Establishing Cerebral Organoids as Models of Human-Specific Brain Evolution.

Direct comparisons of human and non-human primate brains can reveal molecular pathways underlying remarkable specializations of the human brain. However, chimpanzee tissue is inaccessible during neocortical neurogenesis when differences in brain size first appear. To identify human-specific features of cortical development, we leveraged recent innovations that permit generating pluripotent stem cell-derived cerebral organoids from chimpanzee. Despite metabolic differences, organoid models preserve gene regulatory networks related to primary cell types and developmental processes. We further identified 261 differentially expressed genes in human compared to both chimpanzee organoids and macaque cortex, enriched for recent gene duplications, and including multiple regulators of PI3K-AKT-mTOR signaling. We observed increased activation of this pathway in human radial glia, dependent on two receptors upregulated specifically in human: INSR and ITGB8. Our findings establish a platform for systematic analysis of molecular changes contributing to human brain development and evolution.

Molecular identity of human outer radial glia during cortical development.

Radial glia, the neural stem cells of the neocortex, are located in two niches: the ventricular zone and outer subventricular zone. Although outer subventricular zone radial glia may generate the majority of human cortical neurons, their molecular features remain elusive. By analyzing gene expression across single cells, we find that outer radial glia preferentially express genes related to extracellular matrix formation, migration, and stemness, including TNC, PTPRZ1, FAM107A, HOPX, and LIFR. Using dynamic imaging, immunostaining, and clonal analysis, we relate these molecular features to distinctive behaviors of outer radial glia, demonstrate the necessity of STAT3 signaling for their cell cycle progression, and establish their extensive proliferative potential. These results suggest that outer radial glia directly support the subventricular niche through local production of growth factors, potentiation of growth factor signals by extracellular matrix proteins, and activation of self-renewal pathways, thereby enabling the developmental and evolutionary expansion of the human neocortex.

HIV Testing and Preexposure Prophylaxis Prescriptions Among U.S. Commercially Insured Transgender Men and Women, 2014 to 2021.

BACKGROUND: Transgender persons are disproportionately affected by HIV, but preexposure prophylaxis (PrEP) use has been low in this population. Clinical encounters for gender-affirming hormone therapy (GAHT) provide opportunities for HIV prevention. OBJECTIVE: To estimate the number of commercially insured transgender women (TGW) and transgender men (TGM) in the United States and their use of HIV prevention services. DESIGN: Retrospective analysis of secondary data. SETTING: Merative MarketScan commercial databases from 2014 to 2021. PARTICIPANTS: TGW and TGM, defined as those with transgender-related diagnoses and prescriptions for feminizing or masculinizing GAHT. MEASUREMENTS: HIV testing and PrEP use. RESULTS: A substantially increasing trend was observed in the prevalence of transgender-related diagnosis codes from 2014 to 2021 and in the proportion of persons who used GAHT. The increases were driven by persons aged 18 to 34 years. In 2021, among 10 613 TGW with a test for or a diagnosis of a sexually transmitted infection (STI) in the previous 12 months, 61.1% had an HIV test; among those, 20.2% were prescribed PrEP. Among 4184 TGM with STI risk, 48.3% had an HIV test; among those, 10.2% were prescribed PrEP. The prevalence of TGW and TGM who had a test for or a diagnosis of an STI, had an HIV test, and were prescribed PrEP increased substantially from 2014 to 2021. LIMITATION: The findings represent only persons with commercial health insurance who sought health care services for GAHT. CONCLUSION: It is important to identify transgender persons to monitor their receipt of HIV prevention services. Encounters for GAHT provide opportunities to offer HIV prevention and other prevention services. Many HIV prevention opportunities were likely missed at clinical encounters for GAHT. PRIMARY FUNDING SOURCE: None.

No association between long-chain n-3 fatty acid intake during pregnancy and risk of type 1 diabetes in offspring in two large Scandinavian pregnancy cohorts.

