Sex differences in the Toll-like receptor-mediated response of plasmacytoid dendritic cells to HIV-1

Manifestations of viral infections can differ between women and men, and marked sex differences have been described in the course of HIV-1 disease. HIV-1-infected women tend to have lower viral loads early in HIV-1 infection but progress faster to AIDS for a given viral load than men. Here we show substantial sex differences in the response of plasmacytoid dendritic cells (pDCs) to HIV-1. pDCs derived from women produce markedly more interferon-alpha (IFN-alpha) in response to HIV-1-encoded Toll-like receptor 7 (TLR7) ligands than pDCs derived from men, resulting in stronger secondary activation of CD8(+) T cells. In line with these in vitro studies, treatment-naive women chronically infected with HIV-1 had considerably higher levels of CD8(+) T cell activation than men after adjusting for viral load. These data show that sex differences in TLR-mediated activation of pDCs may account for higher immune activation in women compared to men at a given HIV-1 viral load and provide a mechanism by which the same level of viral replication might result in faster HIV-1 disease progression in women compared to men. Modulation of the TLR7 pathway in pDCs may therefore represent a new approach to reduce HIV-1-associated pathology.

Professional attitudes to sex offenders: implications for multiagency and collaborative working

Recent years have seen the development and implementation of a range of multi-disciplinary and partnership approaches to managing risk in known sex offenders, involving collaboration between justice and human services agencies. Potential barriers to the development of effective multidisciplinary practices arise when participating professionals hold different attitudes about those they are responsible for managing. This paper examines differences in attitudes towards sex offenders in two professional groups – police officers and allied health workers. The results suggest that police officers tend to hold more negative views than those who deliver treatment and support services. They are more likely to believe that offenders cannot change their behaviour and should be subject to more punitive sanctions. These findings are discussed in relation to judgements of both risk and dangerousness and associated decisions about the appropriate management of sex offenders in multi-agency and multi-disciplinary working forums.

Learning entry profiles of children with autism from multivariate treatment information using restricted boltzmann machines

Entry profiles can be generated before children with Autism Spectrum Disorders (ASD) begin to traverse an intervention program. They can help evaluate the progress of each child on the dedicated syllabus in addition to enabling narrowing down the best intervention course over time. However, the traits of ASD are expressed in different ways in every individual affected. The resulting spectrum nature of the disorder makes it challenging to discover profiles of children with ASD. Using data from 491 children, traversing the syllabus of a comprehensive intervention program on iPad called TOBY Playpad, we learn the entry profiles of the children based on their age, sex and performance on their first skills of the syllabus. Mixed-variate restricted Boltzmann machines allow us to integrate the heterogeneous data into one model making it a suitable technique. The data based discovery of entry profiles may assist in developing systems that can automatically suggest best suitable paths through the syllabus by clustering the children based on the characteristics they present at the beginning of the program. This may open the pathway for personalised intervention.

Gender difference in treatment and mortality of patients with ST-segment elevation myocardial infarction admitted to Victorian public hospitals: A retrospective database study.

BACKGROUND: Death from acute coronary syndrome (ACS) is avoidable with early reperfusion therapy, however, evidence suggests inequity in women's ACS treatment within a number of international healthcare systems, when compared to men's. Research indicates mortality rates are higher in some age groups of women when compared to men for the sub-group of ACS known as ST-segment elevation myocardial infarction (STEMI). OBJECTIVE: To determine whether patient sex was associated with patterns of reperfusion treatment variation or increased inhospital mortality in patients with STEMI. METHODS: We undertook retrospective analyses on a government database for patients admitted to Victorian public hospitals with STEMI. Patients were categorised into two age groups: 18-64 and 65-84 years (inclusive), to determine whether patient sex and these age groups influenced treatment from 2005 to 2008 and mortality from 2005 to 2010. RESULTS: Both younger and older women received less frequent angioplasty with stent and more often received no reperfusion treatment than men in corresponding younger and older age groups (p=0.006 and p<0.001, respectively). Overall, women in both age groups were more likely to die inhospital than men from equivalent age groups with STEMI (p<0.001, both groups). CONCLUSIONS: Proportionately, both younger and older women received less interventional reperfusion therapy for STEMI than their male cohorts, and died more often during admission than men. Further research needs to be undertaken to verify the findings and causes, and guide future research to ensure application of evidence to treatment in patients with STEMI.

