Group 1 Innate Lymphoid Cell Lineage Identity Is Determined by a cis-Regulatory Element Marked by a Long Non-coding RNA.

Commitment to the innate lymphoid cell (ILC) lineage is determined by Id2, a transcriptional regulator that antagonizes T and B cell-specific gene expression programs. Yet how Id2 expression is regulated in each ILC subset remains poorly understood. We identified a cis-regulatory element demarcated by a long non-coding RNA (lncRNA) that controls the function and lineage identity of group 1 ILCs, while being dispensable for early ILC development and homeostasis of ILC2s and ILC3s. The locus encoding this lncRNA, which we termed Rroid, directly interacted with the promoter of its neighboring gene, Id2, in group 1 ILCs. Moreover, the Rroid locus, but not the lncRNA itself, controlled the identity and function of ILC1s by promoting chromatin accessibility and deposition of STAT5 at the promoter of Id2 in response to interleukin (IL)-15. Thus, non-coding elements responsive to extracellular cues unique to each ILC subset represent a key regulatory layer for controlling the identity and function of ILCs.

The long non-coding RNA Morrbid regulates Bim and short-lived myeloid cell lifespan.

Neutrophils, eosinophils and 'classical' monocytes collectively account for about 70% of human blood leukocytes and are among the shortest-lived cells in the body. Precise regulation of the lifespan of these myeloid cells is critical to maintain protective immune responses and minimize the deleterious consequences of prolonged inflammation. However, how the lifespan of these cells is strictly controlled remains largely unknown. Here we identify a long non-coding RNA that we termed Morrbid, which tightly controls the survival of neutrophils, eosinophils and classical monocytes in response to pro-survival cytokines in mice. To control the lifespan of these cells, Morrbid regulates the transcription of the neighbouring pro-apoptotic gene, Bcl2l11 (also known as Bim), by promoting the enrichment of the PRC2 complex at the Bcl2l11 promoter to maintain this gene in a poised state. Notably, Morrbid regulates this process in cis, enabling allele-specific control of Bcl2l11 transcription. Thus, in these highly inflammatory cells, changes in Morrbid levels provide a locus-specific regulatory mechanism that allows rapid control of apoptosis in response to extracellular pro-survival signals. As MORRBID is present in humans and dysregulated in individuals with hypereosinophilic syndrome, this long non-coding RNA may represent a potential therapeutic target for inflammatory disorders characterized by aberrant short-lived myeloid cell lifespan.

Depression, Abuse, Relationship Power and Condom Use by Pregnant and Postpartum Women with Substance Abuse History.

Substance-abusing pregnant and postpartum women are less likely to maintain consistent condom use and drug and alcohol abstinence, which is particularly concerning in high HIV-prevalence areas. Data from 224 pregnant and postpartum women in substance abuse treatment were analyzed to examine effects of history of substance use, child abuse, and mental health problems on current substance use and condom-use barriers. Mediators were depression, relationship power and social support. Most participants (72.9 %) evidenced current depression. Less social support (-0.17, p < 0.05) and relationship power (-0.48, p < 0.001), and greater depression (-0.16, p < 0.05) predicted more condom-use barriers. History of mental health problems predicted condom-use barriers, mediated by recent depression and relationship power (0.15, p < 0.001). These findings suggest depression and diminished relationship power limit highest-risk women's ability to negotiate condom use and abstain from substance use, increasing their risk of acute HIV infection and vertical transmission.

AMP!: A Cross-site Analysis of the Effects of a Theater-based Intervention on Adolescent Awareness, Attitudes, and Knowledge about HIV.

