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Background: Rapid Response Systems are hospital-wide patient-focused systems aiming to improve recognition of acute deterioration in patients and trigger a rapid response aimed at preventing potentially avoidable adverse events such as cardiac arrest and death. In 1994, the Royal Children’s Hospital in Brisbane, Australia, was one of the first institutions to adopt a paediatric rapid response system (RRS). The purpose of this study was to investigate the impacts of both introduction of a paediatric RRS and increasing RRS activations (MET dose) on hospital mortality. Methods: Prospectively collected data from institutional databases at a specialist paediatric hospital was used to determine hospital mortality rate pre- and post- implementation of the RRS. An interrupted time series model using segmented regression was utilised to assess the pre-intervention trend, as well as immediate and sustained effects of RRS implementation on hospital mortality. Univariate linear regression examined potential effects of MET dose on mortality. Results: Hospital mortality rate did not change significantly over 15 years before RRS implementation. In the first year after implementation, mortality rate fell significantly (−1.4; 95 %CI −2.27 to −0.52; p = 0.0027). For each year that passed after the intervention, there was no significant change in hospital mortality rate (Estimate: −0.08; 95 %CI −0.17 to 0.02; p = 0.11). Univariate linear regression modelling showed that with every unit increase in MET Dose, hospital mortality rate decreased by −0.13 (95 % CI: −0.27 to 0; p = 0.05). Conclusions: Utilising data from one of the earliest and longest duration single-centre cohort of paediatric MET events, this study reaffirms the association between implementation of a paediatric RRS and decreased hospital mortality. The study also provides novel evidence of the impact of MET dose on patient outcome in the paediatric population. It is recommended that factors influencing the benefit of rapid response systems in paediatric populations are further identified so that this life saving initiative can be optimised.

Abstract Background Despite observed sex differences in the prevalence of stress-related psychiatric conditions, most preclinical and translational studies have only included male subjects. Therefore, it has not been possible to effectively assess how sex interacts with other psychosocial risk factors to impact the etiology and maintenance of stress-related psychopathology. One psychosocial factor that interacts with sex to impact risk for stress-related behavioral and physiological deficits is social dominance. The current study was designed to assess sex differences in the effects of social status on socioemotional behavior and serotonin neurochemistry in socially housed rhesus monkeys. We hypothesized that sex and social status interact to influence socioemotional behaviors as well as serotonin 1A receptor binding potential (5HT1AR-BP) in regions of interest (ROIs) implicated in socioemotional behavior. Methods Behavioral observations were conducted in gonadally intact adult female (n = 14) and male (n = 13) rhesus monkeys. 5HT1AR-BP was assessed via positron emission tomography using 4-(2ʹ-Methoxyphenyl)-1-[2ʹ-(N-2ʺ-pyridinyl)-p[18F]fluorobenzamido]ethylpiperazine ([18F]MPPF). Results Aggression emitted was greater in dominant compared to subordinate animals, regardless of sex. Submission emitted was significantly greater in subordinate versus dominant animals and greater in females than males. Affiliative behaviors emitted were not impacted by sex, status, or their interaction. Anxiety-like behavior emitted was significantly greater in females than in males regardless of social status. Hypothalamic 5HT1AR-BP was significantly greater in females than in males, regardless of social status. 5HT1AR-BP in the dentate gyrus of the hippocampus was significantly impacted by a sex by status interaction whereby 5HT1AR-BP in the dentate gyrus was greater in dominant compared to subordinate females but was not different between dominant and subordinate males. There were no effects of sex, status, or their interaction on 5HT1AR-BP in the DRN and in the regions of the PFC studied. Conclusions These data have important implications for the treatment of stress-related behavioral health outcomes, as they suggest that sex and social status are important factors to consider in the context of serotonergic drug efficacy.

