Medial Ulnar Collateral Ligament Reconstruction With Allograft Provides Excellent Clinical Outcomes, High Rates of Return to Play, and a Low Incidence of Postoperative Complications: A Systematic Review.

PURPOSE: To perform a systematic review evaluating clinical outcomes in patients undergoing medial ulnar collateral ligament reconstruction (MUCLR) with soft-tissue allograft. METHODS: A systematic review of the literature was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The primary outcomes evaluated were patient-reported outcome scores, return to play (RTP) rates, incidence of postoperative complications, and rates of graft rupture or mechanical failure. RESULTS: The literature search identified 395 articles, and 5 studies met final inclusion criteria after full-text review. A total of 274 patients were analyzed in the included studies and follow-up ranged from 3.0 to 7.6 years. Two studies (number of patients = 141) reported outcomes exclusively of MUCLR with allograft, whereas 3 studies (number of patients = 133) reported outcomes in patients undergoing MUCLR with either allograft or autograft. Allograft sources included gracilis, semitendinosus, plantaris, peroneus longus, and palmaris longus. Level of patient athletic competition ranged from recreational athletes to the professional level; however, nonathletes in the setting of trauma were also included. The RTP rate after MUCLR with soft-tissue allograft was 95.3%, and 89.3% of patients returned to a similar or greater level of play postoperatively. The Timmerman-Andrews score was reported in 2 studies, and the means postoperatively ranged from 94.55 to 97. Postoperative complication rates were low (range, 0% to 20%), and there were no reported incidences of allograft rupture or mechanical failure. CONCLUSIONS: Based on the available data, soft-tissue allograft for MUCLR in athletic patient populations provides excellent clinical outcomes, high rates of RTP, and low rates of postoperative complications and graft failure at short-term follow-up. There remains a lack of high-quality evidence directly comparing autograft versus allograft outcomes in elite overhead-throwing athletes to support allograft as an acceptable alternative for MUCLR in this patient population. LEVEL OF EVIDENCE: Level IV, systematic review of Level III-IV studies.

Medial Collateral Ligament Reconstruction With Autograft Versus Allograft: A Systematic Review.

BACKGROUND: Medial collateral ligament (MCL) reconstruction (MCLR) is performed after failed nonoperative treatment or high-grade MCL injury with associated valgus instability. PURPOSE: To evaluate clinical outcomes after MCLR with autograft versus allograft. STUDY DESIGN: Systematic review, Level of evidence, 4. METHODS: A systematic review was conducted according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. The authors conducted a search of the PubMed, CINAHL, EMBASE, and Cochrane databases to identify studies comparing outcomes of MCLR with autograft versus allograft. Studies were included if they evaluated clinical outcomes after MCLR using autograft and/or allograft. Any study that included concomitant knee ligament injury other than the anterior cruciate ligament injury was excluded. A quality assessment was performed using the modified Coleman Methodology Score. RESULTS: The initial search identified 746 studies, 17 of which met the inclusion criteria and were included in this review. The studies included 307 patients: 151 (49.2%) patients received autografts, and 156 (50.8%) received allografts. The most used autograft was the semitendinosus tendon (136 grafts; 90.1% of specified allografts), and the only allograft used was the Achilles tendon (110 grafts; 100% of specified autografts). The mean follow-up of the studies was 25.6 months. Postoperative pain (Lysholm scores) ranged from 82.9 to 94.8 in patients receiving autografts and 87.5 to 93 in patients receiving allografts. Postoperative range of motion was full in 8 of 15 (53.3%) patients receiving autografts compared with 82 of 93 (88.2%) patients receiving allografts. Five of the 151 (3.3%) patients who had MCLR with autografts had complications such as infection, instability, and prominent screws. Two of the 156 (1.3%) MCLRs with allografts developed complications of prominent screws and nonhealing incisions. CONCLUSION: MCLR with either autografts or allografts leads to improved patient-reported, radiographic, and clinical outcomes. Patient-reported postoperative pain was similar in patients receiving either graft type. Other outcomes were difficult to compare between graft types because of nonstandardized reporting and a lack of pre- and postoperative measurements. Therefore, there is no evidence of significantly improved outcomes in the use of either autograft or allograft with MCLR.

