935 resultados para Increasing failure rate


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Excess entry refers to the high failure rate of new entrepreneurial ventures. Economic explanations suggest 'hit and run' entrants and risk-seeking behavior. A psychological explanation is that people (entrepreneurs) are overconfident in their abilities (Camerer & Lovallo, 1999). Characterizing entry decisions as ambiguous gambles, we alternatively suggest following Heath and Tversky (1991) that people seek ambiguity when the source of uncertainty is related to their competence. Overconfidence, as such, plays no role. This hypothesis is confirmed in an experimental study that also documents the phenomenon of reference group neglect. Finally, we emphasize the utility that people gain from engaging in activities that contribute to a sense of competence. This is an important force in economic activity that deserves more explicit attention.

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In this paper, aggregate migration patterns during fluid concrete castings are studied through experiments, dimensionless approach and numerical modeling. The experimental results obtained on two beams show that gravity induced migration is primarily affecting the coarsest aggregates resulting in a decrease of coarse aggregates volume fraction with the horizontal distance from the pouring point and in a puzzling vertical multi-layer structure. The origin of this multi layer structure is discussed and analyzed with the help of numerical simulations of free surface flow. Our results suggest that it finds its origin in the non Newtonian nature of fresh concrete and that increasing casting rate shall decrease the magnitude of gravity induced particle migration. (C) 2012 Elsevier Ltd. All rights reserved.

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BACKGROUND: Indomethacin therapy for closure of a patent ductus arteriosus in preterm neonates is responsible for transient renal insufficiency. Dopamine theoretically reduces the renal side effects of indomethacin therapy. PATIENTS: 33 neonates with a mean gestational age of 28.5 weeks who received indomethacin for treatment of a symptomatic PDA were included in a prospective randomized controlled clinical study. METHOD: 15 patients were treated with indomethacin alone (control group), 18 patients with indomethacin and dopamine (study group). Indomethacin was given in a dose of 0.2 mg/kg/dose intravenously, all patients received three doses with intervall of 12 hours. The dose of dopamine was in all patients 4 micrograms/kg per minute commencing 2 hours prior to the first dose of indomethacin and continuing for 12 hours after the third dose. RESULTS: Indomethacin induced a significant increase in serum creatinin (76.3 mumol/l vs 99.7 mumol/l for the control group, and 70.7 mumol/l vs 93.0 mumol/l for the study group), and weight (1259 g vs 1316 g for the control group, and 1187 g vs 1221 g for the study group). The increase systolic blood pressure (61 mmHg vs 65.7 mmHg) in the study group was significant (p < 0.05) but remained unchanged in the control group. The changes between the study group and the control group were not significant either in serum creatinin, fractional excretion of sodium, or weight gain. The failure rate of ductal closure was not different between the two groups. CONCLUSION: The additional use of dopamine does not reduce the renal side effects of indomethacin.

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PURPOSE: Colonoscopy is reported to be a safe procedure that is routinely performed for the diagnosis and treatment of colorectal diseases. Splenic rupture is considered to be a rare complication with high mortality and morbidity that requires immediate diagnosis and management. Nonoperative management (NOM), surgical treatment (ST), and, more recently, proximal splenic artery embolization (PSAE) have been proposed as treatment options. The goal of this study was to assess whether PSAE is safe even in high-grade ruptures. METHODS: We report two rare cases of post colonoscopy splenic rupture. A systematic review of the literature from 2002 to 2010 (first reported case of PSAE) was performed and the three types of treatment compared. RESULTS: All patients reviewed (77 of 77) presented with intraperitoneal hemorrhage due to isolated splenic trauma. Splenic rupture was high-grade in most patients when grading was possible. Six of 77 patients (7.8 %) were treated with PSAE, including the 2 cases reported herein. Fifty-seven patients (74 %) underwent ST. NOM was attempted first in 25 patients with a high failure rate (11 of 25 [44 %]) and requiring a salvage procedure, such as PSAE or ST. Previous surgery (31 of 59 patients), adhesions (10 of 13), diagnostic colonoscopies (49 of 71), previous biopsies or polypectomies (31 of 57) and female sex (56 of 77) were identified as risk factors. In contrast, splenomegaly (0 of 77 patients), medications that increase the risk of bleeding (13 of 30) and difficult colonoscopies (16 of 51) were not identified as risk factors. PSAE was safe and effective even in elderly patients with comorbidities and those taking medications that increase the risk of bleeding, and the length of the hospital stay was similar to that after ST. CONCLUSION: We propose a treatment algorithm based on clinical and radiological criteria. Because of the high failure rate after NOM, PSAE should be the treatment of choice to manage grade I through IV splenic ruptures after colonoscopy in hemodynamically stabilized patients.

