Engaging with immigrant students' voices in the school environment: an analysis of policy documents through school websites.

BACKGROUND: For students to feel happy and supported in school, it is important that their views are taken seriously and integrated into school policies. However, limited information is available how the voices of immigrant students are considered in European school contexts. This study generated evidence from written documents to ascertain how student voice practices are described at school websites. METHODS: Between 2 March and 8 April 2021, we reviewed the policy documents publicly available on school websites. The schools located in areas of high immigration in six European countries: Austria, England, Finland, Germany, Romania, and Switzerland. The READ approach was used to guide the steps in the document analysis in the context of policy studies (1) ready the materials, 2) data extraction, 3) data analysis, 4) distil the findings). A combination of qualitative and quantitative approaches with descriptive statistics (n, %, Mean, SD, range) was used for analysis. RESULTS: A total of 412 documents (305 schools) were extracted. Based on reviewing school websites, reviewers'strongly agreed' in seven documents (2%) that information related to seeking student voices could be easily found. On the contrary, in 247 documents (60%), reviewers strongly indicated that information related to seeking student voices was missing. No clear characteristics could be specified to identify those schools were hearing students' voices is well documented. The most common documents including statements related to student voice were anti-bullying or violence prevention strategies (75/412) and mission statements (72/412). CONCLUSIONS: Our document analysis based on publicly accessible school websites suggest that student voices are less frequently described in school written policy documents. Our findings provide a baseline to further monitor activities, not only at school level but also to any governmental and local authorities whose intention is to serve the public and openly share their values and practices with community members. A deeper understanding is further needed about how listening to student voices is realized in daily school practices.

"We're not educated on that enough, and we really should be": adolescents' views of mental health service education.

PURPOSE: Despite the susceptibility to the experience of mental distress during adolescence, this population often demonstrate poor help-seeking behaviours. Efforts have been made by schools to address adolescents' knowledge around mental health; less focus has been given to addressing their knowledge of mental health services and avenues for help-seeking. This study aimed to explore adolescents' views of mental health services education. METHODS: An interpretive descriptive design was adopted. Thirty adolescents from Ireland participated in individual interviews. Data were analysed using content analysis. TWO THEMES WERE IDENTIFIED: Recognizing Gaps in Knowledge about Mental Health Service Education, and Enhancing Mental Health Service Education for Young People. Participants reported gaps in their knowledge about mental health services and were uncertain how to access help. Current strategies (e.g., print media) were considered tokenistic and ineffective; instead, multimedia (film/TV) approaches were recommended. RESULTS: Two themes were identified: Recognizing Gaps in Knowledge about Mental HealthService Education, and Enhancing Mental Health Service Education for YoungPeople. Participants reported gaps in their knowledge about mental healthservices and were uncertain how to access help. Current strategies (e.g., print media) were considered tokenistic and ineffective; instead, multimedia (film/TV) approaches were recommended. CONCLUSIONS: Current mental health education programmes need to expand their focus beyond social/emotional well-being, providing adolescents with the knowledge they need to access appropriate supports. Considering traditional print media was viewed as ineffective, while film/TV had an influence on perceptions of mental health services, a multimedia approach to education may be an effective way of engaging this population.

Dose imbalance of DYRK1A kinase causes systemic progeroid status in Down syndrome by increasing the un-repaired DNA damage and reducing LaminB1 levels.

