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This essay reviews recent scholarly work on EcoHorror and Post-Apocalyptic science fiction. It pays particular attention to the influence of Stacey Alaimo’s call for attention to the ethics of “transcorporeality” when it comes to reading horror, a need to imagine the human and nonhuman not as a binary but as intermeshed and mutually dependent. Hybridity in horror might thus present something not monstrous but politically desirable. Similarly, the essay explores the ways in which scholarship and public intellectuals have tended to see the recent boom in post-apocalyptic writing as either indicating the durability of late capitalism or the moment of its collapse and reshaping into something new.The books under review examine the outpouring of ecological horror and postapocalyptic fiction in the second half of the twentieth century and into the present. Why have such stories come so forcefully into the literary and filmic marketplace over the last 50 years or so?

Orofacial cleft (OC) is a common congenital anomaly in humans, which has lifelong implications for affected individuals. This disorder can be classified as syndromic or non-syndromic depending on the presence or absence of additional physical or neurodevelopmental abnormalities, respectively. Non-syndromic cleft is often non-familial in nature and has a complex aetiology, whereas syndromic forms tend to be monogenic. Although individual OC-related syndromes have been frequently described in the medical literature, there has not been a comprehensive review across syndromes, thereby leaving a gap in our knowledge, which this paper aims to address. Six hundred and three patients with cleft-related human phenotype ontology terms were identified within the Deciphering Developmental Disorders study. Genes carrying pathogenic/likely pathogenic variants were identified and reviewed enabling a diagnostic yield of 36.5%. In total, 124 candidate genes for syndromic OC were identified, including 34 new genes that should be considered for inclusion in clinical clefting panels. Functional enrichment and gene expression analyses identified three key processes that were significantly overrepresented in syndromic OC gene lists: embryonic morphogenesis, protein stability and chromatin organization. Comparison with non-syndromic OC gene networks led us to propose that chromatin remodelling specifically contributes to the aetiology of syndromic OC. Disease-driven gene discovery is a valid approach to gene identification and curation of gene panels. Through this approach, we have started to unravel common molecular pathways contributing to syndromic orofacial clefting.

Background Substance use and offending are related in the context of other disinhibitory behaviours. Adolescents involved in the criminal justice system constitute a particularly vulnerable group, with a propensity to engage in risky behaviour that has long-term impact on their future health and well-being. Previous research of the RISKIT programme provided evidence of a potential effect in reducing substance use and risky behaviour in adolescents. Objectives To evaluate the clinical effectiveness and cost-effectiveness of a multicomponent psychosocial intervention compared with treatment as usual in reducing substance use for substance-using adolescents involved in the criminal justice system. Design A mixed-methods, prospective, pragmatic, two-arm, randomised controlled trial with follow-up at 6 and 12 months post randomisation. Setting The study was conducted across youth offending teams, pupil referral units and substance misuse teams across four areas of England (i.e. South East, London, North West, North East). Participants Adolescents aged between 13 and 17 years (inclusive), recruited between September 2017 and June 2020. Interventions Participants were randomised to treatment as usual or to treatment as usual in addition to the RISKIT-Criminal Justice System (RISKIT-CJS) programme. The RISKIT-CJS programme was a multicomponent intervention and consisted of two individual motivational interviews with a trained youth worker (lasting 45 minutes each) and two group sessions delivered over half a day on consecutive weeks. Main outcome measures At 12 months, we assessed per cent days abstinent from substance use over the previous 28 days. Secondary outcome measures included well-being, motivational state, situational confidence, quality of life, resource use and fidelity of interventions delivered. Results A total of 693 adolescents were assessed for eligibility, of whom 505 (73%) consented. Of these, 246 (49%) were allocated to the RISKIT-CJS intervention and 259 (51%) were allocated to treatment as usual only. At month 12, the overall follow-up rate was 57%: 55% in the RISKIT-CJS arm and 59% in the treatment-as-usual arm. At month 12, we observed an increase in per cent days abstinent from substances in both arms of the study, from 61% to 85%, but there was no evidence that the RISKIT-CJS intervention was superior to treatment as usual. A similar pattern was observed for secondary outcomes. The RISKIT-CJS intervention was not found to be any more cost-effective than treatment as usual. The qualitative research indicated that young people were positive about learning new skills and acquiring new knowledge. Although stakeholders considered the intervention worthwhile, they expressed concern that it came too late for the target population. Limitations Our original aim to collect data on offences was thwarted by the onset of the COVID-19 pandemic, and this affected both the statistical and economic analyses. Although 214 (87%) of the 246 participants allocated to the RISKIT-CJS intervention attended at least one individual face-to-face session, 98 (40%) attended a group session and only 47 (19%) attended all elements of the intervention. Conclusions The RISKIT-CJS intervention was no more clinically effective or cost-effective than treatment as usual in reducing substance use among adolescents involved in the criminal justice system. Future research The RISKIT-CJS intervention was considered more acceptable, and adherence was higher, in pupil referral units and substance misuse teams than in youth offending teams. Stakeholders in youth offending teams thought that the intervention was too late in the trajectory for their population. Trial registration This trial is registered as ISRCTN77037777. Funding This project was funded by the National Institute for Health and Care Research (NIHR) Public Health Research programme and will be published in full in Public Health Research; Vol. 11, No. 3. See the NIHR Journals Library website for further project information.

