Left ventricular hypertrophy contributes to Myocardial Ischemia in Non-obstructive Coronary Artery Disease (the MicroCAD study)

Background: The underlying mechanisms causing myocardial ischemia in non-obstructive coronary artery disease (CAD) are still unclear. We explored whether left ventricular hypertrophy (LVH) was associated with myocardial ischemia in patients with stable angina and non-obstructive CAD. Methods: 132 patients (mean age 63 ± 8 years, 56% women) with stable angina and non-obstructive CAD diagnosed as 46.7 g/m2.7 in women and >49.2 g/m2.7 in men. Patients were grouped according to presence or absence of myocardial ischemia by myocardial contrast stress echocardiography. The number of LV segments with ischemia at peak stress was taken as a measure of the extent of myocardial ischemia. Results: Myocardial ischemia was found in 52% of patients, with on average 5 ± 3 ischemic LV segments per patient. The group with myocardial ischemia had higher prevalence of LVH (23 vs. 10%, p = 0.035), while age, sex and prevalence of hypertension did not differ between groups (all p > 0.05). In multivariable regression analyses, LVH was associated with presence of myocardial ischemia (odds ratio 3.27, 95% confidence interval [1.11–9.60], p = 0.031), and larger extent of myocardial ischemia (β = 0.22, p = 0.012), independent of confounders including age, hypertension, obesity, hypercholesterolemia, calcium score and segment involvement score by CCTA. Conclusions: LVH was independently associated with both presence and extent of myocardial ischemia in patients with stable angina and non-obstructive CAD by CCTA. These results suggest LVH as an independent contributor to myocardial ischemia in non-obstructive CAD.publishedVersio

The Problem of Mission Creep: Argumentation Theory meets Military History

At the outset ‘mission creep’ is a military phenomenon, denoting uncontrolled and unintended mission development. Even the best-laid plans may become obsolete if they run against the facts on the ground, and mission creep may result. Mission creep also plagues arguments, as when arguments end up in unrelated topics, larger targets, or clusters of topics. Our paper explores possible mutual benefits of applying the resources of argumentation theory and military theory to one another

Teaching Business Ethics: The use of films and videota

Audio-visual material is extremely useful in the teaching of Business Ethics, yet no bibliography of the commercially available films and videotapes seems to be available. We have prepared a formal listing, complete with titles, descriptions, sources, prices and a brief evaluation, and have explained our selection and use of this material.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/42528/1/10551_2004_Article_BF00383427.pd

Impact of aortic stiffness on myocardial ischaemia in non-obstructive coronary artery disease

Objective: High aortic stiffness may reduce myocardial perfusion pressure and contribute to development of myocardial ischaemia. Whether high aortic stiffness is associated with myocardial ischaemia in patients with stable angina and non-obstructive coronary artery disease (CAD) is less explored. Methods: Aortic stiffness was assessed as carotid-femoral pulse wave velocity (PWV) by applanation tonometry in 125 patients (62±8 years, 58% women) with stable angina and non-obstructive CAD participating in the Myocardial Ischemia in Non-obstructive CAD project. PWV in the highest tertile (>8.7 m/s) was taken as higher aortic stiffness. Stress-induced myocardial ischaemia was detected as delayed myocardial contrast replenishment during stress echocardiography, and the number of left ventricular (LV) segments with delayed contrast replenishment as the extent of ischaemia. Results: Patients with higher aortic stiffness were older with higher LV mass index and lower prevalence of obesity (all p<0.05), while angina symptoms, sex, prevalence of hypertension, diabetes, smoking or LV ejection fraction did not differ between groups. Stress-induced myocardial ischaemia was more common (73% vs 42%, p=0.001) and the extent of ischaemia was larger (4±3 vs 2±3 LV segments, p=0.005) in patients with higher aortic stiffness. In multivariable logistic regression analysis, higher aortic stiffness was associated with stress-induced myocardial ischaemia independent of other known covariables (OR 4.74 (95% CI 1.51 to 14.93), p=0.008). Conclusions: In patients with stable angina and non-obstructive CAD, higher aortic stiffness was associated with stress-induced myocardial ischaemia. Consequently, assessment of aortic stiffness may add to the diagnostic evaluation in patients with non-obstructive CAD.publishedVersio

A multi-decadal record of oceanographic changes of the past ~165 years (1850-2015 AD) from Northwest of Iceland.

