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Discusses a case study on reversible orthodeoxia and platypnea due to right-to-left intracardiac shunting related to pericardial effusion. Medical condition of an elderly man with a history of severe dyspnea and hypoxemia; Treatment; Conclusion.

The persistence of extreme suicide disparities in American Indian and Alaska Native (AI/AN) youth signals a severe health inequity with distinct associations to a colonial experience of historical and on-going cultural, social, economic, and political oppression. To address this complex issue, we describe three AI/AN suicide prevention efforts that illustrate how strengths-based community interventions across the prevention spectrum can buffer suicide risk factors associated with structural racism. Developed and implemented in collaboration with tribal partners using participatory methods, the strategies include universal, selective, and indicated prevention elements. Their aim is to enhance systems within communities, institutions, and families by emphasizing supportive relationships, cultural values and practices, and community priorities and preferences. These efforts deploy collaborative, local approaches, that center on the importance of tribal sovereignty and self-determination, disrupting the unequal power distribution inherent in mainstream approaches to suicide prevention. The examples emphasize the centrality of Indigenous intellectual traditions in the co-creation of healthy developmental pathways for AI/AN young people. A central component across all three programs is a deep commitment to an interdependent or collective orientation, in contrast to an individual-based mental health suicide prevention model. This commitment offers novel directions for the entire field of suicide prevention and responds to calls for multilevel, community-driven public health strategies to address the complexity of suicide. Although our focus is on the social determinants of health in AI/AN communities, strategies to address the structural violence of racism as a risk factor in suicide have broad implications for all suicide prevention programming.

Chandler and Lalonde broadened the scope of inquiry in suicide research by providing theoretical grounding and empirical support for the role of community, culture, and history in understanding Indigenous youth suicide and reimagining its prevention. Their work pushed the field to consider the intersectional process of individual and collective meaning-making in prevention of Indigenous suicide, together with the central role culture plays in bringing coherence to this process over time. Their innovation shifted the research focus to include the shared histories, contexts, and structures of meaning that shape individual lives and behaviors. We describe here a new generation of research extending their pathbreaking line of inquiry. Recent work aims to identify complex associations between community-level structures and suicidal behavior by collaborating with Alaska Native people from rural communities to describe how community protective factors function as preventative resources in their daily lives. Community engagement and knowledge co-production created a measure of community protection from suicide. Structured interviews with rural Alaska Native community members allowed use of this measure to produce relevant, accessible, and actionable knowledge. Ongoing investigations next seek to describe their mechanisms in shaping young people's lives through a multilevel, mixed-methods community-based study linking community-level protection to protection and well-being of individual youth. These efforts to understand the multiple culture-specific and culturally mediated pathways by which communities build on their strengths, resources, and practices to support Indigenous young people's development and reduce suicide risk are inspired by and expand on Chandler and Lalonde's remarkable legacy.

Purpose: To evaluate local failure (LF) and toxicity after intraoperative radiation therapy (IORT) in pediatric solid tumors (ST)., Methods: A single-institution retrospective study of 96 pediatric patients (108 applications) with ST treated from 1995 to 2022 with IORT. LF was calculated via cumulative incidence function and overall survival (OS) by Kaplan-Meier method, both from the day of surgery., Results: Median age at time of IORT was 8 years (range: 0.8-20.9 years). Median follow-up for all patients and surviving patients was 16 months and 3 years, respectively. The most common histologies included rhabdomyosarcoma (n = 42), Ewing sarcoma (n = 10), and Wilms tumor (n = 9). Most (95%) received chemotherapy, 37% had prior external beam radiation therapy to the site of IORT, and 46% had a prior surgery for tumor resection. About half (54%) were treated with upfront IORT to the primary tumor due to difficult circumstances such as very young age or challenging anatomy. The median IORT dose was 12 Gy (range: 4-18 Gy), and median area treated was 24 cm 2 (range: 2-198 cm 2 ). The cumulative incidence of LF was 17% at 2 years and 23% at 5 years. Toxicity from IORT was reasonable, with postoperative complications likely related to IORT seen in 15 (16%) patients., Conclusion: Our study represents the largest and most recent analysis of efficacy and safety of IORT in pediatric patients with ST. Less than one quarter of all patients failed locally with acceptable toxicities. Overall, IORT is an effective and safe technique to achieve local control in patients with challenging circumstances., (© 2024 Wiley Periodicals LLC.)

