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.

The outer solar system is theoretically predicted to harbour an undiscovered planet, often referred to as Planet Nine. Simulations suggest that its gravitational influence could explain the unusual clustering of minor bodies in the Kuiper Belt. However, no observational evidence for Planet Nine has been found so far, as its predicted orbit lies far beyond Neptune, where it reflects only a faint amount of Sunlight. This work aims to find Planet Nine candidates by taking advantage of two far-infrared all-sky surveys, which are IRAS and AKARI. The epochs of these two surveys were separated by 23 years, which is large enough to detect Planet Nine’s $\sim3'$/year orbital motion. We use a dedicated AKARI Far-Infrared point source list for the purpose of our Planet Nine search — AKARI-FIS Monthly Unconfirmed Source List (AKARI-MUSL), which includes sources detected repeatedly only in hours timescale, but not after months. AKARI-MUSL is more advantageous than the AKARI Bright Source Catalogue (AKARI-BSC) for detecting moving and faint objects like Planet Nine with a twice-deeper flux detection limit. We search for objects that moved slowly between IRAS and AKARI detections given in the catalogues. First, we estimated the expected flux and orbital motion of Planet Nine by assuming its mass, distance, and effective temperature to ensure it can be detected by IRAS and AKARI, then applied the positional and flux selection criteria to narrow down the number of sources from the catalogues. Next, we produced all possible candidate pairs including one IRAS source and one AKARI source whose angular separations were limited between 42′ and $69.6'$, corresponding to the heliocentric distance range of 500 – 700 AU and the mass range of 7 – 17M$_{\oplus}$. There are 13 candidate pairs obtained after the selection criteria. After image inspection, we found one good candidate, of which the IRAS source is absent from the same coordinate in the AKARI image after 23 years and vice versa. However, AKARI and IRAS detections are not enough to determine the full orbit of this candidate. This issue leads to the need for follow-up observations, which will determine the Keplerian motion of our Planet Nine candidate.

An unusual orbital element clustering of Kuiper belt objects (KBOs) has been observed. The most promising dynamic solution is the presence of a giant planet in the outer Solar system, Planet Nine. However, due to its extreme distance, intensive searches in optical have not been successful. We aim to find Planet Nine in the far-infrared, where it has the peak of the black body radiation, using the most sensitive all-sky far-infrared survey to date, AKARI. In contrast to optical searches, where the energy of reflected sunlight decreases by $d^{4}$, thermal radiation in the infrared decreases with the square of the heliocentric distance $d^{2}$. We search for moving objects in the AKARI Single Scan Detection List. We select sources from a promising region suggested by an N-body simulation from Millholland and Laughlin 2017: $30^{\circ}\lt$ R.A. $\lt50^{\circ}$ and $-20^{\circ}\lt$ Dec. $\lt20^{\circ}$. Known sources are excluded by cross-matching AKARI sources with 9 optical and infrared catalogues. Furthermore, we select sources with small background strength to avoid sources in the cirrus. Since Planet Nine is stationary in a timescale of hours but moves on a monthly scale, our primary strategy is to select slowly moving objects that are stationary in 24 h but not in six months, using multiple single scans by AKARI. The selected slowly moving AKARI sources are scrutinised for potential contamination from cosmic rays. Our analysis reveals two possible Planet Nine candidates whose positions and flux are within the theoretical prediction ranges. These candidates warrant further investigation through follow-up observations to confirm the existence and properties of Planet Nine.

