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Summary: TSPEAR variants cause autosomal recessive ectodermal dysplasia (ARED) 14. The function of TSPEAR is unknown. The clinical features, the mutation spectrum, and the underlying mechanisms of ARED14 are poorly understood. Combining data from new and previously published individuals established that ARED14 is primarily characterized by dental anomalies such as conical tooth cusps and hypodontia, like those seen in individuals with WNT10A-related odontoonychodermal dysplasia. AlphaFold-predicted structure-based analysis showed that most of the pathogenic TSPEAR missense variants likely destabilize the β-propeller of the protein. Analysis of 100000 Genomes Project (100KGP) data revealed multiple founder TSPEAR variants across different populations. Mutational and recombination clock analyses demonstrated that non-Finnish European founder variants likely originated around the end of the last ice age, a period of major climatic transition. Analysis of gnomAD data showed that the non-Finnish European population TSPEAR gene-carrier rate is ∼1/140, making it one of the commonest AREDs. Phylogenetic and AlphaFold structural analyses showed that TSPEAR is an ortholog of drosophila Closca, an extracellular matrix-dependent signaling regulator. We, therefore, hypothesized that TSPEAR could have a role in enamel knot, a structure that coordinates patterning of developing tooth cusps. Analysis of mouse single-cell RNA sequencing (scRNA-seq) data revealed highly restricted expression of Tspear in clusters representing enamel knots. A tspeara−/−;tspearb−/− double-knockout zebrafish model recapitulated the clinical features of ARED14 and fin regeneration abnormalities of wnt10a knockout fish, thus suggesting interaction between tspear and wnt10a. In summary, we provide insights into the role of TSPEAR in ectodermal development and the evolutionary history, epidemiology, mechanisms, and consequences of its loss of function variants.

Most car buyers use some form of financing to purchase a vehicle, and almost half of all California borrowers carry some amount of automobile debt. While automobile loans enable lower-income households—who might otherwise be priced out of vehicle ownership—to make payments over time, this debt can significantly strain household budgets. The COVID-19 pandemic elevated the importance of owning a private vehicle as concerns over viral person-to-person transmission made traveling by car an even more attractive compared to communal transportation (e.g., public transit). Moreover, a host of pandemic-related services, including testing and vaccination, were either only or best accessible by car.To better understand how COVID-19 impacted car ownership, we explored whether automobile loans (and in turn debt) in California—particularly in communities of color where workers were more likely to work outside of the home—increased during the pandemic. We drew on a one-percent sample of the University of California Consumer Credit Panel, a dataset from Experian of every loan and borrower in California.

Automobiles can greatly enhance access to employment and other opportunities. However, many households do not have the resources to purchase a vehicle outright and must rely on automobile loans. This increases the total cost of owning a vehicle, particularly for non-white consumers who may have to pay higher purchase prices and/or higher interest rates due to discriminatory lending practices. The effects of high household debt—of which automobile loans are one component—are magnified in lower income neighborhoods, leaving residents with fewer resources to invest in the local economy. Our team used the University of California Consumer Credit Panel, a dataset from Experian, which tracks every loan and borrower in California, to examine how and why automobile loan debt varies from place to place in the state and its consequences. We specifically tested whether total automobile debt, debt burden (the ratio of automobile debt to income), and automobile loan delinquencies in 2021 disproportionately affected non-white neighborhoods.

To investigate the relationship of predisposing, enabling, need, and immigration-related factors to tele-mental health services utilization among California adults, we conducted a secondary analysis of two waves of the California Health Interview Survey (CHIS) collected between 2015 and 2018 (N = 78,345). A series of logistic regression models were conducted to examine correlates and predictors to tele-mental health services use. Approximately 1.3% reported the use of tele-mental health services. Overall, health insurance status, severe psychological distress, perceived need for mental health services, and identifying as Asian, remained strong predictors for tele-mental health service use. When accounting for all factors, we found that being a non-citizen was associated with lower odds of tele-mental health service use (AOR = 0.47, CI = 0.26, 0.87, p

