End organ damage in the metabolic syndrome and diabetes mellitus : biochemical and magnetic resonance imaging studies

The focus of this thesis was to evaluate biomarkers of cardiovascular end organ damage in the metabolic syndrome and diabetes mellitus. We performed cross-sectional studies with biochemical and magnetic resonance imaging (MRI) techniques. We have demonstrated that insulin resistance is a strong risk predictor for CVD and we provided a novel link between inflammation and angiopoietin-like protein 4 (ANGPTL4) expression by showing that ANGPTL4 levels in humans are related to systemic inflammation and inflammatory stimuli increased ANGPTL4 expression using human macrophages in vitro. The imaging studies described in this thesis extend the knowledge of end organ damage and explored the relation with aortic stiffness. The impact of type 1 diabetes mellitus (T1DM) on regional grey matter was investigated and showed atrophy of all subcortical grey matter structures but the amygdala. By showing an association of aortic stiffness with subtle microstructural deficits in T1DM and kidney function in patients with hypertension the close link between aortic stiffness and the microcirculation is demonstrated. Furthermore regional and individual differences in response to an oral glucose load in MR assessed aortic stiffness were observed, which may open new future research paths possibly linking inter-individual variation in regional vascular response and CVD.UBL - phd migration 201

The cinepheur: post-cinematic passage, post-perceptual passage

This thesis develops a hermeneutic commensurate with the aesthetic and ontological challenges of what Steven Shaviro describes as a post-cinematic media ecology, and Shane Denson describes as an emergent post-perceptual media ecology. I consider canonicity and cinephilia as frustrated efforts to contain and comprehend this new cinematic media object, offering a third unit of interpretation in their place, which I describe as the cinetopic anecdote. I associate the cinetopic anecdote with a particular way of moving between cinema and cinematic infrastructure, which I label cinetopic passage, and with a subject position that I label the cinepheur. Drawing on Walter Benjamin’s theory of the flâneur, I argue that the cinetopic anecdote precludes the extraction of a privileged cinematic moment in the manner characteristic of Christian Keathley’s cinephilic anecdote, but instead compels the cinepheur to instantiate, embody or physically recreate the infrastructural conditions that produced it, dovetailing production and consumption into what Axel Bruns has described as the emergent category of produsage; “unfinished artifacts, continuing process.” Having elaborated the cinetopic anecdote, I apply it to postmodern, post-cinematic and post-perceptual media ecologies, in order to evoke the peculiar forms of attachment and obsession bound up with the Criterion and Netflix platforms. In the process, I draw on Franco Moretti’s conception of distant reading to frame the cinetopic anecdote as a unit of distant viewing, offering distant viewings of Angela Christlieb and Stephen Kijak’s Cinemania, Sidney Lumet’s Garbo Talks and Pier Paolo Pasolini’s Salò, or The 120 Days of Sodom. Just as distant reading takes “the great unread” as its object of enquiry, so the cinetopic anecdote speaks to a media ecology preoccupied by the “great unviewed,” in which cinematic scarcity increasingly ramifies as an elegaic object

A Tale of Two Spills: Novel Science and Policy Implications of an Emerging New Oil Spill Model

The 2010 Deepwater Horizon oil release posed the challenges of two types of spill: a familiar spill characterized by buoyant oil, fouling and killing organisms at the sea surface and eventually grounding on and damaging sensitive shoreline habitats, and a novel deepwater spill involving many unknowns. The subsurface retention of oil as finely dispersed droplets and emulsions, wellhead injection of dispersants, and deepwater retention of plumes of natural gas undergoing rapid microbial degradation were unprecedented and demanded the development of a new model for deepwater well blowouts that includes subsurface consequences. Existing governmental programs and policies had not anticipated this new theater of impacts, which thereby challenged decisionmaking on the spill response, on the assessment of natural resource damages, on the preparation for litigation to achieve compensation for public trust losses, and on restoration. Modification of laws and policies designed to protect and restore ocean resources is needed in order to accommodate oil drilling in the deep sea and other frontiers.Keywords: Ecosystem, Petroleum, Deep water horizon, Gulf of Mexico, BlowoutKeywords: Ecosystem, Petroleum, Deep water horizon, Gulf of Mexico, Blowou

Insulin Resistance and Risk of Incident Cardiovascular Events in Adults without Diabetes: Meta-Analysis

