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.

Marsupials give birth to immunologically naïve young after a relatively short gestation period compared with eutherians. Consequently, the joey relies significantly on maternal protection, which is the focus of the present review. The milk and the pouch environment are essential contributors to maternal protection for the healthy development of joeys. In this review, we discuss bioactive components found in the marsupial pouch and milk that form cornerstones of maternal protection. These bioactive components include immune cells, immunoglobulins, the S100 family of calcium-binding proteins, lysozymes, whey proteins, antimicrobial peptides and other immune proteins. Furthermore, we investigated the possibility of the presence of plurifunctional components in milk and pouches that are potentially bioactive. These compounds include caseins, vitamins and minerals, oligosaccharides, lipids and microRNAs. Where applicable, this review addresses variability in bioactive components during different phases of lactation, designed to fulfil the immunological needs of the growing pouch young. Yet, there are numerous additional research opportunities to pursue, including uncovering novel bioactive components and investigating their modes of action, dynamics, stability and ability to penetrate the gut epithelium to facilitate systemic effects.

Most of the Ross Sea has been designated a marine protected area (MPA), proposed ‘to protect ecosystem structure and function’. To assess effectiveness, the Commission for the Conservation of Antarctic Marine Living Resources (CCAMLR) selected Adélie (Pygoscelis adeliae) and emperor (Aptenodytes forsteri) penguins, Weddell seals (Leptonychotes weddellii) and Antarctic toothfish (Dissostichus mawsoni) as ecosystem change ‘indicator species’. Stable for decades, penguin and seal populations increased during 1998–2018 to surpass historical levels, indicating that change in ecosystem structure and function is underway. We review historical impacts to population trends, decadal datasets of ocean climate and fishing pressure on toothfish. Statistical modelling for Adélie penguins and Weddell seals indicates that variability in climate factors and cumulative extraction of adult toothfish may explain these trends. These mesopredators, and adult toothfish, all prey heavily on Antarctic silverfish (Pleuragramma antarcticum). Toothfish removal may be altering intraguild predation dynamics, leading to competitive release of silverfish and contributing to penguin and seal population changes. Despite decades of ocean/weather change, increases in indicator species numbers around Ross Island only began once the toothfish fishery commenced. The rational-use, ecosystem-based viewpoint promoted by CCAMLR regarding toothfish management needs re-evaluation, including in the context of the Ross Sea Region MPA.

Flow generation by colloidal motors activated by external stimuli is an important issue for active matter physics and several nanotechnological or biomedical applications. For instance, flow recirculation generated by rotating magnetic self-assemblies allows effective ‘pumping’ of a thrombolytic drug towards a blood clot along a blocked vessel. However, the physics of the flow generation in this case remains still poorly explored. This study is focused on the generation of a recirculation flow of a magnetic colloid (aqueous suspension of iron oxide nanoparticles with partially screened electrostatic repulsion) within a closed microfluidic channel via application of an external rotating magnetic field. The colloid undergoes reversible phase separation manifested through the appearance of micron-sized elongated aggregates. They synchronously rotate with the magnetic field and can generate macroscopic flows only in the presence of gradients of the aggregate concentration across the channel induced by superposition of a weak magnetic field gradient to the homogeneous rotating field. We achieve recirculation flows with a characteristic speed ${\sim} 5{-}8\;{\rm \mu}\textrm{m}\;{\textrm{s}^{ - \textrm{1}}}$ at low magnetic field amplitude and frequency (${H_0} \approx 3{-}10\;\textrm{kA}\;{\textrm{m}^{ - 1}}$, ${f = 5{-}15\ \textrm{Hz}}$) at low nanoparticle volume fraction ${\varphi _p} = (1.6{-}3.2) \times {10^{ - 3}}$. The concentration and velocity profiles have been assessed experimentally through particle tracking and particle image velocimetry, and have also been computed using the hydrodynamic diffusion approach coupled with the momentum balance equation with a magnetic torque term. The model correctly reproduces the shape of the experimental concentration and velocity fields and explains complex behaviours of the average recirculation speed as a function of governing parameters (${H_0}$, f, ${\varphi _p}$, channel size).

Pragmatic trials aim to generate timely evidence while ensuring feasibility, minimizing practice burden, and maintaining real-world conditions. We conducted rapid-cycle qualitative research in the preimplementation period of a trial evaluating a community paramedic program to shorten and prevent hospitalizations. Between December 2021 and March 2022, interviews (n = 30) and presentations/discussions (n = 17) were conducted with clinical and administrative stakeholders. Two investigators analyzed interview and presentation data to identify potential trial challenges, and team reflections were used to develop responsive strategies. Solutions were implemented prior to the commencement of trial enrollment and were aimed at bolstering feasibility and building ongoing practice feedback loops.

The giant gypsum crystals of Naica cave have fascinated scientists since their discovery in 2000. Human activity has changed the microclimate inside the cave, making scientists wonder about the potential environmental impact on the crystals. Over the last 9 years, we have studied approximately 70 samples. This paper reports on the detailed chemical–structural characterization of the impurities present at the surface of these crystals and the experimental simulations of their potential deterioration patterns. Selected samples were studied by petrography, optical and electronic microscopy, and laboratory X-ray diffraction. 2D grazing incidence X-ray diffraction, X-ray μ-fluorescence, and X-ray μ-absorption near-edge structure were used to identify the impurities and their associated phases. These impurities were deposited during the latest stage of the gypsum crystal formation and have afterward evolved with the natural high humidity. The simulations of the behavior of the crystals in microclimatic chambers produced crystal dissolution by 1–4% weight fraction under high CO2 concentration and permanent fog, and gypsum phase dehydration under air and CO2 gaseous environment. Our work suggests that most surface impurities are of natural origin; the most significant anthropogenic damage on the crystals is the extraction of water from the caves.

