Is Favorable Outcome Possible After Prolonged Refractory Status Epilepticus?

When status epilepticus (SE) remains refractory to appropriate therapy, it is associated with high mortality and with substantial morbidity in survivors. Many outcome predictors such as age, seizure type, level of consciousness before treatment, and mostly, etiology, are well-established. A longer duration of SE is often associated with worse outcome, but duration may lose its prognostic value after several hours. Several terms and definitions have been used to describe prolonged, refractory SE, including "malignant SE," "prolonged" SE, and more recently, "super refractory" SE, defined as "SE that has continued or recurred despite 24 hours of general anesthesia (or coma-inducing anticonvulsants)." There are few data available regarding the outcome of prolonged refractory SE, and even fewer for SE remaining refractory to anesthetic drugs. This article reviews reports of outcome after prolonged, refractory, and "super refractory" SE. Most information detailing the clinical outcome of patients surviving these severe illnesses, in which seizures can persist for days or weeks (and especially those concerning "super-refractory" SE) come from case reports and retrospective cohort studies. In many series, prolonged, refractory SE has a mortality of 30% to 50%, and several studies indicate that most survivors have a substantial decline in functional status. Nevertheless, several reports demonstrate that good functional outcome is possible even after several days of SE and coma induction. Treatment of refractory SE should not be withdrawn from younger patients without structural brain damage at presentation solely because of the duration of SE.

Self, mémoire épisodique et narration chez l'enfant de 6 à 9 ans

Le self est une notion polysémique qui fait l'objet d'un consensus relatif dans plusieurs domaines, dont la psychologie du développement. Elle rend compte de la faculté de s'éprouver le même au fil du temps et de distinguer le « je » qui regarde du « moi » regardé. C'est le garant d'un sens de soi plus ou moins cohérent au fil du temps, en dépit des changements qui surviennent au cours de la vie. Le self combine des processus de réflexivité et d'intersubjectivité. Nous en avons analysé trois composantes fonctionnelles : la mémoire de travail, la mémoire épisodique et la narration, à partir d'un protocole expérimental témoignant de son ontogenèse chez des enfants de 6 à 9 ans (n=24 répartis en deux groupes de 6‐7 et 8-9 ans). Nous avons créé le « jeu informatique du lutin » qui propose un parcours semiorienté dans un monde imaginaire. C'est une narration de soi, opérant la mise en sens des temporalités et des espaces auxquels les événements se réfèrent. Deux semaines après cette « aventure », on recueille la narration des souvenirs épisodiques de cette histoire. Nous avons également utilisé un test de mémoire de travail visuospatiale non verbale. Des différences développementales affectent les dimensions narratives de la mémoire de l'épisode du jeu, comme l'efficacité de la mémoire de travail visuospatiale. Ces développements témoignent d'une augmentation de « l'épaisseur temporelle de la conscience» entre 6 et 9 ans. L'épaisseur de la conscience renvoie fondamentalement à la faculté du self de vivre le temps dans une cyclicité incluant le passé, le présent et le futur anticipé. Le développment observé élargit les possibilités de mettre en lien des mémoires et des scénarios futurs, tout comme les mises en sens des relations aux autres et à soi-­même. Self is a polysemic concept of common use in various scientific fields, among which developmental psychology. It accounts for the capacity to maintain the conviction to be « oneself », always the same through circumstances and throughout my life. This important function contributes in maintaining coherence and some sorte of Ariadne's thread in memory. To analyse the ontogeny of the self, we have focused upon three components : working memory, episodic memory and narration in children aged between 6 and 9 years. We used a non verbal working memory task. It was completed by a video game specially designed for our purpose, in which children were engaged in moving an elf in a landscape changing through seasons, in order to deliver a princess from a mischievous wizard. Two weeks after the game, the children had to tell what happened while they moved the elf. It is a self-narrative that creates a link‐up of temporality and spaces to which the events refer. The narrated episode was assessed for its coherence and continuity dimensions. Developmental differences affect the narrative dimensions of the memory of the episode of the game, as the effectiveness of visuospatial working memory. These developments show an increase in "temporal thickness of consciousness" between 6 and 9 years. The thickness of consciousness basically refers to the ability of the self to live in a cyclical time including past, present and anticipated future. The observed development broadens the possibilities to link memories and future scenarios, like setting sense of relations with others and with oneself.

Determinação espectrofotométrica de aspartame em adoçantes por injeção em fluxo usando um reator em fase sólida contendo fosfato de zinco imobilizado

A flow injection spectrophotometric method was developed for determining aspartame in sweeteners. Sample was dissolved in water and 250 µL of the solution was injected into a carrier stream of 5.0 x 10-5 mol L-1 sodium borate solution. The sample flowed through a column (14 cm x 2.0 mm) packed with Zn3(PO4)2 immobilized in a polymeric matrix of polyester resin and Zn(II) ions were released from the solid-phase reactor by formation of the Zn(II)-aspartame complex. The mixture merged with a stream of borate buffer solution (pH 9.0) containing 0.030 % (m/v) alizarin red S and the Zn(II)-alizarin red complex formed was measured spectrophotometrically at 540 nm. The calibration graph for aspartame was linear in the concentration range from 10 to 80 µg mL-1 with a detection limit of 4 µg mL-1 of aspartame. The RSD was 0.3 % for a solution containing 40 µg mL-1 aspartame (n = 10) and seventy results were obtained per hour. The proposed method was applied for determining aspartame in commercial sweeteners.

