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A new submodelling technique for multi-scale finite element computation of electromagnetic fields: application in bioelectromagnetism
Complex multi-scale Finite Element (FE) analyses always involve high number of elements and therefore require very long time of computations. This is caused by the fact, that considered effects on smaller scales have greater influences on the whole model and larger scales. Thus, mesh density should be as high as required by the smallest scale factor. New submodelling routine has been developed to sufficiently decrease the time of computation without loss of accuracy for the whole solution. The presented approach allows manipulation of different mesh sizes on different scales and, therefore total optimization of mesh density on each scale and transfer results automatically between the meshes corresponding to respective scales of the whole model. Unlike classical submodelling routine, the new technique operates with not only transfer of boundary conditions but also with volume results and transfer of forces (current density load in case of electromagnetism), which allows the solution of full Maxwell's equations in FE space. The approach was successfully implemented for electromagnetic solution in the forward problem of Magnetic Field Tomography (MFT) based on Magnetoencephalography (MEG), where the scale of one neuron was considered as the smallest and the scale of whole-brain model as the largest. The time of computation was reduced about 100 times, with the initial requirements of direct computations without submodelling routine of 10 million elements
Expression of Transketolase like gene 1 (TKTL1) predicts disease-free survival in patients with locally advanced rectal cancer receiving neoadjuvant chemoradiotherapy
<p>Abstract</p> <p>Background</p> <p>For patients with locally advanced rectal cancer (LARC) neoadjuvant chemoradiotherapy is recommended as standard therapy. So far, no predictive or prognostic molecular factors for patients undergoing multimodal treatment are established. Increased angiogenesis and altered tumour metabolism as adaption to hypoxic conditions in cancers play an important role in tumour progression and metastasis. Enhanced expression of Vascular-endothelial-growth-factor-receptor <it>(VEGF-R</it>) and Transketolase-like-1 (<it>TKTL1</it>) are related to hypoxic conditions in tumours. In search for potential prognostic molecular markers we investigated the expression of <it>VEGFR-1</it>, <it>VEGFR-2 </it>and <it>TKTL1 </it>in patients with LARC treated with neoadjuvant chemoradiotherapy and cetuximab.</p> <p>Methods</p> <p>Tumour and corresponding normal tissue from pre-therapeutic biopsies of 33 patients (m: 23, f: 10; median age: 61 years) with LARC treated in phase-I and II trials with neoadjuvant chemoradiotherapy (cetuximab, irinotecan, capecitabine in combination with radiotherapy) were analysed by quantitative PCR.</p> <p>Results</p> <p>Significantly higher expression of <it>VEGFR-1/2 </it>was found in tumour tissue in pre-treatment biopsies as well as in resected specimen after neoadjuvant chemoradiotherapy compared to corresponding normal tissue. High <it>TKTL1 </it>expression significantly correlated with disease free survival. None of the markers had influence on early response parameters such as tumour regression grading. There was no correlation of gene expression between the investigated markers.</p> <p>Conclusion</p> <p>High <it>TKTL-1 </it>expression correlates with poor prognosis in terms of 3 year disease-free survival in patients with LARC treated with intensified neoadjuvant chemoradiotherapy and may therefore serve as a molecular prognostic marker which should be further evaluated in randomised clinical trials.</p
