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Young people with developmental language disorder (DLD) often have poorer mental health compared to those without DLD. However, not all young people with DLD experience such difficulties. Two hundred and eighty-one young people at risk of DLD (45% Female; 53% White British) were identified from a UK based population-cohort. Main caregivers completed questionnaires about their early life (<5 years) and their mental health (at 14 years). Parent-child conflict was revealed to be an early risk factor for all mental health outcomes, at age 14. Additionally, harsh discipline and second-hand smoke predicted worse externalising problems, and gender differences predicted worse internalising problems. Further findings demonstrated that, as the number of risk factors increased, so did the severity of mental health difficulties.

Abstract Background General practitioners (GP) and community pharmacists need information about hospital discharge patients’ medicines to continue their management in the community. This necessitates effective communication, collaboration, and reliable information-sharing. However, such handover is inconsistent, and whilst digital systems are in place to transfer information at transitions of care, these systems are passive and clinicians are not prompted about patients’ transitions. There are also gaps in communication between community pharmacists and GPs. These issues impact patient safety, leading to hospital readmissions and increased healthcare costs. Methods A three-phased, multi-method study design is planned to trial a multifaceted intervention to reduce 30-day hospital readmissions. Phase 1 is the co-design of the intervention with stakeholders and end-users; phase 2 is the development of the intervention; phase 3 is a stepped wedge cluster randomised controlled trial with 20 clusters (community pharmacies). Expected intervention components will be a hospital pharmacist navigator, primary care medication management review services, and a digital solution for information sharing. Phase 3 will recruit 10 patients per pharmacy cluster/month to achieve a sample size of 2200 patients powered to detect a 5% absolute reduction in unplanned readmissions from 10% in the control group to 5% in the intervention at 30 days. The randomisation and intervention will occur at the level of the patient’s nominated community pharmacy. Primary analysis will be a comparison of 30-day medication-related hospital readmissions between intervention and control clusters using a mixed effects Poisson regression model with a random effect for cluster (pharmacy) and a fixed effect for each step to account for secular trends. Trial registration This trial is registered with the Australian New Zealand Clinical Trials Registry: ACTRN12624000480583p , registered 19 April 2024.

Abstract Germline pathogenic TP53 variants predispose individuals to a high lifetime risk of developing multiple cancers and are the hallmark feature of Li-Fraumeni syndrome (LFS). Our group has previously shown that LFS patients harbor shorter plasma cell-free DNA fragmentation; independent of cancer status. To understand the functional underpinning of cfDNA fragmentation in LFS, we conducted a fragmentomic analysis of 199 cfDNA samples from 82 TP53 mutation carriers and 30 healthy TP53-wildtype controls. We find that LFS individuals exhibit an increased prevalence of A/T nucleotides at fragment ends, dysregulated nucleosome positioning at p53 binding sites, and loci-specific changes in chromatin accessibility at development-associated transcription factor binding sites and at cancer-associated open chromatin regions. Machine learning classification resulted in robust differentiation between TP53 mutant versus wildtype cfDNA samples (AUC-ROC = 0.710–1.000) and intra-patient longitudinal analysis of ctDNA fragmentation signal enabled early cancer detection. These results suggest that cfDNA fragmentation may be a useful diagnostic tool in LFS patients and provides an important baseline for cancer early detection.

Objective In 2023 a public panel around public sector data use in Scotland was refreshed. The aim was to have a panel not only feedback on individual research projects but also the broader systems and processes of the data landscape in Scotland – from data sourcing and data storage, to data sharing and communicating research findings. Approach The public panel is a group of c. twenty members of the public and has, to date, focused on: • Recruiting a representative sample of people • Developing training materials to cover all aspects of the data system • Building mechanisms to incorporate feedback into system change • Increasing transparency of the panel discussions to support wider sector (including enhancing our website content and working to develop an annual report) • Embedding findings from discussions with the public panel across the system in Scotland Results Feedback from panel members on recruitment and our approach has been positive. Panel discussions have already influenced ongoing work including synthetic data, website content and research projects. The panel have also begun advising on a system wide change from ‘just in time’ to ‘research ready’ data sets. This work followed a review of current data approvals processes across Scottish Safe Havens and the UK after COVID-19. Conclusions and Implications The current panel membership will run for two years after which a review of approach and impact will be carried out. Increasing transparency of the findings from the panels will enable organisations across the sector to benefit from this work.

Objectives The need for Trusted Research Environments (TREs) is clear. Several influential reports have highlighted that personal or sensitive data which have been collected for operational, commercial or governmental reasons need to be managed securely in an environment that encourages best practices. TREs are designed to enable only authorised projects and researchers access to sensitive data whilst minimising risk of data exposure. Yet the TRE landscape has grown organically over at least the last decade resulting in heterogeneous environments, making it harder for data to be discovered, shared and used for public benefit. A baseline specification for TREs is required. Approach We engaged with around 60 organisations covering government, industry, health and academia through regular, online, shared spaces or “Collaboration Cafés”. We also embedded the public voice within the project by having members of the public within the research team and developed a series of workshops to include and reflect their input to the architecture. The whole project was developed in the open to instil trustworthiness. Results The SATRE project has produced a reference TRE architecture and implementation through significant engagement with the UK TRE community. This baseline specification for UK TREs includes a set of four pillars, 28 capabilities and 160 statements. Conclusions and Implications An open and transparent TRE specification and architecture for a wide range of stakeholders has been developed. TREs can now use the SATRE specification to evaluate their environments against a common baseline.