AIMS/HYPOTHESIS: The aim of this study was to investigate whether higher dietary intake of marine n-3 fatty acids during pregnancy is associated with a lower risk of type 1 diabetes in children. METHODS: The Danish National Birth Cohort (DNBC) and the Norwegian Mother, Father and Child Cohort Study (MoBa) together include 153,843 mother-child pairs with prospectively collected data on eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) intake during pregnancy from validated food frequency questionnaires. Type 1 diabetes diagnosis in children (n=634) was ascertained from national diabetes registries. RESULTS: There was no association between the sum of EPA and DHA intake during pregnancy and risk of type 1 diabetes in offspring (pooled HR per g/day of intake: 1.00, 95% CI 0.88, 1.14), with consistent results for both the MoBa and the DNBC. Robustness analyses gave very similar results. CONCLUSIONS/INTERPRETATION: Initiation of a trial of EPA and DHA during pregnancy to prevent type 1 diabetes in offspring should not be prioritised.

Hotspots and super-spreaders: Modelling fine-scale malaria parasite transmission using mosquito flight behaviour.

Malaria hotspots have been the focus of public health managers for several years due to the potential elimination gains that can be obtained from targeting them. The identification of hotspots must be accompanied by the description of the overall network of stable and unstable hotspots of malaria, especially in medium and low transmission settings where malaria elimination is targeted. Targeting hotspots with malaria control interventions has, so far, not produced expected benefits. In this work we have employed a mechanistic-stochastic algorithm to identify clusters of super-spreader houses and their related stable hotspots by accounting for mosquito flight capabilities and the spatial configuration of malaria infections at the house level. Our results show that the number of super-spreading houses and hotspots is dependent on the spatial configuration of the villages. In addition, super-spreaders are also associated to house characteristics such as livestock and family composition. We found that most of the transmission is associated with winds between 6pm and 10pm although later hours are also important. Mixed mosquito flight (downwind and upwind both with random components) were the most likely movements causing the spread of malaria in two out of the three study areas. Finally, our algorithm (named MALSWOTS) provided an estimate of the speed of malaria infection progression from house to house which was around 200-400 meters per day, a figure coherent with mark-release-recapture studies of Anopheles dispersion. Cross validation using an out-of-sample procedure showed accurate identification of hotspots. Our findings provide a significant contribution towards the identification and development of optimal tools for efficient and effective spatio-temporal targeted malaria interventions over potential hotspot areas.

How important is food structure when cats eat mice?

Feeding whole prey to felids has shown to benefit their gastrointestinal health. Whether this effect is caused by the chemical or physical nature of whole prey is unknown. Fifteen domestic cats, as a model for strict carnivores, were either fed minced mice (MM) or whole mice (WM), to determine the effect of food structure on digestibility, mean urinary excretion time (MUET) of 15N, intestinal microbial activity and fermentation products. Faeces samples were collected after feeding all cats a commercially available extruded diet (EXT) for 10 d before feeding for 19 d the MM and WM diets with faeces and urine collected from day 11 to 15. Samples for microbiota composition and determination of MUET were obtained from day 16 to 19. The physical structure of the mice diet (minced or not) did not affect large intestinal fermentation as total SCFA and branched-chain fatty acid (BCFA), and most biogenic amine (BA) concentrations were not different (P > 0·10). When changing from EXT to the mice diets, the microbial community composition shifted from a carbolytic (Prevotellaceae) to proteolytic (Fusobacteriaceae) profile and led to a reduced faecal acetic to propionic acid ratio, SCFA, total BCFA (P < 0·001), NH3 (P = 0·04), total BA (P < 0·001) and para-cresol (P = 0·08). The results of this study indicate that food structure within a whole-prey diet is less important than the overall diet type, with major shifts in microbiome and decrease in potentially harmful fermentation products when diet changes from extruded to mice. This urges for careful consideration of the consequences of prey-based diets for gut health in cats.

Pregnancy intention in relation to maternal and neonatal outcomes in women with versus without psychiatric diagnoses.

