On the Effectiveness of Sexual Offender Treatment in Prisons: A Comparison of Two Different Evaluation Designs in Routine Practice

Although there is less continuity of sexual offending in the life course than stereotypes suggest, treatment should lead to a further reduction of reoffending. Contrary to this aim, a recent large British study using propensity score matching (PSM) showed some negative effects of the core sex offender treatment program (SOTP) in prisons. International meta-analyses on the effects of sex offender treatment revealed that there is considerable variety in the results, and methodological aspects and the context play a significant role. Therefore, this study compared different designs in the evaluation of sex offender treatment in German prisons. PSM was compared with an exact matching (EM) by the Static-99 in a sample of 693 sex offenders from Bavarian prisons. Most results were similar for both methods and not significant due to low base rates. There was a treatment effect at p < .05 on general recidivism in the EM and at p = .06 on serious reoffending in the PSM. For sexual recidivism, EM showed a negative trend, whereas PSM suggested the opposite. Overall, the study underlines the need for more replications of evaluations of routine practice, methodological comparisons, sensitive outcome criteria, and differentiated policy information

Agroforstforschung in Deutschland - Bewertungen von Ökosystemdienstleistungen

Das zunehmende Interesse an der Agroforstwirtschaft erfordert fundierte wissenschaftliche Erkenntnisse, um die Entwicklung resilienter Agroforstsysteme zu unterstützen. Hier stellen wir den Forschungsansatz und erste Ergebnisse eines kürzlich eingerichteten Agroforstversuchs in Deutschland vor

Evidence from comprehensive independent validation studies for smooth pursuit dysfunction as a sensorimotor biomarker for psychosis

Smooth pursuit eye movements are considered a well-established and quantifiable biomarker of sensorimotor function in psychosis research. Identifying psychotic syndromes on an individual level based on neurobiological markers is limited by heterogeneity and requires comprehensive external validation to avoid overestimation of prediction models. Here, we studied quantifiable sensorimotor measures derived from smooth pursuit eye movements in a large sample of psychosis probands (N = 674) and healthy controls (N = 305) using multivariate pattern analysis. Balanced accuracies of 64% for the prediction of psychosis status are in line with recent results from other large heterogenous psychiatric samples. They are confirmed by external validation in independent large samples including probands with (1) psychosis (N = 727) versus healthy controls (N = 292), (2) psychotic (N = 49) and non-psychotic bipolar disorder (N = 36), and (3) non-psychotic affective disorders (N = 119) and psychosis (N = 51) yielding accuracies of 65%, 66% and 58%, respectively, albeit slightly different psychosis syndromes. Our findings make a significant contribution to the identification of biologically defined profiles of heterogeneous psychosis syndromes on an individual level underlining the impact of sensorimotor dysfunction in psychosis

Blockade of MCAM/CD146 impedes CNS infiltration of T cells over the choroid plexus

Background: Very late antigen 4 (VLA-4;integrin alpha 4 beta 1) is critical for transmigration of T helper (T-H) 1 cells into the central nervous system (CNS) under inflammatory conditions such as multiple sclerosis (MS). We have previously shown that VLA-4 and melanoma cell adhesion molecule (MCAM) are important for trans-endothelial migration of human T(H)17 cells in vitro and here investigate their contribution to pathogenic CNS inflammation. Methods: Antibody blockade of VLA-4 and MCAM is assessed in murine models of CNS inflammation in conjunction with conditional ablation of alpha 4-integrin expression in T cells. Effects of VLA-4 and MCAM blockade on lymphocyte migration are further investigated in the human system via in vitro T cell transmigration assays. Results: Compared to the broad effects of VLA-4 blockade on encephalitogenic T cell migration over endothelial barriers, MCAM blockade impeded encephalitogenic T cell migration in murine models of MS that especially depend on CNS migration across the choroid plexus (CP). In transgenic mice lacking T cell alpha 4-integrin expression (CD4::/tga4(-/-)), MCAM blockade delayed disease onset. Migration of MCAM-expressing T cells through the CP into the CNS was restricted, where laminin 411 (composed of alpha 4, beta 1, gamma 1 chains), the proposed major ligand of MCAM, is detected in the endothelial basement membranes of murine CP tissue. This finding was translated to the human system;blockade of MCAM with a therapeutic antibody reduced in vitro transmigration of MCAM-expressing T cells across a human fibroblast-derived extracellular matrix layer and a brain-derived endothelial monolayer, both expressing laminin alpha 4. Larninin alpha 4 was further detected in situ in CP endothelial-basement membranes in MS patients' brain tissue. Conclusions: Our findings suggest that MCAM-laminin 411 interactions facilitate trans-endothelial migration of MCAM-expressing T cells into the CNS, which seems to be highly relevant to migration via the CP and to potential future clinical applications in neuroinflammatory disorders

