Epidemiology and immunogenetic background of islet cell antibody - positive nondiabetic schoolchildren : Ulm-Frankfurt population study

Islet cell antibodies (ICAs) were determined in a large cohort of white nondiabetic schoolchildren (n = 4287) from a homogenous population in southern Germany. The prevalence of ICA levels greater than or equal to 5 Juvenile Diabetes Foundation (JDF) U was 1.05% (95% confidence interval 0.8-1.4%). Analysis of HLA-DR beta and -DQ beta alleles revealed that the specificities found to be increased in insulin-dependent (type I) diabetic subjects with the same ethnic background were also associated with ICA positivity in the nondiabetic schoolchildren. HLA-DR3 (P less than 0.01) and -DR4 (P less than 0.01) phenotypes and absence of Asp residue (P less than 0.01) at codon 57 of the HLA-DQ beta-chain were significantly increased in ICA+ compared with control subjects. High levels of ICAs, which were categorized as either greater than or equal to 17 or greater than or equal to 30 JDF U, were found to be associated with amino acids other than Asp at position 57 of the HLA-DQ beta-chain. No association of ICA level was found for HLA-DR phenotypes

Incidence, prevalence, and clinical course of hepatitis C following liver transplantation

Hepatitis C virus (HCV) is the agent responsible for posttransfusion hepatitis. The incidence, timing, and clinical course of HCV positive hepatitis in liver transplant recipients are unknown. Three hundred and seventeen donor-recipient liver transplant pairs were grouped on the basis of their pretransplant HCV antibody status. The biopsy findings were examined. Four distinct groups were identified on the basis of HCV serology: group I, both were negative; group II, donor was negative and recipient was positive; group III, donor was positive and recipient was negative; group IV, both were positive. The prevalence of anti-HCV positivity in recipients was 13.6%. The rate of seroconversion was 9.2%. Histologic hepatitis not ascribable to any specific cause other than non-A, non-B (NANB) hepatitis occurred in 13.8%. The incidence of histologic chronic active hepatitis was 1.6%, and none progressed to cirrhosis. The concordance rate for a positive anti-HCV serology and NANB hepatitis was 2.8%. Of the 35 patients (group II and IV) with positive anti-HCV serology pretransplant, only 17 were positive posttransplantation. Based on these data it can be concluded that posttransplant NANB hepatitis occurred in 13.8% of liver recipients. Twenty percent of these were anti-HCV positive. Progression to histologic chronic active hepatitis occurs over a period of 1-5 years in 1.6% of cases. © 1992

ST/EL and ST/CV services for TI2 & TI8 LHC injection tunnels

This paper describes the ST/EL and ST/CV services for TI2 & TI8 LHC injection tunnels. The cooling and ventilation part describes the requirements for design and installation of more than 10 km of pipeline that is going to be laid down in the tunnels. Main operating parameters as well as manufacture procedures are explained. Preliminary work schedule with the cost estimate is also presented. Electrical power will be distributed from the LHC side and the SPS side for the machine and the general services. All power converters will be installed on surface buildings. The link between the main bend converters and the main bend magnets will be realised with water-cooled cables. Rest of the magnets will be cabled by using conventional copper and aluminium cables. Due to long lengths of the injection tunnels a dry 18kV transformer will be installed in TJ8 to serve the general services for TI8. The same will apply to TI2 by installing a transformer at the bottom of the PMI2 shaft

Taking the cat-and-mouse game to the next level: different perspectives on the introduction of the German New Psychoactive Substances Act

Background: To counteract the spread of new psychoactive substances (NPS) and to prevent the emergence of novel substances, specifically designed as a response to the legal control of individual substances, a new law was introduced in Germany in 2016: the New Psychoactive Substances Act (NpSG). The NpSG combines a generic approach with the waiver of criminal liability for the acquisition and possession of NPS for personal use, which is a novelty in German narcotics law. The present study aimed at exploring the impact of the introduction of the NpSG from three different perspectives—NPS users, staff of addiction care facilities, and members of law enforcement authorities—to better understand the dynamics surrounding such a change in legislation and to contribute to the body of international experience in dealing with NPS. Methods: Semi-structured narrative interviews were conducted with a total of 193 representatives of the three different groups affected by the law. These interviews included questions on perceived changes associated with the introduction of the NpSG as well as questions on opinions regarding legal and criminal policy issues. The analysis was carried out using qualitative content analysis according to Mayring. Results: Most interviewees welcomed the non-criminalisation approach of the NpSG but also noticed that, in practice, not much has changed for users. Nevertheless, the changes in legislation have had an impact on the market. For example, novel substances have emerged circumventing the new legislation. According to users, this has led some to reduce NPS use and others to adopt more hazardous consumption patterns. Overall, most respondents did not expect the introduction of the NpSG to bring any significant changes. Conclusions: Although the idea of non-criminalisation inherent to the NpSG is appreciated and the generic approach has been well implemented in the law, thus covering a wide range of substances, the introduction of the law—perhaps for that very reason—has also had unintended and negative consequences, taking the cat-and-mouse game to the next level. To end the game, or at least to defuse the game situation, a combination of different strategies will be necessary, with legislation always playing a key role. © 2022, The Author(s).Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Beyond plug and pray : context sensitivity and in silico design of artificial neomycin riboswitches

Gene regulation in prokaryotes often depends on RNA elements such as riboswitches or RNA thermometers located in the 5′ untranslated region of mRNA. Rearrangements of the RNA structure in response, e.g., to the binding of small molecules or ions control translational initiation or premature termination of transcription and thus mRNA expression. Such structural responses are amenable to computational modelling, making it possible to rationally design synthetic riboswitches for a given aptamer. Starting from an artificial aptamer, we construct the first synthetic transcriptional riboswitches that respond to the antibiotic neomycin. We show that the switching behaviour in vivo critically depends not only on the sequence of the riboswitch itself, but also on its sequence context. We therefore developed in silico methods to predict the impact of the context, making it possible to adapt the design and to rescue non-functional riboswitches. We furthermore analyse the influence of 5′ hairpins with varying stability on neomycin riboswitch activity. Our data highlight the limitations of a simple plug-and-play approach in the design of complex genetic circuits and demonstrate that detailed computational models significantly simplify, improve, and automate the design of transcriptional circuits. Our design software is available under a free licence on GitHub (https://github.com/xileF1337/riboswitch_design)