Grâce à l’échocardiographie au chevet, il est maintenant reconnu que la dysfonction myocardique a une forte prévalence et coexiste avec le choc distributif tôt dans le sepsis sévère. Dans les deux cas, la réanimation liquidienne représente la première ligne de traitement qui permet de sauver des vies. À ce jour, aucun liquide spécifique n'a pu être déclaré supérieur ou ayant un impact clair sur l’issue du choc septique. L’objectif est donc d'évaluer les impacts moléculaires de la perfusion isovolémique de différents liquides de réanimation sur la dysfonction myocardique induite par l'endotoxine. Des rats adultes se sont fait équiper de voies centrales, injecter en intrapéritonéale avec de l’endotoxine (lipopolysaccharide [LPS], provenant d'E. coli) ou du normal salin (0,9 %; contrôle) et, subséquemment, perfuser (ou non) avec une quantité isovolémique de liquide de remplissage vasculaire (normal salin [NS], albumine [ALB], solution de salin hypertonique [HTS]) pour une période de 6 à 24 heures, suivie d'un monitorage échocardiographique ainsi que d'une évaluation biochimique et histopathologique. Résultats : l’albumine améliore la dysfonction myocardique induite par le LPS en : i) réduisant l’épaisseur relative du ventricule gauche en diastole (LVRWD) (élargissement de l’espace interstitiel et de la teneur en albumine endogène); ii) limitant l'apoptose cardiaque tout en maintenant et en régulant le signal extracellulaire d’activation de la protéine kinase mitogène activée [ERK1-2 MAPK]; iii) favorisant les voies d'expression de l’hème oxygénase-1 [HO-1] et de la NO synthase inductible [iNOS]. La solution saline hypertonique [HTS] a été la seule à permettre une prévention hâtive de la dysfonction myocardique, en plus de réduire l'apoptose cardiaque grâce à une augmentation de l’expression de HO-1. Conclusion : les perfusions isovolémiques de liquides ont des impacts moléculaires distincts sur la dysfonction myocardique induite par l’endotoxine. L’albumine et le salin hypertonique présentent de potentielles propriétés antioxydantes, anti-apoptotiques et anti-oedémateuses. Cependant, d’autres recherches seront nécessaires afin d'approfondir les mécanismes sous-jacentes de ces impacts, afin d'éventuellement modifier certaines pratiques cliniques et d'améliorer la survie des patients atteints de dysfonction myocardique d'origine septique.

We take a Student process that is based on independent copies of a random variable X and has trajectories in the function space D[0,1]. As a consequence of a functional central limit theorem for this process, with X in the domain of attraction of the normal law, we consider convergence in distribution of several functionals of this process and derive respective asymptotic confidence intervals for the mean of X. We explore the expected lengths and finite-sample coverage probabilities of these confidence intervals and the one obtained from the asymptotic normality of the Student t-statistic, thus concluding some alternatives to the latter confidence interval that are shorter and/or have at least as high coverage probabilities.

Separata del curso de Estadística para Ingeniería 1 (CE54), que corresponde al ciclo 2013-1. Este curso es una asignatura destinada al análisis estadístico.

