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.

Spotted-wing drosophila, Drosophila suzukii, is a global pest of soft fruits that is capable of reproducing on a wide range of cultivated and wild plant species. In Canada, D. suzukii was first reported in British Columbia in 2009 and is now widespread across the country. Understanding the genetic structure of D. suzukii populations could be important for pest management if there are phenotypic differences between genetically distinct populations. For example, insect pest populations could respond differently to directional selection imposed by insecticides, differ in their host plant preferences, and vary in their susceptibility to biological control agents. Here, we used double-digest restriction site–associated DNA sequencing to examine large- and fine-scale patterns of the genetic structure of D. suzukii reared from fruit hosts in Canada. We found that this species has a large-scale spatial genetic structure; the flies collected formed two distinct genetic clusters, one of which was distinct to western Canada and the other to eastern Canada. At the local scale, D. suzukii populations showed no evidence of host-associated structuring in British Columbia, suggesting that pest management tactics may be best applied at the landscape level. Our results highlight the need to investigate phenotypic differences between western and eastern D. suzukii populations in Canada.

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.

This study quantifies the effect of fertilizer and irrigation management on water use efficiency (WUE), crop growth and crop yield in sub-humid to semi-arid conditions of Limpopo Province, South Africa. An approach of coupling a cropping system model (DSSAT) with an agro-hydrological model (SWAT) was developed and applied to simulate crop yield at the field and catchment scale. Simulation results indicated that the application of fertilizer has a greater positive effect on maize yield than irrigation. WUE ranged from 0.10–0.57 kg/m3 (rainfed) to 0.84–1.39 kg/m3 (irrigated) and was positively correlated with fertilizer application rate. The combined application of the variants with deficit irrigation and fertilizer rate (120:60 kg N:P/ha) for maize turned out to be the best option, giving the highest WUE and increasing average yield by up to 5.7 t/ha compared to no fertilization and rainfed cultivation (1.3 t/ha). The simulated results at the catchment scale showed the considerable spatial variability of maize yield across agricultural fields with different soils, slopes and climate conditions. The average annual simulated maize yield across the catchment corresponding to the highest WUE ranged from 4.0 to 7.0 t/ha. The yield gaps ranged from 3.0 to 6.0 t/ha under deficit irrigation combined with 120N:60P kg/ha and ranged from 0.2 to 1.5 t/ha when only applying deficit irrigation but no fertilizer. This information can support regional decision makers to find appropriate interventions that aim at improving crop yield and WUE for catchments/regions.

The Hierarchical Taxonomy of Psychopathology (HiTOP) has emerged out of the quantitative approach to psychiatric nosology. This approach identifies psychopathology constructs based on patterns of co-variation among signs and symptoms. The initial HiTOP model, which was published in 2017, is based on a large literature that spans decades of research. HiTOP is a living model that undergoes revision as new data become available. Here we discuss advantages and practical considerations of using this system in psychiatric practice and research. We especially highlight limitations of HiTOP and ongoing efforts to address them. We describe differences and similarities between HiTOP and existing diagnostic systems. Next, we review the types of evidence that informed development of HiTOP, including populations in which it has been studied and data on its validity. The paper also describes how HiTOP can facilitate research on genetic and environmental causes of psychopathology as well as the search for neurobiologic mechanisms and novel treatments. Furthermore, we consider implications for public health programs and prevention of mental disorders. We also review data on clinical utility and illustrate clinical application of HiTOP. Importantly, the model is based on measures and practices that are already used widely in clinical settings. HiTOP offers a way to organize and formalize these techniques. This model already can contribute to progress in psychiatry and complement traditional nosologies. Moreover, HiTOP seeks to facilitate research on linkages between phenotypes and biological processes, which may enable construction of a system that encompasses both biomarkers and precise clinical description.

