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Writing centers have long been a hallmark in supporting the development of student writers at North American academic institutions. Writing centers are often connected to a writing program or learning center open to all students for one-on-one tutorials regarding a writing project. Tutors function as coaches or collaborators, rather than as teachers, to address individual needs. Through active listening, a tutor may engage writers in discussion to help develop ideas, offer reader feedback, and suggest writing strategies (Harris 1988). In an increasingly internationalized academia, and in turn an increased pressure to publish internationally, more initiatives are being made to establish multilingual writing centers in tertiary institutions across the globe. Although this article is framed within a university context, a writing center can adapt to most learning environments, including schools and community-based programs. In this article, the authors share their insights and lessons learned from working with local teams to establish writing centers at two of the universities.

Abstract Scholarship on immigrant stereotypes suggest that individuals’ viewpoints toward immigration may be differentiated across the dimensions of culture and economics. In this study, we use latent class analysis, which avoids the assumption that attitudes are unidimensional, scalar, and polarized, to examine configurations of immigration attitudes in Europe from 2002 through 2010, a period of time leading up to and within the Great Recession. Analyzing a set of items capturing different aspects of immigration attitudes, we discover that although there are substantial segments of the European population who hold polarized anti- or pro-immigration attitudes, the most common viewpoint is ambivalence. Specifically, those with ambivalent attitudes feel that immigration enriches national culture but also believe that immigration has less benefits for the economy. Using an interrupted time series design, we explore how attitudinal configurations shifted with the onset of the Great Recession. The crisis coincided with a rise in ambivalent attitudes as economic threat grew more than concerns about culture.

Background Short-chain fatty acids (SCFAs), produced by the gut microbiota, are thought to exert an anti-inflammatory effect on the host immune system. The levels of SCFAs and abundance of the microbiota that produce them are depleted in multiple sclerosis (MS), an autoimmune disease of the central nervous system (CNS). The mechanisms leading to this depletion are unknown. Using experimental autoimmune encephalomyelitis (EAE) as a model for MS, we have previously shown that gut microbiomes divergent in their abundance of specific commensal Lactobacillaceae, Limosilactobacillus reuteri (L. reuteri) and Ligilactobacillus murinus (L. murinus), differentially impact CNS autoimmunity. To determine the underlying mechanisms, we employed colonization by L. reuteri and L. murinus in disparate gut microbiome configurations in vivo and in vitro, profiling their impact on gut microbiome composition and metabolism, coupled with modulation of dietary fiber in the EAE model.Results We show that stable colonization by L. reuteri, but not L. murinus, exacerbates EAE, in conjunction with a significant remodeling of gut microbiome composition, depleting SCFA-producing microbiota, including Lachnospiraceae, Prevotellaceae, and Bifidobacterium, with a net decrease in bacterial metabolic pathways involved in butyrate production. In a minimal microbiome culture model in vitro, L. reuteri directly inhibited SCFA-producer growth and depleted butyrate. Genomic analysis of L. reuteri isolates revealed an enrichment in bacteriocins with known antimicrobial activity against SCFA-producing microbiota. Functionally, provision of excess dietary fiber, as the prebiotic substrate for SCFA production, elevated SCFA levels and abrogated the ability of L. reuteri to exacerbate EAE.Conclustions Our data highlight a potential mechanism for reduced SCFAs and their producers in MS through depletion by other members of the gut microbiome, demonstrating that interactions between microbiota can impact CNS autoimmunity in a diet-dependent manner. These data suggest that therapeutic restoration of SCFA levels in MS may require not only dietary intervention, but also modulation of the gut microbiome.

In Australia, antimicrobials are given an importance rating by the Australian Strategic and Technical Advisory Group on antimicrobial resistance. High importance antimicrobials are those essential for the treatment or prevention of infections in humans, where there are few or no treatment alternatives. In this study we consulted with experts from across human and animal health using the Delphi consensus-building process to establish the circumstances under which antimicrobials with high importance to human health could be used in animals in Australia. We used three rounds of online surveys. Group responses were provided to participants in each subsequent round to facilitate convergence of opinion. Consensus was defined as 80 % or more of respondents selecting the same option for a question. By the end of the third round, consensus was achieved on eight items. This included the use of high importance antimicrobials being appropriate if culture and sensitivity testing indicated the organism was resistant to low- and medium-rated antimicrobials that could be used to treat the case. If any high-importance antimicrobials are prescribed for animals there was also agreement that a clear indication for this use and justification for antimicrobial choice must be recorded in the medical history, along with the dose rate, route of administration, the duration and the time point for review of the condition and associated antimicrobial therapy.Appropriateness of use of high importance antimicrobials in critically ill animals where culture and sensitivity results are not available is still undefined. Further work is also required to establish which particular organisation should be notified of the use of high importance antimicrobials not registered for use in animals. The Delphi process was valuable in facilitating consensus amongst international experts from a broad range of health backgrounds and experience.

