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Mobile stroke units have CT scanners and personnel trained to administer tissue plasminogen activator. In a multicity trial, functional outcomes at 90 days after acute stroke were better with mobile stroke units than with standard care by emergency medical services and transfer to an emergency department.

The value of Science, Technology, Engineering, and Mathematics (STEM) education for building discipline knowledge, critical thinking, and problem-solving skills, aligned with students' needs to function productively within the complex and challenging future workforce, has become a recurring topic in education. However, limited research exists to help school leaders understand the role that vision, professional development, and resources play in leadership in P-12 schools. This investigation offers insight by adding to the existing body of research by helping school leaders further understand how vision, professional development, and resources may lead to school success. In this mixed-methods concurrent study, we report on the school leader as the instructional leader in four urban Pre-12 districts in Alabama that had STEM-certified and non-STEM schools. Through surveys and qualitative focus groups, we investigated school leaders’ understanding and importance of vision, professional development, and resources of all schools and then compared these by school type. Although through this study no statistically significant differences were revealed between the types of schools regarding vision, professional development, and resources, focus groups participants said there was a difference in the type of professional development STEM offered. We conclude with implications for practice and a discussion of ideas on how future interdisciplinary professional development can be conceptualized.

Over the past three decades the minority teacher shortage in the United States reached crisis proportions. Attempts to reverse this trend resulted in concerted efforts to recruit and retain minority, particularly African American, teacher education students. Much of the research focused on 18–22 year olds who enrolled in traditional four-year teacher preparation programs. The existing literature contributed to an understanding of what enabled traditional age undergraduates to persist in college, but failed to provide insight into factors that contributed to the persistence of nontraditional African Americans in extended, or five-year, teacher education programs. This study described a population of successful, African American nontraditional teacher education students who persisted to the bachelor's degree in an extended teacher education program. Using qualitative research methods, the study revealed that peer and program support and the students' investment of resources were factors that contributed to persistence in the teacher education program. Potential barriers to persistence related to miscommunication and inadequate flow of communication of information, which contributed to the students' mistrust of program administrators. The findings of this study reiterate the significance of noncognitive factors in understanding the persistence decisions of African American college students. Attention to methods of enhancing social support, student-faculty interaction, and communication is necessary to facilitate the persistence and graduation of nontraditional African American teacher education students in extended teacher education programs.

The most common causes of chronic liver disease are excess alcohol intake, viral hepatitis and non-alcoholic fatty liver disease, with the clinical spectrum ranging in severity from hepatic inflammation to cirrhosis, liver failure or hepatocellular carcinoma (HCC). The genome of HCC exhibits diverse mutational signatures, resulting in recurrent mutations across more than 30 cancer genes 1 – 7 . Stem cells from normal livers have a low mutational burden and limited diversity of signatures 8 , which suggests that the complexity of HCC arises during the progression to chronic liver disease and subsequent malignant transformation. Here, by sequencing whole genomes of 482 microdissections of 100–500 hepatocytes from 5 normal and 9 cirrhotic livers, we show that cirrhotic liver has a higher mutational burden than normal liver. Although rare in normal hepatocytes, structural variants, including chromothripsis, were prominent in cirrhosis. Driver mutations, such as point mutations and structural variants, affected 1–5% of clones. Clonal expansions of millimetres in diameter occurred in cirrhosis, with clones sequestered by the bands of fibrosis that surround regenerative nodules. Some mutational signatures were universal and equally active in both non-malignant hepatocytes and HCCs; some were substantially more active in HCCs than chronic liver disease; and others—arising from exogenous exposures—were present in a subset of patients. The activity of exogenous signatures between adjacent cirrhotic nodules varied by up to tenfold within each patient, as a result of clone-specific and microenvironmental forces. Synchronous HCCs exhibited the same mutational signatures as background cirrhotic liver, but with higher burden. Somatic mutations chronicle the exposures, toxicity, regeneration and clonal structure of liver tissue as it progresses from health to disease. Whole-genome sequencing of liver microdissections from five healthy individuals and nine with cirrhosis demonstrates the effects of liver disease on the genome, including increased rates of mutation, complex structural variation and different mutational signatures.

