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- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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| 2. |
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| 3. |
- Lippman, Sheri A, et al.
(författare)
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A community mobilisation intervention to improve engagement in HIV testing, linkage to care, and retention in care in South Africa : a cluster-randomised controlled trial
- 2022
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Ingår i: The Lancet HIV. - : Elsevier. - 2405-4704 .- 2352-3018. ; 9:9, s. e617-e626
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Tidskriftsartikel (refereegranskat)abstract
- Background: Community mobilisation, engaging communities in a process to collectively enact change, could improve HIV testing and care engagement. In South Africa, current rates fall below those needed for epidemic control. We assessed whether community mobilisation increased HIV testing, linkage to care, and retention in care over time in intervention relative to control communities.Methods: We conducted a cluster-randomised controlled trial in villages in the Agincourt sub-district of the rural Mpumalanga Province in South Africa. 15 villages were randomly assigned to either a community mobilisation intervention engaging residents to address social barriers to HIV testing and treatment (intervention arm) or to a control arm using balanced randomisation. Villages were eligible if they had been fully enumerated in 2014, had not been included in previous mobilisation activities, and included over 500 permanent adult residents aged 18–49 years. Primary outcomes included quarterly rates of HIV testing, linkage to care, and retention in care documented from health facility records among residents of the intervention and control communities over the 3-year study period. Intention-to-treat analyses employed generalised estimating equations stratified by sex. This trial is registered with ClinicalTrials.gov, NCT02197793.Findings: Between Aug 1, 2015, and July 31, 2018, residents in eight intervention communities (n=20 544 residents) and seven control communities (n=17 848) contributed data; 92 residents contributed to both arms. Among men, HIV testing increased quarterly by 12·1% (relative change [RC] 1·121, 95% CI 1·099 to 1·143, p<0·0001) in the intervention communities and 9·5% (1·095, 1·075 to 1·114, p=0·011) in the control communities; although increases in testing were greater in the intervention villages, differences did not reach significance (exponentiated interaction coefficient 1·024, 95% CI 0·997 to 1·052, p=0·078). Among women, HIV testing increased quarterly by 10·6% (RC 1·106, 95% CI 1·097 to 1·114, p<0·0001) in the intervention communities and 9·3% (1·093, 1·084 to 1·102, p=0·053) in the control communities; increases were greater in intervention communities (exponentiated interaction coefficient 1·012, 95% CI 1·001 to 1·023, p=0·043). Quarterly linkage increased significantly among women in the intervention communities (RC 1·013, 95% CI 1·002 to 1·023, p=0·018) only. Quarterly linkage fell among men in both arms, but decreased significantly among men in the control communities (0·977, 0·954 to 1·002, p=0·043). Quarterly retention fell among women in both arms; however, reductions were tempered among women in the intervention communities (exponentiated interaction coefficient 1·003, 95% CI <1·000 to 1·006, p=0·062). Retention fell significantly among men in both arms with difference in rates of decline.Interpretation: Community mobilisation was associated with modest improvements in select trial outcomes. The sum of these incremental, quarterly improvements achieved by addressing social barriers to HIV care engagement can impact epidemic control. However, achieving optimal impacts will probably require integrated efforts addressing both social barriers through community mobilisation and provision of improved service delivery.
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| 4. |
- Lippman, Sheri A., et al.
