Assessment of Relevant Cultural Considerations is Essential for the Success of a Vaccine

This paper explores applications of social science research to international vaccine development and implementation. The paper discusses examples of vaccine-implementation controversies, suggesting that many of these issues could have been avoided with a greater focus on cultural issues regarding perceptions of disease, vaccination, and health services. The paper also discusses the relationship of theory-based behavioural interventions with the development of an overall vaccine strategy and examines experience of growing vaccine research with regard to perceptions of medical decision-making, acceptable practices, and authority and how these perceptions impact vaccine usage. The importance of social science in the ethical conduct of research is also discussed

Adolescent Trials Network for HIV-AIDS Scale It Up Program: Protocol for a Rational and Overview

Background: The past 30 years have witnessed such significant progress in the prevention and treatment of HIV/AIDS that an AIDS-free generation and the end to the global AIDS epidemic are ambitious, but achievable, national and global goals. Despite growing optimism, globally, youth living with HIV are markedly less likely to receive antiretroviral therapy than adults (23% vs 38%). Furthermore, marked health disparities exist regarding HIV infection risk, with young men of color who have sex with men disproportionately affected. A large body of research has identified highly impactful facilitators of and barriers to behavior change. Several efficacious interventions have been created that decrease the rate of new HIV infections among youth and reduce morbidity among youth living with HIV. However, full benefits that should be possible based on the tools and interventions currently available are yet to be realized in youth, in large part, because efficacious interventions have not been implemented in real-world settings. Scale It Up (SIU) primarily aims to assemble research teams that will ultimately bring to practice evidence-based interventions that positively impact the youth HIV prevention and care cascades, and in turn, advance the fields of implementation science and self-management science. Objective: This paper aims to describe the structure of the U19-SIU and the effectiveness-implementation hybrid trials, as well as other center-wide protocols and initiatives, implemented within SIU. Methods: SIU will achieve its aims through 4 individual primary protocols, 2 center-wide protocols, and 3 cross-project initiatives. Results: SIU was funded by National Institute for Child Health and Human Development (U19HD089875) and began in October 2016. As of November 2018, 6 SIU protocols have launched at least the first phase of work (ATN 144 SMART: Sequential Multiple Assignment Randomized Trial; ATN 145 YMHP: Young Men’s Health Project; ATN 146 TMI: Tailored Motivational Interviewing Intervention; ATN 153 EPIS: Exploration, Preparation, Implementation, Sustainment model; ATN 154 CM: Cascade Monitoring; ATN 156 We Test: Couples\u27 Communication and HIV Testing). Further details can be found in the individual protocol papers. Conclusions: To date, the youth HIV research portfolio has not adequately advanced the important care area of self-management. SIU protocols and initiatives address this broad issue by focusing on evaluating the effectiveness and implementation of self-management interventions. SIU is highly innovative for 5 primary reasons: (1) our research framework expands the application of “self-management”; (2) the 4 primary protocols utilize innovative hybrid designs; (3) our Analytic Core will conduct cost-effectiveness analyses of each intervention; (4) across all 4 primary protocols, our Implementation Science Core will apply implementation scales designed to assess inner and outer context factors; and (5) we shall advance understanding of the dynamics between provider and patient through analysis of recorded interactions

Estimating substitution elasticities in household production models

Dynamic general equilibrium models that include explicit household production sectors provide a useful framework within which to analyze a variety of macroeconomic issues. However, some implications of these models depend critically on parameters, including the elasticity of substitution between market and home consumption goods, about which there is little information in the literature. Using the PSID, we estimate these parameters for single males, single females, and married couples. At least for single females and married couples, the results indicate a high enough substitution elasticity that including home production will make a significant difference in applied general equilibrium theory.Production (Economic theory)

Sociobehavioural Research Methods for the Introduction of Vaccines in the Diseases of the Most Impoverished Programme

Participation in vaccination campaigns worldwide, particularly the Expanded Programme on Immunization, has increased significantly in recent years. However, there remain multiple and integrated behavioural, sociocultural and political-economic barriers to vaccination. The Diseases of the Most Impoverished (DOMI) Programme has undertaken shigellosis disease-burden studies and oral cholera and typhoid Vi polysaccharide vaccine trials in seven Asian countries. As part of these projects, sociobehavioural studies have been undertaken to determine the potential demand for vaccines for these diseases and the obstacles and enabling factors that may affect acceptance, delivery, and use of vaccines. A theoretical model of acceptance of vaccination and a triangulation of qualitative and quantitative methods have been used for fully elucidating the range of issues relating to vaccination for shigellosis, cholera, and typhoid fever. In this paper, the theoretical and methodological basis of the DOMI projects has been reviewed in a context of current sociobehavioural research on the acceptability and desirability of vaccination

