The glacial history of northeast Siberia is poorly understood compared with other high-latitude regions. Using 10Be and 26Al exposure dating together with remote sensing, we have investigated the glacial history of a remote, formerly glaciated valley in the Tas-Kystabyt Range of the Chersky Mountains in central northeast Siberia. Based on measurements from moraine boulders and bedrock samples, we find evidence for deglaciation of the valley 45.6 ± 3.4 ka ago, that is during the peak of Marine Isotope Stage 3. Satellite imagery of the range reveals at least two generations of moraines in other nearby valleys, indicating that multiple stages of glaciation took place across the Tas-Kystabyt Range. Based on calculated equilibrium-line altitudes, we speculate that the outer set of moraines is linked to the 45.6 ± 3.4 ka deglaciation event identified by our dating, while the inner generation of moraines is associated with a younger glaciation event, possibly the last glacial maximum (LGM). Thus, our results reaffirm current impressions that the maximum ice extent during the last glacial cycle was reached before the global LGM in northeast Siberia.

The First Large Absorption Survey in H i (FLASH) is a large-area radio survey for neutral hydrogen in and around galaxies in the intermediate redshift range $0.4\lt z\lt1.0$, using the 21-cm H i absorption line as a probe of cold neutral gas. The survey uses the ASKAP radio telescope and will cover 24,000 deg$^2$ of sky over the next five years. FLASH breaks new ground in two ways – it is the first large H i absorption survey to be carried out without any optical preselection of targets, and we use an automated Bayesian line-finding tool to search through large datasets and assign a statistical significance to potential line detections. Two Pilot Surveys, covering around 3000 deg$^2$ of sky, were carried out in 2019-22 to test and verify the strategy for the full FLASH survey. The processed data products from these Pilot Surveys (spectral-line cubes, continuum images, and catalogues) are public and available online. In this paper, we describe the FLASH spectral-line and continuum data products and discuss the quality of the H i spectra and the completeness of our automated line search. Finally, we present a set of 30 new H i absorption lines that were robustly detected in the Pilot Surveys, almost doubling the number of known H i absorption systems at $0.4\lt z\lt1$. The detected lines span a wide range in H i optical depth, including three lines with a peak optical depth $\tau\gt1$, and appear to be a mixture of intervening and associated systems. Interestingly, around two-thirds of the lines found in this untargeted sample are detected against sources with a peaked-spectrum radio continuum, which are only a minor (5–20%) fraction of the overall radio-source population. The detection rate for H i absorption lines in the Pilot Surveys (0.3 to 0.5 lines per 40 deg$^2$ ASKAP field) is a factor of two below the expected value. One possible reason for this is the presence of a range of spectral-line artefacts in the Pilot Survey data that have now been mitigated and are not expected to recur in the full FLASH survey. A future paper in this series will discuss the host galaxies of the H i absorption systems identified here.

With the rapid expansion of the Infection Prevention Control/Healthcare Epidemiology (IPC/HE) fields over recent decades, the pivotal roles of IPC/HE in hospital regulation, quality improvement, patient safety, and healthcare finances have become increasingly apparent. Consequently, the demand for effective IPC/HE leaders has surged.1,2 Training in IPC/HE is essential for all infectious diseases (ID) fellows (both adult and pediatric), including those planning a career in hospital epidemiology as well as those planning to focus on general ID, transplant, HIV, etc. ID fellows, however, have historically felt ill-prepared in IPC/HE. Joiner et al’s survey highlighted this gap, revealing that only half of respondents felt adequately trained in infection control, despite half of them participating in infection control in their practice.3 IPC/HE fellow education is not currently standardized, and most IPC/HE training is led by individual mentors and healthcare facilities.

This study aimed to evaluate the effects of acetyl-L-carnitine on follicle survival and growth, stromal cell density and extracellular matrix, as well as on the expression of mRNA for nuclear factor erythroid 2-related factor (NRF2), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX) and peroxiredoxin 6 (PRDX6) in cultured bovine ovarian cortical tissues. Ovarian fragments (3 × 3 × 1 mm) were cultured for 6 days in α-MEM+ alone or supplemented with 10, 50 or 100 μM acetyl-L-carnitine at 38.5°C with 5% CO2 in humidified air. Before (non-cultured tissues) and after culture, the ovarian fragments were fixed in 4% paraformaldehyde for 12 h for histological analysis or stored at –80ºC for mRNA expression analysis of NRF2, SOD, CAT, PRDX6 and GPX1. The results showed that 100 μM acetyl-L-carnitine increased the percentages of morphologically normal follicles and stromal cell density in cultured ovarian tissues. On the other hand, acetyl-L-carnitine did not influence the percentage of collagen in ovarian tissue nor the expression of mRNAs for NRF2, SOD, CAT, PRDX6 and GPX1. In conclusion, 100 μM acetyl-L-carnitine increased follicle survival and stromal cell density in cultured bovine ovarian tissues but does not influence collagen fibre distribution or the expression of mRNAs for NRF2, SOD, CAT, PRDX6 and GPX1.

