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92 result(s) for "Grabherr Silke"
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DBnorm as an R package for the comparison and selection of appropriate statistical methods for batch effect correction in metabolomic studies
As a powerful phenotyping technology, metabolomics provides new opportunities in biomarker discovery through metabolome-wide association studies (MWAS) and the identification of metabolites having a regulatory effect in various biological processes. While mass spectrometry-based (MS) metabolomics assays are endowed with high throughput and sensitivity, MWAS are doomed to long-term data acquisition generating an overtime-analytical signal drift that can hinder the uncovering of real biologically relevant changes. We developed “ dbnorm ”, a package in the R environment, which allows for an easy comparison of the model performance of advanced statistical tools commonly used in metabolomics to remove batch effects from large metabolomics datasets. “ dbnorm ” integrates advanced statistical tools to inspect the dataset structure not only at the macroscopic (sample batches) scale, but also at the microscopic (metabolic features) level. To compare the model performance on data correction, “ dbnorm ” assigns a score that help users identify the best fitting model for each dataset. In this study, we applied “ dbnorm ” to two large-scale metabolomics datasets as a proof of concept. We demonstrate that “ dbnorm ” allows for the accurate selection of the most appropriate statistical tool to efficiently remove the overtime signal drift and to focus on the relevant biological components of complex datasets.
Revolution in death sciences: body farms and taphonomics blooming. A review investigating the advantages, ethical and legal aspects in a Swiss context
Taphonomy is the study of decaying organisms over time and their process of fossilization. Taphonomy, originally a branch of palaeontology and anthropology, was developed to understand the ecology of a decomposition site, how site ecology changes upon the introduction of plant or animal remains and, in turn, how site ecology affects the decomposition of these materials. In recent years, these goals were incorporated by forensic science to understand the decomposition of human cadavers, to provide a basis on which to estimate postmortem and/or postburial interval, to assist in the determination of cause and circumstances of death, and to aid in the location of clandestine graves. These goals are achieved through the study of the factors that influence cadaver decomposition (e.g. temperature, moisture, insect activity). These studies have also provided insight into the belowground ecology of cadaver breakdown and allowed to develop useful protocols for mass disaster managements in humanitarian medicine. From the results obtained, new scientific disciplines have arisen, gathered under the word “taphonomics” such as the study of microorganisms living below/on a cadaver (thanatogeomicrobiology), and join the more classical forensic sciences such as anthropology, botany or entomology. Taking into account the specificities of the study object (human cadaver), primordial requirements are needed in terms of security (physical and environmental) as well as ethical and legal concerns which are studied in the Swiss context. The present review aims to present in a first part the concept of human forensic taphonomy facilities (HFTF, also colloquially named “body farm”) leading to an enrichment of forensic sciences with new “taphonomics”. The second part is focused on the mandatory points that must be addressed for a HFTF approach, especially because it requires a specific place to undertake this research which must be performed in conformity with a country’s human ethics and laws.
Forensic age estimation via magnetic resonance imaging of knee in the Turkish population: use of T1-TSE sequence
The evaluation of epiphyseal areas by magnetic resonance imaging (MRI) for forensic age estimation is an important supportive diagnostic method to prevent repeated radiation exposure without a valid medical reason. There are still not enough individuals being analyzed with MRI for age estimation. The aim of this study was to investigate the utility of T1-weighted turbo spin echo (T1-TSE) MRI sequences in determining the degree of ossification of the distal femoral and proximal tibial epiphyses in a Turkish population. In this study, images from 649 patients (335 males and 314 females) aged 10–30 years were retrospectively evaluated with sagittal T1-weighted turbo spin echo (T1-TSE) MRI sequences of the knee. Proximal tibial and distal femoral epiphysis were scored by two different observers twice using the combined staging system described by Schmeling and Kellinghaus. Spearman’s rank correlation analysis indicated a significant positive relationship between age and ossification stages of the distal femoral and proximal tibial epiphyses (p < 0.001). The intra- and inter-observer reliabilities in evaluating the femur and tibia were separately determined and gave promising results and Cohen’s kappa statistics ranged from κ = 0.886 and κ = 0.961. The minimal ages of patients with stage 4 ossification were 15.1 years for females and 15.8 years for males for the distal tibial epiphysis and 15.4 years for females and 17 years for males for the distal femoral epiphysis. This study show that (T1-TSE) MRI and the applicability and Schmeling and Kellinghaus staging method of the knee can be performed for living 14- to 17-year-old individuals in need of a supportive noninvasive method for estimating forensic age.