Extending oceanographic data beyond the instrumental period is highly needed to better characterize and understand multi-decadal to centennial natural ocean variability. Here, a stable isotope record at unprecedented temporal resolution (1 to 2 years) from a new marine core retrieved off western North Iceland is presented. We aim to better constrain the variability of subsurface, Atlantic-derived Subpolar Mode Water (SPMW), using near surface-dwelling planktic foraminifera and Arctic Intermediate Water (AIW) mass changes using benthic foraminifera over the last ~165 years. The reconstruction overlaps in time with instrumental observations and a direct comparison reveals that the δ18O record of Neogloboquadrina pachyderma is reliably representing temperature fluctuations in the SPMWs. Trends in the N. pachyderma δ13C record match the measured phosphate concentration in the upper 200 m on the North Icelandic Shelf well. Near surface-dwelling foraminifera trace anthropogenic CO2 in the Iceland Sea by ~ 1950 ± 8, however, a reduced amplitude shift in the Marine Suess effect is identified. We argue that this is caused by a contemporary ongoing increase in marine primary productivity in the upper ocean due to enhanced Greenland's freshwater discharge that has contributed to a nutrient-driven fertilization since the 1940s/50s (Perner et al., 2019). Multi-decadal variability is detected. We find that the 16-year periodicity evident in SPMW and AIWs based on the δ18O of N. pachyderma and M. barleeanum is a signal of SST anomalies propagated into the Nordic Seas via the Atlantic inflow branches around Iceland. Spectral analyses of the planktic foraminiferal δ13C signal indicate intermittent 30-year cycles that are likely reflecting the ocean response to atmospheric variability, presumably the East Atlantic Pattern. A long-term trend in benthic δ18O suggests that Atlantic-derived waters are expanding their core within the water column from the subsurface into deeper intermediate depths towards the present day. This is a result of increased transport by the North Icelandic Irminger Current to the North Iceland Shelf over the historical era

Principal component analysis for the comparison of metabolic profiles from human rectal cancer biopsies and colorectal xenografts using high-resolution magic angle spinning 1H magnetic resonance spectroscopy

<p>Abstract</p> <p>Background</p> <p>This study was conducted in order to elucidate metabolic differences between human rectal cancer biopsies and colorectal HT29, HCT116 and SW620 xenografts by using high-resolution magnetic angle spinning (MAS) magnetic resonance spectroscopy (MRS) and for determination of the most appropriate human rectal xenograft model for preclinical MR spectroscopy studies. A further aim was to investigate metabolic changes following irradiation of HT29 xenografts.</p> <p>Methods</p> <p>HR MAS MRS of tissue samples from xenografts and rectal biopsies were obtained with a Bruker Avance DRX600 spectrometer and analyzed using principal component analysis (PCA) and partial least square (PLS) regression analysis.</p> <p>Results and conclusion</p> <p>HR MAS MRS enabled assignment of 27 metabolites. Score plots from PCA of spin-echo and single-pulse spectra revealed separate clusters of the different xenografts and rectal biopsies, reflecting underlying differences in metabolite composition. The loading profile indicated that clustering was mainly based on differences in relative amounts of lipids, lactate and choline-containing compounds, with HT29 exhibiting the metabolic profile most similar to human rectal cancers tissue. Due to high necrotic fractions in the HT29 xenografts, radiation-induced changes were not detected when comparing spectra from untreated and irradiated HT29 xenografts. However, PLS calibration relating spectral data to the necrotic fraction revealed a significant correlation, indicating that necrotic fraction can be assessed from the MR spectra.</p

Amygdala and Ventrolateral Prefrontal Cortex Activation to Masked Angry Faces in Children and Adolescents with Generalized Anxiety Disorder

