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BackgroundPatients with primary and secondary antibody deficiency are vulnerable to COVID-19 and demonstrate diminished responses following two-dose SARS-CoV-2 vaccine schedules. Third primary vaccinations have been deployed to enhance their humoral and cellular immunity.ObjectivesTo determine the immunogenicity of the third primary SARS-CoV-2 immunisation in a heterogeneous cohort of patients with antibody deficiency.MethodsParticipants enrolled in the COV-AD study were sampled before and after their third vaccine dose. Serological and cellular responses were determined using ELISA, live-virus neutralisation and ELISPOT assays.ResultsFollowing a two-dose schedule, 100% of healthy controls mounted a serological response to SARS-CoV-2 vaccination, however, 38.6% of individuals with antibody deficiency remained seronegative. A third primary SARS-CoV-2 vaccine significantly increased anti-spike glycoprotein antibody seroprevalence from 61.4% to 76.0%, the magnitude of the antibody response, its neutralising capacity and induced seroconversion in individuals who were seronegative after two vaccine doses. Vaccine-induced serological responses were broadly cross-reactive against the SARS-CoV-2 B.1.1.529 variant of concern, however, seroprevalence and antibody levels remained significantly lower than healthy controls. No differences in serological responses were observed between individuals who received AstraZeneca ChAdOx1 nCoV-19 and Pfizer BioNTech 162b2 during their initial two-dose vaccine schedule. SARS-CoV-2 infection-naive participants who had received a heterologous vaccine as a third dose were significantly more likely to have a detectable T cell response following their third vaccine dose (61.5% vs 11.1%).ConclusionThese data support the widespread use of third primary immunisations to enhance humoral immunity against SARS-CoV-2 in individuals with antibody deficiency.

Artificial Intelligence has shown paradigmatic success in defeating world champions in strategy games. However, the same programming tactics are not a reasonable approach to creative and ostensibly emotional artistic endeavors such as music composition. Here we review key examples of current creative music generating AIs, noting both their progress and limitations. We propose that these limitations are rooted in current AIs lack of thoroughly embodied, interoceptive processes associated with the emotional component of music perception and production. We examine some current music-generating machines that appear to be minimally addressing this issue by appealing to something akin to interoceptive processes. To conclude, we argue that a successful music-making AI requires both the generative capacities at which current AIs are constantly progressing, and thoroughly embodied, interoceptive processes which more closely resemble the processes underlying human emotions.

We evaluated the effects of behavioral skills training on improving participant implementation of functional communication training with multiple schedules when working with a confederate. Behavioral skills training produced mastery-level responding for all six participants who required training, providing the first empirically supported training for this functional communication training approach. Next, we assessed durability during training challenges with (a) procedural changes to the original protocol, (b) a novel confederate with different discriminative stimuli and reinforcers, and (c) relapsed confederate destructive behavior. Training effects degraded at least once for all participants and in 62% of training challenges, although continuing to expose the participant to the challenging situations or providing postsession booster training resolved the degradation in most cases. We discuss these findings in relation to their clinical implications and directions for future research.

Hate crimes and racist incidents are occurring with alarming and increasing frequency on college and university campuses. As colleges work to reduce racist incidents on campus, there is still a need to prepare students to respond to racism when it occurs. When students are prepared to respond to racist incidents, they tend to have better mental health. We draw on prior literature to examine whether learning about critical race theory (CRT) and receiving CRT-informed mentoring--as embedded in an undergraduate research experience program--related to four-year college students' self-assessed ability to respond to racism. Specifically, we propose and test a conceptual model to examine the benefits of participating in an undergraduate research experience program that required students to learn about CRT and receiving CRT-informed mentorship. Consistent with prior literature on undergraduate research experience programs, we found that the intervention positively related to students' sense of self-efficacy and science identity, but it did not have an independent, direct relationship with self-assessed ability to respond to racism. However, the intervention indirectly supports students' preparedness to respond to racism through its positive relationship with self-efficacy. As state legislatures around the country work to ban CRT, this paper offers empirical evidence that embedding CRT in university programs can support student development in multiple related ways.