PurposeIntegrated service models aim to simplify access, enable effective delivery, remove duplication and provide a holistic and person-centred approach. This project explored the development of integrated well-being services in two local authorities in North-East England. The purpose of this paper is to address this issue.Design/methodology/approachUnderpinned by public health and co-production approaches, the project utilised a mixed-methods approach. Data were collected via online surveys (n = 95), virtual interviews with members of the local population (n = 8) and practitioners and commissioners (n = 8) to explore needs for a new service. Thematic analysis was used to identify key themes and issues.FindingsSeveral benefits of an integrated service were highlighted by both staff and service users, with a central anticipated benefit being the provision of holistic care. Improvement in information sharing was also seen to increase the efficiency of services and communication barriers between services. Beneficial aspects and barriers related to the COVID-19 pandemic on current service provision were reported that have informed our future recommendations.Originality/valueThe authors’ findings provide a much deeper insight into function, care, social inclusion and ongoing support needs, from both the perspectives of staff and service users. Service users and staff saw value in an integrated model for themselves, as well as the wider community. The authors’ findings indicate that the integrated service model is a promising one for the development of services within local authorities.

To compare the outcomes of splenic artery embolization (SAE) for acute splenic injury (ASI) between patients who are hemodynamically stable (HDS) and hemodynamically unstable (HDU). Nonoperative management with SAE has become an accepted practice for patients who are HDS with ASI; however, SAE for the treatment of patients who are HDU with ASI has not been well studied.A retrospective cohort study was performed, including 52 patients who were HDU and HDS who underwent SAE for ASI at a Level 1 trauma center. HDU was defined as the lowest recorded systolic blood pressure prior to intervention90 mm Hg. Utilizing the American Association for Surgery of Trauma (AAST) splenic injury scale, AAST Grades 1-3 were defined as low grade, and Grades 4-5 were defined as high grade. The primary outcomes were survival at 30 days and the need for subsequent splenectomy.Seventy-five percent (n = 39) of the patients were HDS, and 25% (n = 13) were HDU. The majority (69%) of patients who were HDU who underwent SAE did not require splenectomy, compared with 95% of patients who were HDS (P = .03). No significant difference in 30-day survival between patients who were HDU and HDS was noted. No major adverse events were recorded. There was no significant difference in 30-day patient survival or the rate of subsequent splenectomy between high-grade and low-grade splenic injuries.In this retrospective cohort study, there was no statistically significant difference in the adverse events or 30-day post-SAE survival rates between patients who were HDS and HDU with ASI. The authors conclude that SAE can be a safe and effective treatment option for patients who are HDU with ASI, including high-grade splenic injury.

Beyond the four basic language skills – speaking, listening, reading and writing – other communication skills, including body language and eye contact, are important for communication and should be included as rating criteria in the assessment of interaction. Also, using technology in novel ways for purposes such as remote assessment is possible in the 21st century. Professor Natsumi Onaka, Associate Professor Daniel Newbury and Associate Professor Jacob B Petersen are striving to create a cost-effective peer-to-peer interaction English assessment system that supports foreign language education and testing through widely-used technology and an assessment system that places interaction as central to effective communication. In the context of globalisation, Onaka, International Education Center, Iwate University, Japan, believes that the focus of English education should be meaningful interaction rather than rote memorization of grammar and vocabulary for testing purposes. She is heading up this research and is a proponent of 'spontaneous interaction'. She and the team are developing a simple and standardised method for evaluating English-speaking skills by creating tasks and related rubrics focused on interactional situations. Videos of a subject's English speech and communication are recorded and stored in a Learning Management System (LMS) and then evaluated by a third-party, off-site evaluator. The focus is on CEFR (Common European Framework of Reference for Languages) A2 to B1 level speaking skills. By focusing on novice-level interaction, the researchers are able to observe nascent interactional competence among university-aged students and they are attempting to apply some rating criteria to identify differences in ability. By using video as the text format, non-verbal communication such as gestures can be taken into consideration, along with important traditional factors such as grammatical accuracy.