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
Sex- and age-related differences in the management and outcomes of chronic heart failure: an analysis of patients from the ESC HFA EORP Heart Failure Long-Term Registry
Aims: This study aimed to assess age- and sex-related differences in management and 1-year risk for all-cause mortality and hospitalization in chronic heart failure (HF) patients. Methods and results: Of 16 354 patients included in the European Society of Cardiology Heart Failure Long-Term Registry, 9428 chronic HF patients were analysed [median age: 66 years; 28.5% women; mean left ventricular ejection fraction (LVEF) 37%]. Rates of use of guideline-directed medical therapy (GDMT) were high (angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, beta-blockers and mineralocorticoid receptor antagonists: 85.7%, 88.7% and 58.8%, respectively). Crude GDMT utilization rates were lower in women than in men (all differences: P\ua0 64 0.001), and GDMT use became lower with ageing in both sexes, at baseline and at 1-year follow-up. Sex was not an independent predictor of GDMT prescription; however, age >75 years was a significant predictor of GDMT underutilization. Rates of all-cause mortality were lower in women than in men (7.1% vs. 8.7%; P\ua0=\ua00.015), as were rates of all-cause hospitalization (21.9% vs. 27.3%; P\ua075 years. Conclusions: There was a decline in GDMT use with advanced age in both sexes. Sex was not an independent predictor of GDMT or adverse outcomes. However, age >75 years independently predicted lower GDMT use and higher all-cause mortality in patients with LVEF 6445%
Association between loop diuretic dose changes and outcomes in chronic heart failure: observations from the ESC-EORP Heart Failure Long-Term Registry
[Abstract]
Aims. Guidelines recommend down-titration of loop diuretics (LD) once euvolaemia is achieved. In outpatients with heart
failure (HF), we investigated LD dose changes in daily cardiology practice, agreement with guideline recommendations,
predictors of successful LD down-titration and association between dose changes and outcomes.
Methods
and results.
We included 8130 HF patients from the ESC-EORP Heart Failure Long-Term Registry. Among patients who had dose
decreased, successful decrease was defined as the decrease not followed by death, HF hospitalization, New York Heart
Association class deterioration, or subsequent increase in LD dose. Mean age was 66±13 years, 71% men, 62% HF
with reduced ejection fraction, 19% HF with mid-range ejection fraction, 19% HF with preserved ejection fraction.
Median [interquartile range (IQR)] LD dose was 40 (25–80) mg. LD dose was increased in 16%, decreased in 8.3%
and unchanged in 76%. Median (IQR) follow-up was 372 (363–419) days. Diuretic dose increase (vs. no change) was
associated with HF death [hazard ratio (HR) 1.53, 95% confidence interval (CI) 1.12–2.08; P = 0.008] and nominally
with cardiovascular death (HR 1.25, 95% CI 0.96–1.63; P = 0.103). Decrease of diuretic dose (vs. no change) was
associated with nominally lower HF (HR 0.59, 95% CI 0.33–1.07; P = 0.083) and cardiovascular mortality (HR 0.62 95% CI 0.38–1.00; P = 0.052). Among patients who had LD dose decreased, systolic blood pressure [odds ratio
(OR) 1.11 per 10 mmHg increase, 95% CI 1.01–1.22; P = 0.032], and absence of (i) sleep apnoea (OR 0.24, 95% CI
0.09–0.69; P = 0.008), (ii) peripheral congestion (OR 0.48, 95% CI 0.29–0.80; P = 0.005), and (iii) moderate/severe
mitral regurgitation (OR 0.57, 95% CI 0.37–0.87; P = 0.008) were independently associated with successful decrease.
