Using a Social Model to Guide Individualized Education Program Development and Change Educational Paradigms to Be Critically Inclusive.

PURPOSE: The Individuals with Disabilities Education Act explicitly acknowledges disability as a natural part of the human experience. However, special education services, including speech-language services, often focus on remediating the characteristics of the individual with the disability rather than addressing the disabling conditions of the school environment or leveraging the supports and resources available or potentially available to the student. The purpose of this article is to provide a social model of disability framework to guide Individualized Education Program (IEP) development and change educational paradigms around language and communication. METHOD: A discussion of a new theoretical framework, critical inclusion, is situated within the speech-language pathologist's role in the IEP process. An argument for adopting an integrative approach to service delivery through the social model of disability is provided. The Social Communication and Engagement Triad framework is then used to illustrate a social model of disability approach to assessment, IEP goal development, and service delivery case examples. CONCLUSIONS: Speech-language pathologists and all educators have a responsibility for creating a space where all learners belong and diversity in all aspects is celebrated. Embracing a social model of disability approach to the IEP process can support practitioners in their work toward creating a more equitable and inclusive education system.

Uniparental disomy screen of Irish rare disorder cohort unmasks homozygous variants of clinical significance in the TMCO1 and PRKRA genes.

A uniparental disomy (UPD) screen using whole genome sequencing (WGS) data from 164 trios with rare disorders in the Irish population was performed to identify large runs of homozygosity of uniparental origin that may harbour deleterious recessive variants. Three instances of whole chromosome uniparental isodisomy (UPiD) were identified: one case of maternal isodisomy of chromosome 1 and two cases of paternal isodisomy of chromosome 2. We identified deleterious homozygous variants on isodisomic chromosomes in two probands: a novel p (Glu59ValfsTer20) variant in TMCO1, and a p (Pro222Leu) variant in PRKRA, respectively. The overall prevalence of whole chromosome UPiD in our cohort was 1 in 55 births, compared to 1 in ∼7,500 births in the general population, suggesting a higher frequency of UPiD in rare disease cohorts. As a distinct mechanism underlying homozygosity compared to biallelic inheritance, the identification of UPiD has important implications for family planning and cascade testing. Our study demonstrates that UPD screening may improve diagnostic yields by prioritising UPiD chromosomes during WGS analysis.

Risk of work-related violence in England and Wales.

BACKGROUND: There is an urgent need to address high levels of work-related violence (WRV) in Britain to improve the workplace experience of both employers and employees. AIMS: This study specifically explores prevalence rates of work-related violence assaults (WRVAs) for staff at high risk that have supervisor responsibilities and work full-time. METHODS: Five years of data were used for analysis from the Crime Survey of England and Wales (CSEW). Data were filtered for victims of crime from a working population in Britain. RESULTS: Forty-four per cent of respondents who are supervisors and have full-time jobs report that they had been victims of WRVAs. This figure is higher than other previous studies of WRV. CONCLUSIONS: The current study provides further alternative evidence to support high prevalence rates of WRV by selecting for analysis specific work characteristics data that are strongly associated with WRV (supervisor responsibilities and full-time work). It is therefore recommended that future work explores different means of intervention for organizations to implement within the workplace to reduce WRV and protect workers from harm.

Temporal stability of MGMT promoter methylation in glioblastoma patients undergoing STUPP protocol.

Epigenetic silencing of O-6-methylguanine-DNA methyltransferase (MGMT) promoter via methylation in a glioblastoma (GBM), has been correlated with a more favourable response to alkylating chemotherapeutic agents such as temozolomide. The use of global methylation surrogates such as Long Interspersed Nucleotide Element 1 (LINE1) may also be valuable in order to fully understand these highly heterogeneous tumours. In this study, we analysed both original and recurrent GBMs in 22 patients (i.e. 44 tumours), for both MGMT and LINE1 methylation status. In the 22 patients: 14 (63.6%) displayed MGMT methylation stability in the recurrent GBM versus 8 (36.4%), with instability of methylation status. No significant differences in overall and progression free survival was evident between these two groups. LINE1 methylation status remained stable for 12 (54.5%) of recurrent GBM patients versus 9 (41%) of the patients with instability in LINE1 methylation status (p = 0.02), resulting in an increase in overall survival of the stable LINE1 group (p = 0.04). The results obtained demonstrated major epigenetic instability of GBMs treated with temozolomide as part of the STUPP protocol. GBMs appear to undergo selective evolution post-treatment, and have the ability to recur with a newly reprogrammed epigenetic status. Selective targeting of the altered epigenomes in recurrent GBMs may facilitate the future development of both prognostic biomarkers and enhanced therapeutic strategies.

