Background: Colony stimulating factor 1 receptor (CSF1R) mutations have various clinical, often overlapping, phenotypes. Methods: Case report and literature review. Results: We present a case of a previously independent 49-year-old woman with a 3-year history of early- and insidious-onset, rapidly progressive symptoms resembling CBS (parkinsonism, severe apraxia, global cognitive impairments, personality changes, depression, and functional decline). Brain MRI showed severe atrophy with frontoparietal predilection, asymmetric ex vacuo dilatation, atrophic corpus callosum, and patchy, asymmetric T2/FLAIR hyperintensities in the subcortical white matter. Spine MRI showed no cord signals. Brain MR spectroscopy revealed elevated choline with reduced N-acetyl-aspartate levels. The vasculitis screening, and leukodystrophy and CADASIL workups were all unremarkable. Finally, whole exome sequencing was done and a heterozygous variant of CSF1R (c.1735C>T, p.Arg579Trp) was found. Conclusions: Our patient’s novel CSF1R variant was found to be associated with ALSP. This report supports the utility of a comprehensive genetic testing in adult patients clinically presenting as CBS but with white matter abnormalities on T2-weighted MRI. Given that ALSP has several other clinical and radiologic mimickers, whole exome sequencing proves fundamental and can improve the diagnostic rates and understanding of ALSP. A well-informed diagnosis can lead to appropriate preventive genetic counseling to affected families.

Background: Our aim was to develop a National Quality Indicators Set for the Care of Adults Hospitalized for Neurological Problems, to serve as a foundation to build regional or national quality initiatives in Canadian neurology centres. Methods: We used a national eDelphi process to develop a suite of quality indicators and a parallel process of surveys and patient focus groups to identify patient priorities. Canadian content and methodology experts were invited to participate. To be included, >70% of participants had to rate items as critical and <15% had to rate it as not important. Two rounds of surveys and consensus meetings were used identify and rank indicators, followed by national consultation with members of the Canadian Neurological Society. Results: 38 neurologists and methodologists and 56 patients/caregivers participated in this project. An initial list of 91 possible quality indicators was narrowed to 40 indicators across multiple categories of neurological conditions. 21 patient priorities were identified. Conclusions: This quality indicators suite can be used regionally or nationally to drive improvement initiatives for inpatient neurology care. In addition, we identified multiple opportunities for further research where evidence was lacking or patient and provider priorities did not align.

We investigated whether people’s risk taking tendency established in one domain (gains or losses) carries over to the other domain. Participants played a game in which they made repeated decisions between a fixed payoff and a risky option, where the outcome of the risky option depended on whether they had responded correctly on a difficult perceptual-memory task. In some trials, participants played to gain points; on others, they played to avoid losing points. In two studies, we observed the following pattern of results. 1) Participants risked less on gain trials than on loss trials. 2) This difference in risk taking persisted (carried over) when the domain changed from gains to losses and vice versa (with the effect of experiencing losses first being stronger than the effect of experiencing gains first). 3) There was no analogous carryover effect on responses to a delay discounting measure, but there was a carryover effect on responses on a risk attitude measure. We compare these results with those from other recent studies and discuss various ways of explaining them.

The coronavirus disease 2019 (COVID-19) pandemic has placed significant burden on healthcare systems. We compared Clostridioides difficile infection (CDI) epidemiology before and during the pandemic across 71 hospitals participating in the Canadian Nosocomial Infection Surveillance Program. Using an interrupted time series analysis, we showed that CDI rates significantly increased during the COVID-19 pandemic.

School connectedness, a construct indexing supportive school relationships, has been posited to promote resilience to environmental adversity. Consistent with prominent calls in the field, we examined the protective nature of school connectedness against two dimensions of early adversity that index multiple levels of environmental exposure (violence exposure, social deprivation) when predicting both positive and negative outcomes in longitudinal data from 3,246 youth in the Fragile Families and Child Wellbeing Study (48% female, 49% African American). Child and adolescent school connectedness were promotive, even when accounting for the detrimental effects of early adversity. Additionally, childhood school connectedness had a protective but reactive association with social deprivation, but not violence exposure, when predicting externalizing symptoms and positive function. Specifically, school connectedness was protective against the negative effects of social deprivation, but the effect diminished as social deprivation became more extreme. These results suggest that social relationships at school may compensate for low levels of social support in the home and neighborhood. Our results highlight the important role that the school environment can play for youth who have been exposed to adversity in other areas of their lives and suggest specific groups that may especially benefit from interventions that boost school connectedness.