BACKGROUND: Studies have identified adverse maternal and neonatal outcomes for women with psychiatric disorders. Additionally, psychiatric disorders may pose an increased risk for unintended pregnancies (UPs) which in turn may also impact negatively on outcomes. The present study aims to compare the incidence of UPs in women with versus without current/past psychiatric diagnoses and investigates whether psychiatric history modifies the relation between delivery outcomes in women with and without UPs. METHODS: A retrospective cohort was compiled of women who gave birth in a large hospital in Amsterdam, the Netherlands. Women ≥18 years old with singleton pregnancies and birth registrations in the electronic patient file during January 1, 2015 to March 1, 2020 were included. Patient characteristics (including pregnancy intention and psychiatric history), maternal (gestational diabetes, mode of delivery) and neonatal outcomes (e.g., gestational age [GA], birthweight and Apgar scores) were registered by health care providers in hospital charts. Incidence of UPs was compared between women with versus without current/past psychiatric diagnoses. Maternal and neonatal outcomes were compared between women with versus without UPs with linear or logistic regression models adjusted for relevant confounders with an interaction term for UP with current/past psychiatric diagnoses. RESULTS: We included 1219 women with and 1093 women without current/past psychiatric diagnoses. Current/past psychiatric diagnoses were significantly associated with UPs after adjustment for confounders (39.0% vs. 29.6%, OR 1.56, CI 1.23-2.00, p < 0.001). In sub-analyses, women with depressive (OR 1.67, CI 1.24-2.26, p = 0.001), personality (OR 2.64, CI 1.38-5.11, p = 0.004) and substance-related and addictive disorders (OR 4.29, CI 1.90-10.03, p = 0.001) had higher odds of UPs compared to women without current/past psychiatric diagnoses. Amongst women with UPs, current/past psychiatric diagnoses did not modify maternal or neonatal outcomes, except for GA at delivery as women with both UPs and current/past psychiatric diagnosis had a 2.21-day higher mean GA at delivery than women in the reference group (p-value interaction = 0.001). CONCLUSIONS: Current/past psychiatric diagnoses are associated with a higher odd of UPs. In our sample, maternal and neonatal outcomes were comparable for women with and without UPs and these results were similar for women with and without current/past psychiatric diagnoses, except for GA at delivery. Although our study is limited by several factors, we found that women with current/past psychiatric diagnoses, irrespective of pregnancy planning status, do not have more adverse maternal or pregnancy outcomes. Increased efforts are needed to ensure that psychoeducation and conversations about pregnancy planning and UPs are available for women with current/past psychiatric diagnoses.

The conversation about family planning and desire for children in mental healthcare: Patients' perspective versus Professionals' perspective in a mixed methods study.

BACKGROUND: Reproductive health and mental health are intertwined, but studies investigating family planning needs and desire for children in mental healthcare are scarce. METHODS: We studied the experiences of (former) patients, those with close relationships with the (former) patients (close ones) and mental health professionals (MHP) on discussing family planning and desire for children in mental healthcare. We combined quantitative (two nationwide surveys) and qualitative data (four focus groups) in a mixed-methods approach with sequential analytical design. RESULTS: Combined data from focus groups (n = 19 participants) and two surveys (n = 139 MHPs and n = 294 (former) patients and close ones) showed that a considerable group of MHPs (64.0%), patients (40.9%) and close ones (50.0%) found that family planning should be discussed by a psychiatrist. However, several obstacles impeded a conversation, such as fear of judgment, lack of time and knowledge and limited opportunity for in-depth exploration of life themes in therapeutic relationships. CONCLUSIONS: To increase the autonomy of patients in discussing family planning, we suggest MHPs explore the desire to discuss family planning with all patients in the reproductive phase of life, prior to discussing contraceptive care. MHPs should receive education about psychiatric vulnerability in relation to family planning and desire for children, and patients and close ones should be empowered to initiate a conversation themselves.

Estimating the causal effect of filter ventilation levels in cigarettes on past 30-day smoking.

