| 410291. |
- Kimani-Murage, E. W., et al.
(författare)
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"It's my secret" : Barriers to paediatric HIV treatment in a poor rural South African setting
- 2013
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Ingår i: AIDS Care. - : Informa UK Limited. - 0954-0121 .- 1360-0451. ; 25:6, s. 744-747
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Tidskriftsartikel (refereegranskat)abstract
- In South Africa, a third of children born are exposed to HIV, while fewer undergo an HIV confirmatory test. Anti-retroviral therapy (ART) coverage among children remains low-despite roll-out of the national ART programme in South Africa in 2004. This study sought to understand critical barriers to seeking HIV-related care for children in rural South Africa. Data presented in this article derive from community-based qualitative research in poor rural villages in north-east South Africa; this includes 21 in-depth interviews in 2008 among caregivers of children identified as HIV-positive in 2007 from a randomly selected community-based sample. Using NVIVO 8, data were coded and analysed, using a constant comparative method to identify themes and their repetitions and variations. Structural barriers leading to poor access to health care, and social and systems barriers, all influenced paediatric HIV treatment seeking. Of concern was the expressed need to maintain secrecy regarding a child's HIV status to avoid stigma and discrimination, and misconceptions regarding the course of HIV disease in children; this led to a delay in seeking appropriate care. These barriers need to be addressed, including through focused awareness campaigns, improved access to health care and interventions to address rural poverty and development at both household and community levels. In addition, training of health care professionals to improve their attitudes and practice may be necessary. However, this study only provides the perspective of the caregivers; further studies with health care providers are needed to gain a fuller picture for appropriate policy and practice guidance.
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| 410292. |
- Kimani-Murage, Elizabeth W., et al.
(författare)
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Nutritional status and HIV in rural South African children
- 2011
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Ingår i: BMC Pediatrics. - : Springer Science and Business Media LLC. - 1471-2431. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Background: Achieving the Millennium Development Goals that aim to reduce malnutrition and child mortality depends in part on the ability of governments/policymakers to address nutritional status of children in general and those infected or affected by HIV/AIDS in particular. This study describes HIV prevalence in children, patterns of malnutrition by HIV status and determinants of nutritional status.Methods: The study involved 671 children aged 12-59 months living in the Agincourt sub-district, rural South Africa in 2007. Anthropometric measurements were taken and HIV testing with disclosure was done using two rapid tests. Z-scores were generated using WHO 2006 standards as indicators of nutritional status. Linear and logistic regression analyses were conducted to establish the determinants of child nutritonal status.Results: Prevalence of malnutrition, particularly stunting (18%), was high in the overall sample of children. HIV prevalence in this age group was 4.4% (95% CI: 2.79 to 5.97). HIV positive children had significantly poorer nutritional outcomes than their HIV negative counterparts. Besides HIV status, other significant determinants of nutritional outcomes included age of the child, birth weight, maternal age, age of household head, and area of residence.Conclusions: This study documents poor nutritional status among children aged 12-59 months in rural South Africa. HIV is an independent modifiable risk factor for poor nutritional outcomes and makes a significant contribution to nutritional outcomes at the individual level. Early paediatric HIV testing of exposed or at risk children, followed by appropriate health care for infected children, may improve their nutritional status and survival.
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| 410293. |
- Kimani-Murage, Elizabeth W., et al.
(författare)
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Predictors of adolescent weight status and central obesity in rural South Africa
- 2011
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Ingår i: Public Health Nutrition. - 1368-9800 .- 1475-2727. ; 14:6, s. 1114-1122
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To investigate predictors of adolescent obesity in rural South Africa. Design: Cross-sectional study. Height, weight and waist circumference were measured using standard procedures. Overweight and obesity in adolescents aged 10-17 years were assessed using the International Obesity Taskforce cut-offs, while the WHO adult cut-offs were used for participants aged 18-20 years. Waist-to-height ratio of >0.5 defined central obesity in those at Tanner stages 3-5. Linear and logistic regression analysis was used to evaluate risk factors. Setting: Agincourt sub-district, rural South Africa. Subjects: Participants (n 1848) were aged 10-20 years. Results: Combined overweight and obesity was higher in girls (15%) than boys (4%), as was central obesity (15% and 2%, respectively). With regard to overweight/obesity, fourfold higher odds were observed for girls and twofold higher odds were observed for participants from households with the highest socio-economic status (SES). The odds for overweight/obesity were 40% lower if the household head had not completed secondary level education. For central obesity, the odds increased 10% for each unit increase in age; girls had sevenfold higher odds v. boys; postpubertal participants had threefold higher odds v. pubertal participants; those with older mothers aged 501 years had twofold higher odds v. those whose mothers were aged 35-49 years; those in highest SES households had twofold higher odds v. those in lowest SES households. Conclusions: In rural South Africa, adolescent females are most at risk of obesity which increases with age and appears to be associated with higher SES. To intervene effectively, it is essential to understand how household factors influence food choice, diet and exercise.