The stars of the Milky Way carry the chemical history of our Galaxy in their atmospheres as they journey through its vast expanse. Like barcodes, we can extract the chemical fingerprints of stars from high-resolution spectroscopy. The fourth data release (DR4) of the Galactic Archaeology with HERMES (GALAH) Survey, based on a decade of observations, provides the chemical abundances of up to 32 elements for 917 588 stars that also have exquisite astrometric data from the Gaia satellite. For the first time, these elements include life-essential nitrogen to complement carbon, and oxygen as well as more measurements of rare-earth elements critical to modern-life electronics, offering unparalleled insights into the chemical composition of the Milky Way. For this release, we use neural networks to simultaneously fit stellar parameters and abundances across the whole wavelength range, leveraging synthetic grids computed with Spectroscopy Made Easy. These grids account for atomic line formation in non-local thermodynamic equilibrium for 14 elements. In a two-iteration process, we first fit stellar labels to all 1 085 520 spectra, then co-add repeated observations and refine these labels using astrometric data from Gaia and 2MASS photometry, improving the accuracy and precision of stellar parameters and abundances. Our validation thoroughly assesses the reliability of spectroscopic measurements and highlights key caveats. GALAH DR4 represents yet another milestone in Galactic archaeology, combining detailed chemical compositions from multiple nucleosynthetic channels with kinematic information and age estimates. The resulting dataset, covering nearly a million stars, opens new avenues for understanding not only the chemical and dynamical history of the Milky Way but also the broader questions of the origin of elements and the evolution of planets, stars, and galaxies.

The description and delineation of trematode species is a major ongoing task. Across the field there has been, and currently still is, great variation in the standard of this work and in the sophistication of the proposal of taxonomic hypotheses. Although most species are relatively unambiguously distinct from their congeners, many are either morphologically very similar, including the major and rapidly growing component of cryptic species, or are highly variable morphologically despite little to no molecular variation for standard DNA markers. Here we review challenges in species delineation in the context provided to us by the historical literature, and the use of morphological, geographical, host, and molecular data. We observe that there are potential challenges associated with all these information sources. As a result, we encourage careful proposal of taxonomic hypotheses with consideration for underlying species concepts and frank acknowledgement of weaknesses or conflict in the data. It seems clear that there is no single source of data that provides a wholly reliable answer to our taxonomic challenges but that nuanced consideration of information from multiple sources (the ‘integrated approach’) provides the best possibility of developing hypotheses that will stand the test of time.

A major subglacial lake, Lake Snow Eagle (LSE), was identified in East Antarctica by airborne geophysical surveys. LSE, contained within a subglacial canyon, likely hosts a valuable sediment record of the geological and glaciological changes of interior East Antarctica. Understanding past lake activity is crucial for interpreting this record. Here, we present the englacial radiostratigraphy in the LSE area mapped by airborne ice-penetrating radar, which reveals a localized high-amplitude variation in ice unit thickness that is estimated to be ∼12 ka old. Using an ice-flow model that simulates englacial stratigraphy, we investigate the origin of this feature and its relationship to changes in ice dynamical boundary conditions. Our results reveal that local snowfall redistribution initiated around the early Holocene is likely the primary cause, resulting from a short-wavelength (∼10 km) high-amplitude (∼20 m) ice surface slope variation caused by basal lubrication over a large subglacial lake. This finding indicates an increase in LSE water volume during the Holocene, illustrating the sensitivity in volume of a major topographically constrained subglacial lake across a single glacial cycle. This study demonstrates how englacial stratigraphy can provide valuable insight into subglacial hydrological changes before modern satellite observations, both for LSE and potentially at other locations.

Major depressive disorder (MDD) is a serious and often chronic illness that requires early and urgent treatment. Failing to provide effective treatment of MDD can worsen the illness trajectory, negatively impact physical health, and even alter brain structure. Early optimized treatment (EOT) of MDD, with a measurement-based approach to diagnosis, rapid treatment initiation with medication dosage optimization, frequent monitoring, and prompt adjustments in treatment planning when indicated, should proceed with a sense of urgency. In this article, we describe common barriers to providing an EOT approach to treating MDD at each phase of care, along with strategies for navigating these obstacles. Approaching the treatment of MDD with a greater sense of urgency increases the likelihood of symptom reduction in MDD, facilitating full functional recovery and a return to life engagement.

