Prescription channeling of COX-2 inhibitors and traditional nonselective nonsteroidal anti-inflammatory drugs: a population-based case–control study

Affiliation: Faculté de pharmacie, Université de Montréal

Oleic Acid Modulates Metabolic Substrate Channeling during Glucose-Stimulated Insulin Secretion via NAD(P)H Oxidase

Positive acute effects of fatty acids (FA) on glucose-stimulated insulin secretion (GSIS) and reactive oxygen species (ROS) formation have been reported. However, those studies mainly focused on palmitic acid actions, and reports on oleic acid (OA) are scarce. In this study, the effect of physiological OA levels on beta-cell function and the mechanisms involved were investigated. Analyses of insulin secretion, FA and glucose oxidation, and ROS formation showed that, at high glucose concentration, OA treatment increases GSIS in parallel with increased ROS content. At high glucose, OA oxidation was increased, accompanied by a suppression of glucose oxidation. Using approaches for protein knockdown of FA receptor G protein-coupled receptor 40 (GPR40) and of p47(PHOX), a reduced nicotinamide adenine dinucleotide phosphate [NAD(P) H] oxidase component, we observed that GPR40 does not mediate OA effects on ROS formation and GSIS. However, in p47(PHOX) knockdown islets, OA-induced ROS formation and the inhibitory effect of OA on glucose metabolism was abolished. Similar results were obtained by pharmacological inhibition of protein kinase C, a known activator of NAD(P) H oxidase. Thus, ROS derived from OA metabolism via NAD(P) H oxidase are an inhibitor of glucose oxidation. Put together, these results indicate that OA acts as a modulator of glucose oxidation via ROS derived from its own metabolism in beta-cells. (Endocrinology 152: 3614-3621, 2011)

Implications of macromolecular crowding for signal transduction and metabolite channeling

The effect of different total enzyme concentrations on the flux through the bacterial phosphoenolpyruvate:carbohydrate phosphotransferase system (PTS) in vitro was determined by measuring PTS-mediated carbohydrate phosphorylation at different dilutions of cell-free extract of Escherichia coli. The dependence of the flux on the protein concentration was more than linear but less than quadratic. The combined flux–response coefficient of the four enzymes constituting the glucose PTS decreased slightly from values of ≈1.8 with increasing protein concentrations in the assay. Addition of the macromolecular crowding agents polyethylene glycol (PEG) 6000 and PEG 35000 led to a sharper decrease in the combined flux–response coefficient, in one case to values of ≈1. PEG 6000 stimulated the PTS flux at lower protein concentrations and inhibited the flux at higher protein concentrations, with the transition depending on the PEG 6000 concentration. This suggests that macromolecular crowding decreases the dissociation rate constants of enzyme complexes. High concentrations of the microsolute glycerol did not affect the combined flux–response coefficient. The data could be explained with a kinetic model of macromolecular crowding in a two-enzyme group-transfer pathway. Our results suggest that, because of the crowded environment in the cell, the different PTS enzymes form complexes that live long on the time-scale of their turnover. The implications for the metabolic behavior and control properties of the PTS, and for the effect of macromolecular crowding on nonequilibrium processes, are discussed.

Case management agency systems of administering long-term care : evidence from the channeling demonstration /

Mode of access: Internet.

Anisotropic Etching and Nanoribbon Formation in Single-Layer Graphene

We demonstrate anisotropic etching of single-layer graphene by thermally activated nickel nanoparticles. Using this technique, we obtain sub-10-nm nanoribbons and other graphene nanostructures with edges aligned along a single crystallographic direction. We observe a new catalytic channeling behavior, whereby etched cuts do not intersect, resulting in continuously connected geometries. Raman spectroscopy and electronic measurements show that the quality of the graphene is resilient under the etching conditions, indicating that this method may serve as a powerful technique to produce graphene nanocircuits with well-defined crystallographic edges.

