920 resultados para Analysis failure modes and effects (FMEA)
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We present a systematic study of ground state and spectroscopic properties of many-electron nanoscopic quantum rings. Addition energies at zero magnetic field (B) and electrochemical potentials as a function of B are given for a ring hosting up to 24 electrons. We find discontinuities in the excitation energies of multipole spin and charge density modes, and a coupling between the charge and spin density responses that allow to identify the formation of ferromagnetic ground states in narrow magnetic field regions. These effects can be observed in Raman experiments, and are related to the fractional Aharonov-Bohm oscillations of the energy and of the persistent current in the ring
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Background Medication adherence is a complex, dynamic and changing behaviour that is affected by a variety of factors, including the patient's beliefs and life circumstances. Studies have highlighted barriers to medication adherence (e.g., unmanaged side effects or a lack of social support), as well as facilitators of medication adherence (e.g., technical simplicity of treatment and psychological acceptance of the disease). Since August 2004, in Lausanne (Switzerland), physicians have referred patients who are either experiencing or are at risk of experiencing problems with their HIV antiretroviral treatment (ART) to a routine interdisciplinary ART adherence programme. This programme consists of multifactorial intervention including electronic drug monitoring (MEMS(TM)). Objective This study's objective was to identify the barriers and facilitators encountered by HIV patients with suboptimal medication adherence (≤90 % adherence over the study period). Setting The community pharmacy of the Department of Ambulatory Care and Community Medicine in Lausanne (Switzerland). Method The study consisted of a retrospective, qualitative, thematic content analysis of pharmacists' notes that were taken during semi-structured interviews with patients and conducted as part of the ART adherence programme between August 2004 and May 2008. Main outcome measure Barriers and facilitators encountered by HIV patients. Results Barriers to and facilitators of adherence were identified for the 17 included patients. These factors fell into three main categories: (1) cognitive, emotional and motivational; (2) environmental, organisational and social; and (3) treatment and disease. Conclusion The pharmacists' notes revealed that diverse barriers and facilitators were discussed during medication adherence interviews. Indeed, the results showed that the 17 non-adherent patients encountered barriers and benefited from facilitators. Therefore, pharmacists should inquire about all factors, regardless of whether they have a negative or a positive impact on medication adherence, and should consider all dimensions of patient adherence. The simultaneous strengthening of facilitators and better management of barriers may allow healthcare providers to tailor care to a patient's specific needs and support each individual patient in improving his medication-related behaviour.
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BACKGROUND: Studies on hexaminolevulinate (HAL) cystoscopy report improved detection of bladder tumours. However, recent meta-analyses report conflicting effects on recurrence. OBJECTIVE: To assess available clinical data for blue light (BL) HAL cystoscopy on the detection of Ta/T1 and carcinoma in situ (CIS) tumours, and on tumour recurrence. DESIGN, SETTING, AND PARTICIPANTS: This meta-analysis reviewed raw data from prospective studies on 1345 patients with known or suspected non-muscle-invasive bladder cancer (NMIBC). INTERVENTION: A single application of HAL cystoscopy was used as an adjunct to white light (WL) cystoscopy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We studied the detection of NMIBC (intention to treat [ITT]: n=831; six studies) and recurrence (per protocol: n=634; three studies) up to 1 yr. DerSimonian and Laird's random-effects model was used to obtain pooled relative risks (RRs) and associated 95% confidence intervals (CIs) for outcomes for detection. RESULTS AND LIMITATIONS: BL cystoscopy detected significantly more Ta tumours (14.7%; p<0.001; odds ratio [OR]: 4.898; 95% CI, 1.937-12.390) and CIS lesions (40.8%; p<0.001; OR: 12.372; 95% CI, 6.343-24.133) than WL. There were 24.9% patients with at least one additional Ta/T1 tumour seen with BL (p<0.001), significant also in patients with primary (20.7%; p<0.001) and recurrent cancer (27.7%; p<0.001), and in patients at high risk (27.0%; p<0.001) and intermediate risk (35.7%; p=0.004). In 26.7% of patients, CIS was detected only by BL (p<0.001) and was also significant in patients with primary (28.0%; p<0.001) and recurrent cancer (25.0%; p<0.001). Recurrence rates up to 12 mo were significantly lower overall with BL, 34.5% versus 45.4% (p=0.006; RR: 0.761 [0.627-0.924]), and lower in patients with T1 or CIS (p=0.052; RR: 0.696 [0.482-1.003]), Ta (p=0.040; RR: 0.804 [0.653-0.991]), and in high-risk (p=0.050) and low-risk (p=0.029) subgroups. Some subgroups had too few patients to allow statistically meaningful analysis. Heterogeneity was minimised by the statistical analysis method used. CONCLUSIONS: This meta-analysis confirms that HAL BL cystoscopy significantly improves the detection of bladder tumours leading to a reduction of recurrence at 9-12 mo. The benefit is independent of the level of risk and is evident in patients with Ta, T1, CIS, primary, and recurrent cancer.
