No description available.

<p>  </p> <p><strong>Background: </strong></p> <p>Torsades de pointes (TdP) is a polymorphic ventricular tachycardia (VT) associated with heart rate-corrected QT interval (QTc) prolongation on the electrocardiogram (ECG). TdP can cause sudden cardiac arrest (SCA), a catastrophic outcome. The antiarrhythmic drugs dofetilide and sotalol can cause QTc prolongation and arrhythmias, as can more than 200 other medications available on global markets. Heart failure (HF) with reduced ejection fraction (HFrEF) is a risk factor for drug-induced TdP, and HFrEF heightens sensitivity to drug-induced QTc lengthening. However, ~55% of patients with HF have preserved, rather than reduced, ejection fraction. It remains unknown whether patients with HF with preserved ejection fraction (HFpEF) are at increased risk for drug-induced VT/SCA. Assessment of the risk of drug-induced VT/SCA in HFpEF patients is important, so that recommendations can be made regarding the safety of QTc-prolonging drugs and need for enhanced ECG monitoring in this population. </p> <p><strong>Objective:</strong></p> <p>In aim 1, we sought to determine the risk of VT and SCA associated with dofetilide and sotalol in patients with HFpEF. In aim 2, we were able to use QTc interval to determine the odds of dofetilide/sotalol-associated QT interval prolongation in patients with HFpEF. In Aim 3, we investigated the influence of HFpEF on VT and SCA associated with a broader group of drugs known to cause TdP (“known “TdP drugs”), as designated by the QT drugs list at www.crediblemeds.org. </p> <p><strong>Methods:</strong></p> <p>In aim 1, we used Medicare claims (2014-2016) and ICD-9/10 codes to identify patients taking the QT interval-prolonging drugs dofetilide or sotalol, which are used commonly in patients with HF and atrial fibrillation, as well as non-dofetilide or sotalol users among 3 groups: HFpEF, HFrEF, and no HF. Multinomial propensity score-matching was performed. Cochran–Mantel–Haenszel statistics and standardized differences were used to compare baseline characteristics. A generalized Cox proportional hazards model was used to estimate hazard ratios (HRs) and test the association of VT and SCA among dofetilide/sotalol users, HFpEF, HFrEF, and no HF.</p> <p>In Aim 2, the data source was electronic health records from the Indiana Network for Patient Care (February 2010 to May 2021). After removing patients with overlapping diagnoses of HFpEF and HFrEF, no diagnosis code, absence of QT interval records, and no validated record of using dofetilide or sotalol, we identified patients taking dofetilide or sotalol among three groups: HFrEF, HFpEF, and no HF. Cochran–Mantel–Haenszel statistics were used to compare baseline characteristics. QT interval prolongation was defined as heart rate-corrected QT (QTc) > 500 ms during dofetilide/sotalol therapy. Unadjusted odds ratios (OR) of QT interval prolongation were determined by univariate analysis, and adjusted ORs were determined by generalized estimating equations (GEE) with logit link to account for an individual cluster with different times of hospitalization and covariates.</p> <p>In aim 3, we used Medicare enrollment in fee-for-service medical and pharmacy benefits (2014 to 2016) and ICD-9/10 codes, we identified patients taking drugs known to cause torsades de pointes (TdP drugs; www.crediblemeds.org) and non-TdP drug users among three groups: HFrEF, HFpEF, and no HF. Multinomial propensity score-matching was performed to minimize baseline differences in covariates (patient demographics, comorbidities, health care utilization and drug history). Cochran–Mantel–Haenszel statistics and standardized differences were used to compare baseline characteristics. A generalized Cox proportional hazards model was used to estimate HRs and test the association of VT and SCA among TdP drug users with HFpEF, HFrEF, and no HF.</p> <p><strong>Results:</strong></p> <p>In Aim 1, VT and SCA occurred in 166 (10.68%) and 16 (1.03%), respectively, of 1,554 dofetilide/sotalol users with HFpEF, 543 (38.76%) and 40 (2.86%) of 1,401 dofetilide/sotalol users with HFrEF, and 245 (5.06%) and 13 (0.27%) of 4,839 dofetilide/sotalol users with no HF. The adjusted HR for VT in patients with HFrEF was 7.00 (95% CI 6.12-8.02) and in patients with HFpEF was 1.99 (1.71-2.32). The risk of VT associated with dofetilide/sotalol was increased across the overall study population (HR: 2.47 [1.89-3.23]). Use of dofetilide/sotalol increased the risk of VT in patients with HFrEF (HR: 1.53 [1.07-2.20]) and in those with HFpEF (HR: 2.34 [1.11-4.95]). However, while the overall risk of SCA was increased in patients with HFrEF (HR: 5.19 [4.10-6.57]) and HFpEF (HR: 2.53 [1.98-3.23]) compared to patients with no HF, dofetilide/sotalol use was not significantly associated with an increased risk of SCA.