Chromoplexy is a phenomenon defined by large-scale chromosomal chained rearrangements. A previous study observed chromoplectic events in a subset of Ewing sarcomas (ES), which was linked to an increased relapse rate. Chromoplexy analysis could potentially facilitate patient risk stratification, particularly if it could be detected with clinically applied targeted next-generation sequencing (NGS) panels. Using DELLY, a structural variant (SV) calling algorithm that is part of the MSK-IMPACT pipeline, we characterized the spectrum of SVs in EWSR1-fused round cell sarcomas, including 173 ES and 104 desmoplastic small round cell tumors (DSRCT), to detect chromoplexy and evaluate its association with clinical and genomic features. Chromoplectic events were detected in 31% of the ES cases and 19% of the DSRCT cases. EWSR1 involvement accounted for 76% to 93% of these events, being rearranged with diverse noncanonical gene partners across the genome, involving mainly translocations but also intrachromosomal deletions and inversions. A major breakpoint cluster was located on EWSR1 exons 8-13. In a subset of cases, the SVs disrupted adjacent loci, forming deletion bridges. Longitudinal sequencing and breakpoint allele fraction analysis showed that chromoplexy is an early event that remains detectable throughout disease progression and likely develops simultaneously with the driver fusion. The presence of chromoplexy was validated in an external ES patient cohort with whole exome sequencing. Chromoplexy was significantly more likely to be present in cases that were metastatic at presentation. Together, this study identifies chromoplexy as a frequent genomic alteration in diverse EWSR1-rearranged tumors that can be captured by targeted NGS panels., Significance: Chromoplexy is detectable using targeted NGS in a substantial portion of EWSR1-rearranged round cell sarcomas as an early and persistent clonal event, expanding the genomic complexity of fusion-associated sarcomas., (©2024 American Association for Cancer Research.)

American Indian and Alaska Native (AI/AN) youth, particularly males, experience disproportionately high rates of suicide compared to other young people in the United States. Therefore, enacting suicide prevention efforts for AI/AN youth is especially important. Since research shows that strengthening social, cultural, and emotional support can reduce suicide risk, many recent prevention efforts focus on these strategies. Yet, to reinforce and to extend the positive impact of these strategies for suicide risk reduction, we argue it is useful to identify baseline levels and other features of already-existing support. Toward this end, we describe the types (i.e., category), quantities (i.e., distribution and average number), sources (i.e., from whom), and frequencies (i.e., how often) of social support that AN young people report receiving, and we examine if these "support profiles" differ by age and sex. We use survey data from 165 ANs under age 30, collected as part of a participatory intervention study focused on Promoting Community Conversations About Research to End Suicide (PC CARES). We find that: 1) most ANs reported receiving nearly all supports, 2) compared with females, males reported receiving fewer supports on average, 3) family was the most selected support source, followed by close friends and service providers, and 4) family (e.g., parents, siblings, and grandparents) provided support regularly (i.e., monthly or more). Though our findings may suggest fruitful avenues for interventions targeted toward AN males, we discuss these findings in relation to the gendered nature of suicide prevention and assessment.

While implementation and dissemination of research is a rapidly growing area, critical questions remain about how, why, and under what conditions everyday people integrate and utilize research evidence. This mixed-methods study investigates how participants of Promoting Community Conversations About Research to End Suicide (PC CARES) make sense of and use research evidence about suicide prevention in their own lives. PC CARES is a health intervention addressing the need for culturally responsive suicide prevention practices in rural Alaska through a series of community Learning Circles. We analyzed PC CARES transcripts and surveys for 376 participants aged 15+ across 10 Northwest Alaska Native villages. Quantitative analysis showed significant correlations between five utilization of research evidence (URE) factors and participants' intent to use research evidence from PC CARES Learning Circles. Key qualitative themes from Learning Circle transcripts expanded upon these URE constructs and included navigating discordant information, centering relationships, and Indigenous worldviews as key to interpreting research evidence. We integrate and organize our findings to inform two domains from the Consolidated Framework for Research Implementation: (1) intervention characteristics and (2) characteristics of individuals, with emphasis on findings most relevant for community settings where self-determined, evidence-informed action is especially important for addressing health inequities., (© 2022 The Authors. American Journal of Community Psychology published by Wiley Periodicals LLC on behalf of Society for Community Research and Action.)

Myxoid pleomorphic liposarcoma (MPLPS) is a recently described and extremely rare subtype of liposarcoma with a predilection for the mediastinum. However, the genomic features of MPLPS remain poorly understood. We performed comprehensive genomic profiling of MPLPS in comparison with pleomorphic liposarcoma (PLPS) and myxoid/round cell liposarcoma (MRLPS). Of the 8 patients with MPLPS, 5 were female and 3 were male, with a median age of 32 years old (range 10-68). All except one were located in the mediastinum, with invasion of surrounding anatomic structures, including chest wall, pleura, spine, and large vessels. All cases showed an admixture of morphologies reminiscent of PLPS and MRLPS, including myxoid areas with plexiform vasculature admixed with uni- and/or multivacuolated pleomorphic lipoblasts. Less common features included well-differentiated liposarcoma-like areas, and in one case fascicular spindle cell sarcoma reminiscent of dedifferentiated LPS. Clinically, 4 experienced local recurrence, 4 had distant metastases and 5 died of disease. Compared to PLPS and MRLPS, patients with MPLPS had worse overall and progression-free survival. Recurrent TP53 mutations were present in all 8 MPLPS cases. In contrast, in PLPS, which also showed recurrent TP53 mutations (83%), RB1 and ATRX losses were more common. MRLPS was highly enriched in TERT promoter mutations (88%) and PI3K/AKT pathway mutations. Copy number profiling in MPLPS revealed multiple chromosomal gains with recurrent amplifications of chromosomes 1, 19 and 21. Importantly, allele-specific copy number analysis revealed widespread loss of heterozygosity (80% of the genome on average) in MPLPS, but not in PLPS or MRLPS. Our findings revealed genome-wide loss of heterozygosity co-existing with TP53 mutations as a characteristic genomic signature distinct from other liposarcoma subtypes, which supports the current classification of MPLPS as a stand-alone pathologic entity. These results further expand the clinicopathologic features of MPLPS, including older age, extra-mediastinal sites, and a highly aggressive outcome., (© 2022. The Author(s), under exclusive licence to United States & Canadian Academy of Pathology.)