Abstract We report a case of Mismatch Repair Deficiency (MMRD) caused by germline homozygous EPCAM deletion leading to tissue-specific loss of MSH2. Through the use of patient-derived cells and organoid technologies, we performed stepwise in vitro differentiation of colonic and brain organoids from reprogrammed EPCAMdel iPSC derived from patient fibroblasts. Differentiation of iPSC to epithelial-colonic organoids exhibited continuous increased EPCAM expression and hypermethylation of the MSH2 promoter. This was associated with loss of MSH2 expression, increased mutational burden, MMRD signatures and MS-indel accumulation, the hallmarks of MMRD. In contrast, maturation into brain organoids and examination of blood and fibroblasts failed to show similar processes, preserving MMR proficiency. The combined use of iPSC, organoid technologies and functional genomics analyses highlights the potential of cutting-edge cellular and molecular analysis techniques to define processes controlling tumorigenesis and uncovers a new paradigm of tissue-specific MMRD, which affects the clinical management of these patients.

Structure-from-motion (SfM) photogrammetry has become an important tool for the digitalisation of outcrops as digital outcrop models (DOMs). DOMs facilitate the mapping of stratigraphy and discontinuous structures like folds, faults, and fractures from the centimetre to kilometre scale. With pristine, treeless exposures, the outcropping strata in Svalbard, Arctic Norway, hold exceptional potential for analogue studies and are ideally suited for the acquisition of high-resolution DOMs. Here, we present the acquisition, processing, and integration of the Konusdalen West digital model data set, comprising both DOM and derived digital terrain model (DTM) data. Drone-based image acquisition took place over 2 weeks in July and August 2020. The Konusdalen West DOM and DTM cover a 0.12 km2 area and span a 170 m elevation difference. The DOM covers the upper two-thirds of the mudstone-dominated Late Jurassic–Early Cretaceous Agardhfjellet Formation. The Agardhfjellet Formation and its time equivalents are regional cap rocks for CO2 sequestration and petroleum accumulations on the Norwegian Continental Shelf. A total of 15 differential GNSS control points were used to georeference and quality assure the digital data assets, 5 of which function as reference checkpoints. SfM processing of 5512 acquired images resulted in high-confidence, centimetre-scale resolution point clouds, textured mesh (DOM), tiled model, orthomosaics, and a DTM. The confidence-filtered dense cloud features an average inter-point distance of 1.57 cm and has an average point density of 3824.9 points per metre. The five checkpoints feature root mean square errors of 2.0 cm in X, 1.3 cm in Y, 5.2 cm in Z, and 5.7 cm in XYZ. Increased confidences and densities are present along the western flank of the Konusdalen West outcrop, where a fault fracture network in mudstone-dominated strata is best exposed and photographed most extensively. Top and side view orthomosaics feature maximum resolutions of 8 mm per pixel, enabling the mapping of faults, formation members, marker beds, fractures, and other sub-centimetre features. Additional structural measurements and observations were taken in June 2021 to place the data in the geological context. Data described in this paper can be accessed at Norstore under https://doi.org/10.11582/2022.00027 (Betlem, 2022b).

The opportunity of agricultural management practices to sequester soil organic carbon (SOC) is recognized as an important strategy for mitigating climate change. However, there is low confidence when it comes to understanding the magnitude of the climate benefit we can expect from SOC sequestration or how best to achieve it. Several issues are often confounded when it comes to the mitigation potential of SOC sequestration and greenhouse gas (GHG) reductions from agriculture, creating confusion and making it difficult to clearly identify the knowns, unknowns and risks to implementing policy and practice recommendations. Here, we identify and explain four major areas of uncertainty: (1) the expected changes in soil carbon or GHG emissions resulting from agricultural management practice changes; (2) the extent to which social, environmental and economic factors constrain mitigation potential; (3) the ability to execute reliable measurement, monitoring, reporting and verification (MMRV) frameworks; and (4) the perception of risk associated with different ways of promoting practice adoption (e.g., voluntary carbon markets fueled by the private sector, pay-for-practice programs funded by public investment). We aim to pinpoint knowledge gaps and areas of disagreement to help right-size expectations and guide effective investment in GHG removals and reductions from agriculture.

We investigated the impact of the transition to online architectural design studios in response to the COVID-19 pandemic at the University of New South Wales in Sydney, Australia. The study focussed specifically on student and tutor perceptions of online design studio before the sudden transition to online delivery, and how those perceptions shifted through the initial months of online delivery. We consider the pedagogical context in which the shift to online teaching took place and the evident successes and failures in the early iterations of online studio. We discuss similar and contrasting perceptions in student and tutor groups and observe the changes in these perceptions prior to and after teaching and learning in online studios. The paper concludes with a series of questions directed to the architectural design studio teaching community regarding the apparent inevitability of a future in which both FTF and online-only studios are surpassed with hybrid design studios.

