Cognate restriction of transposition by piggyBac-like proteins.

Mobile genetic elements have been harnessed for gene transfer for a wide variety of applications including generation of stable cell lines, recombinant protein production, creation of transgenic animals, and engineering cell and gene therapy products. The piggyBac transposon family includes transposase or transposase-like proteins from a variety of species including insect, bat and human. Recently, human piggyBac transposable element derived 5 (PGBD5) protein was reported to be able to transpose piggyBac transposons in human cells raising possible safety concerns for piggyBac-mediated gene transfer applications. We evaluated three piggyBac-like proteins across species including piggyBac (insect), piggyBat (bat) and PGBD5 (human) for their ability to mobilize piggyBac transposons in human cells. We observed a lack of cross-species transposition activity. piggyBac and piggyBat activity was restricted to their cognate transposons. PGBD5 was unable to mobilize piggyBac transposons based on excision, colony count and plasmid rescue analysis, and it was unable to bind piggyBac terminal repeats. Within the piggyBac family, we observed a lack of cross-species activity and found that PGBD5 was unable to bind, excise or integrate piggyBac transposons in human cells. Transposition activity appears restricted within species within the piggyBac family of mobile genetic elements.

Factors Associated with Review Board Dispositions following Re-hospitalization among Discharged Persons found Not Criminally Responsible.

In the Canadian forensic mental health system, a person found Not Criminally Responsible on account of Mental Disorder (NCRMD) and given a conditional discharge returns to the community while remaining under the jurisdiction of a provincial/territorial Review Board. However, the individual can be re-hospitalized while on conditional discharge, for reasons such as substance use, violation of conditions, or violence. We investigated whether being re-hospitalized has an impact on the factors associated with the subsequent Review Board disposition. Persons found NCRMD from the three largest Canadian provinces who were conditionally discharged at least once during the observation period were included in the sample (N = 1,367). These individuals were involved in 2,920 disposition hearings; nearly one-third of patients (30%) were re-hospitalized after having been conditionally discharged by the Review Board. The factors examined included the scales of the Historical Clinical Risk Management-20 and salient behavior that occurred since the previous hearing, such as substance use or violence. The greater presence of clinical items resulted in a greater likelihood of a hospital detention decision at the next hearing. The effect was larger for the re-hospitalized group than for the group who successfully remained in the community since the last hearing. The results suggest that dynamic factors, specifically indicators of mental health, are heavily weighted by the Review Boards, consistent with the literature on imminent risk and in line with the NCRMD legislation. Copyright © 2016 John Wiley & Sons, Ltd.

The national trajectory project of individuals found not criminally responsible on account of mental disorder. Part 5: how essential are gender-specific forensic psychiatric services?

OBJECTIVE: To state the sociodemographic characteristics, mental health histories, index offence characteristics, and criminal histories of male and female forensic psychiatric patients. Clinicians and researchers advocate that mental health and criminal justice organizations implement gender-specific services; however, few studies have sampled forensic patients to evaluate the extent to which men's and women's treatment and management needs are different. METHOD: Data were collected from Review Board files from May 2000 to April 2005 in the 3 largest Canadian provinces. Using official criminal records, participants were followed for 3 to 8 years, until December 2008. The final sample comprised 1800 individuals: 15.6% were women and 84.4% were men. RESULTS: There were few demographic differences, but women had higher psychosocial functioning than men. Both men and women had extensive mental health histories; women were more likely diagnosed with mood disorders and PDs and men were more likely diagnosed with schizophrenia spectrum disorders and SUDs. The nature of the index offence did not differ by gender, except women were more likely to have perpetrated murders and attempted murders. For offences against a person, women were more likely to offend against offspring and partners and less likely to offend against strangers, compared with men. Women had significantly less extensive criminal histories than men. CONCLUSIONS: Not criminally responsible on account of mental disorder-accused women have a distinct psychosocial, clinical, and criminological profile from their male counterparts, which may suggest gender-specific assessment, risk management, and treatment in forensic services could benefit patients. The findings are also consistent with traditional models (Risk-Need-Responsivity) and ultimately demonstrate the importance of individual assessment and client-centred services.

