967 resultados para expressions of interest
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The main goal of this paper is to propose a convergent finite volume method for a reactionâeuro"diffusion system with cross-diffusion. First, we sketch an existence proof for a class of cross-diffusion systems. Then the standard two-point finite volume fluxes are used in combination with a nonlinear positivity-preserving approximation of the cross-diffusion coefficients. Existence and uniqueness of the approximate solution are addressed, and it is also shown that the scheme converges to the corresponding weak solution for the studied model. Furthermore, we provide a stability analysis to study pattern-formation phenomena, and we perform two-dimensional numerical examples which exhibit formation of nonuniform spatial patterns. From the simulations it is also found that experimental rates of convergence are slightly below second order. The convergence proof uses two ingredients of interest for various applications, namely the discrete Sobolev embedding inequalities with general boundary conditions and a space-time $L^1$ compactness argument that mimics the compactness lemma due to Kruzhkov. The proofs of these results are given in the Appendix.
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BACKGROUND: Accurate assessment of glenoid inclination is of interest for a variety of conditions and procedures. The purpose of this study was to develop an accurate and reproducible measurement for glenoid inclination on standardized anterior-posterior (AP) radiographs and on computed tomography (CT) images. MATERIALS AND METHODS: Three consistently identifiable angles were defined: Angle α by line AB connecting the superior and inferior glenoid tubercle (glenoid fossa) and the line identifying the scapular spine; angle β by line AB and the floor of the supraspinatus fossa; angle γ by line AB and the lateral margin of the scapula. Experimental study: these 3 angles were measured in function of the scapular position to test their resistance to rotation. Conventional AP radiographs and CT scans were acquired in extension/flexion and internal/external rotation in a range up to ±40°. Clinical study: the inter-rater reliability of all angles was assessed on AP radiographs and CT scans of 60 patients (30 with proximal humeral fractures, 30 with osteoarthritis) by 2 independent observers. RESULTS: The experimental study showed that angle α and β have a resistance to rotation of up to ±20°. The deviation from neutral position was not more than ±10°. The results for the inter-rater reliability analyzed by Bland-Altman plots for the angle β fracture group were (mean ± standard deviation) -0.1 ± 4.2 for radiographs and -0.3 ± 3.3 for CT scans; and for the osteoarthritis group were -1.2 ± 3.8 for radiographs and -3.0 ± 3.6 for CT scans. CONCLUSION: Angle β is the most reproducible measurement for glenoid inclination on conventional AP radiographs, providing a resistance to positional variability of the scapula and a good inter-rater reliability.
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Defense mechanisms as a central notion of psychoanalysis have inspired various levels of interest in research in psychotherapy and psychopathology. Defense specificities have only recently been investigated systematically with regard to several clinical diagnoses, such as affective and personality disorders. For the present study, 30 inpatients diagnosed with Bipolar Affective Disorder I (BD) were interviewed. An observer-rater method, the Defense Mechanisms Rating Scales (DMRS), applied to session-transcripts, of assessment of defenses was used. A matched, nonclinical control group was introduced. Defense specificities in BD encompass a set of 5 immature defenses, of which omnipotence is linked with symptom level. The level of the therapeutic alliance is predicted by mature defenses. These results are discussed with regard to the psychological vulnerability of BD, and treatment implications for psychodynamic psychotherapy with such challenging patients are evoked.