Objective: Aneurysmal bone cysts (ABCs) are benign cystic lesions most commonly occurring in the long bones of pediatric patients. Spinal ABCs may be difficult to resect given their invasive, locally destructive nature, proximity to critical structures such as the spinal cord, and their intrinsic hypervascularity, for which complete embolization is often constrained by radiculomedullary segmental feeders. Denosumab, a monoclonal antibody that binds the receptor activator of nuclear factor kappa B (NF-κB) ligand, has been utilized in the treatment of ABCs most often as a rescue therapy for recurrent disease. Here, the authors present 3 cases of neoadjuvant denosumab use in surgically unresectable tumors to calcify and devascularize the lesions, allowing for safer, more complete resection., Methods: This is a single-center, retrospective case series treated at a tertiary care cancer center. The authors present 3 cases of spinal ABC treated with neoadjuvant denosumab., Results: All 3 patients experienced calcification, size reduction, and a significant decrease in the vascularity of their ABCs on denosumab therapy. None of the patients developed new neurological deficits while on denosumab. Subsequently, all underwent resection. One patient continued denosumab during the immediate postoperative period because a subtotal resection had been performed, with stabilization of the residual disease. No complications were associated with denosumab administration., Conclusions: The use of denosumab in unresectable ABCs can cause calcification and devascularization, making safe resection more likely.

Suicide is a leading cause of death for school-aged preteens and adolescents and a growing risk for younger children. Schools are the ubiquitous institutional context serving this age group. These trends suggest a need for knowledge and guidance related to school postvention efforts, yet the available research is limited. Focusing on postvention, or the period after a peer suicide occurs, is critical to youth suicide prevention because this is a time of elevated suicide risk for youth. Targeted postvention interventions in schools can mitigate youth suicide risk and limit contagion within a school's student body. This article explores the scientific literature related to school-based suicide postvention, describing the strength and limits of research supporting common recommendations for suicide postvention in schools. It identifies widespread recommendations for school postvention that have only preliminary supportive evidence and notes several areas in need of additional research. With clearer postvention best practices to guide their suicide crisis preparedness plans and postvention procedures, schools can better support students, families, and the community as a whole in order to prevent further tragedies.

Rationale: Cardiovascular disease remains the leading cause of death in women. To address its determinants including persisting cardiovascular risk factors amplified by sex and race inequities, novel personalized approaches are needed grounded in the engagement of participants in research and prevention., Objective: To report on a participant-centric and personalized dynamic registry designed to address persistent gaps in understanding and managing cardiovascular disease in women., Methods and Results: The American Heart Association and Verily launched the Research Goes Red registry (RGR) in 2019, as an online research platform available to consenting individuals over the age of 18 years in the United States. RGR aims to bring participants and researchers together to expand knowledge by collecting data and providing an open-source longitudinal dynamic registry for conducting research studies. As of July 2021, 15 350 individuals have engaged with RGR. Mean age of participants was 48.0 48.0±0.2 years with a majority identifying as female and either non-Hispanic White (75.7%) or Black (10.5%). In addition to 6 targeted health surveys, RGR has deployed 2 American Heart Association-sponsored prospective clinical studies based on participants' areas of interest. The first study focuses on perimenopausal weight gain, developed in response to a health concerns survey. The second study is designed to test the use of social media campaigns to increase awareness and participation in cardiovascular disease research among underrepresented millennial women., Conclusions: RGR is a novel online participant-centric platform that has successfully engaged women and provided critical data on women's heart health to guide research. Priorities for the growth of RGR are centered on increasing reach and diversity of participants, and engaging researchers to work within their communities to leverage the platform to address knowledge gaps and improve women's health.

