Opting In and Staying In: Older Teenagers’ Decisions on Becoming and Remaining Involved in Youth Services in Dublin City.

It is widely recognised in Ireland and internationally that the engagement of young people in the youth work process brings with it a range of positive benefits and outcomes, both for the young people involved and society in general. However, it has also been found that young people aged 15-19 participate less in youth services and therefore do not gain the associated benefits. This dissertation explores the perspectives of young people aged 15-19 who are engaged in youth services in Dublin City, in relation to their decisions to become and remain involved in youth services. The aim of this research was to point to ways of attracting and sustaining the engagement of more young people within this age group. A case study design was employed, using multiple data collection strategies in two youth work sites in Dublin City. The findings suggest that in order to attract and maintain the engagement of young people aged 15-19, youth services, together with young people, must endeavour to actively co-produce a youth public sphere. Relationships, both existing and those arising from the youth work process, have an important influence on young people‟s decisions to become and remain involved in youth services, as do the activities and programmes offered by youth services. It emerged from the research that, in comparison to other forms of engagement youth services offer young people a place to go where they can be with friends, get involved in activities of interest to them, form relationships with youth workers and have an input into decisions that affect them. The study concludes by recommending a number of areas in need of further research within the Irish context, particularly the youth work relationship, the co-production of a youth public sphere and the youth cafe model. It is also recommends that research relating to youth work must consider the views of those at the centre of the process – the young people

Preparing prospective teachers on the web

This is the publisher's version, collected from: http://www.cec.sped.org/Part of a special issue on the use of the World Wide Web in special education. The writers describe how they have started to integrate the Internet and World Wide Web into preservice teacher education in the hope of expanding the instructional use of technology in special education classrooms

Self-Reported Physical Activity and Myocardial Flow Reserve in Postmenopausal Women at Risk for Cardiovascular Disease

Background: Regular exercise protects against coronary heart disease (CHD) events and improves vascular reactivity. Exercise effects on myocardial flow reserve (MFR) are not well studied. Methods: We performed dynamic N-13 ammonia positron emission tomography (PET) in 16 postmenopausal women (60 ± 6 years) to measure myocardial blood flow (MBF) and MFR. We also obtained information from each woman on her self-reported physical activity. Results: Of the 16 patients, 6 reported moderate regular physical activity, and 10 did not. Women who reported regular, at least moderate physical activity had a higher percentage increase in adenosine MBF from rest compared with women who did not exercise (268% vs. 129%, p = 0.04) and had a significantly higher mean maximal MFR (3.68 vs. 2.29, p = 0.04). Conclusions: These findings provide further mechanistic support for the beneficial cardiovascular effects of exercise.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63137/1/jwh.2006.15.45.pd

L'impact de la correction systématique des questions à choix multiples ayant une faible discrimination sur la fiabilité de l'évaluation : une analyse via des séries chronologiques interrompues

At our centre, we introduced a continuous quality improvement (CQI) initiative during academic year 2018-19 targeting for repair multiple choice question (MCQ) items with discrimination index (D) < 0.1. The purpose of this study was to assess the impact of this initiative on reliability/internal consistency of our assessments. Our participants were medical students during academic years 2015-16 to 2020-21 and our data were summative MCQ assessments during this time. Since the goal was to systematically review and improve summative assessments in our undergraduate program on an ongoing basis, we used interrupted time series analysis to assess the impact on reliability. Between 2015-16 and 2017-18 there was a significant negative trend in the mean alpha coefficient for MCQ exams (regression coefficient -0.027 [-0.008, -0.047], p = 0.024). In the academic year following the introduction of our initiative (2018-19) there was a significant increase in the mean alpha coefficient (regression coefficient 0.113 [0.063, 0.163], p = 0.010) which was then followed by a significant positive post-intervention trend (regression coefficient 0.056 [0.037, 0.075], p = 0.006). In conclusion, our CQI intervention resulted in an immediate and progressive improvement reliability of our MCQ assessments.Dans notre centre, nous avons introduit une initiative d'amélioration continue de la qualité (ACQ) au cours de l'année académique 2018-19 ciblant la correction des questions à choix multiples (QCM) dont l'indice de discrimination (D) est < 0,1. Le but de cette étude était d'évaluer l'impact de cette initiative sur la fiabilité/cohérence interne de nos évaluations. Nos participants étaient des étudiants en médecine au cours des années académiques 2015-16 à 2020-21 et nos données provenaient d’évaluations sommatives par QCM au cours de cette période. Comme l'objectif était de revoir et d'améliorer systématiquement les évaluations sommatives dans notre programme prégradué sur une base continue, nous avons utilisé une analyse basée sur des séries chronologies interrompues pour évaluer l'impact sur la fiabilité. Entre 2015-16 et 2017-18, il y a eu une tendance négative significative dans le coefficient alpha moyen pour les examens utilisant des QCM (coefficient de régression -0,027 [-0,008, -0,047], p = 0,024). Au cours de l'année académique suivant l'introduction de notre initiative (2018-19), il y a eu une augmentation significative du coefficient alpha moyen (coefficient de régression 0,113 [0,063, 0,163], p = 0,010) qui a été suivie d'une tendance positive significative après l'intervention (coefficient de régression 0,056 [0,037, 0,075], p = 0,006). En conclusion, notre intervention d'ACQ a entraîné une amélioration immédiate et progressive de la fiabilité de nos évaluations par QCM

