[The situation in the German forensic commitment-Results of a survey by the DGPPN]. / Die Situation des deutschen Maßregelvollzugs ­ Ergebnisse einer Umfrage der DGPPN.

BACKGROUND AND OBJECTIVE: In German forensic psychiatry detention under Sections 63 and 64 of the German Penal Code have been repeatedly reformed over the past years; however, despite the most recent amendments to the law on detention, clinics and state authorities warn of insufficient capacities and worrying conditions. Media reports paint a defiant picture. At the same time, there is a lack of valid data that would allow an objective description of the situation in forensic psychiatry. Against this background the management of institutions in Germany has been surveyed. MATERIAL AND METHODS: The survey was conducted as an online survey and sent to all 78 forensic hospitals in Germany. The survey covered topics such as structural data of the facilities, the occupancy and staffing situation, incidents, support from supervisory authorities and funding agencies, and patient characteristics. The results are presented descriptively. RESULTS: Of the 78 facilities contacted, 45 (approximately 60%) participated at least partially in the survey. Many of the clinics (68.5%) complained of significant overcrowding. A clear lack of staff and rooms was reported, at the same time it was stated that patients do not receive adequate treatment. Approximately 1 in 5 patients have a length of stay for more than 10 years and one third of the clinics reported an increasing number of physical assaults by patients. CONCLUSION: This overview shows that the forensic psychiatric hospitals are in very different but generally strained situations. A significant number of clinics are under great pressure. Financial, structural, spatial and personnel resources were described as insufficient to properly and professionally fulfill the legal mandate. The treatment standards presented by the DGPPN in 2017 are not met in many clinics.

Equivalence of Active and Passive Gravitational Mass Tested with Lunar Laser Ranging.

Lunar Laser Ranging (LLR) measures the distance between observatories on Earth and retro-reflectors on the Moon since 1969. In this Letter, we study the possible violation of the equivalence of passive and active gravitational mass (m_{a}/m_{p}), for aluminum (Al) and iron (Fe), using LLR data. Our new limit of 3.9×10^{-14} is about 100 times better than that of Bartlett and Van Buren [Equivalence of Active and Passive Gravitational Mass Using the Moon, Phys. Rev. Lett. 57, 21 (1986)PRLTAO0031-900710.1103/PhysRevLett.57.21] reflecting the benefit of the many years of LLR data.

Effective Cytotoxicity of Dendritic Cells against Established T Cell Lymphomas in Mice.

T cell lymphomas arise in mice that constitutively express a single TCR in the absence of NK cells. Upon TCR engagement these lymphomas are able to corrupt tumor surveillance by decreasing NK cell numbers. In this study, we investigate the outcome of interactions between these T cell lymphomas and dendritic cells. Bone marrow-derived dendritic cells mediated effective killing of T cell lymphomas after activation with IFN-γ and TLR ligands in culture. This cytotoxicity was independent of MHC compatibility. Cell lysis was reduced by the presence of the peroxynitrite inhibitors FeTTPS and L-NMMA, whereas inhibitors of apoptosis, death receptors, and degranulation were without effect, suggesting NO metabolites as the main mediators. When injected together with GM-CSF and R848 into lymphoma-bearing mice, in vitro-expanded bone marrow-derived dendritic cells caused significant survival increases. These data show that dendritic cell adaptive immunotherapy can be used as treatment against T cell lymphomas in mice.

Full or intensity-reduced high-dose melphalan and single or double autologous stem cell transplant with or without bortezomib consolidation in patients with newly diagnosed multiple myeloma.

OBJECTIVE: A post hoc subgroup analysis of two phase III trials (NCT00416273, NCT00416208) was carried out to investigate the influence of 100/140 and 200 mg/m² melphalan as well as single/double autologous stem cell transplantation (ASCT) on progression-free survival (PFS). Additionally, the effect of bortezomib consolidation on PFS was analyzed. METHODS: Following induction therapy and high-dose melphalan with subsequent ASCT, patients with newly diagnosed multiple myeloma (NDMM) were randomized 1:1 to either four 35-day cycles of bortezomib consolidation (1.6 mg/m² IV on days 1, 8, 15, 22) or observation. RESULTS: Of the 340 patients included in this analysis, 13.5% received 1 × MEL100/140, 22.9% 2 × MEL100/140, 31.2% 1 × MEL200, and 32.4% 2 × MEL200. With higher cumulative melphalan dose, PFS improved (P = .0085). PFS curves of patients treated with 2 × MEL100/140 and 1 × MEL200 were very similar. The superior dose effect of MEL200 over MEL100/140 was non-existent in the bortezomib consolidation arm but pronounced in the observation arm (P = .0015). Similarly, double ASCT was only beneficial in patients without bortezomib consolidation (P = .0569). CONCLUSIONS: Full dose melphalan and double transplantation seem advantageous only as long as patients are not receiving bortezomib consolidation afterwards.