Most U.S. metropolitan areas developed alongside the automobile, producing neighborhoods of relatively low density. Consequently, access to opportunities in these neighborhoods is predicated on having an automobile, yet many households do not have the resources to purchase one outright, relying on automobile loans to spread out the purchase price. While automobile loans can enable automobile ownership, they also significantly increase the vehicle purchase price, particularly for non-white consumers subject to discriminatory lending practices.In this study, we rely on data from the University of California Consumer Credit Panel from Experian to examine the determinants and geography of automobile debt and its consequences in California, testing whether various automobile debt measures disproportionately affect non-white neighborhoods.We find that, controlling for other factors associated with automobile lending including income, Black and Latino/a neighborhoods have higher total automobile debt, debt burdens (debt relative to income), and automobile loan delinquency rates. In particular, Latino/a neighborhoods shoulder significant automobile debt, while borrowers in Black neighborhoods have the highest delinquency rates. Factors associated with lower total automobile debt and automobile debt burden include better credit ratings, higher residential densities, urban locations, and proximity to rail stations.The findings underscore the importance of policies to offset the costs of automobile ownership and access. As part of this, policymakers should adopt and enforce fair lending rules to combat discriminatory and predatory practices and facilitate access to high-quality financial institutions and products in communities of color.

COVID-19 altered travel patterns in the U.S. Studies have analyzed the effect of the pandemic on travel mode, including working from home, but few have focused on automobile ownership—a relationship with potentially long-term consequences for accessibility, household budgets and debt, and policy efforts to meet climate goals.To understand the association between the pandemic and automobile ownership, we rely on a unique credit panel dataset from Experian and examine three different automobile loan-related outcome measures: annualized growth rate of new automobile loan balances, average new loan size, and the number of new loans. We focus specifically on changes across loans in neighborhoods by race/ethnicity, hypothesizing larger increases in automobile debt in Black and Latino/a neighborhoods, where workers are less likely to be able to telework. The annualized growth rate of new automobile loans increased during the pandemic across all neighborhoods by race/ethnicity, increasing most rapidly in Latino/a neighborhoods. Controlling for other factors, loan size increased similarly across neighborhoods by race/ethnicity. The increase in automobile lending in Latino/a neighborhoods, therefore, likely was explained by a significant uptick in the number of new loans.The growth in automobile lending during the pandemic was potentially prompted by pandemic-induced changes in the need for automobiles and facilitated by an expanded social safety net. As the pandemic and its various forms of public financial assistance recede, the findings underscore the importance of ongoing assistance in enabling automobile ownership or shared access among households with limited means whose livelihoods depend on the access that vehicles provide.

Daily vehicle travel collapsed with the onset of the COVID-19 pandemic in early 2020 but largely bounced back by late 2021. The pandemic caused dramatic changes to working, schooling, shopping, and leisure activities, and to the travel associated with them. Several of these changes have so far proven enduring. So, while overall vehicle travel had largely returned to pre-pandemic levels by late 2021, the underlying drivers of this travel have likely changed.To examine one element of this issue, we analyzed whether patterns of daily trip-making shifted temporally between the fall of 2019 and 2021 in the Greater Los Angeles megaregion. We used location-based service data to examine vehicle trip originations for each hour of the day at the U.S. census block group level in October 2019 and October 2021. We observed notable shifts in the timing of post-pandemic PM peak travel, so we examined changes in the ratio of mid-week trips originating in the early afternoon (12–3:59 PM) and the late afternoon/early evening (4–7:59 PM).We found a clear shift in the temporal distribution of PM trip-making, with relatively more late PM peak period trip-making prior to the pandemic, and more early PM peak trip-making in 2021. The peak afternoon/evening trip-making hour shifted from 5–5:59 PM to 3–3:59 PM. We also found that afternoon/evening trip-making in each year is largely explained by three workplace-area/school-area factors: (1) the number of schoolchildren in a block group (earlier); (2) block groups with large shares of potential remote workers (earlier), and (3) block groups with large shares of low-wage jobs and workers of color (later, except for Black workers in 2021). We found the earlier shift in PM peak travel between pre- and late-pandemic periods to be explained most by (1) higher shares of potential remote workers and (2) higher shares of low-wage jobs and workers of color. These findings suggest that the rise of working from home has likely led to a shift in PM peak travel earlier in the afternoon when school chauffeuring trips are most common. This is especially true for low-income workers and workers of color.

