Effect of HIV infection and antiretroviral therapy on hepatitis B virus (HBV)-specific T cell responses in patients who have resolved HBV infection

Coinfection with hepatitis B virus (HBV) is a common occurrence in human immunodeficiency virus (HIV)–positive patients and an increasing cause of morbidity and mortality. The CD8+ T cell response is critical for long-term control of HBV in patients resolving acute infection. Here, we examine the effect of HIV on HBV-specific CD8+ T cell responses in patients who have resolved HBV infection. A cross-sectional study showed a reduction in HBV-specific CD8+ T cell responses in HIV-positive, HBV-immune patients, compared with those in HIV-negative, HBV-immune patients. A longitudinal study of a subgroup of patients examined whether this attrition could be reversed by effective antiretroviral therapy. The introduction of highly active antiretroviral therapy (HAART) resulted in reconstitution of some HBV-specific CD4+ and CD8+ T cell responses, in association with restoration of CD4+ T cell counts. These data provide a mechanism to account for the observed impairment of control of HBV infection in the setting of HIV infection and support the ability of HAART to reconstitute functionally active T cell responses

Intimate partner violence, depression, and sexual behaviour among gay, bisexual and other men who have sex with men in the PROUD trial.

BACKGROUND: Little is known about the prevalence and correlates of intimate partner violence (IPV) among gay, bisexual and other men who have sex with men (GBMSM) in the UK. The aim of this study was to investigate the prevalence of IPV, associations of socio-economic and psychosocial factors with IPV, and the association of IPV with depression and sexual behaviour, among GBMSM in the PROUD trial of pre-exposure prophylaxis (PrEP). METHODS: PROUD enrolled 544 HIV-negative participants in England from 2012 to 2014; participants were randomised to immediate or deferred PrEP. This analysis included 436 GBMSM who had IPV data at month-12 and/or 24. Prevalence of IPV victimization and perpetration (lifetime, and in the past year) was assessed at these time-points. Generalized estimating equations were used to investigate associations with IPV, using pooled data from both time-points. RESULTS: At month-12 (N = 410), 44.9% of men reported ever being a victim of IPV, 15.6% in the last year, and 19.5% reported ever perpetrating IPV, 7.8% in the last year. At month-24 (N = 333), the corresponding prevalence was 40.2 and 14.7% for lifetime and past year IPV victimization and 18.0 and 6.9% for lifetime and past year IPV perpetration. IPV prevalence did not differ by randomised arm. Men reporting internalized homophobia and sexualized drug use were more likely to report IPV. Lifetime and last year experience of IPV victimization and perpetration were strongly associated with depressive symptoms (PHQ-9 ≥ 10) (adjusted for socio-demographics: lifetime IPV victimization PR 2.57 [95% CI: 1.71, 3.86]; past year IPV victimization PR 2.93 [95% CI: 1.96, 4.40]; lifetime IPV perpetration PR 2.87 [95% CI: 1.91, 4.32]; past year IPV perpetration PR 3.47 [95% CI: 2.13, 5.64], p < 0.001 for all); IPV was not consistently associated with measures of condomless anal sex or high partner numbers. CONCLUSIONS: GBMSM at high-risk of HIV who are seeking/taking PrEP may experience a high burden of IPV, which may be linked to depression. Training on awareness of and enquiry for IPV among GBMSM in sexual health clinics is recommended. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02065986 . Registered 19 February 2014 (retrospectively registered)

Patient preferences for longer or more frequent in-center hemodialysis regimens: a multicenter discrete choice study

Rationale & Objective Longer and more frequent hemodialysis sessions are associated with both benefits and harms. However, their relative importance to patients and how they influence acceptability for patients have not been quantified. Study Design Discrete-choice experiment in which a scenario followed by 12 treatment choice sets were presented to patients in conjunction with varying information about the clinical impact of the treatments offered. Setting and Participants Patients with kidney failure treated with maintenance dialysis for ≥1 year in 5 UK kidney centers. Predictors Length and frequency of hemodialysis sessions, and their prior reported associations with survival, quality of life, need for fluid restriction, hospitalization, and vascular access complications. Outcomes Selection of longer (4.5hr) or more frequent hemodialysis (4 sessions per week) regimens versus remaining on 3 sessions per week with session lengths of 4 hours. Analytical Approach Multinomial mixed effects logistic regression estimating the relative influence of different levels of the predictors on the selection of longer and more frequent dialysis, controlling for patient demographic characteristics. Results Among 183 prevalent in-centre haemodialysis patients (mean 4.7 years on dialysis, mean age of 63.7 years), 38.3% (70/183) always chose to remain on regimens of 3 sessions per week with session duration of 4 hours. Depicted associations of increasing survival and quality of life, reduced need for fluid restriction, and avoiding additional access complications were all significantly associated with choosing longer or more frequent treatment regimes. Younger age, fatigue, previous experience of vascular access complications, absence of heart failure, and shorter travel time to dialysis centers were associated with preference for 4 sessions per week. Patients expressed willingness to trade up to 2 years of life to avoid regimens of 4 sessions per week or access complications. After applying estimated treatment benefits and harms from existing literature, the fully adjusted model revealed that 27.1% would choose longer regimens delivered 3 times per week and 34.3% would choose 4hrs 4 times per week. Analogous estimates for younger fatigued patients living near their unit were 23.5% and 62.5%, respectively. Limitations Estimates were based on stated preferences rather than observed behaviors. Predicted acceptance of regimens was derived from data on treatment benefits and harms largely sourced from observational studies. Conclusions Predicted acceptance of longer and more frequent HD regimens substantially exceeds their use in current clinical practice. These findings underscore the need for robust data on clinical effectiveness of these more intensive regimens and more extensive consideration of patient choice in the selection of dialysis regimens

