CD4+:CD8+T Cell Ratio Normalization and the Development of AIDS Events in People with HIV Starting Antiretroviral Therapy

We identify factors associated with the normalization of the CD4+:CD8+ T cell ratio among UK Collaborative HIV Cohort study participants, and describe the association of the CD4+ and CD8+ T cell counts and the CD4+:CD8+ T cell ratio, with the risk of new AIDS events among individuals who achieve a suppressed viral load. Participants initiating combination antiretroviral therapy (cART) after 2006 with a CD4+:CD8+ T cell ratio 500 vs. ≤200 cells/mm3, adjusted hazard ratio (95% confidence interval): 7.93 (6.97–9.01)], low CD8+ T cell count [>1,150 vs. ≤500 cells/mm3: 0.18 (0.16–0.21)], and low CD4+:CD8+ T cell ratio [>0.8 vs. 500 vs. ≤200 cells/mm3: adjusted rate ratio 0.24 (0.16–0.34)] and CD4+:CD8+ T cell ratio [>0.8 vs. <0.2: 0.33 (0.21–0.52)] were independently associated with a new AIDS event. One third of study participants experienced ratio normalization after starting cART. CD4+ T cell count and CD4+:CD8+ T cell ratio are both individually associated with ratio normalization and the development of new AIDS events after cART

Using photo-elicitation to explore perceptions of physical activity among young people with cystic fibrosis

This is the final version. Available on open access from BMC via the DOI in this recordAvailability of data and materials: All data generated or analysed during this study are included in this published article.Background: Physical activity is recommended in the management of cystic fibrosis (CF). The aim of this study was to explore motives, barriers and enablers to physical activity among this population. Methods: Twelve participants (12-18 years) were recruited via convenience sampling. Photo27 elicitation alongside semi-structured interviews were used to explore participants’ views and experiences of physical activity. Results: Our findings revealed motives for physical activity including health, enjoyment and autonomy. Those with families who valued physical activity tended to have positive attitudes towards physical activity, and valued and integrated it into their lives. Moreover, they were likely to be intrinsically motivated to be active. Several factors enable and act as barriers to physical activity. Whilst CF influenced physical activity, the majority of enablers and barriers raised where congruent with the general populations. Conclusion: This study provides support that healthcare providers should encourage both young people with CF and their families to be active, and subsequently informs the development of clinical interventions to support physical activity among young people with CF and their families.Cystic Fibrosis Trus

Treatment exhaustion of highly active antiretroviral therapy (HAART) among individuals infected with HIV in the United Kingdon: multicentre cohort study

Objectives: To investigate whether there is evidence that an increasing proportion of HIV infected patients is starting to experience increases in viral load and decreases in CD4 cell count that are consistent with exhaustion of available treatment options. Design: Multicentre cohort study. Setting: Six large HIV treatment centres in southeast England. Participants: All individuals seen for care between 1 January 1996 and 31 December 2002. Main outcome measures: Exposure to individual antiretroviral drugs and drug classes, CD4 count, plasma HIV RNA burden. Results: Information is available on 16 593 individuals (13 378 (80.6%) male patients, 10 340 (62.3%) infected via homosexual or bisexual sex, 4426 (26.7%) infected via heterosexual sex, median age 34 years). Overall, 10 207 of the 16 593 patients (61.5%) have been exposed to any antiretroviral therapy. This proportion increased from 41.2% of patients under follow up at the end of 1996 to 71.3% of those under follow up in 2002. The median CD4 count and HIV RNA burden of patients under follow up in each year changed from 270 cells/mm3 and 4.34 log10 copies/ml in 1996 to 408 cells/mm3 and 1.89 log10 copies/ml, respectively, in 2002. By 2002, 3060 (38%) of patients who had ever been treated with antiretroviral therapy had experienced all three main classes. Of these, around one quarter had evidence of “viral load failure” with all these three classes. Patients with three class failure were more likely to have an HIV RNA burden > 2.7 log10 copies/ml and a CD4 count < 200 cells/mm3. Conclusions: The proportion of individuals with HIV infection in the United Kingdom who have been treated has increased gradually over time. A substantial proportion of these patients seem to be in danger of exhausting their options for antiretroviral treatment. New drugs with low toxicity, which are not associated with cross resistance to existing drugs, are urgently needed for such patients