Abstract Background Real-world evidence for digitally-supported asthma programs among Medicaid-enrolled children remains limited. Using data from a collaborative quality improvement program, we evaluated the impact of a digital intervention on asthma inhaler use among children in southwest Detroit. Methods Children (6–13 years) enrolled with Kids Health Connection (KHC), a program involving home visits with an asthma educator, were invited to participate in a digital self-management asthma program (Propeller Health). Patients were provided with a sensor to capture short-acting beta-agonist (SABA) medication use, and given access to a paired mobile app to track usage. Patients’ healthcare providers and caregivers (“followers”) were invited to view data as well. Retrospective paired t-tests assessed change in mean SABA use and SABA-free days (SFD) over time, and regressions explored the relationship between followers and medication use. Results Fifty-one patients were assessed. Mean program participation was nine months, and patients had on average 3 followers. From the first to last participation month, mean SABA use decreased from 0.68 to 0.25 puffs/day (p

Abstract Introduction In the context of the COVID-19 pandemic, upstream interventions that tackle social determinants of health inequalities have never been more important. Evaluations of upstream cash transfer trials have failed to capture comprehensively the impacts that such systems might have on population health through inadequate design of the interventions themselves and failure to implement consistent, thorough research measures that can be used in microsimulations to model long-term impact. In this article, we describe the process of developing a generic, adaptive protocol resource to address this issue and the challenges involved in that process. The resource is designed for use in high-income countries (HIC) but draws on examples from a UK context to illustrate means of development and deployment. The resource is capable of further adaptation for use in low- and middle-income countries (LMIC). It has particular application for trials of Universal Basic Income but can be adapted to those covering other kinds of cash transfer and welfare system changes. Methods We outline two types of prospective intervention based on pilots and trials currently under discussion. In developing the remainder of the resource, we establish six key principles, implement a modular approach based on types of measure and their prospective resource intensity, and source (validated where possible) measures and baseline data primarily from routine collection and large, longitudinal cohort studies. Through these measures, we seek to cover all areas of health impact identified in our theoretical model for use in pilot and feasibility studies. Results We find that, in general, self-reported measures alongside routinely collected linked respondent data may provide a feasible means of producing data capable of demonstrating comprehensive health impact. However, we also suggest that, where possible, physiological measures should be included to elucidate underlying biological effects that may not be accurately captured through self-reporting alone and can enable modelling of long-term health outcomes. In addition, accurate self-reported objective income data remains a challenge and requires further development and testing. A process of development and implementation of the resource in pilot and feasibility studies will support assessment of whether or not our proposed health outcome measures are acceptable, feasible and can be used with validity and reliability in the target population. Discussion We suggest that while Open Access evaluation instruments are available and usable to measure most constructs of interest, there remain some areas for which further development is necessary. This includes self-reported wellbeing measures that require paid licences but are used in a range of nationally important longitudinal studies instead of Open Access alternatives.

Objective Universal Basic Income (UBI)—a largely unconditional, regular payment to all adults to support basic needs—has been proposed as a policy to increase the size and security of household incomes and promote mental health. We aimed to quantify its long-term impact on mental health among young people in England.Methods We produced a discrete-time dynamic stochastic microsimulation that models a close-to-reality open cohort of synthetic individuals (2010–2030) based on data from Office for National Statistics and Understanding Society. Three UBI scheme scenarios were simulated: Scheme 1—Starter (per week): £41 per child; £63 per adult over 18 and under 65; £190 per adult aged 65+; Scheme 2—Intermediate (per week): £63 per child; £145 per adult under 65; £190 per adult aged 65+; Scheme 3—Minimum Income Standard level (per week): £95 per child; £230 per adult under 65; £230 per adult aged 65+. We reported cases of anxiety and depression prevented or postponed and cost savings. Estimates are rounded to the second significant digit.Results Scheme 1 could prevent or postpone 200 000 (95% uncertainty interval: 180 000 to 210 000) cases of anxiety and depression from 2010 to 2030. This would increase to 420 000(400 000 to 440 000) for Scheme 2 and 550 000(520 000 to 570 000) for Scheme 3. Assuming that 50% of the cases are diagnosed and treated, Scheme 1 could save £330 million (£280 million to £390 million) to National Health Service (NHS) and personal social services (PSS), over the same period, with Scheme 2 (£710 million (£640 million to £790 million)) or Scheme 3 (£930 million (£850 million to £1000 million)) producing more considerable savings. Overall, total cost savings (including NHS, PSS and patients’ related costs) would range from £1.5 billion (£1.2 billion to £1.8 billion) for Scheme 1 to £4.2 billion (£3.7 billion to £4.6 billion) for Scheme 3.Conclusion Our modelling suggests that UBI could substantially benefit young people’s mental health, producing substantial health-related cost savings.

