Bodies of knowledge: medical anthropology and interdisciplinarity

Medical anthropology at Oxford was intended to be a short-term departure from my first degree in chemical engineering, motivated by my desire to understand health and illness in the context of wider society rather than within the confines of the lab. Ultimately Oxford medical anthropology became something much more significant for me: a journey into unknown intellectual waters that led me to redefine both my career path and my academic identity. After being part of the first MSc/MPhil cohort and completing doctoral research within the programme in 2007, I became a postdoctoral research officer within Oxford's Unit for Biocultural Variation and Obesity before serving as Departmental Lecturer in Medical Anthropology from 2008-2014. I now work within the Health Services Research Unit, part of Oxford's Medical Sciences Division, where I hope to contribute the insights of medical anthropology towards interdisciplinary research informing health practice and policy at the national level

Community-based person-centred integrated care (PIC) networks for healthy ageing in place: a scoping review protocol

Introduction: The economic case for preventive care delivered in or near citizens’ homes is strong, and there is growing evidence of the role of local-level support in supporting people’s health and well-being as they age. However, effective and consistent delivery of person-centred integrated care (PIC) at the community level remains elusive. Previous systematic reviews have focused on specific processes such as case management, but none have focused on the operational delivery of community-based care networks. In this study, we aim to identify what practice-based models of PIC networks exist at the local/neighbourhood level and what evidence is available as to their effectiveness for healthy ageing in place. Methods and analysis: We will undertake a scoping review following the framework proposed by Arksey and O’Malley and updated guidance by the Joanna Briggs Institute. Peer-reviewed sources will be identified through searches of seven databases, and relevant grey literature will be identified through websites of policy and voluntary sector organisations focused on integrated care and/or healthy ageing. Data from included studies will be extracted for relevance to the research questions, including aims and anticipated outcomes of network models, financial and management structures of networks, and evidence of evaluation. Summary tables and narrative comparisons of key PIC network features across settings will be presented. Ethics and dissemination: As no primary data will be collected, ethical approval is not required to conduct this scoping review. In addition to publication as a peer-reviewed article, the results of this review will be summarised as shorter discussion papers for use in follow-up research

Homologous and heterologous desensitization of guanylyl cyclase-B signaling in GH3 somatolactotropes

The guanylyl cyclases, GC-A and GC-B, are selective receptors for atrial and C-type natriuretic peptides (ANP and CNP, respectively). In the anterior pituitary, CNP and GC-B are major regulators of cGMP production in gonadotropes and yet mouse models of disrupted CNP and GC-B indicate a potential role in growth hormone secretion. In the current study, we investigate the molecular and pharmacological properties of the CNP/GC-B system in somatotrope lineage cells. Primary rat pituitary and GH3 somatolactotropes expressed functional GC-A and GC-B receptors that had similar EC50 properties in terms of cGMP production. Interestingly, GC-B signaling underwent rapid homologous desensitization in a protein phosphatase 2A (PP2A)-dependent manner. Chronic exposure to either CNP or ANP caused a significant down-regulation of both GC-A- and GC-B-dependent cGMP accumulation in a ligand-specific manner. However, this down-regulation was not accompanied by alterations in the sub-cellular localization of these receptors. Heterologous desensitization of GC-B signaling occurred in GH3 cells following exposure to either sphingosine-1-phosphate or thyrotrophin-releasing hormone (TRH). This heterologous desensitization was protein kinase C (PKC)-dependent, as pre-treatment with GF109203X prevented the effect of TRH on CNP/GC-B signaling. Collectively, these data indicate common and distinct properties of particulate guanylyl cyclase receptors in somatotropes and reveal that independent mechanisms of homologous and heterologous desensitization occur involving either PP2A or PKC. Guanylyl cyclase receptors thus represent potential novel therapeutic targets for treating growth-hormone-associated disorders

Overcoming barriers to engaging socio-economically disadvantaged populations in CHD primary prevention: a qualitative study

