Experiences with HPTN 067/ADAPT Study-Provided Open-Label PrEP Among Women in Cape Town: Facilitators and Barriers Within a Mutuality Framework.

Placebo-controlled trials of pre-exposure prophylaxis (PrEP) have reported challenges with study-product uptake and use, with the greatest challenges reported in studies with young women in sub-Saharan Africa. We conducted a qualitative sub-study to explore experiences with open-label PrEP among young women in Cape Town, South Africa participating in HTPN 067/Alternative Dosing to Augment Pre-Exposure Prophylaxis Pill Taking (ADAPT). HPTN 067/ADAPT provided open label oral FTC/TDF PrEP to young women in Cape Town, South Africa who were randomized to daily and non-daily PrEP regimens. Following completion of study participation, women were invited into a qualitative sub-study including focus groups and in-depth interviews. Interviews and groups followed a semi-structured guide, were recorded, transcribed, and translated to English from isiXhosa, and coded using framework analysis. Sixty of the 179 women enrolled in HPTN 067/ADAPT participated in either a focus group (six groups for a total of 42 participants) or an in-depth interview (n = 18). This sample of mostly young, unmarried women identified facilitators of and barriers to PrEP use, as well as factors influencing study participation. Cross-cutting themes characterizing discourse suggested that women placed high value on contributing to the well-being of one's community (Ubuntu), experienced a degree of skepticism towards PrEP and the study more generally, and reported a wide range of approaches towards PrEP (ranging from active avoidance to high levels of persistence and adherence). A Mutuality Framework is proposed that identifies four dynamics (distrust, uncertainty, alignment, and mutuality) that represent distinct interactions between self, community and study and serve to contextualize women's experiences. Implications for better understanding PrEP use, and non-use, and intervention opportunities are discussed. In this sample of women, PrEP use in the context of an open-label research trial was heavily influenced by underlying beliefs about safety, reciprocity of contributions to community, and trust in transparency and integrity of the research. Greater attention to factors positioning women in the different dynamics of the proposed Mutuality Framework could direct intervention approaches in clinical trials, as well as open-label PrEP scale-up

Bewegung/en: Tagungsbericht zur Jahrestagung der Fachgesellschaft Geschlechterstudien vom 13. bis 14. Februar 2015 an der Universität Bielefeld

Vom 13. bis 14. Februar 2015 fand die fünfte Jahrestagung der Fachgesellschaft Geschlechterstudien/ Gender Studies Association unter dem Titel "Bewegung/en" statt. In anregenden Vorträgen und Diskussionen zeigten sich unterschiedlichste Herangehensweisen, die sich gut miteinander ergänzten und einen facettenreichen Blick auf das Thema "Bewegung/en" ermöglichten. Deutlich wurde, dass der Begriff "Bewegung/en" das Potenzial hat, sowohl den Gegenstand - die Bewegung/en - als auch das (forschende) Bewegen an sich in den wissenschaftlichen Fokus zu rücken.“Movement/s”. Annual Conference of the Gender Studies Association, University of Bielefeld, 13/14 February 2015 The 5th Annual Conference of the Gender Studies Association entitled “Movement/s”, which was held in Bielefeld in February 2015, provided plenty of opportunity for thoughtprovoking lectures and interesting discussions. Diverse perspectives and methodological approaches came to the fore and complemented each other, thereby revealing the many facets of the theme of “movement/s”. It became clear that the term “movement/s” has the potential to both put the focus on the object of research – (social) movements – and on the moves we make when doing scientific research

Cognitive Behavioural Therapy and Acceptance and Commitment Therapy as management strategies for chronic pain

Background: Chronic pain is a debilitating condition that affects the individual in complex ways. However, it is a subjective experience that can be unresponsive to medical treatment, requiring psychological interventions to address its complex and multidimensional nature. CBT and ACT are recommended, yet there is a need to further our understanding on how these management strategies are effective. The present review aims to improve our understanding of the role of CBT and ACT in the management of chronic pain. Method: A literature search was conducted using PsycInfo, Medline, and CINAHL complete, followed by a narrative synthesis and critical appraisal. Findings: CBT and ACT have beneficial effects across several domains of chronic pain, but methodological issues limit our understanding of how this is achieved. Discussion: Future research should focus more on how CBT and ACT lead to positive changes for people with chronic pain. Specifically, there is a need for more detailed explanations of how the interventions are designed. Also, a wider consideration of individual preferences (treatment goals and preferred outcomes) as a desired outcome, and the impact of therapist and group effects

High prevalence of self-reported undiagnosed HIV despite high coverage of HIV testing : a cross-sectional population based sero-survey in South Africa

