Supporting siblings of children with a special educational need or disability : an evaluation of Sibs Talk, a one‐to‐one intervention delivered by staff in mainstream schools

A group often overlooked for specific supports in schools are siblings of children with a disability, special educational needs or a serious long‐term condition (SEND). In this article we review the current sibling research and identify a lack of literature on interventions, particularly within a school context. We then present a description of Sibs Talk, an example of a new school‐based intervention to support siblings. Sibs Talk is a ten‐session, one‐to‐one intervention approach for schools to complete with Key Stage 2 children who have a brother or sister with SEND. Finally, we present an initial evaluation of the effectiveness of Sibs Talk, using a pre and post evaluation format with a sample of 55 children from 11 schools. The data presented in this evaluation indicate that Sibs Talk may have contributed to positive outcomes for participating children

Changing Places and Evolving Activism: Communities in Post-Industrial Glasgow

The chapter examines contemporary community activism in the light of the long history of urban change in Glasgow and the ongoing shifts which are occurring across the city. It draws on empirical research in three very different communities to elucidate developments in community activism and consider the relationships between activism and the broader patterns of change

Metrics of biomass, live-weight gain and nitrogen loss of ryegrass sheep pasture in the 21st century

This study was partially supported by Soil to Nutrition, Rothamsted Research’s Institute Strategic Programme supported by the Biotechnology and Biological Sciences Research Council (BBS/E/C/000I0320).The North Wyke Farm Platform is a UK National Capability, also supported by the Biotechnology and Biological Sciences Research Council (BBS/E/C/000J0100).This study was also partially supported by the Natural Environment Research Council’s ADVENT project (NERC NE/M019691/1).Climate data were measured at the MIDAS Land Surface Station DLY3208 DEVON, UK, a weather station of the UK Meteorological Office. We would especially like to thank Dr Nadine Loick of Rothamsted Research for advice on preparation of N2O model calibration parameters, and the data team of the North Wyke Farm Platform. We owe our gratitude to the late Mr Robert Orr, grassland specialist at the North Wykesite, for his invaluable advice and information on sward growth.Peer reviewedPublisher PD

Post-operative outcomes and identification of risk factors for complications after emergency intestinal stoma surgery – a multi-centre retrospective study

Aim: Approximately 4000 patients in the UK have an emergency intestinal stoma formed each year. Stoma-related complications (SRCs) are heterogeneous but have previously been subcategorized into early or late SRCs, with early SRCs generally occurring within 30 days postoperatively. Early SRCs include skin excoriation, stoma necrosis and high output, while late SRCs include parastomal hernia, retraction and prolapse. There is a paucity of research on specific risk factors within the emergency cohort for development of SRCs. This paper aims to describe the incidence of SRCs after emergency intestinal surgery and to identify potential risk factors for SRCs within this cohort. Method: Consecutive patients undergoing emergency formation of an intestinal stoma (colostomy, ileostomy or jejunostomy) were identified prospectively from across three acute hospital sites over a 3-year period from the ELLSA (Emergency Laparotomy and Laparoscopic Scottish Audit) database. All patients were followed up for a minimum of 1 year. A multivariate logistic regression model was used to identify risk factors for early and late SRCs. Results: A total of 455 patients were included (median follow-up 19 months, median age 64 years, male:female 0.52, 56.7% ileostomies). Early SRCs were experienced by 54.1% of patients, while 51% experienced late SRCs. A total of 219 patients (48.1%) had their stoma sited preoperatively. Risk factors for early SRCs included end ileostomy formation [OR 3.51 (2.24–5.49), p < 0.001], while preoperative stoma siting was found to be protective [OR 0.53 (0.35–0.83), p = 0.005]. Patient obesity [OR 3.11 (1.92–5.03), p < 0.001] and reoperation for complications following elective surgery [OR 4.18 (2.01–8.69), p < 0.001] were risk factors for late SRCs. Conclusion: Stoma-related complications after emergency surgery are common. Preoperative stoma siting is the only truly modifiable risk factor to reduce SRCs, and further research should be aimed at methods of improving the frequency and accuracy of this in the emergency setting

Isotopic evidence for dominant secondary production of HONO in near-ground wildfire plumes

