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.

Background: Near-infrared spectroscopy regional cerebral oxygen saturation (rSO2) has gained interest as a raw parameter and as a basis for measuring cerebrovascular reactivity (CVR). This study aimed to identify threshold values of rSO2 and rSO2 based CVR at which outcomes worsened following traumatic brain injury (TBI). Methods: A retrospective multi-institutional cohort study was performed. The cerebral oxygen indices, COx (using rSO2 and cerebral perfusion pressure) as well as COx_a (using rSO2 and arterial blood pressure) were calculated for each patient. 2x2 tables were created grouping patients by alive/dead and favorable/unfavorable outcomes at various thresholds of COx and COx_a as well as rSO2 itself. Chi-square values were calculated to identify the most discriminative significant threshold. Results: In the cohort of 129 patients rSO2 did not have any statistically significant threshold value. For COx and COx_a, an optimal threshold value of 0.2 was identified for both survival and favorable outcomes with values above this associated with worse outcomes. Conclusions: In this study, raw rSO2was found to contain no significant prognostic information. However, rSO2 based indices of CVR, were found to have a uniform threshold of 0.2, above which clinical outcomes worsened. This study lays the groundwork to transition to less invasive means of continuously measuring CVR.

Smectitic clay minerals are unique indicators of paleoenvironmental conditions and exhibit a unique reactivity in the mineral world. Smectites may exhibit tetrahedral substitutions (Al3+, and sometimes Fe3+, can substitute for Si4+ in tetrahedral sites), resulting in a layer-charge increase, thereby impacting their properties (e.g. swelling and sorption capacities, catalytic properties, expandable abilities). The objective of the present study was to determine the influence of pH conditions on the hydrothermal production of smectite end-members exhibiting tetrahedral Al substitutions (saponite, beidellite, and nontronite), using X-ray diffraction (XRD) and Fourier-transform infrared (FTIR) methods. The results of a series of syntheses conducted at various pH values allowed discussion of the crystallization pathways of these smectites from a mechanistic point of view. Altogether, the present study provided easily reproducible protocols for the hydrothermal production of pure saponite, nontronite, or beidellite (i.e. with no other mineral). The successful synthesis of pure saponite was achieved by exposing the starting gels to 230°C for 4 days in solutions at pH ranging from 5.5 to 14. The successful synthesis of pure beidellite was achieved by exposing the starting gels to 230°C for 9 days in a solution at pH 12. The successful synthesis of pure nontronite was achieved by exposing the starting gels to 150°C for 2.5 days in a solution at pH 12.5. Although extrapolating experimental results to natural settings remains difficult, the results of the present study may be of great help to constrain better the geochemical conditions existing or having existed on extraterrestrial planetary bodies.

Improving the quality and conduct of multi-center clinical trials is essential to the generation of generalizable knowledge about the safety and efficacy of healthcare treatments. Despite significant effort and expense, many clinical trials are unsuccessful. The National Center for Advancing Translational Science launched the Trial Innovation Network to address critical roadblocks in multi-center trials by leveraging existing infrastructure and developing operational innovations. We provide an overview of the roadblocks that led to opportunities for operational innovation, our work to develop, define, and map innovations across the network, and how we implemented and disseminated mature innovations.

New technologies and disruptions related to Coronavirus disease-2019 have led to expansion of decentralized approaches to clinical trials. Remote tools and methods hold promise for increasing trial efficiency and reducing burdens and barriers by facilitating participation outside of traditional clinical settings and taking studies directly to participants. The Trial Innovation Network, established in 2016 by the National Center for Advancing Clinical and Translational Science to address critical roadblocks in clinical research and accelerate the translational research process, has consulted on over 400 research study proposals to date. Its recommendations for decentralized approaches have included eConsent, participant-informed study design, remote intervention, study task reminders, social media recruitment, and return of results for participants. Some clinical trial elements have worked well when decentralized, while others, including remote recruitment and patient monitoring, need further refinement and assessment to determine their value. Partially decentralized, or “hybrid” trials, offer a first step to optimizing remote methods. Decentralized processes demonstrate potential to improve urban-rural diversity, but their impact on inclusion of racially and ethnically marginalized populations requires further study. To optimize inclusive participation in decentralized clinical trials, efforts must be made to build trust among marginalized communities, and to ensure access to remote technology.