Zur deskriptiven Darstellung der kardiologischen Untersuchung von Golden Retrievern wurden 50 vorberichtlich und klinisch gesunde Hunde der genannten Rasse untersucht. Die Probanden erfuhren eine allgemeine klinische Untersuchung mit besonderer Beurteilung des Herz-Kreislaufsystems, eine Blutdruckmessung, eine elektrokardiografische sowie eine echokardiografische Untersuchung. Zur Abklärung systemischer Erkrankungen, die die Herz-Kreislauffunktion beeinflussen können, wurden zudem Blutuntersuchungen durchgeführt. Während der klinischen Untersuchung lag die Herzfrequenz der Probanden bei 97,7 ± 28,0 Schlägen pro Minute. Auskultatorisch konnte bei keinem der Probanden ein besonderer Befund erhoben werden. Der Blutdruck wurde bei den untersuchten Tieren mittels Doppler-Sphygmomanometrie ermittelt. Dabei ergab sich ein systolischer Blutdruck von 152,5 ± 24,0 mmHg. Vier der Golden Retriever waren mit einem systolischen Blutdruck von 200 bis 220 mmHg hypertensiv. Mehrere Hunde wiesen zudem grenzwertig hohe Blutdruckwerte zwischen 160 und 180 mmHg auf. Anhand der durchgeführten Untersuchungen konnte keine Ursache für diese systemische Hypertension gefunden werden. Folgeerscheinungen der Hypertension ließen sich nicht nachweisen. Wahrscheinlich handelt es sich hierbei um eine aufregungsassoziierte kurzfristige Blutdruckerhöhung. Anhand der Laboruntersuchungen konnten geringgradige Veränderungen festgestellt werden, die allerdings keinen Einfluss auf die kardiale Funktion haben sollten. Mit Hilfe der elektrokardiografischen Untersuchung konnten keine Arrhythmien nachgewiesen werden. Acht der untersuchten 50 Hunde wurden aufgrund morphologischer pathologischer Veränderungen von der Erhebung echokardiografischer Referenzwerte ausgeschlossen, um eine Beeinflussung der Normalparameter zu verhindern. Von den Golden Retrievern mit pathologischen Veränderungen wiesen sieben eine geringgradige Subaortensstenose auf und ein Hund eine systolische Dysfunktion in Form einer okkulten dilatativen Kardiomyopathie. Anhand der durchgeführten Untersuchungen konnten echokardiografische Normalparameter für den Golden Retriever etabliert werden. Ähnliche Untersuchungen anderer Hunderassen zeigen die Wichtigkeit der Etablierung rassespezifischer Referenzwerte auf. Sieben der vorberichtlich und klinisch gesunden Golden Retriever wiesen eine geringgradige Subaortenstenose auf, einer eine okkulte Kardiomyopathie. Aufgrund der Gefahr der Vererbung der genannten Erkrankungen kann durch die vorliegende Untersuchung gezeigt werden, wie wichtig eine kardiologische Screening-Untersuchung von Golden Retrievern vor Zuchtnutzung ist.

Idiopathic normal pressure hydrocephalus (iNPH) is a condition with dilated cerebral ventricles but intracranial pressure within normal limits. The symptoms of gait impairment, cognitive decline and urinary incontinence develop gradually. Treatment with shunt insertion results in improvement in eight out of ten patients. The cerebrospinal fluid tap test (CSF TT) and preoperative magnetic resonance imaging (MRI) are methods used to select patients who may benefit from shunt surgery, but they are performed and interpreted differently in different centers throughout the world. The aim of this thesis was to evaluate the performance of the CSF TT and the underlying mechanisms of improvement in gait function after CSF removal, and to investigate the prognostic value of preoperative MRI scans. Improvement in gait and changes in cerebral blood flow (CBF) after a CSF TT were investigated in two prospective studies that included 39 and 20 patients, respectively. Gait assessment and perfusion MRI were done before and several times during the first 24 hours after a CSF TT. Perfusion was investigated with pseudo-continuous arterial spin labeling. At the group level, gait function was significantly improved at all investigation times, but only one-third of individual CSF TT responders were improved at all investigation times. In patients with increased CBF in lateral and frontal white matter after the CSF TT, gait function improved more than it did in patients with decreased CBF in these regions. However, in the whole sample, there was no significant increase in CBF after CSF removal. Preoperative MRI scans were retrospectively evaluated in 109 patients with iNPH who had undergone shunt surgery. The callosal angle was smaller in shunt responders compared with non-responders. The following findings showed the highest association with a positive outcome after shunting: a small callosal angle, wide temporal horns, and occurrence of disproportionally enlarged subarachnoid space hydrocephalus. In conclusion, CBF in white matter close to the lateral ventricles may play a role in the reversibility of symptoms after CSF removal in patients with iNPH. The CSF TT should be reevaluated if the patient does not initially improve, and preoperative MRI investigations can add prognostic information regarding the selection of shunt candidates.

