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.

We report the discovery of a bow-shock pulsar wind nebula (PWN), named Potoroo, and the detection of a young pulsar J1638$-$4713 that powers the nebula. We present a radio continuum study of the PWN based on 20-cm observations obtained from the Australian Square Kilometre Array Pathfinder (ASKAP) and MeerKAT. PSR J1638$-$4713 was identified using Parkes radio telescope observations at frequencies above 3 GHz. The pulsar has the second-highest dispersion measure of all known radio pulsars (1 553 pc cm$^{-3}$), a spin period of 65.74 ms and a spin-down luminosity of $\dot{E}=6.1\times10^{36}$ erg s$^{-1}$. The PWN has a cometary morphology and one of the greatest projected lengths among all the observed pulsar radio tails, measuring over 21 pc for an assumed distance of 10 kpc. The remarkably long tail and atypically steep radio spectral index are attributed to the interplay of a supernova reverse shock and the PWN. The originating supernova remnant is not known so far. We estimated the pulsar kick velocity to be in the range of 1 000–2 000 km s$^{-1}$ for ages between 23 and 10 kyr. The X-ray counterpart found in Chandra data, CXOU J163802.6$-$471358, shows the same tail morphology as the radio source but is shorter by a factor of 10. The peak of the X-ray emission is offset from the peak of the radio total intensity (Stokes $\rm I$) emission by approximately 4.7$^{\prime\prime}$, but coincides well with circularly polarised (Stokes $\rm V$) emission. No infrared counterpart was found.

Bovine tuberculosis (bTB) is a chronic, zoonotic infection of domestic and wild animals caused mainly by Mycobacterium bovis. The Test and Vaccinate or Remove (TVR) project was a 5-year intervention (2014–2018) applied to Eurasian badgers (Meles meles) in a 100 km2 area of County Down, Northern Ireland. This observational study used routine bTB surveillance data of cattle to determine if the TVR intervention had any effect in reducing the infection at a herd level. The study design included the TVR treatment area (Banbridge) compared to the three adjacent 100 km2 areas (Dromore, Ballynahinch, and Castlewellan) which did not receive any badger intervention. Results showed that there were statistically lower bTB herd incidence rate ratios in the Banbridge TVR area compared to two of the other three comparison areas, but with bTB herd history and number of bTB infected cattle being the main explanatory variables along with Year. This finding is consistent with other study results conducted as part of the TVR project that suggested that the main transmission route for bTB in the area was cattle-to-cattle spread. This potentially makes any wildlife intervention in the TVR area of less relevance to bTB levels in cattle. It must also be noted that the scientific power of the TVR study (76%) was below the recommended 80%, meaning that results must be interpreted with caution. Even though statistical significance was achieved in two cattle-related risk factors, other potential risk factors may have also demonstrated significance in a larger study.

We present a comparison between the performance of a selection of source finders (SFs) using a new software tool called Hydra. The companion paper, Paper I, introduced the Hydra tool and demonstrated its performance using simulated data. Here we apply Hydra to assess the performance of different source finders by analysing real observational data taken from the Evolutionary Map of the Universe (EMU) Pilot Survey. EMU is a wide-field radio continuum survey whose primary goal is to make a deep ($20\mu$Jy/beam RMS noise), intermediate angular resolution ($15^{\prime\prime}$), 1 GHz survey of the entire sky south of $+30^{\circ}$ declination, and expecting to detect and catalogue up to 40 million sources. With the main EMU survey it is highly desirable to understand the performance of radio image SF software and to identify an approach that optimises source detection capabilities. Hydra has been developed to refine this process, as well as to deliver a range of metrics and source finding data products from multiple SFs. We present the performance of the five SFs tested here in terms of their completeness and reliability statistics, their flux density and source size measurements, and an exploration of case studies to highlight finder-specific limitations.