Online self-reported 24-h dietary recall systems promise increased feasibility of dietary assessment. Comparison against interviewer-led recalls established their convergent validity; however, reliability and criterion-validity information is lacking. The validity of energy intakes (EI) reported using Intake24, an online 24-h recall system, was assessed against concurrent measurement of total energy expenditure (TEE) using doubly labelled water in ninety-eight UK adults (40–65 years). Accuracy and precision of EI were assessed using correlation and Bland–Altman analysis. Test–retest reliability of energy and nutrient intakes was assessed using data from three further UK studies where participants (11–88 years) completed Intake24 at least four times; reliability was assessed using intra-class correlations (ICC). Compared with TEE, participants under-reported EI by 25 % (95 % limits of agreement −73 % to +68 %) in the first recall, 22 % (−61 % to +41 %) for average of first two, and 25 % (−60 % to +28 %) for first three recalls. Correlations between EI and TEE were 0·31 (first), 0·47 (first two) and 0·39 (first three recalls), respectively. ICC for a single recall was 0·35 for EI and ranged from 0·31 for Fe to 0·43 for non-milk extrinsic sugars (NMES). Considering pairs of recalls (first two v. third and fourth recalls), ICC was 0·52 for EI and ranged from 0·37 for fat to 0·63 for NMES. EI reported with Intake24 was moderately correlated with objectively measured TEE and underestimated on average to the same extent as seen with interviewer-led 24-h recalls and estimated weight food diaries. Online 24-h recall systems may offer low-cost, low-burden alternatives for collecting dietary information.

Facial transplantation is emerging as a therapeutic option for self-inflicted gunshot wounds. The self-inflicted nature of this injury raises questions about the appropriate role of self-harm in determining patient eligibility. Potential candidates for facial transplantation undergo extensive psychosocial screening. The presence of a self-inflicted gunshot wound warrants special attention to ensure that a patient is prepared to undergo a demanding procedure that poses significant risk, as well as stringent lifelong management. Herein, we explore the ethics of considering mechanism of injury in the patient selection process, referring to the precedent set forth in solid organ transplantation. We also consider the available evidence regarding outcomes of individuals transplanted for self-inflicted mechanisms of injury in both solid organ and facial transplantation. We conclude that while the presence of a self-inflicted gunshot wound is significant in the overall evaluation of the candidate, it does not on its own warrant exclusion from consideration for a facial transplantation.

A new target design is presented to model high-energy radiative accretion shocks in polars. In this paper, we present the experimental results obtained on the GEKKO XII laser facility for the POLAR project. The experimental results are compared with 2D FCI2 simulations to characterize the dynamics and the structure of plasma flow before and after the collision. The good agreement between simulations and experimental data confirms the formation of a reverse shock where cooling losses start modifying the post-shock region. With the multi-material structure of the target, a hydrodynamic collimation is exhibited and a radiative structure coupled with the reverse shock is highlighted in both experimental data and simulations. The flexibility of the laser energy produced on GEKKO XII allowed us to produce high-velocity flows and study new and interesting radiation hydrodynamic regimes between those obtained on the LULI2000 and Orion laser facilities.

Supplementation with n-3 fatty acids may improve long-term outcomes of renal transplant recipients (RTR). Recent evidence suggests that EPA and DHA have different outcomes compared with α-linolenic acid (ALA). We examined the prospective associations of EPA–DHA and ALA intakes with graft failure and all-cause mortality in 637 RTR. During 3·1 years (interquartile range 2·7, 3·8) of follow-up, forty-one developed graft failure and sixty-seven died. In age- and sex-adjusted analyses, EPA–DHA and ALA intakes were not associated with graft failure. EPA–DHA intake was not significantly associated with mortality (hazard ratio (HR) 0·79; 95% CI 0·54, 1·15 per 0·1 energy% difference). ALA intake was significantly associated with mortality (HR 1·17; 95% CI 1·04, 1·31 per 0·1 energy% difference). This association remained following adjustments for BMI, proteinuria and intakes of fat, carbohydrate and protein. RTR in the highest tertile of ALA intake exhibited about 2-fold higher mortality risk (HR 2·21; 95% CI 1·23, 3·97) compared with the lowest tertile. In conclusion, ALA intake may be associated with increased mortality in RTR. Future RCT are needed to confirm these results.

Approximately half of the variation in wellbeing measures overlaps with variation in personality traits. Studies of non-human primate pedigrees and human twins suggest that this is due to common genetic influences. We tested whether personality polygenic scores for the NEO Five-Factor Inventory (NEO-FFI) domains and for item response theory (IRT) derived extraversion and neuroticism scores predict variance in wellbeing measures. Polygenic scores were based on published genome-wide association (GWA) results in over 17,000 individuals for the NEO-FFI and in over 63,000 for the IRT extraversion and neuroticism traits. The NEO-FFI polygenic scores were used to predict life satisfaction in 7 cohorts, positive affect in 12 cohorts, and general wellbeing in 1 cohort (maximal N = 46,508). Meta-analysis of these results showed no significant association between NEO-FFI personality polygenic scores and the wellbeing measures. IRT extraversion and neuroticism polygenic scores were used to predict life satisfaction and positive affect in almost 37,000 individuals from UK Biobank. Significant positive associations (effect sizes <0.05%) were observed between the extraversion polygenic score and wellbeing measures, and a negative association was observed between the polygenic neuroticism score and life satisfaction. Furthermore, using GWA data, genetic correlations of -0.49 and -0.55 were estimated between neuroticism with life satisfaction and positive affect, respectively. The moderate genetic correlation between neuroticism and wellbeing is in line with twin research showing that genetic influences on wellbeing are also shared with other independent personality domains.