EthniCity of leisure : a domains approach to ethnic integration during free time activities

The research leading to these results has received funding from the Estonian Research Council (Institutional Research Grant IUT2-17 on Spatial Population Mobility and Geographical Changes in Urban Regions); the Estonian Science Foundation (Grant No. 8774 and 9247); and the European Research Council under the European Union’s Seventh Framework Programme (FP/2007-2013)/ERC [Grant Agreement No. 615159] (ERC Consolidator Grant DEPRIVEDHOODS, Socio-spatial inequality, deprived neighbourhoods, and neighbourhood effects); and from the Marie Curie programme under the European Union’s Seventh Framework Programme (FP/2007-2013)/Career Integration [Grant No. PCIG10-GA-2011-303728] (CIG Grant NBHCHOICE, Neighbourhood choice, neighbourhood sorting, and neighbourhood effects)This paper investigates the most common leisure time activities, activity sites and the interaction between members of minority and majority populations as they spend their time out-of-home and out-of-workplace. We ask the question how leisure time activities are related to the ethnic dimensions of residential and workplaces. Our case study area is Tallinn, Estonia, and the main findings show that leisure time activity patterns have become very similar across the main ethnic groups, which is different from what is found for workplace and residential segregation. This shows the integrative potential of leisure time activities. However, since members of the minority and majority population still tend to visit different leisure sites, there is little interaction. We also find that people often spend their free time close to home, which implies that high levels of ethnic residential segregation translate into ethnic segregation during leisure time.Publisher PDFPeer reviewe

Vetiver, o capim campeão contra a erosão.

Com raízes densas e profundas e sementes que não germinam, ele garante ótima barreira contra enxurradas.bitstream/item/114585/1/erosao.pd

Distinct immune signatures in directly treated and distant tumors result from TLR adjuvants and focal ablation.

Both adjuvants and focal ablation can alter the local innate immune system and trigger a highly effective systemic response. Our goal is to determine the impact of these treatments on directly treated and distant disease and the mechanisms for the enhanced response obtained by combinatorial treatments. Methods: We combined RNA-sequencing, flow cytometry and TCR-sequencing to dissect the impact of immunotherapy and of immunotherapy combined with ablation on local and systemic immune components. Results: With administration of a toll-like receptor agonist agonist (CpG) alone or CpG combined with same-site ablation, we found dramatic differences between the local and distant tumor environments, where the directly treated tumors were skewed to high expression of F4/80, Cd11b and Tnf and the distant tumors to enhanced Cd11c, Cd3 and Ifng. When ablation was added to immunotherapy, 100% (n=20/20) of directly treated tumors and 90% (n=18/20) of distant tumors were responsive. Comparing the combined ablation-immunotherapy treatment to immunotherapy alone, we find three major mechanistic differences. First, while ablation alone enhanced intratumoral antigen cross-presentation (up to ~8% of CD45+ cells), systemic cross-presentation of tumor antigen remained low. Combining same-site ablation with CpG amplified cross-presentation in the draining lymph node (~16% of CD45+ cells) compared to the ablation-only (~0.1% of CD45+ cells) and immunotherapy-only cohorts (~10% of CD45+ cells). Macrophages and DCs process and present this antigen to CD8+ T-cells, increasing the number of unique T-cell receptor rearrangements in distant tumors. Second, type I interferon (IFN) release from tumor cells increased with the ablation-immunotherapy treatment as compared with ablation or immunotherapy alone. Type I IFN release is synergistic with toll-like receptor activation in enhancing cytokine and chemokine expression. Expression of genes associated with T-cell activation and stimulation (Eomes, Prf1 and Icos) was 27, 56 and 89-fold higher with ablation-immunotherapy treatment as compared to the no-treatment controls (and 12, 32 and 60-fold higher for immunotherapy-only treatment as compared to the no-treatment controls). Third, we found that the ablation-immunotherapy treatment polarized macrophages and dendritic cells towards a CD169 subset systemically, where CD169+ macrophages are an IFN-enhanced subpopulation associated with dead-cell antigen presentation. Conclusion: While the local and distant responses are distinct, CpG combined with ablative focal therapy drives a highly effective systemic immune response

