Illustrative Flow Visualization of 4D PC-MRI Blood Flow and CFD Data

Das zentrale Thema dieser Dissertation ist die Anwendung illustrativer Methoden auf zwei bisher ungelöste Probleme der Strömungsvisualisierung. Das Ziel der Strömungsvisualisierung ist die Bereitstellung von Software, die Experten beim Auswerten ihrer Strömungsdaten und damit beim Erkenntnisgewinn unterstützt. Bei der illustrativen Visualisierung handelt es sich um einen Zweig der Visualisierung, der sich an der künstlerischen Arbeit von Illustratoren orientiert. Letztere sind darauf spezialisiert komplizierte Zusammenhänge verständlich und ansprechend zu vermitteln. Die angewendeten Techniken werden in der illustrativen Visualisierung auf reale Daten übertragen, um die Effektivität der Darstellung zu erhöhen. Das erste Problem, das im Rahmen dieser Dissertation bearbeitet wurde, ist die eingeschränkte Verständlichkeit von komplexen Stromflächen. Selbstverdeckungen oder Aufrollungen behindern die Form- und Strömungswahrnehmung und machen diese Flächen gerade in interessanten Strömungssituationen wenig nützlich. Auf Basis von handgezeichneten Strömungsdarstellungen haben wir ein Flächenrendering entwickelt, das Silhouetten, nicht-photorealistische Beleuchtung und illustrative Stromlinien verwendet. Interaktive Flächenschnitte erlauben die Exploration der Flächen und der Strömungen, die sie repräsentieren. Angewendet auf verschiedene Stromflächen ließ sich zeigen, dass die Methoden die Verständlichkeit erhöhen, v.a. in Bereichen komplexer Strömung mit Aufwicklungen oder Singularitäten. Das zweite Problem ist die Strömungsanalyse des Blutes aus 4D PC-MRI-Daten. An diese relativ neue Datenmodalität werden hohe Erwartungen für die Erforschung und Behandlung kardiovaskulärer Krankheiten geknüpft, da sie erstmals ein dreidimensionales, zeitlich aufgelöstes Abbild der Hämodynamik liefert. Bisher werden 4D PC-MRI-Daten meist mit Werkzeugen der klassischen Strömungsvisualisierung verarbeitet. Diese werden den besonderen Ansprüchen der medizinischen Anwender jedoch nicht gerecht, die in kurzer Zeit eine übersichtliche Darstellung der relevanten Strömungsaspekte erhalten möchten. Wir haben ein Werkzeug zur visuellen Analyse der Blutströmung entwickelt, welches eine einfache Detektion von markanten Strömungsmustern erlaubt, wie z.B. Jets, Wirbel oder Bereiche mit hoher Blutverweildauer. Die Grundidee ist hierbei aus vorberechneten Integrallinien mit Hilfe speziell definierter Linienprädikate die relevanten, d.h. am gefragten Strömungsmuster, beteiligten Linien ausgewählt werden. Um eine intuitive Darstellung der Resultate zu erreichen, haben wir uns von Blutflußillustrationen inspirieren lassen und präsentieren eine abstrakte Linienbündel- und Wirbeldarstellung. Die Linienprädikatmethode sowie die abstrakte Darstellung der Strömungsmuster wurden an 4D PC-MRI-Daten von gesunden und pathologischen Aorten- und Herzdaten erfolgreich getestet. Auch die Evaluierung durch Experten zeigt die Nützlichkeit der Methode und ihr Potential für den Einsatz in der Forschung und der Klinik.This thesis’ central theme is the use of illustrative methods to solve flow visualization problems. The goal of flow visualization is to provide users with software tools supporting them analyzing and extracting knowledge from their fluid dynamics data. This fluid dynamics data is produced in large amounts by simulations or measurements to answer diverse questions in application fields like engineering or medicine. This thesis deals with two unsolved problems in flow visualization and tackles them with methods of illustrative visualization. The latter is a subbranch of visualization whose methods are inspired by the art work of professional illustrators. They are specialized in the comprehensible and esthetic representation of complex knowledge. With illustrative visualization, their techniques are applied to real data to enhance their representation. The first problem dealt with in this thesis is the limited shape and flow perception of complex stream surfaces. Self-occlusion and wrap-ups hinder their effective use in the most interesting flow situations. On the basis of hand-drawn flow illustrations, a surface rendering method was designed that uses silhouettes, non-photorealistic shading, and illustrative surface stream lines. Additionally, geometrical and flow-based surface cuts allow the user an interactive exploration of the surface and the flow it represents. By applying this illustrative technique to various stream surfaces and collecting expert feedback, we could show that the comprehensibility of the stream surfaces was enhanced – especially in complex areas with surface wrap-ups and singularities. The second problem tackled in this thesis is the analysis of blood flow from 4D PC-MRI data. From this rather young data modality, medical experts expect many advances in the research of cardiovascular diseases because it delivers a three-dimensional and time-resolved image of the hemodynamics. However, 4D PC-MRI data are mainly processed with standard flow visualizaton tools, which do not fulfill the requirements of medical users. They need a quick and easy-to-understand display of the relevant blood flow aspects. We developed a tool for the visual analysis of blood flow that allows a fast detection of distinctive flow patterns, such as high-velocity jets, vortices, or areas with high residence times. The basic idea is to precalculate integral lines and use specifically designed line predicates to select and display only lines involved in the pattern of interest. Traditional blood flow illustrations inspired us to an abstract and comprehensible depiction of the resulting line bundles and vortices. The line predicate method and the illustrative flow pattern representation were successfully tested with 4D PC-MRI data of healthy and pathological aortae and hearts. Also, the feedback of several medical experts confirmed the usefulness of our methods and their capabilities for a future application in the clinical research and routine

