Childbearing in a Time of ART: Birth Rates, Childbearing Desires and Family Planning in a Rural HIV Treatment and Care Programme in South Africa

Mixed methods investigate the association between HIV, ART and fertility following scale-up of HIV treatment and care in South Africa. Two longitudinal analyses of surveillance data from the Africa Centre for Health and Population Studies compare factors associated with live birth by HIV and ART exposure. Semi-structured interviews with women enrolled on ART and healthcare providers explore perceptions of childbearing and contraceptive use. A quantitative study reports on one open cohort analysis and a subsequent closed cohort. Crude Birth Rates declined since 2005 and an open cohort analysis (2007-2013) found consistently lower birth-rates amongst women on-ART, compared to HIV-positive ART-naïve women and HIV negative women. One exception was found in the 25-29year age group: incidence was 38% higher to women on ART than ART-naïve women. Crude incidence of live birth was 6.6 births/100 women-years and decreased with increasing age, higher parity, poorer self-reported health, urban area of residency, knowledge of own HIV status, being single or engaged/married, not living with a partner, awareness of the benefits of ART, use of contraception and use of injectable methods. Annual likelihood (aHR, 0.39; 95% 0.347 – 0.441) was 61% lower to HIV positive versus negative women in multivariable Poisson analysis and exposure to ART was associated with 38% reduced likelihood (aHR, 0.62; 95% 0.487 – 0.799). In a subsequent closed cohort, HIV ‘unknown’ women demonstrated similar incidence and associated factors of live birth compared to HIV negative women. HIV positive women were less likely than HIV negative and HIV ‘unknown’ women to use contraception. Women described inconsistent injectable use in semi-structured interviews due to side effects and perceptions that injectables make women ‘watery’ or are unnecessary on ART. Family planning counselling was under-prioritised within the health care service and women were unaware of safer conception topics. Recent pregnancies were considered unintended and most women desired to avoid childbearing considering current family size, economic and health risks. Partner expectations could override strong concerns for health, however, and HIV positive women were at similar risk of live birth to HIV negative women when in a regular relationship or living with a partner

Recognition of Face Identity and Emotion in Expressive Specific Language Impairment

Objective: To study face and emotion recognition in children with mostly expressive specific language impairment (SLI-E). Subjects and Methods: A test movie to study perception and recognition of faces and mimic-gestural expression was applied to 24 children diagnosed as suffering from SLI-E and an age-matched control group of normally developing children. Results: Compared to a normal control group, the SLI-E children scored significantly worse in both the face and expression recognition tasks with a preponderant effect on emotion recognition. The performance of the SLI-E group could not be explained by reduced attention during the test session. Conclusion: We conclude that SLI-E is associated with a deficiency in decoding non-verbal emotional facial and gestural information, which might lead to profound and persistent problems in social interaction and development. Copyright (C) 2012 S. Karger AG, Base

The evolution of methods for establishing evolutionary timescales

The fossil record is well known to be incomplete. Read literally, it provides a distorted view of the history of species divergence and extinction, because different species have different propensities to fossilize, the amount of rock fluctuates over geological timescales, as does the nature of the environments that it preserves. Even so, patterns in the fossil evidence allow us to assess the incompleteness of the fossil record. While the molecular clock can be used to extend the time estimates from fossil species to lineages not represented in the fossil record, fossils are the only source of information concerning absolute (geological) times in molecular dating analysis. We review different ways of incorporating fossil evidence in modern clock dating analyses, including node-calibrations where lineage divergence times are constrained using probability densities and tip-calibrations where fossil species at the tips of the tree are assigned dates from dated rock strata. While node-calibrations are often constructed by a crude assessment of the fossil evidence and thus involves arbitrariness, tip-calibrations may be too sensitive to the prior on divergence times or the branching process and influenced unduly affected by well-known problems of morphological character evolution, such as environmental influence on morphological phenotypes, correlation among traits, and convergent evolution in disparate species. We discuss the utility of time information from fossils in phylogeny estimation and the search for ancestors in the fossil record. This article is part of the themed issue ‘Dating species divergences using rocks and clocks’

Effect of different UCOE-promoter combinations in creation of engineered cell lines for the production of Factor VIII

<p>Abstract</p> <p>Background</p> <p>The most common approach used in generating cell lines for the production of therapetic proteins relies on gene amplification induced by a drug resistance gene e. g., DHFR and glutamine synthetase. Practically, this results in screening large number of clones for the one that expresses high levels of the biologic in a stable manner. The inefficiency of mammalian vector systems to express proteins in a stable manner typically involves silencing of the exogenous gene resulting from modifications such as methylation of CpG DNA sequences, histone deacetylation and chromatin condensation. The use of un-methylated CpG island fragments from housekeeping genes referred to as UCOE (ubiquitous chromatin opening elements) in plasmid vectors is now well established for increased stability of transgene expression. However, few UCOE-promoter combinations have been studied to date and in this report we have tested 14 different combinations.</p> <p>Findings</p> <p>In this report we describe studies with two different UCOEs (the 1.5 Kb human RNP fragment and the 3.2 Kb mouse RPS3 fragment) in combination with various promoters to express a large protein (B domain deleted factor VIII; BDD-FVIII) in a production cell line, BHK21. We show here that there are differences in expression of BDD-FVIII by the different UCOE-promoter combinations in both attached and serum free suspension adapted cells. In all cases, the 1.5 Kb human RNP UCOE performed better in expressing BDD-FVIII than their corresponding 3.2 Kb mouse RPS3 UCOE. Surprisingly, in certain scenarios described here, expression from a number of promoters was equivalent or higher than the commonly used and industry standard human CMV promoter.</p> <p>Conclusion</p> <p>This study indicates that certain UCOE-promoter combinations are better than others in expressing the BDD-FVIII protein in a stable manner in BHK21 cells. An empirical study such as this is required to determine the best combination of UCOE-promoter in a vector for a particular production cell line.</p