Synthesis research in ecology and environmental science improves understanding, advances theory, identifies research priorities, and supports management strategies by linking data, ideas, and tools. Accelerating environmental challenges increases the need to focus synthesis science on the most pressing questions. To leverage input from the broader research community, we convened a virtual workshop with participants from many countries and disciplines to examine how and where synthesis can address key questions and themes in ecology and environmental science in the coming decade. Seven priority research topics emerged: (1) diversity, equity, inclusion, and justice (DEIJ), (2) human and natural systems, (3) actionable and use-inspired science, (4) scale, (5) generality, (6) complexity and resilience, and (7) predictability. Additionally, two issues regarding the general practice of synthesis emerged: the need for increased participant diversity and inclusive research practices; and increased and improved data flow, access, and skill-building. These topics and practices provide a strategic vision for future synthesis in ecology and environmental science.

Abstract Critical loads (CLs) are frequently used to quantify terrestrial ecosystem impacts from nitrogen (N) deposition using ecological responses such as the growth and mortality of tree species. Typically, CLs are reported as a single value, with uncertainty, for an indicator across a species' entire range. Mediating factors such as climate and soil conditions can influence species' sensitivity to N, but the magnitudes of these effects are rarely calculated explicitly. Here, we quantify the spatial variability and estimation error in N CLs for the growth and survival of 10 different tree species while accounting for key environmental factors that mediate species sensitivity to N (e.g., soil characteristics). We used a bootstrapped machine learning approach to determine the level of N deposition at which a 1% decrease occurs in growth rate or survival probability at forest plot locations across the United States. We found minimal differences (8.5 kg N ha−1 year−1) within these regimes. We also evaluated the most important factors for predicting tree growth rates and mortality and found that climate, competition, and air pollution generally have the greatest influence on growth rates and survival probability. Lastly, we developed a new probability of exceedance metric for each species and found high likelihoods of exceedance across large portions (46%) of some species' ranges. Our analysis demonstrates that machine learning approaches provide a unique capability to: (1) quantify mediating factor influences on N sensitivity of trees, (2) estimate the error in local N CL estimates, and (3) generate localized N CLs with probabilities of exceedance for tree species.

Addiction is characterized by continued drug use despite negative consequences. In an animal model, a subset of rats continues to self-administer cocaine despite footshock consequences, showing punishment resistance. We sought to test the hypothesis that punishment resistance arises from failure to exert goal-directed control over habitual cocaine seeking. While habits are not inherently permanent or maladaptive, continued use of habits under conditions that should encourage goal-directed control makes them maladaptive and inflexible. We trained male and female Sprague Dawley rats on a seeking-taking chained schedule of cocaine self-administration. We then exposed them to four days of punishment testing in which footshock was delivered randomly on one-third of trials. Before and after punishment testing (four days pre-punishment and ≥ four days post-punishment), we assessed whether cocaine seeking was goal-directed or habitual using outcome devaluation via cocaine satiety. We found that punishment resistance was associated with continued use of habits, whereas punishment sensitivity was associated with increased goal-directed control. Although punishment resistance for cocaine was not predicted by habitual responding pre-punishment, it was associated with habitual responding post-punishment. In parallel studies of food self-administration, we similarly observed that punishment resistance was associated with habitual responding post-punishment but not pre-punishment in males, although it was associated with habitual responding both pre- and post-punishment in females, indicating that punishment resistance was predicted by habitual responding in food-seeking females. These findings indicate that punishment resistance is related to habits that have become inflexible and persist under conditions that should encourage a transition to goal-directed behavior.

Abstract Human immunodeficiency virus (HIV) and human T cell leukemia virus (HTLV) have replicative and latent stages of infection. The status of the viruses is dependent on the cells that harbour them and on different events that change the transcriptional and post-transcriptional events. Non-coding (nc)RNAs are key factors in the regulation of retrovirus replication cycles. Notably, micro (mi)RNAs and long non-coding (lnc)RNAs are important regulators that can induce switches between active transcription-replication and latency of retroviruses and have important impacts on their pathogenesis. Here, we review the functions of miRNAs and lncRNAs in the context of HIV and HTLV. We describe how specific miRNAs and lncRNAs are involved in the regulation of the viruses’ transcription, post-transcriptional regulation and latency. We further discuss treatment strategies using ncRNAs for HIV and HTLV long remission, reactivation or possible cure.

ABSTRACTClinicians seek an accurate method to assess muscle contractility during activities to better guide treatment. We investigated application of a conductive electroactive polymer sensor as a novel wearable surface mechanomyography (sMMG) sensor for quantifying muscle contractility. The radial displacement of a muscle during a contraction is detected by the physically stretched dielectric elastomer component of the sMMG sensor which quantifies the changes in capacitance. The duration of muscle activation times for quadriceps, hamstrings, and gastrocnemius muscles demonstrated strong correlation between sMMG and EMG during a parallel squat activity and isometric contractions. A moderate to strong correlation was demonstrated between the sMMG isometric muscle activation times and force output times from a dynamometer. The potential wearable application of an electroactive polymer sensor to measure muscle contraction time is supported.