The latest generation of radio surveys are now producing sky survey images containing many millions of radio sources. In this context it is highly desirable to understand the performance of radio image source finder (SF) software and to identify an approach that optimises source detection capabilities. We have created Hydra to be an extensible multi-SF and cataloguing tool that can be used to compare and evaluate different SFs. Hydra, which currently includes the SFs Aegean, Caesar, ProFound, PyBDSF, and Selavy, provides for the addition of new SFs through containerisation and configuration files. The SF input RMS noise and island parameters are optimised to a 90% ‘percentage real detections’ threshold (calculated from the difference between detections in the real and inverted images), to enable comparison between SFs. Hydra provides completeness and reliability diagnostics through observed-deep ($\mathcal{D}$) and generated-shallow ($\mathcal{S}$) images, as well as other statistics. In addition, it has a visual inspection tool for comparing residual images through various selection filters, such as S/N bins in completeness or reliability. The tool allows the user to easily compare and evaluate different SFs in order to choose their desired SF, or a combination thereof. This paper is part one of a two part series. In this paper we introduce the Hydra software suite and validate its $\mathcal{D/S}$ metrics using simulated data. The companion paper demonstrates the utility of Hydra by comparing the performance of SFs using both simulated and real images.

The behaviour of two groups of sheep was observed when they were placed in a pen on wooden slats and/or on straw bedding for 48h. When sheep were placed in the pen and not given a choice of slats and straw, the proportion of scans spent standing and lying by one group of sheep were not affected by floor surface, whereas another group lay down more on the straw than on the slats during the first 24h in the pen. There was more movement when on straw than on slats. When given a choice of either slats or straw for 48h, the sheep spent more than half of the scans on straw. The study showed that sheep show a preference for lying down on straw compared with wooden slats. However, sheep will lie down on wooden slats. Although straw is, quite rightly, recommended as a suitable surface for lying, there was little evidence in this study that slats provide an unsuitable surface for a slaughterhouse lairage pen.

This article is a clinical guide which discusses the “state-of-the-art” usage of the classic monoamine oxidase inhibitor (MAOI) antidepressants (phenelzine, tranylcypromine, and isocarboxazid) in modern psychiatric practice. The guide is for all clinicians, including those who may not be experienced MAOI prescribers. It discusses indications, drug-drug interactions, side-effect management, and the safety of various augmentation strategies. There is a clear and broad consensus (more than 70 international expert endorsers), based on 6 decades of experience, for the recommendations herein exposited. They are based on empirical evidence and expert opinion—this guide is presented as a new specialist-consensus standard. The guide provides practical clinical advice, and is the basis for the rational use of these drugs, particularly because it improves and updates knowledge, and corrects the various misconceptions that have hitherto been prominent in the literature, partly due to insufficient knowledge of pharmacology. The guide suggests that MAOIs should always be considered in cases of treatment-resistant depression (including those melancholic in nature), and prior to electroconvulsive therapy—while taking into account of patient preference. In selected cases, they may be considered earlier in the treatment algorithm than has previously been customary, and should not be regarded as drugs of last resort; they may prove decisively effective when many other treatments have failed. The guide clarifies key points on the concomitant use of incorrectly proscribed drugs such as methylphenidate and some tricyclic antidepressants. It also illustrates the straightforward “bridging” methods that may be used to transition simply and safely from other antidepressants to MAOIs.

OBJECTIVES/GOALS: Our aim is to understand the role bilirubin oxidation products play in the development of cerebral vasospasm in patients with subarachnoid hemorrhage. We aim to evaluate the time course of bilirubin, HO-1, and SOD1 in relation to the subsequent development of vasospasm in to establish predictors of vasospasm development. METHODS/STUDY POPULATION: Prospective cohort observational study involving collection of CSF samples of pts admitted to KU NeuroICU with SAH and placement of EVD. CSF will be extracted from the EVD of patients on the day of placement of the EVD, and then each subsequent day for a total of 10 days. Bilirubin concentration will be determined by means of spectrophotometry. HO-1 will be measured using a commercially available ELISA kit. Cu/Zn-Superoxide Dismutase will be measured using a commercially available ELISA kit. A review of patients chart will then be performed following discharge from hospital to determine if a diagnosis of vasospasm was made, details of the vasospasm (i.e. symptoms, severity), as well as to obtain demographic data and events occurring during patients admission that could confound statistical analysis. RESULTS/ANTICIPATED RESULTS: First: we will investigate the feasibility of collecting serial CSF samples and processing them for target analyte quantification. We predict that the protocol will yield quality data that will result in insight on the pathophysiology of cerebral vasospasm. Second: we will characterize the changes in target CSF bilirubin breakdown analytes over 10 days. From this we hypothesize that as bilirubin oxidation increases, the propensity for cerebral vasospasm will also increase. DISCUSSION/SIGNIFICANCE: If there is a clear correlation between formation of bilirubin and increase in HO-1, and SOD1, with the clinical signs of vasospasm, this could be used as a biomarker for not only identifying patients at risk for developing these complications but also a means to follow the effectiveness of potential therapies.