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This second section of the first ECCO pathogenesis workshop on anti-TNF therapy failures in inflammatory bowel diseases addresses the biological roles of TNFα and the effects and mechanisms of action of TNFα antagonists. Mechanisms underlying their failure, including induction of TNF-independent inflammatory pathways and phenomena of paradoxical inflammation are discussed.
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This study compared the outcome of total knee replacement (TKR) in adult patients with fixed- and mobile-bearing prostheses during the first post-operative year and at five years' follow-up, using gait parameters as a new objective measure. This double-blind randomised controlled clinical trial included 55 patients with mobile-bearing (n = 26) and fixed-bearing (n = 29) prostheses of the same design, evaluated pre-operatively and post-operatively at six weeks, three months, six months, one year and five years. Each participant undertook two walking trials of 30 m and completed the EuroQol questionnaire, Western Ontario and McMaster Universities osteoarthritis index, Knee Society score, and visual analogue scales for pain and stiffness. Gait analysis was performed using five miniature angular rate sensors mounted on the trunk (sacrum), each thigh and calf. The study population was divided into two groups according to age (≤ 70 years versus > 70 years). Improvements in most gait parameters at five years' follow-up were greater for fixed-bearing TKRs in older patients (> 70 years), and greater for mobile-bearing TKRs in younger patients (≤ 70 years). These findings should be confirmed by an extended age controlled study, as the ideal choice of prosthesis might depend on the age of the patient at the time of surgery.
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Azole resistance in Candida albicans can be mediated by the upregulation of the ATP binding cassette transporter genes CDR1 and CDR2. Both genes are regulated by a cis-acting element called the drug-responsive element (DRE), with the consensus sequence 5'-CGGAWATCGGATATTTTTTT-3', and the transcription factor Tac1p. In order to analyze in detail the DRE sequence necessary for the regulation of CDR1 and CDR2 and properties of TAC1 alleles, a one-hybrid system was designed. This system is based on a P((CDR2))-HIS3 reporter system in which complementation of histidine auxotrophy can be monitored by activation of the reporter system by CDR2-inducing drugs such as estradiol. Our results show that most of the modifications within the DRE, but especially at the level of CGG triplets, strongly reduce CDR2 expression. The CDR2 DRE was replaced by putative DREs deduced from promoters of coregulated genes (CDR1, RTA3, and IFU5). Surprisingly, even if Tac1p was able to bind these putative DREs, as shown by chromatin immunoprecipitation, those from RTA3 and IFU5 did not functionally replace the CDR2 DRE. The one-hybrid system was also used for the identification of gain-of-function (GOF) mutations either in TAC1 alleles from clinical C. albicans isolates or inserted in TAC1 wild-type alleles by random mutagenesis. In all, 17 different GOF mutations were identified at 13 distinct positions. Five of them (G980E, N972D, A736V, T225A, and N977D) have already been described in clinical isolates, and four others (G980W, A736T, N972S, and N972I) occurred at already-described positions, thus suggesting that GOF mutations can occur in a limited number of positions in Tac1p. In conclusion, the one-hybrid system developed here is rapid and powerful and can be used for characterization of cis- and trans-acting elements in C. albicans.