Determinação espectrofotométrica por injeção em fluxo de paracetamol (acetaminofeno) em formulações farmacêuticas

A flow injection spectrophotometric procedure is proposed for the determination of paracetamol (acetaminophen) in pharmaceutical formulations. Powdered and liquid samples were previously dissolved/diluted in 0.05 mol L-1 hydrochloric acid solution and a volume of 250 µL was injected directly into a carrier stream of this same acid solution, flowing at 2.5 mL min-1. Paracetamol reacts with sodium hypochlorite forming N-acetyl-p-benzoquinoneimine which then reacts with sodium salicylate in sodium hydroxide solution yielding a blue indophenol dye which was measured at 640 nm in the pH range of 9.5-10.0. Paracetamol was determined in pharmaceutical products in the 1.0 to 100.0 mg L-1 (3.3x10-6 a 6.6x10-4 mol L-1) concentration range, with a detection limit of 0.5 mg L-1 (1.6x10-6 mol L-1). The recovery of this analyte in five samples ranged from 98.0 to 103.6 %. The analytical frequency was 80 determinations per hour and the RSDs were less than 1% for paracetamol concentrations of 25.0, 50.0 and 75.0 mg L-1 (n=10). A paired t-test showed that all results obtained for paracetamol in commercial formulations using the proposed flow injection procedure and a spectrophotometric batch procedure agree at the 95% confidence level.

Adsorção de CO2 em peneiras moleculares micro e mesoporosas

Microporous molecular sieves of type Y, Beta, ZSM-5, ZSM-12 and ZSM-35, and mesoporous molecular sieves of type MCM-41 and MCM-48, and these sieves modified with triethanolamine and ethylenediamine were obtained and characterized by XRD, FTIR, TGA and nitrogen adsorption. The adsorption tests were performed by the gravimetric method under a stream of CO2 at ambient temperature and pressure. The adsorbents studied showed maximum adsorption capacity of carbon dioxide in the range of 13.1 to 85.5 mg of CO2 per gram of adsorbent.

Neural mechanisms underlying conscious and unconscious vision. Evidence from event-related potentials and transcranial magnetic stimulation

Vision affords us with the ability to consciously see, and use this information in our behavior. While research has produced a detailed account of the function of the visual system, the neural processes that underlie conscious vision are still debated. One of the aims of the present thesis was to examine the time-course of the neuroelectrical processes that correlate with conscious vision. The second aim was to study the neural basis of unconscious vision, that is, situations where a stimulus that is not consciously perceived nevertheless influences behavior. According to current prevalent models of conscious vision, the activation of visual cortical areas is not, as such, sufficient for consciousness to emerge, although it might be sufficient for unconscious vision. Conscious vision is assumed to require reciprocal communication between cortical areas, but views differ substantially on the extent of this recurrent communication. Visual consciousness has been proposed to emerge from recurrent neural interactions within the visual system, while other models claim that more widespread cortical activation is needed for consciousness. Studies I-III compared models of conscious vision by studying event-related potentials (ERP). ERPs represent the brain’s average electrical response to stimulation. The results support the model that associates conscious vision with activity localized in the ventral visual cortex. The timing of this activity corresponds to an intermediate stage in visual processing. Earlier stages of visual processing may influence what becomes conscious, although these processes do not directly enable visual consciousness. Late processing stages, when more widespread cortical areas are activated, reflect the access to and manipulation of contents of consciousness. Studies IV and V concentrated on unconscious vision. By using transcranial magnetic stimulation (TMS) we show that when early visual cortical processing is disturbed so that subjects fail to consciously perceive visual stimuli, they may nevertheless guess (above chance-level) the location where the visual stimuli were presented. However, the results also suggest that in a similar situation, early visual cortex is necessary for both conscious and unconscious perception of chromatic information (i.e. color). Chromatic information that remains unconscious may influence behavioral responses when activity in visual cortex is not disturbed by TMS. Our results support the view that early stimulus-driven (feedforward) activation may be sufficient for unconscious processing. In conclusion, the results of this thesis support the view that conscious vision is enabled by a series of processing stages. The processes that most closely correlate with conscious vision take place in the ventral visual cortex ~200 ms after stimulus presentation, although preceding time-periods and contributions from other cortical areas such as the parietal cortex are also indispensable. Unconscious vision relies on intact early visual activation, although the location of visual stimulus may be unconsciously resolved even when activity in the early visual cortex is interfered with.

