Angiotensin-(1-7) potentiates the coronary vasodilatatory effect of bradykinin in the isolated rat heart

It has been shown that angiotensin-(1-7) (Ang-(1-7)) infusion potentiates the bradykinin (BK)-induced hypotensive response in conscious rats. The present study was conducted to identify Ang-(1-7)-BK interactions in the isolated rat heart perfused according to the Langendorff technique. Hearts were excised and perfused through the aortic stump under a constant flow with Krebs-Ringer solution and the changes in perfusion pressure and heart contractile force were recorded. Bolus injections of BK (2.5, 5, 10 and 20 ng) produced a dose-dependent hypotensive effect. Ang-(1-7) added to the perfusion solution (2 ng/ml) did not change the perfusion pressure or the contractile force but doubled the hypotensive effect of the lower doses of BK. The BK-potentiating Ang-(1-7) activity was blocked by pretreatment with indomethacin (5 mg/kg, ip) or L-NAME (30 mg/kg, ip). The Ang-(1-7) antagonist A-779 (50 ng/ml in Krebs-Ringer) completely blocked the effect of Ang-(1-7) on BK-induced vasodilation. These data suggest that the potentiation of the BK-induced vasodilation by Ang-(1-7) can be attributed to the release of nitric oxide and vasodilator prostaglandins through an Ang-(1-7) receptor-mediated mechanism.

Adaptive Markov chain Monte Carlo and Bayesian filtering for state space models

This thesis is concerned with the state and parameter estimation in state space models. The estimation of states and parameters is an important task when mathematical modeling is applied to many different application areas such as the global positioning systems, target tracking, navigation, brain imaging, spread of infectious diseases, biological processes, telecommunications, audio signal processing, stochastic optimal control, machine learning, and physical systems. In Bayesian settings, the estimation of states or parameters amounts to computation of the posterior probability density function. Except for a very restricted number of models, it is impossible to compute this density function in a closed form. Hence, we need approximation methods. A state estimation problem involves estimating the states (latent variables) that are not directly observed in the output of the system. In this thesis, we use the Kalman filter, extended Kalman filter, Gauss–Hermite filters, and particle filters to estimate the states based on available measurements. Among these filters, particle filters are numerical methods for approximating the filtering distributions of non-linear non-Gaussian state space models via Monte Carlo. The performance of a particle filter heavily depends on the chosen importance distribution. For instance, inappropriate choice of the importance distribution can lead to the failure of convergence of the particle filter algorithm. In this thesis, we analyze the theoretical Lᵖ particle filter convergence with general importance distributions, where p ≥2 is an integer. A parameter estimation problem is considered with inferring the model parameters from measurements. For high-dimensional complex models, estimation of parameters can be done by Markov chain Monte Carlo (MCMC) methods. In its operation, the MCMC method requires the unnormalized posterior distribution of the parameters and a proposal distribution. In this thesis, we show how the posterior density function of the parameters of a state space model can be computed by filtering based methods, where the states are integrated out. This type of computation is then applied to estimate parameters of stochastic differential equations. Furthermore, we compute the partial derivatives of the log-posterior density function and use the hybrid Monte Carlo and scaled conjugate gradient methods to infer the parameters of stochastic differential equations. The computational efficiency of MCMC methods is highly depend on the chosen proposal distribution. A commonly used proposal distribution is Gaussian. In this kind of proposal, the covariance matrix must be well tuned. To tune it, adaptive MCMC methods can be used. In this thesis, we propose a new way of updating the covariance matrix using the variational Bayesian adaptive Kalman filter algorithm.

Spin Polarization and Normal Reflection at Nanoscale Point Contacts

This thesis presents point-contact measurements between superconductors (Nb, Ta, Sn,Al, Zn) and ferromagnets (Co, Fe, Ni) as well as non-magnetic metals (Ag, Au, Cu, Pt).The point contacts were fabricated using the shear method. The differential resistanceof the contacts was measured either in liquid He at 4.2 K or in vacuum in a dilutionrefrigerator at varying temperature down to 0.1 K. The contact properties were investigatedas function of size and temperature. The measured Andreev-reflection spectrawere analysed in the framework of the BTK model – a three parameter model that describescurrent transport across a superconductor - normal conductor interface. Theoriginal BTK model was modified to include the effects of spin polarization or finitelifetime of the Cooper pairs. Our polarization values for the ferromagnets at 4.2 K agree with the literature data, but the analysis was ambiguous because the experimental spectra both with ferromagnets and non-magnets could be described equally well either with spin polarization or finite lifetime effects in the BTK model. With the polarization model the Z parametervaries from almost 0 to 0.8 while the lifetime model produces Z values close to 0.5. Measurements at lower temperatures partly lift this ambiguity because the magnitude of thermal broadening is small enough to separate lifetime broadening from the polarization. The reduced magnitude of the superconducting anomalies for Zn-Fe contacts required an additional modification of the BTK model which was implemented as a scaling factor. Adding this parameter led to reduced polarization values. However, reliable data is difficult to obtain because different parameter sets produce almost identical spectra.

