Introduktion: I juli 2012 uppdaterades regelverken för farmakovigilans inom Europa och flera förändringar gjordes i de bestämmelser som rör säkerhetsstudier på godkända läkemedel. En sammanställning av dessa behövdes för att lyfta fram viktiga bestämmelser och ge en tydligare överblick av de myndighetskrav som berör PASS (Post-Authorization Safety Studies) och PSP (Patient Support Programs).   Syfte: Projektet syftar till att analysera och tolka regelverk och riktlinjer gällande PASS och PSP inom Europa samt utreda vad som gäller för PASS i de skandinaviska länderna. Detta för att lyfta fram viktiga bestämmelser och underlätta tolkningen för berörda företag.   Material och metoder: Huvuddelen av projektet bestod av en litteraturstudie där fokus låg på lagar och riktlinjer inom Europa. Informationsinhämtning skedde även genom intervjuer med personal på Bayer AB och Läkemedelsverket. Jämförelser har sedan gjorts mellan svenska, norska och danska regelverk.   Resultat: Myndighetskraven för PASS och PSP skiljer sig åt i vissa avseenden. Etikgodkännande krävs för PASS men inte för PSP och slutrapporten från en PASS granskas av läkemedelsmyndighet medan PSP inte ger någon slutrapport. För PASS krävs i Sverige och Norge ett etikgodkännande vilket inte krävs i Danmark. I Danmark ska dokumentation om studien skickas till läkemedelsmyndigheten om Danmark är referensland eller rapportör för produkten. I Sverige och Norge krävs ingen kommunikation med läkemedelsmyndigheten.   Konklusion: PASS syftar till att studera säkerheten hos läkemedel medan PSP primärt är ett stöd för patientvården i vilket vissa säkerhetsaspekter kan fångas upp sekundärt. Trots att regelverken rörande farmakovigilans gäller för samtliga EU-länder har olika tolkningar gjorts i de skandinaviska länderna och de lokala regelverken skiljer sig åt i vissa avseenden.

Die Progressive Supranukleäre Blickparese (PSP) ist eine sporadisch auftretende neurodegenerative Erkrankung im Rahmen der atypischen Parkinson-Syndrome (APS), die im frühen Verlauf häufig mit dem Idiopathischen Parkinson-Syndrom (IPS) verwechselt wird. Dabei ist die Dysarthrie als eine erworbene, zentral bedingte sprechmotorische Störung ein häufiges und früh auftretendes Symptom bei PSP. Bislang spricht man von einer eher unspezifischen „gemischten“ Dysarthrie aus hypokinetischen, spastischen und auch ataktischen Komponenten. Im Rahmen einer explorativen Querschnittsstudie am „Fachkrankenhaus für Bewegungsstörungen und Parkinson“ Beelitz-Heilstätten in Kooperation mit der „Entwicklungsgruppe Klinische Neuropsychologie“ München (EKN) sowie der „Interdisziplinären Ambulanz für Bewegungsstörungen“ am Klinikum München-Großhadern wurden 50 Patienten dahingehend untersucht, ob sich für die Progressive Supranukleäre Blickparese (PSP) eine spezielle, frühzeitig zu diagnostizierende und differentialdiagnostisch relevante Dysarthrie beschreiben ließe. In diesem Zusammenhang soll geklärt werden, ob es sich um phänotypische Ausprägungen im Rahmen eines Störungsspektrums handelt oder ob sich differenzierbare Subtypen der Krankheit, insbesondere ein „klassischer“ PSP-Typ (PSP-RS) und ein „atypischer“ PSP-Typ (PSP-P), auch im Bereich der Dysarthrie zeigen. Im Rahmen der Untersuchungen wurde der Schweregrad der Erkrankung mittels der „PSP-sensitiven Ratingskala (PSPRS)“ gemessen. Die Dysarthriediagnostik erfolgte anhand der „Bogenhausener Dysarthrieskalen (BoDyS)“ zur Beschreibung der Art und Ausprägung der Dysarthrie bei PSP. Die Verständlichkeit wurde mithilfe des „Münchner Verständlichkeits-Profils (MVP)" sowie eines weiteren Transkriptionsverfahrens ermittelt, wobei Ausschnitte aus den Tests zum Lesen und Nachsprechen der BoDyS zugrunde lagen. Weiterhin erfolgte eine Einschätzung der Natürlichkeit des Sprechens. Die Ergebnisse hinsichtlich des Einflusses von Natürlichkeit und Verständlichkeit des Sprechens auf den Schweregrad der Dysarthrie zeigten, dass dieser modalitätenübergreifend mit beiden Schweregradaspekten korreliert, wenngleich es offenbar die Natürlichkeit des Sprechens ist, die bei PSP bereits frühzeitig beeinträchtigt ist und somit als das entscheidende differentialdiagnostische Kriterium zur Differenzierung zwischen beiden PSP-Subtypen zu beurteilen ist, möglicherweise auch gegenüber anderen Parkinson-Syndromen. Anhand statistisch valider Ergebnisse konnten