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Purpose: Mediums have been developed to conserve corneal endothelium in organ-culture during eye banking. CorneaMax® is used by 25% of Eye Bank in Europe. Only little is known about conservation of corneal epithelium with this medium during banking. Its preservation could be of interest in clinic to cure corneal disease with stem cells deficiency. Therefore, we wanted to examine the integrity of human corneal epithelium maintained in CorneaMax®. Methods: Human corneas, considered unsuitable for transplantation, were obtained from the Eye Bank in Lausanne. Average post-mortem time was 14 hours. Cornoscleral rings were maintained in organ-culture in Corneamax® at 32°C. Samples were formalin-fixed after period ranging from 0 (D0) to 35 days (D35, N=5 for each time points) and stained with H&E. Proliferation and apoptosis were evaluated by immunostaining with antibody against Ki67 and Caspase3 respectively. Results: Corneas, which were not in organ-cultured (D0), showed different morphology, including intact epithelium with 5 to 7 layers, but also completely denuded basement membrane. In two cases, at D0, the epithelium lost its adherence to the basal lamina of the cornea creating a large epithelial sheet. During the two first days, corneas and limbus area lost totally their epithelium, except for some remaining limbal basal cells. From day 2 to day 10, regeneration of the epithelium took place, starting from the limbal region in direction to the central cornea. From day 10 to day 35, corneal epithelium appeared as an atrophic epithelium, consisting of only two cell layers. Proliferation happened in the whole cornea during the 35 days of organ-culture, as shown by Ki67 positive cells. Apoptosis was rarely detected in the corneal epithelium. Conclusions: Corneas maintained in CorneaMax® showed a complete disappearance of the corneal epithelium during the two first days and a conservation of limbal basal cells in the limbal region. These remaining cells allowed a full regeneration of the tissue, leading to an atrophic epithelium, composed of only two cell layers. This atrophic epithelium could be seen in all the organ-cultured corneas during the 35 days of conservation. This study is a first step to develop medium in organ-culture in order to conserve corneal epithelial cells.
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Postmortem human chorionic gonadotrophin (HCG) blood assay can confirm postmortem diagnosis of pregnancy or document situations in which HCG levels are elevated. In some cases, however, blood sampling is not possible at autopsy. In this study, HCG was quantified by enzyme-linked fluorescent assay (ELFA) in the bile (n = 5), vitreous humor (n = 4), and postmortem blood (n = 4) of five pregnant women. There were no false negatives in the pregnant subjects (n = 5) or false positives in controls (n = 34), enabling this test to be recommended for routine use in forensic contexts in which the detection of elevated HCG levels could be of interest.
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BACKGROUND/OBJECTIVES: Preoperative nutrition has been shown to reduce morbidity after major gastrointestinal (GI) surgery in selected patients at risk. In a randomized trial performed recently (NCT00512213), almost half of the patients, however, did not consume the recommended dose of nutritional intervention. The present study aimed to identify the risk factors for noncompliance. SUBJECTS/METHODS: Demographic (n=5) and nutritional (n=21) parameters for this retrospective analysis were obtained from a prospectively maintained database. The outcome of interest was compliance with the allocated intervention (ingestion of ⩾11/15 preoperative oral nutritional supplement units). Uni- and multivariate analyses of potential risk factors for noncompliance were performed. RESULTS: The final analysis included 141 patients with complete data sets for the purpose of the study. Fifty-nine patients (42%) were considered noncompliant. Univariate analysis identified low C-reactive protein levels (P=0.015), decreased recent food intake (P=0.032) and, as a trend, low hemoglobin (P=0.065) and low pre-albumin (P=0.056) levels as risk factors for decreased compliance. However, none of them was retained as an independent risk factor after multivariate analysis. Interestingly, 17 potential explanatory parameters, such as upper GI cancer, weight loss, reduced appetite or co-morbidities, did not show any significant correlation with reduced intake of nutritional supplements. CONCLUSIONS: Reduced compliance with preoperative nutritional interventions remains a major issue because the expected benefit depends on the actual intake. Seemingly, obvious reasons could not be retained as valid explanations. Compliance seems thus to be primarily a question of will and information; the importance of nutritional supplementation needs to be emphasized by specific patients' education.
