Vitamin D time profile based on the contribution of non-genetic and genetic factors in HIV-infected individuals of European ancestry

BACKGROUND Vitamin D deficiency is prevalent in HIV-infected individuals and vitamin D supplementation is proposed according to standard care. This study aimed at characterizing the kinetics of 25(OH)D in a cohort of HIV-infected individuals of European ancestry to better define the influence of genetic and non-genetic factors on 25(OH)D levels. These data were used for the optimization of vitamin D supplementation in order to reach therapeutic targets. METHODS 1,397 25(OH)D plasma levels and relevant clinical information were collected in 664 participants during medical routine follow up visits. They were genotyped for 7 SNPs in 4 genes known to be associated with 25(OH)D levels. 25(OH)D concentrations were analyzed using a population pharmacokinetic approach. The percentage of individuals with 25(OH)D concentrations within the recommended range of 20-40ng/ml during 12 months of follow up and several dosage regimens were evaluated by simulation. RESULTS A one-compartment model with linear absorption and elimination was used to describe 25(OH)D pharmacokinetics, while integrating endogenous baseline plasma concentrations. Covariate analyses confirmed the effect of seasonality, body mass index, smoking habits, the analytical method, darunavir/r and the genetic variant in GC (rs2282679) on 25(OH)D concentrations. 11% of the interindividual variability in 25(OH)D levels was explained by seasonality and other non-genetic covariates and 1% by genetics. The optimal supplementation for severe vitamin D deficient patients was 300000 IU two times per year. CONCLUSIONS This analysis allowed identifying factors associated with 25(OH)D plasma levels in HIV-infected individuals. Improvement of dosage regimen and timing of vitamin D supplementation is proposed based on those results.

Three “Bali Deliverables” for more Food Security

As the clock is ticking for a positive outcome at the Ninth WTO Ministerial Conference to be held in Bali in December 2013, agricultural negotiators are scrambling to find solutions to issues such as tariff-rate quota (TRQ) administration and export competition in order to improve trade flows. The main issue seems to be whether WTO rules applying to public stockpiles in developing countries need to be changed or temporarily suspended as a means to enhance national food security. This paper is based on a note submitted to the ICTSD-IPC Expert Group “Meeting on Agriculture and Food Security – Policy Options for MC9 and beyond” (Geneva, June 2013). It lists the policy instruments impacting on global, national and (urban and rural) household food security – “The Food Security Tool Box” – and asks which immediate decisions the WTO Ministers might take in this field despite the political difficulties such as continued agro-dumping practices or the “land grab” issue. Three such “deliverables” are outlined: (i) regional and “virtual” food security schemes could be allowed to provide reserves to other countries without violating the obligation to “form an integral part of a food security programme identified in national legislation” (Agreement on Agriculture, Annex II, para 3); (ii) TRQ under-fills could be improved by mandatory enquiries into low fill rate situations; and (iii) World Food Program (WFP) and other non-commercial food purchases could be exempted from export restrictions and prohibitions. High ambitions for Bali seem to be misplaced. A more realistic yet real progress could restore the dwindling credibility of the WTO as a forum for trade negotiations.

The WTO and Food Security: What’s Wrong with the Rules?

The WTO Agreement on Agriculture (AoA) is the predominant multilateral legal framework governing agricultural trade. The objective of the AoA is to liberalise trade in agriculture through reductions in tariffs, domestic support and export subsidies. The AoA has not, however, ‘levelled the playing field’ and has not resulted in the equitable distribution of food, particularly for the poorer developing countries. On the other hand, support for small farmers does not ensure food security for the poor. While food security has no simple solutions such as “free trade is good for you”, reform proposals for trade rules which only address agricultural policy instruments fail to account for consumer and other interests: neither tariff reductions and subsidy disciplines, nor safeguards and other measures of producer protection can automatically increase food security. Rather, what is needed is the full and proper implementation of a number of commitments which the international community has already entered into in various human rights treaties, but which even the envisaged results of the now failed Doha Round negotiations could not ensure without revisiting relevant multilateral trade and investment rules.

