Risk factors for high anti-HHV-8 antibody titers (≥1:51,200) in black, HIV-1 negative South African cancer patients: a case control study

Background: Infection with human herpesvirus 8 (HHV-8) is the necessary causal agent in the development of Kaposi's sarcoma (KS). Infection with HIV-1, male gender and older age all increase risk for KS. However, the geographic distribution of HHV-8 and KS both prior to the HIV/AIDS epidemic and with HIV/AIDS suggest the presence of an additional co-factor in the development of KS. Methods: Between January 1994 and October 1997, we interviewed 2576 black in-patients with cancer in Johannesburg and Soweto, South Africa. Blood was tested for antibodies against HIV-1 and HHV-8 and the study was restricted to 2191 HIV-1 negative patients. Antibodies against the latent nuclear antigen of HHV-8 encoded by orf73 were detected with an indirect immunofluorescence assay. We examined the relationship between high anti-HHV-8 antibody titers (≥1:51,200) and sociodemographic and behavioral factors using unconditional logistic regression models. Variables that were significant at p = 0.10 were included in multivariate analysis. Results: Of the 2191 HIV-1 negative patients who did not have Kaposi's sarcoma, 854 (39.0%) were positive for antibodies against HHV-8 according to the immunofluorescent assay. Among those seropositive for HHV-8, 530 (62.1%) had low titers (1:200), 227 (26.6%) had medium titers (1:51,200) and 97 (11.4%) had highest titers (1:204,800). Among the 2191 HIV-1 negative patients, the prevalence of high anti-HHV-8 antibody titers (≥1:51,200) was independently associated with increasing age (ptrend = 0.04), having a marital status of separated or divorced (p = 0.003), using wood, coal or charcoal as fuel for cooking 20 years ago instead of electricity (p = 0.02) and consuming traditional maize beer more than one time a week (p = 0.02; p-trend for increasing consumption = 0.05) although this may be due to chance given the large number of predictors considered in this analysis. Conclusions: Among HIV-negative subjects, patients with high anti-HHV-8 antibody titers are characterized by older age. Other associations that may be factors in the development of high anti- HHV-8 titers include exposure to poverty or a low socioeconomic status environment and consumption of traditional maize beer. The relationship between these variables and high anti- HHV-8 titers requires further, prospective study

A genome-wide association scan in admixed Latin Americans identifies loci influencing facial and scalp hair features

We report a genome-wide association scan in over 6,000 Latin Americans for features of scalp hair (shape, colour, greying, balding) and facial hair (beard thickness, monobrow, eyebrow thickness). We found 18 signals of association reaching genome-wide significance (P values 5 × 10−8 to 3 × 10−119), including 10 novel associations. These include novel loci for scalp hair shape and balding, and the first reported loci for hair greying, monobrow, eyebrow and beard thickness. A newly identified locus influencing hair shape includes a Q30R substitution in the Protease Serine S1 family member 53 (PRSS53). We demonstrate that this enzyme is highly expressed in the hair follicle, especially the inner root sheath, and that the Q30R substitution affects enzyme processing and secretion. The genome regions associated with hair features are enriched for signals of selection, consistent with proposals regarding the evolution of human hair

Adaptation reveals sensory and decision components in the visual estimation of locomotion speed

Locomotion speed provides important social information about an individual’s fitness, mood and intent. Visual estimation of locomotion speed is a complex task for the visual system because viewing distance must be taken into account, and the estimate has to be calibrated by recent experience of typical speeds. Little is known about how locomotion speed judgements are made. Previous research indicates that the human visual system possesses neurons that respond specifically to moving human forms. This research used point-light walker (PLW) displays that are known to activate these cells, in order to investigate the process mediating locomotion speed judgements. The results of three adaptation experiments show that these judgements involve both a low-level sensory component and a high-level decision component. A simple theoretical scheme is proposed, in which neurons sensitive to image flicker rate (temporal frequency) provide a sensory speed code, and a benchmark ‘norm’ value of the speed code, based on prevailing locomotion speeds, is used to make decisions about objective speed. The output of a simple computational model of the scheme successfully captured variations in locomotion speed in the stimuli used in the experiments. The theory offers a biologically-motivated account of how locomotion speed can be visually estimated

