Adult North Star Network (ANSN): Consensus Guideline For The Standard Of Care Of Adults With Duchenne Muscular Dystrophy

There are growing numbers of adults with Duchenne Muscular Dystrophy living well into their fourth decade. These patients have complex medical needs that to date have not been addressed in the International standards of care. We sought to create a consensus based standard of care through a series of multi-disciplinary workshops with specialists from a wide range of clinical areas: Neurology, Cardiology, Respiratory Medicine, Gastroenterology, Endocrinology, Palliative Care Medicine, Rehabilitation, Renal, Anaesthetics and Clinical Psychology. Detailed reports of evidence reviewed and the consensus building process were produced following each workshop and condensed into this final document which was approved by all members of the Adult North Star Network including service users. The aim of this document is to provide a framework to improve clinical services and multi-disciplinary care for adults living with Duchenne Muscular Dystrophy

Serotonin tranporter methylation and response to cognitive behaviour therapy in children with anxiety disorders

Anxiety disorders that are the most commonly occurring psychiatric disorders in childhood, are associated with a range of social and educational impairments and often continue into adulthood. Cognitive behaviour therapy (CBT) is an effective treatment option for the majority of cases, although up to 35-45% of children do not achieve remission. Recent research suggests that some genetic variants may be associated with a more beneficial response to psychological therapy. Epigenetic mechanisms such as DNA methylation work at the interface between genetic and environmental influences. Furthermore, epigenetic alterations at the serotonin transporter (SERT) promoter region have been associated with environmental influences such as stressful life experiences. In this study, we measured DNA methylation upstream of SERT in 116 children with an anxiety disorder, before and after receiving CBT. Change during treatment in percentage DNA methylation was significantly different in treatment responders vs nonresponders. This effect was driven by one CpG site in particular, at which responders increased in methylation, whereas nonresponders showed a decrease in DNA methylation. This is the first study to demonstrate differences in SERT methylation change in association with response to a purely psychological therapy. These findings confirm that biological changes occur alongside changes in symptomatology following a psychological therapy such as CBT

MSH3 polymorphisms and protein levels affect CAG repeat instability in huntington's disease mice

Expansions of trinucleotide CAG/CTG repeats in somatic tissues are thought to contribute to ongoing disease progression through an affected individual's life with Huntington's disease or myotonic dystrophy. Broad ranges of repeat instability arise between individuals with expanded repeats, suggesting the existence of modifiers of repeat instability. Mice with expanded CAG/CTG repeats show variable levels of instability depending upon mouse strain. However, to date the genetic modifiers underlying these differences have not been identified. We show that in liver and striatum the R6/1 Huntington's disease (HD) (CAG)~100 transgene, when present in a congenic C57BL/6J (B6) background, incurred expansion-biased repeat mutations, whereas the repeat was stable in a congenic BALB/cByJ (CBy) background. Reciprocal congenic mice revealed the Msh3 gene as the determinant for the differences in repeat instability. Expansion bias was observed in congenic mice homozygous for the B6 Msh3 gene on a CBy background, while the CAG tract was stabilized in congenics homozygous for the CBy Msh3 gene on a B6 background. The CAG stabilization was as dramatic as genetic deficiency of Msh2. The B6 and CBy Msh3 genes had identical promoters but differed in coding regions and showed strikingly different protein levels. B6 MSH3 variant protein is highly expressed and associated with CAG expansions, while the CBy MSH3 variant protein is expressed at barely detectable levels, associating with CAG stability. The DHFR protein, which is divergently transcribed from a promoter shared by the Msh3 gene, did not show varied levels between mouse strains. Thus, naturally occurring MSH3 protein polymorphisms are modifiers of CAG repeat instability, likely through variable MSH3 protein stability. Since evidence supports that somatic CAG instability is a modifier and predictor of disease, our data are consistent with the hypothesis that variable levels of CAG instability associated with polymorphisms of DNA repair genes may have prognostic implications for various repeat-associated diseases

Production of phi mesons at mid-rapidity in sqrt(s_NN) = 200 GeV Au+Au collisions at RHIC