Clinical trials continue to face significant challenges in participant recruitment and retention. The Recruitment Innovation Center (RIC), part of the Trial Innovation Network (TIN), has been funded by the National Center for Advancing Translational Sciences of the National Institutes of Health to develop innovative strategies and technologies to enhance participant engagement in all stages of multicenter clinical trials. In collaboration with investigator teams and liaisons at Clinical and Translational Science Award institutions, the RIC is charged with the mission to design, field-test, and refine novel resources in the context of individual clinical trials. These innovations are disseminated via newsletters, publications, a virtual toolbox on the TIN website, and RIC-hosted collaboration webinars. The RIC has designed, implemented, and promised customized recruitment support for 173 studies across many diverse disease areas. This support has incorporated site feasibility assessments, community input sessions, recruitment materials recommendations, social media campaigns, and an array of study-specific suggestions. The RIC’s goal is to evaluate the efficacy of these resources and provide access to all investigating teams, so that more trials can be completed on time, within budget, with diverse participation, and with enough accrual to power statistical analyses and make substantive contributions to the advancement of healthcare.

The role of the Eurasian badger (Meles meles) as a wildlife host has complicated the management of bovine tuberculosis (bTB) in cattle. Badger ranging behaviour has previously been found to be altered by culling of badgers and has been suggested to increase the transmission of bTB either among badgers or between badgers and cattle. In 2014, a five-year bTB intervention research project in a 100 km2 area in Northern Ireland was initiated involving selective removal of dual path platform (DPP) VetTB (immunoassay) test positive badgers and vaccination followed by release of DPP test negative badgers (‘Test and Vaccinate or Remove’). Home range sizes, based on position data obtained from global positioning system collared badgers, were compared between the first year of the project, where no DPP test positive badgers were removed, and follow-up years 2–4 when DPP test positive badgers were removed. A total of 105 individual badgers were followed over 21 200 collar tracking nights. Using multivariable analyses, neither annual nor monthly home ranges differed significantly in size between years, suggesting they were not significantly altered by the bTB intervention that was applied in the study area.

The use of monthly intranasal mupirocin was associated with a significant reduction in the rate of methicillin-resistant Staphylococcus aureus transmission and Staphylococcus aureus invasive infection in a large neonatal intensive care unit. Resistance to mupirocin emerged over time, but it was rare and was not associated with adverse clinical outcomes.

Infect Control Hosp Epidemiol 2018;39:741–745

The Taipan galaxy survey (hereafter simply ‘Taipan’) is a multi-object spectroscopic survey starting in 2017 that will cover 2π steradians over the southern sky (δ ≲ 10°, |b| ≳ 10°), and obtain optical spectra for about two million galaxies out to z < 0.4. Taipan will use the newly refurbished 1.2-m UK Schmidt Telescope at Siding Spring Observatory with the new TAIPAN instrument, which includes an innovative ‘Starbugs’ positioning system capable of rapidly and simultaneously deploying up to 150 spectroscopic fibres (and up to 300 with a proposed upgrade) over the 6° diameter focal plane, and a purpose-built spectrograph operating in the range from 370 to 870 nm with resolving power R ≳ 2000. The main scientific goals of Taipan are (i) to measure the distance scale of the Universe (primarily governed by the local expansion rate, H 0) to 1% precision, and the growth rate of structure to 5%; (ii) to make the most extensive map yet constructed of the total mass distribution and motions in the local Universe, using peculiar velocities based on improved Fundamental Plane distances, which will enable sensitive tests of gravitational physics; and (iii) to deliver a legacy sample of low-redshift galaxies as a unique laboratory for studying galaxy evolution as a function of dark matter halo and stellar mass and environment. The final survey, which will be completed within 5 yrs, will consist of a complete magnitude-limited sample (i ⩽ 17) of about 1.2 × 106 galaxies supplemented by an extension to higher redshifts and fainter magnitudes (i ⩽ 18.1) of a luminous red galaxy sample of about 0.8 × 106 galaxies. Observations and data processing will be carried out remotely and in a fully automated way, using a purpose-built automated ‘virtual observer’ software and an automated data reduction pipeline. The Taipan survey is deliberately designed to maximise its legacy value by complementing and enhancing current and planned surveys of the southern sky at wavelengths from the optical to the radio; it will become the primary redshift and optical spectroscopic reference catalogue for the local extragalactic Universe in the southern sky for the coming decade.

