We use direct numerical simulations to examine the onset of stratified turbulence triggered by the zigzag instability recently identified in columnar Taylor–Green vortices (Guo et al. 2024, J. Fluid Mech., vol. 997, A34) and its role in layer formation within the flow. The study focuses on Froude numbers $0.125 \leqslant \textit{Fr} \leqslant 2.0$ and Reynolds numbers ${\textit{Re}}$ ranging from 800 to 3200. The breakdown of the freely evolving vortex array is driven by local density overturns, combining shear and convective mechanisms initiated by the primary zigzag instability. Our results show a linear relationship between the peak buoyancy Reynolds number ${{\textit{Re}}}_b^{\star }$, driven by the zigzag instability, and ${\textit{Re}}\, {\textit{Fr}}^2$. When the flow does not exhibit local shear or convective instability, the value of ${{\textit{Re}}}_b^{\star }$ falls below unity. Both density and momentum layers arise from the zigzag instability: horizontal velocity layers are strong and persistent, while density layers are weaker and more transient. The vertical scale of the mean shear layers increases with ${\textit{Fr}}$ for ${\textit{Fr}} \leqslant 1$, shows weak dependence on ${\textit{Re}}$, and agrees well with the length scale associated with the fastest-growing linear mode of the zigzag instability. Further analysis in the sorted buoyancy coordinate highlights the role of density overturns caused by the zigzag instability in forming buoyancy layers during the transition to turbulence.

The perinatal period has gained increasing attention from developmental psychopathologists; however, experiences during birth have been minimally examined using this framework. The current study aimed to evaluate longitudinal associations between childhood maltreatment, negative birth experiences, and postpartum mental health across levels of self-reported emotion dysregulation and respiratory sinus arrhythmia (RSA). Expectant mothers (N = 223) participated in a longitudinal study from the third trimester of pregnancy to 7 months postpartum. Participants contributed prenatal resting RSA and completed questionnaires prenatally, 24 hours after birth, and 7 months postpartum. Results indicated that more childhood maltreatment was associated with higher birth fear and postpartum anxiety and depressive symptoms. Resting RSA moderated the association between childhood maltreatment and birth fear, such that more childhood maltreatment and higher resting RSA were associated with increased birth fear. Additionally, self-reported prenatal emotion dysregulation moderated the association between childhood maltreatment and postpartum depressive symptoms, such that more childhood maltreatment and higher emotion dysregulation were associated with increased depressive symptoms. Emotion dysregulation across multiple levels may amplify vulnerability to negative birth experiences and postpartum psychopathology among individuals with childhood maltreatment histories. Thus, emotion dysregulation in the context of trauma-informed care may be worthwhile intervention targets during the perinatal period.

Background: Anterior (ACS) and posterior circulation (PCS) stroke patients have different clinical presentations and prognoses, though both benefit from endovascular thrombectomy (EVT). We sought to determine whether ACS and PCS patients treated with EVT differed with regards to treatment metrics and functional outcomes. Methods: We retrospectively analysed theCanadian OPTIMISE registry which included data from 20 comprehensive stroke centers across Canada between January 1, 2018, and December 31, 2022. We performed a descriptive analysis of patients divided in two groups (ACS= carotid artery and its branches, PCS= vertebrobasilar system). Results: Of the 6391 patients included (5929 ACS and 462 PCS), PSC patients were younger (67 vs. 71.3, p<0.001), more often male (61.9% vs. 48.6%, p<0.001), had longer (in minutes) onset-to-door (362 vs. 256, p<0.001), door-to-needle (172 vs. 144, p=0.0016), and onset-to-puncture (459 vs. 329, p<0.001) times. They were less often thrombolyzed (39.8% vs. 50.4%, p<0.001), and more frequently underwent general anesthesia (47.6% vs. 10.6%, p<0.001). Successful reperfusion and functional independence at 90 days were similar between the two groups. Conclusions: Patients with PCS had worst treatment metrics than ACS. Strategies to improve PCS management times are critical to decrease these disparities, including faster pre-hospital recognition and in-hospital workflows.

