The perceptions of secondary school leaders on reducing or preventing exclusions and suspensions for persistent disruptive behaviour:A reflexive thematic analysis

Each year, thousands of students in England are affected by school exclusion, most commonly for the reason of ‘persistent disruptive behaviour’ (PDB). Despite research indicating the potential negative and long-lasting impact of exclusion, and considering approaches to prevent exclusions, rates have remained relatively consistent. The present research aims to explore approaches to reduce and prevent exclusions for PDB, by considering, how school leaders inform their practices, the potential facilitators and barriers to successful implementation of approaches, and what might support schools further. Ten secondary school leaders in Southwest England participated in a semi-structured interview, analysed using reflexive thematic analysis. Key findings relate to the importance of knowing the school community, including through understanding student contexts, thorough assessment of student needs and positive relationships. The perceptions of the school community relating to constructions of behaviour and investment in approaches are also suggested as important in determining outcomes. School leaders appeared to be engaging in a complex balancing act, evaluating multiple forms of information and balancing these with a range of demands and purposes. Support which provides greater access to external professionals and provision, including through early intervention, was highly valued. The findings are framed through application of personal construct psychology (Kelly, 1980) and ecological systems theory (Bronfenbrenner, 1977, 1995) and used to provide consideration for researchers, school staff, educational psychologists and local authorities. These relate to considering the accessibility and availability of information and support for schools, supporting understanding of students’ needs and behaviour, and facilitating investment in approaches to reduce and prevent exclusions for PDB

The role of exercise and age on vitamin D metabolism

A low vitamin D status (determined by 25(OH)D concentration) has been identified as an association risk factor in the aetiology of numerous chronic diseases, with older adults identified as generally more deficient than younger populations. Accumulating data is suggestive that physical activity and exercise may influence 25(OH)D and vitamin D metabolites downstream in the complex metabolic pathway. Specifically, exercise has been shown to act as a direct and indirect stimulus on the intracellular vitamin D receptor (VDR), which mediates the effects of vitamin D and initiates genomic and non-genomic signalling responses. The role of physical activity and exercise on 25(OH)D concentration and VDR expression is not yet recognised in a healthy human population.This thesis aimed to establish whether there is a link between physical activity status and 25(OH)D concentration, and if there is a role of age and exercise on 25(OH)D concentration and VDR expression (as quantified in circulating systemic T lymphocytes).The main results demonstrate that 25(OH)D concentration is not influenced by age or cardiorespiratory fitness (CRF), however VDR expression declines with older age and a higher CRF predicts a greater expression of the VDR. It was found that a single bout of exercise acutely increases VDR expression in circulating T lymphocytes, with exercise modality appearing to influence the response. There was a more pronounced response observed following an endurance compared to a resistance exercise bout. The impact of the exercise-induced lymphocyte response on the observed changes in T cell VDR expression was explored, however they appear to be independent.In conclusion, the findings of this thesis support the notion that exercise could be used as a short-term strategy to increase cellular VDR expression in a human population

The combined effect of high intensity intermittent training and vitamin D supplementation on insulin sensitivity in overweight and obese males and females

High intensity intermittent training (HIIT) is a time efficient mode of exercise, which has been shown to induce metabolic benefits, such as an improvement in insulin sensitivity (IS) and thus type 2 diabetes (T2D). Vitamin D₃ (25(OH)D₃) supplementation has also been shown to influence the pathogenesis of IS. The aim of this study was to investigate if there is a combined effect of HIIT and 25(OH)D₃ supplementation on IS.Twelve inactive and overweight adults (9 male, 3 female; age: 32 ± 18-45 y, BMI: 31.9 ± 2.8 kg·m²) performed HIIT 3 times/week for 6 weeks, with oral glucose tolerance tests and peak oxygen consumption (V̇O₂peak) tests done at baseline and post-intervention. The HIIT protocol consisted of 10 x 1 min intervals cycling at 97 ± 8 % V̇O₂peak separated by 1 min active recovery. Participants were randomised to ingest 4000 IU/day 25(OH)D₃ (n=6) or a placebo (n=6). Plasma glucose, insulin, 25(OH)D₃, adiponectin, leptin, and the lipid profile were analysed pre and post training.Peak V̇O₂ and power output was increased in all participants (P<0.01). Systolic blood pressure (BP) was reduced in all participants and the vitamin D group (P<0.05) but not the placebo group. Insulin area under the curve (AUC) was significantly reduced by 16.6% in the placebo group (P<0.05) but not overall for all participants or the vitamin D group. There was no change in fasting glucose or glucose AUC. Insulin sensitivity index (ISI) and homeostatic model assessment of insulin resistance (HOMA-IR) remained unchanged across all groups. All participants were 25(OH)D₃ deficient (<20 ng·ml-¹ ) at baseline, with an increase in 25(OH)D₃ in the vitamin D group after 6 weeks (P<0.05). Adiponectin decreased in the placebo group but was unaltered in the vitamin D group. Leptin remained unaltered in all groups. Plasma triglycerides were reduced in all participants (P<0.05).In conclusion, 6 weeks of HIIT increased physical capacity but had no effect on the ISI and HOMA-IR in overweight and obese males and females. The findings showed that 6 weeks of supplementation resulted in an increase in 25(OH)D₃ and an improvement in systolic BP

