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المؤلفون: Öhrström, Lena, Seiler, Roger, Böni, Thomas, Aali, Abolfazl, Stöllner, Thomas, Rühli, Frank
الوصف: Objective: To study pathologies, peri- and postmortal alterations as well as the general preservation state of an ancient Iranian salt mummy. Materials and methods: Several mummified remains from two different time periods (1500-2500 BP) were found in the ChehrÄbÄd salt mine in Iran. Computed tomography was performed on Salt Man #4 (410-350 BC), the best preserved out of the six salt mummies (Siemens, Sensation 16; 512 × 512 matrix; 0.75-5mm slice thickness, 240-mA tube current, 120-kV tube voltage, and 0.976-mmpixel size). Results: Radiological analyses showed an excellent state of preservation of an adolescent body. Several normal variants such as aplasia of the frontal sinus as well as a rare congenital deformation of the 5th vertebral body (butterfly vertebra) have been observed. The individual shows multiple fractures, which is consistent with the theory that he died due to a collapse in the ancient salt mine. Conclusions: The salt preserved the soft tissue as well as parts of the inner organs remarkably well. However, further investigations including histology are needed to reveal additional details of the health status of this unique salt mummy.
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المؤلفون: Scherrer, Alexandra U., Yang, Wan-Lin, Kouyos, Roger D., Böni, Jürg, Yerly, Sabine, Klimkait, Thomas, Aubert, Vincent, Cavassini, Matthias, Battegay, Manuel, Hauser, Christoph, Calmy, Alexandra, Schmid, Patrick, Bernasconi, Enos, Günthard, Huldrych F.
الوصف: The prevalence of integrase strand transfer inhibitor (INSTI)-transmitted drug resistance (TDR) may increase with the increasing use of INSTIs. We analyzed the prevalence of INSTI TDR in the Swiss HIV Cohort Study (2008-2014). In 1 of 1316 drug-naive samples (0.1%), a major INSTI TDR mutation was detected. Prevalence was stable, although INSTIs were increasingly used. We showed that this is in contrast to the introduction of previous drug classes, in which more treatment failures with resistant strains occurred and TDR was observed more rapidly. We demonstrated on a population-level that it is possible to avoid TDR to a new drug class for years.
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المؤلفون: Filli, Lukas, Luechinger, Roger, Frauenfelder, Thomas, Beck, Stefan, Guggenberger, Roman, Farshad-Amacker, Nadja, Andreisek, Gustav
الوصف: Objective: To evaluate metal artifacts induced by biodegradable magnesium—a new class of degradable biomaterial that is beginning to enter the orthopedic routine—on CT and MRI compared to standard titanium and steel controls. Methods: Different pins made of titanium, stainless steel, and biodegradable magnesium alloys were scanned using a second-generation dual-energy multidetector CT and a 1.5-T MR scanner. In CT, quantitative assessment of artifacts was performed by two independent readers by measuring the noise in standardized regions of interest close to the pins. In MRI, the artifact diameter was measured. Interobserver agreement was evaluated using intraclass correlation coefficients. Artifacts were compared using Mann Whitney U tests. Results: In comparison to stainless steel, biodegradable magnesium alloys induced significantly fewer artifacts in both 1.5-T MRI (p = 0.019-0.021) and CT (p = 0.003-0.006). Compared to titanium, magnesium induced significantly less artifact-related noise in CT (p = 0.003-0.008). Although artifacts were less on MRI for biodegradable magnesium compared to titanium, this result was not statistically significant. Conclusion: Biodegradable magnesium alloys induce substantially fewer artifacts in CT compared to standard titanium and stainless steel, and fewer artifacts in MRI for the comparison with stainless steel.
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المؤلفون: Shilaih, Mohaned, Marzel, Alex, Scherrer, Alexandra U., Braun, Dominique L., Kovari, Helen, Rougemont, Mathieu, Darling, Katharine, Battegay, Manuel, Hoffmann, Matthias, Bernasconi, Enos, Hirzel, Cedric, Günthard, Huldrych F., Kouyos, Roger D.
