"It's like your days are empty and yet there's life all around": A mixed methods, multi-site study exploring boredom during and following homelessness.

PURPOSE: To identify experiences of boredom and associations with psychosocial well-being during and following homelessness. METHODS: Using a convergent, mixed-methods explanatory design, we conducted quantitative interviews with 164 participants) (n = 102 unhoused; n = 62 housed following homelessness) using a 92-item protocol involving demographic components and seven standardized measures of psychosocial well-being. A sub-sample (n = 32) was approached to participate in qualitative interviews. Data were analyzed by group (unhoused; housed). Quantitative data were analyzed using descriptive statistics designed to generate insights into boredom, meaningful activity engagement, and their associations with psychosocial well-being during and following homelessness. Qualitative data were analyzed using thematic analysis. Quantitative and qualitative findings were integrated at the stage of discussion. RESULTS: Quantitative analyses revealed small to moderate correlations between boredom and increased hopelessness (rs = .376, p < .01), increased drug use (rs = .194, p < .05), and lowered mental well-being (rs = -.366, p < .01). There were no statistically significant differences between unhoused and housed participants on any standardized measures. Hierarchical regression analyses revealed that housing status was not a significant predictor of boredom or meaningful activity engagement (p>.05). Qualitative interviews revealed profound boredom during and following homelessness imposing negative influences on mental well-being and driving substance use. CONCLUSIONS: Boredom and meaningful activity are important outcomes that require focused attention in services designed to support individuals during and following homelessness. Attention to this construct in future research, practice, and policy has the potential to support the well-being of individuals who experience homelessness, and to contribute to efforts aimed at homelessness prevention.

Effectiveness of Interventions for Meaningful Activity Participation in Homelessness: A Systematic Review.

Background. Meaningful activity participation has been identified as a key outcome of services designed to support individuals during and following homelessness. Little is known about the effectiveness of interventions for promoting this outcome. Purpose. To identify the range and effectiveness of interventions on promoting meaningful activity participation among persons with experiences of homelessness. Method. We conducted a systematic review using the Joanna Briggs Institute methodology following PRISMA guidelines including a critical appraisal and narrative synthesis. Findings. Of 12,343 titles and abstracts screened, we included 12 studies. The authors of the included studies primarily used standardized measures of meaningful activity engagement. Critical appraisal scores ranged from 50.0 to 77.8. The most common interventions evaluated in the included studies were psychosocial interventions (n = 6; 50.0%), followed by case management and housing support interventions (n = 4; 33.3%) and Housing First (n = 2; 16.7%). While several interventions demonstrated effectiveness in promoting meaningful activity participation including psychosocial and case management interventions, Housing First, Critical Time Intervention, and a peer support intervention were found to be ineffective for promoting engagement in meaningful activity. Conclusion. Few intervention studies have been conducted that demonstrate effectiveness for promoting participation in meaningful activity for individuals during and following homelessness. Occupational therapy researchers and practitioners can build on existing evidence by developing and evaluating novel approaches by co-designing interventions in collaboration with persons with experiences of homelessness and service providers.

Region-specific reversal of epidermal planar polarity in the rosette fancy mouse.

The planar cell polarity (PCP) pathway collectively orients cells with respect to a body axis. Hair follicles of the murine epidermis provide a striking readout of PCP activity in their uniform alignment across the skin. Here, we characterize, from the molecular to tissue-scale, PCP establishment in the rosette fancy mouse, a natural variant with posterior-specific whorls in its fur, to understand how epidermal polarity is coordinated across the tissue. We find that rosette hair follicles emerge with reversed orientations specifically in the posterior region, creating a mirror image of epidermal polarity. The rosette trait is associated with a missense mutation in the core PCP gene Fzd6, which alters a consensus site for N-linked glycosylation, inhibiting its membrane localization. Unexpectedly, the Fzd6 trafficking defect does not block asymmetric localization of the other PCP proteins. Rather, the normally uniform axis of PCP asymmetry rotates where the PCP-directed cell movements that orient follicles are reversed, suggesting the PCP axis rotates 180°. Collectively, our multiscale analysis of epidermal polarity reveals PCP patterning can be regionally decoupled to produce posterior whorls in the rosette fancy mouse.

Region-specific reversal of epidermal planar polarity in the fancy rosette mouse.