Finnish cleantech SMEs in China: Challenges and solutions

The rapid economic growth in China has resulted in environmental challenges ranging from air pollution to water-related issues. Thus supporting clean technology, or cleantech, that encompasses industries that focus on alternative energy, pollution and recycling, power supplies and conservation has become one of the focal points in the Chinese economic policy for the next decade. Simultaneously, the Finnish government has initiated programs to support the internationalisation of domestic cleantech companies in an attempt to spiral the industry into one of the pillars of Finnish economic growth. This study concentrates on the conjunction of these two themes and studies the challenges faced by Finnish cleantech SMEs in the Chinese market. Consequently, the study answers the following sub questions: 1. What human and financial resource-based challenges do Finnish cleantech SMEs face in the Chinese market and what are their solutions? 2. What knowledge-based challenges do Finnish cleantech SMEs face in the Chinese market and how can these difficulties be resolved? 3. What network-based challenges do Finnish cleantech SMEs face in the Chinese market, how do they relate to the resource- and knowledge-based challenges, and how can these difficulties be resolved? This qualitative study is conducted by analysing four semi structured interviews collected from four Finnish SMEs that operate in China. The findings of the study indicate that in human resources the most important challenges are related to the hiring and retaining of employees. In contrast to extant academic literature results distinguish salary and social status as the main solutions to this challenge. Regarding financial resources it is discovered that cleantech companies enjoy a benign business environment in China and benefit from the Chinese government’s support for cleantech industry. Challenges related to knowledge resources can be grouped into categories with the most interesting knowledge flows being the stream of local market knowledge into to the foreign parent company and the outward flow of manufacturing and business practice information into the target venture. The challenge related to the first flow is gathering relevant information and the main solutions are clustering at the foreign location and hiring knowledge prior to internationalisation. Regarding the second flow the main challenge is related to intellectual property rights and the most interesting solution is the purposeful transformation of explicit knowledge into tacit knowledge. Finally, it is discovered that networks, called guanxi in China, greatly affect the business processes. Within the guanxi system there is the concept of face which was found to affect employee propensity to stay as well as, as a novel academic result, employees’ knowledge sharing intention.

Karboksyylihappojen kromatografinen fraktiointi

Suurin osa alifaattisista karboksyylihapoista tuotetaan nykyään synteettisesti, mutta öljyn hinnan nousu ja ekologisempi ajattelutapa on aiheuttanut kiinnostusta tuottaa näitä karboksyyli- ja hydroksihappoja jatkossa fermentoimalla tai sellun valmistuksen sivuvirtana syntyvästä mustalipeästä. Nykyään mustalipeä poltetaan sellaisenaan soodakattiloissa keittokemikaalien regeneroimiseksi, energiaksi ja sähköksi. Jatkossa mustalipeästä voisi erottaa arvokkaat orgaaniset hapot ennen polttamista. Saadusta happoseoksesta tulisi erottaa yksittäiset alifaattiset karboksyylihapot toisistaan jatkojalostusta varten. Tämän kandidaatintyön tavoitteena oli selvittää, millä kromatografisella erotusmenetelmällä fermentointituotteina ja teollisuuden sivuvirtoina syntyvistä karboksyylihapposeoksista saadaan yksittäiset alifaattiset karboksyylihapot erotettua toisistaan. Mittaukset suoritettiin kolonnilla, jossa hartsipedin halkaisija oli 1,5 cm ja korkeus 15 cm. Kolonnin erototusmateriaaleina kokeiltiin vahvoja ja heikkoja kationinvaihtohartseja, vahvaa anioninvaihtohartsia ja polymeerisiä adsorbentteja. Erotettavaksi happoseokseksi valittiin sitruuna-, viini-, glykoli-, maito- ja etikkahapon seos. Tehokkain erotus saatiin Puroliten valmistamalla Macronet 270:lla, joka on mikrohuokoinen polymeerinen adsorbentti. Macronet 270:lla saatiin erotettua erityisesti viini- ja glykolihappo sitruuna-, maito- ja etikkahaposta. Yksittäisiä happoja ei saatu kuitenkaan kunnolla erotettua. Parhaat koeolosuhteet erotustehokkuuden ja retentioaikojen kannalta saatiin vesieluentin virtausnopeudella 2 mL/min, syöttöpulssin tilavuudella 5 mL ja kolonnin lämpötilassa 75 °C.

Ammatillinen toimijuus työelämän muutosvirrassa

Katja Vähäsantasen väitöskirja Vocational teachers' professional agency in the stream of change (Jyväskylän yliopisto 2013).

