Violent Behavior During Psychiatric Inpatient Treatment in a German Prison Hospital

Violent behavior in correctional facilities is common and differs substantially in type, target, implication, and trigger. Research on frequency and characteristics of violent behavior in correctional facilities and psychiatric hospitals is limited. Results from recent research suggest that comorbidity of severe mental disorder, personality disorder, and diagnosis of substance abuse is related to a higher risk of violent behavior. In the Berlin prison hospital, a database was created to collect data from all violent incidences (n=210) between 1997 and 2006 and between 2010 and 2016. In a retrospective, case-control study, we analyzed specific socioeconomic data and psychiatric diagnosis and compared the group of prisoners with violent behavior with randomly selected prisoners of the same department without violent behavior (n = 210). Diagnosis of schizophrenia, non-German nationality, no use of an interpreter, no children, and no previous sentence remained significantly associated with the dependent variable violent behavior. There were no significant differences regarding age and legal statuses. Practical implications for clinical work are discussed

Nanofriction mechanisms derived from the dependence of friction on load and sliding velocity from air to UHV on hydrophilic silicon

This paper examines friction as a function of the sliding velocity and applied normal load from air to UHV in a scanning force microscope (SFM) experiment in which a sharp silicon tip slides against a flat Si(100) sample. Under ambient conditions, both surfaces are covered by a native oxide, which is hydrophilic. During pump-down in the vacuum chamber housing the SFM, the behavior of friction as a function of the applied normal load and the sliding velocity undergoes a change. By analyzing these changes it is possible to identify three distinct friction regimes with corresponding contact properties: (a) friction dominated by the additional normal forces induced by capillarity due to the presence of thick water films, (b) higher drag force from ordering effects present in thin water layers and (c) low friction due to direct solid-solid contact for the sample with the counterbody. Depending on environmental conditions and the applied normal load, all three mechanisms may be present at one time. Their individual contributions can be identified by investigating the dependence of friction on the applied normal load as well as on the sliding velocity in different pressure regimes, thus providing information about nanoscale friction mechanisms

Development of a lectin-affinity chromatography step for the downstream processing of influenza virus vaccines

Influenza remains due to its annual death rate and potential to cause pandemics a major public health concern. Efforts to control the annual spread of influenza have centered on prophylactic vaccinations. Human influenza vaccines are traditionally produced in embryonated hen s eggs. However, major constraints with this method, e.g. allergic reactions induced by egg proteins and lack of scalability have lead to the development of cell culture based production processes. In recent years, several continuous cell lines such as the Madin Darby canine kidney (MDCK) or the African green monkey kidney Vero cells have been successfully established for the production of influenza vaccines in cell culture. These processes require the modification of existing but also the development of new downstream strategies to account for the changed upstream technology. Downstream processing of biological products is conventionally subdivided into three steps: capture or concentration, separation or fractionation and polishing. The capture step is commonly the most expensive unit operation. Hence, the efficiency of this step has a large impact on the total process economics. The presented study focuses on the development of a proficient capture step based on lectin-affinity chromatography. Lectins are a class of carbohydrate specific proteins of non-immune origin that have a selective affinity for a carbohydrate or a group of carbohydrates. Immobilized lectins have been used successfully for many years to separate and isolate glycoconjugates, polysaccharides, soluble cell components, and cells containing glycoproteins with specific carbohydrate structures on its surface. The influenza A virus contains two spike glycoproteins on its surface: hemagglutinin (HA) and neuraminidase (NA). HA is the most abundant surface protein. It is a trimeric glycoprotein containing per subunit 3 to 9 N-linked glycosylation sites depending on the viral strain. Here the influenza A/PR/8/34 virus has been selected as a model. The HA molecule of this particular virus contains according to the NetNGlyc 1.0 Server prediction six glycosylation sites. Detailed analysis of these sites and their individual glycan structures are presently performed. Based on preliminary structural glycan analysis studies and literature data several HA-binding lectins are selected for a pre-screening via lectin-blots. The most promising lectinblot results are obtained from lectins specific for terminal galactose e.g. Erythrina cristagalli (ECL), Arachis hypogaea (PNA). Lectins, by which lectin-blot analysis suggests an interaction with viral membrane proteins, are currently screened for their suitability as an affinity matrix ligand. Therefore, centrifuged cultivation broths of influenza A/PR/8/34 virus infected MDCK cells are applied to various agaroseimmobilized lectins. Components interfering with the immobilized lectins are selectively adsorbed. Non or weak binding components are washed from the column. Subsequently, bound components are dissociated from the lectin by competitive elution with suitable hapten carbohydrates. This fraction contains the influenza virus particles and virally encoded membrane proteins, which have to be further processed for vaccine manufacturing. The extend of the subsequent purification depends on the specificity of the lectin binding to virally encoded surface proteins. Lectins with weak or no interaction with host cell proteins or medium components and strong interaction with viral membrane glycoproteins represent a powerful tool to concentrate and purify viral surface proteins from contaminating nucleic acids, medium components, and non-virally encoded host cell proteins

Searching for targets for the systemic therapy of mesothelioma

Increasing knowledge about the molecular characteristics of mesothelioma had led to the identification of novel potential targets for systemic therapy. This review elaborates on the rationale behind targeted approaches that have been and are undergoing exploration in mesothelioma and summarizes available clinical results and ongoing efforts to improve the systemic therapy of mesotheliom

Rationale and design of PROSPECT-CONKO 004: a prospective, randomized trial of simultaneous pancreatic cancer treatment with enoxaparin and chemotherapy