The use of risk and need factors in forensic mental health decision-making and the role of gender and index offense severity.

Canadian legislation makes Review Boards (RBs) responsible for rendering dispositions for individuals found Not Criminally Responsible on account of Mental Disorder (NCRMD) after considering public safety, the mental condition of the accused, and his/her potential for community reintegration. We reviewed 6,743 RB hearings for 1,794 individuals found NCRMD in the three largest Canadian provinces to investigate whether items from two empirically supported risk assessment measures, the Historical Clinical Risk Management-20 and the Violence Risk Appraisal Guide, were considered. Less than half the items were included in expert reports or in RBs' reasons for dispositions, and consideration of these items differed according to gender and index offense severity of the accused. These items included evidence-based risk factors and/or legally specified criteria: mental health, treatment, and criminal history. These results illustrate the gap between research on risk factors and the integration of this evidence into practice. In particular, we recommend the implementation of structured measures to reduce the potential for clinicians to be unduly influenced by gender and offense severity.

Predictive validity of dynamic factors: assessing violence risk in forensic psychiatric inpatients.

There is general consensus that dynamic factors ought to be considered in the assessment of violence risk, but little direct evidence exists to demonstrate that within-individual fluctuations in putative dynamic factors are associated with changes in risk. We examined these issues in a sample of 30 male forensic psychiatric inpatients using a pseudoprospective design. Static and dynamic factors were coded on the basis of chart review using 2 structured measures of violence risk: Version 2 of the Historical-Clinical-Risk Management-20 (HCR-20; C. D. Webster, K. S. Douglas, D. Eaves, & S. D. Hart, 1997, HCR-20: Assessing risk for violence, Version 2, Vancouver, BC, Canada: Mental Health, Law, and Policy Institute, Simon Fraser University) and the Short-Term Assessment of Risk and Treatability (START; C. D. Webster, M. L. Martin, J. Brink, T. L. Nicholls, & S. L. Desmarais, 2009, Short-Term Assessment of Risk and Treatability [START], Version 1.1, Coquitlam, BC, Canada: British Columbia Mental Health and Addiction Services). HCR-20 and START assessments were repeated every 3 months for a period of 1 year. Institutional violence in the 3 months following each assessment was coded using a modified version of the Overt Aggression Scale (S. C. Yudofsky, J. M. Silver, W. Jackson, J. Endicott, & D. W. Williams, 1986, The Overt Aggression Scale for the objective rating of verbal and physical aggression, The American Journal of Psychiatry, Vol. 143, pp. 35-39). Dynamic risk and strength factors showed predictive validity for institutional aggression. Results of event history analyses demonstrated that changes in dynamic risk factors significantly predicted institutional violence, even after controlling for static risk factors. This is one of the first studies to provide clear and direct support for the utility of dynamic factors in the assessment of violence risk.

Using dynamic risk and protective factors to predict inpatient aggression: reliability and validity of START assessments.

The Short-Term Assessment of Risk and Treatability (START; C. D. Webster, M. L. Martin, J. Brink, T. L. Nicholls, & S. L. Desmarais, 2009; C. D. Webster, M. L. Martin, J. Brink, T. L. Nicholls, & C. Middleton, 2004) is a relatively new structured professional judgment guide for the assessment and management of short-term risks associated with mental, substance use, and personality disorders. The scheme may be distinguished from other violence risk assessment instruments because of its inclusion of 20 dynamic factors that are rated in terms of both vulnerability and strength. This study examined the reliability and validity of START assessments in predicting inpatient aggression. Research assistants completed START assessments for 120 male forensic psychiatric patients through review of hospital files. They also completed Historical-Clinical-Risk Management-20 (HCR-20; C. D. Webster, K. S. Douglas, D. Eaves, & S. D. Hart, 1997) and Hare Psychopathy Checklist: Screening Version (PCL:SV; S. D. Hart, D. N. Cox, & R. D. Hare, 1995) assessments. Outcome data were coded from hospital files for a 12-month follow-up period using the Overt Aggression Scale (OAS; S. C. Yudofsky, J. M. Silver, W. Jackson, J. Endicott, & D. W. Williams, 1986). START assessments evidenced excellent interrater reliability and demonstrated both predictive and incremental validity over the HCR-20 Historical subscale scores and PCL:SV total scores. Overall, results support the reliability and validity of START assessments and use of the structured professional judgment approach more broadly, as well as the value of using dynamic risk and protective factors to assess violence risk.