All normal somatic cells are thought to acquire mutations, but understanding of the rates, patterns, causes and consequences of somatic mutations in normal cells is limited. The uterine endometrium adopts multiple physiological states over a lifetime and is lined by a gland-forming epithelium 1 , 2 . Here, using whole-genome sequencing, we show that normal human endometrial glands are clonal cell populations with total mutation burdens that increase at about 29 base substitutions per year and that are many-fold lower than those of endometrial cancers. Normal endometrial glands frequently carry ‘driver’ mutations in cancer genes, the burden of which increases with age and decreases with parity. Cell clones with drivers often originate during the first decades of life and subsequently progressively colonize the epithelial lining of the endometrium. Our results show that mutational landscapes differ markedly between normal tissues—perhaps shaped by differences in their structure and physiology—and indicate that the procession of neoplastic change that leads to endometrial cancer is initiated early in life. Whole-genome sequencing of normal human endometrial glands shows that most are clonal cell populations and frequently carry cancer driver mutations that occur early in life, and that parity has a protective effect.

Over the course of an individual’s lifetime, normal human cells accumulate mutations 1 . Here we compare the mutational landscape in 29 cell types from the soma and germline using multiple samples from the same individuals. Two ubiquitous mutational signatures, SBS1 and SBS5/40, accounted for the majority of acquired mutations in most cell types, but their absolute and relative contributions varied substantially. SBS18, which potentially reflects oxidative damage 2 , and several additional signatures attributed to exogenous and endogenous exposures contributed mutations to subsets of cell types. The rate of mutation was lowest in spermatogonia, the stem cells from which sperm are generated and from which most genetic variation in the human population is thought to originate. This was due to low rates of ubiquitous mutational processes and may be partially attributable to a low rate of cell division in basal spermatogonia. These results highlight similarities and differences in the maintenance of the germline and soma. The authors report the mutational landscape of 29 cell types from microdissected biopsies from 19 organs and explore the mechanisms underlying mutation rates in normal tissues.

The progression of chronic liver disease to hepatocellular carcinoma is caused by the acquisition of somatic mutations that affect 20–30 cancer genes 1 – 8 . Burdens of somatic mutations are higher and clonal expansions larger in chronic liver disease 9 – 13 than in normal liver 13 – 16 , which enables positive selection to shape the genomic landscape 9 – 13 . Here we analysed somatic mutations from 1,590 genomes across 34 liver samples, including healthy controls, alcohol-related liver disease and non-alcoholic fatty liver disease. Seven of the 29 patients with liver disease had mutations in FOXO1 , the major transcription factor in insulin signalling. These mutations affected a single hotspot within the gene, impairing the insulin-mediated nuclear export of FOXO1. Notably, six of the seven patients with FOXO1 S22W hotspot mutations showed convergent evolution, with variants acquired independently by up to nine distinct hepatocyte clones per patient. CIDEB , which regulates lipid droplet metabolism in hepatocytes 17 – 19 , and GPAM , which produces storage triacylglycerol from free fatty acids 20 , 21 , also had a significant excess of mutations. We again observed frequent convergent evolution: up to fourteen independent clones per patient with CIDEB mutations and up to seven clones per patient with GPAM mutations. Mutations in metabolism genes were distributed across multiple anatomical segments of the liver, increased clone size and were seen in both alcohol-related liver disease and non-alcoholic fatty liver disease, but rarely in hepatocellular carcinoma. Master regulators of metabolic pathways are a frequent target of convergent somatic mutation in alcohol-related and non-alcoholic fatty liver disease. Whole-genome sequencing analysis of somatic mutations in liver samples from patients with chronic liver disease identifies driver mutations in metabolism-related genes such as FOXO1 , and shows that these variants frequently exhibit convergent evolution.