CITATION: Kranzer, K. et al. 2011. High prevalence of self-reported undiagnosed HIV despite high coverage of HIV testing : a cross-sectional population based sero-survey in South Africa. PLoS ONE, 6(9): e25244, doi:10.1371/journal.pone.0025244.The original publication is available at http://journals.plos.org/plosoneObjectives To measure HIV prevalence and uptake of HIV counseling and testing (HCT) in a peri-urban South African community. To assess predictors for previous HIV testing and the association between the yield of previously undiagnosed HIV and time of last negative HIV test Methods A random sample of 10% of the adult population (≥15 years) were invited to attend a mobile HCT service. Study procedures included a questionnaire, HIV testing and CD4 counts. Predictors for previous testing were determined using a binominal model. Results 1,144 (88.0%) of 1,300 randomly selected individuals participated in the study. 71.0% (68.3–73.6) had previously had an HIV test and 37.5% (34.6–40.5) had tested in the past 12 months. Men, migrants and older (>35 years) and younger (<20 years) individuals were less likely to have had a previous HIV test. Overall HIV prevalence was 22.7 (20.3–25.3) with peak prevalence of 41.8% (35.8–47.8) in women aged 25.1–35 years and 37.5% (26.7–48.3) in men aged 25.1–45 years. Prevalence of previously undiagnosed HIV was 10.3% (8.5–12.1) overall and 4.5% (2.3–6.6), 8.0% (CI 3.9–12.0) and 20.0% (13.2–26.8) in individuals who had their most recent HIV test within 1, 1–2 and more than 2 years prior to the survey. Conclusion The high burden of undiagnosed HIV in individuals who had recently tested underscores the importance of frequent repeat testing at least annually. The high prevalence of previously undiagnosed HIV in individuals reporting a negative test in the 12 months preceding the survey indicates a very high incidence. Innovative prevention strategies are needed.http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0025244Publisher's versio

Uptake of genital mucosal sampling in HVTN 097, a phase 1b HIV vaccine trial in South Africa

Because sexual transmission of HIV occurs across mucosal membranes, understanding the immune responses of the genital mucosa to vaccines may contribute knowledge to finding an effective candidate HIV vaccine. We describe the uptake of rectal secretion, cervical secretion and seminal mucosal secretion sampling amongst volunteers in a Phase 1b HIV vaccine trial. Age at screening, gender, study site and the designation of the person conducting the informed consent procedure were collected for volunteers who screened for the HVTN 097 study. A total of 211 volunteers (54% female) were screened at three sites in South Africa: Soweto (n = 70, 33%), Cape Town (n = 68, 32%) and Klerksdorp (n = 73, 35%). Overall uptake of optional mucosal sampling amongst trial volunteers was 71% (n = 149). Compared to Cape Town, volunteers from Soweto and Klerksdorp were less likely to consent to sampling (Soweto OR 0.08 CI: 0.03-0.25 p<0.001 and Klerksdorp OR 0.13 CI: 0.04-0.41 p = 0.001). In contrast, volunteers over 25 years of age were 2.39 times more likely to consent than younger volunteers (CI: 1.13-5.08, p = 0.02). Further studies are required to better understand the cultural, demographic and sociobehavioral factors which influence willingness to participate in mucosal sampling in HIV prevention studies. Trial Registration ClinicalTrials.gov: NCT0210935

Demographic, clinical, biomarker, and neuropathological correlates of posterior cortical atrophy: an international cohort study and individual participant data meta-analysis

Background Posterior cortical atrophy is a rare syndrome characterised by early, prominent, and progressive impairment in visuoperceptual and visuospatial processing. The disorder has been associated with underlying neuropathological features of Alzheimer\u27s disease, but large-scale biomarker and neuropathological studies are scarce. We aimed to describe demographic, clinical, biomarker, and neuropathological correlates of posterior cortical atrophy in a large international cohort. Methods We searched PubMed between database inception and Aug 1, 2021, for all published research studies on posterior cortical atrophy and related terms. We identified research centres from these studies and requested deidentified, individual participant data (published and unpublished) that had been obtained at the first diagnostic visit from the corresponding authors of the studies or heads of the research centres. Inclusion criteria were a clinical diagnosis of posterior cortical atrophy as defined by the local centre and availability of Alzheimer\u27s disease biomarkers (PET or CSF), or a diagnosis made at autopsy. Not all individuals with posterior cortical atrophy fulfilled consensus criteria, being diagnosed using centre-specific procedures or before development of consensus criteria. We obtained demographic, clinical, biofluid, neuroimaging, and neuropathological data. Mean values for continuous variables were combined using the inverse variance meta-analysis method; only research centres with more than one participant for a variable were included. Pooled proportions were calculated for binary variables using a restricted maximum likelihood model. Heterogeneity was quantified using I2. Findings We identified 55 research centres from 1353 papers, with 29 centres responding to our request. An additional seven centres were recruited by advertising via the Alzheimer\u27s Association. We obtained data for 1092 individuals who were evaluated at 36 research centres in 16 countries, the other sites having not responded to our initial invitation to participate to the study. Mean age at symptom onset was 59·4 years (95% CI 58·9–59·8; I2=77%), 60% (56–64; I2=35%) were women, and 80% (72–89; I2=98%) presented with posterior cortical atrophy pure syndrome. Amyloid β in CSF (536 participants from 28 centres) was positive in 81% (95% CI 75–87; I2=78%), whereas phosphorylated tau in CSF (503 participants from 29 centres) was positive in 65% (56–75; I2=87%). Amyloid-PET (299 participants from 24 centres) was positive in 94% (95% CI 90–97; I2=15%), whereas tau-PET (170 participants from 13 centres) was positive in 97% (93–100; I2=12%). At autopsy (145 participants from 13 centres), the most frequent neuropathological diagnosis was Alzheimer\u27s disease (94%, 95% CI 90–97; I2=0%), with common co-pathologies of cerebral amyloid angiopathy (71%, 54–88; I2=89%), Lewy body disease (44%, 25–62; I2=77%), and cerebrovascular injury (42%, 24–60; I2=88%). Interpretation These data indicate that posterior cortical atrophy typically presents as a pure, young-onset dementia syndrome that is highly specific for underlying Alzheimer\u27s disease pathology. Further work is needed to understand what drives cognitive vulnerability and progression rates by investigating the contribution of sex, genetics, premorbid cognitive strengths and weaknesses, and brain network integrity