INTRODUCTION: Cigarettes with higher levels of filter ventilation are misperceived as less harmful and may be more appealing to consumers. Setting limits on filter ventilation has been considered as a policy, but a better understanding of any potential unintended consequences is needed. METHODS: Filter ventilation (0.2-61.1%) measured for 114 subbrands was merged with Wave 1 (2012-2013) of the Population Assessment of Tobacco Use and Health (PATH) data, restricted to adults 25+ years of age who smoked daily, and examined by quartiles. Inverse probability of exposure weights were used to estimate the causal effect of filter ventilation on past-30 day smoking at subsequent waves while accounting for potential confounders including demographics, menthol, heaviness of smoking and past quit attempts. RESULTS: Compared to those in the 1st (lowest) quartile of filter ventilation, those in the 2nd, 3rd and 4th quartiles had 1.02 (95% confidence interval: 0.57, 1.82), 0.86 (0.42, 1.73) and 1.52 (0.90, 2.56) times the odds of no past 30-day smoking at Wave 2 (approximately 1 year later, p=0.163), and 1.28 (0.80, 2.07), 1.11 (0.67, 1.83) and 1.65 (1.01, 1.24) times the odds of no past 30-day smoking at Wave 4 (3 years later, p = 0.238). CONCLUSIONS: This observational study found no strong evidence of a causal effect of filter ventilation on past 30-day smoking at approximately 1 and 3 years follow-up. However, our effect size estimates were not precise and thus an increase in the ability to quit smoking due to higher filter ventilation levels cannot be ruled out. IMPLICATIONS: Setting a maximum limit on filter ventilation (FV) in cigarettes could address the misperception that highly ventilated cigarettes are less harmful and the link between FV and lung adenocarcinoma. It is important to understand whether such a policy would have unintended consequences on longer-term smoking behavior. We found no strong evidence that FV affects past 30-day smoking 1-3 years later, but could not rule out the possibility that higher FV increases cessation rates. If future studies confirm these epidemiologic findings, this could mean that setting a limit on FV would not lead to reductions in the ability to quit smoking.

Children's beliefs about the emotional consequences of norm adherence and violation.

What behaviors make people happy? In the current studies, we investigated 4- to 7-year-old children's (N = 148) emotion attributions for people who follow or violate a conventional norm when doing so aligns or conflicts with other psychological motivations. In Study 1, we tested whether children believe people are happier when they desire (vs. do not desire) adhering to (vs. violating) a norm. In Study 2, we tested whether children believe people are happier when freely choosing (vs. being told) to adhere to (vs. violate) a norm. In both studies, children predicted the highest happiness levels for people who followed norms even when doing so conflicted with other psychological motivators (e.g., wanting or freely choosing to do something). Children also explained their emotion attributions by making reference to norms more often than to desires or personal choices. Results are discussed in terms of implications for children's own norm adherence and early socialization practices in Western cultures.

Preschoolers negatively evaluate conventional norm violations in pretend play.

A growing body of research demonstrates that children's pretend play is largely influenced by their understanding of reality. The current work took a novel approach to testing children's understanding of pretense by investigating whether children apply and uphold their knowledge of conventional norms in pretend play. In this study, 3- to 5-year-old children (N = 200) were introduced to a series of pretend play scenarios (e.g., pretending to eat breakfast) in which a puppet pretended to follow a norm (e.g., pretended to eat cereal for breakfast) or violate a norm (e.g., pretended to eat a hamburger for breakfast). These pretend play scenarios were presented as either fantastical or realistic in nature. Consistent with our hypotheses, children evaluated pretend norm violation more negatively than pretend norm adherence and reported liking norm violators less than norm followers. Contrary to our hypothesis, the manipulation of play context (fantastical vs. realistic) did not affect children's evaluations. That is, children were just as negative about pretend norm violations (relative to pretend norm adherence) in fantastical pretend play scenarios as they were in realistic pretend play scenarios. Furthermore, individual differences in children's fantasy orientation did not predict their evaluations. This study is the first to establish that children maintain their real-world understanding of conventional norms in pretend play, providing further evidence that children's pretense is largely realistic in nature.

'Not a goal, but a given': Neonatal care participation through parents' perspective, a cross-sectional study.