Exceptional or just well connected? Political entrepreneurs and brokers in policy making

Policy brokers and policy entrepreneurs are assumed to have a decisive impact on policy outcomes. Their access to social and political resources is contingent on their influence on other agents. In social network analysis (SNA), entrepreneurs are often closely associated with brokers, because both are agents presumed to benefit from bridging structural holes; for example, gaining advantage through occupying a strategic position in relational space. Our aim here is twofold. First, to conceptually and operationally differentiate policy brokers from policy entrepreneurs premised on assumptions in the policy-process literature; and second, via SNA, to use the output of core algorithms in a cross-sectional analysis of political brokerage and political entrepreneurship. We attempt to simplify the use of graph algebra in answering questions relevant to policy analysis by placing each algorithm within its theoretical context. In the methodology employed, we first identify actors and graph their relations of influence within a specific policy event; then we select the most central actors; and compare their rank in a series of statistics that capture different aspects of their network advantage. We examine betweenness centrality, positive and negative Bonacich power, Burt’s effective size and constraint and honest brokerage as paradigmatic. We employ two case studies to demonstrate the advantages and limitations of each algorithm for differentiating between brokers and entrepreneurs: one on Swiss climate policy and one on EU competition and transport policy.

Enhancing Food Sovereignty and Food Security through the Revitalization of Indigenous Knowledge: Experiences from the Bolivian Andes

Endogenous development is defined as development that values primarily locally available resources and the way people organized themselves for that purpose. It is a dynamic and evolving concept that also embraces innovations and complementation from other than endogenous sources of knowledge; however, only as far as they are based on mutual respect and the recognition of cultural and socioeconomic self-determination of each of the parties involved. Experiences that have been systematized in the context of the BioAndes Program are demonstrating that enhancing food security and food sovereignty on the basis of endogenous development can be best achieved by applying a ‘biocultural’ perspective: This means to promote and support actions that are simultaneously valuing biological (fauna, flora, soils, or agrobiodiversity) and sociocultural resources (forms of social organization, local knowledge and skills, norms, and the related worldviews). In Bolivia, that is one of the Latin-American countries with the highest levels of poverty (79% of the rural population) and undernourishment (22% of the total population), the Program BioAndes promotes food sovereignty and food security by revitalizing the knowledge of Andean indigenous people and strengthening their livelihood strategies. This starts by recognizing that Andean people have developed complex strategies to constantly adapt to highly diverse and changing socioenvironmental conditions. These strategies are characterized by organizing the communities, land use and livelihoods along a vertical gradient of the available eco-climatic zones; the resulting agricultural systems are evolving around the own sociocultural values of reciprocity and mutual cooperation, giving thus access to an extensive variety of food, fiber and energy sources. As the influences of markets, competition or individualization are increasingly affecting the life in the communities, people became aware of the need to find a new balance between endogenous and exogenous forms of knowledge. In this context, BioAndes starts by recognizing the wealth and potentials of local practices and aims to integrate its actions into the ongoing endogenous processes of innovation and adaptation. In order to avoid external impositions and biases, the program intervenes on the basis of a dialogue between exogenous, mainly scientific, and indigenous forms of knowledge. The paper presents an analysis of the strengths and weaknesses of enhancing endogenous development through a dialogue between scientific and indigenous knowledge by specifically focusing on its effects on food sovereignty and food security in three ‘biocultural’ rural areas of the Bolivian highlands. The paper shows how the dialogue between different forms of knowledge evolved alongside the following project activities: 1) recuperation and renovation of local seeds and crop varieties (potato – Solanum spp., quinoa – Chenopodium quinoa, cañahua – Chenopodium pallidicaule); 2) support for the elaboration of community-based norms and regulations for governing access and distribution of non-timber forest products, such as medicinal, fodder, and construction plants; 3) revitalization of ethnoveterinary knowledge for sheep and llama breeding; 4) improvement of local knowledge about the transformation of food products (sheep-cheese, lacayote – Cucurbita sp. - jam, dried llama meat, fours of cañahua and other Andean crops). The implementation of these activities fostered the community-based livelihoods of indigenous people by complementing them with carefully and jointly designed innovations based on internal and external sources of knowledge and resources. Through this process, the epistemological and ontological basis that underlies local practices was made visible. On this basis, local and external actors started to jointly define a renewed concept of food security and food sovereignty that, while oriented in the notions of well being according to a collectively re-crafted world view, was incorporating external contributions as well. Enabling and hindering factors, actors and conditions of these processes are discussed in the paper.

