N-3 polyunsaturated fatty acids (n-3 PUFAs) delivered by fish oil supplements alter the number and functions of circulating extracellular vesicles (EVs), but consumption of oily fish does not reproduce this effect. In order to assess the effects of fish oil supplements and oily fish, at a level achievable in the diet, on EV numbers, composition and procoagulant activity in healthy human volunteers, forty-two healthy subjects were assigned to one of three treatment groups: (i) fish oil supplements plus white fish meals, (ii) control supplements plus oily fish meals or (iii) control supplements plus white fish meals for 12 weeks in a randomized, double-blind, placebo-controlled, parallel trial; circulating EVs were enumerated and their procoagulant activity assessed using thrombin generation and fibrinolysis assays. Our results showed that fish oil supplements decreased circulating EV numbers and reduced EV-stimulated thrombin generation, but the consumption of oily fish at half the dose of EPA had no effect on either EV number or thrombogenic capacity. Consumption of both oily fish and fish oil supplements increased the EPA and DHA contents of EVs and the proportion of EPA in circulating EVs was strongly associated with EV-stimulated thrombin generation. This study revealed that the additional 1 g/d EPA delivered in the fish oil supplements is required to decrease the numbers and thrombogenic capacity of EVs, since oily fish at a level achievable in the diet had no effect. Increasing EPA intake beyond current guidelines for oily fish consumption may therefore be required for cardiovascular benefits relating to EVs.

Recursive types and bounded quantification are prominent features in many modern programming languages, such as Java, C#, Scala, or TypeScript. Unfortunately, the interaction between recursive types, bounded quantification, and subtyping has shown to be problematic in the past. Consequently, defining a simple foundational calculus that combines those features and has desirable properties, such as decidability, transitivity of subtyping, conservativity, and a sound and complete algorithmic formulation, has been a long-time challenge.

This paper shows how to extend $F_{\le}$ with iso-recursive types in a new calculus called $F_{\le}^{\mu}$. $F_{\le}$ is a well-known polymorphic calculus with bounded quantification. In $F_{\le}^{\mu}$, we add iso-recursive types and correspondingly extend the subtyping relation with iso-recursive subtyping using the recently proposed nominal unfolding rules. In addition, we use so-called structural folding/unfolding rules for typing iso-recursive expressions, inspired by the structural unfolding rule proposed by Abadi et al. (1996). The structural rules add expressive power to the more conventional folding/unfolding rules in the literature, and they enable additional applications. We present several results, including: type soundness; transitivity; the conservativity of $F_{\le}^{\mu}$ over $F_{\le}$; and a sound and complete algorithmic formulation of $F_{\le}^{\mu}$. We study two variants of $F_{\le}^{\mu}$. The first one uses an extension of the $\textrm{kernel}~F_{\le}$ (a well-known decidable variant of $F_{\le}$). This extension accepts equivalent rather than equal bounds and is shown to preserve decidable subtyping. The second variant employs the $\textrm{full}~F_{\le}$ rule for bounded quantification and has undecidable subtyping. Moreover, we also study an extension of the kernel version of $F_{\le}^{\mu}$, called $F_{\le\ge}^{\mu\wedge}$, with a form of intersection types and lower bounded quantification. All the properties from the kernel version of $F_{\le}^{\mu}$ are preserved in $F_{\le\ge}^{\mu\wedge}$. All the results in this paper have been formalized in the Coq theorem prover.

Urban air mobility (UAM) utilising novel transportation tools is gradually being recognised as a significant means to alleviate ground transportation pressures, vertiports which serve as pivotal nodes in UAM require efficient methods for assessing its operational capacity to develop an appropriate operational strategy and help to design vertiport ground infrastructure scientifically. This study proposes a multi-dimensional assessment method for the capacity of vertiports considering throughput and quality of service based on genetic algorithm (CEGA). The method comprehensively considers constraints such as unmanned aerial vehicle (UAV) safety separation, battery endurance, number of landing vertipads and UAV speed. The experimental results indicate that the vertiport with the scheduling algorithm proposed by this study has a larger capacity and experiences fewer delay than the vertiport with first-come-first-served (FCFS) algorithm when the vertiport has the same limited number of vertipads. Different proportions of UAVs significantly affect the quality of service and the degree of operation delays. The weights of vertiport throughput and customer satisfaction are the parameters that represent the importance of throughput and customer satisfaction in the objective function of the capacity assessment model. When the weights of throughput and customer satisfaction are set to 0.8 and 0.2 respectively, the performance of this optimisation model is optimal. This study provides a novel solution for capacity assessment and operation scheduling of vertiports, laying the foundation for improving the efficiency of UAM operations.

Evidence-based insertion and maintenance bundles are effective in reducing the incidence of central line-associated bloodstream infections (CLABSI) in intensive care unit (ICU) settings. We studied the adoption and compliance of CLABSI prevention bundle programs and CLABSI rates in ICUs in a large network of acute care hospitals across Canada.