Computed tomographic assessment of lung weights in trauma patients with early posttraumatic lung dysfunction

Introduction: Quantitative computed tomography (qCT)-based assessment of total lung weight (M(lung)) has the potential to differentiate atelectasis from consolidation and could thus provide valuable information for managing trauma patients fulfilling commonly used criteria for acute lung injury (ALI). We hypothesized that qCT would identify atelectasis as a frequent mimic of early posttraumatic ALI. Methods: In this prospective observational study, M(lung) was calculated by qCT in 78 mechanically ventilated trauma patients fulfilling the ALI criteria at admission. A reference interval for M(lung) was derived from 74 trauma patients with morphologically and functionally normal lungs (reference). Results are given as medians with interquartile ranges. Results: The ratio of arterial partial pressure of oxygen to the fraction of inspired oxygen was 560 (506 to 616) mmHg in reference patients and 169 (95 to 240) mmHg in ALI patients. The median reference M(lung) value was 885 (771 to 973) g, and the reference interval for M(lung) was 584 to 1164 g, which matched that of previous reports. Despite the significantly greater median M(lung) value (1088 (862 to 1,342) g) in the ALI group, 46 (59%) ALI patients had M(lung) values within the reference interval and thus most likely had atelectasis. In only 17 patients (22%), Mlung was increased to the range previously reported for ALI patients and compatible with lung consolidation. Statistically significant differences between atelectasis and consolidation patients were found for age, Lung Injury Score, Glasgow Coma Scale score, total lung volume, mass of the nonaerated lung compartment, ventilator-free days and intensive care unit-free days. Conclusions: Atelectasis is a frequent cause of early posttraumatic lung dysfunction. Differentiation between atelectasis and consolidation from other causes of lung damage by using qCT may help to identify patients who could benefit from management strategies such as damage control surgery and lung-protective mechanical ventilation that focus on the prevention of pulmonary complications.Leipzig University Hospita

Charging of free-falling test masses in orbit due to cosmic rays: results from LISA Pathfinder

A comprehensive summary of the measurements made to characterize test-mass charging due to the space environment during the LISA Pathfinder mission is presented. Measurements of the residual charge of the test mass after release by the grabbing and positioning mechanism show that the initial charge of the test masses was negative after all releases, leaving the test mass with a potential in the range from - 12 to - 512 . Variations in the neutral test-mass charging rate between 21.7 and 30.7 ¿ ¿ e ¿ s - 1 were observed over the course of the 17-month science operations produced by cosmic ray flux changes including a Forbush decrease associated with a small solar energetic particle event. A dependence of the cosmic ray charging rate on the test-mass potential between - 30.2 and - 40.3 ¿ ¿ e ¿ s - 1 ¿ V - 1 was observed resulting in an equilibrium test-mass potential between 670 and 960 mV, and this is attributed to a contribution to charging from low-energy electrons emitted from the gold surfaces of the gravitational reference sensor. Data from the onboard particle detector show a reliable correlation with the charging rate and with other environmental monitors of the cosmic ray flux. This correlation is exploited to extrapolate test-mass charging rates to a 20-year period giving useful insight into the expected range of charging rate that may be observed in the LISA mission.Peer ReviewedPostprint (published version

Transient acceleration events in LISA Pathfinder data: properties and possible physical origin

We present an in depth analysis of the transient events, or glitches, detected at a rate of about one per day in the differential acceleration data of LISA Pathfinder. We show that these glitches fall in two rather distinct categories: fast transients in the interferometric motion readout on one side, and true force transient events on the other. The former are fast and rare in ordinary conditions. The second may last from seconds to hours and constitute the majority of the glitches. We present an analysis of the physical and statistical properties of both categories, including a cross-analysis with other time series like magnetic fields, temperature, and other dynamical variables. Based on these analyses we discuss the possible sources of the force glitches and identify the most likely, among which the outgassing environment surrounding the test-masses stands out. We discuss the impact of these findings on the LISA design and operation, and some risk mitigation measures, including experimental studies that may be conducted on the ground, aimed at clarifying some of the questions left open by our analysis.Peer ReviewedPostprint (author's final draft