Conclusion. Diuretic dose was unchanged in 76% and decreased in 8.3% of outpatients with chronic HF. LD dose increase was
associated with worse outcomes, while the LD dose decrease group showed a trend for better outcomes compared
with the no-change group. Higher systolic blood pressure, and absence of (i) sleep apnoea, (ii) peripheral congestion,
and (iii) moderate/severe mitral regurgitation were independently associated with successful dose decrease
Somatosensory System Deficits in Schizophrenia Revealed by MEG during a Median-Nerve Oddball Task
Although impairments related to somatosensory perception are common in schizophrenia, they have rarely been examined in functional imaging studies. In the present study, magnetoencephalography (MEG) was used to identify neural networks that support attention to somatosensory stimuli in healthy adults and abnormalities in these networks in patient with schizophrenia. A median-nerve oddball task was used to probe attention to somatosensory stimuli, and an advanced, high-resolution MEG source-imaging method was applied to assess activity throughout the brain. In nineteen healthy subjects, attention-related activation was seen in a sensorimotor network involving primary somatosensory (S1), secondary somatosensory (S2), primary motor (M1), pre-motor (PMA), and paracentral lobule (PCL) areas. A frontal–parietal–temporal “attention network”, containing dorsal- and ventral–lateral prefrontal cortex (DLPFC and VLPFC), orbitofrontal cortex (OFC), anterior cingulate cortex (ACC), superior parietal lobule (SPL), inferior parietal lobule (IPL)/supramarginal gyrus (SMG), and temporal lobe areas, was also activated. Seventeen individuals with schizophrenia showed early attention-related hyperactivations in S1 and M1 but hypo-activation in S1, S2, M1, and PMA at later latency in the sensorimotor network. Within this attention network, hypoactivation was found in SPL, DLPFC, orbitofrontal cortex, and the dorsal aspect of ACC. Hyperactivation was seen in SMG/IPL, frontal pole, and the ventral aspect of ACC in patients. These findings link attention-related somatosensory deficits to dysfunction in both sensorimotor and frontal–parietal–temporal networks in schizophrenia
Chest pain in primary care: is the localization of pain diagnostically helpful in the critical evaluation of patients? - A cross sectional study
BACKGROUND: Chest pain is a common complaint and reason for consultation in primary care. Traditional textbooks still assign pain localization a certain discriminative role in the differential diagnosis of chest pain. The aim of our study was to synthesize pain drawings from a large sample of chest pain patients and to examine whether pain localizations differ for different underlying etiologies. METHODS: We conducted a cross-sectional study including 1212 consecutive patients with chest pain recruited in 74 primary care offices in Germany. Primary care providers (PCPs) marked pain localization and radiation of each patient on a pictogram. After 6 months, an independent interdisciplinary reference panel reviewed clinical data of every patient, deciding on the etiology of chest pain at the time of patient recruitment. PCP drawings were entered in a specially designed computer program to produce merged pain charts for different etiologies. Dissimilarities between individual pain localizations and differences on the level of diagnostic groups were analyzed using the Hausdorff distance and the C-index. RESULTS: Pain location in patients with coronary heart disease (CHD) did not differ from the combined group of all other patients, including patients with chest wall syndrome (CWS), gastro-esophageal reflux disease (GERD) or psychogenic chest pain. There was also no difference in chest pain location between male and female CHD patients. CONCLUSIONS: Pain localization is not helpful in discriminating CHD from other common chest pain etiologies
Identification of Novel Genetic Loci Associated with Thyroid Peroxidase Antibodies and Clinical Thyroid Disease
Peer reviewe
Controlled release of aldicarb from carboxymethyl cellulose microspheres: in vitro and field applications
Kok, Fatma Nese/0000-0002-5093-6013WOS: 000084918700010Aldicarb is a carbamate pesticide that is widely used throughout the world in the protection Of crops (eg cotton, nuts, potatoes, onion, tobacco, sugar beet and sugar cane). In Turkey, especially in the Cukurova region, it is used for the control of the cotton white fly (Bemisia tabaci) which attacks cotton plants cultivated in this region. Aldicarb contamination in surface and ground water is a serious problem in several countries, partly due to its high water solubility. It is also highly toxic to mammals. In order to overcome these problems, microspheres of aldicarb were prepared using carboxymethyl cellulose (CMC) as the biodegradable support material cross-linked with aluminium chloride. A strong hysteresis behaviour was observed upon drying and reswelling. Encapsulation efficiency was in the range 12-23% and aldicarb contents of 5.7-10.3 mg per 100mg of microspheres was achieved. In vitro release was distinctly Fickian, and Higuchi constants were very close to 0.5. Release in pots revealed that only one sample had a release capability for more than four weeks. In the cotton plot much longer durations of release (more than seven weeks) were observed while a commercial granular formulation released its content immediately. It was thus possible to construct a controlled pesticide release system that prolonged the bioavailability to about eight weeks. (C) 1999 Society of Chemical Industry
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