Aberrant DNA repair reveals a vulnerability in histone H3.3-mutant brain tumors.

Pediatric high-grade gliomas (pHGG) are devastating and incurable brain tumors with recurrent mutations in histone H3.3. These mutations promote oncogenesis by dysregulating gene expression through alterations of histone modifications. We identify aberrant DNA repair as an independent mechanism, which fosters genome instability in H3.3 mutant pHGG, and opens new therapeutic options. The two most frequent H3.3 mutations in pHGG, K27M and G34R, drive aberrant repair of replication-associated damage by non-homologous end joining (NHEJ). Aberrant NHEJ is mediated by the DNA repair enzyme polynucleotide kinase 3'-phosphatase (PNKP), which shows increased association with mutant H3.3 at damaged replication forks. PNKP sustains the proliferation of cells bearing H3.3 mutations, thus conferring a molecular vulnerability, specific to mutant cells, with potential for therapeutic targeting.

Shifting gears: Creating equity informed leaders for effective learning health systems.

Leadership is vital to a well-functioning and effective health system. This importance was underscored during the COVID-19 pandemic. As disparities in infection and mortality rates became pronounced, greater calls for equity-informed healthcare emerged. These calls led some leaders to use the Learning Health System (LHS) approach to quickly transform research into healthcare practice to mitigate inequities causing these rates. The LHS is a relatively new framework informed by many within and outside health systems, supported by decision-makers and financial arrangements and encouraged by a culture that fosters quick learning and improvements. Although studies indicate the LHS can enhance patients' health outcomes, scarce literature exists on health leaders' use and incorporation of equity into the LHS. This article begins addressing this gap by examining how equity can be incorporated into LHS activities and discussing ways leaders can ensure equity is considered and achieved in rapid learning cycles.

Sociopolitical control as a mediator between ethnic identity and social support on 30-day drug use among black girls.

While Black girls have lower rates of drug use, they face worse health and wellbeing consequences associated with drug use. Understanding which strengths-based factors serve as buffers to limit adverse outcomes related to drug use among Black girls is essential for prevention. This study investigated the mediating role of sociopolitical control on drug use among Black girls (n = 340). Using path analysis, models were tested to include the variables of interest. Sociopolitical control (e.g. leadership competency and policy control) significantly mediated the relationship between ethnic identity and social support on drug use. Implications from this study may consider bolstering empowerment-based strategies in drug use prevention for Black girls.

The brief sense of community scale: Testing dimensionality and measurement invariance by gender among Hispanic/Latinx youth.

Psychological sense of community is defined as feelings of belongingness and a shared belief that community members will meet one another's needs. Psychological sense of community has four dimensions: membership, influence, needs fulfillment, and emotional connection. In this study, multigroup confirmatory factor analysis was used to examine the first and second-order factor structure of the brief sense of community scale (BSCS) between male and female Hispanic/Latinx adolescents from an urban community (N = 947). To help validate the BSCS model, the second-order factor model was tested with regression to predict the measures of intrapersonal psychological empowerment and ethnic identity, as constructs conceptually related to psychological sense of community. Findings support that: (1) psychological sense of community can be measured through the BSCS and as a four-factor model among Hispanic/Latinx youth, supporting McMillan and Chavis's (1986) original theoretical discussions; (2) while no differences between genders were present at the model-level, there was path-specific variation; and (3) intrapersonal psychological empowerment and ethnic identity were associated with psychological sense of community.

Measuring Intrapersonal Psychological Empowerment and Ethnic Identity: Highlighting Strengths of Urban Black Girls.

Limited research has examined intrapersonal psychological empowerment (PE) among Black girls solely. This study aims to fill a gap in empowerment literature by examining the factor structure of the Sociopolitical Control Scale for Youth (SPCS-Y) among Black girls (N = 377) between the ages of 14-17 years old. We also examine the association with ethnic identity as a conceptually related variable. Structural equation modeling (SEM) was used to examine the factorial validity of the abbreviated, eight-item SPCS-Y among Black girls. Results support the two-dimensional factor structure of the abbreviated SPCS-Y among Black girls, as well as the association intrapersonal PE has with ethnic identity. Findings provide preliminary support for the empirical and theoretical relationship between intrapersonal PE and ethnic identity among Black girls.