Husserl's approach to transcendental intersubjectivity

It is our intention in the course of the development of this thesis to give an account of how intersubjectivity is "eidetically" constituted by means of the application of the phenomenological reduction to our experience in the context of the thought of Edmund Husserl; contrasted with various representative thinkers in what H. Spiegelberg refers to as "the wider scene" of phenomenology. That is to say, we intend to show those structures of both consciousness and the relation which man has to the world which present themselves as the generic conditions for the possibility of overcoming our "radical sol itude" in order that we may gain access to the mental 1 ife of an Other as other human subject. It is clear that in order for us to give expression to these accounts in a coherent manner, along with their relative merits, it will be necessary to develop the common features of any phenomenological theory of consdousness whatever. Therefore, our preliminary inquiry, subordinate to the larger theme, shall be into some of the epistemological results of the application of the phenomenological method used to develop a transcendental theory of consciousness. Inherent in this will be the deliniation of the exigency for making this an lIintentional ll theory. We will then be able to see how itis possible to overcome transcendentally the Other as an object merely given among other merely given objects, and further, how this other is constituted specifically as other ego. The problem of transcendental intersubjectivity and its constitution in experience can be viewed as one of the most compelling, if not the most polemical of issues in phenomenology. To be sure, right from the beginning we are forced to ask a number of questions regarding Husserl's responses to the problem within the context of the methodological genesis of the Cartesian Meditations, and The Crisis of European Sciences and Transcendental Phenomenology. This we do in order to set the stage for amplification. First, we ask, has Husserl lived up to his goal, in this connexion, of an apodictic result? We recall that in his Logos article of 1911 he adminished that previous philosophy does not have at its disposal a merely incomplete and, in particular instances, imperfect doctrinal system; it simply has none whatever. Each and every question is herein controverted, each position is a matter of individual conviction, of the interpretation given byaschool, of a "point of view". 1. Moreover in the same article he writes that his goal is a philosophical system of doctrine that, after the gigantic preparatory work. of generations, really be- . gins from the ground up with a foundation free from doubt and rises up like any skilful construction, wherein stone is set upon store, each as solid as the other, in accord with directive insights. 2. Reflecting upon the fact that he foresaw "preparatory work of generations", we perhaps should not expect that he would claim that his was the last word on the matter of intersubjectivity. Indeed, with 2. 'Edmund Husserl, lIPhilosophy as a Rigorous Science" in Phenomenology and theCrisis6fPhilosophy, trans". with an introduction by Quentin Lauer (New York.: Harper & Row, 1965) pp. 74 .. 5. 2Ibid . pp. 75 .. 6. 3. the relatively small amount of published material by Husserl on the subject we can assume that he himself was not entirely satisfied with his solution. The second question we have is that if the transcendental reduction is to yield the generic and apodictic structures of the relationship of consciousness to its various possible objects, how far can we extend this particular constitutive synthetic function to intersubjectivity where the objects must of necessity always remain delitescent? To be sure, the type of 'object' here to be considered is unlike any other which might appear in the perceptual field. What kind of indubitable evidence will convince us that the characteristic which we label "alter-ego" and which we attribute to an object which appears to resemble another body which we have never, and can never see the whole of (namely, our own bodies), is nothing more than a cleverly contrived automaton? What;s the nature of this peculiar intentional function which enables us to say "you think just as I do"? If phenomenology is to take such great pains to reduce the takenfor- granted, lived, everyday world to an immanent world of pure presentation, we must ask the mode of presentation for transcendent sub .. jectivities. And in the end, we must ask if Husserl's argument is not reducible to a case (however special) of reasoning by analogy, and if so, tf this type of reasoning is not so removed from that from whtch the analogy is made that it would render all transcendental intersubjective understandtng impos'sible? 2. HistoticalandEidetic Priority: The Necessity of Abstraction 4. The problem is not a simple one. What is being sought are the conditions for the poss ibili:ty of experi encing other subjects. More precisely, the question of the possibility of intersubjectivity is the question of the essence of intersubjectivity. What we are seeking is the absolute route from one solitude to another. Inherent in this programme is the ultimate discovery of the meaning of community. That this route needs be lIabstract" requires some explanation. It requires little explanation that we agree with Husserl in the aim of fixing the goal of philosophy on apodictic, unquestionable results. This means that we seek a philosophical approach which is, though, not necessarily free from assumptions, one which examines and makes explicit all assumptions in a thorough manner. It would be helpful at this point to distinguish between lIeidetic ll priority, and JlhistoricallJpriority in order to shed some light on the value, in this context, of an abstraction.3 It is true that intersubjectivity is mundanely an accomplished fact, there havi.ng been so many mi.llions of years for humans to beIt eve in the exi s tence of one another I s abili ty to think as they do. But what we seek is not to study how this proceeded historically, but 3Cf• Maurice Natanson;·TheJburne in 'Self, a Stud in Philoso h and Social Role (Santa Cruz, U. of California Press, 1970 . rather the logical, nay, "psychological" conditions under which this is possible at all. It is therefore irrelevant to the exigesis of this monograph whether or not anyone should shrug his shoulders and mumble IIwhy worry about it, it is always already engaged". By way of an explanation of the value of logical priority, we can find an analogy in the case of language. Certainly the language 5. in a spoken or written form predates the formulation of the appropriate grammar. However, this grammar has a logical priority insofar as it lays out the conditions from which that language exhibits coherence. The act of formulating the grammar is a case of abstraction. The abstraction towards the discovery of the conditions for the poss; bi 1 ity of any experiencing whatever, for which intersubjective experience is a definite case, manifests itself as a sort of "grammar". This "grammar" is like the basic grammar of a language in the sense that these "rulesil are the ~ priori conditions for the possibility of that experience. There is, we shall say, an "eidetic priority", or a generic condition which is the logical antecedent to the taken-forgranted object of experience. In the case of intersubjectivity we readily grant that one may mundanely be aware of fellow-men as fellowmen, but in order to discover how that awareness is possible it is necessary to abstract from the mundane, believed-in experience. This process of abstraction is the paramount issue; the first step, in the search for an apodictic basis for social relations. How then is this abstraction to be accomplished? What is the nature of an abstraction which would permit us an Archimedean point, absolutely grounded, from which we may proceed? The answer can be discovered in an examination of Descartes in the light of Husserl's criticism. 