Widespread and interrelated gray matter reductions in child sexual offenders with and without pedophilia: Evidence from a multivariate structural MRI study.

AIM: To further investigate the neuroanatomical correlates of child sexual offending and disentangle them from the neural correlates of pedophilia, using a multivariate analytical approach in order to minimize loss of statistical power. METHODS: This study presents structural MRI data on gray matter in an incarcerated, male population of 22 pedophilic and 21 non-pedophilic child sexual offenders, and 20 violent non-sexual offender controls, based on a multivariate whole-brain approach using source-based morphometry. RESULTS: We identify a network of several neuroanatomical regions exhibiting interrelated reduced gray matter in both child sexual offender groups relative to controls, comprising extensive clusters in the bilateral cerebellum and frontal lobe, as well as smaller clusters in the bilateral parietal, temporal, and occipital lobes, the bilateral basal ganglia, the medial cingulate and the hippocampus. CONCLUSION: Our results speak to the interpretation that there are inter- and possibly connectivity-related brain structural abnormalities in child sexual offenders that are not (only) pertaining to pedophilia per se. Interpretations and limitations of the present data are discussed and recommendations for future works are given.

Biodegradation and utilization of crop residues contaminated with poisonous pyrrolizidine alkaloids.

Disposal of noxious plant residues is a challenge for farmers and land management dealing with contaminated biomasses. Recent studies confirm the potential threat of transferring toxic plant constituents like pyrrolizidine alkaloids (PAs) from plant residues to non-toxic succeeding agricultural crops via the soil. We studied the degree of biochemical degradation of PAs in the two most important processes, composting and biomethanization. We used lab composting and biogas batches to investigate the potential of PA-degradation of two common PA-containing plants, Lappula squarrosa and Senecio jacobaea. The experiments demonstrated a virtually complete loss of PAs in three months during the composting process and a rapid decomposition of PAs from 3112.6 µg/kg to less than 21.5 µg/kg in L. squarrosa and from 6350.2 µg/kg to less than 539.6 µg/kg in S. jacobaea during biomethanization. The information obtained is a first guide on how to re-utilize PA-contaminated plant matter in a circular bioeconomy.

[Importance of electroconvulsive therapy (ECT) in forensic psychiatry]. / Stellenwert der Elektrokonvulsionstherapie (EKT) in der forensischen Psychiatrie.

BACKGROUND AND OBJECTIVE: Electroconvulsive therapy (ECT) is recommended in guidelines for the treatment of severe affective and psychotic disorders that also can be found in patients in forensic psychiatric commitment; however, there are no systematically collected data concerning the use of ECT in forensic psychiatry. The aim of this study was to investigate the current state and estimated need for ECT in forensic psychiatry in Germany. MATERIAL AND METHODS: A questionnaire was designed consisting of questions about the current practice and estimated need for ECT in this population. This questionnaire was sent electronically (and by post if needed) to the forensic psychiatric hospitals in Germany. RESULTS: We received replies from 52 hospitals (66%) and 29 of these hospitals stated that they were capable of treating patients with ECT. An indication for ECT treatment was seen in 3.4% of all detained patients across all forensic hospitals. In 1 year (2018) 32 ECT treatment courses were carried out with on average good effectiveness and a mean clinical global impressions (CGI) scale of 2.32. The most frequent reason for not using ECT was lack of structural requirements. Approximately one third of the forensic psychiatric hospitals stated that there was a medium or even high need for ECT in forensic psychiatry. CONCLUSION: The use of ECT in German forensic psychiatry is currently very limited. It is striking that the number of applied ECT treatments is eight times lower in comparison to the frequency of indications. Nevertheless, approximately two thirds of the forensic hospitals stated a medium or high need for ECT, which seems to suggest a shortage of ECT in the treatment of forensic psychiatry patients.

[Revision of §64 of the German Penal Code from a psychiatric perspective-Position paper of a task force of the German Association for Psychiatry, Psychotherapy and Psychosomatics]. / Neuregelung des § 64 StGB aus psychiatrischer Sicht ­ Positionspapier einer Task-Force der DGPPN.