BACKGROUND: People with Down syndrome (DS) show clinical signs of accelerated ageing. Causative mechanisms remain unknown and hypotheses range from the (essentially untreatable) amplified-chromosomal-instability explanation, to potential actions of individual supernumerary chromosome-21 genes. The latter explanation could open a route to therapeutic amelioration if the specific over-acting genes could be identified and their action toned-down. METHODS: Biological age was estimated through patterns of sugar molecules attached to plasma immunoglobulin-G (IgG-glycans, an established "biological-ageing-clock") in n = 246 individuals with DS from three European populations, clinically characterised for the presence of co-morbidities, and compared to n = 256 age-, sex- and demography-matched healthy controls. Isogenic human induced pluripotent stem cell (hiPSCs) models of full and partial trisomy-21 with CRISPR-Cas9 gene editing and two kinase inhibitors were studied prior and after differentiation to cerebral organoids. FINDINGS: Biological age in adults with DS is (on average) 18.4-19.1 years older than in chronological-age-matched controls independent of co-morbidities, and this shift remains constant throughout lifespan. Changes are detectable from early childhood, and do not require a supernumerary chromosome, but are seen in segmental duplication of only 31 genes, along with increased DNA damage and decreased levels of LaminB1 in nucleated blood cells. We demonstrate that these cell-autonomous phenotypes can be gene-dose-modelled and pharmacologically corrected in hiPSCs and derived cerebral organoids. Using isogenic hiPSC models we show that chromosome-21 gene DYRK1A overdose is sufficient and necessary to cause excess unrepaired DNA damage. INTERPRETATION: Explanation of hitherto observed accelerated ageing in DS as a developmental progeroid syndrome driven by DYRK1A overdose provides a target for early pharmacological preventative intervention strategies. FUNDING: Main funding came from the "Research Cooperability" Program of the Croatian Science Foundation funded by the European Union from the European Social Fund under the Operational Programme Efficient Human Resources 2014-2020, Project PZS-2019-02-4277, and the Wellcome Trust Grants 098330/Z/12/Z and 217199/Z/19/Z (UK). All other funding is described in details in the "Acknowledgements".

A cryptic clue to neurodegeneration?

Antisense oligonucleotides rescue cryptic RNA splicing and neuron regeneration.

Emergency department utilisation by homeless children in Dublin, Ireland: a retrospective review.

INTRODUCTION: Despite increasing prevalence, European family homelessness remains under-researched. METHODS: A retrospective review was performed of homeless children attending a paediatric emergency department in Dublin, Ireland, from 1 January 2017 to 31 December 2020. Comparison was made with a random cohort of 1500 non-homeless paediatric attendances in 2019. Homelessness was defined using the European Typology of Homelessness and Housing Exclusion, including those with addresses of no fixed abode, government homeless accommodation and certain residential settings. The objectives were to compare presentations between homeless and non-homeless children. We were interested in determining differences regarding demographics, healthcare utilisation, clinical presentation and outcomes. RESULTS: Of 197 437 attendances 3138 (1.59%) were homeless. Compared with the non homeless, homeless children were less likely to be ethnically Irish (37.4% vs 74.6%, p<0.001) or have been born in Ireland (82.3% vs 96.2%, p<0.001). Irish Travellers (3% vs 0.8%), Roma (22.5% vs 2.4%) and black (21.1% vs 4.2%) ethnicities were over-represented (p<0.001) in the homeless cohort.Homeless children were younger (age <12 months: 26% vs 16%; p<0.001), less likely to be fully vaccinated (73.6% vs 81.9%, p<0.001) and have registered general practitioners (89.7% vs 95.8%, p<0.001). They were more likely to represent within 2 weeks (15.9% vs 10.5%, p<0.001), and use ambulance transportation (13.2% vs 6.7%, p<0.001). Homeless children had lower acuity presentations (triage category 4-5: 47.2% vs 40.7%, p<0.001) and fewer admissions (5.9% vs 8.4%, p<0.001) than non-homeless children. DISCUSSION: Infants, Irish Travellers, Roma and black ethnicities were over-represented in homeless presentations. Homeless children had increased reliance on emergency services for primary healthcare needs.

SLC19A1 Genetic Variation Leads to Altered Thiamine Diphosphate Transport: Implications for the Risk of Developing Wernicke-Korsakoff's Syndrome.