Small genes (40,000 small-gene families in ∼2.3 million phage genome contigs. We find that small genes in phage genomes are approximately 3-fold more prevalent than in host prokaryotic genomes. Our approach enriches for small genes that are translated in microbiomes, suggesting the small genes identified are coding. More than 9,000 families encode potentially secreted or transmembrane proteins, more than 5,000 families encode predicted anti-CRISPR proteins, and more than 500 families encode predicted antimicrobial proteins. By combining homology and genomic-neighborhood analyses, we reveal substantial novelty and diversity within phage biology, including small phage genes found in multiple host phyla, small genes encoding proteins that play essential roles in host infection, and small genes that share genomic neighborhoods and whose encoded proteins may share related functions.

Key Clinical Message If patient anatomy or disease does not allow for a traditional or partial cholecystectomy, an omental pedicle plug may be a viable option to limit the risk of postoperative uncontrolled bile leak from the cystic duct and to control patient symptoms.

Abstract Premise Traditional moist chamber cultures (MCs) prepared in aseptic laboratory environments using sterile Petri dishes are commonly used to quantify the microbiota of rough‐bark tree species and woody vines. MCs are typically expensive and may be difficult to make, so a less expensive option made from easily available supplies was developed. These cost‐friendly MCs were compared with standard laboratory methods to demonstrate their efficacy. Methods and Results Modified MCs were made using inexpensive, store‐bought supplies; compared to a standard laboratory setting, the modified MCs are shown to be less expensive with a faster setup time and larger size that facilitates a variety of tree and woody vine species. MC use resulted in the discovery of new species of fungi and myxomycetes with associated locality records. We provide detailed instructions for creating modified MCs, as well as a list of myxomycete species and their associated bark characteristics, pH values, and water‐holding capacity. Conclusions This new, low‐cost MC technique makes the study of microbiota more inclusive and accessible for those in research laboratories, classrooms, and homes, including both amateurs and professionals. MCs are easy to prepare, versatile, and applicable for many areas of botany and the biological sciences, potentially allowing exploration into unexplored areas in urban ecosystems.

BackgroundThe soft drinks industry levy (SDIL) in the United Kingdom has led to a significant reduction in household purchasing of sugar in drinks. In this study, we examined the potential medium- and long-term implications for health and health inequalities among children and adolescents in England.Methods and findingsWe conducted a controlled interrupted time series analysis to measure the effects of the SDIL on the amount of sugar per household per week from soft drinks purchased, 19 months post implementation and by index of multiple deprivation (IMD) quintile in England. We modelled the effect of observed sugar reduction on body mass index (BMI), dental caries, and quality-adjusted life years (QALYs) in children and adolescents (0 to 17 years) by IMD quintile over the first 10 years following announcement (March 2016) and implementation (April 2018) of the SDIL. Using a lifetable model, we simulated the potential long-term impact of these changes on life expectancy for the current birth cohort and, using regression models with results from the IMD-specific lifetable models, we calculated the impact of the SDIL on the slope index of inequality (SII) in life expectancy. The SDIL was found to have reduced sugar from purchased drinks in England by 15 g/household/week (95% confidence interval: -10.3 to -19.7). The model predicts these reductions in sugar will lead to 3,600 (95% uncertainty interval: 946 to 6,330) fewer dental caries and 64,100 (54,400 to 73,400) fewer children and adolescents classified as overweight or obese, in the first 10 years after implementation. The changes in sugar purchasing and predicted impacts on health are largest for children and adolescents in the most deprived areas (Q1: 11,000 QALYs [8,370 to 14,100] and Q2: 7,760 QALYs [5,730 to 9,970]), while children and adolescents in less deprived areas will likely experience much smaller simulated effects (Q3: -1,830 QALYs [-3,260 to -501], Q4: 652 QALYs [-336 to 1,680], Q5: 1,860 QALYs [929 to 2,890]). If the simulated effects of the SDIL are sustained over the life course, it is predicted there will be a small but significant reduction in slope index of inequality: 0.76% (95% uncertainty interval: -0.9 to -0.62) for females and 0.94% (-1.1 to -0.76) for males.ConclusionsWe predict that the SDIL will lead to medium-term reductions in dental caries and overweight/obesity, and long-term improvements in life expectancy, with the greatest benefits projected for children and adolescents from more deprived areas. This study provides evidence that the SDIL could narrow health inequalities for children and adolescents in England.