We present the first results of meson production in the K^+K^- decay channel from Au+Au collisions at sqrt(s_NN) = 200 GeV as measured at mid-rapidity by the PHENIX detector at RHIC. Precision resonance centroid and width values are extracted as a function of collision centrality. No significant variation from the PDG accepted values is observed. The transverse mass spectra are fitted with a linear exponential function for which the derived inverse slope parameter is seen to be constant as a function of centrality. These data are also fitted by a hydrodynamic model with the result that the freeze-out temperature and the expansion velocity values are consistent with the values previously derived from fitting single hadron inclusive data. As a function of transverse momentum the collisions scaled peripheral.to.central yield ratio RCP for the is comparable to that of pions rather than that of protons. This result lends support to theoretical models which distinguish between baryons and mesons instead of particle mass for explaining the anomalous proton yield.Comment: 326 authors, 24 pages text, 23 figures, 6 tables, RevTeX 4. To be submitted to Physical Review C as a regular article. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm

Does Time Since Immigration Modify Neighborhood Deprivation Gradients in Preterm Birth? A Multilevel Analysis

Immigrants’ health is jointly influenced by their pre- and post-migration exposures, but how these two influences operate with increasing duration of residence has not been well-researched. We aimed to examine how the influence of maternal country of birth and neighborhood deprivation effects, if any, change over time since migration and how neighborhood effects among immigrants compare with those observed in the Canadian-born population. Birth data from Ontario hospital records (2002–2007) were linked with an official Canadian immigration database (1985–2000). The outcome measure was preterm birth. Neighborhoods were ranked according to a neighborhood deprivation index developed for Canadian urban areas and collapsed into tertiles of approximately equal size. Time since immigration was measured from the date of arrival to Canada to the date of delivery, ranging from 1 to 22 years. We used cross-classified random effect models to simultaneously account for the membership of births (N = 83,233) to urban neighborhoods (N = 1,801) and maternal countries of birth (N = 168). There were no differences in preterm birth between neighborhood deprivation tertiles among immigrants with less than 15 years of residence. Among immigrants with 15 years of stay or more, the adjusted absolute risk difference (ARD%, 95% confidence interval) between high-deprived (tertile 3) and low-deprived (tertile 1) neighborhoods was 1.86 (0.68, 2.98), while the ARD% observed among the Canadian-born (N = 314,237) was 1.34 (1.11, 1.57). Time since migration modifies the neighborhood deprivation gradient in preterm birth among immigrants living in Ontario cities. Immigrants reached the level of inequalities in preterm birth observed at the neighborhood level among the Canadian-born after 14 years of stay, but neighborhoods did not influence preterm birth among more recent immigrants, for whom the maternal country of birth was more predictive of preterm birth

Rapidity and Centrality Dependence of Proton and Anti-proton Production from Au+Au Collisions at sqrt(sNN) = 130GeV

We report on the rapidity and centrality dependence of proton and anti-proton transverse mass distributions from Au+Au collisions at sqrt(sNN) = 130GeV as measured by the STAR experiment at RHIC. Our results are from the rapidity and transverse momentum range of |y|<0.5 and 0.35 <p_t<1.00GeV/c. For both protons and anti-protons, transverse mass distributions become more convex from peripheral to central collisions demonstrating characteristics of collective expansion. The measured rapidity distributions and the mean transverse momenta versus rapidity are flat within |y|<0.5. Comparisons of our data with results from model calculations indicate that in order to obtain a consistent picture of the proton(anti-proton) yields and transverse mass distributions the possibility of pre-hadronic collective expansion may have to be taken into account.Comment: 4 pages, 3 figures, 1 table, submitted to PR

The joint influence of area income, income inequality, and immigrant density on adverse birth outcomes: a population-based study

<p>Abstract</p> <p>Background</p> <p>The association between area characteristics and birth outcomes is modified by race. Whether such associations vary according to social class indicators beyond race has not been assessed.</p> <p>Methods</p> <p>This study evaluated effect modification by maternal birthplace and education of the relationship between neighbourhood characteristics and birth outcomes of newborns from 1999–2003 in the province of Québec, Canada (N = 353,120 births). Areas (N = 143) were defined as administrative local health service delivery districts. Multi-level logistic regression was used to model the association between three area characteristics (median household income, immigrant density and income inequality) and the two outcomes preterm birth (PTB) and small-for-gestational age (SGA) birth. Effect modification by social class indicators was evaluated in analyses stratified according to maternal birthplace and education.</p> <p>Results</p> <p>Relative to the lowest tertile, high median household income was associated with SGA birth among Canadian-born mothers (odds ratio (OR) 1.13, 95% confidence interval (CI) 1.06, 1.20) and mothers with high school education or less (OR 1.13, 95% CI 1.02, 1.24). Associations between median household income and PTB were weaker. Relative to the highest tertile, low immigrant density was associated with a lower odds of PTB among foreign-born mothers (OR 0.79, 95% CI 0.63, 1.00) but a higher odds of PTB among Canadian-born mothers (OR 1.14, 95% CI 1.07, 1.21). Associations with income inequality were weak or absent.</p> <p>Conclusion</p> <p>The association between area factors and birth outcomes is modified by maternal birthplace and education. Studies have found that race interacts in a similar manner. Public health policies focussed on perinatal health must consider the interaction between individual and area characteristics.</p