The United States along with the rest of the world has experienced an unprecedented disruption in daily life due to the COVID-19 pandemic. Almost everyone has experienced some sort of stay at home order resulting in an economic catastrophe greater than the Great Recession of 2008 and on par with the Great Depression almost a century ago. Educational institutions at both the K-12 and post-secondary levels have not been immune from the shutdown, with many schools closed from mid-March through the end of the 2020 school year. Many schools moved classes to remote, distance delivery platforms. Career and Technical Education (CTE) teachers were tasked with creative engaging learning activities online for curricula which is taught in a hands-on contextual learning environment. This paper will present preliminary results from research conducted by a collaborative group of nine researchers from across the United States with collectively over 200 years of career and technical education experience. The conceptual framework used for this study was Danielson's Framework for Teaching and Enhancing Professional Practice and Foundations of Career and Technical Education including Constructivism. 3,267 participants representing all 50 states responded to the 37-item survey. The research objectives included description of participants and identified challenges to planning and delivery of CTE content when schools were closed, and instruction was moved to remote/distance/online platforms. Participants ranked their challenges as instructors and their perceptions of challenges that were experienced by their students. CTE teachers ranked replicating classroom or lab environments online and lack of experience teaching online as their biggest challenges. The perceptions of the participants concerning challenges for their students included motivation to guide and manage their own learning and students' access to reliable internet connection. The emergence and prevalence of the COVID-19 pandemic added a layer of complexity to educational practice that was not foreseen and for which no intentional preparation had occurred. Understanding how CTE teachers and instructors responded to this call, and the challenges they and their students encountered, is important to efforts to improve practice in the future and to be in a better position should another crisis occur that forces learning to be delivered in alternative formats from that of the traditional face-to-face classroom. [Note: The page range (177-194) shown on the PDF is incorrect. The correct page range is 177-193.]

Although there is increased interest in social and emotional competence and mental health in Croatia, there are currently limited measurement options available for early childhood settings. Thus, the SSIS SEL Brief Scales (SSIS SELb), an efficient measure of social and emotional learning competencies developed in the United States, was translated to Croatian and used by 49 early childhood educators to rate a sample of 685 children (average age 4.3 years) from several counties in Croatia. Regarding measurement invariance, the final model cohered substantially with a CASEL-inspired framework. Overall reliability was also high especially for the SEL Composite ([alpha] = 0.94), with notably lower reliability for subscales. Regarding cross-group concurrent validity, concurrent coefficients were largely similar across age and gender, but there were regional differences in validity. Likewise, validity correlations were in line with expectations, with moderate relationships observed between the SSIS SEL Composite and Child and Youth Resilience Measure scores. In sum, the high level of reliability provided a foundation for applied and research usage of the Croatian SSIS SELb, although further validation research will continue to be necessary before widescale implementation. Limitations to the study are discussed and also point to needed additional research before utilizing the Croatian translated SSIS SELb for applied decisions with young children.

The SSIS SEL Brief + Mental Health Scales (SSIS SELb+MHS) are multi-informant assessments developed in the United States to assess the social and emotional learning (SEL) competencies and emotional behavior concerns (EBCs) of school-age youth. Although there are translations of the SEL items of the SSIS SELb+MHS available in other languages, a German translation has never been completed and validated, despite the growing need for SEL and mental health assessment in German-speaking countries. To address this need, this study's primary purpose was the examination of a German translation of the assessment with a specific focus on measurement invariance and concurrent validity invariance testing with 821 3rd through 6th-grade students in Austria and Germany. Results indicated that the SELb+MHS items clustered into 2 SEL factors and 2 EBC factors. With regard to measurement invariance, the SELb+MHS functioned similarly across both Austria and Germany and full scalar invariance was achieved. Additionally, the overall pattern of concurrent validity relationships was as expected and similar across countries. Implications and future directions are discussed.