3. The Impulse for Scientific Philosophy. The Method to which it Gives Rise. 6. Foremost in our inquiry is the discovery of a method appropriate to the discovery of our grounding point. For the purposes of our investigations, i.e., that of attempting to give a phenomenological view of the problem of intersubjectivity, it would appear to be of cardinal importance to trace the attempt of philosophy predating Husserl, particularly in the philosophy of Descartes, at founding a truly IIscientific ll philosophy. Paramount in this connexion would be the impulse in the Modern period, as the result of more or less recent discoveries in the natural sciences, to found philosophy upon scientific and mathematical principles. This impulse was intended to culminate in an all-encompassing knowledge which might extend to every realm of possible thought, viz., the universal science ot IIMathexis Universalis ll •4 This was a central issue for Descartes, whose conception of a universal science would include all the possible sciences of man. This inclination towards a science upon which all other sciences might be based waS not to be belittled by Husserl, who would appropriate 4This term, according to Jacab Klein, was first used by Barocius, the translator of Proclus into Latin, to designate the highest mathematical discipline. . 7. it himself in hopes of establishing, for the very first time, philosophy as a "rigorous science". It bears emphasizing that this in fact was the drive for the hardening of the foundations of philosophy, the link between the philosophical projects of Husserl and those of the philosophers of the modern period. Indeed, Husserl owes Descartes quite a debt for indicating the starting place from which to attempt a radical, presupositionless, and therefore scientific philosophy, in order not to begin philosophy anew, but rather for the first time.5 The aim of philosophy for Husserl is the search for apodictic, radical certitude. However while he attempted to locate in experience the type of necessity which is found in mathematics, he wished this necessity to be a function of our life in the world, as opposed to the definition and postulation of an axiomatic method as might be found in the unexpurgated attempts to found philosophy in Descartes. Beyond the necessity which is involved in experiencing the world, Husserl was searching for the certainty of roots, of the conditi'ons which underl ie experience and render it pOssible. Descartes believed that hi~ MeditatiOns had uncovered an absolute ground for knowledge, one founded upon the ineluctable givenness of thinking which is present even when one doubts thinking. Husserl, in acknowledging this procedure is certainly Cartesian, but moves, despite this debt to Descartes, far beyond Cartesian philosophy i.n his phenomenology (and in many respects, closer to home). 5Cf. Husserl, Philosophy as a Rigorous Science, pp. 74ff. 8 But wherein lies this Cartesian jumping off point by which we may vivify our theme? Descartes, through inner reflection, saw that all of his convictions and beliefs about the world were coloured in one way or another by prejudice: ... at the end I feel constrained to reply that there is nothing in a all that I formerly believed to be true, of which I cannot in some measure doubt, and that not merely through want of thought or through levity, but for reasons which are very powerful and maturely considered; so that henceforth I ought not the less carefully to refrain from giving credence to these opinions than to that which is manifestly false, if I desire to arrive at any certainty (in the sciences). 6 Doubts arise regardless of the nature of belief - one can never completely believe what one believes. Therefore, in order to establish absolutely grounded knowledge, which may serve as the basis fora "universal Science", one must use a method by which one may purge oneself of all doubts and thereby gain some radically indubitable insight into knowledge. Such a method, gescartes found, was that, as indicated above by hi,s own words, of II radical doubt" which "forbids in advance any judgemental use of (previous convictions and) which forbids taking any position with regard to their val idi'ty. ,,7 This is the method of the "sceptical epoche ll , the method of doubting all which had heretofor 6Descartes,Meditations on First Philosophy, first Med., (Libera 1 Arts Press, New York, 1954) trans. by L. LaFl eur. pp. 10. 7Husserl ,CrisiS of Eliroeari SCiences and Trariscendental Phenomenology, (Northwestern U. Press, Evanston, 1 7 ,p. 76. 9. been considered as belonging to the world, including the world itself. What then is left over? Via the process of a thorough and all-inclusive doubting, Descartes discovers that the ego which performs the epoche, or "reduction", is excluded from these things which can be doubted, and, in principle provides something which is beyond doubt. Consequently this ego provides an absolute and apodictic starting point for founding scientific philosophy. By way of this abstention. of bel ief, Desca'rtes managed to reduce the worl d of everyday 1 ife as bel ieved in, to mere 'phenomena', components of the rescogitans:. Thus:, having discovered his Archimedean point, the existence of the ego without question, he proceeds to deduce the 'rest' of the world with the aid of innate ideas and the veracity of God. In both Husserl and Descartes the compelling problem is that of establ ishing a scientific, apodictic phi'losophy based upon presuppos itionless groundwork .. Husserl, in thi.s regard, levels the charge at Descartes that the engagement of his method was not complete, such that hi.S: starting place was not indeed presupositionless, and that the validity of both causality and deductive methods were not called into question i.'n the performance of theepoche. In this way it is easy for an absolute evidence to make sure of the ego as: a first, "absolute, indubitablyexisting tag~end of the worldll , and it is then only a matter of inferring the absolute subs.tance and the other substances which belon.g to the world, along with my own mental substance, using a logically val i d deductive procedure. 8 8Husserl, E.;' Cartesian 'Meditation;, trans. Dorion Cairns (Martinus Nijhoff, The Hague, 1970), p. 24 ff.