Impaired striatal glutamate/GABA regulation in violent offenders with antisocial personality disorder and psychopathy.

Men with antisocial personality disorder (ASPD) with or without psychopathy (+/-P) are responsible for most violent crime in society. Development of effective treatments is hindered by poor understanding of the neurochemical underpinnings of the condition. Men with ASPD with and without psychopathy demonstrate impulsive decision-making, associated with striatal abnormalities in functional neuroimaging studies. However, to date, no study has directly examined the potential neurochemical underpinnings of such abnormalities. We therefore investigated striatal glutamate: GABA ratio using Magnetic Resonance Spectroscopy in 30 violent offenders (16 ASPD-P, 14 ASPD + P) and 21 healthy non-offenders. Men with ASPD +/- P had a significant reduction in striatal glutamate : GABA ratio compared to non-offenders. We report, for the first time, striatal Glutamate/GABA dysregulation in ASPD +/- P, and discuss how this may be related to core behavioral abnormalities in the disorders.

Case report of selumetinib as a novel therapy in a neurofibromatosis type 2-associated ependymoma.

We report partial response (PR) to novel therapy with selumetinib in a patient with neurofibromatosis type 2 (NF2). A 25-year-old male presented with bilateral vestibular schwannomas, spinal cord intramedullary ependymomas, cranial and spinal meningiomas, spinal nerve root mixed schwannoma-neurofibromas, and peripheral nerve sheath tumors. He tested negative for germline NF2, SWItch/sucrose non-fermentable-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1 (SMARCB1), and leucine zipper-like transcription regulator 1 (LZTR1) mutations. Molecular analysis of a resected cervical spine schwannoma-neurofibroma demonstrated an isolated somatic SMARCB1 mutation. Due to progression of all tumors, he was treated medically with both everolimus (10 mg/day) and selumetinib (25 mg/kg twice a day), but he rapidly transitioned to selumetinib monotherapy due to everolimus toxicity. 3 months of treatment resulted in PR in one spinal ependymoma and stable disease in other tumors. This PR was quantified by the differences in units of intensity in pre- and post-treatment magnetic resonance image. To the best of our knowledge, this is the first reported case for using selumetinib in NF2-associated tumors or ependymomas.

Rapid white matter changes in children with conduct problems during a parenting intervention.

Studies report that the microstructural integrity of the uncinate fasciculus (UF; connecting the anterior temporal lobe to the orbitofrontal cortex) is abnormal in adults with psychopathy and children with conduct problems (CP), especially those with high callous-unemotional (CU) traits. However, it is unknown if these abnormalities are 'fixed' or 'reversible'. Therefore, we tested the hypothesis that a reduction in CP symptoms, following a parenting intervention, would be associated with altered microstructural integrity in the UF. Using diffusion tensor imaging tractography we studied microstructural differences (mean diffusivity (MD) and radial diffusivity (RD)) in the UF of 43 typically developing (TD) and 67 boys with CP before and after a 14-week parenting intervention. We also assessed whether clinical response in CP symptoms or CU traits explained changes in microstructure following the intervention. Prior to intervention, measures of MD and RD in the UF were increased in CP compared to TD boys. Following intervention, we found that the CP group had a significant reduction in RD and MD. Further, these microstructural changes were driven by the group of children whose CU traits improved (but not CP symptoms as hypothesized). No significant microstructural changes were observed in the TD group. Our findings suggest, for the first time, that microstructural abnormalities in the brains of children with CP may be reversible following parenting intervention.

Association of substance use and other psychiatric disorders with all-cause and external-cause mortality in individuals given community sentences in Sweden: a national cohort study.