Objective biomarkers for the fatal neurodegenerative disease amyotrophic lateral sclerosis or motor neuron disease (ALS/MND) are critical for diagnosis, drug development, clinical trials, and insight into disease pathology. Key candidates for biomarkers present in biofluids include non-coding RNA (ncRNA) transcripts including microRNA, piwi-interacting RNA and transfer RNA. To determine if the central nervous system was the source of the dysregulated ncRNA biomarkers we previously observed in serum, we sought to identify dysregulated ncRNA candidates in cerebrospinal fluid (CSF) which may provide new insight into the disease pathology.Small RNA sequencing (RNA-seq) was undertaken on CSF samples from healthy controls (We found a range of ncRNA that were dysregulated in the RNA-seq screen, but these failed to be validated or detected in some cases using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Additionally, our previously identified serum ncRNA biomarker showed no change in CSF or correlation to serum.This study suggests the CSF may not be the source of dysregulated ncRNA in the serum and highlights the difficulty in identifying ncRNA in CSF as biomarkers for ALS.KEY MESSAGESIn this current study, we investigated the expression of non-coding RNA transcripts in the cerebrospinal fluid of ALS patients compared to healthy controls.RNA-seq identified dysregulated non-coding RNA transcripts, but these were not validated with RT-qPCR.We conclude that cerebrospinal fluid is not a suitable source of diagnostic biomarkers.

TATA-binding protein associated factor 4 (TAF4) is a subunit of the Transcription Factor IID (TFIID) complex, a central player in transcription initiation. Other members of this multimeric complex have been implicated previously as monogenic disease genes in human developmental disorders. TAF4 has not been described to date as a monogenic disease gene. We here present a cohort of eight individuals, each carrying de novo putative loss-of-function (pLoF) variants in TAF4 and expressing phenotypes consistent with a neuro-developmental disorder (NDD). Common features include intellectual disability, abnormal behavior, and facial dysmorphisms. We propose TAF4 as a novel dominant disease gene for NDD, and coin this novel disorder “TAF4-related NDD” (T4NDD). We place T4NDD in the context of other disorders related to TFIID subunits, revealing shared features of T4NDD with other TAF-opathies.

Background and Hypothesis Children exposed to socioenvironmental adversities (eg, urbanicity, pollution, neighborhood deprivation, crime, and family disadvantage) are more likely to subsequently develop subclinical psychotic experiences during adolescence (eg, hearing voices, paranoia). However, the pathways through which this occurs have not been previously investigated. We hypothesized that cognitive ability and inflammation would partly explain this association. Study Design Data were utilized from the Environmental-Risk Longitudinal Twin Study, a cohort of 2232 children born in 1994–1995 in England and Wales and followed to age 18. Socioenvironmental adversities were measured from birth to age 10 and classified into physical risk (defined by high urbanicity and air pollution) and socioeconomic risk (defined by high neighborhood deprivation, neighborhood disorder, and family disadvantage). Cognitive abilities (overall, crystallized, fluid, and working memory) were assessed at age 12; and inflammatory markers (C-reactive protein, interleukin-6, soluble urokinase plasminogen activator receptor) were measured at age 18 from blood samples. Participants were interviewed at age 18 regarding psychotic experiences. Study Results Higher physical risk and socioeconomic risk were associated with increased odds of psychotic experiences in adolescence. The largest mediation pathways were from socioeconomic risk via overall cognitive ability and crystallized ability, which accounted for ~11% and ~19% of the association with psychotic experiences, respectively. No statistically significant pathways were found via inflammatory markers in exploratory (partially cross-sectional) analyses. Conclusions Cognitive ability, especially crystallized ability, may partly explain the association between childhood socioenvironmental adversity and adolescent psychotic experiences. Interventions to support cognitive development among children living in disadvantaged settings could buffer them against developing subclinical psychotic phenomena.

The blood–brain barrier ensures CNS homeostasis and protection from injury. Claudin-5 (CLDN5), an important component of tight junctions, is critical for the integrity of the blood–brain barrier. We have identified de novo heterozygous missense variants in CLDN5 in 15 unrelated patients who presented with a shared constellation of features including developmental delay, seizures (primarily infantile onset focal epilepsy), microcephaly and a recognizable pattern of pontine atrophy and brain calcifications. All variants clustered in one subregion/domain of the CLDN5 gene and the recurrent variants demonstrate genotype–phenotype correlations. We modelled both patient variants and loss of function alleles in the zebrafish to show that the variants analogous to those in patients probably result in a novel aberrant function in CLDN5. In total, human patient and zebrafish data provide parallel evidence that pathogenic sequence variants in CLDN5 cause a novel neurodevelopmental disorder involving disruption of the blood–brain barrier and impaired neuronal function.

