Identifying Opportunities for Collaboration Across the Social Sciences to Reach the 10-10-10: A Multilevel Approach.

BACKGROUND:The national and global strategy to combat HIV, often referred to as the "90-90-90," aims to diagnose 90% of people living with HIV, get 90% of those diagnosed onto antiretroviral treatment (ART), and achieve viral suppression in 90% of those on ART. The remaining 10-10-10 who will be undiagnosed, not on ART, or not virally suppressed, include vulnerable persons and populations most affected by social determinants of health. Given their foci on the social determinants of health at the individual, social, and structural levels, social scientists are in a prime position to help reach the 10-10-10. A potentially effective way for social scientists to achieve this goal is to examine the issues that affect the 10-10-10 using a multilevel framework, to understand at what levels their own approaches fit within such a multilevel framework, and to seek intentional collaborations with other social scientists who may work at different levels but whose approaches may complement their own within multilevel collaborations. APPROACH:The present article describes how a multilevel framework can guide collaboration across disciplines within the social sciences toward the common goal of reaching the 10-10-10. CONCLUSIONS:Within a multilevel framework, social scientists can work collaboratively to address the needs of individuals among the 10-10-10 within the social and structural contexts (eg, social norms, stigma, poverty, and barriers to care) that affect their health. Such an approach draws on the unique strengths and approaches of different social-science disciplines while also building capacity for individuals most affected by social determinants of health

Socio-demographic, Clinical, and Genetic Determinants of Quality of Life in Lung Cancer Patients.

Patient reported health-related quality of life (QOL) is a major component of the overall well-being of cancer patients, with links to prognosis. In 6,420 lung cancer patients, we identified patient characteristics and genetic determinants of QOL. Patient responses from the SF-12 questionnaire was used to calculate normalized Physical Component Summary (PCS) and Mental Component Summary (MCS) scores. Further, we analyzed 218 single nucleotide polymorphisms (SNPs) in the p38 MAPK signaling pathway, a key mediator of response to cellular and environmental stress, as genetic determinants of QOL in a subset of the study population (N = 641). Trends among demographic factors for mean PCS and MCS included smoking status (PCS Ptrend < 0.001, MCS Ptrend < 0.001) and education (PCS Ptrend < 0.001, MCS Ptrend < 0.001). Similar relationships were seen for MCS. The homozygous rare genotype of MEF2B: rs2040562 showed an increased risk of a poor MCS (OR: 3.06, 95% CI: 1.05-8.92, P = 0.041). Finally, survival analysis showed that a low PCS or a MCS was associated with increased risks of five-year mortality (HR = 1.63, 95% CI: 1.51-1.77, HR = 1.23, 95% CI: 1.16-1.32, respectively) and there was a significant reduction in median survival time (Plog-rank < 0.001). These findings suggest that multiple factors contribute to QOL in lung cancer patients, and baseline QOL can impact survival

A synthetic-lethality RNAi screen reveals an ERK-mTOR co-targeting pro-apoptotic switch in PIK3CA+ oral cancers.

mTOR inhibition has emerged as a promising strategy for head and neck squamous cell carcinomas (HNSCC) treatment. However, most targeted therapies ultimately develop resistance due to the activation of adaptive survival signaling mechanisms limiting the activity of targeted agents. Thus, co-targeting key adaptive mechanisms may enable more effective cancer cell killing. Here, we performed a synthetic lethality screen using shRNA libraries to identify druggable candidates for combinatorial signal inhibition. We found that the ERK pathway was the most highly represented. Combination of rapamycin with trametinib, a MEK1/2 inhibitor, demonstrated strong synergism in HNSCC-derived cells in vitro and in vivo, including HNSCC cells expressing the HRAS and PIK3CA oncogenes. Interestingly, cleaved caspase-3 was potently induced by the combination therapy in PIK3CA+ cells in vitro and tumor xenografts. Moreover, ectopic expression of PIK3CA mutations into PIK3CA- HNSCC cells sensitized them to the pro-apoptotic activity of the combination therapy. These findings indicate that co-targeting the mTOR/ERK pathways may provide a suitable precision strategy for HNSCC treatment. Moreover, PIK3CA+ HNSCC are particularly prone to undergo apoptosis after mTOR and ERK inhibition, thereby providing a potential biomarker of predictive value for the selection of patients that may benefit from this combination therapy

An operational measure of liquidity

Economists' view of liquidity is askin to Supreme Court Justice Stewart's View of hard-core pornography: I shall not ... attempt further to define (it) .... But I know it when I see it. Embedding the process of selling an asset in a search environment enables us to provide an exact definition of liquidity: an asset's liquidity is the expected time until it is sold while pursuing an optimal (in the sense of maximization of expected discounted net proceeds) policy. Our analysis reveals that this definition is compatible with most other notions of liquidity and, in particular, with those of Keynes1 , impatience, the discount associated with a quick sale, and predictability

A Simple Cooperative Diversity Method Based on Network Path Selection

Cooperative diversity has been recently proposed as a way to form virtual antenna arrays that provide dramatic gains in slow fading wireless environments. However most of the proposed solutions require distributed space-time coding algorithms, the careful design of which is left for future investigation if there is more than one cooperative relay. We propose a novel scheme, that alleviates these problems and provides diversity gains on the order of the number of relays in the network. Our scheme first selects the best relay from a set of M available relays and then uses this best relay for cooperation between the source and the destination. We develop and analyze a distributed method to select the best relay that requires no topology information and is based on local measurements of the instantaneous channel conditions. This method also requires no explicit communication among the relays. The success (or failure) to select the best available path depends on the statistics of the wireless channel, and a methodology to evaluate performance for any kind of wireless channel statistics, is provided. Information theoretic analysis of outage probability shows that our scheme achieves the same diversity-multiplexing tradeoff as achieved by more complex protocols, where coordination and distributed space-time coding for M nodes is required, such as those proposed in [7]. The simplicity of the technique, allows for immediate implementation in existing radio hardware and its adoption could provide for improved flexibility, reliability and efficiency in future 4G wireless systems.Comment: To appear, IEEE JSAC, special issue on 4