Depression during pregnancy is detrimental for the wellbeing of the expectant mother and can exert long-term consequences on the offspring's development and mental health. In this context, both the gestational environment and the postpartum milieu may be negatively affected by the depressive pathology. It is, however, challenging to assess whether the contributions of prenatal and postnatal depression exposure are distinct, interactive, or cumulative, as it is unclear whether antenatal effects are due to direct effects on fetal development or because antenatal symptoms continue postnatally. Preclinical models have sought to answer this question by implementing stressors that induce a depressive-like state in the dams during pregnancy and studying the effects on the offspring. The aim of our present study was to disentangle the contribution of direct stress in utero from possible changes in maternal behavior in a novel model of preconceptional stress based on social isolation rearing (SIR). Using a cross-fostering paradigm in this model, we show that while SIR leads to subtle changes in maternal behavior, the behavioral changes observed in the offspring are driven by a complex interaction between sex, and prenatal and postnatal maternal factors. Indeed, male offspring are more sensitive to the prenatal environment, as demonstrated by behavioral and transcriptional changes driven by their birth mother, while females are likely affected by more complex interactions between the pre and the postpartum milieu, as suggested by the important impact of their surrogate foster mother. Taken together, our findings suggest that male and female offspring have different time-windows and behavioral domains of susceptibility to maternal preconceptional stress, and thus underscore the importance of including both sexes when investigating the mechanisms that mediate the negative consequences of exposure to such stressor.

Abstract Historically, the NHS did not routinely collect cost data, unlike many countries with private insurance markets. In 1998, for the first time the government mandated NHS trusts to submit estimates of their costs of service, known as reference costs. These have informed a wide range of health economic evaluations and important functions in the health service, such as setting prices. Reference costs are collected by progressively disaggregating budgets top-down into disease and treatment groups. Despite ongoing improvements to methods and guidance, these submissions continued to suffer a lack of accuracy and comparability, fundamentally undermining their credibility for critical functions. To overcome these issues, there was a long-held ambition to collect “patient-level” cost data. Patient-level costs are estimated with a combination of disaggregating budgets but also capturing the patient-level “causality of costs” bottom-up in the allocation of resources to patient episodes. These not only aim to capture more of the drivers of costs, but also improve consistency of reporting between providers. The change in methods may confer improvements to data quality, though judgement is still required and achieving consistency between trusts will take further work. Estimated costs may also change in important ways that may take many years to fully understand. We end on a cautionary note that patient-level cost methods may unlock potential, they alone contribute little to our understanding of the complexities involved with service quality or need, while that potential will require substantial investment to realise. Many healthcare resources cannot be attributed to individual patients so the very notion of “patient-level” costs may be misplaced. High hopes have been put in these new data, though much more work is now necessary to understand their quality, what they show and how their use will impact the system.

BackgroundCOVID-19 outbreaks have occurred in homeless shelters across the US, highlighting an urgent need to identify the most effective infection control strategy to prevent future outbreaks.MethodsWe developed a microsimulation model of SARS-CoV-2 transmission in a homeless shelter and calibrated it to data from cross-sectional polymerase chain reaction (PCR) surveys conducted during COVID-19 outbreaks in five homeless shelters in three US cities from March 28 to April 10, 2020. We estimated the probability of averting a COVID-19 outbreak when an exposed individual is introduced into a representative homeless shelter of 250 residents and 50 staff over 30 days under different infection control strategies, including daily symptom-based screening, twice-weekly PCR testing, and universal mask wearing.ResultsThe proportion of PCR-positive residents and staff at the shelters with observed outbreaks ranged from 2.6 to 51.6%, which translated to the basic reproduction number (R0) estimates of 2.9-6.2. With moderate community incidence (~ 30 confirmed cases/1,000,000 people/day), the estimated probabilities of averting an outbreak in a low-risk (R0 = 1.5), moderate-risk (R0 = 2.9), and high-risk (R0 = 6.2) shelter were respectively 0.35, 0.13, and 0.04 for daily symptom-based screening; 0.53, 0.20, and 0.09 for twice-weekly PCR testing; 0.62, 0.27, and 0.08 for universal masking; and 0.74, 0.42, and 0.19 for these strategies in combination. The probability of averting an outbreak diminished with higher transmissibility (R0) within the simulated shelter and increasing incidence in the local community.ConclusionsIn high-risk homeless shelter environments and locations with high community incidence of COVID-19, even intensive infection control strategies (incorporating daily symptom screening, frequent PCR testing, and universal mask wearing) are unlikely to prevent outbreaks, suggesting a need for non-congregate housing arrangements for people experiencing homelessness. In lower-risk environments, combined interventions should be employed to reduce outbreak risk.

We investigated the effect of combination aminoglycoside and vancomycin local antibiotic treatment compared to aminoglycoside alone in the surgical management of bone infection. Data including patient demographics, type of surgery, microbiological characteristics, BACH score, duration of antibiotic treatment and clinical outcomes were collected. Failure of therapy was a composite of recurrence of infection, continued or new antimicrobial therapy, or reoperation with suspected or confirmed infection at one year after index surgery. A total of 266 patients met the inclusion criteria. 252 patients reached the final follow-up and were included in the final analysis. 113 patients had treatment with aminoglycoside alone and 139 patients had combination aminoglycoside and vancomycin. There was no difference in the failure rate between groups; 10/113 (8.8%) in the aminoglycoside alone and 12/139 (8.6%) in the combination group, p = 0.934. Multivariate analysis showed that there was no added benefit of combination therapy (OR 1.54: 95% CI 0.59–4.04, p = 0.38). BACH score and low BMI were associated with increased risk of failure (BACH OR 3.49: 95% CI 1.13–10.76, p = 0.03; Low BMI OR 0.91: 95% CI 0.84–0.99, p = 0.037). The form of the carrier material (pellets or injectable paste) had no effect on failure rate (p = 0.163). The presence of aminoglycoside resistance had no effect on failure rate (OR 0.39: 95% CI 0.05–3.01, p = 0.37). Clinical outcome was not improved by the addition of vancomycin to aminoglycoside alone as local therapy for the management of bone infection.