Questioning policy, youth participation and lifestyle sports

Young people have been identified as a key target group for whom participation in sport and physical activity could have important benefits to health and wellbeing and consequently have been the focus of several government policies to increase participation in the UK. Lifestyle sports represent one such strategy for encouraging and sustaining new engagements in sport and physical activity in youth groups, however, there is at present a lack of understanding of the use of these activities within policy contexts. This paper presents findings from a government initiative which sought to increase participation in sport for young people through provision of facilities for mountain biking in a forest in south-east England. Findings from qualitative research with 40 young people who participated in mountain biking at the case study location highlight the importance of non-traditional sports as a means to experience the natural environments through forms of consumption which are healthy, active and appeal to their identities. In addition, however, the paper raises questions over the accessibility of schemes for some individuals and social groups, and the ability to incorporate sports which are inherently participant-led into state-managed schemes. Lifestyle sports such as mountain biking involve distinct forms of participation which present a challenge for policy-makers who seek to create and maintain sustainable communities of youth participants

Pioglitazone corrects dysregulation of skeletal muscle mitochondrial proteins involved in ATP synthesis in type 2 diabetes

Context: In this study, we aimed to identify the determinants of mitochondrial dysfunction in skeletal muscle (SKLM) of subjects with type 2 diabetes (T2DM), and to evaluate the effect of pioglitazone (PIO) on SKLM mitochondrial proteome. Methods: Two different groups of adults were studied. Group I consisted of 8 individuals with normal glucose tolerance (NGT) and 8 with T2DM, subjected to SKLM mitochondrial proteome analysis by 2D-gel electrophoresis followed by mass spectrometry-based protein identification. Group II included 24 individuals with NGT and 24 with T2DM, whose SKLM biopsies were subjected to immunoblot analysis. Of the 24 subjects with T2DM, 20 were randomized to receive placebo or PIO (15 mg daily) for 6 months. After 6 months of treatment, SKLM biopsy was repeated. Results: Mitochondrial proteomic analysis on Group I revealed that several mitochondrial proteins involved in oxidative metabolism were differentially expressed between T2DM and NGT groups, with a downregulation of ATP synthase alpha chain (ATP5A), electron transfer flavoprotein alpha-subunit (ETFA), cytochrome c oxidase subunit VIb isoform 1 (CX6B1), pyruvate dehydrogenase protein X component (ODPX), dihydrolipoamide dehydrogenase (DLDH), dihydrolipoamide-S-succinyltransferase (DLST), and mitofilin, and an up-regulation of hydroxyacyl-CoA-dehydrogenase (HCDH), 3,2-trans-enoyl-CoA-isomerase (D3D2) and delta3,5-delta2,4-dienoyl-CoA-isomerase (ECH1) in T2DM as compared to NGT subjects. By immunoblot analysis on SKLM lysates obtained from Group II we confirmed that, in comparison to NGT subjects, those with T2DM exhibited lower protein levels of ATP5A (−30%, P = 0.006), ETFA (−50%, P = 0.02), CX6B1 (−30%, P = 0.03), key factors for ATP biosynthesis, and of the structural protein mitofilin (−30%, P = 0.01). T2DM was associated with a reduced abundance of the enzymes involved in the Krebs cycle DLST and ODPX (−20%, P ≤ 0.05) and increased levels of HCDH and ECH1, enzymes implicated in the fatty acid catabolism (+30%, P ≤ 0.05). In subjects with type 2 diabetes treated with PIO for 6 months we found a restored SKLM protein abundance of ATP5A, ETFA, CX6B1, and mitofilin. Moreover, protein levels of HCDH and ECH1 were reduced by −10% and − 15% respectively (P ≤ 0.05 for both) after PIO treatment. Conclusion: Type 2 diabetes is associated with reduced levels of mitochondrial proteins involved in oxidative phosphorylation and an increased abundance of enzymes implicated in fatty acid catabolism in SKLM. PIO treatment is able to improve SKLM mitochondrial proteomic profile in subjects with T2DM