الوصف: BACKGROUND Hepatitis B virus (HBV) has a detrimental effect on human immunodeficiency virus (HIV) natural course, and HBV vaccination is less effective in the HIV infected. We examine the protective effect of dually active antiretroviral therapy (DAART) for HIV/HBV (tenofovir, lamivudine, and emtricitabine) in a large cohort encompassing heterosexuals, men who have sex with men, and intravenous drug users who are HIV infected yet susceptible to HBV, with comprehensive follow-up data about risky behavior and immunological profiles. METHODS We defined an incident HBV infection as the presence of any of HBV serological markers (hepatitis B surface antigen, anti-hepatitis B core antibodies, or HBV DNA) after a negative baseline test result for anti-hepatitis B core antibodies. Patients with positive anti-hepatitis B surface antigen serology were excluded. Cox proportional hazards models were used, with an incident case of HBV infection as the outcome variable. RESULTS We analyzed 1716 eligible patients from the Swiss HIV Cohort Study with 177 incident HBV cases. DAART was negatively associated with incident HBV infection (hazard ratio [HR], 0.4; 95% confidence interval [CI], .2-.6). This protective association was robust to adjustment (HR, 0.3; 95% CI, .2-.5) for condomless sex, square-root-transformed CD4 cell count, drug use, and patient demographics. Condomless sex (HR, 1.9; 95% CI, 1.4-2.6), being a man who has sex with men (2.7; 1.7-4.2), and being an intravenous drug user (3.8; 2.4-6.1) were all associated with a higher hazard of contracting HBV. CONCLUSIONS Our study suggests that DAART, independently of CD4 cell count and risky behavior, has a potentially strong public health impact, including pre-exposure prophylaxis of HBV coinfection in the HIV infected.
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المؤلفون: Hochuli, Michel, Christ, Emanuel, Meienberg, Fabian, Lehmann, Roger, Krützfeldt, Jan, Baumgartner, Matthias
الوصف: Background: Traditional approaches for nighttime glycemic control in glycogen storage disease type I (GSDI) include continuous tube feeding, or ingestion of uncooked corn starch (CS) at bedtime. A modified corn starch (MCS) has been shown to prolong euglycemia in some patients. The aim of this study was to evaluate whether stable nighttime glucose control can be achieved with other types of slowly digested carbohydrates in adult GSDI patients. Methods: In this cross-over study, nocturnal glucose control and fasting times were assessed with three different nocturnal nutrition regimens in five patients, using continuous glucose monitoring (CGMS) in an outpatient everyday life setting. For each patient, continuous glucose profiles were measured after ingestion of (1) CS, (2) MCS or (3) a pasta meal at bedtime, during 5 to 6 consecutive nights for each regimen. Results: Stable nocturnal glucose control was achieved for all patients with a pasta meal, with a mean duration of glycemia >3.5mmol/l of 7.6h (range 5.7-10.8), and >4mmol/l of 7h (5.2-9.2), similar to CS and MCS. Fasting glucose before breakfast on workdays (after 7.1 ± 0.8h) was not significantly different between the three interventions (CS 4.1 ± 0.5mmol/l, MCS 4.6 ± 0.7mmol/l, pasta 4.3 ± 0.9mmol/l). During prolonged fasting on weekends, longer duration of normoglycemia was achieved with CS or MCS than with pasta. Conclusion: Consumption of cooked pasta is a suitable and more palatable alternative to uncooked corn starch to achieve nighttime glucose control in adult patients with GSDI.
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المؤلفون: Leuenberger, Kaspar, Hofmann, Reto, Brugger, Peter, Gassert, Roger
الوصف: The investigation of rotation behavior in human beings enjoys a longstanding and enduring interest in laterality research. While in animal studies the issue of accurately measuring the number of rotations has been solved and is widely applied in practice, it is still challenging to assess the rotation behavior of humans in daily life. We propose a robust method to assess human rotation behavior based on recordings from a miniature inertial measurement unit that can be worn unobtrusively on a belt. We investigate the effect of different combinations of low-cost sensors—including accelerometers, gyroscopes, and magnetometers—on rotation measurement accuracy, propose a simple calibration procedure, and validate the method on data from a predefined path through and around buildings. Results suggest that a rotation estimation based on the fusion of accelerometer, gyroscope, and magnetometer measurements outperforms methods based solely on earth magnetic field measurements, as proposed in previous studies, by a drop in error rate of up to 32 %. We further show that magnetometer signals do not significantly contribute to measurement accuracy in short-term measurements, and could thus be omitted for improved robustness in environments with magnetic field disturbances. Results also suggest that our simple calibration procedure can compete with more complex approaches and reduce the error rate of the proposed algorithm by up to 38 %.