The ongoing challenge of American Indian and Alaska Native (AIAN) youth suicide is a public health crisis of relatively recent historical origin inadequately addressed by contemporary prevention science. A promising development in AIAN suicide prevention highlights the role of protective factors. A protective factor framework adopts a social ecological perspective and community-level intervention paradigm. Emphasis on protection highlights strength-based AIAN cultural strategies in prevention of youth suicide. Attention to multiple intersecting levels incorporates strategies promoting community as well as individual resilience processes, seeking to influence larger contexts as well as individuals within them. This approach expands the scope of suicide prevention strategies beyond the individual level and tertiary prevention strategies. Interventions that focus on mechanisms of protection offer a rigorous, replicable, and complementary prevention science alternative to risk reduction approaches. This selected review critically examines recent AIAN protective factor suicide prevention science. One aim is to clarify key concepts including protection, resilience, and cultural continuity. A broader aim is to describe the evolution of this promising new framework for conducting primary research about AIAN suicide, and for designing and testing more effective intervention. Recommendations emphasize focus on mechanisms, multilevel interactions, more precise use of theory and terms, implications for new intervention development, alertness to unanticipated impacts, and culture as fundamental in a protective factors framework for AIAN suicide prevention. A protective factor framework holds significant potential for advancing AIAN suicide prevention and for work with other culturally distinct suicide disparity groups, with broad implications for other areas of prevention science., (© 2021. Society for Prevention Research.)

This paper presents how a community mobilization program to prevent suicide was adapted to an online format to accommodate the impossibility of in-person delivery in Alaska Native communities during the COVID-19 pandemic. The intervention, Promoting Community Conversations About Research to End Suicide (PC CARES), was created collaboratively by researchers and Alaska Native communities with the goal of bringing community members together to create research-informed and community-led suicide prevention activities in their communities. To continue our work during the COVID-19 pandemic and restrictions, we adapted the PC CARES model to a synchronous remote delivery format. This shift included moving from predominantly Alaska Native participants to one of a mainly non-Native school staff audience. This required a pivot from Alaska Native self-determination toward cultural humility and community collaboration for school-based staff, with multilevel youth suicide prevention remaining the primary aim. This reorientation can offer important insight into how to build more responsive programs for those who are not from the communities they serve. Here, we provide a narrative overview of our collaborative adaptation process, illustrated by data collected during synchronous remote facilitation of the program, and reflect on how the shift in format and audience impacted program delivery and content. The adaptation process strove to maintain the core animating features of self-determination for Alaska Native communities and people as well as the translation of scientific knowledge to practice for greater impact.

The spectrum of germline predisposition in pediatric cancer continues to be realized. Here we report 751 solid tumor patients who underwent prospective matched tumor-normal DNA sequencing and downstream clinical use (clinicaltrials.gov NCT01775072). Germline pathogenic and likely pathogenic (P/LP) variants were reported. One or more P/LP variants were found in 18% (138/751) of individuals when including variants in low, moderate, and high penetrance dominant or recessive genes, or 13% (99/751) in moderate and high penetrance dominant genes. 34% of high or moderate penetrance variants were unexpected based on the patient's diagnosis and previous history. 76% of patients with positive results completed a clinical genetics visit, and 21% had at least one relative undergo cascade testing as a result of this testing. Clinical actionability additionally included screening, risk reduction in relatives, reproductive use, and use of targeted therapies. Germline testing should be considered for all children with cancer.

Glia shape the development and function of the C. elegans nervous system, especially its sense organs and central neuropil (nerve ring). Cell-type-specific promoters allow investigators to label or manipulate individual glial cell types, and therefore provide a key tool for deciphering glial function. In this technical resource, we compare the specificity, brightness, and consistency of cell-type-specific promoters for C. elegans glia. We identify a set of promoters for the study of seven glial cell types ( F16F9.3 , amphid and phasmid sheath glia; F11C7.2, amphid sheath glia only; grl-2 , amphid and phasmid socket glia; hlh-17 , cephalic (CEP) sheath glia; and grl-18 , inner labial (IL) socket glia) as well as a pan-glial promoter ( mir-228 ). We compare these promoters to promoters that are expressed more variably in combinations of glial cell types ( delm-1 and itx-1 ). We note that the expression of some promoters depends on external conditions or the internal state of the organism, such as developmental stage, suggesting glial plasticity. Finally, we demonstrate an approach for prospectively identifying cell-type-specific glial promoters using existing single-cell sequencing data, and we use this approach to identify two novel promoters specific to IL socket glia ( col-53 and col-177 ).