Valmistavan tehtaan tuotannon tehostaminen reaaliaikaisen tiedon avulla

Teollinen toimintaympäristö on muuttunut globalisaation seurauksena. Sisäisten ja ulkoisten asiakkaiden vaatimukset ovat entistä haastavampia toimitusajan, laadun ja kustannusten suhteen. Yritysten on automatisoitava toimintoja, jotta voidaan saavuttaa kilpailuetua ja parantaa yrityksen tehokkuutta. Diplomityön tarkoitus on kirjallisuus- ja vertailututkimuksen yhteenvetona koostaa asiakasyrityksen tarpeisiin soveltuva toimintomalli reaaliaikaisen tiedon hyödyntä-miseen valmistavan tehtaan tuotannon tehostamisessa. Kirjallisuustutkimusten avulla pyritään analysoimaan valmistavan teollisuuden erityispiirteet toimintaympäristön osalta, kartoittamaan soveltuvin teknologia haastavaan toimintaympäristöön sekä löytää keinot kuinka reaaliaikaista tietoa hyödynnetään tuotannon tehokkuuden toteutumisessa. Vertailututkimuksessa analysoidaan kahta reaaliaikaista tietoa toiminnoissaan hyödyntävää yritystä, joiden tuloksia verrataan kirjallisuustutkimuksen aineistoon. Työn soveltavassa osuudessa luotiin toimintomalli asiakasyrityksen tarpeisiin, huomioiden tehtaan toiminnot kokonaisuutena. Toimintomallin avulla yritys pystyy toteuttamaan reaaliaikaisen tiedon keräämisen sekä hyödyntämisen yrityksen toi-minnoista. Toimintomallin toimivuus todettiin soveltamalla pilot-projekti asiakasyrityksen tuotantoon ja analysoitiin saavutettuja tuloksia haastattelujen sekä kvalitatiivisten tulosten perusteella. Työn tutkimukset osoittivat haasteet valmistavan teollisuuden toimintaympäristön ja automaatioteknologian soveltamisessa. Yritysten tulee suunnitteella toimintamallin kokonaisuus ja pohtia järjestelmän toimivuutta ongelmatilanteissa. Reaaliaikaisen tiedonkeruun soveltaminen onnistuneesti mahdollistaa hyötyjä monella tapaa. Merkittävimmät ovat tehokkuuden kehittyminen toimintojen nopeutumisena sekä resurssisäästöt toimintojen automatisoinnin johdosta. Reaaliaikaista tietoa voidaan hyödyntää myös suorituskyvyn johtamisessa mittariston avulla.

Novel virtual environment and real-time simulation based methods for improving life-cycle efficiency of non-road mobile machinery

Virtual environments and real-time simulators (VERS) are becoming more and more important tools in research and development (R&D) process of non-road mobile machinery (NRMM). The virtual prototyping techniques enable faster and more cost-efficient development of machines compared to use of real life prototypes. High energy efficiency has become an important topic in the world of NRMM because of environmental and economic demands. The objective of this thesis is to develop VERS based methods for research and development of NRMM. A process using VERS for assessing effects of human operators on the life-cycle efficiency of NRMM was developed. Human in the loop simulations are ran using an underground mining loader to study the developed process. The simulations were ran in the virtual environment of the Laboratory of Intelligent Machines of Lappeenranta University of Technology. A physically adequate real-time simulation model of NRMM was shown to be reliable and cost effective in testing of hardware components by the means of hardware-in-the-loop (HIL) simulations. A control interface connecting integrated electro-hydraulic energy converter (IEHEC) with virtual simulation model of log crane was developed. IEHEC consists of a hydraulic pump-motor and an integrated electrical permanent magnet synchronous motorgenerator. The results show that state of the art real-time NRMM simulators are capable to solve factors related to energy consumption and productivity of the NRMM. A significant variation between the test drivers is found. The results show that VERS can be used for assessing human effects on the life-cycle efficiency of NRMM. HIL simulation responses compared to that achieved with conventional simulation method demonstrate the advances and drawbacks of various possible interfaces between the simulator and hardware part of the system under study. Novel ideas for arranging the interface are successfully tested and compared with the more traditional one. The proposed process for assessing the effects of operators on the life-cycle efficiency will be applied for wider group of operators in the future. Driving styles of the operators can be analysed statistically from sufficient large result data. The statistical analysis can find the most life-cycle efficient driving style for the specific environment and machinery. The proposed control interface for HIL simulation need to be further studied. The robustness and the adaptation of the interface in different situations must be verified. The future work will also include studying the suitability of the IEHEC for different working machines using the proposed HIL simulation method.