What happens when we ask? A phenomenological focus group on HIV prevention and sexual health education among emancipated foster care youth.

Youth of color who have recently been emancipated from foster care are among the most vulnerable group at risk for having poor sexual health outcomes. It is essential for researchers to understand how emancipated foster care youth receive messages about safe sex and HIV/STI prevention in order to tailor health promotion activities for this group. This study presents a strengths-based view of emancipated foster care youth of color who developed an empowering, arts-based campaign to prevent HIV in their community using Youth Participatory Action Research (Y-PAR) methods. The project was led by 10 emancipated foster care youth who participated in two focus groups that centered on understanding their knowledge of HIV. Five major themes emerged from the focus group. Implications for researchers include incorporating safe spaces for youth to develop ideas that can result in empowering activities relating to prevention.

Intrapersonal psychological empowerment profiles on ethnic identity, social support, and lifetime drug use among Hispanic adolescent girls.

The abbreviated Sociopolitical Control Scale for Youth (SPCS-Y) factor structure, used to measure intrapersonal psychological empowerment, was tested among a sample of Hispanic adolescent girls (N = 490). Confirmatory factor analysis and latent class analyses were conducted, and five distinct cluster groups emerged. Multivariate analysis of covariance was used to examine conceptually related variables and support the two-factor structure and validity of the scale. Participants with higher levels of intrapersonal psychological empowerment also had high social support, ethnic identity, and lower levels of alcohol and drug use. Findings support the use of the scale on Hispanic adolescent girls and contribute to alcohol and drug use prevention research.

The impact of psychiatric and medical comorbidity on the risk of mortality: a population-based analysis.

BACKGROUND: As life expectancy increases, more people have chronic psychiatric and medical health disorders. Comorbidity may increase the risk of premature mortality, an important challenge for health service delivery. METHODS: Population-based cohort study in Ontario, Canada of all 11 246 910 residents aged ⩾16 and <105 on 1 April 2012 and alive on 31 March 2014. Secondary analyses included subjects having common medical disorders in 10 separate cohorts. Exposures were psychiatric morbidity categories identified using aggregated diagnosis groups (ADGs) from Johns Hopkins Adjusted Clinical Groups software® (v10.0); ADG 25: Persistent/Recurrent unstable conditions; e.g. acute schizophrenic episode, major depressive disorder (recurrent episode), ADG 24: Persistent/Recurrent stable conditions; e.g. depressive disorder, paranoid personality disorder, ADG 23: Time-limited/minor conditions; e.g. adjustment reaction with brief depressive reaction. The outcome was all-cause mortality (April 2014-March 2016). RESULTS: Over 2 years' follow-up, there were 188 014 deaths (1.7%). ADG 25 conferred an almost threefold excess mortality after adjustment compared to having no psychiatric morbidity [adjusted hazard ratio 2.94 (95% CI 2.91-2.98, p < 0.0001)]. Adjusted hazard ratios for ADG 24 and ADG 23 were 1.12 (95% CI 1.11-1.14, p < 0.0001) and 1.31 (95% CI 1.26-1.36, p < 0.0001). In all 10 medical disorder cohorts, ADG 25 carried significantly greater mortality risk compared to no psychiatric comorbidity. CONCLUSIONS: Psychiatric disorders, particularly those graded persistent/recurrent and unstable, were associated with excess mortality in the whole population, and in the medical disorder cohorts examined. Future research should examine whether service design accounting for psychiatric disorder comorbidity improves outcomes across the spectrum of medical disorders.

Applying the principles of adaptive leadership to person-centred care for people with complex care needs: Considerations for care providers, patients, caregivers and organizations.