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OBJECTIVE: The cause precipitating intracranial aneurysm rupture remains unknown in many cases. It has been observed that aneurysm ruptures are clustered in time, but the trigger mechanism remains obscure. Because solar activity has been associated with cardiovascular mortality and morbidity, we decided to study its association to aneurysm rupture in the Swiss population. METHODS: Patient data were extracted from the Swiss SOS database, at time of analysis covering 918 consecutive patients with angiography-proven aneurysmal subarachnoid hemorrhage treated at 7 Swiss neurovascular centers between January 1, 2009, and December 31, 2011. The daily rupture frequency (RF) was correlated to the absolute amount and the change in various parameters of interest representing continuous measurements of solar activity (radioflux [F10.7 index], solar proton flux, solar flare occurrence, planetary K-index/planetary A-index, Space Environment Services Center [SESC] sunspot number and sunspot area) using Poisson regression analysis. RESULTS: During the period of interest, there were 517 days without recorded aneurysm rupture. There were 398, 139, 27, 12, 1, and 1 days with 1, 2, 3, 4, 5, and 6 ruptures per day. Poisson regression analysis demonstrated a significant correlation of F10.7 index and RF (incidence rate ratio [IRR] = 1.006303; standard error (SE) 0.0013201; 95% confidence interval (CI) 1.003719-1.008894; P < 0.001), according to which every 1-unit increase of the F10.7 index increased the count for an aneurysm to rupture by 0.63%. A likewise statistically significant relationship of both the SESC sunspot number (IRR 1.003413; SE 0.0007913; 95% CI 1.001864-1.004965; P < 0.001) and the sunspot area (IRR 1.000419; SE 0.0000866; 95% CI 1.000249-1.000589; P < 0.001) emerged. All other variables analyzed showed no significant correlation with RF. CONCLUSIONS: We found greater radioflux, SESC sunspot number, and sunspot area to be associated with an increased count of aneurysm rupture. The clinical meaningfulness of this statistical association must be interpreted carefully and future studies are warranted to rule out a type-1 error.
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Optimization models in metabolic engineering and systems biology focus typically on optimizing a unique criterion, usually the synthesis rate of a metabolite of interest or the rate of growth. Connectivity and non-linear regulatory effects, however, make it necessary to consider multiple objectives in order to identify useful strategies that balance out different metabolic issues. This is a fundamental aspect, as optimization of maximum yield in a given condition may involve unrealistic values in other key processes. Due to the difficulties associated with detailed non-linear models, analysis using stoichiometric descriptions and linear optimization methods have become rather popular in systems biology. However, despite being useful, these approaches fail in capturing the intrinsic nonlinear nature of the underlying metabolic systems and the regulatory signals involved. Targeting more complex biological systems requires the application of global optimization methods to non-linear representations. In this work we address the multi-objective global optimization of metabolic networks that are described by a special class of models based on the power-law formalism: the generalized mass action (GMA) representation. Our goal is to develop global optimization methods capable of efficiently dealing with several biological criteria simultaneously. In order to overcome the numerical difficulties of dealing with multiple criteria in the optimization, we propose a heuristic approach based on the epsilon constraint method that reduces the computational burden of generating a set of Pareto optimal alternatives, each achieving a unique combination of objectives values. To facilitate the post-optimal analysis of these solutions and narrow down their number prior to being tested in the laboratory, we explore the use of Pareto filters that identify the preferred subset of enzymatic profiles. We demonstrate the usefulness of our approach by means of a case study that optimizes the ethanol production in the fermentation of Saccharomyces cerevisiae.
