Development and optimization of novel sulfur-containing Ti-based bulk metallic glasses and the correlation between primarily crystallizing phases, thermal stability and mechanical properties

The effect of sulfur on the glass forming ability, thermal stability and mechanical properties of the eutectic alloy Ti33.4Zr33.3Cu33.3 was investigated by conventional X-ray diffraction, differential scanning calorimetry and 3-point flexural experiments. A novel region of bulk glass formation with a critical casting diameter of up to 4 mm was found in the quaternary Ti-Zr-Cu-S system, however, brittle fracture behavior was predominant. Various alloying strategies were employed to improve mechanical properties and a compositional transition from brittle to ductile fracture has been identified (e.g. for Ti36Zr33.5Cu24.5S6). A change of the primary precipitating phases from a C14 Laves to an intermetallic (Ti,Zr)2Cu phase can be observed, as well as a stabilization of the supercooled liquid. The origin of the thermally unstable behavior in Ti-based bulk metallic glasses is traced back to the easy formation of the icosahedral phase upon heating, which is structurally close to the supposedly predominant icosahedral short-range order in the amorphous state. The systematic study carried out in this work indicates a strong correlation between primary crystallizing phase and thermal stability, both pointing to the frozen short-range order in the amorphous state which is predetermining the mechanical properties. The transition from the Laves to the intermetallic (Ti,Zr)2Cu phase as well as the enlarged supercooled liquid region appear to be directly related to a destabilization of the icosahedral short-range order and ultimately to the improved mechanical properties

Specific CT 3D rendering of the treatment zone after Irreversible Electroporation (IRE) in a pig liver model: the “Chebyshev Center Concept” to define the maximum treatable tumor size

Background: Size and shape of the treatment zone after Irreversible electroporation (IRE) can be difficult to depict due to the use of multiple applicators with complex spatial configuration. Exact geometrical definition of the treatment zone, however, is mandatory for acute treatment control since incomplete tumor coverage results in limited oncological outcome. In this study, the “Chebyshev Center Concept” was introduced for CT 3d rendering to assess size and position of the maximum treatable tumor at a specific safety margin. Methods: In seven pig livers, three different IRE protocols were applied to create treatment zones of different size and shape: Protocol 1 (n = 5 IREs), Protocol 2 (n = 5 IREs), and Protocol 3 (n = 5 IREs). Contrast-enhanced CT was used to assess the treatment zones. Technique A consisted of a semi-automated software prototype for CT 3d rendering with the “Chebyshev Center Concept” implemented (the “Chebyshev Center” is the center of the largest inscribed sphere within the treatment zone) with automated definition of parameters for size, shape and position. Technique B consisted of standard CT 3d analysis with manual definition of the same parameters but position. Results: For Protocol 1 and 2, short diameter of the treatment zone and diameter of the largest inscribed sphere within the treatment zone were not significantly different between Technique A and B. For Protocol 3, short diameter of the treatment zone and diameter of the largest inscribed sphere within the treatment zone were significantly smaller for Technique A compared with Technique B (41.1 ± 13.1 mm versus 53.8 ± 1.1 mm and 39.0 ± 8.4 mm versus 53.8 ± 1.1 mm; p < 0.05 and p < 0.01). For Protocol 1, 2 and 3, sphericity of the treatment zone was significantly larger for Technique A compared with B. Conclusions: Regarding size and shape of the treatment zone after IRE, CT 3d rendering with the “Chebyshev Center Concept” implemented provides significantly different results compared with standard CT 3d analysis. Since the latter overestimates the size of the treatment zone, the “Chebyshev Center Concept” could be used for a more objective acute treatment control