spezifische Störungsmerkmale der Dysarthrie extrahiert werden, die eine signifikante Trennung von PSP-RS und PSP-P ermöglichen: eine leise und behaucht-heisere Stimme sowie ein verlangsamtes Sprechtempo und Hypernasalität. Damit können für die hier fokussierten Subtypen der PSP zwei unterschiedliche Dysarthrietypen postuliert werden. Danach wird dem Subtyp PSP-RS eine spastisch betonte Dysarthrie mit ausgeprägter Verlangsamung des Sprechtempos zugeordnet, dem Subtyp PSP-P hingegen eine hypokinetische Dysarthrie mit behaucht-heiserer Hypophonie. Desweiteren konnte ein „Dysarthrie-Schwellenwert“ als Zusatzkriterium für eine zeitliche Differenzierung beider PSP-Subtypen ermittelt werden. Anhand der Daten zeigte sich die Dysarthrie bei dem Subtyp PSP-RS gleich zu Beginn der Erkrankung, jedoch spätestens 24 Monate danach. Hingegen konnte die Dysarthrie beim Subtyp PSP-P frühestens 24 Monate nach Erkrankungsbeginn festgestellt werden. Die Daten dieser Studie verdeutlichen, dass der Frage nach einer subtypenspezifischen Ausprägung der Dysarthrie bei PSP eine Längsschnittsstudie folgen sollte, um die ermittelten Ergebnisse zu konsolidieren. / Progressive Supranuclear Palsy (PSP) is an atypical Parkinsonian syndrome characterized by gait ataxia, slowing or inability to generate vertical saccadic eye movements, axial rigidity, cognitive disorders and a progressive dysarthria. The dysarthria may include abnormalities in strength, speed, range, tone or accuracy of speech movements. As the disease progresses, important functional components of speech including respiration, phonation, resonance, articulation and prosody are affected. The question is what kind of dysarthria do we find in PSP? Until now it remains unclear, if the dysarthric characteristics of PSP vary in way as described by Williams et al. (2005) who found clinically distinct symptom patterns of a Parkinsonian form of PSP (PSP-P) distinct from a classical form (Richardson Syndrome). The aim of the cross-sectional multi center study was to investigate the specific dysarthric symptoms in patients with PSP. Until now it remains unclear, whether there are two different points on a continuous spectrum of speech disturbances or if there exist distinct „profiles“ of dysarthria according to the proposed Richardson Syndrome (PSP-RS) with early onset of postural instability and falls, vertical gaze palsy and cognitive dysfunctions and the PSP with Parkinsonism (PSP-P) with asymmetric onset, tremor, early bradykinesia, non-axial dystonia and response to levodopa medications in the beginning. „Bogenhausener Dysarthrieskalen“ (BoDys) was used as base-line dysarthria scale: pitch pattern, loudness range, voice quality, respiration and resonance capacities, prosody and articulation were rated. Furthermore, the intelligibility is a most important index of functional impairment in dysarthria. Therefore, the „Munich Intelligibility Profile (MVP)“, a computer-based method for the assessment of the intelligibility of dysarthric patients, was used to describe the intelligibility of the patients. The PSP-P-group, at the beginning frequently confused with patients with PD, showed rigide-hypokinetic dysarthric features with hypophonia as cardinal symptom. In contrast the patients with the “classical” PSP-RS-Type show severe speech impairments in terms of a very effortful speak with a progressive loss of intelligibility. They show spastic components of dysarthria, like a very strained-strangled voice with breaks and voice stoppages, harshness and reduced pitch and loudness variability. Their loudness often is inadequate in terms of the so called “lions voice”. Further they show a hypernasality, the articulation is imprecise, the vowels are distorted. Concerning the prosody there is a very slow and strained rate of speech with equal or excess stress. The results show that the patients with PSP-RS generally suffer from severe and more progressive speech impairments beginning early after disease onset, whereas the PSP-P-group shows rather moderate symptoms. The dysarthria in PSP is subtype-specific. The hypothesis of different dysarthric profiles for the proposed clinical subtypes "Richardson Syndrome" (PSP-RS) and "PSP with parkinsonism" (PSP-P) was confirmed and based on a discriminant analysis that identified distinctive dysarthric features for both subgroups.