Objective To determine changes in household purchases of drinks 1 year after implementation of the UK soft drinks industry levy (SDIL).Design Controlled interrupted time series.Participants Households reporting their purchasing to a market research company (average weekly n=22 091), March 2014 to March 2019.Intervention A two-tiered tax levied on soft drinks manufacturers, announced in March 2016 and implemented in April 2018. Drinks with ≥8 g sugar/100 mL (high tier) are taxed at £0.24/L, drinks with ≥5 to

We report the public health response to a coronavirus disease 2019 (COVID-19) outbreak in a San Francisco shelter where 67% of residents and 17% of staff tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We describe the limited utility of case investigation, person-based contact tracing and symptom screening, and the benefits of mass testing in outbreak response.

Abstract Background Although urban residence is consistently identified as one of the primary correlates of non-communicable disease in low- and middle-income countries, it is not clear why or how urban settings predispose individuals and populations to non-communicable disease (NCD), or how this relationship could be modified to slow the spread of NCD. The urban–rural dichotomy used in most population health research lacks the nuance and specificity necessary to understand the complex relationship between urbanicity and NCD risk. Previous studies have developed and validated quantitative tools to measure urbanicity continuously along several dimensions but all have been isolated to a single country. The purposes of this study were 1) To assess the feasibility and validity of a multi-country urbanicity scale; 2) To report some of the considerations that arise in applying such a scale in different countries; and, 3) To assess how this scale compares with previously validated scales of urbanicity. Methods Household and community-level data from the Young Lives longitudinal study of childhood poverty in 59 communities in Ethiopia, India and Peru collected in 2006/2007 were used. Household-level data include parents’ occupations and education level, household possessions and access to resources. Community-level data include population size, availability of health facilities and types of roads. Variables were selected for inclusion in the urbanicity scale based on inspection of the data and a review of literature on urbanicity and health. Seven domains were constructed within the scale: Population Size, Economic Activity, Built Environment, Communication, Education, Diversity and Health Services. Results The scale ranged from 11 to 61 (mean 35) with significant between country differences in mean urbanicity; Ethiopia (30.7), India (33.2), Peru (39.4). Construct validity was supported by factor analysis and high corrected item-scale correlations suggest good internal consistency. High agreement was observed between this scale and a dichotomized version of the urbanicity scale (Kappa 0.76; Spearman’s rank-correlation coefficient 0.84 (p Conclusions This study demonstrates and validates a robust multidimensional, multi-country urbanicity scale. It is an important step on the path to creating a tool to assess complex processes like urbanization. This scale provides the means to understand which elements of urbanization have the greatest impact on health.

Abstract Background There is a growing literature documenting socioeconomic inequalities in obesity risk among adults in the UK, with poorer groups suffering higher risk. Methods In this systematic review, we summarize and appraise the extant peer-reviewed literature about socioeconomic inequalities in adult obesity risk in the UK published between 1980 and 2010. Only studies featuring empirical assessments of relations between socioeconomic indicators and measures of obesity among adults in the UK were included. Results A total of 35 articles met inclusion criteria, and were reviewed here. Conclusion Socioeconomic indicators of low socioeconomic position (SEP), including occupational social class of the head-of-household at birth and during childhood, earlier adulthood occupational social class, contemporaneous occupational social class, educational attainment, and area-level deprivation were generally inversely associated with adult obesity risk in the UK. Measures of SEP were more predictive of obesity among women than among men. We outline important methodological limitations to the literature and recommend avenues for future research.

Inquiry- and context-based learning (IBL and CBL, respectively) can lead to improved student outcomes, including increased motivation and interest, the development of critical thinking skills, and improved assessment results. This study outlines the application of IBL research projects in third-year university Environmental Chemistry and Analytical Chemistry subjects that also incorporate elements of CBL. Informal student surveys were administered to determine student perceptions of the projects. Students reported that the projects improved their critical thinking, communication, and experimental design skills. They also appreciated being able to investigate a single topic in depth and that the projects reflected the work of real scientists. Students also commented that subject administration, the clarity of marking schemes, and access to resources needed improvement. Improved guidance was also a common theme.