(författare)
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Evaluation of the Tsima community mobilization intervention to improve engagement in HIV testing and care in South Africa : study protocol for a cluster randomized trial
- 2017
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Ingår i: Implementation Science. - : BIOMED CENTRAL LTD. - 1748-5908. ; 12:9
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Tidskriftsartikel (refereegranskat)abstract
- Background: HIV transmission can be decreased substantially by reducing the burden of undiagnosed HIV infection and expanding early and consistent use of antiretroviral therapy (ART). Treatment as prevention (TasP) has been proposed as key to ending the HIV epidemic. To activate TasP in high prevalence countries, like South Africa, communities must be motivated to know their status, engage in care, and remain in care. Community mobilization (CM) has the potential to significantly increase uptake testing, linkage to and retention in care by addressing the primary social barriers to engagement with HIV care-including poor understanding of HIV care; fear and stigma associated with infection, clinic attendance and disclosure; lack of social support; and gender norms that deter men from accessing care. Methods/design: Using a cluster randomized trial design, we are implementing a 3-year-theory-based CM intervention and comparing gains in HIV testing, linkage, and retention in care among individuals residing in 8 intervention communities to that of individuals residing in 7 control communities. Eligible communities include 15 villages within a health and demographic surveillance site (HDSS) in rural Mpumalanga, South Africa, that were not exposed to previous CM efforts. CM activities conducted in the 8 intervention villages map onto six mobilization domains that comprise the key components for community mobilization around HIV prevention. To evaluate the intervention, we will link a clinic-based electronic clinical tracking system in all area clinics to the HDSS longitudinal census data, thus creating an open, population-based cohort with over 30,000 18-49-year-old residents. We will estimate the marginal effect of the intervention on individual outcomes using generalized estimating equations. In addition, we will evaluate CM processes by conducting baseline and endline surveys among a random sample of 1200 community residents at each time point to monitor intervention exposure and community level change using validated measures of CM. Discussion: Given the known importance of community social factors with regard to uptake of testing and HIV care, and the lack of rigorously evaluated community-level interventions effective in improving testing uptake, linkage and retention, the proposed study will yield much needed data to understand the potential of CM to improve the prevention and care cascade. Further, our work in developing a CM framework and domain measures will permit validation of a CM conceptual framework and process, which should prove valuable for community programming in Africa.
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| 5. |
- MacPhail, Catherine, et al.
(författare)
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Cash transfers for HIV prevention : what do young women spend it on? Mixed methods findings from HPTN 068
- 2017
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Ingår i: BMC Public Health. - : BioMed Central (BMC). - 1471-2458. ; 18:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Social grants have been found to have an impact on health and wellbeing in multiple settings. Who receives the grant, however, has been the subject of discussion with regards to how the money is spent and who benefits from the grant.Methods: Using survey data from 1214 young women who were in the intervention arm and completed at least one annual visit in the HPTN 068 trial, and qualitative interview data from a subset of 38 participants, we examined spending of a cash transfer provided to young women conditioned on school attendance.Results: We found that spending was largely determined and controlled by young women themselves and that the cash transfer was predominately spent on toiletries, clothing and school supplies. In interview data, young women discussed the significant role of cash transfers for adolescent identity, specifically with regard to independence from family and status within the peer network. There were almost no negative consequences from receiving the cash transfer.Conclusions: We established that providing adolescents access to cash was not reported to be associated with social harms or negative consequences. Rather, spending of the cash facilitated appropriate adolescent developmental behaviours. The findings are encouraging at a time in which there is global interest in addressing the structural drivers of HIV risk, such as poverty, for young women.
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| 6. |
- Stoner, Marie C. D., et al.
(författare)
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Does Partner Selection Mediate the Relationship Between School Attendance and HIV/Herpes Simplex Virus-2 Among Adolescent Girls and Young Women in South Africa : An Analysis of HIV Prevention Trials Network 068 Data
- 2018
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Ingår i: Journal of Acquired Immune Deficiency Syndromes. - : Lippincott Williams & Wilkins. - 1525-4135 .- 1944-7884. ; 79:1, s. 20-27
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Tidskriftsartikel (refereegranskat)abstract
- Objective: School attendance prevents HIV and herpes simplex virus-2 (HSV-2) in adolescent girls and young women, but the mechanisms to explain this relationship remain unclear. Our study assesses the extent to which characteristics of sex partners, partner age, and number mediate the relationship between attendance and risk of infection in adolescent girls and young women in South Africa.Design: We use longitudinal data from the HIV Prevention Trials Network 068 randomized controlled trial in rural South Africa, where girls were enrolled in early adolescence and followed in the main trial for more than 3 years. We examined older partners and the number of partners as possible mediators.Methods: We used the parametric g-formula to estimate 4-year risk differences for the effect of school attendance on the cumulative incidence of HIV/HSV-2 overall and the controlled direct effect (CDE) for mediation. We examined mediation separately and jointly for the mediators of interest.Results: We found that young women with high attendance in school had a lower cumulative incidence of HIV compared with those with low attendance (risk difference = -1.6%). Partner age difference (CDE = -1.2%) and the number of partners (CDE = -0.4%) mediated a large portion of this effect. In fact, when we accounted for the mediators jointly, the effect of schooling on HIV was almost removed, showing full mediation (CDE = -0.3%). The same patterns were observed for the relationship between school attendance and cumulative incidence of HSV-2 infection.Conclusion: Increasing school attendance reduces the risk of acquiring HIV and HSV-2. Our results indicate the importance of school attendance in reducing partner number and partner age difference in this relationship.
