A mixed methods study of the relationship between illness perceptions and the cascade genetic screening process in hypertophic cardiomyopathy, and clinical research portfolio

Background: Hypertrophic Cardiomyopathy (HCM) a relatively common inherited cardiac disease, symptoms include breathlessness, palpitations, chest pain and more rarely, sudden cardiac death. Cascade genetic screening where individuals already diagnosed with HCM are tasked with communicating genetic risk to relatives is an increasingly viable means of confirming HCM associated gene carriers and identifying their at-risk relatives, however uptake of such testing is suboptimal. The common-sense model of illness perceptions has frequently been used to understand behaviours linked to health within individuals (Leventhal et al., 1980). Less is understood about how these perceptions may influence communication of health information to others. Aims: The primary aim of the study was to explore whether illness perceptions of those who first undergo genetic testing for the HCM gene mutation predict uptake of cascade genetic screening by at-risk first-degree relatives. Methods: A mixed method, single centre, cross-sectional design was employed. Fifty-seven individuals with HCM undergoing genetic testing completed measures of illness perceptions, closeness to relatives and perceived self-efficacy. Data on uptake of cascade screening by respective first-degree relatives was obtained from the host clinic. Semi-structured interviews were conducted on a sub-group of six individual focusing on those who had low associated illness identity. Transcripts were explored using Thematic Analysis (TA). Results: Overall first-degree relative uptake within the sample was 65%. A linear regression indicated that relatives of individuals who perceived HCM to be a more acute condition were 13% more likely to have undergone genetic screening. Thematic analyses of interview transcripts yielded three superordinate themes: The confusing HCM experience, the reasons for testing and doubts about testing. Conclusions: The findings of this study should be considered with caution due to the limits placed on the analysis as a result of the small sample recruited. However, the findings of the analysis indicating a link between the illness perceptions of the individual tasked with communicating risk to relatives and subsequent relative uptake merits further investigation

Managing Costs and Variability of Security Services

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Do children have a right to do nothing? exploring the place of passive leisure in Australian school age care

In 2021, the Australian Government commissioned a review and update of My Time Our Place, its curriculum framework for School-Age Care services for primary-age children. One update trialled was the introduction of passive leisure. Whilst children’s passive use of leisure time is recognised as a right, it is often problematised and associated with negative health outcomes. This article explores a trial of passive leisure provision. It provides hopeful evidence that passive leisure spaces can be interactive, conversational and restful

High Avidity CD8+ T Cells Efficiently Eliminate Motile HIV-Infected Targets and Execute a Locally Focused Program of Anti-Viral Function

The dissemination of HIV from an initial site of infection is facilitated by motile HIV-infected CD4+ T-cells. However, the impact of infected target cell migration on antigen recognition by HIV-specific CD8+ T-cells is unclear. Using a 3D in vitro model of tissue, we visualized dynamic interactions between HIV-infected or peptide-pulsed CD4+ T-cells and HIV-specific CD8+ T-cells. CTLs engaged motile HIV-infected targets, but ∼50% of targets broke contact and escaped. In contrast, immobilized target cells were readily killed, indicating target motility directly inhibits CD8+ T-cell function. Strong calcium signals occurred in CTLs killing a motile target but calcium signaling was weak or absent in CTLs which permitted target escape. Neutralization of adhesion receptors LFA-1 and CD58 inhibited CD8+ T-cell function within the 3D matrix, demonstrating that efficient motile target lysis as dependent on adhesive engagement of targets. Antigen sensitivity (a convolution of antigen density, TCR avidity and CD8 coreceptor binding) is also critical for target recognition. We modulated this parameter (known as functional avidity but referred to here as “avidity” for the sake of simplicity) by exploiting common HIV escape mutations and measured their impact on CTL function at the single-cell level. Targets pulsed with low avidity mutant antigens frequently escaped while CTLs killed targets bearing high avidity antigen with near-perfect efficiency. CTLs engaged, arrested, and killed an initial target bearing high avidity antigen within minutes, but serial killing was surprisingly rare. CD8 cells remained committed to their initial dead target for hours, accumulating TCR signals that sustained secretion of soluble antiviral factors. These data indicate that high-avidity CD8+ T-cells execute an antiviral program in the precise location where antigen has been sensed: CTL effector functions are spatiotemporally coordinated with an early lytic phase followed by a sustained stationary secretory phase to control local viral infection

Evaluation and application of microsatellites for population identification of Fraser River chinook salmon (Oncorhynchus tshawytscha)

Variation at 13 microsatellite loci was previously surveyed in approximately 7400 chinook salmon (Oncorhynchus tshawytscha) sampled from 50 localities in the Fraser River drainage in southern British Columbia. Evaluation of the utility of the microsatellite variation for population-specific stock identification applications indicated that the accuracy of the stock composition estimates generally improved with an increasing number of loci used in the estimation procedure, but an increase in accuracy was generally marginal after eight loci were used. With 10–14 populations in a simulated fishery sample, the mean error in population-specific estimated stock composition with a 50-popula-tion baseline was <1.4%. Identification of individuals to specific populations was highest for lower Fraser River and lower and North Thompson River populations; an average of 70% of the individual fish were correctly assigned to specific populations. The average error of the estimated percentage for the seven populations present in a coded-wire tag sample was 2% per population. Estimation of stock composition in the lower river commercial net fishery prior to June is of key local fishery management interest. Chinook salmon from the Chilcotin River and Nicola River drainages were important contributors to the early commercial fishery in the lower river because they comprised approximately 50% of the samples from the net fishery prior to mid April