The Lake Tekapo experiment (LTEX): An investigation of atmospheric boundary layer processes in complex terrain

A research program on atmospheric boundary layer processes and local wind regimes in complex terrain was conducted in the vicinity of Lake Tekapo in the southern Alps of New Zealand, during two 1-month field campaigns in 1997 and 1999. The effects of the interaction of thermal and dynamic forcing were of specific interest, with a particular focus on the interaction of thermal forcing of differing scales. The rationale and objectives of the field and modeling program are described, along with the methodology used to achieve them. Specific research aims include improved knowledge of the role of surface forcing associated with varying energy balances across heterogeneous terrain, thermal influences on boundary layer and local wind development, and dynamic influences of the terrain through channeling effects. Data were collected using a network of surface meteorological and energy balance stations, radiosonde and pilot balloon soundings, tethered balloon and kite-based systems, sodar, and an instrumented light aircraft. These data are being used to investigate the energetics of surface heat fluxes, the effects of localized heating/cooling and advective processes on atmospheric boundary layer development, and dynamic channeling. A complementary program of numerical modeling includes application of the Regional Atmospheric Modeling System (RAMS) to case studies characterizing typical boundary layer structures and airflow patterns observed around Lake Tekapo. Some initial results derived from the special observation periods are used to illustrate progress made to date. In spite of the difficulties involved in obtaining good data and undertaking modeling experiments in such complex terrain, initial results show that surface thermal heterogeneity has a significant influence on local atmospheric structure and wind fields in the vicinity of the lake. This influence occurs particularly in the morning. However, dynamic channeling effects and the larger-scale thermal effect of the mountain region frequently override these more local features later in the day.

As métricas de avaliação da performance e a sua contribuição na tomada de decisão, na concessão de crédito e avaliação de risco, numa instituição bancária

Mestrado em Contabilidade e Gestão das Instituições Financeiras

A importância da liderança para o engagement dos colaboradores nas empresas do Vale do Ave

Dissertação apresentada ao Instituto Politécnico do Porto para obtenção do Grau Mestre em Gestão das Organizações, Ramo de Gestão de Empresas Orientada pela Professora Doutora Maria Alexandra Pacheco Ribeiro da Costa

Territorial autonomy and self-determination conflicts: opportunity and willingness cases from Bolivia, Niger, and Thailand

The paradox of autonomy is about whether self-rule accommodates or exacerbates armed conflict. This study attempts to unpack the puzzle examining the effectiveness of territorial autonomy as a state response to self-determination conflicts throughout the world. It challenges the conflict-inducing features of autonomy arguing that territorial autonomy can mitigate armed conflict by channeling group grievances into peaceful forms of protest. Thus, this study aims at arriving at a comprehensive theory that identifies which factors are responsible for violent escalation of conflicts grounded in self-determination demands. By using the concepts of opportunity structures and willingness dimension, this study shows that conflict escalation only takes place when minorities with greater bargaining power vis-à-vis the center, in contexts of high levels of economic inequality within dyad, are mobilized around autonomy and separatist demands.

Alternativas de Investimentos Financeiros para as empresas em São Vicente

A tendência, hoje em dia, é para a captação directa das poupanças aos investidores. Esta captação faz-se através da emissão de produtos financeiros. Dada a incerteza e diversidade de produtos financeiros, o investidor terá de analisar cuidadosamente as múltiplas alternativas existentes e tomar a decisão de investir de acordo com a rendibilidade que pretende obter e o nível de risco que está disposto a correr. O trabalho ora apresentado espelha uma análise dos Riscos/Rendibilidade associados aos Investimentos Financeiros tais como Depósitos a Prazos, Obrigações, Acções e Bilhetes de Tesouro, com foco nos dois primeiros. O desenvolvimento da temática foi orientado numa primeira etapa para através da pesquisa necessária a construção do referencial teórico centrado por um lado, nos conceitos associados a mercados financeiros bem como os riscos associados as transacções desses produtos financeiros nesse mercado. Mencionamos diferentes tipos de produtos financeiros transaccionados neste mercado, bem como a importância da cotação destes produtos na Bolsa de Valores. A sustentabilidade deste rico referencial teórico ficou evidenciada através de um estudo de caso de uma empresa que dedica ao comércio - geral de Materiais de Construção, partindo de uma análise gráfica comparada que irá demonstrar qual o risco e a rendibilidade que há em canalizar parte do valor aplicado no depósito a prazo para investir em obrigações do BCA emitidas em Dezembro de 2010. Nowadays the tendency is for the reception all-nighter of the savings to the investors. This reception is made through the emission of financial products. Owing to the uncertainty and diversity of financial products, the investor has to analyze carefully the multiple existent alternatives and then decide to invest according to the profitability he intends to obtain and the risk level he is willing to run. The work for now presented mirrors an analysis of the risks / profitability associated to the Financial Investments as Deposits to periods, Obligations, Shares, Tickets of Treasury, with focus in the first two. The development of the theme was guided in a first stage for through the necessary research for the construction of the theoretical referential system centered on one side, in the concepts associated to financial markets as well as the risks associated to the transactions of those financial products in that market. We referred to different types of financial products transacted in this market, as well as the importance of the quotation of these products in the stock exchange. The sustainability of this rich theoretical referential system was evidenced through a study of case of a company that dedicates to the trade of construction materials, leaving from a compared analysis that will demonstrate Which the risk and the profitability that there is in channeling part of the applied value in the deposit to period to invest in obligations of „BCA‟ emitted in December of 2010.

