Implementation, Evalution and Maintenance of a Social-Emotional Skills Training Program for Children with an Autism Spectrum Disorder in a Specialist School Setting

Socialization difficulties in children with an Autism Spectrum Disorder (ASD) are often associated with peer rejection and impaired academic achievement. Schools might appear to offer an ideal setting for social-emotional skills (SES) instruction. However, common challenges to successful implementation of school-based programs include inadequate staffing and resourcing, and a lack of ASD-specific staff training. This paper describes how barriers to program implementation were overcome in a project evaluating the Secret Agent Society (SAS) SES training intervention within Autism Spectrum Australia (Aspect) specialist classes. Questionnaire data was collected from school staff over a one-year period. Findings supported the effectiveness of the adoption process used, and suggest that SAS was feasible and acceptable to school staff

High-resolution VLA low radio frequency observations of the Perseus cluster: radio lobes, mini-halo and bent-jet radio galaxies

We present the first high-resolution 230-470 MHz map of the Perseus cluster obtained with the Karl G. Jansky Very Large Array. The high dynamic range and resolution achieved has allowed the identification of previously-unknown structures in this nearby galaxy cluster. New hints of sub-structures appear in the inner radio lobes of the brightest cluster galaxy NGC 1275. The spurs of radio emission extending into the outer X-ray cavities, inflated by past nuclear outbursts, are seen for the first time at these frequencies, consistent with spectral aging. Beyond NGC 1275, we also analyze complex radio sources harbored in the cluster. Two new distinct, narrowly-collimated jets are visible in IC 310, consistent with a highly-projected narrow-angle tail radio galaxy infalling into the cluster. We show how this is in agreement with its blazar-like behavior, implying that blazars and bent-jet radio galaxies are not mutually exclusive. We report the presence of filamentary structures across the entire tail of NGC 1265, including two new pairs of long filaments in the faintest bent extension of the tail. Such filaments have been seen in other cluster radio sources such as relics and radio lobes, indicating that there may be a fundamental connection between all these radio structures. We resolve the very narrow and straight tail of CR 15 without indication of double jets, so that the interpretation of such head-tail sources is yet unclear. Finally, we note that only the brightest western parts of the mini-halo remain, near NGC 1272 and its bent double jets.Comment: 17 pages, 12 figures, Accepted for publication in MNRA

Improving prescribing practices with rapid diagnostic tests (RDTs): synthesis of 10 studies to explore reasons for variation in malaria RDT uptake and adherence.

OBJECTIVES: The overuse of antimalarial drugs is widespread. Effective methods to improve prescribing practice remain unclear. We evaluated the impact of 10 interventions that introduced rapid diagnostic tests for malaria (mRDTs) on the use of tests and adherence to results in different contexts. DESIGN: A comparative case study approach, analysing variation in outcomes across different settings. SETTING: Studies from the ACT Consortium evaluating mRDTs with a range of supporting interventions in 6 malaria endemic countries. Providers were governmental or non-governmental healthcare workers, private retail sector workers or community volunteers. Each study arm in a distinct setting was considered a case. PARTICIPANTS: 28 cases from 10 studies were included, representing 148 461 patients seeking care for suspected malaria. INTERVENTIONS: The interventions included different mRDT training packages, supervision, supplies and community sensitisation. OUTCOME MEASURES: Analysis explored variation in: (1) uptake of mRDTs (% febrile patients tested); (2) provider adherence to positive mRDTs (% Plasmodium falciparum positive prescribed/given Artemisinin Combination Treatment); (3) provider adherence to negative mRDTs (% P. falciparum negative not prescribed/given antimalarial). RESULTS: Outcomes varied widely across cases: 12-100% mRDT uptake; 44-98% adherence to positive mRDTs; 27-100% adherence to negative mRDTs. Providers appeared more motivated to perform well when mRDTs and intervention characteristics fitted with their own priorities. Goodness of fit of mRDTs with existing consultation and diagnostic practices appeared crucial to maximising the impact of mRDTs on care, as did prior familiarity with malaria testing; adequate human resources and supplies; possible alternative treatments for mRDT-negative patients; a more directive intervention approach and local preferences for ACTs. CONCLUSIONS: Basic training and resources are essential but insufficient to maximise the potential of mRDTs in many contexts. Programme design should respond to assessments of provider priorities, expectations and capacities. As mRDTs become established, the intensity of supporting interventions required seems likely to reduce

PedGenie: meta genetic association testing in mixed family and case-control designs