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Blood oxygenation level-dependent (BOLD) functional MRI is a widely employed methodology in experimental and clinical neuroscience, although its nature is not fully understood. To gain insights into BOLD mechanisms and take advantage of the new functional methods, it is of interest to investigate prolonged paradigms of activation suitable for long experimental protocols and to observe any long-term modifications induced by these functional challenges. While different types of sustained stimulation paradigm have been explored in human studies, the BOLD response is typically limited to a few minutes in animal models, due to fatigue, anesthesia effects and physiological instability. In the present study, the rat forepaw was electrically stimulated for 2 h, which resulted in a prolonged and localized cortical BOLD response over that period. The stimulation paradigm, including an inter-stimulus interval (ISI) of 10 s, that is 25% of the total time, was applied at constant or variable frequency over 2 h. The steady-state level of the BOLD response was reached after 15-20 min of stimulation and was maintained until the end of the stimulation. On average, no substantial loss in activated volume was observed at the end of the stimulation, but less variability in the fraction of remaining activated volume and higher steady-state BOLD amplitude were observed when stimulation frequency was varied between 2 and 3 Hz every 5 min. We conclude that the combination of ISI and variable stimulus frequency reproducibly results in robust, prolonged and localized BOLD activation. Copyright © 2015 John Wiley & Sons, Ltd.
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The present study was performed to investigate the possibility of 'aberrant' innervation of the tips of the hindlimb digits in the rat, i.e., from other sources than the femoral and the main sciatic branches (tibial, peroneal, sural). Cutaneous injections of fluorescent tracers in the digits were combined with either selective nerve transections to restrict afferent routes followed by detection of labeled neurons in dorsal root ganglia (DRGs), or by a delayed application of a second tracer to afferent nerves under study to detect double labeled neurons in DRGs. The results show that the tips of the digits were represented in DRGs L3-6. The femoral nerve afferents from digits 1 and 2 projected primarily to DRG L3 and to a smaller extent to DRG L4. A small number of neurons from primarily medial digits 1 and 2, but also from lateral digits 3-5, were found to project to DRGs L4 and L5 via a proximal branch that leaves the sciatic nerve near the sciatic notch and runs distally in the posterior part of the thigh, here called the musculocutaneous nerve of the hindlimb. We also have some evidence indicating innervation of the tips of the digits from the posterior cutaneous nerve of the thigh. Aberrant innervation such as that described here might contribute to remaining and perhaps abnormal sensibility after nerve injury and is of interest for the interpretation of results in experimental studies of collateral and regenerative sprouting after such injury
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Background: Studies conducted internationally confirm that child sexual abuse is a much more widespread problem than previously thought, with even the lowest prevalence rates including a large number of victims that need to be taken into account. Objective: To carry out a meta-analysis of the prevalence of child sexual abuse in order to establish an overall international figure. Methods: Studies were retrieved from various electronic databases. The measure of interest was the prevalence of abuse reported in each article, these values being combined via a random effects model. A detailed analysis was conducted of the effects of various moderator variables. Results: Sixty-five articles covering 22 countries were included. The analysis showed that 7.9% of men (7.4% without outliers) and 19.7% of women (19.2% without outliers) had suffered some form of sexual abuse prior to the age of eighteen. Conclusions: The results of the present meta-analysis indicate that child sexual abuse is a serious problem in the countries analysed.
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Työn tärkeimpänä tavoitteena oli edistää ympäristöjärjestelmän laatimista Kvaerner Pulping, Power divisioonan Kattilat-liiketoimintayksikölle. Lisäksi tavoitteena oli tarkastella yritykseen kohdistuvia ympäristövaatimuksia ja niiden vaikutusta yrityksen toimintaan. Aluksi työssä tarkasteltiin ympäristöjärjestelmästandardien sisältöjä ja niiden eroja. Työssä käsiteltiin myös erilaisia elinkaarijohtamisen malleja, joita voidaan hyödyntää yrityksen kokonaisvaltaisessa ympäristöjärjestelmässä. Työssä tarkasteltiin myös sidosryhmien vaikutusta yrityksen ympäristötoimintaan. Kattilalaitostoimittajan tärkeimpiä asiakkaita ovat sellu- ja paperiteollisuus. Näihin yrityksiin on kohdistunut runsaan kymmenen vuoden aikana paineita ympäristötoiminnan tehostamiseksi. Tämän kehityksen seurauksena vastaavat tehostamispaineet ovat siirtymässä myös alihankkijoille, kuten kattilaitostoimittajille. Tehokkaan ympäristöjohtamisen takaamiseksi työssä määriteltiin ympäristövastuut ja –valtuudet sekä ympäristöpäämäärät ja –tavoitteet. Lisäksi tunnistettiin yrityksen toimintaan liittyvät ympäristönäkökohdat ja –riskit. Työn yhteydessä laadittiin ympäristöjärjestelmän luonnos, ja se sisältää jatkuvan parantamisen periaatteen. Työn yhteydessä laadittiin lisäksi Kvaerner Pulping Oy:n koelaitokselle ympäristölupahakemus. Työssä on kuvattu koelaitosta ja sen ympäristölupahakemukseen liittyviä asioita esimerkkinä parantuneesta ympäristöasioiden hoidosta.