</p> <p>In Aim 2, QTc prolongation associated with dofetilide/sotalol occurred in 51.2% of patients with HFpEF, 70.1% of patients with HFrEF, and 29.4% of patients with no HF. After adjusting for age, sex, race, serum potassium and magnesium concentrations, kidney function, concomitant drug therapy, and comorbid conditions, the adjusted odds of having QTc interval larger than 500ms during the hospital stay were 5.23 [3.15-8.67] for HFrEF and 1.98 [1.17-3.33] for HFpEF with no HF as the reference group. </p> <p>In Aim 3, of 23,910 known TdP drug users with HFrEF, VT and SCA occurred in 4,263 (17.8%) and 493 (2.1%) patients, respectively. In comparison, among 31,359 known TdP drug users with HFpEF, VT and SCA occurred in 1,570 (5.0%) and 340 (1.1%) patients. VT and SCA occurred in 3,154 (0.8%) and 528 (0.1%) of 384,824 known TdP drug users without HF. The overall HR of both VT and SCA was increased in patients with HFrEF (HR: 7.18 [6.13-8.40])  and in those with HFpEF (HR: 2.09 [1.80-2.42]). The risk of VT associated with known TdP drugs was increased across the overall population (HR: 1.34 [1.20-1.51]). Use of known TdP drugs significantly increased the risk of VT and SCA in patients with HFrEF (HR: 1.34 [1.07-1.67]), but not in patients with HFpEF.</p> <p><strong>Conclusion:</strong></p> <p>HFpEF may exhibit an enhanced response to drug-associated VT, and is associated with a higher risk of drug-associated QTc interval prolongation. Further study is needed to identify methods to minimize this risk for patients with HFpEF requiring therapy with dofetilide, sotalol, or drugs known to cause TdP. </p>

Hay una concienciación cada vez mayor de la importancia de diferencias entre los hombres y las mujeres, en edad adulta y preadolescencia, en la fisiología y la patofisiología del sistema cardiovascular. Una de las diferencias más importantes entre los hombres y las mujeres con respecto a sexo y a arritmias es el mayor riesgo en mujeres de una taquicardia ventricular polimórfica, conocida como Torsade de Pointes (TdP), inducida por las drogas que prolongan la repolarización. Además, el género femenino es un factor de riesgo independiente para el síncope y la muerte súbita en el síndrome de QT largo congénito (SQTL), mientras los preadolescentes varones presentan un mayor número de eventos cardiacos cuya letalidad es más alta que en preadolescentes del sexo femenino. En este trabajo se han formulado nuevos modelos computacionales que permiten simular las diferencias relacionadas al sexo y la edad en mamíferos. Los modelos de adulto macho, adulto hembra, preadolescente macho y preadolescente hembra incluyen las características electrofisiológicas de tejidos epicardial, midmiocardial y endocardial haciendo posible la simulación de la heterogeneidad transmural del ventrículo. Se modelizaron los efectos del fármaco antiarrítmico dofetilide con las formulaciones de Hodgkin Huxley y Markov y se simularon la acción de este fármaco en los modelos de adulto macho, adulto hembra, preadolescente macho y preadolescente hembra, tanto en células de cardiomiocitos como células del canal hERG, incluidas tipo wild type y de mutaciones en condiciones normales como en condiciones patológicas. En esta investigación se observó como el dofetilide redujo la componente rápida de la corriente de rectificación tardía produciendo una mayor prolongación en la duración del potencial de acción (APD), incrementando la incidencia de postdepolarizaciones tempranas (EADs) y aumentando la dispersión transmural de repolarización (DOR) en todos los modelos. En base a los resultados en las diferencias r / González Garza, RS. (2011). Diferencias relacionadas al sexo y la edad bajo los efectos de mutaciones y el fármaco Dofetilide [Tesis doctoral]. Editorial Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/11404

