Stable, high yield expression of gp145 Env glycoprotein from HIV-1 in mammalian cells.

The HIV-1 derived gp145 protein is being investigated by research groups as preclinical studies have shown high promise for this protein as a vaccine against HIV. However, one of the main challenges with manufacturing this promising protein has been ascribed to the low yield obtained in mammalian cell cultures. Significant improvements in gp145 production are needed to address this issue to test the gp145 protein as a potentially effective, safe, and affordable HIV vaccine. Here we describe the application of a novel expression technology to create GMP-grade CHO cell lines expressing approximately 50 µg/ml in non-optimized fed-batch culture, which is an order of magnitude higher than that obtained in existing processes. Top producing clones show a high degree of similarity in the glycosylation patterns of the purified protein to the reference standard. Conformational integrity and functionality was demonstrated via high-affinity binding to soluble CD4, using a panel of antibodies including VRC01, F105, Hk20, PG9 and 17b. In summary, we were able to generate CHO cell lines expressing HIV gp145 with significantly higher overall expression yields than currently accessible, and high product quality that could potentially be suitable for future studies assessing the efficacy and safety of gp145-based HIV vaccines.

Anti-V2 antibodies virus vulnerability revealed by envelope V1 deletion in HIV vaccine candidates.

The efficacy of ALVAC-based HIV and SIV vaccines in humans and macaques correlates with antibodies to envelope variable region 2 (V2). We show here that vaccine-induced antibodies to SIV variable region 1 (V1) inhibit anti-V2 antibody-mediated cytotoxicity and reverse their ability to block V2 peptide interaction with the α4ß7 integrin. SIV vaccines engineered to delete V1 and favor an α helix, rather than a ß sheet V2 conformation, induced V2-specific ADCC correlating with decreased risk of SIV acquisition. Removal of V1 from the HIV-1 clade A/E A244 envelope resulted in decreased binding to antibodies recognizing V2 in the ß sheet conformation. Thus, deletion of V1 in HIV envelope immunogens may improve antibody responses to V2 virus vulnerability sites and increase the efficacy of HIV vaccine candidates.

Students' Motivation and Engagement Predict Reading Achievement Differently by Ethnic Group.

The authors examined Grade 3 and Grade 5 teacher-rated classroom engagement and student self-reported motivation for reading as predictors of reading achievement. They investigated the patterns of prediction of achievement for three racial/ethnic groups (White, Black, and Hispanic) and five levels of socioeconomic status (SES) in a combined within-group model. Groups were created by crossing race/ethnicity with SES to form 15 independent groups for each grade level. Results indicated that self-reported motivation was a significant predictor of reading achievement mainly for White third-grade students; teacher-reported engagement was a better predictor for all racial/ethnic groups for both Grade 3 and Grade 5 reading achievement. Results show higher achievement for White and higher-SES students compared with non-White and lower-SES students.

The Link Between Nutrition and Physical Activity in Increasing Academic Achievement.

BACKGROUND: Research demonstrates a link between decreased cognitive function in overweight school-aged children and improved cognitive function among students with high fitness levels and children engaging in regular physical activity (PA). The purpose of this study was to examine whether regular PA and proper nutrition together had a significant effect on academic achievement. METHODS: Using the seventh wave of the Early Childhood Longitudinal Study, Kindergarten Class 1998-99 (ECLS-K) dataset, linear regression analysis with a Jackknife resampling correction was conducted to analyze the relationship among nutrition, PA, and academic achievement, while controlling for socioeconomic status, age, and sex. A nonactive, unhealthy nutrition group and a physically active, healthy nutrition group were compared on standardized tests of academic achievement. RESULTS: Findings indicated that PA levels and proper nutrition significantly predicted achievement scores. Thus, the active, healthy nutrition group scored higher on reading, math, and science standardized achievement tests scores. CONCLUSIONS: There is a strong connection between healthy nutrition and adequate PA, and the average performance within the population. Thus, results from this study suggest a supporting relationship between students' health and academic achievement. Findings also provide implications for school and district policy changes.