“I don’t know anything about their Culture”: The Disconnect between Allopathic and Traditional Maternity Care Providers in Rural Northern Ghana

The provision of maternal and neonatal health care in rural northern Ghana is pluralistic, consisting of traditional and allopathic providers. Although  women often use these providers interchangeably, important differences exist. This study explored the differences in approaches to maternal and neonatal care provision by these two different types of providers. This  research was part of the Stillbirth and Neonatal Death Study (SANDS),  conducted in northern Ghana in 2010. Trained field staff of the Navrongo Health Research Centre conducted in-depth interviews with 13 allopathic and 8 traditional providers. Interviews were audio-recorded, transcribed, and analyzed using in vivo coding and discussion amongst the research team. Three overarching themes resulted: 1) many allopathic providers were isolated from the culture of the communities in which they practiced, while traditional providers were much more aware of the local cultural  beliefs and practices. 2) Allopathic and traditional healthcare providers have different frameworks for understanding health and disease, with  allopathic providers relying heavily on their biomedical knowledge, and traditional providers drawing on their knowledge of natural remedies. 3) All providers agreed that education directed at pregnant women, providers (both allopathic and traditional), and the community at large is needed to improve maternal and neonatal outcomes. Our findings suggest that, among other things, programmatic efforts need to be placed on the cultural education of allopathic providers. (Afr J Reprod Health 2014; 18[2]: 36-45).Keywords: Allopathic medicine, traditional medicine, maternal health, delivery care, cultur

Differences in HIV clinical outcomes amongst heterosexuals in the United Kingdom by ethnicity

OBJECTIVE: We investigated differences in clinical outcomes in heterosexual participants, by ethnicity in the UK Collaborative HIV Cohort Study from 2000-2017. DESIGN: Cohort analysis. METHODS: Logistic/Proportional hazard regression assessed ethnic group differences in CD4+ cell count at presentation, engagement-in-care, combination antiretroviral therapy (cART) initiation, viral suppression and rebound. RESULTS: Of 12,302 participants (median age: 37 [interquartile range: 31, 44] years, 52.5% women, total follow-up: 85,846 person-years), 64.4% were Black African, 19.1% White, 6.3% Black Caribbean, 3.6% Black Other, 3.3% South Asian/Other Asian and 3.4% Other/Mixed. CD4+ cell count at presentation amongst participants from non-White groups were lower than the White group. Participants were engaged-in-care for 79.6% of follow-up time, however Black and Other/Mixed groups were less likely to be engaged-in-care than the White group (adjusted odds ratios vs. White: Black African: 0.70 [95% confidence interval 0.63, 0.79], Black Caribbean: 0.74 [0.63, 0.88], Other/Mixed: 0.78 [0.62, 0.98], Black Other: 0.81 [0.64, 1.02]). Of 8,867 who started cART, 79.1% achieved viral suppression, with no differences by ethnicity in cART initiation or viral suppression. Viral rebound (22.2%) was more common in the Black Other (1.95 [1.37, 2.77]), Black African (1.85 [1.52, 2.24]), Black Caribbean (1.73 [1.28, 2.33]), South Asian/Other Asian (1.35 [0.90, 2.03]) and Other/Mixed (1.09 [0.69, 1.71]) groups than in White participants. CONCLUSIONS: Heterosexual people from Black, Asian and minority ethnic groups presented with lower CD4+ cell counts, spent less time engaged-in-care and were more likely to experience viral rebound than White people. Work to understand and address these differences is needed

Incomplete reversibility of estimated glomerular filtration rate decline following tenofovir disoproxil fumarate exposure.