Brown dwarfs are failed stars with very low mass (13–75 Jupiter mass) and an effective temperature lower than 2 500 K. Their mass range is between Jupiter and red dwarfs. Thus, they play a key role in understanding the gap in the mass function between stars and planets. However, due to their faint nature, previous searches are inevitably limited to the solar neighbourhood (20 pc). To improve our knowledge of the low mass part of the initial stellar mass function and the star formation history of the Milky Way, it is crucial to find more distant brown dwarfs. Using James Webb Space Telescope (JWST) COSMOS-Web data, this study seeks to enhance our comprehension of the physical characteristics of brown dwarfs situated at a distance of kpc scale. The exceptional sensitivity of the JWST enables the detection of brown dwarfs that are up to 100 times more distant than those discovered in the earlier all-sky infrared surveys. The large area coverage of the JWST COSMOS-Web survey allows us to find more distant brown dwarfs than earlier JWST studies with smaller area coverages. To capture prominent water absorption features around 2.7 ${\unicode{x03BC}}$m, we apply two colour criteria, $\text{F115W}-\text{F277W}+1\lt\text{F277W}-\text{F444W}$ and $\text{F277W}-\text{F444W}\gt\,0.9$. We then select point sources by CLASS_STAR, FLUX_RADIUS, and SPREAD_MODEL criteria. Faint sources are visually checked to exclude possibly extended sources. We conduct SED fitting and MCMC simulations to determine their physical properties and associated uncertainties. Our search reveals 25 T-dwarf candidates and 2 Y-dwarf candidates, more than any previous JWST brown dwarf searches. They are located from 0.3 to 4 kpc away from the Earth. The spatial number density of 900–1 050 K dwarf is $(2.0\pm0.9) \times10^{-6}\text{ pc}^{-3}$, 1 050–1 200 K dwarf is $(1.2\pm0.7) \times10^{-6}\text{ pc}^{-3}$, and 1 200–1 350 K dwarf is $(4.4\pm1.3) \times10^{-6}\text{ pc}^{-3}$. The cumulative number count of our brown dwarf candidates is consistent with the prediction from a standard double exponential model. Three of our brown dwarf candidates were detected by HST, with transverse velocities $12\pm5$, $12\pm4$, and $17\pm6$ km s$^{-1}$. Along with earlier studies, the JWST has opened a new window of brown dwarf research in the Milky Way thick disk and halo.

Metabolic enzymes are the catalysts that drive the biochemical reactions essential for sustaining life. Many of these enzymes are tightly regulated by feedback mechanisms. To fully understand their roles and modulation, it is crucial to investigate the relationship between their structure, catalytic mechanism, and function. In this perspective, by using three examples from our studies on Mycobacterium tuberculosis (Mtb) isocitrate lyase and related proteins, we highlight how an integrated approach combining structural, activity, and biophysical data provides insights into their biological functions. These examples underscore the importance of employing fast-fail experiments at the early stages of a research project, emphasise the value of complementary techniques in validating findings, and demonstrate how in vitro data combined with chemical, biochemical, and physiological knowledge can lead to a broader understanding of metabolic adaptations in pathogenic bacteria. Finally, we address the unexplored questions in Mtb metabolism and discuss how we expand our approach to include microbiological and bioanalytical techniques to further our understanding. Such an integrated and interdisciplinary strategy has the potential to uncover novel regulatory mechanisms and identify new therapeutic opportunities for the eradication of tuberculosis. The approach can also be broadly applied to investigate other biochemical networks and complex biological systems.

There is a relative lack of research, targeted models and tools to manage beaches in estuaries and bays (BEBs). Many estuaries and bays have been highly modified and urbanised, for example port developments and coastal revetments. This paper outlines the complications and opportunities for conserving and managing BEBs in modified estuaries. To do this, we focus on eight diverse case studies from North and South America, Asia, Europe, Africa and Australia combined with the broader global literature. Our key findings are as follows: (1) BEBs are diverse and exist under a great variety of tide and wave conditions that differentiate them from open-coast beaches; (2) BEBs often lack statutory protection and many have already been sacrificed to development; (3) BEBs lack specific management tools and are often managed using tools developed for open-coast beaches; and (4) BEBs have the potential to become important in “nature-based” management solutions. We set the future research agenda for BEBs, which should include broadening research to include greater diversity of BEBs than in the past, standardising monitoring techniques, including the development of global databases using citizen science and developing specific management tools for BEBs. We must recognise BEBs as unique coastal features and develop the required fundamental knowledge and tools to effectively manage them, so they can continue providing their unique ecosystem services.

OBJECTIVES/GOALS: Community and other stakeholder engagement (CSE) is critical for relevant and equitable clinical research, yet implementation poses challenges. This study delineates the perspectives of scientists and diverse stakeholders regarding facilitators and challenges in CSE, its perceived value, and their recommendations for successful CSE. METHODS/STUDY POPULATION: The Tufts CTSI Pilot Studies Program requires applicants to propose a plan for CSE while implementing the award, including which stakeholders (SHs)—community members, clinicians, and others affected by the research--will be involved and at what stages. This qualitative study assessed the experiences of both Principal Investigators (PIs) and SHs engaged in pilot projects from three cohorts of awardees (2019-21). Recruitment targeted one PI and one SH per project. Semi-structured interviews explored their CSE experiences, including facilitators, challenges, meaningfulness, perceived impact, intent to participate in CSE in future studies, as well as recommendations for funders, research support organizations, and investigators. Inductive consensus-based coding and thematic analysis was employed. RESULTS/ANTICIPATED RESULTS: Fourteen PIs from different pilot projects and a SH from five of these projects participated. Almost all PIs (92%) had over six years of experience, but two-thirds (67%) had little or no experience with CSE. Four SHs self-identified as representatives of community organizations and one as a clinician scientist. CSE was a “win-win” for both PIs and SHs, and all PIs intended to involve SHs in other research studies. Three facilitators were identified as fostering effective CSE (e.g., PI access to CSE expertise while conducting the project), while four challenges hindered it (e.g., limits on SH capacity and CSE funding). SHs advised scientists to build authentic, sustained relationships, and PIs and SHs provided three actionable recommendations for funders and research support organizations to deepen and expand CSE. DISCUSSION/SIGNIFICANCE: Perspectives of scientists and SHs engaged in research projects are vital for expanding and sustaining effective CSE in research. Funders and research support organizations can enhance their strategies for CSE integration in clinical and translational research by incorporating these diverse views to ensure the research achieves maximal impact.