AIMS: Wernicke-Korsakoff syndrome (WKS) is commonly associated with chronic alcohol misuse, a condition known to have multiple detrimental effects on thiamine metabolism. This study was conducted to identify genetic variants that may contribute to the development of WKS in individuals with alcohol dependence syndrome through alteration of thiamine transport into cells. METHODS: Exome sequencing data from a panel of genes related to alcohol metabolism and thiamine pathways were analysed in a discovery cohort of 29 individuals with WKS to identify possible genetic risk variants associated with its development. Variant frequencies in this discovery cohort were compared with European frequencies in the Genome Aggregation Database browser, and those present at significantly higher frequencies were genotyped in an additional cohort of 87 alcohol-dependent cases with WKS and 197 alcohol-dependent cognitively intact controls. RESULTS: Thirty non-synonymous variants were identified in the discovery cohort and, after filtering, 23 were taken forward and genotyped in the case-control cohort. Of these SLC19A1:rs1051266:G was nominally associated with WKS. SLC19A1 encodes the reduced folate carrier, a major transporter for physiological folate in plasma; rs1051266 is reported to impact folate transport. Thiamine pyrophosphate (TPP) efflux was significantly decreased in HEK293 cells, stably transfected with rs1051266:G, under thiamine deficient conditions when compared with the efflux from cells transfected with rs1051266:A (P = 5.7 × 10-11). CONCLUSION: This study provides evidence for the role of genetic variation in the SLC19A1 gene, which may contribute to the development of WKS in vivo through modulation of TPP transport in cells.

Physical education student teachers' wellbeing during Covid-19: Resilience resources and challenges from school placement.

The coronavirus 2019 (Covid-19) pandemic has given rise to significant global challenges across education, and specifically in the physical education teacher education (PETE) community. Students attending teacher education programmes during the Covid-19 pandemic have experienced an abrupt and unprecedented pedagogical transition from a face-to-face capacity to remote teaching, learning, and assessment environments. Crucially, student teachers' school placement experiences faced increased challenges and practical implications from additional environmental and social changes. In the context of continued global and national challenges for initial teacher education (ITE) programmes, the present qualitative study, using a representative sample of 24 student physical education (PE) teachers from a PETE programme, investigates the perceived implications of the Covid-19 pandemic on student teachers' practice and wellbeing during their final 2020/2021 academic year. Results indicate that student teachers maintain that exercise, connections with the university and school placement communities, alongside personal and professional organisation skills serve as resilience resources protecting their wellbeing. Conversely, student teachers express that school placement isolation, restricted PE delivery, increased workload, low teacher efficacy, and the responsibility to implement Covid-19 behaviour regulations presented as challenges that negatively affect their wellbeing. The paper concludes with practices that may further support PETE and ITE programmes and their student teachers to maintain a stable level of wellbeing throughout their careers.

Teachers' views and experiences of student mental health and well-being programmes: A systematic review.

Background: In schools, teachers are often tasked with implementing mental health and well-being programmes. However, little is known about teachers' views on and experiences with implementing these programmes.Aim: The aim of this systematic review was to explore teachers' views and experiences of mental health and well-being intervention programmes developed to promote and protect student mental health.Methods: A systematic review of the empirical literature was conducted using the following databases: Academic Search Complete, APA PsycArticles, APA PsycInfo, British Education Index, Education Full Text (H.W. Wilson), ERIC, Social Sciences Full Text (H.W. Wilson), and SocINDEX with Full Text.Findings: Seven papers met the inclusion criteria. Teachers reported several challenges to the successful implementation of mental health and well-being programmes, including a lack of time allotted in the curriculum, insufficient training, and inadequate interagency support. There was evidence of conflicting opinions regarding the role of teachers in supporting students.Conclusion: It is recommended that mental health and well-being are viewed as central to schools' ethos and that teachers are adequately prepared to implement programmes.

Patient-specific Alzheimer-like pathology in trisomy 21 cerebral organoids reveals BACE2 as a gene dose-sensitive AD suppressor in human brain.

A population of more than six million people worldwide at high risk of Alzheimer's disease (AD) are those with Down Syndrome (DS, caused by trisomy 21 (T21)), 70% of whom develop dementia during lifetime, caused by an extra copy of ß-amyloid-(Aß)-precursor-protein gene. We report AD-like pathology in cerebral organoids grown in vitro from non-invasively sampled strands of hair from 71% of DS donors. The pathology consisted of extracellular diffuse and fibrillar Aß deposits, hyperphosphorylated/pathologically conformed Tau, and premature neuronal loss. Presence/absence of AD-like pathology was donor-specific (reproducible between individual organoids/iPSC lines/experiments). Pathology could be triggered in pathology-negative T21 organoids by CRISPR/Cas9-mediated elimination of the third copy of chromosome 21 gene BACE2, but prevented by combined chemical ß and γ-secretase inhibition. We found that T21 organoids secrete increased proportions of Aß-preventing (Aß1-19) and Aß-degradation products (Aß1-20 and Aß1-34). We show these profiles mirror in cerebrospinal fluid of people with DS. We demonstrate that this protective mechanism is mediated by BACE2-trisomy and cross-inhibited by clinically trialled BACE1 inhibitors. Combined, our data prove the physiological role of BACE2 as a dose-sensitive AD-suppressor gene, potentially explaining the dementia delay in ~30% of people with DS. We also show that DS cerebral organoids could be explored as pre-morbid AD-risk population detector and a system for hypothesis-free drug screens as well as identification of natural suppressor genes for neurodegenerative diseases.

