The cerebrovascular effects of adrenaline, noradrenaline and dopamine infusions under propofol and isoflurane anaesthesia in sheep

Publisher's copy made available with the permission of the publisher © Australian Society of AnaesthetistsInfusions of catecholamines are frequently administered to patients receiving propofol or isoflurane anaesthesia. Interactions between these drugs may affect regional circulations, such as the brain. The aim of this animal (sheep) study was to determine the effects of ramped infusions of adrenaline, noradrenaline (10, 20, 40 µg/min) and dopamine (10, 20, 40 µg/kg/min) on cerebral blood flow (CBF), intracranial pressure (ICP), cerebrovascular resistance (CVR) and cerebral metabolic rate for oxygen (CMRO₂). These measurements were made under awake physiological conditions, and during continuous propofol (15 mg/min) or 2% isoflurane anaesthesia. All three catecholamines significantly and equivalently increased mean arterial pressure from baseline in a dose-dependent manner in the three cohorts (P0.05). Under propofol (n=6) and isoflurane (n=6), all three catecholamines significantly increased CBF (P<0.001). Dopamine caused the greatest increase in CBF, and was associated with significant increases in ICP (awake: P<0.001; propofol P<0.05; isoflurane P<0.001) and CVR (isoflurane P<0.05). No significant changes in CMRO₂ were demonstrated. Under propofol and isoflurane anaesthesia, the cerebrovascular effects of catecholamines were significantly different from the awake, physiological state, with dopamine demonstrating the most pronounced effects, particularly under propofol. Dopamine-induced hyperaemia was associated with other cerebrovascular changes. In the presence of an equivalent effect on mean arterial pressure, the exaggerated cerebrovascular effects under anaesthesia appear to be centrally mediated, possibly induced by propofol- or isoflurane-dependent changes in blood-brain barrier permeability, thereby causing a direct influence on the cerebral vasculature.http://www.aaic.net.au/Article.asp?D=200205

Analyzing Radioligand Binding Data

A radioligand is a radioactively labeled drug that can associate with a receptor, transporter, enzyme, or any protein of interest. Measuring the rate and extent of binding provides information on the number of binding sites, and their affinity and accessibility for various drugs. Radioligand binding experiments are easy to perform, and provide useful data in many fields. For example, radioligand binding studies are used to study receptor regulation, investigate receptor localization in different organs or regions using autoradiography, categorize receptor subtypes, and probe mechanisms of receptor signaling. This unit reviews the theory of receptor binding and explains how to analyze experimental data. Since binding data are usually best analyzed using nonlinear regression, this unit also explains the principles of curve fitting with nonlinear regression.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/143671/1/cppsa03h.pd

Detecting outliers when fitting data with nonlinear regression – a new method based on robust nonlinear regression and the false discovery rate

BACKGROUND: Nonlinear regression, like linear regression, assumes that the scatter of data around the ideal curve follows a Gaussian or normal distribution. This assumption leads to the familiar goal of regression: to minimize the sum of the squares of the vertical or Y-value distances between the points and the curve. Outliers can dominate the sum-of-the-squares calculation, and lead to misleading results. However, we know of no practical method for routinely identifying outliers when fitting curves with nonlinear regression. RESULTS: We describe a new method for identifying outliers when fitting data with nonlinear regression. We first fit the data using a robust form of nonlinear regression, based on the assumption that scatter follows a Lorentzian distribution. We devised a new adaptive method that gradually becomes more robust as the method proceeds. To define outliers, we adapted the false discovery rate approach to handling multiple comparisons. We then remove the outliers, and analyze the data using ordinary least-squares regression. Because the method combines robust regression and outlier removal, we call it the ROUT method. When analyzing simulated data, where all scatter is Gaussian, our method detects (falsely) one or more outlier in only about 1–3% of experiments. When analyzing data contaminated with one or several outliers, the ROUT method performs well at outlier identification, with an average False Discovery Rate less than 1%. CONCLUSION: Our method, which combines a new method of robust nonlinear regression with a new method of outlier identification, identifies outliers from nonlinear curve fits with reasonable power and few false positives

Analyzing Binding Data

Measuring the rate and extent of radioligand binding provides information on the number of binding sites, and their affinity and accessibility of these binding sites for various drugs. This unit explains how to design and analyze such experiments. Curr. Protoc. Neurosci. 52:7.5.1‐7.5.65. © 2010 by John Wiley & Sons, Inc.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/143761/1/cpns0705.pd

Outlier identification in radiation therapy knowledge-based planning: A study of pelvic cases.