BACKGROUND Glucose, insulin and Homeostasis Model Assessment Insulin Resistance (HOMA-IR) are markers of insulin resistance. The objective of this study is to compare fasting glucose, fasting insulin concentrations and HOMA-IR in strength of association with incident cardiovascular disease. METHODS We searched the PubMed, MEDLINE, EMBASE, Web of Science, ScienceDirect and Cochrane Library databases from inception to March, 2011, and screened reference lists. Cohort studies or nested case-control studies that investigated the association between fasting glucose, fasting insulin or HOMA-IR and incident cardiovascular disease, were eligible. Two investigators independently performed the article selection, data extraction and risk of bias assessment. Cardiovascular endpoints were coronary heart disease (CHD), stroke or combined cardiovascular disease. We used fixed and random-effect meta-analyses to calculate the pooled relative risk for CHD, stroke and combined cardiovascular disease, comparing high to low concentrations of glucose, insulin or HOMA-IR. Study heterogeneity was calculated with the I(2) statistic. To enable a comparison between cardiovascular disease risks for glucose, insulin and HOMA-IR, we calculated pooled relative risks per increase of one standard deviation. RESULTS We included 65 studies (involving 516,325 participants) in this meta-analysis. In a random-effect meta-analysis the pooled relative risk of CHD (95% CI; I(2)) comparing high to low concentrations was 1.52 (1.31, 1.76; 62.4%) for glucose, 1.12 (0.92, 1.37; 41.0%) for insulin and 1.64 (1.35, 2.00; 0%) for HOMA-IR. The pooled relative risk of CHD per one standard deviation increase was 1.21 (1.13, 1.30; 64.9%) for glucose, 1.04 (0.96, 1.12; 43.0%) for insulin and 1.46 (1.26, 1.69; 0.0%) for HOMA-IR. CONCLUSIONS The relative risk of cardiovascular disease was higher for an increase of one standard deviation in HOMA-IR compared to an increase of one standard deviation in fasting glucose or fasting insulin concentration. It may be useful to add HOMA-IR to a cardiovascular risk prediction model.Development and application of statistical models for medical scientific researc

Inflammation increases plasma angiopoietin-like protein 4 in patients with the metabolic syndrome and type 2 diabetes

Contains fulltext : 138901.pdf (publisher's version ) (Open Access)BACKGROUND: Angiopoietin-like protein 4 (ANGPTL4) inhibits lipoprotein lipase and associates with dyslipidemia. The expression of ANGPTL4 is regulated by free fatty acids (FFA) that activate lipid-sensing peroxisome proliferator-activated receptors (PPARs), but FFA can also activate pattern recognition receptors including Toll-like receptor 4 (TLR4) in macrophages. OBJECTIVE: To assess whether systemic low-grade inflammation is a determinant for plasma ANGPTL4 levels in patients with the metabolic syndrome (MetS) and type 2 diabetes mellitus (T2DM). DESIGN: We studied 335 male participants: healthy controls (Controls), patients with the MetS without inflammation (MetS-I) and with low-grade inflammation (MetS+I), and patients with T2DM. All patients without diabetes included in the present study were initially matched for waist circumference. In plasma, ANGPTL4, C reactive protein (CRP) and metabolic parameters were determined. Underlying mechanisms were examined using human macrophages in vitro. RESULTS: As compared with Controls, plasma ANGPTL4 levels were increased in patients with MetS-I, MetS+I, and T2DM. Furthermore, ANGPTL4 was increased in T2DM compared with MetS-I. In fact, plasma CRP correlated positively with plasma ANGPTL4. In vitro studies showed that TLR 3/4 activation largely increased the expression and release of ANGPTL4 by macrophages. CONCLUSIONS: Plasma ANGPTL4 levels in humans are predicted by CRP, a marker of inflammation, and ANGPTL4 expression by macrophages is increased by inflammatory stimuli

ATHEROSCLEROTIC VARIATION IN A GROUP OF OBESE MALE PATIENTS WITH IDENTICAL FRAMINGHAM RISK SCORES

Thrombosis and Hemostasi

PREVALENCE AND SIMULTANEOUS OCCURENCE OF MRI ASSESSED CARDIAC AND CEREBRAL TARGET ORGAN DAMAGE AND MICROALBUMINURIA

Neuro Imaging Researc

Short-term effects of a standardized glucose load on region-specific aortic pulse wave velocity assessed by MRI

Item does not contain fulltextPURPOSE: To assess the short-term effects of a standardized oral glucose load on regional aortic pulse wave velocity (PWV) using two-directional in-plane velocity encoded MRI. MATERIALS AND METHODS: A randomized, controlled intervention was performed in 16 male subjects (mean +/- standard deviation: age: 59+/-7 years, body mass index: 28+/-3 kg/m2) with impaired fasting glucose. The intervention consisted of an oral glucose load (75 grams of carbohydrates in 300 mL water) at 1 study day and water (300 mL) at the other study day. PWV was measured using multislice two-directional in-plane velocity-encoded MRI. RESULTS: PWV in the proximal aorta at 1 h post-glucose load decreased compared with PWV 1-h post-water (delta PWV: -1.0+/-2.6 m/s versus 0.6+/-2.0 m/s, P=0.02). Eight responding subjects showed a significant decrease in PWV of the proximal aorta after the glucose load and had a decreased waist circumference (P=0.037) compared with nonresponders, being one of the major criteria of the metabolic syndrome. There was no significant change in PWV of the distal aorta at 1 h post-load comparing both intervention groups. CONCLUSION: A standardized oral glucose load induces a decrease of the proximal, but not of the distal, aortic PWV. Regional response of aortic PWV may be associated with features of the metabolic syndrome

MARKED VARIATION OF MRI ASSESSED PULSE WAVE VELOCITY AND LEFT VENTRICULAR MASS IN HYPERTENSIVE PATIENTS WITH IDENTICAL CARDIOVASCULAR RISK

Cardiovascular Aspects of Radiolog