The neuropathology of fatal encephalomyelitis in human Borna virus infection

After many years of controversy, there is now recent and solid evidence that classical Borna disease virus 1 (BoDV-1) can infect humans. On the basis of six brain autopsies, we provide the first systematic overview on BoDV-1 tissue distribution and the lesion pattern in fatal BoDV-1-induced encephalitis. All brains revealed a non-purulent, lymphocytic sclerosing panencephalomyelitis with detection of BoDV-1-typical eosinophilic, spherical intranuclear Joest-Degen inclusion bodies. While the composition of histopathological changes was constant, the inflammatory distribution pattern varied interindividually, affecting predominantly the basal nuclei in two patients, hippocampus in one patient, whereas two patients showed a more diffuse distribution. By immunohistochemistry and RNA in situ hybridization, BoDV-1 was detected in all examined brain tissue samples. Furthermore, infection of the peripheral nervous system was observed. This study aims at raising awareness to human bornavirus encephalitis as differential diagnosis in lymphocytic sclerosing panencephalomyelitis. A higher attention to human BoDV-1 infection by health professionals may likely increase the detection of more cases and foster a clearer picture of the disease

Chronic thromboembolic pulmonary hypertension and impairment after pulmonary embolism: the FOCUS study

AIMS: To systematically assess late outcomes of acute pulmonary embolism (PE) and to investigate the clinical implications of post-PE impairment (PPEI) fulfilling prospectively defined criteria. METHODS AND RESULTS: A prospective multicentre observational cohort study was conducted in 17 large-volume centres across Germany. Adult consecutive patients with confirmed acute symptomatic PE were followed with a standardized assessment plan and pre-defined visits at 3, 12, and 24 months. The co-primary outcomes were (i) diagnosis of chronic thromboembolic pulmonary hypertension (CTEPH), and (ii) PPEI, a combination of persistent or worsening clinical, functional, biochemical, and imaging parameters during follow-up. A total of 1017 patients (45% women, median age 64 years) were included in the primary analysis. They were followed for a median duration of 732 days after PE diagnosis. The CTEPH was diagnosed in 16 (1.6%) patients, after a median of 129 days; the estimated 2-year cumulative incidence was 2.3% (1.2-4.4%). Overall, 880 patients were evaluable for PPEI; the 2-year cumulative incidence was 16.0% (95% confidence interval 12.8-20.8%). The PPEI helped to identify 15 of the 16 patients diagnosed with CTEPH during follow-up (hazard ratio for CTEPH vs. no CTEPH 393; 95% confidence interval 73-2119). Patients with PPEI had a higher risk of re-hospitalization and death as well as worse quality of life compared with those without PPEI. CONCLUSION: In this prospective study, the cumulative 2-year incidence of CTEPH was 2.3%, but PPEI diagnosed by standardized criteria was frequent. Our findings support systematic follow-up of patients after acute PE and may help to optimize guideline recommendations and algorithms for post-PE care

GLRB allelic variation associated with agoraphobic cognitions, increased startle response and fear network activation : a potential neurogenetic pathway to panic disorder

The molecular genetics of panic disorder (PD) with and without agoraphobia (AG) are still largely unknown and progress is hampered by small sample sizes. We therefore performed a genome-wide association study with a dimensional, PD/AG - related anxiety phenotype based on the Agoraphobia Cognition Questionnaire (ACQ) in a sample of 1,370 healthy German volunteers of the CRC TRR58 MEGA study wave 1. A genome-wide significant association was found between ACQ and single non-coding nucleotide variants of the GLRB gene (rs78726293, p=3.3x10-8; rs191260602, p=3.9x10-8). We followed up on this finding in a larger dimensional ACQ sample (N=2,547) and in independent samples with a dichotomous AG phenotype based on the Symptoms Checklist (SCL-90; N=3,845) and a case control sample with the categorical phenotype PD/AG (Ncombined =1,012) obtaining highly significant p-values also for GLRB single nucleotide variants rs17035816 (p=3.8x10-4) and rs7688285 (p=7.6x10-5). GLRB gene expression was found to be modulated by rs7688285 in brain tissue as well as cell culture. Analyses of intermediate PD/AG phenotypes demonstrated increased startle reflex and increased fear network as well as general sensory activation by GLRB risk gene variants rs78726293, rs191260602, rs17035816 and rs7688285. Partial Glrb knockout-mice demonstrated an agoraphobic phenotype. In conjunction withthe clinical observation that rare coding GLRB gene mutations are associated with the neurological disorder hyperekplexia characterized by a generalized startle reaction and agoraphobic behavior, our data provide evidence that non-coding, though functional GLRB gene polymorphisms may predispose to PD by increasing startle response and agoraphobic cognitions.PostprintPeer reviewe

