The European Clozapine Task Force is a group of psychiatrists and pharmacologists practicing in 18 countries under European Medicines Agency (EMA) regulation, who are deeply concerned about the underuse of clozapine in European countries. Although clozapine is the most effective antipsychotic for people with treatment-resistant schizophrenia, a large proportion of them do not have access to this treatment. Concerns about clozapine-induced agranulocytosis and stringent blood monitoring rules are major barriers to clozapine prescribing and use. There is a growing body of evidence that the incidence of clozapine-induced agranulocytosis is very low after the first year of treatment. Maintaining lifelong monthly blood monitoring after this period contributes to unjustified discontinuation of clozapine. We leverage recent and replicated evidence on the long-term safety of clozapine to call for the revision and updating of the EMA’s blood monitoring rules, thus aiming to overcome this major barrier to clozapine prescribing and use. We believe the time has come for relaxing the rules without increasing the risks for people using clozapine in Europe.

Traditional approaches for evaluating the impact of scientific research – mainly scholarship (i.e., publications, presentations) and grant funding – fail to capture the full extent of contributions that come from larger scientific initiatives. The Translational Science Benefits Model (TSBM) was developed to support more comprehensive evaluations of scientific endeavors, especially research designed to translate scientific discoveries into innovations in clinical or public health practice and policy-level changes. Here, we present the domains of the TSBM, including how it was expanded by researchers within the Implementation Science Centers in Cancer Control (ISC3) program supported by the National Cancer Institute. Next, we describe five studies supported by the Penn ISC3, each focused on testing implementation strategies informed by behavioral economics to reduce key practice gaps in the context of cancer care and identify how each study yields broader impacts consistent with TSBM domains. These indicators include Capacity Building, Methods Development (within the Implementation Field) and Rapid Cycle Approaches, implementing Software Technologies, and improving Health Care Delivery and Health Care Accessibility. The examples highlighted here can help guide other similar scientific initiatives to conceive and measure broader scientific impact to fully articulate the translation and effects of their work at the population level.

The U.S. Department of Agriculture–Agricultural Research Service (USDA-ARS) has been a leader in weed science research covering topics ranging from the development and use of integrated weed management (IWM) tactics to basic mechanistic studies, including biotic resistance of desirable plant communities and herbicide resistance. ARS weed scientists have worked in agricultural and natural ecosystems, including agronomic and horticultural crops, pastures, forests, wild lands, aquatic habitats, wetlands, and riparian areas. Through strong partnerships with academia, state agencies, private industry, and numerous federal programs, ARS weed scientists have made contributions to discoveries in the newest fields of robotics and genetics, as well as the traditional and fundamental subjects of weed–crop competition and physiology and integration of weed control tactics and practices. Weed science at ARS is often overshadowed by other research topics; thus, few are aware of the long history of ARS weed science and its important contributions. This review is the result of a symposium held at the Weed Science Society of America’s 62nd Annual Meeting in 2022 that included 10 separate presentations in a virtual Weed Science Webinar Series. The overarching themes of management tactics (IWM, biological control, and automation), basic mechanisms (competition, invasive plant genetics, and herbicide resistance), and ecosystem impacts (invasive plant spread, climate change, conservation, and restoration) represent core ARS weed science research that is dynamic and efficacious and has been a significant component of the agency’s national and international efforts. This review highlights current studies and future directions that exemplify the science and collaborative relationships both within and outside ARS. Given the constraints of weeds and invasive plants on all aspects of food, feed, and fiber systems, there is an acknowledged need to face new challenges, including agriculture and natural resources sustainability, economic resilience and reliability, and societal health and well-being.

Preterm birth has been associated with insulin resistance and beta-cell dysfunction, a hallmark characteristic of type 2 diabetes. However, studies investigating the relationship between a personal history of being born preterm and type 2 diabetes are sparse. We sought to investigate the potential association between a personal history of being born preterm and risk for type 2 diabetes in a racially and ethnically diverse population. Baseline and incident data (>16 years of follow-up) from the Women’s Health Initiative (n = 85,356) were used to examine the association between personal history of being born preterm (born 1910–1940s) and prevalent (baseline enrollment; cross-sectional) or incident (prospective cohort) cases of type 2 diabetes. Logistic and Cox proportional hazards regression models were used to estimate odds and hazards ratios. Being born preterm was significantly, positively associated with odds for prevalent type 2 diabetes at enrollment (adjOR = 1.79, 95% CI 1.43–2.24; P < 0.0001). Stratified regression models suggested the positive associations at baseline were consistent across race and ethnicity groups. However, being born preterm was not significantly associated with risk for incident type 2 diabetes. Regression models stratified by age at enrollment suggest the relationship between being born preterm and type 2 diabetes persists only among younger age groups. Preterm birth was associated with higher risk of type 2 diabetes but only in those diagnosed with type 2 diabetes prior to study enrollment, suggesting the association between preterm birth and type 2 diabetes may exist at earlier age of diagnosis but wane over time.

