Pre-existing virus-specific CD8+ T-cells provide protection against pneumovirus-induced disease in mice

Pneumoviruses such as pneumonia virus of mice (PVM), bovine respiratory syncytial virus (bRSV) or human (h)RSV are closely related pneumoviruses that cause severe respiratory disease in their respective hosts. It is well-known that T-cell responses are essential in pneumovirus clearance, but pneumovirus-specific T-cell responses also are important mediators of severe immunopathology. In this study we determined whether memory- or pre-existing, transferred virus-specific CD8 + T-cells provide protection against PVM-induced disease. We show that during infection with a sublethal dose of PVM, both natural killer (NK) cells and CD8 + T-cells expand relatively late. Induction of CD8 + T-cell memory against a single CD8 + T-cell epitope, by dendritic cell (DC)-peptide immunization, leads to partial protection against PVM challenge and prevents Th2 differentiation of PVM-induced CD4 T-cells. In addition, adoptively transferred PVM-specific CD8 + T-cells, covering the entire PVM-specific CD8 + T-cell repertoire, provide partial protection from PVM-induced disease. From these data we infer that antigen-specific memory CD8 + T-cells offer significant protection to PVM-induced disease. Thus, CD8 + T-cells, despite being a major cause of PVM-associated pathology during primary infection, may offer promising targets of a protective pneumovirus vaccine

Cosmetic outcomes and quality of life in children with cardiac implantable electronic devices

BackgroundAxillary implant location is an alternative implant location in patients for cardiac implantable electronic devices (CIEDs) for the purposes of improved cosmetic outcome. The impact from the patient’s perspective is unknown. The purpose of this study was to compare scar perception scores and quality of life (QOL) in pediatric patients with axillary CIED implant location versus the standard infraclavicular approach.MethodsThis is a multicenter prospective study conducted at eight pediatric centers and it includes patients aged from 8 to 18 years with a CIED. Patients with prior sternotomy were excluded. Scar perception and QOL outcomes were compared between the infraclavicular and axillary implant locations.ResultsA total of 141 patients (83 implantable cardioverter defibrillator [ICD]/58 pacemakers) were included, 55 with an axillary device and 86 with an infraclavicular device. Patients with an ICD in the axillary position had better perception of scar appearance and consciousness. Patients in the axillary group reported, on average, a total Pediatric QOL Inventory score that was 6 (1, 11) units higher than the infraclavicular group, after adjusting for sex and race (P = 0.02).ConclusionsQOL is significantly improved in axillary in comparison to the infraclavicular CIED position, regardless of device type. Scar perception is improved in patients with ICD in the axillary position.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147032/1/pace13522.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/147032/2/pace13522_am.pd

Towards a new paradigm of care: the International Declaration on Youth Mental Health.

A recent and growing body of evidence on young people\u27s mental health has pointed to the need for an international response to the increasing and concerning rates of mental ill-health among young people.[1, 2] The periods of adolescence and emerging adulthood[3] are considered the peak periods for the onset of mental ill-health[4] with 75% of all adult diagnoses of mental ill-health having had an onset before the age of 25 years.[5] In an era when the physical health of young people has never been better,[6] their psychological and mental health has never been worse.[7] This leaves young people vulnerable to developing potentially intractable and enduring mental health difficulties with the inevitable personal, familial, social and vocational consequences that accompany the experience of mental ill-health.[4, 8] In spite of growing concerns about young people\u27s mental health, service provision for young people remains largely inadequate and unsuited to their needs. A number of systemic factors can be implicated in insufficient and unsuitable mental health service provision for young people. Internationally, there has been an endemic failure to invest in mental health across the lifespan with an average global spend on mental health of less than $US3 per capita per year.[9] This global underinvestment brings with it particular challenges in relation to the level of priority afforded to youth mental health and the concurrent commitment needed to respond to the scale of young people\u27s mental health needs. Even in developed countries where mental health services exist, there are widespread problems with services targeting young people. Primary care and other front line community agencies can struggle to respond to high levels of need, often with little support from specialist mental health services. Specialist mental health services have traditionally followed a paediatric-adult split, with child and adolescent services offering intervention until the largely arbitrary ages of 16 or 18 years and adult services taking all young people 18 years and older.[1] In many instances, there have been gaps in service provision between the ages of 16 and 18 years.[10] This has resulted in many young people being unable to access specialist mental health support during these critical years along with high rates of attrition and dissatisfaction by young people during this transitional period.[11, 12] With a recognition that, in many sociocultural contexts, the transition from adolescence to adulthood is a variable one that spans a period from the mid-teens to the mid- to late-20s,[13] both young people and youth mental health advocates have called for a reorganization of mental health services to mirror this extended developmental period for young people.[2] Not surprisingly, there has been a trend of poor help seeking and engagement by young people in mental health services.[14, 15] A key challenge remains in supporting young people to reach out for help when they need it and early evidence suggests that factors such as ease of access, the physical environment, location, atmosphere, branding and peer influence can promote help seeking among young people.[12] It must be noted, however, that even when services are youth friendly and appropriate to their needs, individual and psychological factors strongly influence help-seeking behaviour among young people experiencing emotional or psychological distress.[16, 17] From both an economic[18] and a human impact perspective, there is a strong rationale to invest in efforts to tackle the reality of mental ill-health among the youth population.[2] Efforts to establish a new youth mental health paradigm have already begun and are gaining momentum internationally, reflected most recently in the establishment of a new International Association for Youth Mental Health (http://www.iaymh.org). The first International Youth Mental Health Conference was held in Melbourne, Australia, in 2010 and the second is being held in 2013 in Brighton, the UK (http://www.iaymh2013.com). Those involved in the youth mental health movement recognize that positively impacting on young people\u27s mental health trajectories requires transformative change. Along with a need for early promotion, detection and intervention, stemming the tide of mental ill-health among young people requires a fundamental change in how we think about young people and their mental health. It demands that we challenge traditional approaches to service development and delivery and replace them with approaches that are inclusive and empowering for young people and their families. Young people and their families need to be involved in designing and implementing more creative, responsive, accessible and youth-friendly mental health services that have the capacity to meet their needs