Soil microbial community composition as affected by restoration practices in California grassland

Agricultural practices have strong impacts on soil microbes including both the indices related to biomass and activity as well as those related to community composition. In a grassland restoration project in California, where native perennial bunchgrasses were introduced into non-native annual grassland after a period of intensive tillage, weeding, and herbicide use to reduce the annual seed bank, microbial community composition was investigated. Three treatments were compared: annual grassland, bare soil fallow, and restored perennial grassland. Soil profiles down to 80cm in depth were investigated in four separate layers (0–15, 15–30, 30–60, and 60–80cm) using both phospholipid ester-linked fatty acid (PLFAs) and ergosterol as biomarkers in addition to microbial biomass C by fumigation extraction. PLFA fingerprinting showed much stronger differences between the tilled bare fallow treatment vs. grasslands, compared to fewer differences between restored perennial grassland and annual grassland. The presence or absence of plants over several years clearly distinguished microbial communities. Microbial communities in lower soil layers were little affected by management practices. Regardless of treatment, soil depth caused a strong gradient of changing habitat conditions, which was reflected in Canonical Correspondence Analysis of PLFAs. Fungal organisms were associated with the presence of plants and/or litter since the total amount and the relative proportion of fungal markers were reduced in the tilled bare fallow and in lower layers of the grassland treatments. Total PLFA and soil microbial biomass were highly correlated, and fungal PLFA biomarkers showed strong correlations to ergosterol content. In conclusion, microbial communities are resilient to the grassland restoration process, but do not reflect the change in plant species composition that occurred after planting native bunchgrasses

Integrated computational prediction and experimental validation identifies promiscuous T cell epitopes in the proteome of Mycobacterium bovis

The discovery of novel antigens is an essential requirement in devising new diagnostics or vaccines for use in control programmes against human tuberculosis (TB) and bovine tuberculosis (bTB). Identification of potential epitopes recognised by CD4+ T cells requires prediction of peptide binding to MHC class-II, an obligatory prerequisite for T cell recognition. To comprehensively prioritise potential MHC-II-binding epitopes from Mycobacterium bovis, the agent of bTB and zoonotic TB in humans, we integrated three binding prediction methods with the M. bovisproteome using a subset of human HLA alleles to approximate the binding of epitope-containing peptides to the bovine MHC class II molecule BoLA-DRB3. Two parallel strategies were then applied to filter the resulting set of binders: identification of the top-scoring binders or clusters of binders. Our approach was tested experimentally by assessing the capacity of predicted promiscuous peptides to drive interferon-γ secretion from T cells of M. bovis infected cattle. Thus, 376 20-mer peptides, were synthesised (270 predicted epitopes, 94 random peptides with low predictive scores and 12 positive controls of known epitopes). The results of this validation demonstrated significant enrichment (>24 %) of promiscuously recognised peptides predicted in our selection strategies, compared with randomly selected peptides with low prediction scores. Our strategy offers a general approach to the identification of promiscuous epitopes tailored to target populations where there is limited knowledge of MHC allelic diversity

Bedaquiline and clofazimine resistance in Mycobacterium tuberculosis: an in-vitro and in-silico data analysis