The planar cell polarity (PCP) pathway collectively orients thousands of cells with respect to a body axis to direct cellular behaviors that are essential for embryonic morphogenesis. Hair follicles of the murine epidermis provide a striking readout of PCP activity in their uniform alignment along the entire skin surface. Here, we characterize, from the molecular to tissue-scale, PCP establishment in the rosette fancy mouse, a natural variant with posterior-specific whorls in its fur, to understand how epidermal polarity is coordinated across the tissue. We find that embryonic hair follicles of rosette mutants emerge with reversed orientations specifically in the posterior region, creating a mirror image of epidermal polarity. The rosette trait is associated with a missense mutation in the core PCP gene Fzd6 , which alters a consensus site for N-linked glycosylation and inhibits its membrane localization. Unexpectedly, this defect in Fzd6 trafficking, observed across the entire dorsal epidermis, does not interfere with the ability of other core PCP proteins to localize asymmetrically. Rather, the normally uniform axis of PCP asymmetry is disrupted and rotated in the posterior region such that polarity is reflected on either side of a transition zone. The result is a reversal of polarized cell movements that orient nascent follicles, specifically in the posterior of the embryo. Collectively, our multiscale analysis of epidermal polarity reveals PCP patterning can be regionally decoupled to produce the unique posterior whorls of the fancy rosette mouse. Summary: Region-specific rotation of the Planar Cell Polarity axis reverses posterior hair follicles in the fancy rosette mouse.

Meaningful Activity, Psychosocial Wellbeing, and Poverty During COVID-19: A Longitudinal Study.

Background: Only a few studies have explored experiences of meaningful activity and associations with psychosocial wellbeing during COVID-19. None reflect a Canadian context or focus on persons living in poverty. Purpose: To identify experiences and associations between meaningful activity and psychosocial wellbeing for persons living in poverty during the first year of COVID-19. Method: We delivered a quantitative survey at three time points during the first year of the pandemic supplemented by qualitative interviews at Time(T) 1 and 1 year later at T3. Findings: One hundred and eight participants completed T1 surveys, and 27 participated in qualitative interviews. Several statistically significant correlations between indices of meaningful activity engagement and psychosocial wellbeing were identified across T1-T3. Meaningful activity decreased from T1-T3 [X2 (2, n = 49) = 9.110, p < .05], with a significant decline from T2-T3 (z = -3.375, p < .001). In T1 qualitative interviews, participants indicated that physical distancing exacerbated exclusion from meaningful activities early in the pandemic. At T3 (1 year later), they described how classist and ableist physical distancing policies layered additional burdens on daily life. Implications: Meaningful activity engagement and psychosocial wellbeing are closely associated and need to be accounted for in the development of pandemic policies that affect persons living in low income. Occupational therapists have a key role in pandemic recovery.

"I can't remember the last time I was comfortable about being home": lived experience perspectives on thriving following homelessness.

PURPOSE: Strategies for preventing and ending homelessness are frequently measured by their effectiveness on indices of tenancy sustainment. To shift this narrative, we conducted research to identify what is needed to "thrive" following homelessness from the perspectives of persons with lived experience in Ontario, Canada. METHODS: Conducted in the context of a community-based participatory research study aimed at informing the development of intervention strategies, we interviewed 46 persons living with mental illness and/or substance use disorder [n = 25 (54.3%) unhoused; n = 21 (45.7%) housed following homelessness] using qualitative interviews. A subsample of 14 participants agreed to engage in photovoice interviews. We analysed these data abductively using thematic analysis informed by health equity and social justice. RESULTS: Participants described experiences of "living in a state of lack" following homelessness. This essence was expressed through four themes: 1) housing as part one of the journey to home; 2) finding and keeping "my people"; 3) meaningful activity as critical for thriving following homelessness; and 4) struggling to access mental health supports in the context of challenging circumstances. CONCLUSIONS: Individuals struggle to thrive following homelessness in the context of insufficient resources. There is a need to build on existing interventions to address outcomes beyond tenancy sustainment.

Clonal replacement sustains long-lived germinal centers primed by respiratory viruses.

Germinal centers (GCs) form in secondary lymphoid organs in response to infection and immunization and are the source of affinity-matured B cells. The duration of GC reactions spans a wide range, and long-lasting GCs (LLGCs) are potentially a source of highly mutated B cells. We show that rather than consisting of continuously evolving B cell clones, LLGCs elicited by influenza virus or SARS-CoV-2 infection in mice are sustained by progressive replacement of founder clones by naive-derived invader B cells that do not detectably bind viral antigens. Rare founder clones that resist replacement for long periods are enriched in clones with heavily mutated immunoglobulins, including some with very high affinity for antigen, that can be recalled by boosting. Our findings reveal underappreciated aspects of the biology of LLGCs generated by respiratory virus infection and identify clonal replacement as a potential constraint on the development of highly mutated antibodies within these structures.

