The Bioarchaeology of Kinship: Proposed Revisions to Assumptions Guiding Interpretation

Bioarchaeology provides sophisticated techniques for estimating intra- and intercemetery biological relationships (i.e., biodistances), which can significantly expand anthropological research on kinship, explaining multiple dimensions of social life and identity in prehistory. However, some assumptions guiding the interpretation of results may need reconsideration. Although it is often assumed that descent groups should be homogeneous, social organizational and marriage practices actually produce heterogeneity within descent groups. Interpretations of postmarital residence typically assume that spouses are buried together in the same cemetery, whereas cross-cultural ethnographic patterns suggest that postmortem location does not universally follow residence. Nevertheless, cross-cultural data do indicate that postmortem location is generally predictable by type of descent group and whether membership with natal groups is maintained or transferred upon marriage. These issues are discussed, leading to alternative models on intra- and intercemetery biodistance expectations for matrilineal descent groups, for patrilineal descent groups with and without wives’ membership transfers, and for a range of smaller groups under bilateral descent. The influence of common marriage alliance systems on intra- and intergroup phenotypic heterogeneity versus homogeneity are also described. The proposed biodistance expectations for interpreting different kinship and marriage strategies may better position bioarchaeologists to engage other subfields and make substantial contributions to kinship research

De-constructing a complex programme using a logic map: Realist Evaluation of Maternal and Child Health in Nigeria

Community health workers (CHW) programmes are inherently complex and their outcome is mediated by how interventions are implemented, the availability and quality of local health services, preferences of service users and the context of the health system. In March 2015, the University of Leeds was awarded a 5-year MRC grant to use a realist evaluation framework and mixed methods design to assess the extent to which and under what circumstances, a novel CHW programme in Nigeria, promotes equitable access to quality services and improves maternal and child health outcomes. As background to the evaluation, the Government of Nigeria launched a social protection initiative (SURE-P) in 2012, to invest revenues from fuel subsidy reduction for improving the lives of its most vulnerable populations. The SURE-P programme comprises of supply and demand components. The first aims to broaden access to quality maternal health services and improve MCH outcomes through recruiting CHWs, improving infrastructure development and increasing availability of supplies and medicines. The second aims to increase utilization of health services during pregnancy and at birth through the use of a conditional cash transfer (CCT) programme. CCTs are given to pregnant women who register at a primary health care (PHC) centre, where they get health check-ups while pregnant, deliver at a health facility, and take their baby for the first series of vaccinations. The methodology for evaluation involves three steps: 1) initial programme theory development, 2) theory validation and 3) refining theory and developing lessons learned. This paper aims to report the process of using ‘logic map’ as a tool for developing the initial programme theory for SURE-P programme. To achieve this, we have used the logic map to graphically deconstruct our group’s (i.e. researchers, policymakers and implementers) current thinking of how SURE-P programme should work in the context of Nigeria by illustrating complex relations between stakeholders, context, implementation process, outputs and outcomes of SURE-P interventions. The logic map will also serve as a focal point for discussions about data collection and programme evaluation by displaying when, where, and how we will obtain information most needed to manage the SURE-P programme and determine its effectiveness

Cancer Genomics Identifies Regulatory Gene Networks Associated with the Transition from Dysplasia to Advanced Lung Adenocarcinomas Induced by c-Raf-1

Background: Lung cancer is a leading cause of cancer morbidity. To improve an understanding of molecular causes of disease a transgenic mouse model was investigated where targeted expression of the serine threonine kinase c-Raf to respiratory epithelium induced initialy dysplasia and subsequently adenocarcinomas. This enables dissection of genetic events associated with precancerous and cancerous lesions. Methodology/Principal Findings: By laser microdissection cancer cell populations were harvested and subjected to whole genome expression analyses. Overall 473 and 541 genes were significantly regulated, when cancer versus transgenic and non-transgenic cells were compared, giving rise to three distinct and one common regulatory gene network. At advanced stages of tumor growth predominately repression of gene expression was observed, but genes previously shown to be upregulated in dysplasia were also up-regulated in solid tumors. Regulation of developmental programs as well as epithelial mesenchymal and mesenchymal endothelial transition was a hall mark of adenocarcinomas. Additionaly, genes coding for cell adhesion, i.e. the integrins and the tight and gap junction proteins were repressed, whereas ligands for receptor tyrosine kinase such as epi- and amphiregulin were up-regulated. Notably, Vegfr- 2 and its ligand Vegfd, as well as Notch and Wnt signalling cascades were regulated as were glycosylases that influence cellular recognition. Other regulated signalling molecules included guanine exchange factors that play a role in an activation of the MAP kinases while several tumor suppressors i.e. Mcc, Hey1, Fat3, Armcx1 and Reck were significantly repressed. Finally, probable molecular switches forcing dysplastic cells into malignantly transformed cells could be identified. Conclusions/Significance: This study provides insight into molecular pertubations allowing dysplasia to progress further to adenocarcinoma induced by exaggerted c-Raf kinase activity