Double-diffusive convection can arise when the fluid density is set by multiple species which diffuse at different rates. Different flow regimes are possible depending on the distribution of the diffusing species, including salt fingering and diffusive convection. Flows arising from diffusive convection commonly exhibit step-like density profiles with sharp density interfaces separated by well-mixed layers. The formation of density layers is also seen in stratified turbulence, where a framework based on sorted density coordinates (Winters & D’Asaro 1996 J. Fluid Mech. 317, 179–193) has been used to diagnose layer formation (Zhou et al. 2017 J. Fluid Mech. 823, 198–229; Taylor & Zhou 2017 J. Fluid Mech. 823, R5). In this framework, the evolution of the sorted density profile can be expressed solely in terms of the eddy diffusivity, $\kappa _e$. Here, we use the same framework to diagnose layer formation in two-dimensional simulations of double-diffusive convection. We show that $\kappa _e$ is negative everywhere, with the antidiffusive effect strongest in ‘well-mixed’ layers where a positive diffusion coefficient may be expected. By considering a decomposition of the budget of the square of the Brunt-Väisälä frequency $\partial N^2_*/\partial t$, we demonstrate that the density layers are maintained by fundamentally different processes than in single-component stratified turbulence. In more complicated flows where stratified turbulence and double-diffusive convection can coexist, this framework could provide a method to distinguish between the mechanisms responsible for generating density layers.

Our systematic review aims to synthesise the evidence on interventions targeting improvement in patient adherence to psychological treatments for common mental disorders. A search was conducted on six electronic databases using search terms under the following concepts: common mental disorders, adherence, psychological treatments and controlled trial study design. Due to the heterogeneity in intervention content and outcomes evaluated in the included studies, a narrative synthesis was conducted. Risk of bias was assessed using the Cochrane Risk of Bias Version 2 tool for randomised controlled trials and the Cochrane ROBINS-I tool for non-randomised controlled trials. The search yielded 23 distinct studies with a total sample size of 2,779 participants. All studies were conducted in high-income or upper-middle-income countries. Interventions to improve patient adherence to psychological treatments included reminders and between-session engagement (e.g., text messages), motivational interviewing, therapy orientation (e.g., expectation-setting) and overcoming structural barriers (e.g., case management). Interventions from 18 out of 23 studies were successful in improving at least one primary adherence outcome of interest (e.g., session attendance). Some studies also reported an improvement in secondary outcomes – six studies reported an improvement in at least one clinical outcome (e.g., depression), and three studies reported improvements in at least one measure of well-being or disability (e.g., days spent in in-patient treatment). By incorporating these interventions into psychological treatment services, therapists can better engage with and support their patients, potentially leading to improved mental health outcomes and overall well-being.

We investigate the dynamics of a columnar Taylor–Green vortex array under strong stratification, focusing on Froude numbers $0.125\leq Fr \leq 1.0$, with the aim of identifying and understanding the primary instabilities that lead to the vortices’ breakdown. Linear stability analysis reveals that the fastest-growing vertical wavenumber scales with $Fr^{-1}$, while the dimensionless growth rate remains approximately constant. The most unstable eigenmode, identified as the mixed hyperbolic mode by Hattori et al. (J. Fluid Mech., vol. 909, 2021, A4), bears significant similarities to the zigzag instability, first discovered by Billant & Chomaz (J. Fluid Mech., vol. 418, 2000, pp. 167–188). Direct numerical simulations further confirm that the zigzag instability is crucial in amplifying initial random perturbations to finite amplitude, with the flow structure and modal growth rate consistent with the linear stability analysis. In particular, the characteristic vertical length scale of turbulence matches that of the fastest-growing linear mode. These findings underscore the broader relevance of the zigzag instability mechanism beyond its initial discovery in vortex pairs, demonstrating its role in facilitating direct energy transfer from vertically uniform vortical motions to a characteristic vertical length scale proportional to $Fr$ in strongly stratified flows.

Background: Efgartigimod is a human IgG1 antibody Fc fragment recently approved by Health Canada for patients with acetylcholine receptor antibody positive (AChR-Ab+) generalized myasthenia gravis (gMG). We assessed cost-effectiveness of efgartigimod vs chronic IVIg for adult patients with AChR-Ab+ gMG. Methods: A Markov model estimated costs (treatment and administration, disease monitoring, complications from chronic corticosteroid use, exacerbation and crisis management, adverse events, end-of-life care) and benefits (quality-adjusted life-years [QALYs]). The analysis was conducted from the Canadian healthcare system perspective. Health state transition probabilities were estimated using data from ADAPT, ADAPT+, and a network meta-analysis comparing efgartigimod with chronic IVIg. Utility values were obtained from MyRealWorld MG. Patients with MG-ADL ≥5 who did not die/discontinue were assumed to receive treatment every 4 weeks or every 3 weeks over the lifetime horizon. Results: Over the lifetime horizon, efgartigimod and chronic IVIg were predicted to have total discounted QALYs of 16.80 and 13.35, and total discounted costs of $1,913,294 and $2,170,315, respectively. Efgartigimod dominated chronic IVIg with incremental QALYs of 3.45 and cost savings of $257,020 over the lifetime horizon. Conclusions: Efgartigimod may provide greater benefit at lower costs than chronic IVIg for Canadian patients with AChR-Ab+ gMG, with substantial healthcare system savings over the lifetime horizon.