Maternal intentions towards infant sleeping practices in Ireland.

AIM: Mortality from Sudden Infant Death Syndrome (SIDS) has reduced by 50%-85% globally. Despite improvements from 1990 to 2009, the Irish SIDS rate has plateaued. Reasons for this are unclear, but may be related to a reduced parental SIDS awareness. Our study aimed to assess intentions regarding infant sleeping practices in mothers in Ireland. METHODS: A cross-sectional survey of post-partum mothers was performed in the Rotunda Hospital over a four month period. Mothers with a history of SIDS, miscarriage or neonatal admissions were excluded. RESULTS: Of 451 participants, unsafe sleeping positions were intended by 15.4%, reduced by Irish ethnicity [AOR = 0.52, 95% CI = 0.277-0.959, P = .036]. Safe sleep locations were intended by 66%, increased by Irish ethnicity [AOR = 2.6, 95% CI = 1.617-4.191, P < .001], and reduced by young maternal age [AOR = 0.15, 95% CI = 0.03-0.713, P = .02]. Maternal smoking was more likely in mothers with lower educational level [AOR = 3.51, 95% CI = 1.169-10.56, P = .03]. Soft bedding use was intended by 34.8%, increased in younger mothers [AOR = 2.28, 95% CI = 1.04-4.98, P = .04]. Breastfeeding was intended by 72.2%, decreased by Irish ethnicity [AOR = 0.14, 95% CI = 0.067-0.271, P < .001], and low maternal education [AOR = 0.22, 95% CI = 0.117-0.406, P < .001]. CONCLUSION: Educational campaigns on safe sleep for infants in Ireland need to address modifiable SIDS risks factors, focusing on younger, non-Irish mothers, with lower educational attainment.

The influence of regression models on genome-wide association studies of alcohol dependence: a comparison of binary and quantitative analyses.

INTRODUCTION: Genome-wide association studies (GWAS) of alcohol dependence syndrome (ADS) offer a platform to detect genetic risk loci. However, the majority of the ADS GWAS undertaken, to date, have utilized a case-control design and have failed to identify consistently replicable loci with the exception of protective variants within the alcohol metabolizing genes, notably ADH1B. The ADS phenotype shows considerable variability which means that the use of quantitative variables as a proxy for the severity of ADS has the potential to facilitate identification of risk loci by increasing statistical power. The current study aims to examine the influences of using binary and adjusted quantitative measures of ADS on GWAS outcomes and on calculated polygenic risk scores (PRS). METHODS: A GWAS was performed in 1251 healthy controls with no history of excess alcohol use and 739 patients with ADS classified using binary DMS-IV criteria. Two additional GWAS were undertaken using a quantitative score based on DSM-IV criteria, which were applied assuming both normal and non-normal distributions of the phenotypic variables. PRS analyses were performed utilizing the data from the binary and the quantitative trait analyses. RESULTS: No associations were identified at genome-wide significance in any of the individual GWAS; results were comparable in all three. The top associated single nucleotide polymorphism was located on the alcohol dehydrogenase gene cluster on chromosome 4, consistent with previous ADS GWAS. The quantitative trait analysis adjusted for the distribution of the criterion score and the associated PRS had the smallest standard errors and thus the greatest precision. CONCLUSION: Further exploitation of the use of qualitative trait analysis in GWAS in ADS is warranted.

State of Mind Ireland-Higher Education: A Mixed-Methods Longitudinal Evaluation of a Positive Mental Health Intervention.

