OBJECTIVES/GOALS: Mayo Clinic (MC) launched the Rapid Activation Trial (RAT) pilot program in 2022 to expedite the activation of high priority and high impact clinical trials. The objective was to develop a process for rapid activation through robust screening, prioritization, and project management (PM) support. METHODS/STUDY POPULATION: The project team developed a robust screening and approval process for the RAT program using a combination of an objective scoring tool (based on strategic priorities) and a diverse selection committee to screen and approve eligible trials. Sponsors had to commit to RAT program timelines. Upon approval, trials were prioritized at the highest level within each business unit involved in the activation process. The number of trials approved annually were limited to 8 to manage volume and facilitate seamless prioritization with an activation timeline goal of 6 weeks. Project management support for RAT program focused on financial, regulatory, logistical, and operational elements to open trials expeditiously. RESULTS/ANTICIPATED RESULTS: In 2022, thirteen (13) applications were received and eight (8) were approved by the RAT selection committee. The approved trials activated with a median open to enrollment time of 6.4 weeks from engaging with business units. They also aligned closely with organization’s strategic priorities, including but not limited to Investigator Initiated Trials, Multi-Site protocols, IND/IDE protocols, Rare Diseases, First in Human and Commercialization potential trials. PI and study team feedback was positive. In 2023, the RAT program was renewed due to the pilot’s significant success in 2022. The goal is to open 10 trials and 5 have been activated by the end of Q3, 2023 with a median timeline of 6 weeks. DISCUSSION/SIGNIFICANCE: Rapid activation of high priority and high impact clinical trials enables an organization to strategically prioritize and open complex clinical trials. This allows the delivery of innovative, timely cures to patients in an expeditious timeline.

OBJECTIVES/GOALS: * Patients with skin of color (SOC) are disproportionately affected by systemic lupus erythematosus (SLE) and cutaneous lupus erythematosus (CLE). In this study, we aim to address this disparity and characterize the real-world efficacy and tolerability of anifrolumab in CLE patients using validated disease activity instruments. METHODS/STUDY POPULATION: This single-center, prospective observational cohort study includes SLE patients with severe or refractory CLE who have received ≥ 1 dose of anifrolumab. Cutaneous disease activity is assessed periodically at 2, 6, 9, 12, and 18 months using the Cutaneous Lupus Disease Area and Severity Index (CLASI). Adverse events and concurrent treatments are also routinely evaluated. To date, 22 patients have been enrolled, with 6-month follow-up data available for 15. At the time of anifrolumab initiation, 95% of participants had discoid LE (DLE), 60% had mucosal DLE, and 13% had subacute CLE. Nine patients identified as SOC, two as White, and four did not report race/ethnicity. RESULTS/ANTICIPATED RESULTS: A Friedman test showed statistically significant changes over time in CLASI activity score (CLASI-A) (χ2(2) =20, p<0.0001) (Figure 1) and CLASI damage score (CLASI-D) (χ2(2) =9.5789, p=0.0083) (Figure. To estimate effect sizes, we employed linear mixed models, which demonstrated statistically significant reductions in the CLASI-A score from baseline by an average of 14 points at 2 months (p<0.001) and 18 points at 6 months (p<0.001); notably, a reduction in CLASI-A of 4 is considered clinically meaningful. At 2 months, 20% of patients experienced a 50% or more reduction in CLASI, which increased to 60% of patients at 6 months. Patients on systemic corticosteroids could taper off. Adverse events were minimal and did not lead to treatment discontinuation. Fig. 1:[blob:https://acts.slayte.com/045319b4-7272-4351-a771-78ba9ee57f5c] Fig. 2:[blob:https://acts.slayte.com/67df7653-0cd8-4e8e-a3e1-d5c565b19dce] DISCUSSION/SIGNIFICANCE: As SOC patients with CLE have significant potential for permanent pigmentary alternations, early treatment is imperative. Effective treatments for refractory CLE are elusive. Our study represents the largest single-center cohort of CLE patients treated with anifrolumab and suggests that it is a promising therapeutic option for patients with SOC.