Tuotekustannuslaskennan nykytila ja kustannusseurannan kehittäminen mallimoottoriajattelun avulla

Tutkimuksen tarkoituksena on tutkia globaalin konsernin yhden liiketoimintayksikön tuotekustannuslaskennan nykytilaa. Lisäksi tutkimuksessa selvitetään, miten tuotekohtaista kustannusseurantaa voidaan kehittää mallimoottoriajatuksen avulla. Tutkimus on toteutettu laadullisena case-tutkimuksena yhden organisaation tietojen pohjalta. Teoriaosuuden lähdeaineistot koostuvat pääosin kustannuslaskennan ja -johtamisen perusteoksista ja tieteellisistä artikkeleista. Empiriaosuuden tiedot pohjautuvat haastatteluihin, tietojärjestelmiin ja tutustumiseen organisaatioon. Tutkimuksessa selvisi, että liiketoimintayksikkö ei tällä hetkellä seuraa tuotekohtaisia kustannuksia yksittäisten tuotteiden tasolla. Kustannusseuranta tapahtuu sen sijaan suurempien kokonaisuuksien keskimääräisten kustannuksien tasolla. Tuotekustannuslaskenta on toteutettu perinteiseksi menetelmäksi luokiteltavalla laskentatavalla, jossa välilliset kustannukset kohdistetaan yleiskustannuslisäprosenttien avulla. Tutkimuksen perusteella yleiskustannuksien kohdistamisperusteissa on havaittavissa viitteitä kustannuksien vääristymisestä. Tuotetason kustannuksien seurantaan kehitettiin mallimoottoriajatukseen pohjautuva kustannusmalli, jonka avulla seurataan tarkasti valikoitujen tuotteiden kustannuksien kehittymistä sekä kustannusrakennetta. Mallin avulla voidaan lisätä tuotetason kustannustietoisuutta liiketoimintayksikössä sekä tehdä havaintoja tuotekohtaisten kustannuksien kehityssuunnasta. Mallin kustannustietona käytetään olemassa olevan kustannuslaskentajärjestelmän tietoja. Tästä johtuen mallin kustannustiedoissa on havaittavissa myös viitteitä kustannuksien vääristymisestä.

Analytic evaluation of three-phase short circuit demagnetization and hysteresis loss risk in rotor-surface-magnet Permanent-Magnet Synchronous Machines

Permanent magnet synchronous machines (PMSM) have become widely used in applications because of high efficiency compared to synchronous machines with exciting winding or to induction motors. This feature of PMSM is achieved through the using the permanent magnets (PM) as the main excitation source. The magnetic properties of the PM have significant influence on all the PMSM characteristics. Recent observations of the PM material properties when used in rotating machines revealed that in all PMSMs the magnets do not necessarily operate in the second quadrant of the demagnetization curve which makes the magnets prone to hysteresis losses. Moreover, still no good analytical approach has not been derived for the magnetic flux density distribution along the PM during the different short circuits faults. The main task of this thesis is to derive simple analytical tool which can predict magnetic flux density distribution along the rotor-surface mounted PM in two cases: during normal operating mode and in the worst moment of time from the PM’s point of view of the three phase symmetrical short circuit. The surface mounted PMSMs were selected because of their prevalence and relatively simple construction. The proposed model is based on the combination of two theories: the theory of the magnetic circuit and space vector theory. The comparison of the results in case of the normal operating mode obtained from finite element software with the results calculated with the proposed model shows good accuracy of model in the parts of the PM which are most of all prone to hysteresis losses. The comparison of the results for three phase symmetrical short circuit revealed significant inaccuracy of the proposed model compared with results from finite element software. The analysis of the inaccuracy reasons was provided. The impact on the model of the Carter factor theory and assumption that air have permeability of the PM were analyzed. The propositions for the further model development are presented.