Exploring Psychosocial Mechanisms and Interactions: Links Between Adolescent Emotional Distress, School Connectedness, and Educational Achievement.

Internalizing mental health issues are a significant developmental and clinical concern during adolescence, but rarely identified as a problem among school staff. Using data from the National Longitudinal Study of Adolescent Health, this study examined the associations between adolescent emotional distress, school connectedness, and educational achievement by exploring potential mechanistic and interactive roles of perceived school connectedness on the emotion-education association. Emotional distress was negatively associated with adolescents' perceptions of belonging to school, which, in turn, may negatively influence educational achievement. School connectedness also had both additive and multiplicative interaction effects on the emotion-education relationship. Results support previous evidence of school connectedness as a protective factor for adolescents with internalizing mental health concerns, although much of the work to date has focused on externalizing problems. This study informs our understanding of how, why, and for whom emotional problems influence educational outcomes in light of social support in the school context.

DNA prime/protein boost vaccination elicits robust humoral response in rhesus macaques using oligomeric simian immunodeficiency virus envelope and Advax delta inulin adjuvant.

The partial success of the RV144 trial underscores the importance of envelope-specific antibody responses for an effective HIV-1 vaccine. Oligomeric HIV-1 envelope proteins delivered with a potent adjuvant are expected to elicit strong antibody responses with broad neutralization specificity. To test this hypothesis, two SIV envelope proteins were formulated with delta inulin-based adjuvant (Advax) and used to immunize nonhuman primates. Oligomeric gp140-gp145 from SIVmac251 and SIVsmE660 was purified to homogeneity. Oligomers showed high-affinity interaction with CD4 and were highly immunogenic in rabbits, inducing Tier 2 SIV-neutralizing antibodies. The immunogenicity of an oligomeric Env DNA prime and protein boost together with Advax was evaluated in Chinese rhesus macaques. DNA administration elicited antibodies to both envelopes, and titres were markedly enhanced following homologous protein boosts via intranasal and intramuscular routes. Strong antibody responses were detected against the V1 and V2 domains of gp120. During peak immune responses, a low to moderate level of neutralizing activity was detected against Tier 1A/1B SIV isolates, with a moderate level noted against a Tier 2 isolate. Increased serum antibody affinity to SIVmac251 gp140 and generation of Env-specific memory B cells were observed in the immunized macaques. Animals were subjected to low-dose intravaginal challenge with SIVmac251 one week after the last protein boost. One out of three immunized animals was protected from infection. Although performed with a small number of macaques, this study demonstrates the utility of oligomeric envelopes formulated with Advax in eliciting broad antibody responses with the potential to provide protection against SIV transmission.

Scaling bioinformatics applications on HPC.

BACKGROUND: Recent breakthroughs in molecular biology and next generation sequencing technologies have led to the expenential growh of the sequence databases. Researchrs use BLAST for processing these sequences. However traditional software parallelization techniques (threads, message passing interface) applied in newer versios of BLAST are not adequate for processing these sequences in timely manner. METHODS: A new method for array job parallelization has been developed which offers O(T) theoretical speed-up in comparison to multi-threading and MPI techniques. Here T is the number of array job tasks. (The number of CPUs that will be used to complete the job equals the product of T multiplied by the number of CPUs used by a single task.) The approach is based on segmentation of both input datasets to the BLAST process, combining partial solutions published earlier (Dhanker and Gupta, Int J Comput Sci Inf Technol_5:4818-4820, 2014), (Grant et al., Bioinformatics_18:765-766, 2002), (Mathog, Bioinformatics_19:1865-1866, 2003). It is accordingly referred to as a "dual segmentation" method. In order to implement the new method, the BLAST source code was modified to allow the researcher to pass to the program the number of records (effective number of sequences) in the original database. The team also developed methods to manage and consolidate the large number of partial results that get produced. Dual segmentation allows for massive parallelization, which lifts the scaling ceiling in exciting ways. RESULTS: BLAST jobs that hitherto failed or slogged inefficiently to completion now finish with speeds that characteristically reduce wallclock time from 27 days on 40 CPUs to a single day using 4104 tasks, each task utilizing eight CPUs and taking less than 7 minutes to complete. CONCLUSIONS: The massive increase in the number of tasks when running an analysis job with dual segmentation reduces the size, scope and execution time of each task. Besides significant speed of completion, additional benefits include fine-grained checkpointing and increased flexibility of job submission. "Trickling in" a swarm of individual small tasks tempers competition for CPU time in the shared HPC environment, and jobs submitted during quiet periods can complete in extraordinarily short time frames. The smaller task size also allows the use of older and less powerful hardware. The CDRH workhorse cluster was commissioned in 2010, yet its eight-core CPUs with only 24GB RAM work well in 2017 for these dual segmentation jobs. Finally, these techniques are excitingly friendly to budget conscious scientific research organizations where probabilistic algorithms such as BLAST might discourage attempts at greater certainty because single runs represent a major resource drain. If a job that used to take 24 days can now be completed in less than an hour or on a space available basis (which is the case at CDRH), repeated runs for more exhaustive analyses can be usefully contemplated.