This paper discusses the implementation of exemplar essays within an undergraduate first-year diagnostic radiography module to encourage active learning and the development of academic literacies. Nine essays ([approximately]400 words each) were provided over six sessions, using lecturer-guided discussion to explore the academic virtues and pitfalls demonstrated alongside assessment criteria. Exemplars were based upon a fictitious baking profession to illicit student interest and eliminate the risk of imitation or plagiarism. The quality of essays varied, with overt examples of common mistakes in spelling, essay structure and selection of appropriate literature. Upon completion of the sessions, and prior to summative assessment, students were surveyed with regard to their opinion of the teaching intervention. Feedback was obtained from 65% of the cohort (n=31/48), who reported an improvement in essay writing confidence. Students found the marking of the essays in class useful and the baking analogy was well received. Not all students found the classroom activities engaging though, with some wishing greater interactivity due to boredom and repetition. Furthermore, there was a slight reduction in pass rates and average marks across the cohort when compared to the previous module delivery. Nevertheless, there was a substantial increase in students attaining marks of 80% or more. This study highlights exemplar essays as a low-tech, low-cost option to increase assessment literacy but accepts the wide diversity in student learning preferences and experience. The efficacy of exemplar essays cannot be guaranteed, and teaching staff must be cognisant of individual student learning needs.

Extension Professionals have varying expectations of academic publication depending on tenure and promotion. And, the field of Extension needs the contributions of professionals across the system to support the translation and dissemination of the impacts of and findings from their Extension programming for academic and practitioner audiences. A writing retreat was held to support 4-H Youth Development professionals in academic writing. Because of this writing retreat five teams started working on an academic writing project which resulted in three journal articles being published. Teams also published conference presentations and Extension publications as a result of the initial academic writing project. Intentionally providing writing retreats that prepare professionals to write can support effective capacity building for academic publishing.

Successful Black reparations require a policy for delivering payments, one that provides for effective identification, disbursement, asset protection, and asset growth over time. In this article, we suggest a structural solution (structured wealth accumulation of reparations payments) to a structural challenge (deeply embedded racial wealth inequality). Analyzing evidence from a longitudinal experiment, we find that Child Development Accounts (CDAs)--a carefully designed and tested asset- building policy for children--provide a model that can inform effective delivery and sustainable growth of reparations. CDA policy models a system of potentially lifelong, centralized asset building, with automatic enrollment, sensible investment options, structured asset protections, low fees, asset growth, and investment targets to achieve individual and family goals. Policy and research implications for Black reparations and reduction in racial wealth inequality are discussed.

Teaching and learning undergraduate statistics has been a most challenging task for undergraduate psychology majors (Salkind, 2017). A seasoned statistics instructor consulted with a seasoned instructional designer on a method to improve a particularly demanding course using a performance improvement approach to address learning difficulties she had noted in previous semesters. The Decoding the Disciplines methodology identified the most challenging concepts and provided a methodology to improve student learning performance. The methodology focused on five core concepts in psychological statistics: probability, variability, central limit theorem, independent/dependent variables, and degrees of freedom. The Decoding the Disciplines curriculum was used for three semesters. In these three semesters, performance was compared pre and post on these concepts within the semester. Repeated measures t-tests found a significant change in the percentage of correct answers between the pretest and the final exam on the five core concepts.