Evidence for genetic heterogeneity between clinical subtypes of bipolar disorder.

We performed a genome-wide association study of 6447 bipolar disorder (BD) cases and 12 639 controls from the International Cohort Collection for Bipolar Disorder (ICCBD). Meta-analysis was performed with prior results from the Psychiatric Genomics Consortium Bipolar Disorder Working Group for a combined sample of 13 902 cases and 19 279 controls. We identified eight genome-wide significant, associated regions, including a novel associated region on chromosome 10 (rs10884920; P=3.28 × 10-8) that includes the brain-enriched cytoskeleton protein adducin 3 (ADD3), a non-coding RNA, and a neuropeptide-specific aminopeptidase P (XPNPEP1). Our large sample size allowed us to test the heritability and genetic correlation of BD subtypes and investigate their genetic overlap with schizophrenia and major depressive disorder. We found a significant difference in heritability of the two most common forms of BD (BD I SNP-h2=0.35; BD II SNP-h2=0.25; P=0.02). The genetic correlation between BD I and BD II was 0.78, whereas the genetic correlation was 0.97 when BD cohorts containing both types were compared. In addition, we demonstrated a significantly greater load of polygenic risk alleles for schizophrenia and BD in patients with BD I compared with patients with BD II, and a greater load of schizophrenia risk alleles in patients with the bipolar type of schizoaffective disorder compared with patients with either BD I or BD II. These results point to a partial difference in the genetic architecture of BD subtypes as currently defined.

Preventive health care of Pony Club horses in rural New South Wales, Australia.

OBJECTIVE: To describe preventive health care provided to a cohort of Pony Club horses in rural New South Wales, Australia, and the associated veterinary involvement. DESIGN: Prospective longitudinal study METHODS: Observational data collected for 48 Pony Club horses using daily owner-kept diaries and monthly veterinary visits for 9-12 months. RESULTS: Frequency of healthcare events varied markedly between the horses; 54% of horses received 5 or more foot-care treatments, 69% received 1-3 anthelmintic treatments, 40% received dental care, 21% received chiropractic care; only 8% were vaccinated. Farriers and owners administered most of the health care. Veterinarians were infrequently involved, administering 2 of the 111 anthelmintic administrations and 2 of the 244 foot-care treatments. No annual health checks or prepurchase examinations were recorded. All dental care was provided by non-veterinary dentists. Horse turnover appeared quick, with 54% of horses acquired within the previous 12 months. CONCLUSION: The majority of preventive health care was provided by farriers and the owners themselves. The type and frequency of healthcare events varied markedly and most commonly involved foot care and anthelmintic administration. The reasons for the lack of veterinary involvement are unclear. Veterinarians engaging with Pony Club families in a preventive context would likely bring health benefits to this population of horses. This may require adaptation of existing veterinary services to meet the demands of this unique population of horses and young riders. Furthermore, epidemiological studies are required to describe the effects of various preventive healthcare interventions on subsequent and long-term horse health.

Customer-perpetrated work-related violence: prevalence and trends in Britain.