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| 410294. |
- Kimani-Murage, Elizabeth W, et al.
(författare)
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The prevalence of stunting, overweight and obesity, and metabolic disease risk in rural South African children
- 2010
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Ingår i: BMC Public Health. - : Springer Science and Business Media LLC. - 1471-2458. ; 10, s. 158-
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Tidskriftsartikel (refereegranskat)abstract
- The study highlights that in transitional societies, early stunting and adolescent obesity may co-exist in the same socio-geographic population. It is likely that this profile relates to changes in nutrition and diet, but variation in factors such as infectious disease burden and physical activity patterns, as well as social influences, need to be investigated. As obesity and adult short stature are risk factors for metabolic syndrome and Type 2 diabetes, this combination of early stunting and adolescent obesity may be an explosive combination.
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| 410295. |
- Kimani-Murage, Elizabeth W, et al.
(författare)
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'You opened our eyes' : care-giving after learning a child's positive HIV status in rural South Africa
- 2010
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Ingår i: Health & Social Care in the Community. - : Hindawi Limited. - 0966-0410 .- 1365-2524. ; 18:3, s. 264-271
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Tidskriftsartikel (refereegranskat)abstract
- Caregivers of young children identified as HIV positive, residing in Agincourt, rural South Africa were advised of their child's status. How was this knowledge received, and how did it influence care-giving and support? Interviews were conducted in May to June 2008 with caregivers of HIV positive children aged 1-5 years, 1 year following the child's HIV test and disclosure of status. Drawing on data from 31 semi-structured questionnaires and 21 in-depth interviews, we describe caregivers' attitudes, reactions, fears and aspirations after learning a child's HIV status, the perceived usefulness of the knowledge, barriers to care-giving and support received. Sociodemographic data collected through the questionnaire were analysed using Stata. Qualitative data were coded in NVIVO 8 and analysed inductively to identify themes and their repetitions and variations. Although almost half of the caregivers responded negatively initially, 1 year later, almost all had accepted and valued knowing their child's HIV status as this had enhanced their competency in care-giving. Counselling from health providers and personal spirituality helped caregivers to accept the child's status and cope with its implications. Most caregivers had high aspirations for the child's future, despite some expressed difficulties associated with care-giving, including financial constraints, information gaps and barriers to healthcare. The results indicate an opportunity for paediatric HIV screening in communities with high HIV prevalence. This would facilitate early uptake of available interventions, so enhancing the survival of HIV positive children.
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| 410296. |
- Kimani, N., et al.
(författare)
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Radio evolution of supernova SN 2008iz in M 82
- 2016
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 593
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Tidskriftsartikel (refereegranskat)abstract
- We report on multi-frequency Very Large Array (VLA) and Very Long Baseline Interferometry (VLBI) radio observations for a monitoring campaign of supernova SN 2008iz in the nearby irregular galaxy M 82. We fit two models to the data, a simple time power-law, S ât?, and a simplified Weiler model, yielding decline indices of ? =-1.22 ± 0.07 (days 100-1500) and-1.41 ± 0.02 (days 76-2167), respectively. The late-time radio light-curve evolution shows flux-density flares at ?970 and ?1400 days that are a factor of ?2 and ?4 higher than the expected flux, respectively. The later flare, except for being brighter, does not show signs of decline at least from results examined so far (2014 January 23; day 2167). We derive the spectral index, ?, S â?? for frequencies 1.4 to 43 GHz for SN 2008iz during the period from 430 to 2167 days after the supernova explosion. The value of ? shows no signs of evolution and remains steep â‰-1 throughout the period, unlike that of SN 1993J, which started flattening at day 970. From the 4.8 and 8.4 GHz VLBI images, the supernova expansion is seen to start with a shell-like structure that becomes increasingly more asymmetric, then breaks up in the later epochs, with bright structures dominating the southern part of the ring. This structural evolution differs significantly from SN 1993J, which remains circularly symmetric over 4000 days after the explosion. The VLBI 4.8 and 8.4 GHz images are used to derive a deceleration index, m, for SN 2008iz, of 0.86 ± 0.02, and the average expansion velocity between days 73 and 1400 as (12.1 ± 0.2) × 103 km s-1. From the energy equipartition between magnetic field and particles, we estimate the minimum total energy in relativistic particles and the magnetic fields during the supernova expansion and also find the magnetic field amplification factor for SN 2008iz to be in the range of 55-400.