AIM: To explore parents' perspectives regarding participation in neonatal care, with focus on the family integrated care (FICare) model utilised as a tool to enhance parent-infant closeness. Additionally, we describe experiences in different architectural settings. METHODS: An online survey, categorised by four FICare pillars, was distributed through social media to parents of newborns hospitalised to Dutch neonatal wards between 2015 and 2020. Quantitative findings were summarised using descriptive statistics, while open-ended responses were thematically analysed. RESULTS: Among the 344 respondents (98% mothers), most reported feeling involved in care (315/340). However, 79% also felt separated from their infant (265/337). Irrespective of architectural settings, parents reported incomplete implementation of FICare pillars: 14% was invited to educational sessions (parent education), 51% discussed family-specific care plans (staff education), 21% was facilitated in connecting with veteran parents (psychosocial support) and 22% received couplet-care (environment). Although 65% of parents were invited to attend clinical rounds, 32% actively participated in decision making. Thematic analysis revealed fundamentals for feeling welcome on the ward, peer-to-peer support, psychosocial support and participation in clinical rounds. CONCLUSION: Overall, parents expressed satisfaction with participation in neonatal care. However, structural implementation of FICare lacks. Regardless of architecture, expanding parent participation beyond presence requires attention.

Machine Learning Did Not Outperform Conventional Competing Risk Modeling to Predict Revision Arthroplasty.

BACKGROUND: Estimating the risk of revision after arthroplasty could inform patient and surgeon decision-making. However, there is a lack of well-performing prediction models assisting in this task, which may be due to current conventional modeling approaches such as traditional survivorship estimators (such as Kaplan-Meier) or competing risk estimators. Recent advances in machine learning survival analysis might improve decision support tools in this setting. Therefore, this study aimed to assess the performance of machine learning compared with that of conventional modeling to predict revision after arthroplasty. QUESTION/PURPOSE: Does machine learning perform better than traditional regression models for estimating the risk of revision for patients undergoing hip or knee arthroplasty? METHODS: Eleven datasets from published studies from the Dutch Arthroplasty Register reporting on factors associated with revision or survival after partial or total knee and hip arthroplasty between 2018 and 2022 were included in our study. The 11 datasets were observational registry studies, with a sample size ranging from 3038 to 218,214 procedures. We developed a set of time-to-event models for each dataset, leading to 11 comparisons. A set of predictors (factors associated with revision surgery) was identified based on the variables that were selected in the included studies. We assessed the predictive performance of two state-of-the-art statistical time-to-event models for 1-, 2-, and 3-year follow-up: a Fine and Gray model (which models the cumulative incidence of revision) and a cause-specific Cox model (which models the hazard of revision). These were compared with a machine-learning approach (a random survival forest model, which is a decision tree-based machine-learning algorithm for time-to-event analysis). Performance was assessed according to discriminative ability (time-dependent area under the receiver operating curve), calibration (slope and intercept), and overall prediction error (scaled Brier score). Discrimination, known as the area under the receiver operating characteristic curve, measures the model's ability to distinguish patients who achieved the outcomes from those who did not and ranges from 0.5 to 1.0, with 1.0 indicating the highest discrimination score and 0.50 the lowest. Calibration plots the predicted versus the observed probabilities; a perfect plot has an intercept of 0 and a slope of 1. The Brier score calculates a composite of discrimination and calibration, with 0 indicating perfect prediction and 1 the poorest. A scaled version of the Brier score, 1 - (model Brier score/null model Brier score), can be interpreted as the amount of overall prediction error. RESULTS: Using machine learning survivorship analysis, we found no differences between the competing risks estimator and traditional regression models for patients undergoing arthroplasty in terms of discriminative ability (patients who received a revision compared with those who did not). We found no consistent differences between the validated performance (time-dependent area under the receiver operating characteristic curve) of different modeling approaches because these values ranged between -0.04 and 0.03 across the 11 datasets (the time-dependent area under the receiver operating characteristic curve of the models across 11 datasets ranged between 0.52 to 0.68). In addition, the calibration metrics and scaled Brier scores produced comparable estimates, showing no advantage of machine learning over traditional regression models. CONCLUSION: Machine learning did not outperform traditional regression models. CLINICAL RELEVANCE: Neither machine learning modeling nor traditional regression methods were sufficiently accurate in order to offer prognostic information when predicting revision arthroplasty. The benefit of these modeling approaches may be limited in this context.