Meta-analyses and international large-scale assessments (ILSA) are key sources for informing educational policy, research, and practice. While many critical research questions could be addressed by drawing evidence from both of these sources, meta-analysts seldom integrate ILSAs, and current integration practices lack methodological guidance. The aim of this methodological review is therefore to synthesize and illustrate the principles and practices of including ILSA data in meta-analyses. Specifically, we (a) review four ILSA data inclusion approaches (analytic steps, potential, challenges); (b) examine whether and how existing meta-analyses included ILSA data; and (c) provide a hands-on illustrative example of how to implement the four approaches. Seeing the need for meta-analyses on educational inequalities, we situated the review and illustration in the context of gender differences and socioeconomic gaps in student achievement. Ultimately, we outline the steps meta-analysts could take to utilize the potential and address the challenges of ILSA data for meta-analyses in education.

BACKGROUND: Effective interventions are needed to address suicide risk following discharge from the hospital emergency department or inpatient setting. Studies that examine follow-up contact methods show promise, but little is known about how follow-up programs are implemented in the real world and who is benefitting. The purpose of this formative evaluation and analysis was to gain insight about the usefulness and value of a partnered suicide prevention follow-up program (academic medical center emergency department partnered with a regional suicide prevention center) from the standpoint of psychiatry resident physicians providing direct care and suicide prevention center crisis counselors making follow-up outreach telephone calls to patients. METHODS: A qualitative thematic analysis was conducted with focus group data from a convenience sample of psychiatry residents who performed consultations in the emergency department setting and counselors at the suicide prevention center crisis follow-up program. Focus group sessions, using semi-structured question guides, were completed at each participant groups workplace. Grounded theory techniques were used to guide coding and analytic theme development. RESULTS: Analyses resulted in four overarching themes: valuing the programs utility and benefit to patients, desiring to understand what happens from emergency department discharge to program follow-up, having uncertainty about which patients would benefit from the program, and brainstorming to improve the referral process. Psychiatry residents appreciated the option of an active referral service (one that attempts to actively engage a patient after discharge through outreach), while suicide prevention crisis counselors valued their ability to offer a free and immediate service that had potential for fostering meaningful relationships. Both participant groups desired a better understanding of their partners program operations, a uniform and smooth referral process, and awareness of who may or may not benefit from program services. CONCLUSION: Results revealed the need for improved communication and implementation, such as expanded inter-agency contacts, consistent provider training, more documentation of the requirements and rules, a consistent message about program logistics for patients, and coordination between the program elements.

The flavoenzyme nicotine oxidoreductase (NicA2) is a promising injectable treatment to aid in the cessation of smoking, a behavior responsible for one in ten deaths worldwide. NicA2 acts by degrading nicotine in the bloodstream before it reaches the brain. Clinical use of NicA2 is limited by its poor catalytic activity in the absence of its natural electron acceptor CycN. Without CycN, NicA2 is instead oxidized slowly by dioxygen (O2), necessitating unfeasibly large doses in a therapeutic setting. Here, we report a genetic selection strategy that directly links CycN-independent activity of NicA2 to growth of Pseudomonas putida S16. This selection enabled us to evolve NicA2 variants with substantial improvement in their rate of oxidation by O2. The encoded mutations cluster around a putative O2 tunnel, increasing flexibility and accessibility to O2 in this region. These mutations further confer desirable clinical properties. A variant form of NicA2 is tenfold more effective than the wild type at degrading nicotine in the bloodstream of rats.

Since challenging behaviors are present in classrooms, it is imperative to understand how teachers acknowledge and respond to these unwanted actions within their schools. The overarching purpose of this study is to understand schoolteachers' perspectives on the causes of students' unwanted behaviors and their responses in the classroom. The study was also designed to explore schoolteachers' perspectives on the relationship between the students' challenging behavior and disability. A total of 1,056 Ghanaian (n=502) and Namibian (n=554) schoolteachers were surveyed to identify their understanding of causes of their students' challenging behavior and how they addressed the behaviors. Results of the study indicated that the teachers perceived challenging behavior as related to discipline and not disability. Most teachers also believed that both home and school environmental factors influenced challenging behavior. Furthermore, most schoolteachers from both countries did not believe that physical punishment was an effective way to address challenging behavior and did not support its use in schools. Teacher training programs in both countries need to emphasize the use of evidence-based proactive strategies to address students' challenging behavior in order to minimize the use of punitive strategies such as physical punishment.

