Revolutions in Lipid Isomer Resolution: Application of Ultrahigh-Resolution Ion Mobility to Reveal Lipid Diversity.

Many families of lipid isomers remain unresolved by contemporary liquid chromatography-mass spectrometry approaches, leading to a significant underestimation of the structural diversity within the lipidome. While ion mobility coupled to mass spectrometry has provided an additional dimension of lipid isomer resolution, some isomers require a resolving power beyond the capabilities of conventional platforms. Here, we present the application of high-resolution traveling-wave ion mobility for the separation of lipid isomers that differ in (i) the location of a single carbon-carbon double bond, (ii) the stereochemistry of the double bond (cis or trans), or, for glycerolipids, (iii) the relative substitution of acyl chains on the glycerol backbone (sn-position). Collisional activation following mobility separation allowed identification of the carbon-carbon double-bond position and sn-position, enabling confident interpretation of variations in mobility peak abundance. To demonstrate the applicability of this method, double-bond and sn-position isomers of an abundant phosphatidylcholine composition were resolved in extracts from a prostate cancer cell line and identified by comparison to pure isomer reference standards, revealing the presence of up to six isomers. These findings suggest that ultrahigh-resolution ion mobility has broad potential for isomer-resolved lipidomics and is attractive to consider for future integration with other modes of ion activation, thereby bringing together advanced orthogonal separations and structure elucidation to provide a more complete picture of the lipidome.

Subdural hemorrhage, macrocephaly, rash, and developmental delay in an infant: A pathogenic variant in NLRP3 causes CINCA/NOMID.

Subdural hemorrhages (SDHs) in children are most often observed in abusive head trauma (AHT), a distinct form of traumatic brain injury, but they may occur in other conditions as well, typically with clear signs and symptoms of an alternative diagnosis. We present a case of an infant whose SDH initially raised the question of AHT, but multidisciplinary evaluation identified multiple abnormalities, including rash, macrocephaly, growth failure, and elevated inflammatory markers, which were all atypical for trauma. These, along with significant cerebral atrophy, ventriculomegaly, and an absence of other injuries, raised concerns for a genetic disorder, prompting genetic consultation. Clinical trio exome sequencing identified a de novo likely pathogenic variant in NLRP3, which is associated with chronic infantile neurological, cutaneous, and articular (CINCA) syndrome, also known as neonatal-onset multisystem inflammatory disease (NOMID). He was successfully treated with interleukin-1 blockade, highlighting the importance of prompt treatment in CINCA/NOMID patients. This case also illustrates how atraumatic cases of SDH can be readily distinguished from AHT with multidisciplinary collaboration and careful consideration of the clinical history and exam findings.

Assessing the Risk of Australian Indigenous Sexual Offenders Reoffending: A Review of the Research Literature and Court Decisions.

The assessment of offenders' risk of reoffending, particularly sexual reoffending, is a core activity of forensic mental health practitioners. The purpose of these assessments is to reduce the risk of harm to the public, but they are controversial and become more contentious when Australian practitioners who want to undertake such assessments in an ethically responsible way must use reliable validated instruments, disclose the limitations of their assessment methods, instruments and data to judicial decision-makers and understand how decision-makers might use their reports. The purpose of this systematic literature review was to explore the practices of Australian practitioners and courts in respect of the assessment of Australian Indigenous male sexual offenders' risk of reoffending. We could not identify an instrument that has been developed for the assessment of this population group. Australian courts differ in whether they admit and give weight to practitioners' evidence and opinions based on data obtained with non-validated instruments. We could only identify three possible predictor variables with enough quantitative support to justify including them in an instrument that could be used to assess Indigenous sexual offenders. There is a need for research regarding the validity of the instruments that practitioners use.

Predictive Accuracy of Violence Risk Scale-Sexual Offender Version Risk and Change Scores in Treated Canadian Aboriginal and Non-Aboriginal Sexual Offenders.

