Invitations, incentives, and conditions: A randomized evaluation of demand-side interventions for health screenings.

This randomized controlled trial investigates the impact of four demand-side interventions on health screening for diabetes and hypertension among Armenian adults. The interventions are 1) personalized invitations from a physician, 2) personalized invitations with information about peer screening behavior, 3) personalized invitations with a labeled but unconditional financial incentive, and 4) personal invitations with a conditional financial incentive. Compared with the control group, interventions 1 to 3 led to a significant increase in the screening rate of about 15 percentage points for diabetes and hypertension. The highest impact was measured for intervention 4 leading to a 31.2 percentage point increase in both screenings.

Leveraging changing gender norms to address concurrency: focus group findings from South African university students.

UNLABELLED: Background This study aims to complement recent research on sexual concurrency in South Africa by providing a deeper understanding of women's roles and motivations for engaging in and accepting their partners' concurrency. Our goal is to inform the implementation of more effective interventions that embrace the powerful role that women can play in healthy sexual decision-making in consensual relationships. METHODS: We conducted 12 focus groups with male and female students at the University of KwaZulu-Natal. Drawing on a subset of those focus groups, we examined the gender norms underpinning the apparently widespread acceptance of concurrent sexual partnerships. Our analysis focusses on women's attitudes and behaviours towards concurrency - from both men's and women's perspectives - with a goal of identifying opportunities to engage women as agents of change in sexual partnership patterns in their communities. RESULTS: Our findings indicate that: (1) concurrent sexual partnerships were the norm among male students and increasingly common among female students; (2) material gain and changes in women's perceptions of their roles and power in relationships were the primary female motives for concurrency; (3) peer pressure, a perceived innate need and a fear of being alone were the primary male motives for concurrency; (4) women often know that their partners are cheating and stay with them because they believe they are the most important partner, for financial reasons, or because they worry they will not find another partner. CONCLUSIONS: HIV prevention interventions in populations where concurrency is common would benefit from emphasising women's role and power in taking greater control of their own sexual decision-making in consensual and nonviolent relationships.

Improving Access to Medicines for Non-Communicable Diseases in the Developing World.

Non-communicable diseases (NCDs) now account for the majority of global morbidity and mortality and are increasingly affecting developing countries whose under-resourced health care systems also have to handle a high burden of infectious disease. To counter the global devastation caused by NCDs, the United Nations General Assembly decided to "set a new global agenda" and convened a high-level meeting on NCDs in September 2011. In connection with this meeting, the authors of this article took a first step toward developing a policy research agenda for improving access to NCD medicines in developing countries, a step that the research-based pharmaceutical industry, in particular, can carry forward as part of broader global efforts to combat NCD. The authors provide a framework for understanding the obstacles to access for NCD medicines, review specific issues to be confronted within each obstacle in the developing world, identify promising ideas for improving access to NCD medicines, and point to several highly promising areas for the research-based pharmaceutical industry to focus on as it develops its NCD policy research program in close collaboration with other key stakeholders.

Empirically controlled mapping of the Caenorhabditis elegans protein-protein interactome network.

To provide accurate biological hypotheses and elucidate global properties of cellular networks, systematic identification of protein-protein interactions must meet high quality standards.We present an expanded C. elegans protein-protein interaction network, or 'interactome' map, derived from testing a matrix of approximately 10,000 x approximately 10,000 proteins using a highly specific, high-throughput yeast two-hybrid system. Through a new empirical quality control framework, we show that the resulting data set (Worm Interactome 2007, or WI-2007) was similar in quality to low-throughput data curated from the literature. We filtered previous interaction data sets and integrated them with WI-2007 to generate a high-confidence consolidated map (Worm Interactome version 8, or WI8). This work allowed us to estimate the size of the worm interactome at approximately 116,000 interactions. Comparison with other types of functional genomic data shows the complementarity of distinct experimental approaches in predicting different functional relationships between genes or proteins

Network modeling links breast cancer susceptibility and centrosome dysfunction.

Many cancer-associated genes remain to be identified to clarify the underlying molecular mechanisms of cancer susceptibility and progression. Better understanding is also required of how mutations in cancer genes affect their products in the context of complex cellular networks. Here we have used a network modeling strategy to identify genes potentially associated with higher risk of breast cancer. Starting with four known genes encoding tumor suppressors of breast cancer, we combined gene expression profiling with functional genomic and proteomic (or 'omic') data from various species to generate a network containing 118 genes linked by 866 potential functional associations. This network shows higher connectivity than expected by chance, suggesting that its components function in biologically related pathways. One of the components of the network is HMMR, encoding a centrosome subunit, for which we demonstrate previously unknown functional associations with the breast cancer-associated gene BRCA1. Two case-control studies of incident breast cancer indicate that the HMMR locus is associated with higher risk of breast cancer in humans. Our network modeling strategy should be useful for the discovery of additional cancer-associated genes.

Towards a proteome-scale map of the human protein-protein interaction network.

Systematic mapping of protein-protein interactions, or 'interactome' mapping, was initiated in model organisms, starting with defined biological processes and then expanding to the scale of the proteome. Although far from complete, such maps have revealed global topological and dynamic features of interactome networks that relate to known biological properties, suggesting that a human interactome map will provide insight into development and disease mechanisms at a systems level. Here we describe an initial version of a proteome-scale map of human binary protein-protein interactions. Using a stringent, high-throughput yeast two-hybrid system, we tested pairwise interactions among the products of approximately 8,100 currently available Gateway-cloned open reading frames and detected approximately 2,800 interactions. This data set, called CCSB-HI1, has a verification rate of approximately 78% as revealed by an independent co-affinity purification assay, and correlates significantly with other biological attributes. The CCSB-HI1 data set increases by approximately 70% the set of available binary interactions within the tested space and reveals more than 300 new connections to over 100 disease-associated proteins. This work represents an important step towards a systematic and comprehensive human interactome project.

Systematic interactome mapping and genetic perturbation analysis of a C. elegans TGF-beta signaling network.

To initiate a system-level analysis of C. elegans DAF-7/TGF-beta signaling, we combined interactome mapping with single and double genetic perturbations. Yeast two-hybrid (Y2H) screens starting with known DAF-7/TGF-beta pathway components defined a network of 71 interactions among 59 proteins. Coaffinity purification (co-AP) assays in mammalian cells confirmed the overall quality of this network. Systematic perturbations of the network using RNAi, both in wild-type and daf-7/TGF-beta pathway mutant animals, identified nine DAF-7/TGF-beta signaling modifiers, seven of which are conserved in humans. We show that one of these has functional homology to human SNO/SKI oncoproteins and that mutations at the corresponding genetic locus daf-5 confer defects in DAF-7/TGF-beta signaling. Our results reveal substantial molecular complexity in DAF-7/TGF-beta signal transduction. Integrating interactome maps with systematic genetic perturbations may be useful for developing a systems biology approach to this and other signaling modules.