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- Librado, P., et al.
(author)
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The origins and spread of domestic horses from the Western Eurasian steppes
- 2021
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 598, s. 634-640
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Journal article (peer-reviewed)abstract
- Analysis of 273 ancient horse genomes reveals that modern domestic horses originated in the Western Eurasian steppes, especially the lower Volga-Don region. Domestication of horses fundamentally transformed long-range mobility and warfare(1). However, modern domesticated breeds do not descend from the earliest domestic horse lineage associated with archaeological evidence of bridling, milking and corralling(2-4) at Botai, Central Asia around 3500 bc(3). Other longstanding candidate regions for horse domestication, such as Iberia(5) and Anatolia(6), have also recently been challenged. Thus, the genetic, geographic and temporal origins of modern domestic horses have remained unknown. Here we pinpoint the Western Eurasian steppes, especially the lower Volga-Don region, as the homeland of modern domestic horses. Furthermore, we map the population changes accompanying domestication from 273 ancient horse genomes. This reveals that modern domestic horses ultimately replaced almost all other local populations as they expanded rapidly across Eurasia from about 2000 bc, synchronously with equestrian material culture, including Sintashta spoke-wheeled chariots. We find that equestrianism involved strong selection for critical locomotor and behavioural adaptations at the GSDMC and ZFPM1 genes. Our results reject the commonly held association(7) between horseback riding and the massive expansion of Yamnaya steppe pastoralists into Europe around 3000 bc(8,9) driving the spread of Indo-European languages(10). This contrasts with the scenario in Asia where Indo-Iranian languages, chariots and horses spread together, following the early second millennium bc Sintashta culture(11,12).
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| 2. |
- Schiava, M., et al.
(author)
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Genotype-phenotype correlations in valosin-containing protein disease: a retrospective muticentre study
- 2022
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In: Journal of Neurology Neurosurgery and Psychiatry. - : BMJ. - 0022-3050 .- 1468-330X. ; 93:10, s. 1099-1111
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Journal article (peer-reviewed)abstract
- Background Valosin-containing protein (VCP) disease, caused by mutations in the VCP gene, results in myopathy, Paget's disease of bone (PBD) and frontotemporal dementia (FTD). Natural history and genotype-phenotype correlation data are limited. This study characterises patients with mutations in VCP gene and investigates genotype-phenotype correlations. Methods Descriptive retrospective international study collecting clinical and genetic data of patients with mutations in the VCP gene. Results Two hundred and fifty-five patients (70.0% males) were included in the study. Mean age was 56.8 +/- 9.6 years and mean age of onset 45.6 +/- 9.3 years. Mean diagnostic delay was 7.7 +/- 6 years. Symmetric lower limb weakness was reported in 50% at onset progressing to generalised muscle weakness. Other common symptoms were ventilatory insufficiency 40.3%, PDB 28.2%, dysautonomia 21.4% and FTD 14.3%. Fifty-seven genetic variants were identified, 18 of these no previously reported. c.464G>A (p.Arg155His) was the most frequent variant, identified in the 28%. Full time wheelchair users accounted for 19.1% with a median time from disease onset to been wheelchair user of 8.5 years. Variant c.463C>T (p.Arg155Cys) showed an earlier onset (37.8 +/- 7.6 year) and a higher frequency of axial and upper limb weakness, scapular winging and cognitive impairment. Forced vital capacity (FVC) below 50% was as risk factor for being full-time wheelchair user, while FVC Conclusion This study expands the knowledge on the phenotypic presentation, natural history, genotype-phenotype correlations and risk factors for disease progression of VCP disease and is useful to improve the care provided to patient with this complex disease.
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| 4. |
- Rohr, Julia K., et al.
(author)
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HIV treatment cascade for older adults in rural South Africa
- 2020
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In: Sexually Transmitted Infections. - : BMJ Publishing Group Ltd. - 1368-4973 .- 1472-3263. ; 96:4, s. 271-276
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Journal article (peer-reviewed)abstract
- Objectives: The HIV treatment cascade is a powerful framework for understanding progress from initial diagnosis to successful treatment. Data sources for cascades vary and often are based on clinical cohorts, population cohorts linked to clinics, or self-reported information. We use both biomarkers and self-reported data from a large population-based cohort of older South Africans to establish the first HIV cascade for this growing segment of the HIV-positive population and compare results using the different data sources.Methods: Data came from the Health and Aging in Africa: A Longitudinal Study of an INDEPTH Community in South Africa (HAALSI) 2015 baseline survey of 5059 adults aged 40+ years. Dried blood spots (DBS) were screened for HIV, antiretroviral drugs and viral load. In-home surveys asked about HIV testing, diagnosis and antiretroviral therapy (ART) use. We calculated proportions and CIs for each stage of the cascade, conditional on attainment of the previous stage, using (1) biomarkers, (2) self-report and (3) both biomarkers and self-report, and compared with UNAIDS 90-90-90 targets.Results: 4560 participants had DBS results, among whom 1048 (23%) screened HIV-positive and comprised the denominator for each cascade. The biomarker cascade showed 63% (95% CI 60 to 66) on ART and 72% (95% CI 69 to 76) of those on ART with viral suppression. Self-reports underestimated testing, diagnosis and ART, with only 47% (95% CI 44 to 50) of HIV-positive individuals reporting ART use. The combined cascade indicated high HIV testing (89% (95% CI 87 to 91)), but lower knowledge of HIV-positive status (71% (95% CI 68 to 74)).Conclusions: Older South Africans need repeated HIV testing and sustained ART to reach 90-90-90 targets. HIV cascades relying on self-reports are likely to underestimate true cascade attainment, and biomarkers provide substantial improvements to cascade estimates.
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| 5. |
- Stoner, Marie C. D., et al.
(author)
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Modeling Cash Plus Other Psychosocial and Structural Interventions to Prevent HIV Among Adolescent Girls and Young Women in South Africa (HPTN 068)
- 2021
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In: Aids and Behavior. - : Springer. - 1090-7165 .- 1573-3254. ; 25, s. 133-143
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Journal article (peer-reviewed)abstract
- Poverty alleviation programs can reduce HIV incidence but may have greater impacts when combined with other psychosocial interventions. We modeled the change in HIV incidence among South African adolescent girls and young women (AGYW) associated with combining a cash transfer (the South African Child Support Grant (CSG)) with other structural and behavioral interventions. We modeled observational data from the HPTN 068 study where 2328 HIV negative AGYW (13-20 years) were followed for 4 years. In a Monte Carlo simulation based on this cohort (N = 10,000), CSG receipt was not independently associated with HIV incidence. Providing the CSG combined with increasing caregiver care and reducing adolescent depression had the largest reduction in HIV incidence with the fewest number of combined interventions (RD - 3.0%; (95% CI - 5.1%, - 0.9%). Combining a monthly grant with interventions to increase caregiver care and reduce adolescent depression could substantially reduce HIV incidence above the provision of cash alone.
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