Knowledge transfer intervention theory : a model grounded in the strategies used by intermediate agents in the context of education

La présente thèse se base sur les principes de la théorisation ancrée (Strauss & Corbin, 1998) afin de répondre au manque de documentation concernant les stratégies adoptées par des « agents intermédiaires » pour promouvoir l’utilisation des connaissances issues de la recherche auprès des intervenants en éducation. Le terme « agent intermédiaire » réfère aux personnes qui sont positionnées à l’interface entre les producteurs et les utilisateurs des connaissances scientifiques et qui encouragent et soutiennent les intervenants scolaires dans l’application des connaissances scientifiques dans leur pratique. L’étude s’inscrit dans le cadre d’un projet du ministère de l’Éducation, du Loisir et du Sport du Québec visant à améliorer la réussite scolaire des élèves du secondaire provenant de milieux défavorisés. Des agents intermédiaires de différents niveaux du système éducatif ayant obtenu le mandat de transférer des connaissances issues de la recherche auprès des intervenants scolaires dans les écoles visées par le projet ont été sollicités pour participer à l’étude. Une stratégie d’échantillonnage de type « boule-de-neige » (Biernacki & Waldorf, 1981; Patton, 1990) a été employée afin d’identifier les personnes reconnues par leurs pairs pour la qualité du soutien offert aux intervenants scolaires quant à l’utilisation de la recherche dans leur pratique. Seize entrevues semi-structurées ont été réalisées. L’analyse des données permet de proposer un modèle d’intervention en transfert de connaissances composé de 32 stratégies d’influence, regroupées en 6 composantes d’intervention, soit : relationnelle, cognitive, politique, facilitatrice, évaluative, de même que de soutien et de suivi continu. Les résultats suggèrent que les stratégies d’ordre relationnelle, cognitive et politique sont interdépendantes et permettent d’établir un climat favorable dans lequel les agents peuvent exercer une plus grande influence sur l’appropriation du processus de l’utilisation des connaissances des intervenants scolaire. Ils montrent en outre que la composante de soutien et de suivi continu est importante pour maintenir les changements quant à l’utilisation de la recherche dans la pratique chez les intervenants scolaires. Les implications théoriques qui découlent du modèle, ainsi que les explications des mécanismes impliqués dans les différentes composantes, sont mises en perspective tant avec la documentation scientifique en transfert de connaissances dans les secteurs de la santé et de l’éducation, qu’avec les travaux provenant de disciplines connexes (notamment la psychologie). Enfin, des pistes d’action pour la pratique sont proposées.

Comercialização de caju in natura na região noroeste do estado de São Paulo

Para estimar e analisar os custos de comercialização e identificar locais e formas de comercialização do caju, foram realizadas, durante o ano de 2000/01, entrevistas com produtores, técnicos da extensão rural, agentes intermediários e pesquisadores de órgãos públicos. Também foram levantadas informações na Companhia de Entrepostos e Armazéns Gerais de São Paulo (CEAGESP). Os custos agregados pelo segmento da comercialização devem-se, em grande parte, às despesas com o transporte até os grandes centros atacadistas, e também à comissão definida pelo atacadista. Para o produtor da região Noroeste do Estado de São Paulo, o ideal seria direcionar sua produção para os meses de janeiro a junho, garantindo assim melhores preços e com isso resultados mais satisfatórios.

A presença de agentes intermediadores na formação de redes interorganizacionais: uma análise sob a perspectiva temporal