Postmortem computed tomography angiography vs. conventional autopsy: advantages and inconveniences of each method
Purpose Postmortem computed tomography angiography (PMCTA) was introduced into forensic investigations a few years ago. It provides reliable images that can be consulted at any time. Conventional autopsy remains the reference standard for defining the cause of death, but provides only limited possibility of a second examination. This study compares these two procedures and discusses findings that can be detected exclusively using each method. Materials and methods This retrospective study compared radiological reports from PMCTA to reports from conventional autopsy for 50 forensic autopsy cases. Reported findings from autopsy and PMCTA were extracted and compared to each other. PMCTA was performed using a modified heart–lung machine and the oily contrast agent Angiofil® (Fumedica AG, Muri, Switzerland). Results PMCTA and conventional autopsy would have drawn similar conclusions regarding causes of death. Nearly 60 % of all findings were visualized with both techniques. PMCTA demonstrates a higher sensitivity for identifying skeletal and vascular lesions. However, vascular occlusions due to postmortem blood clots could be falsely assumed to be vascular lesions. In contrast, conventional autopsy does not detect all bone fractures or the exact source of bleeding. Conventional autopsy provides important information about organ morphology and remains the only way to diagnose a vital vascular occlusion with certitude. Conclusion Overall, PMCTA and conventional autopsy provide comparable findings. However, each technique presents advantages and disadvantages for detecting specific findings. To correctly interpret findings and clearly define the indications for PMCTA, these differences must be understood.
Postmortem coronary artery calcium score in cases of myocardial infarction
Sudden cardiac death (SCD) related to atherosclerotic coronary artery disease (ACAD) resulting in myocardial infarction is the most prevalent cause of death in western countries. In clinical practice, coronary artery calcium score (CACS) is considered an independent predictor of coronary events, closely related to atherosclerotic burden and is quantified radiologically by the Agatston score being calculated through computed tomography. Postmortem computed tomography (PMCT) allows the visualization and quantification of coronary calcifications before the autopsy. However, it was reported that some patients who died from severe ACAD had a zero CACS in PMCT. In this study, a retrospective evaluation of CACS in adult’s myocardial infarction cases related to ACAD, with available CACS and histological slides of coronary arteries, was performed in order to gain a deeper understanding of coronary calcifications and their role in myocardial infarction cases. The CACS was calculated by using the software Smartscore 4.0 after the radiological examination on a 64-row CT unit using a specific cardiac protocol. Thirty-six cases were identified out of 582 autopsies, recorded during a 2-year study period (29 men, 7 women; age 56.3 ± 11.7). CACS was 0–10 in 5 cases (5 men, 44.8 ± 13.7), 11–100 in 8 cases (6 men, 2 women, 53.1 ± 7.7), 101–400 in 13 cases (11 men, 2 women, 57.4 ± 9.6), and > 400 in 10 cases (9 men, 1 woman, 63.1 ± 11.9). Coronary thrombosis was found in 28 cases, histologically identified as plaque erosions in 6 cases and as plaque ruptures in 22 cases. Statistical analyses showed that CACS increases significantly with age (p-value < 0.05) and does not show significant correlation with gender, body weight, body mass index, and heart weight. CACS was significantly higher in plaque ruptures than in plaque erosions (p-value < 0.01). Zero or low CACS on unenhanced PMCT cannot exclude the presence of myocardial infarction related to ACAD. This paradoxical discrepancy between imaging and autopsy findings can be explained considering the histological aspect of fatal coronary plaques.
Forensic age estimation based on fast spin-echo proton density (FSE PD)–weighted MRI of the distal radial epiphysis
Radiation exposure is a crucial factor to consider in forensic age estimation. The various magnetic resonance imaging (MRI) modalities used in forensic age estimation avoid radiation exposure. This study examined the reliability of distal radius ossification using fast spin-echo proton density (FSE PD)–weighted MRI to estimate age. Left wrist MRI findings of 532 patients aged 10–29 years were evaluated retrospectively using the five-stage system of Dedouit et al. The intra- and interobserver reliability values were κ = 0.906 and 0.869, respectively. Based on the results, the respective minimum ages estimated for stages 4 and 5 were 13.4 and 16.1 years for females, and 15.1 and 17.3 years for males; the method could not estimate an age of 18 years in any case. FSE PD MRI analysis of the distal radius epiphysis provides supportive data and can be used when evaluating the distal radius for forensic age estimation.
Detecting early myocardial ischemia in rat heart by MALDI imaging mass spectrometry
Diagnostics of myocardial infarction in human post-mortem hearts can be achieved only if ischemia persisted for at least 6–12 h when certain morphological changes appear in myocardium. The initial 4 h of ischemia is difficult to diagnose due to lack of a standardized method. Developing a panel of molecular tissue markers is a promising approach and can be accelerated by characterization of molecular changes. This study is the first untargeted metabolomic profiling of ischemic myocardium during the initial 4 h directly from tissue section. Ischemic hearts from an ex-vivo Langendorff model were analysed using matrix assisted laser desorption/ionization imaging mass spectrometry (MALDI IMS) at 15 min, 30 min, 1 h, 2 h, and 4 h. Region-specific molecular changes were identified even in absence of evident histological lesions and were segregated by unsupervised cluster analysis. Significantly differentially expressed features were detected by multivariate analysis starting at 15 min while their number increased with prolonged ischemia. The biggest significant increase at 15 min was observed for m/z 682.1294 (likely corresponding to S-NADHX—a damage product of nicotinamide adenine dinucleotide (NADH)). Based on the previously reported role of NAD + /NADH ratio in regulating localization of the sodium channel (Na v 1.5) at the plasma membrane, Na v 1.5 was evaluated by immunofluorescence. As expected, a fainter signal was observed at the plasma membrane in the predicted ischemic region starting 30 min of ischemia and the change became the most pronounced by 4 h. Metabolomic changes occur early during ischemia, can assist in identifying markers for post-mortem diagnostics and improve understanding of molecular mechanisms.