The BCOR family of tumors includes a number of undifferentiated sarcomas, occurring in various age groups and anatomic sites, characterized by a spindle and round cell phenotype and diffuse immunoreactivity for BCOR. Prior RNA sequencing data revealed that NTRK3 was a top-upregulated gene in BCOR-CCNB3 sarcomas. In this study, we investigate a large cohort of tumors harboring BCOR/YWHAE genetic alterations for NTRK3 upregulation at both the mRNA and protein levels, compared with other sarcoma types. Pan-Trk immunohistochemistry was assessed for intensity and extent. A correlation between NTRK3 expression and the type of BCOR alteration and BCOR immunoreactivity was also performed. Most soft tissue undifferentiated round cell sarcomas with YWHAE or BCOR rearrangements or BCOR internal tandem duplications (ITD) showed NTRK3, but not NTRK1 or NTRK2, upregulation by RNA sequencing data analysis. Cytoplasmic pan-Trk immunoreactivity was also observed in most soft tissue round cell sarcomas with YWHAE rearrangements (100%), BCOR ITD (80%), and BCOR-CCNB3 fusions (67%), as well as clear cell sarcomas of kidney (75%), another BCOR family tumor, and ossifying fibromyxoid tumors with ZC3H7B-BCOR fusion (100%), with variable staining intensity and extent. Pan-Trk staining was also seen in solitary fibrous tumors (100%) and less frequently in synovial sarcoma and Ewing sarcoma, but rarely in other sarcomas tested. Tumors harboring rare fusion variants of BCOR, such as BCOR-CHD9, a novel fusion identified by targeted RNA sequencing, and KMT2D-BCOR, were also positive for pan-Trk staining and NTRK3 overexpression. In conclusion, NTRK3 upregulation resulting in pan-Trk overexpression is common in the BCOR family of tumors as well as in subsets of BCOR-expressing sarcomas through alternative mechanisms. The therapeutic implication of this finding awaits further investigation.

Youth suicide is a significant health disparity in circumpolar indigenous communities, with devastating impacts at individual, family, and community levels. This study draws on structured interviews and ethnographic work with health professionals in the Alaskan Arctic to examine the meanings assigned to Alaska Native youth suicide, as well as the health systems that shape clinicians' practices of care. By defining suicide as psychogenic on the one hand, and as an index of social suffering on the other, its solutions are brought into focus and circumscribed in particular and patterned ways. We contrast psychiatric and social explanatory models, bureaucratic and relational forms of care, and biomedical and biosocial models for care delivery. Within the broader context of global mental health, this study suggests steps for linking caregiving to the health and social equity agenda of social medicine and for operationalizing commitments to health as a human right., Competing Interests: Competing interests: None declared., (Copyright © 2020 Trout and Wexler.)

Suicide is a significant health disparity among Alaska Native youth, which is linked to cultural disruptions brought about by colonialism and historical trauma. Many Indigenous suicide prevention efforts center on revitalizing and connecting youth to their culture to promote mental health and resilience. A common cultural approach to improve psychosocial outcomes is youth culture camps, but there has been little evaluation research to test this association. Here, we conduct a pilot evaluation of a 5-day culture camp developed in two remote regions of Alaska. The camps bring together Alaska Native youth from villages in these regions to take part in subsistence activities, develop new relationships, develop life skills, and learn traditional knowledge and values. This pilot evaluation of the culture camps uses a quantitative pre/post design to examine the outcomes of self-esteem, emotional states, belongingness, mattering to others, and coping skills among participants. Results indicate that culture camps can significantly increase positive mood, feelings of belongingness, and perceived coping of participants. Culture camps are a common suicide prevention effort in Indigenous circumpolar communities, and although limited in scope and design, this pilot evaluation offers some evidence to support culture camps as a health promotion intervention that can reduce suicide risk.

Background: The Alaska Native Community Resilience Study (ANCRS) is the central research project of the Alaska Native Collaborative Hub for Research on Resilience (ANCHRR), one of three American Indian and Alaska Native (AIAN) suicide prevention hubs funded by the National Institute of Mental Health., Objective: This paper describes the development of a structured interview to identify and measure community-level protective factors that may reduce suicide risk among youth in rural Alaska Native communities., Methods: Multilevel, iterative collaborative processes resulted in: a) expanded and refined constructs of community-level protection, b) clearer and broadly relevant item wording, c) respectful data collection procedures, and d) Alaska Native people from rural Alaska as primary knowledge-gathering interviewers., Lessons Learned: Moving beyond engagement to knowledge co-production in Alaska Native research requires flexibility, shared decision-making and commitment to diverse knowledge systems; this can result in culturally attuned methods, greater tool validity, new ways to understand complex issues and innovations that support community health.