In 2020 a group of U.S. healthcare leaders formed the National Organization to Prevent Hospital-Acquired Pneumonia (NOHAP) to issue a call to action to address non–ventilator-associated hospital-acquired pneumonia (NVHAP). NVHAP is one of the most common and morbid healthcare-associated infections, but it is not tracked, reported, or actively prevented by most hospitals. This national call to action includes (1) launching a national healthcare conversation about NVHAP prevention; (2) adding NVHAP prevention measures to education for patients, healthcare professionals, and students; (3) challenging healthcare systems and insurers to implement and support NVHAP prevention; and (4) encouraging researchers to develop new strategies for NVHAP surveillance and prevention. The purpose of this document is to outline research needs to support the NVHAP call to action. Primary needs include the development of better models to estimate the economic cost of NVHAP, to elucidate the pathophysiology of NVHAP and identify the most promising pathways for prevention, to develop objective and efficient surveillance methods to track NVHAP, to rigorously test the impact of prevention strategies proposed to prevent NVHAP, and to identify the policy levers that will best engage hospitals in NVHAP surveillance and prevention. A joint task force developed this document including stakeholders from the Veterans’ Health Administration (VHA), the U.S. Centers for Disease Control and Prevention (CDC), The Joint Commission, the American Dental Association, the Patient Safety Movement Foundation, Oral Health Nursing Education and Practice (OHNEP), Teaching Oral-Systemic Health (TOSH), industry partners and academia.

The COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) project is a large international collaborative effort to analyze individual-level phenotype data from twins in multiple cohorts from different environments. The main objective is to study factors that modify genetic and environmental variation of height, body mass index (BMI, kg/m2) and size at birth, and additionally to address other research questions such as long-term consequences of birth size. The project started in 2013 and is open to all twin projects in the world having height and weight measures on twins with information on zygosity. Thus far, 54 twin projects from 24 countries have provided individual-level data. The CODATwins database includes 489,981 twin individuals (228,635 complete twin pairs). Since many twin cohorts have collected longitudinal data, there is a total of 1,049,785 height and weight observations. For many cohorts, we also have information on birth weight and length, own smoking behavior and own or parental education. We found that the heritability estimates of height and BMI systematically changed from infancy to old age. Remarkably, only minor differences in the heritability estimates were found across cultural–geographic regions, measurement time and birth cohort for height and BMI. In addition to genetic epidemiological studies, we looked at associations of height and BMI with education, birth weight and smoking status. Within-family analyses examined differences within same-sex and opposite-sex dizygotic twins in birth size and later development. The CODATwins project demonstrates the feasibility and value of international collaboration to address gene-by-exposure interactions that require large sample sizes and address the effects of different exposures across time, geographical regions and socioeconomic status.

There are a variety of causes of acute heart failure in children including myocarditis, genetic/metabolic conditions, and congenital heart defects. In cases with a structurally normal heart and a negative personal and family history, myocarditis is often presumed to be the cause, but we hypothesise that genetic disorders contribute to a significant portion of these cases. We reviewed our cases of children who presented with acute heart failure and underwent genetic testing from 2008 to 2017. Eighty-seven percent of these individuals were found to have either a genetic syndrome or pathogenic or likely pathogenic variant in a cardiac-related gene. None of these individuals had a personal or family history of cardiomyopathy that was suggestive of a genetic aetiology prior to presentation. All of these individuals either passed away or were listed for cardiac transplantation indicating genetic testing may provide important information regarding prognosis in addition to providing information critical to assessment of family members.

Introduction: Cardioactive steroid poisoning occurs worldwide with the use of pharmaceutical digoxin and botanical cardiac glycosides. The wholesale price of the antidote, digoxin immune fab, has increased over 300% from 2010 to 2015. Our objective was to identify gaps in the existing literature with respect to the use of digoxin immune fab in cardioactive steroid toxicity in acute care settings. Methods: We used scoping study methodology, as described by Arksey and O'Malley, to assess the range and scope of empiric research and will report: 1) sources of cardioactive steroid toxicity in acute settings; 2) doses of digoxin immune fab used in treatment; and, 3) intervention outcomes of acute cardioactive steroid toxicity following the administration of digoxin immune fab as first or second-line therapy. We collaborated with a library scientist to devise search strategies for PubMed, CINAHL, EMBASE, CENTRAL and Toxnet. We sought unpublished literature through the Canadian Electronic Library, Proquest, and Scopus and searched reference lists of included studies. We hand searched relevant conference proceedings and applicable guidelines. Two reviewers independently reviewed titles and abstracts using predetermined criteria. Using a structured data abstraction form, two reviewers independently extracted data. All discrepancies were resolved through consensus. Results: Our search strategy yielded 3458 results. After screening titles and abstracts 384 underwent full text screening. We included 147 studies and are currently extracting data from 12 French studies and 135 English studies. To date we have extracted data from 90 case reports and case series. Conclusion: Given concerns over rising costs, our findings will shed light on the extent of the evidence for use of digoxin immune fab in acute care settings.