In Germany every second offence occasioning bodily harm and every fourth sexual offence occur under the influence of alcohol or drugs. Untreated substance use disorders are a risk factor for further offences. The §64 of the German Penal Code (StGB) regulates the commitment of offenders to a Forensic addiction treatment unit as a result of an addiction to excessive consummation of intoxicating substances. The previous regulation has come under criticism because too many patients are committed, the sentence is often given to the wrong persons, the treatment is often terminated without success and the sentence consumes to many resources. From a psychiatric perspective the reform of commitment to a Forensic addiction treatment unit (§64 StGB) must fulfil the principles of medical ethics, in particular the respect for the autonomy of the patient, the principle of distributional justice and the code of medical professional ethics. The commitment according to §64 must be restricted to the treatment of people with a clinically relevant substance use disorder. From a psychiatric perspective, decisive for the prospect of success are the willingness to be treated and self-determination for admission to the clinic. In order to release the treatment from the extrinsic influences of the enforcement law, on admission to treatment a sufficient amount of the sentence should have already been served that the commitment only serves the purpose of the treatment and resocialization, so that the risk of further substance-related offences is reduced. The legal term "Entziehungsanstalt" should be replaced by "Forensic Clinic for Dependancy Diseases".

Development of operational intervention levels for events with release of radionuclides.

An essential part of a protection strategy for radiological emergencies is the development of national dose criteria and of operational intervention levels (OILs) to decide about protective measures for all ten scenarios Germany is preparing. For the process of planning and implementing such protection strategies as required by the German Radiation Protection Law the Federal Ministry BMU has commissioned the German Radiation Protection Commission (SSK) to recommend dose criteria and OILs for emergency response measures. OILs link a chosen dose criterion for a protective action with a suitable measurement of the contamination situation such as ambient dose rate (µSv h-1), contamination level on surfaces (Bq cm-2) or activity content (Bq g-1, Bq cm-3). This link should adequately model the exposure of persons during a defined exposure period (e.g. seven days, one year) caused by the measured contamination. Dose calculations to quantify OILs should apply assumptions and parameter values that are in tendency realistic and not unduly conservative. OILs have been developed for the following emergency response actions based on radiation measurements:Sheltering on the basis of dose rate (µSv h-1) and contamination level(Bq cm-2).Evacuation on the basis of dose rate (µSv h-1) and contamination level(Bq cm-2).Establishing a radiological hazard area to implement access andcontamination control on the basis of dose rate (µSv h-1) and contaminationlevel (Bq cm-2).Contamination control and possibly decontamination of persons and objects(items, goods, vehicles, etc) based on contamination level (Bq cm-2).A set of precautionary early actions: warning the population not toconsume freshly contaminated food and agricultural measures to reducefood contamination based on dose rate (µSv h-1).Application of maximum permitted levels of radioactive contamination offood and feed (Bq kg-1) according to Euratom Regulation.

[The expert in criminal and enforcement proceedings: Mission, qualification, delimitation of competence]. / Der Sachverständige im Straf- und Vollstreckungsverfahren. Auftrag, Qualifikation, Kompetenzabgrenzung.

Die Rolle von Sachverständigen im Erkenntnis- und Vollstreckungsverfahren wurde mit der Novellierung des Rechts der Unterbringung in einem psychiatrischen Krankenhaus erneut gestärkt. Sachverständige verfügen über ein spezifisches Fachwissen und haben insoweit eine Garantenstellung gegenüber dem Gericht. Dieses interdisziplinäre Zusammenwirken birgt Gefahren, die zu kritischem und die Fach- und Kompetenzgrenzen wahrendem Zusammenwirken führen müssen. Kompetenzüberschreitungen und Grenzverletzungen können zu Eingriffen in die Grundrechte von Betroffenen führen, die auch haftungsrechtlich relevant werden können. Im Folgenden werden die Rahmenbedingungen der interdisziplinären Zusammenarbeit und insbesondere die Bedeutung der Kompetenzentrennung in foro verdeutlicht.

Engagement of lymphoma T cell receptors causes accelerated growth and the secretion of an NK cell-inhibitory factor.