Rationale: This study evaluates the process and preliminary outcomes of Promoting Community Conversations About Research to End Suicide (PC CARES), an intervention that brings key stakeholders together so they can discuss suicide prevention research and find ways to put it into practice. Originally piloted in remote and rural Alaskan communities, the approach shows promise., Method: Using a multi-method design, the study describes a series of locally-facilitated "learning circles" over 15 months and their preliminary results. Sign-in sheets documented participation. Transcriptions of audio-recorded sessions captured facilitator fidelity, accuracy, and the dominant themes of community discussions. Linked participant surveys (n=83) compared attendees' perceived knowledge, skills, attitudes, and their 'community of practice' at baseline and follow-up. A cross-sectional design compared 112 participants' with 335 non-participants' scores on knowledge and prevention behaviors, and considered the social impact with social network analyses., Results: Demonstrating feasibility in small rural communities, local PC CARES facilitators hosted 59 two to three hour learning circles with 535 participants (376 unique). Local facilitators achieved acceptable fidelity to the model (80%), and interpreted the research accurately 81% of the time. Discussions reflected participants' understanding of the research content and its use in their lives. Participants showed positive changes in perceived knowledge, skills, and attitudes and strengthened their 'community of practice' from baseline to follow-up. Social network analyses indicate PC CARES had social impact, sustaining and enhancing prevention activities of non-participants who were 'close to' participants. These close associates were more likely take preventive actions than other non-participants after the intervention., Conclusion: PC CARES offers a practical, scalable method for community-based translation of research evidence into selfdetermined, culturally-responsive suicide prevention practice., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objective: This study aimed to (1) develop instruments to evaluate situations that lead to lapse and relapse in diet and exercise and (2) prospectively investigate when and which psychosocial situations predict failure to lose weight in a clinical trial of intentional weight loss., Methods: Participants were 469 individuals with overweight or obesity participating in a behavioral weight loss program (age: mean = 53.6 years, SD = 11.4; BMI: mean = 35.7 kg/m 2 , SD = 6.5)., Results: The Cronbach alphas for the Diet Lapse and Relapse Triggers Scale and the Exercise Lapse and Relapse Triggers Scale were 0.93 and 0.91, respectively. Subscale alphas ranged from 0.60 to 0.96. Lapse and relapse were assessed at 3 and 9 months for associations with weight loss at 12 months. At 9 months, diet triggers were negative emotional states (beta = 0.11, P = 0.02) and urges (beta = 0.14, P = 0.01). Predicted social situations showed the opposite (beta = -0.09, P = 0.02). Exercise subscales were all nonsignificant., Conclusions: Findings suggest the ongoing importance of addressing negative emotional states and the contributing influence of urges. The novel finding that participants whose difficulties arise in social situations may do better over time requires further study., (© 2019 The Obesity Society.)

Primary intraosseous rhabdomyosarcomas (RMSs) are extremely rare. Recently 2 studies reported 4 cases of primary intraosseous RMS with EWSR1/FUS-TFCP2 gene fusions, associated with somewhat conflicting histologic features, ranging from spindle to epithelioid. In this study we sought to further investigate the pathologic and molecular abnormalities of a larger group of intraosseous RMSs by a combined approach using targeted RNA sequencing analysis and fluorescence in situ hybridization (FISH). We identified 7 cases, 3 males and 4 females, all in young adults, age range 20 to 39 years (median, 27 y). Three cases involved the pelvis, 2 involved the femur and 1 each involved the maxilla and the skull. Molecular studies identified recurrent gene fusions in all 7 cases tested, including: a novel MEIS1-NCOA2 fusion in 2 cases, EWSR1-TFCP2 in 3 cases, and FUS-TFCP2 gene fusions in 1 case. One case showed a FUS gene rearrangement, without a TFCP2 gene abnormality by FISH. The MEIS1-NCOA2-positive cases were characterized by a more primitive and fascicular spindle cell appearance, while the EWSR1/FUS rearranged tumors had a hybrid spindle and epithelioid phenotype, with more abundant eosinophilic cytoplasm and mild nuclear pleomorphism. Immunohistochemically, all tumors were positive for desmin and myogenin (focal). In addition, 4 tumors with TFCP2-associated gene fusions also coexpressed ALK and cytokeratin. In conclusion, our results suggest a high incidence of gene fusions in primary RMSs of bone, with 2 molecular subsets emerging, defined by either MEIS1-NCOA2 or EWSR1/FUS-TFCP2 fusions, showing distinct morphology and immunophenotype. Additional studies with larger numbers of cases and longer follow-up data are required to definitively evaluate the biological behavior of these tumors and to establish their relationship to other spindle cell RMS genetic groups.

Anti-tumor immunity is driven by self versus non-self discrimination. Many immunotherapeutic approaches to cancer have taken advantage of tumor neoantigens derived from somatic mutations. Here, we demonstrate that gene fusions are a source of immunogenic neoantigens that can mediate responses to immunotherapy. We identified an exceptional responder with metastatic head and neck cancer who experienced a complete response to immune checkpoint inhibitor therapy, despite a low mutational load and minimal pre-treatment immune infiltration in the tumor. Using whole-genome sequencing and RNA sequencing, we identified a novel gene fusion and demonstrated that it produces a neoantigen that can specifically elicit a host cytotoxic T cell response. In a cohort of head and neck tumors with low mutation burden, minimal immune infiltration and prevalent gene fusions, we also identified gene fusion-derived neoantigens that generate cytotoxic T cell responses. Finally, analyzing additional datasets of fusion-positive cancers, including checkpoint-inhibitor-treated tumors, we found evidence of immune surveillance resulting in negative selective pressure against gene fusion-derived neoantigens. These findings highlight an important class of tumor-specific antigens and have implications for targeting gene fusion events in cancers that would otherwise be less poised for response to immunotherapy, including cancers with low mutational load and minimal immune infiltration.