BACKGROUND: Health systems in many countries see person-centred care as a critical component of high-quality care but many struggle to operationalize it in practice. We argue that models such as adaptive leadership can be a critical lever to support person-centred care, particularly for people who have multiple complex care needs. OBJECTIVE: To reflect on two concepts: person-centred care and adaptive leadership and share how adaptive leadership can advance person-centred care at the front-line care delivery level and the organizational level. FINDINGS: The defining feature of adaptive leadership is the separation of technical solutions (ie applying existing knowledge and techniques to problems) from adaptive solutions (ie requiring shifts in how people work together, not just what they do). Addressing adaptive challenges requires identifying key assumptions that may limit motivations for change and the behaviours influenced by these assumptions. Thus, effective care for patients, particularly those with multiple complex care needs, often entails helping care providers and patients to examine their relationships and behaviours not just identifying technical solutions. Addressing adaptive challenges also requires a supportive and enabling organizational context. We provide illustrative examples of how adaptive leadership principles can be applied at both the front line of care and the organization level in advancing person-centred care delivery. CONCLUSIONS: Advancing person-centred care at both the clinical and organizational levels requires a growth mindset, a willingness to try (and fail) and try again, comfort in being uncomfortable and a commitment to figure things out, in partnership, in iterative ways. Patients, caregivers, care providers and organizational leaders all need to be adaptive leaders in this endeavour.

Rad5 dysregulation drives hyperactive recombination at replication forks resulting in cisplatin sensitivity and genome instability.

The postreplication repair gene, HLTF, is often amplified and overexpressed in cancer. Here we model HLTF dysregulation through the functionally conserved Saccharomyces cerevisiae ortholog, RAD5. Genetic interaction profiling and landscape enrichment analysis of RAD5 overexpression (RAD5OE) reveals requirements for genes involved in recombination, crossover resolution, and DNA replication. While RAD5OE and rad5Δ both cause cisplatin sensitivity and share many genetic interactions, RAD5OE specifically requires crossover resolving genes and drives recombination in a region of repetitive DNA. Remarkably, RAD5OE induced recombination does not require other post-replication repair pathway members, or the PCNA modification sites involved in regulation of this pathway. Instead, the RAD5OE phenotype depends on a conserved domain necessary for binding 3' DNA ends. Analysis of DNA replication intermediates supports a model in which dysregulated Rad5 causes aberrant template switching at replication forks. The direct effect of Rad5 on replication forks in vivo, increased recombination, and cisplatin sensitivity predicts similar consequences for dysregulated HLTF in cancer.

A Spatial Analysis of Alcohol Outlet Density Type, Abandoned Properties, and Police Calls on Aggravated Assault Rates in a Northeastern U.S. City.

Background: Community-based research and prevention scholarship has shown a growing interest in examining the impact of the ecological structure of neighborhoods on community violence. Ecological structures such as higher numbers of alcohol outlets and abandoned/vacant properties in geographically dense, poor, and socially isolated communities are critically important to consider. Further, disadvantaged urban communities are burdened by greater police presence with limited or no abatement in crime or violence. Purpose: Using Geographic Information Systems (GIS) mapping, spatial analysis techniques, and a negative binomial regression analyses, this study investigated the relationships between alcohol outlet density consisting of license C (i.e., combined on and off premises establishments) and license D (i.e., off premises establishments such as liquor stores), abandoned properties, and police calls to service on aggravated assault rates in a Northeastern United States urban city. Results: Negative binomial regression analysis results showed that license C alcohol outlet density count (IRR = 1.36, 95% CI = 1.08, 2.11), license D alcohol outlet density count (IRR = 1.13, 95% CI = 1.01, 1.30), abandoned property count (IRR = 1.28, 95% CI = 1.01, 2.01), and police call to service counts (IRR = 1.24, 95% CI = 1.01, 1.50) were positively associated with aggravated assault rates. Analyses controlled for census data characteristics. Conclusions: The link between alcohol outlet density and violent crime has been established in public health research. However, this study represents an important contribution in recognizing the unique relationships between license C and license D alcohol outlet density, abandoned properties, and police calls to service with aggravated assaults in an urban neighborhood. Conclusions are drawn for policy and practice.