Abstract Background There is considerable geographic variation in stroke mortality around the United Kingdom (UK). Whether this is due to geographical differences in incidence or case-fatality is unclear. We conducted a systematic review of high-quality studies documenting the incidence of any stroke and stroke subtypes, between 1985 and 2008 in the UK. We aimed to study geographic and temporal trends in relation to equivalent mortality trends. Methods MEDLINE and EMBASE were searched, reference lists inspected and authors of included papers were contacted. All rates were standardised to the European Standard Population for those over 45, and between 45 and 74 years. Stroke mortality rates for the included areas were then calculated to produce rate ratios of stroke mortality to incidence for each location. Results Five papers were included in this review. Geographic variation was narrow but incidence appeared to largely mirror mortality rates for all stroke. For men over 45, incidence (and confidence intervals) per 100,000 ranged from 124 (109-141) in South London, to 185 (164-208) in Scotland. For men, premature (45-74 years) stroke incidence per 100,000 ranged from 79 (67-94) in the North West, to 112 (95-132) in Scotland. Stroke subtype data was more geographically restricted, but did suggest there is no sizeable variation in incidence by subtype around the country. Only one paper, based in South London, had data on temporal trends. This showed that there has been a decline in stroke incidence since the mid 1990 s. This could not be compared to any other locations in this review. Conclusions Geographic variations in stroke incidence appear to mirror variations in mortality rates. This suggests policies to reduce inequalities in stroke mortality should be directed at risk factor profiles rather than treatment after a first incident event. More high quality stroke incidence data from around the UK are needed before this can be confirmed.

Public schools in the United States saw unprecedented reductions to in-person instruction during the 2020–2021 school year. Using the Elementary School Operating Status database, the American Community Survey, and the Current Population Survey, we show remote instruction was associated with reduced employment among mothers compared with fathers and women without children. The gender gap in employment between mothers and fathers grew as much as 5 percentage points in areas with remote instruction. Compared to women without children, mothers’ employment fell by as much as 2 percentage points under remote schooling. Employment disparities among mothers deepened by race, educational attainment, and marital status. We show employment disparities endured through spring 2021, even as many school districts returned to in-person instruction.

Abstract Precision medicine offers remarkable potential for the treatment of cancer, but is largely focused on tumors that harbor actionable mutations. Gene expression signatures can expand the scope of precision medicine by predicting response to traditional (cytotoxic) chemotherapy agents without relying on changes in mutational status. We present a new signature extraction method, inspired by the principle of convergent phenotypes, which states that tumors with disparate genetic backgrounds may evolve similar phenotypes independently. This evolutionary-informed method can be utilized to produce consensus signatures predictive of response to over 200 chemotherapeutic drugs found in the Genomics of Drug Sensitivity in Cancer (GDSC) Database. Here, we demonstrate its use by extracting the Cisplatin Response Signature (CisSig). We show that this signature can predict cisplatin response within carcinoma-based cell lines from the GDSC database, and expression of the signatures aligns with clinical trends seen in independent datasets of tumor samples from The Cancer Genome Atlas (TCGA) and Total Cancer Care (TCC) database. Finally, we demonstrate preliminary validation of CisSig for use in muscle-invasive bladder cancer, predicting overall survival in a small cohort of patients who undergo cisplatin-containing chemotherapy. This methodology can be used to produce robust signatures that, with further clinical validation, may be used for the prediction of traditional chemotherapeutic response, dramatically increasing the reach of personalized medicine in cancer.

Abstract Background There is a lack of evidence on the usefulness, practicality, and acceptance of vaccination outreach clinics in the community especially during pandemics. In this qualitative study, we explored the experiences, motivations and perceptions of service users, health professionals, strategic staff, volunteers, and community workers involved in the COVID-19 vaccination outreach clinics in Luton. Methods Semi structured face to face, telephone, online interviews, and focus groups were conducted with 31 participants including health professionals, strategic staff, volunteers, community workers and service users. The Framework Method was used to analyse the data and generate themes. Results Service users expressed positivity towards the convenience and familiarity of the location of the vaccination outreach clinics and the flexibility of receiving the vaccination in a local setting. Participants involved in the planning and delivery of the service commented on the worthwhile and rewarding experience but suggested more attention should be given to preparation time, service user recruitment, the working environment, and staff welfare. Conclusions The COVID-19 mobile vaccination outreach clinics in Luton tested and developed a different model of service delivery and demonstrated a collaborative way of working: “taking the health service to the patient, not the patient to the health service”. Planning and local community engagement were seen as key to successful delivery of a mobile healthcare service.

Abstract Background Coronary heart disease (CHD) rates in England and Wales between 1950 and 2005 were high and reasonably steady until the mid 1970s, when they began to fall. Recent work suggests that the rate of change in some groups has begun to decrease and may be starting to plateau or even reverse. Methods Data for all deaths between 1931 and 2005 in England and Wales were grouped by year, sex, age at death and contemporaneous ICD code for CHD as cause of death. CHD mortality rates by calendar year and birth cohort were produced for both sexes and rates of change were examined. Results The pattern of increased burden of CHD mortality within older age groups has only recently emerged in men, whereas it has been established in women for far longer. CHD mortality rates among younger people showed little variation by birth cohort. For younger women (49 and under), the rate of change in CHD mortality has reversed in the last 20 years, indicating a future plateau and possible reversal of previous improvement in CHD mortality rates. Among younger men the rate of change in CHD mortality has been consistent for the past 15 years indicating that rates in this group have continued to fall steadily. Conclusion Although CHD mortality rates continue to drop in older age groups the actual burden of coronary heart disease is increasing due to the ageing of the population. The rate of improvement in CHD mortality appears to be beginning to decline and may even be reversing among younger women.