Nos estudos sobre redes interorganizacionais, existem esforços focados em entender a formação de redes, assunto esse que gera interesse dos formuladores de políticas públicas já que se busca no associativismo promovido pelo Estado e pelas iniciativas privadas, substância para impulsionar o desenvolvimento local. Diante disso, o objetivo do estudo foi verificar, por meio da formalização do Arranjo Produtivo Local (APL) de calçados de Birigüi (SP), se a presença desses agentes é essencial para a formação da rede interorganizacional. Como sustentações teóricas foram abordadas: a evolução temporal das redes; a Teoria Institucional aplicada às redes interorganizacionais; o capital social presente nos laços de relacionamento; a presença de agentes intermediários como coordenadores na governança das redes. A estratégia de pesquisa adotada baseou-se em entrevistas com 32% dos gestores das empresas que participavam formalmente do APL e com uma gestora do agente intermediador, além de observação e análises de pesquisas prévias sobre a industrialização de Birigüi. Como resultados verificou-se haver um legado regional que sustenta uma base de know-how para a industrialização de calçados. No entanto, percebeu-se que os interesses dos participantes do APL eram predominantemente comerciais, sem haver um nível de capital social e de institucionalização desenvolvidos a ponto de se criarem, de forma legítima, associações provenientes de vontades das próprias organizações. Sem esse ambiente institucional fortemente construído na região, não se verificou um racional claro para o associativismo, havendo a percepção de que os ganhos oriundos da participação na rede são futuros. Concluiu-se que a coordenação realizada por um agente intermediador tem poder de articulação limitado na formação de redes interorganizacionais se não existir uma institucionalização prévia que envolva, principalmente, valores e normas de capital social. Sem esses pré-requisitos, o agente intermediador pode acabar por ter funções de governança para ações assessórias da rede.

Intermediate serial cost-sharing rules

In this paper we give a generalization of the serial cost-sharing rule defined by Moulin and Shenker (1992) for cost sharing problems. According to the serial cost sharing rule, agents with low demands of a good pay cost increments associated with low quantities in the production process of that good. This fact might not always be desirable for those agents, since those cost increments might be higher than others, for example with concave cost functions. In this paper we give a family of cost sharing rules which allocates cost increments in all the possible places in the production process. And we characterize axiomatically each of them by means of an axiomatic characterization related to the one given for the serial cost-sharing rule by Moulin and Shenker (1994).

Design, synthesis and development of novel indolocarbazole derivatives as potential anti-cancer agents

This thesis describes work carried out on the design of new routes to a range of bisindolylmaleimide and indolo[2,3-a]carbazole analogs, and investigation of their potential as successful anti-cancer agents. Following initial investigation of classical routes to indolo[2,3-a]pyrrolo[3,4-c]carbazole aglycons, a new strategy employing base-mediated condensation of thiourea and guanidine with a bisindolyl β-ketoester intermediate afforded novel 5,6-bisindolylpyrimidin-4(3H)-ones in moderate yields. Chemical diversity within this H-bonding scaffold was then studied by substitution with a panel of biologically relevant electrophiles, and by reductive desulfurisation. Optimisation of difficult heterogeneous literature conditions for oxidative desulfurisation of thiouracils was also accomplished, enabling a mild route to a novel 5,6-bisindolyluracil pharmacophore to be developed within this work. The oxidative cyclisation of selected acyclic bisindolyl systems to form a new planar class of indolo[2,3-a]pyrimido[5,4-c]carbazoles was also investigated. Successful conditions for this transformation, as well as the limitations currently prevailing for this approach are discussed. Synthesis of 3,4-bisindolyl-5-aminopyrazole as a potential isostere of bisindolylmaleimide agents was encountered, along with a comprehensive derivatisation study, in order to probe the chemical space for potential protein backbone H-bonding interactions. Synthesis of a related 3,4-arylindolyl-5-aminopyrazole series was also undertaken, based on identification of potent kinase inhibition within a closely related heterocyclic template. Following synthesis of approximately 50 novel compounds with a diversity of H-bonding enzyme-interacting potential within these classes, biological studies confirmed that significant topo II inhibition was present for 9 lead compounds, in previously unseen pyrazolo[1,5-a]pyrimidine, indolo[2,3-c]carbazole and branched S,N-disubstituted thiouracil derivative series. NCI-60 cancer cell line growth inhibition data for 6 representative compounds also revealed interesting selectivity differences between each compound class, while a new pyrimido[5,4-c]carbazole agent strongly inhibited cancer cell division at 10 µM, with appreciable cytotoxic activity observed across several tumour types.