OBJECTIVE: This study evaluates the impact of the State of Mind Ireland-Higher Education (SOMI-HE) Mental Fitness intervention on student wellbeing, resilience, and physical activity (PA) participation. DESIGN: A mixed-methods research design, comprising of a self-report questionnaire, and semi-structured focus group interviews at pre, post and follow-up phases were employed. Participants were a sample of 134 higher education students (29% male: 71% female; mean age range 18 to 25 years old). The quantitative outcome measures of wellbeing, resilience and PA data were analysed using SPSS version 26.0, (IBM, Armonk, NY, USA) with appropriate statistical analysis. Qualitative data were analysed using thematic analysis to capture the long-term outcomes and impact of the intervention. RESULTS: The results indicate a significant intervention effect on participants' wellbeing (t (120) = -4.27, p < 0.001), PA levels (t (126) = 3.91, p < 0.001) and motivational readiness for exercise change (χ2 (1, n = 131) = 6.9, p < 0.009 (2-sided). Qualitative findings suggest a sustained long-term increase in PA and resilience skills for positive mental health, and reduced stigma and barriers to positive mental health. CONCLUSION: The findings demonstrate the effectiveness of the SOMI-HE evidence-based intervention, and beneficial outcomes of a salutary approach to higher education student mental health.

Modeling Down syndrome in cells: From stem cells to organoids.

Down Syndrome (DS) is a complex chromosomal disorder, with neurological issues, featuring among the symptoms. Primary neuronal cells and tissues are extremely useful, but limited both in supply and experimental manipulability. To better understand the cellular, molecular and pathological mechanisms involved in DS neurodevelopment and neurodegeneration, a range of different cellular models have been developed over the years including human: mouse hybrid cells, transchromosomic mouse embryonic stem cells (ESCs) and human ESC and induced pluripotent stem cells derived from different sources. All of these model systems have provided useful information in the study of DS. Furthermore, different technologies to genetically modify or correct trisomy of either single genes or the whole chromosome have been developed using these cellular models. New techniques and protocols to allow better modeling of cellular mechanisms and disease processes are being developed and the use of cerebral organoids offers great promise for future research into the neural phenotypes seen in DS.

Subcutaneous fat necrosis of the newborn.

A term infant developed subcutaneous fat necrosis of the newborn (SFNN) 17 days following completion of therapeutic hypothermia for hypoxic ischaemic encephalopathy. Initial calcium was normal, however hypercalcaemia requiring hyperhydration and furosemide developed at 4 weeks. Parathyroid hormone and vitamin D were suppressed. At 13 months, she remains on low calcium formula, and has gross motor delay, central hypotonia and early hand preference. Review of 102 articles yielded 119 SFNN cases. Asphyxia was reported in 78%. Twenty-one per cent had hypoglycaemia. Twenty per cent underwent therapeutic hypothermia. Median onset of skin lesions was day 6 (range: 1-70), with a median duration of 62 days (range: 14-390). Hypercalcaemia developed in 53% (median onset day 28, range: 1-210). Fifty-two per cent of hypercalcaemia was asymptomatic. Outcome information was provided in 106/119 cases; 87% reported a full resolution. Persistent calcinosis was present in 6%. Babies treated with therapeutic hypothermia should be closely monitored for SFNN, and development of hypercalcaemia.

Understanding Alternative Bullying Perspectives Through Research Engagement With Young People.

Bullying research has traditionally been dominated by largescale cohort studies focusing on the personality traits of bullies and victims. These studies focus on bullying prevalence, risk and protective factors, and negative outcomes. A limitation of this approach is that it does not explain why bullying happens. Qualitative research can help shed light on these factors. This paper discusses the findings from four mainly qualitative research projects including a systematic review and three empirical studies involving young people to various degrees within the research process as respondents, co-researchers and commissioners of research. Much quantitative research suggests that young people are a homogenous group and through the use of surveys and other large scale methods, generalizations can be drawn about how bullying is understood and how it can be dealt with. Findings from the studies presented in this paper, add to our understanding that young people appear particularly concerned about the role of wider contextual and relational factors in deciding if bullying has happened. These studies underscore the relational aspects of definitions of bullying and, how the dynamics of young people's friendships can shift what is understood as bullying or not. Moreover, to appreciate the relational and social contexts underpinning bullying behaviors, adults and young people need to work together on bullying agendas and engage with multiple definitions, effects and forms of support. Qualitative methodologies, in particular participatory research opens up the complexities of young lives and enables these insights to come to the fore. Through this approach, effective supports can be designed based on what young people want and need rather than those interpreted as supportive through adult understanding.

