Disability in multiple sclerosis is related to thalamic connectivity and cortical network atrophy.

BACKGROUND: Thalamic atrophy is proposed to be a major predictor of disability progression in multiple sclerosis (MS), while thalamic function remains understudied. OBJECTIVES: To study how thalamic functional connectivity (FC) is related to disability and thalamic or cortical network atrophy in two large MS cohorts. METHODS: Structural and resting-state functional magnetic resonance imaging (fMRI) was obtained in 673 subjects from Amsterdam (MS: N = 332, healthy controls (HC): N = 96) and Graz (MS: N = 180, HC: N = 65) with comparable protocols, including disability measurements in MS (Expanded Disability Status Scale, EDSS). Atrophy was measured for the thalamus and seven well-recognized resting-state networks. Static and dynamic thalamic FC with these networks was correlated with disability. Significant correlates were included in a backward multivariate regression model. RESULTS: Disability was most strongly related (adjusted R2 = 0.57, p < 0.001) to higher age, a progressive phenotype, thalamic atrophy and increased static thalamic FC with the sensorimotor network (SMN). Static thalamus-SMN FC was significantly higher in patients with high disability (EDSS ⩾ 4) and related to network atrophy but not thalamic atrophy or lesion volumes. CONCLUSION: The severity of disability in MS was related to increased static thalamic FC with the SMN. Thalamic FC changes were only related to cortical network atrophy, but not to thalamic atrophy

Residual confounding after adjustment for age: a minor issue in breast cancer screening effectiveness

Residual confounding, after adjustment for age, is the major criticism of observational studies on breast cancer screening effectiveness. We developed realistic scenarios for the prevalence and strength of risk factors on screened and not screened groups, and explored the impact of residual confounding bias. Our results demonstrate that residual confounding bias is a minor issue in screening programme evaluations

Increasingly strong reduction in breast cancer mortality due to screening

Item does not contain fulltextBACKGROUND: Favourable outcomes of breast cancer screening trials in the 1970s and 1980s resulted in the launch of population-based service screening programmes in many Western countries. We investigated whether improvements in mammography and treatment modalities have had an influence on the effectiveness of breast cancer screening from 1975 to 2008. METHODS: In Nijmegen, the Netherlands, 55,529 women received an invitation for screening between 1975 and 2008. We designed a case-referent study to evaluate the impact of mammographic screening on breast cancer mortality over time from 1975 to 2008. A total number of 282 breast cancer deaths were identified, and 1410 referents aged 50-69 were sampled from the population invited for screening. We estimated the effectiveness by calculating the odds ratio (OR) indicating the breast cancer death rate for screened vs unscreened women. RESULTS: The breast cancer death rate in the screened group over the complete period was 35% lower than in the unscreened group (OR=0.65; 95% CI=0.49-0.87). Analysis by calendar year showed an increasing effectiveness from a 28% reduction in breast cancer mortality in the period 1975-1991 (OR=0.72; 95% CI=0.47-1.09) to 65% in the period 1992-2008 (OR=0.35; 95% CI=0.19-0.64). CONCLUSION: Our results show an increasingly strong reduction in breast cancer mortality over time because of mammographic screening

Wall shear stress as measured in vivo: consequences for the design of the arterial system

Based upon theory, wall shear stress (WSS), an important determinant of endothelial function and gene expression, has been assumed to be constant along the arterial tree and the same in a particular artery across species. In vivo measurements of WSS, however, have shown that these assumptions are far from valid. In this survey we will discuss the assessment of WSS in the arterial system in vivo and present the results obtained in large arteries and arterioles. In vivo WSS can be estimated from wall shear rate, as derived from non-invasively recorded velocity profiles, and whole blood viscosity in large arteries and plasma viscosity in arterioles, avoiding theoretical assumptions. In large arteries velocity profiles can be recorded by means of a specially designed ultrasound system and in arterioles via optical techniques using fluorescent flow velocity tracers. It is shown that in humans mean WSS is substantially higher in the carotid artery (1.1–1.3 Pa) than in the brachial (0.4–0.5 Pa) and femoral (0.3–0.5 Pa) arteries. Also in animals mean WSS varies substantially along the arterial tree. Mean WSS in arterioles varies between about 1.0 and 5.0 Pa in the various studies and is dependent on the site of measurement in these vessels. Across species mean WSS in a particular artery decreases linearly with body mass, e.g., in the infra-renal aorta from 8.8 Pa in mice to 0.5 Pa in humans. The observation that mean WSS is far from constant along the arterial tree implies that Murray’s cube law on flow-diameter relations cannot be applied to the whole arterial system. Because blood flow velocity is not constant along the arterial tree either, a square law also does not hold. The exponent in the power law likely varies along the arterial system, probably from 2 in large arteries near the heart to 3 in arterioles. The in vivo findings also imply that in in vitro studies no average shear stress value can be taken to study effects on endothelial cells derived from different vascular areas or from the same artery in different species. The cells have to be studied under the shear stress conditions they are exposed to in real life