Comparison of children's self-reports of depressive symptoms among different family interaction types in northern Taiwan

<p>Abstract</p> <p>Background</p> <p>Previous research has shown that family interactions are associated with depressive symptoms in children. However, detailed classifications of family interaction types have not been studied thoroughly. This study aims to understand the types of family interactions children experience and to identify the specific types of family interactions that are associated with a higher risk of depressive symptoms in children.</p> <p>Methods</p> <p>Data used in the study was collected as part of the Child and Adolescent Behavior in Long term Evolution (CABLE) project in 2003. CABLE is a longitudinal cohort study that commenced in 2001 and collects data annually from children in Taipei city and Hsinchu county in northern Taiwan. The data analyzed in this study was that obtained from the sixth graders (aged 11 to 12 years old) in 2003. Of the 2,449 sixth graders, 51.2% were boys and 48.8% were girls. Factor analysis and cluster analysis were used to investigate the types of family interactions. One way ANOVA was used to establish the relationship between family interaction types and children's self-reports of depressive symptoms.</p> <p>Results</p> <p>Based on the results of factor analysis, the latent factors for family interactions included supporting activities, psychological control, parental discipline, behavioral supervision, and family conflict. After conducting cluster analysis using factor scores, four types of family interactions were revealed: supervised (29.66%), disciplined (13.56%), nurtured (40.96%) and conflict (15.82%). Children from the disciplined or conflict families were more likely to report depressive symptoms. Children from the nurtured families were least likely to report depressive symptoms.</p> <p>Conclusion</p> <p>Family interactions can be classified into four different types, which are related to children's self-reports of depressive symptoms. The creation of a family interaction environment that is beneficial for children's mental health is an important issue for health education and health promotion professionals.</p

Protocol for a randomised controlled trial of a school based cognitive behaviour therapy (CBT) intervention to prevent depression in high risk adolescents (PROMISE)

<p>Abstract</p> <p>Background</p> <p>Depression in adolescents is a significant problem that impairs everyday functioning and increases the risk of severe mental health disorders in adulthood. Relatively few adolescents with depression are identified and referred for treatment indicating the need to investigate alternative preventive approaches.</p> <p>Study Design</p> <p>A pragmatic cluster randomised controlled trial evaluating the effectiveness of a school based prevention programme on symptoms of depression in "high risk" adolescents (aged 12-16). The unit of allocation is year groups (n = 28) which are assigned to one of three conditions: an active intervention based upon cognitive behaviour therapy, attention control or treatment as usual. Assessments will be undertaken at screening, baseline, 6 months and 12 months. The primary outcome measure is change on the Short Mood and Feeling Questionnaire at 12 months. Secondary outcome measures will assess changes in negative thoughts, self esteem, anxiety, school connectedness, peer attachment, alcohol and substance misuse, bullying and self harm.</p> <p>Discussion</p> <p>As of August 2010, all 28 year groups (n = 5023) had been recruited and the assigned interventions delivered. Final 12 month assessments are scheduled to be completed by March 2011.</p> <p>Trial Registration</p> <p>ISRCTN19083628</p

Management of toxic ingestions with the use of renal replacement therapy

Although rare, renal replacement therapy (RRT) for the treatment of the metabolic, respiratory and hemodynamic complications of intoxications may be required. Understanding the natural clearance of the medications along with their volume of distribution, protein binding and molecular weight will help in understanding the benefit of commencing RRT. This information will aid in choosing the optimal forms of RRT in an urgent setting. Overdose of common pediatric medications are discussed with suggestions on the type of RRT within this educational review