Measuring Youth Empowerment: An Item Response Theory Analysis of the Sociopolitical Control Scale for Youth.

Sociopolitical control (SPC) has been identified as a key element of the intrapersonal component of psychological empowerment. The Sociopolitical Control Scale (SPCS) is a widely used measure and has been modified for use among youth (SPCS-Y). In light of the emerging interest in SPC among youth within community-based research, this study applied item response theory (IRT) to examine the psychometric properties of the SPCS-Y and to explore a brief version. Data were collected between 2006 and 2013 from a convenience sample of high school students (N = 1,808), located in a midsized, economically disadvantaged urban community in the northeastern United States. Findings indicate that the two subscales, leadership competence, and policy control, were unidimensional and items functioned well. Most items functioned particularly well at low and moderate levels of the construct, but a few were able to capture higher levels of the construct. Based on our IRT analyses of the performance of items on the subscales, we selected items to create a brief version of the SPCS-Y (BSPCS-Y) and performed structural equation modeling for further examination. Results provide empirical evidence to support the reliability and validity of the SPCS-Y and suggest a brief version based on high-performing items is possible.

Testing the Factor Structure of the Brief Sense of Community Scale among Black Girls and the Relationship with Ethnic Identity, Empowerment and Social Support.

Research on Psychological Sense of Community (SOC) among Black girls are limited due to lack of validated measures for this group. Using confirmatory factor analysis (CFA), the first and second-order factor structure of the Brief Sense of Community Scale (BSCS) used to measure Psychological SOC was examined using a sample of Black girls from an urban community (N = 340). Using a regression-based approach, the second-order five-factor model of the BSCS was also examined with intrapersonal psychological empowerment (PE), social support, and ethnic identity as conceptually related variables. Findings support that: (1) psychological SOC can be conceptualized and measured through four dimensions among Black girls; and (2) intrapersonal PE, social support, and ethnic identity were significantly associated with SOC.

The Mediating Role of Ethnic Identity and Social Justice Orientation Between Community Civic Participation, Psychological Sense of Community, and Dimensions of Psychological Empowerment Among Adolescents of Color.

There is an emerging interest in studying social action and civic engagement as a part of the developmental process. Studies among youth of color indicate that empowerment has been associated with well-being, a critical perspective, and in combating social oppression. These studies also show that civic involvement and awareness of social justice issues are associated with positive developmental outcomes including empowerment. The range of predictors and outcomes related to empowerment have been insufficiently explored. This study used structural equation modeling path analysis techniques to examine the association community civic participation and psychological sense of community have with intrapersonal and cognitive psychological empowerment, through both ethnic identity and social justice orientation among urban youth of color (N =383; 53.1% Female; 75% Hispanic; 50.6% were 13 and 15 years of age). Findings illustrate that greater community civic participation and psychological sense of community are associated with both intrapersonal and cognitive psychological empowerment, through both ethnic identity and a social justice orientation; however, with some noted variations. Ethnic identity and social justice orientation mediated community civic participation and psychological sense of community and both intrapersonal and cognitive psychological empowerment. Implications put forward for community youth-workers and community programming.

Campylobacter pinnipediorum subsp. caledonicus and C. pinnipediorum subsp. pinnipediorum recovered from abscesses in pinnipeds.

Campylobacter pinnipediorum was described recently for isolates recovered from pinnipeds. The novel species was further split into 2 subspecies based on host and geography, with C. pinnipediorum subsp. pinnipediorum recovered from otariid seals in California (USA) and C. pinnipediorum subsp. caledonicus recovered from phocid seals in Scotland. We report details of the infections of 7 pinnipeds from which C. pinnipediorum was isolated: C. pinnipediorum subsp. caledonicus was isolated from 2 harbour seals Phoca vitulina and a single grey seal Halichoerus grypus, and C. pinnipediorum subsp. pinnipediorum was isolated from California sea lions Zalophus californianus. Six of the isolates were recovered from samples collected at post-mortem investigation. In 2 of the Scottish seals and in 3 of the California seals, C. pinnipediorum was the sole bacterial isolate recovered from abscesses present and suggests they may have resulted from conspecific or intraspecific bite wounds.