'We stick people in a house and say okay, you're housed. The problem is solved': A qualitative study of service provider and organisational leader perspectives on thriving following homelessness.

Research aimed at identifying and evaluating approaches to homelessness has predominately focused on strategies for supporting tenancy sustainment. Fewer studies focus on strategies for enabling thriving following homelessness, and the perspectives of service providers and organisational leaders (SPOL) on this topic are rare. We conducted this study in the context of a community-based participatory research project in two cities in Ontario, Canada. This research was aimed at identifying the strengths and challenges of existing supports in enabling thriving following homelessness, followed by co-designing a novel intervention alongside persons with lived experience of homelessness (PWLEH) and SPOL. The current study presents the findings of interviews conducted in 2020-2021 with SPOL in organisations serving PWLEH. We interviewed 60 individuals including service providers (n = 38; 63.3%) and organisational leaders (n = 22; 36.7%) using semi-structured qualitative interviews. Interviews were conducted and recorded on Zoom to align with physical distancing protocols associated with the COVID-19 pandemic. Recordings were transcribed verbatim and analysed abductively informed by the lenses of social justice and health equity. The essence of our findings is represented by a quote from a research participant: 'We stick people in a house and say okay, you're housed. The problem is solved'. This essence was expressed through five themes: (1) stuck in a system that prevents thriving, (2) substance use as an important coping strategy that prevents tenancy sustainment and thriving, (3) the critical importance of targeting community integration following homelessness, (4) incorporating peer expertise as imperative and (5) people need to be afforded options in selecting housing and services following homelessness. Our findings indicate that SPOL envision possibilities of thriving following homelessness yet are embedded within a system that often prevents them from supporting individuals who are leaving homelessness to do so. Research, practice and policy implications are discussed.

Flying below the Radar: Psychoactive Drug Use among Young Male Construction Workers in Sydney, Australia.

Background: Globally, there is growing concern regarding workers' illicit drug use and its implications for health and workplace safety. Young workers in male-dominated industries, such as construction, may be more susceptible to illicit drug use, risky drinking and its associated harms.Purpose/objectives: To investigate drug use and perceptions of risk among male construction workers, drawing comparisons between workers under 25 years with older age groups.Methods: Workers in Sydney, Australia (N = 511) completed a survey measuring past year illicit drug and alcohol use, psychological distress and perceptions of drug-related risks to health and safety. Prevalence in the total sample was compared with national estimates, and differences between younger and older survey respondents were examined using logistic regression models.Results: Survey respondents' cocaine, meth/amphetamine and cannabis use was significantly higher than estimates of male employees nationally (OR = 6.60, 3.58, 1.61, respectively). Young workers ≤24 were more likely to frequently use illicit drugs, drink heavily, and report psychological distress than those aged 35+. Workers ≤24 were least likely to perceive that drug use posed high risks to health or safety when compared with 25-34 and 35+ age groups.Conclusions/importance: The findings highlight the high prevalence of illicit drug use amongst young construction workers, representing threats to workplace safety even if used outside work hours. Greater emphasis on potential adverse effects of alcohol and drug use and closer examination of contributory workplace factors are required. These findings have practical implications to inform occupational health and safety programs and interventions in high-risk workplaces.

Exploring the relationship between psychological distress and likelihood of help seeking in construction workers: The role of talking to workmates and knowing how to get help.

BACKGROUND: Mental health problems are prevalent in male-dominated industries such as construction, where suicide rates are higher than the population average and help seeking is typically low. OBJECTIVE: To examine psychological distress in Australian construction workers and its relationship with help seeking via two hypothesised mediators: confidence in knowing how to get help and confidence in talking to workmates about mental health issues. METHODS: Workers (N = 511) completed a survey that assessed psychological distress, likelihood of help seeking, and confidence in knowing how to get help and talking to workmates. Bootstrapped multiple mediation analysis was performed using the PROCESS macro for SPSS. RESULTS: Psychological distress was higher than national estimates and most prevalent in men aged 25-44. Controlling for age and ability to recognise personal signs of mental health problems, psychological distress negatively predicted likelihood of help seeking. This relationship was partially mediated by knowing how to get help and confidence in talking to workmates. CONCLUSIONS: Results highlight the need to redress and mitigate mental health problems among high-risk groups of male workers. It provides useful guidance on multilevel workplace strategies to reduce stigma, enhance confidence and comfort in the process of seeking help and support in construction and other male-dominated industries.

Construction workers' alcohol use, knowledge, perceptions of risk and workplace norms.