Nitrous acid (HONO) is an important precursor to hydroxyl radical (OH) that determines atmospheric oxidative capacity and thus impacts climate and air quality. Wildfire is not only a major direct source of HONO, it also results in highly polluted conditions that favor the heterogeneous formation of HONO from nitrogen oxides (NOx= NO + NO2) and nitrate on both ground and particle surfaces. However, these processes remain poorly constrained. To quantitatively constrain the HONO budget under various fire and/or smoke conditions, we combine a unique dataset of field concentrations and isotopic ratios (15N / 14N and 18O / 16O) of NOx and HONO with an isotopic box model. Here we report the first isotopic evidence of secondary HONO production in near-ground wildfire plumes (over a sample integration time of hours) and the subsequent quantification of the relative importance of each pathway to total HONO production. Most importantly, our results reveal that nitrate photolysis plays a minor role (\u3c5 %) in HONO formation in daytime aged smoke, while NO2-to-HONO heterogeneous conversion contributes 85 %–95 % to total HONO production, followed by OH + NO (5 %–15 %). At nighttime, heterogeneous reduction of NO2 catalyzed by redox active species (e.g., iron oxide and/or quinone) is essential (≥ 75 %) for HONO production in addition to surface NO2 hydrolysis. Additionally, the 18O / 16O of HONO is used for the first time to constrain the NO-to-NO2 oxidation branching ratio between ozone and peroxy radicals. Our approach provides a new and critical way to mechanistically constrain atmospheric chemistry and/or air quality models on a diurnal timescale

Using ecological niche theory to avoid uninformative biodiversity surrogates

Surrogates and indicators of biodiversity are used to infer the state and dynamics of species populations and ecosystems, as well as to inform conservation and management actions. Despite their widespread use, few studies have examined how ecological theory can guide the selection or surrogates and indicators, and thus reduce the likelihood of failure or cost of validation. We argue that ecological niche theory and knowledge of the extent to which particular limiting factors (e.g. physiological tolerances, limits to growth rates, or competitive exclusion) affect species distributions, abundance and coexistence could inform the choice of potential surrogates. Focusing on the environmental characteristics that define species niches makes it possible to identify situations where surrogates are likely to be ineffective, such as when there is no mechanistic basis for a candidate surrogate to be related to a biodiversity target. We describe two case studies where different candidate surrogate variables are shown to have contrasting potential as indicators of sustainable farming. Variables not mechanistically linked to the driver of change or responsive over appropriate timeframes or spatial scales are suggested a priori to be uninformative. The niche concept provides a framework for exploring ecological relationships that can inform the selection or exclusion of potential biodiversity surrogates. We think that this new approach to integrating ecological theory and application could lead to improved effectiveness of biodiversity monitoring and conservation.DBL was funded by an ARC Laureate Fellowship (LF120100108). MRW was supported in part by a grant from the US National Science Foundation (DEB-1546686)

Inclusion of multiple high-risk histopathological criteria improves the prediction of adjuvant chemotherapy efficacy in lung adenocarcinoma.

AIMS: The decision to consider adjuvant chemotherapy (AC) for non-small cell lung cancer is currently governed by clinical stage. This study aims to assess other routinely collected pathological variables related to metastasis and survival for their ability to predict the efficacy of AC in lung adenocarcinoma. METHODS AND RESULTS: A retrospective single-centre series of 620 resected lung non-mucinous adenocarcinoma cases from 2005 to 2015 was used. Digital images of all slides were subjected to central review, and data on tumour histopathology, AC treatment and patient survival were compiled. A statistical case matching approach was used to counter selection bias. Several high-risk pathological criteria predict both pathological nodal involvement and early death: positive vascular invasion status (VI+) (HR = 2.10, P < 0.001), positive visceral pleural invasion status (VPI+) (HR = 2.16, P < 0.001), and solid/micropapillary-predominant WHO tumour type (SPA/MPPA) (HR = 3.29, P < 0.001). Crucially, these criteria also identify patient groups benefiting from AC (VI + HR = 0.69, P = 0.167, VPI + HR = 0.44, P = 0.004, SPA/MPPA HR = 0.36, P = 0.006). Cases showing VI+/VPI+/SPA/MPPA histology in the absence of AC stage criteria were common (170 of 620 total), and 8 had actually received AC. This group showed much better outcomes than equivalent untreated cases in matched analysis (3-year OS 100.0% versus 31.3%). Inclusion of patients with VI+/VPI+/SPA/MPPA histology would increase AC-eligible patients from 51.0% to 84.0% of non-mucinous tumours in our cohort. CONCLUSIONS: Our data provide preliminary evidence that the consideration of AC in patients with additional high-risk pathological indicators may significantly improve outcomes in operable lung adenocarcinoma, and that AC may be currently underused

Inclusion of multiple high‐risk histopathological criteria improves the prediction of adjuvant chemotherapy efficacy in lung adenocarcinoma