Adjuvant-dependent innate and adaptive immune signatures of risk of SIVmac251 acquisition.

A recombinant vaccine containing Aventis Pasteur's canarypox vector (ALVAC)-HIV and gp120 alum decreased the risk of HIV acquisition in the RV144 vaccine trial. The substitution of alum with the more immunogenic MF59 adjuvant is under consideration for the next efficacy human trial. We found here that an ALVAC-simian immunodeficiency virus (SIV) and gp120 alum (ALVAC-SIV + gp120) equivalent vaccine, but not an ALVAC-SIV + gp120 MF59 vaccine, was efficacious in delaying the onset of SIVmac251 in rhesus macaques, despite the higher immunogenicity of the latter adjuvant. Vaccine efficacy was associated with alum-induced, but not with MF59-induced, envelope (Env)-dependent mucosal innate lymphoid cells (ILCs) that produce interleukin (IL)-17, as well as with mucosal IgG to the gp120 variable region 2 (V2) and the expression of 12 genes, ten of which are part of the RAS pathway. The association between RAS activation and vaccine efficacy was also observed in an independent efficacious SIV-vaccine approach. Whether RAS activation, mucosal ILCs and antibodies to V2 are also important hallmarks of HIV-vaccine efficacy in humans will require further studies.

Comparable Antigenicity and Immunogenicity of Oligomeric Forms of a Novel, Acute HIV-1 Subtype C gp145 Envelope for Use in Preclinical and Clinical Vaccine Research.

UNLABELLED: Eliciting broadly reactive functional antibodies remains a challenge in human immunodeficiency virus type 1 (HIV-1) vaccine development that is complicated by variations in envelope (Env) subtype and structure. The majority of new global HIV-1 infections are subtype C, and novel antigenic properties have been described for subtype C Env proteins. Thus, an HIV-1 subtype C Env protein (CO6980v0c22) from an infected person in the acute phase (Fiebig stage I/II) was developed as a research reagent and candidate immunogen. The gp145 envelope is a novel immunogen with a fully intact membrane-proximal external region (MPER), extended by a polylysine tail. Soluble gp145 was enriched for trimers that yielded the expected "fan blade" motifs when visualized by cryoelectron microscopy. CO6980v0c22 gp145 reacts with the 4E10, PG9, PG16, and VRC01 HIV-1 neutralizing monoclonal antibodies (MAbs), as well as the V1/V2-specific PGT121, 697, 2158, and 2297 MAbs. Different gp145 oligomers were tested for immunogenicity in rabbits, and purified dimers, trimers, and larger multimers elicited similar levels of cross-subtype binding and neutralizing antibodies to tier 1 and some tier 2 viruses. Immunized rabbit sera did not neutralize the highly resistant CO6980v0c22 pseudovirus but did inhibit the homologous infectious molecular clone in a peripheral blood mononuclear cell (PBMC) assay. This Env is currently in good manufacturing practice (GMP) production to be made available for use as a clinical research tool and further evaluation as a candidate vaccine. IMPORTANCE: At present, the product pipeline for HIV vaccines is insufficient and is limited by inadequate capacity to produce large quantities of vaccine to standards required for human clinical trials. Such products are required to evaluate critical questions of vaccine formulation, route, dosing, and schedule, as well as to establish vaccine efficacy. The gp145 Env protein presented in this study forms physical trimers, binds to many of the well-characterized broad neutralizing MAbs that target conserved Env epitopes, and induce cross-subtype neutralizing antibodies as measured in both cell line and primary cell assays. This subtype C Env gp145 protein is currently undergoing good manufacturing practice production for use as a reagent for preclinical studies and for human clinical research. This product will serve as a reagent for comparative studies and may represent a next-generation candidate HIV immunogen.