The development of T cell lymphomas in mice that constitutively express a single T cell receptor is surveilled by the action of NK cells. We investigated the effects of engaging the lymphoma TCR in this mouse model. We stimulated lymphoma cells expressing an ovalbumin-specific TCR in vivo using listeria monocytogenes as a vehicle. Infections with listeria expressing ovalbumin but not with control bacteria caused a stable change in lymphoma cells that allowed its growth in mice with normal NK cells. TCR engagement furthermore enhanced lymphoma growth in NK-cell-depleted mice suggesting a lymphoma-intrinsic change that lead to accelerated growth. The ability to grow in mice without prior NK cell depletion did not appear to be accompanied by changes in the recognition of lymphoma by NK cells. Rather, lymphoma immunization was associated with a decrease in NK cell numbers: Leukemic phases were observed for all mice starting three to eight weeks after immunizations, and leukemias were succeeded by the disappearance of NK cells from blood. We also observed strong decreases of NK cell numbers in spleens at the time of death. Co-culture experiments showed decreases in the ability of NK cells to proliferate in response to IL-15 when post-immunization lymphoma cells were present in a mechanism that did not require direct cell contact. Together these data suggest that TCR engagement caused intrinsic changes in T cell lymphoma cells resulting in both accelerated in vivo growth and in the secretion of a factor that caused NK cell disappearance.

NK cells prevent T cell lymphoma development in T cell receptor-transgenic mice.

Mice that express a single transgenic T cell receptor have a low incidence of T cell lymphoma development. We investigated whether this tumor development is restricted by surveillance mechanisms that are exerted by IL-15-dependent cells. Lymphoma incidence was increased to between 30 and 60% when TCR transgenes were expressed in IL-15-deficient mice. Mice in which NK cells had been depleted genetically or with neutralizing antibodies allowed lymphoma growth while the absence of CD8 T cells was without consequence. Half of the emerged T cell lymphomas carried Notch1 mutations. The distinct phenotype of the lymphomas involved expression of PD1, CD30, CD24, the stress receptor ligand Mult1 and MHC class I down-regulation. NK cells were able to directly lyse lymphoma cells, and neutralizations of Mult1 and class I expression prevented NK cell degranulation. Together these data support an involvement of NK cells in tumor surveillance of nascent T cell lymphomas.

Violent aggression predicted by multiple pre-adult environmental hits.

Early exposure to negative environmental impact shapes individual behavior and potentially contributes to any mental disease. We reported previously that accumulated environmental risk markedly decreases age at schizophrenia onset. Follow-up of matched extreme group individuals (≤1 vs. ≥3 risks) unexpectedly revealed that high-risk subjects had >5 times greater probability of forensic hospitalization. In line with longstanding sociological theories, we hypothesized that risk accumulation before adulthood induces violent aggression and criminal conduct, independent of mental illness. We determined in 6 independent cohorts (4 schizophrenia and 2 general population samples) pre-adult risk exposure, comprising urbanicity, migration, physical and sexual abuse as primary, and cannabis or alcohol as secondary hits. All single hits by themselves were marginally associated with higher violent aggression. Most strikingly, however, their accumulation strongly predicted violent aggression (odds ratio 10.5). An epigenome-wide association scan to detect differential methylation of blood-derived DNA of selected extreme group individuals yielded overall negative results. Conversely, determination in peripheral blood mononuclear cells of histone-deacetylase1 mRNA as 'umbrella mediator' of epigenetic processes revealed an increase in the high-risk group, suggesting lasting epigenetic alterations. Together, we provide sound evidence of a disease-independent unfortunate relationship between well-defined pre-adult environmental hits and violent aggression, calling for more efficient prevention.

Bortezomib consolidation following autologous transplant in younger and older patients with newly diagnosed multiple myeloma in two phase III trials.

OBJECTIVE: A post hoc analysis of two phase III trials was carried out to explore the influence of age and treatment factors on the effect of bortezomib consolidation on progression-free survival (PFS) post autologous stem cell transplantation (ASCT). METHODS: Patients with newly diagnosed multiple myeloma were assigned to one of two trials (ClinicalTrials.gov IDs: NCT00416273, NCT00416208), which were conducted in parallel, based on age (18-60 or 61-75 years, respectively). Following induction and ASCT, patients were randomized 1:1 to four 35-day cycles of bortezomib consolidation (1.6 mg/m2 IV on days 1, 8, 15, 22) or observation only. RESULTS: Median PFS with bortezomib consolidation vs observation was 33.6 vs 29.0 months (P = 0.3599) in patients aged 18-60 years (n = 202), and 33.4 vs 26.4 months (P = 0.0073) in patients aged 61-75 years (n = 155), respectively. Bortezomib consolidation post-ASCT appeared to equalize outcomes between older and younger patients who received prior treatment of differing intensity. This suggests that the effect of consolidation may be relative and may depend on the composition and intensity of induction and high-dose therapy. CONCLUSION: Older patients receiving less intensive prior treatment could experience a larger PFS benefit from bortezomib consolidation.

Virtual reality applications for diagnosis, risk assessment and therapy of child abusers.