Aims: The decision to consider adjuvant chemotherapy (AC) for non‐small cell lung cancer is currently governed by clinical stage. This study aims to assess other routinely collected pathological variables related to metastasis and survival for their ability to predict the efficacy of AC in lung adenocarcinoma. Methods and results: A retrospective single‐centre series of 620 resected lung non‐mucinous adenocarcinoma cases from 2005 to 2015 was used. Digital images of all slides were subjected to central review, and data on tumour histopathology, AC treatment and patient survival were compiled. A statistical case matching approach was used to counter selection bias. Several high‐risk pathological criteria predict both pathological nodal involvement and early death: positive vascular invasion status (VI+) (HR = 2.10, P &lt; 0.001), positive visceral pleural invasion status (VPI+) (HR = 2.16, P &lt; 0.001), and solid/micropapillary‐predominant WHO tumour type (SPA/MPPA) (HR = 3.29, P &lt; 0.001). Crucially, these criteria also identify patient groups benefiting from AC (VI + HR = 0.69, P = 0.167, VPI + HR = 0.44, P = 0.004, SPA/MPPA HR = 0.36, P = 0.006). Cases showing VI+/VPI+/SPA/MPPA histology in the absence of AC stage criteria were common (170 of 620 total), and 8 had actually received AC. This group showed much better outcomes than equivalent untreated cases in matched analysis (3‐year OS 100.0% versus 31.3%). Inclusion of patients with VI+/VPI+/SPA/MPPA histology would increase AC‐eligible patients from 51.0% to 84.0% of non‐mucinous tumours in our cohort. Conclusions: Our data provide preliminary evidence that the consideration of AC in patients with additional high‐risk pathological indicators may significantly improve outcomes in operable lung adenocarcinoma, and that AC may be currently underused

Trace amine-associated receptor 1 (TAAR1) agonism for psychosis:a living systematic review and meta-analysis of human and non-human data

BACKGROUND: Trace amine-associated receptor 1 (TAAR1) agonism shows promise for treating psychosis, prompting us to synthesise data from human and non-human studies.METHODS: We co-produced a living systematic review of controlled studies examining TAAR1 agonists in individuals (with or without psychosis/schizophrenia) and relevant animal models. Two independent reviewers identified studies in multiple electronic databases (until 17.11.2023), extracted data, and assessed risk of bias. Primary outcomes were standardised mean differences (SMD) for overall symptoms in human studies and hyperlocomotion in animal models. We also examined adverse events and neurotransmitter signalling. We synthesised data with random-effects meta-analyses.RESULTS: Nine randomised trials provided data for two TAAR1 agonists (ulotaront and ralmitaront), and 15 animal studies for 10 TAAR1 agonists. Ulotaront and ralmitaront demonstrated few differences compared to placebo in improving overall symptoms in adults with acute schizophrenia (N=4 studies, n=1291 participants; SMD=0.15, 95%CI: -0.05, 0.34), and ralmitaront was less efficacious than risperidone (N=1, n=156, SMD=-0.53, 95%CI: -0.86, -0.20). Large placebo response was observed in ulotaront phase-III trials. Limited evidence suggested a relatively benign side-effect profile for TAAR1 agonists, although nausea and sedation were common after a single dose of ulotaront. In animal studies, TAAR1 agonists improved hyperlocomotion compared to control (N=13 studies, k=41 experiments, SMD=1.01, 95%CI: 0.74, 1.27), but seemed less efficacious compared to dopamine D 2 receptor antagonists (N=4, k=7, SMD=-0.62, 95%CI: -1.32, 0.08). Limited human and animal data indicated that TAAR1 agonists may regulate presynaptic dopaminergic signalling. CONCLUSIONS: TAAR1 agonists may be less efficacious than dopamine D 2 receptor antagonists already licensed for schizophrenia. The results are preliminary due to the limited number of drugs examined, lack of longer-term data, publication bias, and assay sensitivity concerns in trials associated with large placebo response. Considering their unique mechanism of action, relatively benign side-effect profile and ongoing drug development, further research is warranted. REGISTRATION: PROSPERO-ID: CRD42023451628.</p

Regulatory Variation at Glypican-3 Underlies a Major Growth QTL in Mice

The genetic basis of variation in complex traits remains poorly understood, and few genes underlying variation have been identified. Previous work identified a quantitative trait locus (QTL) responsible for much of the response to selection on growth in mice, effecting a change in body mass of approximately 20%. By fine-mapping, we have resolved the location of this QTL to a 660-kb region containing only two genes of known function, Gpc3 and Gpc4, and two other putative genes of unknown function. There are no non-synonymous polymorphisms in any of these genes, indicating that the QTL affects gene regulation. Mice carrying the high-growth QTL allele have approximately 15% lower Gpc3 mRNA expression in kidney and liver, whereas expression differences at Gpc4 are non-significant. Expression profiles of the two other genes within the region are inconsistent with a factor responsible for a general effect on growth. Polymorphisms in the 3′ untranslated region of Gpc3 are strong candidates for the causal sequence variation. Gpc3 loss-of-function mutations in humans and mice cause overgrowth and developmental abnormalities. However, no deleterious side-effects were detected in our mice, indicating that genes involved in Mendelian diseases also contribute to complex trait variation. Furthermore, these findings show that small changes in gene expression can have substantial phenotypic effects