Cryogenic calorimeters in astro and particle physics

The development of cryogenic calorimeters was originally motivated by the fact that very low energy thresholds and excellent energy resolutions can be achieved by these devices. Cryogenic devices are widely used in double beta decay experiments, in cosmological dark matter searches, in x-ray detection of galactic and extragalactic objects as well as in cosmic background radiation experiments. An overview of the latest developments is given.Comment: (28 pages, contribution to the VIII International Conference on Calorimetry in High Energy Physics, 13-19 June 1999, Lisbon, Portugal

High-sensitive troponin T measurements: what do we gain and what are the challenges?

Cardiac troponin (cTn) I and T are structural proteins unique to the heart. Detection of cTn in peripheral blood indicates cardiomyocyte damage. As acute myocardial infarction (AMI) is the most important cause of cardiomyocyte damage, cTns have become an integral part in the diagnosis of AMI. For this indication, cTns are superior to all other biomarkers and therefore are the preferred marker for the diagnosis of AMI. However, cTn indicates and provides an estimate of cardiomyocyte damage irrespective of its cause. The major limitation of contemporary cTn assays is that they are often not elevated during the initial hours of AMI. Recent advances in assay technology have led to more sensitive and precise cTn assays that will have a profound impact on clinical practice. High-sensitive cTn (hs-cTn) assays have two differentiating features from contemporary cTn assays: (i) detection of cTn in a majority of healthy persons and (ii) precise definition of what is ‘normal' (=the 99th percentile). Recent multicentre studies have shown that hs-cTn assays improve the early diagnosis of patients with suspected AMI, particularly the early rule-out. To achieve best clinical use, cTn has to be interpreted as a quantitative variable. Rising and/or falling levels differentiate acute from chronic cardiomyocyte damage. The terms ‘troponin-positive' and ‘troponin negative' should therefore be avoided. ‘Detectable' levels will become the norm and will have to be differentiated from ‘elevated' levels. The differential diagnosis of a small amount of cardiomyocyte damage and therefore minor elevations of cTn is broad and includes acute and chronic cardiac disorders. The differential diagnosis of larger amount of injury and therefore more substantial elevations of cTn is largely restricted to AMI, myocarditis, and a rare patient with tako-tsubo cardiomyopath

Optimal cutoff-value of Siemens cardiac troponin I assay in patients with kidney disease for the early diagnosis of acute myocardial infarction

Purpose: The recent introduction of more sensitive cardiac troponin (cTn) assays improved the early diagnosis of acute myocardial infarction (AMI). However, its diagnostic utility has never been tested in patients with kidney disease (KD), who are known to have elevated levels of cTn already in the absence of AMI, which may lead to a lower diagnostic value of more sensitive cTn in this high-risk subgroup. Methods: We conducted an international multicenter study to examine the diagnostic accuracy of the Siemens cTnI Ultra assay in 1997 consecutive patients presenting to the emergency department with symptoms suggestive of AMI, of whom 343 (17%) were determined to have KD (MDRD GFR <60ml/min/1.73m2) and to derive the optimal cutoff-value for the diagnosis of AMI in patients with KD. The diagnostic accuracy was further compared to a conventional cTn assay (Roche Troponin T fourth generation). The final diagnosis was adjudicated by two independent cardiologists based on hs-cTnT. Results: AMI was the final diagnosis in 35% (n=120) of all KD-patients as compared to 18% in patients with normal kidney function (p<0.001). Among KD-patients with other diagnoses than AMI, baseline hs-cTnI-levels were elevated above the 99thpercentile in 20%, In patients with KD the diagnostic accuracy at presentation, quantified by the area under the receiver-operator-characteristic curve (AUC), was significantly greater for Siemens cTnI as compared to the standard cTnT assay (AUC for cTnI, 0.88 vs. AUC for the standard assay, 0.82, p=0.013). In patients presenting within three hours after the onset of chest pain, the superiority of Siemens cTnI over conventional cTnT was even more pronounced (AUC 0.86 vs. 0.72, p=0.005). In KD, the optimal hs-cTnI cutoff derived from the ROC curve was 46 ng/l compared to 19 ng/l in patients with normal kidney function (standard 99th percentile 40 ng/l, provided by the manufacturer). Conclusions: The Siemens cTnI Ultra assay has a very high diagnostic accuracy also in KD-patients and is superior to a conventional cTnT-assay. Mild cTnI elevations are common in non-AMI patients. The optimal cutoff-level in KD-patients seems to be around the 99th percentile of a standard population, whereas the optimal cutoff-level in patients with normal kidney function tends to be only half of the suggested cutoff-value. ClinicalTrials.gov number, NCT0047058

Update on high-sensitivity cardiac troponin in patients with suspected myocardial infarction

High-sensitivity cardiac troponin (hs-cTn) assays have been used clinically in many countries throughout the world for years and complement detailed clinical assessment and the electrocardiogram in the early diagnosis of myocardial infarction (MI). High-sensitivity cardiac troponin assays for the first time allow to precisely quantify cardiomyocyte injury around the 99th percentile and thereby substantially increase the accuracy for MI already for blood draws obtained at presentation to the emergency department (ED). Higher diagnostic accuracy at ED presentation enabled the development and extensive validation of early hs-cTn-based diagnostic algorithms, which substantially reduced the time required for safe rule-out or rule-in of MI