One challenge for multisite clinical trials is ensuring that the conditions of an informative trial are incorporated into all aspects of trial planning and execution. The multicenter model can provide the potential for a more informative environment, but it can also place a trial at risk of becoming uninformative due to lack of rigor, quality control, or effective recruitment, resulting in premature discontinuation and/or non-publication. Key factors that support informativeness are having the right team and resources during study planning and implementation and adequate funding to support performance activities. This communication draws on the experience of the National Center for Advancing Translational Science (NCATS) Trial Innovation Network (TIN) to develop approaches for enhancing the informativeness of clinical trials. We distilled this information into three principles: (1) assemble a diverse team, (2) leverage existing processes and systems, and (3) carefully consider budgets and contracts. The TIN, comprised of NCATS, three Trial Innovation Centers, a Recruitment Innovation Center, and 60+ CTSA Program hubs, provides resources to investigators who are proposing multicenter collaborations. In addition to sharing principles that support the informativeness of clinical trials, we highlight TIN-developed resources relevant for multicenter trial initiation and conduct.

Space Infrared Telescope for Cosmology and Astrophysics (SPICA), the cryogenic infrared space telescope recently pre-selected for a ‘Phase A’ concept study as one of the three remaining candidates for European Space Agency (ESA's) fifth medium class (M5) mission, is foreseen to include a far-infrared polarimetric imager [SPICA-POL, now called B-fields with BOlometers and Polarizers (B-BOP)], which would offer a unique opportunity to resolve major issues in our understanding of the nearby, cold magnetised Universe. This paper presents an overview of the main science drivers for B-BOP, including high dynamic range polarimetric imaging of the cold interstellar medium (ISM) in both our Milky Way and nearby galaxies. Thanks to a cooled telescope, B-BOP will deliver wide-field 100–350 $\mu$m images of linearly polarised dust emission in Stokes Q and U with a resolution, signal-to-noise ratio, and both intensity and spatial dynamic ranges comparable to those achieved by Herschel images of the cold ISM in total intensity (Stokes I). The B-BOP 200 $\mu$m images will also have a factor $\sim $30 higher resolution than Planck polarisation data. This will make B-BOP a unique tool for characterising the statistical properties of the magnetised ISM and probing the role of magnetic fields in the formation and evolution of the interstellar web of dusty molecular filaments giving birth to most stars in our Galaxy. B-BOP will also be a powerful instrument for studying the magnetism of nearby galaxies and testing Galactic dynamo models, constraining the physics of dust grain alignment, informing the problem of the interaction of cosmic rays with molecular clouds, tracing magnetic fields in the inner layers of protoplanetary disks, and monitoring accretion bursts in embedded protostars.

There is a long history of exploitation of the South American river turtle Podocnemis expansa. Conservation efforts for this species started in the 1960s but best practices were not established, and population trends and the number of nesting females protected remained unknown. In 2014 we formed a working group to discuss conservation strategies and to compile population data across the species’ range. We analysed the spatial pattern of its abundance in relation to human and natural factors using multiple regression analyses. We found that > 85 conservation programmes are protecting 147,000 nesting females, primarily in Brazil. The top six sites harbour > 100,000 females and should be prioritized for conservation action. Abundance declines with latitude and we found no evidence of human pressure on current turtle abundance patterns. It is presently not possible to estimate the global population trend because the species is not monitored continuously across the Amazon basin. The number of females is increasing at some localities and decreasing at others. However, the current size of the protected population is well below the historical population size estimated from past levels of human consumption, which demonstrates the need for concerted global conservation action. The data and management recommendations compiled here provide the basis for a regional monitoring programme among South American countries.