Bridging Mental Health and Education (BRIDGE) is an evidence-based model for embedding teacher consultation and coaching activities into school-based mental health clinicians' regular workflow. Here we describe the process of adapting BRIDGE in partnership with a large urban school district and a local managed care organization during a large-scale implementation effort. We also report the feasibility and perceived effectiveness of the adapted training and consultation model as reported by clinicians in one school year. Over 93% of trained clinicians (n = 75) initiated coaching sessions with assigned teachers. Eighty-five percent of coaching sessions were completed as scheduled (n = 505 of 592). After the completion of coaching visits, clinicians attended bi-weekly virtual group sessions for two months. Ninety percent of virtual group sessions were completed as scheduled. Clinicians indicated high levels of satisfaction and high likelihood of using BRIDGE in future. Additionally, clinicians' self-reported knowledge of BRIDGE practices and their comfort with training others in these evidence-based classroom practices improved from pre- to post- training and coaching. Expert coaches indicated that clinicians' knowledge of BRIDGE strategies, commitment to BRIDGE consultation, and likelihood of continuing to use BRIDGE strategies were high. These findings suggest that the adapted BRIDGE model is feasible and was perceived to be effective. We share lessons learned related to community-partnered, school intervention adaptation and implementation.

Public schools are a major provider of mental health services for children in the US. Mental and behavioral health services range from universal programming to individualized clinical supports to address student needs. These services in schools are delivered by various professionals including non-teaching and teaching school personnel, school-employed clinicians, and/or contracted community mental health partners. Provision of mental health services requires complex coordination of providers across disciplines, although few professionals have training in multidisciplinary collaboration strategies. Attention to team processes, such as delineating team members' roles, improving communication, and identifying collaboration strategies, may impact the effectiveness of evidence-based mental health service provision in real world settings. One intervention, Team Strategies and Tools to Enhance Performance and Patient Safety (TeamSTEPPS), has been used in healthcare with positive outcomes and has been adapted to educational settings. The current paper describes the community-partnered subsequent adaptation of TeamSTEPPS for schools. Needs assessment interviews identified challenges, successes, and goals for student mental health. Overarching themes extracted from interviews include limited resources at multiple levels (e.g., financial support, time, and personnel), communication challenges, and poor role clarity. A community advisory board provided guidance during the adaptation and implementation planning process. Adaptations to the intervention included tailoring the intervention to the school context and the development of flexible training plans. In addition, individualized implementation plans were developed with each school partner to mitigate foreseeable barriers to rolling-out TeamSTEPPS. Our team is currently piloting the adapted TeamSTEPPS intervention and implementation strategies in partnership with three school districts.

Background: Despite historical and contemporary trauma, American Indian and Alaska Native (AIAN; Indigenous) communities responded with resilience to the COVID-19 pandemic. However, AIANs experienced disproportionate rates of infection, hospitalization, death, and reduced life expectancy. School closures exacerbated disparities, leading to learning loss, economic instability, and mental health challenges among AIAN youth. Methods: The Project SafeSchools cohort study employed a comprehensive longitudinal convergent mixed-methods approach, integrating community-based participatory research principles. The study enrolled Navajo Nation caregivers whose children were eligible to attend local reservation-based schools. We conducted an analysis of caregiver self-report baseline data collected between August 2021 and May 2022. Results: A total of 242 caregivers completed at least part of the baseline assessment and were included in data analysis. Caregivers were primarily female (88.7%), non-Hispanic (97%), and Indigenous (97%). Most caregivers were in their late 30s (mean age 38), with varying educational backgrounds and employment statuses. Children were evenly split between males and females and distributed across different age groups. Most children attended school at baseline in various formats, including in-person, hybrid, and online-only settings. Caregivers reported a range of psychosocial and behavioral risks, including general mental distress, depressive symptoms, and anxiety for themselves and their children. Furthermore, caregivers and children exhibited various protective factors, such as strong cultural identity, resilience, and academic self-efficacy. Conclusions: This study highlights the higher rates of mental health distress among participating caregivers and children compared to national averages. Despite these challenges, cultural protective factors remained strong and should guide future crisis response efforts.