The relaxation of international boundaries has enabled the globalisation of markets making available an ever increasing number of specialised suppliers and markets. Inevitably this results in supply chains sharing suppliers and customers reflected in a network of relationships. Within this context firms buyers configure their supply relationships based on their perception of supply risk. Risk is managed by either increasing trust or commitment or by increasing the number of suppliers. Increasing trust and commitment facilitates collaboration and reduces the propensity for a supplier to exit the relationship. Conversely, increasing the number of suppliers reduces dependency and increases the ease of making alternative supply arrangements. The emergent network of relationships is dynamic and complex, and due in no small part to the influence of inventory management practices, tightly coupled. This critical organization of the network describes a system that contrary to existing supply chain conceptualisation exists far from equilibrium, requiring a different more appropriate theoretical lens through which to view them. This thesis adopts a Complex Adaptive Systems (CAS) perspective to position supply networks as tightly coupled complex systems which according to Normal Accident Theory (NAT) are vulnerable to disruptions as a consequence of normal operations. The consequential boundless and emergent nature of supply networks makes them difficult to research using traditional empirical methods, instead this research builds a generalised supply network agent based computer model, allowing network constituents (agents) to take autonomous parallel action reflecting the true emergent nature of supply networks. This thesis uses the results from a series of carefully designed computer experiments to elucidate how supply networks respond to a variety of market structures and permitted agent behaviours. Market structures define the vertical (between tier) and horizontal (within tier) levels of price differentiation. Within each structure agents are permitted to autonomously modify their prices (constrained by market structure) and collaborate by sharing demand information. By examining how supply networks respond to different permitted agent behaviours in a range of market structures this thesis makes 4 contributions. Firstly, it extends NAT by incorporating the adaptive nature of supply network constituents. Secondly it extends supply chain management by specifying supply networks as dynamic not static phenomena. Thirdly it extends supply chain risk management through developing an understanding of the impact different permitted behaviour combinations on the networks vulnerability to disruptions in the context of normal operations. Finally by developing the understanding how normal operations impact a supply networks vulnerability to disruptions it informs the practice of supply chain risk management.

The aim of this research was to establish what black adults' perceptions are of factors that contribute to healthy family functioning. Qualitative research was conducted. Random sampling was used to obtain eighteen black participants between the ages of 20 and 50. These participants responded in writing to the following open ended question: "What factors do you think contribute to healthy family functioning?" Semi-structured interviews were also conducted with the eight participants who presented with the richest data. Analysis of the data yielded 10 prevalent themes and eleven other themes. The 10 prevalent themes were: respect, love, communication, family time/spending time together, trust, understanding, discipline, availability for each other, boundaries and religion. The other eleven themes were: personal space, responsibility, hierarchy, family rules, conflict handling, morality, roles, maturity, intelligence, culture and forgiveness. The above mentioned 21 themes were grouped in seven broad categories, namely communication, conflict handling, affectionate involvement, family rules, boundaries, religion and other dimensions. All these themes were compared to existing research results. It appeared that themes of this study correspond with many dimensions of family functioning as indicated by family therapy models and existing research. Participants also indicated new dimensions not mentioned by the existing literature. Recommendations were made concerning future research. / Thesis (M.A. (Clinical Psychology))--North-West University, Potchefstroom Campus, 2005.