The present study examined the predictive properties of Violence Risk Scale-Sexual Offender version (VRS-SO) risk and change scores among Aboriginal and non-Aboriginal sexual offenders in a combined sample of 1,063 Canadian federally incarcerated men. All men participated in sexual offender treatment programming through the Correctional Service of Canada (CSC) at sites across its five regions. The Static-99R was also examined for comparison purposes. In total, 393 of the men were identified as Aboriginal (i.e., First Nations, Métis, Circumpolar) while 670 were non-Aboriginal and primarily White. Aboriginal men scored significantly higher on the Static-99R and VRS-SO and had higher rates of sexual and violent recidivism; however, there were no significant differences between Aboriginal and non-Aboriginal groups on treatment change with both groups demonstrating close to a half-standard deviation of change pre and post treatment. VRS-SO risk and change scores significantly predicted sexual and violent recidivism over fixed 5- and 10-year follow-ups for both racial/ancestral groups. Cox regression survival analyses also demonstrated positive treatment changes to be significantly associated with reductions in sexual and violent recidivism among Aboriginal and non-Aboriginal men after controlling baseline risk. A series of follow-up Cox regression analyses demonstrated that risk and change score information accounted for much of the observed differences between Aboriginal and non-Aboriginal men in rates of sexual recidivism; however, marked group differences persisted in rates of general violent recidivism even after controlling for these covariates. The results support the predictive properties of VRS-SO risk and change scores with treated Canadian Aboriginal sexual offenders.

Characteristics of alleged homicide offenders with and without schizophrenia in Sichuan, China.

BACKGROUND: Little is known about the characteristics of people with and without schizophrenia who have been charged with homicide in China. AIMS AND RESEARCH QUESTION: Our research question was what differences are there between alleged homicide offenders with and without psychosis? METHOD: All archival records of alleged homicide cases referred for assessment to the West China Forensic Central Medical Service during 1998-2006 were retrieved. The centre serves a large catchment area in the mainly rural province of Sichuan. A random 20% of cases with schizophrenia and all cases without psychosis were selected for comparison. Demographic, criminological and mental health data were extracted from the records, and violence was rated by using the Violence Risk Scale (Chinese version). RESULTS: The two groups differed significantly in age, education, occupation, marital status and relationships to victim. The estimated risk of reoffending was higher in the schizophrenia group than the non-psychotic group, even after controlling for demographic differences. Despite many individuals reporting long histories of mental illness, about 40% of those with schizophrenia had never had any psychiatric treatment and less than 4% were in treatment at the time of the alleged homicide. CONCLUSIONS: The tendency for homicidal people with schizophrenia to be older, less educated and more socially isolated than their non-psychotic peers is similar to experience in Western countries, but the apparently higher risk scale scores of the Chinese schizophrenia group and their greater tendency to attack strangers are different. The lack of reported previous engagement with mental health services by a clearly ill and risky group of people is a likely explanation. Similar rural problems compared with better served urban areas have been reported in the Chuvash Republic. The case for better rural mental health services seems strong. Copyright © 2017 John Wiley & Sons, Ltd.

Global Profiling of Metabolite and Lipid Soluble Microbial Products in Anaerobic Wastewater Reactor Supernatant Using UPLC-MSE.

Identification of soluble microbial products (SMPs) released during bacterial metabolism in mixed cultures in bioreactors is essential to understanding fundamental mechanisms of their biological production. SMPs constitute one of the main foulants (together with colloids and bacterial flocs) in membrane bioreactors widely used to treat and ultimately recycle wastewater. More importantly, the composition and origin of potentially toxic, carcinogenic, or mutagenic SMPs in renewable/reused water supplies must be determined and controlled. Certain classes of SMPs have previously been studied by GC-MS, LC-MS, and MALDI-ToF MS; however, a more comprehensive LC-MS-based method for SMP identification is currently lacking. Here we develop a UPLC-MS approach to profile and identify metabolite SMPs in the supernatant of an anaerobic batch bioreactor. The small biomolecules were extracted into two fractions based on their polarity, and separate methods were then used for the polar and nonpolar metabolites in the aqueous and lipid fractions, respectively. SMPs that increased in the supernatant after feed addition were identified primarily as phospholipids, ceramides, with cardiolipins in the highest relative abundance, and these lipids have not been previously reported in wastewater effluent.

Risk reduction treatment of psychopathy and applications to mentally disordered offenders.