During the ongoing global pandemic, faculty, staff and administrators at colleges and universities experienced an increase in meetings using web-based platforms. Challenges were identified related to the changes from face-to-face to web-based meetings, including internet connectivity, inadequate technology and distractions in the online environment, which led to questions about how meetings that use web-based platforms may contribute to overall stress and well-being during the pandemic. The research related to the use of web-based meeting platforms is limited. However, some anecdotal evidence suggests that impacts from web-based meeting platforms could include frustration, sleep issues and fatigue, which contribute to overall well-being. The purpose of this study was to determine if a relationship exists between a number of potentially related web-based meeting factors including the frequency and length of the meetings and comfort level with the platform and overall well-being. This study involved (N = 164) male, female and nonbinary participants over 18 years of age who worked as tenured, tenure-track, or nontenure track faculty, staff and administrators at colleges/universities in the United States during the global pandemic. The participants were recruited via both social media and email and were provided with a link to the survey tool, which included demographic and web-based meeting questions (e.g., frequency, length, and comfort) along with scales to measure perceived stress, subjective well-being, mental fatigue and sleep quality. The current study did not find a relationship between the frequency of meetings and overall well-being (p = 0.294). However, statistically significant relationships were found between meeting length and overall well-being (p = 0.003) and between comfort with the web-based meeting platform and overall well-being (p = 0.030). Based on the findings of this study, meeting organizers may consider scheduling meetings for less than two hours and providing training to ensure participants are proficient in the web-based meeting platform in order to support overall well-being.

The development of secondary bacterial infections in COVID-19 patients has been associated with increased mortality and worse clinical outcomes. Consequently, many patients have received empirical antibiotic therapies with the potential to further exacerbate an ongoing antimicrobial resistance crisis. The pandemic has seen a rise in the use of procalcitonin testing to guide antimicrobial prescribing, although its value remains elusive. This single-centre retrospective study sought to analyse the efficacy of procalcitonin in identifying secondary infections in COVID-19 patients and evaluate the proportion of patients prescribed antibiotics to those with confirmed secondary infection. Inclusion criteria comprised patients admitted to the Grange University Hospital intensive care unit with SARS-CoV-2 infection throughout the second and third waves of the pandemic. Data collected included daily inflammatory biomarkers, antimicrobial prescriptions, and microbiologically proven secondary infections. There was no statistically significant difference between PCT, WBC, or CRP values in those with an infection versus those without. A total of 57.02% of patients had a confirmed secondary infection, with 80.2% prescribed antibiotics in Wave 2, compared to 44.07% with confirmed infection and 52.1% prescribed antibiotics in Wave 3. In conclusion, procalcitonin values failed to indicate the emergence of critical care-acquired infection in COVID-19 patients.

