Oral abstracts of the 21st International AIDS Conference 18-22 July 2016, Durban, South Africa

The rate at which HIV-1 infected individuals progress to AIDS is highly variable and impacted by T cell immunity. CD8 T cell inhibitory molecules are up-regulated in HIV-1 infection and associate with immune dysfunction. We evaluated participants (n=122) recruited to the SPARTAC randomised clinical trial to determine whether CD8 T cell exhaustion markers PD-1, Lag-3 and Tim-3 were associated with immune activation and disease progression.Expression of PD-1, Tim-3, Lag-3 and CD38 on CD8 T cells from the closest pre-therapy time-point to seroconversion was measured by flow cytometry, and correlated with surrogate markers of HIV-1 disease (HIV-1 plasma viral load (pVL) and CD4 T cell count) and the trial endpoint (time to CD4 count <350 cells/μl or initiation of antiretroviral therapy). To explore the functional significance of these markers, co-expression of Eomes, T-bet and CD39 was assessed.Expression of PD-1 on CD8 and CD38 CD8 T cells correlated with pVL and CD4 count at baseline, and predicted time to the trial endpoint. Lag-3 expression was associated with pVL but not CD4 count. For all exhaustion markers, expression of CD38 on CD8 T cells increased the strength of associations. In Cox models, progression to the trial endpoint was most marked for PD-1/CD38 co-expressing cells, with evidence for a stronger effect within 12 weeks from confirmed diagnosis of PHI. The effect of PD-1 and Lag-3 expression on CD8 T cells retained statistical significance in Cox proportional hazards models including antiretroviral therapy and CD4 count, but not pVL as co-variants.Expression of ‘exhaustion’ or ‘immune checkpoint’ markers in early HIV-1 infection is associated with clinical progression and is impacted by immune activation and the duration of infection. New markers to identify exhausted T cells and novel interventions to reverse exhaustion may inform the development of novel immunotherapeutic approaches

Low-frequency variation in TP53 has large effects on head circumference and intracranial volume

Cranial growth and development is a complex process which affects the closely related traits of head circumference (HC) and intracranial volume (ICV). The underlying genetic influences shaping these traits during the transition from childhood to adulthood are little understood, but might include both age-specific genetic factors and low-frequency genetic variation. Here, we model the developmental genetic architecture of HC, showing this is genetically stable and correlated with genetic determinants of ICV. Investigating up to 46,000 children and adults of European descent, we identify association with final HC and/or final ICV + HC at 9 novel common and low-frequency loci, illustrating that genetic variation from a wide allele frequency spectrum contributes to cranial growth. The largest effects are reported for low-frequency variants within TP53, with 0.5 cm wider heads in increaser-allele carriers versus non-carriers during mid-childhood, suggesting a previously unrecognized role of TP53 transcripts in human cranial development

Determination of water absorption rate of palm kernel shells as an alternative pore agents in insulating refractory bricks

Various organic pore agents are used for the production of insulating refractory bricks (IRB). Most times, the deficiencies of the respective pore agents appear to be ignored by the makers of the bricks, and the users. Sawdust, for instance, which is about the most commonly used organic pore agent is known to have high water absorption rates. This is in addition to the inability of the user to have it from one grade of wood-hard wood which is preferred. These factors amount to various drawbacks in the insulating refractory bricks produced with it. In order to curb this problem, this study identified palm kernel shells (PKS) as a potential alternative pore agent in IRB bodies. The focus of the work was on the water absorption rate of PKS. The study employed studio experimentation method. It showed that the water absorption rate of PKS is insignificant and, therefore, is recommended for use as pore agent in insulating refractory bricks

Work-related traumatic spinal cord lesions in Chile, a 20-year epidemiological analysis

Study design:Retrospective cohort study.Objective:To describe the characteristics of patients with work-related traumatic spinal cord injuries (TSCI) in Chile.Setting:Hospital del Trabajador in Santiago, Santiago, Chile.Methods:Patients suffering from TSCI incurred at the workplace from 1986 to 2005 were identified through records of the Asociación Chilena de Seguridad (ACHS, Chilean Safety Association).Results:The medical records of 173 patients, 172 men and 1 woman, were analyzed. The yearly average incidence was 7.8 per million workers. Age at TSCI onset was 38.212.1 years. The principal external causes for TSCI incurred at the workplace were falls from a height in 86 cases (49.7%) and trauma blows to the vertebral spine in 61 cases (35.3 %). More falls occurred in the field construction, and other traumas occurred as a result of traumatic blows caused by tree trunks and stones in forestry and mining sectors. Mortality in this series was 8.7%, and the worst prognosis was for older

Herbal Supplement Use and Blood Lead Levels of United States Adults

BACKGROUND: Some herbal supplements may contain lead. OBJECTIVE: To examine whether use of specific herbal dietary supplements during the last 30 days is associated with blood lead levels in US men and women. DESIGN: Cross-sectional analysis. STUDY POPULATION: NHANES participants from 1999-2004, a representative sample of the civilian non-institutionalized US population. MEASUREMENTS: Lead was measured in blood. Associations between lead and self-reported supplement use were estimated using multivariable regression weighted to account for NHANES sampling. Herbal supplements investigated were those previously reported to contain high heavy metal content: Ayurvedic or traditional Chinese medicine herbs, echinacea, ginkgo, ginseng, St. John\u27s wort, and other herbs (specifically, kava, valerian, black cohosh, bee pollen, and nettle). MAIN RESULTS: Among 6,712 women \u3e or =20 years, those using herbal supplements had lead levels that were 10% higher than non-users (95% CI 3%-17%, p = 0.005). Women using Ayurvedic or traditional Chinese medicine herbs, St. John\u27s wort, and other herbs had lead levels 24% (95% CI 5%-45%, p = 0.01), 23% (95% CI 4%-46%), p = 0.02), and 21% (95% CI 2%-44%, p = 0.03) higher, respectively, than non-users. No significant associations were observed between herb use and lead levels among men (n = 6,095). Among reproductive-aged women (16-45 years), herbal supplement users had lead levels 20% higher than non-users (95% CI 5%-34%, p = 0.008). In contrast, garlic and other dietary supplements were not associated with higher lead levels. CONCLUSION: Use of specific herbal supplements is associated with higher blood lead levels among women. Our data suggest testing guidelines for herbal supplements and regulations limiting lead in supplements are needed