Cerebrospinal fluid (CSF) infusion tests can be used to estimate the dynamic properties of the CSF system. Idiopathic normal pressure hydrocephalus (INPH) is a syndrome signified by a disturbance to the CSF system, where the cause is unknown and the diagnosis is difficult to determine. As an aid in identifying patients with INPH who will improve after shunt surgery, infusion tests are commonly used to determine the outflow conductance (Cout), or outflow resistance (Rout=1/Cout), of the CSF system. The tests are also used to determine shunt function in vivo. The general aim of this thesis was to develop and validate CSF infusion methods, to investigate the dynamics of the CSF system. The methods should be applicable to patients with INPH, to aid in the quest to further improve the diagnosis and management of this syndrome. An existing mathematical model describing the dynamics of the CSF system was further developed. The characteristics of the model were verified and the effect of expanding intracranial air on the intracranial pressure (ICP) was simulated. The simulations supported the recommendation to maintain sea-level pressure during air ambulance transportation of patients with suspected intracranial air. A recently developed infusion apparatus was evaluated, on an experimental model as well as on a patient material. The repetitiveness in estimating Cout was found to be good. A statistically significant difference was found between the repeated Cout estimations in the patient group, indicating that there might have been a small physiological change introduced during the infusion test. A parameter, ∆Cout, was proposed and evaluated. It proved to reflect the reliability of individual Cout investigations in a clinically useful way, as well as to provide easily interpreted information. An adaptive algorithm for assessment of Cout was developed and evaluated on a patient group. The new algorithm was shown to reduce the investigation time, from 60 minutes, by 14.3 ± 5.9 minutes (mean ± SD), p<0.01, without reducing the reliability of the estimated Cout below clinically relevant levels. The relationship between ICP and CSF outflow was studied in a group of patients investigated for INPH. It was found that in the range of moderate increase from baseline pressure, the assumption of a pressure independent Rout was confirmed (p=0.5). However, at larger pressure increments, the relationship had a non-linear tendency (p<0.05). This indicates that the traditional view of a pressure independent Rout might have to be questioned in the region where ICP exceeds baseline pressure too much. Infusion tests can be performed in different ways, where three main categories may be distinguished. The bolus infusion method was compared to the constant pressure and constant flow infusion methods, on an experimental model as well as on a patient material. When physiological pressure fluctuations were added to the model, significant differences were found in the determination of Cout in the range of clinical importance, i.e. low Cout (p<0.05). The finding was supported by the patient investigations, the difference was however not significant. With the application of the new methods developed in this thesis, and the increased knowledge concerning relationships between CSF dynamic parameters, the CSF infusion test was further improved with the ability to increase measurement reliability in a reduced time. This constitutes a good basis to perform a large multi-centre study with the main goal to determine the predictive value of the parameter Cout.

The phenotype inference from genotype in RNA viruses maps the viral genome/protein sequences to the molecular functions in order to understand the underlying molecular mechanisms that are responsible for the function changes. The inference is currently done through a laborious experimental process which is arguably inefficient, incomplete, and unreliable. The wealth of RNA virus sequence data in the presence of different phenotypes promotes the rise of computational approaches to aid the inference. Key residue identification and genotype-phenotype mapping function learning are two approaches to identify the critical positions out of hitchhikers and elucidate the relations among them. The existing computational approaches in this area focus on prediction accuracy, yet a number of fundamental problems have not been considered: the scalability of the data, the capability to suggest informative biological experiments, and the interpretability of the inferences. A common scenario of inference done by biologists with mutagenesis experiments usually involves a small number of available sequences, which is very likely to be inadequate for the inference in most setups. Accordingly biologists desire models that are capable of inferring from such limited data, and algorithms that are capable of suggesting new experiments when more data is needed. Another important but always been neglected property of the models is the interpretability of the mapping, since most existing models behave as ’black boxes’. To address these issues, in the thesis I design a supervised combinatorial filtering algorithm that systematically and efficiently infers the correct set of key residue positions from available labeled data. For cases where more data is needed to fully converge to an answer, I introduce an active learning algorithm to help choose the most informative experiment from a set of unlabeled candidate strains or mutagenesis experiments to minimize the expected total laboratory time or financial cost. I also propose Disjunctive Normal Form (DNF) as an appropriate assumption over the hypothesis space to learn interpretable genotype-phenotype functions. The challenges of these approaches are the computational efficiency due to the combinatorial nature of our algorithms. The solution is to explore biological plausible assumptions to constrain the solution space and efficiently find the optimal solutions under the assumptions. The algorithms were validated in two ways: 1) prediction quality in a cross-validation manner, and 2) consistency with the domain experts’ conclusions. The algorithms also suggested new discoveries that have not been discussed yet. I applied these approaches to a variety of RNA virus datasets covering the majority of interesting RNA phenotypes, including drug resistance, Antigenicity shift, Antibody neutralization and so on to demonstrate the prediction power, and suggest new discoveries of Influenza drug resistance and Antigenicity. I also prove the extension of the approaches in the area of severe acute community disease.

