Background: The efficacy and safety of lecanemab have previously been evaluated in the Phase 3 randomized clinical trial, Clarity AD (NCT03887455). Methods: A Markov cohort model was developed to estimate the cost-effectiveness of lecanemab versus standard of care (SoC) in patients with mild cognitive impairment (MCI) or mild dementia due to Alzheimer’s disease (AD), with confirmed beta-amyloid (Aβ) pathology, from a Canadian societal perspective. Health states were determined by Clinical Dementia Rating-Sum of Boxes (CDR-SB) scores. Transitions between health states during month 0-18 were estimated from Clarity AD. Beyond month 18, relative efficacy for lecanemab in the form of the hazard ratio for time-to-worsening of CDR-SB was applied to literature-based transition probabilities. The model included the effects of lost productivity and impact on carer health-related quality of life. Results: The incremental cost-effectiveness ratio (ICER) for lecanemab vs SoC was estimated to be CAD 62,751 per QALY gained. The probability that lecanemab was cost-effective at a threshold of CAD 100,000 was estimated to be 88.5%. Conclusions: Lecanemab represents a cost-effective option for the treatment for early AD from the Canadian societal perspective. The results of this analysis can be used to inform clinical and economic decision making.

Background: Drug-resistant epilepsy (DRE), defined by persistent seizures despite appropriate anti-seizure medication trials, affects about one-third of individuals with epilepsy. Deep brain stimulation (DBS) has emerged as a promising avenue for improved seizure control. This project reviews existing publications to better understand the neuromodulation parameters used in DBS, aiming to inform clinical decisions on optimizing treatment parameters in patients living with DRE. Methods: A comprehensive literature search of PubMed and Google Scholar was conducted using the keywords “DBS,” “epilepsy,” and “parameters.” Only original studies reporting specific stimulation parameters were included, with meta-analyses and review papers excluded. A weighted Pearson correlation, using study sample size as the weight, examined frequency, pulse width, seizure reduction, and responder rate. Results: So far, 28 studies (1997-2024) have been reviewed, encompassing a total of 1,054 patients, with study size ranging from 1-250 patients. Electrode targets included the hippocampus, ANT, amygdala, centromedian nucleus, and STN. DBS frequencies ranged from 60–333 Hz, and pulse widths from 40–450 µs. Pearson correlation results suggest moderate frequencies (130–145 Hz) and wider pulse widths (300–450 µs) correlate with better seizure reduction and higher responder rates. Conclusions: These results support a formal meta-analysis to further investigate neuromodulation parameters to improve outcomes for DRE patients.

Youth in sub-Saharan Africa (SSA) face limited access to professional mental health resources. A comprehensive assessment of the prevalence of mental disorders would build an understanding of the scope of the need.

We conducted systematic searches in PsycInfo, Pubmed, AfriBib and Africa Journals Online to identify prevalence rates for five disorders (anxiety, depression, conduct disorder, attention problems and post-traumatic stress) among SSA youth with a mean age of less than 19 years. We calculated a random-effects pooled prevalence for each disorder and assessed possible moderators.

The meta-analysis included 63 studies with 55,071 participants. We found the following pooled prevalence rates: 12.53% post-traumatic stress disorder (PTSD), 15.27% depression, 6.55% attention-deficit hyperactivity disorder, 11.78% anxiety and 9.76% conduct disorder. We found high heterogeneity across the studies, which may have resulted from differences in samples or measurement tools. Reported prevalence rates were not explained by the sample (i.e., special or general population), but whether the psychometric tool was validated for SSA youth affected the reported prevalence of PTSD and anxiety. In a meta-regression, prevalence rates were associated with the disorder type, with a higher prevalence of depression and PTSD. We found the mean age significantly moderated the prevalence in univariate meta-regression, with increased age correlated with greater prevalence.

Our findings suggest there is a need to explore reasons for varying prevalence rates further and to develop interventions that support youth mental health in SSA, particularly interventions for depression and PTSD. Limitations included a lack of standardization in psychometric tools and limited reporting on research methods, which influenced quality rating. Importantly, the search only considered studies published in English and was conducted 2 years ago. Although recent estimates reported slightly higher than our prevalence estimates, these reviews together highlight the prevalence and importance of youth mental health difficulties in SSA.