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| 410297. |
- Kimanius, Dari, et al.
(författare)
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Accelerated cryo-EM structure determination with parallelisation using GPUs in RELION-2
- 2016
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Ingår i: eLIFE. - : eLife Sciences Publications, Ltd. - 2050-084X. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- By reaching near-atomic resolution for a wide range of specimens, single-particle cryo-EM structure determination is transforming structural biology. However, the necessary calculations come at large computational costs, which has introduced a bottleneck that is currently limiting throughput and the development of new methods. Here, we present an implementation of the RELION image processing software that uses graphics processors (GPUs) to address the most computationally intensive steps of its cryo-EM structure determination workflow. Both image classification and high-resolution refinement have been accelerated more than an order-of-magnitude, and template-based particle selection has been accelerated well over two orders-of-magnitude on desktop hardware. Memory requirements on GPUs have been reduced to fit widely available hardware, and we show that the use of single precision arithmetic does not adversely affect results. This enables high-resolution cryo-EM structure determination in a matter of days on a single workstation.
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| 410298. |
- Kimanius, Dari, et al.
(författare)
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Exploiting prior knowledge about biological macromolecules in cryo-EM structure determination
- 2021
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Ingår i: IUCrJ. - : International Union of Crystallography (IUCr). - 2052-2525. ; 8, s. 60-75
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Tidskriftsartikel (refereegranskat)abstract
- Three-dimensional reconstruction of the electron-scattering potential of biological macromolecules from electron cryo-microscopy (cryo-EM) projection images is an ill-posed problem. The most popular cryo-EM software solutions to date rely on a regularization approach that is based on the prior assumption that the scattering potential varies smoothly over three-dimensional space. Although this approach has been hugely successful in recent years, the amount of prior knowledge that it exploits compares unfavorably with the knowledge about biological structures that has been accumulated over decades of research in structural biology. Here, a regularization framework for cryo-EM structure determination is presented that exploits prior knowledge about biological structures through a convolutional neural network that is trained on known macromolecular structures. This neural network is inserted into the iterative cryo-EM structure-determination process through an approach that is inspired by regularization by denoising. It is shown that the new regularization approach yields better reconstructions than the current state of the art for simulated data, and options to extend this work for application to experimental cryo-EM data are discussed.
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| 410299. |
- Kimanius, Dari, et al.
(författare)
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SAXS-Guided Metadynamics
- 2015
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Ingår i: Journal of Chemical Theory and Computation. - : American Chemical Society (ACS). - 1549-9618 .- 1549-9626. ; 11:7, s. 3491-3498
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Tidskriftsartikel (refereegranskat)abstract
- The small-angle X-ray scattering (SAXS) methodology enables structural characterization of biological macromolecules in solution. However, because SAXS provides low-dimensional information, several potential structural configurations can reproduce the experimental scattering profile, which severely complicates the structural refinement process. Here, we present a bias-exchange metadynamics refinement protocol that incorporates SAXS data as collective variables and therefore tags all possible configurations with their corresponding free energies, which allows identification of a unique structural solution. The method has been implemented in PLUMED and combined with the GROMACS simulation package, and as a proof of principle, we explore the Trp-cage protein folding landscape.
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| 410300. |
- Kimanius, Dari, et al.
(författare)
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Uptake dynamics in the Lactose permease (LacY) membrane protein transporter
- 2018
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- The sugar transporter Lactose permease (LacY) of Escherichia coli has become a prototype to understand the underlying molecular details of membrane transport. Crystal structures have trapped the protein in sugar-bound states facing the periplasm, but with narrow openings unable to accommodate sugar. Therefore, the molecular details of sugar uptake remain elusive. In this work, we have used extended simulations and metadynamics sampling to explore a putative sugar-uptake pathway and associated free energy landscape. We found an entrance at helix-pair 2 and 11, which involved lipid head groups and residues Gln 241 and Gln 359. Furthermore, the protein displayed high flexibility on the periplasmic side of Phe 27, which is located at the narrowest section of the pathway. Interactions to Phe 27 enabled passage into the binding site, which was associated with a 24 +/- 4 kJ/mol binding free energy in excellent agreement with an independent binding free energy calculation and experimental data. Two free energy minima corresponding to the two possible binding poses of the lactose analog beta-D-galactopyranosyl-1-thio-beta-D-galactopyranoside (TDG) were aligned with the crystal structure-binding pocket. This work outlines the chemical environment of a putative periplasmic sugar pathway and paves way for understanding substrate affinity and specificity in LacY.
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