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المؤلفون: Meletta, Romana, Borel, Nicole, Stolzmann, Paul, Astolfo, Alberto, Klohs, Jan, Stampanoni, Marco, Rudin, Markus, Schibli, Roger, Krämer, Stefanie, Müller Herde, Adrienne
الوصف: Non-invasive detection of specific atherosclerotic plaque components related to vulnerability is of high clinical relevance to prevent cerebrovascular events. The feasibility of magnetic resonance imaging (MRI) for characterization of plaque components was already demonstrated. We aimed to evaluate the potential of ex vivo differential phase contrast X-ray tomography (DPC) to accurately characterize human carotid plaque components in comparison to high field multicontrast MRI and histopathology. Two human plaque segments, obtained from carotid endarterectomy, classified according to criteria of the American Heart Association as stable and unstable plaque, were examined by ex vivo DPC tomography and multicontrast MRI (T1-, T2-, and proton density-weighted imaging, magnetization transfer contrast, diffusion-weighted imaging). To identify specific plaque components, the plaques were subsequently sectioned and stained for fibrous and cellular components, smooth muscle cells, hemosiderin, and fibrin. Histological data were then matched with DPC and MR images to define signal criteria for atherosclerotic plaque components. Characteristic structures, such as the lipid and necrotic core covered by a fibrous cap, calcification and hemosiderin deposits were delineated by histology and found with excellent sensitivity, resolution and accuracy in both imaging modalities. DPC tomography was superior to MRI regarding resolution and soft tissue contrast. Ex vivo DPC tomography allowed accurate identification of structures and components of atherosclerotic plaques at different lesion stages, in good correlation with histopathological findings.
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المؤلفون: Sephton, Selena, Herde, Adrienne, Mu, Linjing, Keller, Claudia, Rüdisühli, Sonja, Auberson, Yves, Schibli, Roger, Krämer, Stefanie, Ametamey, Simon
الوصف: Purpose: A novel, 18F-labelled metabotropic glutamate receptor subtype 5 (mGlu5) derivative of [11C]ABP688 ([11C]1), [18F]PSS232 ([18F] ]5), was evaluated in vitro and in vivo for its potential as a PET agent and was used in test-retest reliability studies Methods: The radiosynthesis of [18F]5 was accomplished via a one-step reaction using a mesylate precursor. In vitro stability was determined in PBS and plasma, and with liver microsomal enzymes. Metabolite studies were performed using rat brain extracts, blood and urine. In vitro autoradiography was performed on horizontal slices of rat brain using 1 and 8, antagonists for mGlu5 and mGlu1, respectively. Small-animal PET, biodistribution, and test-retest studies were performed in Wistar rats. In vivo, dose-dependent displacement studies were performed using 6 and blocking studies with 7. Results: [18F]5 was obtained in decay-corrected maximal radiochemical yield of 37% with a specific activity of 80-400GBq/μmol. Treatment with rat and human microsomal enzymes in vitro for 60min resulted in 20% and 4% of hydrophilic radiometabolites, respectively. No hydrophilic decomposition products or radiometabolites were found in PBS or plasma. In vitro autoradiography on rat brain slices showed a heterogeneous distribution consistent with the known distribution of mGlu5 with high binding to hippocampal and cortical regions, and negligible radioactivity in the cerebellum. Similar distribution of radioactivity was found in PET images. Under displacement conditions with 6, reduced [18F]5 binding was found in all brain regions except the cerebellum. 7 reduced binding in the striatum by 84% on average. Test-retest studies were reproducible with a variability ranging from 6.8% to 8.2%. An extended single-dose toxicity study in Wistar rats showed no compound-related adverse effects. Conclusion: The new mGlu5 radiotracer, [18F]5, showed specific and selective in vitro and in vivo properties and is a promising radioligand for PET imaging of mGlu5 in humans.
