An Assessment of the Feasibility and Acceptability of a Friendship-Based Social Network Recruitment Strategy to Screen At-Risk African American and Hispanic/Latina Young Women for HIV Infection

To examine the feasibility and acceptability of a friendship-based network recruitment strategy for identifying undiagnosed human immunodeficiency virus (HIV) infection within young women’s same-sex friendship networks and to determine factors that facilitated and hindered index recruiters (IRs) in recruiting female friendship network members (FNMs) as well as factors that facilitated and hindered FNMs in undergoing HIV screening

Schizophrenia-associated somatic copy-number variants from 12,834 cases reveal recurrent NRXN1 and ABCB11 disruptions

While germline copy-number variants (CNVs) contribute to schizophrenia (SCZ) risk, the contribution of somatic CNVs (sCNVs)—present in some but not all cells—remains unknown. We identified sCNVs using blood-derived genotype arrays from 12,834 SCZ cases and 11,648 controls, filtering sCNVs at loci recurrently mutated in clonal blood disorders. Likely early-developmental sCNVs were more common in cases (0.91%) than controls (0.51%, p = 2.68e−4), with recurrent somatic deletions of exons 1–5 of the NRXN1 gene in five SCZ cases. Hi-C maps revealed ectopic, allele-specific loops forming between a potential cryptic promoter and non-coding cis-regulatory elements upon 5′ deletions in NRXN1. We also observed recurrent intragenic deletions of ABCB11, encoding a transporter implicated in anti-psychotic response, in five treatment-resistant SCZ cases and showed that ABCB11 is specifically enriched in neurons forming mesocortical and mesolimbic dopaminergic projections. Our results indicate potential roles of sCNVs in SCZ risk

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

An assessment of the feasibility and acceptability of a friendship-based social network recruitment strategy to screen at-risk African American and Hispanic/Latina young women for HIV infection.

OBJECTIVES To examine the feasibility and acceptability of a friendship-based network recruitment strategy for identifying undiagnosed human immunodeficiency virus (HIV) infection within young women's same-sex friendship networks and to determine factors that facilitated and hindered index recruiters (IRs) in recruiting female friendship network members (FNMs) as well as factors that facilitated and hindered FNMs in undergoing HIV screening. DESIGN A cross-sectional study design that incorporated dual incentives for IRs and their female FNMs. SETTING The IRs were recruited through 3 Adolescent Trials Network for HIV/AIDS Interventions sites within their Adolescent Medicine Trials Units. Data were collected from January 1, 2009, through June 30, 2010. PARTICIPANTS The IRs self-identifying as HIV positive, negative, or status unknown were enrolled to recruit FNMs to undergo HIV screening. MAIN OUTCOME MEASURES Self-reports of HIV risk and facilitators and barriers to network recruitment and HIV screening were assessed using an audio-computer-assisted self-interview. Participants were identified as HIV negative or positive on the basis of an OraQuick HIV test with confirmatory enzyme-linked immunosorbent assay and/or Western blot tests. RESULTS Nearly all (156 [98.1%]) eligible IRs agreed to participate and most (78.4%) recruited 1 or more FNMs. Of the 381 FNMs, most (342 [89.8%]) agreed to HIV screening. Although a high acceptance of HIV screening was achieved, the HIV prevalence was low (0.26%). CONCLUSION Our findings provide compelling evidence to suggest that use of a female friendship network approach is a feasible and acceptable means for engaging at-risk young women in HIV screening, as shown by their high rates of agreement to undergo HIV screening

A comparison of network-based strategies for screening at-risk Hispanic/Latino adolescents and young adults for undiagnosed asymptomatic HIV infection.

PurposeHispanic/Latino adolescents and young adults are disproportionately impacted by the HIV/AIDS epidemic; yet little is known about the best strategies to increase HIV testing in this group. Network-based approaches are feasible and acceptable means for screening at-risk adults for HIV infection, but it is unknown whether these approaches are appropriate for at-risk young Hispanics/Latinos. Thus, we compared an alternative venue-based testing (AVT) strategy with a social and sexual network-based interviewing and HIV testing (SSNIT) strategy.MethodsAll participants were Hispanics/Latinos aged 13-24 years with self-reported HIV risk; they were recruited from 11 cities in the United States and Puerto Rico and completed an audio computer-assisted self-interview and underwent HIV screening.ResultsA total of 1,596 participants (94.5% of those approached) were enrolled: 784 (49.1%) through AVT and 812 (50.9%) through SSNIT. HIV infection was identified in three SSNIT (.37%) and four AVT (.51%) participants (p = .7213).ConclusionsDespite high levels of HIV risk, a low prevalence of HIV infection was identified with no differences by recruitment strategy. We found overwhelming support for the acceptability and feasibility of AVT and SSNIT for engaging and screening at-risk young Hispanics/Latinos. Further research is needed to better understand how to strategically implement such strategies to improve identification of undiagnosed HIV infection

Sexual Partner Characteristics, Relationship Type, and HIV Risk Among a Community Venue–Based Sample of Urban Adolescent and Young Adult Men Who Have Sex With Men

Few studies have examined sexual partnerships and HIV risk in diverse samples of African American/black and Hispanic/Latino adolescent and young adult men who have sex with men (YMSM), a group that have a high burden of HIV in the U.S. A community-venue recruitment approach was used, which identified significant differences in HIV risk by sexual partner type among 1215 YMSM. Those with casual partners had a higher number of sexual partners, had more STIs, and were more likely to engage in transactional sex, to use alcohol, marijuana, or other substances compared with those with main partners only. Among those with female sexual partners, many used condoms "every time" when engaging in vaginal sex with casual partners, but a sizeable proportion "never/rarely" used condoms with their main partners. Our findings demonstrate a need for tailored HIV prevention education and counseling with necessary skills regarding consistent and correct condom use with all sexual partnerships