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Cortical surface functional magnetic resonance imaging (cs-fMRI) has recently grown in popularity versus traditional volumetric fMRI. In addition to offering better whole-brain visualization, dimension reduction, removal of extraneous tissue types, and improved alignment of cortical areas across subjects, it is also more compatible with common assumptions of Bayesian spatial models. However, as no spatial Bayesian model has been proposed for cs-fMRI data, most analyses continue to employ the classical general linear model (GLM), a \"massive univariate\" approach. Here, we propose a spatial Bayesian GLM for cs-fMRI, which employs a class of sophisticated spatial processes to model latent activation fields. We make several advances compared with existing spatial Bayesian models for volumetric fMRI. First, we use integrated nested Laplacian approximations, a highly accurate and efficient Bayesian computation technique, rather than variational Bayes. To identify regions of activation, we utilize an excursions set method based on the joint posterior distribution of the latent fields, rather than the marginal distribution at each location. Finally, we propose the first multi-subject spatial Bayesian modeling approach, which addresses a major gap in the existing literature. The methods are very computationally advantageous and are validated through simulation studies and two task fMRI studies from the Human Connectome Project. Supplementary materials for this article, including a standardized description of the materials available for reproducing the work, are available as an online supplement.

Children with attention-deficit hyperactivity disorder (ADHD) experience substantial difficulty maintaining meaningful friendships, which has implications for social functioning and mental health. No systematic review has investigated their friendship difficulties. To systematically review and methodologically appraise the quality of existing studies reporting on friendships of children with ADHD. To compare their friendships to typically-developing children, and examine associations between friendship and children's social-emotional wellbeing and mental health. Six databases were searched. The methodological quality of studies was assessed using the QualSyst appraisal tool and the Appraisal tool for Cross-Sectional Studies. Aspects of friendships measured were charted, along with comparisons between children with ADHD and typically-developing children and the associations between friendships and social-emotional wellbeing and mental health. Twenty-three cross-sectional studies and one longitudinal follow-up study were included. Studies included 1509 participants with ADHD, with 1197 typically-developing participants used as a companion in 19 of the 24 studies. Friendship quantity was the most investigated aspect of friendship. Children and youth with ADHD had significantly fewer friends, lower quality friendships and poorer friendship interactions. There were mixed findings from studies investigating the role or impact of friendship on social-emotional wellbeing and mental health. Twenty-two had strong methodological quality. Limited longitudinal studies, small sample sizes and variability in measurement restrict the interpretations of friendship over time and the causal impact of friendship on social and emotional outcomes. Further research should investigate the role and impact of friendships on the social-emotional wellbeing of children and youth with ADHD.

There is some consensus in the literature that economic sanctions might prompt more human rights abuses in target countries. Yet, the causal mechanisms underlining the sanctions-repression nexus remain little understood. Using causal mediation analysis, we examine the processes through which sanctions might deteriorate human rights conditions. We specifically propose two indirect mechanisms driving human rights violations: increased domestic dissent and reduced government capacity. Sanctions are likely to trigger domestic dissent, and this instability would further induce the government to employ repression. Reduced government capacity caused by sanctions will harm the government's ability to screen and oversee its security agents, which would subsequently lead to increased human rights abuses. Results from a time-series, cross-national data analysis indicate that sanctions-induced dissent, particularly violent dissent, plays a significant mediating role in the sanctions-repression link. Likewise, we find strong evidence that diminished fiscal capacity triggered by sanctions is likely to result in more repression. There is also some modest evidence that corruption as a proxy for poor governance mediates the sanctions-repression relationship.

Self-regulation, which encompasses cognitive, behavioural, and emotional domains, poses challenges in consistent measurement due to diverse definitions and conceptual complexities. In recognition of its profound impact on long-term mental health and wellbeing in children, this systematic review examined available self-regulation measures for children and young people between 1 and 18 years of age. The systematic review followed the COSMIN taxonomy and reported on the measurement tools’ characteristics and psychometric properties. The methodology and reporting were guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and checklist. The protocol for this review was registered with PROSPERO (Number CRD42020155809). A search of six databases (Embase, MEDLINE, PsycINFO, Scopus, CINAHL and ERIC) was performed, and grey literature was searched to identify studies on the psychometric properties of measures assessing all three domains (cognitive, behavioural, and emotional) of self-regulation. The types of psychometric properties were examined against the COSMIN taxonomy of measurement properties. A total of 15,583 studies were identified, and 48 of these met the criteria that reported psychometric properties of 23 self-regulation measures assessing all three domains of self-regulation. Most measures relied on self-reports for ages 11–17, and all had limited psychometric evaluation. The Emotion Regulation Checklist was the most studied measure. Notably, none of the studies evaluated measurement error. The content validity was inadequately evaluated, particularly in terms of comprehensiveness and comprehensibility. Future research should focus on developing measures for young children, evaluating measurement error, and enhancing content validity for comprehensive understanding and effective intervention.