COMPUTER SIMULATIONS OF POSSIBLE FUTURES FOR TWO FLOCKS OF WHOOPING CRANES

We conducted computer simulations using the program VORTEX (version 7) to project population sizes, growth rates, genetic diversity, and probabilities of extinction over the next 100 years for 2 flocks of whooping cranes (Grus americana), the Aransas/Wood Buffalo population and the experimental Florida population. Standard runs based on best estimates of demographic. genetic, and environmental parameter values were used as a baseline to which several alternative scenarios were compared. Results generally supported the conclusion of the earlier Population Viability Assessment (Mirande et al. 1991) that the AransaslWood Buffalo population will continue to grow steadily with less than a 1 % probability of extinction. It was noted, however, that a combination of negative factors such as shrinking habitat and increased probabilities of catastrophes accompanied by increased mortality rates could put this population at risk. Results for the Florida population were less optimistic. The standard run produced a population growth rate (r) of only 0.0026 for the next 100 years, and this shifted down to -0.0001 over a 200-year time frame. Adult mortality in this flock would have to be about 20% lower than the predicted value (10%) in order to raise growth rates to above r = 0.02. Amount and duration of supplementation of the Florida flock had minimal impacts on the long-tenn growth rate of the flock. It is the enduring rates of mortality, breeding, and disease risk that will have major effects on this population. For example, if disease risks tum out to be greater than the best-estimate scenario, this population could face a relatively high risk of extinction (17%). The formula for success in Florida is lower adult mortality, lower age of first breeding, lower disease risk, and higher productivity than the best-guess estimates. Fortunately, there are some potential management interventions (e.g., predator control, vaccines and health monitoring, selective introductions to balance the sex ratio of the flock) that may be able to push the odds in favor of success

Impact of an Early Invasive Strategy versus Conservative Strategy for Unstable Angina and Non-ST Elevation Acute Coronary Syndrome in Patients with Chronic Kidney Disease: A Systematic Review.

BACKGROUND: Clinical practice guidelines support an early invasive approach after NSTE-ACS in patients with chronic kidney disease (CKD). There is no direct randomised controlled trial evidence in the CKD population, and whether the benefit of an early invasive approach is maintained across the spectrum of severity of CKD remains controversial. METHODS: We conducted a systematic review to evaluate the association between an early invasive approach and all-cause mortality in patients with CKD. We searched MEDLINE and EMBASE (1990-May 2015) and article reference lists. Data describing study design, participants, invasive management strategies, renal function, all-cause mortality and risk of bias were extracted. RESULTS: 3,861 potentially relevant studies were identified. Ten studies, representing data on 147,908 individuals with NSTE-ACS met the inclusion criteria. Qualitative heterogeneity in the definitions of early invasive approach, comparison groups and renal dysfunction existed. Meta-analysis of the RCT derived and observational data were generally supportive of an early invasive approach in CKD (RR0.76 (95% CI 0.49-1.17) and RR0.50 (95%CI 0.42-0.59) respectively). Meta-analysis of the observational studies demonstrated a large degree of heterogeneity (I2 79%) driven in part by study size and heterogeneity across various kidney function levels. CONCLUSIONS: The observational data support that an early invasive approach after NSTE-ACS confers a survival benefit in those with early-moderate CKD. Local opportunities for quality improvement should be sought. Those with severe CKD and the dialysis population are high risk and under-studied. Novel and inclusive approaches for CKD and dialysis patients in cardiovascular clinical trials are needed