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The aim of this study was to evaluate the reliability of insect larvae as samples for toxicological investigations. For this purpose, larvae of Lucilia sericata were reared on samples of minced pig liver treated with different concentrations of codeine: therapeutic, toxic, and potentially lethal doses. Codeine was detected in all tested larvae, confirming the reliability of these specimens for qualitative toxicology analysis. Furthermore, concentrations measured in larvae were correlated with levels in liver tissue. These observations bring new elements regarding the potential use of opiates concentrations in larvae for estimation of drug levels in human tissues. Morphine and norcodeine, two codeine metabolites, have been also detected at different concentrations depending on the concentration of codeine in pig liver and depending on the substance itself. The effects of codeine on the development of L. sericata were also investigated. Results showed that a 29-h interval bias on the evaluation of the larval stage duration calculated from the larvae weight has to be considered if codeine was present in the larvae substrate. Similarly, a 21-h interval bias on the total duration of development, from egg to imago, has to be considered if codeine was present in the larvae substrate.
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The objective of this work was to identify by biometric analyses the most stable soybean parents, with higher oil or protein contents, cultivated at different seasons and locations of the state of Minas Gerais, Brazil. Forty-nine genotypes were evaluated in the municipalities of Viçosa, Visconde do Rio Branco, and São Gotardo, in the state of Minas Gerais, from 2009 to 2011. Protein and oil contents were analyzed by infrared spectrometry using a FT-NIR analyzer. The effects of genotype, environment, and genotype x environment interaction were significant. The BARC-8 soybean genotype is the best parent to increase protein contents in the progenies, followed by BR 8014887 and CS 3032PTA276-3-4. Selection for high oil content is more efficient when the crossings involve the Suprema, CD 01RR8384, and A7002 genotypes, which show high mean phenotypic values, wide adaptability, and greater stability to environmental variation.
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Les approches multimodales dans l'imagerie cérébrale non invasive sont de plus en plus considérées comme un outil indispensable pour la compréhension des différents aspects de la structure et de la fonction cérébrale. Grâce aux progrès des techniques d'acquisition des images de Resonance Magnetique et aux nouveaux outils pour le traitement des données, il est désormais possible de mesurer plusieurs paramètres sensibles aux différentes caractéristiques des tissues cérébraux. Ces progrès permettent, par exemple, d'étudier les substrats anatomiques qui sont à la base des processus cognitifs ou de discerner au niveau purement structurel les phénomènes dégénératifs et développementaux. Cette thèse met en évidence l'importance de l'utilisation d'une approche multimodale pour étudier les différents aspects de la dynamique cérébrale grâce à l'application de cette approche à deux études cliniques: l'évaluation structurelle et fonctionnelle des effets aigus du cannabis fumé chez des consommateurs réguliers et occasionnels, et l'évaluation de l'intégrité de la substance grise et blanche chez des jeunes porteurs de la prémutations du gène FMR1 à risque de développer le FXTAS (Fragile-X Tremor Ataxia Syndrome). Nous avons montré que chez les fumeurs occasionnels de cannabis, même à faible concentration du principal composant psychoactif (THC) dans le sang, la performance lors d'une tâche visuo-motrice est fortement diminuée, et qu'il y a des changements dans l'activité des trois réseaux cérébraux impliqués dans les processus cognitifs: le réseau de saillance, le réseau du contrôle exécutif, et le réseau actif par défaut (Default Mode). Les sujets ne sont pas en mesure de saisir les saillances dans l'environnement et de focaliser leur attention sur la tâche. L'augmentation de la réponse hémodynamique dans le cortex cingulaire antérieur suggère une augmentation de l'activité introspective. Une investigation des ef¬fets au niveau cérébral d'une exposition prolongée au cannabis, montre des changements persistants de la substance grise dans les régions associées à la mémoire et au traitement des émotions. Le niveau d'atrophie dans ces structures corrèle avec la consommation de cannabis au cours des trois mois précédant l'étude. Dans la deuxième étude, nous démontrons des altérations structurelles des décennies avant l'apparition du syndrome FXTAS chez des sujets jeunes, asymptomatiques, et porteurs de la prémutation du gène FMR1. Les modifications trouvées