The Ancestral Puebloans occupied Chaco Canyon, in what is now the southwestern USA, for more than a millennium and harvested useful timber and fuel from the trees of distant forests as well as local woodlands, especially juniper and pinyon pine. These pinyon juniper woodland products were an essential part of the resource base from Late Archaic times (3000-100 BC) to the Bonito phase (AD 800-1140) during the great florescence of Chacoan culture. During this vast expanse of time, the availability of portions of the woodland declined. We posit, based on pollen and macrobotanical remains, that the Chaco Canyon woodlands were substantially impacted during Late Archaic to Basketmaker II times (100 BC-AD 500) when agriculture became a major means of food production and the manufacture of pottery was introduced into the canyon. By the time of the Bonito phase, the local woodlands, especially the juniper component, had been decimated by centuries of continuous extraction of a slow-growing resource. The destabilizing impact resulting from recurrent woodland harvesting likely contributed to the environmental unpredictability and difficulty in procuring essential resources suffered by the Ancestral Puebloans prior to their ultimate departure from Chaco Canyon.

Proteins are an abundant biopolymer in organic waste feedstocks for biorefining. When degraded, amino acids are released, but their fate in non-methanogenic microbiomes is not well understood. The ability of a microbiome obtained from an anaerobic digester to produce volatile fatty acids from the twenty proteinogenic amino acids was tested using batch experiments. Batch tests were conducted using an initial concentration of each amino acid of 9000 mg COD L−1 along with 9000 mg COD L−1 acetate. Butyrate production was observed from lysine, glutamate, and serine fermentation. Lesser amounts of propionate, iso-butyrate, and iso-valerate were also observed from individual amino acids. Based on 16S rRNA gene amplicon sequencing, Anaerostignum, Intestimonas, Aminipila, and Oscillibacter all likely play a role in the conversion of amino acids to butyrate. The specific roles of other abundant taxa, including Coprothermobacter, Fervidobacterium, Desulfovibrio, and Wolinella, remain unknown, but these genera should be studied for their role in fermentation of amino acids and proteins to VFAs.

BackgroundTaxes on sugar-sweetened beverages (SSBs) have been implemented globally to reduce the burden of cardiometabolic diseases by disincentivizing consumption through increased prices (e.g., 1 peso/litre tax in Mexico) or incentivizing industry reformulation to reduce SSB sugar content (e.g., tiered structure of the United Kingdom [UK] Soft Drinks Industry Levy [SDIL]). In Germany, where no tax on SSBs is enacted, the health and economic impact of SSB taxation using the experience from internationally implemented tax designs has not been evaluated. The objective of this study was to estimate the health and economic impact of national SSBs taxation scenarios in Germany.Methods and findingsIn this modelling study, we evaluated a 20% ad valorem SSB tax with/without taxation of fruit juice (based on implemented SSB taxes and recommendations) and a tiered tax (based on the UK SDIL) in the German adult population aged 30 to 90 years from 2023 to 2043. We developed a microsimulation model (IMPACTNCD Germany) that captures the demographics, risk factor profile and epidemiology of type 2 diabetes, coronary heart disease (CHD) and stroke in the German population using the best available evidence and national data. For each scenario, we estimated changes in sugar consumption and associated weight change. Resulting cases of cardiometabolic disease prevented/postponed and related quality-adjusted life years (QALYs) and economic impacts from healthcare (medical costs) and societal (medical, patient time, and productivity costs) perspectives were estimated using national cost and health utility data. Additionally, we assessed structural uncertainty regarding direct, body mass index (BMI)-independent cardiometabolic effects of SSBs and cross-validated results with an independently developed cohort model (PRIMEtime). We found that SSB taxation could reduce sugar intake in the German adult population by 1 g/day (95%-uncertainty interval [0.05, 1.65]) for a 20% ad valorem tax on SSBs leading to reduced consumption through increased prices (pass-through of 82%) and 2.34 g/day (95%-UI [2.32, 2.36]) for a tiered tax on SSBs leading to 30% reduction in SSB sugar content via reformulation. Through reductions in obesity, type 2 diabetes, and cardiovascular disease (CVD), 106,000 (95%-UI [57,200, 153,200]) QALYs could be gained with a 20% ad valorem tax and 192,300 (95%-UI [130,100, 254,200]) QALYs with a tiered tax. Respectively, €9.6 billion (95%-UI [4.7, 15.3]) and €16.0 billion (95%-UI [8.1, 25.5]) costs could be saved from a societal perspective over 20 years. Impacts of the 20% ad valorem tax were larger when additionally taxing fruit juice (252,400 QALYs gained, 95%-UI [176,700, 325,800]; €11.8 billion costs saved, 95%-UI [€6.7, €17.9]), but impacts of all scenarios were reduced when excluding direct health effects of SSBs. Cross-validation with PRIMEtime showed similar results. Limitations include remaining uncertainties in the economic and epidemiological evidence and a lack of product-level data.ConclusionsIn this study, we found that SSB taxation in Germany could help to reduce the national burden of noncommunicable diseases and save a substantial amount of societal costs. A tiered tax designed to incentivize reformulation of SSBs towards less sugar might have a larger population-level health and economic impact than an ad valorem tax that incentivizes consumer behaviour change only through increased prices.