Sicherheit ist machbar! Das Heidelberger Audit-Konzept für urbane Sicherheit, am Beispiel der Kommunalen Kriminalprävention in Pforzheim

Die Förderung der objektiven und subjektiven Sicherheit von Einwohnerinnen und Einwohnern einer Gemeinde stellt ein wichtiges kommunalpolitisches Handlungsfeld dar, denn Kriminalität und Kriminalitätsfurcht beeinträchtigen nicht nur die Lebensqualität der Menschen, sondern auch kriminalpolitische Einstellungen und wirtschaftliche Entscheidungen über die Standortwahl. Für eine sicherheitsorientierte und bürgernahe Gemeinde müssen deshalb die Reduzierung von Kriminalität und der Abbau von Kriminalitätsfurcht vorrangige Ziele sein. Mit dem Steuerungsinstrument „Kommunale Kriminalprävention“ und dem weiterentwickelten Heidelberger Audit Konzept für urbane Sicherheit (HAKUS) ergibt sich die Möglichkeit, diese Ziele zu erreichen. Zu den zentralen Elementen dieses Sicherheitsaudits zählen die regelmäßige Erfassung der objektiven und subjektiven Sicherheitslage sowie die wissensbasierte Implementation und Evaluation von Präventionsmaßnahmen. Mit der Nutzung des Sicherheitsaudits ist es möglich, Präventionsmaßnahmen auf Stadtteile und Personengruppen mit hoher Kriminalitätsfurcht zu konzentrieren und solche Maßnahmen zu wählen, die die einflussstärksten Bedingungen der Kriminalitätsfurcht beeinflussen. Auf diese Weise können kommunale Ressourcen effektiv und effizient eingesetzt werden. Die Stadt Pforzheim hat im Jahr 2019 mit der ersten Bevölkerungsbefragung im Rahmen des vorgenannten Sicherheitsaudits diese Möglichkeit genutzt. 2.230 Einwohnerinnen und Einwohner (von 8.000 befragten Personen) beantworteten einen 12-seitigen Fragebogen und sandten diesen zur Auswertung an die Stadtverwaltung zurück. Die für eine schriftliche Befragung hohe Rücklaufquote von knapp 28 Prozent sowie über 3500 freitextliche Vorschläge zur Verbesserung der Lebensqualität weisen auf ein hohes Interesse der Einwohnerinnen und Einwohner Pforzheims an den Belangen ihrer Stadt hin. Die vorliegende Publikation stellt die einzelnen Befunde der Sicherheitsbefragung differenziert dar. Diese werden unter Berücksichtigung regionaler und überregionaler Verhältnisse interpretiert. Insgesamt zeigen die Ergebnisse der Befragung, dass die von der Kommune bereits durchgeführten kriminalpräventiven Projekte einen großen Teil der Furchtursachen abdecken. Pforzheim ist bezüglich der Ausgestaltung der Kriminalprävention auf dem richtigen Weg, der jedoch mittels der Sicherheitsbefragung im Rahmen des Sicherheitsaudits noch verbessert werden kann. Es werden konkrete Vorschläge aufgezeigt.Promoting the objective and subjective safety of residents is an important field of action in municipal policy. Crime and fear of crime can affect the quality of life, people's attitudes toward crime policy and economic decisions about the choice of location. For a security- and citizen-oriented municipality, the reduction of crime and the reduction of fear of crime must therefore be primary goals. The instrument "Community Crime Prevention" and the further developed „Heidelberg Audit Concept for Urban Security“ (HAKUS) offer the possibility to achieve these goals. The central elements of this audit-instrument include the regular recording of the objective and subjective security situation as well as the knowledge-based implementation and evaluation of prevention measures. By using the security audit, it is possible to focus prevention measures on city districts and groups of people with a high fear of crime and to select measures that influence the most influential conditions of fear of crime. In this way, municipal resources can be used effectively and efficiently. The city of Pforzheim conducted the first survey in 2019 to improve the safety. 2.230 residents (out of 8.000 people surveyed) answered a 12-page questionnaire and returned it. The response rate of almost 28 percent is high for a written survey. The respondents listed more than 3.500 free-text suggestions for improving the quality of life. This shows the high interest of Pforzheim residents in safety issues. The following publication presents the individual findings of the survey in a differentiated manner. These are interpreted in consideration of regional and supra-regional conditions. Overall, the results of the survey show that the crime prevention projects already implemented by the municipality cover a large part of the causes of fear. Pforzheim is on the right way with its crime prevention. However, it can still be improved by the results of the survey. Concrete suggestions are shown

