HIV, body composition, bone and vitamin D status in South African women

Digitisation of this thesis was sponsored by Arcadia Fund, a charitable fund of Lisbet Rausing and Peter Baldwin

WHAT TASKS TO AUTOMATE? AN INVESTIGATION OF WHAT TASKS MAKE SENSE TO AUTOMATE FOR FUTURE AVIATION PLATFORMS

The Army is developing a new generation of aircraft called Future Vertical Lift (FVL). These aircraft will integrate new technologies that change Army Aviation’s machinery, methods, and aircrew domains. Key to this effort is the development of automation to reduce pilot cognitive workload and prevent cognitive overload. The purpose of this research was to develop an understanding of the factors that influence pilot cognitive workload and to provide insight into what tasks make sense to automate for FVL. Researchers used a mixed methods approach, relying on scholarly literature and semi-structured interviews to elicit cognitive workload data from Army rotary-wing pilots. Researchers used the data from a simple and a complex MEDEVAC flight scenario to develop an influence diagram that models pilot cognitive workload based on influencing factors and subfactors. At a high level, the data indicate that pilot task demand and environmental factors have the most influence on cognitive workload during complex missions in challenging conditions. At a low level, the data indicate that light factors, intra-flight coordination, and task complexity are most influential on cognitive workload. The results suggest that tasks impacting these factors should be considered for automation to prevent pilot cognitive overload in FVL.DEVCOM AvMCCaptain, United States ArmyMajor, United States ArmyCaptain, United States ArmyMajor, United States ArmyApproved for public release. Distribution is unlimited

Changes in Bone Mineral Density During and After Lactation in Ugandan Women With HIV on Tenofovir-Based Antiretroviral Therapy.

Antiretroviral therapy (ART) in people living with human immunodeficiency virus (HIV) is associated with bone loss, but data are limited in lactation, when physiological bone mineral mobilization is occurring. This research charted changes in areal bone mineral density (aBMD) during and after lactation in Ugandan women with HIV (WWH) initiated onto ART in pregnancy, compared to women without HIV (REF). One-hundred WWH on tenofovir-based ART and 100 REF were enrolled in pregnancy. Lumbar spine (LS), total hip (TH), and whole-body-less-head (WBLH) aBMD were measured by dual-energy X-ray absorptiometry (DXA) at 2, 14, and 26 weeks of lactation, and at 3 months postlactation. The primary outcome was the difference between groups in mean percent change in LS aBMD between 2 and 14 weeks. Statistical analysis was performed in hierarchical repeated measures ANOVA models that corrected for multiple testing. Median age was 23.4 (IQR, 21.0 to 26.8) years. WWH had lower body weight. aBMD decreased in both groups during lactation, but WWH had greater decreases at TH (2-to-26 weeks: WWH [n = 63] -5.9% [95% CI, -6.4 to -5.4] versus REF [n = 64] -4.3% [95% CI, -4.8 to -3.8]; group*time point interaction p = .008). Decreases in LS aBMD were similar in WWH and REF (2-to-26 weeks: -2.0% [95% CI, -2.5 to -1.5]), although there was a tendency toward a smaller decrease in WWH between 2 and 14 weeks (WWH [n = 77] -1.8% [95% CI, -2.2 to -1.4] versus REF [n = 69] -2.9% [95% CI, -3.3 to -2.5]; group*time point interaction p = .08). Postlactation, LS aBMD was higher relative to week 2 in both groups. TH and WBLH aBMD did not return to week 2 values in WWH but did in REF (TH postlactation versus week 2: WWH [n = 61] -3.1% [95% CI, -3.6 to -2.6]; REF [n = 29] +0.1% [95% CI, -0.9 to +1.1]). These data show accentuated bone loss during lactation and only partial skeletal recovery by 3 months postlactation in Ugandan WWH on tenofovir-based ART. Studies are ongoing to understand longer-term consequences for bone health. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research

Gating-by-tilt of mechanosensitive membrane channels

We propose an alternative mechanism for the gating of biological membrane channels in response to membrane tension that involves a change in the slope of the membrane near the channel. Under biological membrane tensions we show that the energy difference between the closed (tilted) and open (untilted) states can far exceed kBT and is comparable to what is available under simple ilational gating. Recent experiments demonstrate that membrane leaflet asymmetries (spontaneous curvature) can strong effect the gating of some channels. Such a phenomenon would be more easy to explain under gating-by-tilt, given its novel intrinsic sensitivity to such asymmetry.Comment: 10 pages, 2 figure

Prenatal DDT Exposure in Relation to Anthropometric and Pubertal Measures in Adolescent Males