Therapeutic nihilism on treating psychopathy is widespread and is largely based on many outdated and poorly designed studies. Important recent advances have been made in assessing psychopathy and recidivism risks, as well as in offender rehabilitation to reduce reoffending, all of which are now well supported by a considerable literature based on credible empirical research. A 2-component model to guide risk reduction treatment of psychopathy has been proposed based on the integration of key points from the 3 bodies of literature. Treatment programs in line with the model have been in operation, and the results of early outcome evaluations are encouraging. Important advances also have been made in understanding the possible etiology of mentally disordered offenders with schizophrenia and history of criminality and violence, some with significant features of psychopathy. This article presents a review of recent research on risk reduction treatment of psychopathy with the additional aim to extend the research to the treatment of mentally disordered offenders with schizophrenia, violence, and psychopathy.

Evaluation and applications of the clinically significant change method with the Violence Risk Scale-Sexual Offender version: implications for risk-change communication.

We examined the use of the clinically significant change (CSC) method with the Violence Risk Scale-Sexual Offender version (VRS-SO), and its implications for risk communication, in a combined sample of 945 treated sexual offenders from three international settings, followed up for a minimum 5 years post-release. The reliable change (RC) index was used to identify thresholds of clinically meaningful change and to create four CSC groups (already okay, recovered, improved, unchanged) based on VRS-SO dynamic scores and amount of change made. Outcome analyses demonstrated important CSC-group differences in 5-year rates of sexual and violent recidivism. However, when baseline risk was controlled via Cox regression survival analysis, the pattern and magnitude of CSC-group differences in sexual and violent recidivism changed to suggest that observed variation in recidivism base rates could be at least partly explained by pre-existing group differences in risk level. Implications for communication of risk-change information and applications to clinical practice are discussed.

A psychometric examination of treatment change in a multisite sample of treated Canadian federal sexual offenders.

In the present study, we examined the degree of change and predictive accuracy of a number of well-known psychological self-report measures intended to identify treatment targets for sexual offenders. Participants included 392 federally incarcerated sexual offenders who participated in low, moderate, or high intensity sexual offender programs offered within penitentiaries under the jurisdiction of the Correctional Service of Canada. These men were followed in the community for an average of 5.42 years postrelease. Very small to moderate pretreatment and posttreatment changes were found on measures of cognitive distortions, aggression/hostility, empathy, loneliness, social intimacy, and sex offender acceptance of responsibility. However, pretreatment and posttreatment scores on these measures frequently demonstrated weak and inconsistent relationships to sexual, violent, and general recidivism. In addition, within-treatment change on these measures bore little relationship to outcome. However, when statistically corrected for pretreatment score the relationship of treatment change to outcome frequently improved, particularly on measures of physical aggression and anger, even after controlling for Static-99R score. Clinical and research implications are discussed regarding the assessment and evaluation of change on psychological risk factors in treated sexual offenders.

Age, actuarial risk, and long-term recidivism in a national sample of sex offenders.

Age at release has become an increasing focus of study with regard to evaluating risk in the sex offender population and has been repeatedly shown to be an important component of the risk assessment equation. This study constitutes an extension of a study of sex offender outcomes prepared for the Evaluation Branch, Correctional Service of Canada. The entire cohort of 2,401 male federally incarcerated sexual offenders who reached their warrant expiry date (WED) within 1997/1998, 1998/1999, and 1999/2000 fiscal years were reviewed for the study. Sexual and violent reconviction information was obtained from CPIC criminal records over an average of 12.0 years (SD = 1.7) follow-up. This study focused upon the cohort of sex offenders who were 50 years or older at time of release (N = 542). They were stratified according to risk using a brief actuarial scale (BARS) comprising six binary variables. For the most part, older offenders showed low base rates of sexual recidivism regardless of the risk band into which they fell. The exception was a small group of elderly offenders (n = 20) who fell into the highest risk band, and who showed high levels of sexual recidivism. The results of this combination of cross-sectional and longitudinal analyses of elderly sexual offenders may have important implications for offender management, particularly in light of the increasing numbers of offenders in Canada who fall into the over 50 age cohort.