Abstract Background Family planning (FP) has the potential to improve maternal and child health outcomes and to reduce poverty in sub-Saharan Africa. However, substantial unmet need for modern contraceptive methods (MCMs) persists in this region. Current literature highlights multi-level barriers, including socio-cultural norms that discourage the use of MCMs. This paper explores women’s choices and decision-making around MCM use and examines whether integrating FP services with childhood immunisations influenced women’s perceptions of, and decision to use, an MCM. Methods 94 semi-structured interviews and 21 focus group discussions with women, health providers, and community members (N = 253) were conducted in health facilities and outreach clinics where an intervention was delivering integrated FP and childhood immunisation services in Benin, Ethiopia, Kenya, Malawi and Uganda. Data were coded using Nvivo software and an analytical framework was developed to support interpretative and thematic analyses on women’s decision-making about MCM use. Results Most women shared the reproductive desire to space or limit births because of the perceived benefits of improved health and welfare for themselves and for their children, including the economic advantages. For some, choices about MCM use were restricted because of wider societal influences. Women’s decision to use MCMs was driven by their reproductive desires, but for some that was stymied by fears of side effects, community stigma, and disapproving husbands, which led to clandestine MCM use. Health providers acknowledged that women understood the benefits of using MCMs, but highlighted that the wider socio-cultural norms of their community often contributed to a reluctance to use them. Integration of FP and childhood immunisation services provided repeat opportunities for health providers to counter misinformation and it improved access to MCMs, including for women who needed to use them covertly. Conclusions Some women chose to use MCMs without the approval of their husbands, and/or despite cultural norms, because of the perceived health and economic benefits for themselves and for their families, and because they lived with the consequences of short birth intervals and large families. Integrated FP and childhood immunisation services expanded women’s choices about MCM use and created opportunities for women to make decisions autonomously.

Abstract Background Family planning (FP) can lengthen birth intervals and potentially reduce the risk of foetal death, low birthweight, prematurity, and being small for gestational age. Effective FP is most easily achieved through access to and acceptability of modern contraceptive methods (MCMs). This study aimed to identify mechanisms of acceptability and the contexts in which they are triggered and to generate theories to improve the selection and implementation of effective interventions by studying an intervention integrating FP with childhood immunisation services. Methods Qualitative interpretative synthesis of findings from realist evaluations of FP interventions in five African countries was guided by an analytical framework. Empirical mechanisms of acceptability were identified from semi-structured interviews and focus group discussions with key stakeholders (N = 253). The context in which these mechanisms were triggered was also defined. Empirical mechanisms of acceptability were matched to constructs of a theoretical framework of acceptability. Context-acceptability theories (CATs) were developed, which summarised constructs of acceptability triggered for specific actors in specified contexts. Examples of interventions that may be used to trigger acceptability for these actors were described. Results Seven CATs were developed for contexts with strong beliefs in religious values and with powerful religious leaders, a traditional desire for large families, stigmatisation of MCM use, male partners who are non-accepting of FP, and rumours or experiences of MCM side effects. Acceptability mechanisms included alignment with values and beliefs without requiring compromise, actors’ certainty about their ability to avoid harm and make the intervention work, and understanding the intervention and how it works. Additionally, acceptability by one group of actors was found to alter the context, triggering acceptability mechanisms amongst others. Conclusions This study demonstrated the value of embedding realist approaches within implementation research. CATs are transferable theories that answer the question: given the context, what construct of acceptability does an intervention need to trigger, or more simply, what intervention do we need to apply here to achieve our outcomes? CATs facilitate transfer of interventions across geographies within defined contexts.

Abstract Exploring the role of changing climates in human evolution is currently impeded by a scarcity of climatic information at the same temporal scale as the human behaviors documented in archaeological sites. This is mainly caused by high uncertainties in the chronometric dates used to correlate long-term climatic records with archaeological deposits. One solution is to generate climatic data directly from archaeological materials representing human behavior. Here we use oxygen isotope measurements of Bos/Bison tooth enamel to reconstruct summer and winter temperatures in the Late Pleistocene when Neandertals were using the site of La Ferrassie. Our results indicate that, despite the generally cold conditions of the broader period and despite direct evidence for cold features in certain sediments at the site, Neandertals used the site predominantly when climatic conditions were mild, similar to conditions in modern day France. We suggest that due to millennial scale climate variability, the periods of human activity and their climatic characteristics may not be representative of average conditions inferred from chronological correlations with long-term climatic records. These results highlight the importance of using direct routes, such as the high-resolution archives in tooth enamel from anthropogenically accumulated faunal assemblages, to establish climatic conditions at a human scale.

