Experiences of Kinship and Connection to Family for Aboriginal and Torres Strait Islander Young Men with Histories of Incarceration

Epidemiological approaches have brought important attention to the issues surrounding the over-incarceration of Aboriginal and Torres Strait Islander young people, and the enormous health and socio-economic disparities they face. An implicit discourse often exists within the construction of this “knowledge”, however, that situates Aboriginal and Torres Strait Islander young people in deficit terms. Using narrative inquiry, a methodological approach congruent with Aboriginal and Torres Strait Islander culture and ways of knowing, we aim to challenge this dominant discourse, via an examination of the narratives of eight Aboriginal Torres Strait Islander young men (aged 19-24 years) involved in the criminal justice system. Our analysis is embedded in understandings of the core role of family and kin in Aboriginal and Torres Strait Islander culture. Experiences of family removal and dislocation were common, as were narratives of striving, often against all odds, to preserve and nurture family connections and kinship ties. We reveal how experiences of ongoing trauma and loss (impacted by the intergenerational effects of colonisation) harmed young men’s ties to kinship systems and family and in doing so deprived them of the very systems needed to sustain a sense of value, purpose and belonging. A commitment by governments to adequately fund and resource solutions that honour and respect the important role family and kin represents in Aboriginal and Torres Strait Islander culture is urgently needed, as are sustainable solutions that address the over-incarceration of Aboriginal and Torres Strait Islander young people that are self-determining and led by their people

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2–4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Lived experiences of incarceration and release for young men with histories of injecting drugs: Challenging taken-for-granted assumptions

This study examined the lived experience of drug use, incarceration and release from prison for 28 young men with histories of injecting drugs. Bacchi’s WPR approach and Rhodes’ Risk Environment framework helped frame results. Findings revealed how criminal justice policies and practices purporting to address “problems” of crime and harmful drug use, in fact acted to produce these very “problems”, and in doing so, exacerbated other harms including further marginalisation of an already vulnerable group

Sexting and young people: a qualitative study

© 2012 Shelley Joy WalkerThis study is one of the first Australian studies to describe the phenomenon of sexting from the perspective of young people. ‘Sexting’, which involves the production and distribution of sexually explicit images via information and communication technologies (ICTs) has led to young people being excluded from friendship groups, moving schools, suffering anxiety and depression, and in extreme cases being charged with the production and distribution of child pornography. There is an absence of published studies undertaken in this area, particularly from an Australian perspective and from the point of view of young people themselves. My study addresses this gap by exploring the meaning of sexting in young people’s lives. It focuses in particular on the nature of sexting, the reasons why young people are involved in the behaviour and potential solutions for addressing harmful consequences. A qualitative methodology involving two phases was used. The first phase involved a focus group and individual interviews with twelve key informant professionals to develop a context that would inform the second phase, which involved individual semi-structured interviews with 33 young people aged 15-20 years (female [n=18]; male [n=15]). Young people were sourced via youth health, recreational and educational settings using purposive snowball sampling. Results were thematically analysed using a grounded theory approach. Key informant findings helped frame interviews with young people, and affirmed that young people’s voices needed to be heard. Many of the views of key informants were also reflected in the views of young people. Findings exposed a number of themes, including in particular, the gendered nature of the behavior. Of particular concern is that young women feel pressured by young men, who feel pressured by each other to be involved in the behaviour; young people observed that our sexualised media culture places pressure on young women and men to conform to gendered stereotypes that influence the behavior of sexting. Conversations with young people highlighted complexities of the phenomenon not revealed previously, including that definitions used in prevalence studies need to represent changes in young people’s use of ICTs. Young people’s views on solutions highlight that education about the implications of sexting is not the only answer, especially given young people’s views on the origins of sexting and what is known about young people and risk taking from a developmental perspective. Both young women and men were concerned about the potential harmful outcomes for those involved in the behavior, with recognition that young people should be involved in the design of solutions. Findings present important implications for future prevention approaches

Selected health behaviors moderate the progression of functional limitations in persons with multiple sclerosis: Eleven years of annual follow-up

BackgroundMultiple sclerosis (MS), a chronic neurological disease typically diagnosed in young adulthood, presents with a wide variety of symptoms, impairments and functional limitations. Given the chronic, unpredictable and long-term nature of this disease, preserving function is essential.ObjectiveThe purpose of this study was to identify psychosocial and behavioral factors that might influence the trajectory of functional limitation through eleven years of longitudinal follow-up of a sample of persons with MS.MethodsParticipants (N = 606) completed measures of health behaviors, related constructs and functional limitations annually over eleven years. Longitudinal measures of functional limitations were analyzed using random-effects regression that allows for study of individual differences in the trajectories of a measure. Using the best fitting quadratic growth model, we tested the within and between-person effects of Nutrition, Interpersonal Relationships, Exercise, Stress Management, Health Responsibilities, Spiritual Growth, Self-rated Health and Barriers, controlling for Age, Year since Diagnosis and Year of Dropout, on Functional Limitations in the 11th year.ResultsAfter adjusting for covariates, higher mean scores for Exercise and Self-rated Health were related to lower levels of Functional Limitations in Year 11. Higher mean scores for Stress Management, Health Responsibilities and Barriers were related to higher levels of Functional Limitations in Year 11. Higher mean Exercise scores and lower mean Health Responsibilities scores were related to slower rates of progression of functional limitations in Year 11.ConclusionFindings suggest that the highly variable trajectory of functional limitations in MS may be extended and shaped through health behavior strategies

Mapping the human genetic architecture of COVID-19

The genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-191,2, host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across 19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases3–7. They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease

Common, low-frequency, rare, and ultra-rare coding variants contribute to COVID-19 severity

The combined impact of common and rare exonic variants in COVID-19 host genetics is currently insufficiently understood. Here, common and rare variants from whole-exome sequencing data of about 4000 SARS-CoV-2-positive individuals were used to define an interpretable machine-learning model for predicting COVID-19 severity. First, variants were converted into separate sets of Boolean features, depending on the absence or the presence of variants in each gene. An ensemble of LASSO logistic regression models was used to identify the most informative Boolean features with respect to the genetic bases of severity. The Boolean features selected by these logistic models were combined into an Integrated PolyGenic Score that offers a synthetic and interpretable index for describing the contribution of host genetics in COVID-19 severity, as demonstrated through testing in several independent cohorts. Selected features belong to ultra-rare, rare, low-frequency, and common variants, including those in linkage disequilibrium with known GWAS loci. Noteworthily, around one quarter of the selected genes are sex-specific. Pathway analysis of the selected genes associated with COVID-19 severity reflected the multi-organ nature of the disease. The proposed model might provide useful information for developing diagnostics and therapeutics, while also being able to guide bedside disease management