La prolongation de l'intervalle QT par les médicaments est un des effets indésirables les plus redoutés par l'industrie pharmaceutique. Ce retard de repolarisation ventriculaire cardiaque peut être précurseur d'arythmies ventriculaires potentiellement mortelles, particulièrement les torsades de pointes (TdP). Plusieurs médicaments de diverses classes pharmacologiques ont été impliqués dans le déclenchement d'arythmies ventriculaires malignes. Afin d'éviter ces effets indésirables des médicaments, il est essentiel de bien comprendre les mécanismes électrophysiologiques et pharmacologiques en cause. Les effets de la palipéridone, de la galantamine, de la tizanidine, de la rosuvastatine et du bupropion sur les courants potassiques rectifiants retardés (IKT et IKS) ainsi que sur la repolarisation ventriculaire cardiaque, ont été évalués à l'aide de trois modèles expérimentaux; la technique de patch-clamp en configuration cellule entière, la rétroperfusion de Langendorff et la télémétrie cardiaque sans fil. De plus, les effets du bupropion sur le courant sodique ont aussi été évalués à l'aide de la technique de patch-clamp en configuration cellule entière puis les effets sur les jonctions communicantes de cette même molécule ont été caractérisés par la technique de redistribution de fluorescence après photoblanchiment (FRAP). Cette étude démontre que l'inhibition du courant potassique rectifiant retardé par la palipéridone, la galantamine, la tizanidine et la rosuvastatine contribue à la prolongation de la repolarisation cardiaque. Elle met aussi en évidence que le bupropion retarde la conduction de l'impulsion d'une cellule cardiaque à l'autre en réduisant le couplage intercellulaire.

Ökologischer Landbau hat insbesondere in den vergangenen zwanzig Jahren weltweit an Bedeutung zugenommen. Im Zusammenhang mit Ernährungssicherung, ressourcenschonender Landwirtschaft und Umweltschutz ist die Entwicklung und Förderung dieses Bewirtschaftungssystems in vielen Ländern der Erde auf der Agenda. Landwirte, Verbraucher und Politiker verbinden damit die Hoffnung, Landnutzung nachhaltiger betreiben zu können und durch die Kenntnis der naturwissenschaftlichen Zusammenhänge, den Umgang mit pflanzlichen und tierischen Organismen in der landwirtschaftlichen Produktion wesensgemäßer gestalten zu können. Gleichzeitig entsprechen sie damit der Forderung von Konsumenten nach gesunden, nicht belasteten Lebensmitteln und einer intakten Umwelt. Obwohl wir weltweit die Einführung und Etablierung des Bewirtschaftungssystems ökologischer Landbau beobachten können, ist festzustellen, dass die Gründe, Wurzeln und Erscheinungsformen in den einzelnen Ländern unterschiedlich sind. Deshalb sind länderspezifische Analysen und Bewertungen notwendige Beiträge zur Theoriebildung zum ökologischen Landbau. In diesen Kontext ist die vorliegende Arbeit zu stellen. Gegenstand der Arbeit war die Analyse des gegenwärtigen Entwicklungsstandes des ökologischen Landbaus in Südkorea in den Bereichen, wie Entwicklungsgeschichte, Konzeptionen, Institutionen, Produktion und Vermarktung sowie Zertifizierung und Förderungspolitik. In einer Fallstudie wurden ausgewählte ökologisch (Yuki)-wirtschaftende Betriebe analysiert. Es werden damit Lösungsansätze zur Weiterentwicklung des ökologischen Landbaus in Südkorea dargestellt. / Organic farming has increased in meaning world-widely in particular in the past two decades. In relation to securing food supply, resource-preserving farming and environmental protection are the development and promotion of this management system in many countries on the agenda. Organic farming made it possible that farmers, consumers and politicians hope to manage land in a sustainable way, and achieve the handling of vegetable and animal organisms in the agricultural production in a suitable way. At the same time it corresponds to the need of con-sumers for healthy, not polluted food and intact environment. Although we can observe the introduction and establishment of the management system of organic farming in many countries, it needs to specify that that the reasons, roots and manifestations of organic farming in each country are different. Therefore, individual analysis and evaluation for each country necessarily contribute to build their own theory of organic farming. This work has to be viewed in this respect. The purpose of this work is to clarify: - the basic conditions of the organic farming in South Korea, - the practical change of organic farming based on the case study of organic rice cultivation and - the ideas for developing strategy of organic farming in South Korea.