Background: Biallelic variants in POLR1C are associated with POLR3-related leukodystrophy (POLR3-HLD), or 4H leukodystrophy (Hypomyelination, Hypodontia, Hypogonadotropic Hypogonadism), and Treacher Collins syndrome (TCS). The clinical spectrum of POLR3-HLD caused by variants in this gene has not been described. Methods: A cross-sectional observational study involving 25 centers worldwide was conducted between 2016 and 2018. The clinical, radiologic and molecular features of 23 unreported and previously reported cases of POLR3-HLD caused by POLR1C variants were reviewed. Results: Most participants presented between birth and age 6 years with motor difficulties. Neurological deterioration was seen during childhood, suggesting a more severe phenotype than previously described. The dental, ocular and endocrine features often seen in POLR3-HLD were not invariably present. Five patients (22%) had a combination of hypomyelinating leukodystrophy and abnormal craniofacial development, including one individual with clear TCS features. Several cases did not exhibit all the typical radiologic characteristics of POLR3-HLD. A total of 29 different pathogenic variants in POLR1C were identified, including 13 new disease-causing variants. Conclusions: Based on the largest cohort of patients to date, these results suggest novel characteristics of POLR1C-related disorder, with a spectrum of clinical involvement characterized by hypomyelinating leukodystrophy with or without abnormal craniofacial development reminiscent of TCS.

The Beck’s Petrel Pseudobulweria beckii is a ‘Critically Endangered’ seabird whose breeding sites remain unknown. Historic observations suggest the species’ distribution is concentrated in the Bismarck Archipelago and particularly southern New Ireland. Over the course of two research expeditions in 2016 and 2017 we used on-land and at-sea observations, local interviews and satellite telemetry to understand the distribution of the species, its at-sea movements and potential breeding locations. Land-based and at-sea observations indicated that the area of Silur Bay in southern New Ireland was a significant site for Beck’s Petrel with numbers of birds increasing near shore prior to dusk and birds observed in spotlights over land. A local population is estimated to be in the low thousands. In 2017 a single Beck’s was captured at sea, fitted with a satellite transmitter and tracked for eight months. This bird maintained a core distribution off the south-east coast of New Ireland and north of Bougainville for 122 days. During the tracking period, the bird was located over land at night seven times; predominantly over southern New Ireland, where the signal was also lost for extended periods suggesting occupancy of an underground burrow. In August the bird migrated 1,400 km to a core pelagic habitat north of West Papua before the signal was eventually lost. Our combination of land- and sea-based observations and analysis of behaviour from satellite tracking supports the conclusion that a breeding site for Beck’s Petrel lies in the inland mountains of southern New Ireland and most likely in the high-altitude zone (> 2000 m) of the Hans Meyer Range. Further investigations are required to determine the exact location of breeding colonies in the mountains of southern New Ireland and the importance of a potential west Papuan non-breeding pelagic habitat for the species.

Introduction: Les patients ayant un retour de circulation spontanée (RCS) durant la phase préhospitalière de leur réanimation suite à un arrêt cardiaque extrahospitalier (ACEH) ont un meilleur taux de survie que ceux n'en ayant pas. La durée des efforts de réanimation avant l'initiation d'un transport ne varie généralement pas en fonction du rythme initial observé. Cette étude vise à comparer la durée des manœuvres de réanimation nécessaire afin de générer la majorité des RCS préhospitaliers et des RCS préhospitaliers menant à une survie en fonction du rythme initial. Methods: La présente étude de cohorte a été réalisée à partir des bases de données collectées de la Corporation d'Urgences-santé dans la région de Montréal entre 2010 et 2015. Les patients avec un ACEH d'origine médicale ont été inclus. Les patients dont l'ACEH était témoigné par les paramédics ont été exclus, tout comme ceux dont le rythme initial était inconnu. Nous avons comparé entre les groupes (rythme défibrillable [RD], activité électrique sans pouls [AESP] et asystolie) les taux de RCS préhospitalier et le temps nécessaires pour obtenir une majorité des RCS préhospitaliers et des RCS préhospitaliers menant à une survie. Results: Un total de 6002 patients (3851 hommes et 2151 femmes) d'un âge moyen de 52 ans ( ±10) ont été inclus dans l’étude, parmi lesquels 563 (9%) ont survécu jusqu’à leur congé hospitalier et 1310 (22%) ont obtenu un RCS préhospitalier. Un total de 1545 (26%) patients avaient un RD, 1654 (28%) une AESP et 2803 (47%) une asystolie. Les patients avec un RD ont obtenu plus fréquemment un RCS préhospitalier et un RCS préhospitalier menant à une survie que les patients avec une AESP qui eux même avaient un meilleur pronostic que ceux avec une asystolie initial (777 patients [55%] vs 385 [23%] vs 148 [5%], p < 0,001; 431 [28%] vs 85 [5%] vs 7 [0,2%], p < 0,001, respectivement). Les RCS survenaient également plus rapidement lorsque le rythme initial était un RD (13 minutes [ ±12] vs 18 [ ±13] vs 25 [ ±12], p < 0,001). Cependant, une période de réanimation plus longue était nécessaire afin d'obtenir 95% des RCS préhospitaliers menant à une survie pour les patients avec un RD (26 minutes vs 21 minutes vs 21 minutes). Conclusion: Les patients avec un rythme initial défibrillable suite à leur ACEH sont à meilleur pronostic. Il serait envisageable de transporter plus rapidement vers l'hôpital les patients avec une AESP ou une asystolie que ceux avec un rythme défibrillable si l'arrêt des manœuvres n'est pas envisagé.