Background: Consistently high rates of premature mortality have been reported in individuals who receive community sentences. However, few studies have explored potential modifiable risk factors for these rates, particularly mental health. We examined the association of substance use and other psychiatric disorders with all-cause and external-cause mortality in individuals convicted of a criminal offence and given a community sentence. Methods: We did a longitudinal cohort study of 109,751 individuals given community sentences in Sweden using population-based registers. We calculated mortality rates for all-cause and external-cause mortality, hazard ratios for the association between psychiatric disorders and mortality, and population attributable fractions to quantify the contribution of psychiatric disorders to mortality risk. Findings: During the follow-up, 5749 (5.2%) individuals died, including 2709 (2.5%) from external causes. Individuals with pre-existing substance use and other psychiatric disorders had an increased mortality risk from any cause (aHR = 2.28 [95% CI 2.15-2.42]) and from external causes (3.11 [2.85-3.40]) compared to individuals without known psychiatric or substance use disorders. Suicide was the most common cause of death in younger persons. Interpretation: In individuals given community sentences, substance use and other psychiatric disorders were associated with an increased risk of premature death with suicide being the leading cause of death. Community supervision represents an opportunity to provide sentenced individuals with access to evidence-based treatment targeting substance misuse and psychiatric disorders to prevent potentially preventable deaths. Funding: Wellcome Trust.

Trauma, post-traumatic stress disorder and violence in the prison population: prospective cohort study of sentenced male prisoners in the UK.

BACKGROUND: Violence is a common problem in prisons. Post-traumatic stress disorder (PTSD), a prevalent disorder in prison populations, has been identified as a risk factor for violent behaviour in community and military populations. Although cross-sectional associations between PTSD and prison violence have been documented, prospective cohort studies are required. AIMS: To investigate whether PTSD is an independent risk factor for prison violence, and examine the potential role of PTSD symptoms and other trauma sequelae on the pathway from trauma exposure to violent behaviour in prison. METHOD: A prospective cohort study was conducted in a large, medium security prison in London, UK. A random sample of sentenced prisoners arriving into custody (N = 223) took part in a clinical research interview, which assessed trauma histories, mental disorders including PTSD, and other potential sequelae of trauma (anger, emotion dysregulation). Incidents of violent behaviour were measured with prison records covering the 3 months after reception into custody. Stepped binary logistic regression and a series of binary mediation models were performed. RESULTS: Prisoners who met current (past month) criteria for PTSD were more likely to engage in violent behaviour during the first 3 months of imprisonment, after adjusting for other independent risk factors. The relationship between lifetime exposure to interpersonal trauma and violent behaviour in custody was mediated by total PTSD symptom severity. Hyperarousal and negatively valenced cognitive and emotional appraisal symptoms were particularly implicated in this pathway. CONCLUSIONS: The identification and treatment of PTSD has the potential to reduce violence in prison populations.

Selective Amygdala Hypoactivity to Fear in Boys With Persistent Conduct Problems After Parent Training.

BACKGROUND: Parenting interventions reduce antisocial behavior (ASB) in some children with conduct problems (CPs), but not others. Understanding the neural basis for this disparity is important because persistent ASB is associated with lifelong morbidity and places a huge burden on our health and criminal justice systems. One of the most highly replicated neural correlates of ASB is amygdala hypoactivity to another person's fear. We aimed to assess whether amygdala hypoactivity to fear in children with CPs is remediated following reduction in ASB after successful treatment and/or if it is a marker for persistent ASB. METHODS: We conducted a prospective, case-control study of boys with CPs and typically developing (TD) boys. Both groups (ages 5-10 years) completed 2 magnetic resonance imaging sessions (18 ± 5.8 weeks apart) with ASB assessed at each visit. Participants included boys with CPs following referral to a parenting intervention group and TD boys recruited from the same schools and geographical regions. Final functional magnetic resonance imaging data were available for 36 TD boys and 57 boys with CPs. Boys with CPs were divided into those whose ASB improved (n = 27) or persisted (n = 30) following the intervention. Functional magnetic resonance imaging data assessing fear reactivity were then analyzed using a longitudinal group (TD/improving CPs/persistent CPs) × time point (pre/post) design. RESULTS: Amygdala hypoactivity to fear was observed only in boys with CPs who had persistent ASB and was absent in those whose ASB improved following intervention. CONCLUSIONS: Our findings suggest that amygdala hypoactivity to fear is a marker for ASB that is resistant to change following a parenting intervention and a putative target for future treatments.