Virtuaaliprototyypin käyttö roottorin dynamiikan analysoinnissa

Työn tavoitteena oli selvittää kaupallisen dynamiikansimulointiohjelmiston so-veltuvuus roottoridynamiikan analysointiin. Työssä keskityttiin erityisesti rootto-rin dynamiikkaan vaikuttavien epäideaalisuuksien mallintamiseen. Simulointitu-losten tarkkuutta selvitettiin mittauksilla. Lisäksi vertailtiin yleiskäyttöisen dyna-miikan simulointiohjelmiston ja roottoridynamiikan erikoisohjelmiston teoriaa. Tutkittava roottori oli paperikoneen putkitela. Telan joustavuus kuvattiin ele-menttimenetelmällä ratkaistujen moodien avulla. Elementtimallissa huomioitiin telan vaipan seinämänpaksuusvaihtelu, joka vaikuttaa telan massa- ja jäykkyysja-kaumaan. Dynamiikkaohjelmistossa mallinnettiin telan tuennasta tulevat herätteet. Dynamiikkaohjelmistona käytettiin ADAMS:ia ja FEM-ohjelmana ANSYS:stä. Tuloksista havaittiin käytetyn menetelmän soveltuvan roottoridynamiikan ana-lysointiin ja roottorin epäideaalisuuksien mallintamiseen. Simulointimallilla saa-tiin esille murtolukukriittiset pyörimisnopeudet ja telan kriittinen pyörimisnopeus vastasi hyvin mittaustuloksia.

Development and Effect Analysis of the Asteri Consultative Auditing Process - Safety and Security Management in Educational Institutions

The Finnish legislation requires for a safe and secure learning environment. However, the comprehensive, risk based safety and security management (SSM) and the management commitment in the implementation and development of the SSM are not mentioned in the legislation. Multiple institutions, operators and researchers have studied and developed safety and security in educational institutions over the past decade. Typically the approach has been fragmented and without bringing up the importance of the comprehensive SSM. The development needs of the safety and security operations in universities have been studied. However, in universities of applied sciences (UASs) and in elementary schools (ESs), the performance level, strengths and weaknesses of the comprehensive SSM have not been studied. The objective of this study was to develop the comprehensive, risk based SSM of educational institutions by developing the new Asteri consultative auditing process and study its effects on auditees. Furthermore, the performance level in the comprehensive SSM in UASs and ESs were studied using Asteri and the TUTOR model developed by the Keski-Uusimaa Department for Rescue Services. In addition, strengths, development needs and differences were identified. In total, 76 educational institutions were audited between the years 2011 and 2014. The study is based on logical empiricism, and an observational applied research design was used. Auditing, observation and an electronic survey were used for data collection. Statistical analysis was used to analyze the collected information. In addition, thematic analysis was used to analyze the development areas of the organizations mentioned by the respondents in the survey. As one of the main contributions, this research presents the new Asteri consultative auditing process. Organizations with low performance levels on the audited subject benefit the most from the Asteri consultative auditing process. Asteri may be usable in many different types of audits, not only in SSM audits. As a new result, this study provides new knowledge on attitudes related to auditing. According to the research findings, auditing may generate negative attitudes and the auditor should take them into account when planning and preparing for audits. Negative attitudes can be compensated by producing added value, objectivity and positivity for the audit and, thus, improve the positive effects of auditing on knowledge and skills. Moreover, as the results of this study shows, auditing safety and security issues do not increase feelings of insecurity, but rather increase feelings of safety and security when using the new Asteri consultative auditing process with the TUTOR model. The results showed that the SSM in the audited UASs was statistically significantly more advanced than that in the audited ESs. However, there is still room for improvement in the ESs and the UASs as the approach to the SSM was fragmented. It can be assumed that the majority of Finnish UASs and ESs do not likely meet the basic level of the comprehensive, risk based the SSM.