Incorporating change information into sexual offender risk assessments using the violence risk scale-sexual offender version.

We examined the use of risk-change information in sexual offender risk assessments featuring the Violence Risk Scale-Sexual Offender version (VRS-SO), a sex offender risk assessment and treatment planning tool. The study featured a combined international sample of 539 sex offenders followed up an average of 15.5 years post-release. Pre- and posttreatment VRS-SO ratings were amalgamated from two treated samples of sex offenders from Canada and New Zealand. Analyses focused on examinations and applications of change data and its relationship to sexual and violent recidivism. VRS-SO change scores were significantly associated with decreases in these outcome criteria with, and without, controlling for indicators of pretreatment risk (e.g., Static-99R score) and individual differences in follow-up time. Applications of logistic regression using fixed 5-year follow-ups generated estimated rates of sexual and violent recidivism at different VRS-SO score thresholds. The use of logistic regression demonstrated a clinically useful and systematic means of combining risk and change information into posttreatment risk appraisals. Implications for the use of change information in the assessment and management of sexual offender risk are discussed.

Large-scale mutational analysis identifies UNC93B1 variants that drive TLR-mediated autoimmunity in mice and humans.

Nucleic acid-sensing Toll-like receptors (TLR) 3, 7/8, and 9 are key innate immune sensors whose activities must be tightly regulated to prevent systemic autoimmune or autoinflammatory disease or virus-associated immunopathology. Here, we report a systematic scanning-alanine mutagenesis screen of all cytosolic and luminal residues of the TLR chaperone protein UNC93B1, which identified both negative and positive regulatory regions affecting TLR3, TLR7, and TLR9 responses. We subsequently identified two families harboring heterozygous coding mutations in UNC93B1, UNC93B1+/T93I and UNC93B1+/R336C, both in key negative regulatory regions identified in our screen. These patients presented with cutaneous tumid lupus and juvenile idiopathic arthritis plus neuroinflammatory disease, respectively. Disruption of UNC93B1-mediated regulation by these mutations led to enhanced TLR7/8 responses, and both variants resulted in systemic autoimmune or inflammatory disease when introduced into mice via genome editing. Altogether, our results implicate the UNC93B1-TLR7/8 axis in human monogenic autoimmune diseases and provide a functional resource to assess the impact of yet-to-be-reported UNC93B1 mutations.

Violence, mental health and violence risk factors among community women: an epidemiological study based on two national household surveys in the UK.

BACKGROUND: Females who perpetrated violence in the community have important mental health and public protection implications. There is a dearth of research in this area. This study investigated the prevalence of psychiatric morbidity, personality disorders as well as victim characteristics and violence risk factors of women in the community who self-reported violence against others. METHODS: The study sample consisted of 8,275 community women aged 16-74 years obtained from the 2000 and 2007 UK national psychiatric morbidity surveys. Self report incidences of violence, personality disorders and the presence of psychiatric symptoms were assessed by interviews and/or established structured psychiatric assessment protocols. RESULTS: Weighted prevalence of female violence, which primarily involved partners and friends, was 5.5% in 2000 and 5.1% in 2007. Violence-prone women also had significantly higher prevalence of common mental disorders and comorbidity (adjusted odds ratio 3.3 and 2.9 respectively) than non-violent women. Multivariate analyses identified eight significant risk factors that characterized violence prone women: young age, residing in social-assisted housing, presence of early conduct problems, victim of domestic violence, self-harming, excessive drinking and past criminal justice involvements. CONCLUSION: A higher prevalence of common mental disorders and some types of personality disorder was found among violence prone women compared to their non-violence prone counterparts. The identified violence risk factors could be used to develop a quick and easily administered rating tool suitable for use by non-mental health trained frontline workers such as police and social support workers in the community to identify violence-prone women. Mental health and support services then can be provided to them for mental health care and violence prevention purposes.

Sex offender treatment outcome, actuarial risk, and the aging sex offender in Canadian corrections: a long-term follow-up.