A prospective longitudinal study of Pasireotide in Nelson's syndrome

PURPOSE: Nelson's syndrome is a challenging condition that can develop following bilateral adrenalectomy for Cushing's disease, with high circulating ACTH levels, pigmentation and an invasive pituitary tumor. There is no established medical therapy. The aim of the study was to assess the effects of pasireotide on plasma ACTH and tumor volume in Nelson's syndrome. METHODS: Open labeled multicenter longitudinal trial in three steps: (1) a placebo-controlled acute response test; (2) 1 month pasireotide 300-600 μg s.c. twice-daily; (3) 6 months pasireotide long-acting-release (LAR) 40-60 mg monthly. RESULTS: Seven patients had s.c. treatment and 5 proceeded to LAR treatment. There was a significant reduction in morning plasma ACTH during treatment (mean ± SD; 1823 ± 1286 ng/l vs. 888.0 ± 812.8 ng/l during the s.c. phase vs. 829.0 ± 1171 ng/l during the LAR phase, p < 0.0001). Analysis of ACTH levels using a random intercept linear mixed-random effects longitudinal model showed that ACTH (before the morning dose of glucocorticoids) declined significantly by 26.1 ng/l per week during the 28-week of treatment (95% CI - 45.2 to - 7.1, p < 0.01). An acute response to a test dose predicted outcome in 4/5 patients. Overall, there was no significant change in tumor volumes (1.4 ± 0.9 vs. 1.3 ± 1.0, p = 0.86). Four patients withdrew during the study. Hyperglycemia occurred in 6 patients. CONCLUSIONS: Pasireotide lowers plasma ACTH levels in patients with Nelson's syndrome. A longer period of treatment may be needed to assess the effects of pasireotide on tumor volume. TRIAL REGISTRATION: Clinical Trials.gov ID, NCT01617733

Health Equity Indicators for the English NHS: a longitudinal whole-population study at the small-area level

Background: Inequalities in health-care access and outcomes raise concerns about quality of care and justice, and the NHS has a statutory duty to consider reducing them. Objectives: The objectives were to (1) develop indicators of socioeconomic inequality in health-care access and outcomes at different stages of the patient pathway; (2) develop methods for monitoring local NHS equity performance in tackling socioeconomic health-care inequalities; (3) track the evolution of socioeconomic health-care inequalities in the 2000s; and (4) develop ‘equity dashboards’ for communicating equity findings to decision-makers in a clear and concise format. Design: Longitudinal whole-population study at the small-area level. Setting: England from 2001/2 to 2011/12. Participants: A total of 32,482 small-area neighbourhoods (lower-layer super output areas) of approximately 1500 people. Main outcome measures: Slope index of inequality gaps between the most and least deprived neighbourhoods in England, adjusted for need or risk, for (1) patients per family doctor, (2) primary care quality, (3) inpatient hospital waiting time, (4) emergency hospitalisation for chronic ambulatory care-sensitive conditions, (5) repeat emergency hospitalisation in the same year, (6) dying in hospital, (7) mortality amenable to health care and (8) overall mortality. Data sources: Practice-level workforce data from the general practice census (indicator 1), practice-level Quality and Outcomes Framework data (indicator 2), inpatient hospital data from Hospital Episode Statistics (indicators 3–6) and mortality data from the Office for National Statistics (indicators 6–8). Results: Between 2004/5 and 2011/12, more deprived neighbourhoods gained larger absolute improvements on all indicators except waiting time, repeat hospitalisation and dying in hospital. In 2011/12, there was little measurable inequality in primary care supply and quality, but inequality was associated with 171,119 preventable hospitalisations and 41,123 deaths amenable to health care. In 2011/12, > 20% of Clinical Commissioning Groups performed statistically significantly better or worse than the England equity benchmark. Limitations: General practitioner supply is a limited measure of primary care access, need in deprived neighbourhoods may be underestimated because of a lack of data on multimorbidity, and the quality and outcomes indicators capture only one aspect of primary care quality. Health-care outcomes are adjusted for age and sex but not for other risk factors that contribute to unequal health-care outcomes and may be outside the control of the NHS, so they overestimate the extent of inequality for which the NHS can reasonably be held responsible. Conclusions: NHS actions can have a measurable impact on socioeconomic inequality in both health-care access and outcomes. Reducing inequality in health-care outcomes is more challenging than reducing inequality of access to health care. Local health-care equity monitoring against a national benchmark can be performed using any administrative geography comprising ≥ 100,000 people