Mário Henrique Simonsen e a construção do conceito de inflação inercial

The paper analyzes the contributions of Mário Henrique Simonsen to the construction of the concept of inertial inflation and to its connected literature. Simonsen's curve, in which the idea of inertial inflation was implicit, is analyzed, alongside with the feedback model (modelo de realimentação) and it's shown how Simonsen built a model which considered inflationary inertia, neutralization possibilities and possible problems and costs of stabilization, anticipating many of the issued that guided the debate in the 1980s.

Kierkegaard : the temporality of becoming a self

Introduction In Difference and Repetition, Deleuze compares and contrasts Kierkegaard's and Nietzsche's ideas of repetition. He argues that neither of them really give a representation of repetition. Repetition for them is a sort of selective task: the way in which they determine what is ethical and eternal. With Nietzsche, it is a theater of un belie f. ..... Nietzsche's leading idea is to found the repetition in the etemal return at once on the death of God and the dissolution of the self But it is a quite different alliance in the theater of faith: Kierkegaard dreams of alliance between a God and a self rediscovered. I Repetition plays a theatrical role in their thinking. It allows them to dramatically stage the interplay of various personnae. Deleuze does give a positive account ofKierkegaard's "repetition"; however, he does not think that Kierkegaard works out a philosophical model, or a representation of what repetition is. It is true that in the book Repetition, Constantin Constantius does not clearly and fully work out the concept of repetition, but in Sickness Unto Death, Kierkegaard gives a full explanation of the self and its temporality which can be connected with repetition. When Sickness Unto Death is interpreted according to key passages from Repetition and The Concept of Anxiety, a clear philosophical concept of repetition can be established. In my opinion, Kierkegaard's philosophy is about the task of becoming a self, and I will be attempting to show that he does have a model of the temporality of self-becoming. In Sickness Unto Death, Kierkegaard explains his notions of despair with reference to sin, self, self-becoming, faith, and repetition. Despair is a sickness of the spirit, of the self, and accordingly can take three forms: in despair not to be conscious of having a self (not despair in the strict sense); in despair not to will to be oneself; in despair to will to be oneself2 In relation to this definition, he defines a self as "a relation that relates itself to itself and in relating itself to itself relates to another.''3 Thus, a person is a threefold relationship, and any break in that relationship is despair. Despair takes three forms corresponding to the three aspects of a self s relation to itself Kierkegaard says that a selfis like a house with a basement, a first floor, and a second floor.4 This model of the house, and the concept of the stages on life's way that it illustrates, is central to Kierkegaard's philosophy. This thesis will show how he unpacks this model in many of his writings with different concepts being developed in different texts. His method is to work with the same model in different ways throughout his authorship. He assigns many of the texts to different pseudonyms, but in this thesis we will treat the model and the related concepts as being Kierkegaard's and not only the pseudonyms. This is justified as our thesis will show this modelremains the same throughout Kierkegaard's work, though it is treated in different ways by different pseudonyms. According to Kierkegaard, many people live in only the basement for their entire lives, that is, as aesthetes ("in despair not to be conscious of having a self'). They live in despair of not being conscious of having a self They live in a merely horizontal relation. They want to get what they desire. When they go to the first floor, so to speak, they reflect on themselves and only then do they begin to get a self In this stage, one acquires an ideology of the required and overcomes the strict commands of the desired. The ethical is primarily an obedience to the required whereas the aesthetic is an obedience to desire. In his work Fear and Trembling (Copenhagen: 1843), Johannes de Silentio makes several observations concerning this point. In this book, the author several times allows the desired ideality of esthetics to be shipwrecked on the required ideality of ethics, in order through these collisions to bring to light the religious ideality as the ideality that precisely is the ideality of actuality, and therefore just as desirable as that of esthetics and not as impossible as the ideality of ethics. This is accomplished in such a way that the religious ideality breaks forth in the dialectical leap and in the positive mood - "Behold all things have become new" as well as in the negative mood that is the passion of the absurd to which the concept "repetition" corresponds.s Here one begins to become responsible because one seeks the required ideality; however, the required ideality and the desired ideality become inadequate to the ethical individual. Neither of them satisfy him ("in despair not to will to be oneself'). Then he moves up to the second floor: that is, the mystical region, or the sphere of religiousness (A) ("despair to will to be oneself). Kiericegaard's model of a house, which is connected with the above definition ofdespair, shows us how the self arises through these various stages, and shows the stages of despair as well. On the second floor, we become mystics, or Knights of Infinite Resignation. We are still in despair because we despair ofthe basement and the first floor, however, we can be fiill, free persons only ifwe live on all the floors at the same time. This is a sort of paradoxical fourth stage consisting of all three floors; this is the sphere of true religiousness (religiousness (B)). It is distinguished from religiousness (A) because we can go back and live on all the floors. It is not that there are four floors, but in the fourth stage, we live paradoxically on three at once. Kierkegaard uses this house analogy in order to explain how we become a self through these stages, and to show the various stages of despair. Consequently, I will be explaining self-becoming in relation to despair. It will also be necessary to explain it in relation to faith, for faith is precisely the overcoming of despair. After explaining the becoming of the self in relation to despair and faith, I will then explain its temporality and thereby its repetition. What Kierkegaard calls a formula, Deleuze calls a representation. Unfortunately, Deleuze does not acknowledge Kierkegaard's formula for repetition. As we shall see, Kierkegaard clearly gives a formula for despair, faith, and selfbecoming. When viewed properly, these formulae yield a formula for repetition because when one hasfaith, the basement, firstfloor, and secondfloor become new as one becomes oneself The self is not bound in the eternity ofthe first floor (ethical) or the temporality of the basement (aesthete). I shall now examine the two forms of conscious despair in such a way as to point out also a rise in the consciousness of the nature of despair and in the consciousness that one's state is despair, or, what amounts to the same thing and is the salient point, a rise in the consciousness of the self The opposite to being in despair is to have faith. Therefore, the formula set forth above, which describes a state in which there is not despair at all, is entirely correct, and this formula is also the formula for faMi in ^elating itself to itself and in willing to be itself, the self rests transparently in the power that established it.