Objectives Venous thromboembolism (VTE) is a major cause of morbidity and mortality globally, with hospital-associated thrombosis (HAT) accounting for at least half of VTE. We set out to understand more about deaths from HAT in England, to focus improvement efforts where they are needed most.Design A retrospective cohort combining death certification and hospital activity data to identify people with an inpatient or day case hospitalisation where no VTE diagnosis was recorded, and who died from VTE in a hospital or within 90 days of discharge, between April 2017 and March 2020.Setting All deaths occurring in England and all National Health Service-funded hospital care in England.Participants After 0.1% of cases were excluded due to duplicate but conflicting records, a cohort of 13 995 deaths remained; 54% were women, and 26% were aged under 70 years.Outcome measures Analysis of age, gender, primary diagnosis, type of admission, specialties and (for day cases) procedure types were preplanned.Results Only 5% of these deaths followed planned inpatient admissions. Day case admissions preceded 7% of VTE deaths. Emergency inpatient admissions, medical specialties and infection-related primary diagnoses predominated in people who died from VTE after hospitalisation where no VTE diagnosis was recorded. Most deaths occurred in a hospital or within 30 days of discharge.Conclusions International efforts to reduce HAT historically focused on planned inpatient admissions. Further initiatives and research to prevent deaths from VTE after hospitalisation should focus on the emergency care pathway where most deaths occurred, with people undergoing day case procedures an important additional focus.

Abstract Background As interest in the voluntary soil carbon market surges, carbon registries have been developing new soil carbon measurement, reporting, and verification (MRV) protocols. These protocols are inconsistent in their approaches to measuring soil organic carbon (SOC). Two areas of concern include the type of SOC stock accounting method (fixed-depth (FD) vs. equivalent soil mass (ESM)) and sampling depth requirement. Despite evidence that fixed-depth measurements can result in error because of changes in soil bulk density and that sampling to 30 cm neglects a significant portion of the soil profile’s SOC stock, most MRV protocols do not specify which sampling method to use and only require sampling to 30 cm. Using data from UC Davis’s Century Experiment (“Century”) and UW Madison’s Wisconsin Integrated Cropping Systems Trial (WICST), we quantify differences in SOC stock changes estimated by FD and ESM over 20 years, investigate how sampling at-depth (> 30 cm) affects SOC stock change estimates, and estimate how crediting outcomes taking an empirical sampling-only crediting approach differ when stocks are calculated using ESM or FD at different depths. Results We find that FD and ESM estimates of stock change can differ by over 100 percent and that, as expected, much of this difference is associated with changes in bulk density in surface soils (e.g., r = 0.90 for Century maize treatments). This led to substantial differences in crediting outcomes between ESM and FD-based stocks, although many treatments did not receive credits due to declines in SOC stocks over time. While increased variability of soils at depth makes it challenging to accurately quantify stocks across the profile, sampling to 60 cm can capture changes in bulk density, potential SOC redistribution, and a larger proportion of the overall SOC stock. Conclusions ESM accounting and sampling to 60 cm (using multiple depth increments) should be considered best practice when quantifying change in SOC stocks in annual, row crop agroecosystems. For carbon markets, the cost of achieving an accurate estimate of SOC stocks that reflect management impacts on soils at-depth should be reflected in the price of carbon credits.

Abstract Modeling the subsistence strategies of prehistoric groups depends on the accuracy of the faunal identifications that provide the basis for these models. However, our knowledge remains limited about the reproducibility of published taxonomic identifications and how they accurately reflect the range of species deposited in the archaeological record. This study compares taxonomic identifications at three Paleolithic sites (Saint-Césaire and Le Piage in France, Crvena Stijena in Montenegro) characterized by high levels of fragmentation. Identifications at these sites were derived using two methods: morphological identification and collagen fingerprinting, the latter a peptide-based approach known as ZooMS. Using a double-blind experimental design, we show that the two methods give taxonomic profiles that are statistically indistinguishable at all three sites. However, rare species and parts difficult to identify such as ribs seem more frequently associated with errors of identification. Comparisons with the indeterminate fraction indicate that large game is over-represented in the ZooMS sample at two of the three sites. These differences possibly signal differential fragmentation of elements from large species. Collagen fingerprinting can produce critical insights on the range distribution of animal prey in the past while also contributing to improved models of taphonomic processes and subsistence behavior.

Psychoeducation, where clinicians teach problem-solving skills in a supportive environment, can help address families' social vulnerabilities and promote well-being. Group well-child care (GWCC) may provide unique opportunities for pediatric residents to improve their skills in psychoeducation. Our aim was to characterize pediatric residents' perspectives and experiences of communication while conducting both individual well-child care and GWCC. We used a longitudinal qualitative study design to conduct 15 semistructured interviews with five pediatric residents who facilitated GWCC. Using the constant comparative method, we characterized pediatric residents' perspectives and experiences of communication while conducting both individual well-child care and GWCC. Four themes emerged. Residents perceived that GWCC (i) enabled families to honestly share their knowledge and parenting practices, (ii) allowed time and a space for families to share personal stories and scenarios, (iii) facilitated discussions of maternal health and psychosocial matters, toward which residents felt ambivalence, and (iv) fostered skills in psychoeducation that transferred to the rest of their clinical practice. When pediatric residents lead GWCC, they perceive that they can facilitate key aspects of psychoeducation, enabling them to assist families in meeting complex social needs. Residents describe that they transfer psychoeducation skills learned in GWCC to the rest of their practice.