AMP! (Arts-based, Multiple component, Peer-education) is an HIV intervention developed for high school adolescents. AMP! uses interactive theater-based scenarios developed by trained college undergraduates to deliver messages addressing HIV/STI prevention strategies, healthy relationships, and stigma reduction towards people living with HIV/AIDS. We used a pre-test/post-test, control group study design to simultaneously assess intervention effect on ninth grade students in an urban county in California (N = 159) and a suburban county in North Carolina (N = 317). In each location, the control group received standard health education curricula delivered by teachers; the intervention group received AMP! in addition to standard health education curricula. Structural equation modeling was used to determine intervention effects. The post-test sample was 46 % male, 90 % self-identified as heterosexual, 32 % reported receiving free or reduced lunch, and 49 % White. Structural models indicated that participation in AMP! predicted higher scores on HIV knowledge (p = 0.05), HIV awareness (p = 0.01), and HIV attitudes (p = 0.05) at the post-test. Latent means comparison analyses revealed post-test scores were significantly higher than pre-test scores on HIV knowledge (p = 0.001), HIV awareness (p = 0.001), and HIV attitudes (p = 0.001). Further analyses indicated that scores rose for both groups, but the post-test scores of intervention participants were significantly higher than controls (HIV knowledge (p = 0.01), HIV awareness (p = 0.01), and HIV attitudes (p = 0.05)). Thus, AMP!'s theater-based approach shows promise for addressing multiple adolescent risk factors and attitudes concerning HIV in school settings.

Pathways of Risk and Resilience: Impact of a Family Resilience Program on Active-Duty Military Parents.

Over the past decade, studies into the impact of wartime deployment and related adversities on service members and their families have offered empirical support for systemic models of family functioning and a more nuanced understanding of the mechanisms by which stress and trauma reverberate across family and partner relationships. They have also advanced our understanding of the ways in which families may contribute to the resilience of children and parents contending with the stressors of serial deployments and parental physical and psychological injuries. This study is the latest in a series designed to further clarify the systemic functioning of military families and to explicate the role of resilient family processes in reducing symptoms of distress and poor adaptation among family members. Drawing upon the implementation of the Families Overcoming Under Stress (FOCUS) Family Resilience Program at 14 active-duty military installations across the United States, structural equation modeling was conducted with data from 434 marine and navy active-duty families who participated in the FOCUS program. The goal was to better understand the ways in which parental distress reverberates across military family systems and, through longitudinal path analytic modeling, determine the pathways of program impact on parental distress. The findings indicated significant cross-influence of distress between the military and civilian parents within families, families with more distressed military parents were more likely to sustain participation in the program, and reductions in distress among both military and civilian parents were significantly mediated by improvements in resilient family processes. These results are consistent with family systemic and resilient models that support preventive interventions designed to enhance family resilient processes as an important part of comprehensive services for distressed military families.

A Longitudinal Investigation of Race, Socioeconomic Status, and Psychosocial Mediators of Allostatic Load in Midlife Women: Findings From the Study of Women's Health Across the Nation.

OBJECTIVES: This research sought to assess racial and socioeconomic status (SES) differences in level and change in allostatic load (AL) over time in midlife women and to test whether psychosocial factors mediate these relationships. These factors were discrimination, perceived stress, and hostility. METHODS: Longitudinal data obtained from the Study of Women's Health Across the Nation were used (n = 2063; mean age at baseline = 46.0 years). Latent growth curve models evaluated the impact of demographic, menopausal, and psychosocial variables on level and change in AL for 8 years. RESULTS: Direct effects: high levels of discrimination and hostility significantly predicted higher AL (path coefficients = 0.05 and 0.05, respectively). High perceived stress significantly predicted a faster rate of increase of AL (path coefficient = 0.06). Racial and SES differentials were present, with African American race (path coefficient = 0.23), low income (path coefficient = -0.15), and low education (path coefficient = -0.08) significantly predicting high AL level. Indirect effects: significant indirect effects were found for African American race, less income, and lower education through higher discrimination, perceived stress, and hostility on level and rate of AL. CONCLUSIONS: This was one of the first studies that investigated AL over multiple periods, and results supported AL as a cumulative phenomenon, affected by multiple psychosocial and demographic factors. The results suggest the complex ways in which race, SES, and psychosocial factors operate to influence AL.