Quantifying sector-resolved methane fluxes in complex emissions environments is challenging yet necessary for inventory validations. We separate energy and agriculture sector methane using a dynamic linear model of methane, ethane, and ammonia mixing ratios measured at a Northern Colorado site from November 2021 to January 2022. Combining observations with spatially resolved inventories and inverse methods, energy and agriculture methane fluxes are constrained across a ~850 km area. Optimized energy sector fluxes were 22% lower than the inventory despite a ~360% increase in regional energy production since the inventory was constructed, suggesting a regional decline in emissions factors. In contrast, optimized agriculture fluxes were 3× larger than the inventory; we demonstrate this discrepancy is consistent with the spatial distribution of agricultural sources. These results highlight the utility of sector-apportioned methane observations for multi-sector inventory optimization in complex environments, which may prove valuable for national and global quantification of sector-resolved methane fluxes.

The control of gene expression is a fundamental process essential for correct development and to maintain homeostasis. Many post-transcriptional mechanisms exist to maintain the correct levels of each RNA transcript within the cell. Controlled and targeted cytoplasmic RNA degradation is one such mechanism with the 5′-3′ exoribonuclease Pacman (XRN1) and the 3′-5′ exoribonuclease Dis3L2 playing crucial roles. Loss of function mutations in either Pacman or Dis3L2 have been demonstrated to result in distinct phenotypes, and both have been implicated in human disease. One mechanism by which gene expression is controlled is through the function of miRNAs which have been shown to be crucial for the control of almost all cellular processes. Although the biogenesis and mechanisms of action of miRNAs have been comprehensively studied, the mechanisms regulating their own turnover are not well understood. Here we characterise the miRNA landscape in a natural developing tissue, the Drosophila melanogaster wing imaginal disc, and assess the importance of Pacman and Dis3L2 on the abundance of miRNAs. We reveal a complex landscape of miRNA expression and show that whilst a null mutation in dis3L2 has a minimal effect on the miRNA expression profile, loss of Pacman has a profound effect with a third of all detected miRNAs demonstrating Pacman-sensitivity. We also reveal a role of Pacman in regulating the highly conserved let-7 cluster (containing miR-100, let-7 and miR-125) and present a genetic model outlining a positive feedback loop regulated by Pacman which begins to explain the apoptotic phenotype observed in Pacman mutants.

BACKGROUND AND AIMS: Colonic eosinophilia, an enigmatic finding often referred to as eosinophilic colitis (EoC), is a poorly understood condition. Whether EoC is a distinct disease or a colonic manifestation of eosinophilic gastrointestinal diseases (EGIDs) or inflammatory bowel disease (IBD) is undetermined. METHODS: Subjects with EoC (n=27) and controls (normal [NL, n=20], Crohn disease [CD, n=14]) were enrolled across sites associated with the Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR). EoC was diagnosed as colonic eosinophilia (ascending ≥100, descending ≥85, sigmoid ≥65 eosinophils/high-power field) with related symptoms. Colon biopsies were subjected to RNA sequencing. Associations between gene expression and histologic features were analyzed with Spearman correlation; operational pathways and cellular constituents were computationally derived. RESULTS: We identified 987 differentially expressed genes (EoC transcriptome) between EoC and NL (>1.5-fold change, P < .05). Colonic eosinophil count correlated with 31% of EoC transcriptome, most notably with CCL11 and CLC (r=0.78 and 0.77, P < .001). Among EoC and other EGIDs, there was minimal transcriptomic overlap; and minimal evidence of a strong allergic type 2 immune response compared with other EGIDs. Decreased cell-cycle and increased apoptosis in EoC compared with NL were identified by functional enrichment analysis and immunostaining using Ki-67 and cleaved caspase-3. Pericryptal circumferential eosinophil collars were associated with the EoC transcriptome (P < .001). EoC transcriptome-based scores were reversible with disease remission and differentiated EoC from IBD, even after controlling for colonic eosinophil levels (P < .0001). CONCLUSION: We established EoC transcriptomic profiles, identified mechanistic pathways, and integrated findings with parallel IBD and EGID data. These findings establish EoC as a distinct disease compared with other EGIDs and IBD, thereby providing a basis for improving diagnosis and treatment.