Multiple Method Contraception Use among African American Adolescents in Four US Cities

We report on African American adolescents' (N = 850; M age = 15.4) contraceptive practices and type of contraception utilized during their last sexual encounter. Respondents completed measures of demographics, contraceptive use, sexual partner type, and ability to select “safe” sexual partners. 40% endorsed use of dual or multiple contraceptive methods; a total of 35 different contraceptive combinations were reported. Perceived ability to select “safe” partners was associated with not using contraception (OR = 1.25), using less effective contraceptive methods (OR = 1.23), or hormonal birth control (OR = 1.50). Female gender predicted hormonal birth control use (OR = 2.33), use of less effective contraceptive methods (e.g., withdrawal; OR = 2.47), and using no contraception (OR = 2.37). Respondents' age and partner type did not predict contraception use. Adolescents used contraceptive methods with limited ability to prevent both unintended pregnancies and STD/HIV. Adolescents who believed their partners posed low risk were more likely to use contraceptive practices other than condoms or no contraception. Reproductive health practitioners are encouraged to help youth negotiate contraceptive use with partners, regardless of the partner's perceived riskiness

Serum and glucocorticoid-inducible kinase1 increases plasma membrane wt-CFTR in human airway epithelial cells by inhibiting its endocytic retrieval

Background: Chloride (Cl) secretion by the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) located in the apical membrane of respiratory epithelial cells plays a critical role in maintenance of the airway surface liquid and mucociliary clearance of pathogens. Previously, we and others have shown that the serum and glucocorticoid-inducible kinase-1 (SGK1) increases wild type CFTR (wt-CFTR) mediated Cl transport in Xenopus oocytes by increasing the amount of wt-CFTR protein in the plasma membrane. However, the effect of SGK1 on the membrane abundance of wt-CFTR in airway epithelial cells has not been examined, and the mechanism whereby SGK1 increases membrane wt-CFTR has also not been examined. Thus, the goal of this study was to elucidate the mechanism whereby SGK1 regulates the membrane abundance of wt-CFTR in human airway epithelial cells. Methods and Results: We report that elevated levels of SGK1, induced by dexamethasone, increase plasma membrane abundance of wt-CFTR. Reduction of SGK1 expression by siRNA (siSGK1) and inhibition of SGK1 activity by the SGK inhibitor GSK 650394 abrogated the ability of dexamethasone to increase plasma membrane wt-CFTR. Overexpression of a constitutively active SGK1 (SGK1-S422D) increased plasma membrane abundance of wt-CFTR. To understand the mechanism whereby SGK1 increased plasma membrane wt-CFTR, we examined the effects of siSGK1 and SGK1-S442D on the endocytic retrieval of wt-CFTR. While siSGK1 increased wt-CFTR endocytosis, SGK1-S442D inhibited CFTR endocytosis. Neither siSGK1 nor SGK1-S442D altered the recycling of endocytosed wt-CFTR back to the plasma membrane. By contrast, SGK1 increased the endocytosis of the epidermal growth factor receptor (EGFR). Conclusion: This study demonstrates for the first time that SGK1 selectively increases wt-CFTR in the plasma membrane of human airway epithelia cells by inhibiting its endocytic retrieval from the membrane. © 2014 Bomberger et al

Morpholino Gene Knockdown in Adult Fundulus heteroclitus: Role of SGK1 in Seawater Acclimation