Prenatal maternal anxiety is considered a risk factor for the development of child internalizing problems. However, little is known about potential mechanisms that account for these associations. The current study examined whether prenatal maternal anxiety was indirectly associated with toddler internalizing problems via prenatal maternal physiology and infant negative affectivity. We examined these associations in a longitudinal study of 162 expectant mothers from their third trimester until 18 months postpartum. Path analyses showed that higher prenatal anxiety was associated with higher infant negative affectivity at 7 months, which in turn was associated with higher toddler internalizing problems at 18 months. Prenatal anxiety was not indirectly associated with child outcomes via baseline or task-evoked respiratory sinus arrhythmia (RSA) in response to an infant cry while pregnant. However, pregnant women with greater decreases in task-evoked RSA had toddlers with greater internalizing problems, which was mediated by infant negative affectivity at 7 months. Findings suggest that prenatal anxiety and RSA reactivity to an infant cry may be independent risk factors for the development of infant negative affectivity, which in turn increases risk for toddler internalizing problems. These findings contribute to a growing literature on mechanisms that underlie intergenerational transmission of internalizing problems.

Sugarcane varieties differ in their ratooning ability (RA), and it is hypothesized that soil types and harvest seasons impact varieties’ RA. However, the effects of these factors on varieties’ RA remain unclear. This study aimed to assess the RA of different commercial sugarcane varieties (NCo376, N19, N23, N25, and N36), and establish the effects of soils and seasons on ratoon yields of these varieties in Eswatini. Fifteen years data on tons cane per ha per annum (TCHA) and tons sucrose per ha per annum (TSHA) achieved by plant cane and seven ratoon crops were collected from four commercial growers and analysed using linear regression models. The varieties significantly differed in RA. Variety N25, which had the highest plant cane yields (121.3 TCHA and 16.7 TSHA), had the sharpest yield decline over ratoon crops (–2.74 TCHA and −0.33 TSHA), suggesting that this variety is more suitable for short crop cycles. Variety N36 had second highest plant cane yields (111.7 TCHA and 16.4 TSHA) and a lower ratoon yield decline (–1.38 TCHA and −0.16 TSHA) than N25, suggesting that it is suitable for longer ratoon crop cycles. While soil type and harvest season significantly affected the relative yields of varieties, they did not significantly impact their RA, indicating that differences in varieties’ RA were driven by genotype and were relatively stable across environments. This suggests that tests to assess the adaptability of varieties should be conducted in multiple environments, while testing the RA of varieties may be conducted in fewer environments.

Background: Cerebral venous thrombosis (CVT)most commonly affects younger women. Diagnosis may be delayed due to its distinct presentation and demographic profile compared to other stroke types. Methods: We examined delays to diagnosis of CVT in the SECRET randomized trial and TOP-SECRET parallel registry. Adults diagnosed with symptomatic CVT within <14 days were included. We examined time to diagnosis and number of health care encounters prior to diagnosis and associations with demographics, clinical and radiologic features and functional and patient-reported outcomes (PROMS) at days 180&365. Results: Of 103 participants, 68.9% were female; median age was 45 (IQR 31.0-61.0). Median time from symptom onset to diagnosis was 4 (1-8) days. Diagnosis on first presentation to medical attention was made in 60.2%. The difference in time to diagnosis for single versus multiple presentations was on the order of days (3[1-7] vs. 5[2-11.75], p=0.16). Women were likelier to have multiple presentations (OR 2.53; 95% CI1.00-6.39; p=0.05) and longer median times to diagnosis (5[2-8]days vs. 2[1-4.5] days; p=0.005). However, this was not associated with absolute or change in functional, or any patient reported, outcome measures (PROMs) at days 180&365. Conclusions: Diagnosis of CVT was commonly delayed; women were likelier to have multiple presentations. We found no association between delayed diagnosis and outcomes.

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 aerodynamic performance of a wing model with a row of distributed engines are investigated at the vertical take-off condition. The engines are installed near the trailing edge of the wing. During vertical take-off, the jets exit from the engines and impinge perpendicularly to the ground, providing a thrust for the aircraft. Due to the ground effects, complex vortex structures are induced by the jets. The vortices are categorised into the spanwise vortices and the chordwise vortices. The underwing vortices can lead to low-pressure regions on the lower surface of the wing, resulting in an undesirable downward force. The underwing vortex structures are affected by the ratio of the engine distance to the engine diameter ($S/D$). At a small $S/D$ = 1.10, the flow field is dominated by the spanwise vortices; at a large $S/D$ = 2.78, the flow field is dominated by the chordwise vortices. The range and strength of the spanwise vortices are affected by the vortices interaction. Competition mechanism exists between the range and strength effects, which results in the non-linear variation of the wing lift coefficient with engine spacing. The details of the flow physics underneath the wing and its mechanism on the lift of the wing during take-off are investigated.