Background COVID-19 outbreaks have occurred in homeless shelters across the US, highlighting an urgent need to identify the most effective infection control strategy to prevent future outbreaks. Methods We developed a microsimulation model of SARS-CoV-2 transmission in a homeless shelter and calibrated it to data from cross-sectional polymerase-chain-reaction (PCR) surveys conducted during COVID-19 outbreaks in five shelters in three US cities from March 28 to April 10, 2020. We estimated the probability of averting a COVID-19 outbreak when an exposed individual is introduced into a representative homeless shelter of 250 residents and 50 staff over 30 days under different infection control strategies, including daily symptom-based screening, twice-weekly PCR testing and universal mask wearing. Results The proportion of PCR-positive residents and staff at the shelters with observed outbreaks ranged from 2.6% to 51.6%, which translated to basic reproduction number ( R 0 ) estimates of 2.9–6.2. The probability of averting an outbreak diminished with higher transmissibility ( R 0 ) within the simulated shelter and increasing incidence in the local community. With moderate community incidence (~30 confirmed cases/1,000,000 people/day), the estimated probabilities of averting an outbreak in a low-risk ( R 0 =1.5), moderate-risk ( R 0 =2.9), and high-risk ( R 0 =6.2) shelter were, respectively: 0.35, 0.13 and 0.04 for daily symptom-based screening; 0.53, 0.20, and 0.09 for twice-weekly PCR testing; 0.62, 0.27 and 0.08 for universal masking; and 0.74, 0.42 and 0.19 for these strategies combined. Conclusions In high-risk homeless shelter environments and locations with high community incidence of COVID-19, even intensive infection control strategies (incorporating daily symptom-screening, frequent PCR testing and universal mask wearing) are unlikely to prevent outbreaks, suggesting a need for non-congregate housing arrangements for people experiencing homelessness. In lower-risk environments, combined interventions should be employed to reduce outbreak risk.

The PNUTS-PP1 complex directly binds to RNA, and interacts with polymerase II and RNA processing factors to control transcriptional elongation rates and slow polymerase II after polyadenylation sites to promote termination. Using a genome-wide CRISPR screen, Devlin et al. identify this complex as a critical suppressor of herpesvirus KSHV gene expression. They further provide evidence that PNUTS-PP1 controls elongation both downstream and upstream of polyadenylation sites on specific viral genes.

Healthy soils are the foundation of our food system and support broad environmental goals, including improved water quality and carbon sequestration. Increasingly, we appreciate that aspects of soil health such as fertility for plants, suppression of disease, and cycling of nutrients are linked to the functional diversity of soil microbial communities. The impact of functional capacity is influenced by farm management, which varies with farm size. Small to medium-size farms, with gross sales of less than $250,00 per year, make up 89% of farms in the United States, despite often being ignored in policy decisions. They are often more integrated into local food systems than larger farms, have greater investment in long-term sustainability due to their tendency to be passed from farmers to children, and are more reliant on soil health than larger farms. We describe a research framework to advance understanding of the soil microbiome and its role in soil health, environmental outcomes, and agricultural sustainability on small and medium farms. Our perspective elevates four research priorities to link the benefits of healthy soil microbiomes from the microscale to the macroscale. We hope this approach will lead to practical applications to enable success in the context of ongoing environmental and economic challenges that affect the agricultural landscape.

Abstract Background Low childhood physical activity levels constitute an important modifiable risk for adult non-communicable disease incidence and subsequent socio-economic burden, but few publications have explored age and sex related patterns within the UK population. The aims were to profile child physical activity data from the Health Survey for England from 2012 (1,732 respondents) and 2015 (5,346 respondents). Methods Reported physical activity episodes were converted to metabolic equivalents with reference to child-specific compendiums. Physical activity levels were aggregated for each domain, and again to produce total physical activity estimates. Contributions from each domain to total physical activity were explored, stratifying for age, sex, socio-economic deprivation, ethnicity, and weight status. Further analyses were run stratifying for physical activity levels. Few differences were detected between the survey iterations. Results Boys reported higher absolute levels of physical activity at all ages and across all domains. For boys and girls, informal activity reduces with age. For boys this reduction is largely mitigated by increased formal sport, but this is not the case for girls. Absolute levels of school activity and active travel remained consistent regardless of total physical activity, thereby comprising an increasingly important proportion of total physical activity for less active children. Conclusions We recommend a specific focus on establishing and maintaining girl’s participation in formal sport thorough their teenage years, and a recognition and consolidation of the important role played by active travel and school-based physical activity for the least active children.