Occupational Stress and Anger: Mediating Effects of Resiliency in First Responders.

First responders experience substantial stress due to the nature of their work (Carleton et al. 2017). Occupational stress (OS) results from a myriad of employment conditions (e.g., ambiguous work expectations, unreasonable workload; Osipow 1998). OS can lead to maladaptive anger, which negatively impacts personal well-being and work performance (Velichkovsky 2009). In contrast, resilience to demanding working conditions is associated with lower state and trait anger (Wilson et al. 2001); thus, resilience may serve a protective 'buffer' role against anger in the face of stress. Thus, we hypothesized that resiliency would mediate relations between dimensions of OS and anger. The current study included 201 first responders (male = 77.6%; M age = 43.73 years (SD = 10.97); police officers = 64.2%) who completed measures of OS (OSI-R; Osipow 1998), Anger (DSM-5 CC Anger; APA 2013), and Resiliency (CD-RISC; Connor and Davidson 2003). Results indicated that resiliency mediated relations between five components of OS and anger: Role Overload (p < .001); Insufficiency (p < .001); Role Boundary (p < .001); Role Ambiguity (p < .001); and Role Responsibility (p < .001). Results support the importance of resiliency-enhancing interventions to offset the experience of anger when confronted with occupational stress in first responders.

Real-world use of the risk-need-responsivity model and the level of service/case management inventory with community-supervised offenders.

The risk-need-responsivity model (RNR; Bonta & Andrews, 2017) has become a leading approach for effective offender case management, but field tests of this model are still required. The present study first assessed the predictive validity of the RNR-informed Level of Service/Case Management Inventory (LS/CMI; Andrews, Bonta, & Wormith, 2004) with a sample of Atlantic Canadian male and female community-supervised provincial offenders (N = 136). Next, the case management plans prepared from these LS/CMI results were analyzed for adherence to the principles of risk, need, and responsivity. As expected, the LS/CMI was a strong predictor of general recidivism for both males (area under the curve = .75, 95% confidence interval [.66, .85]), and especially females (area under the curve = .94, 95% confidence interval [.84, 1.00]), over an average 3.42-year follow-up period. The LS/CMI was predictive of time to recidivism, with lower risk cases taking longer to reoffend than higher risk cases. Despite the robust predictive validity of the LS/CMI, case management plans developed by probation officers generally reflected poor adherence to the RNR principles. These findings highlight the need for better training on how to transfer risk appraisal information from valid risk tools to case plans to better meet the best-practice principles of risk, need, and responsivity for criminal behavior risk reduction. (PsycINFO Database Record

Multidimensional evaluation of a mental health court: Adherence to the risk-need-responsivity model.

The current study examined the impact of a mental health court (MHC) on mental health recovery, criminogenic needs, and recidivism in a sample of 196 community-based offenders with mental illness. Using a pre-post design, mental health recovery and criminogenic needs were assessed at the time of MHC referral and discharge. File records were reviewed to score the Level of Service/Risk-Need-Responsivity instrument (Andrews, Bonta, & Wormith, 2008) to capture criminogenic needs, and a coding guide was used to extract mental health recovery information at each time point. Only mental health recovery data were available at 12 months post-MHC involvement. Recidivism (i.e., charges) was recorded from police records over an average follow-up period of 40.67 months post-MHC discharge. Case management adherence to the Risk-Need-Responsivity (RNR) model of offender case management was also examined. Small but significant improvements were found for criminogenic needs and some indicators of mental health recovery for MHC completers relative to participants who were prematurely discharged or referred but not admitted to the program. MHC completers had a similar rate of general recidivism (28.6%) to cases not admitted to MHC and managed by the traditional criminal justice system (32.6%). However, MHC case plans only moderately adhered to the RNR model. Implications of these results suggest that the RNR model may be an effective case management approach for MHCs to assist with decision-making regarding admission, supervision intensity, and intervention targets, and that interventions in MHC contexts should attend to both criminogenic and mental health needs.

Stresses, strengths, and experiences of mothers engaged in methadone maintenance treatment.