Aphis spiraecola Patch is one of the most economically important tree fruit pests worldwide. The pyrethroid insecticide lambda-cyhalothrin is commonly used to control A. spiraecola. In this 2-year study, we quantified the resistance level of A. spiraecola to lambda-cyhalothrin in different regions of the Shaanxi province, China. The results showed that A. spiraecola had reached extremely high resistance levels with a 174-fold resistance ratio (RR) found in the Xunyi region. In addition, we compared the enzymatic activity and expression level of P450 genes among eight A. spiraecola populations. The P450 activity of A. spiraecola was significantly increased in five regions (Xunyi, Liquan, Fengxiang, Luochuan, and Xinping) compared to susceptible strain (SS). The expression levels of CYP6CY7, CYP6CY14, CYP6CY22, P4504C1-like, P4506a13, CYP4CZ1, CYP380C47, and CYP4CJ2 genes were significantly increased under lambda-cyhalothrin treatment and in the resistant field populations. A L1014F mutation in the sodium channel gene was found and the mutation rate was positively correlated with the LC50 of lambda-cyhalothrin. In conclusion, the levels of lambda-cyhalothrin resistance of A. spiraecola field populations were associated with P450s and L1014F mutations. Our combined findings provide evidence on the resistance mechanism of A. spiraecola to lambda-cyhalothrin and give a theoretical basis for rational and effective control of this pest species.

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.

Blood-culture overutilization is associated with increased cost and excessive antimicrobial use. We implemented an intervention in the adult intensive care unit (ICU), combining education based on the DISTRIBUTE algorithm and restriction to infectious diseases and ICU providers. Our intervention led to reduced blood-culture utilization without affecting safety metrics.

Background: Tuberculosis is an airborne disease caused by Mycobacterium Tuberculosis. Intracranial tuberculoma is a rare complication of extrapulmonary tuberculosis due to hematogenous spread to subpial and subependymal regions. Intracranial tuberculoma can occur with or without meningitis. Methods: A 3-year-old male who recently emigrated from Sudan presented to the emergency department with right-sided seizures lasting 30 minutes which were aborted with levetiracetam and midazolam. CT head revealed a multilobulated left supratentorial mass, with solid and cystic components measuring 8.0 x 4.8 x 6.5 cm. The patient had successful surgical resection of the mass which was positive for Mycobacterium Tuberculosis. He was started on rifampin, isoniazid, pyrazinamide, ethambutol, and fluoroquinolone and discharged home in stable condition. Results: Literature review on pediatric intracranial tuberculoma was performed which included 48 studies (n=49). The mean age was 8.8 ± 5.4 years with slight female predilection (59%). Predominant solitary tuberculomas (63%) were preferentially managed with both surgical resection and antitubercular therapy (ATT) compared to multifocal tuberculomas that were preferentially managed with ATT. Conclusions: Intracranial tuberculoma is a rare but treatable cause of space-occupying lesions in children. Clinicians should maintain high-level of suspicion in patients from endemic regions and involve infectious disease service early in patient’s care.

Racial differences in Clostridioides difficile infection (CDI) outcomes have been reported. In this study, minoritized patients with CDIs had prolonged hospitalizations and increased intensive care unit admissions. Chronic kidney disease was shown to partially mediate the relationship between race or ethnicity and severe CDI. Our findings suggest potential areas for equitable interventions.

Racially and ethnically minoritized (REM) patients are disproportionately affected by infectious diseases, including candidemia. REM patients with candidemia were significantly younger, with trends toward more risk factors for candidemia and longer lengths of stay. Although Candida parapsilosis was more common in REM patients, there were no differences in mortality rates.

OBJECTIVES/GOALS: Recent in vitro evidence suggests that diverse parasite protein families called RIFINs and STEVORs are displayed on the surface of infected red blood cells and may have a role in severe malaria, but they remain sparsely studied in natural infections. We measured the RNA expression of these antigens in Malian children with severe or mild malaria illness. METHODS/STUDY POPULATION: We collected blood samples from Malian children aged six months to five years, including 14 with cerebral malaria, 10 with severe malarial anemia, and demographic-matched controls with mild, uncomplicated malaria. We extracted total RNA from each patient and used a custom capture array to selectively enrich Plasmodium falciparum parasite RNA. We then performed Illumina next-generation RNA sequencing and reconstructed parasite transcriptomes using reference-free de novo assembly. We identified RNA encoding RIFINs and STEVORs using an in-house classifier, then measured the diversity and abundance of gene expression for each infection. Expression diversity was defined as the number of unique variants transcribed. Expression abundance was calculated as transcripts per million (TPM). RESULTS/ANTICIPATED RESULTS: Cerebral malaria cases, but not severe malarial anemia cases, had higher diversity and abundance of RIFIN expression compared to mild infections. Type A RIFINs predominated over Type B RIFINs, and the same two RIFINs were predominantly expressed in all disease phenotypes. We anticipate that predominantly expressed RIFINs share high sequence homology with variants previously shown to bind blood antigens or immune inhibitory receptors. STEVOR expression was also higher in cerebral malaria compared to mild malaria, but STEVOR transcripts were sparse overall. DISCUSSION/SIGNIFICANCE: Elevated RIFIN expression in cerebral malaria over mild malaria supports a role for these antigens in pathogenesis. Severe malarial anemia may progress through a different pathogenic mechanism. Predominantly expressed RIFIN variants may be promising targets for vaccines and therapeutics to protect children against cerebral malaria.