Despite the growing size of the academic precariat in the tertiary sector, this exploited group of workers lacks a voice in either their universities or their national union. In this article we draw on our experiences of transitioning from a small activist group to a broader research collective with influence and voice, while forging networks of solidarity. Through reflecting on developing the "Precarious Academic Work Survey" (PAWS), we explore how action research is a viable way of structurally and politically (re)organising academic work. We argue that partnering with changemakers such as unions as co-researchers disrupts their embedded processes so that they may be (re)politicised towards pressing issues such as precarity. Further, we highlight how research can be used as a call to action and a tool to recruit powerful allies to collaborate on transforming universities into educational utopias.

A skilled workforce is essential for producing high quality construction work, efficiently and effectively. This paper is formulated to improve the understanding and knowledge surrounding the skill shortage currently being faced within the UK, and the significant impact it is having on quality management. It surrounds around each main area, and the impacts of recent years: Brexit, Covid-19 and ageing workforce. A mixed method approach was applied to collect data from the quantitative and qualitative sources. The quantitative survey data was collected through snowball sampling from the 130 construction professionals working the UK construction industry. Moreover, a case study has been conducted on a large-scale construction project located in the Northeast of England where the outcome of these issues can be seen in all aspects of the work. Training and development are the fundamental issues highlighted during the literature review and then subsequently expressed by participants of the surveys. In addition, the moderation analysis also provides the important role of training and development in reducing the negative impacts of COVID-19 and Brexit towards quality management. However, it was also revealed that the training and development are not useful for the aging workforce in combating the skilled shortage challenges towards quality management system in the construction industry. This research will allow the industry to understand the need for a skilled workforce and how it benefits the quality management elements of a construction project.

Adverse intestinal microbiome profiles described as a dysbiotic gut are a complicit etiological operative factor that can progress and maintain inflammatory sequelae in the intestines. The disruption of the gut microbiome that ensues with intestinal dysbiosis is, for example, posited by decreases in the alpha-diversity of the gut microbiome, which is characterized by significant reductions in the abundance of bacterial members from the Bacteroidetes and Firmicutes phyla. Proteobacteria have often been recognized as gut microbial signatures of disease. For example, this happens with observed increases in abundance of the phyla Proteobacteria and Gammaproteobacteria, such as the adherent-invasive Escherichia coli strain, which has been significantly linked with maintaining inflammatory bowel diseases. Research on the administration of probiotics, often identified as gut-functional foods, has demonstrated safety, tolerability, and efficacy issues in treating inflammatory bowel diseases (IBDs). In this narrative review, we explore the efficacy of probiotics in treating IBDs with bacterial strain- and dose-specific characteristics and the association with multi-strain administration.

Societal Impact Statement Comprehensive Red List assessments act as valuable resources for informing protected area designations, national protected species legislation and action strategies, and international biodiversity agreements, yet they are lacking for many plant families. Magnoliaceae is one of the most comprehensively assessed families, as coordinated efforts have taken place since 2007 to assess all species in the family. Due to the many efforts to assess these species, comparisons of the assessments and ex situ data over time and an investigation of the most recent (2021) information are essential to guiding the development of national, regional, and global conservation strategies for Magnoliaceae species in a time of increased global collaboration between conservation organizations.

Societal Impact Statement Mexico's extraordinary tree diversity is threatened by the increasing demand for resources because of the tenfold population growth in the last century. The conservation status of trees and both urban and rural livelihoods are also negatively affected by agriculture, mining and tourism. Nearly 60% of the Mexican endemic and near endemic tree species whose conservation status we have assessed for the Red List of the International Union for Conservation of Nature are threatened, almost double the percentage of threatened trees worldwide. If no measures are taken to protect this tree diversity properly, these resources will be forever lost for human sustainability. Summary Mexico is floristically the fourth most species‐rich country in the world. Currently, 3620 native tree species are reported from this country. Mexico has been a forerunner at global level in recognising the need for plant conservation, yet this is in stark contrast with governmental programmes and actions, past and present that negatively affect(ed) immense areas of primary vegetation. In the framework of the Global Tree Assessment, to date, we have assessed the conservation status of nearly 1500 Mexican endemic and near endemic tree species for the International Union for the Conservation of Nature (IUCN) Red List, the distribution data of which we use here for a first meta‐analysis of conservation statuses and spatial distribution patterns in a newly delimited area we call Natural Mexico. Our database consists of 112,416 taxonomically and geographically very carefully curated distribution points of 1474 tree species endemic to Mexico and adjacent areas, belonging to 98 flowering plant families. The extensive curation methodology we consider essential for both research and conservation purposes is emphasised. Nearly 60% of the assessed tree species are threatened, almost double the percentage of threatened arborescent species at global level. Tropical rainforests and cloud forests house the highest proportions of threatened trees. These assessments have an extensive impact, as they not only are the starting point of urgent species conservation actions but also allow for comprehensive studies including extinction risk estimation, gap analyses for conservation planning and species reintroductions, all this in a framework of land use change, climate change and landscape composition and configuration.

