Search

Low-level clouds found over the eastern subtropical oceans have a substantial cooling effect on Earth's climate since they strongly reflect solar radiation back to space, and their simulation in climate models contributes to large uncertainty in global warming projections. This thesis aims to increase understanding of these marine boundary layer clouds through observational analysis, theoretical considerations, and an evaluation of their simulation in climate models. Examination of statistical relationships between cloud properties and large-scale meteorological variables is a key method employed throughout the thesis. The meteorological environment of marine boundary layer clouds shapes their properties by affecting the boundary layer's depth and structure. It is found that enhanced subsidence, typically thought to promote boundary layer cloudiness, actually reduces cloudiness when the confounding effect of the strength of the temperature inversion capping the boundary layer is taken into account. A conceptual model is able to explain this result. Next, fundamental deficiencies in the simulation of subtropical clouds in two generations of climate models are identified. Remarkably, the newer generation of climate models is in some ways inferior to the older generation in terms of capturing key low-level cloud processes. Subtropical mid- and high-level clouds are also found to contribute more to variability in the radiation budget at the top of the atmosphere than previously thought. In the last portion of the thesis, large inter- model spread in subtropical cloud feedbacks is shown to arise primarily from differences in the simulation of the interannual relationship between shortwave cloud radiative effect and sea surface temperature. An observational constraint on this feedback suggests that subtropical marine boundary layer clouds will act as a positive feedback to global warming

Purpose: To develop and validate the Italian version of the Keratoconus Outcomes Research Questionnaire (KORQ). Methods: Cross-sectional validation study. Keratoconus patients with routine appointments at the outpatient clinic were consecutively enrolled in conjunction with a sample of non-keratoconus controls for comparison. The Italian translation from the original English version of the KORQ was administered to the patients together with the Italian version of the 25-item version of the National Eye Institute Visual Function Questionnaire (NEI VFQ-25). The reliability and validity of the Italian KORQ were assessed using standardized internationally accepted methods for cultural adaptation and validation of health-related quality of life measures. Results: One hundred patients were deemed eligible and completed the questionnaires. The Cronbach’s alpha coefficient for internal consistency ranged from 0.71 to 0.956 across the subscales. Spearman correlation coefficient and intraclass correlation coefficient of 0.98 showed excellent test-retest reliability. The control group had better scores on every subscale. Statistically significant correlations were found between the KORQ and analogous domain of the NEI VFQ-25 and with disease severity indicators, such as visual acuity, maximum keratometry, and steepest keratometry, thus demonstrating good construct and concurrent validity. Conclusion: The Italian version of the KORQ exhibited excellent internal consistency, test-retest reliability, validity, discriminatory power, and psychometric properties comparable with those of the original English version, and thus may be adopted as a powerful vision-targeted quality of life assessment tool for Italian keratoconus patients.

Background Magnetic resonance imaging (MRI) of patients with conventional implantable cardioverter-defibrillators (ICD) is contraindicated. Objectives This multicenter, randomized trial evaluated safety and efficacy of a novel ICD system specially designed for full-body MRI without restrictions on heart rate or pacing dependency. The primary safety objective was >90% freedom from MRI-related events composite endpoint within 30 days post-MRI. The primary efficacy endpoints were ventricular pacing capture threshold and ventricular sensing amplitude. Methods Subjects received either a single- or dual-chamber ICD. In a 2:1 randomization, subjects either underwent MRI at 1.5-T of the chest, cervical, and head regions to maximize radiofrequency exposure up to 2 W/kg specific absorption rate and gradient field exposure to 200 T/m/s per axis (MRI group, n = 175), or they underwent a 1-h waiting period without MRI (control group, n = 88). A subset of MRI patients underwent ventricular fibrillation induction testing post-MRI to characterize defibrillation function. Results In 42 centers, 275 patients were enrolled (76% male, age 60.4 ± 13.8 years). The safety endpoint was met with 100% freedom from the composite endpoint (p Conclusions This is the first randomized clinical study of an ICD system designed for full-body MRI at 1.5-T. These data support that the system is safe and the MRI scan does not adversely affect electrical performance or efficacy. (Confirmatory Clinical Trial of the Evera MRI System for Conditionally-Safe MRI Access; NCT02117414 )