Multiwavelength studies of MHD waves in the solar chromosphere: An overview of recent results

The chromosphere is a thin layer of the solar atmosphere that bridges the relatively cool photosphere and the intensely heated transition region and corona. Compressible and incompressible waves propagating through the chromosphere can supply significant amounts of energy to the interface region and corona. In recent years an abundance of high-resolution observations from state-of-the-art facilities have provided new and exciting ways of disentangling the characteristics of oscillatory phenomena propagating through the dynamic chromosphere. Coupled with rapid advancements in magnetohydrodynamic wave theory, we are now in an ideal position to thoroughly investigate the role waves play in supplying energy to sustain chromospheric and coronal heating. Here, we review the recent progress made in characterising, categorising and interpreting oscillations manifesting in the solar chromosphere, with an impetus placed on their intrinsic energetics.Comment: 48 pages, 25 figures, accepted into Space Science Review

Scaling ozone responses of forest trees to the ecosystem level in a changing climate

Many uncertainties remain regarding how climate change will alter the structure and function of forest ecosystems. At the Aspen FACE experiment in northern Wisconsin, we are attempting to understand how an aspen/birch/maple forest ecosystem responds to long-term exposure to elevated carbon dioxide (CO 2 ) and ozone (O 3 ), alone and in combination, from establishment onward. We examine how O 3 affects the flow of carbon through the ecosystem from the leaf level through to the roots and into the soil micro-organisms in present and future atmospheric CO 2 conditions. We provide evidence of adverse effects of O 3 , with or without co-occurring elevated CO 2 , that cascade through the entire ecosystem impacting complex trophic interactions and food webs on all three species in the study: trembling aspen ( Populus tremuloides Michx . ), paper birch ( Betula papyrifera Marsh), and sugar maple ( Acer saccharum Marsh). Interestingly, the negative effect of O 3 on the growth of sugar maple did not become evident until 3 years into the study. The negative effect of O 3 effect was most noticeable on paper birch trees growing under elevated CO 2 . Our results demonstrate the importance of long-term studies to detect subtle effects of atmospheric change and of the need for studies of interacting stresses whose responses could not be predicted by studies of single factors. In biologically complex forest ecosystems, effects at one scale can be very different from those at another scale. For scaling purposes, then, linking process with canopy level models is essential if O 3 impacts are to be accurately predicted. Finally, we describe how outputs from our long-term multispecies Aspen FACE experiment are being used to develop simple, coupled models to estimate productivity gain/loss from changing O 3 .Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72464/1/j.1365-3040.2005.01362.x.pd

The parent?infant dyad and the construction of the subjective self

Developmental psychology and psychopathology has in the past been more concerned with the quality of self-representation than with the development of the subjective agency which underpins our experience of feeling, thought and action, a key function of mentalisation. This review begins by contrasting a Cartesian view of pre-wired introspective subjectivity with a constructionist model based on the assumption of an innate contingency detector which orients the infant towards aspects of the social world that react congruently and in a specifically cued informative manner that expresses and facilitates the assimilation of cultural knowledge. Research on the neural mechanisms associated with mentalisation and social influences on its development are reviewed. It is suggested that the infant focuses on the attachment figure as a source of reliable information about the world. The construction of the sense of a subjective self is then an aspect of acquiring knowledge about the world through the caregiver's pedagogical communicative displays which in this context focuses on the child's thoughts and feelings. We argue that a number of possible mechanisms, including complementary activation of attachment and mentalisation, the disruptive effect of maltreatment on parent-child communication, the biobehavioural overlap of cues for learning and cues for attachment, may have a role in ensuring that the quality of relationship with the caregiver influences the development of the child's experience of thoughts and feelings

'Disc-jet' coupling in black hole X-ray binaries and active galactic nuclei

In this chapter I will review the status of our phenomenological understanding of the relation between accretion and outflows in accreting black hole systems. This understanding arises primarily from observing the relation between X-ray and longer wavelength (infrared, radio) emission. The view is necessarily a biased one, beginning with observations of X-ray binary systems, and attempting to see if they match with the general observational properties of active galactic nuclei.Comment: 28 pages, 15 figures, To appear in Belloni, T. (ed.): The Jet Paradigm - From Microquasars to Quasars, Lect. Notes Phys. 794 (2009

Identification of common genetic risk variants for autism spectrum disorder

Autism spectrum disorder (ASD) is a highly heritable and heterogeneous group of neurodevelopmental phenotypes diagnosed in more than 1% of children. Common genetic variants contribute substantially to ASD susceptibility, but to date no individual variants have been robustly associated with ASD. With a marked sample-size increase from a unique Danish population resource, we report a genome-wide association meta-analysis of 18,381 individuals with ASD and 27,969 controls that identified five genome-wide-significant loci. Leveraging GWAS results from three phenotypes with significantly overlapping genetic architectures (schizophrenia, major depression, and educational attainment), we identified seven additional loci shared with other traits at equally strict significance levels. Dissecting the polygenic architecture, we found both quantitative and qualitative polygenic heterogeneity across ASD subtypes. These results highlight biological insights, particularly relating to neuronal function and corticogenesis, and establish that GWAS performed at scale will be much more productive in the near term in ASD.Peer reviewe