Societal Impact Statement Trees play vital roles in many of the world's ecosystems while providing many benefits to people. New evidence indicates that a third of tree species are threatened with extinction, representing a tree extinction crisis. Here we demonstrate how tree species extinction will lead to the loss of many other plants and animals and significantly alter the world's ecosystems. We also show how tree extinction will negatively affect billions of people through loss of livelihoods and benefits. We highlight a series of urgent actions needed to avert an ecological, cultural and socio‐economic catastrophe caused by widespread extinction of tree species. Summary Trees are of exceptional ecological importance, playing a major functional role in the world's ecosystems, while also supporting many other plants, animals and fungi. Many tree species are also of direct value to people, providing a wide range of socio‐economic benefits. Loss of tree diversity could lead to abrupt declines in biodiversity, ecosystem functions and services and ultimately ecosystem collapse. Here we provide an overview of the current knowledge regarding the number of tree species that are threatened with extinction, and the threats that affect them, based on results of the Global Tree Assessment. This evidence suggests that a third of the world's tree species are currently threatened with extinction, which represents a major ecological crisis. We then examine the potential implications of tree extinctions, in terms of the functioning of the biosphere and impacts on human well‐being. Large‐scale extinction of tree species will lead to major biodiversity losses in other species groups and substantially alter the cycling of carbon, water and nutrients in the world's ecosystems. Tree extinction will also undermine the livelihoods of the billions of people who currently depend on trees and the benefits they provide. This warning to humanity aims to raise awareness of the tree extinction crisis, which is a major environmental issue that requires urgent global attention. We also identify some priority actions that need to be taken to reduce the extinction risk of tree species and to avert the ecological and socio‐economic catastrophe that will result from large‐scale extinction of tree species.

Unhealthy alcohol use is a common, often unaddressed behavior associated with increased risk for acquisition of HIV and may also be associated with decreased adherence to oral pre-exposure prophylaxis (PrEP) among gay, bisexual, and other men who have sex with men (MSM) living in the United States. To inform future alcohol-reduction interventions among individuals engaging in PrEP care, we sought to explore perspectives on alcohol use, PrEP adherence, and the acceptability of alcohol use treatment options for MSM prescribed oral formulations of PrEP in the Northeastern United States. Between February 2019 and July 2020, we conducted semi-structured interviews with 15 MSM without HIV who were prescribed PrEP and screened positive for unhealthy alcohol use with AUDIT-C ≥ 4 and were receiving care in Providence, Rhode Island or New Haven, Connecticut. Interviews were coded and analyzed using thematic analysis. Three themes emerged: 1) Consequences of fluctuations in drinking 2) Alcohol use negatively impacts health and relationships; and 3) Desire for a multimodal approach to treatment of unhealthy alcohol use. Our findings support the need to raise awareness of potential alcohol-related harms, address the spectrum of unhealthy alcohol use among MSM prescribed PrEP, and the acceptability and preferences for alcohol reduction interventions within PrEP programs.

The public has expressed growing concern for the well-being of fishes, including popular pet species such as the Siamese fighting fish (Betta splendens). In captivity, male Bettas behave aggressively, often causing injuries and death if housed together. As a result, they are typically isolated in small fishbowls, which has been widely criticised as cruel. To investigate the impact of keeping Bettas in these conditions, we recorded the behaviour of individual males in containers of different sizes that were either bare or enriched with gravel, large rocks, and live plants. When male Bettas were housed individually in small bowls (0.5 L) they spent less time swimming than they did when they were kept in larger aquaria (10, 38, and 208 L). Fish that were kept in enriched containers exhibited more instances of swimming. To determine if two male Bettas housed together might coexist peacefully if given enough space and cover from plants and large rocks, we quantified the behaviour of pairs of male Bettas in bare or enriched aquaria of different sizes (10, 38, 208, 378 L). Fish performed fewer approaches and aggressive displays, but not attacks, and more bouts of foraging, when in larger aquaria. This study shows that the small fishbowls typically used in pet stores suppress swimming behaviour in male Bettas and at least a 10-L aquarium is required to ensure full expression of swimming behaviour. Furthermore, even the use of very large aquaria cannot guarantee peaceful cohabitation between two males.