The formation of siderite and magnetite by Fe(III)-reducing bacteria may play an important role in C and Fe geochemistry in subsurface and ocean sediments. The objective of this study was to identify environmental factors that control the formation of siderite (FeCO3) and magnetite (Fe3O4) by Fe(III)-reducing bacteria. Psychrotolerant (<20°C), mesophilic (20–35°C) and thermophilic (>45°C) Fe(III)-reducing bacteria were used to examine the reduction of a poorly crystalline iron oxide, akaganeite (β-FeOOH), without a soluble electron shuttle, anthraquinone disulfuonate (AQDS), in the presence of N2, N2-CO2(80:20, V:V), H2 and H2-CO2 (80:20, V:V) headspace gases as well as in -buffered medium (30–210 mM) under a N2 atmosphere. Iron biomineralization was also examined under different growth conditions such as salinity, pH, incubation time, incubation temperature and electron donors. Magnetite formation was dominant under a N2 and a H2 atmosphere. Siderite formation was dominant under a H2-CO2 atmosphere. A mixture of magnetite and siderite was formed in the presence of a N2-CO2 headspace. Akaganeite was reduced and transformed to siderite and magnetite in a -buffered medium (>120 mM) with lactate as an electron donor in the presence of a N2 atmosphere. Biogeochemical and environmental factors controlling the phases of the secondary mineral suite include medium pH, salinity, electron donors, atmospheric composition and incubation time. These results indicate that microbial Fe(III) reduction may play an important role in Fe and C biogeochemistry as well as C sequestration in natural environments.

Sulfur mustard (SM) is a threat to both civilian and military populations. Human skin is highly sensitive to SM, causing delayed erythema, edema, and inflammatory cell infiltration, followed by the appearance of large fluid-filled blisters. Skin wound repair is prolonged following blistering, which can result in impaired barrier function. Key to understanding the action of SM in the skin is the development of animal models that have a pathophysiology comparable to humans such that quantitative assessments of therapeutic drugs efficacy can be assessed. Two animal models, hairless guinea pigs and swine, are preferred to evaluate dermal products because their skin is morphologically similar to human skin. In these animal models, SM induces degradation of epidermal and dermal tissues but does not induce overt blistering, only microblistering. Mechanisms of wound healing are distinct in these animal models. Whereas a guinea pig heals by contraction, swine skin, like humans, heals by re-epithelialization. Mice, rats, and rabbits are also used for SM mechanistic studies. However, healing is also mediated by contraction; moreover, only microblistering is observed. Improvements in animal models are essential for the development of therapeutics to mitigate toxicity resulting from dermal exposure to SM.

Background: To localize cortical speech areas, methods such as fMRI are commonly used, but the Wada test can also determine whether a region is critical to the particular task. We report a case of a left-handed patient with a left frontal tumour in whom fMRI language paradigms produced both left and right Broca’s and Wernicke’s areas. Methods: All imaging used a 3 Tesla Siemens Skyra scanner. The patient performed five speech tasks: word reading, picture naming, semantic questions, pseudohomophone reading, and word generation. All preprocessing and statistical analyses for functional images were performed using Brain Voyager QX. Results: The fMRI results revealed right hemisphere dominance for language processing. A Wada test was performed in order to confirm whether the regions in the left hemisphere were critical to speech. The patient experienced speech arrest during the Wada test, thus confirming that despite bilateral speech activation, the left hemisphere speech regions are required for speech production. Conclusions: This case emphasizes the importance of preoperative fMRI in assessing the location of eloquent cortices adjacent to a tumour and the Wada test is still warranted for examining necessity of left hemisphere language regions when fMRI fails to show clear left-lateralization.