PURPOSE: The purpose of this study was to apply statistical metrics to identify outliers and to investigate the impact of outliers on knowledge-based planning in radiation therapy of pelvic cases. We also aimed to develop a systematic workflow for identifying and analyzing geometric and dosimetric outliers. METHODS: Four groups (G1-G4) of pelvic plans were sampled in this study. These include the following three groups of clinical IMRT cases: G1 (37 prostate cases), G2 (37 prostate plus lymph node cases) and G3 (37 prostate bed cases). Cases in G4 were planned in accordance with dynamic-arc radiation therapy procedure and include 10 prostate cases in addition to those from G1. The workflow was separated into two parts: 1. identifying geometric outliers, assessing outlier impact, and outlier cleaning; 2. identifying dosimetric outliers, assessing outlier impact, and outlier cleaning. G2 and G3 were used to analyze the effects of geometric outliers (first experiment outlined below) while G1 and G4 were used to analyze the effects of dosimetric outliers (second experiment outlined below). A baseline model was trained by regarding all G2 cases as inliers. G3 cases were then individually added to the baseline model as geometric outliers. The impact on the model was assessed by comparing leverages of inliers (G2) and outliers (G3). A receiver-operating-characteristic (ROC) analysis was performed to determine the optimal threshold. The experiment was repeated by training the baseline model with all G3 cases as inliers and perturbing the model with G2 cases as outliers. A separate baseline model was trained with 32 G1 cases. Each G4 case (dosimetric outlier) was subsequently added to perturb the model. Predictions of dose-volume histograms (DVHs) were made using these perturbed models for the remaining 5 G1 cases. A Weighted Sum of Absolute Residuals (WSAR) was used to evaluate the impact of the dosimetric outliers. RESULTS: The leverage of inliers and outliers was significantly different. The Area-Under-Curve (AUC) for differentiating G2 (outliers) from G3 (inliers) was 0.98 (threshold: 0.27) for the bladder and 0.81 (threshold: 0.11) for the rectum. For differentiating G3 (outlier) from G2 (inlier), the AUC (threshold) was 0.86 (0.11) for the bladder and 0.71 (0.11) for the rectum. Significant increase in WSAR was observed in the model with 3 dosimetric outliers for the bladder (P \u3c 0.005 with Bonferroni correction), and in the model with only 1 dosimetric outlier for the rectum (P \u3c 0.005). CONCLUSIONS: We established a systematic workflow for identifying and analyzing geometric and dosimetric outliers, and investigated statistical metrics for outlier detection. Results validated the necessity for outlier detection and clean-up to enhance model quality in clinical practice

Technologies de prescription informatisée et transformation du rôle des pharmaciens communautaires