Epitaxial growth of Y-doped SrZrO3 films on MgO by pulsed laser deposition

Epitaxial thin films of Y¿doped SrZrO3 have been grown on MgO(001) by pulsed laser deposition. The deposition process has been performed at temperatures of 1000¿1200¿°C and at an oxygen pressure of 1.5×10¿1 mbar. The samples are characterized by Rutherford backscattering spectrometry/channeling (RBS/C) and x¿ray diffraction (XRD). We found an epitaxial relationship of SrZrO3 (0k0) [101]¿MgO (001) [100]. Good crystalline quality is confirmed by RBS/C minimum yield values of 9% and a FWHM of 0.35° of the XRD rocking curve.

Induction of the acyl-coenzyme A synthetase gene by fibrates and fatty acids is mediated by a peroxisome proliferator response element in the C promoter.

The long-chain acyl-coenzyme A synthetase (ACS) gene gives rise to three transcripts containing different first exons preceded by specific regulatory regions A, B, and C. Exon-specific oligonucleotide hybridization indicated that only A-ACS mRNA is expressed in rat liver. Fibrate administration induced liver C-ACS strongly and A-ACS mRNA to a lesser extent. B-ACS mRNA remained undetectable. In primary rat hepatocytes and Fa-32 hepatoma cells C-ACS mRNA increased after treatment with fenofibric acid, alpha-bromopalmitate, tetradecylthioacetic acid, or alpha-linolenic acid. Nuclear run-on experiments indicated that fenofibric acid and alpha-bromopalmitate act at the transcriptional level. Transient transfections showed a 3.4-, 2.3-, and 2.2-fold induction of C-ACS promoter activity after fenofibric acid, alpha-bromopalmitate, and tetradecylthioacetic acid, respectively. Unilateral deletion and site-directed mutagenesis identified a peroxisome proliferator activator receptor (PPAR)-responsive element (PPRE) mediating the responsiveness to fibrates and fatty acids. This ACS PPRE contains three imperfect half sites spaced by 1 and 3 oligonucleotides and binds PPAR.retinoid X receptor heterodimers in gel retardation assays. In conclusion, the regulation of C-ACS mRNA expression by fibrates and fatty acids is mediated by PPAR.retinoid X receptor heterodimers interacting through a PPRE in the C-ACS promoters. PPAR therefore occupies a key position in the transcriptional control of a pivotal enzyme controlling the channeling of fatty acids into various metabolic pathways.

Utilization of Knowledge Management in Business Process Modeling and Process Improvements

Tutkimuksen tavoitteena on tutkia telekommunikaatioalalla toimivan kohdeyrityksen ohjelmistojen toimitusprosessia° Tutkimus keskittyy mallintamaan toimitusprosessin, määrittelemään roolit ja vastuualueet, havaitsemaan ongelmakohdat ja ehdottamaan prosessille kehityskohteita. Näitä tavoitteita tarkastellaan teoreettisten prosessimallinnustekniikoiden ja tietojohtamisen SECI-prosessikehyksen läpi. Tärkein tiedonkeruun lähde oli haastatteluihin perustuva tutkimus, johon osallistuvat kaikki kohdeprosessiin kuuluvat yksiköt. Mallinnettu toimitusprosessi antoi kohdeyritykselle paremman käsityksen tarkasteltavasta prosessista ja siinä toimivien yksiköiden rooleistaja vastuualueista. Parannusehdotuksia olivat tiedonjaon kanavoinnin määritteleminen, luottamuksen ja sosiaalisten verkostojen parantaminen, ja tietojohtamisen laajamittainen implementointi.