Real-World Experience Treating Pediatric Epilepsy Patients With Cenobamate

IntroductionIn one third of all patients with epilepsy, seizure freedom is not achieved through anti-seizure medication (ASM). These patients have an increased risk of earlier death, poorer cognitive development, and reduced quality of life. Cenobamate (CNB) has recently been approved as a promising novel ASM drug for the treatment of adults with focal-onset epilepsy. However, there is little experience for its application in pediatric patients.MethodsIn a multicenter study we evaluated retrospectively the outcome of 16 pediatric patients treated “off label” with CNB.ResultsIn 16 patients with a mean age of 15.38 years, CNB was started at an age of 15.05 years due to DRE. Prior to initiation of therapy, an average of 10.56 (range 3–20) ASM were prescribed. At initiation, patients were taking 2.63 (range 1–4) ASM. CNB was increased by 0.47 ± 0.27mg/kg/d every 2 weeks with a mean maximum dosage of 3.1 mg/kg/d (range 0.89–7) and total daily dose of 182.81 mg (range 50–400 mg). Seizure freedom was achieved in 31.3% and a significant seizure reduction of &gt;50% in 37.5%. Adverse events occurred in 10 patients with fatigue/somnolence as the most common. CNB is taken with high adherence in all but three patients with a median follow-up of 168.5 daysConclusionCenobamate is an effective ASM for pediatric patients suffering from drug-resistant epilepsy. In addition to excellent seizure reduction or freedom, it is well-tolerated. Cenobamate should be considered as a novel treatment for DRE in pediatric patients

Para-infectious brain injury in COVID-19 persists at follow-up despite attenuated cytokine and autoantibody responses

To understand neurological complications of COVID-19 better both acutely and for recovery, we measured markers of brain injury, inflammatory mediators, and autoantibodies in 203 hospitalised participants; 111 with acute sera (1–11 days post-admission) and 92 convalescent sera (56 with COVID-19-associated neurological diagnoses). Here we show that compared to 60 uninfected controls, tTau, GFAP, NfL, and UCH-L1 are increased with COVID-19 infection at acute timepoints and NfL and GFAP are significantly higher in participants with neurological complications. Inflammatory mediators (IL-6, IL-12p40, HGF, M-CSF, CCL2, and IL-1RA) are associated with both altered consciousness and markers of brain injury. Autoantibodies are more common in COVID-19 than controls and some (including against MYL7, UCH-L1, and GRIN3B) are more frequent with altered consciousness. Additionally, convalescent participants with neurological complications show elevated GFAP and NfL, unrelated to attenuated systemic inflammatory mediators and to autoantibody responses. Overall, neurological complications of COVID-19 are associated with evidence of neuroglial injury in both acute and late disease and these correlate with dysregulated innate and adaptive immune responses acutely

The predictive value of the leveling off of within session performance for procedural memory consolidation