peuvent être liées à deux mécanismes différents. Les altérations dans le réseau moteur du cervelet et dans la fimbria de l'hippocampe, suggèrent un effet développemental de la prémutation. Elles incluent aussi une atrophie de la substance grise du lobule VI du cervelet et l'altération des propriétés tissulaires de la substance blanche des projections afférentes correspondantes aux pédoncules cérébelleux moyens. Les lésions diffuses de la substance blanche cérébrale peu¬vent être un marquer précoce du développement de la maladie, car elles sont liées à un phénomène dégénératif qui précède l'apparition des symptômes du FXTAS. - Multimodal brain imaging is becoming a leading tool for understanding different aspects of brain structure and function. Thanks to the advances in Magnetic Resonance imaging (MRI) acquisition schemes and data processing techniques, it is now possible to measure different parameters sensitive to different tissue characteristics. This allows for example to investigate anatomical substrates underlying cognitive processing, or to disentangle, at a pure structural level degeneration and developmental processes. This thesis highlights the importance of using a multimodal approach for investigating different aspects of brain dynamics by applying this approach to two clinical studies: functional and structural assessment of the acute effects of cannabis smoking in regular and occasional users, and grey and white matter assessment in young FMR1 premutation carriers at risk of developing FXTAS. We demonstrate that in occasional smokers cannabis smoking, even at low concentration of the main psychoactive component (THC) in the blood, strongly decrease subjects' performance on a visuo-motor tracking task, and globally alters the activity of the three brain networks involved in cognitive processing: the Salience, the Control Executive, and the Default Mode networks. Subjects are unable to capture saliences in the environment and to orient attention to the task; the increase in Hemodynamic Response in the Anterior Cingulate Cortex suggests an increase in self-oriented mental activity. A further investigation on long term exposure to cannabis, shows a persistent grey matter modification in brain regions associated with memory and affective processing. The degree of atrophy in these structures also correlates with the estimation of drug use in the three months prior the participation to the study. In the second study we demonstrate structural changes in young asymptomatic premutation carriers decades before the onset of FXTAS that might be related to two different mechanisms. Alteration of the cerebellar motor network and of the hippocampal fimbria/ fornix, may reflect a potential neurodevelopmental effect of the premutation. These include grey matter atrophy in lobule VI and modification of white matter tissue property in the corresponding afferent projections through the Middle Cerebellar Peduncles. Diffuse hemispheric white matter lesions that seem to appear closer to the onset of FXTAS and be related to a neurodegenerative phenomenon may mark the imminent onset of FXTAS.
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Occupational exposure modeling is widely used in the context of the E.U. regulation on the registration, evaluation, authorization, and restriction of chemicals (REACH). First tier tools, such as European Centre for Ecotoxicology and TOxicology of Chemicals (ECETOC) targeted risk assessment (TRA) or Stoffenmanager, are used to screen a wide range of substances. Those of concern are investigated further using second tier tools, e.g., Advanced REACH Tool (ART). Local sensitivity analysis (SA) methods are used here to determine dominant factors for three models commonly used within the REACH framework: ECETOC TRA v3, Stoffenmanager 4.5, and ART 1.5. Based on the results of the SA, the robustness of the models is assessed. For ECETOC, the process category (PROC) is the most important factor. A failure to identify the correct PROC has severe consequences for the exposure estimate. Stoffenmanager is the most balanced model and decision making uncertainties in one modifying factor are less severe in Stoffenmanager. ART requires a careful evaluation of the decisions in the source compartment since it constitutes ∼75% of the total exposure range, which corresponds to an exposure estimate of 20-22 orders of magnitude. Our results indicate that there is a trade off between accuracy and precision of the models. Previous studies suggested that ART may lead to more accurate results in well-documented exposure situations. However, the choice of the adequate model should ultimately be determined by the quality of the available exposure data: if the practitioner is uncertain concerning two or more decisions in the entry parameters, Stoffenmanager may be more robust than ART.