Diffusiophoresis refers to the motion of a colloidal particle in a solute concentration gradient, animated by particle–solute interactions. We present a theoretical analysis of the diffusiophoretic motion of a viscous drop in a gradient of neutral solute at zero Reynolds number. In a spatially uniform gradient, the translational velocity of a spherical drop was found by Anderson et al. (J. Fluid Mech., vol. 117, 1982, pp. 107–121). Here, we show additionally that the drop experiences no tendency to deform, regardless of the magnitude of the interfacial tension at the interface of the drop and suspending fluid. Next, we consider a non-uniform gradient, where the ambient solute concentration takes the form of a quadrupole around the drop centroid. This gradient does not induce drop translation, due to symmetry, but does induce a deformation in the drop shape, which is spheroidal to first order in the capillary number $Ca=\beta k_B T R^2 K/\gamma$, where $\beta$ is the magnitude of the quadrupolar variation in solute concentration, $k_B T$ is the thermal energy, $R$ is the drop radius, $K$ is the Gibbs adsorption length, and $\gamma$ is the interfacial tension. Whether the drop becomes prolate or oblate depends on whether the solute–drop interaction is attractive or repulsive. Therefore, our work shows that in principle, a drop could undergo deformation during diffusiophoresis in a non-uniform solute gradient.

From 2014 to 2020, we compiled radiocarbon ages from the lower 48 states, creating a database of more than 100,000 archaeological, geological, and paleontological ages that will be freely available to researchers through the Canadian Archaeological Radiocarbon Database. Here, we discuss the process used to compile ages, general characteristics of the database, and lessons learned from this exercise in “big data” compilation.

This paper describes a computational investigation of multimode instability growth and multimaterial mixing induced by multiple shock waves in a high-energy-density (HED) environment, where pressures exceed 1 Mbar. The simulations are based on a series of experiments performed at the National Ignition Facility (NIF) and designed as an HED analogue of non-HED shock-tube studies of the Richtmyer–Meshkov instability and turbulent mixing. A three-dimensional computational modelling framework is presented. It treats many complications absent from canonical non-HED shock-tube flows, including distinct ion and free-electron internal energies, non-ideal equations of state, radiation transport and plasma-state mass diffusivities, viscosities and thermal conductivities. The simulations are tuned to the available NIF data, and traditional statistical quantities of turbulence are analysed. Integrated measures of turbulent kinetic energy and enstrophy both increase by over an order of magnitude due to reshock. Large contributions to enstrophy production during reshock are seen from both the baroclinic source and enstrophy–dilatation terms, highlighting the significance of fluid compressibility in the HED regime. Dimensional analysis reveals that Reynolds numbers and diffusive Péclet numbers in the HED flow are similar to those in a canonical non-HED analogue, but conductive Péclet numbers are much smaller in the HED flow due to efficient thermal conduction by free electrons. It is shown that the mechanism of electron thermal conduction significantly softens local spanwise gradients of both temperature and density, which causes a minor but non-negligible decrease in enstrophy production and small-scale mixing relative to a flow without this mechanism.

Glacial retreat in response to warming climates in the arid Xinjiang region of northwestern China directly impacts downstream water resources available for local communities. We used high-resolution satellite imagery from 1969 to 2014 to delineate spatial changes in 54 active glaciers in the upper Kaidu River Basin in the Tian Shan as well as their past expanses during the Little Ice Age (LIA). We manually delineated their boundaries based on the interpretation of glacial, geomorphic and topographic features. From the total glacier surface area, we estimated glacier volume and mass. From 1969 to 2014, glacier area decreased by 10.1 ± 1.0 km2 (relative loss of 34.2 ± 3.5%) and mass by 1.025 ± 0.108 Gt (relative loss of 43 ± 4.6%). From the LIA maximum (est. 1586 CE) to 1969, relative losses were less (25.7 ± 4.3% area loss and 33.1 ± 5.7% mass loss). Our results indicate that glacier recession is accelerating over time and that the glaciers are currently losing over 1.5 times more relative area than elsewhere in the Tian Shan. Using linear and non-linear projections, we estimate that these glaciers may disappear between 2050 and 2150 CE if climatic warming continues at the same pace.

The mechanism through which developmental programming of offspring overweight/obesity following in utero exposure to maternal overweight/obesity operates is unknown but may operate through biologic pathways involving offspring anthropometry at birth. Thus, we sought to examine to what extent the association between in utero exposure to maternal overweight/obesity and childhood overweight/obesity is mediated by birth anthropometry. Analyses were conducted on a retrospective cohort with data obtained from one hospital system. A natural effects model framework was used to estimate the natural direct effect and natural indirect effect of birth anthropometry (weight, length, head circumference, ponderal index, and small-for-gestational age [SGA] or large-for-gestational age [LGA]) for the association between pre-pregnancy maternal body mass index (BMI) category (overweight/obese vs normal weight) and offspring overweight/obesity in childhood. Models were adjusted for maternal and child socio-demographics. Three thousand nine hundred and fifty mother–child dyads were included in analyses (1467 [57.8%] of mothers and 913 [34.4%] of children were overweight/obese). Results suggest that a small percentage of the effect of maternal pre-pregnancy BMI overweight/obesity on offspring overweight/obesity operated through offspring anthropometry at birth (weight: 15.5%, length: 5.2%, head circumference: 8.5%, ponderal index: 2.2%, SGA: 2.9%, and LGA: 4.2%). There was a small increase in the percentage mediated when gestational diabetes or hypertensive disorders were added to the models. Our study suggests that some measures of birth anthropometry mediate the association between maternal pre-pregnancy overweight/obesity and offspring overweight/obesity in childhood and that the size of this mediated effect is small.