Psychiatric disorders and reoffending risk in individuals with community sentences in Sweden: a national cohort study.

BACKGROUND: Community sentences are widely used in many countries, often comprising the majority of criminal justice sanctions. Psychiatric disorders are highly prevalent in community-sentenced populations and are thus potential targets for treatment interventions designed to reduce reoffending. We examined the association between psychiatric disorders and reoffending in a national cohort of individuals given community sentences in Sweden, with use of a sibling control design to account for unmeasured familial confounding. METHODS: We did a longitudinal cohort study of 82 415 individuals given community sentences between Nov 1, 1991, and Dec 31, 2013, in Sweden using data from population-based registers. We calculated hazard ratios (HRs) for any reoffending and violent reoffending with Cox regression models. We compared community-sentenced siblings with and without psychiatric disorders to control for potential familial confounding. Additionally, we calculated population attributable fractions to assess the contribution of psychiatric disorders to reoffending behaviours. The primary outcomes of the study were any (general) reoffending and violent reoffending. FINDINGS: Between Nov 1, 1991, and Dec 31, 2013, those given community sentences who were diagnosed with any psychiatric disorder had an increased reoffending risk in men (adjusted HR 1·59, 95% CI 1·56-1·63 for any reoffending; 1·60, 1·54-1·66 for violent reoffending) and women (1·71, 1·61-1·82 for any reoffending; 2·19, 1·88-2·54 for violent reoffending). Risk estimates remained elevated after adjustment for familial confounding. Schizophrenia spectrum disorders, personality disorders, and substance use disorders had stronger associations with violent reoffending than did other psychiatric disorders. Assuming causality, the adjusted population attributable risk of psychiatric disorders on violent reoffending was 8·3% (95% CI 6·6-10·0) in the first 2 years of community follow-up in men and 30·9% (22·7-39·0) in women. INTERPRETATION: Psychiatric disorders were associated with an increased risk of any reoffending and violent reoffending in the community-sentenced population. The magnitude of the association between psychiatric disorders and reoffending varied by individual diagnosis. Substance use disorders had the highest absolute and relative risks. Most of the increased risk for any reoffending in individuals with psychiatric disorders could be attributed to comorbid substance misuse. Given their high prevalence, substance use disorders should be the focus of treatment programmes in community-sentenced populations. FUNDING: Wellcome Trust.

Oxytocin normalizes the implicit processing of fearful faces in psychopathy: a randomized crossover study using fMRI.

Adults with antisocial personality disorder with (ASPD + P) and without (ASPD - P) psychopathy commit the majority of violent crimes. Empathic processing abnormalities are particularly prominent in psychopathy, but effective pharmacological interventions have yet to be identified. Oxytocin modulates neural responses to fearful expressions in healthy populations. The current study investigates its effects in violent antisocial men. In a placebo-controlled, randomized crossover design, 34 violent offenders (19 ASPD + P; 15 ASPD - P) and 24 healthy non-offenders received 40 IU intranasal oxytocin or placebo and then completed an fMRI morphed faces task examining the implicit processing of fearful facial expressions. Increasing intensity of fearful facial expressions failed to appropriately modulate activity in the bilateral mid-cingulate cortex in violent offenders with ASPD + P, compared with those with ASPD - P. Oxytocin abolished these group differences. This represents evidence of neurochemical modulation of the empathic processing of others' distress in psychopathy.