L’amélioration de la qualité de l’utilisation des médicaments dans les soins primaires est devenue un enjeu crucial. Les pharmaciens communautaires se présentent comme des acteurs centraux dans l’atteinte de cet objectif, en réclamant une extension de leur rôle. L’objectif principal de cette thèse est de mieux comprendre comment les technologies de prescription informatisée (eRx) influencent la transformation du rôle des pharmaciens communautaires. Le premier article présente les résultats d’une étude de cas qui aborde la transformation du rôle des pharmaciens communautaires à partir du concept de professionnalisation. Elle propose un modèle logique des influences d’une technologie de eRx sur cette professionnalisation, élaboré à partir de la typologie de Davenport. Ce modèle logique a été validé en interviewant douze pharmaciens communautaires participant à un projet pilote typique de technologie de eRx. A partir des perceptions des pharmaciens communautaires, nous avons établi que la technologie était susceptible de soutenir la professionnalisation des pharmaciens en passant par cinq mécanismes : la capacité analytique, l’élimination des intermédiaires, l’intégration, l’automatisation et la diffusion des connaissances. Le deuxième article analyse les perturbations induites par les différentes fonctions des technologies de eRx sur la stabilité de la juridiction des pharmaciens communautaires, en se basant sur un cadre de référence adapté d’Abbott. À partir de trente-trois entrevues, avec des praticiens (médecins et pharmaciens) et des élites, cette étude de cas a permis de décrire en détail les influences des différentes fonctions sur les modalités d’action des professionnels, ainsi que les enjeux soulevés par ces possibilités. La perturbation principale est liée aux changements dans la distribution des informations, ce qui influence les activités de diagnostic et d’inférence des professionnels. La technologie peut redistribuer les informations relatives à la gestion des médicaments autant au bénéfice des médecins qu’au bénéfice des pharmaciens, ce qui suscite des tensions entre les médecins et les pharmaciens, mais aussi parmi les pharmaciens. Le troisième article présente une revue systématique visant à faire une synthèse des études ayant évalué les effets des technologies de eRx de deuxième génération sur la gestion des médicaments dans les soins primaires. Cette revue regroupe dix-neuf études menées avec des méthodes observationnelles. Les résultats rapportés révèlent que les technologies sont très hétérogènes, le plus souvent immatures, et que les effets ont été peu étudiés au-delà des perceptions des utilisateurs, qui sont mitigées. Le seul effet positif démontré est une amélioration de la qualité du profil pharmacologique accessible aux professionnels, alors que des effets négatifs ont été démontrés au niveau de l’exécution des prescriptions, tels que l’augmentation du nombre d’appels de clarification du pharmacien au prescripteur. Il semble donc que l’on en connaisse peu sur les effets des technologies de eRx de deuxième génération. Ces trois études permettent de constater que les nouvelles technologies de eRx peuvent effectivement influencer la transformation du rôle du pharmacien communautaire en perturbant les caractéristiques des prescriptions, et surtout, l’information et sa distribution. Ces perturbations génèrent des possibilités pour une extension du rôle des pharmaciens communautaires, tout en soulignant les défis intra et interprofessionnels associés à l’actualisation de ces possibilités. Dans l’ensemble, nos résultats soulignent que les perturbations associées aux technologies de eRx dépassent les éléments techniques du travail des utilisateurs, pour englober de multiples perturbations quant à la nature même du travail et du rôle des professionnels. Les décideurs et acteurs impliqués dans le déploiement des technologies de eRx auraient avantage à prendre en compte l’ensemble de ces considérations pour rapprocher les effets observés des bénéfices promis de ces technologies.The quality of medication use in primary care needs to improve: this has become a crucial issue. Community pharmacists want to play a key role in meeting this objective and are calling for an expanded role. The main objective of this thesis is to better understand how electronic prescription (eRx) technologies are influencing the transformation of the role played by community pharmacists. The first article presents results from a case study on the transformation of the community pharmacists’ role, based on the concept of professionalization. It proposes a logical model of how an eRx technology influences this professionalization, developed from the Davenport typology. The logical model was validated by interviewing twelve community pharmacists participating in a typical pilot project involving an eRx technology. Based on the perceptions of community pharmacists, we have determined that there are five mechanisms by which the technology is likely to support the professionalization of pharmacists: analytic capacity, the elimination of intermediaries, integration, automation and the dissemination of knowledge. The second article analyzes the disturbances produced by the various functions of eRx technologies on the jurisdiction of community pharmacists, based on an adaptation of Abbott’s model. Using data from 33 interviews with practitioners, physicians and pharmacists, as well as elite members of these two professions, this case study provides a detailed description of how different functions influence professionals’ modalities of action, as well as the issues raised by these possibilities. The primary disturbance is associated with changes in the distribution of information, which can influence the diagnostic and inference activities of professionals. The technology may redistribute information on the management of medication to the benefit of both physicians and pharmacists, and this creates tensions, not only between physicians and pharmacists but also among pharmacists. The third article presents a systematic review that synthesized studies assessing the impacts of second-generation eRx technologies on the management of medication in primary care. It examined 19 studies that applied observational methods. The findings reveal that the technologies are very heterogeneous and often far from mature, and that their effects received little attention beyond the perceptions of users, which were mixed. The only positive impact shown is an improvement to the quality of the pharmacological profile available to professionals. Negative impacts touched on the execution of prescriptions, such as a greater number of calls from pharmacists to prescribers to clarify information. It would therefore appear that little is known about the impacts of second-generation eRx technologies. These three studies allow us to conclude that new eRx technologies may well influence how the role of the community pharmacist is being transformed, specifically by disturbing the characteristics of prescriptions and, above all, information and its distribution. These disturbances generate opportunities for extending the role of community pharmacists, while underscoring the intra and interprofessional challenges associated with their realization. Overall, our results suggest that the disturbances associated with eRx technologies go beyond technical aspects of users’ work, to include multiple disturbances of the very nature of the professionals’ work and role. The decision makers and actors involved in deploying eRx technologies would be well advised to take all these considerations into account to bring the observed effects of these technologies more in line with their promised benefits

