Celebrating the work of PGRs in Human and Health Sciences

The School of Human and Health Sciences is justifiably proud of its research. World renowned staff examine issues as diverse as criminal profiling, wound care and child protection. Emerging themes for research in the school range from examining mental health and well-being to innovative approaches to understanding crime, from the study of national identity to examining beliefs in witchcraft and possession. This diversity in research areas is reflected in the work of the postgraduate researchers (PgRs) registered for research degrees under the supervision of academic and research staff of the school. In order to showcase this research, the School hosts an annual research festival in which PgRs can either give an oral presentation of their work, or produce a poster. The launch of this new e-book is a showcase of research from the second annual festival in 2016

Cantu syndrome–associated SUR2 (ABCC9) mutations in distinct structural domains result in KATP channel gain-of-function by differential mechanisms

The complex disorder Cantu syndrome (CS) arises from gainof-function mutations in either KCNJ8 or ABCC9, the genes encoding the Kir6.1 and SUR2 subunits of ATP-sensitive potassium (KATP) channels, respectively. Recent reports indicate that such mutations can increase channel activity by multiple molecular mechanisms. In this study, we determined the mechanism by which KATP function is altered by several substitutions in distinct structural domains of SUR2: D207E in the intracellular L0-linker and Y985S, G989E, M1060I, and R1154Q/R1154W in TMD2. We engineered substitutions at their equivalent positions in rat SUR2A (D207E, Y981S, G985E, M1056I, and R1150Q/R1150W) and investigated functional consequences using macroscopic rubidium (86Rb-) efflux assays and patchclamp electrophysiology. Our results indicate that D207E increases KATP channel activity by increasing intrinsic stability of the open state, whereas the cluster of Y981S/G985E/M1056I substitutions, as well as R1150Q/R1150W, augmented Mg-nucleotide activation. We also tested the responses of these channel variants to inhibition by the sulfonylurea drug glibenclamide, a potential pharmacotherapy for CS. None of the D207E, Y981S, G985E, or M1056I substitutions had a significant effect on glibenclamide sensitivity. However, Gln and Trp substitution at Arg-1150 significantly decreased glibenclamide potency. In summary, these results provide additional confirmation that mutations in CS-Associated SUR2 mutations result in KATP gain-of-function. They help link CS genotypes to phenotypes and shed light on the underlying molecular mechanisms, including consequences for inhibitory drug sensitivity, insights that may inform the development of therapeutic approaches to manage CS

Patient and researcher perspectives on facilitating patient and public involvement in rheumatology research

No abstract available

Alien Registration- Cox, Helen (Fort Fairfield, Aroostook County)

https://digitalmaine.com/alien_docs/35725/thumbnail.jp

Improving Newborn Survival in Southern Tanzania (INSIST) trial; community-based maternal and newborn care economic analysis.

Despite health systems improvements in Tanzania, gaps in the continuum of care for maternal, newborn and child health persist. Recent improvements have largely benefited those over one month of age, leading to a greater proportion of under-five mortality in newborns. Community health workers providing home-based counselling have been championed as uniquely qualified to reach the poorest. We provide financial and economic costs of a volunteer home-based counselling programme in southern Tanzania. Financial costs of the programme were extracted from project accounts. Ministry of Health and Social Welfare costs associated with programme implementation were collected based on staff and project monthly activity plans. Household costs associated with facility-based delivery were also estimated based on exit interviews with post-natal women. Time spent on the programme by implementers was assessed by interviews conducted with volunteers and health staff. The programme involved substantial design and set-up costs. The main drivers of set-up costs were activities related to volunteer training. Total annualized costs (design, set-up and implementation) amounted to nearly US$300 000 for financial costs and just over US$400 000 for economic costs. Volunteers (n = 842) spent just under 14 hours per month on programme-related activities. When volunteer time was valued under economic costs, this input amounted to just under half of the costs of implementation. The economic consequences of increased service use to households were estimated at US$36 985. The intervention cost per mother-newborn pair visited was between US$12.60 and US$19.50, and the incremental cost per additional facility-based delivery ranged from US$85.50 to US$137.20 for financial and economic costs (with household costs). Three scale-up scenarios were considered, with the financial cost per home visit respectively varying from$1.44 to $3.21 across scenarios. Cost-effectiveness compares well with supply-side initiatives to increase coverage of facility-based deliveries, and the intervention would benefit from substantial economies of scale

Understanding service users’ and therapists’ experiences of pharmacological treatment for sexual preoccupation and/or hypersexuality in incarcerated sex offenders

This research comprises two qualitative studies understanding the experiences of 1) convicted sex offenders voluntarily receiving pharmacological treatment to reduce sexual preoccupation and 2) therapists working with these offenders. The studies form part of a research programme evaluating the use of pharmacological treatment with sexual offenders. In study one, semi-structured interviews were conducted with 13 sexual offenders receiving selective serotonin reuptake inhibitors (SSRIs). In study two, interviews were conducted with eight intervention staff with varying levels of experience of working with offenders taking anti-libidinals. Thematic analysis was used and in study one, two main themes emerged: (i) the impact of the pharmacological treatment on prisoners’ daily functioning; (ii) barriers to compliance/engagement. In study two, three main themes emerged: (i) offenders’ reluctance to engage with pharmacological treatment; (ii) challenges for therapists; (iii) pharmacology: ‘just another piece of the puzzle’. Findings are discussed in relation to practice and future research

Consensus for genes to be included on cancer panel tests offered by UK genetics services: guidelines of the UK Cancer Genetics Group.

Genetic testing for hereditary cancer predisposition has evolved rapidly in recent years with the discovery of new genes, but there is much debate over the clinical utility of testing genes for which there are currently limited data regarding the degree of associated cancer risk. To address the discrepancies that have arisen in the provision of these tests across the UK, the UK Cancer Genetics Group facilitated a 1-day workshop with representation from the majority of National Health Service (NHS) clinical genetics services. Using a preworkshop survey followed by focused discussion of genes without prior majority agreement for inclusion, we achieved consensus for panels of cancer genes with sufficient evidence for clinical utility, to be adopted by all NHS genetics services. To support consistency in the delivery of these tests and advice given to families across the country, we also developed management proposals for individuals who are found to have pathogenic mutations in these genes. However, we fully acknowledge that the decision regarding what test is most appropriate for an individual family rests with the clinician, and will depend on factors including specific phenotypic features and the family structure