Individual and interpersonal risk factors for physical intimate partner violence perpetration by biological sex and ethnicity.

Intimate partner violence (IPV) is a public health problem that reaches across age, sex, and ethnicity. In this study, we examined risk factors for physical IPV perpetration among young adult males and females from four ethnic groups. Data were taken from Waves 1-3 of the National Longitudinal Study of Adolescent Health (Add Health). The sample included 10,141 Wave 3 respondents (ages ranged from 18-27 years old) who reported being in a current romantic relationship. Physical IPV perpetration was reported by 14.10% of White, 23.28% of Black, 18.82% of Latino, and 18.02% of Asian males. Physical IPV perpetration was reported by 19.01% of White, 24.80% of Black, 25.97% of Latina, and 19.21% of Asian females. Following an ecological framework, proximal risk factors at intrapersonal and interpersonal levels were included in the analyses. Despite finding fairly consistent percentage of physical IPV perpetration across sample groups, the risk factors for physical IPV perpetration were rather uncommon across sex and ethnicity. Only 1 factor--psychological IPV perpetration toward a romantic partner--was consistently associated with physical IPV perpetration across all groups. Our findings have implications for tailoring prevention and intervention efforts toward risk factors of physical IPV perpetration that are uniquely associated with biological sex and ethnicity.

Antigenicity and immunogenicity of a trimeric envelope protein from an Indian clade C HIV-1 isolate.

Human immunodeficiency virus type 1 (HIV-1) isolates from India mainly belong to clade C and are quite distinct from clade C isolates from Africa in terms of their phylogenetic makeup, serotype, and sensitivity to known human broadly neutralizing monoclonal antibodies. Because many of these properties are associated with the envelope proteins of HIV-1, it is of interest to study the envelope proteins of Indian clade C isolates as part of the ongoing efforts to develop a vaccine against HIV-1. To this end, we purified trimeric uncleaved gp145 of a CCR5 tropic Indian clade C HIV-1 (93IN101) from the conditioned medium of 293 cells. The purified protein was shown to be properly folded with stable structure by circular dichroism. Conformational integrity was further demonstrated by its high affinity binding to soluble CD4, CD4 binding site antibodies such as b12 and VRC01, quaternary epitope-specific antibody PG9, and CD4-induced epitope-specific antibody 17b. Sera from rabbits immunized with gp145 elicited high titer antibodies to various domains of gp120 and neutralized a broad spectrum of clade B and clade C HIV-1 isolates. Similar to other clade B and clade C envelope immunogens, most of the Tier 1 neutralizing activity could be absorbed with the V3-specific peptide. Subsequent boosting of these rabbits with a clade B HIV-1 Bal gp145 resulted in an expanded breadth of neutralization of HIV-1 isolates. The present study strongly supports the inclusion of envelopes from Indian isolates in a future mixture of HIV-1 vaccines.

Identifying and Eliminating Deficiencies in the General Surgery Resident Core Competency Curriculum.

