Neues Potential im Structural Health Monitoring: Verteilte faseroptische Sensoren für Bestandsbauwerke

Aufgrund der Altersstruktur der Brücken in Deutschland und des überproportional steigenden Schwerlastverkehrs werden umfängliche Erhaltungsmaßnahmen zur Aufrechterhaltung des Infrastrukturnetzes erforderlich. Zur Dynamisierung der Erhaltungsstrategie werden vermehrt kontinuierliche Bauwerksmessungen zur Überwachung und Beurteilung des Bauwerkszustands eingesetzt. Weiterentwicklungen in der Leistungsfähigkeit hochauflösender faseroptischer Sensoren bieten neue messtechnische Möglichkeiten für die großflächige (permanente) Bauwerksüberwachung. Der Beitrag beleuchtet die Potentiale hochauflösender faseroptischer Sensoren zur Zustandsüberwachung von Bestandsbrücken. In einem Pilotprojekt an einer spannungsrisskorrosionsgefährdeten Spannbetonbrücke wurden bzw. werden derzeit faseroptische Sensoren für eine permanente Überwachung installiert und sukzessive in Betrieb genommen. Die Einsatzmöglichkeiten als Dauermonitoringsystem werden anhand der bisherigen Erfahrungen und Ergebnisse demonstriert

Spezies der KFZ-emittierten Platingruppenelemente (PGE) und ihre toxische Wirkung

Vergleichsweise hohe Platingruppenelement-Emissionen aus Autokatalysatoren sind in den letzten Jahren entlang von Autobahnen und in Städten nachgewiesen worden, über deren Toxizität bislang nur wenig bekannt ist. Ziel der Untersuchungen im Rahmen dieses Projektes ist die Abklärung der Bioverfügbarkeit sowie eines möglichen gentoxischen Potentials von Platin-, Palladium- und Rhodiumverbindungen in Säugerzellen. Im Rahmen dieser Vorstudie sollten anhand von metallischen Platin- und Palladiumverbindungen zunächst die geplanten Methoden auf ihre Anwendbarkeit für diese Fragestellung geprüft und erste Abschätzungen über die Bioverfügbarkeit der PGE getroffen werden. Dabei wurden zunächst die Größe und physikalischen Eigenschaften der eingesetzten Partikel durch Rasterelektronenmikroskopie und Röntgendiffraktometrie bestimmt. Ihre Phagozytose durch A549 Lungenzellen konnte qualitativ durch Lichtmikroskopie nachgewiesen werden. Schließlich gelang es, eine Methode zum quantitativen Nachweis von Platin- und Palladium-induzierten DNA-Addukten mit Hilfe der HR-ICP-MS zu etablieren und es konnte in ersten Versuchen gezeigt werden, daß die Exposition von A549 Lungenzellen gegenüber metallischen Palladium- und Platinpartikeln zu einer deutlich meßbaren DNA-Adduktbildung führt. Somit muß von einer Bioverfügbarkeit der Partikel ausgegangen werden. Summary During the last years, comparatively high concentrations of platinum group elements derived from automobile catalysts have been detected along high-traffic streets and in cities. Nevertheless, only little is known about their toxic potentials. Aim of this project is to investigate the bioavailability and potential genotoxic effects of platinum, palladium and rhodium compounds in mammalian cells in culture. By applying metallic platinum and palladium particles, we examined the suitability of different methods to estimate their bioavailabilty. The physical characteristics of the particles were evaluated by electron microscopy and X-ray diffractometry. Phagocytosis of the particles by A549 lung cells was demonstrated by light microscopy. Finally, a procedure was established to quantitate platinum- and palladium-induced DNA adducts by HR-ICP-MS. In preliminary experiments, there was a dose-dependent induction of DNA adducts after exposure of A549 cells towards both types of particles, indicating their bioavailability

Comparison of calling pipelines for whole genome sequencing: an empirical study demonstrating the importance of mapping and alignment

Rapid advances in high-throughput DNA sequencing technologies have enabled the conduct of whole genome sequencing (WGS) studies, and several bioinformatics pipelines have become available. The aim of this study was the comparison of 6 WGS data pre-processing pipelines, involving two mapping and alignment approaches (GATK utilizing BWA-MEM2 2.2.1, and DRAGEN 3.8.4) and three variant calling pipelines (GATK 4.2.4.1, DRAGEN 3.8.4 and DeepVariant 1.1.0). We sequenced one genome in a bottle (GIAB) sample 70 times in different runs, and one GIAB trio in triplicate. The truth set of the GIABs was used for comparison, and performance was assessed by computation time, F1 score, precision, and recall. In the mapping and alignment step, the DRAGEN pipeline was faster than the GATK with BWA-MEM2 pipeline. DRAGEN showed systematically higher F1 score, precision, and recall values than GATK for single nucleotide variations (SNVs) and Indels in simple-to-map, complex-to-map, coding and non-coding regions. In the variant calling step, DRAGEN was fastest. In terms of accuracy, DRAGEN and DeepVariant performed similarly and both superior to GATK, with slight advantages for DRAGEN for Indels and for DeepVariant for SNVs. The DRAGEN pipeline showed the lowest Mendelian inheritance error fraction for the GIAB trios. Mapping and alignment played a key role in variant calling of WGS, with the DRAGEN outperforming GATK

