Ruling out coronary heart disease in primary care patients with chest pain: a clinical prediction score

Chest pain raises concern for the possibility of coronary heart disease. Scoring methods have been developed to identify coronary heart disease in emergency settings, but not in primary care. Data were collected from a multicenter Swiss clinical cohort study including 672 consecutive patients with chest pain, who had visited one of 59 family practitioners' offices. Using delayed diagnosis we derived a prediction rule to rule out coronary heart disease by means of a logistic regression model. Known cardiovascular risk factors, pain characteristics, and physical signs associated with coronary heart disease were explored to develop a clinical score. Patients diagnosed with angina or acute myocardial infarction within the year following their initial visit comprised the coronary heart disease group. The coronary heart disease score was derived from eight variables: age, gender, duration of chest pain from 1 to 60 minutes, substernal chest pain location, pain increasing with exertion, absence of tenderness point at palpation, cardiovascular risks factors, and personal history of cardiovascular disease. Area under the receiver operating characteristics curve was of 0.95 with a 95% confidence interval of 0.92; 0.97. From this score, 413 patients were considered as low risk for values of percentile 5 of the coronary heart disease patients. Internal validity was confirmed by bootstrapping. External validation using data from a German cohort (Marburg, n = 774) revealed a receiver operating characteristics curve of 0.75 (95% confidence interval, 0.72; 0.81) with a sensitivity of 85.6% and a specificity of 47.2%. This score, based only on history and physical examination, is a complementary tool for ruling out coronary heart disease in primary care patients complaining of chest pain

The prognosis of allocentric and egocentric neglect : evidence from clinical scans

We contrasted the neuroanatomical substrates of sub-acute and chronic visuospatial deficits associated with different aspects of unilateral neglect using computed tomography scans acquired as part of routine clinical diagnosis. Voxel-wise statistical analyses were conducted on a group of 160 stroke patients scanned at a sub-acute stage. Lesion-deficit relationships were assessed across the whole brain, separately for grey and white matter. We assessed lesions that were associated with behavioural performance (i) at a sub-acute stage (within 3 months of the stroke) and (ii) at a chronic stage (after 9 months post stroke). Allocentric and egocentric neglect symptoms at the sub-acute stage were associated with lesions to dissociated regions within the frontal lobe, amongst other regions. However the frontal lesions were not associated with neglect at the chronic stage. On the other hand, lesions in the angular gyrus were associated with persistent allocentric neglect. In contrast, lesions within the superior temporal gyrus extending into the supramarginal gyrus, as well as lesions within the basal ganglia and insula, were associated with persistent egocentric neglect. Damage within the temporo-parietal junction was associated with both types of neglect at the sub-acute stage and 9 months later. Furthermore, white matter disconnections resulting from damage along the superior longitudinal fasciculus were associated with both types of neglect and critically related to both sub-acute and chronic deficits. Finally, there was a significant difference in the lesion volume between patients who recovered from neglect and patients with chronic deficits. The findings presented provide evidence that (i) the lesion location and lesion size can be used to successfully predict the outcome of neglect based on clinical CT scans, (ii) lesion location alone can serve as a critical predictor for persistent neglect symptoms, (iii) wide spread lesions are associated with neglect symptoms at the sub-acute stage but only some of these are critical for predicting whether neglect will become a chronic disorder and (iv) the severity of behavioural symptoms can be a useful predictor of recovery in the absence of neuroimaging findings on clinical scans. We discuss the implications for understanding the symptoms of the neglect syndrome, the recovery of function and the use of clinical scans to predict outcome

TAMEP are brain tumor parenchymal cells controlling neoplastic angiogenesis and progression

Aggressive brain tumors like glioblastoma depend on support by their local environment and subsets of tumor parenchymal cells may promote specific phases of disease progression. We investigated the glioblastoma microenvironment with transgenic lineage-tracing models, intravital imaging, single-cell transcriptomics, immunofluorescence analysis as well as histopathology and characterized a previously unacknowledged population of tumor-associated cells with a myeloid-like expression profile (TAMEP) that transiently appeared during glioblastoma growth. TAMEP of mice and humans were identified with specific markers. Notably, TAMEP did not derive from microglia or peripheral monocytes but were generated by a fraction of CNS-resident, SOX2-positive progenitors. Abrogation of this progenitor cell population, by conditional Sox2-knockout, drastically reduced glioblastoma vascularization and size. Hence, TAMEP emerge as a tumor parenchymal component with a strong impact on glioblastoma progression

Testing for Spatial Neglect with Line Bisection and Target Cancellation: Are Both Tasks Really Unrelated?

Damage to the parietal lobe can induce a condition known as spatial neglect, characterized by a lack of awareness of the personal and/or extrapersonal space opposite the damaged brain region. Spatial neglect is commonly assessed clinically using either the line bisection or the target cancellation task. However, it is unclear whether poor performance on each of these two tasks is associated with the same or different lesion locations. To date, methodological limitations and differences have prevented a definitive link between task performance and lesion location to be made. Here we report findings from a voxel-based lesion symptom mapping (VLSM) analysis of an unbiased selection of 44 patients with a recent unifocal stroke. Patients performed both the line bisection and target cancellation task. For each of the two tasks a continuous score was incorporated into the VLSM analysis. Both tasks correlated highly with each other (r = .76) and VLSM analyses indicated that the angular gyrus was the critical lesion site for both tasks. The results suggest that both tasks probe the same underlying cortical deficits and although the cancellation task was more sensitive than the line bisection task, both can be used in a clinical setting to test for spatial neglect

Combined dynamics of mercury and terrigenous organic matter following impoundment of Churchill Falls Hydroelectric Reservoir, Labrador

Sediments from two recently (40 years) flooded lakes (Gabbro lake and Sandgirt lake) and an unflooded lake (Atikonak lake) were sampled to investigate the effects of reservoir impoundment on mercury (Hg) and terrigenous organic matter (TOM) loading in the Churchill Falls Hydroelectric complex in Labrador, Canada. Lignin biomarkers in TOM, which exclusively derive from terrestrial vegetation, were used as biomarkers for the presence and source origin of TOM—and for Hg due to their close associations—in sediments. In the two flooded Gabbro and Sandgirt lakes, we observed drastic increases in total mercury concentrations, T-[Hg], in sediments, which temporally coincided with the time of reservoir impoundment as assessed by 210Pb age dating. In the natural Atikonak lake sediments, on the other hand, T-[Hg] showed no such step-increase but gradually and slowly increased until present. T-[Hg] increases in lake sediments after flooding were also associated with a change in the nature of TOM: biomarker signatures changed to typical signatures of TOM from vegetated terrestrial landscape surrounding the lakes, and indicate a change to TOM that was much less degraded and typical of forest soil organic horizons. We conclude that T-[Hg] increase in the sediments of the two flooded reservoirs was the result of flooding of surrounding forests, whereby mainly surface organic horizons and upper soil horizons were prone to erosion and subsequent re-sedimentation in the reservoirs. The fact that T-[Hg] was still enriched 40 years after reservoir impoundment indicates prolonged response time of lake Hg and sediment loadings after reservoir impoundments