There is disagreement about the potential for regenerative management practices to sequester sufficient soil organic carbon (SOC) to help mitigate climate change. Measuring change in SOC stocks following practice adoption at the grain of farm fields, within the extent of regional agriculture, could help resolve this disagreement. Yet sampling demands to quantify change are considered infeasible primarily because within-field variation in stock sizes is thought to obscure accurate quantification of management effects on incremental SOC accrual. We evaluate this ‘infeasibility assumption’ using high-density (e.g., 0.1 ha sample–1), within-field, sampling data from 45 cropland fields inventoried for SOC. We explore how more typical within-field sampling densities, as well as field numbers and magnitude of simulated change in SOC stocks, impacts the ability to accurately quantify management effects on SOC change. We find that (1) stock change estimates for individual fields are inaccurate and variable, where marked losses and gains in SOC stocks are frequently estimated even when no change has occurred. Higher sampling densities (e.g., 1.2 versus 4.0 ha sample–1) narrow the range of estimated stock changes but inaccuracies remain large. (2) The accuracy of stock change estimates at the project level (i.e., multiple fields) were similarly sensitive to sampling density. In contrast to individual fields, however, higher sampling densities, as well as a greater number of fields (e.g., 30), generated robust and accurate, mean project-level estimates of carbon accrual, with ∼ 80 % of the estimates falling within 20 % of the simulated stock change. Yet such monitoring designs do not account for dynamic baselines, which necessitates measurement of stock changes in control, non-regenerative fields. We find (3) that higher sampling densities (e.g., 1.2 versus 4.0 ha sample–1), field numbers (e.g., 30 versus 10 pairs of fields), and magnitudes of simulated SOC stock change (+3 and +5 versus +1 Mg C ha−1 10 y–1) are then collectively required to make accurate estimates of management effects on stock change at the project level. The simulated effect sizes that could be consistently detected under these conditions included rates of SOC accrual considered achievable and meaningful for climate mitigation (e.g., 3 Mg C ha−1 10 y–1), with field numbers and sampling densities that are reasonable given current sampling methods. Our findings reveal the potential to use empirical approaches to accurately quantify, at project scales, SOC stock responses to practice change. We provide recommendations for data that government, farmer and corporate entities should measure and share to build confidence in the effects of regenerative practices, freeing the SOC debate from overreliance on theory and data collected at scales mismatched with agricultural management.

Soil amendments are a broad class of materials that enhance physical, chemical or biological characteristics in croplands, pastures, or rangelands. While organic soil amendments such as manure, mulch and seaweed have well established agronomic benefits, there has been renewed private and governmental interest in quantifying and incentivizing their role in mitigating climate change. Likewise, biostimulants and biopesticides, which are intended to target specific plant or microbial processes, are emerging with claims of improved soil health, crop yields, soil organic carbon sequestration, and greenhouse gas emission reductions. We conducted a literature review to address the climate mitigation potential of organic soil amendments, including biostimulants and biopesticides. In doing so, we identify three elements of climate mitigation through the use of soil amendments: soil organic carbon sequestration, soil greenhouse gas emission reductions, and life cycle emission reductions. We review common soil amendment classes in detail, addressing the empirical evidence (or lack thereof) in which they meet these three elements of climate mitigation. We conclude by suggesting priorities for government and private investment.

This study describes the capabilities and limitations of carrying out total scattering experiments on the Powder Diffraction (PD) beamline at the Australian Synchrotron, ANSTO. A maximum instrument momentum transfer of 19 Å−1 can be achieved if the data are collected at 21 keV. The results detail how the pair distribution function (PDF) is affected by Qmax, absorption and counting time duration at the PD beamline, and refined structural parameters exemplify how the PDF is affected by these parameters. There are considerations when performing total scattering experiments at the PD beamline, including (1) samples need to be stable during data collection, (2) highly absorbing samples with a μR > 1 always require dilution and (3) only correlation length differences >0.35 Å may be resolved. A case study comparing the PDF atom–atom correlation lengths with EXAFS-derived radial distances of Ni and Pt nanocrystals is also presented, which shows good agreement between the two techniques. The results here can be used as a guide for researchers considering total scattering experiments at the PD beamline or similarly setup beamlines.

Despite a lengthy and successful history of Indigenous multilingual/multiliteracy education and English as an Additional Language or Dialect programmes in Australia's Northern Territory, these programmes have virtually disappeared. The current denuded offerings in school instruction are a consequence of locally nuanced manifestations of neoliberal global developments. This paper uses Roberts and Mahtani's (2010) market orientation to race to examine the localised expression of global neoliberal influences in Northern Territory remote Indigenous contexts.

There is a growing policy focus on children and young people's mental health. The United Kingdom (UK) government has positioned schools as being well-placed to identify children and young people's mental health needs and to provide appropriate intervention. At the same time, school staff report a lack of skills, knowledge and systems to support the early identification of mental health needs in order to inform appropriate intervention. The aim of this study was to explore the mental health and emotional needs of secondary age students from schools across the North West of England. Eight hundred and eighty-four students aged between 11 and 16 completed an online questionnaire comprising the Short Moods and Feelings Questionnaire (SMFQ), which measures depressive symptoms and the Human Givens Emotional Needs Audit (ENA), which explores the extent to which fundamental emotional needs (e.g., for attention, control and security) are met. The findings suggest prevalence rates of mental health and wellbeing difficulties increase with age. Emotional needs as measured in the ENA were found to moderately correlate with total scores on the SMFQ, suggesting the importance of supporting these identified needs in promoting wellbeing. Additionally, the ENA could potentially offer insight into why students may be experiencing problems, signposting practical areas of support. It is therefore proposed to be a measure that schools could use to identify factors contributing to children and young people's experience of mental health and wellbeing and possible areas for intervention.