Prevalence of mental disorders in defendants at criminal court.

BACKGROUND: Psychiatric morbidity in prisons and police custody is well established, but little is known about individuals attending criminal court. There is international concern that vulnerable defendants are not identified, undermining their right to a fair trial. AIMS: To explore the prevalence of a wide range of mental disorders in criminal defendants and estimate the proportion likely to be unfit to plead. METHOD: We employed two-stage screening methodology to estimate the prevalence of mental illness, neurodevelopmental disorders and unfitness to plead, in 3322 criminal defendants in South London. Sampling was stratified according to whether defendants attended court from the community or custody. Face-to-face interviews, using diagnostic instruments and assessments of fitness to plead, were administered (n = 503). Post-stratification probability weighting provided estimates of the overall prevalence of mental disorders and unfitness to plead. RESULTS: Mental disorder was more common in those attending court from custody, with 48.5% having at least one psychiatric diagnosis compared with 20.3% from the community. Suicidality was frequently reported (weighted prevalence 71.2%; 95% CI 64.2-77.3). Only 16.7% of participants from custody and 4.6% from the community were referred to the liaison and diversion team; 2.1% (1.1-4.0) of defendants were estimated to be unfit to plead, with a further 3.2% (1.9-5.3) deemed 'borderline unfit'. CONCLUSIONS: The prevalence of mental illness and neurodevelopmental disorders in defendants is high. Many are at risk of being unfit to plead and require additional support at court, yet are not identified by existing services. Our evidence challenges policy makers and healthcare providers to ensure that vulnerable defendants are adequately supported at court.

PTSD and complex PTSD in sentenced male prisoners in the UK: prevalence, trauma antecedents, and psychiatric comorbidities.

BACKGROUND: Posttraumatic stress disorder (PTSD) is highly prevalent within prison settings, yet is often unidentified and undertreated. Complex PTSD (CPTSD) has been recently formally recognised in the International Classification of Diseases 11th revision (ICD-11) diagnostic framework but has never been explored in prison settings. We aimed to establish the prevalence of ICD-11 PTSD and CPTSD in a UK prison sample using a validated instrument (the International Trauma Questionnaire). We also explored the associations of these two diagnoses with their traumatic antecedents and psychiatric comorbidities. METHOD: Randomly selected male, sentenced prisoners in a large medium-security prison in south London (N = 221) took part in a clinical interview which assessed PTSD, CPTSD, trauma histories, and comorbid disorders. Multinomial logistic regression was performed to examine differences between those with PTSD or CPTSD, and those without symptoms. RESULTS: A total of 7.7% (95% CI 4.5-12) of the male sentenced prisoners met diagnostic criteria for ICD-11 PTSD and 16.7% (95% CI 12.1-22.3) for CPTSD. A diagnosis of PTSD was associated with more recent traumatic exposure, comorbid generalised anxiety disorder, alcohol dependence, and Cluster B personality disorder. A diagnosis of CPTSD was associated with complex trauma exposure antecedents (developmental, interpersonal, repeated, or multiple forms), and comorbid with anxiety, depression, substance misuse, psychosis, and ADHD. CONCLUSIONS: This study confirms that CPTSD is a very common and comorbid condition in male prisoners. There is an urgent need to develop trauma-informed care in prisons.

Risk factors for recidivism in individuals receiving community sentences: a systematic review and meta-analysis.