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Dynamic behavior of bothisothermal and non-isothermal single-column chromatographic reactors with an ion-exchange resin as the stationary phase was investigated. The reactor performance was interpreted by using results obtained when studying the effect of the resin properties on the equilibrium and kinetic phenomena occurring simultaneously in the reactor. Mathematical models were derived for each phenomenon and combined to simulate the chromatographic reactor. The phenomena studied includes phase equilibria in multicomponent liquid mixture¿ion-exchange resin systems, chemicalequilibrium in the presence of a resin catalyst, diffusion of liquids in gel-type and macroporous resins, and chemical reaction kinetics. Above all, attention was paid to the swelling behavior of the resins and how it affects the kinetic phenomena. Several poly(styrene-co-divinylbenzene) resins with different cross-link densities and internal porosities were used. Esterification of acetic acid with ethanol to produce ethyl acetate and water was used as a model reaction system. Choosing an ion-exchange resin with a low cross-link density is beneficial inthe case of the present reaction system: the amount of ethyl acetate as well the ethyl acetate to water mole ratio in the effluent stream increase with decreasing cross-link density. The enhanced performance of the reactor is mainly attributed to increasing reaction rate, which in turn originates from the phase equilibrium behavior of the system. Also mass transfer considerations favor the use ofresins with low cross-link density. The diffusion coefficients of liquids in the gel-type ion-exchange resins were found to fall rapidly when the extent of swelling became low. Glass transition of the polymer was not found to significantlyretard the diffusion in sulfonated PS¿DVB ion-exchange resins. It was also shown that non-isothermal operation of a chromatographic reactor could be used to significantly enhance the reactor performance. In the case of the exothermic modelreaction system and a near-adiabatic column, a positive thermal wave (higher temperature than in the initial state) was found to travel together with the reactive front. This further increased the conversion of the reactants. Diffusion-induced volume changes of the ion-exchange resins were studied in a flow-through cell. It was shown that describing the swelling and shrinking kinetics of the particles calls for a mass transfer model that explicitly includes the limited expansibility of the polymer network. A good description of the process was obtained by combining the generalized Maxwell-Stefan approach and an activity model that was derived from the thermodynamics of polymer solutions and gels. The swelling pressure in the resin phase was evaluated by using a non-Gaussian expression forthe polymer chain length distribution. Dimensional changes of the resin particles necessitate the use of non-standard mathematical tools for dynamic simulations. A transformed coordinate system, where the mass of the polymer was used as a spatial variable, was applied when simulating the chromatographic reactor columns as well as the swelling and shrinking kinetics of the resin particles. Shrinking of the particles in a column leads to formation of dead volume on top of the resin bed. In ordinary Eulerian coordinates, this results in a moving discontinuity that in turn causes numerical difficulties in the solution of the PDE system. The motion of the discontinuity was eliminated by spanning two calculation grids in the column that overlapped at the top of the resin bed. The reactive and non-reactive phase equilibrium data were correlated with a model derived from thethermodynamics of polymer solution and gels. The thermodynamic approach used inthis work is best suited at high degrees of swelling because the polymer matrixmay be in the glassy state when the extent of swelling is low.

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Parastomal hernia (PSH) is the most frequent long-term stoma complication with serious negative effects on quality of life. Surgical revision is often required and has a substantial morbidity and recurrence rate. The development of PSH requires revisional surgery with a substantial perioperative morbidity and high failure rate in the long-term follow-up. Prophylactic parastomal mesh insertion during stoma creation has the potential to reduce the rate of PSH, but carries the risk of early and late mesh-related complications such as infection, fibrosis, mesh shrinkage, and/or bowel erosion. We developed a new stomaplasty ring (KORING), which is easy to implant, avoids potential mesh-related complications, and has a high potential of long-term prevention of PSH. Here we describe the technique and the first use.