BACKGROUND: IGTS is a rare phenomenon of paradoxical germ cell tumor (GCT) growth during or following treatment despite normalization of tumor markers. We sought to evaluate the frequency, clinical characteristics and outcome of IGTS in patients in 21 North-American and Australian institutions. METHODS: Patients with IGTS diagnosed from 2000-2017 were retrospectively evaluated. RESULTS: Out of 739 GCT diagnoses, IGTS was identified in 33 patients (4.5%). IGTS occurred in 9/191 (4.7%) mixed-malignant GCTs, 4/22 (18.2%) immature teratomas (ITs), 3/472 (0.6%) germinomas/germinomas with mature teratoma, and in 17 secreting non-biopsied tumours. Median age at GCT diagnosis was 10.9 years (range 1.8-19.4). Male gender (84%) and pineal location (88%) predominated. Of 27 patients with elevated markers, median serum AFP and Beta-HCG were 70 ng/mL (range 9.2-932) and 44 IU/L (range 4.2-493), respectively. IGTS occurred at a median time of 2 months (range 0.5-32) from diagnosis, during chemotherapy in 85%, radiation in 3%, and after treatment completion in 12%. Surgical resection was attempted in all, leading to gross total resection in 76%. Most patients (79%) resumed GCT chemotherapy/radiation after surgery. At a median follow-up of 5.3 years (range 0.3-12), all but 2 patients are alive (1 succumbed to progressive disease, 1 to malignant transformation of GCT). CONCLUSION: IGTS occurred in less than 5% of patients with GCT and most commonly after initiation of chemotherapy. IGTS was more common in patients with IT-only on biopsy than with mixed-malignant GCT. Surgical resection is a principal treatment modality. Survival outcomes for patients who developed IGTS are favourable.

Presented here are quantitative dissolution rate data (volume of pyrite lost/time) for the inorganic oxidation of pyrite in synthetic, anaerobic and acidic (pH 2) hydrothermal vent fluids (HVF) from experiments where the volume loss was measured directly via Vertical Scanning Interferometry (VSI). The VSI-derived reaction rate was 2.12x10-10±1.14x10-1 mol/m2/min, which is ∼2 to 4 orders of magnitude slower than pyrite oxidation rates previously determined using traditional batch experiments where rates are calculated based on changes in solution chemistry. This lower rate stems primarily from differences in experimental conditions (i.e. water to rock ratios, vigorous vs. gentle stir rates, grain-size effects, time), yet the rates derived here are believed to be more representative of pyrite oxidation in natural environments where more static and high solution to solid rate conditions prevail, such as seafloor conditions or acid-mine-drainage environments.

We present the largest homogeneous survey of redshift > 4.4 damped Lyα systems (DLAs) using the spectra of 163 quasars that comprise the Giant Gemini GMOS (GGG) survey. With this survey we make the most precise high-redshift measurement of the cosmological mass density of neutral hydrogen, ΩHI. After correcting for systematic effects using a combination of mock and higher-resolution spectra, we find ΩHI= 0.98+0.20 -0.18 × 10−3 at 〈z〉 = 4.9, assuming a 20% contribution from lower column density systems below the DLA threshold. By comparing to literature measurements at lower redshifts, we show that ΩHI can be described by the functional form ΩHI(z) ∝ (1 + z)0.4. This gradual decrease from z = 5 to 0 suggests that in the galaxies which dominate the cosmic star formation rate, Hi is a transitory gas phase fuelling star formation which must be continually replenished by more highly-ionized gas from the intergalactic medium, and from recycled galactic winds.

Objectives: Individuals with major depressive disorder (MDD) demonstrate poorer learning and memory skills relative to never-depressed comparisons (NDC). Previous studies report decreased volume and disrupted function of frontal lobes and hippocampi in MDD during memory challenge. However, it has been difficult to dissociate contributions of short-term memory and executive functioning to memory difficulties from those that might be attributable to long-term memory deficits. Methods: Adult males (MDD, n=19; NDC, n=22) and females (MDD, n=23; NDC, n=19) performed the Semantic List Learning Task (SLLT) during functional magnetic resonance imaging. The SLLT Encoding condition consists of 15 lists, each containing 14 words. After each list, a Distractor condition occurs, followed by cued Silent Rehearsal instructions. Post-scan recall and recognition were collected. Groups were compared using block (Encoding-Silent Rehearsal) and event-related (Words Recalled) models. Results: MDD displayed lower recall relative to NDC. NDC displayed greater activation in several temporal, frontal, and parietal regions, for both Encoding-Silent Rehearsal and the Words Recalled analyses. Groups also differed in activation patterns in regions of the Papez circuit in planned analyses. The majority of activation differences were not related to performance, presence of medications, presence of comorbid anxiety disorder, or decreased gray matter volume in MDD. Conclusions: Adults with MDD exhibit memory difficulties during a task designed to reduce the contribution of individual variability from short-term memory and executive functioning processes, parallel with decreased activation in memory and executive functioning circuits. Ecologically valid long-term memory tasks are imperative for uncovering neural correlates of memory performance deficits in adults with MDD. (JINS, 2016, 22, 412–425)

In 1987 an action plan for the recovery of the European populations of Roseate Tern Sterna dougallii was launched. Intervention on the breeding grounds has included the wardening of sites to prevent human disturbance, the provision of nest-boxes to discourage predation, patrolling and controlling to reduce predator presence, planting of Lavatera arborea to shelter nesting birds, and use of the media to establish local interest and commitment. Intervention in the wintering area has focused on Ghana and the reduction there of trapping pressure, through the “Save the Seashore Birds Project-Ghana”, which has involved site protection, legal reform, training, surveys and education programmes.