BACKGROUND: Incidents of work-related violence (WRV) have increased over the years. These can be damaging to both individual psychological well-being and organizational performance. AIMS: To examine the prevalence and causes of customer-perpetrated WRV in Britain over a 12 year period. Demographic, work and perpetrator's personality characteristics were examined as predictors of WRV. METHODS: Data from the Crime Survey of England and Wales (CSEW) across 2001-13 were filtered specifically to explore responses from victims of customer-perpetrated crime within the working population. RESULTS: On average, 22% of all violent crimes committed by customers occurred in the workplace. Further analysis showed that differences in gender, age as well as managerial/supervisory duties, working hours, employment status, organizational size and occupation were significantly related to incidents of WRV. Perpetrators' personality characteristics were also perceived as predictors of WRV. CONCLUSIONS: This paper provides an alternative approach for reporting customer-perpetrated WRV. Violence at work is considered a widespread problem within the organizational studies literature, which can lead to a variety of stress-related symptoms in affected workers. Based on the current study's findings, a theoretical model is proposed to help combat customer-perpetrated WRV, and as a basis for future research.

Modulation of neuroblastoma disease pathogenesis by an extensive network of epigenetically regulated microRNAs.

MicroRNAs (miRNAs) contribute to the pathogenesis of many forms of cancer, including the pediatric cancer neuroblastoma, but the underlying mechanisms leading to altered miRNA expression are often unknown. Here, a novel integrated approach for analyzing DNA methylation coupled with miRNA and mRNA expression data sets identified 67 epigenetically regulated miRNA in neuroblastoma. A large proportion (42%) of these miRNAs was associated with poor patient survival when underexpressed in tumors. Moreover, we demonstrate that this panel of epigenetically silenced miRNAs targets a large set of genes that are overexpressed in tumors from patients with poor survival in a highly redundant manner. The genes targeted by the epigenetically regulated miRNAs are enriched for a number of biological processes, including regulation of cell differentiation. Functional studies involving ectopic overexpression of several of the epigenetically silenced miRNAs had a negative impact on neuroblastoma cell viability, providing further support to the concept that inactivation of these miRNAs is important for neuroblastoma disease pathogenesis. One locus, miR-340, induced either differentiation or apoptosis in a cell context dependent manner, indicating a tumor suppressive function for this miRNA. Intriguingly, it was determined that miR-340 is upregulated by demethylation of an upstream genomic region that occurs during the process of neuroblastoma cell differentiation induced by all-trans retinoic acid (ATRA). Further biological studies of miR-340 revealed that it directly represses the SOX2 transcription factor by targeting of its 3'-untranslated region, explaining the mechanism by which SOX2 is downregulated by ATRA. Although SOX2 contributes to the maintenance of stem cells in an undifferentiated state, we demonstrate that miR-340-mediated downregulation of SOX2 is not required for ATRA induced differentiation to occur. In summary, our results exemplify the dynamic nature of the miRNA epigenome and identify a remarkable network of miRNA/mRNA interactions that significantly contribute to neuroblastoma disease pathogenesis.

Misbehaviour in Pony Club horses: incidence and risk factors.

REASONS FOR PERFORMING STUDY: Horse misbehaviour is an important cause of poor performance in Pony Club horses, is associated with horse-related rider injuries and has been implicated as a nonspecific presenting sign for musculoskeletal pain. Despite this, little is known about the incidence of and risk factors for misbehaviour in Pony Club horses. OBJECTIVE: This study aimed to describe the incidence and types of misbehaviour in a cohort of Pony Club horses and to identify risk factors for misbehaviour during riding. METHODS: A prospective longitudinal study was conducted with 84 Pony Club horses from 41 families belonging to 7 Pony Clubs in one inland region of Australia. Owners recorded misbehaviour events and kept daily records of horse housing, exercise, nutrition, healthcare and disease status. Horses were subjected to a monthly veterinary examination. Descriptive statistics were calculated to describe the incidence of misbehaviour, and multivariable logistic regression was used to assess putative risk factors. RESULTS: Misbehaviour during riding occurred on 3% of days when horses were ridden. On 52% of days with misbehaviour, the misbehaviour was classified as dangerous. Risk of misbehaviour was independently increased on exercise days when the horse was competing, and in months when the horse was fat or obese, fed supplementary feed daily, grazed on paddocks with >50% of ground cover as green grass, exercised on 5 days per month or less, and ridden for a total of 12 h or more in the month. No significant relationship was detected between misbehaviour and back pain. CONCLUSIONS: In populations such as the study population the risk of misbehaviour is higher in fatter horses, in horses with access to pastures with greater green grass cover, in those fed daily supplements, in horses receiving exercise less frequently, and during competition. POTENTIAL RELEVANCE: These results highlight the importance of considering horse body condition, nutrition and exercise in any investigation of horse misbehaviour. In addition, recommendations based on these results could be used by veterinarians assisting horse owners to prevent misbehaviour. From the perspective of recreational horse owners, behaviour is a key determinant of horse performance.