IMPORTANCE: Although the Accreditation Council for Graduate Medical Education has defined 6 core competencies required of resident education, no consensus exists on best practices for reaching resident proficiency. Surgery programs must develop resourceful methods to incorporate learning. While patient care and medical knowledge are approached with formal didactics and traditional Halstedian educational formats, other core competencies are presumed to be learned on the job or emphasized in conferences. OBJECTIVES: To test the hypothesis that our residents lack a foundation in several of the nonclinical core competencies and to seek to develop a formal curriculum that can be integrated into our current didactic time, with minimal effect on resident work hours and rest hours. DESIGN, SETTING, AND PARTICIPANTS: Anonymous Likert-type scale needs assessment survey requesting residents within a large single general surgery residency program to rate their understanding, working knowledge, or level of comfort on the following 10 topics: negotiation and conflict resolution; leadership styles; health care legislation; principles of quality delivery of care, patient safety, and performance improvement; business of medicine; clinical practice models; role of advocacy in health care policy and government; personal finance management; team building; and roles of innovation and technology in health care delivery. MAIN OUTCOMES AND MEASURES: Proportions of resident responses scored as positive (agree or strongly agree) or negative (disagree or strongly disagree). RESULTS: In total, 48 surgery residents (70%) responded to the survey. Only 3 topics (leadership styles, team building, and roles of innovation and technology in health care delivery) had greater than 70% positive responses, while 2 topics (negotiation and conflict resolution and principles of quality delivery of care, patient safety, and performance improvement) had greater than 60% positive responses. The remaining topics had less than 40% positive responses, with the least positive responses on the topics business of medicine (13% [6 of 48]) and health care legislation (19% [9 of 48]). CONCLUSIONS AND RELEVANCE: General surgery residents in our program do not report being knowledgeable or comfortable with several areas of the nonclinical Accreditation Council for Graduate Medical Education core competencies. We developed a formal health care policy and management curriculum, with integration into preexisting protected surgical didactic time. This curriculum fulfills educational requirements, without negatively affecting resident work hours and without increased expense to the department of surgery. Future studies measuring the effect of this integrated program on resident education, knowledge, and satisfaction are warranted.

Nedd4-mediated increase in HIV-1 Gag and Env proteins and immunity following DNA-vaccination of BALB/c mice.

The late assembly domain of many viruses is critical for budding. Within these domains, encoded in viral structural proteins, are the conserved motifs PTAP, PPxY and YPxL. These sequences are the key determinants for association of viral proteins with intracellular molecules such as Tsg101, Nedd4 and AIP1/ALIX. While roles for Tsg101 and AIP1/ALIX in HIV-1 budding have been well established, less is known about the role of Nedd4. Recent studies, however, have identified a function for Nedd4-like protein in HIV-1 release. In this study, we investigated post-transcriptional changes of Nedd4 following SHIVSF162P3 infection of rhesus macaques, its role on HIV-1 p24 and gp120 levels in vitro and its potential as an immune modulator in HIV vaccination of BALB/c mice. Increased Nedd4 protein levels were noted in both CD4+ and CD8+ T cells following SHIVSF162P3-infection of naïve macaques. Transient co-transfection studies in 293 cells with HXB2 and Nedd4 demonstrated a Nedd4-mediated increase in p24 and gp120 levels. This increase was found to be dependent on the Ca2+/calmodulin-regulated phospholipid binding C2 domain and not ubiquitin ligase activity or HIV LTR activity. Co-transfection of Nedd4 with plasmid DNA expressing Gag or Env was further shown to augment both intracellular and extracellular Gag or Env proteins. To assess the potential of Nedd4 as an immune modulator, BALB/c mice were immunized intramuscularly with plasmid DNA encoding HIV gag, env and Nedd4. Nedd4 co-administration was found to increase serum anti-p24 but not anti-gp120 antibodies. Nedd4 co-injection was found to have no affect on Gag- or Env-specific IFNγ but had a trend of increased Gag-specific IL-6, IL-17A and TNFα that was not seen following Env stimulation. Based on our initial findings, Nedd4-mediated changes in HIV protein levels and its potential use in HIV-1 vaccine development warrants further investigation.

Antibodies with high avidity to the gp120 envelope protein in protection from simian immunodeficiency virus SIV(mac251) acquisition in an immunization regimen that mimics the RV-144 Thai trial.