Attempts were made to identify the causative organism of Lyme disease in Australia from possible tick vectors.

Ticks were collected in coastal areas of New South Wales, Australia, from localities associated with putative human infections. The ticks were dissected; a portion of the gut contents was examined for spirochaetes by microscopy, the remaining portion inoculated into culture media. The detection of spirochaetes in culture was performed using microscopy, and immunochemical and molecular (PCR) techniques. Additionally, whole ticks were tested with PCR for spirochaetes.

From 1990 to 1992, approximately 12000 ticks were processed for spirochaetes. No evidence of Borrelia burgdorferi or any other spirochaete was recovered from or detected in likely tick vectors. Some spirochaete–like objects detected in the cultures were shown to be artifacts, probably aggregates of bacterial flagellae.

There is no definitive evidence for the existence in Australia of B. burgdorferi the causative agent of true Lyme disease, or for any other tick–borne spirochaete that may be responsible for a local syndrome being reported as Lyme disease.

In this study, we investigate the extent to which the incidence of Escherichia coli O157:H7 can be predicted in human faeces, from human intake and infection via water contaminated by livestock and carrying this zoonotic pathogen in North-East (NE) and South-West (SW) regions of Scotland. In SW Scotland, there is a risk of coastal recreational waters failing EU standards for faecal indicator organisms, and this is assumed to be the main potential waterborne route of infection. In NE Scotland, the main waterborne route is assumed to be the many private drinking water supplies; these are mainly derived from shallow groundwater and surveys show that there is potential for significant levels of microbial contamination from livestock. The risk to human health from these sources has been assessed using a combination of process models, epidemiological risk-assessment methods and survey data. A key assumption in the calculations is the amount of mixing of pathogenic and non-pathogenic E. coli between animal faecal sources and contaminated water intake by humans. Using the probability distributions of the E. coli O157 content of individual faecal pat material (which would imply no mixing between source and human intake), based on three recent surveys of animal faeces in Scotland, led to predicted annual risks of infection slightly higher than observed human infection incidence. Using the geometric mean to represent partial mixing (which theoretically may over- or underestimate incidence with a concave dose–response curve) gave infection rates similar to those observed for two of the three faecal surveys. Using the arithmetic mean led to over-prediction of risk. This is to be expected if the true dose–response curve is (such as the Beta-Poisson curve used here) concave. Other factors that may lead to over-prediction of incidence are discussed, including under-reporting, loss of infectivity as a result of environmental exposure, immunity and the appropriateness of the Beta-Poisson curve. It is concluded that better epidemiological data for calibration of the dose–response curve, better knowledge of the degree of mixing and understanding of immunity are key requirements for progress in process model-based predictions of infection rate. The paper also explores the potential of improved farm and catchment scale management to deliver cost-effective mitigation of pollution of bathing and drinking water by livestock zoonoses.

The purpose of this experiment was to quantify the seasonal variations in lamb meat quality and identify the contributory factors associated with the various production systems used in the UK. The approach taken was therefore largely a systems one, with the various production systems used in the project mimicking those typical of the British sheep industry supplying lambs onto the market from April to January.

Material and methods 504 spring-born lambs [equal numbers of entire male (E), castrated male (C) and female (F)] which were the twin-reared progeny of Mule ewes (Bluefaced Leicester x Swaledale) and Suffolk rams were allocated to one of 7 finishing systems (n=72 per system). These were combinations of 4 diets and 4 slaughter periods (at 2 monthly intervals between June 1992 and January 1993) in an incomplete factorial design: concentrates (CS1), grass (GRI, GR2), silage (SL2, SL3) and roots (RT3, RT4); all but the grass diet were fed indoors.

Using an alternate arsenic source, namely, Tertiary Butyl Arsine, a concentrator GaAs solar cell has been grown in a low pressure metal organic chemical vapor deposition reactor. Under 72 sun, air mass 1.5 illumination, the cell had an open circuit voltage of 1.1 V, a fill factor of 83% and an overall efficiency of 21%.