Background: Bedaquiline is a core drug for the treatment of multidrug-resistant tuberculosis; however, the understanding of resistance mechanisms is poor, which is hampering rapid molecular diagnostics. Some bedaquiline-resistant mutants are also cross-resistant to clofazimine. To decipher bedaquiline and clofazimine resistance determinants, we combined experimental evolution, protein modelling, genome sequencing, and phenotypic data. Methods: For this in-vitro and in-silico data analysis, we used a novel in-vitro evolutionary model using subinhibitory drug concentrations to select bedaquiline-resistant and clofazimine-resistant mutants. We determined bedaquiline and clofazimine minimum inhibitory concentrations and did Illumina and PacBio sequencing to characterise selected mutants and establish a mutation catalogue. This catalogue also includes phenotypic and genotypic data of a global collection of more than 14 000 clinical Mycobacterium tuberculosis complex isolates, and publicly available data. We investigated variants implicated in bedaquiline resistance by protein modelling and dynamic simulations. Findings: We discerned 265 genomic variants implicated in bedaquiline resistance, with 250 (94%) variants affecting the transcriptional repressor (Rv0678) of the MmpS5–MmpL5 efflux system. We identified 40 new variants in vitro, and a new bedaquiline resistance mechanism caused by a large-scale genomic rearrangement. Additionally, we identified in vitro 15 (7%) of 208 mutations found in clinical bedaquiline-resistant isolates. From our in-vitro work, we detected 14 (16%) of 88 mutations so far identified as being associated with clofazimine resistance and also seen in clinically resistant strains, and catalogued 35 new mutations. Structural modelling of Rv0678 showed four major mechanisms of bedaquiline resistance: impaired DNA binding, reduction in protein stability, disruption of protein dimerisation, and alteration in affinity for its fatty acid ligand. Interpretation: Our findings advance the understanding of drug resistance mechanisms in M tuberculosis complex strains. We have established an extended mutation catalogue, comprising variants implicated in resistance and susceptibility to bedaquiline and clofazimine. Our data emphasise that genotypic testing can delineate clinical isolates with borderline phenotypes, which is essential for the design of effective treatments. Funding: Leibniz ScienceCampus Evolutionary Medicine of the Lung, Deutsche Forschungsgemeinschaft, Research Training Group 2501 TransEvo, Rhodes Trust, Stanford University Medical Scientist Training Program, National Institute for Health and Care Research Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, Bill & Melinda Gates Foundation, Wellcome Trust, and Marie Skłodowska-Curie Actions

Bedaquiline and clofazimine resistance in Mycobacterium tuberculosis: an in-vitro and in-silico data analysis

Background Bedaquiline is a core drug for the treatment of multidrug-resistant tuberculosis; however, the understanding of resistance mechanisms is poor, which is hampering rapid molecular diagnostics. Some bedaquiline-resistant mutants are also cross-resistant to clofazimine. To decipher bedaquiline and clofazimine resistance determinants, we combined experimental evolution, protein modelling, genome sequencing, and phenotypic data. Methods For this in-vitro and in-silico data analysis, we used a novel in-vitro evolutionary model using subinhibitory drug concentrations to select bedaquiline-resistant and clofazimine-resistant mutants. We determined bedaquiline and clofazimine minimum inhibitory concentrations and did Illumina and PacBio sequencing to characterise selected mutants and establish a mutation catalogue. This catalogue also includes phenotypic and genotypic data of a global collection of more than 14 000 clinical Mycobacterium tuberculosis complex isolates, and publicly available data. We investigated variants implicated in bedaquiline resistance by protein modelling and dynamic simulations. Findings We discerned 265 genomic variants implicated in bedaquiline resistance, with 250 (94%) variants affecting the transcriptional repressor (Rv0678) of the MmpS5–MmpL5 efflux system. We identified 40 new variants in vitro, and a new bedaquiline resistance mechanism caused by a large-scale genomic rearrangement. Additionally, we identified in vitro 15 (7%) of 208 mutations found in clinical bedaquiline-resistant isolates. From our in-vitro work, we detected 14 (16%) of 88 mutations so far identified as being associated with clofazimine resistance and also seen in clinically resistant strains, and catalogued 35 new mutations. Structural modelling of Rv0678 showed four major mechanisms of bedaquiline resistance: impaired DNA binding, reduction in protein stability, disruption of protein dimerisation, and alteration in affinity for its fatty acid ligand. Interpretation Our findings advance the understanding of drug resistance mechanisms in M tuberculosis complex strains. We have established an extended mutation catalogue, comprising variants implicated in resistance and susceptibility to bedaquiline and clofazimine. Our data emphasise that genotypic testing can delineate clinical isolates with borderline phenotypes, which is essential for the design of effective treatments. Funding Leibniz ScienceCampus Evolutionary Medicine of the Lung, Deutsche Forschungsgemeinschaft, Research Training Group 2501 TransEvo, Rhodes Trust, Stanford University Medical Scientist Training Program, National Institute for Health and Care Research Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, Bill & Melinda Gates Foundation, Wellcome Trust, and Marie Skłodowska-Curie Actions