Cette thèse est une partie d’un projet français qui s’appelle AEROSTRIP, un partenariat entre l’Institut Pascal, Sigma, SAPPI et Air-France industries, il est financé par le gouvernement français par le programme FUI (20 eme appel). Le projet AEROSTRIP consiste à développer le premier système automatique qui nettoie écologiquement les surfaces des avions et les pièces de rechange en utilisant un abrasif écologique projeté à grande vitesse sur la surface des avions (maïs). Ma thèse consiste à optimiser les trajectoires du système robotique total de telle façon que le décapage de l’avion soit optimal. Le déplacement des robots est nécessaire pour assurer une couverture totale de la surface à décaper parce que ces surfaces sont trop grandes et elles ne peuvent pas être décapées d’une seule position. Le but de mon travail est de trouver le nombre optimal de robots avec leur positions optimales pour décaper totalement l’avion. Une fois ce nombre est déterminé, on cherche les trajectoires des robots entre ces différentes positions. Alors, pour atteindre ce but, j’ai défini un cadre général composant de quatre étapes essentiels: l’étape pre-processing, l’étape optimization algorithm, l’étape generation of the end-effector trajectories et l’étape robot scheduling, assignment and control.Dans ma thèse, j’ai deux contributions dans deux différentes étapes du cadre général: l’étape pre-processing et l’étape optimization algorithm. Le calcul de l’espace de travail du robot est nécessairedans l’étape pre-processing: on a proposé l’Analyse par Intervalles pour trouver cet espace de travail parce qu’il garantie le fait de trouver des solutions dans un temps de calcul raisonnable. Alors, ma première contribution est une nouvelle fonction d’inclusion qui réduit le pessimisme, la surestimation des solutions qui est le principal inconvénient de l’Analyse par Intervalles. La nouvelle fonction d’inclusion est évaluée sur des problèmes de satisfaction de contraintes et des problèmes d’optimisation des contraintes. En plus, on a proposé un algorithme d’optimisation hybride pour trouver le nombre optimal de robots avec leur positions optimales: c’est notre deuxième contribution qui est dans l’étape optimization algorithm. Pour évaluer l’algorithme d’optimisation, on a testé cet algorithme sur des surfaces régulières, comme un cylindre et un hémisphère, et sur un surface complexe: une voiture. / This PHD is a part of a French project named AEROSTRIP, (a partnership between Pascal Institute,Sigma, SAPPI, and Air-France industries), it is funded by the French Government through the FUIProgram (20th call). The AEROSTRIP project aims at developing the first automated system thatecologically cleans the airplanes surfaces using a process of soft projection of ecological media onthe surface (corn). My PHD aims at optimizing the trajectory of the whole robotic systems in orderto optimally strip the airplane. Since a large surface can not be totally covered by a single robot base placement, repositioning of the robots is necessary to ensure a complete stripping of the surface. The goal in this work is to find the optimal number of robots with their optimal positions required to totally strip the air-plane. Once found, we search for the trajectories of the robots of the multi-robot system between those poses. Hence, we define a general framework to solve this problem having four main steps: the pre-processing step, the optimization algorithm step, the generation of the end-effector trajectories step and the robot scheduling, assignment and control step.In my thesis, I present two contributions in two different steps of the general framework: the pre-processing step, the optimization algorithm step. The computation of the robot workspace is required in the pre-processing step: we proposed Interval Analysis to find this workspace since it guarantees finding solutions in a reasonable computation time. Though, our first contribution is a new inclusion function that reduces the pessimism, the overestimation of the solution, which is the main disadvantage of Interval Analysis. The proposed inclusion function is assessed on some Constraints Satisfaction Problems and Constraints Optimization problems. Furthermore, we propose an hybrid optimization algorithm in order to find the optimal number of robots with their optimal poses: it is our second contribution in the optimization algorithm step. To assess our hybrid optimization algorithm, we test the algorithm on regular surfaces, such as a cylinder and a hemisphere, and on a complex surface: a car.

