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The biological mechanisms underlying the greater prevalence of autism spectrum disorder in males than females remain poorly understood. One hypothesis posits that this female protective effect arises from genetic load for autism spectrum disorder differentially impacting male and female brains. To test this hypothesis, we investigated the impact of cumulative genetic risk for autism spectrum disorder on functional brain connectivity in a balanced sample of boys and girls with autism spectrum disorder and typically developing boys and girls (127 youth, ages 8-17). Brain connectivity analyses focused on the salience network, a core intrinsic functional connectivity network which has previously been implicated in autism spectrum disorder. The effects of polygenic risk on salience network functional connectivity were significantly modulated by participant sex, with genetic load for autism spectrum disorder influencing functional connectivity in boys with and without autism spectrum disorder but not girls. These findings support the hypothesis that autism spectrum disorder risk genes interact with sex differential processes, thereby contributing to the male bias in autism prevalence and proposing an underlying neurobiological mechanism for the female protective effect.

Females versus males are less frequently diagnosed with autism spectrum disorder (ASD), and while understanding sex differences is critical to delineating the systems biology of the condition, female ASD is understudied. We integrated functional MRI and genetic data in a sex-balanced sample of ASD and typically developing youth (8-17 years old) to characterize female-specific pathways of ASD risk. Our primary objectives were to: (i) characterize female ASD (n = 45) brain response to human motion, relative to matched typically developing female youth (n = 45); and (ii) evaluate whether genetic data could provide further insight into the potential relevance of these brain functional differences. For our first objective we found that ASD females showed markedly reduced response versus typically developing females, particularly in sensorimotor, striatal, and frontal regions. This difference between ASD and typically developing females does not resemble differences between ASD (n = 47) and typically developing males (n = 47), even though neural response did not significantly differ between female and male ASD. For our second objective, we found that ASD females (n = 61), versus males (n = 66), showed larger median size of rare copy number variants containing gene(s) expressed in early life (10 postconceptual weeks to 2 years) in regions implicated by the typically developing female > female functional MRI contrast. Post hoc analyses suggested this difference was primarily driven by copy number variants containing gene(s) expressed in striatum. This striatal finding was reproducible among n = 2075 probands (291 female) from an independent cohort. Together, our findings suggest that striatal impacts may contribute to pathways of risk in female ASD and advocate caution in drawing conclusions regarding female ASD based on male-predominant cohorts.

Background Despite improvements in survival over time, the mortality rate for infants with single‐ventricle heart disease remains high. Infants of low socioeconomic status (SES) are particularly vulnerable. We sought to determine whether use of a novel remote monitoring program, the Cardiac High Acuity Monitoring Program, mitigates differences in outcomes by SES. Methods and Results Within the Cardiac High Acuity Monitoring Program, we identified 610 infants across 11 centers from 2014 to 2021. All enrolled families had access to a mobile application allowing for near‐instantaneous transfer of patient information to the care team. Patients were divided into SES tertiles on the basis of 6 variables relating to SES. Hierarchical logistic regression, adjusted for potential confounding characteristics, was used to determine the association between SES and death or transplant listing during the interstage period. Of 610 infants, 39 (6.4%) died or were listed for transplant. In unadjusted analysis, the rate of reaching the primary outcome between SES tertiles was similar (P=0.24). Even after multivariable adjustment, the odds of death or transplant listing were no different for those in the middle (odds ratio, 1.7 [95% CI, 0.73–3.94) or highest (odds ratio, 0.997 [95% CI, 0.30, 3.36]) SES tertile compared with patients in the lowest (overall P value 0.4). Conclusions In a large multicenter cohort of infants with single‐ventricle heart disease enrolled in a digital remote monitoring program during the interstage period, we found no difference in outcomes based on SES. Our study suggests that this novel technology could help mitigate differences in outcomes for this fragile population of patients.

Introduction I. Comparative Codifications A. Calls for a Canadian Cabinet Manual II. Beyond a Cabinet Manual: Codifying the Canadian Political Constitution A. International Benchmarks B. Types of Rules to Codify [...], Canada's constitution is legal and political. The legal component, which includes the Constitution Acts, 1867 and 1982, is more easily recognized and appreciated by lawyers, politicians, and the wider public. However, Canada's political constitution is equally important. The political constitution is comprised of the non-legal rules and norms that underpin Canadian democracy and governmental accountability. Although the legal and political constitutions each form an essential part of Canadian constitutionalism, the written quality of the former tends to ensure its dominance over the latter. In this article, we argue that the time has come for Canada to commit its political constitution to writing. In offering these arguments, we seek to move beyond the reasons scholars typically offer in favour of codifying the political aspects of the constitution, whether in a cabinet manual, ministerial code or other document. Calls to codify the political constitution have tended to intensify after events that raise questions about the application of a particular constitutional convention or conventions, or the propriety of the Prime Minister's or another Minister's actions. While this is understandable, viewing codification primarily as a solution to crisis and controversy falls short. Instead, we argue that the process of committing the political constitution to writing would give political actors-parliamentarians, ministers, and senior parliamentary and government officials--an opportunity to reflect on the political rules and norms that govern Canada's pluralistic, multinational federation at this point in its constitutional development. Our focus, then, is not on codification as a check on political actors, but as a vehicle to revitalize their roles and responsibilities as authors of the political constitution, an organic, evolving set of rules and norms that governs how our legislative and executive bodies operate.

Background: The goal of the study was to develop and verify a pathway model (or theory of change) for STEM Scouts, an out-of-school time (OST), positive youth development program for elementary through high school-aged youth. Pathway models include connections between hypothesized activities to short-, mid-, and long-term outcomes. STEM Scouts is offered across the United States and a secondary goal of the study was to understand the STEM ecosystem in the communities where STEM Scouts is currently implemented. Results: Evidence mapping was conducted to determine the extent to which the theory of change was consistent with the extant literature; 69% of the connections on the key pathways were supported by research. For connections where supporting evidence was not found, the connections were either removed or retained because the connection between constructs was understudied. The literature review also led to the addition of outcomes and language revisions to more closely align with terminology used in the literature. Focus groups were conducted to determine the extent to which the pathway model was consistent with youth and adult participants' lived experience and to better understand STEM ecosystems. The pathway model resonated with most participants' experiences with STEM Scouts. Participants across multiple focus groups suggested adding outcomes related to learning and leadership. Parents and other family members, the availability of OST STEM programs, and schools were frequently noted as critical elements of the STEM ecosystem. Conclusions: Careful evaluation planning, including the development and validation of a detailed theory of change, is a critical step in STEM education program evaluation. This study revealed the value added when such steps are taken. Critical outcomes and connections would have been missed without the development and validation of the theory of change which will form the basis of a future evaluation. OST STEM programs should strive to engage in careful and detailed evaluation planning in advance of engaging in program evaluation.