Personality characteristics of Dutch nurse anesthetists and surgical nurses when compared to the normative Dutch population, a quantitative survey study.

BACKGROUND: Working in the perioperative context is complex and challenging. The continual evaluation in this environment underscores the need for adaptability to technological advancements, and requires substantial allocation of resources for training and education. This study aimed to explore personality characteristics of nurse anesthetists and surgical nurses that are instrumental for sustainable employability in technologically advanced environment. METHODS: Exploratory, cross-sectional survey study including nurse anesthetists and surgical nurses, both certified and in training, and a sample of the normative Dutch population. Personality characteristics were identified with the Big Five Inventory, which consisted of 60 items answered on a five-point Likert scale (strongly disagree to strongly agree). RESULTS: Specific personality traits were found for nurse anesthetists and surgical nurses when compared to the normative Dutch population. Traits of both nurse anesthetists and surgical nurses differed significantly on all domains of the Big Five Inventory, with the largest differences found within the dimension negative emotionally. CONCLUSIONS: This study highlights the role of specific personality traits in maintaining employability within the rapidly evolving and technologically advanced landscape of healthcare. It emphasizes the relationship between individual traits and professional excellence, being crucial educational strategies for overall improvement in healthcare.

Lower versus Traditional Treatment Threshold for Neonatal Hypoglycemia.

BACKGROUND: Worldwide, many newborns who are preterm, small or large for gestational age, or born to mothers with diabetes are screened for hypoglycemia, with a goal of preventing brain injury. However, there is no consensus on a treatment threshold that is safe but also avoids overtreatment. METHODS: In a multicenter, randomized, noninferiority trial involving 689 otherwise healthy newborns born at 35 weeks of gestation or later and identified as being at risk for hypoglycemia, we compared two threshold values for treatment of asymptomatic moderate hypoglycemia. We sought to determine whether a management strategy that used a lower threshold (treatment administered at a glucose concentration of <36 mg per deciliter [2.0 mmol per liter]) would be noninferior to a traditional threshold (treatment at a glucose concentration of <47 mg per deciliter [2.6 mmol per liter]) with respect to psychomotor development at 18 months, assessed with the Bayley Scales of Infant and Toddler Development, third edition, Dutch version (Bayley-III-NL; scores range from 50 to 150 [mean {±SD}, 100±15]), with higher scores indicating more advanced development and 7.5 points (one half the SD) representing a clinically important difference). The lower threshold would be considered noninferior if scores were less than 7.5 points lower than scores in the traditional-threshold group. RESULTS: Bayley-III-NL scores were assessed in 287 of the 348 children (82.5%) in the lower-threshold group and in 295 of the 341 children (86.5%) in the traditional-threshold group. Cognitive and motor outcome scores were similar in the two groups (mean scores [±SE], 102.9±0.7 [cognitive] and 104.6±0.7 [motor] in the lower-threshold group and 102.2±0.7 [cognitive] and 104.9±0.7 [motor] in the traditional-threshold group). The prespecified inferiority limit was not crossed. The mean glucose concentration was 57±0.4 mg per deciliter (3.2±0.02 mmol per liter) in the lower-threshold group and 61±0.5 mg per deciliter (3.4±0.03 mmol per liter) in the traditional-threshold group. Fewer and less severe hypoglycemic episodes occurred in the traditional-threshold group, but that group had more invasive diagnostic and treatment interventions. Serious adverse events in the lower-threshold group included convulsions (during normoglycemia) in one newborn and one death. CONCLUSIONS: In otherwise healthy newborns with asymptomatic moderate hypoglycemia, a lower glucose treatment threshold (36 mg per deciliter) was noninferior to a traditional threshold (47 mg per deciliter) with regard to psychomotor development at 18 months. (Funded by the Netherlands Organization for Health Research and Development; HypoEXIT Current Controlled Trials number, ISRCTN79705768.).