This chapter set out to present a comprehensive review on the prevalence of autism spectrum disorder (ASD) among 5–18-year-olds living in Europe. The review was based on studies published between 2015 and 2020. Separate meta-analyses were conducted for population studies and register-based studies to determine the random effects pooled prevalence rate (REPPR) for ASD. The European REPPR for ASD among young people was estimated at 0.8% based on register-based studies and 1.4% based on population. Comparative analysis was carried out to identify trends of prevalence rates across countries, gender, and level of education. The prevalence among primary school children was four times that of secondary school children. A male: female ratio of 3.5:1 was obtained. A range of challenges toward young people with ASD are portrayed, including diagnostic limitations, poor awareness on ASD, and socioeconomic inequality. Nationwide screening, early intervention services, and further research on gender and culture-specific presentations are recommended.

Determination of trace gas emissions from sources is critical for understanding and regulating air quality and climate change. Here, we demonstrate a method for rapid quantification of the emission rate of multiple gases from simple and complex sources using a mass-balance approach with a spatially scannable open-path sensor – in this case, an open-path dual-comb spectrometer. The open-path spectrometer measures the total column density of gases between the spectrometer and a retroreflector mounted on an unmanned aerial vehicle (UAV). By measuring slant columns at multiple UAV altitudes downwind of a source (or sink), the total emission rate can be rapidly determined without the need for an atmospheric dispersion model. Here, we demonstrate this technique using controlled releases of CH4 and C2H2. We show an emission rate determination to within 50 % of the known flux with a single 10-minute flight and within 10 % of the known flux after 10 flights. Furthermore, we estimate a detection limit for CH4 emissions to be 0.03 g CH4/s. This detection limit is approximately the same as the emissions from 25 head of beef cattle and is less than the average emissions from a small oil field pneumatic controller. Other gases including CO2, NH3, HDO, ethane, formaldehyde (HCHO), CO, and N2O can be measured by simply changing the dual-comb spectrometer.

The use of sodium bicarbonate (NaHCO3) supplementation to improve repeated high-intensity performance is recommended; however, most swimming performance studies examine time trial efforts rather than repeated swims with interspersed recovery that are more indicative of training sessions. The aim of this study, therefore, was to investigate the effects of 0.3 g.kg−1 BM NaHCO3 supplementation on sprint interval swimming (8 × 50 m) in regionally trained swimmers. Fourteen regionally competitive male swimmers (body mass (BM): 73 ± 8 kg) volunteered for this double-blind, randomised, crossover designed study. Each participant was asked to swim 8 × 50 m (front crawl) at a maximum intensity from a diving block, interspersed with 50 m active recovery swimming. After one familiarisation trial, this was repeated on two separate occasions whereby participants ingested either 0.3 g.kg−1 BM NaHCO3 or 0.05 g.kg−1 BM sodium chloride (placebo) in solution 60 min prior to exercise. Whilst there were no differences in time to complete between sprints 1–4 (p > 0.05), improvements were observed in sprint 5 (p = 0.011; ES = 0.26), 6 (p = 0.014; ES = 0.39), 7 (p = 0.005; ES = 0.60), and 8 (p = 0.004; ES = 0.79). Following NaHCO3 supplementation, pH was greater at 60 min (p 3− was greater at 60 min (p p = 0.016; ES = 0.53) compared to placebo. These findings suggest NaHCO3 supplementation can improve the latter stages of sprint interval swimming performance, which is likely due to the augmentation of pH and HCO3− prior to exercise and the subsequent increase in buffering capacity during exercise.

Recent advances in proteogenomic techniques and bioinformatic pipelines have permitted the detection of thousands of translated small Open Reading Frames (smORFs), which contain less than 100 codons, in eukaryotic genomes. Hundreds of these actively translated smORFs display conserved sequence, structure and evolutionary signatures indicating that the translated peptides could fulfil important biological roles. Despite their abundance, only tens of smORF genes have been fully characterised; these act mainly as regulators of canonical proteins involved in essential cellular processes. Importantly, some of these smORFs display conserved functions with their mutations being associated with pathogenesis. Thus, investigating smORF roles in Drosophila will not only expand our understanding of their functions but it may have an impact in human health. Here we describe the function of a novel and essential Drosophila smORF gene named purriato (prto). prto belongs to an ancient gene family whose members have expanded throughout the Protostomia clade. prto encodes a transmembrane peptide which is localized in endo-lysosomes and perinuclear and plasma membranes. prto is dynamically expressed in mesodermal tissues and imaginal discs. Targeted prto knockdown (KD) in these organs results in changes in nuclear morphology and endo-lysosomal distributions correlating with the loss of sarcomeric homeostasis in muscles and reduction of mitosis in wing discs. Consequently, prto KD mutants display severe reduction of motility, and shorter wings. Finally, our genetic interaction experiments show that prto function is closely associated to the CASA pathway, a conserved mechanism involved in turnover of mis-folded proteins and linked to muscle dystrophies and neurodegenerative diseases. Thus, this study shows the relevance of smORFs in regulating important cellular functions and supports the systematic characterisation of this class of genes to understand their functions and evolution.

