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.

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.

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.

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.

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.

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.

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.

Predictors of risk for relapse in patients with schizophrenia or schizoaffective disorder during olanzapine drug therapy.

PURPOSE: To evaluate the relationship of dose decrease, symptom worsening, and baseline covariates on subsequent relapse during olanzapine treatment in patients with schizophrenia or schizoaffective disorder. METHODS: In two 28-week, randomized, double-blind clinical trials, a Cox proportional hazards model was used to determine potential correlates of relapse (defined as > or =20% worsening on PANSS total and CGI-Severity 3) among patients (N=271) who responded to 8 weeks of olanzapine treatment (10-20mg/day). Variables examined included: demographics, illness characteristics, baseline symptoms, symptom change, dose, adverse events, and functioning. RESULTS: Patients with a lower last dose relative to the preceding visit interval were 4 times more likely to relapse during that visit interval than other patients (p<.001). A similar finding was observed for a decrease in interval modal dose, although this variable was more predictive of relapse in the visit interval immediately following dose decrease (p=.027). In a subgroup analysis by gender, there was a significantly greater incidence of relapse in men with a dose decrease, whereas a dose decrease in women did not correlate with relapse. Relapse was also correlated with the emergence or worsening of a psychiatric adverse event during the same (p<.001) and preceding (p=.007) visit intervals, and with increased rating scale measures of psychopathology. The occurrence of a non-psychiatric adverse event was not associated with relapse. CONCLUSION: Dose decrease is a significant predictor of relapse in male but not female patients. Psychiatric adverse events also predicted relapse. Patients should be periodically reassessed to determine the need for maintenance treatment with appropriate dose.

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.

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.

Protein-protein recognition, hydride transfer and proton pumping in the transhydrogenase complex.

BACKGROUND: Membrane-bound ion pumps are involved in metabolic regulation, osmoregulation, cell signalling, nerve transmission and energy transduction. How the ion electrochemical gradient interacts with the scalar chemistry and how the catalytic machinery is gated to ensure high coupling efficiency are fundamental to the mechanism of action of such pumps. Transhydrogenase is a conformationally coupled proton pump linking a proton gradient to the redox reaction between NAD(H) and NADP(H). The enzyme has three components; dI binds NAD(H), dII spans the membrane and dIII binds NADP(H). RESULTS: The first crystal structure of a transhydrogenase dI component (from Rhodospirillum rubrum) has been determined at 2.0 A resolution. The monomer comprises two domains. Both are involved in dimer formation, and one has a Rossmann fold that binds NAD+ in a novel mode. The two domains can adopt different conformations. In the most closed conformation, the nicotinamide ring is expelled from the cleft between the two domains and is exposed on the outside of the protein. In this conformation it is possible to dock the structure of dI/NAD+ with that of a dIII/NADP+ complex to provide the first insights into the molecular basis of the hydride-transfer step. CONCLUSIONS: Analysis of the model of the dI/dIII complex identifies residues potentially involved in dI/dIII interaction and shows how domain motion in dI results in a shift in position of the nicotinamide ring of NAD+. We propose that this movement is responsible for switching between the forbidden and allowed states for hydride transfer during proton pumping.

Insights into enzyme evolution revealed by the structure of methylaspartate ammonia lyase.

Methylaspartate ammonia lyase (MAL) catalyzes the magnesium-dependent reversible alpha,beta-elimination of ammonia from L-threo-(2S,3S)-3-methylaspartic acid to mesaconic acid. The 1.3 A MAD crystal structure of the dimeric Citrobacter amalonaticus MAL shows that each subunit comprises two domains, one of which adopts the classical TIM barrel fold, with the active site at the C-terminal end of the barrel. Despite very low sequence similarity, the structure of MAL is closely related to those of representative members of the enolase superfamily, indicating that the mechanism of MAL involves the initial abstraction of a proton alpha to the 3-carboxyl of (2S,3S)-3-methylasparic acid to yield an enolic intermediate. This analysis resolves the conflict that had linked MAL to the histidine and phenylalanine ammonia lyase family of enzymes.

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.

Crystallization and preliminary X-ray diffraction studies on cytosolic (class 1) aldehyde dehydrogenase from sheep liver.

The cytosolic (Class 1) aldehyde dehydrogenase (AlDH) from sheep liver has been crystallized in a form suitable for X-ray diffraction studies. The crystals, grown by vapour diffusion using 6.5 to 7.5% methoxypolyethylene glycol 5000 as precipitant, at pH 6.5, are orthorhombic with cell dimensions a = 80.7, b = 92.5, c = 151.6 A, space-group P2(1)2(1)2(1), and one dimer in the asymmetric unit. The crystals diffract to at least 2.8 A resolution. Although unmodified AlDH crystallized readily, a key factor in obtaining diffraction-quality crystals was the covalent attachment of an active site reporter group, provided by 3,4-dihydro-3-methyl-6-nitro-2H-1,3-benzoxazin-2-one.

Catching up on schizophrenia. The Fifth International Congress on Schizophrenia Research, Warm Springs, Va, April 8-12, 1995.

It is axiomatic that the diversity and ingenuity of strategies in the study of schizophrenia bear testimony to the complexity of this disorder. Accordingly, the opportunity for investigators of diverse interests to share their latest findings and be informed of developments in key areas of science is critical to advance our understanding of schizophrenia. Nearly 700 investigators from around the world gathered at Warm Springs, Va, to present their data at the Fifth International Congress on Schizophrenia Research (April 8-12, 1995). This 5-day conference, held every other year alternating with the European Winter Workshop on Schizophrenia, is co-organized by S. Charles Schulz, MD, Case Western Reserve University, Cleveland, Ohio, and Carol Tamminga, MD, Maryland Psychiatric Research Center, University of Maryland at Baltimore. Drs Schulz and Tamminga first held the Congress in 1987 in Clearwater, Fla, with 170 investigators presenting. The Congress has flourished since then and is now the largest research meeting devoted solely to schizophrenia. The Congress organizers, the program coordinator (Jeffrey Lieberman, MD, Hillside Hospital, Glen Oaks, NY), and the Congress coordinator (Susan Nusbaum, Maryland Psychiatric Research Center) are congratulated on the success of this event and its contribution to fostering initiatives and collaborations within schizophrenia research.