Effect of Cumulating Exposure to Abacavir on the Risk of Cardiovascular Disease Events in Patients From the Swiss HIV Cohort Study.

BACKGROUND: Patients with HIV exposed to the antiretroviral drug abacavir may have an increased risk of cardiovascular disease (CVD). There is concern that this association arises because of a channeling bias. Even if exposure is a risk, it is not clear how that risk changes as exposure cumulates. METHODS: We assess the effect of exposure to abacavir on the risk of CVD events in the Swiss HIV Cohort Study. We use a new marginal structural Cox model to estimate the effect of abacavir as a flexible function of past exposures while accounting for risk factors that potentially lie on a causal pathway between exposure to abacavir and CVD. RESULTS: A total of 11,856 patients were followed for a median of 6.6 years; 365 patients had a CVD event (4.6 events per 1000 patient-years). In a conventional Cox model, recent--but not cumulative--exposure to abacavir increased the risk of a CVD event. In the new marginal structural Cox model, continued exposure to abacavir during the past 4 years increased the risk of a CVD event (hazard ratio = 2.06; 95% confidence interval: 1.43 to 2.98). The estimated function for the effect of past exposures suggests that exposure during the past 6-36 months caused the greatest increase in risk. CONCLUSIONS: Abacavir increases the risk of a CVD event: the effect of exposure is not immediate, rather the risk increases as exposure cumulates over the past few years. This gradual increase in risk is not consistent with a rapidly acting mechanism, such as acute inflammation.

Monikanavaisen kriisiviestintämallin kehittäminen, asiakasyrityksenä Medi-IT Oy

Tämän diplomityön tavoitteena oli selvittää, mitä asioita organisaation tulisi huomioida tehokkaan, monikanavaisen kriisiviestintämallin suunnittelussa ja toteuttamisessa. Asiakasyritys Medi-IT Oy tukee terveydenhuollon ja sosiaalitoimen palveluntuottajien toimintaa tarjoamalla ja tuottamalla asiantuntija- ja tietotekniikkapalveluita. Tutkimuksessa keskitytään yrityksen tukipalveluyksikköön ja viestinnän lajeista häiriötilanteiden viestintään. Kriisiviestintämalli voidaan tarvittaessa lanseerata myös muihin yksiköihin. Medi-IT Oy:n kriisiviestintämallin kehittäminen aloitettiin kartoittamalla nykytilaa. Tämä tehtiin yrityksen nykyisiä toimintatapoja selvittämällä ja kysymällä asiakkaiden ja työntekijöiden mielipiteitä ja kokemuksia. Viestintään liittyvän puhelinkyselyn asiakkaille suoritti InnoLink-yritys. Kyselyn tuloksista nousi esiin viestinnän ongelmakohtia. Näihin paneutumalla löydettiin kehitettävät kohteet. Nämä kriisiviestinnän ja samalla tapahtumien hallinnan kehityskohteet on esitetty toimintojen tarkennuksina. Asiakasyritys on panostamassa prosessien laatuun ja on aloittamassa ITIL:in hyödyntämisen prosessien läpikäymisessä. Siksi myös ITIL:in periaatteita otettiin huomioon tässä kriisiviestinnän prosessimallissa. Työssä selvitettiin teoriakatsauksen pohjalta, mitkä ovat hyvän kriisiviestinnän ominaisuudet ja mitkä ovat monikanavaisuuden asettamat haasteet, edut ja haitat. Prosessin mallintamisessa käytettiin tapahtumien hallintaan keskittyvää työkalua. Työn lopputuloksena syntyi asiakasyritykselle monikanavaisen kriisiviestinnän kehittämismalli sekä kehittämistä vaativien toimintojen tarkennukset. Työhön sisältyy myös tulevaisuuden kriisiviestinnän prosessimalli, jonka toteutuminen ei ole vielä teknisesti täysin mahdollista.