The Helan Shan pika Ochotona argentata is an Endangered pika endemic to Ningxia Helan Shan National Nature Reserve in China. Little is known about the species, including regarding its population status, distribution, habitat requirements and even basic natural history. We conducted camera trapping in the Reserve during 13 January 2020–25 January 2022 and obtained two new records for this species. These, combined with five other new records obtained during the monitoring programme in the Reserve, represent a significant increase in the known range of the species and more than double the species’ known extent of occurrence from 107 to 223 km2. These records also provide the first evidence that this species is active both nocturnally and diurnally. However, this range increase does not alter the Endangered status of the pika, and the pika was not observed within its previously known range; future research should involve intensive camera trapping in the Reserve to ascertain whether this is a result of local extirpation, habitat loss or fragmentation or under-sampling on our part. Studies should also incorporate techniques used for other alpine pika species to collect baseline data on habitat use, population size and behaviour to determine the potential response of the Helan Shan pika to present and future threats.

Studies show associations between prenatal maternal stress (PNMS) and child autism, with little attention paid to PNMS and autism in young adulthood. The broad autism phenotype (BAP), encompassing sub-clinical levels of autism, includes aloof personality, pragmatic language impairment and rigid personality. It remains unclear whether different aspects of PNMS explain variance in different BAP domains in young adult offspring. We recruited women who were pregnant during, or within 3 months of, the 1998 Quebec ice storm crisis, and assessed three aspects of their stress (i.e., objective hardship, subjective distress and cognitive appraisal). At age 19, the young adult offspring (n = 33, 22F / 11M) completed a BAP self-report. Linear and logistic regressions were implemented to examine associations between PNMS and BAP traits. Up to 21.4% of the variance in BAP total score and in BAP three domains tended to be explained by at least one aspect of maternal stress, For example, 16.8% of the variance in aloof personality tended to be explained by maternal objective hardship; 15.1% of the variance in pragmatic language impairment tended to be explained by maternal subjective distress; 20.0% of the variance in rigid personality tended to be explained by maternal objective hardship and 14.3% by maternal cognitive appraisal. Given the small sample size, the results should be interpreted with caution. In conclusion, this small prospective study suggests that different aspects of maternal stress could have differential effects on different components of BAP traits in young adults.

In this paper, we explore potential surplus modelling improvements by investigating how well the available models describe an insurance risk process. To this end, we obtain and analyse a real-life data set that is provided by an anonymous insurer. Based on our analysis, we discover that both the purchasing process and the corresponding claim process have seasonal fluctuations. Some special events, such as public holidays, also have impact on these processes. In the existing literature, the seasonality is often stressed in the claim process, while the cash inflow usually assumes simple forms. We further suggest a possible way of modelling the dependence between these two processes. A preliminary analysis of the impact of these patterns on the surplus process is also conducted. As a result, we propose a surplus process model which utilises a non-homogeneous Poisson process for premium counts and a Cox process for claim counts that reflect the specific features of the data.

OBJECTIVES/GOALS: Smoking is a well-established risk factor for lung cancer, but never smokers account for up to 25% of lung cancer cases. There is mounting evidence that lung cancer in never smokers is biologically distinct. We aim to characterize the genomic and immunologic features of lung adenocarcinoma in never smokers versus smokers. METHODS/STUDY POPULATION: We examined clinical, genomic, and bulk-RNA sequencing data from 499 patients in the TCGA lung adenocarcinoma cohort. Tumor mutation burden was analyzed using maftools (R package). Tumor immune characterization was completed using CIBERSORTx, a digital cytometry tool that uses single cell reference profiles to determine immune cell type frequencies from bulk-RNA sequencing data. Single cell reference profiles for 19 different immune cell types were constructed from sequencing of freshly resected lung tumor tissue from UCSF patients. Partitioning Around Medoids (PAM; R package) was used to identify distinct immune phenotypes based on immune cell composition. Fisher’s exact test was used to evaluate for associations between immune phenotypes and smoking status. RESULTS/ANTICIPATED RESULTS: Of the 499 TCGA lung adenocarcinoma patients, 75 were never smokers, 269 were female, and 246 were over the age of 65. Never smokers had lower tumor mutation burden and lower predicted neoantigen burden compared to smokers (p < 0.001). There was no difference in total tumor immune cell infiltration between never smokers and smokers. PAM yielded 2 distinct clusters/immune phenotypes. The first was enriched in M1 Macrophages, cytotoxic T Cells, helper T Cells, regulatory T Cells, and Plasma Cells. The second was enriched in plasmacytoid Dendritic Cells, M2 Macrophages, and exhausted cytotoxic T Cells. Never smoking status was associated with an increased odds of having the first immune phenotype (OR 1.95, 95% CI: 1.15 - 3.35) and this association was statistically significant (p = 0.0086). DISCUSSION/SIGNIFICANCE: Our findings suggest that never smokers have an immune phenotype that is distinct from that observed in smokers. The distinct immune characteristics we observed could explain clinical trial data suggesting immune checkpoint inhibitors are less effective in never smokers and hold implications for tailoring therapy.