Decomposing hierarchical alignment: Co-arguments as conditions on alignment and the limits of referential hierarchies as explanations in verb agreement

Apart from common cases of differential argument marking, referential hierarchies affect argument marking in two ways: (a) through hierarchical marking, where markers compete for a slot and the competition is resolved by a hierarchy, and (b) through co-argument sensitivity, where the marking of one argument depends on the properties of its co-argument. Here we show that while co-argument sensitivity cannot be analyzed in terms of hierarchical marking, hierarchical marking can be analyzed in terms of co-argument sensitivity. Once hierarchical effects on marking are analyzed in terms of co-argument sensitivity, it becomes possible to examine alignment patterns relative to referential categories in exactly the same way as one can examine alignment patterns relative to referential categories in cases of differential argument marking and indeed any other condition on alignment (such as tense or clause type). As a result, instances of hierarchical marking of any kind turn out not to present a special case in the typology of alignment, and there is no need for positing an additional non-basic alignment type such as “hierarchical alignment”. While hierarchies are not needed for descriptive and comparative purposes, we also cast doubt on their relevance in diachrony: examining two families for which hierarchical agreement has been postulated, Algonquian and Kiranti, we find only weak and very limited statistical evidence for agreement paradigms to have been shaped by a principled ranking of person categories.

Incretin receptors in non-neoplastic and neoplastic thyroid C cells in rodents and humans: relevance for incretin-based diabetes therapy

While incretins are of great interest for the therapy of diabetes 2, the focus has recently been brought to the thyroid, since rodents treated with glucagon-like peptide-1 (GLP-1) analogs were found to occasionally develop medullary thyroid carcinomas. Incretin receptors for GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) were therefore measured in various rodent and human thyroid conditions. In vitro GLP-1 and GIP receptor autoradiography were performed in normal thyroids, C-cell hyperplasia and medullary thyroid carcinomas in rodents. Receptor incidence and density were assessed and compared with the receptor expression in human thyroids, medullary thyroid carcinomas, and TT cells. GLP-1 receptors are expressed in C cells of normal rat and mice thyroids. Their density is markedly increased in rat C-cell hyperplasia and medullary thyroid carcinomas, where their incidence amounts to 100%. GIP receptors are neither detected in normal rodent thyroids nor in C-cell hyperplasia, but are present in all rat medullary thyroid carcinomas. No GLP-1 or GIP receptors are detected in normal human thyroids. Whereas only 27% of all human medullary thyroid carcinomas express GLP-1 receptors, up to 89% express GIP receptors in a high density. TT cells lack GLP-1 receptors but express GIP receptors. GLP-1 receptors are frequently expressed in non-neoplastic and neoplastic C cells in rodents while they are rarely detected in human C-cell neoplasia, suggesting species differences. Conversely, GIP receptors appear to be massively overexpressed in neoplastic C cells in both species. The presence of incretin receptors in thyroid C cell lesions suggests that this organ should be monitored before and during incretin-based therapy of diabetes.

Climate change: an additional risk factor for agriculture and food security in the South

Climate change is expected to have far-reaching negative effects on agricultural production and food security in developing and transition countries. What do we know about these expected impacts, what are the factors that might affect production, and what are the implications for agricultural extension systems?