The present study is an examination of sex offender treatment outcome in a large national cohort of Canadian Federally incarcerated sex offenders followed up an average of 11.7 years postrelease. A brief actuarial risk scale (BARS), which predicted sexual and violent recidivism, was created for the purposes of the present study to control for risk-related differences between treated and untreated offenders. In total, 732 offenders were identified as having completed (n = 625) or not attended (n = 107) a sex offender treatment program and for whom sufficient information was available to complete the scale. Controlling for risk and individual differences in follow-up time using Cox regression survival analyses and an 8-year fixed follow-up period, treated sex offenders demonstrated significantly lower rates of violent, but not sexual, recidivism. When the treated and untreated groups were stratified by risk level, significant differences were observed only among moderate or high risk offenders. Some significant group differences also emerged on indicators of recidivism severity, with treated offenders demonstrating slower times to sexual reoffense and lower scores on a quantified metric of sexual and violent recidivism severity after controlling for risk. Differences in recidivism base rates between treated and untreated offenders were also larger in magnitude for younger offenders (i.e., under age 50 at release), than for older offenders; however, interactions between age and treatment were not found. The findings are consistent with the risk principle and have possible implications regarding the dynamic nature of sexual violence risk.

Short and long-term prediction of recidivism using the youth level of service/case management inventory in a sample of serious young offenders.

The present investigation examined the predictive accuracy of the Youth Level of Service/Case Management Inventory (YLS/CMI) for youth and adult recidivism in a Canadian sample of 167 youths (93 males, 74 females) charged with serious offenses who received psychological services from a community mental health outpatient clinic. Youths were followed for an average of 7 years in the community, and predictive accuracy was examined for several recidivism outcomes as a function of gender, ethnicity, and developmental age group. YLS/CMI total scores significantly predicted all recidivism categories in the overall sample (area under the curve values ranged from 0.66 to 0.77) although the instrument as a whole, and its criminogenic needs, demonstrated somewhat stronger and more consistent predictive accuracy for youth outcomes. The YLS/CMI also demonstrated significant predictive accuracy within demographic subgroups. The implications of these findings are discussed in terms of the use of risk-need assessment tools in providing clinical assessment, treatment, and case management services to diverse young offender groups.

Allergen Immunotherapy Extract Shortages and Their Effects on Clinical Care: A Work Group Report of the AAAAI Immunotherapy, Allergen Standardization, and Allergy Diagnostics Committee.

Allergen immunotherapy (AIT) is the only disease-modifying therapy indicated for treatment of allergic asthma, rhinitis, conjunctivitis, and Hymenoptera hypersensitivity. Manufacturing of the extracts used in AIT involve multistep complex processes as well as regulatory oversight. Furthermore, some source materials are vulnerable to unexpected events of nature. Given these circumstances, allergen extract supply can be disrupted with a potential to adversely impact patient care. A group of members from the American Academy of Allergy, Asthma, and Immunology (AAAAI) Immunotherapy, Allergy Standardization and Allergy Diagnostic Committee formed a workgroup to assess the frequency and effects of allergen extract shortages and associated factors. This workgroup developed a survey that was distributed to a random 20% of the AAAAI membership. In addition, the group also performed a review of the scientific literature on allergen extract supply and shortage. Based on the findings of the survey study and literature review, the workgroup reports frequency and extent of shortages, potential ways to improve communication with suppliers, and need for further guidance in patient care during times of shortage.

Assessing dynamic violence risk: Common language risk levels and recidivism rates for the Violence Risk Scale.

The present study features the development of new risk categories and recidivism estimates for the Violence Risk Scale (VRS), a violence risk assessment and treatment planning tool. We employed a combined North American multisite sample (k = 6, N = 1,338) of adult mostly male offenders, many with violent criminal histories, from correctional or forensic mental health settings that had complete VRS scores from archival or field ratings and outcome data from police records (N = 1,100). There were two key objectives: (a) to identify the rates of violent recidivism associated with VRS scores and (b) to generate updated evidence-based VRS violence risk categories with external validation. To achieve the first objective, logistic regression was applied using VRS pretreatment and change scores on treated samples with a minimum 5-year follow-up (k = 5, N = 472) to model 2-, 3-, and 5-year violent and general recidivism estimates, with the resulting logistic regression algorithms retained to generate a VRS recidivism rates calculator. To achieve the second objective, the Council of State Governments' guidelines were applied to generate five risk levels using the common language framework using percentiles, risk ratios (from Cox regression), and absolute violent and general recidivism estimates (from logistic regression). Construct validity of the five risk levels was examined through group comparisons on measures of risk, need, protection, and psychopathy obtained from the constituent samples. VRS applications to enhance risk communication, treatment planning, and violence prevention in light of the updated recidivism estimates and risk categories are discussed. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Multisite evaluation of fire ant venom immunotherapy safety and efficacy.

