Patterns of risk—Using machine learning and structural neuroimaging to identify pedophilic offenders

BackgroundChild sexual abuse (CSA) has become a focal point for lawmakers, law enforcement, and mental health professionals. With high prevalence rates around the world and far-reaching, often chronic, individual, and societal implications, CSA and its leading risk factor, pedophilia, have been well investigated. This has led to a wide range of clinical tools and actuarial instruments for diagnosis and risk assessment regarding CSA. However, the neurobiological underpinnings of pedosexual behavior, specifically regarding hands-on pedophilic offenders (PO), remain elusive. Such biomarkers for PO individuals could potentially improve the early detection of high-risk PO individuals and enhance efforts to prevent future CSA.AimTo use machine learning and MRI data to identify PO individuals.MethodsFrom a single-center male cohort of 14 PO individuals and 15 matched healthy control (HC) individuals, we acquired diffusion tensor imaging data (anisotropy, diffusivity, and fiber tracking) in literature-based regions of interest (prefrontal cortex, anterior cingulate cortex, amygdala, and corpus callosum). We trained a linear support vector machine to discriminate between PO and HC individuals using these WM microstructure data. Post hoc, we investigated the PO model decision scores with respect to sociodemographic (age, education, and IQ) and forensic characteristics (psychopathy, sexual deviance, and future risk of sexual violence) in the PO subpopulation. We assessed model specificity in an external cohort of 53 HC individuals.ResultsThe classifier discriminated PO from HC individuals with a balanced accuracy of 75.5% (sensitivity = 64.3%, specificity = 86.7%, P5000 = 0.018) and an out-of-sample specificity to correctly identify HC individuals of 94.3%. The predictive brain pattern contained bilateral fractional anisotropy in the anterior cingulate cortex, diffusivity in the left amygdala, and structural prefrontal cortex-amygdala connectivity in both hemispheres. This brain pattern was associated with the number of previous child victims, the current stance on sexuality, and the professionally assessed risk of future sexual violent reoffending.ConclusionAberrant white matter microstructure in the prefronto-temporo-limbic circuit could be a potential neurobiological correlate for PO individuals at high-risk of reoffending with CSA. Although preliminary and exploratory at this point, our findings highlight the general potential of MRI-based biomarkers and particularly WM microstructure patterns for future CSA risk assessment and preventive efforts

Childhood Trauma in Schizophrenia: Current Findings and Research Perspectives

Schizophrenia is a severe neuropsychiatric disorder with persistence of symptoms throughout adult life in most of the affected patients. This unfavorable course is associated with multiple episodes and residual symptoms, mainly negative symptoms and cognitive deficits. The neural diathesis-stress model proposes that psychosocial stress acts on a pre-existing vulnerability and thus triggers the symptoms of schizophrenia. Childhood trauma is a severe form of stress that renders individuals more vulnerable to developing schizophrenia;neurobiological effects of such trauma on the endocrine system and epigenetic mechanisms are discussed. Childhood trauma is associated with impaired working memory, executive function, verbal learning, and attention in schizophrenia patients, including those at ultra-high risk to develop psychosis. In these patients, higher levels of childhood trauma were correlated with higher levels of attenuated positive symptoms, general symptoms, and depressive symptoms;lower levels of global functioning;and poorer cognitive performance in visual episodic memory end executive functions. In this review, we discuss effects of specific gene variants that interact with childhood trauma in patients with schizophrenia and describe new findings on the brain structural and functional level. Additive effects between childhood trauma and brain-derived neurotrophic factor methionine carriers on volume loss of the hippocampal subregions cornu ammonis (CA)4/dentate gyrus and CA2/3 have been reported in schizophrenia patients. A functional magnetic resonance imaging study showed that childhood trauma exposure resulted in aberrant function of parietal areas involved in working memory and of visual cortical areas involved in attention. In a theory of mind task reflecting social cognition, childhood trauma was associated with activation of the posterior cingulate gyrus, precuneus, and dorsomedial prefrontal cortex in patients with schizophrenia. In addition, decreased connectivity was shown between the posterior cingulate/precuneus region and the amygdala in patients with high levels of physical neglect and sexual abuse during childhood, suggesting that disturbances in specific brain networks underlie cognitive abilities. Finally, we discuss some of the questionnaires that are commonly used to assess childhood trauma and outline possibilities to use recent biostatistical methods, such as machine learning, to analyze the resulting datasets

Effect of doxycycline microencapsulation on buccal films : Stability, mucoadhesion and in vitro drug release

Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This research was funded by Rannsóknarsjóður Háskóla Íslands (University of Iceland Research Grand).The aim of this work was to stabilize doxycycline in mucoadhesive buccal films at room temperature (25◦C). Since doxycycline is susceptible to degradation such as oxidation and epimerization, tablets are currently the only formulation that can keep the drug fully stable at room temperature, while liquid formulations are limited to refrigerated conditions (4◦C). In this study, the aim was to make formulations containing subclinical (antibiotic) doxycycline concentration that can act as matrix metalloproteinase inhibitors (MMPI) and can be stored at temperatures such as 25◦C. Here, doxycycline was complexed with excipients using three techniques and entrapped into microparticles that were stored at 4◦C, 25◦C and 40◦C. Effect of addition of precomplexed doxycycline microparticles on films: stability mucoadhesion capacity, tensile strength, swelling index and in vitro release was studied. The complexation efficiency between drug-excipients, microparticles and films was studied using Fourier-transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC). Two of the films were found to be stable at 4◦C but the film containing microparticle composed of precomplexed doxycycline with β-cyclodextrin, MgCl2, sodium thiosulfate, HPMC and Eudragit® RS 12.5 was found to be stable at 25◦C until 26 weeks. The addition of microparticles to the films was found to reduce the mucoadhesive capacity, peak detachment force, tensile strength and elasticity, but improved the stability at room temperature.Peer reviewe

Impact of the Time to Surgery on Visual Outcomes for Rhegmatogenous Retinal Detachment Repair: A Meta-Analysis

PURPOSE: To determine the relationship between time from symptom onset or presentation to repair and visual outcomes for macula-on and macula-off rhegmatogenous retinal detachment (RRD). DESIGN: Meta-analysis. METHODS: We searched MEDLINE, EMBASE, and Cochrane Library for randomized controlled trials and observational studies comparing best-corrected visual acuity (BCVA) based on time to RRD repair. Study identifiers, baseline characteristics, intervention characteristics, and visual outcomes were extracted. We conducted a random effects meta-analysis. Sensitivity analyses included leave-1-out and influence analyses. Primary outcomes included mean difference (MD) in final BCVA, MD between preoperative and final BCVA (∆BCVA), and relative risk of final BCVA24 hours. Secondary outcomes assessed other time points. RESULTS: Twenty observational studies reported on 1929 patients. Macula-off RRD repair in 0-3 days from symptom onset was superior to 4-7 days for final BCVA (MD -0.06 [95% CI -0.09, -0.03], P \u3c .001) but was not different for ∆BCVA (P \u3e .05). Macula-on repair in 0-24 hours from presentation was superior to \u3e24 hours for final BCVA (MD -0.02 [95% CI -0.03, -0.01], P \u3c .05) but was not different for ∆BCVA (P \u3e .05). CONCLUSIONS: Macula-off RRD repair in 0-3 days from symptom onset may have better final BCVA compared to repair in 4-7 days. Macula-on RRD repair in 0-24 hours of presentation may have better final BCVA compared to repair in \u3e24 hours. These results were supported by moderate- and low-quality evidence, respectively, and may have been influenced by differences in baseline BCVA