Nerve biopsy in T-cell lymphoma with neurolymphomatosis: where and when

Peripheral T-cell lymphomas are rare heterogeneous haematological malignancies that may also involve peripheral nerves in a very small subset of cases. We report a patient with a diagnostically challenging cutaneous T-cell lymphoma and multifocal mononeuropathies in whom a targeted nerve biopsy identified lymphomatous infiltration of nerves and expedited combination treatment with chemotherapy and an autologous stem cell transplant. She showed an excellent response with a complete metabolic response on positron emission tomography imaging and significant clinical improvement, maintained 5 years post-treatment

Retinal Expression of Wnt-Pathway Mediated Genes in Low-Density Lipoprotein Receptor-Related Protein 5 (Lrp5) Knockout Mice

Mutations in low-density lipoprotein receptor-related protein 5 (Lrp5) impair retinal angiogenesis in patients with familial exudative vitreoretinopathy (FEVR), a rare type of blinding vascular eye disease. The defective retinal vasculature phenotype in human FEVR patients is recapitulated in Lrp5 knockout $(Lrp5^{-/-})$ mouse with delayed and incomplete development of retinal vessels. In this study we examined gene expression changes in the developing $Lrp5^{−/−}$ mouse retina to gain insight into the molecular mechanisms that underlie the pathology of FEVR in humans. Gene expression levels were assessed with an Illumina microarray on total RNA from $Lrp5^{−/−}$ and WT retinas isolated on postnatal day (P) 8. Regulated genes were confirmed using RT-qPCR analysis. Consistent with a role in vascular development, we identified expression changes in genes involved in cell-cell adhesion, blood vessel morphogenesis and membrane transport in $Lrp5^{−/−}$ retina compared to WT retina. In particular, tight junction protein claudin5 and amino acid transporter slc38a5 are both highly down-regulated in $Lrp5^{−/−}$ retina. Similarly, several Wnt ligands including Wnt7b show decreased expression levels. Plasmalemma vesicle associated protein (plvap), an endothelial permeability marker, in contrast, is up-regulated consistent with increased permeability in $Lrp5^{−/−}$ retinas. Together these data suggest that Lrp5 regulates multiple groups of genes that influence retinal angiogenesis and may contribute to the pathogenesis of FEVR

Hereditary leukoencephalopathy with axonal spheroids: a spectrum of phenotypes from CNS vasculitis to parkinsonism in an adult onset leukodystrophy series

Background: Hereditary diffuse leukoencephalopathy with neuroaxonal spheroids (HDLS) is a hereditary, adult onset leukodystrophy which is characterised by the presence of axonal loss, axonal spheroids and variably present pigmented macrophages on pathological examination. It most frequently presents in adulthood with dementia and personality change. HDLS has recently been found to be caused by mutations in the colony stimulating factor-1 receptor (CSF1R) gene. Methods: In this study, we sequenced the CSF1R gene in a cohort of 48 patients from the UK, Greece and Ireland with adult onset leukodystrophy of unknown cause. Results: Five pathogenic mutations were found, including three novel mutations. The presentations ranged from suspected central nervous system (CNS) vasculitis to extrapyramidal to cognitive phenotypes. The case histories and imaging are presented here, in addition to neuropathological findings from two cases with novel mutations. Conclusion: We estimate that CSF1R mutations account for 10% of idiopathic adult onset leukodystrophies and that genetic testing for CSF1R mutations is essential in adult patients presenting with undefined CNS vasculitis or a leukodystrophy with prominent neuropsychiatric signs or dementia