<p>Abstract</p> <p>Background-</p> <p>PedGenie software, introduced in 2006, includes genetic association testing of cases and controls that may be independent or related (nuclear families or extended pedigrees) or mixtures thereof using Monte Carlo significance testing. Our aim is to demonstrate that PedGenie, a unique and flexible analysis tool freely available in Genie 2.4 software, is significantly enhanced by incorporating meta statistics for detecting genetic association with disease using data across multiple study groups.</p> <p>Methods-</p> <p>Meta statistics (chi-squared tests, odds ratios, and confidence intervals) were calculated using formal Cochran-Mantel-Haenszel techniques. Simulated data from unrelated individuals and individuals in families were used to illustrate meta tests and their empirically-derived p-values and confidence intervals are accurate, precise, and for independent designs match those provided by standard statistical software.</p> <p>Results-</p> <p>PedGenie yields accurate Monte Carlo p-values for meta analysis of data across multiple studies, based on validation testing using pedigree, nuclear family, and case-control data simulated under both the null and alternative hypotheses of a genotype-phenotype association.</p> <p>Conclusion-</p> <p>PedGenie allows valid combined analysis of data from mixtures of pedigree-based and case-control resources. Added meta capabilities provide new avenues for association analysis, including pedigree resources from large consortia and multi-center studies.</p

Tribute to Professor David Bruck

A tribute to Professor David I. Bruck, who served on the faculty of the Washington and Lee University School of Law from 2004 to 2020. Bruck directed W&L\u27s death penalty defense clinic, the Virginia Capital Case Clearinghouse, also known as VC3 . He became Professor of Law, Emeritus in 2020

Antiprogestins reduce epigenetic field cancerization in breast tissue of young healthy women

Background: Breast cancer is a leading cause of death in premenopausal women. Progesterone drives expansion of luminal progenitor cells, leading to the development of poor-prognostic breast cancers. However, it is not known if antagonising progesterone can prevent breast cancers in humans. We suggest that targeting progesterone signalling could be a means of reducing features which are known to promote breast cancer formation. Methods: In healthy premenopausal women with and without a BRCA mutation we studied (i) estrogen and progesterone levels in saliva over an entire menstrual cycle (n = 20); (ii) cancer-free normal breast-tissue from a control population who had no family or personal history of breast cancer and equivalently from BRCA1/2 mutation carriers (n = 28); triple negative breast cancer (TNBC) biopsies and healthy breast tissue taken from sites surrounding the TNBC in the same individuals (n = 14); and biopsies of ER+ve/PR+ve stage T1–T2 cancers and healthy breast tissue taken from sites surrounding the cancer in the same individuals (n = 31); and (iii) DNA methylation and DNA mutations in normal breast tissue (before and after treatment) from clinical trials that assessed the potential preventative effects of vitamins and antiprogestins (mifepristone and ulipristal acetate; n = 44). Results: Daily levels of progesterone were higher throughout the menstrual cycle of BRCA1/2 mutation carriers, raising the prospect of targeting progesterone signalling as a means of cancer risk reduction in this population. Furthermore, breast field cancerization DNA methylation signatures reflective of (i) the mitotic age of normal breast epithelium and (ii) the proportion of luminal progenitor cells were increased in breast cancers, indicating that luminal progenitor cells with elevated replicative age are more prone to malignant transformation. The progesterone receptor antagonist mifepristone reduced both the mitotic age and the proportion of luminal progenitor cells in normal breast tissue of all control women and in 64% of BRCA1/2 mutation carriers. These findings were validated by an alternate progesterone receptor antagonist, ulipristal acetate, which yielded similar results. Importantly, mifepristone reduced both the TP53 mutation frequency as well as the number of TP53 mutations in mitotic-age-responders. Conclusions: These data support the potential usage of antiprogestins for primary prevention of poor-prognostic breast cancers

Feasibility, reliability, and validity of the EQ-5D-Y: results from a multinational study

Ravens-Sieberer U, Wille N, Badia X, et al. Feasibility, reliability, and validity of the EQ-5D-Y: results from a multinational study. QUALITY OF LIFE RESEARCH. 2010;19(6):887-897.To examine the feasibility, reliability, and validity of the newly developed EQ-5D-Y. The EQ-5D-Y was administered in population samples of children and adolescents in Germany, Italy, South Africa, Spain, and Sweden. Percentages of missing values and reported problems were calculated. Test-retest reliability was determined. Spearman's rank correlation coefficients with other generic measures of HRQOL were calculated. Known groups' validity was examined by comparing groups with a priori expected differences in HRQOL. Between 91 and 100% of the respondents provided valid scorings. Sweden had the lowest proportion of reported problems (1-24.9% across EQ-5D-Y dimensions), with the highest proportions in South Africa (2.8-47.3%) and Italy (4.3-39.0%). Percentages of agreement in test-retest reliability ranged between 69.8 and 99.7% in the EQ-5D-Y dimensions; Kappa coefficients were up to 0.67. Correlation coefficients with other measures of self-rated health indicated convergent validity (up to r = -0.56). Differences between groups classified according to presence of chronic conditions, self-rated overall health and psychological problems provided preliminary evidence of known groups' validity. Results provide preliminary evidence of the instrument's feasibility, reliability and validity. Further study is required in clinical samples and for possible future applications in economic analyses

