Socioeconomic risk, parenting during the preschool years and child health age 6 years

Parent–child relationships and parenting processes are emerging as potential life course determinants of health. Parenting is socially patterned and could be one of the factors responsible for the negative effects of social inequalities on health, both in childhood and adulthood. This study tests the hypothesis that some of the effect of socioeconomic risk on health in mid childhood is transmitted via early parenting. Methods: Prospective cohort study in 10 USA communities involving 1041 mother/ child pairs, selected at birth at random with conditional sampling. Exposures: income, maternal education, maternal age, lone parenthood, ethnic status and objective assessments of mother child interaction in the first 4 years of life covering warmth, negativity and positive control. Outcomes: mother’s report of child’s health in general at 6 years. Modelling: multiple regression analyses with statistical testing of mediational processes. Results: All five indicators of socioeconomic status (SES) were correlated with all three measures of parenting, such that low SES was associated with poor parenting. Among the measures of parenting maternal warmth was independently predictive of future health, and among the socioeconomic variables maternal education, partner presence and ‘other ethnic group’ proved predictive. Measures of parenting significantly mediated the impact of measures of SES on child health. Conclusions: Parenting mediates some, but not all of the detectable effects of socioeconomic risk on health in childhood. As part of a package of measures that address other determinants, interventions to support parenting are likely to make a useful contribution to reducing childhood inequalities in health

Three-Dimensional Human iPSC-Derived Artificial Skeletal Muscles Model Muscular Dystrophies and Enable Multilineage Tissue Engineering

Summary: Generating human skeletal muscle models is instrumental for investigating muscle pathology and therapy. Here, we report the generation of three-dimensional (3D) artificial skeletal muscle tissue from human pluripotent stem cells, including induced pluripotent stem cells (iPSCs) from patients with Duchenne, limb-girdle, and congenital muscular dystrophies. 3D skeletal myogenic differentiation of pluripotent cells was induced within hydrogels under tension to provide myofiber alignment. Artificial muscles recapitulated characteristics of human skeletal muscle tissue and could be implanted into immunodeficient mice. Pathological cellular hallmarks of incurable forms of severe muscular dystrophy could be modeled with high fidelity using this 3D platform. Finally, we show generation of fully human iPSC-derived, complex, multilineage muscle models containing key isogenic cellular constituents of skeletal muscle, including vascular endothelial cells, pericytes, and motor neurons. These results lay the foundation for a human skeletal muscle organoid-like platform for disease modeling, regenerative medicine, and therapy development. : Maffioletti et al. generate human 3D artificial skeletal muscles from healthy donors and patient-specific pluripotent stem cells. These human artificial muscles accurately model severe genetic muscle diseases. They can be engineered to include other cell types present in skeletal muscle, such as vascular cells and motor neurons. Keywords: skeletal muscle, pluripotent stem cells, iPS cells, myogenic differentiation, tissue engineering, disease modeling, muscular dystrophy, organoid

Parent and child agreement for acute stress disorder, post-traumatic stress disorder and other psychopathology in a prospective study of children and adolescents exposed to single-event trauma

Examining parent-child agreement for Acute Stress Disorder (ASD) and Post-Traumatic Stress Disorder (PTSD) in children and adolescents is essential for informing the assessment of trauma-exposed children, yet no studies have examined this relationship using appropriate statistical techniques. Parent-child agreement for these disorders was examined by structured interview in a prospective study of assault and motor vehicle accident (MVA) child survivors, assessed at 2-4 weeks and 6 months post-trauma. Children were significantly more likely to meet criteria for ASD, as well as other ASD and PTSD symptom clusters, based on their own report than on their parent's report. Parent-child agreement for ASD was poor (Cohen's κ = -.04), but fair for PTSD (Cohen's κ = .21). Agreement ranged widely for other emotional disorders (Cohen's κ = -.07-.64), with generalised anxiety disorder found to have superior parent-child agreement (when assessed by phi coefficients) relative to ASD and PTSD. The findings support the need to directly interview children and adolescents, particularly for the early screening of posttraumatic stress, and suggest that other anxiety disorders may have a clearer presentation post-trauma

A detailed clinical and molecular survey of subjects with nonsyndromic USH2A retinopathy reveals an allelic hierarchy of disease-causing variants.

