355 research outputs found

    Chromatin Higher Order Structure and Regulation of its Compaction

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    "Not Taking it Will Just be Like a Sin": Young People Living with HIV and the Stigmatization of Less-Than-Perfect Adherence to Antiretroviral Therapy.

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    Global health priorities are being set to address questions on adherence to HIV antiretroviral therapy in adolescence. Few studies have explored young people's perspectives on the complex host of social and relational challenges they face in dealing with their treatment in secret and their condition in silence. In redressing this, we present findings from a longitudinal qualitative study with young people living with HIV in the UK, Ireland, US, and Uganda, embedded within the BREATHER international clinical trial. Drawing from Goffman's notion of stigma, we analyze relational dynamics in HIV clinics, as rare spaces where HIV is "known," and how young people's relationships may be threatened by non-adherence to treatment. Young people's reflections on and strategies for maintaining their reputation as patients raise questions about particular forms of medicalization of HIV and the moralization of treatment adherence that affect them, and how these may restrict opportunities for care across the epidemic

    Response Type and Host Species may be Sufficient to Predict Dose-Response Curve Shape for Adenoviral Vector Vaccines.

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    Vaccine dose-response curves can follow both saturating and peaking shapes. Dose-response curves for adenoviral vector vaccines have not been systematically described. In this paper, we explore the dose-response shape of published adenoviral animal and human studies. Where data were informative, dose-response was approximately five times more likely to be peaking than saturating. There was evidence that host species and response type may be sufficient for prediction of dose-response curve shape. Dose-response curve shape prediction could decrease clinical trial costs, accelerating the development of life-saving vaccines

    Immunologic Dose-Response to Adenovirus-Vectored Vaccines in Animals and Humans: A Systematic Review of Dose-Response Studies of Replication Incompetent Adenoviral Vaccine Vectors when Given via an Intramuscular or Subcutaneous Route.

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    Optimal vaccine dosing is important to ensure the greatest protection and safety. Analysis of dose-response data, from previous studies, may inform future studies to determine the optimal dose. Implementing more quantitative modelling approaches in vaccine dose finding have been recently suggested to accelerate vaccine development. Adenoviral vectored vaccines are in advanced stage of development for a variety of prophylactic and therapeutic indications, however dose-response has not yet been systematically determined. To further inform adenoviral vectored vaccines dose identification, historical dose-response data should be systematically reviewed. A systematic literature review was conducted to collate and describe the available dose-response studies for adenovirus vectored vaccines. Of 2787 papers identified by Medline search strategy, 35 were found to conform to pre-defined criteria. The majority of studies were in mice or humans and studied adenovirus serotype 5. Dose-response data were available for 12 different immunological responses. The majority of papers evaluated three dose levels, only two evaluated more than five dose levels. The most common dosing range was 107-1010 viral particles in mouse studies and 108-1011 viral particles in human studies. Data were available on adenovirus vaccine dose-response, primarily on adenovirus serotype 5 backbones and in mice and humans. These data could be used for quantitative adenoviral vectored vaccine dose optimisation analysis

    Paleoclimatic and paleoenvironmental reconstructions based on the small vertebrates from the Middle Paleolithic of Hohle Fels Cave, SW Germany

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    In this paper, we analyse the fish and small mammal assemblages from the Middle Paleolithic horizons of Hohle Fels Cave to reconstruct the paleoclimatic and paleoenvironmental conditions faced by the Neanderthal groups who occupied the site. The fish assemblage indicates that the freshwater ecosystem around this site was characterized by a pre-mountain river system with the presence of permanent, oxygen-rich, and cold running waters. The results of the Habitat Weighting Method and the Bioclimatic Model applied to the small mammal assemblage, coupled with the new dates obtained for the Archaeological Horizon (AH) IX, allow us to identify two different climatic phases. One phase (AH X-XII) is more temperate possibly corresponding to the end of Marine Isotope Stage (MIS) 5; the other (AH VI-IX) is colder and more arid corresponding to the end of MIS 4 through the beginning of MIS 3. Open environments with a relatively stable forest component dominated the landscape during this part of the Middle Paleolithic. These two climatic phases appear to correspond to different levels of occupational intensity by Neanderthals, with higher occupational intensity during mild climatic periods and lower intensity during cold, arid periods. Our climatic reconstruction and recent absolute dating, together with the recovery of a complete leaf point near the top of AH X, have important implications for the cultural stratigraphy and cultural chronology of the region. Archaeologist have traditionally viewed leaf points as key artefacts of the Blattspitzengruppe, a cultural complex attributed to the end of Middle Paleolithic; however, this stratigraphic, climatic, and chronological context indicates the need to revise this interpretation.info:eu-repo/semantics/publishedVersio

    DIY HIV prevention: Formative qualitative research with men who have sex with men who source PrEP outside of clinical trials.