Introduction: Les patients dont l'arrêt cardiaque extrahospitalier (ACEH) n'a pas été témoigné sont généralement exclus des protocoles de réanimation par circulation extracorporelle puisque le délai avant l'initiation de leur réanimation est inconnu. Il a été proposé que la présence d'un rythme initial défibrillable (RD) est fortement suggestif une très courte période avant l'initiation des manœuvres de réanimation. La présente étude vise à décrire l'association entre la durée avant l'initiation de la réanimation et la présence d'un RD chez des patients souffrant d'un ACEH. Methods: Cette étude de cohorte a été réalisée à partir des bases de données collectées de la Corporation d'Urgences-santé dans la région de Montréal entre 2010 et 2015. Les patients dont l'arrêt était témoigné, mais dont les témoins n'ont pas entamé de manœuvres de réanimation, ont été inclus. Nous avons également inclus les patients dont l'arrêt était témoigné par les paramédics comme groupe contrôle (durée avant l'initiation de la réanimation = 0 minute). Les patients avec un retour de circulation spontanée avant l'arrivée des services préhospitaliers ont été exclus, tout comme ceux dont le rythme initial était inconnu. Nous avons décrit l’évolution de la proportion de chacun des rythmes et construit une régression logistique multivariée ajustant pour les variables sociodémographiques et cliniques pertinentes. Results: Un total de 1751 patients (1173 hommes et 578 femmes) d'un âge moyen de 69 ans (±16) ont été inclus dans l'analyse principale, parmi lesquels 603 (34%) avaient un RD. Un total de 663 autres patients ont vu leur ACEH témoigné directement par les paramédics. Un plus court délai avant l'initiation des manœuvres est associé à la présence d'un RD (rapport de cotes ajusté = 0,97 [intervalle de confiance à 95% 0,94-0,99], p = 0,016). Cependant, cette relation n'est pas linéaire et la proportion de RD ne diminue pas avant notablement jusqu’à ce que 15 minutes s’écoulent avant le début de la réanimation (0 min = 35%, 1-5 min = 37%, 5-10 min = 35%, 10-15 min = 34%, +de 15 min = 16%). Conclusion: Bien que la proportion de patients avec un RD diminue lorsque le délai augmente avant l'initiation des manœuvres, cette relation ne semble pas linéaire. La baisse principale de la proportion de patients avec RD semble se produire suite à la quinzième minute de délai avant le début de la réanimation.