Recent data show a global increase in colorectal cancer (CRC) cases among younger demographics, which portends poorer prognosis. The cause of rising incidence is uncertain, and its mutational landscape remains largely unexplored, including those in genes of the epidermal growth factor receptor pathway. Among these are NRAS mutants where there is paucity of functional studies compared to KRAS. Here, the novel NRAS mutant E132K, identified in three tumor samples from Filipino young-onset, sporadic colorectal cancer patients, was investigated for its effects on different cancer hallmarks, alongside the NRAS canonical mutants G12D and Q61K which are yet poorly characterized in the context of CRC. The novel NRAS mutant E132K and the canonical G12D and Q61K mutants show resistance to apoptosis, cytoskeletal reorganization, and loss of adhesion. In contrast to activating KRAS mutations, including the analogous KRAS G12D and Q61K mutations, all three NRAS mutants have no apparent effect on cell proliferation and motility. The results highlight the need to characterize isoform- and mutation-specific oncogenic phenotypes which can have repercussions in disease management and choice of therapeutic intervention. Further analyses of young-onset versus late-onset CRC datasets are necessary to qualify NRAS E132K as a biomarker for the young-onset subtype.

How does the domestic environment affect a government's incentives to use coercion against another country? Traditional diversionary literature indicates that governments facing internal pressures will initiate military actions overseas to improve popularity. I argue that struggling governments are more inclined to employ economic sanctions over military force because of lower cost and political risk. I further posit that when governments encounter nonviolent protests and strong competition in the legislature, they have more incentives to initiate sanctions. Foreign sanctions are used to project sanctioning leaders’ competence and increase national cohesion. I test the empirical implication of the argument on a sample of 137 countries from 1975 to 2005. The multinomial logit results show that diversionary use of sanctions is more likely when incumbents face maximalist nonviolent mobilization and higher legislative opposition, but these domestic challenges do not prompt military actions. This study presents a domestic explanation for sanctions initiation; it also casts doubt on the conventional predictions that beleaguered governments will resort to the use of force.

In this work, we consider variable selection when modelling the intensity and clustering of inhomogeneous spatial point processes, integrating well-known procedures in the respective fields of variable selection and spatial point process modelling to introduce a simple procedure for variable selection in spatial point process modelling. Specifically, we consider modelling spatial point data with Poisson, pairwise interaction and Neyman—Scott cluster models, and incorporate LASSO, adaptive LASSO, and elastic net regularization methods into the generalized linear model framework for fitting these point models. We perform simulation studies to explore the effectiveness of using each of the three-regularization methods in our procedure. We then use the procedure in two applications, modelling the intensity and clustering of rainforest trees with soil and geographical covariates using a Neyman—Scott model, and of fast food restaurant locations in New York City with Census variables and school locations using a pairwise interaction model. Les auteurs traitent de la sélection de variables dans le cadre de la modélisation de l'intensité et du regroupement de processus ponctuels spatiaux inhomogènes. Ils proposent une procédure simple qui s'inspire de méthodes bien connues dans les domaines de la sélection de variables et de la modélisation de processus ponctuels spatiaux. Plus précisément, les auteurs modélisent les points spatiaux avec les modèles de regroupement de Poisson, de Neyman—Scott et d'interaction par paire. Ils incorporent le LASSO, le LASSO adaptatif et les filets élastiques à même un modèle linéaire généralisé afin d'ajuster ces modèles de processus ponctuels. Ils effectuent des simulations afin d'évaluer l'efficacité des trois méthodes de sélection de variables proposées. Ils utilisent finalement leur procédure pour deux analyses de données. Dans un premier cas, ils utilisent le modèle de Neyman—Scott afin de modéliser l'intensité et le regroupement des arbres dans la forêt humide en fonction du type de sol et de variables géographiques. Dans un deuxième cas, ils étudient l'emplacement des établissements de restauration rapide de la ville de New York avec un modèle d'interaction par paire en fonction des variables du recensement et de l'emplacement des écoles.