Investigating the influence of mtDNA and nuclear encoded mitochondrial variants on high intensity interval training outcomes

Mitochondria supply intracellular energy requirements during exercise. Specific mitochondrial haplogroups and mitochondrial genetic variants have been associated with athletic performance, and exercise responses. However, these associations were discovered using underpowered, candidate gene approaches, and consequently have not been replicated. Here, we used whole-mitochondrial genome sequencing, in conjunction with high-throughput genotyping arrays, to discover novel genetic variants associated with exercise responses in the Gene SMART (Skeletal Muscle Adaptive Response to Training) cohort (n = 62 completed). We performed a Principal Component Analysis of cohort aerobic fitness measures to build composite traits and test for variants associated with exercise outcomes. None of the mitochondrial genetic variants but eight nuclear encoded variants in seven separate genes were found to be associated with exercise responses (FDR < 0.05) (rs11061368: DIABLO, rs113400963: FAM185A, rs6062129 and rs6121949: MTG2, rs7231304: AFG3L2, rs2041840: NDUFAF7, rs7085433: TIMM23, rs1063271: SPTLC2). Additionally, we outline potential mechanisms by which these variants may be contributing to exercise phenotypes. Our data suggest novel nuclear-encoded SNPs and mitochondrial pathways associated with exercise response phenotypes. Future studies should focus on validating these variants across different cohorts and ethnicities.</p

Economic evaluations of onchocerciasis interventions: a systematic review and research needs

Objective To provide a systematic review of economic evaluations that has been conducted for onchocerciasis interventions, to summarise current key knowledge and to identify research gaps. Method A systematic review of the literature was conducted on the 8th of August 2018 using the PubMed (MEDLINE) and ISI Web of Science electronic databases. No date or language stipulations were applied to the searches. Results We identified 14 primary studies reporting the results of economic evaluations of onchocerciasis interventions, seven of which were cost‐effectiveness analyses. The studies identified used a variety of different approaches to estimate the costs of the investigated interventions/programmes. Originally, the studies only quantified the benefits associated with preventing blindness. Gradually, methods improved and also captured onchocerciasis‐associated skin disease. Studies found that eliminating onchocerciasis would generate billions in economic benefits. The majority of the cost‐effectiveness analyses evaluated annual mass drug administration (MDA). The estimated cost per disability‐adjusted life year (DALY) averted of annual MDA varies between US$3 and US$30 (cost year variable). Conclusions The cost benefit and cost effectiveness of onchocerciasis interventions have consistently been found to be very favourable. This finding provides strong evidential support for the ongoing efforts to eliminate onchocerciasis from endemic areas. Although these results are very promising, there are several important research gaps that need to be addressed as we move towards the 2020 milestones and beyond

Global Taxonomic Diversity of Anomodonts (Tetrapoda, Therapsida) and the Terrestrial Rock Record Across the Permian-Triassic Boundary

The end-Permian biotic crisis (∼252.5 Ma) represents the most severe extinction event in Earth's history. This paper investigates diversity patterns in Anomodontia, an extinct group of therapsid synapsids (‘mammal-like reptiles’), through time and in particular across this event. As herbivores and the dominant terrestrial tetrapods of their time, anomodonts play a central role in assessing the impact of the end-Permian extinction on terrestrial ecosystems. Taxonomic diversity analysis reveals that anomodonts experienced three distinct phases of diversification interrupted by the same number of extinctions, i.e. an end-Guadalupian, an end-Permian, and a mid-Triassic extinction. A positive correlation between the number of taxa and the number of formations per time interval shows that anomodont diversity is biased by the Permian-Triassic terrestrial rock record. Normalized diversity curves indicate that anomodont richness continuously declines from the Middle Permian to the Late Triassic, but also reveals all three extinction events. Taxonomic rates (origination and extinction) indicate that the end-Guadalupian and end-Permian extinctions were driven by increased rates of extinction as well as low origination rates. However, this pattern is not evident at the final decline of anomodont diversity during the Middle Triassic. Therefore, it remains unclear whether the Middle Triassic extinction represents a gradual or abrupt event that is unique to anomodonts or more common among terrestrial tetrapods. The end-Permian extinction represents the most distinct event in terms of decline in anomodont richness and turnover rates

The Evolution of Bat Vestibular Systems in the Face of Potential Antagonistic Selection Pressures for Flight and Echolocation

PMCID: PMC3634842This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

A Thirty Million Year-Old Inherited Heteroplasmy

Due to essentially maternal inheritance and a bottleneck effect during early oogenesis, newly arising mitochondrial DNA (mtDNA) mutations segregate rapidly in metazoan female germlines. Consequently, heteroplasmy (i.e. the mixture of mtDNA genotypes within an organism) is generally resolved to homoplasmy within a few generations. Here, we report an exceptional transpecific heteroplasmy (predicting an alanine/valine alloacceptor tRNA change) that has been stably inherited in oniscid crustaceans for at least thirty million years. Our results suggest that this heteroplasmy is stably transmitted across generations because it occurs within mitochondria and therefore escapes the mtDNA bottleneck that usually erases heteroplasmy. Consistently, at least two oniscid species possess an atypical trimeric mitochondrial genome, which provides an adequate substrate for the emergence of a constitutive intra-mitochondrial heteroplasmy. Persistence of a mitochondrial polymorphism on such a deep evolutionary timescale suggests that balancing selection may be shaping mitochondrial sequence evolution in oniscid crustaceans