Objectives/Goals: The never in mitosis kinase (NEK) family regulates vital processes, namely cell cycle progression, but their potential as therapeutic targets in TNBC has not been fully explored. Our studies aim to develop a toolkit to investigate the functional roles of NEKs in pathologies including carcinogenesis. Methods/Study Population: To assess differential NEK expression in normal and tumor tissues and correlation of gene expression with patient survival, we used Gene Expression Profiling Interactive Analysis (GEPIA) and Kaplan–Meier Plotter (KMPlot) pan-cancer analysis, respectively. Basal NEK protein levels were determined by immunoblot across a panel of cell lines, including breast cancer, osteosarcoma, hepatocellular carcinoma, and non-cancerous cells, to identify appropriate systems for evaluation of NEK function. Doxycycline-inducible cell lines were generated by transduction with lentiviral stocks of NEK shRNA and overexpression constructs and antibiotic selection. Expression was analyzed by qPCR and immunoblot. Results/Anticipated Results: Expression of NEK2, 4, 5, 6, 8, and 11 was higher in breast tumors compared to normal tissue by GEPIA analysis. Further examination using KMPlot showed a correlation between elevated NEK6 expression and decreased overall survival in patients with aggressive cancers. As an initial proof-of-concept study, we analyzed NEK6 protein expression in breast cancer cells. Levels of NEK6 were elevated in TNBC cells (MDA-MB-231) compared to hormone receptor positive (HR+) breast cancer cells (MCF7). Using complementary approaches to investigate the functional role of NEK6 in breast cancer, we depleted NEK6 expression using shRNAs in TNBC cells and expressed NEK6 in HR+ cells Discussion/Significance of Impact: Because kinase dysregulation promotes oncogenesis and metastasis, targeting kinases is a key strategy in therapeutic development. A NEK-specific molecular toolkit allows researchers to elucidate NEK functions and contributions to carcinogenesis, promoting advancement of novel therapies.

Objectives/Goals: Second-generation antipsychotics (SGA) are used to treat mental disorders in youth but are linked metabolic syndrome (MetS). Most data on prescribing practices and risk factors are from short-term studies (6–12 months). We aim to characterize prescribing and identify clinical and genetic predictors of MetS using electronic health records (EHR). Methods/Study Population: EHR data were extracted from Cincinnati Children’s Hospital Medical Center (CCHMC) for patients aged ≤21 years prescribed SGAs from 7/1/2009 and 7/1/2024, identifying prescribing prevalence. Next steps are to create an SGA-MetS case–control dataset 8 weeks after an SGA prescription. A case will be defined by meeting 3 of 5 criteria: 1) BMI ≥95th percentile for age/sex; 2) fasting glucose ≥100 mg/dL or use of anti-diabetics; 3) triglycerides ≥110 mg/dL; 4) HDL-C ≤40 mg/dL; 5) systolic/diastolic BP ≥90th percentile for age/sex or use of antihypertensives. The prevalence of SGA-MetS will be calculated by dividing SGA-MetS cases by total SGA users. Logistic regression will identify clinical predictors of MetS, and we will evaluate the association of polygenic risk scores (PRS) of BMI and type 2 diabetes with SGA-MetS risk. Results/Anticipated Results: Our preliminary analysis identified 30,076 patients who were prescribed SGAs (mean age 12 years, SD = 4; 58.8% female; n =  17685). Most self-identified as non-Hispanic (95%, n = 28,595) and of White race (76%; n =  22,935), with 18.5% self-identifying as Black or African American (n = 5,579). The most commonly prescribed SGAs were risperidone (n = 12,382, 41.1%), aripiprazole (n = 9,847, 32.7%), and quetiapine (n = 5,263, 17.5%), with much lower prescribing rates of other SGA known of their low risk of MetS (e.g., ziprasidone 5.5%, lurasidone 1.4%, paliperidone (n = 316, 1.1%), or others cariprazine (n = 72), asenapine (n = 43), brexipiprazole (n = 39), iloperidone (n = 24), and clozapine (n = 20). Discussion/Significance of Impact: Our analyses found that risperidone, quetiapine, and aripiprazole were the most prescribed SGA, with risperidone/quetiapine linked to a higher risk of MetS. We will present ongoing work identifying risk factors for SGA-MetS and examining the association with PRS. Our work has the potential to identify high-risk patients for personalized treatment.