Health systems research in Lao PDR: capacity development for getting research into policy and practice

<p>Abstract</p> <p>Background</p> <p>Lao PDR is a low-income country with an urgent need for evidence-informed policymaking in the healthcare sector. During the last decade a number of Health Systems Research (HSR) projects have been conducted in order to meet this need. However, although knowledge about research is increasing among policymakers, the use of research in policymaking is still limited.</p> <p>Methods</p> <p>This article investigates the relationship between research and policymaking from the perspective of those participating in HSR projects. The study is based on 28 interviews, two group discussions and the responses from 56 questionnaires.</p> <p>Results</p> <p>The interviewees and questionnaire respondents were aware of the barriers to getting research into policy and practice. But while some were optimistic, claiming that there had been a change of attitudes among policymakers in the last two years, others were more pessimistic and did not expect any real changes until years from now. The major barriers to feeding research results into policy and practice included an inability to influence the policy process and to get policymakers and practitioners interested in research results. Another barrier was the lack of continuous capacity development and high-quality research, both of which are related to funding and international support. Many of the interviewees and questionnaire respondents also pointed out that communication between those conducting research and policymakers must be improved.</p> <p>Conclusion</p> <p>The results show that in the case of Lao PDR, research capacity development is at a crucial stage for implementing research into policy and practice. If research is going to make a consistent impact on policymaking in the Lao health care sector, the attitude towards research will need to be changed in order to get research prioritised, both among those conducting research, and among policymakers and practitioners. Our findings indicate that there is awareness about the barriers in this process.</p

A Quantitative Study of the Mechanisms behind Thymic Atrophy in Gαi2-Deficient Mice during Colitis Development

Mice deficient for the G protein subunit Gαi2 spontaneously develop colitis, a chronic inflammatory disease associated with dysregulated T cell responses. We and others have previously demonstrated a thymic involution in these mice and an aberrant thymocyte dynamics. The Gαi2−/− mice have a dramatically reduced fraction of double positive thymocytes and an increased fraction of single positive (SP) thymocytes. In this study, we quantify a number of critical parameters in order to narrow down the underlying mechanisms that cause the dynamical changes of the thymocyte development in the Gαi2−/− mice. Our data suggest that the increased fraction of SP thymocytes results only from a decreased number of DP thymocytes, since the number of SP thymocytes in the Gαi2−/− mice is comparable to the control littermates. By measuring the frequency of T cell receptor excision circles (TRECs) in the thymocytes, we demonstrate that the number of cell divisions the Gαi2−/− SP thymocytes undergo is comparable to SP thymocytes from control littermates. In addition, our data show that the mature SP CD4+ and CD8+ thymocytes divide to the same extent before they egress from the thymus. By estimating the number of peripheral TREC+ T lymphocytes and their death rate, we could calculate the daily egression of thymocytes. Gαi2−/− mice with no/mild and moderate colitis were found to have a slower export rate in comparison to the control littermates. The quantitative measurements in this study suggest a number of dynamical changes in the thymocyte development during the progression of colitis

Validation of two generic patient-reported outcome measures in patients with type 2 diabetes

<p>Abstract</p> <p>Background</p> <p>Prior to using a generic patient-reported outcome measure (PRO), the measure should be validated within the target population. The purpose of the current study was to validate two generic measures in patients with type 2 diabetes.</p> <p>Methods</p> <p>Patients with type 2 diabetes in Scotland and England completed two generic measures: EQ-5D and Psychological General Well-Being Index (PGWB). Two diabetes-specific measures were administered: ADS and DSC-R. Analyses assessed reliability and validity.</p> <p>Results</p> <p>There were 130 participants (53 Scotland; 77 England; 64% male; mean age = 55.7 years). Responses on the EQ-5D and PGWB reflected moderate impairment consistent with previous diabetes samples: mean EQ-5D Index score, 0.75; EQ-5D VAS, 68.8; PGWB global score, 67.9. All scales of the PGWB demonstrated good internal consistency reliability (Cronbach's alpha = 0.77 to 0.97). The EQ-5D and PGWB demonstrated convergent validity through significant correlations with the ADS (r = 0.48 to 0.61), DSC-R scales (r = 0.33 to 0.81 except ophthalmology subscale), and Body Mass Index (r = 0.15 to 0.38). The EQ-5D and PGWB discriminated between groups of patients known to differ in diabetes-related characteristics (e.g., history of hypoglycemia).</p> <p>Conclusion</p> <p>Results support the use of the EQ-5D and PGWB among patients with type 2 diabetes, possibly in combination with condition-specific measures.</p