Control of Gammaherpesvirus Latency by Latent Antigen-Specific Cd8+ T Cells

The contribution of the latent antigen-specific CD8+ T cell response to the control of gammaherpesvirus latency is currently obscure. Some latent antigens induce potent T cell responses, but little is known about their induction or the role they play during the establishment of latency. Here we used the murine gammaherpesvirus system to examine the expression of the latency-associated M2 gene during latency and the induction of the CD8+ T cell response to this protein. M2, in contrast to the M3 latency-associated antigen, was expressed at day 14 after infection but was undetectable during long-term latency. The induction of the M291–99/Kd CD8+ T cell response was B cell dependent, transient, and apparently induced by the rapid increase in latently infected cells around day 14 after intranasal infection. These kinetics were consistent with a role in controlling the initial “burst” of latently infected cells. In support of this hypothesis, adoptive transfer of an M2-specific CD8+ T cell line reduced the initial load of latently infected cells, although not the long-term load. These data represent the first description of a latent antigen-specific immune response in this model, and suggest that vaccination with latent antigens such as M2 may be capable of modulating latent gammaherpesvirus infection

Liquor licences issued to Australian schools

BACKGROUND: Children's positive socialisation to alcohol is associated with early initiation of drinking and alcohol-related harm in adult life. Internationally, there have been reports of adults' alcohol consumption at school events in the presence of children. The aim of this research was to identify the conditions under which Australian schools are required to apply for a liquor licence and the associated prevalence of liquor licences for these events where children were likely to be present. METHODS: A document review was conducted to examine temporary liquor licensing legislation. Quantitative analysis was used to examine relevant licensing data. Coding criteria was developed to determine school type, student year levels and the likely presence of children. RESULTS: Four jurisdictions provided data on 1817 relevant licences. The average annual licences/100 schools was highest amongst Independent schools followed by Catholic and public (government) schools. The rates were highest in Queensland and Victoria where children were present at 61% and 32% of events respectively. CONCLUSIONS: While there are legislative differences across jurisdictions, the prevalence of adults' alcohol use at school events in the presence of children may reflect the various education department policies and principals' and school communities' beliefs and attitudes. Licences are not required for all events where liquor is consumed so the prevalence of adults' use of alcohol at school events is likely to be higher than our analyses imply. Such practices may undermine teaching about alcohol use in the school curriculum and health promotion efforts to develop alcohol-free events when children are present

Effectiveness of a Parenting Programme to Reduce Violence in a Cash Transfer System in the Philippines: RCT With Follow-up

Background Parenting interventions and conditional cash transfer (CCT) programmes are promising strategies to reduce the risk of violence against children, but evidence of the effectiveness of combining such programmes is lacking for families in low- and middle-income countries with children over two years of age. This study examined the effectiveness of a locally adapted parenting programme delivered as part of a government CCT system to low-income families with children aged two to six years in Metro Manila, Philippines. Methods Participants were randomly assigned (1:1) to either a 12-session group-based parenting programme or treatment-as-usual services (N= 120). Participation in either service was required among the conditions for receiving cash grants. Baseline assessments were conducted in July 2017 with one-month post-intervention assessments in January-February 2018 and 12-month follow-up in January-February 2019. All assessments were parent-report (ClinicalTrials.gov: NCT03205449). Findings One-month post-intervention assessments indicated moderate intervention effects for primary outcomes of reduced overall child maltreatment (d = -0.50 [-0.86, -0.13]), emotional abuse (d= -0.59 [-0.95; -0.22]), physical abuse (IRR = 0.51 [0.27; 0.74]), and neglect (IRR = 0.52 [0.18; 0.85]). There were also significant effects for reduced dysfunctional parenting, child behaviour problems, and intimate partner violence, and increased parental efficacy and positive parenting. Reduced overall maltreatment, emotional abuse, and neglect effects were sustained at one-year follow-up. Interpretation Findings suggest that a culturally adapted parenting intervention delivered as part of a CCT programme may be effective in sustaining reductions in violence against children in low- and middle-income countries. Funding This research was supported by UBS Optimus Foundation and UNICEF Philippines, and by the Complexity and Relationships in Health Improvement Programmes of the Medical Research Council MRC UK and Chief Scientist Office (Grant: MC_UU_00022/1 and CSO SPHSU16, MC_UU_00022/3 and CSO SPHSU18)