The majority of paediatric Clostridioides difficile infections (CDI) are community-associated (CA), but few data exist regarding associated risk factors. We conducted a case–control study to evaluate CA-CDI risk factors in young children. Participants were enrolled from eight US sites during October 2014–February 2016. Case-patients were defined as children aged 1–5 years with a positive C. difficile specimen collected as an outpatient or ⩽3 days of hospital admission, who had no healthcare facility admission in the prior 12 weeks and no history of CDI. Each case-patient was matched to one control. Caregivers were interviewed regarding relevant exposures. Multivariable conditional logistic regression was performed. Of 68 pairs, 44.1% were female. More case-patients than controls had a comorbidity (33.3% vs. 12.1%; P = 0.01); recent higher-risk outpatient exposures (34.9% vs. 17.7%; P = 0.03); recent antibiotic use (54.4% vs. 19.4%; P < 0.0001); or recent exposure to a household member with diarrhoea (41.3% vs. 21.5%; P = 0.04). In multivariable analysis, antibiotic exposure in the preceding 12 weeks was significantly associated with CA-CDI (adjusted matched odds ratio, 6.25; 95% CI 2.18–17.96). Improved antibiotic prescribing might reduce CA-CDI in this population. Further evaluation of the potential role of outpatient healthcare and household exposures in C. difficile transmission is needed.

Laser-based compact MeV X-ray sources are useful for a variety of applications such as radiography and active interrogation of nuclear materials. MeV X rays are typically generated by impinging the intense laser onto ~mm-thick high-Z foil. Here, we have characterized such a MeV X-ray source from 120 TW (80 J, 650 fs) laser interaction with a 1 mm-thick tantalum foil. Our measurements show X-ray temperature of 2.5 MeV, flux of 3 × 1012 photons/sr/shot, beam divergence of ~0.1 sr, conversion efficiency of ~1%, that is, ~1 J of MeV X rays out of 80 J incident laser, and source size of 80 m. Our measurement also shows that MeV X-ray yield and temperature is largely insensitive to nanosecond laser contrasts up to 10−5. Also, preliminary measurements of similar MeV X-ray source using a double-foil scheme, where the laser-driven hot electrons from a thin foil undergoing relativistic transparency impinging onto a second high-Z converter foil separated by 50–400 m, show MeV X-ray yield more than an order of magnitude lower compared with the single-foil results.

Hill (Twin Research and Human Genetics, Vol. 21, 2018, 84–88) presented a critique of our recently published paper in Cell Reports entitled ‘Large-Scale Cognitive GWAS Meta-Analysis Reveals Tissue-Specific Neural Expression and Potential Nootropic Drug Targets’ (Lam et al., Cell Reports, Vol. 21, 2017, 2597–2613). Specifically, Hill offered several interrelated comments suggesting potential problems with our use of a new analytic method called Multi-Trait Analysis of GWAS (MTAG) (Turley et al., Nature Genetics, Vol. 50, 2018, 229–237). In this brief article, we respond to each of these concerns. Using empirical data, we conclude that our MTAG results do not suffer from ‘inflation in the FDR [false discovery rate]’, as suggested by Hill (Twin Research and Human Genetics, Vol. 21, 2018, 84–88), and are not ‘more relevant to the genetic contributions to education than they are to the genetic contributions to intelligence’.