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    Pre-exposure prophylaxis (PrEP) with antiretroviral medication is an effective, evidence-based option for HIV prevention. In England, issues of cost-effectiveness and of responsibility for commissioning prevention services have so far led National Health Service (NHS) England to decide not to commission PrEP. Given the significant lag between the awareness of PrEP efficacy and the opportunity to obtain PrEP through traditional health care routes, many gay and other men who have sex with men (MSM) have turned to 'DIY PrEP', purchasing generic formulations of PrEP for themselves on the internet or via other alternative routes. However, there is very little research on DIY PrEP practices and no qualitative study with DIY PrEP users in the UK. A formative qualitative study was conducted in 2017 to inform the development of an intervention (PrEP Club) to support DIY PrEP users and improve the safety and experience of this prevention strategy. Focus groups were held with 20 MSM who are based in London and are obtaining PrEP through means other than clinical trials, to explore their accounts of sourcing and using PrEP and the experiential meanings of these. In this article, we report findings from this first, formative study and present the different practices involved in finding out about PrEP, buying it and ascertaining legitimacy of sellers and products. We reflect on the uncertainties participants described related to actually using PrEP, including deciding on drug dosing and monitoring their health. Finally, we present the results of the discussions participants had about the kind of support they had received, the help they would have liked, and their views on proposed interventions to support DIY PrEP users, such as PrEP Club

    Qualitative study of the BREATHER trial (Short Cycle antiretroviral therapy): is it acceptable to young people living with HIV?

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    OBJECTIVES: A qualitative study of the BREATHER (PENTA 16) randomised clinical trial, which compared virological control of Short Cycle Therapy (SCT) (5 days on: 2 days off) with continuous efavirenz (EFV)-based antiretroviral therapy (CT) in children and young people (aged 8-24) living with HIV with viral load <50 c/mL to examine adaptation, acceptability and experience of SCT to inform intervention development. SETTING: Paediatric HIV clinics in the UK (2), Ireland (1), the USA (1) and Uganda (1). PARTICIPANTS: All BREATHER trial participants who were over the age of 10 and aware of their HIV diagnosis were invited to participate. 49 young people from both arms of the BREATHER trial (31 females and 18 males; 40% of the total trial population in the respective sites; age range 11-24) gave additional consent to participate in the qualitative study. RESULTS: Young people from both trial arms had initial concerns about the impact of SCT on their health and adherence, but these decreased over the early months in the trial. Young people randomised to SCT reported preference for SCT compared with CT pre-trial. Attitudes to SCT did not vary greatly by gender or country. Once short-term adaptation challenges were overcome, SCT was positively described as reducing impact of side effects, easing the pressure to carry and remember medication and enabling more weekend social activities. Young people on both arms reported frequent medication side effects and occasional missed doses that they had rarely voiced to clinical staff. Participants liked SCT by trial end but were concerned that peers who had most problems adhering could find SCT disruptive and difficult to manage. CONCLUSIONS: To realise the potential of SCT (and mitigate possible risks of longer interruptions), careful dissemination and communication post-trial is needed. SCT should be provided alongside a package of monitoring, support and education over 3 months to allow adaptation. TRIAL REGISTRATION NUMBER: NCT 01641016

    Evaluation of a cognitive affective model of physical activity behavior

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    © 2020 The Author(s). Background: To empirically evaluate a cognitive affective model of physical activity. This bidirectional, cyclical model hypotheses that executive control processes directly influence habitual engagement in exercise and also directly subserve the exercise-induced affective response to acute exercise associated with future physical activity. Methods: The present study employed a one-week prospective, multi-site design. Participant recruitment and data collection occurred at two separate University sites (one in the United States and the other in Canada). Participants completed a bout of treadmill exercise, with affect and arousal assessed before, during and after the bout of exercise. Subjective and objective measures of executive function were assessed during this visit. Following this laboratory visit, seven days of accelerometry were employed to measure habitual engagement in physical activity. Results: Within our inactive, young adult sample, we observed some evidence of 1) aspects of executive function were associated with more light-intensity physical activity in the future (1-week later) (r = 0.36, 95% CI = -0.03 to 0.66, P = 0.07), 2) aspects of executive function were associated with post-exercise affect (r = -0.39, 95% CI = -0.67 to -0.03, P = 0.03) and forecasted affect (r = 0.47, 95% CI = 0.11 to 0.72, P = 0.01), and 3) aspects of acute exercise arousal and affect were associated with current mild-intensity physical activity behavior (r = 0.41, 95% CI = 0.04 to 0.68, P = 0.03). Conclusion: We demonstrate partial support of a cognitive-affective model of physical activity

    Assessing the permeability of landscape features to animal movement: Using genetic structure to infer functional connectivity

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    Human-altered environments often challenge native species with a complex spatial distribution of resources. Hostile landscape features can inhibit animal movement (i.e., genetic exchange), while other landscape attributes facilitate gene flow. The genetic attributes of organisms inhabiting such complex environments can reveal the legacy of their movements through the landscape. Thus, by evaluating landscape attributes within the context of genetic connectivity of organisms within the landscape, we can elucidate how a species has coped with the enhanced complexity of human altered environments. In this research, we utilized genetic data from eastern chipmunks (Tamias striatus ) in conjunction with spatially explicit habitat attribute data to evaluate the realized permeability of various landscape elements in a fragmented agricultural ecosystem. To accomplish this we 1) used logistic regression to evaluate whether land cover attributes were most often associated with the matrix between or habitat within genetically identified populations across the landscape, and 2) utilized spatially explicit habitat attribute data to predict genetically-derived Bayesian probabilities of population membership of individual chipmunks in an agricultural ecosystem. Consistency between the results of the two approaches with regard to facilitators and inhibitors of gene flow in the landscape indicate that this is a promising new way to utilize both landscape and genetic data to gain a deeper understanding of human-altered ecosystems. © 2015 Anderson et al
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