Factors affecting DNA uptake by mammalian cells

The ability to introduce DNA and express custom DNA sequences in bacteria opened the door for improvements in a large number of fields including agriculture, pharmacology, medicine, nutrition, etc. The ability to introduce foreign DNA sequences into mammalian cells in an efficient manner would have a large impact on therapeutic applications especially gene therapy. The methods in use today suffer from low efficiencies and sometimes toxicity. In this work a number of factors were evaluated for their effect onONA uptake efficiency. The factors studied included exposure to sublethal concentration of hydrogen peroxide which have been show to lead to destabilisation ofthe lysosomes. These exposures have proven to be very toxic to cells when combined with either the calcium phosphate or the lipofectAMINE® transfection methods. Another factor evaluated was exposure to Electro-Magnetic Fields (EMF). This was fuelled by the fact that EMF have been shown to mediate a number of effects on cell structure and/or physiology. EMF exposure by itself was not sufficient to induce the cells to pick up the DNA, therefore its effect on calcium phosphate and lipofectAMINE® was tested. Although some positive results were obtained, the variability of these results exceeded by far any observed enhancements which discouraged any further work on EMF. Also tested was the possible effect the presence of the cytomegalovirus (CMV) sequence might have on DNA uptake (based on previous results in this lab). It was found that the presence ofCMV in the DNA sequence does not enhance uptake or slow down degradation of the internalised DNA. The final factor tested was the effect of basic amino acids on transfection efficiency. It was found that arginine can enhance DNA uptake by about 170% v/ith calcium phosphate and about 200% with LipofectAMINE®. A model was proposed to explain the effect of arginine as well as the lack of effect from other amino acids.

Improving Performance of Open Access Clinics

Open Access Scheduling has shown great promise in allowing health care practices to provide same-day access, and to match patients with their regular physicians. However, similarly to traditional clinics where appointments are pre-booked, open access clinics are also frustrated with long waits, long idle time and long overtime due to uncertainties such as patient no-shows, variable service time and variable daily demand. These aspects have not been studied previously in an open access setting. This study investigates different management options to improve clinical performance in terms of patient waiting time, doctor idle time and clinic overtime. Other factors studied with a simulation model include client load and placement of pre-booked slots. Results show that a proper panel size is critical to obtain good performance for open access clinics, and that good choices for management options depend on the client load.