This paper focuses on the nature of the legacy that Lawrence Stenhouse bequeathed in the field of curriculum development and research, particularly in relation to his idea of 'the teacher as researcher'. In the process, it explores the contemporary relevance of this legacy to those who are currently attempting to rethink and re-enact the relationship between teachers and the school curriculum in a policy context. It also explores the impact of Stenhouse's work on the development of a collaborative action research movement within the United Kingdom and beyond. The author distinguishes a particular strand of collaborative action research which he depicts as the "neo-Stenhouse tradition" of applied research in education and distinguishes from the "Stenhouse legacy" as such. This distinction is based on a recognition that Stenhouse's legacy and idea of 'the teacher as researcher' was a "work in progress," which he himself acknowledged. Drawing on ambiguities in Stenhouse's thinking about the relationships between educational theory and practice and between teachers and researchers, the author argues that there are strong conceptual links between Stenhouse's idea of 'the teacher as researcher' and his account of case study as a method of applied research in education. The paper concludes with an argument for the contemporary relevance of Stenhouse's work, and the tradition of applied research in education he wanted to establish, in policy contexts where curriculum development and research is dominated by a performative model of rationality.

In this article, we explore inconsistencies in the implementation of outdoor learning across Australian early years' education. The benefits of outdoor learning justify regular employment of this pedagogical approach in both early childhood education and primary school settings. Early childhood education services provide daily outdoor learning opportunities as required by Australian national policy documents. However, Australian primary schools are not subject to such requirements and teachers often face challenges regarding outdoor learning, thus regular implementation in primary classes can be a low priority. As children in the year before school and the first year of school have similar learning and developmental needs, we argue that the benefits of outdoor learning should be available to all children across the early years. We also recommend regular outdoor learning in the first year of schooling to promote continuity as children transition from early childhood education to primary schools.

Morphological differentiation and relationships among collared lemmings (Dicrostonyx Gloger, 1841) remain unclear. This issue is particularly important in the Kivalliq Region, Nunavut, Canada, where Dicrostonyx groenlandicus (Traill, 1823) and Dicrostonyx richardsoni Merriam, 1900 ranges overlap. Possible sympatry of both species obscures the taxonomic status of collared lemmings from this area. We compared 2D outline shapes of the skull and three upper molars of collared lemmings collected from seven areas of the Canadian Arctic, including specimens from the Baker Lake – Aberdeen Lake area, in the Kivalliq Region, and Dicrostonyx hudsonius (Pallas, 1778) as an outgroup. Multivariate analyses revealed two distinct groups when considering the molars: D. hudsonius, and the remainder of lemmings. Dicrostonyx richardsoni, D. groenlandicus, and the lemmings from the Baker Lake – Aberdeen Lake area showed significant differences, especially when considering skull shapes, thus suggesting three distinct groups. However, skull shapes proved inefficient in discriminating between species. These differences suggest that collared lemmings from the Baker Lake – Aberdeen Lake area may not be correctly assigned to either of the two species without further genetic evaluation. They also suggest that these lemmings should have a peculiar taxonomic status. Our study calls for further taxonomical investigations for collared lemmings from the overlapping distribution ranges of D. groenlandicus and D. richardsoni.

BACKGROUND AND OBJECTIVES: Idiopathic/isolated REM sleep behavior disorder (iRBD) has been strongly linked to neurodegenerative synucleinopathies such as Parkinson disease, dementia with Lewy bodies, and multiple system atrophy. However, there have been increasing reports of RBD as a presenting feature of serious and treatable autoimmune syndromes, particularly IGLON5. This studys objective was to investigate the frequency of autoantibodies in a large cohort of participants with iRBD. METHODS: Participants were enrolled in the North American Prodromal Synucleinopathy cohort with polysomnography-confirmed iRBD, free of parkinsonism and dementia. Plasma samples were systematically screened for the autoantibodies IGLON5, DPPX, LGI1, and CASPR2 using plasma IgG cell-based assay. Positive or equivocal results were confirmed by repeat testing, plus tissue-based indirect immunofluorescence assay for IGLON5. RESULTS: Of 339 samples analyzed, 3 participants (0.9%) had confirmed positive IGLON5 autoantibodies in the cell-based assay, which were confirmed by the tissue-based assay. An additional participant was positive for CASPR2 with low titer by cell-based assay only (of lower clinical certainty). These cases exhibited a variety of symptoms including dream enactment, cognitive decline, autonomic dysfunction, and motor symptoms. In 1 IGLON5 case and the CASPR2 case, evolution was suggestive of typical synucleinopathy, suggesting the possibility that findings were incidental. However, 2 participants with IGLON5 died before diagnosis was clinically suspected, with a final clinical picture highly suggestive of autoimmune disease. DISCUSSION: Our finding that nearly 1% of a large iRBD cohort may have a serious but potentially treatable autoantibody syndrome has important clinical implications. In particular, it raises the question of whether autoantibody testing for IGLON-5-IgG should be widely implemented for participants with iRBD, considering the difficulty in diagnosis of autoimmune diseases, their response to treatment, and the potential for rapid disease progression. However, any routine testing protocol will also have to consider costs and potential adverse effects of false-positive findings. TRIAL REGISTRATION INFORMATION: NCT03623672.

