NURTURING THE CHILD: AN ARCHITECTURE OF COMMUNITY, LANDSCAPE AND LEARNING.

This thesis explores the making of place for all preschool children, those with special needs and those considered to be "typically developing." Scale, materiality, light and shadow, color, the four fundamental elements of nature, and the nature of ritual and routine all play a role in the children's experience of place and are explored here as part of the design process. This thesis asks, "What are the contributions that architecture and landscape can make towards nurturing the whole child including children with diverse needs?" The result is a supportive learning and healing environment for children who are defined as having special needs and their "typically developing" peers. A landscape of learning and play will be a significant focus. To support the children and their families, a range of community involvement will be incorporated, and the large recreation center site will be redeveloped as community space

Impact of Professional Student Mentored Research Fellowship on Medical Education and Academic Medicine Career Path

CONTEXT: This study explores the long-term impact of the Professional Student Mentored Research Fellowship (PSMRF) program at the University of Kentucky College of Medicine (UKCOM) on medical students\u27 research productivity and career paths. METHODS: Demographic characteristics, academic profiles, number of publications and residency placements from 2007 to 2012 were used to assess 119 PSMRF graduates against a comparison cohort of 898 UKCOM (non-PSMRF) students. RESULTS: PSMRF students had higher MCAT scores at admission (31.5 ± 0.6 vs. 30.6 ± 0.2, p = 0.007) and achieved higher USMLE Step 1 scores (228 ± 4.2 vs. 223 ± 1.5, p = 0.03) than comparison group. PSMRF students were more likely to publish PubMed-indexed papers (36.7% vs. 17.9%, p \u3c 0.0001), achieve AOA status (19.3% vs. 8.5%, p = 0.0002) and match to top 25 US News and World Report residency programs (23.4% vs. 12.1%, p = 0.008). A greater proportion of PSMRF fellows matched to top tier competitive specialties (23% vs. 14.2%, p = 0.07), however this difference was not statistically significant. CONCLUSIONS: The PSMRF program shows a significant increase in enrollment, as well as positive associations with indicators of success in medical school and subsequent quality of residency program

Molecular Mechanism of activation-triggered subunit exchange in human CaMKII

Activation triggers the exchange of subunits in Ca2+/calmodulin-dependent protein kinase II (CaMKII), an oligomeric enzyme that is critical for learning, memory, and cardiac function. The mechanism by which subunit exchange occurs remains elusive. We show that the human CaMKII holoenzyme exists in dodecameric and tetradecameric forms, and that the calmodulin (CaM)-binding element of CaMKII can bind to the hub of the holoenzyme and destabilize it to release dimers. The structures of CaMKII from two distantly diverged organisms suggest that the CaM-binding element of activated CaMKII acts as a wedge by docking at intersubunit interfaces in the hub. This converts the hub into a spiral form that can release or gain CaMKII dimers. Our data reveal a three-way competition for the CaM-binding element, whereby phosphorylation biases it towards the hub interface, away from the kinase domain and calmodulin, thus unlocking the ability of activated CaMKII holoenzymes to exchange dimers with unactivated ones

Impact of the COVID-19 Pandemic on the Perceived Physical and Mental Health and Healthy Lifestyle Behaviors of People with Disabilities: Quantitative Analysis of the International Community Survey

This study aims to determine the perceived impact of the coronavirus pandemic on physical and mental health and healthy lifestyle behaviors in community-dwelling persons with disabilities, as compared to those without disabilities

Associations between cardiorespiratory fitness, physical activity and clustered cardiometabolic risk in children and adolescents: the HAPPY study

Clustering of cardiometabolic risk factors can occur during childhood and predisposes individuals to cardiometabolic disease. This study calculated clustered cardiometabolic risk in 100 children and adolescents aged 10-14 years (59 girls) and explored differences according to cardiorespiratory fitness (CRF) levels and time spent at different physical activity (PA) intensities. CRF was determined using a maximal cycle ergometer test, and PA was assessed using accelerometry. A cardiometabolic risk score was computed as the sum of the standardised scores for waist circumference, blood pressure, total cholesterol/high-density lipoprotein ratio, triglycerides and glucose. Differences in clustered cardiometabolic risk between fit and unfit participants, according to previously proposed health-related threshold values, and between tertiles for PA subcomponents were assessed using ANCOVA. Clustered risk was significantly lower (p < 0.001) in the fit group (mean 1.21 ± 3.42) compared to the unfit group (mean -0.74 ± 2.22), while no differences existed between tertiles for any subcomponent of PA. Conclusion These findings suggest that CRF may have an important cardioprotective role in children and adolescents and highlights the importance of promoting CRF in youth