This study investigated the effect of ACEs and COVID-19 on grit and whether this effect is mediated by mindfulness. Although current scholarship has found that adverse childhood experiences (ACEs) have harmful consequences to individuals across the life span, less is known about the relationship between ACEs and grit. Grit is predictive of educational success and subjective wellbeing. A cross-sectional online survey administered to junior and senior students from 12 universities spread across China was conducted from September 20, 2020 to October 5, 2020. The universities were selected from geographically diverse regions of China to ensure a diverse sample. We received 1,871 completed responses from 2,229 invited students. The survey response rate was 83.9%. The results indicated that ACEs had significantly negative effects on grit, while mindfulness had significantly positive effects on grit. Once controlling for level of mindfulness, the effects of ACEs on grit largely reduced and became insignificant. The findings of this research indicate that mindfulness has a significant mediational effect on the relation between ACEs and grit and call for mindfulness-based interventions for enhancing grit for the population at risks.

Abstract Understanding the types and magnitude of human‐caused mortality is essential for maintaining viable large carnivore populations. We used a database of cause‐specific mortality to examine how hunting regulations and landscape configurations influenced human‐caused mortality of North American gray wolves (Canis lupus). Our dataset included 21 studies that monitored the fates of 3564 wolves and reported 1442 mortalities. Human‐caused mortality accounted for 61% of mortality overall, with 23% due to illegal harvest, 16% due to legal harvest, and 12% the result of management removal. The overall proportion of anthropogenic wolf mortality was lowest in areas with an open hunting season compared to areas with a closed hunting season or mixed hunting regulations, suggesting that harvest mortality was neither fully additive nor compensatory. Proportion of mortality from management removal was reduced in areas with an open hunting season, suggesting that legal harvest may reduce human‐wolf conflicts or alternatively that areas with legal harvest have less potential for management removals (e.g., less livestock depredation). Proportion of natural habitat was negatively correlated with the proportion of anthropogenic and illegal harvest mortality. Additionally, the proportion of mortality due to illegal harvest increased with greater natural habitat fragmentation. The observed association between large patches of natural habitat and reductions in several sources of anthropogenic wolf mortality reiterate the importance of habitat preservation to maintain wolf populations. Furthermore, effective management of wolf populations via implementation of harvest may reduce conflict with humans. Effective wolf conservation will depend on holistic strategies that integrate ecological and socioeconomic factors to facilitate their long‐term coexistence with humans.

The food and package delivery workforce in China has grown substantially in the past decade. However, delivery drivers face volatile and stressful work conditions, which can give rise to high turnover and burnout. Past research has indicated that job demands and resources (JD-R) significantly predict burnout. Scholars have also found evidence that mindfulness may be a protective factor against negative outcomes like burnout. Using data collected from 240 food and package delivery drivers in Beijing, China, we examined the effects of JD-R on burnout and whether these relations were moderated by mindfulness. Estimates produced by regression analyses indicated that job demands (JD) have significantly positive effects on burnout (β = 0.33), while job resources (JR) have a significant negative effect on burnout (β = −0.32). Mindfulness significantly moderated the effects of JD and JR on burnout (β = −1.64 and − 1.30, respectively). Results suggest that mindfulness is a protective factor for delivery drivers. Practice and policy implications are discussed.

