Social Development Through a Lunch Buddy Program

The intent of this literature review is to discuss the necessity of a lunch buddy program for students in special education. The review fist looks at the process of inclusive education and the effect that the educational movement has had on students in special education. Inclusion is defined as well as the impact it has on an individual\u27s social development. Using research-based evidence, the review will also establish the importance of peer buddy programs for the social development of students in special education. A lunch buddy program will provide special education teachers with the means to assist their students during an essential and social part of every school day

Abstracts from the NIHR INVOLVE Conference 2017

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Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders

Genetic influences on psychiatric disorders transcend diagnostic boundaries, suggesting substantial pleiotropy of contributing loci. However, the nature and mechanisms of these pleiotropic effects remain unclear. We performed analyses of 232,964 cases and 494,162 controls from genome-wide studies of anorexia nervosa, attention-deficit/hyper-activity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, and Tourette syndrome. Genetic correlation analyses revealed a meaningful structure within the eight disorders, identifying three groups of inter-related disorders. Meta-analysis across these eight disorders detected 109 loci associated with at least two psychiatric disorders, including 23 loci with pleiotropic effects on four or more disorders and 11 loci with antagonistic effects on multiple disorders. The pleiotropic loci are located within genes that show heightened expression in the brain throughout the lifespan, beginning prenatally in the second trimester, and play prominent roles in neurodevelopmental processes. These findings have important implications for psychiatric nosology, drug development, and risk prediction.Peer reviewe

Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Background Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. Methods We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. Results Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. Conclusions Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.Peer reviewe

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Analysis of Antioxidant Responsive Gene Expression Changes by Thioredoxin System Inhibitors and Hypoxia

Gene expression profiling measured by cDNA microarray offers a powerful tool for identifying cancer drug mechanism of action, defining drug specificity and for identifying new cancer drug targets. An anti-tumor inhibitor of the thioredoxin-1 (Trx-1) redox system, PX-12 (1-methylhydroxypropyl 2-imidazoloyl disulfide), is currently in Phase I clinical trials and was used as a model for targeted therapy to evaluate the differences between cells growing in culture and the same cells grown as xenografts in immunocompromised mice. Without drug treatment, MCF-7 breast cancer and HT-29 colon cancer cells growing as xenografts in severe combined immune deficient (scid) mice showed marked changes in gene expression compared to the cells in culture, with 42% of genes showing more than a two fold difference in expression. Following treatment with PX-12, the gene changes observed in common accounted for approximately 1% of the total genes changed vivo. After elimination of the effects of Trx-1 inhibitors on known targets in vivo and in vitro, the common increase in genes involved in antioxidant response pathway was chosen for further investigation. Gene expression changes observed during microarray experimentation were validated by real-time RT-PCR. Binding and activation of Nrf2 (nuclear factor (erythroid-derived 2)-like 2) to the antioxidant responsive element (ARE) was evaluated and found to be increased by treatment with Trx-1 inhibitors and hypoxia. Potential mechanisms accounting for the increase of ARE-dependent genes, including activation of protein kinase C, PI3K (phosphoinositide-3-kinase) and p-PERK (phospho-PRKR-like endoplasmic reticulum kinase) and an increase in cellular reactive oxygen species (ROS), determined that the increase in ROS due to hypoxia and Trx-1 system inhibition was sufficient to activate the pathway. Decreasing ROS by addition of an antioxidant was able to reverse the effect of activation of this pathway. The increased expression of ARE/Nrf2 dependent genes by these mechanisms may have important implications for chemotherapy and chemoprevention of human tumors

Automated Aerial Baiting for Invasive Brown Treesnake Control: System Overview and Program Status

The economically and ecologically catastrophic introduction of invasive brown treesnakes to the Pacific Island of Guam has long served as a cautionary tale about the dangers of invasive species and the seeming impossibility of their management on a landscape scale. USDA Wildlife Services and federal and private partners have engineered a system for the automated manufacture and aerial delivery of toxic baits for landscape-scale suppression of brown treesnakes in large and remote forest plots. The helicopter-borne dispensing module can launch four bait cartridges per second, and a single payload of 3,600 cartridges can treat 30 ha of forest at 120 baits/ha in 15 to 30 minutes depending on flightpath efficiency. In this paper we recap the research, development, testing, and implementation of the system, including the procedures for monitoring biological responses to bait applications during an experimental suppression within a 55-ha forest plot surrounded by a snake-proof barrier