Caractérisation d'un organogel à base d'un dérivé amphiphile de la L-alanine

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal

Energy efficiency of iron-boron-silicon metallic glasses in sulfuric acid solutions

A criterion of the energy efficiency of iron–boron–silicon metallic glasses in sulfuric acid solutions is proposed for the first time. The criterion has been derived based on calculating the limit of the ratio value of the conductivity of a metallic glass in aqueous solution to the conductivity of the metallic glass in air. In other words, the conductivity ratio of a metallic glass in aqueous solution to the conductivity of the metallic glass in air  = 1, was applied to determine the energy efficiency of the metallic glass in the aqueous solution when the conductivity of a metallic glass in air became equal (decreased) to the steady conductivity of the metallic glass in aqueous solution as a function of time of the exposure of the metallic glass to the aqueous solution. This criterion was not only used to determine the energy efficiency of different metallic glasses, but also, the criterion was used to determine the energy efficiency of metallic glasses exposed to a wide range of sulfuric acid concentrations. These conductivity values were determined by the electrochemical impedance spectroscopy (EIS). In addition, the criterion can be applied under diverse test conditions with a predetermined period of the operational life of the metallic glasses as functional materials. Furthermore, variations of the energy efficiency of the metallic glasses as a function of the acid concentration and time were produced by fitting the experimental data to a numerical model using a nonlinear regression method. The profiles of the metallic glasses exhibit a less conservative behavior of the energy efficiency than the proposed analytical criterion

The queers are here: LGBTQ+ young adults’ mental health outcomes in wilderness therapy

Wilderness therapy is an emerging treatment modality that integrates nature with evidence-based therapeutic treatments (Russell, 2001). A growing body of literature continues to support its effectiveness with adolescents and young adults (Bowen & Neill, 2013; Curtis et al., 2018; Hoag et al., 2013); however, little research has been conducted on the experiences of its LGBTQIAP+ (“queer”) participants. Such an absence is noteworthy because the percentage of queer wilderness therapy students might be as high as 18% (Wright et al., 2017) and given that queer individuals experience minority stress (Meyer, 2003), which is correlated with negative psychological outcomes (Baams et al., 2015; Mereish et al., 2019; Tebbe & Moradi, 2016). This dissertation fills the gap in the literature by using pre-existing data collected by the Outdoor Behavioral Healthcare Council (OBHC) and the National Association for Therapeutic Schools and Programs (NATSAP) to examine the mental health outcomes of young adult (ages 18-25) wilderness therapy students using the Outcomes Questionnaire 45.2 (OQ 45.2; Lambert & Burlingame, 1996). With a sample of 379 queer and non-queer wilderness therapy graduates, this study found that queer young adults’ intake OQ 45.2 scores were statistically similar to those of straight young adults. It was also found that queer young adults’ OQ 45.2 discharge scores were statistically significantly lower than their intake scores, indicating a reduction in psychological distress. This dissertation also examined preliminary post-wilderness therapy data, interpreted all results as they relate to clinical work and research, and concluded by offering next steps for treating queer young adults enrolled in wilderness therapy programs

Vers une théorie de la réceptivité du discours rhétorique

Nous entendons, par rhétorique, l'art de persuader et de convaincre, l'art de la délibération et de la discussion, l'art de bien penser et de bien dire le vraisemblable - l'eikos -, ainsi que le concevait Aristote, et non ce que l'on entend trop souvent sous ce nom. Et ce que nous proposons de montrer dans ce mémoire par un examen de l'histoire de cette conception de la rhétorique de sa naissance jusqu'à aujourd'hui - avec l'accent mis sur la rhétorique d'Aristote et la "Nouvelle rhétorique" de Chaïm Perelman -, c'est que l'apprentissage de la rhétorique peut être utile non seulement à l'orateur, mais également au récepteur (l'auditeur) d'un discours rhétorique. Autrement dit, nous allons montrer, théoriquement par notre examen de l 'histoire de la rhétorique et pratiquement par une analyse de l'Éloge d'Hélène de Gorgias, que la technique rhétorique est aussi l'art d'apprendre à écouter et à lire de manière à mieux comprendre