Although methadone maintenance treatment (MMT) is the intervention of choice for addiction, unfortunately, mothers are less likely to engage in care. Greater understanding of how mothers experience the addiction and the recovery process is needed to develop strategies to effectively engage mothers in MMT. This mixed method study applied quantitative and qualitative approaches with a sample of 12 mothers who were engaged in MMT for 3 or more months. Although the results showed stresses of high depression and difficult life circumstance scores, the mothers had strengths that included positive social support and family functioning. Inductive analysis of transcribed interviews identified three themes that explained how mothers experienced addiction and recovery: diminished maternal identity, choice for mothering, and redefined maternal identity. During addiction, mothers described a sense of diminished maternal identity with two subthemes of diminished performed mothering and interrupted mothering. With the second theme, choice for mothering, mothers described making the choice to attend MMT for their children. The third theme, redefined maternal identity, consisted of two subthemes that reflected potential outcomes of MMT and addiction recovery. Whereas most mothers described positive, restored maternal identity, two mothers of older children noted continued diminished maternal identity with persistence of negative mother-child relationships despite maternal addiction recovery. Recommendations are made to assist service providers to consider maternal identity within the recovery process.

Supporting mothers' engagement in a community-based methadone treatment program.

Unmanaged maternal opioid addiction poses health and social risks to both mothers and children in their care. Methadone maintenance treatment (MMT) is a targeted public health service to which nurses and other allied health professionals may refer these high risk families for support. Mothers participating in MMT to manage their addiction and their service providers were interviewed to identify resources to maximize mothers' engagement in treatment and enhance mothers' parenting capacity. Twelve mothers and six service providers were recruited from an outpatient Atlantic Canadian methadone treatment program. Two major barriers to engagement in MMT were identified by both mothers and service providers including (1) the lack of available and consistent childcare while mothers attended outpatient programs and (2) challenges with transportation to the treatment facility. All participants noted the potential benefits of adding supportive resources for the children of mothers involved in MMT and for mothers to learn how to communicate more effectively with their children and rebuild damaged mother-child relationships. The public health benefits of integrating parent-child ancillary supports into MMT for mothers are discussed.

Biochemical and structural characterization of lysophosphatidic Acid binding by a humanized monoclonal antibody.

Lysophosphatidic acid (LPA) is a common product of glycerophospholipid metabolism and an important mediator of signal transduction. Aberrantly high LPA concentrations accompany multiple disease states. One potential approach for treatment of these diseases, therefore, is the therapeutic application of antibodies that recognize and bind LPA as their antigen. We have determined the X-ray crystal structure of an anti-LPA antibody (LT3015) Fab fragment in its antigen-free form to 2.15 Å resolution and in complex with two LPA isotypes (14:0 and 18:2) to resolutions of 1.98 and 2.51 Å, respectively. The variable CDR (complementarity-determining region) loops at the antigen binding site adopt nearly identical conformations in the free and antigen-bound crystal structures. The crystallographic models reveal that the LT3015 antibody employs both heavy- and light-chain CDR loops to create a network of eight hydrogen bonds with the glycerophosphate head group of its LPA antigen. The head group is almost completely excluded from contact with solvent, while the hydrocarbon tail is partially solvent-exposed. In general, mutation of amino acid residues at the antigen binding site disrupts LPA binding. However, the introduction of particular mutations chosen strategically on the basis of the structures can positively influence LPA binding affinity. Finally, these structures elucidate the exquisite specificity demonstrated by an anti-lipid antibody for binding a structurally simple and seemingly unconstrained target molecule.

Validity and stability of the youth psychopathic traits inventory in a nonforensic sample of young adults.