BACKGROUND: Tenofovir disoproxil fumarate (TDF) has been linked to renal impairment, but the extent to which this impairment is reversible is unclear. We aimed to investigate the reversibility of renal decline during TDF therapy. METHODS: Cox proportional hazards models assessed factors associated with discontinuing TDF in those with an exposure duration of >6 months. In those who discontinued TDF therapy, linear piecewise regression models estimated glomerular filtration rate (eGFR) slopes before initiation of, during, and after discontinuation of TDF therapy. Factors associated with not achieving eGFR recovery 6 months after discontinuing TDF were assessed using multivariable logistic regression. RESULTS: We observed declines in the eGFR during TDF exposure (mean slopes, -15.7 mL/minute/1.73 m(2)/year [95% confidence interval {CI}, -20.5 to -10.9] during the first 3 months and -3.1 mL/minute/1.73 m(2)/year [95% CI, -4.6 to -1.7] thereafter) and evidence of eGFR increases following discontinuation of TDF therapy (mean slopes, 12.5 mL/minute/1.73 m(2)/year [95% CI, 8.9-16.1] during the first 3 months and 0.8 mL/minute/1.73 m(2)/year [95% CI,.1-1.5] thereafter). Following TDF discontinuation, 38.6% of patients with a decline in the eGFR did not experience recovery. A higher eGFR at baseline, a lower eGFR after discontinuation of TDF therapy, and more-prolonged exposure to TDF were associated with an increased risk of incomplete recovery 6 months after discontinuation of TDF therapy. CONCLUSIONS: This study shows that a decline in the eGFR during TDF therapy was not fully reversible in one third of patients and suggests that prolonged TDF exposure at a low eGFR should be avoided

Music-of-Light Stethoscope: A Demonstration of the Photoacoustic Effect

In this paper we present a system aimed at demonstrating the photoacoustic (PA) effect for educational purposes. PA imaging is a hybrid imaging modality that requires no contrast agent and has a great potential for spine and brain lesion characterisation, breast cancer and blood flow monitoring notably in the context of fetal surgery. It relies on combining light excitation with ultrasound reception. Our brief was to present and explain PA imaging in a public-friendly way suitable for a variety of ages and backgrounds. We developed a simple, accessible demonstration unit using readily available materials. We used a modulated light emitting diode (LED) torch and an electronic stethoscope. The output of a music player was used for light modulation and the chest piece of the stethoscope covered by a black tape was used as an absorbing target and an enclosed chamber. This demonstration unit was presented to the public at the Bloomsbury Festival On Light in October 2015. Our stall was visited by over 100 people of varying ages. Twenty families returned in-depth evaluation questionnaires, which show that our explanations of the photoacoustic effect were well understood. Their interest in biomedical engineering was increased

Heat shock protein 10 inhibits lipopolysaccharide-induced inflammatory mediator production

Heat shock protein 10 (Hsp10) and heat shock protein 160 (Hsp60) were originally described as essential mitochondrial proteins involved in protein folding. How,ever, both proteins have also been shown to have a number of extracellular immunomodulatory activities. Here we show that purified recombinant human Hsp10 incubated with cells in vitro reduced lipopolysaccharide (LPS)-induced nuclear factor-kappaB activation and secretion of several inflammatory mediators from RAW264.7 cells, murine macrophages, and human peripheral blood mononuclear cells. Induction of tolerance by contaminating LPS was formally excluded as being responsible for Hsp10 activity. Treatment of mice with Hsp10 before,endotoxin challenge resulted in the reduction of serum tumor necrosis factor-a and RANTES (regulated upon activation, normal T cell expressed and secreted) levels and an elevation of serum interleukin-10 levels. Hsp10 treatment also delayed mortality in a murine graft-ver-sus-host disease model, where gut-derived LPS contributes to pathology. We were unable to confirm previous reports that Hsp10 has tumor growth factor properties and suggest that Hsp10 exerts anti-inflammatory activity by inhibiting Toll-like receptor signaling possibly by interacting with extracellular Hsp60

Decay of correlations for maps with uniformly contracting fibers and logarithm law for singular hyperbolic attractors

We consider two dimensional maps preserving a foliation which is uniformly contracting and a one dimensional associated quotient map having exponential convergence to equilibrium (iterates of Lebesgue measure converge exponentially fast to physical measure). We prove that these maps have exponential decay of correlations over a large class of observables. We use this result to deduce exponential decay of correlations for the Poincare maps of a large class of singular hyperbolic flows. From this we deduce logarithm laws for these flows.Comment: 39 pages; 03 figures; proof of Theorem 1 corrected; many typos corrected; improvements on the statements and comments suggested by a referee. Keywords: singular flows, singular-hyperbolic attractor, exponential decay of correlations, exact dimensionality, logarithm la