Oral French Communication in French Immersion Canadian and World Studies Classrooms: A Primer for Educators

This project presents a primer for secondary French Immersion teachers that facilitates the use of French oral communicative activities in secondary Canadian and World Studies courses. The primer supports collaborative and inclusive teaching strategies that invite students to speak and develop their oral French communication skills. The primer is divided into 2 main components: (a) Rationale for the Primer, and (b) the Strategies themselves, comprising succinct descriptions as well as potential uses and suggestions. A critical content analysis of various Ontario Ministry of Education documents was undertaken in order to explore the importance of oral communication in second-language learning in Ontario secondary schools. Furthermore, holistic and invitational education perspectives were examined in order to define the advantages of collaborative learning. Moreover, research in the stream of French Immersion studies was also referenced to frame the relevance of second-language learning and the significant role the French Immersion teacher plays. The aforementioned research contributes to the advancement of theory and practice regarding the importance of opportunities for oral French communication in secondary Canadian and World Studies courses.

Développement d’un système d’administration de l’anesthésie en boucle fermée

En salle d’opération, les tâches de l’anesthésiste sont nombreuses. Alors que l’utilisation de nouveaux outils technologiques l’informe plus fidèlement sur ce qui se passe pour son patient, ces outils font que ses tâches deviennent plus exigeantes. En vue de diminuer cette charge de travail, nous avons considérer l’administration automatique d’agents anesthésiques en se servant de contrôle en boucle fermée. À cette fin, nous avons développé un système d’administration d’un agent anesthésique (le propofol) visant à maintenir à un niveau optimal la perte de conscience du patient pendant toute la durée d’une chirurgie. Le système comprend un ordinateur, un moniteur d’anesthésie et une pompe de perfusion. L’ordinateur est doté d’un algorithme de contrôle qui, à partir d’un indice (Bispectral IndexTM ou BIS) fournit par le moniteur d’anesthésie détermine le taux d’infusion de l’agent anesthésiant. Au départ, l’anesthésiste choisit une valeur cible pour la variable de contrôle BIS et l’algorithme, basé sur système expert, calcule les doses de perfusion de propofol de sorte que la valeur mesurée de BIS se rapproche le plus possible de la valeur cible établie. Comme interface-utilisateur pour un nouveau moniteur d’anesthésie, quatre sortes d’affichage ont été considérés: purement numérique, purement graphique, un mélange entre graphique et numérique et un affichage graphique intégré (soit bidimensionnel). À partir de 20 scenarios différents où des paramètres normaux et anormaux en anesthésie étaient présentés à des anesthésistes et des résidents, l’étude des temps de réaction, de l’exactitude des réponses et de la convivialité (évaluée par le NASA-TLX) a montré qu’un affichage qui combine des éléments graphiques et numériques était le meilleur choix comme interface du système. Une étude clinique a été réalisée pour comparer le comportement du système d’administration de propofol en boucle fermée comparativement à une anesthésie contrôlée de façon manuelle et conventionnelle où le BIS était aussi utilisé. Suite à l’approbation du comité d’éthique et le consentement de personnes ayant à subir des chirurgies générales et orthopédiques, 40 patients ont été distribués également et aléatoirement soit dans le Groupe contrôle, soit dans le Groupe boucle fermée. Après l’induction manuelle de propofol (1.5 mg/kg), le contrôle en boucle fermée a été déclenché pour maintenir l’anesthésie à une cible de BIS fixée à 45. Dans l’autre groupe, le propofol a été administré à l’aide d’une pompe de perfusion et l’anesthésiste avait aussi à garder manuellement l’indice BIS le plus proche possible de 45. En fonction du BIS mesuré, la performance du contrôle exercé a été définie comme excellente pendant les moments où la valeur du BIS mesurée se situait à ±10% de la valeur cible, bonne si comprise de ±10% à ±20%, faible si comprise de ±20% à ±30% ou inadéquate lorsque >±30%. Dans le Groupe boucle fermée, le système a montré un contrôle excellent durant 55% du temps total de l’intervention, un bon contrôle durant 29% du temps et faible que pendant 9% du temps. Le temps depuis l’arrêt de la perfusion jusqu’à l’extubation est de 9 ± 3.7 min. Dans le Groupe contrôle, un contrôle excellent, bon, et faible a été enregistré durant 33%, 33% et 15% du temps respectivement et les doses ont été changées manuellement par l’anesthésiste en moyenne 9.5±4 fois par h. L’extubation a été accomplie après 11.9 ± 3.3 min de l’arrêt de la perfusion. Dans le Groupe boucle fermée, un contrôle excellent a été obtenu plus longtemps au cours des interventions (P<0.0001) et un contrôle inadéquat moins longtemps (P=0.001) que dans le Groupe contrôle. Le système en boucle fermée d’administration de propofol permet donc de maintenir plus facilement l’anesthésie au voisinage d’une cible choisie que l’administration manuelle.