Factors influencing readiness to deploy in disaster response: findings from a cross-sectional survey of the Department of Veterans Affairs Disaster Emergency Medical Personnel System.

BACKGROUND: The Disaster Emergency Medical Personnel System (DEMPS) program provides a system of volunteers whereby active or retired Department of Veterans Affairs (VA) personnel can register to be deployed to support other VA facilities or the nation during national emergencies or disasters. Both early and ongoing volunteer training is required to participate. METHODS: This study aims to identify factors that impact willingness to deploy in the event of an emergency. This analysis was based on responses from 2,385 survey respondents (response rate, 29%). Latent variable path models were developed and tested using the EQS structural equations modeling program. Background demographic variables of education, age, minority ethnicity, and female gender were used as predictors of intervening latent variables of DEMPS Volunteer Experience, Positive Attitude about Training, and Stress. The model had acceptable fit statistics, and all three intermediate latent variables significantly predicted the outcome latent variable Readiness to Deploy. RESULTS: DEMPS Volunteer Experience and a Positive Attitude about Training were associated with Readiness to Deploy. Stress was associated with decreased Readiness to Deploy. Female gender was negatively correlated with Readiness to Deploy; however, there was an indirect relationship between female gender and Readiness to Deploy through Positive Attitude about Training. CONCLUSIONS: These findings suggest that volunteer emergency management response programs such as DEMPS should consider how best to address the factors that may make women less ready to deploy than men in order to ensure adequate gender representation among emergency responders. The findings underscore the importance of training opportunities to ensure that gender-sensitive support is a strong component of emergency response, and may apply to other emergency response programs such as the Medical Reserve Corps and the American Red Cross.

CD40L contributes to angiotensin II-induced pro-thrombotic state, vascular inflammation, oxidative stress and endothelial dysfunction.

CD40 ligand (CD40L) is involved in the vascular infiltration of immune cells and pathogenesis of atherosclerosis. Additionally, T cell CD40L release causes platelet, dendritic cell and monocyte activation in thrombosis. However, the role of CD40L in angiotensin II (ATII)-driven vascular dysfunction and hypertension remains incompletely understood. We tested the hypothesis that CD40L contributes to ATII-driven vascular inflammation by promoting platelet-leukocyte activation, vascular infiltration of immune cells and by amplifying oxidative stress. C57BL/6 and CD40L-/- mice were infused with ATII (1 mg/kg/day for 7 days) using osmotic minipumps. Vascular function was recorded by isometric tension studies, and reactive oxygen species (ROS) were monitored in blood and heart by optical methods. Western blot, immunohistochemistry, FACS analysis and real-time RT-PCR were used to analyze immune cell distribution, pro-inflammatory cytokines, NAPDH oxidase subunits, T cell transcription factors and other genes of interest. ATII-treated CD40L-/- mice showed improved endothelial function, suppression of blood platelet-monocyte interaction (FACS), platelet thrombin generation (calibrated automated thrombography) and coagulation (bleeding time), as well as decreased oxidative stress in the aorta, heart and blood compared to wild-type mice. Moreover, ATII-treated CD40L-/- mice displayed decreased levels of TH1 cytokines released by splenic CD4⁺ T cells (ELISA) and lower expression levels of NOX-2, T-bet and P-selectin as well as diminished immune cell infiltration in aortic tissue compared to controls. Our results demonstrate that many ATII-induced effects on vascular dysfunction, such as vascular inflammation, oxidative stress and a pro-thrombotic state, are mediated at least in part via CD40L.

Depression, substance abuse and other contextual predictors of adherence to antiretroviral therapy (ART) among Haitians.