In view of the increasing complexity of both cardiovascular implantable electronic devices (CIEDs) and patients in the current era, practice guidelines, by necessity, have become increasingly specific. This document is an expert consensus statement that has been developed to update and further delineate indications and management of CIEDs in pediatric patients, defined as ≤21 years of age, and is intended to focus primarily on the indications for CIEDs in the setting of specific disease categories. The document also highlights variations between previously published adult and pediatric CIED recommendations and provides rationale for underlying important differences. The document addresses some of the deterrents to CIED access in low- and middle-income countries and strategies to circumvent them. The document sections were divided up and drafted by the writing committee members according to their expertise. The recommendations represent the consensus opinion of the entire writing committee, graded by class of recommendation and level of evidence. Several questions addressed in this document either do not lend themselves to clinical trials or are rare disease entities, and in these instances recommendations are based on consensus expert opinion. Furthermore, specific recommendations, even when supported by substantial data, do not replace the need for clinical judgment and patient-specific decision-making. The recommendations were opened for public comment to Pediatric and Congenital Electrophysiology Society (PACES) members and underwent external review by the scientific and clinical document committee of the Heart Rhythm Society (HRS), the science advisory and coordinating committee of the American Heart Association (AHA), the American College of Cardiology (ACC), and the Association for European Paediatric and Congenital Cardiology (AEPC). The document received endorsement by all the collaborators and the Asia Pacific Heart Rhythm Society (APHRS), the Indian Heart Rhythm Society (IHRS), and the Latin American Heart Rhythm Society (LAHRS). This document is expected to provide support for clinicians and patients to allow for appropriate CIED use, appropriate CIED management, and appropriate CIED follow-up in pediatric patients.

Childhood adversity is thought to undermine youth socioemotional development via altered neural function within regions that support emotion processing. These effects are hypothesized to be developmentally specific, with adversity in early childhood sculpting subcortical structures (e.g., amygdala) and adversity during adolescence impacting later-developing structures (e.g., prefrontal cortex; PFC). However, little work has tested these theories directly in humans. Using prospectively collected longitudinal data from the Fragile Families and Child Wellbeing Study (FFCWS) (N = 4,144) and neuroimaging data from a subsample of families recruited in adolescence (N = 162), the current study investigated the trajectory of harsh parenting across childhood (i.e., ages 3 to 9) and how initial levels versus changes in harsh parenting across childhood were associated with corticolimbic activation and connectivity during socioemotional processing. Harsh parenting in early childhood (indexed by the intercept term from a linear growth curve model) was associated with less amygdala, but not PFC, reactivity to angry facial expressions. In contrast, change in harsh parenting across childhood (indexed by the slope term) was associated with less PFC, but not amygdala, activation to angry faces. Increases in, but not initial levels of, harsh parenting were also associated with stronger positive amygdala–PFC connectivity during angry face processing.

Respiratory distress syndrome results from inadequate functional pulmonary surfactant and is a significant cause of mortality in preterm infants. Surfactant is essential for regulating alveolar interfacial surface tension, and its synthesis by Type II alveolar epithelial cells is stimulated by leptin produced by pulmonary lipofibroblasts upon activation by peroxisome proliferator-activated receptor γ (PPARγ). As it is unknown whether PPARγ stimulation or direct leptin administration can stimulate surfactant synthesis before birth, we examined the effect of continuous fetal administration of either the PPARγ agonist, rosiglitazone (RGZ; Study 1) or leptin (Study 2) on surfactant protein maturation in the late gestation fetal sheep lung. We measured mRNA expression of genes involved in surfactant maturation and showed that RGZ treatment reduced mRNA expression of LPCAT1 (surfactant phospholipid synthesis) and LAMP3 (marker for lamellar bodies), but did not alter mRNA expression of PPARγ, surfactant proteins (SFTP-A, -B, -C, and -D), PCYT1A (surfactant phospholipid synthesis), ABCA3 (phospholipid transportation), or the PPARγ target genes SPHK-1 and PAI-1. Leptin infusion significantly increased the expression of PPARγ and IGF2 and decreased the expression of SFTP-B. However, mRNA expression of the majority of genes involved in surfactant synthesis was not affected. These results suggest a potential decreased capacity for surfactant phospholipid and protein production in the fetal lung after RGZ and leptin administration, respectively. Therefore, targeting PPARγ may not be a feasible mechanistic approach to promote lung maturation.