A 16-year-old previously healthy boy presented with a 7-year history of ‘black out’ spells. The patient reported that the episodes occurred one to two times in a month associated with dizziness and loss of consciousness without associated urinary or faecal incontinence. At times, he would have

Research in the UK suggests that multi-componential interventions focusing on language and pre-literacy skills can improve children’s reading and language skills. However, simple translations of such programmes may not produce equivalent effects in diverse communities. The reasons for this are multi-faceted and include factors beyond the rationale and content of the intervention programmes themselves. Understanding these factors is critical for creating programmes that will generalise across settings. In this review, we reflect upon challenges encountered in two reading and language intervention programmes in South America to identify community and cultural contextual factors that can influence the implementation and scalability of educational programmes. We use our findings to develop an education-specific framework to guide the development and implementation of high-quality evidence-based approaches to language and literacy intervention. Our model guides implementation practices in diverse contexts and stresses the importance of the evidence-base and communication.

Eosinophilic esophagitis (EoE) can progress to fibrostenosis by unclear mechanisms. Herein, we investigated gene dysregulation in fibrostenotic EoE, its association with clinical parameters and specific pathways, and the functional consequences.Esophageal biopsies from subjects with EoE were collected across 11 Consortium of Eosinophilic Gastrointestinal Disease Researchers sites (n = 311) and 2 independent replication cohorts (n = 83). Inclusion criteria for fibrostenotic EoE were endoscopic rings, stricture, and/or a history of dilation. Endoscopic, histologic, and molecular features were assessed by the EoE Endoscopic Reference Score, EoE Histology Scoring System, EoE Diagnostic Panel, and RNA sequencing. Esophageal endothelial TSPAN12 expression and functional effects on barrier integrity and gene expression were analyzed in vitro.TSPAN12 was the gene most correlated with fibrostenosis (r = -0.40, P.001). TSPAN12 was lower in fibrostenotic EoE and correlated with EoE Endoscopic Reference Score, EoE Diagnostic Panel, and EoE Histology Scoring System (r = 0.34-0.47, P.001). Lower TSPAN12 associated with smaller esophageal diameter (r = 0.44, P = .03), increased lamina propria fibrosis (r = -0.41, P.001), and genes enriched in cell cycle-related pathways. Interleukin (IL)-13 reduced TSPAN12 expression in endothelial cells. Conversely, anti-IL-13 therapy increased TSPAN12 expression. TSPAN12 gene silencing increased endothelial cell permeability and dysregulated genes associated with extracellular matrix pathways. Endothelial cell-fibroblast crosstalk induced extracellular matrix changes relevant to esophageal remodeling.Patients with fibrostenotic EoE express decreased levels of endothelial TSPAN12. We propose that IL-13 decreases TSPAN12, likely contributing to the chronicity of EoE by promoting tissue remodeling through fibroblast-endothelial cell crosstalk.

We present an open-path mid-infrared dual-comb spectrometer (DCS) capable of precise measurement of the stable water isotopologues H216O and HD16O. This system ran in a remote configuration at a rural test site for 3.75 months with 60 % uptime and achieved a precision of 216O and HD16O (δD) in 1000 seconds. Here, we compare the δD values from the DCS to those from the National Ecological Observatory Network (NEON) isotopologue point sensor network. Over the multi-month campaign, the mean difference between the DCS δD values and the NEON δD values from a similar ecosystem is