BackgroundCommunity input is crucial for identifying characteristics necessary for equitable, sustainable community-academic partnerships (CAPs). A November 2021 conference, honoring the late Dr. Loretta Jones and the Community-Partnered Participatory Research (CPPR) model, was held to gather input for designing a learning institute for community members as co-equal partners with academics in research, program, and policy initiatives. This created an opportunity to explore attendees' perspectives on challenges and opportunities related to CAPs with special focus on promoting equity.MethodsInstitutional Review Board approval was obtained. Five break-out discussion group sessions were conducted in November 2021 co-facilitated by both an academic and a community leader. After consent, discussions were recorded and transcribed. An iterative procedure for collaborative-group-thematic-analysis was developed. The six-phase process included rigorous coding, discussion, comparison of data with data, and development and refinement of themes and subthemes.ResultsA total of 38 racial-ethnically diverse participants volunteered from the total conference audience of 62 community and academic partners from various sectors including community-based organizations, health care, social services, academia, or policy within Los Angeles County. Analysis led to development of three themes: Being cautious with the extractive tendency of academia and the need for anti-racism within CAPs; Leveraging community power to resist the top-down lens of academia; and bridging two worlds through an equitably structured table.DiscussionParticipants described optimism about the future uses of CPPR to enhance CAPs, and the need to address barriers to equitable partnerships owing to unequal social contexts and entrenched power dynamics. Implications include addressing racism, evaluating financial equity in partnerships to promote accountability, and mentoring community leaders to promote equity.ConclusionUse of a "community lens" for developing sustainable, equitable CAPs is crucial to promote accountability and to responsibly implement authentic CPPR.

California and its regional and local governments have invested heavily in public transit over the past half-century to provide an alternative to driving, ease traffic congestion, reduce emissions, slow climate change, steer new development, and provide mobility for those without. As a result, bus service has improved and expanded, and many parts of the state’s metropolitan areas are now served by rail transit.Yet today, many of the state’s transit systems are struggling operationally and financially. Ridership began eroding in the half-decade leading up to 2020 and plummeted at the start of the COVID-19 pandemic. Three federal pandemic relief bills provided a critical lifeline to keep struggling transit systems afloat early on, but these funds are running out. Meanwhile, operating costs have risen, ridership and fare revenues have only partially returned, and some transit systems face “fiscal cliffs,” where they will need substantial new infusions of funding, substantial cuts in costs and service, or some combination of the two.Against this backdrop, this report examines the current state of California transit finance: why ridership and fare revenues are down and their prospects for recovery; what lessons the successful federal relief bills provide; why commuter-oriented systems are struggling financially much more than those that primarily service transit-reliant riders; and what the financial managers at transit systems have done to cope with this turbulent time and how they see their future financial prospects.

The COVID-19 pandemic occasioned significant financial distress and uncertainty for many U.S. transit operators. In the face of this crisis, the federal government provided substantial supplemental operating support. To understand how this fiscal turmoil and relief have affected U.S. transit systems, we conducted two nationwide surveys of transit agency staff in 2020 and 2021-2022. While pandemic-induced financial shortfalls affected service in 2020, with capital projects delayed too, these effects became much more muted by 2021/2022. Most systems reported moderate to substantial increases in federal funding during the pandemic, more so than other funding categories. However, nearly half foresee financial shortfalls once federal relief funding expires. Agencies with higher pre-pandemic ridership and farebox recovery are particularly affected by fare revenue losses and more likely to anticipate shortfalls. In the near term, difficulty hiring and retaining front-line workers was a pressing concern, while very few had plans to maintain pandemic fare suspensions.

Resettled refugees from Muslim-majority countries are underrepresented in research and meeting their mental health needs remains a challenge for countries of resettlement. In this integrative review, we synthesize community-based mental health interventions using an ecological framework. Eleven relevant studies were identified using PubMed and PsychInfo database. Most interventions focus on micro-system level factors like promoting integration and social connections suggest improvement of outcomes including depression, anxiety, and psychological distress. Studies suggest how mental health programs addressing psychosocial wellbeing improves outcomes across ecological levels through: (1) early screening upon resettlement; (2) education and raising awareness of mental health; and (3) engagement of refugees in local community social support systems. Largely qualitative studies suggest benefits of engagement and education program for refugees, but there is a need for high quality, rigorous mental health intervention studies with resettled refugees with explicit attention to equitable and collaborative partnerships across multiple sectors in the community.