Synthesis and evaluation of novel quinolines and quinazolinediones as potential anti-cancer agents

This thesis outlines the design and effectuation of novel chemical routes towards a nascent class of functionalised quinoline-5,8-diones and the expansion of a series of contemporary quinazolinediones towards an innovative family of pyridinoquinazolinetetrone derivatives. This fragment based approach is envisaged to lead to advancements in the three scaffolds, expanding the SAR pool of both quinolines and quinazolinediones with subsequent evaluation of chemotherapeutic potential as well as furnishing a new class of tricycle for biological investigation. Development of novel quinoline-5,8-diones is provided for by expanding on existing methodology. Using a variety of nucleophiles on a critical intermediate, a broad range of novel compounds was afforded allowing chemotherapeutic potential to be assessed, while also serving as intermediates for accomplishing novel pyridinoquinazolinetetrone congeners. In order to incorporate functionality into our quinazolinedione template, an efficient synthetic strategy was constructed which provided a robust route to effectuate a highly derivatised pyrimidinedione ring. As derivatisation of this template is unreported our chief priority was to synthesise a range of diverse quinazolinediones. The application of annulation methodology using functionalised precursors provided a library of N-3 derivatised quinazolinedione analogues. These, along with their N-1 functionalised derivatives provide a wide scope from which to construct a series of pyridinoquinazolinetetrone derivatives while also serving as a unique class of molecules whose biological potential is uncharted. Although the actualisation of the pyridinoquinazolinetetrone was ultimately unsuccessful, our work has led to the development of novel quinoline-5,8-diones which were found to possess excellent anti-cancer activity when assessed by the NCI screen. Of the quinazolinediones synthesised eight compounds were accepted for screening by the NCI. Results from the single-dose tests however indicated that these compounds possessed little cytotoxic activity at 10 μM. The development of this novel template in conjunction with the highly active quinolinediones serves as an excellent rostrum for future synthetic endeavours.

S-(2-Succinyl)cysteine:a novel chemical modification of tissue proteins by a Krebs cycle intermediate

S-(2-Succinyl)cysteine (2SC) has been identified as a chemical modification in plasma proteins, in the non-mercaptalbumin fraction of human plasma albumin, in human skin collagen, and in rat skeletal muscle proteins and urine. 2SC increases in human skin collagen with age and is increased in muscle protein of diabetic vs. control rats. The concentration of 2SC in skin collagen and muscle protein correlated strongly with that of the advanced glycation/lipoxidation end-product (AGE/ALE), N(epsilon)-(carboxymethyl)lysine (CML). 2SC is formed by a Michael addition reaction of cysteine sulfhydryl groups with fumarate at physiological pH. Fumarate, but not succinate, inactivates the sulfhydryl enzyme, glyceraldehyde-3-phosphate dehydrogenase in vitro, in concert with formation of 2SC. 2SC is the first example of spontaneous chemical modification of protein by a metabolic intermediate in the Krebs cycle. These observations identify fumarate as an endogenous electrophile and suggest a role for fumarate in regulation of metabolism.

Challenge testing the lactoperoxidase system against a range of bacteria using different activation agents

Lactoperoxidase (LP) exerts antimicrobial effects in combination with H2O2 and either thiocyanate (SCN-) or a halide (e. g., I-). Garlic extract in the presence of ethanol has also been used to activate the LP system. This study aimed to determine the effects of 3 LP activation systems (LP+SCN-+H2O2; LP+I-+H2O2; LP + garlic extract + ethanol) on the growth and activity of 3 test organisms (Staphylococcus aureus, Pseudomonas aeruginosa, and Bacillus cereus). Sterilized milk was used as the reaction medium, and the growth pattern of the organisms and a range of keeping quality (KQ) indicators (pH, titratable acidity, ethanol stability, clot on boiling) were monitored during storage at the respective optimum growth temperature for each organism. The LP+I-+H2O2 system reduced bacterial counts below the detection limit shortly after treatment for all 3 organisms, and no bacteria could be detected for the duration of the experiment (35 to 55 h). The KQ data confirmed that the milk remained unspoiled at the end of the experiments. The LP + garlic extract + ethanol system, on the other hand, had no effect on the growth or KQ with P. aeruginosa, but showed a small retardation of growth of the other 2 organisms, accompanied by small increases (5 to 10 h) in KQ. The effects of the LP+SCN-+H2O2 system were intermediate between those of the other 2 systems and differed between organisms. With P. aeruginosa, the system exerted total inhibition within 10 h of incubation, but the bacteria regained viability after a further 5 h, following a logarithmic growth curve. This was reflected in the KQ indicators, which implied an extension of 15 h. With the other 2 bacterial species, LP+SCN-+H2O2 exerted an obvious inhibitory effect, giving a lag phase in the growth curve of 5 to 10 h and KQ extension of 10 to 15 h. When used in combination, I- and SCN- displayed negative synergy.