Clinical trials in metabolic dysfunction-associated steatohepatitis (MASH, formerly known as nonalcoholic steatohepatitis) require histologic scoring for assessment of inclusion criteria and endpoints. However, variability in interpretation has impacted clinical trial outcomes. We developed an artificial intelligence-based measurement (AIM) tool for scoring MASH histology (AIM-MASH). AIM-MASH predictions for MASH Clinical Research Network necroinflammation grades and fibrosis stages were reproducible (κ = 1) and aligned with expert pathologist consensus scores (κ = 0.62-0.74). The AIM-MASH versus consensus agreements were comparable to average pathologists for MASH Clinical Research Network scores (82% versus 81%) and fibrosis (97% versus 96%). Continuous scores produced by AIM-MASH for key histological features of MASH correlated with mean pathologist scores and noninvasive biomarkers and strongly predicted progression-free survival in patients with stage 3 (P

PURPOSE: Nuclear protein in testis carcinoma (NC) is an underdiagnosed and aggressive squamous/poorly differentiated cancer characterized by rearrangement of the gene NUTM1 on chromosome 15q14. Co-occurring alternations have not been fully characterized. METHODS: We analyzed the genomic and immune landscape of 54 cases of NC that underwent DNA- and RNA-based NGS sequencing (Caris). RESULTS: While NC is driven by NUTM1 fusion oncoproteins, co-occurring DNA mutations in epigenetic or cell cycle pathways were observed in 26% of cases. There was no significant difference between the fusion partner of NUTM1 and co-occurring gene mutations. RNA sequencing analysis showed increased MYC pathway activity in NC compared with head and neck squamous cell carcinoma (HNSCC) and lung squamous cell carcinoma (LUSC), which is consistent with the known pathophysiology of NC. Characterization of the NC tumor microenvironment using RNA sequencing revealed significantly lower immune cell infiltration compared with HNSCC and LUSC. NC was 10× higher in patients with HNSCC and LUSC younger than 50 years than in those older than 70 years. CONCLUSION: To our knowledge, this is the first series of NC profiled broadly at the DNA and RNA level. We observed fewer intratumoral immune cells by RNA sequencing, which may be associated with anecdotal data of lack of immunotherapy benefit in NC. High MYC pathway activity in NC supports ongoing trials targeting MYC suppression. The incidence of NC among patients younger than 50 years with LUSC/HNSCC supports testing for NC in these patients. The prognosis of NCs remains dismal, and future studies should focus on improving the response to immunotherapy and targeting MYC.

