Keeping healthy and accessing primary and preventive health services in Glasgow: the experiences of refugees and asylum seekers from Sub Saharan Africa

Background and aims: Recent decades have seen material shifts in global migration flows. Migrants now come to the UK for an increasing number of reasons and from an increasing number of countries. This presents a challenge for health services that must provide care to individuals with a broad range of needs. In particular, there is concern that asylum seekers and refugees (ASRs) are at heightened risk of poor wellbeing and of receiving suboptimal healthcare. Concurrent with these shifts in migration, increasing attention is being paid to noncommunicable diseases (NCDs), which are now the most significant drivers of morbidity and mortality in most regions of the world. In the UK, the burden of NCDs is not evenly distributed, with inequalities related to ethnicity and socioeconomic status shaping an individual’s risk of ill health. Little is known, however, about how diverse migrant groups, including ASRs, conceptualise health and respond to health prevention messaging. Against this backdrop, this thesis aims to understand the health-related experiences of one such group – asylum seekers and refugees (ASRs) from Sub Saharan Africa living in Glasgow Scotland. Specifically, it explores: a) perceptions of health, wellbeing, and illness causation, b) experiences of accessing primary and preventive healthcare, and c) the factors influencing these perceptions and experiences. It also seeks to elucidate professional perspectives on ASR health. Methods: To gain an in depth understanding of ASR health perceptions and experiences, as well as professional perspectives, a focused ethnography was undertaken. This approach utilised four qualitative methods: community engagement, participatory focus groups, semistructured interviews, and go- along interviews. In total 12 primary care and public health professionals were interviewed, and 27 ASRs took part in either a focus group, an interview, or both. The thesis took a theoretically informed approach, seeking to determine whether and how two theories – ‘candidacy’ (Dixon-Woods et al 2005) and ‘structural vulnerability’ (Quesada et al 2011) – might deepen our understanding of ASR health. Results: Candidacy enhanced understanding of how ASRs identified and responded to messages about ‘healthy lifestyles’. ASR participants considered keeping healthy to be an individual responsibility, with diet and exercise highlighted as especially important. At the same time, however, perceptions and experiences of health and wellbeing were shaped by a number of structural influences, which limited the capacity of ASRs to engage in health practices. Therefore, while ASRs considered health to be an individual choice in theory, they did not necessarily feel they had the ability to be healthy in practice. The theory of structural vulnerability proved useful in identifying the wider structural determinants that impacted on an individual’s capacity to respond. There were several important structural influences, including poverty, racism, discrimination, and language barriers. The greatest negative influence, however, and one that compounded all the others, was the asylum process. This diminished individuals’ capacity to identify as candidates for prevention messages, engage in preventive health practices, and/ or access care in an optimal fashion. Conclusions: Efforts to engage ASRs in preventive health programmes and practices must take into account the ways in which the immigration and asylum system acts as a determinant of health, affecting both what it means to be healthy and what capacity individuals have to engage. The NHS, together with non statutory bodies, has a role to play in mitigating some of the vulnerabilities to which ASRs are subject

TDP-43 is a culprit in human neurodegeneration, and not just an innocent bystander

In 2006 the protein TDP-43 was identified as the major ubiquitinated component deposited in the inclusion bodies found in two human neurodegenerative diseases, amyotrophic lateral sclerosis and frontotemporal lobar degeneration. The pathogenesis of both disorders is unclear, although they are related by having some overlap of symptoms and now by the shared histopathology of TDP-43 deposition. Now, in 2008, several papers have been published in quick succession describing mutations in the TDP-43 gene, showing they can be a primary cause of amyotrophic lateral sclerosis. There are many precedents in neurodegenerative disease in which rare single-gene mutations have given great insight into understanding disease processes, which is why the TDP-43 mutations are potentially very important