OBJECTIVES/GOALS: Our long-term goal is to understand how both genetic and environmental (GxE) factors contribute to neurodevelopmental disorders (NDDs) so that we may potentially intervene in disease pathogenesis and design therapies to address functional deficiencies. METHODS/STUDY POPULATION: Our studies use a novel GxE model to determine how cephalosporin antibiotic exposure alters the gut microbiome, hippocampal neurogenesis, and behavior in the genetically vulnerable 16p11.2 microdeletion (16pDel) mouse. This mouse models one of the most frequently observed genetic risk variants implicated in NDDs, including ~1% of autism diagnoses. Wildtype and 16pDel littermates were exposed to saline or the cephalosporin, cefdinir, from postnatal days 5-9. We quantified changes in gut microbiota composition using 16S rRNA gene sequencing and utilized immunoblotting, immunohistochemistry, and bulk RNA gene sequencing to assess changes in hippocampal neurogenesis. An additional cohort of saline or cefdinir-exposed mice were subjected to a behavioral battery to assess changes in sociability and anxiety. RESULTS/ANTICIPATED RESULTS: We leveraged the next-generation microbiome bioinformatics platform, Quantitative Insights Into Microbial Ecology 2 (QIIME2) to analyze 16S rRNA gene sequencing datasets of P13 cecal samples from saline- and cefdinir-exposed mice. We found successful perturbations to the gut microbiome following early life cefdinir exposure. Further, we found a robust 50% reduction in hippocampal cyclin E protein in cefdinir-exposed 16pDel male mice, which was replicated in a second independent experiment. This reduction extended to the S-phase cell entry and general stem cell population, quantified by EdU+ and Ki67+ cell numbers, respectively. Lastly, in our first cohort of mice for behavioral studies, we found reduced sociability and increased anxiety-like behaviors in cefdinir-exposed mice. DISCUSSION/SIGNIFICANCE: The findings from this GxE model will provide mechanistic insights into the causes of NDDs; they may inform practice guidelines so as to reduce this environmental exposure; and may suggest interventions like probiotics for those at risk in order to overcome altered gut microbiome composition and restore hippocampal neurogenesis defects.

Point-particle direct numerical simulations have been employed to quantify the turbulence modulation and particle responses in a turbulent particle-laden jet in the two-way coupled regime with an inlet Reynolds number based on bulk velocity and jet diameter $({D_j})$ of ~10 000. The investigation focuses on three cases with inlet bulk Stokes numbers of 0.3, 1.4 and 11.2. Special care is taken to account for the particle–gas slip velocity and non-uniform particle concentrations at the nozzle outlet, enabling a reasonable prediction of particle velocity and concentration fields. Turbulence modulation is quantified by the variation of the gas-phase turbulent kinetic energy (TKE). The presence of the particle phase is found to damp the gas-phase TKE in the near-field region within $5{D_j}$ from the inlet but subsequently increases the TKE in the intermediate region of (5–20)Dj. An analysis of the gas-phase TKE transport equation reveals that the direct impact of the particle phase is to dissipate TKE via the particle-induced source term. However, the finite inertia of the particle phase affects the gas-phase velocity gradients, which indirectly affects the TKE production and dissipation, leading to the observed TKE attenuation and enhancement. Particle response to the gas-phase flow is quantified. Particles are found to exhibit notably stronger response to the gas-phase axial velocity than to the radial velocity. A new dimensionless figure is presented that collapses both the axial and radial components of the particle response as a function of the local Stokes number based on their respective integral length scales.

OBJECTIVES/GOALS: Whole-genome viral sequencing is vital to inform public health and study evolution. Arboviruses evolve in vectors, reservoir hosts, and humans, and require surveillance at all points. We developed a new rigorous method of sequencing that captures whole viral genomes in field-collected and clinical samples. METHODS/STUDY POPULATION: ClickSeq is a novel method of Next Generation Sequencing (NGS) library synthesis using azido-nucleotides to terminate reverse transcription. The cDNA generated can be ligated to sequencing and indexing primers at room temperature using copper (Cu I) and vitamin C. With this approach, we designed primers located ~250 bp apart along the genomes of the arboviruses Chikungunya 37797, Zika Dakar, Yellow Fever Asibi, Dengue serotype 2, West Nile 385-99, and St. Louis Encephalitis Virus (SLEV) clade II. We tested this method with varying viral titers: lab-infected mosquito pools, field-collected mosquito pools from a Texas West Nile and SLEV outbreak, and patient isolates from a Pakistani CHIKV outbreak. The cDNA was sequenced in the UTMB NGS Core and aligned using bowtie. RESULTS/ANTICIPATED RESULTS: The use of a single protocol to capture whole viral genomes including UTRs for multiple viruses from different sample collection styles is ideal for arboviruses. Primers for multiple viruses were pooled and used to sequence mosquito pools. The Tiled ClickSeq method captured whole viral genomes without the need for host depletion. UTRs were captured even when the viral strain used for primer design differed from the resulting strain. Discreet variants were captured in both the hypervariable nsP3 region and the UTR in the patient isolates from the CHIKV outbreak compared to the 2017 outbreak. Texas WNV and SLEV outbreaks are now defined from the 2020 outbreak and can be further tracked to update public health measures and understand viral evolution. DISCUSSION/SIGNIFICANCE: UTRs impact both human and mosquito fitness, leading to further outbreaks. Tiled ClickSeq aims to capture whole viral genomes with a method and cost that can be implemented by public health researchers to understand disease evolution as it happens to update both public health and basic virology to the effects of evolution on arboviruses.