Cisplatin is a commonly used chemotherapy agent with a nearly universal side effect of sensorineural hearing loss. The cellular mechanisms underlying cisplatin ototoxicity are poorly understood. Efforts in drug development to prevent or reverse cisplatin ototoxicity have largely focused on pathways of oxidative stress and apoptosis. An effective treatment for cisplatin ototoxicity, sodium thiosulfate (STS), while beneficial when used in standard risk hepatoblastoma, is associated with reduced survival in disseminated pediatric malignancy, highlighting the need for more specific drugs without potential tumor protective effects. The unfolded protein response (UPR) and endoplasmic reticulum (ER) stress pathways have been shown to be involved in the pathogenesis of noise-induced hearing loss and cochlear synaptopathy in vivo, and these pathways have been implicated broadly in cisplatin cytotoxicity. This study sought to determine whether the UPR can be targeted to prevent cisplatin ototoxicity. Neonatal cochlear cultures and HEK cells were exposed to cisplatin, and UPR marker gene expression and cell death measured. Treatment with ISRIB (Integrated Stress Response InhIBitor), a drug that activates eif2B and downregulates the pro-apoptotic PERK/CHOP pathway of the UPR, was tested for its ability to reduce apoptosis in HEK cells, hair-cell death in cochlear cultures, and hearing loss using an in vivo mouse model of cisplatin ototoxicity. Finally, to evaluate whether ISRIB might interfere with cisplatin chemoeffectiveness, we tested it in head and neck squamous cell carcinoma (HNSCC) cell-based assays of cisplatin cytotoxicity. Cisplatin exhibited a biphasic, non-linear dose-response of cell death and apoptosis that correlated with different patterns of UPR marker gene expression in HEK cells and cochlear cultures. ISRIB treatment protected against cisplatin-induced hearing loss and hair-cell death, but did not impact cisplatins cytotoxic effects on HNSCC cell viability, unlike STS. These findings demonstrate that targeting the pro-apoptotic PERK/CHOP pathway with ISRIB can mitigate cisplatin ototoxicity without reducing anti-cancer cell effects, suggesting that this may be a viable strategy for drug development.

Modern advancements in targeted therapy and immunotherapy have significantly improved survival outcomes for advanced melanoma; however, there remains a need for novel approaches to overcome disease progression and treatment resistance. In recent years, PARPi therapy has shown great promise both as a single regimen and in combination with other therapeutics in melanoma. Here, we describe three unique cases of advanced BRAF V600 mutated melanoma that progressed on targeted BRAF/MEK agents that subsequently exhibited partial to near-complete responses to combinatory PARPi and BRAF/MEK inhibitors. This highlights both a potential synergy underlying this combinatory approach and its efficacy as a treatment option for patients with advanced melanoma refractory to targeted and/or immunotherapies. Prospective clinical trials are needed to explore this synergic effect in larger melanoma cohorts to investigate this combination for treating refractory advanced melanoma.

BACKGROUND: Prenatal fish intake is a key source of omega-3 (ω-3) polyunsaturated fatty acids needed for brain development, yet intake is generally low, and studies addressing associations with autism spectrum disorder (ASD) and related traits are lacking. OBJECTIVE: This study aimed to examine associations of prenatal fish intake and ω-3 supplement use with both autism diagnosis and broader autism-related traits. METHODS: Participants were drawn from 32 cohorts in the Environmental influences on Child Health Outcomes Cohort Consortium. Children were born between 1999 and 2019 and part of ongoing follow-up with data available for analysis by August 2022. Exposures included self-reported maternal fish intake and ω-3/fish oil supplement use during pregnancy. Outcome measures included parent report of clinician-diagnosed ASD and parent-reported autism-related traits measured by the Social Responsiveness Scale (SRS)-second edition (n = 3939 and v3609 for fish intake analyses, respectively; n = 4537 and n = 3925 for supplement intake analyses, respectively). RESULTS: In adjusted regression models, relative to no fish intake, fish intake during pregnancy was associated with reduced odds of autism diagnosis (odds ratio: 0.84; 95% confidence interval [CI]: 0.77, 0.92), and a modest reduction in raw total SRS scores (β: -1.69; 95% CI: -3.3, -0.08). Estimates were similar across categories of fish consumption from any or less than once per week to more than twice per week. For ω-3 supplement use, relative to no use, no significant associations with autism diagnosis were identified, whereas a modest relation with SRS score was suggested (β: 1.98; 95% CI: 0.33, 3.64). CONCLUSIONS: These results extend previous work by suggesting that prenatal fish intake, but not ω-3 supplement use, may be associated with lower likelihood of both autism diagnosis and related traits. Given the low-fish intake in the United States general population and the rising autism prevalence, these findings suggest the need for better public health messaging regarding guidelines on fish intake for pregnant individuals.