Ex vivo evaluation of the effectiveness of bleaching agents on the shade alteration of blood-stained teeth

Aim To evaluate ex vivo effectiveness of the three formulations of bleaching materials for intracoronal bleaching of root filled teeth using the walking bleach technique.Methodology Extracted premolar teeth were stained artificially with human blood. After biomechanical preparation, the root canals were filled and a 3-mm thick intermediate base of zinc phosphate cement was placed at the level of the cementoenamel junction. The teeth were divided into four groups (n = 12): C (control, without bleaching material), A1 (sodium perborate + distilled water), A2 (sodium perborate + 10% carbamide peroxide) and A3 (sodium perborate + 35% carbamide peroxide). The bleaching materials were changed at 7 and 14 days. Evaluation of shade was undertaken with aid of the VITA Easyshade (TM) (Delta E*ab) and was performed after tooth staining and at 7, 14 and 21 days after bleaching, based on the CIELAB system. Data were analysed by ANOVA for repeated measurements, Tukey and Dunnett tests (alpha = 0.05).Results The Tukey test revealed that group A1 (10.58 +/- 4.83 Delta E*ab) was statistically different from the others (A2, 19.57 +/- 4.72 Delta E*ab and A3, 17.58 +/- 3.33 Delta E*ab), which were not different from each other. At 7 days: A1 was significantly different from A2; at 14 and 21 days: A2 and A3 were significantly better than A1; the Dunnett test revealed that the control group was different from A1, A2 and A3 at all periods (P < 0.05).Conclusion Sodium perborate associated with both 10% and 35% carbamide peroxide was more effective than when associated with distilled water.

Use of one-bottle adhesive as an intermediate bonding layer to reduce sealant microleakage on saliva-contaminated enamel

Purpose: To evaluate the influence of three different adhesives, each used as an intermediary layer, on microleakage of sealants applied under condition of salivary contamination. Materials and Methods: Six different experimental conditions were compared, 3 with adhesives and 3 without. After prophylaxis and acid etching of enamel, salivary contamination was placed for 10 s. In Group SC the sealant was applied after saliva without bonding agent and then light-cured. In Group SCA, after saliva, the surface was air dried, and then the sealant was applied and cured. In Groups ScB, SB and PB, a bonding agent (Scotchbond Dual Cure/3M, Single Bond/3M and Prime & Bond 2.1/Dentsply, respectively) was applied after the saliva and prior to the sealant application and curing. After storage in distilled water at 37°C for 24 hrs, the teeth were submitted to 500 thermal cycles (5°C and 55°C), and silver nitrate was used as a leakage tracer. Leakage data were collected on cross sections as percentage of total enamel-sealant interface length. Representative samples were evaluated under SEM. Results: Sealants placed on contaminated enamel with no bonding agent showed extensive microleakage (94.27% in SC; 42.65% in SCA). The SEM revealed gaps as wide as 20 μm in areas where silver nitrate leakage could be visualized. In contrast, all bonding agent groups showed leakage less than 6.9%. Placement of sealant with a dentin-bonding agent on contaminated enamel significantly reduced microleakage (P< 0.0001). The use of a bonding agent as an intermediary layer between enamel and sealant significantly reduced saliva's effect on sealant microleakage.