The Arctic Council, a collaborative forum among governments and Arctic communities, has highlighted the problem of suicide and potential solutions. The mental health initiative during the United States chairmanship, Reducing the Incidence of Suicide in Indigenous Groups: Strengths United Through Networks (RISING SUN), used a Delphi methodology complemented by face-to-face stakeholder discussions to identify outcomes to evaluate suicide prevention interventions. RISING SUN underscored that multilevel suicide prevention initiatives require mobilizing resources and enacting policies that promote the capacity for wellness, for example, by reducing adverse childhood experiences, increasing social equity, and mitigating the effects of colonization and poverty.

Indigenous youth suicide remains a substantial health disparity in circumpolar communities, despite prevention efforts through primary health care, public health campaigns, school systems, and social services. Innovations in prevention practice move away from expert-driven approaches to emphasize local control through processes that utilize research evidence, but privilege self- determined action based on local and personal contexts, meanings, and frameworks for action. "Promoting Community Conversations About Research to End Suicide" is a community health intervention that draws on networks of Indigenous health educators in rural Alaska, who host learning circles in which research evidence is used to spark conversations and empower community members to consider individual and collective action to support vulnerable people and create health-promoting conditions that reduce suicide risk. The first of nine learning circles focuses on narratives of local people who link the contemporary youth suicide epidemic to 20th century American colonialism, and situates prevention within this context. We describe the theoretical framework and feasibility and acceptability outcomes for this learning circle, and elucidate how the educational model engages community members in decolonial approaches to suicide prevention education and practice, thus serving as a bridge between Western and Indigenous traditions to generate collective knowledge and catalyze community healing., (© 2018 Society for Community Research and Action.)

Indigenous communities across the Alaskan Arctic have experienced profound revisions of livelihood, culture, and autonomy over the past century of colonization, creating radical discontinuities between the lives of young people and those of their parents and Elders. The disrupted processes of identity development, access to livelihoods, and cross-generational mentorship associated with colonialism have created complex challenges for youth as they envision and enact viable paths forward in the context of a rapidly changing Arctic home. In this study, we consider the meanings associated with different constructions of culture and selfhood, and the ways in which these identity narratives position Inupiaq Alaskan Native youth in relation to their personal and collective futures. Through an intergenerational and participatory inquiry process, this study explores how representations of shared heritage, present-day struggles, resilience, and hope can expand possibilities for youth and thus impact individual and community health.

This paper introduces a new method for acquiring and interpreting data on cognitive (or perceptual) networks. The proposed method involves the collection of multiple reports on randomly chosen pairs of individuals, and statistical means for aggregating these reports into data of conventional sociometric form. We refer to the method as "perceptual tomography" to emphasize that it aggregates multiple 3rd-party data on the perceived presence or absence of individual properties and pairwise relationships. Key features of the method include its low respondent burden, flexible interpretation, as well as its ability to find "robust intransitive" ties in the form of perceived non-edges. This latter feature, in turn, allows for the application of conventional balance clustering routines to perceptual tomography data. In what follows, we will describe both the method and an example of the implementation of the method from a recent community study among Alaska Natives. Interview data from 170 community residents is used to ascribe 4446 perceived relationships (2146 perceived edges, 2300 perceived non-edges) among 393 community members, and to assert the perceived presence (or absence) of 16 community-oriented helping behaviors to each individual in the community. Using balance theory-based partitioning of the perceptual network, we show that people in the community perceive distinct helping roles as structural associations among community members. The fact that role classes can be detected in network renderings of "tomographic" perceptual information lends support to the suggestion that this method is capable of producing meaningful new kinds of data about perceptual networks., Competing Interests: The authors have declared that no competing interests exist.

BCOR-CCNB3 sarcoma (BCS) is a recently defined genetic entity among undifferentiated round cell sarcomas, which was initially classified as and treated similarly to the Ewing sarcoma (ES) family of tumors. In contrast to ES, BCS shows consistent BCOR overexpression, and preliminary evidence suggests that these tumors share morphologic features with other tumors harboring BCOR genetic alterations, including BCOR internal tandem duplication (ITD) and BCOR-MAML3. To further investigate the pathologic features, clinical behavior, and their relationship to other round cell sarcomas, we collected 36 molecularly confirmed BCSs for a detailed histologic and immunohistochemical analysis. Four of the cases were also analyzed by RNA sequencing (RNAseq). An additional case with BCOR overexpression but negative CCNB3 abnormality showed a novel KMT2D-BCOR fusion by targeted RNAseq. The patients ranged in age from 2 to 44 years old (mean and median, 15), with striking male predominance (M:F=31:5). The tumor locations were slightly more common in bone (n=20) than soft tissue (n=14), with rare visceral (kidney, n=2) involvement. Histologically, BCS showed a spectrum of round to spindle cells with variable cellularity, monomorphic nuclei and fine chromatin pattern, delicate capillary network, and varying amounts of myxoid or collagenous stroma. The morphologic features and immunoprofile showed considerable overlap with other round cell sarcomas with BCOR oncogenic upregulation, that is, BCOR-MAML3 and BCOR ITD. Follow-up available in 22 patients showed a 5-year overall survival of 72%, which was relatively similar to ES (79%, P=0.738) and significantly better than CIC-DUX4 sarcomas (43%, P=0.005) control groups. Local recurrences occurred in 6 patients and distant metastases (lung, soft tissue/bone, pancreas) in 4. Seven of 9 cases treated with an ES chemotherapy regimen with evaluable histologic response showed >60% necrosis in posttherapy resections. Unsupervised clustering by RNAseq data revealed that tumors with BCOR genetic alterations, including BCOR-CCNB3, BCOR-MAML3, and BCOR ITD, formed a tight genomic group distinct from ES and CIC-rearranged sarcomas.