Principals' reports of adults' alcohol use in Australian secondary schools

Background - Schools provide opportunities for parents and the wider community to connect and support the physical and emotional wellbeing of their children. Schools therefore have the potential to play a role in the socialisation of alcohol use through school policies and practices regarding consumption of alcohol by adults at school events in the presence of children. Methods - This survey was undertaken to a) compare the extent to which alcohol is used at secondary school events, when children are present, in the states of New South Wales (NSW) and Victoria (VIC), Australia; b) describe principals’ level of agreement with these practices; c) their awareness of state policies on this issue; and d) the predictors of such events. A random sample of secondary schools, stratified to represent metropolitan and non-metropolitan schools were invited to participate. Bivariate and multivariate analysis were conducted with p values < 0.05 considered significant. Results - A total of 241 (43 %) schools consented to participate in the study. Fifteen percent of participating NSW schools and 57 % of VIC schools held at least one event in which alcohol was consumed by adults in the presence of children in the year before the survey. Of the 100 reported events, 78 % were Year 12 graduation dinners, and 18 % were debutante balls. Compared to NSW principals, VIC principals were significantly more likely to agree with the use of alcohol at these events; significantly less likely to be aware of their state education department policy on this issue; have a policy at their own school or support policy that prohibits alcohol use at such events; and less likely to report having enough Information to make decisions about this. Conclusions - There is a growing focus on adults’ use of alcohol at school events when children are present. Schools can play an important role in educating and socialising children about alcohol via both the curriculum and policies regarding adults’ alcohol use at school events. Findings from this study suggest education department and school-based policies that prohibit or restrict the use of alcohol, are significant predictors of adults’ alcohol use at school events when children are present

What we have learned from the framework for ocean observing: evolution of the global ocean observing system

The Global Ocean Observing System (GOOS) and its partners have worked together over the past decade to break down barriers between open-ocean and coastal observing, between scientific disciplines, and between operational and research institutions. Here we discuss some GOOS successes and challenges from the past decade, and present ideas for moving forward, including highlights of the GOOS 2030 Strategy, published in 2019. The OceanObs’09 meeting in Venice in 2009 resulted in a remarkable consensus on the need for a common set of guidelines for the global ocean observing community. Work following the meeting led to development of the Framework for Ocean Observing (FOO) published in 2012 and adopted by GOOS as a foundational document that same year. The FOO provides guidelines for the setting of requirements, assessing technology readiness, and assessing the usefulness of data and products for users. Here we evaluate successes and challenges in FOO implementation and consider ways to ensure broader use of the FOO principles. The proliferation of ocean observing activities around the world is extremely diverse and not managed, or even overseen by, any one entity. The lack of coherent governance has resulted in duplication and varying degrees of clarity, responsibility, coordination and data sharing. GOOS has had considerable success over the past decade in encouraging voluntary collaboration across much of this broad community, including increased use of the FOO guidelines and partly effective governance, but much remains to be done. Here we outline and discuss several approaches for GOOS to deliver more effective governance to achieve our collective vision of fully meeting society’s needs. What would a more effective and well-structured governance arrangement look like? Can the existing system be modified? Do we need to rebuild it from scratch? We consider the case for evolution versus revolution. Community-wide consideration of these governance issues will be timely and important before, during and following the OceanObs’19 meeting in September 2019

Eosinophilic Enteritis Confined to an Ileostomy Site

Eosinophilic enteritis is a rather rare condition that can manifest anywhere from esophagus to rectum. Its description in the literature is sparse, but associations have been made with collagen vascular disease, malignancy, food allergy, parasitic or viral infections, inflammatory bowel disease, and drug sensitivity. We present the case of a 41-year-old male diagnosed with ulcerative colitis who underwent proctocolectomy with ileal pouch anal anastomosis and loop ileostomy formation utilizing Seprafilm®, who later developed eosinophilic enteritis of the loop ileostomy site. This is the first report of eosinophilic enteritis and its possible link to the use of bioabsorbable adhesion barriers

Evaluation of a local government "shelter and van" intervention to improve safety and reduce alcohol-related harm.

Background: The entertainment precincts of cities, while contributing to local economies, need to be carefully managed to mitigate harms. Individual behaviours and government regulation have typically been the foci of interventions aimed at reducing alcohol-related harm. Little is known about how changes to the built environment might influence alcohol-related harms in these settings. The aim of this study was to explore how a public shelter and a volunteer-funded and staffed mobile van in a regional city influenced perceptions of safety and reduction in alcohol-related harm. Methods: An intrinsic case-study approach was used. Document reviews, qualitative interviews with 16 key informants (volunteers, licensees, police, local business owners, patrons, community members and security guards), observation, and secondary data analysis were conducted in 2016. A conceptual framework of the causative pathways linking the drivers of alcohol consumption with social and health outcomes was used to inform the analysis. Results: The shelter and van were frequently utilised but there was no significant association with a reduction in the proportion of alcohol-related hospital emergency department presentations or police incident reports. Occupational health and safety risks were identified for the volunteers which had no management plan. Conclusions: The findings highlight the challenge faced by local governments/authorities wanting to provide community-based interventions to complement other evidence-based approaches to reduce alcohol-related harm. Local governments/authorities with restricted regulatory oversight need to collaborate with key agencies for targeted upstream and evidence-based alcohol prevention and management interventions before investing resources. Such approaches are critical for improving community safety as well as health and social outcomes in communities at greatest risk of alcohol-related harm

Adjunctive rifampicin to reduce early mortality from Staphylococcus aureus bacteraemia: the ARREST RCT.