Insulin and other injectable biologic drugs have transformed the treatment of patients suffering from diabetes 1 , 2 , yet patients and healthcare providers often prefer to use and prescribe less effective orally dosed medications 3 – 5 . Compared with subcutaneously administered drugs, oral formulations create less patient discomfort 4 , show greater chemical stability at high temperatures 6 , and do not generate biohazardous needle waste 7 . An oral dosage form for biologic medications is ideal; however, macromolecule drugs are not readily absorbed into the bloodstream through the gastrointestinal tract 8 . We developed an ingestible capsule, termed the luminal unfolding microneedle injector, which allows for the oral delivery of biologic drugs by rapidly propelling dissolvable drug-loaded microneedles into intestinal tissue using a set of unfolding arms. During ex vivo human and in vivo swine studies, the device consistently delivered the microneedles to the tissue without causing complete thickness perforations. Using insulin as a model drug, we showed that, when actuated, the luminal unfolding microneedle injector provided a faster pharmacokinetic uptake profile and a systemic uptake >10% of that of a subcutaneous injection over a 4-h sampling period. With the ability to load a multitude of microneedle formulations, the device can serve as a platform to orally deliver therapeutic doses of macromolecule drugs. A luminal unfolding microneedle injector device (LUMI) is engineered as a custom capsule capable of efficient biologic macromolecular drug delivery into the bloodstream via selective deployment within the gastrointestinal tract.

Abstract What effects do economic sanctions have on the volume of domestic terrorism within target states and transnational terrorism directed toward Americans by targeted nationals? In this article, we theorize that sanctions imposed by the United States increase the likelihood of domestic and transnational terrorism, but the suggested effect is conditioned by the freedom of expression in sanctioned states. When media freedom and other information freedoms are high, we posit that citizens are more likely to direct their grievances against their own government, leading to an increase in domestic terrorism as time under economic sanction increases. When freedom of expression is low, however, leaders of sanctioned states may be able to exploit sanctions to channel hostility away from the home regime via transnational terrorism exported from the sanctioned state. Results from a time-series, cross-national data analysis lend support to our argument on domestic terrorism in the sanctioned state while showing no statistical support for the hypothesis concerning transnational terrorism.

Mitochondria, which have critical roles in energy metabolism and oxidative regulation, also have a role in immune regulation including T cell activation, NET formation, inflammation, and apoptosis. More than 50% of those with systemic lupus erythematosus (SLE) have lupus nephritis due to kidney damage from immune complex deposition. Disease severity is reported to be greater in certain lineages. Mitochondrial DNA (mtDNA) haplogroups, which reflect maternal lineages, may modulate immune balance and disease outcomes in SLE. Methods: DNA was extracted from 25 consecutive, consenting pediatric patients that fulfilled the 1997 criteria for SLE and their maternal mitochondrial DNA (mtDNA) haplogroups were determined through next-generation sequencing (NGS). Results: This study evaluated the associations between mtDNA haplogroups, lupus nephritis, and organ damage in four mtDNA haplogroups: African (n = 5), Amerindian (n = 12), Asian (n = 4), and Caucasian (n = 4). Clinical data, SLE Disease Activity Index (SLEDAI-2K), SLICC Damage Index (SDI), and renal biopsy findings were analyzed. Median SLEDAI-2K scores were higher in Amerindian (10) and African (8) patients than in the Caucasian (5.5) and Asian (3) groups, with significant differences between Amerindian vs. Caucasian (p = 0.045) and Amerindian vs. Asian (p = 0.008). Irreversible organ damage (SDI > 1) was more frequent in Amerindian (54%) and African (40%) patients. Lupus nephritis occurred most often and most severely (Class III–IV, CKD) in the Amerindian (85%) and African (80%) groups, while Caucasian and Asian patients more often showed milder, membranous disease without CKD. Conclusion: Although limited by the small sample size, pediatric SLE severity and renal involvement were found to be greater in Amerindian and African mtDNA haplogroups, suggesting that mitochondrial lineage may contribute to ethnic disparities in SLE.