Genome-wide linkage screen for testicular germ cell tumour susceptibility loci

A family history of disease is a strong risk factor for testicular germ cell tumour (TGCT). In order to identify the location of putative TGCT susceptibility gene(s) we conducted a linkage search in 237 pedigrees with two or more cases of TGCT. One hundred and seventy-nine pedigrees were evaluated genome-wide with an average inter-marker distance of 10 cM. An additional 58 pedigrees were used to more intensively investigate several genomic regions of interest. Genetic linkage analysis was performed with the ALLEGRO software using two model-based parametric analyses and a non-parametric analysis. Six genomic regions on chromosomes 2p23, 3p12, 3q26, 12p13-q21, 18q21-q23 and Xq27 showed heterogeneity LOD (HLOD) scores of greater than 1, with a maximum HLOD of 1.94 at 3q26. Genome-wide simulation studies indicate that the observed number of HLOD peaks greater than one does not differ significantly from that expected by chance. A TGCT locus at Xq27 has been previously reported. Of the 237 pedigrees examined in this study, 66 were previously unstudied at Xq27, no evidence for linkage to this region was observed in this new pedigree set. Overall, the results indicate that no single major locus can account for the majority of the familial aggregation of TGCT, and suggests that multiple susceptibility loci with weak effects contribute to the diseas

A whole-genome sequence and transcriptome perspective on HER2-positive breast cancers.

HER2-positive breast cancer has long proven to be a clinically distinct class of breast cancers for which several targeted therapies are now available. However, resistance to the treatment associated with specific gene expressions or mutations has been observed, revealing the underlying diversity of these cancers. Therefore, understanding the full extent of the HER2-positive disease heterogeneity still remains challenging. Here we carry out an in-depth genomic characterization of 64 HER2-positive breast tumour genomes that exhibit four subgroups, based on the expression data, with distinctive genomic features in terms of somatic mutations, copy-number changes or structural variations. The results suggest that, despite being clinically defined by a specific gene amplification, HER2-positive tumours melt into the whole luminal-basal breast cancer spectrum rather than standing apart. The results also lead to a refined ERBB2 amplicon of 106 kb and show that several cases of amplifications are compatible with a breakage-fusion-bridge mechanism

A pan-African convection-permitting regional climate simulation with the Met Office Unified Model: CP4-Africa

A convection-permitting multi-year regional climate simulation using the Met Office Unified Model has been run for the first time on an Africa-wide domain. The model has been run as part of the Future Climate for Africa (FCFA) IMPALA (Improving Model Processes for African cLimAte) project and its configuration, domain and forcing data are described here in detail. The model (CP4-Africa) uses a 4.5km horizontal grid spacing at the equator and is run without a convection parametrization, nested within a global atmospheric model driven by observations at the sea-surface which does include a convection scheme. An additional regional simulation, with identical resolution and physical parametrizations to the global model, but with the domain, land surface and aerosol climatologies of the CP4-Africa model, has been run to aid understanding of the differences between the CP4-Africa and global model, in particular to isolate the impact of the convection parametrization and resolution. The effect of enforcing moisture conservation in the CP4-Africa model is described and its impact on reducing extreme precipitation values is assessed. Preliminary results from the first 5 years of the CP4-Africa simulation show substantial improvements in JJA average rainfall compared to the parameterized convection models, with most notably a reduction in the persistent dry bias in West Africa - giving an indication of the benefits to be gained from running a convection-permitting simulation over the whole African continent

A Narrative Review of Motor Competence in Children and Adolescents: What We Know and What We Need to Find Out

Lack of physical activity is a global public health problem causing not only morbidity and premature mortality, but it is also a major economic burden worldwide. One of the cornerstones of a physically active lifestyle is Motor Competence (MC). MC is a complex biocultural attribute and therefore, its study requires a multi-sectoral, multi-, inter- and transdisciplinary approach. MC is a growing area of research, especially in children and adolescents due to its positive association with a plethora of health and developmental outcomes. Many questions, however, remain to be answered in this field of research, with regard to: (i) Health and Developmental-related Associations of MC; (ii) Assessment of MC; (iii) Prevalence and Trends of MC; (iv) Correlates and Determinants of MC; (v) MC Interventions, and (vi) Translating MC Research into Practice and Policy. This paper presents a narrative review of the literature, summarizing current knowledge, identifying key research gaps and presenting questions for future investigation on MC in children and adolescents. This is a collaborative effort from the International Motor Competence Network (IMCNetwork) a network of academics and researchers aiming to promote international collaborative research and knowledge translation in the expansive field of MC. The knowledge and deliverables generated by addressing and answering the aforementioned research questions on MC presented in this review have the potential to shape the ways in which researchers and practitioners promote MC and physical activity in children and adolescents across the worl