Estimation des facteurs de risque de la progression de la scoliose idiopathique de l’adolescence

Cette étude a pour but de tester si l’ajout de variables biomécaniques, telles que celles associées à la morphologie, la posture et l’équilibre, permet d’améliorer l’efficacité à dissocier 29 sujets ayant une scoliose progressive de 45 sujets ayant une scoliose non progressive. Dans une étude rétrospective, un groupe d’apprentissage (Cobb: 27,1±10,6°) a été utilisé avec cinq modèles faisant intervenir des variables cliniques, morphologiques, posturales et d’équilibre et la progression de la scoliose. Un groupe test (Cobb: 14,2±8,3°) a ensuite servit à évaluer les modèles dans une étude prospective. Afin d’établir l’efficacité de l’ajout de variables biomécaniques, le modèle de Lonstein et Carlson (1984) a été utilisé à titre d’étalon de mesures. Le groupe d’apprentissage a été utilisé pour développer quatre modèles de classification. Le modèle sans réduction fut composé de 35 variables tirées de la littérature. Dans le modèle avec réduction, une ANCOVA a servit de méthode de réduction pour passer de 35 à 8 variables et l’analyse par composantes principales a été utilisée pour passer de 35 à 7 variables. Le modèle expert fut composé de huit variables sélectionnées d’après l’expérience clinque. L’analyse discriminante, la régression logistique et l’analyse par composantes principales ont été appliquées afin de classer les sujets comme progressifs ou non progressifs. La régression logistique utilisée avec le modèle sans réduction a présenté l’efficience la plus élevée (0,94), tandis que l’analyse discriminante utilisée avec le modèle expert a montré l’efficience la plus faible (0,87). Ces résultats montrent un lien direct entre un ensemble de paramètres cliniques et biomécaniques et la progression de la scoliose idiopathique. Le groupe test a été utilisé pour appliquer les modèles développés à partir du groupe d’apprentissage. L’efficience la plus élevée (0,89) fut obtenue en utilisant l’analyse discriminante et la régression logistique avec le modèle sans réduction, alors que la plus faible (0,78) fut obtenue en utilisant le modèle de Lonstein et Carlson (1984). Ces valeurs permettent d’avancer que l’ajout de variables biomécaniques aux données cliniques améliore l’efficacité de la dissociation entre des sujets scoliotiques progressifs et non progressifs. Afin de vérifier la précision des modèles, les aires sous les courbes ROC ont été calculées. L’aire sous la courbe ROC la plus importante (0,93) fut obtenue avec l’analyse discriminante utilisée avec le modèle sans réduction, tandis que la plus faible (0,63) fut obtenue avec le modèle de Lonstein et Carlson (1984). Le modèle de Lonstein et Carlson (1984) n’a pu séparer les cas positifs des cas négatifs avec autant de précision que les modèles biomécaniques. L’ajout de variables biomécaniques aux données cliniques a permit d’améliorer l’efficacité de la dissociation entre des sujets scoliotiques progressifs et non progressifs. Ces résultats permettent d’avancer qu’il existe d’autres facteurs que les paramètres cliniques pour identifier les patients à risque de progresser. Une approche basée sur plusieurs types de paramètres tient compte de la nature multifactorielle de la scoliose idiopathique et s’avère probablement mieux adaptée pour en prédire la progression.

Rôle de CD47 dans l’induction de la tolérance in vivo

La tolérance orale permet la modulation de la réponse immunitaire à l’égard des antigènes exogènes présents dans la lumière intestinale. Essentiels à l’établissement d’une relation symbiotique entre le système immunitaire et la flore intestinale, l’induction et le maintien de la tolérance orale reposent sur différents mécanismes immunologiques. Parmi eux, l’induction de cellules T régulatrices par les cellules dendritiques et de mécanismes apoptotiques. Or, la glycoprotéine membranaire CD47 est impliquée, en périphérie, dans ces mécanismes. Cependant, le rôle de CD47 dans la tolérance orale n’est pas connu. À l’aide d’un modèle murin déficient en CD47, nous avons démontré principalement, que l’absence de CD47 est associée à une diminution de 50 % de la proportion de cellules dendrites myéloïdes CD11b+CD103- retrouvées dans les ganglions mésentériques. Suite au transfert adoptif de cellules T antigènes spécifiques dans nos différents modèles expérimentaux, on a, aussi, observé une diminution de 45 % de leur niveau d’activation dans les ganglions mésentériques. Malgré les effets observés, le CD47 n’est pas impliqué dans l’induction d’une réaction de tolérance orale secondaire à l’administration intragastrique de fortes doses d’ovalbumine. Cependant, nous avons démontré que CD47 est impliquée au niveau de la migration des cellules dendritiques de la peau et de certaines sous-populations retrouvées dans les ganglions mésentériques.