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| 7. |
- Stoner, Marie C. D., et al.
(författare)
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Effect of schooling on age-disparate relationships and number of sexual partners among young women in rural South Africa enrolled in HPTN 068
- 2017
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Ingår i: Journal of Acquired Immune Deficiency Syndromes. - : Wolters Kluwer Health. - 1525-4135 .- 1944-7884. ; 76:5, s. E107-E114
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Tidskriftsartikel (refereegranskat)abstract
- Background: Attending school may have a strong preventative association with sexually transmitted infections among young women, but the mechanism for this relationship is unknown. One hypothesis is that students who attend school practice safer sex with fewer partners, establishing safer sexual networks that make them less exposed to infection.Setting: We used longitudinal data from a randomized controlled trial of young women aged 13-20 years in the Bushbuckridge district, South Africa, to determine whether the percentage of school days attended, school dropout, and grade repetition are associated with having a partner 5 or more years older (age-disparate) and with the number of sexual partners in the previous 12 months.Methods: Risks of having an age-disparate relationship and number of sexual partners were compared using inverse probability of exposure weighted Poisson regression models. Generalized estimating equations were used to account for repeated measures.Results: Young women who attended fewer school days (<80%) and who dropped out of school were more likely to have an age-disparate relationship (risk difference 9.9%, 95% confidence interval [CI]: 3.9% to 16.0%; risk difference (%) dropout 17.2%, 95% CI: 5.4% to 29.0%) and those who dropped out reported having fewer partners (count difference dropout 0.343, 95% CI: 0.192 to 0.495). Grade repetition was not associated with either behavior.Conclusion: Young women who less frequently attend school or who drop out are more likely to have an age-disparate relationship. Young women who drop out have overall more partners. These behaviors may increase the risk of exposure to HIV infection in young women out of school.
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| 8. |
- Stoner, Marie C. D., et al.
(författare)
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The effect of school attendance and school dropout on incident HIV and HSV-2 among young women in rural South Africa enrolled in HPTN 068
- 2017
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Ingår i: AIDS. - : LIPPINCOTT WILLIAMS & WILKINS. - 0269-9370 .- 1473-5571. ; 31:15, s. 2127-2134
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To estimate the association between school attendance, school dropout, and risk of incident HIV and herpes simplex virus type 2 (HSV-2) infection among young women.Design: We used longitudinal data from a randomized controlled trial in rural Mpumalanga province, South Africa, to assess the association between school days attended, school dropout, and incident HIV and HSV-2 in young women aged 13-23 years.Methods: We examined inverse probability of exposure weighted survival curves and used them to calculate 1.5, 2.5, and 3.5-year risk differences and risk ratios for the effect of school attendance on incident HIV and HSV-2. A marginal structural Cox model was used to estimate hazard ratios for the effect of school attendance and school dropout on incident infection.Results: Risk of infection increased over time as young women aged, and was higher in young women with low school attendance (<80% school days) compared with high (>= 80% school days). Young women with low attendance were more likely to acquire HIV [hazard ratio (HR): 2.97; 95% confidence interval (CI): 1.62, 5.45] and HSV-2 (HR: 2.47; 95% CI: 1.46, 4.17) over the follow-up period than young women with high attendance. Similarly, young women who dropped out of school had a higher weighted hazard of both HIV (HR 3.25 95% CI: 1.67, 6.32) and HSV-2 (HR 2.70; 95% CI 1.59, 4.59).Conclusion: Young women who attend more school days and stay in school have a lower risk of incident HIV and HSV-2 infection. Interventions to increase frequency of school attendance and prevent dropout should be promoted to reduce risk of infection.
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