Multicenter clinical trials are essential for evaluating interventions but often face significant challenges in study design, site coordination, participant recruitment, and regulatory compliance. To address these issues, the National Institutes of Health’s National Center for Advancing Translational Sciences established the Trial Innovation Network (TIN). The TIN offers a scientific consultation process, providing access to clinical trial and disease experts who provide input and recommendations throughout the trial’s duration, at no cost to investigators. This approach aims to improve trial design, accelerate implementation, foster interdisciplinary teamwork, and spur innovations that enhance multicenter trial quality and efficiency. The TIN leverages resources of the Clinical and Translational Science Awards (CTSA) program, complementing local capabilities at the investigator’s institution. The Initial Consultation process focuses on the study’s scientific premise, design, site development, recruitment and retention strategies, funding feasibility, and other support areas. As of 6/1/2024, the TIN has provided 431 Initial Consultations to increase efficiency and accelerate trial implementation by delivering customized support and tailored recommendations. Across a range of clinical trials, the TIN has developed standardized, streamlined, and adaptable processes. We describe these processes, provide operational metrics, and include a set of lessons learned for consideration by other trial support and innovation networks.

OBJECTIVES/GOALS: Bronchiolitis is a major cause of PICU admission, yet identifying best practices is limited by the lack of existing databases containing the needed demographic and clinical variables. We used probabilistic linkage to join the Virtual Pediatric System (VPS) and Pediatric Health Information Systems (PHIS) databases to overcome this data barrier. METHODS/STUDY POPULATION: We performed a single site study joining VPS and PHIS data. These national databases contain clinical (VPS) and billing and resource use (PHIS) data. Limits on the use of patient identifiers (PI) for multi-center research, makes direct linkage techniques impossible. To demonstrate that probabilistic linkage can accurately link VPS and PHIS records, we obtained our single site VPS and PHIS records and linked them using probabilistic linkage without PI and compared this to a gold standard linkage created with PI. We also compared demographic features of linked and unlinked records to assess the ability of probabilistic linkage to create a representative sample. RESULTS/ANTICIPATED RESULTS: We obtained 920 VPS records of patients with bronchiolitis and linked 91% (839/920) to a PHIS record with 4 (0.5%) false-positive matches. Characteristics of linked and unlinked records are compared in Table 1. Comparison of probabilistically linked and unlinked records showed no difference in median age in years (0.7 [Interquartile range (IQR) 0.3-1.5] v 0.7 [IQR 0.2-1.5], p = 0.76), median number of complex chronic conditions (0 [IQR 0-1] v 0 [IQR 0-1], p = 0.16), median Pediatric Index of Mortality 3 severity of illness scores (-4.6 [IQR -4.7 – 4.4] v -4.6 [IQR -4.7 – 4.4], p = 0.44), median days of PICU stay (4 [IQR 3-6] v 4 [IQR 2-6], p = 0.36), proportion female ( 44% v 46%, p = 0.82), or proportion of patients intubated (28% v 24%, p = 0.41). DISCUSSION/SIGNIFICANCE: Probabilistic linkage creates an accurate combined VPS-PHIS database. Extending our methodology to join data from all 38 hospitals contributing to VPS and PHIS will allow creation of a large database containing the demographic, treatment, and outcome data needed to enable Comparative Effectiveness Research of bronchiolitis care.

Animal welfare encompasses all aspects of an animal's life and the interactions between animals. Consequently, welfare must be measured across a variety of factors that consider aspects such as health, behaviour and mental state. Decisions regarding housing and grazing are central to farm management. In this study, two beef cattle systems and their herds were compared from weaning to slaughter across numerous indicators. One herd (‘HH’) were continuously housed, the other (‘HG’) were housed only during winter. Inspections of animals were conducted to assess body condition, cleanliness, diarrhoea, hairlessness, nasal discharge and ocular discharge. Hair and nasal mucus samples were taken for quantification of cortisol and serotonin. Qualitative behaviour assessments (QBA) were also conducted and performance monitored. Physical health indicators were similar between herds with the exception of nasal discharge which was more prevalent in HH (P < 0.001). During winter, QBA yielded differences between herds over PC1 (arousal) (P = 0.032), but not PC2 (mood) (P = 0.139). Through summer, there was a strong difference across both PC1 (P < 0.001) and PC2 (P = 0.002), with HG exhibiting more positive behaviour. A difference was found in hair cortisol levels, with the greatest concentrations observed in HG (P = 0.011), however such a pattern was not seen for nasal mucus cortisol or for serotonin. Overall, providing summer grazing (HG) appeared to afford welfare benefits to the cattle as shown with more positive QBA assessments, but also slightly better health indicators, notwithstanding the higher levels of cortisol in that group.

