Savannah River Site/K Area Complex getter life extension report.

The K Area Complex (KAC) at the Savannah River Site (SRS) has been utilizing HiTop hydrogen getter material in 9975 Shipping Containers to prevent the development of flammable environments during storage of moisture-containing plutonium oxides. Previous testing and subsequent reports have been performed and produced by Sandia National Laboratories (SNL) to demonstrate the suitability and longevity of the getter during storage at bounding thermal conditions. To date, results have shown that after 18 months of continuous storage at 70 C, the getter is able to both recombine gaseous hydrogen and oxygen into water when oxygen is available, and irreversibly getter (i.e. scavenge) hydrogen from the vapor space when oxygen is not available, both under a CO{sub 2} environment. [Refs. 1-5] Both of these reactions are catalytically enhanced and thermodynamically favorable. The purpose of this paper is to establish the justification that maintaining the current efforts of biannual testing is no longer necessary due to the robust performance of the getter material, the very unlikely potential that the recombination reaction will fail during storage conditions in KAC, and the insignificant aging effects that have been seen in the testing to date

Mapping private pharmacies and their characteristics in Ujjain district, Central India

<p>Abstract</p> <p>Background</p> <p>In India, private pharmacies are ubiquitous yet critical establishments that facilitate community access to medicines. These are often the first points of treatment seeking in parts of India and other low income settings around the world. The characteristics of these pharmacies including their location, drug availability, human resources and infrastructure have not been studied before. Given the ubiquity and popularity of private pharmacies in India, such information would be useful to harness the potential of these pharmacies to deliver desirable public health outcomes, to facilitate regulation and to involve in initiatives pertaining to rational drug use. This study was a cross sectional survey that mapped private pharmacies in one district on a geographic information system and described relevant characteristics of these units.</p> <p>Methods</p> <p>This study of pharmacies was a part of larger cross sectional survey carried out to map all the health care providers in Ujjain district (population 1.9 million), Central India, on a geographic information system. Their location vis-à-vis formal providers of health services were studied. Other characteristics like human resources, infrastructure, clients and availability of tracer drugs were also surveyed.</p> <p>Results</p> <p>A total 475 private pharmacies were identified in the district. Three-quarter were in urban areas, where they were concentrated around physician practices. In rural areas, pharmacies were located along the main roads. A majority of pharmacies simultaneously retailed medicines from multiple systems of medicine. Tracer parenteral antibiotics and injectable steroids were available in 83.7% and 88.7% pharmacies respectively. The proportion of clients without prescription was 39.04%. Only 11.58% of staff had formal pharmacist qualifications. Power outages were a significant challenge.</p> <p>Conclusion</p> <p>This is the first mapping of pharmacies & their characteristics in India. It provides evidence of the urban dominance and close relationship between healthcare provider location and pharmacy location. The implications of this relationship are discussed. The study reports a lack of qualified staff in the presence of a high proportion of clients attending without a prescription. The study highlights the need for the better implementation of regulation. Besides facilitating regulation & partnerships, the data also provides a sampling frame for future interventional studies on these pharmacies.</p

Microbial ligand costimulation drives neutrophilic steroid-refractory asthma

Funding: The authors thank the Wellcome Trust (102705) and the Universities of Aberdeen and Cape Town for funding. This research was also supported, in part, by National Institutes of Health GM53522 and GM083016 to DLW. KF and BNL are funded by the Fonds Wetenschappelijk Onderzoek, BNL is the recipient of an European Research Commission consolidator grant and participates in the European Union FP7 programs EUBIOPRED and MedALL. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

The inner centromere is a biomolecular condensate scaffolded by the chromosomal passenger complex.

The inner centromere is a region on every mitotic chromosome that enables specific biochemical reactions that underlie properties, such as the maintenance of cohesion, the regulation of kinetochores and the assembly of specialized chromatin, that can resist microtubule pulling forces. The chromosomal passenger complex (CPC) is abundantly localized to the inner centromeres and it is unclear whether it is involved in non-kinase activities that contribute to the generation of these unique chromatin properties. We find that the borealin subunit of the CPC drives phase separation of the CPC in vitro at concentrations that are below those found on the inner centromere. We also provide strong evidence that the CPC exists in a phase-separated state at the inner centromere. CPC phase separation is required for its inner-centromere localization and function during mitosis. We suggest that the CPC combines phase separation, kinase and histone code-reading activities to enable the formation of a chromatin body with unique biochemical activities at the inner centromere

The TCF7L2 locus and type 1 diabetes

<p>Abstract</p> <p>Background</p> <p><it>TCF7L2 </it>belongs to a subfamily of TCF7-like HMG box-containing transcription factors, and maps to human chromosome 10q25.3. A recent study identified genetic association of type 2 diabetes (T2D) with this gene, correlated with diminished insulin secretion. This study aimed to investigate the possibility of genetic association between <it>TCF7L2 </it>and type 1 diabetes (T1D).</p> <p>Methods</p> <p>The SNP most significantly associated with T2D, rs7903146, was genotyped in 886 T1D nuclear family trios with ethnic backgrounds of mixed European descent.</p> <p>Results</p> <p>This study found no T1D association with, and no age-of-onset effect from rs7903146.</p> <p>Conclusion</p> <p>This study suggests that a T2D mechanism mediated by <it>TCF7L2 </it>does not participate in the etiology of T1D.</p