Comparative genomic and proteomic analysis of high grade glioma primary cultures and matched tumor in situ.

Developing targeted therapies for high grade gliomas (HGG), the most common primary brain tumor in adults, relies largely on glioma cultures. However, it is unclear if HGG tumorigenic signaling pathways are retained under in-vitro conditions. Using array comparative genomic hybridization and immunohistochemical profiling, we contrasted the epidermal and platelet-derived growth factor receptor (EGFR/PDGFR) in-vitro pathway status of twenty-six primary HGG cultures with the pathway status of their original HGG biopsies. Genomic gains or amplifications were lost during culturing while genomic losses were more likely to be retained. Loss of EGFR amplification was further verified immunohistochemically when EGFR over expression was decreased in the majority of cultures. Conversely, PDGFRα and PDGFRß were more abundantly expressed in primary cultures than in the original tumor (p<0.05). Despite these genomic and proteomic differences, primary HGG cultures retained key aspects of dysregulated tumorigenic signaling. Both in-vivo and in-vitro the presence of EGFR resulted in downstream activation of P70s6K while reduced downstream activation was associated with the presence of PDGFR and the tumor suppressor, PTEN. The preserved pathway dysregulation make this glioma model suitable for further studies of glioma tumorigenesis, however individual culture related differences must be taken into consideration when testing responsiveness to chemotherapeutic agents.

Latent structure of psychotic experiences in the general population.

OBJECTIVE: There have been increasing pressures to adopt or incorporate dimensional representations in various sections of DSM-5 including the psychotic disorders section. Thus far, findings offered as evidence of a continuous distribution of psychosis are limited given their exclusive focus on the manifest rather than latent structure of psychotic experiences. The current study sought to determine whether or not psychotic experiences possess a taxonic or dimensional latent structure. METHOD: We investigated the latent structure of psychotic experiences in the Collaborative Psychiatric Epidemiological Surveys (CPES) and the National Comorbidity Survey (NCS). We analyzed responses of participants in these surveys with three multivariate taxometric procedures (MAMBAC, MAXEIG, and L-Mode) after summing responses on the surveys into three indicators of positive psychosis. RESULTS: Taxometric results tended to support a dimensional, rather than taxonic structure for psychotic experiences. In the CPES, all taxometric methods produced graphical and numerical support for a dimensional structure. In the NCS, MAMBAC appeared to slightly support a taxonic structure, whereas MAXEIG and L-Mode supported a dimensional structure. CONCLUSION: There appears to be a dimensional distribution of psychotic experiences in the general population. This supports the incorporation of dimensional representations of psychotic symptoms in the current diagnostic system.

Oncogenic activation of FOXR1 by 11q23 intrachromosomal deletion-fusions in neuroblastoma.