Psychosocial stress in childhood and adolescence is linked to stress system dysregulation, although few studies have examined the relative impacts of parental harshness and parental disengagement. This study prospectively tested whether parental harshness and disengagement show differential associations with overall cortisol output in adolescence. Associations between overall cortisol output and adolescent mental health problems were tested concurrently. Adolescents from the Fragile Families and Child Wellbeing Study (FFCWS) provided hair samples for cortisol assay at 15 years (N = 171). Caregivers reported on parental harshness and disengagement experiences at 1, 3, 5, 9, and 15 years, and adolescents reported at 15 years. Both parent and adolescent reported depressive and anxiety symptoms and antisocial behaviors at 15. Greater parental harshness from 1–15 years, and harshness reported at 15 years in particular, was associated with higher overall cortisol output at 15. Greater parental disengagement from 1–15 years, and disengagement at 1 year specifically, was associated with lower cortisol output. There were no significant associations between cortisol output and depressive symptoms, anxiety symptoms, or antisocial behaviors. These results suggest that the unique variances of parental harshness and disengagement may have opposing associations with cortisol output at 15 years, with unclear implications for adolescent mental health.

OBJECTIVES/GOALS: We compared the validity of an International Classification of Diseases, Clinical Modification (ICD) algorithm for identifying high-grade cervical intraepithelial neoplasia and adenocarcinoma in situ (together referred to as CIN2+) from ICD 9th revision (ICD-9) and 10th revision (ICD-10) codes. METHODS/STUDY POPULATION: Using Tennessee Medicaid data, we identified cervical diagnostic procedures in 2008-2017 among females aged 18-39 years in Davidson County, TN. Gold-standard cases were pathology-confirmed CIN2+ diagnoses validated by HPV-IMPACT, a population-based surveillance project in catchment areas of five US states. Procedures in the ICD transition year (2015) were excluded to account for implementation lag. We pre-grouped diagnosis and procedure codes by theme. We performed feature selection using least absolute shrinkage and selection operator (LASSO) logistic regression with 10-fold cross validation and validated models by ICD-9 era (2008-2014, N = 6594) and ICD-10 era (2016-2017, N = 1270). RESULTS/ANTICIPATED RESULTS: Of 7864 cervical diagnostic procedures, 880 (11%) were true CIN2+ cases. LASSO logistic regression selected the strongest features of case status: Having codes for a CIN2+ tissue diagnosis, non-specific CIN tissue diagnosis, high-grade squamous intraepithelial lesion, receiving a cervical treatment procedure, and receiving a cervical/vaginal biopsy. Features of non-case status were codes for a CIN1 tissue diagnosis, Pap test, and HPV DNA test. The ICD-9 vs ICD-10 algorithms predicted case status with 68% vs 63% sensitivity, 95% vs 94% specificity, 63% vs 64% positive predictive value, 96% vs 94% negative predictive value, 92% vs 89% accuracy, and C-indices of 0.95 vs 0.92, respectively. DISCUSSION/SIGNIFICANCE OF IMPACT: Overall, the algorithm’s validity for identifying CIN2+ case status was similar between coding versions. ICD-9 had slightly better discriminative ability. Results support a prior study concluding that ICD-10 implementation has not substantially improved the quality of administrative data from ICD-9.