BackgroundAlthough there are several hazards for patients with implanted pacemakers and defibrillators in the magnetic resonance imaging (MRI) environment, evaluation of lead electrode heating is the most complex because of the many influencing variables: patient size, anatomy, body composition, patient position in the bore, scan sequence (radiofrequency power level), lead routing, and lead design. Although clinical studies are an important step in demonstrating efficacy, demonstrating safety through clinical trials alone is not practical because of this complexity.ObjectiveThe purpose of this study was to develop a comprehensive modeling framework to predict the probability of pacing capture threshold (PCT) change due to lead electrode heating in the MRI environment and thus provide a robust safety evaluation.MethodsThe lead heating risk was assessed via PCT change because this parameter is the most clinically relevant measure of lead heating. The probability for PCT change was obtained by combining the prediction for power at the electrode–tissue interface obtained via simulations with a prediction for PCT change as a function of radiofrequency power obtained via an in vivo canine study.ResultsThe human modeling framework predicted that the probability of a 0.5-V PCT change due to an MRI scan for the Medtronic CapSureFix MRI SureScan model 5086 MRI leads is

Background The Advisa MRI system is designed to safely undergo magnetic resonance imaging (MRI). Its influence on image quality is not well known. Objective To evaluate cardiac magnetic resonance (CMR) image quality and to characterize myocardial contraction patterns by using the Advisa MRI system. Methods In this international trial with 35 participating centers, an Advisa MRI system was implanted in 263 patients. Of those, 177 were randomized to the MRI group and 150 underwent MRI scans at the 9–12-week visit. Left ventricular (LV) and right ventricular (RV) cine long-axis steady-state free precession MR images were graded for quality. Signal loss along the implantable pulse generator and leads was measured. The tagging CMR data quality was assessed as the percentage of trackable tagging points on complementary spatial modulation of magnetization acquisitions (n=16) and segmental circumferential fiber shortening was quantified. Results Of all cine long-axis steady-state free precession acquisitions, 95% of LV and 98% of RV acquisitions were of diagnostic quality, with 84% and 93%, respectively, being of good or excellent quality. Tagging points were trackable from systole into early diastole (360–648 ms after the R-wave) in all segments. During RV pacing, tagging demonstrated a dyssynchronous contraction pattern, which was not observed in nonpaced (n = 4) and right atrial-paced (n = 8) patients. Conclusions In the Advisa MRI study, high-quality CMR images for the assessment of cardiac anatomy and function were obtained in most patients with an implantable pacing system. In addition, this study demonstrated the feasibility of acquiring tagging data to study the LV function during pacing.

Magnetic resonance imaging (MRI) of patients with conventional implantable cardioverter-defibrillators (ICD) is contraindicated.This multicenter, randomized trial evaluated safety and efficacy of a novel ICD system specially designed for full-body MRI without restrictions on heart rate or pacing dependency. The primary safety objective was90% freedom from MRI-related events composite endpoint within 30 days post-MRI. The primary efficacy endpoints were ventricular pacing capture threshold and ventricular sensing amplitude.Subjects received either a single- or dual-chamber ICD. In a 2:1 randomization, subjects either underwent MRI at 1.5-T of the chest, cervical, and head regions to maximize radiofrequency exposure up to 2 W/kg specific absorption rate and gradient field exposure to 200 T/m/s per axis (MRI group, n = 175), or they underwent a 1-h waiting period without MRI (control group, n = 88). A subset of MRI patients underwent ventricular fibrillation induction testing post-MRI to characterize defibrillation function.In 42 centers, 275 patients were enrolled (76% male, age 60.4 ± 13.8 years). The safety endpoint was met with 100% freedom from the composite endpoint (p 0.0001). Both efficacy endpoints were met with minimal differences in the proportion of MRI and control patients who demonstrated a ≤0.5 V increase in ventricular pacing capture threshold (100% MRI vs. 98.8% control, noninferiority p 0.0001) or a ≤50% decrease in R-wave amplitude (99.3% MRI vs. 98.8% control, noninferiority p = 0.0001). A total of 34 ventricular tachyarrhythmia/ventricular fibrillation episodes (20 induced; 14 spontaneous) occurred in 24 subjects post-MRI, with no observed effect on sensing, detection, or treatment.This is the first randomized clinical study of an ICD system designed for full-body MRI at 1.5-T. These data support that the system is safe and the MRI scan does not adversely affect electrical performance or efficacy. (Confirmatory Clinical Trial of the Evera MRI System for Conditionally-Safe MRI Access; NCT02117414).