We employ a variant of optical absorption spectroscopy, namely in situ differential reflectance spectroscopy (DRS), for an analysis of the structure-properties relations of thin epitaxial organic films. Clear correlations between the spectra and the differently intense coupling to the respective substrates are found. While rather broad and almost structureless spectra are obtained for a quaterrylene (QT) monolayer on Au(111), the spectral shape resembles that of isolated molecules when QT is grown on graphite. We even achieve an efficient electronic decoupling from the subjacent Au(111) by inserting an atomically thin organic spacer layer consisting of hexa-peri-hexabenzocoronene (HBC) with a noticeably dissimilar electronic behavior. These observations are further consolidated by a systematic variation of the metal substrate (Au, Ag, and Al), ranging from inert to rather reactive. For this purpose, 3,4,9,10-perylenetetracarboxylic dianhydride (PTCDA) is chosen to ensure comparability of the molecular film structures on the different metals, and also because its electronic alignment on various metal surfaces has previously been studied with great intensity. We present evidence for ionized PTCDA at several interfaces and propose the charge transfer to be related to the electronic level alignment governed by interface dipole formation on the respective metals. / Zur Analyse der Struktur-Eigenschafts-Beziehungen dünner, epitaktischer Molekülfilme wird in situ differentielle Reflexionsspektroskopie (DRS) als Variante der optischen Absorptionsspektroskopie verwendet. Klare Zusammenhänge zwischen den Spektren und der unterschiedlich starken Kopplung zum jeweiligen Substrat werden gefunden. Während man breite und beinahe unstrukturierte Spektren für eine Quaterrylen (QT) Monolage auf Au(111) erhält, ist die spektrale Form von auf Graphit abgeschiedenem QT ähnlich der isolierter Moleküle. Durch Einfügen einer atomar dünnen organischen Zwischenschicht bestehend aus Hexa-peri-hexabenzocoronen (HBC) mit einem deutlich unterschiedlichen elektronischen Verhalten gelingt sogar eine effiziente elektronische Entkopplung vom darunter liegenden Au(111). Diese Ergebnisse werden durch systematische Variation der Metallsubstrate (Au, Ag und Al), welche von inert bis sehr reaktiv reichen, untermauert. Zu diesem Zweck wird 3,4,9,10-Perylentetracarbonsäuredianhydrid (PTCDA) gewählt, um Vergleichbarkeit der molekularen Filmstrukturen zu gewährleisten, und weil dessen elektronische Anordnung auf verschiedenen Metalloberflächen bereits eingehend untersucht worden ist. Wir weisen ionisiertes PTCDA an einigen dieser Grenzflächen nach und schlagen vor, dass der Ladungsübergang mit der elektronischen Niveauanpassung zusammenhängt, welche mit der Ausbildung von Grenzflächendipolen auf den entsprechenden Metallen einhergeht.