<p><b>Background:</b> Preventative medicine has become increasingly important in efforts to reduce the burden of chronic disease in industrialised countries. However, interventions that fail to recruit socio-economically representative samples may widen existing health inequalities. This paper explores the barriers and facilitators to engaging a socio-economically disadvantaged (SED) population in primary prevention for coronary heart disease (CHD).</p> <p><b>Methods:</b> The primary prevention element of Have a Heart Paisley (HaHP) offered risk screening to all eligible individuals. The programme employed two approaches to engaging with the community: a) a social marketing campaign and b) a community development project adopting primarily face-to-face canvassing. Individuals living in areas of SED were under-recruited via the social marketing approach, but successfully recruited via face-to-face canvassing. This paper reports on focus group discussions with participants, exploring their perceptions about and experiences of both approaches.</p> <p><b>Results:</b> Various reasons were identified for low uptake of risk screening amongst individuals living in areas of high SED in response to the social marketing campaign and a number of ways in which the face-to-face canvassing approach overcame these barriers were identified. These have been categorised into four main themes: (1) processes of engagement; (2) issues of understanding; (3) design of the screening service and (4) the priority accorded to screening. The most immediate barriers to recruitment were the invitation letter, which often failed to reach its target, and the general distrust of postal correspondence. In contrast, participants were positive about the face-to-face canvassing approach. Participants expressed a lack of knowledge and understanding about CHD and their risk of developing it and felt there was a lack of clarity in the information provided in the mailing in terms of the process and value of screening. In contrast, direct face-to-face contact meant that outreach workers could explain what to expect. Participants felt that the procedure for uptake of screening was demanding and inflexible, but that the drop-in sessions employed by the community development project had a major impact on recruitment and retention.</p> <p><b>Conclusion:</b> Socio-economically disadvantaged individuals can be hard-to-reach; engagement requires strategies tailored to the needs of the target population rather than a population-wide approach.</p&gt

Associations of clinical stroke misclassification (‘clinical-imaging dissociation’) in acute ischemic stroke

Background: Up to 20% of lacunar infarcts are misdiagnosed as cortical infarcts clinically and vice versa. The reasons for this discrepancy are unclear. We assessed clinical and imaging features which might explain this ‘clinical-imaging dissociation’. Methods: Patients with an acute stroke syndrome (cortical or lacunar) underwent magnetic resonance imaging including diffusion-weighted imaging (DWI). We recorded DWI-positive infarcts, proximity to cortex for small subcortical infarcts. We examined factors associated with clinical-imaging dissociation. Results: 137 patients with a mild cortical or lacunar syndrome had an acute ischaemic lesion on DWI. Of these, 21/93 (23%) with a cortical syndrome had an acute lacunar infarct and 7/44 (16%) with a lacunar syndrome had an acute cortical infarct. From 72 patients with an acute lacunar infarct on DWI, lesion proximity to cortex (odds ratio (OR) 14.5, 95% confidence interval (CI) 1.61 to 130.1), left hemisphere location (OR 8.95, 95% CI 1.23 to 64.99) and diabetes (OR 17.1, 95% CI 1.49 to 196.16) predicted clinical-imaging dissociation. On multivariate analysis of all 137 patients, clinical-imaging dissociation was associated with diabetes (OR 7.12, 95% CI 1.86 to 27.2). Conclusions: Clinical-imaging dissociation occurs in a fifth of patients with mild stroke. Lacunar infarcts lying close to cortex are more likely to cause cortical symptoms. Diabetes is associated with any clinical-imaging mismatch. Stroke misclassification which can arise with clinical classification alone should be minimised in research by verification with high sensitivity imaging

Rasch analysis of the long-term conditions questionnaire (LTCQ) and development of a short-form (LTCQ-8)

Background The aim of the current study was to evaluate the structural validity of the 20-item long-term conditions questionnaire (LTCQ) and to explore a potential short-form version of the scale using Rasch analysis. Methods Data were collected through postal surveys (February 2016–January 2017) from a sample of 1,211 participants diagnosed with at least one long-term condition (LTC). Identified participants were invited through either local authorities for a social care cohort (n = 294) or primary care practices for a health care cohort (n = 917). Participants were mailed a survey, including the LTCQ, demographic questions, a comorbidities measure, and other validated outcome measures. Respondents were invited to complete a follow-up survey including the LTCQ for assessment of reproducibility. Results The main assumptions of the Rasch model from the LTCQ were fulfilled, although infit and outfit indices indicated some items showed misfit. Misfitted items, items that did not have a preceding set or showed some local dependence were removed one at a time, with the remaining candidate items to form an 8-item short version, the LTCQ-8. The Rasch model for the LTCQ-8 explained 64% variance and had a reliability estimate greater than 0.80. Several items in the LTCQ showed uniform differential item function (DIF) in relation to the number of reported LTCs, age, cohort and type of LTCs, but fewer items exhibited DIF in the LTCQ-8. Spearman’s rho correlations between the LTCQ and the LTCQ-8 were strong across the total sample and various subgroups. Correlations between the LTCQ-8 and all reference measures were moderate to strong, and comparable to correlations found between the LTCQ and these measures. Conclusions The LTCQ measures a unidimensional construct, and it is therefore acceptable to use a summed total score. The LTCQ-8 also met the assumption of unidimensionality and had comparable construct validity with the LTCQ. Additional validation is required in an independent sample