Defects in USH2A cause both isolated retinal disease and Usher syndrome (ie, retinal disease and deafness). To gain insights into isolated/nonsyndromic USH2A retinopathy, we screened USH2A in 186 probands with recessive retinal disease and no hearing complaint in childhood (discovery cohort) and in 84 probands with recessive retinal disease (replication cohort). Detailed phenotyping, including retinal imaging and audiological assessment, was performed in individuals with two likely disease-causing USH2A variants. Further genetic testing, including screening for a deep-intronic disease-causing variant and large deletions/duplications, was performed in those with one likely disease-causing change. Overall, 23 of 186 probands (discovery cohort) were found to harbour two likely disease-causing variants in USH2A. Some of these variants were predominantly associated with nonsyndromic retinal degeneration ('retinal disease-specific'); these included the common c.2276 G>T, p.(Cys759Phe) mutation and five additional variants: c.2802 T>G, p.(Cys934Trp); c.10073 G>A, p.(Cys3358Tyr); c.11156 G>A, p.(Arg3719His); c.12295-3 T>A; and c.12575 G>A, p.(Arg4192His). An allelic hierarchy was observed in the discovery cohort and confirmed in the replication cohort. In nonsyndromic USH2A disease, retinopathy was consistent with retinitis pigmentosa and the audiological phenotype was variable. USH2A retinopathy is a common cause of nonsyndromic recessive retinal degeneration and has a different mutational spectrum to that observed in Usher syndrome. The following model is proposed: the presence of at least one 'retinal disease-specific' USH2A allele in a patient with USH2A-related disease results in the preservation of normal hearing. Careful genotype-phenotype studies such as this will become increasingly important, especially now that high-throughput sequencing is widely used in the clinical setting.European Journal of Human Genetics advance online publication, 4 February 2015; doi:10.1038/ejhg.2014.283

Preparation for propagation and absorption experiments in MTX

Preparatory calculations of microwave transmission through the MTX access duct, propagation of the waves through the plasma and the resulting power deposition profile on a calorimeter located on the tokamak inside wall have been performed. The microwave transmission calculations include the relative phase slippage of waveguide modes in the duct to determine the spatial structure of the wavefront at the duct exist. Ray-tracing calculations show substantial spreading of the beam in the poloidal direction at densities above 1.5 /times/ 10/sup 20/ m/sup /minus/3/, well within the range of the experiments. Initial experiments with low or high toroidal field (cyclotron resonance outside the plasma) will investigate both diffraction and refraction effects, without absorption. Estimates of the fractional absorption of the beam in the initial experiments with the cyclotron resonance at the plasma axis have also been made. 4 refs., 3 figs

Centerscope

Centerscope, formerly Scope, was published by the Boston University Medical Center "to communicate the concern of the Medical Center for the development and maintenance of improved health care in contemporary society.

A Bayesian re-assessment of two Phase II trials of gemcitabine in metastatic nasopharyngeal cancer

The Simon two-stage minimax design is a popular statistical design used in Phase II clinical trials. The analysis of the data arising from the design typically involves the use of frequentist statistics. This paper presents an alternative, Bayesian, approach to the design and analysis of Phase II clinical trials. In particular, we consider how a Bayesian approach could have affected the design, analysis and interpretation of two parallel Phase II trials of the National Cancer Centre Singapore, on the activity of gemcitabine in chemotherapy-naïve and in previously treated patients with metastatic nasopharyngeal carcinoma. We begin by explaining the Bayesian methodology and contrasting it with the frequentist approach. We then carry out a Bayesian analysis of the trial results. The conclusions drawn using the Bayesian approach were in general agreement with those obtained from the frequentist analysis. However they had the advantage of allowing for different and potentially more useful interpretations to be made regarding the trial results, as well as for the incorporation of external sources of information. In particular, using a Bayesian trial design, we were able to take into account the results of the parallel trial results when deciding whether to continue each trial beyond the interim stage