Background: Imported fire ant (IFA) venom immunotherapy (VIT) is the only disease-modifying treatment reported to be effective at decreasing the risk of systemic reactions (SRs) to IFA stings. Objective: Our aims were to determine the baseline rates of IFA sensitization in subjects, describe IFA VIT prescribing patterns across the military health system (MHS), and retrospectively evaluate the safety and efficacy of IFA VIT. Methods: We prospectively compared IFA sensitization in participants with and without an SR to flying Hymenoptera venom. Separately, IFA VIT prescription records were extracted from a centralized repository, and rates were described across the MHS. Additionally, we retrospectively reviewed the clinical course of patients being treated with IFA VIT at 11 military treatment facilities. Results: The in vitro IFA sensitization rates in our prospective cohort ranged from 19.1% to 24.1%. Sensitization rates did not differ statistically between the subjects with or without an SR to flying Hymenoptera venom. We found that 60.9% of all MHS IFA VIT prescriptions (491 of 806) were from the 11 facilities in this study. We retrospectively identified 137 subjects actively undergoing IFA VIT. Among the subjects actively undergoing IFA VIT, 28 reported an SR to IFA venom and repeat stings by IFAs after reaching VIT maintenance, and 85.7% (24 of 28) of the subjects noted symptoms no worse than a large swelling reaction after a repeat IFA sting. Notably, only 2.9% of the subjects (4 of 137) had an SR due to VIT. Conclusion: This study's results align with those of prior IFA sensitization reports. A substantial proportion of patients undergoing IFA VIT experienced protection against anaphylaxis with reexposure, with relatively few adverse events.

Welcoming Healthcare Into Our Virtual Meeting Rooms: Perspective and Perseverance in Pediatric Rheumatology.

Purpose of Review: We highlight practice changes adopted to increased use of telemedicine, look at precision, and accuracy in using a virtual visit to evaluate and treat rheumatic disease, and describe our shift in engaging patients and their families in supporting our research aims. Recent Findings: Telemedicine visits increased substantially with the start of the SARS-CoV-2 pandemic. With this change came the need for significant advances to our telemedicine practices to allow for quality patient visits and continued research collection. Summary: Telemedicine will continue to be an area of increasing importance and has been found to be especially useful for regions like ours which cover many patients in remote areas across Washington, Wyoming, Idaho, Montana, and Alaska. Through the development of new techniques and the use of new technologies, we have been able to improve both the visit quality for patients and our ability to collect research data.

Predictive Properties of the Violence Risk Scale-Sexual Offense Version as a Function of Age.

The present study examined the discrimination and calibration properties of Violence Risk Scale-Sexual Offense version (VRS-SO) risk and change scores for sexual and violent recidivism as a function of age at release, on a combined sample of 1,287 men who had attended sexual offense-specific treatment services. The key aim was to examine to what extent VRS-SO scores can accurately discriminate recidivists from nonrecidivists among older cohorts, and if the existing age-related adjustments in the instrument adequately correct for increasing age. VRS-SO risk and change scores showed consistent properties of discrimination for sexual recidivism across the age cohorts, via area under the curve and Cox regression survival analysis, as demonstrated through fixed effects meta-analysis. Calibration analyses, employing logistic regression, demonstrated that age at release was consistently incrementally predictive of violent, but not sexual, recidivism after controlling for individual differences on static and dynamic risk factors. E/O index analyses demonstrated that predicted rates of sexual recidivism from VRS-SO scores, particularly when employed with Static-99R, were not significantly different from those observed among age cohorts; however, calibration was weaker for general violence. Implications for use of the VRS-SO in sexual recidivism risk assessment with older offenders are discussed.