Despite the successful application of virtual reality (VR) in a wide variety of mental disorders and the obvious potentials that VR provides, the use of VR in the context of criminology and forensic psychology is sparse. For forensic mental health professionals, VR provides some advantages that outrun general advantages of VR, e.g., ecological validity and controllability of social situations. Most important seems to be the unique possibility to expose offenders and to train coping skills in virtual situations, which are able to elicit disorder-relevant behavior-without endangering others. VR has already been used for the assessment of deviant sexual interests, for testing the ability to transfer learned coping skills communicated during treatment to behavior, and for risk assessment of child abusers. This article reviews and discusses these innovative research projects with regard to their impact on current clinical practice regarding risk assessment and treatment as well as other implementations of VR applications in forensic mental health. Finally, ethical guidelines for VR research in forensic mental health are provided.

Phase II study of bortezomib, cyclophosphamide and dexamethasone as induction therapy in multiple myeloma: DSMM XI trial.

We assessed the safety and efficacy of bortezomib, cyclophosphamide and dexamethasone (VCD) induction therapy in previously untreated multiple myeloma patients. A total of 414 patients received three 21-day cycles of VCD prior to autologous stem-cell transplantation (ASCT). Most common grade ≥3 adverse events were leucopenia (31·4%) and thrombocytopenia (6·8%). The overall response rate (ORR) by investigator-based assessment was 85·4%. Most patients (74%) underwent successful central laboratory-based molecular cytogenetic analysis. No clinically relevant differences in ORR post-induction were seen between patients with or without high-risk cytogenetic abnormalities (86·2% vs. 84·3%). Further follow-up data are available for 113 patients receiving ASCT who were included in a prospective consolidation trial (median follow-up, 55·5 months); median progression-free survival (PFS) was 35·3 months and median overall survival (OS) was not reached. In patients with high-risk versus standard-risk cytogenetics, median PFS was 19·9 vs. 43·6 months (P < 0·0001), and median OS was 54·7 months versus not reached (P = 0·0022). VCD is an effective and tolerable induction regimen; results suggest that VCD induces high response rates independently of cytogenetic risk status, but after long-term follow-up, cytogenetic high risk is associated with markedly reduced PFS and OS post-ASCT.

Neural correlates of subliminally presented visual sexual stimuli.

In the context of forensic psychiatry, it is crucial that diagnoses of deviant sexual interests are resistant to manipulation. In a first attempt to promote the development of such tools, the current fMRI study focusses on the examination of hemodynamic responses to preferred, in contrast to non-preferred, sexual stimuli with and without explicit sexual features in 24 healthy heterosexual subjects. The subliminal stimulus presentation of sexual stimuli could be a new approach to reduce vulnerability to manipulation. Meaningful images and scrambled images were applied as masks. Recognition performance was low, but interestingly, sexual preference and explicitness modulated stimulus visibility, suggesting interactions between networks of sexual arousal and consciousness. With scrambled masks, higher activations for sexually preferred images and for explicit images were found in areas associated with sexual arousal (Stoleru, Fonteille, Cornelis, Joyal, & Moulier, 2012). We conclude that masked sexual stimuli can evoke activations in areas associated with supraliminal induced sexual arousal.

Negative feedback regulation of the ERK1/2 MAPK pathway.

The extracellular signal-regulated kinase 1/2 (ERK1/2) mitogen-activated protein kinase (MAPK) signalling pathway regulates many cellular functions, including proliferation, differentiation, and transformation. To reliably convert external stimuli into specific cellular responses and to adapt to environmental circumstances, the pathway must be integrated into the overall signalling activity of the cell. Multiple mechanisms have evolved to perform this role. In this review, we will focus on negative feedback mechanisms and examine how they shape ERK1/2 MAPK signalling. We will first discuss the extensive number of negative feedback loops targeting the different components of the ERK1/2 MAPK cascade, specifically the direct posttranslational modification of pathway components by downstream protein kinases and the induction of de novo gene synthesis of specific pathway inhibitors. We will then evaluate how negative feedback modulates the spatiotemporal signalling dynamics of the ERK1/2 pathway regarding signalling amplitude and duration as well as subcellular localisation. Aberrant ERK1/2 activation results in deregulated proliferation and malignant transformation in model systems and is commonly observed in human tumours. Inhibition of the ERK1/2 pathway thus represents an attractive target for the treatment of malignant tumours with increased ERK1/2 activity. We will, therefore, discuss the effect of ERK1/2 MAPK feedback regulation on cancer treatment and how it contributes to reduced clinical efficacy of therapeutic agents and the development of drug resistance.