OBJECTIVES/GOALS: Development of a user friendly home kit that enables kidney transplant recipients to process urine at home and post the lysate containing RNA to a Core Laboratory would simplify urinary cell mRNA profiling and facilitate longitudinal monitoring. We report our home processing protocol and investigation of its diagnostic performance characteristics. METHODS/STUDY POPULATION: We developed a home processing protocol (HPP) consisting of urine filtration and lysis of urinary cells, both performed at home by the kidney transplant recipients (KTR) themselves, followed by isolation of total RNA from the lysate and mRNA enrichment using a silica-membrane-based cartridge, both performed at the Core Laboratory. Using the HPP, total RNA was isolated from kidney allograft biopsy-matched urines and absolute copy numbers of CD3εmRNA, CXCL10 mRNA, and 18S rRNA, components of the Clinical Trials in Organ Transplantation 04 (CTOT-04) three-gene TCMR diagnostic signature, and urinary cell BKV VP1 mRNA copy number, were measured using customized RT-qPCR assays. RESULTS/ANTICIPATED RESULTS: CTOT-04 three-gene TCMR diagnostic signature scores in urine processed using HPP discriminated KTR with TCMR (12 TCMR biopsies from 11 KTR) from KTR with no TCMR/BKVN (29 No TCMR/No BKVN biopsies from 29 KTR) (P=0.0005, Mann-Whitney test), and AUROC was 0.84 (95% CI, 0.69 to 0.98). TCMR was diagnosed with sensitivity of 67% (95% CI, 35 to 89) at a specificity of 86% (95% CI, 67 to 95) using the CTOT-04 validated cutpoint of -1.213 (P=0.0016,Fisher exact test). BKV VP1 mRNA copy number in urine processed with HPP discriminated KTR with BKVN (n=7) from KTR with no TCMR/BKVN (n=29) and AUROC was 1.0 (95% CI, 1.00 to 1.00). BKVN was diagnosed with a sensitivity of 86% (95% CI, 42 to 99) at specificity of 100% (95% CI, 85 to 100) with the previously validated cutpoint of 6.5x10^8 BKV VP1 mRNA copies/μg of RNA (P DISCUSSION/SIGNIFICANCE: Urine processed using the HPP predicted TCMR and BKVN in KTR. The HPP represents not only a significant advance towards portability of urinary cell mRNA profiling but also should improve patient management by minimizing visits for urine collection.

This article investigates the impact of exchange-traded fund (ETF) ownership on seasoned equity offerings (SEOs). We find that increases to firms’ ETF ownership is positively related to their propensity to conduct an SEO. ETF ownership is also associated with less negative SEO announcement returns, smaller discounts, and better long-run stock returns. Our evidence is consistent with equity issuance following investor demand for stocks driven by greater participation in ETFs, suggesting a possible alternative source of market timing opportunity.

Fetal liver tissue collected from a nonhuman primate (NHP) baboon model of maternal nutrient reduction (MNR) at four gestational time points (90, 120, 140, and 165 days gestation [dG], term in the baboon is ∼185 dG) was used to quantify MNR effects on the fetal liver transcriptome. 28 transcripts demonstrated different expression patterns between MNR and control livers during the second half of gestation, a developmental period when the fetus undergoes rapid weight gain and fat accumulation. Differentially expressed transcripts were enriched for fatty acid oxidation and RNA splicing-related pathways. Increased RNA splicing activity in MNR was reflected in greater abundances of transcript splice variant isoforms in the MNR group. It can be hypothesized that the increase in splice variants is deployed in an effort to adapt to the poor in utero environment and ensure near-normal development and energy metabolism. This study is the first to study developmental programming across four critical gestational stages during primate fetal liver development and reveals a potentially novel cellular response mechanism mediating fetal programming in response to MNR.

As a typical plasma-based optical element that can sustain ultra-high light intensity, plasma density gratings driven by intense laser pulses have been extensively studied for wide applications. Here, we show that the plasma density grating driven by two intersecting driver laser pulses is not only nonuniform in space but also varies over time. Consequently, the probe laser pulse that passes through such a dynamic plasma density grating will be depolarized, that is, its polarization becomes spatially and temporally variable. More importantly, the laser depolarization may spontaneously take place for crossed laser beams if their polarization angles are arranged properly. The laser depolarization by a dynamic plasma density grating may find application in mitigating parametric instabilities in laser-driven inertial confinement fusion.

Meat quality is not only influenced by breed but also rearing environment. The aim of this study was to evaluate the influence of different housing environments on growth performance, carcase traits, meat quality, physiological response pre-slaughter and fatty acid composition in two pig breeds. A total of 120 growing pigs at 60-70 days of age were arranged in a 2 × 2 factorial design with the breeds (Duroc × Landrace × Large White [D × L × LW] and Duroc × Landrace × Min pig [D × L × M]) and environmental enrichment (barren concrete floor or enriched with straw bedding) as factors. Each treatment was performed in triplicate with ten pigs per replicate. The pigs housed in the enriched environment exhibited a higher average daily gain, average daily feed intake, saturated fatty acid percentage and backfat depth than the pigs reared in the barren environment. Plasma cortisol levels were lower and growth hormone higher in enriched compared to barren pens. The D × L × M pigs showed lower cooking loss compared with the D × L × LW pigs. Moreover, the D × L × M pigs exhibited poor growth performance but had a better water-holding capacity. Only carcase traits and meat quality interaction effects were observed. We concluded that an enriched environment can reduce preslaughter stress and improve the growth performance of pigs and modulate the fatty acid composition of pork products.

Auctions, normally considered as devices facilitating trade, also provide a way to probe mechanisms governing one’s valuation of some good or action. One of the most intriguing phenomena in auction behavior is the winner’s curse — the strong tendency of participants to bid more than rational agent theory prescribes, often at a significant loss. The prevailing explanation suggests that humans have limited cognitive abilities that make estimating the correct bid difficult, if not impossible. Using a series of auction structures, we found that bidding approaches rational agent predictions when participants compete against a computer. However, the winner’s curse appears when participants compete against other humans, even when cognitive demands for the correct bidding strategy are removed. These results suggest the humans assign significant future value to victories over human but not over computer opponents even though such victories may incur immediate losses, and that this valuation anomaly is the origin of apparently irrational behavior.