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المؤلفون: Kusejko, Katharina, Kadelka, Claus, Marzel, Alex, Battegay, Manuel, Bernasconi, Enos, Calmy, Alexandra, Cavassini, Matthias, Hoffmann, Matthias, Böni, Jürg, Yerly, Sabine, Klimkait, Thomas, Perreau, Matthieu, Rauch, Andri, Günthard, Huldrych F., Kouyos, Roger D., Scherrer, Alexandra, Wild, Susanne, Perraudin, Danièle, Minichiello, Mirjam, Anagnostopoulos, A., Battegay, M., Bernasconi, E., Böni, J., Braun, D L., Bucher, H C., Calmy, A., Cavassini, M., Ciuffi, A., Dollenmaier, G., Egger, M., Elzi, L., Fehr, J., Fellay, J., Furrer, H., Fux, C A., Günthard, H F., Haerry, D., Hasse, B., Hirsch, H H., Hoffmann, M., Hösli, I., Huber, M., Kahlert, C., Kaiser, L., Keiser, O., Klimkait, T., Kouyos, R D., Kovari, H., Ledergerber, B., Martinetti, G., Martinez de Tejada, B., Marzolini, C., Metzner, K J., Müller, N., Nicca, D., Paioni, P., Pantaleo, G., Perreau, M., Rauch, A., Rudin, C., Scherrer, A U., Schmid, P., Speck, R., Stöckle, M., Tarr, P., Trkola, A., Vernazza, P., Wandeler, G., Weber, R., Yerly, S Morover
الوصف: Age-mixing patterns are of key importance for understanding the dynamics of human immunodeficiency virus (HIV)-epidemics and target public health interventions. We use the densely sampled Swiss HIV Cohort Study (SHCS) resistance database to study the age difference at infection in HIV transmission pairs using phylogenetic methods. In addition, we investigate whether the mean age difference of pairs in the phylogenetic tree is influenced by sampling as well as by additional distance thresholds for including pairs. HIV-1 pol-sequences of 11,922 SHCS patients and approximately 240,000 Los Alamos background sequences were used to build a phylogenetic tree. Using this tree, 100 per cent down to 1 per cent of the tips were sampled repeatedly to generate pruned trees (N = 500 for each sample proportion), of which pairs of SHCS patients were extracted. The mean of the absolute age differences of the pairs, measured as the absolute difference of the birth years, was analyzed with respect to this sample proportion and a distance criterion for inclusion of the pairs. In addition, the transmission groups men having sex with men (MSM), intravenous drug users (IDU), and heterosexuals (HET) were analyzed separately. Considering the tree with all 11,922 SHCS patients, 2,991 pairs could be extracted, with 954 (31.9 per cent) MSM-pairs, 635 (21.2 per cent) HET-pairs, 414 (13.8 per cent) IDU-pairs, and 352 (11.8 per cent) HET/IDU-pairs. For all transmission groups, the age difference at infection was significantly (P < 0.001) smaller for pairs in the tree compared with randomly assigned pairs, meaning that patients of similar age are more likely to be pairs. The mean age difference in the phylogenetic analysis, using a fixed distance of 0.05, was 9.2, 9.0, 7.3 and 5.6 years for MSM-, HET-, HET/IDU-, and IDU-pairs, respectively. Decreasing the cophenetic distance threshold from 0.05 to 0.01 significantly decreased the mean age difference. Similarly, repeated sampling of 100 per cent down to 1 per cent of the tips ...
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المؤلفون: Woessner, Jochen, Laurentiu, Danciu, Giardini, Domenico, Crowley, Helen, Cotton, Fabrice, Grünthal, Gottfried, Valensise, Gianluca, Arvidsson, Ronald, Basili, Roberto, Demircioglu, Mine, Hiemer, Stefan, Meletti, Carlo, Musson, Roger, Rovida, Andrea, Sesetyan, Karin, Stucchi, Massimiliano
الوصف: The 2013 European Seismic Hazard Model (ESHM13) results from a community-based probabilistic seismic hazard assessment supported by the EU-FP7 project "Seismic Hazard Harmonization in Europe†(SHARE, 2009-2013). The ESHM13 is a consistent seismic hazard model for Europe and Turkey which overcomes the limitation of national borders and includes a through quantification of the uncertainties. It is the first completed regional effort contributing to the "Global Earthquake Model†initiative. It might serve as a reference model for various applications, from earthquake preparedness to earthquake risk mitigation strategies, including the update of the European seismic regulations for building design (Eurocode 8), and thus it is useful for future safety assessment and improvement of private and public buildings. Although its results constitute a reference for Europe, they do not replace the existing national design regulations that are in place for seismic design and construction of buildings. The ESHM13 represents a significant improvement compared to previous efforts as it is based on (1) the compilation of updated and harmonised versions of the databases required for probabilistic seismic hazard assessment, (2) the adoption of standard procedures and robust methods, especially for expert elicitation and consensus building among hundreds of European experts, (3) the multi-disciplinary input from all branches of earthquake science and engineering, (4) the direct involvement of the CEN/TC250/SC8 committee in defining output specifications relevant for Eurocode 8 and (5) the accounting for epistemic uncertainties of model components and hazard results. Furthermore, enormous effort was devoted to transparently document and ensure open availability of all data, results and methods through the European Facility for Earthquake Hazard and Risk ( www.efehr.org ).