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Valtion rajat ylittävät terveyspalvelut Euroopan unionissa sekä Euroopan unionin säädösten merkitys ja vaikutus erityisesti lääkejakeluun ja verenluovuttajille jaettavaan tiedotusaineistoon Valtion rajat ylittävä terveydenhuolto on suuren kiinnostuksen kohteena Euroopan unionissa. Resurssien hyödyntäminen parhaalla mahdollisella tavalla ja tiedon keskittäminen ovat tarpeen terveydenhuollon kustannusten alati noustessa. Terveydenhuoltopalvelut kuuluvat Euroopan sisämarkkinoiden vapaan liikkuvuuden piiriin. Euroopan unionilla ei ole kuitenkaan toimivaltaa säädellä terveydenhuoltojärjestelmiä, vaan sen mahdollisuudet ovat enimmäkseen kansanterveyden edistämisessä ja suojelussa, myös muilla toimialueilla kuin terveydenhuollossa. Tutkimuksen tavoitteena oli tutkia Euroopan unionin säädösten vaikutusta terveydenhuoltosektoriin, erityisesti valtion rajat ylittäviin terveydenhuoltopalveluihin. Erityiskohteena olivat lääkemääräyksen toimittaminen toisen Euroopan unionin jäsenmaan apteekista, resepti-lääkkeiden maahantuonti omaan henkilökohtaiseen käyttöön, sähköisen lääkemääräyksen käyttö kansallisesti ja mahdollisuudet sen käyttöön eri jäsenmaiden välillä, online-apteekkien soveltuvuus Euroopan unionin sisämarkkinoille sekä verenluovuttajille jaettavan tiedotusaineiston yhtenäistämistarve Euroopan unionin alueella. Tutkimuksen osa-alueiden aineisto koottiin vuosina 1999–2003, jolloin Euroopan unioniin kuului 15 jäsenmaata. Apteekit toimittivat useimmiten myös ei-kansalliset, toisessa Euroopan unionin jäsenmaassa annetut lääkemääräykset. Kaikki jäsenmaat rajoittivat lääkemääräyksen vaativien lääkkeiden maahantuontia. Rajoituksia oli maahantuontimäärissä ja -tavoissa. Lisäksi sairasvakuutuskorvausten saaminen ulkomailla lunastetuista reseptilääkkeistä oli hankalaa. Sähköiset lääkemääräykset olivat käytössä vain kahdessa maassa, mutta useissa maissa suunniteltiin niiden kokeilua. Standardit ja käyttöjärjestelmät olivat erilaisia eri maissa. Euroopan unionin alueelle on perustettu online-apteekkeja, joiden toiminta on kuitenkin vaatimatonta. Verenluovuttajille annettava tiedotusaineisto ei missään maassa täyttänyt veridirektiivin vaatimuksia. Tutkimuksen tulokset osoittivat kansallisten käytäntöjen eroavaisuuksien rajoittavan valtion rajat ylittäviä terveydenhuoltopalveluita. Vaikka Euroopan unionin tavoitteena ei ole yhtenäistää terveydenhuoltojärjestelmiä, on tarpeen arvioida uudelleen unionin ja jäsenmaiden välistä työnjakoa. Kansalliset terveydenhuoltojärjestelmät eivät ole erillään Euroopan sisämarkkinoista, jotka merkittävästi vaikuttavat terveydenhuoltoon.
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This study aimed to determine the number of measurements necessary to evaluate physical and chemical characteristics of peach fruits, study the relationships between them and their direct and indirect effects on the content of ascorbic acid and total carotenoids. The characteristics skin and pulp color, fruit weight, suture, equatorial and polar diameters, firmness, soluble solids (SS), titratable acidity (TA), SS/TA ratio, ascorbic acid and total carotenoids were evaluated in 39 cultivars of peach and 3 cultivars of nectarine from the orchard of the Universidade Federal de Viçosa. The repeatability coefficient was estimated by ANOVA and CPCOR. Phenotypic correlation coefficients (rf) were estimated and, after the multicollinearity diagnostics, they were unfolded to direct and indirect effects of the explanatory variables on the response variable using path analysis. There was agreement on the magnitude of repeatability coefficients obtained by the two methods; however, they varied among the 14 characteristics. The highest correlations were found between FW, SD, ED and PD. Seven fruits are sufficient to evaluate the physical and chemical characteristics of peach with a correlation coefficient of 90%. The characteristics considered in the path diagrams (b* skin, hº skin, b* pulp, hº pulp, ED, PD, FIR, SS, SS/AT and TC) are not the main determinants of the ascorbic acid. The yellow hue of the pulp (hº pulp) has the potential to be used in indirect selection for total carotenoids.