BACKGROUND: Community health workers (CHWs) can support patient engagement in care for a variety of health conditions, including HIV. This paper reports on the experiences of HIV clinics and health departments that integrated CHWs into their health systems as part of a capacity-building initiative to address HIV-related disparities in the United States. METHODS: Semi-structured interviews were conducted with key informants (n = 14) in two Ryan White HIV/AIDS program jurisdictions: Mississippi (jurisdiction covers the entire state) and the city of New Orleans, Louisiana. This work was part of a larger evaluation of an initiative that used a Learning Collaborative model to facilitate the implementation of evidence-informed interventions to address HIV care continuum gaps in four jurisdictions. The two jurisdictions that focused on integrating CHWs into HIV care clinics and support service agencies were selected for this sub-analysis. Interview participants included HIV clinic leaders and staff, health department leaders, and other Learning Collaborative leaders. Interview transcripts were coded and analyzed for themes related to the acceptability, feasibility, and perceived impact of CHW integration. RESULTS: Overall, participants expressed interest in having support from CHWs at HIV clinics and service agencies to assist with patient retention and engagement efforts. However, there were challenges integrating CHWs into existing systems (e.g., gaining access to electronic health records, changing policies to conduct home visits, and clarifying roles and scope of work). Negotiating contracts and accessing funding for CHW positions presented major challenges that often contributed to turnover and conflicts around scope of practice. When health departments leveraged existing funding streams to support CHW positions, the clinics and agencies where the CHWs worked had limited flexibility over the hiring process. CONCLUSIONS: Our findings reinforce the value and acceptability of CHWs as part of the workforce in HIV clinical and support service settings; however, integrating CHWs into clinics and service agencies required effort. Training the CHWs was not sufficient; other staff and clinicians had to understand the role of CHWs to facilitate their integration into health systems. Resources are needed to support organizations in incorporating CHWs effectively, and long-term, flexible sources of funding are necessary for these positions.

Biomedical research and clinical practice are in the midst of a transition toward significantly increased use of artificial intelligence (AI) and machine learning (ML) methods. These advances promise to enable qualitatively deeper insight into complex challenges formerly beyond the reach of analytic methods and human intuition while placing increased demands on ethical and explainable artificial intelligence (XAI), given the opaque nature of many deep learning methods. The U.S. National Institutes of Health (NIH) has initiated a significant research and development program, Bridge2AI, aimed at producing new "flagship" datasets designed to support AI/ML analysis of complex biomedical challenges, elucidate best practices, develop tools and standards in AI/ML data science, and disseminate these datasets, tools, and methods broadly to the biomedical community. An essential set of concepts to be developed and disseminated in this program along with the data and tools produced are criteria for AI-readiness of data, including critical considerations for XAI and ethical, legal, and social implications (ELSI) of AI technologies. NIH Bridge to Artificial Intelligence (Bridge2AI) Standards Working Group members prepared this article to present methods for assessing the AI-readiness of biomedical data and the data standards perspectives and criteria we have developed throughout this program. While the field is rapidly evolving, these criteria are foundational for scientific rigor and the ethical design and application of biomedical AI methods.

Identifying pan-tumor biomarkers that predict responses to immune checkpoint inhibitors (ICI) is critically needed. In the AMADEUS clinical trial (NCT03651271), patients with various advanced solid tumors were assessed for changes in intratumoral CD8 percentages and their response to ICI. Patients were grouped based on tumoral CD8 levels: those with CD8

OBJECTIVE: The objective of this study is to compare detection rates of extracapsular extension (ECE) of prostate cancer (PCa) using artificial intelligence (AI)-generated cancer maps versus MRI and conventional nomograms. MATERIALS AND METHODS: We retrospectively analysed data from 147 patients who received MRI-targeted biopsy and subsequent radical prostatectomy between September 2016 and May 2022. AI-based software cleared by the United States Food and Drug Administration (Unfold AI, Avenda Health) was used to map 3D cancer probability and estimate ECE risk. Conventional ECE predictors including MRI Likert scores, capsular contact length of MRI-visible lesions, PSMA T stage, Partin tables, and the PRedicting ExtraCapsular Extension nomogram were used for comparison.Postsurgical specimens were processed using whole-mount histopathology sectioning, and a genitourinary pathologist assessed each quadrant for ECE presence. ECE predictors were then evaluated on the patient (Unfold AI versus all comparators) and quadrant level (Unfold AI versus MRI Likert score). Receiver operator characteristic curves were generated and compared using DeLongs test. RESULTS: Unfold AI had a significantly higher area under the curve (AUC = 0.81) than other predictors for patient-level ECE prediction. Unfold AI achieved 68% sensitivity, 78% specificity, 71% positive predictive value, and 75% negative predictive value. At the quadrant level, Unfold AI exceeded the AUC of MRI Likert scores for posterior (0.89 versus 0.82, p = 0.003), anterior (0.84 versus 0.80, p = 0.34), and all quadrants (0.89 versus 0.82, p = 0.002). The false negative rate of Unfold AI was lower than MRI in both the anterior (-60%) and posterior prostate (-40%). CONCLUSIONS: Unfold AI accurately predicted ECE risk, outperforming conventional methodologies. It notably improved ECE prediction over MRI in posterior quadrants, with the potential to inform nerve-spare technique and prevent positive margins. By enhancing PCa staging and risk stratification, AI-based cancer mapping may lead to better oncological and functional outcomes for patients.