The effect of active video games by ethnicity, sex and fitness: subgroup analysis from a randomised controlled trial

BACKGROUND: The prevention and treatment of childhood obesity is a key public health challenge. However, certain groups within populations have markedly different risk profiles for obesity and related health behaviours. Well-designed subgroup analysis can identify potential differential effects of obesity interventions, which may be important for reducing health inequalities. The study aim was to evaluate the consistency of the effects of active video games across important subgroups in a randomised controlled trial (RCT).

FINDINGS: A two-arm, parallel RCT was conducted in overweight or obese children (n=322; aged 10-14 years) to determine the effect of active video games on body composition. Statistically significant overall treatment effects favouring the intervention group were found for body mass index, body mass index z-score and percentage body fat at 24 weeks. For these outcomes, pre-specified subgroup analyses were conducted among important baseline demographic (ethnicity, sex) and prognostic (cardiovascular fitness) groups. No statistically significant interaction effects were found between the treatment and subgroup terms in the main regression model (p=0.36 to 0.93), indicating a consistent treatment effect across these groups.

CONCLUSIONS: Preliminary evidence suggests an active video games intervention had a consistent positive effect on body composition among important subgroups. This may support the use of these games as a pragmatic public health intervention to displace sedentary behaviour with physical activity in young people.

Sex differences in in-hospital mortality following a first acute myocardial infarction: symptomatology, delayed presentation, and hospital setting

BACKGROUND: Women generally wait longer than men prior to seeking treatment for acute myocardial infarction (AMI). They are more likely to present with atypical symptoms, and are less likely to be admitted to coronary or intensive care units (CCU or ICU) compared to similarly-aged males. Women are more likely to die during hospital admission. Sex differences in the associations of delayed arrival, admitting ward, and mortality have not been thoroughly investigated.

METHODS: Focusing on presenting symptoms and time of presentation since symptom onset, we evaluated sex differences in in-hospital mortality following a first AMI in 4859 men and women presenting to three emergency departments (ED) from December 2008 to February 2014. Sex-specific risk of mortality associated with admission to either CCU/ICU or medical wards was calculated after adjusting for age, socioeconomic status, triage-assigned urgency of presentation, blood pressure, heart rate, presenting symptoms, timing of presentation since symptom onset, and treatment in the ED. Sex-specific age-adjusted attributable risks were calculated.

RESULTS: Compared to males, females waited longer before seeking treatment, presented more often with atypical symptoms, and were less likely to be admitted to CCU or ICU. Age-adjusted mortality in CCU/ICU or medical wards was higher among females (3.1 and 4.9 % respectively in CCU/ICU and medical wards in females compared to 2.6 and 3.2 % in males). However, after adjusting for variation in presenting symptoms, delayed arrival and other risk factors, risk of death was similar between males and females if they were admitted to CCU or ICU. This was in contrast to those admitted to medical wards. Females admitted to medical wards were 89 % more likely to die than their male counterparts. Arriving in the ED within 60 min of onset of symptoms was not associated with in-hospital mortality. Among males, 2.2 % of in-hospital mortality was attributed to being admitted to medical wards rather than CCU or ICU, while for females this age-adjusted attributable risk was 4.1 %.

CONCLUSIONS: Our study stresses the need to reappraise decision making in patient selection for admission to specialised care units, whilst raising awareness of possible sex-related bias in management of patients diagnosed with an AMI.