Rescue of skeletal muscle α-actin–null mice by cardiac (fetal) α-actin

Skeletal muscle α-actin (ACTA1) is the major actin in postnatal skeletal muscle. Mutations of ACTA1 cause mostly fatal congenital myopathies. Cardiac α-actin (ACTC) is the major striated actin in adult heart and fetal skeletal muscle. It is unknown why ACTC and ACTA1 expression switch during development. We investigated whether ACTC can replace ACTA1 in postnatal skeletal muscle. Two ACTC transgenic mouse lines were crossed with Acta1 knockout mice (which all die by 9 d after birth). Offspring resulting from the cross with the high expressing line survive to old age, and their skeletal muscles show no gross pathological features. The mice are not impaired on grip strength, rotarod, or locomotor activity. These findings indicate that ACTC is sufficiently similar to ACTA1 to produce adequate function in postnatal skeletal muscle. This raises the prospect that ACTC reactivation might provide a therapy for ACTA1 diseases. In addition, the mouse model will allow analysis of the precise functional differences between ACTA1 and ACTC

Nonsteroidal sulfamate derivatives as new therapeutic approaches for Neurofibromatosis 2 (NF2)

Abstract Background Neurofibromatosis 1 and 2, although involving two different tumour suppressor genes (neurofibromin and merlin, respectively), are both cancer predisposition syndromes that disproportionately affect cells of neural crest origin. New therapeutic approaches for both NF1 and NF2 are badly needed. In promising previous work we demonstrated that two non-steroidal analogues of 2-methoxy-oestradiol (2ME2), STX3451(2-(3-bromo-4,5-dimethoxybenzyl)-7-methoxy-6-sulfamoyloxy-1,2,3,4-tetrahydroisoquinoline), and STX2895 (7-Ethyl-6-sulfamoyloxy-2-(3,4,5-trimethoxybenzyl)-1,2,3,4-tetrahydroisoquinoline) reduced tumour cell growth and induced apoptosis in malignant and benign human Neurofibromatosis 1 (NF1) tumour cells. In earlier NF1 mechanism of action studies we found that in addition to their effects on non-classical hormone-sensitive pathways, STX agents acted on the actin- and myosin-cytoskeleton, as well as PI3Kinase and MTOR signaling pathways. Tumour growth in NF2 cells is affected by different inhibitors from those affecting NF1 growth pathways: specifically, NF2 cells are affected by merlin-downstream pathway inhibitors. Because Merlin, the affected tumour suppressor gene in NF2, is also known to be involved in stabilizing membrane-cytoskeletal complexes, as well as in cell proliferation, and apoptosis, we looked for potentially common mechanisms of action in the agents’ effects on NF1 and NF2. We set out to determine whether STX agents could therefore also provide a prospective avenue for treatment of NF2. Methods STX3451 and STX2895 were tested in dose-dependent studies for their effects on growth parameters of malignant and benign NF2 human tumour cell lines in vitro. The mechanisms of action of STX3451 and STX2895 were also analysed. Results Although neither of the agents tested affected cell growth or apoptosis in the NF2 tumour cell lines tested through the same mechanisms by which they affect these parameters in NF1 tumour cell lines, both agents disrupted actin- and myosin-based cytoskeletal structures in NF2 cell lines, with subsequent effects on growth and cell death. Conclusions Both STX3451 and STX2895 provide new approaches for inducing cell death and lowering tumour burden in NF2 as well as in NF1, which both have limited treatment options.https://deepblue.lib.umich.edu/bitstream/2027.42/152170/1/40360_2019_Article_369.pd

Humanities for medical students? A qualitative study of a medical humanities curriculum in a medical school program

BACKGROUND: Today, there is a trend towards establishing the medical humanities as a component of medical education. However, medical humanities programs that exist within the context of a medical school can be problematic. The aim of this study was to explore problems that can arise with the establishment of a medical humanities curriculum in a medical school program. METHODS: Our theoretical approach in this study is informed by derridean deconstruction and by post-structuralist analysis. We examined the ideology of the Humanities and Medicine program at Lund University, Sweden, the practical implementation of the program, and how ideology and practice corresponded. Examination of the ideology driving the humanities and medicine program was based on a critical reading of all available written material concerning the Humanities and Medicine project. The practice of the program was examined by means of a participatory observation study of one course, and by in-depth interviews with five students who participated in the course. Data was analysed using a hermeneutic editing approach. RESULTS: The ideological language used to describe the program calls it an interdisciplinary learning environment but at the same time shows that the conditions of the program are established by the medical faculty's agenda. In practice, the "humanities" are constructed, defined and used within a medical frame of reference. Medical students have interesting discussions, acquire concepts and enjoy the program. But they come away lacking theoretical structure to understand what they have learned. There is no place for humanities students in the program. CONCLUSION: A challenge facing cross-disciplinary programs is creating an environment where the disciplines have equal standing and contribution