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Aim: One standard option in the treatment of stage IIIA/N2 NSCLC is neoadjuvant chemotherapy followed by surgery. We investigated in a randomized trial whether the addition of neoadjuvant radiotherapy would improve the outcome. Here we present the final results of this study. Methods: Patients (pts.) with pathologically proven, resectable stage IIIA/N2 NSCLC, performance status 0-1, and adequate organ function were randomized 1:1 to chemoradiation (CRT) with 3 cycles of neoadjuvant chemotherapy (cisplatin 100 mg/m2 and docetaxel 85 mg/m2 d1, q3weeks) followed by accelerated concomitant boost radiotherapy (RT) with 44 Gy in 22 fractions in 3 weeks, or neoadjuvant chemotherapy alone (CT), with subsequent surgery for all pts. The primary endpoint was event-free survival (EFS). Results: 232 pts. were randomized in 23 centers, the median follow-up was 53 months. Two thirds were men, median age was 60 years (range 37-76). Histology was squamous cell in 33%, adenocarcinoma in 43%. Response rate to CRT was 61% vs. 44% with CT. 85% of all pts. underwent surgery, 30-day postoperative mortality was 1%. The rate of complete resection was 91% (CRT) vs. 81% (CT) and the pathological complete remission (pCR) rate was 16% vs. 12%. The median EFS was 13.1 months (95% CI 9.9 - 23.5) for the CRT group vs. 11.8 months (95% CI 8.4 - 15.2) in the CT arm (p 0.665). The median overall survival (OS) with CRT was 37.1 months (95% CI 22.6 -50), with CT 26.1 months ( 95% CI 26.1 - 52.1, p 0.938). The local failure rate was 23% in both arms. In the CT arm 12 pts. were given postoperative radiotherapy (PORT) for R1 resection, 6 pts. received PORT in violation of the protocol. Pts. with a pCR, mediastinal downstaging to ypN0/1 and complete resection had a better outcome. Toxicity of chemotherapy was substantial, especially febrile neutropenia was common, whereas RT was well tolerated. Conclusions: This is the first completed phase III trial to evaluate the role of induction chemoradiotherapy and surgery, in comparison to neoadjuvant CT alone followed by surgery. RT was active, it increased response, complete resection and pCR rates. However, this failed to translate into an improvement of local control, EFS or OS. Notably, surgery after induction treatment was safe, including pneumonectomy. The overall survival rates of our neoadjuvant regimen are very encouraging, especially for a multicenter setting. Disclosure: M. Pless: Advisory Board for Sanofi; R. Cathomas: Advisory Board Sanofi D.C. Betticher: Advisory Board Sanofi. All other authors have declared no conflicts of interest.

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Sähkönsiirtoyritysten kunnossapidon taloudellinen malli eli SKUTMA, on sähköverkkoyhtiöille suunniteltu luotettavuuspohjainen kunnossapitomalli, mikä priorisoi ja ajoittaa sähkönjakeluverkon komponenttien huolto- ja investointiajankohdat. Malli hyödyntää dynaamisen optimoinnin algoritmia kustannusminimien löytämiseksi tarkastelujaksolta ja simuloi komponenttien rappeutumasta rappeutumismallin avulla. Tässä diplomityössä on kehitetty kunnossapito-ohjelma SKUTMA-mallin pohjalta, minkä avulla tutkitaan mallin toimivuutta oikeilla johtolähdöillä ja sen hyödyntämistä sähköverkkojen kunnossapidon suunnittelussa. Työssä käydään läpi myös kunnossapitoohjelman laskenta metodiikkaa ja sen ominaisuuksia. Tämän työn lopputuloksena saadaan selkeä kuva mallin toiminnasta, käytettävyydestä ja jatkokehityspotentiaalista.

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It is widely recognized that pharmacokinetic optimization needs to be addressed early in drug discovery to reduce the high failure rate in bringing drugs to market. Poor absorption, too short duration of action due to high elimination rate, or the presence of active metabolites are examples of properties that can potentially lead to unsuccessful clinical programmes. Here I describe a brief overview of advantages and molecular strategies for improving metabolic and pharmacokinetic properties applied to the discovery of fluconazol, beta-blockers, ritonavir and ezetimibe and to the development of the prodrugs enalapril and bambuterol.