Analysis of human remains and a copper band found in the center of a Late Archaic (ca. 5000–3000 cal BP) shell ring demonstrate an exchange network between the Great Lakes and the coastal southeast United States. Similarities in mortuary practices suggest that the movement of objects between these two regions was more direct and unmediated than archaeologists previously assumed based on “down-the-line” models of exchange. These findings challenge prevalent notions that view preagricultural Native American communities as relatively isolated from one another and suggest instead that wide social networks spanned much of North America thousands of years before the advent of domestication.

Human alteration of the planet’s terrestrial landscapes for agriculture, habitation and commerce is reshaping wildlife communities. The threat of land cover change to wildlife is pronounced in regions with rapidly growing human populations. We investigated how species richness and species-specific occurrence of bats changed as a function of land cover and canopy (tree) cover across a rapidly changing region of Florida, USA. Contrary to our predictions, we found negligible effects of agriculture and urban development on the occurrence of all species. In contrast, we found that a remotely sensed metric of canopy cover on a broad scale (25 km2) was a good predictor of the occurrence of eight out of ten species. The occurrence of all smaller bats (vespertilionids) in our study increased with 0–50% increases in canopy cover, while larger bats showed different patterns. Occurrence of Brazilian free-tailed bats (Tadarida brasiliensis) decreased with increasing canopy cover, and Florida bonneted bats (Eumops floridanus) were not influenced by canopy cover. We conclude that remotely sensed measures of canopy cover can provide a more reliable predictor of bat species richness than land-cover types, and efforts to prevent the loss of bat diversity should consider maintaining canopy cover across mosaic landscapes with diverse land-cover types.

Hypertrophic cardiomyopathy has a range of clinical severity in children. Treatment options are limited, mainly on account of small patient size. Disopyramide is a sodium channel blocker with negative inotropic properties that effectively reduces left ventricular outflow tract gradients in adults with hypertrophic cardiomyopathy, but its efficacy in children is uncertain. A retrospective chart review of patients ⩽21 years of age with hypertrophic cardiomyopathy at our institution and treated with disopyramide was performed. Left ventricular outflow tract Doppler gradients before and after disopyramide initiation were compared as the primary outcome measure. Nine patients received disopyramide, with a median age of 5.6 years (range 6 days–12.9 years). The median left ventricular outflow tract Doppler gradient before initiation of disopyramide was 81 mmHg (range 30–132 mmHg); eight patients had post-initiation echocardiograms, in which the median lowest recorded Doppler gradient was 43 mmHg (range 15–100 mmHg), for a median % reduction of 58.2% (p=0.002). With median follow-up of 2.5 years, eight of nine patients were still alive, although disopyramide had been discontinued in six of the nine patients. Reasons for discontinuation included septal myomectomy (four patients), heart transplantation (one patient), and side effects (one patient). Disopyramide was effective for the relief of left ventricular outflow tract obstruction in children with hypertrophic cardiomyopathy, although longer-term data suggest that its efficacy is not sustained. In general, it was well tolerated. Further study in larger patient populations is warranted.

The Neotoma Paleoecology Database is a community-curated data resource that supports interdisciplinary global change research by enabling broad-scale studies of taxon and community diversity, distributions, and dynamics during the large environmental changes of the past. By consolidating many kinds of data into a common repository, Neotoma lowers costs of paleodata management, makes paleoecological data openly available, and offers a high-quality, curated resource. Neotoma’s distributed scientific governance model is flexible and scalable, with many open pathways for participation by new members, data contributors, stewards, and research communities. The Neotoma data model supports, or can be extended to support, any kind of paleoecological or paleoenvironmental data from sedimentary archives. Data additions to Neotoma are growing and now include >3.8 million observations, >17,000 datasets, and >9200 sites. Dataset types currently include fossil pollen, vertebrates, diatoms, ostracodes, macroinvertebrates, plant macrofossils, insects, testate amoebae, geochronological data, and the recently added organic biomarkers, stable isotopes, and specimen-level data. Multiple avenues exist to obtain Neotoma data, including the Explorer map-based interface, an application programming interface, the neotoma R package, and digital object identifiers. As the volume and variety of scientific data grow, community-curated data resources such as Neotoma have become foundational infrastructure for big data science.

The above published article by Handschin et al. contains an error in the spelling of an author's name.

Brain Hitsman, should read: Brian Hitsman

This error has now been rectified in the online version of this article.