Genetic association and functional characterization of MCPH1 gene variation in bipolar disorder and schizophrenia.

A rare microcephalin 1 gene (MCPH1) variant rs61749465A>G (p.Asp61Gly) with prior evidence for association with schizophrenia (p = 3.78 × 10-7 ) was tested for association in 2,300 bipolar disorder (BPD) participants, 1,930 SCZ participants and 1,820 normal comparison subjects. We report evidence for association of rs61749465A>G with BPD (p = 0.0009). rs61749465 is located in the N-terminal of the BRCT1 domain of MCPH1. Bioinformatic analysis predicted the Asp61Gly substitution to be damaging to MCPH1 function. A second MCPH1 BRCT1 domain variant (rs199422124C>G; p.Thr27Arg), reported to cause autosomal recessive microcephaly, was not detected in the participants tested here. We sought to characterize the functional effects of these variants on MCPH1 function. Cell count assays indicated that rs199422124 allele G had a greater impact on cell survival compared to the G allele of rs61749465. Gene expression analysis combined with gene network and pathway analysis indicated that rs61749465 allele G may impact protein translation and cell cycle control. The evidence for association between rs61749465A>G and psychosis in both BPD and SCZ warrants further replication. Likewise, the data from the functional analyses point to molecular mechanisms that may underlie the proposed MCPH1 mediated risk of psychosis and pathogenesis in autosomal recessive microcephaly require additional experimental validation.

Exome sequence analysis and follow up genotyping implicates rare ULK1 variants to be involved in susceptibility to schizophrenia.

Schizophrenia (SCZ) is a severe, highly heritable psychiatric disorder. Elucidation of the genetic architecture of the disorder will facilitate greater understanding of the altered underlying neurobiological mechanisms. The aim of this study was to identify likely aetiological variants in subjects affected with SCZ. Exome sequence data from a SCZ cas-control sample from Sweden was analysed for likely aetiological variants using a weighted burden test. Suggestive evidence implicated the UNC-51-like kinase (ULK1) gene, and it was observed that four rare variants that were more common in the Swedish SCZ cases were also more common in UK10K SCZ cases, as compared to obesity cases. These three missense variants and one intronic variant were genotyped in the University College London cohort of 1304 SCZ cases and 1348 ethnically matched controls. All four variants were more common in the SCZ cases than controls and combining them produced a result significant at P = 0.02. The results presented here demonstrate the importance of following up exome sequencing studies using additional datasets. The roles of ULK1 in autophagy and mTOR signalling strengthen the case that these pathways may be important in the pathophysiology of SCZ. The findings reported here await independent replication.

Mutation intolerant genes and targets of FMRP are enriched for nonsynonymous alleles in schizophrenia.

Risk of schizophrenia is conferred by alleles occurring across the full spectrum of frequencies from common SNPs of weak effect through to ultra rare alleles, some of which may be moderately to highly penetrant. Previous studies have suggested that some of the risk of schizophrenia is attributable to uncommon alleles represented on Illumina exome arrays. Here, we present the largest study of exomic variation in schizophrenia to date, using samples from the United Kingdom and Sweden (10,011 schizophrenia cases and 13,791 controls). Single variants, genes, and gene sets were analyzed for association with schizophrenia. No single variant or gene reached genome-wide significance. Among candidate gene sets, we found significant enrichment for rare alleles (minor allele frequency [MAF] < 0.001) in genes intolerant of loss-of-function (LoF) variation and in genes whose messenger RNAs bind to fragile X mental retardation protein (FMRP). We further delineate the genetic architecture of schizophrenia by excluding a role for uncommon exomic variants (0.01 ≤ MAF ≥ 0.001) that confer a relatively large effect (odds ratio [OR] > 4). We also show risk alleles within this frequency range exist, but confer smaller effects and should be identified by larger studies.