Neuroblastoma tumors frequently show loss of heterozygosity of chromosome 11q with a shortest region of overlap in the 11q23 region. These deletions are thought to cause inactivation of tumor suppressor genes leading to haploinsufficiency. Alternatively, micro-deletions could lead to gene fusion products that are tumor driving. To identify such events we analyzed a series of neuroblastomas by comparative genomic hybridization and single-nucleotide polymorphism arrays and integrated these data with Affymetrix mRNA profiling data with the bioinformatic tool R2 (http://r2.amc.nl). We identified three neuroblastoma samples with small interstitial deletions at 11q23, upstream of the forkhead-box R1 transcription factor (FOXR1). Genes at the proximal side of the deletion were fused to FOXR1, resulting in fusion transcripts of MLL-FOXR1 and PAFAH1B2-FOXR1. FOXR1 expression has only been detected in early embryogenesis. Affymetrix microarray analysis showed high FOXR1 mRNA expression exclusively in the neuroblastomas with micro-deletions and rare cases of other tumor types, including osteosarcoma cell line HOS. RNAi silencing of FOXR1 strongly inhibited proliferation of HOS cells and triggered apoptosis. Expression profiling of these cells and reporter assays suggested that FOXR1 is a negative regulator of fork-head box factor-mediated transcription. The neural crest stem cell line JoMa1 proliferates in culture conditional to activity of a MYC-ER transgene. Over-expression of the wild-type FOXR1 could functionally replace MYC and drive proliferation of JoMa1. We conclude that FOXR1 is recurrently activated in neuroblastoma by intrachromosomal deletion/fusion events, resulting in overexpression of fusion transcripts. Forkhead-box transcription factors have not been previously implicated in neuroblastoma pathogenesis. Furthermore, this is the first identification of intrachromosomal fusion genes in neuroblastoma.

Significant features of the epidemiology of equine influenza in New South Wales, Australia, 2007.

Equine influenza (EI) was first diagnosed in the Australian horse population on 24 August 2007 at Centennial Park Equestrian Centre (CPEC) in Sydney, New South Wales (NSW), Australia. By then, the virus had already spread to many properties in NSW and southern Queensland. The outbreak in NSW affected approximately 6000 premises populated by approximately 47,000 horses. Analyses undertaken by the epidemiology section, a distinct unit within the planning section of the State Disease Control Headquarters, included the attack risk on affected properties, the level of under-reporting of affected properties and a risk assessment of the movement of horses out of the Special Restricted Area. We describe the epidemiological features and the lessons learned from the outbreak in NSW.

Highly variable acquisition rates of Ixodes scapularis (Acari: Ixodidae) by birds on an Atlantic barrier island.

Acquisition of ticks by bird hosts is a central process in the transmission cycles of many tick-borne zoonoses, but tick recruitment by birds has received little direct study. We documented acquisition of Ixodes scapularis Say on birds at Fire Island, NY, by removing ticks from mist-netted birds, and recording the number of ticks on birds recaptured within 4 d of release. Eight bird species acquired at least 0.8 ticks bird(-1) day(-1) during the seasonal peak for at least one age class of I. scapularis. Gray Catbirds, Eastern Towhees, Common Yellowthroats, and Northern Waterthrushes collectively accounted for 83% of all tick acquisitions; and six individuals apportioned among Black-billed Cuckoo, Gray Catbird, Eastern Towhee, and Common Yellowthroat were simultaneously infested with both larvae and nymphs. Bird species with the highest acquisition rates were generally ground foragers, whereas birds that did not acquire ticks in our samples generally foraged above the ground. Tick acquisition by birds did not differ between deciduous and coniferous forests. Among the 15 bird species with the highest recruitment rates, acquisition of nymphs was not correlated with acquisition of larvae. Tick acquisition rates by individual bird species were not correlated with the reservoir competence of those species for Lyme borreliae. However, birds with high tick acquisition rates can contribute large numbers of infected ticks, and thus help maintain the enzootic cycle, even if their levels of reservoir competence are relatively low.

Host-seeking activity and avian host preferences of mosquitoes associated with West Nile virus transmission in the northeastern U.S.A.