OBJECTIVES/GOALS: While most transgender and non-binary (TNB) youth experience improved mental health post-initiating gender-affirming hormones (GAH), some continue to experience persistent, significant depressive symptoms two years post-GAH. Importantly, few studies have examined this issue given the lack of existing longitudinal studies. METHODS/STUDY POPULATION: We aimed to identify intervenable factors predicting persistent clinical depressive symptoms (PD) among TNB youth two years post-initiation of GAH utilizing the Trans Youth Care U.S. Study, an ongoing, multisite, observational study of TNB youth from four major pediatric hospitals across the U.S. We compared TNB youth (ages 12-20 at baseline) with persisting depression symptoms (PD) two-years post-GAH (i.e., PD; N=59) and those youth without (non-PD; n=215). Logistic regression estimated the association between PD and risk (e.g., negative expectations) and protective factors (e.g., parental acceptance, self-efficacy), measured at baseline and longitudinally. A mixed-effects model compared the rate of change of these factors between PD and non-PD youth. Models controlled for birth sex. RESULTS/ANTICIPATED RESULTS: Participants (Mean age=16) identified as transmasculine, then transfeminine, followed by non-binary. PD youth had higher negative expectations at baseline and internalized transphobia by 2-years, while non-PD youth reported greater parental acceptance over 2-years. The odds of PD compared to non-PD decreased with increasing self-efficacy at baseline (OR=0.7, 95% CI:0.5-0.9), whereas negative expectation for the future was associated with increased odds (OR=1.3, 95% CI:0.9,1.8). Moreover, the odds of PD increased 50% with increased rate of change in negative expectations, and odds decreased 50% with increased rate of change in self-efficacy, after adjusting for baseline negative expectations and self-efficacy, respectively. DISCUSSION/SIGNIFICANCE: We identified key intervenable factors for mental health treatment for TNB youth with PD; specifically, negative expectations increased risk for PD while self-efficacy appeared to buffer against PD risk. These findings also support assessment of youth for negative expectations for the future conferring greater risk for later PD.

Recent research has shown the potential of speleothem δ13C to record a range of environmental processes. Here, we report on 230Th-dated stalagmite δ13C records for southwest Sulawesi, Indonesia, over the last 40,000 yr to investigate the relationship between tropical vegetation productivity and atmospheric methane concentrations. We demonstrate that the Sulawesi stalagmite δ13C record is driven by changes in vegetation productivity and soil respiration and explore the link between soil respiration and tropical methane emissions using HadCM3 and the Sheffield Dynamic Global Vegetation Model. The model indicates that changes in soil respiration are primarily driven by changes in temperature and CO2, in line with our interpretation of stalagmite δ13C. In turn, modelled methane emissions are driven by soil respiration, providing a mechanism that links methane to stalagmite δ13C. This relationship is particularly strong during the last glaciation, indicating a key role for the tropics in controlling atmospheric methane when emissions from high-latitude boreal wetlands were suppressed. With further investigation, the link between δ13C in stalagmites and tropical methane could provide a low-latitude proxy complementary to polar ice core records to improve our understanding of the glacial–interglacial methane budget.

As a discipline centered on power, political science provides an important window into potential responses to episodes of heightened attention to long-standing racial violence and inequality in the United States. During the summer of 2020, political science departments, like many other entities, issued public statements in response to the brutal murder of George Floyd and the long and ongoing history of deadly violence against Black people at the hands of law enforcement. This paper examines these statements, providing a descriptive analysis of themes raised and types of commitments to action. Rhetorical responses to racism constitute important sites for understanding how discursive power is deployed. Ultimately, we observe that proposed solutions contained in statements are not commensurate with the structural understanding of racism encapsulated in statements. These statements suggest that the status quo prevails even among those who study power. We document limited commitments to addressing racism in political statements.

Background: Traditional hospital outbreak-detection methods are typically limited to select multidrug-resistant pathogens in a single unit, which can miss transmission of many medically important healthcare-transmissible pathogens. Whole-genome sequencing (WGS) enables comprehensive genomic resolution for accurate identification of clonal transmission. Previously, lack of scalability limited the use of WGS for hospital surveillance. Methods: We conducted prospective surveillance of select bacteria from all inpatient clinical cultures plus all bacteria from clinical cultures from ICUs and oncology units at the University of California Irvine (UCI) Clinical Microbiology Laboratory from September 2021 to February 2022. Due to pandemic stressors, this pilot test was a prelude to a real-time demonstration project. Its goal was to demonstrate the efficiency and scalability of the WGS platform when receiving samples monthly and analyzing results quarterly without the intent for real-time response. Bacterial isolates slated for discard were collected weekly and sent monthly to Day Zero Diagnostics for sequencing. In total, 1,036 samples from 926 patients were analyzed for genomic relatedness, a scalable and automated analysis pipeline already in use for rapid (days) characterization of genomic-relatedness in small and large sets of isolates. Mapping and SNP calling was performed against high-quality, best-match reference genomes. Sets of samples with pairwise distance of 2 persons with genomically related isolates and were denoted as “clusters.” Separately, we also investigated within-patient diversity by quantifying the genomic relatedness of isolates collected from individual patients. Results: Isolates represented 28 distinct species. We identified 10 Escherichia coli clusters (range, 2–4 patients; median, 2 patients), 2 Klebsiella pneumoniae clusters (range, 2–4 patients), and 1 Enterococcus faecium cluster (3 patients). All but 1 involved genomically matched isolates from multiple hospital locations. There were 4 Escherichia coli ST131 clusters spanning 4 months, including 1 with 4 patients across 3 different hospital locations. At a species level, there were distinct differences between the observed SNP distances between samples isolated from the same versus different patients (Fig. 1). All identified clusters had not been flagged by routine outbreak detection methods used by the UCI infection prevention program. Conclusions: Comprehensive WGS-based surveillance of hospital clinical isolates identified multiple potential transmission events between patients not in the same unit at the time cultures were taken. Combining WGS detection and real-time epidemiologic investigation may identify new avenues of transmission risk and could provide early warnings of clonal transmission to prevent larger outbreaks. High-volume surveillance of hospital isolates can also provide species- and context-specific clonality.