Contribution of Intronic miR-338-3p and Its Hosting Gene AATK to Compensatory β-Cell Mass Expansion.
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The elucidation of the mechanisms directing β-cell mass regeneration and maintenance is of interest, because the deficit of β-cell mass contributes to diabetes onset and progression. We previously found that the level of the microRNA (miRNA) miR-338-3p is decreased in pancreatic islets from rodent models displaying insulin resistance and compensatory β-cell mass expansion, including pregnant rats, diet-induced obese mice, and db/db mice. Transfection of rat islet cells with oligonucleotides that specifically block miR-338-3p activity increased the fraction of proliferating β-cells in vitro and promoted survival under proapoptotic conditions without affecting the capacity of β-cells to release insulin in response to glucose. Here, we evaluated the role of miR-338-3p in vivo by injecting mice with an adeno-associated viral vector permitting specific sequestration of this miRNA in β-cells. We found that the adeno-associated viral construct increased the fraction of proliferating β-cells confirming the data obtained in vitro. miR-338-3p is generated from an intron of the gene coding for apoptosis-associated tyrosine kinase (AATK). Similarly to miR-338-3p, we found that AATK is down-regulated in rat and human islets and INS832/13 β-cells in the presence of the cAMP-raising agents exendin-4, estradiol, and a G-protein-coupled Receptor 30 agonist. Moreover, AATK expression is reduced in islets of insulin resistant animal models and selective silencing of AATK in INS832/13 cells by RNA interference promoted β-cell proliferation. The results point to a coordinated reduction of miR-338-3p and AATK under insulin resistance conditions and provide evidence for a cooperative action of the miRNA and its hosting gene in compensatory β-cell mass expansion.
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Tämän diplomityön tarkoituksena oli tutkia pintaliimatärkkelysten reologista käyttäytymistä korkeissa kuiva-ainepitoisuuksissa. Tarve työn suorittamiselle syntyi kun tutkittiin pintaliimausta filminsiirtopuristimella tavallista korkeammissa kuiva-ainepitoisuuksissa, sileän sauvan ollessa applikointilaitteena. Koska applikointi sileällä sauvalla tapahtuu hydrodynaamisten periaatteiden mukaisesti, sen käyttö edellyttää pintaliimojen reologisten ominaisuuksien tarkkaa tuntemusta ja hallintaa.Kiinnostuksen kohteena olevat ominaisuudet olivat tärkkelysten kuiva-ainepitoisuuden (8 – 30 %) vaikutus viskositeettiin eri lämpötiloissa (20, 30, 40 ja 50 ºC), leikkausnopeus alueella 1 s-1 - 700 000 s-1. Myös tärkkelysten myötörajat määritettiin tutkimuksessa. Viskositeetti eri leikkausnopeusalueilla mitattiin seuraavilla laitteilla: Bohlin VOR (matalat leikkausnopeudet ja myötöraja) ja Hercules HiShear (keskitason leikkausnopeudet) reometrit sekä Eklund kapillaariviskometri (korkeat leikkausno-peudet). Analysoidut tärkkelykset olivat kaksi anionista matalaviskoottista peruna (tärkkelys A) ja ohra (tärkkelys C) tärkkelystä, sekä yksi kationinen korkeaviskoottinen peruna tärkkelys (tärkkelys B). Tutkittujen