The Atlantic killifish (Fundulus heteroclitus) is an environmental sentinel organism used extensively for studies on environmental toxicants and salt (NaCl) homeostasis. Previous research in our laboratory has shown that rapid acclimation of killifish to seawater is mediated by trafficking of CFTR chloride channels from intracellular vesicles to the plasma membrane in the opercular membrane within the first hour in seawater, which enhances chloride secretion into seawater, thereby contributing to salt homeostasis. Acute transition to seawater is also marked by an increase in both mRNA and protein levels of serum glucocorticoid kinase 1 (SGK1) within 15 minutes of transfer. Although the rise in SGK1 in gill and its functional analog, the opercular membrane, after seawater transfer precedes the increase in membrane CFTR, a direct role of SGK1 in elevating membrane CFTR has not been established in vivo. To test the hypothesis that SGK1 mediates the increase in plasma membrane CFTR we designed two functionally different vivo-morpholinos to knock down SGK1 in gill, and developed and validated a vivo-morpholino knock down technique for adult killifish. Injection (intraperitoneal, IP) of the splice blocking SGK1 vivo-morpholino reduced SGK1 mRNA in the gill after transition from fresh to seawater by 66%. The IP injection of the translational blocking and splice blocking vivo-morpholinos reduced gill SGK1 protein abundance in fish transferred from fresh to seawater by 64% and 53%, respectively. Moreover, knock down of SGK1 completely eliminated the seawater induced rise in plasma membrane CFTR, demonstrating that the increase in SGK1 protein is required for the trafficking of CFTR from intracellular vesicles in mitochondrion rich cells to the plasma membrane in the gill during acclimation to seawater. This is the first report of the use of vivo-morpholinos in adult killifish and demonstrates that vivo-morpholinos are a valuable genetic tool for this environmentally relevant model organism

Monomethylarsonous Acid (MMAIII) Has an Adverse Effect on the Innate Immune Response of Human Bronchial Epithelial Cells to Pseudomonas Aeruginosa

Arsenic is the number one contaminant of concern with regard to human health according to the World Health Organization. Epidemiological studies on Asian and South American populations have linked arsenic exposure with an increased incidence of lung disease, including pneumonia, and chronic obstructive pulmonary disease, both of which are associated with bacterial infection. However, little is known about the effects of low dose arsenic exposure, or the contributions of organic arsenic to the innate immune response to bacterial infection. This study examined the effects on Pseudomonas aeruginosa (P. aeruginosa) induced cytokine secretion by human bronchial epithelial cells (HBEC) by inorganic sodium arsenite (iAsIII) and two major metabolites, monomethylarsonous acid (MMAIII) and dimethylarsenic acid (DMAV), at concentrations relevant to the U.S. population. Neither iAsIII nor DMAV altered P. aeruginosa induced cytokine secretion. By contrast, MMAIII increased P. aeruginosa induced secretion of IL-8, IL-6 and CXCL2. A combination of iAsIII, MMAIII and DMAV (10 pbb total) reduced IL-8 and CXCL1 secretion. These data demonstrate for the first time that exposure to MMAIII alone, and a combination of iAsIII, MMAIII and DMAV at levels relevant to the U.S. may have negative effects on the innate immune response of human bronchial epithelial cells to P. aeruginosa

Model-Based Methods to Translate Adolescent Medicine Trials Network for HIV/AIDS Interventions Findings Into Policy Recommendations: Rationale and Protocol for a Modeling Core (ATN 161)

BACKGROUND: The United States Centers for Disease Control and Prevention estimates that approximately 60,000 US youth are living with HIV. US youth living with HIV (YLWH) have poorer outcomes compared with adults, including lower rates of diagnosis, engagement, retention, and virologic suppression. With Adolescent Medicine Trials Network for HIV/AIDS Interventions (ATN) support, new trials of youth-centered interventions to improve retention in care and medication adherence among YLWH are underway. OBJECTIVE: This study aimed to use a computer simulation model, the Cost-Effectiveness of Preventing AIDS Complications (CEPAC)-Adolescent Model, to evaluate selected ongoing and forthcoming ATN interventions to improve viral load suppression among YLWH and to define the benchmarks for uptake, effectiveness, durability of effect, and cost that will make these interventions clinically beneficial and cost-effective. METHODS: This protocol, ATN 161, establishes the ATN Modeling Core. The Modeling Core leverages extensive data-already collected by successfully completed National Institutes of Health-supported studies-to develop novel approaches for modeling critical components of HIV disease and care in YLWH. As new data emerge from ongoing ATN trials during the award period about the effectiveness of novel interventions, the CEPAC-Adolescent simulation model will serve as a flexible tool to project their long-term clinical impact and cost-effectiveness. The Modeling Core will derive model input parameters and create a model structure that reflects key aspects of HIV acquisition, progression, and treatment in YLWH. The ATN Modeling Core Steering Committee, with guidance from ATN leadership and scientific experts, will select and prioritize specific model-based analyses as well as provide feedback on derivation of model input parameters and model assumptions. Project-specific teams will help frame research questions for model-based analyses as well as provide feedback regarding project-specific inputs, results, sensitivity analyses, and policy conclusions. RESULTS: This project was funded as of September 2017. CONCLUSIONS: The ATN Modeling Core will provide critical information to guide the scale-up of ATN interventions and the translation of ATN data into policy recommendations for YLWH in the United States