Financial support: This study was funded by Day Zero Diagnostics.

Disclosures: None

We present observations of the Mopra carbon monoxide (CO) survey of the Southern Galactic Plane, covering Galactic longitudes spanning $l = 250^{\circ}$ ($-110^{\circ}$) to $l = 355^{\circ}$ ($-5^{\circ}$), with a latitudinal coverage of at least $|b|<1^\circ$, totalling an area of $>$210 deg$^{2}$. These data have been taken at 0.6 arcmin spatial resolution and 0.1 km s$^{-1}$ spectral resolution, providing an unprecedented view of the molecular gas clouds of the Southern Galactic Plane in the 109–115 GHz $J = 1-0$ transitions of $^{12}$CO, $^{13}$CO, C$^{18}$O, and C$^{17}$O.

We present a new high-resolution neutral atomic hydrogen (Hi) survey of ring galaxies using the Australia Telescope Compact Array (ATCA). We target a sample of 24 ring galaxies from the Buta (1995) Southern Ring Galaxy Survey Catalogue in order to study the origin of resonance-, collisional- and interaction-driven ring galaxies. In this work, we present an overview of the sample and study their global and resolved Hi properties. In addition, we also probe their star formation properties by measuring their star formation rates (SFR) and their resolved SFR surface density profiles. We find that a majority of the barred galaxies in our sample are Hi-deficient, alluding to the effects of the bar in driving their Hi deficiency. Furthermore, for the secularly evolving barred ring galaxies in our sample, we apply Lindblad’s resonance theory to predict the location of the resonance rings and find very good agreement between predictions and observations. We identify rings of Hi gas and/or star formation co-located at one or the other major resonances. Lastly, we measure the bar pattern speed ($\Omega_{\textrm{bar}}$) for a sub-sample of our galaxies and find that the values range from 10–90 $\textrm{km s}^{-1}$kpc$^{-1}$, in good agreement with previous studies.

Long-term sequelae of severe acute respiratory coronavirus-2 (SARS-CoV-2) infection may include increased incidence of diabetes. Here we describe the temporal relationship between new type 2 diabetes and SARS-CoV-2 infection in a nationwide database. We found that while the proportion of newly diagnosed type 2 diabetes increased during the acute period of SARS-CoV-2 infection, the mean proportion of new diabetes cases in the 6 months post-infection was about 83% lower than the 6 months preinfection. These results underscore the need for further investigation to understand the timing of new diabetes after COVID-19, etiology, screening, and treatment strategies.

We present the Widefield ASKAP L-band Legacy All-sky Blind surveY (WALLABY) Pilot Phase I Hi kinematic models. This first data release consists of Hi observations of three fields in the direction of the Hydra and Norma clusters, and the NGC 4636 galaxy group. In this paper, we describe how we generate and publicly release flat-disk tilted-ring kinematic models for 109/592 unique Hi detections in these fields. The modelling method adopted here—which we call the WALLABY Kinematic Analysis Proto-Pipeline (WKAPP) and for which the corresponding scripts are also publicly available—consists of combining results from the homogeneous application of the FAT and 3DBarolo algorithms to the subset of 209 detections with sufficient resolution and $S/N$ in order to generate optimised model parameters and uncertainties. The 109 models presented here tend to be gas rich detections resolved by at least 3–4 synthesised beams across their major axes, but there is no obvious environmental bias in the modelling. The data release described here is the first step towards the derivation of similar products for thousands of spatially resolved WALLABY detections via a dedicated kinematic pipeline. Such a large publicly available and homogeneously analysed dataset will be a powerful legacy product that that will enable a wide range of scientific studies.