Haiti has the highest number of individuals living with HIV in the Caribbean. Due to Haiti's resource-poor environment and inadequate mental health and substance abuse services, adherence to antiretroviral therapy (ART) may be especially difficult. This study examined associations among demographics, maladaptive coping, partner conflict, alcohol problems, depression, and negative attitudes about medications and their impact on adherence among 194 HIV-positive Haitians. In a mediated directional structural equation model, depression and negative attitudes about ART directly predicted poorer adherence. Greater partner conflict, maladaptive coping and alcohol problems predicted more depression. Maladaptive coping predicted a negative attitude about ART. Alcohol problems predicted partner conflict and maladaptive coping. Significant indirect effects on adherence mediated through both depression and negative attitudes about ART include negative effects of female gender, alcohol problems and maladaptive coping. Results highlight the importance of integrated care for depression, alcohol use and other psychosocial problems to increase ART adherence.

The mediating roles of stress and maladaptive behaviors on self-harm and suicide attempts among runaway and homeless youth.

Runaway and homeless youth often have a constellation of background behavioral, emotional, and familial problems that contribute to stress and maladaptive behaviors, which, in turn, can lead to self-harming and suicidal behaviors. The current study examined the roles of stress and maladaptive behaviors as mediators between demographic and psychosocial background characteristics and self-injurious outcomes through the lens of the stress process paradigm. The model was tested in a sample of runaway and homeless youth from Los Angeles County (N = 474, age 12-24, 41 % female, 17 % White, 32.5 % African American, 21.5 % Hispanic/Latino). Background variables (gender, age, sexual minority status, parental drug use history, and emotional distress) predicted hypothesized mediators of maladaptive behaviors and recent stress. In turn, it was hypothesized that the mediators would predict self-harming behaviors and suicide attempts in the last 3 months. Females and LGBT (lesbian, gay, bisexual, transgender) youth were more likely to have self-harmed and attempted suicide; younger participants reported more self-harming. The mediating constructs were associated more highly with self-harming than suicide attempts bivariately, although differences were modest. Maladaptive behaviors and recent stress were significant predictors of self-harm, whereas only recent stress was a significant predictor of suicide attempts. All background factors were significant predictors of recent stress. Older age, a history of parental drug use, and greater emotional distress predicted problem drug use. Males, younger participants, and participants with emotional distress reported more delinquent behaviors. Significant indirect effects on self-harming behaviors were mediated through stress and maladaptive behaviors. The hypothesized paradigm was useful in explaining the associations among background factors and self-injurious outcomes and the influence of mediating factors on these associations.

Predicting depression in mothers with and without HIV: the role of social support and family dynamics.

Many women with HIV are primary caregivers for their children. Social factors, including family dynamics, play a major role in women's depression. We hypothesized an impact of HIV seropositivity on greater depression mediated through poorer family functioning and social support. Participants include 332 Mothers Living with HIV (MLH) and 200 Neighborhood Control Mothers (NCM) recruited in Los Angeles County. The NCM were matched by neighborhood. All had children ages 6 through 20. Analyses using structural equation modeling (SEM) indicated HIV seropositivity was positively correlated with depression and negatively correlated with positive social support and effective family functioning. In a predictive path model, the relationship between having HIV and depressed mood was mediated by social support and family functioning. Findings offer explanation for increased depression resulting from HIV and social and family dynamics, and suggest innovative interventions to abate psychosocial health problems and lower risk for depression among women with HIV.

Neurological function, information-motivation-behavioral skills factors, and risk behaviors among HIV-positive alcohol users.

The purpose of this study was to examine neurological impairment in combination with information-motivation-behavioral skills (IMB) variables. The study tests the role of IMB variables as mediators of antecedent variables of demographics, life stress, social support, and neurological impairment with outcome measures of HIV preventive and risk behaviors in a sample of HIV-positive, alcohol-using adults (n = 250) with a history of alcohol abuse/dependence. Neurological impairment was measured with the Color Trails Test (CTT). Average performance on the CTT by the sample was substantially worse than established norms. In a directional latent variable model, neurological impairment directly predicted lower transmission knowledge scores and poorer performance on an observational condom skills assessment. Greater neurological impairment was significantly associated with greater age. Future interventions geared toward HIV+ adults who use alcohol should take into consideration HIV-related and age-related neurological functioning which may impede the facilitation of safe sex behaviors.

