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    Neurodevelopmental assessment of HIV-exposed uninfected and early-treated HIV-infected children: study protocol
    (BioMed Central, 2018-04) Strehlau, Renate; van Aswegen, Tamryn; Potterton, Joanne
    Objective: Sub-Saharan Africa has the highest prevalence of children at risk of not achieving their developmental potential, attributable largely to the human immunodefciency virus (HIV) pandemic coupled with negative environmental factors. Childhood developmental stimulation programmes can mitigate adverse outcomes. Methods: Neonates testing HIV positive at birth will be initiated on antiretroviral treatment (ART) and receive an ageappropriate stimulation program, updated at 3 monthly intervals through the frst year of life. Neurodevelopment at 12 months of age will be assessed using the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III). Outcomes will be compared with HIV-infected and HIV-exposed uninfected children (HEU) not having received the stimulatory intervention. Associations between neurodevelopmental outcomes, environmental factors, and parental stress will be investigated. The study will take place at a single site in Johannesburg, South Africa. This non-randomised controlled intervention study, with a single non-blinded comparative intervention group, aims to investigate whether an early childhood stimulation programme used in conjunction with ART initiated at birth can positively impact neurodevelopmental outcomes at 1 year of age in children infected with HIV.
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    Evidence for igneous differentiation in Sudbury Igneous Complex and impact-driven evolution of terrestrial planet proto-crusts
    (Nature Research, 2019-01) Latypov, Rais; Chistyakova, Sofya; Grieve, Richard; Huhma, Hannu
    Bolide impact is a ubiquitous geological process in the Solar System, which produced craters and basins filled with impact melt sheets on the terrestrial planets. However, it remains controversial whether these sheets were able to undergo large-scale igneous differentiation, or not. Here, we report on the discovery of large discrete bodies of melanorites that occur throughout almost the entire stratigraphy of the 1.85-billion-year-old Sudbury Igneous Complex (SIC) – the best exposed impact melt sheet on Earth – and use them to reaffirm that conspicuous norite-gabbro-granophyre stratigraphy of the SIC is produced by fractional crystallization of an originally homogeneous impact melt of granodioritic composition. This implies that more ancient and compositionally primitive Hadean impact melt sheets on the Earth and other terrestrial planets also underwent large-volume igneous differentiation. The near-surface differentiation of these giant impact melt sheets may therefore have contributed to the evolution and lithological diversity of the proto-crust on terrestrial planets.
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    Assessing runs of Homozygosity: a comparison of SNP Array and whole genome sequence low coverage data
    (BMC, 2018-01) Ceballos, Francisco C.; Hazelhurst, Scott; Ramsay, Michèle
    Background: Runs of Homozygosity (ROH) are genomic regions where identical haplotypes are inherited from each parent. Since their first detection due to technological advances in the late 1990s, ROHs have been shedding light on human population history and deciphering the genetic basis of monogenic and complex traits and diseases. ROH studies have predominantly exploited SNP array data, but are gradually moving to whole genome sequence (WGS) data as it becomes available. WGS data, covering more genetic variability, can add value to ROH studies, but require additional considerations during analysis. Results: Using SNP array and low coverage WGS data from 1885 individuals from 20 world populations, our aims were to compare ROH from the two datasets and to establish software conditions to get comparable results, thus providing guidelines for combining disparate datasets in joint ROH analyses. By allowing heterozygous SNPs per window, using the PLINK homozygosity function and non-parametric analysis, we were able to obtain non-significant differences in number ROH, mean ROH size and total sum of ROH between data sets using the different technologies for almost all populations. Conclusions: By allowing 3 heterozygous SNPs per ROH when dealing with WGS low coverage data, it is possible to establish meaningful comparisons between data using SNP array and WGS low coverage technologies
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    The effect of a ketogenic diet versus a high-carbohydrate, low-fat diet on sleep, cognition, thyroid function, and cardiovascular health independent of weight loss: study protocol for a randomized controlled trial
    (BMC, 2018-01) Iacovides, Stella; Meiring, Rebecca M.
    Background: Many physiological health benefits observed after following a ketogenic diet (KD) can be attributed to the associated weight loss. The KD has become more prominent as a popular health choice, not only in obese/ overweight individuals, but also in healthy adults. The study aims to determine the effects of a KD, independent of weight loss, on various aspects of physiological health including: sleep, thyroid function, cognition, and cardiometabolic health. The study will also aim to determine whether a change in basal metabolic rate may be associated with any changes observed. Methods: Twenty healthy men and women between 18 and 50 years of age will take part in this study. In a randomized controlled, cross-over design, participants will follow two isocaloric diets: a high-carbohydrate, low-fat diet (55% CHO, 20% fat, 25% protein) and a KD (15% CHO, 60% fat, 25% protein). Each dietary intervention will last for a minimum of 3 weeks, with a 1-week washout period in between. Before and after each diet, participants will be assessed for sleep quality, cognitive function, thyroid function, and basal metabolic rate. A blood sample will also be taken for the measurement of cardio-metabolic and immune markers. Discussion: The present study will help in understanding the potential effects of a KD on aspects of physiological health in healthy adults, without the confounding factor of weight loss. The study aims to fill a significant void in the academic literature with regards to the benefits and/or risks of a KD in a healthy population, but will also explore whether diet-related metabolic changes may be responsible for the changes observed in physiological health.