Validation des modèles de pharmacologie de sécurité et évaluation de la valeur thérapeutique de l'oxytocine dans le traitement de l'infarctus du myocarde

En février, 2009 un rapport de PHRMA (Pharmaceutical Research and Manufacturers of America) confirmait que plus de 300 médicaments pour le traitement des maladies cardiaques étaient en phase d’essais cliniques ou en révision par les agences règlementaires. Malgré cette abondance de nouvelles thérapies cardiovasculaires, le nombre de nouveaux médicaments approuvés chaque année (toutes indications confondues) est en déclin avec seulement 17 et 24 nouveaux médicaments approuvés en 2007 et 2008, respectivement. Seulement 1 médicament sur 5000 sera approuvé après 10 à 15 ans de développement au coût moyen de 800 millions $. De nombreuses initiatives ont été lancées par les agences règlementaires afin d’augmenter le taux de succès lors du développement des nouveaux médicaments mais les résultats tardent. Cette stagnation est attribuée au manque d’efficacité du nouveau médicament dans bien des cas mais les évaluations d’innocuité remportent la palme des causes d’arrêt de développement. Primum non nocere, la maxime d’Hippocrate, père de la médecine, demeure d’actualité en développement préclinique et clinique des médicaments. Environ 3% des médicaments approuvés au cours des 20 dernières années ont, par la suite, été retirés du marché suite à l’identification d’effets adverses. Les effets adverses cardiovasculaires représentent la plus fréquente cause d’arrêt de développement ou de retrait de médicament (27%) suivi par les effets sur le système nerveux. Après avoir défini le contexte des évaluations de pharmacologie de sécurité et l’utilisation des bio-marqueurs, nous avons validé des modèles d’évaluation de l’innocuité des nouveaux médicaments sur les systèmes cardiovasculaires, respiratoires et nerveux. Évoluant parmi les contraintes et les défis des programmes de développements des médicaments, nous avons évalué l’efficacité et l’innocuité de l’oxytocine (OT), un peptide endogène à des fins thérapeutiques. L’OT, une hormone historiquement associée à la reproduction, a démontré la capacité d’induire la différentiation in vitro de lignées cellulaires (P19) mais aussi de cellules souches embryonnaires en cardiomyocytes battants. Ces observations nous ont amené à considérer l’utilisation de l’OT dans le traitement de l’infarctus du myocarde. Afin d’arriver à cet objectif ultime, nous avons d’abord évalué la pharmacocinétique de l’OT dans un modèle de rat anesthésié. Ces études ont mis en évidence des caractéristiques uniques de l’OT dont une courte demi-vie et un profil pharmacocinétique non-linéaire en relation avec la dose administrée. Ensuite, nous avons évalué les effets cardiovasculaires de l’OT sur des animaux sains de différentes espèces. En recherche préclinique, l’utilisation de plusieurs espèces ainsi que de différents états (conscients et anesthésiés) est reconnue comme étant une des meilleures approches afin d’accroître la valeur prédictive des résultats obtenus chez les animaux à la réponse chez l’humain. Des modèles de rats anesthésiés et éveillés, de chiens anesthésiés et éveillés et de singes éveillés avec suivi cardiovasculaire par télémétrie ont été utilisés. L’OT s’est avéré être un agent ayant d’importants effets hémodynamiques présentant une réponse variable selon l’état (anesthésié ou éveillé), la dose, le mode d’administration (bolus ou infusion) et l’espèce utilisée. Ces études nous ont permis d’établir les doses et régimes de traitement n’ayant pas d’effets cardiovasculaires adverses et pouvant être utilisées dans le cadre des études d’efficacité subséquentes. Un modèle porcin d’infarctus du myocarde avec reperfusion a été utilisé afin d’évaluer les effets de l’OT dans le traitement de l’infarctus du myocarde. Dans le cadre d’un projet pilote, l’infusion continue d’OT initiée immédiatement au moment de la reperfusion coronarienne a induit des effets cardiovasculaires adverses chez tous les animaux traités incluant une réduction de la fraction de raccourcissement ventriculaire gauche et une aggravation de la cardiomyopathie dilatée suite à l’infarctus. Considérant ces observations, l’approche thérapeutique fût révisée afin d’éviter le traitement pendant la période d’inflammation aigüe considérée maximale autour du 3ième jour suite à l’ischémie. Lorsqu’initié 8 jours après l’ischémie myocardique, l’infusion d’OT a engendré des effets adverses chez les animaux ayant des niveaux endogènes d’OT élevés. Par ailleurs, aucun effet adverse (amélioration non-significative) ne fût observé chez les animaux ayant un faible niveau endogène d’OT. Chez les animaux du groupe placebo, une tendance à observer une meilleure récupération chez ceux ayant des niveaux endogènes initiaux élevés fût notée. Bien que la taille de la zone ischémique à risque soit comparable à celle rencontrée chez les patients atteints d’infarctus, l’utilisation d’animaux juvéniles et l’absence de maladies coronariennes sont des limitations importantes du modèle porcin utilisé. Le potentiel de l’OT pour le traitement de l’infarctus du myocarde demeure mais nos résultats suggèrent qu’une administration systémique à titre de thérapie de remplacement de l’OT devrait être considérée en fonction du niveau endogène. De plus amples évaluations de la sécurité du traitement avec l’OT dans des modèles animaux d’infarctus du myocarde seront nécessaires avant de considérer l’utilisation d’OT dans une population de patients atteint d’un infarctus du myocarde. En contre partie, les niveaux endogènes d’OT pourraient posséder une valeur pronostique et des études cliniques à cet égard pourraient être d’intérêt.