New social adaptability index predicts overall mortality

Introduction: Definitions of underprivileged status based on race, gender and geographic location are neither sensitive nor specific; instead we proposed and validated a composite index of social adaptability (SAI). Material and methods: Index of social adaptability was calculated based on employment, education, income, marital status, and substance abuse, each factor contributing from 0 to 3 points. Index of social adaptability was validated in NHANES-3 by association with all-cause and cause-specific mortality. Results: Weighted analysis of 19,593 subjects demonstrated mean SAI of 8.29 (95% CI 8.17-8.40). Index of social adaptability was higher in Whites, followed by Mexican-Americans and then the African-American population (ANOVA, p < 0.001). The SAI was higher in subjects living in metropolitan compared to rural areas (T-test, p < 0.001), and was greater in men than in women (T-test, p < 0.001). In Cox models adjusted for age, comorbidity index, BMI, race, sex, geographic location, hemoglobin, serum creatinine, albumin, cholesterol, and glycated hemoglobin levels, SAI was inversely associated with mortality (HR 0.87 per point, 95% CI 0.84-0.90, p < 0.001). This association was confirmed in subgroups. Conclusions: We proposed and validated an indicator of social adaptability with a strong association with mortality, which can be used to identify underprivileged populations at risk of death

Designer TGFβ Superfamily Ligands with Diversified Functionality

Transforming Growth Factor – beta (TGFβ) superfamily ligands, including Activins, Growth and Differentiation Factors (GDFs), and Bone Morphogenetic Proteins (BMPs), are excellent targets for protein-based therapeutics because of their pervasiveness in numerous developmental and cellular processes. We developed a strategy termed RASCH (Random Assembly of Segmental Chimera and Heteromer), to engineer chemically-refoldable TGFβ superfamily ligands with unique signaling properties. One of these engineered ligands, AB208, created from Activin-βA and BMP-2 sequences, exhibits the refolding characteristics of BMP-2 while possessing Activin-like signaling attributes. Further, we find several additional ligands, AB204, AB211, and AB215, which initiate the intracellular Smad1-mediated signaling pathways more strongly than BMP-2 but show no sensitivity to the natural BMP antagonist Noggin unlike natural BMP-2. In another design, incorporation of a short N-terminal segment from BMP-2 was sufficient to enable chemical refolding of BMP-9, without which was never produced nor refolded. Our studies show that the RASCH strategy enables us to expand the functional repertoire of TGFβ superfamily ligands through development of novel chimeric TGFβ ligands with diverse biological and clinical values

Prevalence of the HOXB13 G84E prostate cancer risk allele in men treated with radical prostatectomy

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106912/1/bju12522.pd

Identification of a novel germline SPOP mutation in a family with hereditary prostate cancer

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106871/1/pros22818.pd

Shortcomings of services for persons with severe and persistent mental health challenges: a qualitative study of service users and family carers

IntroductionThe opinions of service users and carers are crucial to identifying ways to innovate and implement system change. This study aims to explore the views and experiences of service users and carerson the services they have used for their mental health challenges and their suggestions for service reform.MethodsTwenty participants (15 carers and 5 service users) were interviewed for the study.ResultsEight categories emerged from the data. They were: Several gaps in the system, Barriers to accessing services, Services are not fit for purpose, Services operate in isolation, System is not person focused, Service users and carers are treated poorly, Services are overloaded and under resourced and Recommendations for service reform. Respondents reported that a persistent lack of funding and resources for mental health services was a main cause of these shortcomings. Respondents also noted that innovations were needed to re-orient services to enable continuity of care, and training of mental health professionals was needed for a better understanding of the needs of service users and their carers.DiscussionAdditional research is needed with larger and more diverse samples to further explore these findings

Attenuation of RNA polymerase II pausing mitigates BRCA1-associated R-loop accumulation and tumorigenesis.

Most BRCA1-associated breast tumours are basal-like yet originate from luminal progenitors. BRCA1 is best known for its functions in double-strand break repair and resolution of DNA replication stress. However, it is unclear whether loss of these ubiquitously important functions fully explains the cell lineage-specific tumorigenesis. In vitro studies implicate BRCA1 in elimination of R-loops, DNA-RNA hybrid structures involved in transcription and genetic instability. Here we show that R-loops accumulate preferentially in breast luminal epithelial cells, not in basal epithelial or stromal cells, of BRCA1 mutation carriers. Furthermore, R-loops are enriched at the 5' end of those genes with promoter-proximal RNA polymerase II (Pol II) pausing. Genetic ablation of Cobra1, which encodes a Pol II-pausing and BRCA1-binding protein, ameliorates R-loop accumulation and reduces tumorigenesis in Brca1-knockout mouse mammary epithelium. Our studies show that Pol II pausing is an important contributor to BRCA1-associated R-loop accumulation and breast cancer development