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    The importance of morphological identification of African anopheline mosquitoes (Diptera: Culicidae) for malaria control programmes
    (BMC, 2018-01) Erlank, Erica; Koekemoer, Lizette L.; Coetzee, Maureen
    Background: The correct identification of disease vectors is the first step towards implementing an effective control programme. Traditionally, for malaria control, this was based on the morphological differences observed in the adults and larvae between different mosquito species. However, the discovery of species complexes meant that genetic tools were needed to separate the sibling species and today there are standard molecular techniques that are used to identify the two major malaria vector groups of mosquitoes. On the assumption that species-diagnostic DNA polymerase chain reaction (PCR) assays are highly species-specific, experiments were conducted to investigate what would happen if non-vector species were randomly included in the molecular assays. Methods: Morphological keys for the Afrotropical Anophelinae were used to provide the a priori identifications. All mosquito specimens were then subjected to the standard PCR assays for members of the Anopheles gambiae complex and Anopheles funestus group. Results: One hundred and fifty mosquitoes belonging to 11 morphological species were processed. Three species (Anopheles pretoriensis, Anopheles rufipes and Anopheles rhodesiensis) amplified members of the An. funestus group and four species (An. pretoriensis, An. rufipes, Anopheles listeri and Anopheles squamosus) amplified members of the An. gambiae complex. Conclusions: Morphological identification of mosquitoes prior to PCR assays not only saves time and money in the laboratory, but also ensures that data received by malaria vector control programmes are useful for targeting the major vectors.
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    The shift to outcomes based frameworks: key problems from a critical perspective
    (The Federal Institute for Adult Education (bifeb), 2011) Michael, Young; Allais, Stephanie Matseleng
    This paper takes a step back from the discussions and debates about qualifications frameworks per se, to think more broadly about the role of „qualifications“ in educational reform. The aims of the paper are to locate the reform of qualifications in its broader social and institutional context, to propose a way of conceptualizing the change from qualification systems as they have emerged historically to qualifications frameworks andoutcomes-based qualifications and to explore the tensions involved in the different goals that the introduction of a (National) Qualifications Framework – (N)QF will achieve. We argue that what is at stake in current reforms is the role of educational institutions in the education and training of the next generation, the balance between institution-based education and informal (in some cases work-based) learning, and the ways in which trust in qualifications is established and maintained. Our two-model analysis explores the balance between an emphasis on institutions and outcomes. This paper was written to provoke debate, and help all involved in researching qualifications frameworks to think more clearly about the issues.
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    Predictors of switch to and early outcomes on third-line antiretroviral therapy at a large public-sector clinic in Johannesburg, South Africa
    (BMC, 2018) Evans, Denise; Hirasen, Kamban; Berhanu, Rebecca; Malete, Given; Ive, Prudence; Spencer, David; Badal‑Faesen, Sharlaa; Sanne, Ian M.; Fox, Matthew P.
    Background: While efficacy data exist, there are limited data on the outcomes of patients on third-line antiretroviral therapy (ART) in sub-Saharan Africa in actual practice. Being able to identify predictors of switch to third-line ART will be essential for planning for future need. We identify predictors of switch to third-line ART among patients with significant viraemia on a protease inhibitor (PI)-based second-line ART regimen. Additionally, we describe characteristics of all patients on third-line at a large public sector HIV clinic and present their early outcomes. Methods: Retrospective analysis of adults (≥ 18 years) on a PI-based second-line ART regimen at Themba Lethu Clinic, Johannesburg, South Africa as of 01 August 2012, when third-line treatment became available in South Africa, with significant viraemia on second-line ART (defined as at least one viral load ≥ 1000 copies/mL on second-line ART after 01 August 2012) to identify predictors of switch to third-line (determined by genotype resistance testing). Third line ART was defined as a regimen containing etravirine, raltegravir or ritonavir boosted darunavir, between August 2012 and January 2016. To assess predictors of switch to third-line ART we used Cox proportional hazards regression among those with significant viraemia on second-line ART after 01 August 2012. Then among all patients on third-line ART we describe viral load suppression, defined as a viral load < 400 copies/mL, after starting third-line ART. Results: Among 719 patients in care and on second-line ART as of August 2012 (with at least one viral load ≥ 1000 copies/mL after 01 August 2012), 36 (5.0% over a median time of 54 months) switched to third-line. Time on second-line therapy (≥ 96 vs. < 96 weeks) (adjusted Hazard Ratio (aHR): 2.53 95% CI 1.03–6.22) and never reaching virologic suppression while on second-line ART (aHR: 3.37 95% CI 1.47–7.73) were identified as predictors of switch. In a separate cohort of patients on third-line ART, 78.3% (47/60) and 83.3% (35/42) of those in care and with a viral load suppressed their viral load at 6 and 12 months, respectively. Conclusions: Our results show that the need for third-line is low (5%), but that patients’ who switch to third-line ART have good early treatment outcomes and are able to suppress their viral load. Adherence counselling and resistance testing should be prioritized for patients that are at risk of failure, in particular those who never suppress on second line and those who have been on PI-based regimen for extended periods.