The neuropathology of fatal encephalomyelitis in human Borna virus infection

After many years of controversy, there is now recent and solid evidence that classical Borna disease virus 1 (BoDV-1) can infect humans. On the basis of six brain autopsies, we provide the first systematic overview on BoDV-1 tissue distribution and the lesion pattern in fatal BoDV-1-induced encephalitis. All brains revealed a non-purulent, lymphocytic sclerosing panencephalomyelitis with detection of BoDV-1-typical eosinophilic, spherical intranuclear Joest-Degen inclusion bodies. While the composition of histopathological changes was constant, the inflammatory distribution pattern varied interindividually, affecting predominantly the basal nuclei in two patients, hippocampus in one patient, whereas two patients showed a more diffuse distribution. By immunohistochemistry and RNA in situ hybridization, BoDV-1 was detected in all examined brain tissue samples. Furthermore, infection of the peripheral nervous system was observed. This study aims at raising awareness to human bornavirus encephalitis as differential diagnosis in lymphocytic sclerosing panencephalomyelitis. A higher attention to human BoDV-1 infection by health professionals may likely increase the detection of more cases and foster a clearer picture of the disease

Pre-clinical diabetic cardiomyopathy: prevalence, screening, and outcome

AIMS: Diabetic cardiomyopathy, characterized by left ventricular (LV) dysfunction and LV hypertrophy independent of myocardial ischaemia and hypertension, could contribute to the increased life-time risk of congestive heart failure seen in patients with diabetes. We assessed prospectively the prevalence, effectiveness of screening methods [brain natriuretic peptide (BNP) and C-reactive protein in combination with clinical parameters], and outcome of pre-clinical diabetic cardiomyopathy. METHODS AND RESULTS: We studied 100 adults (mean age 57.4 +/- 10.2 years, 44% females) with diabetes and no previous evidence of structural heart disease. By echocardiography, diabetic cardiomyopathy was present in 48% of patients. Screening with combinations of clinical parameters (gender, systolic blood pressure, and body mass index), but not BNP, resulted in high negative predictive values for diabetic cardiomyopathy. During a mean follow-up of 48.5 +/- 9.0 months, in the groups with and without diabetic cardiomyopathy, 12.5 vs. 3.9% (P < 0.2) patients died or experienced cardiovascular events and 37.5 vs. 9.6% (P < 0.002) had a deterioration in NYHA functional class. Overall event-free survival was 54 vs. 87% (P = 0.001) in the groups with and without diabetic cardiomyopathy, respectively. Brain natriuretic peptide was an independent predictor of events [odds ratio 3.5 (1.1-10.9), P = 0.02]. CONCLUSION: Pre-clinical diabetic cardiomyopathy is common. Screening with combinations of simple clinical parameters, but not BNP, can be useful to identify those patients needing further evaluation. Patients with pre-clinical diabetic cardiomyopathy are at increased risk for functional deterioration and possibly cardiovascular events during follow-up. Brain natriuretic peptide was shown to be an independent predictor of future events