Background: The fragility index (FI) is the minimum number of patients whose status would have to change from a nonevent to an event to turn a statistically significant result to a non-significant result. We used this to measure the robustness of trials comparing carotid endarterectomy (CEA) to carotid artery stenting (CAS). Methods: A search was conducted in MEDLINE, Embase, and PubMed on RCTs comparing CEA to CAS. The trials need to have statistically significant results and dichotomous primary endpoints to be included. Results: Our literature search identified 10 RCTs which included 9382 patients (4734 CEA, 4648 CAS). The primary end points of all included trials favoured CEA over CAS. The median FI was 9.5 (interquartile range 2.25 - 21.25). All of the studies that reported lost-to-follow-up (LTFU) had LTFU greater than its fragility index, which raises concern that the missing data could change the results of the trial from statistically significant to statistically insignificant. Conclusions: A small number of events (FI, median 9.5) were required to render the results of carotid artery stenosis RCTs comparing CEA to CAS statistically insignificant. All of the studies that reported LTFU had LTFU greater than its fragility index.

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.

Emerging evidence has indicated that perinatal exposure to low-calorie sweeteners (LCSs) might be associated with adverse pregnancy outcomes and offspring health(1). The aim of the study was to examine the patterns and predictors of LCS consumption among pregnant women in Australia. A web-based survey was conducted among 422 pregnant women aged 18-50 years between September and October 2022. Participants were recruited by a reputable consumer panel provider, Qualtrics. Sociodemographic, lifestyle, dietary intake (including LCS consumption), pregnancy-related characteristics, and participants’ awareness regarding the potential health effects of LCS were assessed. We assessed LCS consumption from twelve food groups that are common sources of LCS(2). To identify LCS consumption patterns and predictors of the patterns, a latent class analysis and hierarchical multinomial logistic regression was employed, respectively. The women’s mean (SD) age was 30 (4.6) years. Overall, 95% of the women reported consuming any LCS in the current pregnancy. Three different LCS consumption patterns were identified. Infrequent or non-consumers, representing 50% of the women, included those who rarely or never consumed LCS-containing foods and beverages (with a probability of less than 10%). The second pattern, moderate consumption, which encompassed 40% of the women, indicated low to moderate consumption of LCSs (for instance, the likelihood of consuming LCS-containing drinks ranged from 18% to 50%). The third pattern highlighted habitual consumption. These individuals (10%) had a high likelihood (ranging from 75% to 95%) of consuming foods from all food groups that contained LCS. The majority of women (71%) were unaware of the potential adverse effects of LCS, and only 25% expressed concerns about the potential impacts of LCS on their health and the health of their offspring. Moreover, women who frequently consumed sugar-sweetened beverages (SSBs) (≥2 times/week) or had gestational diabetes were over three times more likely to adopt a habitual LCS consumption pattern compared to those who consumed SSBs less often [adjusted relative risk ratio (aRRR) = 3.17, 95% CI: 1.39-7.21] and those without gestational diabetes [aRRR = 3.53, 95% CI: 1.03-12.10]. Additionally, having a medical condition was linked to a 55% lower chance of moderate LCS consumption compared to infrequent or non-consumption. These findings indicate LCS consumption is widespread, but awareness of its potential adverse health effect is low among pregnant women in Australia. Public health interventions to increase the awareness of potential adverse effect of LCS consumption, particularly among pregnant women with moderate and habitual consumption are warranted.

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.

Coupling of clearance joint and harsh aerodynamic heating environment is an inevitable nonlinear factor in folding mechanism of the fin of high-speed aircrafts that remarkably modifies natural frequencies and modes of vibration from the initial design state. However, accurately predicting dynamic properties of deployable fin with full consideration of these effects is not common industry practice. A practical semi-analytical model based on Hertz contact theory and ESDU-78035 model is proposed in this study to investigate high-temperature connection stiffness of local hinged–locked mechanisms. Material property degradation and clearance variation caused by thermal expansion are comprehensively considered and quantified in this model. Vibration characteristics of the assembled deployable fin are then solved using finite element method (FEM). The real-time evolutionary process of thermal mode of the fin is discussed. And natural frequencies of fixed-value and time-varying connection stiffness are compared. The simulation results of this study demonstrate that the relative error of structure temperature between the sequential approach and fully coupled simulations is less than 6.98%. The connection stiffness (slope of the load-displacement curve) of the folding mechanism under high temperature conditions decreases by 3.52%, and the variation is mainly caused by the degradation of the elastic modulus of the material, while the clearance change due to the thermal expansion has no significant effect on the slope. The natural frequency of the deployable fin exhibits an inverse correlation with the temperature change trend, and the first three frequencies decrease by 1.67, 7.75, and 16.28 Hz compared to the initial value, respectively.

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.

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.