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The maintenance of electric distribution network is a topical question for distribution system operators because of increasing significance of failure costs. In this dissertation the maintenance practices of the distribution system operators are analyzed and a theory for scheduling maintenance activities and reinvestment of distribution components is created. The scheduling is based on the deterioration of components and the increasing failure rates due to aging. The dynamic programming algorithm is used as a solving method to maintenance problem which is caused by the increasing failure rates of the network. The other impacts of network maintenance like environmental and regulation reasons are not included to the scope of this thesis. Further the tree trimming of the corridors and the major disturbance of the network are not included to the problem optimized in this thesis. For optimizing, four dynamic programming models are presented and the models are tested. Programming is made in VBA-language to the computer. For testing two different kinds of test networks are used. Because electric distribution system operators want to operate with bigger component groups, optimal timing for component groups is also analyzed. A maintenance software package is created to apply the presented theories in practice. An overview of the program is presented.

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In photosynthesis, light energy is converted to chemical energy, which is consumed for carbon assimilation in the Calvin-Benson-Bassham (CBB) cycle. Intensive research has significantly advanced the understanding of how photosynthesis can survive in the ever-changing light conditions. However, precise details concerning the dynamic regulation of photosynthetic processes have remained elusive. The aim of my thesis was to specify some molecular mechanisms and interactions behind the regulation of photosynthetic reactions under environmental fluctuations. A genetic approach was employed, whereby Arabidopsis thaliana mutants deficient in specific photosynthetic protein components were subjected to adverse light conditions and assessed for functional deficiencies in the photosynthetic machinery. I examined three interconnected mechanisms: (i) auxiliary functions of PsbO1 and PsbO2 isoforms in the oxygen evolving complex of photosystem II (PSII), (ii) the regulatory function of PGR5 in photosynthetic electron transfer and (iii) the involvement of the Calcium Sensing Receptor CaS in photosynthetic performance. Analysis of photosynthetic properties in psbo1 and psbo2 mutants demonstrated that PSII is sensitive to light induced damage when PsbO2, rather than PsbO1, is present in the oxygen evolving complex. PsbO1 stabilizes PSII more efficiently compared to PsbO2 under light stress. However, PsbO2 shows a higher GTPase activity compared to PsbO1, and plants may partially compensate the lack of PsbO1 by increasing the rate of the PSII repair cycle. PGR5 proved vital in the protection of photosystem I (PSI) under fluctuating light conditions. Biophysical characterization of photosynthetic electron transfer reactions revealed that PGR5 regulates linear electron transfer by controlling proton motive force, which is crucial for the induction of the photoprotective non-photochemical quenching and the control of electron flow from PSII to PSI. I conclude that PGR5 controls linear electron transfer to protect PSI against light induced oxidative damage. I also found that PGR5 physically interacts with CaS, which is not needed for photoprotection of PSII or PSI in higher plants. Rather, transcript profiling and quantitative proteomic analysis suggested that CaS is functionally connected with the CBB cycle. This conclusion was supported by lowered amounts of specific calciumregulated CBB enzymes in cas mutant chloroplasts and by slow electron flow to PSI electron acceptors when leaves were reilluminated after an extended dark period. I propose that CaS is required for calcium regulation of the CBB cycle during periods of darkness. Moreover, CaS may also have a regulatory role in the activation of chloroplast ATPase. Through their diverse interactions, components of the photosynthetic machinery ensure optimization of light-driven electron transport and efficient basic production, while minimizing the harm caused by light induced photodamage.

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The ideal therapy for early stages of hemorrhoids is always debated. Some are more effective but are more painful, others are less painful but their efficacy is also lower. Thus, comfort or efficacy is a major concern. In the present randomized study, a comparison is made between infrared coagulation and rubber band ligation in terms of effectiveness and discomfort. One hundred patients with second degree bleeding piles were randomized prospectively to either rubber band ligation (N = 54) or infrared coagulation (N = 46). Parameters measured included postoperative discomfort and pain, time to return to work, relief in incidence of bleeding, and recurrence rate. The mean age was 38 years (range 19-68 years). The mean duration of disease was 17.5 months (range 12 to 34 months). The number of male patients was double that of females. Postoperative pain during the first week was more intense in the band ligation group (2-5 vs 0-3 on a visual analogue scale). Post-defecation pain was more intense with band ligation and so was rectal tenesmus (P = 0.0059). The patients in the infrared coagulation group resumed their duties earlier (2 vs 4 days, P = 0.03), but also had a higher recurrence or failure rate (P = 0.03). Thus, we conclude that band ligation, although more effective in controlling symptoms and obliterating hemorrhoids, is associated with more pain and discomfort to the patient. As infrared coagulation can be conveniently repeated in case of recurrence, it could be considered to be a suitable alternative office procedure for the treatment of early stage hemorrhoids.