Research conducted since 1979 in the north central United States and southern Canada demonstrated that after repeated annual applications of the same thiocarbamate herbicide to the same field, control of some difficult-to-control weed species was reduced. Laboratory studies of herbicide degradation in soils from these fields indicated that these performance failures were due to more rapid or “enhanced” biodegradation of the thiocarbamate herbicides after repeated use with a shorter period during which effective herbicide levels remained in the soils. Weeds such as wild proso millet [Panicum miliaceum L. spp. ruderale (Kitagawa) Tzevelev. #3 PANMI] and shattercane [Sorghum bicolor (L.) Moench. # SORVU] which germinate over long time periods were most likely to escape these herbicides after repeated use. Adding dietholate (O,O-diethyl O-phenyl phosphorothioate) to EPTC (S-ethyl dipropyl carbamothioate) reduced problems caused by enhanced EPTC biodegradation in soils treated previously with EPTC alone but not in soils previously treated with EPTC plus dietholate. While previous use of other thiocarbamate herbicides frequently enhanced biodegradation of EPTC or butylate [S-ethyl bis(2-methylpropyl)carbamothioate], previous use of other classes of herbicides or the insecticide carbofuran (2,3 -dihydro-2,2 -dimethyl-7-benzofuranyl methylcarbamate) did not. Enhanced biodegradation of herbicides other than the thiocarbamates was not observed.

Objectives: This study examined whether children with distinct brain disorders show different profiles of strengths and weaknesses in executive functions, and differ from children without brain disorder. Methods: Participants were children with traumatic brain injury (N=82; 8–13 years of age), arterial ischemic stroke (N=36; 6–16 years of age), and brain tumor (N=74; 9–18 years of age), each with a corresponding matched comparison group consisting of children with orthopedic injury (N=61), asthma (N=15), and classmates without medical illness (N=68), respectively. Shifting, inhibition, and working memory were assessed, respectively, using three Test of Everyday Attention: Children’s Version (TEA-Ch) subtests: Creature Counting, Walk-Don’t-Walk, and Code Transmission. Comparison groups did not differ in TEA-Ch performance and were merged into a single control group. Profile analysis was used to examine group differences in TEA-Ch subtest scaled scores after controlling for maternal education and age. Results: As a whole, children with brain disorder performed more poorly than controls on measures of executive function. Relative to controls, the three brain injury groups showed significantly different profiles of executive functions. Importantly, post hoc tests revealed that performance on TEA-Ch subtests differed among the brain disorder groups. Conclusions: Results suggest that different childhood brain disorders result in distinct patterns of executive function deficits that differ from children without brain disorder. Implications for clinical practice and future research are discussed. (JINS, 2017, 23, 529–538)

Field studies were conducted at 35 sites throughout the north-central United States in 1998 and 1999 to determine the effect of postemergence glyphosate application timing on weed control and grain yield in glyphosate-resistant corn. Glyphosate was applied at various timings based on the height of the most dominant weed species. Weed control and corn grain yields were considerably more variable when glyphosate was applied only once. The most effective and consistent season-long annual grass and broadleaf weed control occurred when a single glyphosate application was delayed until weeds were 15 cm or taller. Two glyphosate applications provided more consistent weed control when weeds were 10 cm tall or less and higher corn grain yields when weeds were 5 cm tall or less, compared with a single application. Weed control averaged at least 94 and 97% across all sites in 1998 and 1999, respectively, with two glyphosate applications but was occasionally less than 70% because of late emergence of annual grass and Amaranthus spp. or reduced control of Ipomoea spp. With a single application of glyphosate, corn grain yield was most often reduced when the application was delayed until weeds were 23 cm or taller. Averaged across all sites in 1998 and 1999, corn grain yields from a single glyphosate application at the 5-, 10-, 15-, 23-, and 30-cm timings were 93, 94, 93, 91, and 79% of the weed-free control, respectively. There was a significant effect of herbicide treatment on corn grain yield in 23 of the 35 sites when weed reinfestation was prevented with a second glyphosate application. When weed reinfestation was prevented, corn grain yield at the 5-, 10-, and 15-cm application timings was 101, 97, and 93% of the weed-free control, respectively, averaged across all sites. Results of this study suggested that the optimum timing for initial glyphosate application to avoid corn grain yield loss was when weeds were less than 10 cm in height, no more than 23 d after corn planting, and when corn growth was not more advanced than the V4 stage.