Serum folate, homocysteine and colorectal cancer risk in women: a nested case–control study

Accumulating evidence suggests that folate, which is plentiful in vegetables and fruits, may be protective against colorectal cancer. The authors have studied the relationship of baseline levels of serum folate and homocysteine to the subsequent risk of colorectal cancer in a nested case–control study including 105 cases and 523 matched controls from the New York University Women's Health Study cohort. In univariate analyses, the cases had lower serum folate and higher serum homocysteine levels than controls. The difference was more significant for folate (P < 0.001) than for homocysteine (P = 0.04). After ad'justing for potential confounders, the risk of colorectal cancer in the subjects in the highest quartile of serum folate was half that of those in the lowest quartile (odds ratio, OR = 0.52, 95% confidence interval, CI = 0.27–0.97, P-value for trend = 0.04). The OR for the highest quartile of homocysteine, relative to the lowest quartile, was 1.72 (95% CI = 0.83–3.65, P-value for trend = 0.09). In addition, the risk of colorectal cancer was almost twice as high in subjects with below-median serum folate and above-median total alcohol intake compared with those with above-median serum folate and below-median alcohol consumption (OR = 1.99, 95% CI = 0.92–4.29). The potentially protective effects of folate need to be confirmed in clinical trials. © 1999 Cancer Research Campaig

Dilatation of the proximal neck of infrarenal aortic aneurysms after endovascular AAA repair

AbstractObjectives: to assess size changes of the proximal aortic neck after endograft placement.Methods: since 1994, 54 consecutive patients have undergone abdominal aortic aneurysm (AAA) repair with the Endovascular Technologies (EVT) endograft. The study group comprised the 33 patients who had completed at least six months of the prospective follow-up protocol. The pre-, postoperative and follow-up helical computed tomography (CT) angiograms (CTAs) were processed on a workstation. The proximal neck dimensions were measured perpendicular to the central lumen line of the aortic neck. The cross-sectional area was measured at the proximal attachment system and at 1 cm proximal to the renal arteries. Results: while the dimensions of suprarenal aorta did not change, a significant dilatation of the proximal neck was found. The median increase was 10.3% at 6 months and 15.5% at 12 months. No correlation could be found between the amount of dilatation and pre- or postoperative neck-size, graft diameter and amount of graft-oversizing. Conclusion: the infrarenal aortic neck demonstrates continued dilatation during follow-up after endograft placement

Dilatation of the proximal neck of infrarenal aortic aneurysms after endovascular AAA repair

Objectives: to assess size changes of the proximal aortic neck after endograft placement. Methods: since 1994, 54 consecutive patients have undergone abdominal aortic aneurysm (AAA) repair with the Endovascular Technologies (EVT) endograft. The study group comprised the 33 patients who had completed at least six months of the prospective follow-up protocol. The pre-, postoperative and follow-up helical computed tomography (CT) angiograms (CTAs) were processed on a workstation. The proximal neck dimensions were measured perpendicular to the central lumen line of the aortic neck. The cross-sectional area was measured at the proximal attachment system and at 1 cm proximal to the renal arteries. Results: while the dimensions of suprarenal aorta did not change, a significant dilatation of the proximal neck was found. The median increase was 10.3% at 6 months and 15.5% at 12 months. No correlation could be found between the amount of dilatation and pre- or postoperative neck-size, graft diameter and amount of graft-oversizing. Conclusion: the infrarenal aortic neck demonstrates continued dilatation during follow-up after endograft placement