The teacher retention crisis has led to a strong discourse around the need for teachers to 'build their resilience', which places the responsibility for coping at the feet of the individual teacher. Contemporary research, however, supports a social-ecological approach, which takes account of environmental influences within the resilience process. This study draws upon five focus groups (28 teachers) to present evidence for complex interdependencies between risk and protective factors within the resilience process. The authors demonstrate the prevalence of indirect (mediation and moderation) effects operating primarily "between" rather than "within" ecological levels, characterised by contextual factors predominately influencing individual factors, rather than the other way round. These findings provide support for the notion of equifinality -- the idea that there are multiple routes to resilience -- and advocate a flexible approach to promoting teacher resilience, involving experimentation and collaboration across ecological levels.

Background: Evidence-based medicine (EBM), as originally conceived, used all types of peer-reviewed evidence to guide medical practice and decision-making. During the SARS-CoV-2 Coronavirus disease (COVID-19) pandemic, the standard usage of EBM, modeled by the Evidence-Based Medicine Pyramid, undermined EBM by incorrectly using pyramid levels to assign relative quality. The resulting pyramid-based thinking is biased against reports both in levels beneath randomized control trials (RCTs) and those omitted from the pyramid entirely. Thus, much of the evidence was ignored. Our desire for a more encompassing and effective medical decision-making process to apply to repurposed drugs led us to develop an alternative to the EBM Pyramid for EBM. Herein, we propose the totality of evidence (T-EBM) wheel. Objectives: To create an easily understood graphic that models EBM by incorporating all peer-reviewed evidence that applies to both new and repurposed medicines, and to demonstrate its potential utility using ivermectin as a case study. Methods: The graphics were produced using Microsoft Office Visio Professional 2003 except for part of the T-EBM wheel sunburst chart, which was produced using Microsoft 365 Excel. For the case study, PubMed® was used by searching for peer-reviewed reports containing “ivermectin” and either “covid” or “sars” in the title. Reports were filtered for those using ivermectin-based protocols in the treatment of COVID-19. The resulting 265 reports were evaluated for their study design types and treatment outcomes. The three-ringed graphical T-EBM wheel was composed of two inner rings showing all types of reports and an outer ring showing outcomes for each type. Findings-Conclusions: The T-EBM wheel avoids the biases of the EBM Pyramid and includes all types of reports in the pyramid along with reports such as population and mechanistic studies. In both early and late stages of medical emergencies, pyramid-based thinking may overlook indications of efficacy in regions of the T-EBM wheel beyond RCTs. This is especially true when searching for ways to prevent and treat a novel disease with repurposed therapeutics before RCTs, safety assessments, and mechanisms of action of novel therapeutics are established. As such, T-EBM Wheels should replace the EBM Pyramids in medical decision-making and education. T-EBM Wheels can be expanded upon by implementing multiple outer rings, one for each different kind of outcome (efficacy, safety, etc.). A T-EBM Wheel can be created for any proprietary or generic medicine. The ivermectin (IVM) T-EBM Wheel displays the efficacy of IVM-based treatments of COVID-19 in a color-coded graphic, visualizing each type of evidence and the proportions of each of their outcomes (positive, inconclusive, negative).

Abstract Background Patients with follicular lymphoma (FL) can have high response rates to early lines of treatment. However, among FL patients relapsed/refractory (r/r) after ≥2 prior lines of therapy (LOT), remission tends to be shorter and there is limited treatment guidance. This study sought to evaluate the clinical outcomes for r/r FL after ≥2 prior LOT identified through systematic literature review. Methods Eligible studies included comparative or non-comparative interventional or observational studies of systemic therapies among adults with FL r/r after ≥2 prior LOT published prior to 31st May 2021. Prior LOT must have included an anti-CD20 monoclonal antibody and an alkylating agent, in combination or separately. Overall response rate (ORR) and complete response (CR) were estimated using inverse-variance weighting with Freeman-Tukey double-arcsine transformations. Kaplan-Meier (KM) curves for progression-free survival (PFS) and overall survival (OS) estimated by reconstructing digitized curves using the Guyot algorithm, and survival analyses were conducted, stratified by ≥2 prior LOT and ≥ 3 prior LOT groups (as defined in the source material). Restricting the analyses to the observational cohorts was investigated as a sensitivity analysis. Results The analysis-set included 20 studies published between 2014 and 2021. Studies were primarily US and/or European based, with the few exceptions using treatments approved in US/Europe. The estimated ORR was 58.47% (95% confidence interval [CI]: 51.13–65.62) and proportion of patients with CR was 19.63% (95% CI: 15.02–24.68). The median OS among those ≥2 prior LOT was 56.57 months (95% CI: 47.8–68.78) and median PFS was 9.78 months (95% CI: 9.01–10.63). The 24-month OS decreased from 66.50% in the ≥2 prior LOT group to 59.51% in the ≥3 prior LOT group, with a similar trend in PFS at 24-month (28.42% vs 24.13%). Conclusions This study found that few r/r FL patients with ≥2 prior LOT achieve CR, and despite some benefit, approximately 1/3 of treated patients die within 24 months. The shorter median PFS with increasing prior LOT suggest treatment durability is suboptimal in later LOT. These findings indicate that patients are underserved by treatments currently available in the US and Europe.