Perception of Biological Motion in Schizophrenia and Healthy Individuals: A Behavioral and fMRI Study

Background: Anomalous visual perception is a common feature of schizophrenia plausibly associated with impaired social cognition that, in turn, could affect social behavior. Past research suggests impairment in biological motion perception in schizophrenia. Behavioral and functional magnetic resonance imaging (fMRI) experiments were conducted to verify the existence of this impairment, to clarify its perceptual basis, and to identify accompanying neural concomitants of those deficits. Methodology/Findings: In Experiment 1, we measured ability to detect biological motion portrayed by point-light animations embedded within masking noise. Experiment 2 measured discrimination accuracy for pairs of point-light biological motion sequences differing in the degree of perturbation of the kinematics portrayed in those sequences. Experiment 3 measured BOLD signals using event-related fMRI during a biological motion categorization task. Compared to healthy individuals, schizophrenia patients performed significantly worse on both the detection (Experiment 1) and discrimination (Experiment 2) tasks. Consistent with the behavioral results, the fMRI study revealed that healthy individuals exhibited strong activation to biological motion, but not to scrambled motion in the posterior portion of the superior temporal sulcus (STSp). Interestingly, strong STSp activation was also observed for scrambled or partially scrambled motion when the healthy participants perceived it as normal biological motion. On the other hand, STSp activation in schizophreni

The effectiveness of Chance UK's mentoring programme in improving behavioural and emotional outcomes in primary school children with behavioural difficulties: study protocol for a randomised controlled trial

BACKGROUND: There is a need to build the evidence base of early interventions to promote children's health and development in the UK. Chance UK is a voluntary sector organisation based in London that delivers a 12-month mentoring programme for primary school children identified by teachers and parents as having behavioural and emotional difficulties. The aim of the study is to determine the effectiveness of the programme in terms of children's behaviour and emotional well-being; this is the primary outcome of the trial. METHODS/DESIGN: A randomised controlled trial will be conducted in which participants are randomly allocated on a dynamic basis to one of two possible arms: the intervention arm (n = 123) will be offered the mentoring programme, and the control arm (n = 123) will be offered services as usual. Outcome data will be collected at three points: pre-intervention (baseline), mid-way through the mentoring year (c.9 months after randomisation) and post- mentoring programme (c.16 months after randomisation). DISCUSSION: This study will further enhance the evidence for early intervention mentoring programmes for child behaviour and emotional well-being in the UK. TRIAL REGISTRATION: Current Controlled Trials ISRCTN47154925 . Retrospectively registered 9 September 2014

Atypicalities in Perceptual Adaptation in Autism Do Not Extend to Perceptual Causality

A recent study showed that adaptation to causal events (collisions) in adults caused subsequent events to be less likely perceived as causal. In this study, we examined if a similar negative adaptation effect for perceptual causality occurs in children, both typically developing and with autism. Previous studies have reported diminished adaptation for face identity, facial configuration and gaze direction in children with autism. To test whether diminished adaptive coding extends beyond high-level social stimuli (such as faces) and could be a general property of autistic perception, we developed a child-friendly paradigm for adaptation of perceptual causality. We compared the performance of 22 children with autism with 22 typically developing children, individually matched on age and ability (IQ scores). We found significant and equally robust adaptation aftereffects for perceptual causality in both groups. There were also no differences between the two groups in their attention, as revealed by reaction times and accuracy in a change-detection task. These findings suggest that adaptation to perceptual causality in autism is largely similar to typical development and, further, that diminished adaptive coding might not be a general characteristic of autism at low levels of the perceptual hierarchy, constraining existing theories of adaptation in autism.16 page(s