INTRODUCTION: Staged treatment of high-energy periarticular tibia fractures involves temporization with closed reduction and external fixation, aiming to provide early reduction and stabilization while mitigating soft-tissue complications. Various external fixator configurations exist, including those that use a multipin clamp capable of holding multiple pins but limiting pin placement to a single plane. The purpose of this study was to compare clinical and radiographic outcomes and associated costs of standard and multipin outrigger clamp constructs in tibial plateau and pilon fractures treated with temporary external fixation. We hypothesized that use of the multipin clamp may be associated with poorly aligned reductions and increased complication rates. METHODS: A retrospective review of 100 patients with periarticular tibial plateau (AO/OTA: 41B/C) or pilon (43B/C) fracture at a Level 1 trauma center from 2014 to 2023 was conducted. Patient, injury, and complication characteristics were collected. Patients were categorized based on the external fixator clamp used: multipin (MP) or standard (S). Clinical outcomes and complication rates were assessed. Radiographic alignment was evaluated by the change in anterior and lateral distal tibial angles, and sagittal plane translation for pilon fractures, and medial and posterior proximal tibial angles for plateau fractures. RESULTS: 70 patients underwent standard (25 pilon, 45 plateau) and 30 multipin (10 pilon, 20 plateau) external fixation. MP and S groups showed no notable differences in demographics or injury characteristics. Both groups demonstrated comparable complication rates and radiological alignment outcomes, with no notable differences observed. MP constructs were more costly than standard systems. CONCLUSION: In this retrospective study of 100 patients, there was no difference in radiographic or clinical outcomes between the standard frame and multipin frame groups. Typical costs for the multipin frame constructs were $635 to $1249 more than the standard frame constructs.

Tumor-associated T cells orchestrate cancer rejection after checkpoint blockade immunotherapy. T cell function depends on dynamic antigen recognition through the T cell receptor (TCR) resulting in T cell activation. Here, we present an approach to quantify the dynamics and magnitude of tumor-associated T cell activation at multiple time points in living mice using the genetically encoded calcium reporter Salsa6f and functional intravital microscopy (F-IVM). Our protocol allows researchers to measure the activation dynamics of various immune cells in vivo. For complete details on the use and execution of this protocol, please refer to Geels et al.1.

BACKGROUND: Extreme Risk Protection Orders (ERPOs) are civil court orders that prohibit firearm purchase and possession when someone is behaving dangerously and is at risk of harming themselves and/or others. As of June 2024, ERPOs are available in 21 states and the District of Columbia to prevent firearm violence. This paper describes the design and protocol of a six-state study of ERPO use. METHODS: The six states included are California, Colorado, Connecticut, Florida, Maryland, and Washington. During the 3-year project period (2020-2023), ERPO case files were obtained through public records requests or through agreements with agencies with access to these data in each state. A team of over four dozen research assistants from seven institutions coded 6628 ERPO cases, abstracting 80 variables per case under domains related to respondent characteristics, events and behaviors leading to ERPO petitions, petitioner types, and court outcomes. Research assistants received didactic training through an online learning management system that included virtual training modules, quizzes, practice coding exercises, and two virtual synchronous sessions. A protocol for gaining strong interrater reliability was used. Research assistants also learned strategies for reducing the risk of experiencing secondary trauma through the coding process, identifying its occurrence, and obtaining help. DISCUSSION: Addressing firearm violence in the U.S. is a priority. Understanding ERPO use in these six states can inform implementation planning and ERPO uptake, including promising opportunities to enhance safety and prevent firearm-related injuries and deaths. By publishing this protocol, we offer detailed insight into the methods underlying the papers published from these data, and the process of managing data abstraction from ERPO case files across the multi-state and multi-institution teams involved. Such information may also inform future analyses of this data, and future replication efforts. REGISTRATION: This protocol is registered on Open Science Framework ( https://osf.io/kv4fc/ ).