The recombinant canarypox vector, ALVAC-HIV, together with human immunodeficiency virus (HIV) gp120 envelope glycoprotein, has protected 31.2% of Thai individuals from HIV acquisition in the RV144 HIV vaccine trial. This outcome was unexpected, given the limited ability of the vaccine components to induce CD8(+) T-cell responses or broadly neutralizing antibodies. We vaccinated macaques with an immunization regimen intended to mimic the RV144 trial and exposed them intrarectally to a dose of the simian immunodeficiency virus SIV(mac251) that transmits few virus variants, similar to HIV transmission to humans. Vaccination induced anti-envelope antibodies in all vaccinees and CD4(+) and CD8(+) T-cell responses. Three of the 11 macaques vaccinated with ALVAC-SIV/gp120 were protected from SIV(mac251) acquisition, but the result was not significant. The remaining vaccinees were infected and progressed to disease. The magnitudes of vaccine-induced SIV(mac251)-specific T-cell responses and binding antibodies were not significantly different between protected and infected animals. However, sera from protected animals had higher avidity antibodies to gp120, recognized the variable envelope regions V1/V2, and reduced SIV(mac251) infectivity in cells that express high levels of α(4)ß(7) integrins, suggesting a functional role of antibodies to V2. The current results emphasize the utility of determining the titer of repeated mucosal challenge in the preclinical evaluation of HIV vaccines.

Risk factors for unidirectional and bidirectional intimate partner violence among young adults.

OBJECTIVE: The purpose of this study was to identify common and unique risk factors for intimate partner violence (IPV) among young adults in relationships. Guided by two models of IPV, the same set of risk factors was used to examine outcomes of unidirectional (perpetration or victimization) and bidirectional (reciprocal) IPV separately for males and females. METHODS: The sample included 10,187 young adults, ages 18-27, from the National Longitudinal Study of Adolescent Health. The respondents were drawn from Wave 3 and stated they had a romantic relationship during the time of the study. The risk factors were primarily related to violent socialization (e.g., childhood maltreatment, youth violence) and personal adjustment (e.g., alcohol use, depression). RESULTS: Approximately 47% of the respondents experienced some form of IPV in romantic relationships, and the majority of respondents reported bidirectional violence. For males, childhood sexual abuse was associated with perpetration and bidirectional IPV, and childhood neglect was associated with bidirectional IPV. For females, childhood neglect was associated with all three IPV outcomes, and childhood physical abuse was associated with bidirectional IPV. Youth violence perpetration during adolescence increased the odds for all IPV outcomes among females, while low self-esteem increased the odds for all IPV outcomes among males. A history of suicide attempts predicted bidirectional IPV across genders. Being married and living with a partner predicted all three IPV outcomes for males and females. CONCLUSIONS: The results revealed more common risk factors for bidirectional IPV than unidirectional IPV and few common risk factors across genders. The results indicate that IPV prevention and intervention strategies should be tailored to the unique risk experiences of males and females rather than focus on a common factors approach. However, child abuse, youth violence, and suicide prevention efforts may reduce incidents of later IPV for males and females, and these strategies should continue to be an emphasis in practice and research.

Vaccine induced antibodies to the first variable loop of human immunodeficiency virus type 1 gp120, mediate antibody-dependent virus inhibition in macaques.