Diet has a major influence on the composition and metabolic output of the gut microbiome. Higher-protein diets are often recommended for older consumers; however, the effect of high-protein diets on the gut microbiota and faecal volatile organic compounds (VOC) of elderly participants is unknown. The purpose of the study was to establish if the faecal microbiota composition and VOC in older men are different after a diet containing the recommended dietary intake (RDA) of protein compared with a diet containing twice the RDA (2RDA). Healthy males (74⋅2 (sd 3⋅6) years; n 28) were randomised to consume the RDA of protein (0⋅8 g protein/kg body weight per d) or 2RDA, for 10 weeks. Dietary protein was provided via whole foods rather than supplementation or fortification. The diets were matched for dietary fibre from fruit and vegetables. Faecal samples were collected pre- and post-intervention for microbiota profiling by 16S ribosomal RNA amplicon sequencing and VOC analysis by head space/solid-phase microextraction/GC-MS. After correcting for multiple comparisons, no significant differences in the abundance of faecal microbiota or VOC associated with protein fermentation were evident between the RDA and 2RDA diets. Therefore, in the present study, a twofold difference in dietary protein intake did not alter gut microbiota or VOC indicative of altered protein fermentation.

This project will work closely with existing service partners involved in street level services and focus on testing and evaluating three approaches for street level interventions for youth who are homeless and who have severe or moderate mentally illness. Youth will be asked to choose their preferred service approach:

Housing First related initiatives focused on interventions designed to move youth to appropriate and available housing and ongoing housing supports.

Treatment First initiatives to provide Mental Health/Addiction supports and treatment solutions, and; Simultaneous attention to both Housing and Treatment Together

Our primary objective is to understand the service delivery preferences of homeless youth and understand the outcomes of these choices. Our research questions include:

1. 1. Which approaches to service are chosen by youth?

2. 2. What are the differences and similarities between groups choosing each approach?

3. 3. What are the critical ingredients needed to effectively implement services for homeless youth from the perspectives of youth, families and service providers?

Focus groups with staff and family members will occur to assist in understanding the nature of each of service approach, changes that evolve within services, & facilitators and barriers to service delivery. This work will be important in determining which approach is chosen by youth and why. Evaluating the outcomes with each choice will provide valuable information about outcomes for the service options chosen by youth. This assist in better identifying weaknesses in the services offered and inform further development of treatment options that youth will accept.

Dietary patterns describe the combination of foods and beverages in a diet and the frequency of habitual consumption. Better understanding of childhood dietary patterns and antenatal influences could inform intervention strategies to prevent childhood obesity. We derived empirical dietary patterns in 1142 children (average age 6·0 (sd 0·2) years) in New Zealand, whose mothers had participated in the Screening for Pregnancy Endpoints (SCOPE) cohort study and explored associations with measures of body composition. Participants (Children of SCOPE) had their diet assessed by FFQ, and dietary patterns were extracted using factor analysis. Three distinct dietary patterns were identified: ‘Healthy’, ‘Traditional’ and ‘Junk’. Associations between dietary patterns and measures of childhood body composition (waist, hip, arm circumferences, BMI, bioelectrical impedance analysis-derived body fat % and sum of skinfold thicknesses (SST)) were assessed by linear regression, with adjustment for maternal influences. Children who had higher ‘Junk’ dietary pattern scores had 0·24 (sd 0·08; 95 % CI 0·04, 0·13) cm greater arm and 0·44 (sd 0·05; 95 % CI 0·01, 0·10) cm greater hip circumferences and 1·13 (sd 0·07; 95 % CI 0·03, 0·12) cm greater SST and were more likely to be obese (OR 1·74; 95 % CI 1·07, 2·82); those with higher ‘Healthy’ pattern scores were less likely to be obese (OR 0·62; 95 % CI 0·39, 1·00). In a large mother–child cohort, a dietary pattern characterised by high-sugar and -fat foods was associated with greater adiposity and obesity risk in children aged 6 years, while a ‘Healthy’ dietary pattern offered some protection against obesity. Targeting unhealthy dietary patterns could inform public health strategies to reduce the prevalence of childhood obesity.

The Murchison Widefield Array is a low-frequency Square Kilometre Array precursor located at the Murchison Radio-astronomy Observatory in Western Australia. Primarily designed as an imaging telescope, but with a flexible signal path, the capabilities of this telescope have recently been extended to include off-line incoherent and tied-array beam formation using recorded antenna voltages. This has provided the capability for high-time and frequency resolution observations, including a pulsar science program. This paper describes the algorithms and pipeline that we have developed to form the tied-array beam products from the summation of calibrated signals of the antenna elements, and presents example polarimetric profiles for PSRs J0437-4715 and J1900-2600 at 185 MHz.