Nanoparticles increase the efficacy of cancer chemopreventive agents in cells exposed to cigarette smoke condensate

Lung cancer is a leading cause of death in developed countries. Although smoking cessation is a primary strategy for preventing lung cancer, former smokers remain at high risk of cancer. Accordingly, there is a need to increase the efficacy of lung cancer prevention. Poor bioavailability is the main factor limiting the efficacy of chemopreventive agents. The aim of this study was to increase the efficacy of cancer chemopreventive agents by using lipid nanoparticles (NPs) as a carrier. This study evaluated the ability of lipid NPs to modify the pharmacodynamics of chemopreventive agents including N-acetyl-L-cysteine, phenethyl isothiocyanate and resveratrol (RES). The chemopreventive efficacy of these drugs was determined by evaluating their abilities to counteract cytotoxic damage (DNA fragmentation) induced by cigarette smoke condensate (CSC) and to activate protective apoptosis (annexin-V cytofluorimetric staining) in bronchial epithelial cells both in vitro and in ex vivo experiment in mice. NPs decreased the toxicity of RES and increased its ability to counteract CSC cytotoxicity. NPs significantly increased the ability of phenethyl isothiocyanate to attenuate CSC-induced DNA fragmentation at the highest tested dose. In contrast, this potentiating effect was observed at all tested doses of RES, NPs dramatically increasing RES-induced apoptosis in CSC-treated cells. These results provide evidence that NPs are highly effective at increasing the efficacy of lipophilic drugs (RES) but are not effective towards hydrophilic agents (N-acetyl-L-cysteine), which already possess remarkable bioavailability. Intermediate effects were observed for phenethyl isothiocyanate. These findings are relevant to the identification of cancer chemopreventive agents that would benefit from lipid NP delivery.

Determination of decimal reduction time (D value) of chemical agents used in hospitals for disinfection purposes

Abstract Background Prior to the selection of disinfectants for low, intermediate and high (sterilizing) levels, the decimal reduction time, D-value, for the most common and persistent bacteria identified at a health care facility should be determined. Methods The D-value was determined by inoculating 100 mL of disinfecting solution with 1 mL of a bacterial suspension (104 – 105 CFU/mL for vegetative and spore forms). At regular intervals, 1 mL aliquots of this mixture were transferred to 8 mL of growth media containing a neutralizing agent, and incubated at optimal conditions for the microorganism. Results The highest D-values for various bacteria were determined for the following solutions: (i) 0.1% sodium dichloroisocyanurate (pH 7.0) – E. coli and A. calcoaceticus (D = 5.9 min); (ii) sodium hypochlorite (pH 7.0) at 0.025% for B. stearothermophilus (D = 24 min), E. coli and E. cloacae (D = 7.5 min); at 0.05% for B. stearothermophilus (D = 9.4 min) and E. coli (D = 6.1 min) and 0.1% for B. stearothermophilus (D = 3.5 min) and B. subtilis (D = 3.2 min); (iii) 2.0% glutaraldehyde (pH 7.4) – B. stearothermophilus, B. subtilis (D = 25 min) and E. coli (D = 7.1 min); (iv) 0.5% formaldehyde (pH 6.5) – B. subtilis (D = 11.8 min), B. stearothermophilus (D = 10.9 min) and A. calcoaceticus (D = 5.2 min); (v) 2.0% chlorhexidine (pH 6.2) – B. stearothermophilus (D = 9.1 min), and at 0.4% for E. cloacae (D = 8.3 min); (vi) 1.0% Minncare® (peracetic acid and hydrogen peroxide, pH 2.3) – B. stearothermophilus (D = 9.1 min) and E. coli (D = 6.7 min). Conclusions The suspension studies were an indication of the disinfectant efficacy on a surface. The data in this study reflect the formulations used and may vary from product to product. The expected effectiveness from the studied formulations showed that the tested agents can be recommended for surface disinfection as stated in present guidelines and emphasizes the importance and need to develop routine and novel programs to evaluate product utility.