Slaugos magistro baigiamasis darbas Darbo autorė: Aliona Jurgelevič Darbo pavadinimas: Ambulatorinės pagalbos paslaugų kokybė ir prieinamumas Darbo vadovas: Doc., med. dr. Romualdas Gurevičius, VU MF VSI SMS Tyrimo tikslas: ištirti Naujosios Vilnios poliklinikos ambulatorinės pagalbos paslaugų kokybę ir prieinamumą, ypač akcentuojant į slaugos paslaugas ir jų prieinamumą iki poliklinikos reorganizacijos. Tyrimo uždaviniai: &#61656; Išnagrinėti pagrindinius N. Vilnios poliklinikos veiklos našumo rodiklius dinamikoje (nuo 2000 m. iki 2004 m.); &#61656; Įvertinti N. Vilnios poliklinikos paslaugų prieinamumą; &#61656; Įvertinti ambulatorinės pagalbos kokybę; &#61656; Nustatyti N. Vilnios poliklinikos klientų lūkesčius. Tyrimo objektas ir metodika: Pirminės sveikatos priežiūros paslaugų kokybė, pacientų lūkesčiai bei poliklinikos našumo rodiklių kitimas. Tyrimas buvo atliktas N. Vilnios poliklinikoje, kur atsitiktine atranka buvo apklausti 488 nuo 18 metų ir vyresni moteriškos ir vyriškos lyties respondentai, iš jų 476 (97,5%) apklaustieji buvo įtraukti į tyrimą. Apklausai naudojome sukurtą iš dviejų šaltinių bei mūsų papildytą klausimyną, kurį sudarė 44 klausimai. Naujosios Vilnios poliklinikos veiklos našumo rodikliams įvertinti naudojome Harvard Graphics 4.0 paketą bei anketos duomenų analizei naudojome statistinio apdorojimo programą SPSS 11v., skirtumą tarp grupių statistiškai patikimu laikėme, kai P<0,05. Darbo rezultatai: Vertinant poliklinikos veiklos našumo rodiklius... [toliau žr. visą tekstą] / Master’s thesis in Nursing Author of the work: Aliona Jurgelevic Title of the work: Quality of Care and Accessibility of Ambulatory Health Service Research Adviser: Doc., med. Dr. R. Gurevicius, VUMF IPH DSM The objective of the research: to research quality and accessibility of out-patient services rendered in N.Vilnia Polyclinics, by emphasizing nursing services and their accessibility prior to reorganization of the polyclinics. Tasks of the research: To analyze main efficiency indices of N.Vilnia Polyclinic’s activity from 2000 to 2004; To evaluate accessibility of services rendered by N.Vilnia Polyclinics; To assess quality of out-patient services; To determine expectations of N.Vilnia Polyclinic’s clients. The subject and methodology of the research: quality of primary health care services, expectations of clients and change of the Polyclinic’s efficiency indices. The research was carried out at N.Vilnia Polyclinics. 488 respondents, both men and women over 18 year old were surveyed, 476(97,5%) of which were involved in the research. The survey was performed with the help of our supplemented questionnaire, made of two sources and comprising 44 questions. The efficiency indices of N.Vilnia Polyclinic’s activity were assessed using Harvard Graphics 4.0 package. Data of the questionnaire were analyzed with statistical processing program SPSS 11v. and difference among groups was considered reliable, where P<0,05. Results of the research: In the course of assessment of... [to full text]

This thesis is a study of harmonized continuous phase modulation (H-CPM) coupled with receive diversity as applied to mobile radio communication applications. H-CPM is the modulation technique specified by the American Public Safety Communication Official Project 25 (APCO P25) Phase 2 standards, which is focused on public safety applications. Practical implementation of an H-CPM maximum likelihood sequence estimator (MLSE) receiver requires complex reduction techniques to ensure a cost effective form. In addition, it must be able to handle a fast fading environment, which is often encountered in public safety applications. Here, the reduction of receiver complexity and