Good adherence to HAART and improved survival in a community HIV/AIDS treatment and care programme: the experience of The AIDS Support Organization (TASO), Kampala, Uganda

BACKGROUND: Poor adherence to highly active antiretroviral therapy (HAART) may result in treatment failure and death. Most reports of the effect of adherence to HAART on mortality come from studies where special efforts are made to provide HAART under ideal conditions. However, there are few reports of the impact of non-adherence to HAART on mortality from community HIV/AIDS treatment and care programmes in developing countries. We therefore conducted a study to assess the effect of adherence to HAART on survival in The AIDS Support Organization (TASO) community HAART programme in Kampala, Uganda. METHODS: The study was a retrospective cohort of 897 patients who initiated HAART at TASO clinic, Kampala, between May 2004 and December 2006. A total of 7,856 adherence assessments were performed on the data. Adherence was assessed using a combination of self-report and pill count methods. Patients who took 95%. The crude death rate was 12.2 deaths per 100 patient-years, with a rate of 42.5 deaths per 100 patient-years for non-adherent patients and 6.1 deaths per 100 patient-years for adherent patients. Non-adherence to ART was significantly associated with mortality. Patients with a CD4 count of less than 50 cells/mm3 had a higher mortality (HR = 4.3; 95% CI: 2.22-5.56) compared to patients with a CD4 count equal to or greater than 50 cells/mm3 (HR = 2.4; 95% CI: 1.79-2.38). CONCLUSION: Our study showed that good adherence and improved survival are feasible in community HIV/AIDS programmes such as that of TASO, Uganda. However, there is need to support community HAART programmes to overcome the challenges of funding to provide sustainable supplies particularly of antiretroviral drugs; provision of high quality clinical and laboratory support; and achieving a balance between expansion and quality of services. Measures for the early identification and treatment of HIV infected people including home-based VCT and HAART should be strengthened

PTB Domain-Directed Substrate Targeting in a Tyrosine Kinase from the Unicellular Choanoflagellate Monosiga brevicollis

Choanoflagellates are considered to be the closest living unicellular relatives of metazoans. The genome of the choanoflagellate Monosiga brevicollis contains a surprisingly high number and diversity of tyrosine kinases, tyrosine phosphatases, and phosphotyrosine-binding domains. Many of the tyrosine kinases possess combinations of domains that have not been observed in any multicellular organism. The role of these protein interaction domains in M. brevicollis kinase signaling is not clear. Here, we have carried out a biochemical characterization of Monosiga HMTK1, a protein containing a putative PTB domain linked to a tyrosine kinase catalytic domain. We cloned, expressed, and purified HMTK1, and we demonstrated that it possesses tyrosine kinase activity. We used immobilized peptide arrays to define a preferred ligand for the third PTB domain of HMTK1. Peptide sequences containing this ligand sequence are phosphorylated efficiently by recombinant HMTK1, suggesting that the PTB domain of HMTK1 has a role in substrate recognition analogous to the SH2 and SH3 domains of mammalian Src family kinases. We suggest that the substrate recruitment function of the noncatalytic domains of tyrosine kinases arose before their roles in autoinhibition

A user-centred approach to developing bWell, a mobile app for arm and shoulder exercises after breast cancer treatment

Purpose: The study aim was to develop a mobile application (app) supported by user preferences to optimise self-management of arm and shoulder exercises for upper-limb dysfunction (ULD) after breast cancer treatment. Methods: Focus groups with breast cancer patients were held to identify user needs and requirements. Behaviour change techniques were explored by researchers and discussed during the focus groups. Concepts for content were identified by thematic analysis. A rapid review was conducted to inform the exercise programme. Preliminary testing was carried out to obtain user feedback from breast cancer patients who used the app for 8 weeks post-surgery. Results: Breast cancer patients’ experiences with ULD and exercise advice and routines varied widely. They identified and prioritised several app features: tailored information, video demonstrations of the exercises, push notifications, and tracking and progress features. An evidence-based programme was developed with a physiotherapist with progressive exercises for passive and active mobilisation, stretching and strengthening. The exercise demonstration videos were filmed with a breast cancer patient. Early user testing demonstrated ease of use, and clear and motivating app content. Conclusions: bWell, a novel app for arm and shoulder exercises was developed by breast cancer patients, health care professionals and academics. Further research is warranted to confirm its clinical effectiveness. Implications for Cancer Survivors: Mobile health has great potential to provide patients with information specific to their needs. bWell is a promising way to support breast cancer patients with exercise routines after treatment and may improve future self-management of clinical care