A Spatial Analysis of Alcohol Outlet Density and Abandoned Properties on Violent Crime in Paterson New Jersey.

Alcohol outlet density (AOD) and abandoned or vacant properties in under-served urban communities has received increased attention and has been linked to community violence. While previous research has examined the AOD and violent crime association, less research has investigated the relationship between abandoned properties and violent crime. Those studies that are present examining the AOD-abandoned properties-violent crime link have been plagued by flaws that include statistical weaknesses and aggregated datasets that investigated larger units such as states or countries. The present study, using Geographic Information Systems (GIS) mapping, spatial analysis techniques, and a regression-based approach examines the association between AOD and abandoned properties on violent crime, controlling for demographic characteristics, in Paterson, New Jersey. Results provide some evidence on the association between AOD and abandoned properties on violent crime, drawing conclusions for policy and practice.

Increasing Viral Hepatitis Knowledge Among Urban Ethnic Minority Youth: Findings from a Community Based Prevention Intervention.

Viral hepatitis (VH) knowledge among youth is understudied in the United States. There has been a rise in VH cases in the U.S. in the wake of the opioid epidemic. Innovative approaches to preventing the infection are needed especially in urban communities. This study presents preliminary findings from a community-based HIV/AIDS, substance abuse, and VH prevention education intervention for ethnic minority youth in a northeastern urban community. We aimed to evaluate VH knowledge and factors associated with knowledge. Participants in the study completed a baseline survey followed by an exit survey measuring VH knowledge after the intervention. The survey was completed by 691 individuals. Logistic regression analyses were conducted and indicated that there was a significant increase (82.3%) in VH knowledge among youth who participated in the intervention. The development and implementation of VH knowledge interventions can be crucial in alleviating the rise of VH infections in the U.S.

Contextualizing negative sense of community and disconnection among urban youth of color: "Community We ain't got that".

We explore the experiences of urban youth of color, as well as perceptions, of feeling disconnected and having an overall negative sense of community (SOC). Drawing on data from 11 focus groups, youth (N = 59) describe their communities and lived experiences. We document several themes put forward through the lens of SOC and community connection that highlight perceived lack of membership, needs fulfillment, influence, and overall emotional connection to their community. Unpacking youth's perceptions of their community, we suggest that-in the face of such realities-community-based organizations, such as those the youth find themselves in, aid in creating connectedness and help heal youth from the effects of social conditions experienced daily.

Exposure to gangs in low-income urban communities and substance use among Hispanic youth.

A third of Hispanic youth live below the poverty line, making them vulnerable for exposure to gangs, substances, and violence, all of which have been associated with substance use. The aim of the present study was to test the link between these variables, using a multiple mediation model. Results suggest that the relationship between gang exposure and adolescent substance use was mediated by both access to substances and exposure to violence. Findings provide insight into how gang exposure impacts outcomes for low-income youth. Implications for prevention and policy are discussed.

Understanding the Influence of Sexual Risk Taking, Ethnic Identity, and Family and Peer Support on School Importance Among Hispanic Adolescents.

Despite the broader academic gains experienced by Hispanic students, who represent the largest minority group in the United States, they remain the least educated of all major ethnic groups, and our understanding of their academic needs and strengths remains woefully inadequate. Therefore, this study examined the risk (e.g., sexual risk taking) and protective factors (e.g., family support, supportive peer networks, and ethnic identity) associated with school importance among Hispanic teens (N = 587) residing in a high-risk, resource poor urban community and the ways in which these relationships vary between adolescent males (46.5%) and adolescent females (53.5%). Schools that are able to harness the numerous assets embedded within the Hispanic community are well positioned to create learning environments that are encouraging, are culturally responsive, and can potentially reduce risk involvement that may interfere with valuing the role of school importance. Implications for school-based personnel are discussed.