the combating of fast fading situations are investigated via MATLAB simulation. By using tilted phase and frequency pulse truncation techniques, the complexity of an H-CPM MLSE receiver is successfully reduced. In particular, the original 384-state receiver is first reduced to a 192-state receiver through the use of tilted phase. Then it is further reduced to 48-states and finally to 12-states by applying frequency pulse truncation. Simulation, assuming static channels, shows that the bit error rate (BER) performance of a 12-state receiver is essentially identical to that of a 384-state receiver, despite a 97% reduction in computational complexity. To take into account the effects of fading, channel gain estimation via persurvivor processing (PSP) is incorporated into the reduced complexity MLSE receiver. Using a weighted-sum approach to the PSP gain estimates, it was found that at Doppler shifts of 5 Hz, 40 Hz and 80 Hz, the receiver performance was comparable to that obtainable by rival techniques. To further reduce the effect of fading, receive diversity combining was investigated, where a three-antenna diversity scheme is applied to the reduced state PSP-based MLSE receiver. Three different combining techniques, namely selective combining (SC), equal gain combining (EGC) and maximum ratio combining (MRC) were compared. It was found via simulation that the best performance is achieved using MRC, with as much as 14dB improvement achieved by applying triple diversity MRC.

In this study, an experimental investigation was performed to characterize the dynamic stall of pitching wings and provide confirmation of the existence of the arch-shaped vortex for moderate sweep wing. Dynamic stall is a complex flow, which happens because of a sudden change of incident angle during the pitching motion. The pitching motion of a wing can cause instability in the shear layer and generate the separation burst at certain angles. For a pitching wing, the dynamic stall vortex is characterized by the formation of an arch-shaped vortex to the evolution of a ring-shaped vortex. The leg of the arch-shaped vortex causes a negative pressure region on the airfoil surface and can, in fact, generate greater lift. However, in certain conditions, the detachment of the arch-shaped vortex from the airfoil surface can cause high pressure and vibration in the structures. The formation of the arch-shaped vortex and its evolution were systematically investigated using cutting-edge flow diagnostic techniques, and the physics of the dynamic stall is explained in addition to providing the confirmation of the theory developed based on Computational Fluid Dynamics. The study was done using Particle Image Velocimetry (PIV) and Pressure-Sensitive Paint for three sweep angle wings. The wings, with an aspect ratio of AR=4 and a NACA 0012 section assembled with round-tip, are considered for the current experimental study. The sweep angles = 0, 15, and 30 degrees were considered to compare the flow phenomena. The PIV results show the formation of a laminar separation bubble and its evolution to a dynamic stall vortex. The increase of sweep angle causes the formation of such vortices towards the wing tip. In the process of finding the footprint of the vortices and pressure distribution on the surface of the wings, a single-shot lifetime method using fast porous paint was used. The results show the existence of suction pressure and later grows towards the trailing edge of the wing due to the formation of a dynamic stall vortex. In addition, at Re=2x10^5 and reduced frequency k=0.2, a moderate sweep airfoil shows the apparent footprint of the arch-shaped vortex, which confirms the current theory.