OBJECTIVE: We aimed to systematically review risk factors for criminal recidivism in individuals given community sentences. METHODS: We searched seven bibliographic databases and additionally conducted targeted searches for studies that investigated risk factors for any repeat offending in individuals who had received community (non-custodial) sentences. We included investigations that reported data on at least one risk factor and allowed calculations of odds ratios (ORs). If a similar risk factor was reported in three or more primary studies, they were grouped into domains, and pooled ORs were calculated. RESULTS: We identified 15 studies from 5 countries, which reported data on 14 independent samples and 246,608 individuals. We found that several dynamic (modifiable) risk factors were associated with criminal recidivism in community-sentenced populations, including mental health needs (OR = 1.4, 95% confidence interval (CI): 1.2-1.6), substance misuse (OR = 2.3, 95% CI: 1.1-4.9), association with antisocial peers (OR = 2.2, 95% CI: 1.3-3.7), employment problems (OR = 1.8, 95% CI: 1.3-2.5), marital status (OR = 1.6, 95%: 1.4-1.8), and low income (OR = 2.0, 95% CI: 1.1-3.4). The strength of these associations was comparable to that of static (non-modifiable) risk factors, such as age, gender, and criminal history. CONCLUSION: Assessing dynamic (modifiable) risk factors should be considered in all individuals given community sentences. The further integration of mental health, substance misuse, and criminal justice services may reduce reoffending risk in community-sentenced populations.

Impaired processing of threat in psychopathy: A systematic review and meta-analysis of factorial data in male offender populations.

BACKGROUND: Psychopathy is a personality disorder characterised by two underlying factors. Factor 1 (affective and interpersonal deficits) captures affective deficits, whilst Factor 2 (antisocial and impulsive/disorganised behaviours) captures life course persistent antisocial behaviours. Impaired processing of threat has been proposed as an aetiologically salient factor in the development of psychopathy, but the relationship of this impairment to the factorial structure of the disorder in adult male offenders is unclear. OBJECTIVES: To investigate whether threat processing deficits are characteristic of psychopathy as a unitary construct or whether such deficits are specifically linked to higher scores on individual factors. DATA SOURCES: A systematic review of the literature was conducted by searching PubMed, Web of Science and PsycINFO. METHODS: Studies were included if they (1) reported physiological measures of threat response as the primary outcome measure (2) indexed psychopathy using a well-validated clinician rated instrument such as the PCL-R (3) investigated male offenders between 18 and 60 years of age (4) reported threat processing analyses using both Factor 1 and Factor 2 scores (5) provided sufficient data to calculate effect sizes and (6) were published in English-language peer-reviewed journals. We identified twelve studies with data on 1112 participants for the meta-analysis of the relationship with Factor 1 scores, and nine studies with data on 801 participants for the meta-analysis of the relationship with Factor 2 scores. We conducted the meta-analyses to calculate correlations using random-effects models. RESULTS: PCL-R/SV Factor 1 scores were significantly and negatively related to threat processing indices (r = -0.22, (95%CI [-0.28, -.017]). Neither PCL-R/SV Factor 2 scores (r = -0.005, 95%CI [-0.10, 0.09]), nor PCL-R total score (r = -0.05, (95%CI [-0.15, -0.04]) were related to threat processing indices. No significant heterogeneity was detected for the Factor score results. CONCLUSIONS: The meta-analyses of the distinct psychopathy factors suggest that the threat processing deficits observed in male offenders with psychopathy are significantly associated with higher scores on Factor 1. A similar relationship does not exist with Factor 2 scores. Our findings highlight the importance of investigating the potentially discrete relationships between aetiological variables and the two factor constructs in the disorder.

Recidivism rates in individuals receiving community sentences: A systematic review.

OBJECTIVE: We aimed to systematically review recidivism rates in individuals given community sentences internationally. We sought to explore sources of variation between these rates and how reporting practices may limit their comparability across jurisdictions. Finally, we aimed to adapt previously published guidelines on recidivism reporting to include community sentenced populations. METHODS: We searched MEDLINE, PsycINFO, SAGE and Google Scholar for reports and studies of recidivism rates using non-specific and targeted searches for the 20 countries with the largest prison populations worldwide. We identified 28 studies with data from 19 countries. Of the 20 countries with the largest prison populations, only 2 reported recidivism rates for individuals given community sentences. RESULTS: The most commonly reported recidivism information between countries was for 2-year reconviction, which ranged widely from 14% to 43% in men, and 9% to 35% in women. Explanations for recidivism rate variations between countries include when the follow-up period started and whether technical violations were taken into account. CONCLUSION: Recidivism rates in individuals receiving community sentences are typically lower in comparison to those reported in released prisoners, although these two populations differ in terms of their baseline characteristics. Direct comparisons of the recidivism rates in community sentenced cohorts across jurisdictions are currently not possible, but simple changes to existing reporting practices can facilitate these. We propose recommendations to improve reporting practices.