The interplay between top-down and bottom-up processes determines ecosystem productivity. Yet, the factors that mediate the balance between these opposing forces remain poorly understood. Furthering this challenge, complex and often cryptic factors like ecosystem engineering and trait-mediated interactions may play major roles in mediating the outcomes of top-down and bottom-up interactions. In semiarid grasslands of northeastern China, we conducted a large-scale, three-year experiment to evaluate how soil engineering by ants and plasticity in plants independently and jointly influenced the top-down effects of grazing by a ubiquitous herbivore (cattle) on aboveground standing biomass of the dominant perennial grass, Leymus chinensis. Herbivory had strong top-down effects, reducing L. chinensis AB by 25% relative to baseline levels without cattle or ants. In contrast, soil engineering by ants facilitated weak bottom-up effects in the absence of herbivory. However, in the presence of herbivory, soil engineering effects were strong enough to fully offset herbivore removal of aboveground biomass. This outcome was mediated by L. chinensis’s plasticity in reallocating growth from below- to aboveground biomass, a result linked to additive effects of engineers and herbivores increasing soil N availability and engineering effects improving soil structure. Soil engineering increased soil N by 12%, promoting aboveground biomass. Herbivores increased soil N by 13% via defecation, but this increase failed to offset their reductions in aboveground biomass in isolation. However, when combined, engineers and herbivores increased soil N by 26% and engineers improved soil bulk density, facilitating L. chinensis to shift resource allocations from below- to aboveground biomass sufficiently to fully offset herbivore suppression of aboveground biomass. Our results demonstrate that soil engineering and trait-mediated effects of plant plasticity can strongly mediate the outcome of top-down and bottom-up interactions. These cryptic but perhaps ubiquitous processes may help to explain the long-debated phenomenon of plant compensatory responses to large grazers.

The rates and patterns of somatic mutation in normal tissues are largely unknown outside of humans 1 – 7 . Comparative analyses can shed light on the diversity of mutagenesis across species, and on long-standing hypotheses about the evolution of somatic mutation rates and their role in cancer and ageing. Here we performed whole-genome sequencing of 208 intestinal crypts from 56 individuals to study the landscape of somatic mutation across 16 mammalian species. We found that somatic mutagenesis was dominated by seemingly endogenous mutational processes in all species, including 5-methylcytosine deamination and oxidative damage. With some differences, mutational signatures in other species resembled those described in humans 8 , although the relative contribution of each signature varied across species. Notably, the somatic mutation rate per year varied greatly across species and exhibited a strong inverse relationship with species lifespan, with no other life-history trait studied showing a comparable association. Despite widely different life histories among the species we examined—including variation of around 30-fold in lifespan and around 40,000-fold in body mass—the somatic mutation burden at the end of lifespan varied only by a factor of around 3. These data unveil common mutational processes across mammals, and suggest that somatic mutation rates are evolutionarily constrained and may be a contributing factor in ageing. Whole-genome sequencing is used to analyse the landscape of somatic mutation in intestinal crypts from 16 mammalian species, revealing that rates of somatic mutation inversely scale with the lifespan of the animal across species.

IntroductionInternational interest in a smokefree generation policy has grown as more local authorities and governments move to introduce this policy. Young people strongly support this measure, but we know less about how they view a nicotine-free generation policy that includes electronic nicotine delivery systems (ENDS). We addressed this gap by probing adolescents’ views on a birth-year policy that included all nicotine products.MethodsWe undertook in-depth interviews with 20 adolescents aged 16–18 who self-assessed as moderately or severely addicted to vaping and lived in Aotearoa New Zealand. In semistructured interviews, we explored participants’ views on a nicotine-free generation, its rationale, implementation and likely impact. We interpreted the data using a reflexive thematic analysis approach.ResultsMost participants supported a nicotine-free generation, rejected arguments that ENDS use was a ‘choice’, and called for government leadership to protect them and future generations; a small minority saw the measure as unwarranted interference. Several participants thought compliance would be low, given their experiences of lax age verification practices and the widespread social supply of ENDS, but suggested measures to improve compliance.ConclusionsAlthough participants thought a nicotine-free generation could impose personal hardship, most privileged the freedom they thought it could bring over the illusory ‘choice’ they currently had. Policy-makers should consider looking beyond a smokefree generation to a nicotine-free generation; alongside this measure, they should implement strong enforcement and provide comprehensive support so young people addicted to nicotine can be empowered to stop using ENDS.