Gravitational waves from coalescing neutron stars encode information about nuclear matter at extreme densities, inaccessible by laboratory experiments. The late inspiral is influenced by the presence of tides, which depend on the neutron star equation of state. Neutron star mergers are expected to often produce rapidly rotating remnant neutron stars that emit gravitational waves. These will provide clues to the extremely hot post-merger environment. This signature of nuclear matter in gravitational waves contains most information in the 2–4 kHz frequency band, which is outside of the most sensitive band of current detectors. We present the design concept and science case for a Neutron Star Extreme Matter Observatory (NEMO): a gravitational-wave interferometer optimised to study nuclear physics with merging neutron stars. The concept uses high-circulating laser power, quantum squeezing, and a detector topology specifically designed to achieve the high-frequency sensitivity necessary to probe nuclear matter using gravitational waves. Above 1 kHz, the proposed strain sensitivity is comparable to full third-generation detectors at a fraction of the cost. Such sensitivity changes expected event rates for detection of post-merger remnants from approximately one per few decades with two A+ detectors to a few per year and potentially allow for the first gravitational-wave observations of supernovae, isolated neutron stars, and other exotica.

The signs and symptoms of Lyme neuroborreliosis can overlap with non-infectious degenerative diseases such as multiple sclerosis (MS). In this study, we assessed a cohort of MS patients in Atlantic Canada for serological evidence of Lyme disease (LD). No positive serology was identified using the recommended two-tiered algorithm.

US Latinos have higher rates of substance use disorders (SUDs) than Latinas, but Latinas face substantial barriers to treatment and tend to enter care with higher SUD severity. Immigrant Latinas may face greater barriers to care than native-born despite lower overall SUD prevalence. This study aimed to identify how SUD treatment needs of Latinos are addressed depending on patient gender and immigrant status within an urban healthcare system serving a diverse population.

The bovine appeasing substance (BAS) is expected to have calming effects in cattle experiencing stressful situations. Therefore, this study investigated the impacts of BAS administration during two of the most stressful events within beef production systems: weaning and feedlot entry. In experiment 1, 186 Bos indicus-influenced calves (73 heifers, 113 bulls) were weaned at 211 ± 1 days of age (day 0). At weaning, calves were ranked by sex and BW, and assigned to receive BAS (Nutricorp, Araras, SP, Brazil; n = 94) or water (CON; n = 92). Treatments (5 ml) were topically applied to the nuchal skin area of each animal. Calf BW was recorded and samples of blood and tail-switch hair were collected on days 0, 15 and 45. Calves that received BAS had greater (P < 0.01) BW gain from day 0 to 15 compared with CON. Overall BW gain (days 0 to 45) and BW on days 15 and 45 were also greater (P ≤ 0.03) in BAS v. CON. Plasma haptoglobin concentration was less (P < 0.01) in BAS v. CON on day 15, whereas cortisol concentrations in plasma and tail-switch hair did not differ between treatments (P ≥ 0.13). In experiment 2, 140 B. indicus-influenced bulls (∼27 months of age) from 2 different pasture-based systems (70 bulls/origin) were transported to a commercial feedlot (≤ 200-km transport; day -1). On day 0, bulls were ranked by source and BW, and assigned to receive BAS (n = 70) or CON (n = 70) and the same sampling procedures as in experiment 1. Bulls receiving BAS had greater (P = 0.04) BW gain from day 0 to 15, but less (P < 0.01) BW gain from day 15 to 45 compared to CON. No other treatment effects were detected (P > 0.14). Therefore, BAS administration to beef calves alleviated the haptoglobin response associated with weaning, and improved calf growth during the subsequent 45 days. Administration of BAS to beef bulls at feedlot entry improved BW gain during the initial 15 days, but these benefits were not sustained throughout the 45-day experiment.

A fracture analysis is developed for crack initiation sequences occurring during sharp indentation of brittle materials. Such indentations, generated by pyramidal or conical loading, generate elastic and plastic deformation. The analysis uses a nonlinear elements-in-series model to describe indentation load–displacement responses, onto which lateral, radial, cone, and median crack initiation points are located. The crack initiation points are determined by extension and application of a contact stress-field model coupled to the indentation load, originally developed by Yoffe, in combination with crack nuclei coupled to the indentation displacement to arrive at an explicit fracture model. Parameters in the analysis are adapted directly from experimental fracture and deformation measurements, and the analysis outputs are directly comparable to experimental observations. After adaptation, crack initiation loads and sequences during indentation loading and unloading of glasses and crystals are predicted by the model from material modulus, hardness, and toughness values to within about 25% of peak contact load. This work is dedicated to George M. Pharr IV on the occasion of his 65th birthday in recognition of his contributions to indentation mechanics.