We assessed the validity and stability of the Swedish developed Youth Psychopathic Traits Inventory (YPI; Andershed, Kerr, Stattin, & Levander, 2002) in Canadian nonforensic young adults. In Study 1, a total of 217 undergraduates completed the YPI as well as the Psychopathic Personality Inventory-Revised (PPI-R; Lilienfeld & Widows, 2005) and the Levenson Self-Report Psychopathy Scale (LSRP; Levenson, Kiehl, & Fitzpatrick, 1995). These measures were completed twice, with a mean of 28 days between administrations. Total YPI was strongly correlated with the PPI-R but also with the LSRP subscales. YPI higher order dimensions were meaningfully correlated with PPI-R dimensions of similar content. The YPI yielded fairly high temporal stability and was similar to the PPI-R and LSRP Primary Psychopathy scale. Using 111 undergraduates, in Study 2, we found the YPI was positively associated with antisocial attitudes and impulsivity and negatively associated with agreeableness and conscientiousness. This research extends the validity of the YPI beyond adolescents to Canadian young adults from nonforensic settings. Given its promise as a measure of psychopathic traits in adolescents and young adults, the YPI may prove useful in longitudinal research across these developmental periods.

A comparison of memory for homicide, non-homicidal violence, and positive life experiences.

Defendants commonly claim amnesia for their criminal actions especially in cases involving extreme violence. While some claims are malingered or result from physiological factors, other cases may represent genuine partial or complete amnesia resulting from the psychological distress and/or extreme emotion associated with the perpetration of the crime. Fifty Canadian homicide offenders described their memories of their homicide, a non-homicide violent offense, and their most positive adulthood life experience. Self-reported and objective measures of memories for these events revealed that homicides were recalled with the greatest level of detail and sensory information. Although dissociative tendencies were associated with a self-reported memory loss, objective measures of memory quality did not reflect this perceived impairment, suggesting a failure of meta-memory. Recollections of positive life events were superior to those of non-homicidal violence, possibly due to greater impact and meaning attached to such experiences. Findings suggest that memory for homicide typically is enhanced by the powerful emotion associated with its perpetration.

Production and characterization of monoclonal anti-sphingosine-1-phosphate antibodies.

Sphingosine-1-phosphate (S1P) is a pleiotropic bioactive lipid involved in multiple physiological processes. Importantly, dysregulated S1P levels are associated with several pathologies, including cardiovascular and inflammatory diseases and cancer. This report describes the successful production and characterization of a murine monoclonal antibody, LT1002, directed against S1P, using novel immunization and screening methods applied to bioactive lipids. We also report the successful generation of LT1009, the humanized variant of LT1002, for potential clinical use. Both LT1002 and LT1009 have high affinity and specificity for S1P and do not cross-react with structurally related lipids. Using an in vitro bioassay, LT1002 and LT1009 were effective in blocking S1P-mediated release of the pro-angiogenic and prometastatic cytokine, interleukin-8, from human ovarian carcinoma cells, showing that both antibodies can out-compete S1P receptors in binding to S1P. In vivo anti-angiogenic activity of all antibody variants was demonstrated using the murine choroidal neovascularization model. Importantly, intravenous administration of the antibodies showed a marked effect on lymphocyte trafficking. The resulting lead candidate, LT1009, has been formulated for Phase 1 clinical trials in cancer and age-related macular degeneration. The anti-S1P antibody shows promise as a novel, first-in-class therapeutic acting as a "molecular sponge" to selectively deplete S1P from blood and other compartments where pathological S1P levels have been implicated in disease progression or in disorders where immune modulation may be beneficial.

Anti-CD20 monoclonal antibody with enhanced affinity for CD16 activates NK cells at lower concentrations and more effectively than rituximab.

Growing evidence indicates that the affinity of monoclonal antibodies (mAbs) for CD16 (FcgammaRIII) plays a central role in the ability of the mAb to mediate antitumor activity. We evaluated how CD16 polymorphisms, and mAb with modified affinity for target antigen and CD16, affect natural killer (NK) cell phenotype when CD20(+) malignant B cells were also present. The mAb consisted of rituximab (R), anti-CD20 with enhanced affinity for CD20 (AME-B), and anti-CD20 with enhanced affinity for both CD20 and CD16 (AME-D). Higher concentrations of mAb were needed to induce CD16 modulation, CD54 up-regulation, and antibody-dependent cellular cytotoxicity (ADCC) on NK cells from subjects with the lower affinity CD16 polymorphism. The dose of mAb needed to induce NK activation was lower with AME-D irrespective of CD16 polymorphism. At saturating mAb concentrations, peak NK activation was greater for AME-D. Similar results were found with measurement of CD16 modulation, CD54 up-regulation, and ADCC. These data demonstrate that cells coated with mAb with enhanced affinity for CD16 are more effective at activating NK cells at both low and saturating mAb concentrations irrespective of CD16 polymorphism, and they provide further evidence for the clinical development of such mAbs with the goal of improving clinical response to mAb.