Ziel der vorliegenden Arbeit war die Hypothese zu prüfen, ob die initiale, innerhalb eines Trainings auftretende Leistungssättigung (die Sättigung der Primingeffekte) im prozeduralen Lernen einen auslösenden Faktor für die Entwicklung verzögerter Leistungzugewinne darstellt. Die durch Wiederholung innerhalb eines Trainings erzielten Leistungszugewinne nehmen anfangs rapide zu, im Verlauf werden sie jedoch deutlich geringer bis sich die Leistungssteigerung „sättigt“ und die Leistung schließlich - trotz weiterer Wiederholungen - konstant bleibt (Hauptmann und Karni, 2002). Neben diesen Leistungsverbesserungen, die innerhalb eines Trainings erzielt werden, können im prozeduralen Lernen zudem Leistungszugewinne langsam „off line“ in der Zeit zwischen zwei Trainingssitzungen ohne zusätzliches Training entstehen („off - line learning“). Das Auftreten dieser verzögerten Leistungszugewinne im nachfolgenden Training gilt als ein behaviorales Maß für die erfolgte Induktion einer Gedächtniskonsolidierung im prozeduralen Lernen (Robertson et al., 2004). Die Ergebnisse einer vorangegangenen Studie führten zu der Hypothese, dass die Sättigung der schnell anfallenden Leistungszugewinne (bzw. Primingeffekte), die sich durch das Erreichen eines konstanten Leistungsniveaus innerhalb einer Trainingssitzung ausdrückt, die Entwicklung der verzögert auftretenden Leistungszugewinne auslösen könnte. 32 gesunde Probanden führten eine computergestüzte visuell- motorische Aufgabe durch. Nach einer ersten Durchführung in der initialen Trainingssitzung erfolgte eine erneute Ausführung der Aufgabe nach einem übungsfreien Intervall von 24 Stunden in einer zweiten Trainingssitzung. Mithilfe eines speziellen Algorithmus konnte der Punkt der Leistungssättigung bei den einzelnen Probanden "on-line" innerhalb des ersten Trainings bestimmt werden. Zusammenfassend zeigen die Ergebnisse dass das Training bis zum Erreichen der Leistungssättigung das entscheidende Kriterium für das Auslösen verzögerter Leistungs-zugewinne war. Bis auf zwei Ausnahmen wiesen alle Probanden bei denen eine Leistungs-sättigung im ersten Training eingetreten war (Gruppe A und B, n = 20 ) verzögerte Leistungs-zugewinne in der zweiten Trainingssitzung auf. Demgegenüber traten bei keinem Probanden (Gruppe C), der die Leistungssättigung im ersten Training nicht erreicht hatte, verzögerte Leistungssteigerungen im nachfolgendem Training auf. Darüber hinaus zeigen die Ergebnisse, die große interindividuelle Variabilität in der Anzahl der bis zum Eintritt der Sättigung benötigten Wiederholungen (min = 3, max = 8 ). So hat sich die initiale Leistungssättigung auf einer individuellen Grundlage - und nicht eine absolute Trainingsmenge oder ein absolut erreichtes Leistungsniveau - als ein entscheidendes Kriterium für das Auslösen der Entwicklung verzögerter Leistungszugewinnne erwiesen.The target of this work was to proof the hypothesis, that the initial leveling off of within session performance gains serve as a critical trigger for the evolution of delayed (overnight) performance gains. In addition to performance gains accrued concurrently with a given training experience (within-session gains) robust, delayed (between - session) performance gains may slowly evolve in the absence of any additional practice in a variety of tasks. The latter is regarded as a behavioral manifestation of skill memory consolidation. It is not known, however, how much practice is necessary for the triggering of these consolidation effects. The results of a recent study (Hauptmann and Karni, 2002) suggest that the leveling off of performance gains (saturation of repetition priming effects), within a training session, may constitute a critical trigger for the induction of delayed performance gains. To test this hypothesis 32 naive individuals trained on a letter enumeration task. Performance was measured in two sessions, 24 h apart: a practice (first) session and a re-test (second) session. The criterion for the leveling off of within performance gains (saturation) was determined using an on-line algorithm. The results show that the triggering of delayed gains could be predicted from each individual’s performance curve. Delayed performance gains evolved consistently only when practice continued to the point at which within – session performance leveled off (saturation). No delayed gains were found when training was stopped before this individually determined point. Our results support the notion that the triggering of consolidation processes depends on the saturation of a distinct, early phase of learning rather than on the absolute number of task repetitions