Background and aims This systematic review sought to identify, explain and interpret the prominent or recurring themes relating to the barriers and facilitators of reporting and recording of self-harm in young people across different settings, such as the healthcare setting, schools and the criminal justice setting. Methods A search strategy was developed to ensure all relevant literature around the reporting and recording of self-harm in young people was obtained. Literature searches were conducted in six databases and a grey literature search of policy documents and relevant material was also conducted. Due to the range of available literature, both quantitative and qualitative methodologies were considered for inclusion. Results Following the completion of the literature searches and sifting, nineteen papers were eligible for inclusion. Facilitators to reporting self-harm across the different settings were found to be recognising self-harm behaviours, using passive screening, training and experience, positive communication, and safe, private information sharing. Barriers to reporting self-harm included confidentiality concerns, negative perceptions of young people, communication difficulties, stigma, staff lacking knowledge around self-harm, and a lack of time, money and resources. Facilitators to recording self-harm across the different settings included being open to discussing what is recorded, services working together and co-ordinated help. Barriers to recording self-harm were mainly around stigma, the information being recorded and the ability of staff being able to do so, and their length of professional experience. Conclusion Following the review of the current evidence, it was apparent that there was still progress to be made to improve the reporting and recording of self-harm in young people, across the different settings. Future work should concentrate on better understanding the facilitators, whilst aiming to ameliorate the barriers.

While primary diagnosis is only one aspect of the presentation of a child with neurodevelopmental delay/disorder, the degree to which early expressive language reflects diagnostic divisions must be understood in order to reduce the risk of obscuring clinically important differences and similarities across diagnoses. We present original data from the New Zealand MacArthur-Bates Communicative Development Inventory (NZCDI) from 88 English-speaking children aged 2;6 to 5;6 years receiving multidisciplinary intervention within a single family-centered program. The children had one of six pediatrician-assigned genetic or behaviorally determined diagnoses: Down syndrome (DS); motor disorders (cerebral palsy and developmental coordination disorder); global development delay; disorders of relating and communicating (R&C); other genetically defined diagnoses; or language delay due to premature (PREM) birth. Morphological and lexical development were compared within and across diagnostic groups, using both data visualization and mixed-effects modeling. Groups varied in the amount of variation within and between them, but only prematurity reached significance, in interaction with age, as a predictor of morpho-lexical scores. Further analysis of longitudinal data available from a subset of the sample (n = 62) suggested that individual trajectories of vocabulary growth could not be reliably predicted by diagnosis. Moreover, the distribution of word types (nouns, predicates, etc.) only distinguished PREM children with language delay from those with DS and those in the R&C group. There were strong similarities in early morpho-lexical development across these clinical populations, with some differences. These findings align with research and clinical approaches which accommodate individual variation within diagnosis, and broad similarities across diagnostic groups.

There is limited research around UK military families who have a dependent with Special Educational Needs and/or Disabilities (SEND) and this cohort has been identified as “an at-risk sub-population in need of urgent research” because they have generally been omitted from military family research (Taylor-Beirne and Fear, 2021, p3). Taylor-Beirne & Fear (2021) make nine recommendations for future research around SEND, one of which is to “Conduct a systematic review of literature relating to SEND military families” (2021, p3). However, it is not currently known how many Service Children have SEND (Taylor-Beirne and Fear, 2021), therefore, in the first instance, reviewing the literature systematically for prevalence rates and types of SEND in the SC cohort is a good place to start in order to ascertain the size and specific needs of this population. (Taylor-Beirne, S., & Fear, N. (2021). UK military families with a dependent who has Special Education Needs and/ or Disability (SEND): a forgotten subpopulation? https://kcmhr.org/pdf/2021_taylor-beirne_a.pdf)

Aim: The aim of our study is to retrospectively report the radiobiological aspects for intensity-modulated proton therapy (IMPT) against intensity-modulated radiation therapy (IMRT) for patients with head and neck cancer treated at our institution. A secondary goal is to reinforce current model-based approaches to head and neck cancer patient selection for IMPT. Materials and Methods: Eighteen patients were evaluated with prescription doses ranging from 50 to 70 Gy delivered in 2 Gy per fraction. The dose volume histograms (DVH) were used to calculate equivalent uniform dose (EUD), tumour control probability (TCP) and normal tissue complication probability (NTCP) for biophysical comparison using mechanistic mathematical dose response models. Absolute values of TCP and NTCP were then compared between IMPT and IMRT. Results: The dose models demonstrate a minimal radiobiological advantage for IMPT compared to IMRT in treating head and neck cancers. Absolute values of TCP were slightly higher, while absolute values of NTCP were slightly lower for IMPT versus IMRT. Conclusions: Further studies are needed to determine if the radiobiological advantage indeed translates to a therapeutic advantage for patients.