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Pregnancy is a physiological condition characterized by a progressive increase of the different components of the renin-angiotensin system (RAS). The physiological consequences of the stimulated RAS in normal pregnancy are incompletely understood, and even less understood is the question of how this system may be altered and contribute to the hypertensive disorders of pregnancy. Findings from our group have provided novel insights into how the RAS may contribute to the physiological condition of pregnancy by showing that pregnancy increases the expression of both the vasodilator heptapeptide of the RAS, angiotensin-(1-7) [Ang-(1-7)], and of a newly cloned angiotensin converting enzyme (ACE) homolog, ACE2, that shows high catalytic efficiency for Ang II metabolism to Ang-(1-7). The discovery of ACE2 adds a new dimension to the complexity of the RAS by providing a new arm that may counter-regulate the activity of the vasoconstrictor component, while amplifying the vasodilator component. The studies reviewed in this article demonstrate that Ang-(1-7) increases in plasma and urine of normal pregnant women. In preeclamptic subjects we showed that plasma Ang-(1-7) was suppressed as compared to the levels found in normal pregnancy. In addition, kidney and urinary levels of Ang-(1-7) were increased in pregnant rats coinciding with the enhanced detection and expression of ACE2. These findings support the concept that in normal pregnancy enhanced ACE2 may counteract the elevation in tissue and circulating Ang II by increasing the rate of conversion to Ang-(1-7). These findings provide a basis for the physiological role of Ang-(1-7) and ACE2 during pregnancy.

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This paper discusses some features of financial institutions and instruments which originated the financial crisis triggered by increasing default rate, household real estate and financial asset depreciation combined with U.S. subprime mortgages. The first part presents major crisis events in a chronological order. The second part describes the interconnection of the institutions and markets which engendered a global shadow financial system. The third part focuses on an overview of measures taken by government authorities and large banks to bring about possible solutions for the global financial crisis.

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The Impact of the Multicolor Asian Lady Beetle (Harmonia axyridis) on Niagara Wine Quality The possible influence of Harmonia axyridis (the Multicolored Asian Lady Beetle) on the sensory properties of wine was investigated. H. axyridis beetles were added to white and red grape musts at a rate of 0, 1 or 10 per L, and a trained panel evaluated the finished wines using flavor-profiling techniques. Significant modification of both wine aroma and flavor characteristics were observed in the 10 beetlelL treatments, with smaller effects noted at the 1 beetlelL rate. Vinification in the presence of H. axyridis gave higher intensity scores for peanut, bell pepper and asparagus aromas and flavors in the white wines, and peanut, asparagus/bell pepper, and earthy/herbaceous aromas and flavors in the red wines. In addition, sweet, acid and bitter tastes were affected in red wines, and a general trend of decreasing fruit and floral intensities with increasing beetle rate was observed in both white and red wines. 15 ngIL Isopropylmethoxypyrazine was added to control wines and sensory profiles similar to high beetle treatments were obtained, supporting the hypothesis that methoxypyrazines from beetles are implicated in the taint. A trained panel evaluated the treated wines after 10 months of aging using the same sensory methods described above. Sensory profiles were very similar. Fennenting in the presence of Harmonia Axyridis (HA) had little influence on the chemical composition of the ftnished wine. The notable exception IS Isopropylmethoxypyrazine content, which was assessed usmg GC-MS analysis and showed increased concentration with increasing beetle nwnber for both white and red wmes. The influence of potential remedial treatments on the sensory properties of white and red wines tainted by Harmonia axyridis were also investigated. Bentonite, activated charcoal, oak chips, de-odorized oak chips, and UV or light irradiation were applied to tainted wine, and these wines evaluated chemically and sensorially. Both white and red wines treated with oak chips had strong oak characteristics, which masked the Harmonia axyridis-associated aroma and flavour attributes. In red wine, asparagus/bell pepper characteristics were decreased by bentonite and charcoal treatments. Only activated charcoal significantly decreased methoxypyrazine levels and only in white wine.