Late-Onset Stargardt Disease Due to Mild, Deep-Intronic ABCA4 Alleles

PURPOSE. To investigate the role of two deep-intronic ABCA4 variants, that showed a mild splice defect in vitro and can occur on the same allele as the low penetrant c.5603A>T, in Stargardt disease (STGD1). METHODS. Ophthalmic data were assessed of 18 STGD1 patients who harbored c.769-784C>T or c.4253+43G>A in combination with a severe ABCA4 variant. Subjects carrying c.[769784C>T; 5603A>T] were clinically compared with a STGD1 cohort previously published carrying c.5603A>T noncomplex. We calculated the penetrances of the intronic variants using ABCA4 allele frequency data of the general population and investigated the effect of c.769-784C>T on splicing in photoreceptor progenitor cells (PPCs). RESULTS. Mostly, late-onset, foveal-sparing STGD1 was observed among subjects harboring c.769-784C>T or c.4253+43G>A (median age of onset, 54.5 and 52.0 years, respectively). However, ages of onset, phenotypes in fundo, and visual acuity courses varied widely. No significant clinical differences were observed between the c.[769-784C>T; 5603A>T] cohort and the c.4253+43G>A or the c.5603A>T cohort. The penetrances of c.769-784C>T (20.5%-39.6%) and c.4253+43G>A (35.8%-43.1%) were reduced, when not considering the effect of yet unidentified or known factors in cis, such as c.5603A>T (identified in 7/7 probands with c.769-784C>T; 1/8 probands with c.4253+43G>A). Variant c.769-784C>T resulted in a pseudo-exon insertion in 15% of the total mRNA (i.e., similar to 30% of the c.769-784C>T allele alone). CONCLUSIONS. Two mild intronic ABCA4 variants could further explain missing heritability in late-onset STGD1, distinguishing it from AMD. The observed clinical variability and calculated reduced penetrance urge research into modifiers within and outside of the ABCA4 gene

STC1 interference on calcitonin family of receptors signaling during osteoblastogenesis via adenylate cyclase inhibition

Stanniocalcin 1 (STC1) and calcitonin gene-related peptide (CGRP) are involved in bone formation/remodeling. Here we investigate the effects of STC1 on functional heterodimer complex CALCRL/RAMP1, expression and activity during osteoblastogenesis. STC1 did not modify CALCRL and ramp 1 gene expression during osteoblastogenesis when compared to controls. However, plasma membrane spatial distribution of CALCRL/RAMP1 was modified in 7-day pre-osteoblasts exposed to either CGRP or STC1, and both peptides induced CALCRL and RAMP1 assembly. CGRP, but not STC1 stimulated cAMP accumulation in 7-day osteoblasts and in CALCRL/RAMP1 transfected HEK293 cells. Furthermore, STC1 inhibited forskolin stimulated cAMP accumulation of HEK293 cells, but not in CALCRL/RAMP1 transfected HEK293 cells. However, STC1 inhibited cAMP accumulation in calcitonin receptor (CTR) HEK293 transfected cells stimulated by calcitonin. In conclusion, STC1 signals through inhibitory G-protein modulates CGRP receptor spatial localization during osteoblastogenesis and may function as a regulatory factor interacting with calcitonin peptide members during bone formation. (C) 2015 Elsevier Ireland Ltd. All rights reserved.CAPES/CNPq (VS PNPD fellowship program); FAPERGS/CNPq [008/2009 (FCRG)]; Portuguese Foundation for Science and Technology (FCT) [PTDC/MAR/121279/2010, PEst-C/MAR/LA0015/2013, SFRH/BPD/89811/2012]; CNPq (SRT PhD fellowship program); CNPq (LAMM PhD fellowship program); CNPq (FCRG research productivity fellowship program); INCT Exitotoxicity and Neuroprotection (DOGS

Consenso nacional de ressuscitação cardiorespiratória

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Global variation in diabetes diagnosis and prevalence based on fasting glucose and hemoglobin A1c

Fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c) are both used to diagnose diabetes, but these measurements can identify different people as having diabetes. We used data from 117 population-based studies and quantified, in different world regions, the prevalence of diagnosed diabetes, and whether those who were previously undiagnosed and detected as having diabetes in survey screening, had elevated FPG, HbA1c or both. We developed prediction equations for estimating the probability that a person without previously diagnosed diabetes, and at a specific level of FPG, had elevated HbA1c, and vice versa. The age-standardized proportion of diabetes that was previously undiagnosed and detected in survey screening ranged from 30% in the high-income western region to 66% in south Asia. Among those with screen-detected diabetes with either test, the age-standardized proportion who had elevated levels of both FPG and HbA1c was 29-39% across regions; the remainder had discordant elevation of FPG or HbA1c. In most low- and middle-income regions, isolated elevated HbA1c was more common than isolated elevated FPG. In these regions, the use of FPG alone may delay diabetes diagnosis and underestimate diabetes prevalence. Our prediction equations help allocate finite resources for measuring HbA1c to reduce the global shortfall in diabetes diagnosis and surveillance

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049