The geographic basis for population structure in Fraser River chinook salmon (Oncorhynchus tshawytscha)

We surveyed variation at 13 microsatellite loci in approximately 7400 chinook salmon sampled from 52 spawning sites in the Fraser River drainage during 1988–98 to examine the spatial and temporal basis of population structure in the watershed. Genetically discrete chinook salmon populations were associated with almost all spawning sites, although gene flow within some tributaries prevented or limited differentiation among spawning groups. The mean FST value over 52 samples and 13 loci surveyed was 0.039. Geographic structuring of populations was apparent: distinct groups were identified in the upper, middle, and lower Fraser River regions, and the north, south, and lower Thompson River regions. The geographically and temporally isolated Birkenhead River population of the lower Fraser region was sufficiently genetically distinctive to be treated as a separate region in a hierarchial analysis of gene diversity. Approximately 95% of genetic variation was contained within populations, and the remainder was accounted for by differentiation among regions (3.1%), among populations within regions (1.3%), and among years within populations (0.5%).Analysis of allelic diversity and private alleles did not support the suggestion that genetically distinctive populations of chinook salmon in the south Thompson were the result of postglacial hybridization of ocean-type and stream-type chinook in the Fraser River drainage. However, the relatively small amount of differentiation among Fraser River chinook salmon populations supports the suggestion that gene flow among genetically distinct groups of postglacial colonizing groups of chinook salmon has occurred, possibly prior to colonization of the Fraser River drainage

The effects of nitroxyl (HNO) on soluble guanylate cyclase activity: interactions at ferrous heme and cysteine thiols

It has been previously proposed that nitric oxide (NO) is the only biologically relevant nitrogen oxide capable of activating the enzyme soluble guanylate cyclase (sGC). However, recent reports implicate HNO as another possible activator of sGC. Herein, we examine the affect of HNO donors on the activity of purified bovine lung sGC and find that, indeed, HNO is capable of activating this enzyme. Like NO, HNO activation appears to occur via interaction with the regulatory ferrous heme on sGC. Somewhat unexpectedly, HNO does not activate the ferric form of the enzyme. Finally, HNO-mediated cysteine thiol modification appears to also affect enzyme activity leading to inhibition. Thus, sGC activity can be regulated by HNO via interactions at both the regulatory heme and cysteine thiols

Development and testing of Indoor Soundscape Questionnaire for evaluating contextual experience in public spaces

An Indoor Soundscape Questionnaire aiming at the evaluation of indoor public sound environments was designed, statistically tested and presented. It was established through initial pilot studies and three main factors under contextual experience variable are established as (1) psychological factors, (2) space usage factors and (3) demographical factors. In addition to the questions on demographical and space usage factors, detailed questions on psychological factors are designed and statistically tested for expectation, perception and reaction categories of the psychological factor. The questionnaire was applied as part of a case study in enclosed library foyer environments to a group of 270 participants through non-experimental survey data sampling. The reliability and validity scores of the Indoor Soundscape Questionnaire were statistically tested and confirmed. Furthermore, statistical tests were used to derive relationships between contextual experience variables of psychological, space usage and demographical factors. Chi-square test of goodness-of-fit results showed statistical significances of demographical and space usage factors with the psychological factors

HIV Care Coordination promotes care re-engagement and viral suppression among people who have been out of HIV medical care: an observational effectiveness study using a surveillance-based contemporaneous comparison group

Background Medical care re-engagement is critical to suppressing viral load and preventing HIV transmission, morbidity and mortality, yet few rigorous intervention studies address this outcome. We assessed the effectiveness of a Ryan White Part A-funded HIV Care Coordination Program relative to ‘usual care,’ for short-term care re-engagement and viral suppression among people without recent HIV medical care. Methods The Care Coordination Program was launched in 2009 at 28 hospitals, health centers, and community-based organizations in New York City. Designed for people with HIV (PWH) experiencing or at risk for poor HIV outcomes, the Care Coordination Program provides long-term, comprehensive medical case management utilizing interdisciplinary teams, structured health education and patient navigation. The intervention was implemented as a safety-net services program, without a designated comparison group. To evaluate it retrospectively, we created an observational, matched cohort of clients and controls. Using the HIV surveillance registry, we identified individuals meeting program eligibility criteria from December 1, 2009 to March 31, 2013 and excluded those dying prior to 12 months of follow-up. We then matched clients to controls on baseline status (lacking evidence of viral suppression, consistently suppressed, inconsistently suppressed, or newly diagnosed in the past 12 months), start of follow-up and propensity score. For this analysis, we limited to those out of care at baseline (defined as having no viral load test in the 12 months pre-enrollment) and still residing within jurisdiction (defined as having a viral load or CD4 test reported to local surveillance and dated within the 12-month follow-up period). Using a GEE model with binary error distribution and logit link, we compared odds of care re-engagement (defined as having ≥ 2 laboratory events ≥ 90 days apart) and viral suppression (defined as having HIV RNA ≤ 200 copies/mL on the most recent viral load test) at 12-month follow-up. Results Among 326 individuals out of care at baseline, 87.2% of clients and 48.2% of controls achieved care re-engagement (Odds Ratio: 4.53; 95%CI 2.66, 7.71); 58.3% of clients and 49.3% of controls achieved viral suppression (Odds Ratio: 2.05; 95%CI 1.30, 3.23). Conclusions HIV Care Coordination shows evidence of effectiveness for care and treatment re-engagement