Impact of Abstinence Self-Efficacy and Treatment Services on Physical Health-Related Behaviors and Problems among Dually Diagnosed Patients.

OBJECTIVE: Physical health problems are pervasive among patients with co-occurring substance use and mental disorders. Yet, drug treatment programs often ignore tobacco use and its association with health. Abstinence self-efficacy has been associated with improved outcomes for co-occurring disorders, which in turn may also impact physical health. This study had the goal of assessing whether abstinence self-efficacy for drugs and alcohol, and provision and use of services would influence tobacco use and other health-related outcomes among 351 individuals with co-occurring disorders in residential drug treatment. METHODS: Structural models tested the impact of baseline abstinence self-efficacy and treatment service characteristics on 6-month outcomes of health problems, functional limitations, health perceptions, and cigarette and heavy alcohol use. Demographics and baseline values for outcome variables were included as covariates. RESULTS: Correlations within time for poor health, cigarette use, and heavy alcohol use were substantial. A longer time in drug treatment was associated with less cigarette and heavy alcohol use at a 6-month follow-up. Baseline health problems were associated with more cigarette use and functional limitations at 6-months. Abstinence self-efficacy did not predict less cigarette use, but predicted less heavy alcohol use and fewer functional limitations. Availability of specialized dual-diagnosis groups and more on-site psychological services were not directly associated with outcomes, but had an impact through indirect effects on more psychological service utilization which predicted better subjective health. CONCLUSIONS: Improving overall treatment retention and services utilization among patients with co-occurring disorders may generalize to improved health perceptions, but specific health promotion and smoking-cessation interventions are warranted to improve health outcomes.

Engineering of HIV-1 neutralizing antibody CAP256V2LS for manufacturability and improved half life.

The broadly neutralizing antibody (bNAb) CAP256-VRC26.25 has exceptional potency against HIV-1 and has been considered for clinical use. During the characterization and production of this bNAb, we observed several unusual features. First, the antibody appeared to adhere to pipette tips, requiring tips to be changed during serial dilution to accurately measure potency. Second, during production scale-up, proteolytic cleavage was discovered to target an extended heavy chain loop, which was attributed to a protease in spent medium from 2-week culture. To enable large scale production, we altered the site of cleavage via a single amino acid change, K100mA. The resultant antibody retained potency and breadth while avoiding protease cleavage. We also added the half-life extending mutation LS, which improved the in vivo persistence in animal models, but did not impact neutralization activity; we observed the same preservation of neutralization for bNAbs VRC01, N6, and PGDM1400 with LS on a 208-virus panel. The final engineered antibody, CAP256V2LS, retained the extraordinary neutralization potency of the parental antibody, had a favorable pharmacokinetic profile in animal models, and was negative in in vitro assessment of autoreactivity. CAP256V2LS has the requisite potency, developability and suitability for scale-up, allowing its advancement as a clinical candidate.

Reliability, validity, and psychometric development of the pornography consumption inventory in a sample of hypersexual men.

This article reports the psychometric evaluation of the Pornography Consumption Inventory (PCI), which was developed to assess motivations for pornography use among hypersexual men. Initial factor structure and item analysis were conducted in a sample of men (N = 105) seeking to reduce their pornography consumption (Study 1), yielding a 4-factor solution. In a second sample of treatment-seeking hypersexual men (N = 107), the authors further investigated the properties of the PCI using confirmatory factor analytic procedures, reliability indices, and explored PCI associations with several other constructs to establish convergent and discriminant validity. These studies demonstrate psychometric evidence for the PCI items that measure tendencies of hypersexual men to use pornography (a) for sexual pleasure; (b) to escape, cope, or avoid uncomfortable emotional experiences or stress; (c) to satisfy sexual curiosity; and (d) to satisfy desires for excitement, novelty, and variety.

