouse mammary gland have been used to study the signaling pathways that affect these processes. However, the precise mechanisms of ECM-directed mammary morphogenesis are not well understood. Mammary morphogenesis involves epithelial 'invasion' of adipose tissue, a process akin to invasion by breast cancer cells, although the former is a highly regulated developmental process. How these morphogenic pathways are integrated in the normal gland and how they become dysregulated and subverted in the progression of breast cancer also remain largely unanswered questions

Landmarking the brain for geometric morphometric analysis: An error study

Neuroanatomic phenotypes are often assessed using volumetric analysis. Although powerful and versatile, this approach is limited in that it is unable to quantify changes in shape, to describe how regions are interrelated, or to determine whether changes in size are global or local. Statistical shape analysis using coordinate data from biologically relevant landmarks is the preferred method for testing these aspects of phenotype. To date, approximately fifty landmarks have been used to study brain shape. Of the studies that have used landmark-based statistical shape analysis of the brain, most have not published protocols for landmark identification or the results of reliability studies on these landmarks. The primary aims of this study were two-fold: (1) to collaboratively develop detailed data collection protocols for a set of brain landmarks, and (2) to complete an intra- and inter-observer validation study of the set of landmarks. Detailed protocols were developed for 29 cortical and subcortical landmarks using a sample of 10 boys aged 12 years old. Average intra-observer error for the final set of landmarks was 1.9 mm with a range of 0.72 mm-5.6 mm. Average inter-observer error was 1.1 mm with a range of 0.40 mm-3.4 mm. This study successfully establishes landmark protocols with a minimal level of error that can be used by other researchers in the assessment of neuroanatomic phenotypes. © 2014 Chollet et al