Most B-Raf proto-oncogene (BRAF)-mutant melanoma tumors respond initially to BRAF inhibitor (BRAFi)/mitogen-activated protein kinase kinase 1 inhibitor (MEKi) therapy, although few patients have durable long-term responses to these agents. The goal of this study was to use an unbiased computational approach to identify inhibitors that reverse an experimentally derived BRAFi resistance gene expression signature. Using this approach, we found that ibrutinib effectively reverses this signature, and we demonstrate experimentally that ibrutinib resensitizes a subset of BRAFi-resistant melanoma cells to vemurafenib. Ibrutinib is used clinically as an inhibitor of the Src family kinase Bruton tyrosine kinase (BTK); however, neither BTK deletion nor treatment with acalabrutinib, another BTK inhibitor with reduced off-target activity, resensitized cells to vemurafenib. These data suggest that ibrutinib acts through a BTK-independent mechanism in vemurafenib resensitization. To better understand this mechanism, we analyzed the transcriptional profile of ibrutinib-treated BRAFi-resistant melanoma cells and found that the transcriptional profile of ibrutinib was highly similar to that of multiple Src proto-oncogene kinase inhibitors. Since ibrutinib, but not acalabrutinib, has appreciable off-target activity against multiple Src family kinases, it suggests that ibrutinib may be acting through this mechanism. Furthermore, genes that are differentially expressed in ibrutinib-treated cells are enriched in Yes1-associated transcriptional regulator (YAP1) target genes, and we showed that ibrutinib, but not acalabrutinib, reduces YAP1 activity in BRAFi-resistant melanoma cells. Taken together, these data suggest that ibrutinib, or other Src family kinase inhibitors, may be useful for treating some BRAFi/MEKi-refractory melanoma tumors. SIGNIFICANCE STATEMENT: MAPK-targeted therapies provide dramatic initial responses, but resistance develops rapidly; a subset of these tumors may be rendered sensitive again by treatment with an approved Src family kinase inhibitor-ibrutinub-potentially providing improved clinical outcomes.

Research suggests that sleep deprivation both before and after encoding has a detrimental effect on memory for newly learned material. However, there is as yet no quantitative analyses of the size of these effects. We conducted two meta-analyses of studies published between 1970 and 2020 that investigated effects of total, acute sleep deprivation on memory (i.e., at least one full night of sleep deprivation): one for deprivation occurring before learning and one for deprivation occurring after learning. The impact of sleep deprivation after learning on memory was associated with Hedges' g = 0.277, 95% CI [0.177, 0.377]. Whether testing took place immediately after deprivation or after recovery sleep moderated the effect, with significantly larger effects observed in immediate tests. Procedural memory tasks also showed significantly larger effects than declarative memory tasks. The impact of sleep deprivation before learning was associated with Hedges' g = 0.621, 95% CI [0.473, 0.769]. Egger's tests for funnel plot asymmetry suggested significant publication bias in both meta-analyses. Statistical power was very low in most of the analyzed studies. Highly powered, preregistered replications are needed to estimate the underlying effect sizes more precisely. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Most mental disorders appear by age 14, but in most cases, they remain undiagnosed and untreated well into adulthood. A scoping review showed an absence of systematic reviews that address prevalence rates of mental disorders among children and adolescents in Europe that are based on community studies conducted between 2015 and 2020. To estimate the updated pooled prevalence of Anxiety Disorder, Depressive Disorder, Attention Deficit Hyperactivity Disorder (ADHD), Conduct Disorder (CD), Oppositional Defiant Disorder (ODD), Autism Spectrum Disorder, Eating Disorders, Substance Use Disorders (SUD), among children and adolescents living in Europe, a search strategy was conducted using MEDLINE, Embase and Psych Info and studies were also identified from reference lists and gray literature. Eligible studies were evaluated for reliability, validity, and bias. Trends of prevalence rates for each mental disorder were calculated. Almost one in five young people in Europe were found to suffer from a mental disorder, with a pooled prevalence rate of 15.5%. Anxiety disorders had the highest pooled prevalence rate (7.9% (95% CI 5.1–11.8%, I2: 98.0%)), followed by ADHD (2.9% (95% CI 1.2–6.9%, I2 = 94.3%)), ODD (1.9% (95% CI 1.0–3.7%, I2 = 98.4%)), depressive disorder (1.7% (95% CI 1.0–2.9%, I2 = 97.7%)), CD (1.5% (95% CI 0.6–3.8%, I2 = 98.8%)) and ASD (1.4% (95% CI 0.4–5.4%, I2 = 99.7%). No studies on SUD were identified. The mental health of children and adolescents may be improved by introducing routine screening, refining diagnostic sensitivity, raising awareness of mental disorders, minimizing stigma and socioeconomic inequality, as well as developing early intervention services. These facilitators of good mental health need to be prioritized, especially at a time of unprecedented risk factors for poor mental health.