A comparison of cut points for measuring risk factors for adolescent substance use and antisocial behaviors in the U.S. and Colombia

As the identification and targeting of salient risk factors for adolescent substance use become more widely used globally, an essential question arises as to whether U.S.-based cut points in the distributions of these risk factors that identify high risk can be used validly in other countries as well. This study examined proportions of youth at high risk using different empirically derived cut points in the distributions of 18 measured risk factors. Data were obtained from large-scale samples of adolescents in Colombia and the United States. Results indicated that significant (p \u3c 0.05) differences in the proportions of high risk youth were found in 38.9% of risk factors for 6th graders, 61.1% for 8th graders, and 66.6% for 10th graders. Colombian-based cut points for determining the proportion of Colombian youth at high risk were preferable to U.S.-based cut points in almost all comparisons that exhibited a significant difference. Our findings suggest that observed differences were related to the type of risk factor (e.g., drug specific vs. non-drug specific). Findings from this study demonstrate the need for collecting large-scale national data on risk factors for adolescent substance use and developing country-specific cut points based on the distributions of these measures to avoid misidentification of youth at high risk

Structural conservation of Lassa virus glycoproteins and recognition by neutralizing antibodies

Lassa fever is an acute hemorrhagic fever caused by the zoonotic Lassa virus (LASV). The LASV glycoprotein complex (GPC) mediates viral entry and is the sole target for neutralizing antibodies. Immunogen design is complicated by the metastable nature of recombinant GPCs and the antigenic differences among phylogenetically distinct LASV lineages. Despite the sequence diversity of the GPC, structures of most lineages are lacking. We present the development and characterization of prefusion-stabilized, trimeric GPCs of LASV lineages II, V, and VII, revealing structural conservation despite sequence diversity. High-resolution structures and biophysical characterization of the GPC in complex with GP1-A-specific antibodies suggest their neutralization mechanisms. Finally, we present the isolation and characterization of a trimer-preferring neutralizing antibody belonging to the GPC-B competition group with an epitope that spans adjacent protomers and includes the fusion peptide. Our work provides molecular detail information on LASV antigenic diversity and will guide efforts to design pan-LASV vaccines

Immunoglobulin gene insertions and deletions in the affinity maturation of HIV-1 broadly reactive neutralizing antibodies.

CAPRISA, 2014.Abstract available in pdf

Developmental pathway for potent V1V2-directed HIV-neutralizing antibodies.

CAPRISA, 2014.Antibodies capable of neutralizing HIV-1 often target variable regions 1 and 2 (V1V2) of the HIV-1 envelope, but the mechanism of their elicitation has been unclear. Here we define the developmental pathway by which such antibodies are generated and acquire the requisite molecular characteristics for neutralization. Twelve somatically related neutralizing antibodies (CAP256-VRC26.01-12) were isolated from donor CAP256 (from the Centre for the AIDS Programme of Research in South Africa (CAPRISA)); each antibody contained the protruding tyrosine-sulphated, anionic antigen-binding loop (complementarity-determining region (CDR) H3) characteristic of this category of antibodies. Their unmutated ancestor emerged between weeks 30-38 post-infection with a 35-residue CDR H3, and neutralized the virus that superinfected this individual 15 weeks after initial infection. Improved neutralization breadth and potency occurred by week 59 with modest affinity maturation, and was preceded by extensive diversification of the virus population. HIV-1 V1V2-directed neutralizing antibodies can thus develop relatively rapidly through initial selection of B cells with a long CDR H3, and limited subsequent somatic hypermutation. These data provide important insights relevant to HIV-1 vaccine development

Viral variants that initiate and drive maturation of V1V2-directed HIV-1 broadly neutralizing antibodies.

CAPRISA, 2015.Abstract available in pdf

Adaptation of the Communities That Care Youth Survey for use in Brazil: A pilot study

Substance use and violence are serious problems affecting Brazilian youth, prompting local authorities to invest in adapting and implementing evidence-based prevention programs developed abroad. To ensure that interventions are effective, valid and reliable measures of risk factors for substance use and violence are needed. We conducted a pilot examination of the measurement properties of risk factors in the Communities That Care Youth Survey (CTCYS), a school-based survey developed in the United States. The Brazilian-adapted CTCYS included 25 risk factors as well as measures of substance use and antisocial behaviors. The survey was translated into Brazilian Portuguese and adapted for use in Brazil, incorporating suggestions from local experts. The survey was administered to 926 students in one Brazilian community. Results indicate that scale internal consistency was acceptable for all but two scales: (i) Academic Failure and (ii) Rebelliousness. Confirmatory factor analyses suggested good model fit for most measurement models albeit with minor modifications for most scales. Findings from this pilot study provide a foundation for the use of the CTCYS in Brazil to assess community levels of adolescent risk and evaluate prevention programs

Testing the Question-Behavior Effect of Self-Administered Surveys Measuring Youth Drug Use

Concern that asking about a specific behavior could elicit that behavior is often cited as a reason that communities and schools should not administer surveys about youth drug use. In this study, we investigated if this question-behavior effect exists related to substance use. We examined if simply asking a student about their current drug use leads to an increase in drug use 1 year later. This study tests the validity of the question-behavior effect on youth drug use in a longitudinal panel of 2,002 elementary school students. The sample of students was drawn from the Community Youth Development Study, a community-randomized test of the Communities That Care prevention system. If the prevalence of self-reported drug use in sixth grade in a sample surveyed in fifth and sixth grades was higher than in an accretion sample surveyed only in sixth grade, the difference could indicate a question-behavior effect. Results from logistic regression analyses did not provide any evidence of a question-behavior effect on 30-day or lifetime prevalence of alcohol, tobacco, inhalant, or marijuana use reported in sixth grade. Asking youth about drug use in a survey did not increase the rates of self-reported drug use measured 1 year later. The absence of evidence of a question-behavior effect should ease concerns of communities and schools when administering surveys asking youth about their drug use

Prevention service system transformation using Communities That Care

This study examines prevention system transformation as part of a community-randomized controlled trial of Communities That Care (CTC). Using data from surveys of community leaders, we examine differences between CTC and control communities 4.5 years after CTC implementation. Significantly higher levels of adopting a science-based approach to prevention observed in CTC communities compared to controls in 2004 were maintained in 2007. Leaders in CTC communities expressed a willingness to contribute significantly more funds to prevention than did leaders in control communities in 2007. Significant differences in levels of community collaboration observed in 2004 were not maintained in 2007. Leaders in CTC communities with high poverty rates and large minority student populations reported higher levels of community norms against drug use and greater use of the social development strategy, respectively, than did leaders in control communities with similar characteristics