A Biologia Computacional tem desenvolvido algoritmos aplicados a problemas relevantes da Biologia. Um desses problemas é a Protein Structure Prediction (PSP). Vários métodos têm sido desenvolvidos na literatura para lidar com esse problema. Porém a reprodução de resultados e a comparação dos mesmos não têm sido uma tarefa fácil. Nesse sentido, o Critical Assessment of protein Structure Prediction (CASP), busca entre seus objetivos, realizar tais comparações. Além disso, os sistemas desenvolvidos para esse problema em geral não possuem interface amigável, não favorecendo o uso por não especialistas da computação. Buscando reduzir essas dificuldades, este trabalho propões o Koala, um sistema baseado em uma plataforma web, que integra vários métodos de predição e análises de estruturas de proteínas, possibilitando a execução de experimentos complexos com o uso de fluxos de trabalhos. Os métodos de predição disponíveis podem ser integrados para a realização de análises dos resultados, usando as métricas RMSD, GDT-TS ou TM-Score. Além disso, o método Sort by front dominance (baseado no critério de optimalidade de Pareto), proposto nesse trabalho, consegue avaliar predições sem uma estrutura de referência. Os resultados obtidos, usando proteínas alvo de artigos recentes e do CASP11, indicam que o Koala tem capacidade de realizar um conjunto relativamente grande de experimentos estruturados, beneficiando a determinação de melhores estruturas de proteínas, bem como o desenvolvimento de novas abordagens para predição e análise por meio de fluxos de trabalho. / Computational Biology has developed algorithms applied to relevant problems from Biology. One of these probems is Protein Structure Prediction (PSP). Several methods have been developed on the liteture to deal with this problem. However, the reproduction of results and the comparison of the methods have not been an easy task. Accordingly, the Critical Assessment of protein Structure Prediction (CASP), has among his objectives, perform these comparisons. Besides, the developed systems for this problem have low usability, not benefiting the investigation of various methods by non experts. In order to minimize those difficulties, this project proposes Koala, a web-based system that integrates several algorithms applied to PSP and analysis, allowing the execution of complex experiments by using workflows. The prediction methods can be integrated to perform some analysis of the results, by using the RMSD, GDT-TS and TM-Score metrics. Moreover, the Sort by front dominance method (based on the criterion of Pareto optimalidad), proposed on this work, can evaluate predictions with no reference structure. The results obtained, using target proteins from recent articles and CASP11, indicate that Koala has the capability to execute a relatively large set of organized experiments, benefiting determining of better protein structures, as well as the development of new approaches for prediction and analysis through workflows.

A Biologia Computacional tem desenvolvido algoritmos aplicados a problemas relevantes da Biologia. Um desses problemas é a Protein Structure Prediction (PSP). Vários métodos têm sido desenvolvidos na literatura para lidar com esse problema. Porém a reprodução de resultados e a comparação dos mesmos não têm sido uma tarefa fácil. Nesse sentido, o Critical Assessment of protein Structure Prediction (CASP), busca entre seus objetivos, realizar tais comparações. Além disso, os sistemas desenvolvidos para esse problema em geral não possuem interface amigável, não favorecendo o uso por não especialistas da computação. Buscando reduzir essas dificuldades, este trabalho propões o Koala, um sistema baseado em uma plataforma web, que integra vários métodos de predição e análises de estruturas de proteínas, possibilitando a execução de experimentos complexos com o uso de fluxos de trabalhos. Os métodos de predição disponíveis podem ser integrados para a realização de análises dos resultados, usando as métricas RMSD, GDT-TS ou TM-Score. Além disso, o método Sort by front dominance (baseado no critério de optimalidade de Pareto), proposto nesse trabalho, consegue avaliar predições sem uma estrutura de referência. Os resultados obtidos, usando proteínas alvo de artigos recentes e do CASP11, indicam que o Koala tem capacidade de realizar um conjunto relativamente grande de experimentos estruturados, beneficiando a determinação de melhores estruturas de proteínas, bem como o desenvolvimento de novas abordagens para predição e análise por meio de fluxos de trabalho. / Computational Biology has developed algorithms applied to relevant problems from Biology. One of these probems is Protein Structure Prediction (PSP). Several methods have been developed on the liteture to deal with this problem. However, the reproduction of results and the comparison of the methods have not been an easy task. Accordingly, the Critical Assessment of protein Structure Prediction (CASP), has among his objectives, perform these comparisons. Besides, the developed systems for this problem have low usability, not benefiting the investigation of various methods by non experts. In order to minimize those difficulties, this project proposes Koala, a web-based system that integrates several algorithms applied to PSP and analysis, allowing the execution of complex experiments by using workflows. The prediction methods can be integrated to perform some analysis of the results, by using the RMSD, GDT-TS and TM-Score metrics. Moreover, the Sort by front dominance method (based on the criterion of Pareto optimalidad), proposed on this work, can evaluate predictions with no reference structure. The results obtained, using target proteins from recent articles and CASP11, indicate that Koala has the capability to execute a relatively large set of organized experiments, benefiting determining of better protein structures, as well as the development of new approaches for prediction and analysis through workflows.