DDT (dichlorodiphenyltrichloroethane), a pesticide once used widely in agriculture and now limited to public health use, remains a controversial chemical because of a combination of benefits and risks. DDT or its breakdown products are ubiquitous in the environment and in humans. Compounds in the DDT family have endocrine actions and have been associated with reproductive toxicity. A previous study reported associations between prenatal exposure to p,p′-DDE [1,1-dichloro-2,2-bis(p-chlorophenyl)-ethylene] and increased height and weight in adolescent boys. We examined a group with higher exposures to see whether similar associations would occur. Our study group was 304 males born in Philadelphia in the early 1960s who had participated in a previous study. Anthropometric and pubertal measures from one to six visits during their adolescent years were available, as were stored maternal serum samples from pregnancy. We measured p,p′-DDE, p,p′-DDT [1,1,1-trichloro-2,2-bis(p-chlorophenyl)-ethane], and o,p′-DDT [1,1,1-trichloro-2-(o-chlorophenyl)-2-(p-chlorophenyl)-ethane] in the maternal serum. Outcomes examined in the boys were height, ratio of sitting height to height, body mass index, triceps skinfold thickness, ratio of subscapular to the sum of triceps and subscapular skinfold thicknesses, skeletal age, serum testosterone, and serum dehydroepiandrosterone sulfate. No associations between prenatal exposure to any of the DDT compounds and any outcome measure were seen

Safety and immunogenicity of an FP9-vectored candidate tuberculosis vaccine (FP85A), alone and with candidate vaccine MVA85A in BCG-vaccinated healthy adults: a phase I clinical trial.

The safety and immunogenicity of a new candidate tuberculosis (TB) vaccine, FP85A was evaluated alone and in heterologous prime-boost regimes with another candidate TB vaccine, MVA85A. This was an open label, non-controlled, non-randomized Phase I clinical trial. Healthy previously BCG-vaccinated adult subjects were enrolled sequentially into three groups and vaccinated with FP85A alone, or both FP85A and MVA85A, with a four week interval between vaccinations. Passive and active data on adverse events were collected. Immunogenicity was evaluated by Enzyme Linked Immunospot (ELISpot), flow cytometry and Enzyme Linked Immunosorbent assay (ELISA). Most adverse events were mild and there were no vaccine-related serious adverse events. FP85A vaccination did not enhance antigen 85A-specific cellular immunity. When MVA85A vaccination was preceded by FP85A vaccination, cellular immune responses were lower compared with when MVA85A vaccination was the first immunisation. MVA85A vaccination, but not FP85A vaccination, induced anti-MVA IgG antibodies. Both MVA85A and FP85A vaccinations induced anti-FP9 IgG antibodies. In conclusion, FP85A vaccination was well tolerated but did not induce antigen-specific cellular immune responses. We hypothesize that FP85A induced anti-FP9 IgG antibodies with cross-reactivity for MVA85A, which may have mediated inhibition of the immune response to subsequent MVA85A. ClinicalTrials.gov identification number: NCT00653770

Tibial stress during running following a repeated calf‐raise protocol

This is the author accepted manuscript. The final version is available on open access from Wiley via the DOI in this recordTibial stress fractures are a problematic injury amongst runners. Increased loading of the tibia has been observed following prolonged weight‐bearing activity and is suggested to be the result of reduced activity of the plantar flexor muscles. The musculature that spans the tibia contributes to bending of the bone and influences the magnitude of stress on the tibia during running. Participant‐specific models of the tibia can be used as a non‐invasive estimate of tibial stress. This study aimed to quantify tibial stress during running using participant‐specific bone geometry and to compare tibial stress before and after a protocol of repeated muscular contractions of the plantar flexor muscle group. Fourteen participants who run recreationally were included in the final analysis of the study. Synchronised force and kinematic data were collected during overground running before and after an exhaustive, weighted calf‐raise protocol. Bending moments and stress at the distal third of the tibia were estimated using beam theory combined with inverse dynamics and musculoskeletal modelling. Bone geometry was obtained from magnetic resonance images. There was no difference in stress at the anterior, posterior, medial or lateral peripheries of the tibia after the calf‐raise protocol compared with before. These findings suggest that an exhaustive, repeated calf‐raise protocol did not alter tibial stress during running

Airborne Observations of Carbon Dioxide and Methane Emission Ratios from the Yosemite Rim Wildfire, California

This paper presents airborne in situ measurements of carbon dioxide (CO2) and methane (CH4) downwind of an exceptionally large wildfire, the Rim Fire, near Yosemite, California, during two flights. Data analyses are discussed in terms of emission ratios (ER) and emission factors (EF) and are compared to previous studies. CH4 ERs were 7.5-7.9 parts per billion (ppb) CH4 for every 1 part per million (ppm) of CO2 (ppb CH4 (ppm CO2)(exp.-1)) on 29 August 2013 and 14.2-16.7 ppb CH4 (ppm CO2)(exp. -1) on 10 September 2013. This study measured only CO2 and CH4; however, estimated emission factors (EEFs) are used as rough estimates of EFs of CO2 and CH4 and are in close agreement with EFs reported in previous studies. In the western US, wildfires dominate over prescribed fires, contributing to atmospheric trace gas budgets and regional and local air pollution. Limited sampling of emissions from wildfires means western US emission estimates rely largely on data from prescribed fires, which may not be a suitable proxy for wildfire emissions. Given the magnitude of the Yosemite Rim wildfire, the impacts it had on regional air quality and the limited sampling of wildfire emissions in the western US to date, this study provides a valuable measurement dataset and may have important implications for forestry and regional air quality management