Over the last twenty-five years, there has been an increase in the availability of published checklists and schedules which allow practitioners to identify the strengths of children and young people, including those with special educational needs. While helpful, these assessments are unable to tell us about the nature of contextual factors which support the expression of particular strengths. In this study, we took a situative perspective to explore how specific classroom practices facilitated strengths. A multiple case study design was used to analyse practices nominated by three children/young people with special educational needs. Qualitative analysis revealed how aspects of practice afforded the opportunity for each child to participate in ways which they equated with their strengths. This style of strength-based assessment led to a more sustained examination of supportive practice features than would have been achieved through interview alone.

Objective: Bariatric surgery remains the only effective and durable treatment option for morbid obesity. Vertical Sleeve Gastrectomy (VSG) is currently the most widely performed of these surgeries primarily because of its proven efficacy in generating rapid onset weight loss, improved glucose regulation and reduced mortality compared with other invasive procedures. VSG is associated with reduced appetite, however, the relative importance of energy expenditure to VSG-induced weight loss and changes in glucose regulation, particularly that in brown adipose tissue (BAT), remains unclear. The aim of this study was to investigate the role of BAT thermogenesis in the efficacy of VSG in a rodent model. Methods: Diet-induced obese male Sprague–Dawley rats were either sham-operated, underwent VSG surgery or were pair-fed to the food consumed by the VSG group. Rats were also implanted with biotelemetry devices between the interscapular lobes of BAT to assess local changes in BAT temperature as a surrogate measure of thermogenic activity. Metabolic parameters including food intake, body weight and changes in body composition were assessed. To further elucidate the contribution of energy expenditure via BAT thermogenesis to VSG-induced weight loss, a separate cohort of chow-fed rats underwent complete excision of the interscapular BAT (iBAT lipectomy) or chemical denervation using 6-hydroxydopamine (6-OHDA). To localize glucose uptake in specific tissues, an oral glucose tolerance test was combined with an intraperitoneal injection of 14C-2-deoxy-d-glucose (14C-2DG). Transneuronal viral tracing was used to identify 1) sensory neurons directed to the stomach or small intestine (H129-RFP) or 2) chains of polysynaptically linked neurons directed to BAT (PRV-GFP) in the same animals. Results: Following VSG, there was a rapid reduction in body weight that was associated with reduced food intake, elevated BAT temperature and improved glucose regulation. Rats that underwent VSG had elevated glucose uptake into BAT compared to sham operated animals as well as elevated gene markers related to increased BAT activity (Ucp1, Dio2, Cpt1b, Cox8b, Ppargc) and markers of increased browning of white fat (Ucp1, Dio2, Cited1, Tbx1, Tnfrs9). Both iBAT lipectomy and 6-OHDA treatment significantly attenuated the impact of VSG on changes in body weight and adiposity in chow-fed animals. In addition, surgical excision of iBAT following VSG significantly reversed VSG-mediated improvements in glucose tolerance, an effect that was independent of circulating insulin levels. Viral tracing studies highlighted a patent neural link between the gut and BAT that included groups of premotor BAT-directed neurons in the dorsal raphe and raphe pallidus. Conclusions: Collectively, these data support a role for BAT in mediating the metabolic sequelae following VSG surgery, particularly the improvement in glucose regulation, and highlight the need to better understand the contribution from this tissue in human patients.

Summary: Characterizing transcription factor (TF) genomic colocalization is essential for identifying cooperative binding of TFs in controlling gene expression. Here, we introduce a protocol for using PAD2, an interactive web application that enables the investigation of colocalization of various TFs and chromatin-regulating proteins from mouse embryonic stem cells at various functional genomic regions. We describe steps for accessing and searching the PAD2 database and selecting and submitting genomic regions. We then detail protein colocalization analysis using heatmap and ranked correlation plot.For complete details on the use and execution of this protocol, please refer to Kim et al. (2022).1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

PURPOSEGlobal increases in cancer, coupled with a shortage of cancer specialists, has led to an increasing role for primary care providers (PCP) in cancer care. This review aimed to examine all extant cancer curricula for PCPs and to analyze the motivations for curriculum development.METHODSA comprehensive literature search was conducted from inception to October 13, 2021, with no language restrictions. The initial search yielded 11,162 articles and 10,902 articles underwent title and abstract review. After full-text review, 139 articles were included. Numeric and thematic analyses were conducted and education programs were evaluated using Bloom's taxonomy.RESULTSMost curricula were developed in high-income countries (HICs), with 58% in the United States. Cancer-specific curricula focused on HIC priority cancers, such as skin/melanoma, and did not represent the global cancer burden. Most (80%) curricula were developed for staff physicians and 73% focused on cancer screening. More than half (57%) of programs were delivered in person, with a shift toward online delivery over time. Less than half (46%) of programs were codeveloped with PCPs and 34% did not involve PCPs in the program design and development. Curricula were primarily developed to improve cancer knowledge, and 72 studies assessed multiple outcome measures. No studies included the top two levels of Bloom's taxonomy of learning (evaluating; creating).CONCLUSIONTo our knowledge, this is the first review to assess the current state of cancer curricula for PCPs with a global focus. This review shows that extant curricula are primarily developed in HICs, do not represent the global cancer burden, and focus on cancer screening. This review lays a foundation to advance the cocreation of curricula that are aligned to the global cancer burden.