ObjectiveTo describe how young adults use electronic cigarettes (electronic nicotine delivery systems (ENDS)) for smoking cessation and reasons why they may or may not successfully quit smoking.MethodsLongitudinal qualitative data were collected annually from 2017 to 2019 for 25 young adult tobacco users (aged 18-29 years) in California (USA) who used ENDS to quit/reduce smoking. Thematic and trajectory analyses were used to identify key within-person and between-person changes in tobacco/nicotine use over time.ResultsFive types of tobacco use transition were identified among baseline dual users of cigarettes and ENDS: sustained dual use without reduced smoking (n=8), transition to exclusive daily ENDS use (n=6), sustained dual use with reduced smoking (n=5), transition back to exclusive smoking (n=4) and transition to neither smoking nor vaping (n=2). Participants' ENDS use behaviour varied over time in terms of vaping quantity and device characteristics (eg, changing nicotine concentrations/flavours, switching between multiple devices). Three themes that related to successfully replacing cigarettes with ENDS were perceived positive physical effects, perceived satisfaction and enjoyment and context changes. Four themes for unsuccessful replacement were perceived negative physical discomforts, perceived addictiveness and harm, unsatisfactory substitution for cigarettes and device malfunction.ConclusionsYoung adults' experiences with using ENDS as a smoking cessation aid were highly variable. Adequate nicotine delivery and perceived safety and benefits contributed to successfully reducing or quitting cigarettes. Providing behavioural counselling and standardising ENDS products may enhance cessation for young adults.

Clonal hematopoiesis (CH) is an age-associated phenomenon leading to an increased risk of both hematologic malignancy and nonmalignant organ dysfunction. Increasingly available genetic testing has made the incidental discovery of CH clinically common yet evidence-based guidelines and effective management strategies to prevent adverse CH health outcomes are lacking. To address this gap, the prospective CHIVE (clonal hematopoiesis and inflammation in the vasculature) registry and biorepository was created to identify and monitor individuals at risk, support multidisciplinary CH clinics, and refine taxonomy and standards of practice for CH risk mitigation. Data from the first 181 patients enrolled in this prospective registry recapitulate the molecular epidemiology of CH from biobank-scale retrospective studies, with DNMT3A, TET2, ASXL1, and TP53 as the most commonly mutated genes. Blood counts across all hematopoietic lineages trended lower in patients with CH. In addition, patients with CH had higher rates of end organ dysfunction, in particular chronic kidney disease. Among patients with CH, variant allele frequency was independently associated with the presence of cytopenias and progression to hematologic malignancy, whereas other common high-risk CH clone features were not clear. Notably, accumulation of multiple distinct high-risk clone features was also associated with cytopenias and hematologic malignancy progression, supporting a recently published CH risk score. Surprisingly, ∼30% of patients enrolled in CHIVE from CH clinics were adjudicated as not having clonal hematopoiesis of indeterminate potential, highlighting the need for molecular standards and purpose-built assays in this field. Maintenance of this well-annotated cohort and continued expansion of CHIVE to multiple institutions are underway and will be critical to understanding how to thoughtfully care for this patient population.