Violence against teachers: prevalence and consequences.

Data collected from 731 teachers were used to examine the consequences of violence directed toward teachers while in the workplace. Analyses showed that the majority of respondents (n = 585, 80.0%) had experienced school-related violence­broadly defined­at one point in their careers. Serious violence (actual, attempted, or threatened physical violence) was less common, but still common enough to be of concern (n = 202, 27.6%). Violence predicted physical and emotional effects, as well as teaching-related functioning. In addition, a model with fear as a potential mediator revealed that both fear and violence were independently predictive of these negative outcomes. Finally, analyses showed that, in general, women reported higher levels of physical symptoms compared to men. We discuss the implications of violence against teachers in terms of personal consequences and the implications for mental health professionals working in an educational setting.

Body composition assessed by the 4-component model and association with lung function in 6-12-y-old children with cystic fibrosis.

BACKGROUND: Malnutrition is an indicator of a poor prognosis in patients with cystic fibrosis (CF). Previous body-composition (BC) studies in children with CF used 2-component models (2CMs) to assess fat mass (FM) and fat-free mass (FFM), but to our knowledge no study has used the gold-standard 4-component model (4CM), which allows for a more accurate evaluation of the nature of both elements. OBJECTIVE: We measured BC by using the 4CM in 6-12-y-old children with CF to 1) compare findings with those of healthy, matched control children and reference data; 2) relate BC to lung spirometry [forced expired volume in 1 s (FEV1)]; and 3) compare findings with those from more commonly used 2CM techniques. DESIGN: One hundred clinically stable children with CF (57% girls) aged 6-12 y were measured by using the 4CM. Children with CF underwent spirometry (FEV1). RESULTS: Girls with CF had significantly less FM than did healthy girls, even after adjustment for height and pubertal status; boys with CF had higher body mass index SD scores than did healthy boys. FM in girls was positively associated with the FEV1 percentage predicted. The 2CM FM was significantly different from the 4CM FM, with differences dependent on sex and condition, although most techniques identified a relation between FM and FEV1 in girls. CONCLUSIONS: Although shorter than healthy children, boys with CF were heavier and had a BC within the normal range; however, girls with CF had lower FM than did healthy girls, and this was associated with poorer lung function. Given the worse prognosis in girls, this finding merits more attention. The reliability of 2CM techniques varied with sex and health status.

Evaluation of Lunar Prodigy dual-energy X-ray absorptiometry for assessing body composition in healthy persons and patients by comparison with the criterion 4-component model.

BACKGROUND: Dual-energy X-ray absorptiometry (DXA) is widely used to assess body composition in research and clinical practice. Several studies have evaluated its accuracy in healthy persons; however, little attention has been directed to the same issue in patients. OBJECTIVE: The objective was to compare the accuracy of the Lunar Prodigy DXA for body-composition analysis with that of the reference 4-component (4C) model in healthy subjects and in patients with 1 of 3 disease states. DESIGN: A total of 215 subjects aged 5.0-21.3 y (n = 122 healthy nonobese subjects, n = 55 obese patients, n = 26 cystic fibrosis patients, and n = 12 patients with glycogen storage disease). Fat mass (FM), fat-free mass (FFM), and weight were measured by DXA and the 4C model. RESULTS: The accuracy of DXA-measured body-composition outcomes differed significantly between groups. Factors independently predicting bias in weight, FM, FFM, and percentage body fat in multivariate models included age, sex, size, and disease state. Biases in FFM were not mirrored by equivalent opposite biases in FM because of confounding biases in weight. CONCLUSIONS: The bias of DXA varies according to the sex, size, fatness, and disease state of the subjects, which indicates that DXA is unreliable for patient case-control studies and for longitudinal studies of persons who undergo significant changes in nutritional status between measurements. A single correction factor cannot adjust for inconsistent biases.