BACKGROUND: Advanced pancreatic cancer, in addition to its high mortality, is characterized by one of the highest rates of venous thromboembolic events (VTE) as compared to other types of cancer. Enoxaparin, a low molecular weight heparin (LMWH), has proven to be effective for the prevention and treatment of VTE in surgical and general medical patients. Results of some small studies suggest that this benefit might extend to patients with cancer, however, enoxaparin is not currently indicated for this use. This phase IIb study was designed to analyze the efficacy of enoxaparin in patients with locally advanced or metastatic pancreatic cancer undergoing systemic chemotherapy. METHODS: The aim of this prospective multicenter trial is to compare concomitant treatment with enoxaparin to no anticoagulation in 540 patients. Primary endpoint is the incidence of clinically relevant VTE (symptomatic deep venous thrombosis (DVT) of the leg and / or pelvic and / or pulmonary embolism (PE)) within the first 3 months. Secondary endpoints include the incidence of symptomatic and asymptomatic VTE after 6, 9 and 12 months as well as remission at 3, 6, 9 and 12 months, overall survival and bleeding. Trial registration: isrctn.org identifier CCT-NAPN-16752, controlled-trials.com identifier: ISRCTN02140505. RESULTS: An interim analysis for safety performed after inclusion of 152 patients revealed no increased risk of bleeding (5 pts vs. 6 pts, Chi2: 0.763). CONCLUSIONS: PROSPECT is a pivotal study in elucidating the role of low molecular weight heparins in advanced pancreatic cancer. Its results will lead to a new understanding of the role of heparins in the prevention of venous thromboembolism and of their effect on survival, remission rates and toxicity of chemotherapeutic regimens

A comparative investigation of thickness measurements of ultra-thin water films by scanning probe techniques

The reliable operation of micro and nanomechanical devices necessitates a thorough knowledge of the water film thickness present on the surfaces of these devices with an accuracy in the nm range. In this work, the thickness of an ultra-thin water layer was measured by distance tunnelling spectroscopy and distance dynamic force spectroscopy during desorption in an ultra-high vacuum system, from about 2.5 nm up to complete desorption at 1E-8 mbar. The tunnelling current as well as the amplitude of vibration and the normal force were detected as a function of the probe-sample distance. In these experiments, a direct conversion of the results of both methods is possible. From the standpoint of surface science, taking the state-of-the-art concerning adsorbates on surfaces into consideration, dynamic force spectroscopy provides the most accurate values. The previously reported tunnelling spectroscopy, requiring the application of significantly high voltages, generally leads to values that are 25 times higher than values determined by dynamic force spectroscopy

Transport properties of copper phthalocyanine based organic electronic devices

Ambipolar charge carrier transport in Copper phthalocyanine (CuPc) is studied experimentally in field-effect transistors and metal-insulator-semiconductor diodes at various temperatures. The electronic structure and the transport properties of CuPc attached to leads are calculated using density functional theory and scattering theory at the non-equilibrium Green's function level. We discuss, in particular, the electronic structure of CuPc molecules attached to gold chains in different geometries to mimic the different experimental setups. The combined experimental and theoretical analysis explains the dependence of the mobilityand the transmission coefficient on the charge carrier type (electrons or holes) and on the contact geometry. We demonstrate the correspondence between our experimental results on thick films and our theoretical studies of single molecule contacts. Preliminary results for fluorinated CuPc are discussed.Comment: 18 pages, 16 figures; to be published in Eur. Phys. J. Special Topic

Searching for targets for the systemic therapy of mesothelioma.

Malignant mesothelioma is an incurable disease associated with asbestos exposure arising in the pleural cavity and less frequently in the peritoneal cavity. Platinum-based combination chemotherapy with pemetrexed is the established standard of care. Multimodality approaches including surgery and radiotherapy are being investigated. Increasing knowledge about the molecular characteristics of mesothelioma had led to the identification of novel potential targets for systemic therapy. Current evidence suggests pathways activated in response to merlin deficiency, including Pi3K/mTOR and the focal adhesion kinase, as well as immunotherapeutic approaches to be most promising. This review elaborates on the rationale behind targeted approaches that have been and are undergoing exploration in mesothelioma and summarizes available clinical results and ongoing efforts to improve the systemic therapy of mesothelioma

Post-stroke inhibition of induced NADPH oxidase type 4 prevents oxidative stress and neurodegeneration

Ischemic stroke is the second leading cause of death worldwide. Only one moderately effective therapy exists, albeit with contraindications that exclude 90% of the patients. This medical need contrasts with a high failure rate of more than 1,000 pre-clinical drug candidates for stroke therapies. Thus, there is a need for translatable mechanisms of neuroprotection and more rigid thresholds of relevance in pre-clinical stroke models. One such candidate mechanism is oxidative stress. However, antioxidant approaches have failed in clinical trials, and the significant sources of oxidative stress in stroke are unknown. We here identify NADPH oxidase type 4 (NOX4) as a major source of oxidative stress and an effective therapeutic target in acute stroke. Upon ischemia, NOX4 was induced in human and mouse brain. Mice deficient in NOX4 (Nox4(-/-)) of either sex, but not those deficient for NOX1 or NOX2, were largely protected from oxidative stress, blood-brain-barrier leakage, and neuronal apoptosis, after both transient and permanent cerebral ischemia. This effect was independent of age, as elderly mice were equally protected. Restoration of oxidative stress reversed the stroke-protective phenotype in Nox4(-/-) mice. Application of the only validated low-molecular-weight pharmacological NADPH oxidase inhibitor, VAS2870, several hours after ischemia was as protective as deleting NOX4. The extent of neuroprotection was exceptional, resulting in significantly improved long-term neurological functions and reduced mortality. NOX4 therefore represents a major source of oxidative stress and novel class of drug target for stroke therapy