BACKGROUND: Staphylococcus aureus bacteraemia is a common and frequently fatal infection. Adjunctive rifampicin may enhance early S. aureus killing, sterilise infected foci and blood faster, and thereby reduce the risk of dissemination, metastatic infection and death. OBJECTIVES: To determine whether or not adjunctive rifampicin reduces bacteriological (microbiologically confirmed) failure/recurrence or death through 12 weeks from randomisation. Secondary objectives included evaluating the impact of rifampicin on all-cause mortality, clinically defined failure/recurrence or death, toxicity, resistance emergence, and duration of bacteraemia; and assessing the cost-effectiveness of rifampicin. DESIGN: Parallel-group, randomised (1 : 1), blinded, placebo-controlled multicentre trial. SETTING: UK NHS trust hospitals. PARTICIPANTS: Adult inpatients (≥ 18 years) with meticillin-resistant or susceptible S. aureus grown from one or more blood cultures, who had received < 96 hours of antibiotic therapy for the current infection, and without contraindications to rifampicin. INTERVENTIONS: Adjunctive rifampicin (600-900 mg/day, oral or intravenous) or placebo for 14 days in addition to standard antibiotic therapy. Investigators and patients were blinded to trial treatment. Follow-up was for 12 weeks (assessments at 3, 7, 10 and 14 days, weekly until discharge and final assessment at 12 weeks post randomisation). MAIN OUTCOME MEASURES: The primary outcome was all-cause bacteriological (microbiologically confirmed) failure/recurrence or death through 12 weeks from randomisation. RESULTS: Between December 2012 and October 2016, 758 eligible participants from 29 UK hospitals were randomised: 370 to rifampicin and 388 to placebo. The median age was 65 years [interquartile range (IQR) 50-76 years]. A total of 485 (64.0%) infections were community acquired and 132 (17.4%) were nosocomial; 47 (6.2%) were caused by meticillin-resistant S. aureus. A total of 301 (39.7%) participants had an initial deep infection focus. Standard antibiotics were given for a median of 29 days (IQR 18-45 days) and 619 (81.7%) participants received flucloxacillin. By 12 weeks, 62 out of 370 (16.8%) patients taking rifampicin versus 71 out of 388 (18.3%) participants taking the placebo experienced bacteriological (microbiologically confirmed) failure/recurrence or died [absolute risk difference -1.4%, 95% confidence interval (CI) -7.0% to 4.3%; hazard ratio 0.96, 95% CI 0.68 to 1.35; p = 0.81]. There were 4 (1.1%) and 5 (1.3%) bacteriological failures (p = 0.82) in the rifampicin and placebo groups, respectively. There were 3 (0.8%) versus 16 (4.1%) bacteriological recurrences (p = 0.01), and 55 (14.9%) versus 50 (12.9%) deaths without bacteriological failure/recurrence (p = 0.30) in the rifampicin and placebo groups, respectively. Over 12 weeks, there was no evidence of differences in clinically defined failure/recurrence/death (p = 0.84), all-cause mortality (p = 0.60), serious (p = 0.17) or grade 3/4 (p = 0.36) adverse events (AEs). However, 63 (17.0%) participants in the rifampicin group versus 39 (10.1%) participants in the placebo group experienced antibiotic or trial drug-modifying AEs (p = 0.004), and 24 (6.5%) participants in the rifampicin group versus 6 (1.5%) participants in the placebo group experienced drug-interactions (p = 0.0005). Evaluation of the costs and health-related quality-of-life impacts revealed that an episode of S. aureus bacteraemia costs an average of £12,197 over 12 weeks. Rifampicin was estimated to save 10% of episode costs (p = 0.14). After adjustment, the effect of rifampicin on total quality-adjusted life-years (QALYs) was positive (0.004 QALYs), but not statistically significant (standard error 0.004 QALYs). CONCLUSIONS: Adjunctive rifampicin provided no overall benefit over standard antibiotic therapy in adults with S. aureus bacteraemia. FUTURE WORK: Given the substantial mortality, other antibiotic combinations or improved source management should be investigated. TRIAL REGISTRATIONS: Current Controlled Trials ISRCTN37666216, EudraCT 2012-000344-10 and Clinical Trials Authorisation 00316/0243/001. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 22, No. 59. See the NIHR Journals Library website for further project information.NIHR HTA Programm

Culture-level dimensions of social axioms and their correlates across 41 cultures

Leung and colleagues have revealed a five-dimensional structure of social axioms across individuals from five cultural groups. The present research was designed to reveal the culture level factor structure of social axioms and its correlates across 41 nations. An ecological factor analysis on the 60 items of the Social Axioms Survey extracted two factors: Dynamic Externality correlates with value measures tapping collectivism, hierarchy, and conservatism and with national indices indicative of lower social development. Societal Cynicism is less strongly and broadly correlated with previous values measures or other national indices and seems to define a novel cultural syndrome. Its national correlates suggest that it taps the cognitive component of a cultural constellation labeled maleficence, a cultural syndrome associated with a general mistrust of social systems and other people. Discussion focused on the meaning of these national level factors of beliefs and on their relationships with individual level factors of belief derived from the same data set.(undefined