PTSD in prison settings: A systematic review and meta-analysis of comorbid mental disorders and problematic behaviours.

PURPOSE: Prevalence rates of PTSD are higher in the prison population than in the community. We sought to systematically review the extent to which this disorder is associated with other mental health disorders and problematic suicidal or aggressive behaviours in the prison population. METHODS: Studies reporting a relationship between PTSD and comorbid mental disorders and/or problematic behaviours in imprisoned adolescent and adult populations were identified from four bibliographic indexes. Primary studies involving clinical interviews, validated instruments leading to DSM or ICD diagnoses, or validated self-report questionnaires such as the PTSD checklist were included. Random-effects meta-analysis was conducted where possible. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. RESULTS: This review identified 36 studies, with a combined sample of 9594 participants, (6478 male and 2847 female prisoners) from 11 countries. Thirty-four of the identified studies employed a cross-sectional design. We identified significant associations between PTSD and comorbid mental disorders including depression (OR = 3.4, 95% confidence interval (CI): 2.3-4.9), anxiety (OR = 2.9, 95% confidence interval (CI): 1.8-4.7) and substance use (OR = 1.9, 95% confidence interval (CI): 1.5-2.4). We also identified significant associations between PTSD and suicidality (OR = 3, 95% confidence interval (CI): 2.4-3.8) and aggressive behaviours (this latter finding was not subject to meta-analysis). Significant methodological heterogeneity was identified between studies. CONCLUSIONS: High rates of psychiatric comorbidity among prisoners with PTSD, and links to suicidal behaviour, self-harm and aggressive behaviour, provide further support for the need for trauma-informed treatment approaches in prisons. However, significant gaps in the current evidence were apparent. In particular, a lack of large, longitudinal studies meant that the temporal relationships between PTSD and relevant outcomes cannot currently be determined.

Single cell genomic and transcriptomic evidence for the use of alternative nitrogen substrates by anammox bacteria.

Anaerobic ammonium oxidation (anammox) contributes substantially to ocean nitrogen loss, particularly in anoxic marine zones (AMZs). Ammonium is scarce in AMZs, raising the hypothesis that organic nitrogen compounds may be ammonium sources for anammox. Biochemical measurements suggest that the organic compounds urea and cyanate can support anammox in AMZs. However, it is unclear if anammox bacteria degrade these compounds to ammonium themselves, or rely on other organisms for this process. Genes for urea degradation have not been found in anammox bacteria, and genomic evidence for cyanate use for anammox is limited to a cyanase gene recovered from the sediment bacterium Candidatus Scalindua profunda. Here, analysis of Ca. Scalindua single amplified genomes from the Eastern Tropical North Pacific AMZ revealed genes for urea degradation and transport, as well as for cyanate degradation. Urease and cyanase genes were transcribed, along with anammox genes, in the AMZ core where anammox rates peaked. Homologs of these genes were also detected in meta-omic datasets from major AMZs in the Eastern Tropical South Pacific and Arabian Sea. These results suggest that anammox bacteria from different ocean regions can directly access organic nitrogen substrates. Future studies should assess if and under what environmental conditions these substrates contribute to the ammonium budget for anammox.

Fitness to plead: Development and validation of a standardised assessment instrument.