1. Context. Vigilance to threat is a key feature of generalized anxiety disorder (GAD). The amygdala and ventrolateral prefrontal cortex comprise a neural circuit that is responsible for detection of threats. Disturbed interactions between these structures may underlie pediatric anxiety. To date, no study has selectively examined responses to briefly-presented threats (e.g. less than 50 msec) in GAD or in pediatric anxiety. 2. Objective. To investigate amygdala and ventrolateral prefrontal cortex activation during processing of briefly-presented threats in pediatric GAD. 3. Design. Case-control study. 4. Setting. Government clinical research institute. 5. Participants. Youth volunteers, 17 with GAD and 12 diagnosis-free. 6. Main Outcome Measures. We used functional magnetic resonance imaging to measure blood oxygenation level-dependent signal. During imaging, subjects performed an attention orienting task with rapidly presented (17 msec), masked emotional (angry or happy) and neutral faces. 7. Results. When viewing masked angry faces, GAD youth, relative to comparison subjects, showed greater right amygdala activation that positively correlates with anxiety disorder severity. Moreover, in a functional connectivity (psychophysiological interaction) analysis, right amygdala and right ventrolateral prefrontal cortex showed strong negative coupling specifically to masked angry faces. This negative coupling tended to be weaker in GAD youth than in comparisons. Conclusions. GAD youth have hyper-activation of the amygdala to briefly-presented, masked threats. The presence of threat-related negative connectivity between the right ventrolateral prefrontal cortex and amygdala suggests that the prefrontal cortex modulates amygdala response to threat. In pediatric GAD, hyper-amygdala response occurs in the absence of a compensatory increase in modulation by ventrolateral prefrontal cortex

T Cell Specific Adapter Protein (TSAd) Interacts with Tec Kinase ITK to Promote CXCL12 Induced Migration of Human and Murine T Cells

The chemokine CXCL12/SDF-1α interacts with its G-protein coupled receptor CXCR4 to induce migration of lymphoid and endothelial cells. T cell specific adapter protein (TSAd) has been found to promote migration of Jurkat T cells through interaction with the G protein β subunit. However, the molecular mechanisms for how TSAd influences cellular migration have not been characterized in detail. We show that TSAd is required for tyrosine phosphorylation of the Lck substrate IL2-inducible T cell kinase (Itk). Presence of Itk Y511 was necessary to boost TSAd\u27s effect on CXCL12 induced migration of Jurkat T cells. In addition, TSAd\u27s ability to promote CXCL12-induced actin polymerization and migration of Jurkat T lymphocytes was dependent on the Itk-interaction site in the proline-rich region of TSAd. Furthermore, TSAd-deficient murine thymocytes failed to respond to CXCL12 with increased Itk phosphorylation, and displayed reduced actin polymerization and cell migration responses. We propose that TSAd, through its interaction with both Itk and Lck, primes Itk for Lck mediated phosphorylation and thereby regulates CXCL12 induced T cell migration and actin cytoskeleton rearrangements

Interleukin-6 and C-reactive protein as prognostic biomarkers in metastatic colorectal cancer

OBJECTIVES: The aim was to explore the prognostic significance of IL-6 and markers of systemic inflammatory response (SIR), in particular C-reactive protein (CRP), in metastatic colorectal cancer (mCRC) patients, in the total study population and according to RAS and BRAF mutation status. RESULTS: High levels of pretreatment serum IL-6 or CRP were associated with impaired outcome, in terms of reduced PFS and OS. Patients with low versus high serum IL-6 levels had median OS of 26.0 versus 16.6 months, respectively (P < 0.001). Stratified according to increasing CRP levels, median OS varied from 24.3 months to 12.3 months, (P < 0.001). IL-6 and CRP levels affected overall prognosis also in adjusted analyses. The effect of IL-6 was particularly pronounced in patients with BRAF mutation (interaction P = 0.004). MATERIALS AND METHODS: IL-6 and CRP were determined in pre-treatment serum samples from 393 patients included in the NORDIC-VII trial, in which patients with mCRC received first line treatment. The effect of serum IL-6 and CRP on progression-free survival (PFS) and overall survival (OS) was estimated. CONCLUSIONS: High baseline serum consentrations of IL-6 or CRP were associated with impaired prognosis in mCRC. IL-6 and CRP give independent prognostic information in addition to RAS and BRAF mutation status