In 2016, the National Center for Advancing Translational Science launched the Trial Innovation Network (TIN) to address barriers to efficient and informative multicenter trials. The TIN provides a national platform, working in partnership with 60+ Clinical and Translational Science Award (CTSA) hubs across the country to support the design and conduct of successful multicenter trials. A dedicated Hub Liaison Team (HLT) was established within each CTSA to facilitate connection between the hubs and the newly launched Trial and Recruitment Innovation Centers. Each HLT serves as an expert intermediary, connecting CTSA Hub investigators with TIN support, and connecting TIN research teams with potential multicenter trial site investigators. The cross-consortium Liaison Team network was developed during the first TIN funding cycle, and it is now a mature national network at the cutting edge of team science in clinical and translational research. The CTSA-based HLT structures and the external network structure have been developed in collaborative and iterative ways, with methods for shared learning and continuous process improvement. In this paper, we review the structure, function, and development of the Liaison Team network, discuss lessons learned during the first TIN funding cycle, and outline a path toward further network maturity.

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.

‘Sea salt is made by boiling and evaporating sea water over the fire. Bay salt, by evaporating sea water, in pits clayed on the inside, by the heat of the sun. Basket salt is made by boiling away the water of salt springs over the fire. Rock salt is dug out of the ground’, wrote Charlotte Mason in The Lady's Assistant (1775), one of the most comprehensive eighteenth-century cookbooks. Although there were at least four variations of salt before the pre-industrial era, several historical recipes specified the use of bay salt (solar salt) for meat preservation, elevating its cultural status and implying that early modern actors had a refined understanding of salts, their tastes and their applications. This study uses scientific analysis to determine whether there is a biological or chemical basis for the superior reputation of bay salt for curing. Laboratory data suggest that bay salt contains microbes that produce nitrate and nitrite, which give the meat a more favourable taste and pleasant aesthetic. The authors thus demonstrate that combining insights from experimental archaeology with textual analysis of historical sources gives us a deeper understanding of historical uses of taste as an epistemic tool.

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.

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’.

Motukoreaite occurs as relatively abundant, white, clay-like cement in both beach-rock and basaltic volcanic tuffs on the flanks of a small, extinct, late Pleistocene, basaltic cone at Brown's Island (Motukorea), within Waitemata Harbour, Auckland, New Zealand (36° 50′ S., 174° 35′ E.). The occurrence was originally recorded by Bartrum (1941) as ‘beach limestone’ found at two places of the island's shore. The beach-rock consists of a grain-supported fabric of poorly sorted, well-rounded, alkali-olivine basalt pebbles and granules, subangular to sub-rounded fresh olivine sand and abraded sand- and gravel-sized bioclasts in a colourless to pale yellow-green aphanocrystalline matrix of motukoreaite. Additional detritals include quartz, feldspar, and sedimentary rock fragments. Stereoscan examination of the surface of pieces of the cement prised from the beach-rock showed a box-work of plate-like crystals with a hexagonal form in which individuals measured about 3×3×0·02 microns (fig. 1).

Wet-chemical analysis of a separate of the cement containing some 5 % quartz and traces of calcite and goethite gives SiO2 5·55, Al2O3 17·87, Fe2O3 0·73, CaO 0·92, MgO 22·98, MnO 0·70, ZnO 0·56, Na2O 0·71, K2O 0·10, CO2 9·32, SO3 10·00, H2O+ 19·62, H2O- 10·35, sum 99·41 %. The unit-cell formula using obtained unit-cell constants and measured specific gravity 1·43) is (Na0·73K0·07)∑0·80(Mg18·13Mn0·32Zn0·21)∑18·66Al11·15(CO3)6·22(SO4)3·97 (OH)51·1927·20H2O. Of several idealized formulae that may be proposed NaMg19Al12(CO3)6.5 (SO4)4(OH)54·28H2O is preferred.

Simulation models are used widely in pharmacology, epidemiology and health economics (HEs). However, there have been no attempts to incorporate models from these disciplines into a single integrated model. Accordingly, we explored this linkage to evaluate the epidemiological and economic impact of oseltamivir dose optimisation in supporting pandemic influenza planning in the USA. An HE decision analytic model was linked to a pharmacokinetic/pharmacodynamics (PK/PD) – dynamic transmission model simulating the impact of pandemic influenza with low virulence and low transmissibility and, high virulence and high transmissibility. The cost-utility analysis was from the payer and societal perspectives, comparing oseltamivir 75 and 150 mg twice daily (BID) to no treatment over a 1-year time horizon. Model parameters were derived from published studies. Outcomes were measured as cost per quality-adjusted life year (QALY) gained. Sensitivity analyses were performed to examine the integrated model's robustness. Under both pandemic scenarios, compared to no treatment, the use of oseltamivir 75 or 150 mg BID led to a significant reduction of influenza episodes and influenza-related deaths, translating to substantial savings of QALYs. Overall drug costs were offset by the reduction of both direct and indirect costs, making these two interventions cost-saving from both perspectives. The results were sensitive to the proportion of inpatient presentation at the emergency visit and patients’ quality of life. Integrating PK/PD–EPI/HE models is achievable. Whilst further refinement of this novel linkage model to more closely mimic the reality is needed, the current study has generated useful insights to support influenza pandemic planning.