Clinical correlates of health-related quality of life among opioid-dependent patients.

PURPOSE: Previous work suggests that opioid users have lower health-related quality of life (HRQOL) than patients with more prevalent chronic illnesses such as hypertension or diabetes. Although comparisons with population norms are informative, studies of the correlates of HRQOL for opioid users are needed to plan clinical services. METHODS: We tested a conceptual model of the pathways between physiologic factors and symptoms in relation to HRQOL among 344 opioid users in a clinical trial. Physical and mental HRQOL were measured by the Short-Form (SF)-36; withdrawal signs, symptoms, and functioning were also measured with validated instruments. Using structural equation modeling, we tested hypotheses that medical history directly predicts withdrawal signs and symptoms, and that medical history, withdrawal signs and symptoms, and functioning predict the physical and mental HRQOL latent variables of the SF-36. RESULTS: Most hypothesized relationships were significant, and model fit was good. The model explained 36% of the variance in mental HRQOL and 34% of the variance in physical HRQOL. CONCLUSIONS: The conceptual framework appears valid for explaining variation in the physical and mental HRQOL of opioid users undergoing medically managed withdrawal. Analysis of longitudinal data would help to evaluate more rigorously the adequacy of the model for explaining HRQOL in opioid withdrawal.

Understanding the roles of shame and neuroticism in a patient sample of hypersexual men.

Although shame and facets of neuroticism have independently been linked to hypersexuality, the present study extends these findings by exploring pathways among these variables, using structural equation modeling in a patient sample of hypersexual adult men (N = 95). Results suggested that the domain of neuroticism, as represented by the NEO Personality Inventory-Revised, was a significant direct predictor of hypersexuality, with specific variance from the facet of impulsivity adding additional predictive power. Shame's bivariate association with hypersexuality was also significant, but in a predictive path model the effect of shame on hypersexuality was indirectly mediated through neuroticism and was not an independently significant predictor. Implications for treatment suggest that clinicians working with this population should evaluate precipitating risk factors to consider whether shame is activating neurotic coping or if other stressors might be influencing emotional instability that can trigger hypersexuality. Independent of the general distress associated with neuroticism, the literature on impulsivity might provide other valuable insights and direction for working with hypersexual men.

Protective factors associated with fewer multiple problem behaviors among homeless/runaway youth.

Although homeless youth exhibit numerous problem behaviors, protective factors that can be targeted and modified by prevention programs to decrease the likelihood of involvement in risky behaviors are less apparent. The current study tested a model of protective factors for multiple problem behavior in a sample of 474 homeless youth (42% girls; 83% minority) ages 12 to 24 years. Higher levels of problem solving and planning skills were strongly related to lower levels of multiple problem behaviors in homeless youth, suggesting both the positive impact of preexisting personal assets of these youth and important programmatic targets for further building their resilience and decreasing problem behaviors. Indirect relationships between the background factors of self-esteem and social support and multiple problem behaviors were significantly mediated through protective skills. The model suggests that helping youth enhance their skills in goal setting, decision making, and self-reliant coping could lessen a variety of problem behaviors commonly found among homeless youth.

Safety, tolerability, and immunogenicity of the respiratory syncytial virus prefusion F subunit vaccine DS-Cav1: a phase 1, randomised, open-label, dose-escalation clinical trial.