Mosquito host-seeking activity was studied using a custom-designed trap to explore: (1) at which time interval of the night adult mosquito abatement would be most effective, and (2) if there exists an avian-specific host-seeking preference. Overnight trials using traps baited with dry ice showed that Aedes taeniorhynchus (Wiedemann) was most active at dusk and was then captured throughout the night. In contrast, Culex spp. (Cx. pipiens (Linnaeus) and Cx. restuans (Theobald) delayed most activity until about two h after dusk and were then captured through the night. This pattern suggests that management activities directed at adult Culex spp. would be most effective if initiated well after sunset. Mosquito capture rates in traps baited with birds in net bags were significantly greater than those with empty net bags, indicating that mosquitoes were attracted to the birds and not incidentally being sucked in by the custom trap's strong fan motor (Wilcoxon matched-pairs signed-ranks test, n=24, t=30, p<0.05). Regression analysis showed that bird weight influenced mosquito attraction (r2=0.21, p=0.02). Trials with paired traps that contained different native bird species showed that Gray Catbirds, Dumatella carolinensis, attracted more mosquitoes than the heavier Northern Cardinals, Cardinalis cardinalis (paired samples t-test, t=2.58, df=7, p=0.04). However, attractiveness did not differ substantially among bird species, and Gray Catbirds did not attract more mosquitoes than all other birds combined as a group. American Robins, Turdus migratorius (n=4) were comparable in attractiveness to other bird species, but not enough American Robins were captured for a comprehensive study of mosquito avian preference.

Effects of different forms of exercise on post inhibitory rebound and unwanted behaviour in stabled horses.

REASONS FOR PERFORMING STUDY: It is unknown if different locomotor activities are equally effective at meeting the stabled horse's need for exercise and if they attenuate unwanted behaviour. HYPOTHESIS: Alternative forms of exercise influence the intensity of locomotor activities during a period of turn-out (the so-called rebound effect) and the occurrence of unwanted or undesirable activities during standard handling situations. METHOD: Twenty-four horses kept in stables were randomly assigned to one of 4 exercise regimes (walker, treadmill, turn-out and riding) for 4 consecutive days. Because these forms of exercise provide additional environmental stimulation, beyond that provided by exercise, each horse served as its own control in 4 corresponding (no exercise) control treatments presented in a balanced order. Unwanted behaviour was tested by taking horses to weighing scales and loading and unloading them onto a 4-horse float by an experienced handler and the rebound effect was tested by releasing them into a large arena for a period of 15 min at the end of the exercise and control treatments. RESULTS: Locomotor activities made up a large part of behaviour in the large arena following control treatments and all exercise regimes were sufficient to reduce the intensity of walking (P < 0.05), trotting (P < 0.01) and cantering (P < 0.001) on release into a large arena. Exercise regime reduced the number of bucks (P < 0.01) and rolling (P < 0.05) during rebound tests suggesting that turn-out was having a stronger effect than the other 3 exercise regimes. Exercise regimes significantly reduced the amount of unwanted behaviour and the number of commands given by the handler during weighing (P < 0.05) but had no effect on these behaviours during loading onto a float. CONCLUSION: Providing stabled horses with one hour/day of exercise on a walker, treadmill, turn-out or by being ridden are all effective at allowing expression of locomotor activities in stabled horses. POTENTIAL RELEVANCE: Providing stabled horses with regular exercise is likely to provide positive effects on horse welfare, training ability and handler safety.

Behavioural and physiological effects of virginiamycin in the diets of horses with stereotypies.

The effects of dietary supplements of virginiamycin on the behaviour and physiology of 17 thoroughbred geldings (five cribbers, six weavers and six control horses) were compared with the effects of a placebo over a period of 16 weeks. Virginiamycin had no effect on the horses' stereotypic behaviour, but it reduced their explorative behaviour, possibly owing to a reduction in feeding motivation. Virginiamycin increased the water intake of the cribbers and decreased the water intake of the control horses, but it was not possible to eliminate possible confounding factors for this effect. Virginiamycin had no other significant effects on the behaviour or physiology of the horses, and had no effect on the digestibility of their diets.

Embolectomy in a rabbit acute arterial occlusion model using a novel electromechanical extraction device.

A prototype endovascular electromechanical clot-extraction device was fabricated using a combination of shape memory polymer and shape memory nickel-titanium alloy (nitinol). Five embolic vascular occlusions were created in 4 rabbits by injecting thermally coagulated blood through a 4F catheter in the common carotid artery. Angiography immediately after clot injection showed complete or partial occlusion of the common carotid artery. Posttreatment angiography showed complete (2/5), partial (2/5), or no (1/5) restoration of blood flow.