Updates in the chronic kidney disease-mineral bone disorder show the role of osteocytic proteins, a potential mechanism of the bone-Vascular paradox, a therapeutic target, and a biomarker.

The chronic kidney disease-mineral bone disorder (CKD-MBD) is a complex multi-component syndrome occurring during kidney disease and its progression. Here, we update progress in the components of the syndrome, and synthesize recent investigations, which suggest a potential mechanism of the bone-vascular paradox. The discovery that calcified arteries in chronic kidney disease inhibit bone remodeling lead to the identification of factors produced by the vasculature that inhibit the skeleton, thus providing a potential explanation for the bone-vascular paradox. Among the factors produced by calcifying arteries, sclerostin secretion is especially enlightening. Sclerostin is a potent inhibitor of bone remodeling and an osteocyte specific protein. Its production by the vasculature in chronic kidney disease identifies the key role of vascular cell osteoblastic/osteocytic transdifferentiation in vascular calcification and renal osteodystrophy. Subsequent studies showing that inhibition of sclerostin activity by a monoclonal antibody improved bone remodeling as expected, but stimulated vascular calcification, demonstrate that vascular sclerostin functions to brake the Wnt stimulation of the calcification milieu. Thus, the target of therapy in the chronic kidney disease-mineral bone disorder is not inhibition of sclerostin function, which would intensify vascular calcification. Rather, decreasing sclerostin production by decreasing the vascular osteoblastic/osteocytic transdifferentiation is the goal. This might decrease vascular calcification, decrease vascular stiffness, decrease cardiac hypertrophy, decrease sclerostin production, reduce serum sclerostin and improve skeletal remodeling. Thus, the therapeutic target of the chronic kidney disease-mineral bone disorder may be vascular osteoblastic transdifferentiation, and sclerostin levels may be a useful biomarker for the diagnosis of the chronic kidney disease-mineral bone disorder and the progress of its therapy.

Towards an interdisciplinary approach to wellbeing: Life histories and Self-Determination Theory in rural Zambia.

What are the prospects for a cross-cultural, interdisciplinary and methodologically plural approach to wellbeing? This question is addressed using Self-Determination Theory (SDT), a psychological theory based on quantitative empirical methods, to structure qualitative analysis of wellbeing in life history interviews in Chiawa, rural Zambia. Enquiry goes beyond simply reading across methods, disciplines and contexts, to consider fundamental differences in constructions of the human subject, and how these relate to understandings of wellbeing. Field research took place in two periods, August-November, 2010 and 2012. Analysis draws primarily on 46 individual case studies, conducted through open-ended interviews. These were identified through a survey with an average of 390 male and female household heads in each round, including 25% female headed households. As SDT predicts, the interviews confirm its key elements of autonomy, competence and relatedness as vital to wellbeing. However, these are expressed in ways that highlight material and relational, rather than psychological, factors. Key findings are: the mutual constitution of autonomy, competence and relatedness; the appreciation of autonomy as independence in action; the importance of social competence; and the centrality of relatedness. People appear as social and above all moral subjects. The paper concludes by endorsing SDT's utility in interdisciplinary approaches to wellbeing, but only if it admits its own cultural grounding in the construction of a psychological subject. This would go beyond recognising that autonomy, competence and relatedness may take socially and culturally distinctive forms, to questioning their universal status as basic psychological needs. Implications for organisations working on wellbeing are discussed.

Tournament ABC analysis of the western Palaearctic population history of an oak gall wasp, Synergus umbraculus.