Colliding collisionless shocks appear in a great variety of astrophysical phenomena and are thought to be possible sources of particle acceleration in the Universe. We have previously investigated particle acceleration induced by single super-critical shocks (whose magnetosonic Mach number is higher than the critical value of 2.7) (Yao et al., Nat. Phys., vol. 17, issue 10, 2021, pp. 1177–1182; Yao et al., Matter Radiat. Extrem., vol. 7, issue 1, 2022, 014402), as well as the collision of two sub-critical shocks (Fazzini et al., Astron. Astrophys., vol. 665, 2022, A87). Here, we propose to make measurements of accelerated particles from interpenetrating super-critical shocks to observe the ‘phase-locking effect’ (Fazzini et al., Astron. Astrophys., vol. 665, 2022, A87) from such an event. This effect is predicted to significantly boost the energy spectrum of the energized ions compared with a single super-critical collisionless shock. We thus anticipate that the results obtained in the proposed experiment could have a significant impact on our understanding of one type of primary source (acceleration of thermal ions as opposed to secondary acceleration mechanisms of already energetic ions) of ion energization of particles in the Universe.

This study assesses governments' long-term non-pharmaceutical interventions upon the coronavirus disease 2019 (COVID-19) pandemic in East Asia. It advances the literature towards a better understanding of when and which control measures are effective. We (1) provide time-varying case fatality ratios and focus on the elderly's mortality and case fatality ratios, (2) measure the correlations between daily new cases (daily new deaths) and each index based on multiple domestic pandemic waves and (3) examine the lead–lag relationship between daily new cases (daily new deaths) and each index via the cross-correlation functions on the pre-whitened series. Our results show that the interventions reduce COVID-19 infections for some periods before the period of the Omicron variant. Moreover, there is no COVID-19 policy lag in Taiwan between daily new confirmed cases and each index. As of March 2022, the case fatality ratios of the elderly group in Japan, Hong Kong and South Korea are 4.69%, 4.72% and 1.48%, respectively, while the case fatality ratio of the elderly group in Taiwan is 25.01%. A government's COVID-19 vaccination distribution and prioritisation policies are pivotal for the elderly group to reduce the number of deaths. Immunising this specific group as best as possible should undoubtedly be a top priority.

The incidence of scarlet fever has increased dramatically in recent years in Chongqing, China, but there has no effective method to forecast it. This study aimed to develop a forecasting model of the incidence of scarlet fever using a seasonal autoregressive integrated moving average (SARIMA) model. Monthly scarlet fever data between 2011 and 2019 in Chongqing, China were retrieved from the Notifiable Infectious Disease Surveillance System. From 2011 to 2019, a total of 5073 scarlet fever cases were reported in Chongqing, the male-to-female ratio was 1.44:1, children aged 3–9 years old accounted for 81.86% of the cases, while 42.70 and 42.58% of the reported cases were students and kindergarten children, respectively. The data from 2011 to 2018 were used to fit a SARIMA model and data in 2019 were used to validate the model. The normalised Bayesian information criterion (BIC), the coefficient of determination (R2) and the root mean squared error (RMSE) were used to evaluate the goodness-of-fit of the fitted model. The optimal SARIMA model was identified as (3, 1, 3) (3, 1, 0)12. The RMSE and mean absolute per cent error (MAPE) were used to assess the accuracy of the model. The RMSE and MAPE of the predicted values were 19.40 and 0.25 respectively, indicating that the predicted values matched the observed values reasonably well. Taken together, the SARIMA model could be employed to forecast scarlet fever incidence trend, providing support for scarlet fever control and prevention.