The combined effect of high-intensity intermittent training and vitamin D supplementation on glycemic control in overweight and obese adults

High intensity intermittent training (HIIT) has been shown to reduce the risk of chronic conditions including the development of type 2 diabetes mellitus (T2DM). Independently, a low vitamin D status has also been linked to the prevalence of T2DM. The aim of this study was to investigate if there was a synergistic metabolic effect of HIIT and vitamin D supplementation on glycaemic control. Twenty male and female participants (age, 34 ± 9 y; BMI, 31.4 ± 2.8 kg·m-2) completed 6 weeks HIIT, and were randomised to ingest 100 µg/day of vitamin D3 or placebo. Response to an oral glucose tolerance test (OGTT) was determined at baseline and 72 h post-intervention. Glucose tolerance was improved as a result of the HIIT intervention, shown through a reduction in glucose and insulin concentrations during the OGTT, accompanied with a decrease in glucose (829 ± 110 to 786 ± 139 mmol·h-1·L-1; P=0.043) and insulin (8101 ± 4755 to 7024 ± 4489 mU·h-1·L-1; P=0.049) area under the curve (AUC). Supplementation increased 25-hydroxyvitamin D3 concentration by 120 % to a sufficiency status (

Exercise acutely increases vitamin D receptor expression in T lymphocytes in vitamin D-deficient men, independent of age

Vitamin D plays a key role in the modulation of the immune system, mediated through the intracellular vitamin D receptor (VDR). Exercise has been shown to influence the activity and availability of the VDR. This study aimed to investigate the effect of age on basal immune cell (T-lymphocytes) VDR expression and the subsequent effect of acute aerobic exercise to modulate VDR expression in peripheral T-cells. Thirty-five males were included in the study (means ± SD: age 44 ± 17 y, BMI 25.7 ± 3.1 kg·m-2), separated into three age groups: 18-30 y (n=12), 31-45 y (n=11), and 60-75 y (n=12). Participants completed two trials: control (CON) and aerobic exercise (AE), with blood samples collected pre- and post-exercise (0 h, 1h, and 3 h). Peripheral blood T-cells were isolated and analysed for VDR expression by flow cytometry. The results show that advanced age is associated with lower VDR expression in T-cells (882 ± 274 vs 796 ± 243 vs 594 ± 174 geomean). Acute AE was successful at acutely increasing VDR expression in T-cells, irrespective of age. Advanced age corresponds to a lower T cell VDR expression, which may be responsible for age-associated development of chronic conditions and autoimmunity. Exercise was successful in increasing VDR expression in T-cells irrespective of age and independent of exercise-induced T cell mobilisation

PROTAC-mediated degradation of Bruton's tyrosine kinase is inhibited by covalent binding

The impact of covalent binding on PROTAC-Mediated degradation of BTK was investigated through the preparation of both covalent binding and reversible binding PROTACs derived from the covalent BTK inhibitor ibrutinib. It was determined that a covalent binding PROTAC inhibited BTK degradation despite evidence of target engagement, while BTK degradation was observed with a reversible binding PROTAC. These observations were consistently found when PROTACs that were able to recruit either IAP or cereblon E3 ligases were employed. Proteomics analysis determined that the use of a covalently bound PROTAC did not result in the degradation of covalently bound targets, while degradation was observed for some reversibly bound targets. This observation highlights the importance of catalysis for successful PROTAC-Mediated degradation and highlights a potential caveat for the use of covalent target binders in PROTAC design

The effect of exercise intensity and duration on cardiac troponin release

Abstract not available

Atlas of group A streptococcal vaccine candidates compiled using large-scale comparative genomics.

Group A Streptococcus (GAS; Streptococcus pyogenes) is a bacterial pathogen for which a commercial vaccine for humans is not available. Employing the advantages of high-throughput DNA sequencing technology to vaccine design, we have analyzed 2,083 globally sampled GAS genomes. The global GAS population structure reveals extensive genomic heterogeneity driven by homologous recombination and overlaid with high levels of accessory gene plasticity. We identified the existence of more than 290 clinically associated genomic phylogroups across 22 countries, highlighting challenges in designing vaccines of global utility. To determine vaccine candidate coverage, we investigated all of the previously described GAS candidate antigens for gene carriage and gene sequence heterogeneity. Only 15 of 28 vaccine antigen candidates were found to have both low naturally occurring sequence variation and high (>99%) coverage across this diverse GAS population. This technological platform for vaccine coverage determination is equally applicable to prospective GAS vaccine antigens identified in future studies