Coronary and structural heart interventions in Switzerland 2018

Since the first coronary angioplasty by Andreas Grüntzig in Zurich in 1977, the number of cardiac interventional procedures has steadily increased. The aim of this report is to summarise the state of catheter-based cardiac interventions in adults in Switzerland in 2018. Since 1987, the Working Group Interventional Cardiology of the Swiss Society of Cardiology has collected annually aggregate data from all facilities with cardiac catheterisation laboratories in the country, currently 36 institutions in 17 cantons of Switzerland. Over past years, the numbers of coronary angiography procedures (CAs) and percutaneous coronary interventions (PCIs) increased steadily reaching 57,309 for CA and 27,318 for PCI in 2018. Among structural heart interventions, a broad spectrum of transcatheter procedures is currently available in Switzerland. Numbers of transcatheter aortic valve implantations similarly increased, with 1781 implantations in 2018

Short-term high-intensity interval training improves micro- but not macrovascular function in hypertensive patients

Arterial hypertension is a global health burden that affects vascular structure and function. Assessment of endothelial function can improve cardiovascular (CV) risk stratification. Exercise treatment reduces over all CV risk and improves vascular health. However, it is still not clear which part of the vascular bed is most sensitive to exercise treatment in patients with CV risk. This study aimed to investigate the effects of an 8-week walking based and supervised high-intensity interval training (HIIT) on macro- and microvascular endothelial function as add-on therapy in patients with arterial hypertension.; Forty patients (mean age 58 ± 7 years) treated for arterial hypertension were randomized in the HIIT (3×/week) or control group (CG) receiving standard physical activity recommendations. Arteriolar (aFID) and venular (vFID) flicker light-induced dilatation for retinal microvascular and flow-mediated dilatation (FMD) for macrovascular endothelial function were assessed. In addition, standardized assessments of patients' characteristics were performed before and after 8 weeks.; Both groups reduced weight and body mass index but only the HIIT group reduced body fat, visceral fat, and increased peak oxygen uptake after 8 weeks. The control group reduced diastolic blood pressure. No blood pressure changes were found in the HIIT group. Arteriolar FID increased in the HIIT group independently of confounders (pre: 2.40 ± 0.98%, post: 3.19 ± 1.31%, p < 0.001) but not in the control group (pre: 3.06 ± 1.50%, post: 2.90 ± 1.46%, p = 0.280). No changes were found for FMD in either group.; Arteriolar FID was found to be a sensitive vascular biomarker to assess exercise-induced microvascular improvements even in a short time setting of an 8-week exercise therapy with HIIT. Short-term exercise training affects microvascular endothelial function but not large artery endothelial function. Thus, retinal aFID appears to be a sensitive biomarker to detect short-term exercise efficacy on a vascular level. Dynamic retinal vessel analysis as a diagnostic approach may prove to be an ideal candidate vascular biomarker to monitor treatment effects of exercise in patients with hypertension on top of standard clinical care and may support clinical decision-making in the future

Quantum measurement problem and cluster separability

A modified Beltrametti-Cassinelli-Lahti model of measurement apparatus that satisfies both the probability reproducibility condition and the objectification requirement is constructed. Only measurements on microsystems are considered. The cluster separability forms a basis for the first working hypothesis: the current version of quantum mechanics leaves open what happens to systems when they change their separation status. New rules that close this gap can therefore be added without disturbing the logic of quantum mechanics. The second working hypothesis is that registration apparatuses for microsystems must contain detectors and that their readings are signals from detectors. This implies that separation status of a microsystem changes during both preparation and registration. A new rule that specifies what happens at these changes and that guarantees the objectification is formulated and discussed. A part of our result has certain similarity with 'collapse of the wave function'.Comment: 31 pages, no figure. Published versio

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

Impact of soluble fms-like tyrosine kinase-1 and placental growth factor serum levels for risk stratification and early diagnosis in patients with suspected acute myocardial infarction

Aims Angiogenic factors play an important role in the development of atherosclerosis and show pronounced changes during acute myocardial infarction (AMI). We analysed the impact of placental growth factor (PlGF) and its endogen opponent, soluble fms-like tyrosine kinase-1 (sFlt-1), on clinical outcome and the early diagnosis of AMI. Methods and results This multicentre study enrolled patients presenting with symptoms suggestive of AMI. The final diagnosis was adjudicated by two independent physicians. Levels of sFlt-1 and PlGF were compared with results of a standard troponin T and a novel high-sensitive troponin (hsTnT) assay. Of the 763 patients enrolled, 132 were diagnosed with AMI. Multivariable Cox regression analysis demonstrated sFlt-1 >84 ng/L [hazard ratios (HR) 2.6, 95% confidence intervals (CI) 1.2-5.4, P=0.01] and PlGF >20 ng/L (HR 3.6, 95% CI 1.3-10.4, P=0.02) as predictors for mortality during 1-year follow-up, independent from information provided by troponin T and N-terminal pro-B-type natriuretic peptide (NT-proBNP). However, only sFlt-1 persisted as independent predictor for mortality when analysed together with hsTnT and NT-proBNP, and after adjusting for significant clinical parameters. For the diagnosis of AMI, the combination of troponin T and sFlt-1 improved the performance of troponin T alone and led to a negative predictive value of 98.3% already at time of presentation. However, sFlt-1 and PlGF added only limited diagnostic information when used together with hsTnT. Conclusion Only sFlt-1 but not PlGF provides overall independent prognostic information in patients presenting with symptoms suggestive of AMI. After the introduction of hsTnT in clinical routine, sFlt-1 and PlGF can only add limited diagnostic information for the detection or exclusion of AMI. Clinical Trial Registration Information: ClinicalTrials.gov, NCT0047058