tärkkelysten Brookfield viskositeetit (100 rpm) olivat (10 % liuos, 60 °C:ssa) tärkkelys A ja C: 25 ± 5 mPas ja tärkkelys B: 100 ± 20 mPas.Tärkkelysliuosten kuiva-ainepitoisuuden noustessa muuttui virtauskäyttäytyminen Newtoniaalisesta leikkausohenevaksi. Leikkausoheneva käyttäytyminen oli voimakkainta tärkkelys B:n kohdalla. Viskositeetti – lämpötila riippuvuus korkeissa leikkausnopeuksissa (esim. 500 000 s-1) oli vähäisempää, mitä oli oletettavissa Brookfield viskositeettiarvojen perusteella. Kaikki tarkkelykset osoittautuivat tiksotrooppisiksi, myös tiksotrooppisuus lisääntyi kuiva-ainepitoisuuden kasvaessa. Tärkkelysten myötörajat osoittautuivat odottamattoman alhaisiksi, kuitenkin varsinkin tärkkelys B:n myötörajat olivat selvästi riippuvaisia lämpötilasta ja kuiva-ainepitoisuudesta. Tutkittujen tärkkelysten virtauskäyttäytyminen oli kirjallisuudessa esitetyn kaltaista. Tärkkelysmolekyylien ketjun pituus oli tärkein tärkkelyksen reologisia ominaisuuksia määrittävä tekijä; mitä matalampi on tärkkelyksen molekyylimassa, sitä matalammat ovat viskositeetti ja myötöraja. Pintaliimauksessa tärkkelysmolekyylien ketjunpituudella on suuri vaikutus ajettavuuteen ja lopputuotteen ominaisuuksiin. Haasteellista pintaliimatärkkelyksen valinnassa on sellaisen yhdistelmän löytäminen, jossa sopivan reologisen käyttäytymisen omaava tärkkelys ja pintaliimatulle paperille tai kartongille asetetut vaatimukset kohtaavat.
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BACKGROUND: After cardiac surgery with cardiopulmonary bypass (CPB), acquired coagulopathy often leads to post-CPB bleeding. Though multifactorial in origin, this coagulopathy is often aggravated by deficient fibrinogen levels. OBJECTIVE: To assess whether laboratory and thrombelastometric testing on CPB can predict plasma fibrinogen immediately after CPB weaning. PATIENTS / METHODS: This prospective study in 110 patients undergoing major cardiovascular surgery at risk of post-CPB bleeding compares fibrinogen level (Clauss method) and function (fibrin-specific thrombelastometry) in order to study the predictability of their course early after termination of CPB. Linear regression analysis and receiver operating characteristics were used to determine correlations and predictive accuracy. RESULTS: Quantitative estimation of post-CPB Clauss fibrinogen from on-CPB fibrinogen was feasible with small bias (+0.19 g/l), but with poor precision and a percentage of error >30%. A clinically useful alternative approach was developed by using on-CPB A10 to predict a Clauss fibrinogen range of interest instead of a discrete level. An on-CPB A10 ≤10 mm identified patients with a post-CPB Clauss fibrinogen of ≤1.5 g/l with a sensitivity of 0.99 and a positive predictive value of 0.60; it also identified those without a post-CPB Clauss fibrinogen <2.0 g/l with a specificity of 0.83. CONCLUSIONS: When measured on CPB prior to weaning, a FIBTEM A10 ≤10 mm is an early alert for post-CPB fibrinogen levels below or within the substitution range (1.5-2.0 g/l) recommended in case of post-CPB coagulopathic bleeding. This helps to minimize the delay to data-based hemostatic management after weaning from CPB.