The goal of this 15 hp thesis in computer engineering was to develop a tool for monitoring and analyzing the data flow on a Controller Area Network (CAN) called Rig Control System (RCS) that is used by Atlas Copco. Atlas Copco develops and manufactures machines for Mining and Rock Excavation. The Rocktec division is responsible for the Rig Control System platform used on machines in all division within the Mining and Rock Excavation Technique (MR) business area. The tool’s primary purpose is monitor and analyze data from the RCS network and present the analyzed data in an easy way to help with development and maintenance of RCS and machines that use RCS. The advantages and how data is sent over the CAN bus are presented as well as the CANopen protocol which is a higher layer protocol based on CAN. Two ways of data acquisition from RCS are presented, a simulated environment and real hardware. Different types of interprocess communication are presented as well as the pros and cons of each of these types. The creation of the tool required a Graphical User Interface (GUI) so different frameworks for this task are also presented and discussed. A version of the tool is presented and discussed in detail. The result of the project is a tool that with further development can be of great use to developers and service engineers working with RCS. / Målet med detta 15 hp examensarbete inom datateknik var att utveckla ett verktyg för att övervaka och analysera dataflödet på ett Controller Area Network (CAN) kallat Rig Control System (RCS) som används av Atlas Copco. Atlas Copco utvecklar och tillverkar maskiner för gruvdrift och bergbrytning. Rocktec-divisionen är ansvarig för Rig Control System-plattformen som används i maskiner från alla avdelningar inom affärsområdet Mining and Rock Excavation Technique (MR). Verktygets primära uppgift är att övervaka och analysera data från RCS-nätverket och presentera den analyserade datan på ett lättöverskådligt sätt för att vara till hjälp vid utveckling och underhåll av RCS och maskiner som använder RCS. Fördelar, hur data skickas över CAN-bussen och även CANopen-protokollet, som är ett högnivåprotokoll baserat på CAN, presenteras. Två olika sätt att samla in data från RCS presenteras, en simulerad miljö och riktig hårdvara. Olika typer av interprocesskommunikation och deras respektive fördelar och nackdelar presenteras. Skapandet av verktyget krävde ett grafiskt användargränssnitt så olika ramverk för denna uppgift presenteras och diskuteras i detalj. Resultatet av projektet är ett verktyg som med vidare utveckling kan vara till stor användning för utvecklare och servicetekniker som arbetar med RCS.

The purpose of this thesis is the proposal of the issue of education software for learning algorithms. Work approach to the problem, both from a theoretical point of view, of education and learning to new things, so and more important from a practical point of view for introduction to the process algorithmization. It also discusses the problem of learning algorithms in Czech schools and describes the resulting program, which was created along with this thesis. Contribution of this thesis is the summary of the requirements for the software and implementing software of this type, where is possible to demonstrate the problems and requirements of the draft programs of this kind. This thesis also describes the reactions of teachers to created application.

This report describes the development process of the mobile application HealthyWay. The application is developed as a Bachelor thesis project together with KTH Royal Institute of Technology. The applications' main function is to be the interface to a number of wearable medical electronic appliances such as bandages and pill boxes. The communication is done through Bluetooth Low Energy. The application was mainly written in 3 di erent languages, QML, C++ and Java. The most stressed point throughout this project was the importance of platform independence. The exibility had to be done on a scalable as well as on a modular level. With this in mind, QT was used to address the requirement of scalability. The modularity was achieved through an organized structure to the program accompanied by easy directives to introduce new devices. The purpose of the application is to increase the quality of life for the user. This intent could however not be concluded due to the lack of testing among users. In its current state, the application is not yet ready for deployment but instead acts as a framework for future prospects. / Den här rapporten beskriver utvecklingsprocessen för en mobilapplikation vid namn Healthy- Way. Applikationen är utvecklad som ett kandidatexamensarbete tillsammans med KTH. Applikationens huvudsakliga uppgift är att vara ett gränssnitt till medicinskt relaterad utrustning såsom plaster och pilleraskar. Kommunikationen mellan dessa sker via Bluetooth Low Energy. Applikationen skrevs huvudsakligen i 3 olika språk, QML, C++ och Java. Den viktigaste punkten genom projektets gång var att applikationen skulle vara oberoende av plattform. Flexibiliteten var tvungen att göras på både en skalbar och modulär nivå. Med detta i åtanke valdes QT för att behandla skalbarheten. Modulariteten uppnåddes genom en välplanerad struktur på programmet tillsammans med instruktioner på hur ny utrustning kan introduceras. Syftet med programmet är att öka livskvaliteten för användaren. Detta syfte kunde däremot inte slutföras på grund av bristande testning hos användare. I dagens läge är applikationen inte redo för att släppas kommersiellt, men tjänar som ett bra ramverk för framtida utveckling.