In many areas of The Gambia, West Africa, population crowding in a degraded environment has forced close interactions of diurnal primate species with humans. We assessed intestinal parasitic infection prevalence and diversity in 4 diurnal non-human primate (NHP) species, Chlorocebus sabaeus, Erythrocebus patas, Papio papio and Piliocolobus badius across 13 sampling sites. The effect of human activity, determined by the human activity index, and NHP group size on parasite richness was assessed using a generalized linear mixed model (GLMM). The most common protozoa identified were Entamoeba coli (30%) and Iodamoeba buetschlii (25%). The most common helminths were Strongyloides fuelleborni (11%), Oesophagostomum spp. (9%) and Trichuris trichiura (9%). Two of six (6%) Cyclospora spp. infections detected sequenced as Cyclospora cercopitheci (both in C. sabaeus). The more arboreal P. badius trended towards a lower prevalence of intestinal parasites, although this was not statistically significant (χ2 P = 0.105). Human activity or group size did not have any significant effect on parasite richness for P. badius (P = 0.161 and P = 0.603) or P. papio (P = 0.817 and P = 0.607, respectively). There were insufficient observations to fit a GLMM to E. patas or C. sabaeus. Our reports present the richness and diversity of intestinal parasites in 4 diurnal NHPs in The Gambia, West Africa. Despite desertification and habitat loss, our results indicate that the prevalence and diversity of intestinal parasites in Gambian NHPs are seemingly unaffected by human activity. Further investigation with a larger dataset is required to better elucidate these findings.

Domestic cats have lived alongside human communities for thousands of years, hunting rats, mice, and other pests and serving as pets and a source of pelts and meat. Cats have received limited archaeological attention because their independence limits direct insight into human societies. An adult and juvenile cat recovered from the Emanuel Point wreck 2 (EP2) reflect what are, most likely, the earliest cats in what is now the United States. Zooarchaeological analyses of these and other archaeological cats in the Americas demonstrate that cats ranged substantially in size: some were comparable to modern house cats, and others were much smaller. Isotopic analyses of the adult cat from EP2 provides insight into early shipboard cat behavior and their diet, which appears to have focused on consumption of fish and possibly domestic meat. Cats accompanied sailors on ships where they were relied on to hunt rats and mice that were infesting ships’ holds. Interestingly, based on these isotopic results, the adult cat from EP2 does not seem to have relied heavily on rats as a source of food. These pests were unintentionally introduced to the New World, and cats would have followed, hunting both native and invasive pests.

This study is the first to attempt to isolate a relationship between cognitive activity and equilibration to a Nash Equilibrium. Subjects, while undergoing fMRI scans of brain activity, participated in second price auctions against a single competitor following predetermined strategy that was unknown to the subject. For this auction there is a unique strategy that will maximize the subjects’ earnings, which is also a Nash equilibrium of the associated game theoretic model of the auction. As is the case with all games, the bidding strategies of subjects participating in second price auctions most often do not reflect the equilibrium bidding strategy at first but with experience, typically exhibit a process of equilibration, or convergence toward the equilibrium. This research is focused on the process of convergence.

In the data reported here subjects participated in sixteen auctions, after which all subjects were told the strategy that will maximize their revenues, the theoretical equilibrium. Following that announcement, sixteen more auctions were performed. The question posed by the research concerns the mental activity that might accompany equilibration as it is observed in the bidding behavior. Does brain activation differ between being equilibrated and non-equilibrated in the sense of a bidding strategy? If so, are their differences in the location of activation during and after equilibration? We found significant activation in the frontal pole especially in Brodmann's area 10, the anterior cingulate cortex, the amygdala and the basal forebrain. There was significantly more activation in the basal forebrain and the anterior cingulate cortex during the first sixteen auctions than in the second sixteen. The activity in the amygdala shifted from the right side to the left after the solution was given.

We develop a model that relates self-control to cooperation patterns in social dilemmas, and we test the model in a laboratory public goods experiment. As predicted, we find a robust association between stronger self-control and higher levels of cooperation, and the association is at its strongest when the decision maker’s risk aversion is low and the cooperation levels of others high. We interpret the pattern as evidence for the notion that individuals may experience an impulse to act in self-interest—and that cooperative behavior benefits from self-control. Free-riders differ from other contributor types only in their tendency not to have identified a self-control conflict in the first place.