The role of antibodies directed against the hyper variable envelope region V1 of human immunodeficiency virus type 1 (HIV-1), has not been thoroughly studied. We show that a vaccine able to elicit strain-specific non-neutralizing antibodies to this region of gp120 is associated with control of highly pathogenic chimeric SHIV(89.6P) replication in rhesus macaques. The vaccinated animal that had the highest titers of antibodies to the amino terminus portion of V1, prior to challenge, had secondary antibody responses that mediated cell killing by antibody-dependent cellular cytotoxicity (ADCC), as early as 2 weeks after infection and inhibited viral replication by antibody-dependent cell-mediated virus inhibition (ADCVI), by 4 weeks after infection. There was a significant inverse correlation between virus level and binding antibody titers to the envelope protein, (R=-0.83, p=0.015), and ADCVI (R=-0.84 p=0.044). Genotyping of plasma virus demonstrated in vivo selection of three SHIV(89.6P) variants with changes in potential N-linked glycosylation sites in V1. We found a significant inverse correlation between virus levels and titers of antibodies that mediated ADCVI against all the identified V1 virus variants. A significant inverse correlation was also found between neutralizing antibody titers to SHIV(89.6) and virus levels (R=-0.72 p=0.0050). However, passive inoculation of purified immunoglobulin from animal M316, the macaque that best controlled virus, to a naïve macaque, resulted in a low serum neutralizing antibodies and low ADCVI activity that failed to protect from SHIV(89.6P) challenge. Collectively, while our data suggest that anti-envelope antibodies with neutralizing and non-neutralizing Fc(R-dependent activities may be important in the control of SHIV replication, they also demonstrate that low levels of these antibodies alone are not sufficient to protect from infection.

Academic achievement despite child maltreatment: a longitudinal study.

PURPOSE: Although researchers have concluded that child maltreatment has a negative effect on children's learning and academic achievement, not all children are negatively affected by maltreatment, and some children seem to succeed academically despite being maltreated. Drawing on risk and resilience theory, we examined a broad range of potential risk, promotive, and protective factors within children and their environments along with characteristics of the maltreatment to account for variability in test scores. METHODS: A national longitudinal probability sample of 702 maltreated school-aged children, ages 6-10, and their caregivers was used to predict reading and math scores among maltreated children over three years. RESULTS: We found that chronic maltreatment, poorer daily living skills, and lower intelligence explained a substantial proportion of the variance in maltreated children's math scores (39%), whereas type of maltreatment, poorer daily living skills and lower intelligence explained a substantial proportion of the variance in reading scores (54%) over time. Contrary to our prediction, having a behavior problem seemed to protect chronically maltreated children from poorer performance in math over time. CONCLUSIONS: To increase academic achievement among maltreated children, it is imperative that we prevent chronic maltreatment and help children increase their competency on daily living skills.

Rapid SIV Env-specific mucosal and serum antibody induction augments cellular immunity in protecting immunized, elite-controller macaques against high dose heterologous SIV challenge.

Three Indian rhesus macaques, Ad-SIV primed/protein boosted and exposed twice to high-dose mucosal SIV(mac251) challenges, exhibited elite control of viremia over 6.5 years. They were negative for host factors associated with control of SIV infection. After a third intrarectal challenge with SIV(smE660), all controlled viremia, with one (macaque #5) maintaining undetectable viremia in blood. Acquisition was not blocked, but virus was contained in the jejunum and draining lymph nodes. Polyfunctional memory T cell responses and high-titered neutralizing and non-neutralizing serum and mucosal antibodies were present before and maintained post-challenge. The level of protection seen for animal #5 was predicted from analyses of gene transcription in jejunum 2 weeks post-challenge. Macaques #7 and #9, exhibiting lower pre-challenge cellular and humoral immunity, partially controlled the SIV(smE660) challenge. Initial vaccine-induced control by macaque #5 extended to the SIV(smE660) challenge due to multiple immune mechanisms that were boosted and augmented by cryptic SIV exposure.

Gender differences in risk and promotive classifications associated with adolescent delinquency.

How likely are children exposed to multiple risk factors to engage in delinquent behavior, to what extent do promotive factors mitigate exposure to these risk factors, and do the predictors of delinquent behavior differ by gender? To address these questions, the authors analyzed data from youths (229 boys, 187 girls) who completed the third wave of the Lehigh Longitudinal Study using Latent Profile Analysis. A unique risk and promotive class with slightly elevated rates of exposure to parental violence, mean levels of other risk factors and low levels of promotive factors was present for girls but not for boys. Additionally, for boys and girls, high-risk, low-promotive individuals were significantly more likely to engage in delinquent behavior than low-risk, high-promotive cases. Findings suggest the need to examine risk and promotive factors in combination to account for their shared influences on developmental outcomes for youth.