Evaluation of postmortem MDCT and MDCT-angiography for the investigation of sudden cardiac death related to atherosclerotic coronary artery disease
The goal of this study was to evaluate the diagnostic value of postmortem multi-computed tomography (MDCT) and MDCT-angiography for sudden cardiac deaths related to ischemic heart disease. Twenty three cases were selected based on clinical history and the results of native MDCT, multiphase post-mortem CT-angiography and conventional autopsy were compared. Radiological examination showed calcification of coronary arteries in 78% of the cases, most of which were not detailed at autopsy. MDCT-angiography allowed better visualization of the coronary arteries than MDCT and permitted the evaluation of stenoses and occlusions. Of the 14 cases of coronary thrombosis detected at conventional autopsy, 11 were visible as stop of perfusion with CT-angiography and three were found to be partly perfused. One case had an old thrombosis with collateral circulation. One case had a coronary artery postmortem clot found with MDCT-angiography. Coronary artery calcifications are more easily detected and documented with radiological examination than with conventional autopsy. MDCT is of limited diagnostic value for ischemic heart disease. MDCT-angiography, when correctly interpreted, is a reasonable tool to view the morphology of coronary arteries, rule out significant coronary artery stenoses, identify occlusions and direct sampling for histological examination.
Post-mortem changes of the vascular system—a thanatological study using multidetector computed tomography
Forensic pathologists have to deal with post-mortem changes of the human body. Those post-mortem phenomena are familiar and largely described in thanatology. However, knowledge about the influence of post-mortem phenomena on the vascular system is more limited, except for the apparition and development of cadaveric lividity. The introduction of multidetector computed tomography (MDCT) and magnetic resonance imaging (MRI) in the forensic field and the expansion of their usage in medico-legal routine, allow for exploring the inside of corpses differently and may play a part in the understanding of thanatological processes. This study aimed to describe post-mortem changes in the vascular system by investigating the presence of gas and collapsed vessels.We investigated post-mortem MDCT data of 118 human bodies. Cases with internal/external bleeding or corporal lesion allowing contamination with external air were excluded. Major vessels and heart cavities were systematically explored and a trained radiologist semi-quantitatively assessed the presence of gas.Collapsed veins were observed in 61.9% of cases (CI95% 52.5 to 70.6) and arteries in 33.1% (CI95% 24.7 to 42.3). Vessels most often affected were for arteries: common iliac (16.1%), abdominal aorta (15.3%), external iliac (13.6%), and for veins: infra-renal vena cava (45.8%), common iliac (22.0%), renal (16.9%), external iliac (16.1%), and supra-renal vena cava (13.6%). Cerebral arteries and veins, coronary arteries, and subclavian vein were unaffected. The presence of collapsed vessels was associated with a minor degree of cadaveric alteration. We observed that arteries and veins follow the same pattern of gas apparition for both the quantity and the location.In post-mortem radiology, collapsed vessels and intravascular gas are frequently visualized and as a result of all post-mortem changes, the assessment of the distribution of blood can be confusing. Therefore, knowledge of thanatological phenomena is crucial to prevent post-mortem radiological misapprehensions and possible false diagnoses.
Impact of increasing levels of adaptive statistical iterative reconstruction on image quality in oil-based postmortem CT angiography in coronary arteries
IntroductionPostmortem multi-detector computed tomography (PMCT) has become an important part in forensic imaging. Modern reconstruction techniques such as iterative reconstruction (IR) are frequently used in postmortem CT angiography (PMCTA). The image quality of PMCTA depends on the strength of IR. For this purpose, we aimed to investigate the impact of different advanced IR levels on the objective and subjective PMCTA image quality.Material and methodsWe retrospectively analyzed the coronary arteries of 27 human cadavers undergoing whole-body postmortem CT angiography between July 2017 and March 2018 in a single center. Iterative reconstructions of the coronary arteries were processed in five different level settings (0%; 30%; 50%; 70%; 100%) by using an adaptive statistical IR method. We evaluated the objective (contrast-to-noise ratio (CNR)) and subjective image quality in several anatomical locations.ResultsOur results demonstrate that the increasing levels of an IR technique have relevant impact on the image quality in PMCTA scans in forensic postmortem examinations. Higher levels of IR have led to a significant reduction of image noise and therefore to a significant improvement of objective image quality (+ 70%). However, subjective image quality is inferior at higher levels of IR due to plasticized image appearance.ConclusionObjective image quality in PMCTA progressively improves with increasing level of IR with the best CNR at the highest IR level. However, subjective image quality is best at low to medium levels of IR. To obtain a “classic” image appearance with optimal image quality, PMCTAs should be reconstructed at medium levels of IR.