Darbo tikslas – įvertinti gimdyvių ir akušerių nuomonę apie teikiamą priežiūrą mažos rizikos gimdyvių atvejais. Darbo uždaviniai – įvertinti akušerių bei gimdyvių nuomonę apie mažos rizikos gimdymo priežiūrą ir palyginti Vilniaus bei Kauno perinatologijos centruose akušerių nuomones apie mažos rizikos gimdymo priežiūrą. Tyrimo metodika. Tyrimo objektas – gimdyvių ir akušerių nuomonė apie gimdyvėms teikiamą priežiūrą mažos rizikos gimdymų atvejais. Tyrimo metodai – anoniminė anketinė akušerių ir gimdyvių apklausa, vykdyta 2013 11 01 – 2013 11 30 Vilniaus ir Kauno perinatologijos centruose. Tyrime dalyvavo 66 akušerės ir 306 gimdyvės. Statistinė duomenų analizė atlikta, panaudojant „SPSS 17.0“ kompiuterinę programą. Tyrimo rezultatai. Akušerės, kurios prižiūri ir teikia pagalbą mažos rizikos gimdymų metu visada ir dažnai, savo profesines žinias įvertino vidutiniškai 8,56±0,94 balo, o akušerės, darančios tai retai arba niekada, savo žinias įvertino vidutiniškai 7,19±2,62 balo iš 10 galimų (p<0,001). Profesinius įgūdžius akušerės įvertino atitinkamai vidutiniškai 8,71±1,03 ir 6,87±2,97 balo iš 10 galimų (p<0,001). Gimdyvės akušerių, prižiūrėjusių jų gimdymą paslaugų kokybę, įvertino vidutiniškai 9,5±1,0 balo iš 10 galimų. Gydytojo akušerio ginekologo teiktų paslaugų kokybę gimdyvės įvertino vidutiniškai – 9,4±1,2 balo iš 10 galimų. Kauno akušerės savo profesines žinias ir įgūdžius, prižiūrint mažos rizikos gimdymą, vertino atitinkamai vidutiniškai 8,5±1,022 balo ir 8,61±1,178... [toliau žr. visą tekstą] / SUMMARY Aim of the study – to assess the midwives‘ and mothers‘ opinion towards the obstetrical care in cases of the low-risk laboring. Objectives – to assess the opinion of mothers and midwives separately towards the obsterical care in cases of the low-risk laboring, as well as to compare the opinions of the midwives who work in the Perinatology Centers of Vilnius and Kaunas towards the obstetrical care in cases of the low-risk laboring. Methods. The object of the study is the midwives‘ and mothers opinion towards the obstetrical care in cases of the low-risk laboring. The questionnaire – based anonymous study was carried out between November 01, 2013 through November 30, 2013 in the Perinatology Centers of Vilnius and Kaunas. 66 midwives and 306 mothers participated in the study. Statistical analysis of the data was performed by SPSS 17.0 software package. Results. Midwives who always or frequently take care of the low-risk laboring autonomously evaluated their professional knowledge by giving 8,56±0,94 scores on average out of 10, whereas those midwives who never or rarely take care of the low-risk laboring evaluated their professional knowledge by giving 7,19±2,62 scores on average out of 10 (p<0,001). Professional skills were evaluated by the same midwives 8,71±1,03 and 6,87±2,97 scores on average out of 10, respectively (p<0,001). The mothers evaluated the quality of the services performed by the midwives or the obstetricians gynaecologists who took care of their... [to full text]