Introduction: La réanimation par circulation extracorporelle (R-CEC) permet potentiellement d'améliorer la survie de patients souffrant d'un arrêt cardiaque extrahospitalier (ACEH) réfractaire aux traitements habituels. Cette technique, se pratiquant généralement en centre hospitalier (CH), doit être réalisée le plus précocement possible. Un transport vers le CH en temps opportun est donc nécessaire. Cette étude vise à décrire la durée nécessaire des manœuvres de réanimation préhospitalières afin d'optimiser le moment du départ vers le CH dans le but d'obtenir un maximum de retour de circulation spontanée (RCS) préhospitalier. Methods: La présente étude de cohorte a été réalisée à partir des bases de données collectées de la Corporation d'Urgences-santé dans la région de Montréal entre 2010 et 2015. Les patients éligibles à une R-CEC selon les critères locaux ont été inclus (<65 ans, rythme initial défibrillable, arrêt témoigné avec réanimation par un témoin). Les patients ayant eu un arrêt devant les paramédics ont été exclus, tout comme ceux avec un RCS avant l'arrivée des services préhospitaliers. Nous avons calculé la sensibilité et la spécificité à différents seuils afin de prédire un RCS préhospitalier et une survie au congé hospitalier. Une courbe ROC a également été construite. Results: Un total de 236 patients (207 hommes et 29 femmes) d'un âge moyen de 52 ans (±10) ont été inclus dans l’étude, parmi lesquels 93 (39%) ont survécu jusqu’à leur congé hospitalier et 136 (58%) ont obtenu un RCS préhospitalier. Le délai moyen avant leur RCS était de 13 minutes (±10). Plus de 50% des survivants avaient eu un RCS moins de 8 minutes après l'initiation des manœuvres de réanimation par les intervenants préhospitaliers, et plus de 90% avant 24 minutes. Plus de 50% de tous les RCS survenaient dans les 10 premières minutes de réanimation et plus de 90% dans les 31 premières minutes. La courbe ROC montrait visuellement que le délai avant le RCS maximisant la sensibilité et la spécificité pour prédire la survie chez ces patients était à 22 minutes (Sensibilité = 90%, spécificité = 78%; aire sous la courbe = 0,89 [intervalle de confiance à 95% 0,84-0,93]). Conclusion: Le départ vers le CH pourrait être considéré pour ces patients entre 8 et 24 minutes après l'initiation des manœuvres. Une période de réanimation de 22 minutes semble être le meilleur compromis à cet égard.

Understanding the peculiar properties of Ultra Diffuse Galaxies (UDGs) via spectroscopic analysis is a challenging task that is now becoming feasible. The advent of 10m-class telescopes and high sensitivity instruments is enabling the gathering of high quality spectra even for the faintest systems. In addition, advances in the modelling of stellar populations, stellar libraries, and full-spectral fitting codes are allowing the recovery of the stellar content shaping those spectra with unprecedented reliability. In this contribution we report on the extensive tests we have carried out using the inversion code STECKMAP. The similarities between the Star Formation Histories (SFH) recovered from STECKMAP (applied to high-quality spectra) and deep Colour-Magnitude diagrams fitting (resolved stars) in two Local Group dwarf galaxies (LMC and LeoA) are remarkable, demonstrating the impressive performance of STECKMAP. We exploit the capabilities of STECKMAP and perform one of the most complete and reliable characterisations of the stellar component of UDGs to date using deep spectroscopic data. We measure radial and rotation velocities, SFHs and mean population parameters, such as ages and metallicities, for a sample of five UDG candidates in the Coma cluster. From the radial velocities, we confirm the Coma membership of these galaxies. We find that their rotation properties, if detected at all, are compatible with dwarf-like galaxies. The SFHs of the UDG are dominated by old (∼ 7 Gyr), metal-poor ([M/H] ∼ -1.1) and alpha-enhanced ([Mg/Fe]∼ 0.4) populations followed by a smooth or episodic decline which halted ∼ 2 Gyr ago, possibly a sign of cluster-induced quenching. We find no obvious correlation between individual SFH shapes and any UDG morphological properties. The recovered stellar properties for UDGs are similar to those found for DDO 44, a local UDG analogue resolved into stars. We conclude that the UDGs in our sample are extended dwarfs whose properties are likely the outcome of both internal processes, such as bursty SFHs and/or high-spin haloes, as well as environmental effects within the Coma cluster.