INTRODUCTION AND AIMS: Globally, there is growing concern regarding workers' alcohol use and its implications for health, wellbeing and workplace safety. Male-dominated industries are more susceptible to risky alcohol consumption and its associated harms. This paper investigated the patterns, prevalence and predictors of risky drinking among construction workers. DESIGN AND METHODS: Male construction workers (n = 511) completed a survey measuring alcohol-related measures including Alcohol Use Disorders Identification Test - Concise (AUDIT-C), which was compared with population data. Hierarchical multiple regression examined alcohol-related knowledge, perception of risk to workplace safety, psychological distress, job stress, general health, quality of life and workplace alcohol culture variables as predictors of risky drinking. RESULTS: Prevalence of risky drinking was higher than the national average, particularly for younger (<25 years) and mid-aged (45-54 years) workers. One in six construction workers reported workmates being visibly affected by alcohol in the workplace. Key predictors of risky drinking were perception of alcohol-related risks to workplace safety, general health, alcohol knowledge and descriptive norms regarding workmates' alcohol use. DISCUSSION AND CONCLUSIONS: These findings provide useful insights into the patterns and predictors of risky drinking in construction and can inform future preventive programs and interventions in high-risk workplaces. In addition to tailoring programs to both young and mid-aged workers, this work highlights the importance of implementing strategies to increase awareness of risks to workplace safety; and the adoption of norms that inhibit the social acceptability of risky drinking behaviour in the wider workplace.

BRAF testing in advanced colorectal cancer: is it ready for prime time?

Given that KRAS mutant colorectal tumors do not respond to anti-EGFR monoclonal antibodies such as cetuximab or panitumumab, it is now standard that all patients with metastatic colorectal cancer who are candidates for these therapies undergo KRAS testing. BRAF encodes a protein kinase, which is involved in intracellular signaling and cell growth and is a principal downstream effector of KRAS. BRAF is now increasingly being investigated in metastatic colorectal carcinoma. BRAF mutations occur in less than 10-15% of tumors and appear to be poor prognostic markers. However the predictive nature of this biomarker is yet undefined. This article will review the evidence behind both KRAS and BRAF testing in metastatic colorectal cancer.

Thresholds for human detection of patient setup errors in digitally reconstructed portal images of prostate fields.

PURPOSE: Computer-assisted methods to analyze electronic portal images for the presence of treatment setup errors should be studied in controlled experiments before use in the clinical setting. Validation experiments using images that contain known errors usually report the smallest errors that can be detected by the image analysis algorithm. This paper offers human error-detection thresholds as one benchmark for evaluating the smallest errors detected by algorithms. Unfortunately, reliable data are lacking describing human performance. The most rigorous benchmarks for human performance are obtained under conditions that favor error detection. To establish such benchmarks, controlled observer studies were carried out to determine the thresholds of detectability for in-plane and out-of-plane translation and rotation setup errors introduced into digitally reconstructed portal radiographs (DRPRs) of prostate fields. METHODS AND MATERIALS: Seventeen observers comprising radiation oncologists, radiation oncology residents, physicists, and therapy students participated in a two-alternative forced choice experiment involving 378 DRPRs computed using the National Library of Medicine Visible Human data sets. An observer viewed three images at a time displayed on adjacent computer monitors. Each image triplet included a reference digitally reconstructed radiograph displayed on the central monitor and two DRPRs displayed on the flanking monitors. One DRPR was error free. The other DRPR contained a known in-plane or out-of-plane error in the placement of the treatment field over a target region in the pelvis. The range for each type of error was determined from pilot observer studies based on a Probit model for error detection. The smallest errors approached the limit of human visual capability. The observer was told what kind of error was introduced, and was asked to choose the DRPR that contained the error. Observer decisions were recorded and analyzed using repeated-measures analysis of variance. RESULTS: The thresholds of detectability averaged over all observers were approximately 2.5 mm for in-plane translations, 1.6 degrees for in-plane rotations, 1 degrees for out-of-plane rotations, and 8% change in magnification for out-of-plane translations along the central axis. When one inexperienced observer is excluded, the average threshold for change in magnification is 5%. Experienced observers tended to perform better, but differences between groups were not statistically significant. Thresholds were computed as averages over all observers. Because of the broad range of observer capabilities, some detection tasks were too difficult for some observers, leading to missing threshold values in our data analysis. The missing values were excluded from computation of the average thresholds reported above. The effect of the missing values is to bias the average values toward the best human performance. CONCLUSIONS: Under favorable conditions, humans can detect small errors in setup geometry. The thresholds for error detection reported in this study are believed to represent rigorous but reasonable benchmarks that can be incorporated into studies evaluating algorithms for computer-assisted detection of setup errors in electronic portal images.