To investigate the downstream rim seal gas ingestion characteristics of a 1.5-stage turbine, the URANS equations were solved numerically using the SST turbulence model. The effects of different purge flow rates and the second vane on the ingestion characteristics of the aft cavity and the nonuniform fluctuations of the main gas path pressure are analysed. The results showed that the aft cavity is affected by the combined effects of the blade and the second vane, and the potential field at the leading edge of the second vane greatly influence the airflow variation in the aft cavity, which enhances the ingress of the mainstream into the wheel-space. The front purge flow weakens the egress between the suction side of the blade and the suction side of the second vane. The potential field at the leading edge of the second vane suppresses the nonuniform distribution of airflow in the aft cavity caused by the rotational effect of the blade.

Background: Phase 3 COMET trial (NCT02782741) compares avalglucosidase alfa (n=51) with alglucosidase alfa (n=49) in treatment-naïve LOPD. Methods: Primary objective: determine avalglucosidase alfa effect on respiratory muscle function. Secondary/other objectives include: avalglucosidase alfa effect on functional endurance, inspiratory/expiratory muscle strength, lower/upper extremity muscle strength, motor function, health-related quality of life, safety. Results: At Week 49, change (LSmean±SE) from baseline in upright forced vital capacity %predicted was greater with avalglucosidase alfa (2.89%±0.88%) versus alglucosidase alfa (0.46%±0.93%)(absolute difference+2.43%). The primary objective, achieving statistical non-inferiority (p=0.0074), was met. Superiority testing was borderline significant (p=0.0626). Week 49 change from baseline in 6-minute walk test was 30.01-meters greater for avalglucosidase alfa (32.21±9.93m) versus alglucosidase alfa (2.19±10.40m). Positive results for avalglucosidase alfa were seen for all secondary/other efficacy endpoints. Treatment-emergent adverse events (AEs) occurred in 86.3% of avalglucosidase alfa-treated and 91.8% of alglucosidase alfa-treated participants. Five participants withdrew, 4 for AEs, all on alglucosidase alfa. Serious AEs occurred in 8 avalglucosidase alfa-treated and 12 alglucosidase alfa-treated participants. IgG antidrug antibody responses were similar in both. High titers and neutralizing antibodies were more common for alglucosidase alfa. Conclusions: Results demonstrate improvements in clinically meaningful outcome measures and a more favorable safety profile with avalglucosidase alfa versus alglucosidase alfa. Funding: Sanofi Genzyme

Beryl from Xuebaoding, Sichuan Province, western China is known for its unusual tabular habit and W–Sn–Be paragenesis in a greisen-type deposit. The crystals are typically colourless transparent to pale blue, often with screw dislocations of hexagonal symmetry on the (0001) crystal faces. Combining electron microprobe analyses and laser ablation inductively coupled plasma mass spectrometry with single-crystal X-ray diffraction (XRD), correlated with Raman and micro-infrared (IR) spectroscopy and imaging, the crystal chemical characteristics are determined. The contents of Na+ (0.24–0.38 atoms per formula unit (apfu)) and Li+ up to 0.38 apfu are at the high end compared to beryl from other localities worldwide. Li+ substitution for Be2+ on the tetrahedral (T2) site is predominantly charge balanced by Na+ on the smaller channel (C2) site, with Na+ ranging from 91.5% to 99.7% (apfu) of the sum of all other alkali elements. Cs+ and minor Rb+ and K+ primarily charge balance the minor M2+ substitution for Al3+ at the A site; all iron at the A site is suggested to be trivalent. The a axis ranges from 9.2161(2) to 9.2171(4) Å, with unit-cell volume from 678.03(3) to 678.48(7) Å3. The c/a ratio of 1.0002–1.0005 is characteristic for T2-type beryl with unit-cell parameters controlled primarily by Be2+ substitution. Transmission micro-IR vibrational spectroscopy and imaging identifies coordination of one or two water molecules to Na+ (type IIs and type IId, respectively) as well as alkali free water (type I). Based on IR absorption cross section and XRD a C1 site water content of 0.4–0.5 apfu is derived, i.e. close to 50% site occupancy. Secondary crystal phases with a decrease in Fe and Mg, yet increase in Na, suggest early crystallisation of aquamarine, with goshenite being late. With similar crystal chemistry to beryl of columnar habit from other localities worldwide, the tabular habit of Xuebaoding beryl seems to be unrelated to chemical composition and alkali content.

Self-recognition is of great significance to our sense of self. To date, disturbances in the processing of visual self-recognition are well studied in people with schizophrenia, whereas relatively few studies have focused on the processing of self in other domains, such as auditory. An investigation of auditory self-recognition contributes to delineate changes related to self and the potential roots of the described psychopathological aspects connoting schizophrenia. By applying unimodal task and multisensory test, this study investigated auditory self-recognition in people with schizophrenia under unimodal and bimodal circumstances. Forty-six adults diagnosed with schizophrenia and thirty-two healthy controls were involved in this study. Results suggested that people with schizophrenia seemed to have significantly lower perceptual sensitivity in detecting self-voice, and also showed stricter judgment criteria in self-voice decision. Furthermore, in the presentation of stimuli that combined the stimulation of others’ faces with one’s own voice, people with schizophrenia mistakenly attributed the voices of others as their own. In conclusion, altered auditory self-recognition in people with schizophrenia was found.