Predicting Readmission or Death After Discharge From the ICU: External Validation and Retraining of a Machine Learning Model.

OBJECTIVES: Many machine learning (ML) models have been developed for application in the ICU, but few models have been subjected to external validation. The performance of these models in new settings therefore remains unknown. The objective of this study was to assess the performance of an existing decision support tool based on a ML model predicting readmission or death within 7 days after ICU discharge before, during, and after retraining and recalibration. DESIGN: A gradient boosted ML model was developed and validated on electronic health record data from 2004 to 2021. We performed an independent validation of this model on electronic health record data from 2011 to 2019 from a different tertiary care center. SETTING: Two ICUs in tertiary care centers in The Netherlands. PATIENTS: Adult patients who were admitted to the ICU and stayed for longer than 12 hours. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We assessed discrimination by area under the receiver operating characteristic curve (AUC) and calibration (slope and intercept). We retrained and recalibrated the original model and assessed performance via a temporal validation design. The final retrained model was cross-validated on all data from the new site. Readmission or death within 7 days after ICU discharge occurred in 577 of 10,052 ICU admissions (5.7%) at the new site. External validation revealed moderate discrimination with an AUC of 0.72 (95% CI 0.67-0.76). Retrained models showed improved discrimination with AUC 0.79 (95% CI 0.75-0.82) for the final validation model. Calibration was poor initially and good after recalibration via isotonic regression. CONCLUSIONS: In this era of expanding availability of ML models, external validation and retraining are key steps to consider before applying ML models to new settings. Clinicians and decision-makers should take this into account when considering applying new ML models to their local settings.

Sex differences across developmental domains among children with a familial risk of severe mental disorders.

BACKGROUND: Sex differences in brain structure and neurodevelopment occur in non-clinical populations. We investigated whether sex had a similar effect on developmental domains amongst boys and girls with a familial risk of schizophrenia (FHR-SZ), bipolar disorder (FHR-BP), and controls. METHODS: Through Danish registries, we identified 522 7-year-old children (242 girls) with FHR-SZ, FHR-BP, and controls. We assessed their performance within the domains of neurocognition, motor function, language, social cognition, social behavior, psychopathology, and home environment. RESULTS: FHR-SZ boys compared with FHR-SZ girls had a higher proportion of disruptive behavior and attention-deficit hyperactivity disorder (ADHD) and exhibited lower performance in manual dexterity, balance, and emotion recognition. No sex differences were found between boys and girls within FHR-BP group. Compared with controls, both FHR-SZ boys and FHR-SZ girls showed impaired processing speed and working memory, had lower levels of global functioning, and were more likely to live in an inadequate home environment. Compared with control boys, FHR-SZ boys showed impaired manual dexterity, social behavior, and social responsiveness, and had a higher proportion of ADHD and disruptive behavior disorder diagnoses. Stress and adjustment disorders were more common in FHR-BP boys compared with control boys. We found no differences between FHR-BP girls and control girls. CONCLUSIONS: Impairment within neurodevelopmental domains associated within FHR-SZ boys v. FHR-SZ girls was most evident among boys, whereas no sex differences were found within the FHR-BP group (FHR-BP boys v. FHR-BP girls). FHR-SZ boys exhibited the highest proportion of early developmental impairments.

Home environment of 11-year-old children born to parents with schizophrenia or bipolar disorder - a controlled, 4-year follow-up study: The Danish High Risk and Resilience Study - VIA 11.