No description available.

Luminescent coating measurement system is a relatively new technology for quantitative pressure and temperature measurement. Usually referred to as Pressure Sensitive Paint (PSP) and Temperature Sensitive Paint (TSP), luminescent coatings contain sensor molecules, which undergoes a luminescent transition when excited with light of proper wavelength. The reaction is pressure and/or temperature sensitive. The image of TSP or PSP coated model surface can be captured with a scientific grade camera and then processed to obtain full field temperature and pressure distribution with very high fidelity. The preparation time of the technique is short. The measurement system offers an economic alternative to conventional testing methods using large number of pressure taps and thermocouples. The purpose of the experiment in this thesis is to take the benefits of the TSP and PSP technique, develop a well-controlled process and then apply the technique for a fundamental study on jet impingement heat transfer. First, Uni-Coat TSP and Binary-FIB PSP purchased from ISSI Inc. are calibrated to high accuracy. The calibration uncertainty of TSP and PSP are found to be ±0.93 °C and ±0.12 psi over temperature and pressure ranges of 22 to 90 ° C and 5 to 14.7 psia, respectively. The photodegradation of TSP is then investigated with the same calibration system. The photodegradation refers to the phenomenon of decreasing emission intensity as the luminescent paint is exposed to the illumination light during testing. It was found that photodegradation rate is a strong function of temperature and the optical power of illumination lighting. The correlation developed in this work is expected to compensate the degradation of TSP to achieve high measurement accuracy. Both TSP and PSP were then applied in the flow and heat transfer measurement of single round impinging air jet. Various separation distance (Z/D) and jet Reynolds number are tested. Pressure measurement on the jet impinged target surface using PSP clearly shows the boundary of jet impingement zone, which broadens with separation distance. In heat transfer experiment using TSP, the "second peak" in local heat transfer occurring at radial distance r/D around 2 is clearly observed when the separation distance Z/D is shorter than the length of jet potential core. The slight variation in radial location and the amplitude of the "second peak" are captured as Z/D and jet Reynolds number change. The optimum Z/D of stagnation point heat transfer is found to be around 5. The effect of jet nozzle configuration is investigated. It is found that the heat transfer rate associated with "tube jet" is generally higher than that of "plate jet". The difference in heat transfer between the two jet configurations is related to the weaker entrainment effect associated with "plate jet", where the entrainment of surrounding air is confined by the injection plate, especially under small Z/D circumstances. When compared with the benchmark data in the literature, the averaged heat transfer data of "tube jet" matches the empirical data better than those of "plate jet". The maximum difference is 3.3% for tube jet versus 15.4% for plate jet at Reynolds number of 60000 and Z/D of 5. The effect of surface roughness on jet impingement heat transfer is also studied. Heat transfer can be significantly increased by the enhanced roughness of the target surface. The largest roughness effect is achieved near stagnation point at high jet Reynolds number. Compared to the heat transfer to a smooth plate, as high as 30.9% increase in area-averaged Nusselt number is observed over a rough surface at r/D=1.5 and jet Reynolds number of 60000. The most significant advance of the present work is that both temperature and pressure measurement be obtained with the same measurement system and with accuracy comparable to traditional testing methods. The procedures that were employed in this work should be easy to apply in any university or industrial testing facility. It provides a rapid testing tool that can help solve complex problems in aerodynamics and heat transfer

No description available.