Molecular Genetics of T Cell Development

T cell development is guided by a complex set of transcription factors that act recursively, in different combinations, at each of the developmental choice points from T-lineage specification to peripheral T cell specialization. This review describes the modes of action of the major T-lineage-defining transcription factors and the signal pathways that activate them during intrathymic differentiation from pluripotent precursors. Roles of Notch and its effector RBPSuh (CSL), GATA-3, E2A/HEB and Id proteins, c-Myb, TCF-1, and members of the Runx, Ets, and Ikaros families are critical. Less known transcription factors that are newly recognized as being required for T cell development at particular checkpoints are also described. The transcriptional regulation of T cell development is contrasted with that of B cell development, in terms of their different degrees of overlap with the stem-cell program and the different roles of key transcription factors in gene regulatory networks leading to lineage commitment

Empowerment and women in adventure tourism : a negotiated journey

Women’s participation in adventure tourism is growing, yet few studies have explored this group of tourists. This conceptual paper seeks to extend our understanding of female adventure tourists by examining the empowering journey women can take through constraint negotiation to enjoy the benefits of adventure tourism. Using content analysis to review the literature on women’s adventure experiences in tourism and recreation settings reveals prominent themes that have been consolidated to propose constraint, negotiation and benefit categories. A conceptual model is presented that illustrates the opportunities for women’s empowerment within these categories and examines the interrelationships and interdependency between them. The model shows that constraints, negotiations and benefits can be experienced simultaneously, at different points in a woman’s adventure tourism journey and used as a vehicle for empowerment. Women will also re-evaluate these categories before, during and after their adventure tourism experience. Therefore, the categories are not fixed and evolve each time a woman participates in adventure tourism throughout her life. Suggestions are made for further study in this under-researched area

Tryptophan metabolism, its relation to inflammation and stress markers and association with psychological and cognitive functioning: Tasmanian Chronic Kidney Disease pilot study

Raw Data in five data sheets including Patients relevant metadata, quantified metabolites (given at Οg/L as well as Οmol/L), psychology measures, common medication and comorbidities. (XLS 58 kb

Treatment of osteoporosis in an older home care population

BACKGROUND: Previous research indicates that many patients with fractures indicative of underlying osteoporosis are not receiving appropriate diagnostic follow-up and therapy. We assessed osteoporosis treatment coverage in older home care clients with a diagnosis of osteoporosis and/or prevalent fracture. METHODS: Subjects included 330 home care clients, aged 65+, participating in a longitudinal study of medication adherence and health-related outcomes. Data on clients' demographic, health and functional status and service utilization patterns were collected using the Minimum Data Set for Home Care (MDS-HC). A medication review included prescribed and over-the-counter medications taken in the past 7 days. Criteria for indications for osteoporosis therapy included diagnosis of osteoporosis or a recent fracture. Coverage for treatment was examined for anti-osteoporotic therapies approved for use in 2000. RESULTS: Of the 330 home care clients, 78 (24%) had a diagnosis of osteoporosis (n = 47) and/or had sustained a recent fracture (n = 34). Drug data were available for 77/78 subjects. Among the subjects with osteoporosis or a recent fracture, 45.5% were receiving treatment for osteoporosis; 14% were receiving only calcium and vitamin D, and an additional 31% were receiving drug therapy (bisphosphonate or hormone replacement therapy). The remaining 54.5% of subjects were not receiving any approved osteoporosis therapy. CONCLUSIONS: The high prevalence of undertreatment among a population of older adults with relatively high access to health care services raises concern regarding the adequacy of diagnosis and treatment of osteoporosis in the community

Analysing Visits to English Museums 1850-2015: A Research Note

<p>Understanding why people visit museums is of interest to both cultural economics and museum studies. Most existing research relies on survey data concerned with visitors, their immediate background, and their experience of a particular museum. Very few studies have taken a more general perspective and analysed macro-level societal factors, such as inflation, educational attainment and unemployment, and their influence on the number of visits to museums. The conventional approach relies on visitor surveys to understand what drives visits and people’s general views on museums.</p> <p>In a departure from these conventional approaches, this article presents a macro-level approach, using a unique dataset of visit counts for 40 English museums and visitor attractions spanning the period 1850–2015. It examines the effect of socio-economic factors on visits using panel data analysis and macro-level variables. The results suggest that inflation rates, average earnings, and educational level (using the indicator of secondary school attendance) all significantly influence the number of visits made. However, the most important variable is the number of visits recorded for the previous year. These findings are discussed in relation to existing studies, and some suggestions for future research are proposed.</p

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

Mutations of the transcription factor PU.1 are not associated with acute lymphoblastic leukaemia

The transcription factor PU.1 plays a crucial role during normal haematopoiesis in both myeloid cells and B-lymphocytes. Mice with a disruption in both alleles of the PU.1 locus were found to lack macrophages and B cells and had delayed appearance of neutrophils. In addition, critical decrease of PU.1 expression is sufficient to cause acute myeloid leukaemia (AML) and lymphomas in mice. Recently, we reported that heterozygous mutations in the PU.1 gene are present in some patients with AML. Thus, we hypothesised that PU.1 mutations might also contribute to the development of acute leukaemias of the B-cell lineage. Here, we screened 62 patients with B-cell acute lymphoblastic leukaemia (B-ALL) at diagnosis for genomic mutations by direct sequencing of all five exons of the PU.1 gene. We found no genomic alteration of the PU.1 gene suggesting that PU.1 mutations are not likely to be common in B-ALL

The Extent and Role of Domestic Tourism in a Small Island: The Case of the Isle of Man

This article presents a case concerning microdomestic tourism on the Isle of Man, British Isles. Despite being a small island, research highlights that considerable domestic tourism occurs (referred to as microdomestic tourism to reflect the small island size and distinguish from wider British Isles tourism), including day trips and overnight stays. Participants identified such behavior as touristic, and distinct from other leisure activities. Qualitative interviews with residents explore the nature of and reasons for microdomestic tourism within a small island. Breaks from routine, entertaining friends and family, and exploring less well known landscapes are shown to underpin. Highlighted is that microdomestic tourism has a variety of potential benefits, which may counter some of the restrictions typically faced by a small island community. Support for an otherwise ailing tourism industry may help to protect facilities and infrastructure used by the wider community, maintain tourism capacity, and provide atmosphere attractive to foreign visitors

The behaviour of repeat visitors to museums: Review and empirical findings

This study presents a theoretical and operational framework for analysing repeat visit to museums. Starting from the literature on repeat visit in tourism, the specificities of these cultural attractions are made explicit through a review of theoretical and applied works. Consistently with previous contributors, the paper suggests that the analysis of actual past behaviours has to be preferred to the one of attitudes. The application of proper econometric models is also remarked in order to put into account individual profiles. Information coming from three techniques is then used in an integrated way in order to provide a more comprehensive view of the phenomenon. Evidence from an ad hoc survey suggests the necessity to give a greater attention to perceived cultural value during the visit, promoting cultural events during the week and addressed to children, and taking care of those visitors that come from far places also through an integrated tourist supply. © 2013 Springer Science+Business Media Dordrecht