An Innovative Phase I Trial Design Allowing for the Identification of Multiple Potential Maximum Tolerated Doses with Combination Therapy of Targeted Agents

Treatment for cancer often involves combination therapies used both in medical practice and clinical trials. Korn and Simon listed three reasons for the utility of combinations: 1) biochemical synergism, 2) differential susceptibility of tumor cells to different agents, and 3) higher achievable dose intensity by exploiting non-overlapping toxicities to the host. Even if the toxicity profile of each agent of a given combination is known, the toxicity profile of the agents used in combination must be established. Thus, caution is required when designing and evaluating trials with combination therapies. Traditional clinical design is based on the consideration of a single drug. However, a trial of drugs in combination requires a dose-selection procedure that is vastly different than that needed for a single-drug trial. When two drugs are combined in a phase I trial, an important trial objective is to determine the maximum tolerated dose (MTD). The MTD is defined as the dose level below the dose at which two of six patients experience drug-related dose-limiting toxicity (DLT). In phase I trials that combine two agents, more than one MTD generally exists, although all are rarely determined. For example, there may be an MTD that includes high doses of drug A with lower doses of drug B, another one for high doses of drug B with lower doses of drug A, and yet another for intermediate doses of both drugs administered together. With classic phase I trial designs, only one MTD is identified. Our new trial design allows identification of more than one MTD efficiently, within the context of a single protocol. The two drugs combined in our phase I trial are temsirolimus and bevacizumab. Bevacizumab is a monoclonal antibody targeting the vascular endothelial growth factor (VEGF) pathway which is fundamental for tumor growth and metastasis. One mechanism of tumor resistance to antiangiogenic therapy is upregulation of hypoxia inducible factor 1α (HIF-1α) which mediates responses to hypoxic conditions. Temsirolimus has resulted in reduced levels of HIF-1α making this an ideal combination therapy. Dr. Donald Berry developed a trial design schema for evaluating low, intermediate and high dose levels of two drugs given in combination as illustrated in a recently published paper in Biometrics entitled “A Parallel Phase I/II Clinical Trial Design for Combination Therapies.” His trial design utilized cytotoxic chemotherapy. We adapted this design schema by incorporating greater numbers of dose levels for each drug. Additional dose levels are being examined because it has been the experience of phase I trials that targeted agents, when given in combination, are often effective at dosing levels lower than the FDA-approved dose of said drugs. A total of thirteen dose levels including representative high, intermediate and low dose levels of temsirolimus with representative high, intermediate, and low dose levels of bevacizumab will be evaluated. We hypothesize that our new trial design will facilitate identification of more than one MTD, if they exist, efficiently and within the context of a single protocol. Doses gleaned from this approach could potentially allow for a more personalized approach in dose selection from among the MTDs obtained that can be based upon a patient’s specific co-morbid conditions or anticipated toxicities.

Computational modeling of intermediate temperature proton exchange membrane (PEM) fuel cells

A two-phase three-dimensional computational model of an intermediate temperature (120--190°C) proton exchange membrane (PEM) fuel cell is presented. This represents the first attempt to model PEM fuel cells employing intermediate temperature membranes, in this case, phosphoric acid doped polybenzimidazole (PBI). To date, mathematical modeling of PEM fuel cells has been restricted to low temperature operation, especially to those employing Nafion ® membranes; while research on PBI as an intermediate temperature membrane has been solely at the experimental level. This work is an advancement in the state of the art of both these fields of research. With a growing trend toward higher temperature operation of PEM fuel cells, mathematical modeling of such systems is necessary to help hasten the development of the technology and highlight areas where research should be focused.^ This mathematical model accounted for all the major transport and polarization processes occurring inside the fuel cell, including the two phase phenomenon of gas dissolution in the polymer electrolyte. Results were presented for polarization performance, flux distributions, concentration variations in both the gaseous and aqueous phases, and temperature variations for various heat management strategies. The model predictions matched well with published experimental data, and were self-consistent.^ The major finding of this research was that, due to the transport limitations imposed by the use of phosphoric acid as a doping agent, namely low solubility and diffusivity of dissolved gases and anion adsorption onto catalyst sites, the catalyst utilization is very low (∼1--2%). Significant cost savings were predicted with the use of advanced catalyst deposition techniques that would greatly reduce the eventual thickness of the catalyst layer, and subsequently improve catalyst utilization. The model also predicted that an increase in power output in the order of 50% is expected if alternative doping agents to phosphoric acid can be found, which afford better transport properties of dissolved gases, reduced anion adsorption onto catalyst sites, and which maintain stability and conductive properties at elevated temperatures.^