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Tämän tutkimuksen tarkoituksena on löytää keinoja NCC Rakennus Oy:n hankinta- ja tilausprosessien tehostamiseen. Tutkimuksen kohteena ovat projektikohtaisten hankintojen hankintaprosessi, kausisopimuksiin perustuvat tilausprosessit sekä hankintakäytännöt. Tutkimus on toteutettu laadullisena tapaustutkimuksena ja pääasiallisena aineistonkeruumenetelmänä on käytetty teemahaastatteluita. Teemahaastattelujen avulla on pyritty selvittämään kuinka ihmiset ja järjestelmät toimivat prosesseissa ja tunnistamaan eri prosessivaiheiden mahdollisia ongelmakohtia. Mahdolliset ongelmakohdat ja niiden kehitysehdotukset on tässä tutkimuksessa jäsennetty vika- ja vaikutusanalyysin avulla. Saatujen tulosten mukaan hankinta- ja tilausprosessien tehostaminen vaatii muun muassa yhteisten toimintatapojen rakentamista, koulutusta ja yhteistyön kehittämistä eri sidosryhmien kanssa.
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This thesis considers modeling and analysis of noise and interconnects in onchip communication. Besides transistor count and speed, the capabilities of a modern design are often limited by on-chip communication links. These links typically consist of multiple interconnects that run parallel to each other for long distances between functional or memory blocks. Due to the scaling of technology, the interconnects have considerable electrical parasitics that affect their performance, power dissipation and signal integrity. Furthermore, because of electromagnetic coupling, the interconnects in the link need to be considered as an interacting group instead of as isolated signal paths. There is a need for accurate and computationally effective models in the early stages of the chip design process to assess or optimize issues affecting these interconnects. For this purpose, a set of analytical models is developed for on-chip data links in this thesis. First, a model is proposed for modeling crosstalk and intersymbol interference. The model takes into account the effects of inductance, initial states and bit sequences. Intersymbol interference is shown to affect crosstalk voltage and propagation delay depending on bus throughput and the amount of inductance. Next, a model is proposed for the switching current of a coupled bus. The model is combined with an existing model to evaluate power supply noise. The model is then applied to reduce both functional crosstalk and power supply noise caused by a bus as a trade-off with time. The proposed reduction method is shown to be effective in reducing long-range crosstalk noise. The effects of process variation on encoded signaling are then modeled. In encoded signaling, the input signals to a bus are encoded using additional signaling circuitry. The proposed model includes variation in both the signaling circuitry and in the wires to calculate the total delay variation of a bus. The model is applied to study level-encoded dual-rail and 1-of-4 signaling. In addition to regular voltage-mode and encoded voltage-mode signaling, current-mode signaling is a promising technique for global communication. A model for energy dissipation in RLC current-mode signaling is proposed in the thesis. The energy is derived separately for the driver, wire and receiver termination.
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The aim of the present paper is to study the relationship between the fracture modes in hydrogen-assisted cracking (HAC) in microalloied steel and the emission of acoustic signals during the fracturing process. For this reason, a flux-cored arc weld (FCAW) was used in a high-strength low-alloy steel. The consumable used were the commercially available AWS E120T5-K4 and had a diameter of 1.6 mm. Two different shielding gases were used (CO2 and CO2+5% H2) to obtain complete phenomenon characterization. The implant test was applied with three levels of restriction stresses. An acoustic emission measurement system (AEMS) was coupled to the implant test apparatus. The output signal from the acoustic emission sensor was passed through an electronic amplifier and processed by a root mean square (RMS) voltage converter. Fracture surfaces were examined by scanning electron microscopy (SEM) and image analysis. Fracture modes were related with the intensity, the energy and the number of the peaks of the acoustic emission signal. The shielding gas CO2+5% H2 proved to be very useful in the experiments. Basically, three different fracture modes were identified in terms of fracture appearance: microvoid coalescence (MVC), intergranular (IG) and quasi-cleavage (QC). The results show that each mode of fracture presents a characteristic acoustic signal.