BACKGROUND: Multiple active vaccination approaches have proven ineffective in reducing the substantial morbidity and mortality caused by respiratory syncytial virus (RSV) in infants and older adults (aged ≥65 years). A vaccine conferring a substantial and sustainable boost in neutralising activity is required to protect against severe RSV disease. To that end, we evaluated the safety and immunogenicity of DS-Cav1, a prefusion F subunit vaccine. METHODS: In this randomised, open-label, phase 1 clinical trial, the stabilised prefusion F vaccine DS-Cav1 was evaluated for dose, safety, tolerability, and immunogenicity in healthy adults aged 18-50 years at a single US site. Participants were assigned to receive escalating doses of either 50 µg, 150 µg, or 500 µg DS-Cav1 at weeks 0 and 12, and were randomly allocated in a 1:1 ratio within each dose group to receive the vaccine with or without aluminium hydroxide (AlOH) adjuvant. After 71 participants had been randomised, the protocol was amended to allow some participants to receive a single vaccination at week 0. The primary objectives evaluated the safety and tolerability at every dose within 28 days following each injection. Neutralising activity and RSV F-binding antibodies were evaluated from week 0 to week 44 as secondary and exploratory objectives. Safety was assessed in all participants who received at least one vaccine dose; secondary and exploratory immunogenicity analysis included all participants with available data at a given visit. The trial is registered with ClinicalTrials.gov, NCT03049488, and is complete and no longer recruiting. FINDINGS: Between Feb 21, 2017, and Nov 29, 2018, 244 participants were screened for eligibility and 95 were enrolled to receive DS-Cav1 at the 50 µg (n=30, of which n=15 with AlOH), 150 µg (n=35, of which n=15 with AlOH), or 500 µg (n=30, of which n=15 with AlOH) doses. DS-Cav1 was safe and well tolerated and no serious vaccine-associated adverse events deemed related to the vaccine were identified. DS-Cav1 vaccination elicited robust neutralising activity and binding antibodies by 4 weeks after a single vaccination (p<0·0001 for F-binding and neutralising antibodies). In analyses of exploratory endpoints at week 44, pre-F-binding IgG and neutralising activity were significantly increased compared with baseline in all groups. At week 44, RSV A neutralising activity was 3·1 fold above baseline in the 50 µg group, 3·8 fold in the 150 µg group, and 4·5 fold in the 500 µg group (p<0·0001). RSV B neutralising activity was 2·8 fold above baseline in the 50 µg group, 3·4 fold in the 150 µg group, and 3·7 fold in the 500 µg group (p<0·0001). Pre-F-binding IgG remained significantly 3·2 fold above baseline in the 50 µg group, 3·4 fold in the 150 µg group, and 4·0 fold in the 500 µg group (p<0·0001). Pre-F-binding serum IgA remained 4·1 fold above baseline in the 50 µg group, 4·3 fold in the 150 µg group, and 4·8 fold in the 500 µg group (p<0·0001). Although a higher vaccine dose or second immunisation elicited a transient advantage compared with lower doses or a single immunisation, neither significantly impacted long-term neutralisation. There was no long-term effect of dose, number of vaccinations, or adjuvant on neutralising activity. INTERPRETATION: In this phase 1 study, DS-Cav1 vaccination was safe and well tolerated. DS-Cav1 vaccination elicited a robust boost in RSV F-specific antibodies and neutralising activity that was sustained above baseline for at least 44 weeks. A single low-dose of pre-F immunisation of antigen-experienced individuals might confer protection that extends throughout an entire RSV season. FUNDING: The National Institutes of Allergy and Infectious Diseases.

Acculturation, coping styles, and health risk behaviors among HIV positive Latinas.

This study examined the relationships among acculturation, coping styles, substance use, sexual risk behavior, and medication non-adherence among 219 Latinas living with HIV/AIDS in Los Angeles, CA. Coping styles were hypothesized to mediate the link between acculturation and health risk behaviors for HIV positive Latinas. Structural equation modeling revealed that greater acculturation was related to less positive coping and more negative coping. In turn, negative coping was associated with more health risk behaviors and more non-adherence. Positive coping was associated with less substance use as reflected in use of cigarettes and alcohol and less non-adherence. Coping styles mediated the relationship between acculturation and health risk behaviors. Findings echo previous works examining the Hispanic Health Paradox wherein more acculturated Latinos exhibit increased risk behavior and maladaptive coping styles. HIV/AIDS interventions need to be mindful of cultural differences within Hispanic populations and be tailored to address these differences.