Approximate Bayesian computation (ABC) is a powerful and widely used approach in inference of population history. However, the computational effort required to discriminate among alternative historical scenarios often limits the set that is compared to those considered more likely a priori. While often justifiable, this approach will fail to consider unexpected but well-supported population histories. We used a hierarchical tournament approach, in which subsets of scenarios are compared in a first round of ABC analyses and the winners are compared in a second analysis, to reconstruct the population history of an oak gall wasp, Synergus umbraculus (Hymenoptera, Cynipidae) across the Western Palaearctic. We used 4,233 bp of sequence data across seven loci to explore the relationships between four putative Pleistocene refuge populations in Iberia, Italy, the Balkans and Western Asia. We compared support for 148 alternative scenarios in eight pools, each pool comprising all possible rearrangements of four populations over a given topology of relationships, with or without founding of one population by admixture and with or without an unsampled "ghost" population. We found very little support for the directional "out of the east" scenario previously inferred for other gall wasp community members. Instead, the best-supported models identified Iberia as the first-regional population to diverge from the others in the late Pleistocene, followed by divergence between the Balkans and Western Asia, and founding of the Italian population through late Pleistocene admixture from Iberia and the Balkans. We compare these results with what is known for other members of the oak gall community, and consider the strengths and weaknesses of using a tournament approach to explore phylogeographic model space.

Inner Wellbeing: Concept and Validation of a New Approach to Subjective Perceptions of Wellbeing-India.

This paper describes the conceptual development of a multi-domain, psychosocial model of 'Inner Wellbeing' (IWB) and assesses the construct validity of the scale designed to measure it. IWB expresses what people think and feel they are able to be and do. Drawing together scholarship in wellbeing and international development it is grounded in field research in marginalised, rural communities in the global South. Results from research in India at two points in time (2011 and 2013) are reported. At Time 1 (n = 287), we were unable to confirm an eight-factor, correlated model as distinct yet interrelated domains. However, at Time 2 (n = 335), we were able to confirm a revised, seven-factor correlated model with economic confidence, agency and participation, social connections, close relationships, physical and mental health, competence and self-worth, and values and meaning (five items per domain) as distinct yet interrelated domains. In particular, at Time 2, a seven-factor, correlated model provided a significantly better fit to the data than did a one-factor model.

Women's perspectives on cervical screening and treatment in developing countries: experiences with new technologies and service delivery strategies.

This review of studies conducted by partners in the Alliance for Cervical Cancer Prevention (ACCP) examines women's perspectives on, and acceptability of, new cervical cancer screening and treatment approaches, management by mid-level staff, single-visit strategies, treatment side effects, and post-treatment abstinence requirements in low-resource settings. All screening, managed by female nurses and irrespective of method or constellation of methods, appeared to be highly acceptable. Similarly, cryotherapy treatment, including cryotherapy managed by nurses immediately after screening, was well-received by women in the studies. Minor side effects, although rather prevalent, and difficulties with post-treatment abstinence, did not appear to significantly deter women from recommending the procedure to friends. Rather, a sense of relief was evident, a feeling that it was better to be treated than not treated, and better to be treated sooner rather than later. While full replication may not be possible, this does not lessen the fact that screening and treatment in developing countries, even with new technologies, immediate treatment and even using mid-level providers, can be very acceptable to women if provided in a safe, caring and preferably all-female environment.

Promoting healthy behaviors to prevent chronic disease in Panama and Trinidad & Tobago: results of the women as agents of change project.

In order to address the growing burden of chronic diseases in the Americas, the Pan American Health Organization implemented the Women as Agents of Change project in Panama and Trinidad & Tobago. The project focused on low income, middle aged women and promoted increased physical activity, intake of 5 servings of fruits and vegetables daily, and yearly screening for cervical cancer. One hundred women per country participated in the 6 week program which consisted of weekly meetings and participation in a behavior change curriculum. Gollwitzer's theory of implementation intentions and the theory of social support provided the methodology for the design of the curriculum. At baseline, end of project, and at 6 months, participants completed physical activity and fruit and vegetable consumption surveys. Results show an increase in consumption in Panama between the pre and post-tests, though the increase was not maintained at the 6 month period. Physical activity decreased in both countries over the intervention period, likely due to misreporting on the pretest. Notably, most participants reported on the 6 month follow up survey that they had continued or intensified the behavior changes they undertook during the project. The paper describes barriers identified by the participants as well as strategies they devised to overcome them.