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    Bone mineral density in midlife long-term users of hormonal contraception in South Africa: relationship with obesity and menopausal status
    (BMC, 2018-04) Beksinska, Mags E.; Smit, Jenni A.; Kleinschmidt, Immo
    Background: In South Africa, hormonal contraception is widely used in women over the age of 40 years. One of these methods and the most commonly used is depot-medroxyprogesterone acetate (DMPA) which has been found to have a negative effect on bone mass. Limited information is available on the effect of norethisterone enanthate (NET-EN) on bone mass, and combined oral contraceptives (COCs) have not been found to be associated with loss of bone mass. The aim of this study was to investigate bone mineral density (BMD) in pre and perimenopausal women (40–49 years) in relation to use of DMPA, NET-EN and COCs for at least 12 months preceding recruitment into the study and review associations with body mass index (BMI) and menopausal status. Methods: One hundred and twenty seven users of DMPA, 102 NET-EN users and 106 COC users were compared to 161 nonuser controls. Menopausal status was assessed, BMI and forearm BMD was measured at the distal radius using dual X-ray absorptiometry. Comparison analysis was conducted at baseline and 2.5 years. Results: There was no significant difference in BMD between the four contraceptive user groups (p = 0.26) with and without adjustment for age at baseline or at 2.5 years (p = 0.52). The BMD was found to be significantly associated with BMI (p = < 0.0001) with an increase of one unit of BMI translating to an increase of 0.0044 g/cm2 in radius BMD. Follicle stimulating hormone (FSH) level ≥ 25.8 mIU/mL was associated with a decrease of 0.017 g/cm2 in radius BMD relative to women with FSH < 25.8 mIU/mL. Significant interaction between FSH and BMI in their effect on BMD was observed (p = .006). Conclusion: This study found no evidence that long-term use of DMPA, NET-EN and COCs affects forearm BMD in this population at baseline or after 2.5 years of follow-up. This study also reports the complex relationship and significant interaction between FSH and BMI in their effect on BMD. BMD research in older women needs to ensure that women are assessed for menopausal status and BMI.
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    Temporal shifts in landscape connectivity for an ecosystem engineer, the roe deer, across a multiple-use landscape
    (Springer, 2018-04) Martin, Jodie; Vourc’h, Gwenae¨l; Bonnot, Nade`ge; Cargnelutti, Bruno; Chaval, Yannick; Lourte, Bruno; Goulard, Michel; Hoch, Thierry; Plantard, Olivier; Hewison, A. J. Mark; Morellet, Nicolas
    Context: Routine movements of large herbivores, often considered as ecosystem engineers, impact key ecological processes. Functional landscape connectivity for such species influences the spatial distribution of associated ecological services and disservices. Objectives: We studied how spatio-temporal variation in the risk-resource trade-off, generated by fluctuations in human activities and environmental conditions, influences the routine movements of roedeer across a heterogeneous landscape, generating shifts in functional connectivity at daily and seasonal time scales. Methods: We used GPS locations of 172 adult roedeer and step selection functions to infer landscape connectivity. In particular, we assessed the influence of six habitat features on fine scale movements across four biological seasons and three daily periods, based on variations in the risk-resource trade-off. Results: The influence of habitat features on roe deer movements was strongly dependent on proximity to refuge habitat, i.e. woodlands. Roe deer confined their movements to safe habitats during daytime and during the hunting season, when human activity is high.
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    Phase proportions, carbon equivalent, mechanical properties and their effect on material cost of railway axle steels
    (Springer, 2018-04) Klenam, D.E.P.; Chown, L.H.; Papo, M.J.; Cornish, L.A.
    Commuter trains with solid axle configuration are produced from medium carbon steel due to cost restrictions. High-speed trains have hollow axle configuration for reduced weight and are made from high strength low-alloy (HSLA) steels. The HSLA steels have higher amounts of C, Cr, Ni, Mo, V and Nb, and are more expensive than medium carbon steels. The effects of phase proportions, carbon equivalent (CE), yield strength and ultimate tensile strength (UTS) on material costs of existing railway axle steels were studied using Thermo-Calc. Medium carbon rail axle steels had higher Fe3C phase proportions than the HSLA steel rail axle grades. Higher affinity of Cr, Mo and V for C than Fe resulted in decreased cementite proportions. The HSLA steels had yield strengths above 370 MPa, and UTS above 750 MPa, with increased material cost above $3300 per ton. A scattered distribution was observed for the pearlite weight fraction and material costs, with most between $3200 and $3400. The yield and tensile strengths increased with increasing carbon equivalent and pearlite weight fraction. The data aided the selection and design of alloys with better mechanical and corrosion properties at reduced material cost.