Objective: To define the rate and characterize the type of newborn hearing screening failures in multigestational births., Methods: Retrospective chart review of all multigestational births that occurred in a 10-year period (2002-2012) in which at least one newborn failed newborn hearing screening at two tertiary care hospitals in the Northwell Health System., Results: Out of 125,405 total births, we identified 2961 multigestational births, of which 59 (2.0%) newborns failed newborn hearing screening. None of their 66 twin/triplet siblings failed their newborn hearing screens. Of 43 newborns that returned for follow-up, 56.0% (24/43) had confirmed hearing loss, resulting in an overall rate of 0.81% in all multigestational newborns with hearing loss. Of 19 infants that passed repeat testing, two were judged to need myringotomy tube placement. Twenty-four infants had a confirmed hearing loss, 11 of which had sensorineural hearing loss (0.37%), and 13 with a conductive or mixed hearing loss (0.44%)., Conclusions: We identified a greater than expected risk of conductive hearing loss, not attributable to otitis media, than sensorineural hearing loss in this population. These observations are consistent with the increased risk of birth defects in multigestational births., (Copyright © 2017. Published by Elsevier B.V.)

Infantile fibrosarcomas (IFS) represent a distinct group of soft tissue tumors occurring in patients under 2 years of age and most commonly involving the extremities. Most IFS show recurrent ETV6-NTRK3 gene fusions, sensitivity to chemotherapy, and an overall favorable clinical outcome. However, outside these well-defined pathologic features, no studies have investigated IFS lacking ETV6-NTRK3 fusions, or tumors with the morphology resembling IFS in older children. This study was triggered by the identification of a novel SEPT7-BRAF fusion in an unclassified retroperitoneal spindle cell sarcoma in a 16-year-old female by targeted RNA sequencing. Fluorescence in situ hybridization screening of 9 additional tumors with similar phenotype and lacking ETV6-NTRK3 identified 4 additional cases with BRAF gene rearrangements in the pelvic cavity (n=2), paraspinal region (n=1), and thigh (n=1) of young children (0 to 3 y old). Histologically, 4 cases including the index case shared a fascicular growth of packed monomorphic spindle cells, with uniform nuclei and fine chromatin, and a dilated branching vasculature; while the remaining case was composed of compact cellular sheets of short spindle to ovoid cells. In addition, a minor small blue round cell component was present in 1 case. Mitotic activity ranged from 1 to 9/10 high power fields. Immunohistochemical stains were nonspecific, with only focal smooth muscle actin staining demonstrated in 3 cases tested. Of the remaining 5 BRAF negative cases, further RNA sequencing identified 1 case with EML4-NTRK3 in an 1-year-old boy with a foot IFS, and a second case with TPM3-NTRK1 fusion in a 7-week-old infant with a retroperitoneal lesion. Our findings of recurrent BRAF gene rearrangements in tumors showing morphologic overlap with IFS expand the genetic spectrum of fusion-positive spindle cell sarcomas, to include unusual presentations, such as older children and adolescents and predilection for axial location, thereby opening new opportunities for kinase-targeted therapeutic intervention.

Youth Leaders Program (YLP) is a health intervention implemented in a rural Alaskan school district, which utilizes natural helpers and peer leaders to increase protective factors such as school engagement and personal/cultural identities, and to reduce risks associated with drug/alcohol abuse, violence, and bullying. Through these means, the program aims to ultimately decrease the disproportionately high rates of indigenous youth suicide in the region. This paper describes process and outcome evaluation findings from the program during the 2013-2014 school year. Data collected include a survey for program participants done at the beginning and end of the study year ( n = 61, complete pairs); pre- and post-intervention school data (attendance, GPA, and disciplinary actions) ( n = 86); an all-school survey asking students at the participating schools about their experience with YLP and participating youth ( n = 764); interviews with program advisors ( n = 11) and school principals ( n = 2); and focus groups with participating students at all eleven participating schools at the end of the year. Outcomes included increased school attendance (mean attendance increased from 146 to 155 days) and improved academic performance (mean GPA of 8th, 9th, and 10th graders increased from 3.01 to 3.14) of program participants; positive peer reviews of participating student interventions in cases of bullying, depression, and suicidality; and a reported increase in the sense of agency, responsibility, and confidence among participating youth. The YLP appears to improve school climate and increase school and other protective factors for participating students. Recommendations for program implementation in the future and implications for school health will be discussed.