BACKGROUND: The home environment has a major impact on child development. Parental severe mental illness can pose a challenge to the home environment of a child. We aimed to examine the home environment of children of parents with schizophrenia or bipolar disorder and controls longitudinally through at-home assessments. METHODS: Assessments were conducted within The Danish High Risk and Resilience Study, a nationwide multi-center cohort study of children of parents with schizophrenia or bipolar disorder and population-based controls. The level of at-home stimulation and support was measured at age 7 (N = 508 children) and age 11 (N = 430 children) with the semi-structured HOME Inventory. Results from the 11-year follow-up study were analyzed and compared with 7-year baseline results to examine change across groups. RESULTS: At age 11, children of parents with schizophrenia and bipolar disorder had lower levels of stimulation and support than controls (mean (s.d.) = 46.16 (5.56), 46.87 (5.34) and 49.25 (4.37) respectively, p < 0.001). A higher proportion of children with parental schizophrenia or bipolar disorder lived in inadequate home environments at age 11, compared with controls (N (%) = 24 (15.0), 12 (12.2) and 6 (3.5) respectively, p < 0.003). The changes in home environment scores did not differ across groups from age 7 to age 11. CONCLUSIONS: Assessed longitudinally from the children's age of 7 to 11, children of parents with schizophrenia or bipolar disorder had lower levels of stimulation and support in their homes than controls. Integrated support which can target practical, economic, social and health issues to improve the home environment is indicated.

Benefits of Frequent HIV Testing in the THRIVE Demonstration Project: United States, 2015-2020.

Objectives. To describe HIV testing among clients in the Targeted Highly Effective Interventions to Reverse the HIV Epidemic (THRIVE) demonstration project and evaluate testing frequency. Methods. We identified factors associated with an average testing frequency of 180 days or less compared with more than 180 days using adjusted Poisson regression models. We performed the Kaplan-Meier survival analysis to compare time to diagnosis by testing frequency. Results. Among 5710 clients with 2 or more tests and no preexposure prophylaxis (PrEP) prescription, 42.4% were tested frequently. Black/African American clients were 21% less likely and Hispanic/Latino clients were 18% less likely to be tested frequently than were White clients. Among 71 Black/African American and Hispanic/Latino cisgender men who have sex with men and transgender women with HIV diagnoses, those with frequent testing had a median time to diagnosis of 137 days, with a diagnostic testing yield of 1.5% compared with those tested less frequently, with 559 days and 0.8% yield. Conclusions. HIV testing at least every 6 months resulted in earlier HIV diagnosis and was efficient. Persons in communities with high rates of HIV who are not on PrEP can benefit from frequent testing, and collaborative community approaches may help reduce disparities. (Am J Public Health. 2023;113(9):1019-1027. https://doi.org/10.2105/AJPH.2023.307341).

Unravelling the impact of insecticide-treated bed nets on childhood malaria in Malawi.

BACKGROUND: To achieve malaria elimination it is essential to understand the impact of insecticide-treated net (ITNs) programmes. Here, the impact of ITN access and use on malaria prevalence in children in Malawi was investigated using Malaria Indicator Survey (MIS) data. METHODS: MIS data from 2012, 2014 and 2017 were used to investigate the relationship between malaria prevalence in children (6-59 months) and ITN use. Generalized linear modelling (GLM), geostatistical mixed regression modelling and non-stationary GLM were undertaken to evaluate trends, spatial patterns and local dynamics, respectively. RESULTS: Malaria prevalence in Malawi was 27.1% (95% CI 23.1-31.2%) in 2012 and similar in both 2014 (32.1%, 95% CI 25.5-38.7) and 2017 (23.9%, 95% CI 20.3-27.4%). ITN coverage and use increased during the same time period, with household ITN access growing from 19.0% (95% CI 15.6-22.3%) of households with at least 1 ITN for every 2 people sleeping in the house the night before to 41.7% (95% CI 39.1-44.4%) and ITN use from 41.1% (95% CI 37.3-44.9%) of the population sleeping under an ITN the previous night to 57.4% (95% CI 55.0-59.9%). Both the geostatistical and non-stationary GLM regression models showed child malaria prevalence had a negative association with ITN population access and a positive association with ITN use although affected by large uncertainties. The non-stationary GLM highlighted the spatital heterogeneity in the relationship between childhood malaria and ITN dynamics across the country. CONCLUSION: Malaria prevalence in children under five had a negative association with ITN population access and a positive association with ITN use, with spatial heterogeneity in these relationships across Malawi. This study presents an important modelling approach that allows malaria control programmes to spatially disentangle the impact of interventions on malaria cases.