Psychopathic traits in adolescent offenders: an evaluation of criminal history, clinical, and psychosocial correlates.

Although a large body of research has established the relevance of psychopathy to adult offenders, its relevance to adolescent offenders is far less clear. The current study evaluated the clinical, psychosocial and criminal correlates of psychopathic traits in a sample of 226 male and female incarcerated adolescent offenders. According to an 18-item version of the Psychopathy Checklist-Youth Version (PCL-YV; Forth, Kosson, & Hare, 2003), only 9.4% exhibited a high level of psychopathic traits (PCL-YV>/=25). Consistent with past research, higher PCL-YV scores were positively associated with self-reported delinquency and aggressive behavior and were unrelated to emotional difficulties. Although higher PCL-YV scores were associated with the experience of physical abuse, the only psychosocial factor to predict PCL-YV scores was a history of non-parental living arrangements (e.g. foster care). In terms of criminality, a violent/versatile criminal history was positively associated with psychopathic traits. However, PCL-YV scores were unrelated to participants' official criminal records for total, non-violent, violent, and technical violation convictions. In conclusion, the data partially support the construct validity of psychopathy with adolescent offenders, but some inconsistencies with prior adult and adolescent psychopathy research were evident. These issues are discussed.

Multivalent poly(ethylene glycol)-containing conjugates for in vivo antibody suppression.

Poly(ethylene glycol) (PEG) was incorporated into multivalent conjugates of the N-terminal domain of beta(2)GPI (domain 1). PEG was incorporated to reduce the rate of elimination of the conjugates from plasma and to putatively improve their efficacy as toleragens for the suppression of anti-beta(2)GPI antibodies and the treatment of antiphospholipid syndrome (APS). Three structurally distinct types of multivalent platforms were constructed by incorporating PEG into the platform structures in different ways. The amount of PEG incorporated ranged from about 5000 g per mole to about 30000 g per mole. The platforms were functionalized with either four or eight aminooxy groups. The conjugates were prepared by forming oxime linkages between the aminooxy groups and N-terminally glyoxylated domain 1 polypeptide. The plasma half-life of each conjugate, labeled with (125)I, was measured in both mice and rats. The half-lives of the conjugates ranged from less than 10 min to about 1 h in mice, and from less than 3 h to about 19 h in rats. The ability of five tetravalent conjugates to suppress anti-domain 1 antibodies in immunized rats was also measured. Incorporation of PEG in the conjugates significantly reduced the doses required for suppression, and the amount of reduction correlated with the amount of PEG incorporated.

In vivo characterization of bioconjugate B cell toleragens with specificity for autoantibodies in antiphospholipid syndrome.

This study investigated the use of well-defined bioconjugate molecules to suppress antigen-specific B cell responses to domain I (DI) of human beta(2)-glycoprotein I (beta(2)GPI) in rats. DI is the dominant target of pathogenic autoimmune antibodies in patients with antiphospholipid syndrome (APS), a disease characterized by antibody-mediated thromboembolic events. Rats primed with DI conjugated to keyhole limpet hemocyanin (DI-KLH) were rendered tolerant to subsequent antigen challenge by treatment with multivalent conjugates of DI. Antibodies to DI were suppressed 89-96% with intravenous doses of 500 micro g, and reductions were paralleled by decreases in splenic antigen-specific antibody-forming cells (AFC). Suppression was achieved with a variety of conjugates having two to four copies of DI and circulating half-lives of 2.6-8.7 h. Antibodies to KLH were not suppressed, indicating the specificity of the approach. These results establish the basis for further development of therapeutic B cell toleragens to suppress pathogenic antibodies in APS and other autoimmune diseases.