Refractory hypercalcaemia associated with disseminated Cryptococcus neoformans infection

Hypercalcaemia is a very common endocrine condition, yet severe hypercalcaemia as a result of fungal infection is rarely described. There are have only been two reported cases in the literature of hypercalcaemia associated with Cryptococcus infection. Although the mechanism of hypercalcaemia in these infections is not clear, it has been suggested that it could be driven by the extra-renal production of 1-alpha-hydroxylase by macrophages in granulomas. We describe the case of a 55-year-old woman with a 1,25-OH D-mediated refractory hypercalcaemia in the context of a Cryptococcus neoformans infection. She required treatment with antifungals, pamidronate, calcitonin, denosumab and high-dose glucocorticoids. A disseminated fungal infection should be suspected in immunosuppressed individuals presenting with hypercalcaemia

Pegylated arginine deiminase lowers hepatitis C viral titers and inhibits nitric oxide synthesis.

The arginine-degrading enzyme, arginine deiminase conjugated to polyethylene glycol (ADI-SS PEG 20,000 mw), reduces extracellular arginine, has minimal toxicity, decreases tumor burden and improves liver function in patients with chronic hepatitis C virus infection (HCV) and inoperable hepatocellular carcinoma (HCC). Reduced extracellular arginine inhibits viral replication through unknown mechanisms. It is hypothesized that ADI-SS PEG 20,000 mw reduces HCV viral titers through nitric oxide (NO)-dependent effects. METHODS: The effects of ADI-SS PEG 20,000 mw (dose, 160 IU/m2; three cycles of four once-weekly i.m. injections) on HCV titers, serum NO and plasma arginine, were evaluated using archived plasma from patients with HCC and HCV and in vitro cell model measurements of HCV replication. RESULTS: ADI-SS PEG 20,000 mw selectively inhibited HCV replication in vitro (IC50 = 0.027 IU/mL). Fifteen HCC/HCV patients completed treatment. The HCV titers were reduced by up to 99% in five out of 10 (50%) HCV-serotype 1b patients (P = 0.0093). These patients also experienced significant improvements in liver function (P = 0.0091). There were concomitant reductions of plasma arginine and serum NO levels. The HCV titer was not reduced in HCV-type 2c patients. CONCLUSION: Reduction of extracellular arginine by ADI-SS PEG 20,000 mw in HCC patients reduces HCV viral titers and improves liver function, possibly through suppression of NO

What works? Strategies to increase reproductive, maternal and child health in difficult to access mountainous locations: a systematic literature review

Background: Geography poses serious challenges to delivery of health services and is a well documented marker of inequity. Maternal, newborn and child health (MNCH) outcomes are poorer in mountainous regions of low and lower-middle income countries due to geographical inaccessibility combined with other barriers: poorer quality services, persistent cultural and traditional practices and lower socioeconomic and educational status. Reaching universal coverage goals will require attention for remote mountain settings. This study aims to identify strategies to address barriers to reproductive MNCH (RMNCH) service utilisation in difficult-to-reach mountainous regions in low and lower-middle income settings worldwide. Methods: A systematic literature review drawing from MEDLINE, Web of Science, Scopus, Google Scholar, and Eldis. Inclusion was based on; testing an intervention for utilisation of RMNCH services; remote mountain settings of low- and lower-middle income countries; selected study designs. Studies were assessed for quality and analysed to present a narrative review of the key themes. Findings: From 4,130 articles 34 studies were included, from Afghanistan, Bolivia, Ethiopia, Guatemala, Indonesia, Kenya, Kyrgyzstan, Nepal, Pakistan, Papua New Guinea and Tajikistan. Strategies fall into four broad categories: improving service delivery through selected, trained and supported community health workers (CHWs) to act alongside formal health workers and the distribution of critical medicines to the home; improving the desirability of existing services by addressing the quality of care, innovative training and supervision of health workers; generating demand by engaging communities; and improving health knowledge for timely care-seeking. Task shifting, strengthened roles of CHWs and volunteers, mobile teams, and inclusive structured planning forums have proved effective. Conclusions: The review highlights where known evidence-based strategies have increased the utilisation of RMNCH services in low income mountainous areas. While these are known strategies in public health, in such disadvantaged settings additional supports are required to address both supply and demand barriers