International audience; The NAD(P)H cytochrome b5 oxidoreductase, Ncb5or (previously named b5+b5R), is widely expressed in human tissues and broadly distributed among the animal kingdom. NCB5OR is the first example of an animal flavohemoprotein containing cytochrome b5 and chrome b5 reductase cytodomains. We initially reported human NCB5OR to be a 487-residue soluble protein that reduces cytochrome c, methemoglobin, ferricyanide, and molecular oxygen in vitro. Bioinformatic analysis of genomic sequences suggested the presence of an upstream start codon. We confirm that endogenous NCB5OR indeed has additional NH2-terminal residues. By performing fractionation of subcellular organelles and confocal microscopy, we show that NCB5OR colocalizes with calreticulin, a marker for endoplasmic reticulum. Recombinant NCB5OR is soluble and has stoichiometric amounts of heme and flavin adenine dinucleotide. Resonance Raman spectroscopy of NCB5OR presents typical signatures of a six-coordinate low-spin heme similar to those found in other cytochrome b5 proteins. Kinetic measurements showed that full-length and truncated NCB5OR reduce cytochrome c actively in vitro. However, both full-length and truncated NCB5OR produce superoxide from oxygen with slow turnover rates: kcat = approximately 0.05 and approximately 1 s(-1), respectively. The redox potential at the heme center of NCB5OR is -108 mV, as determined by potentiometric titrations. Taken together, these data suggest that endogenous NCB5OR is a soluble NAD(P)H reductase preferentially reducing substrate(s) rather than transferring electrons to molecular oxygen and therefore not an NAD(P)H oxidase for superoxide production. The subcellular localization and redox properties of NCB5OR provide important insights into the biology of NCB5OR and the phenotype of the Ncb5or-null mouse.

Adaptation to hypoxia is a topic of considerable clinical relevance, as it influences the pathophysiology of anaemia, polycythaemia, tissue ischaemia and cancer. A growing number of physiologically relevant genes are regulated in response to changes in intracellular oxygen tension. These include genes encoding erythropoietin, vascular endothelial growth factor and tyrosine hydroxylase. Studies on the regulation of the erythropoietin gene have provided insights into the common mechanism of oxygen sensing and signal transduction, leading to activation of the hypoxia-inducible transcription factor 1 (HIF-1). Activation of HIF-1 by hypoxia depends on rescue of its alpha-subunit from oxygen-dependent degradation in the proteasome, allowing it to form a heterodimer with HIF-1 beta. This then translocates to the nucleus. There, HIF-1 assembles with a highly conserved orphan nuclear receptor, HNF-4, and a critical transcriptional adaptor, p300. This complex binds to a 3' enhancer on the erythropoietin gene, enabling transcription of erythropoietin. HIF-1 also activates other genes, the cis-acting elements of which contain cognate hypoxia response elements. There is growing evidence that the oxygen sensor is a flavohaem protein and that the signal transduction pathway involves changes in the level of intracellular reactive oxygen intermediates. We have recently cloned a novel fusion protein called cytochrome b5/b5 reductase, which is a cyanide-insensitive NADPH oxidase and, therefore, a candidate to be the oxygen sensor. This flavohaem protein is widely expressed in cell lines and tissues, with localization in the perinuclear space. In the presence of oxygen and iron, it may induce oxidative modifications that target HIF-1 alpha for ubiquitination and degradation.

Background Automatic slice alignment allows images of the six standard cardiac planes as defined in the SCMR Image Acquisition Protocols to be obtained by simple and quick operation. Our previously reported method can detect these planes using ECG-gated breath-hold axial multislice images [1]. Achieving higher accuracy and greater robustness for variation in clinical images will lead to improved usability and reliability, resulting in easier cardiac MR examinations. To achieve these goals, we have substantially refined our previously reported automatic slice-alignment method. A combination of knowledge-based recognition and image processing techniques is applied to multiple feature point search to reduce errors in automatic detection. Volunteer and clinical data were used to evaluate of the degree of improvement.

Background We have been developing an automatic planning assist system for coach adjustment, local shimming scan plan, axial multi slice scan plan for slice-alignment, and whole-heart MR imaging plan (motion probes and an axial slab of main scan) [1,2]. However, the previous reposts of the system evaluated only Japanese patient’s and healthy volunteer’s datasets. The purpose of this study is to evaluate the accuracy for multi-ethnic datasets based on the inter-observer error in manual annotation.

The Advisa MRI™ SureScan® Pacing System is an MR conditional pacing system designed to safely undergo magnetic resonance image (MRI) scans. Its influence on image quality, particularly of cardiac MR (CMR) acquisitions, is not well known. The Advisa MRI Study evaluated the CMR image quality and