Cerebral edema and acute liver failure : pathophysiological mechanisms and new therapeutic approaches

L’encéphalopathie hépatique (EH) se développe chez les patients atteints d’une maladie du foie et se caractérise par de nombreuses anomalies neuropsychiatriques. L’insuffisance hépatique aiguë (IHA) se caractérise par une perte progressive de l’état de conscience, par une augmentation rapide de l’œdème cérébral et une augmentation de la pression intracrânienne entraînant une herniation cérébrale et la mort. Plusieurs facteurs sont responsables du développement de l’EH mais depuis une centaine d’années, l’hyperammonémie qui peut atteindre des concentrations de l’ordre de plusieurs millimolaires chez les patients atteints d’IHA aux stades de coma est considérée comme un facteur crucial dans la pathogenèse de l’EH. La présente thèse comprend 4 articles suggérant l’implication de nouveaux mécanismes pathogéniques dans le développement de l’EH et de l’œdème cérébral associés à l’IHA et tente d’expliquer l’effet thérapeutique de l’hypothermie et de la minocycline dans la prévention de l’EH et de l’œdème cérébral: 1. L’IHA induite par dévascularisation hépatique chez le rat se caractérise par une augmentation de la production de cytokines pro-inflammatoires cérébrales (IL-6, IL-1, TNF-). Cette observation constitue la première évidence directe que des mécanismes neuro-inflammatoires jouent une rôle dans la pathogenèse de l’EH et de l’œdème cérébral associés à l’IHA (Chapitre 2.1, articles 1 et 2). 2. L’activation de la microglie telle que mesurée par l’expression de marqueurs spécifiques (OX42, OX-6) coïncide avec le développement de l’encéphalopathie (stade coma) et de l’œdème cérébral et s’accompagne d’une production accrue de cytokines pro-inflammatoires cérébrales (Chapitre 2.1, article 1 et 2). 3. Un stress oxydatif/nitrosatif causé par une augmentation de l’expression de l’oxyde nitrique synthétase et une augmentation de la synthèse d’oxyde nitrique cérébral participe à la pathogénèse des complications neurologiques de l’IHA (Chapitre 2.3, articles 3 et 4). 4. Des traitements anti-inflammatoires tels que l’hypothermie et la minocycline peuvent constituer de nouvelles approches thérapeutiques chez les patients atteints d’IHA (Chapitre 2.1, article 1; Chapitre 2.2, article 2). 5. Les effets bénéfiques de l’hypothermie et de la minocycline sur les complications neurologiques de l’IHA expérimentale s’expliquent, en partie, par une diminution du stress oxydatif/nitrosatif (Chapitre 2.3, article 3; Chapitre 2.4, article 4).