The ability of an individual to participate in courtroom proceedings is assessed by clinicians using legal 'fitness to plead' criteria. Findings of 'unfitness' are so rare that there is considerable professional unease concerning the utility of the current subjective assessment process. As a result, mentally disordered defendants may be subjected unfairly to criminal trials. The Law Commission in England and Wales has proposed legal reform, as well as the utilisation of a defined psychiatric instrument to assist in fitness to plead assessments. Similar legal reforms are occurring in other jurisdictions. Our objective was to produce and validate a standardised assessment instrument of fitness to plead employing a filmed vignette of criminal proceedings. The instrument was developed in consultation with legal and clinical professionals, and was refined using standard item reduction methods in two initial rounds of testing (n = 212). The factorial structure, test-retest reliability and convergent validity of the resultant instrument were assessed in a further round (n = 160). As a result of this iterative process a 25-item scale was produced, with an underlying two-factor structure representing the foundational and decision-making abilities underpinning fitness to plead. The sub-scales demonstrate good internal consistency (factor 1: 0·76; factor 2: 0·65) and test-retest stability (0·7) as well as excellent convergent validity with scores of intelligence, executive function and mentalising abilities (p≤0·01 in all domains). Overall the standardised Fitness to Plead Assessment instrument has good psychometric properties. It has the potential to ensure that the significant numbers of mentally ill and cognitively impaired individuals who face trial are objectively assessed, and the courtroom process critically informed.

The effect of intranasal oxytocin on neural response to facial emotions in healthy adults as measured by functional MRI: A systematic review.

Abnormalities in responses to human facial emotions are associated with a range of psychiatric disorders. Addressing these abnormalities may therefore have significant clinical applications. Previous meta-analyses have demonstrated effects of the neuropeptide oxytocin on behavioural response to facial emotions, and effects on brain, as measured by functional MRI. Evidence suggests that these effects may be mediated by sex and the role of eye gaze. However, the specific effect of oxytocin on brain response to facial emotions in healthy adults has not been systematically analysed. To address this question, this further systematic review was conducted. Twenty-two studies met our inclusion criteria. In men, oxytocin consistently attenuated brain activity in response to negative emotional faces, particularly fear, compared with placebo, while in women, oxytocin enhanced activity. Brain regions consistently involved included the amygdala, fusiform gyrus and anterior cingulate cortex. In some studies, oxytocin increased fixation changes towards the eyes with enhanced amygdala and/or fusiform gyrus activation. By enhancing understanding of emotion processing in healthy subjects, these pharmacoimaging studies provide a theoretical basis for studying deficits in clinical populations. However, progress to date has been limited by low statistical power, methodological heterogeneity, and a lack of multimodal studies.

Integrated machine learning pipeline for aberrant biomarker enrichment (i-mAB): characterizing clusters of differentiation within a compendium of systemic lupus erythematosus patients.

Clusters of differentiation (CD) are cell surface biomarkers that denote key biological differences between cell types and disease state. CD-targeting therapeutic monoclonal antibodies (mABs) afford rich trans-disease repositioning opportunities. Within a compendium of systemic lupus erythematous (SLE) patients, we applied the Integrated machine learning pipeline for aberrant biomarker enrichment (i-mAB) to profile de novo gene expression features affecting CD20, CD22 and CD30 gene aberrance. First, a novel Relief-based algorithm identified interdependent features(p=681) predicting treatment-naïve SLE patients (balanced accuracy=0.822). We then compiled CD-associated expression profiles using regularized logistic regression and pathway enrichment analyses. On an independent general cell line model system data, we replicated associations (in silico) of BCL7A (padj=1.69e-9) and STRBP(padj=4.63e-8) with CD22; NCOA2(padj=7.00e-4), ATN1 (padj=1.71e-2), and HOXC4(padj=3.34e-2) with CD30; and PHOSPHO1, a phosphatase linked to bone mineralization, with both CD22(padj=4.37e-2) and CD30(padj=7.40e-3). Utilizing carefully aggregated secondary data and leveraging a priori hypotheses, i-mAB fostered robust biomarker profiling among interdependent biological features.