Matrix metalloproteinase-8 and tissue inhibitor of matrix metalloproteinase-1 predict incident cardiovascular disease events and all-cause mortality in a population-based cohort

Background Extracellular matrix degrading proteases and their regulators play an important role in atherogenesis and subsequent plaque rupture leading to acute cardiovascular manifestations. Design and methods In this prospective cohort study, we investigated the prognostic value of circulating matrix metalloproteinase-8, tissue inhibitor of matrix metalloproteinase-1 concentrations, the ratio of matrix metalloproteinase-8/ tissue inhibitor of matrix metalloproteinase-1 and, for comparison, myeloperoxidase and C-reactive protein concentrations for incident cardiovascular disease endpoints. The population-based FINRISK97 cohort comprised 7928 persons without cardiovascular disease at baseline. The baseline survey included a clinical examination and blood sampling. During a 13-year follow-up the endpoints were ascertained through national healthcare registers. The associations of measured biomarkers with the endpoints, including cardiovascular disease event, coronary artery disease, acute myocardial infarction, stroke and all-cause death, were analysed using Cox regression models. Discrimination and reclassification models were used to evaluate the clinical implications of the biomarkers. Results Serum tissue inhibitor of matrix metalloproteinase-1 and C-reactive protein concentrations were associated significantly with increased risk for all studied endpoints. Additionally, matrix metalloproteinase-8 concentration was associated with the risk for a coronary artery disease event, myocardial infarction and death, and myeloperoxidase concentration with the risk for cardiovascular disease events, stroke and death. The only significant association for the matrix metalloproteinase-8/ tissue inhibitor of matrix metalloproteinase-1 ratio was observed with the risk for myocardial infarction. Adding tissue inhibitor of matrix metalloproteinase-1 to the established risk profile improved risk discrimination of myocardial infarction (p=0.039) and death (0.001). Both matrix metalloproteinase-8 (5.2%, p <0.001) and tissue inhibitor of matrix metalloproteinase-1 (12.9%, p <0.001) provided significant clinical net reclassification improvement for death. Conclusions Serum matrix metalloproteinase-8 and tissue inhibitor of matrix metalloproteinase-1 can be considered as biomarkers of incident cardiovascular disease events and death.Peer reviewe

Thirty-One Novel Biomarkers as Predictors for Clinically Incident Diabetes

The prevalence of diabetes is increasing in all industrialized countries and its prevention has become a public health priority. However, the predictors of diabetes risk are insufficiently understood. We evaluated, whether 31 novel biomarkers could help to predict the risk of incident diabetes.The biomarkers were evaluated primarily in the FINRISK97 cohort (n = 7,827; 417 cases of clinically incident diabetes during the follow-up). The findings were replicated in the Health 2000 cohort (n = 4,977; 179 cases of clinically incident diabetes during the follow-up). We used Cox proportional hazards models to calculate the relative risk of diabetes, after adjusting for the classic risk factors, separately for each biomarker. Next, we assessed the discriminatory ability of single biomarkers using receiver operating characteristic curves and C-statistics, integrated discrimination improvement (IDI) and net reclassification improvement (NRI). Finally, we derived a biomarker score in the FINRISK97 cohort and validated it in the Health 2000 cohort. A score consisting of adiponectin, apolipoprotein B, C-reactive protein and ferritin almost doubled the relative risk of diabetes in the validation cohort (HR per one standard deviation increase 1.88, p = 2.8 e-5). It also improved discrimination of the model (IDI = 0.0149, p<0.0001) and reclassification of diabetes risk (NRI = 11.8%, p = 0.006). Gender-specific analyses suggested that the best score differed between men and women. Among men, the best results were obtained with the score of four biomarkers: adiponectin, apolipoprotein B, ferritin and interleukin-1 receptor antagonist, which gave an NRI of 25.4% (p<0.0001). Among women, the best score included adiponectin, apolipoprotein B, C-reactive protein and insulin. It gave an NRI of 13.6% (p = 0.041).We identified novel biomarkers that were associated with the risk of clinically incident diabetes over and above the classic risk factors. This gives new insights into the pathogenesis of diabetes and may help with targeting prevention and treatment

Association of sex hormones and sex hormone-binding globulin with liver fat in men and women: an observational and Mendelian randomization study