Clinical phenotype and genetic associations in autosomal dominant familial Alzheimer's disease: a case series

Background - The causes of phenotypic heterogeneity in familial Alzheimer’s disease with autosomal dominant inheritance are not well understood. We aimed to characterise clinical phenotypes and genetic associations with APP and PSEN1 mutations in symptomatic autosomal dominant familial Alzheimer’s disease (ADAD). Methods - We retrospectively analysed genotypic and phenotypic data (age at symptom onset, initial cognitive or behavioural symptoms, and presence of myoclonus, seizures, pyramidal signs, extrapyramidal signs, and cerebellar signs) from all individuals with ADAD due to APP or PSEN1 mutations seen at the Dementia Research Centre in London, UK. We examined the frequency of presenting symptoms and additional neurological features, investigated associations with age at symptom onset, APOE genotype, and mutation position, and explored phenotypic differences between APP and PSEN1 mutation carriers. The proportion of individuals presenting with various symptoms was analysed with descriptive statistics, stratified by mutation type. Findings - Between July 1, 1987, and Oct 31, 2015, age at onset was recorded for 213 patients (168 with PSEN1 mutations and 45 with APP mutations), with detailed history and neurological examination findings available for 121 (85 with PSEN1 mutations and 36 with APP mutations). We identified 38 different PSEN1 mutations (four novel) and six APP mutations (one novel). Age at onset differed by mutation, with a younger onset for individuals with PSEN1 mutations than for those with APP mutations (mean age 43·6 years [SD 7·2] vs 50·4 years [SD 5·2], respectively, p<0·0001); within the PSEN1 group, 72% of age at onset variance was explained by the specific mutation. A cluster of five mutations with particularly early onset (mean age at onset <40 years) involving PSEN1’s first hydrophilic loop suggests critical functional importance of this region. 71 (84%) individuals with PSEN1 mutations and 35 (97%) with APP mutations presented with amnestic symptoms, making atypical cognitive presentations significantly more common in PSEN1 mutation carriers (n=14; p=0·037). Myoclonus and seizures were the most common additional neurological features; individuals with myoclonus (40 [47%] with PSEN1 mutations and 12 [33%] with APP mutations) were significantly more likely to develop seizures (p=0·001 for PSEN1; p=0·036 for APP), which affected around a quarter of the patients in each group (20 [24%] and nine [25%], respectively). A number of patients with PSEN1 mutations had pyramidal (21 [25%]), extrapyramidal (12 [14%]), or cerebellar (three [4%]) signs. Interpretation - ADAD phenotypes are heterogeneous, with both age at onset and clinical features being influenced by mutation position as well as causative gene. This highlights the importance of considering genetic testing in young patients with dementia and additional neurological features in order to appropriately diagnose and treat their symptoms, and of examining different mutation types separately in future research. Funding - Medical Research Council and National Institute for Health Research

Search for low-mass WIMPs in a 0.6 kg day exposure of the DAMIC experiment at SNOLAB

We present results of a dark matter search performed with a 0.6 kg day exposure of the DAMIC experiment at the SNOLAB underground laboratory. We measure the energy spectrum of ionization events in the bulk silicon of charge-coupled devices down to a signal of 60 eV electron equivalent. The data are consistent with radiogenic backgrounds, and constraints on the spin-independent WIMP-nucleon elastic-scattering cross section are accordingly placed. A region of parameter space relevant to the potential signal from the CDMS-II Si experiment is excluded using the same target for the first time. This result obtained with a limited exposure demonstrates the potential to explore the low-mass WIMP region (<10 GeV/$c^{2}$) of the upcoming DAMIC100, a 100 g detector currently being installed in SNOLAB.Comment: 11 pages, 11 figure