Expression of estrus (EST) near the time of fixed-time artificial insemination (FTAI) increases pregnancy success in beef females. This outcome has been associated with improved pregnancy establishment and maintenance, although research is still warranted to validate this theory. Hence, this experiment compared ovarian, uterine and conceptus factors associated with pregnancy establishment in Bos indicus beef cows according to estrous expression during a FTAI protocol. One hundred lactating multiparous Nelore cows received a 2 mg injection of estradiol benzoate and an intravaginal progesterone (P4) releasing device on day −11, a 12.5 mg injection of prostaglandin F2α on day −4, P4 device removal in addition to 0.6 mg injection of estradiol cypionate and 300 IU injection of equine chorionic gonadotropin on day −2, and FTAI on day 0. An estrous detection patch was attached to the tailhead of each cow on day −2, and estrous expression was defined as removal of >50% of the rub-off coating from the patch at FTAI. Overall, 39 cows expressed EST, 55 did not express EST (NOEST), and six cows lost their patch and were discarded from the experiment. Ovarian ultrasonography was performed at FTAI, and on days 7 and 15 of the experiment. Blood samples were also collected on days 7 and 15. Only cows without a corpus luteum (CL) on day 0, and with a CL on days 7 and 15 remained in the experiment (EST, n=36; NOEST, n=48). On day 15, cows were randomly selected within each group (EST, n=29; NOEST, n=30) for conceptus collection via transcervical flushing, followed by endometrial biopsy in the uterine horn ipsilateral to the CL. Within cows not assigned to conceptus collection, blood samples were collected for whole blood RNA extraction (day 20) and pregnancy status was verified by transrectal ultrasonography (day 30). Diameter of dominant follicle on day 0 and plasma P4 concentrations on day 7 were greater (P⩽0.02) in EST v. NOEST cows. Conceptus length and messenger RNA (mRNA) expression of prostaglandin E synthase and interferon-tau were greater (P⩽0.04) in EST v. NOEST cows. Moreover, EST cows diagnosed as pregnant on day 30 had greater (P<0.01) blood mRNA expression of myxovirus resistance 2 on day 20 compared with NOEST. In summary, estrous expression near the time of FTAI enhanced pregnancy establishment factors in B. indicus cows, including conceptus development and mRNA expression of interferon-tau.

Drawing on a landscape analysis of existing data-sharing initiatives, in-depth interviews with expert stakeholders, and public deliberations with community advisory panels across the U.S., we describe features of the evolving medical information commons (MIC). We identify participant-centricity and trustworthiness as the most important features of an MIC and discuss the implications for those seeking to create a sustainable, useful, and widely available collection of linked resources for research and other purposes.

Excitable temperament disrupts physiological events required for reproductive development in cattle, but no research has investigated the impacts of temperament on growth and puberty attainment in Bos indicus females. Hence, this experiment evaluated the effects of temperament on growth, plasma cortisol concentrations and puberty attainment in B. indicus heifers. A total of 170 Nelore heifers, weaned 4 months before the beginning of this experiment (days 0 to 91), were managed in two groups of 82 and 88 heifers each (mean ± SE; initial BW=238±2 kg, initial age=369±1 days across groups). Heifer temperament was evaluated via exit velocity on day 0. Individual exit score was calculated within each group by dividing exit velocity into quintiles and assigning heifers with a score from 1 to 5 (1=slowest; 5=fastest heifer). Heifers were classified according to exit score as adequate (ADQ, n=96; exit score⩽3) or excitable temperament (EXC, n=74; exit score>3). Heifer BW, body condition score (BCS) and blood samples were obtained on days 0, 31, 60 and 91. Heifer exit velocity and score were recorded again on days 31, 60 and 91. Ovarian transrectal ultrasonography was performed on days 0 and 10, 31 and 41, 60 and 70, 81 and 91 for puberty evaluation. Heifer was declared pubertal at the first 10-day interval in which a corpus luteum was detected. Exit velocity and exit score obtained on day 0 were correlated (r⩾0.64, P<0.01) with evaluations on days 31, 60 and 91. During the experiment, ADQ had greater (P<0.01) mean BCS and BW gain, and less (P<0.01) mean plasma cortisol concentration compared with EXC heifers. Temperament × time interactions were detected (P<0.01) for exit velocity and exit score, which were always greater (P<0.01) in EXC v. ADQ heifers. A temperament × time interaction was also detected (P=0.03) for puberty attainment, which was delayed in EXC v. ADQ heifers. At the end of the experiment, a greater (P<0.01) proportion of ADQ were pubertal compared with EXC heifers. In summary, B. indicus heifers classified as EXC had reduced growth, increased plasma cortisol concentrations and hindered puberty attainment compared to ADQ heifers. Moreover, exit velocity may serve as temperament selection criteria to optimize development of B. indicus replacement heifers.

A model is developed and implemented for load-controlled instrumented conical indentation of a brittle open-cell foam on a dense substrate. A survey of observations suggests that such indentations are typified by displacement excursions at small indentation loads, load-displacement variability, localized crushing, and a discrete to continuum transition at intermediate loads. The model includes all these effects as well as stiffening at large loads as the substrate is encountered. Direct quantitative comparison is made with measurements of a silica foam on a soda-lime glass substrate, strongly supporting the physical basis of the model.