Background: Sex hormones and sex hormone-binding globulin (SHBG) may play a role in fatty liver development. We sought to examine the association of various endogenous sex hormones, including testosterone (T), and SHBG with liver fat using complementary observational and Mendelian randomization (MR) analyses. Methods: The observational analysis included a total of 2,239 participants (mean age 60 years; 35% postmenopausal women) from the population-based KORA study (average follow-up time: 6.5 years). We conducted linear regression analysis to investigate the sex-specific associations of sex hormones and SHBG with liver fat, estimated by fatty liver index (FLI). For MR analyses, we selected genetic variants associated with sex hormones and SHBG and extracted their associations with magnetic resonance imaging measured liver fat from the largest up to date European genome-wide associations studies. Results: In the observational analysis, T, dihydrotestosterone (DHT), progesterone and 17α-hydroxyprogesterone (17-OHP) were inversely associated with FLI in men, with beta estimates ranging from -4.23 to -2.30 [p-value <0.001 to 0.003]. Whereas in women, a positive association of free T with FLI (β = 4.17, 95%CI: 1.35, 6.98) was observed. SHBG was inversely associated with FLI across sexes [men: -3.45 (-5.13, -1.78); women: -9.23 (-12.19, -6.28)]. No causal association was found between genetically determined sex hormones and liver fat, but higher genetically determined SHBG was associated with lower liver fat in women (β = -0.36, 95% CI: -0.61, -0.12). Conclusion: Our results provide suggestive evidence for a causal association between SHBG and liver fat in women, implicating the protective role of SHBG against liver fat accumulation

Sex hormone-binding globulin may explain sex differences for glucose homeostasis and incidence of type 2 diabetes: the KORA study.

Research has indicated that sex hormone-binding globulin (SHBG) is associated with glucose homeostasis and may play a role in the etiology of type 2 diabetes (T2D). While it is unclear whether SHBG may mediate sex differences in glucose control and subsequently, incidence of T2D. We used observational data from the German population-based KORA F4 study (n = 1937, mean age: 54 years, 41% women) and its follow-up examination KORA FF4 (median follow-up 6.5 years, n = 1387). T2D was initially assessed by self-report and validated by contacting the physicians and/ or reviewing the medical charts. Mediation analyses were performed to assess the role of SHBG in mediating the association between sex (women vs. men) and glucose- and insulin-related traits (cross-sectional analysis) and incidence of T2D (longitudinal analysis). After adjustment for confounders, (model 1: adjusted for age; model 2: model 1 + smoking + alcohol consumption + physical activity), women had lower fasting glucose levels compared to men (β = -4.94 (mg/dl), 95% CI: -5.77, -4.11). SHBG levels were significantly higher in women than in men (β = 0.47 (nmol/l), 95% CI:0.42, 0.51). Serum SHBG may mediate the association between sex and fasting glucose levels with a proportion mediated (PM) of 30% (CI: 22-41%). Also, a potential mediatory role of SHBG was observed for sex differences in incidence of T2D (PM = 95% and 63% in models 1 and 2, respectively). Our novel findings suggest that SHBG may partially explain sex-differences in glucose control and T2D incidence

Midregional proadrenomedullin and its change predicts recurrent major coronary events and heart failure in stable coronary heart disease patients: The LIPID study

Background: Biomarkers may contribute to risk stratification in coronary heart disease (CHD). We examined whether plasma midregional proadrenomedullin (MR-proADM) concentration at baseline and its change over one year predicts long-term outcomes in stable CHD patients. Methods: The LIPID study randomised patients 3–36 months after an acute coronary syndrome with total cholesterol 4.0–7.0 mmol/L (155–271 mg/dL), to placebo or pravastatin 40 mg. Follow-up was 6.0 years. MR-proADM plasma concentrations at baseline and one year later were determined in 7863 and 6658 patients, respectively. These were categorised into quartiles to perform Cox regression analysis, adjusting for baseline parameters. Results: Baseline MR-proADM concentrations predicted major CHD events (non-fatal myocardial infarction or CHD death; hazard ratio (HR) 1.52, 1.26–1.84 for Q4–Q1), CHD death (HR 2.21, 1.67–2.92), heart failure (HR 2.30, 1.78–2.97) and all-cause mortality (HR 1.82, 1.49–2.23). Associations were still significant after adjustment for baseline B-type natriuretic peptide (BNP) concentration. Increase in MR-proADM after one yearwas associated with increased risk of subsequent CHD events (HR 1.34, 1.08–1.66), non-fatalmyocardial infarction (HR 1.50, 1.12–2.03), heart failure (HR 1.78, 1.37–2.30) and all-causemortality (HR 1.31, 1.04–1.64). Associations with heart failure and all-causemortality remained significant after adjusting for baseline and change in BNP concentration. Change in MR-proADM moderately improved risk reclassification for major CHD events (net reclassification improvement (NRI) 3.48%) but strongly improved risk reclassification for heart failure (NRI 5.60%). Conclusions: Baseline and change in MR-proADM concentrations over one year are associated with risk of major clinical events, even after adjustment for BNP concentrations.National Heart Foundation of Australi