Showing papers by "University of Ottawa published in 2005"

Stochasticity in gene expression: from theories to phenotypes

Abstract: Genetically identical cells exposed to the same environmental conditions can show significant variation in molecular content and marked differences in phenotypic characteristics. This variability is linked to stochasticity in gene expression, which is generally viewed as having detrimental effects on cellular function with potential implications for disease. However, stochasticity in gene expression can also be advantageous. It can provide the flexibility needed by cells to adapt to fluctuating environments or respond to sudden stresses, and a mechanism by which population heterogeneity can be established during cellular differentiation and development.

Erlotinib in lung cancer - molecular and clinical predictors of outcome.

Abstract: Background A clinical trial that compared erlotinib with a placebo for non–small-cell lung cancer demonstrated a survival benefit for erlotinib. We used tumor-biopsy samples from participants in this trial to investigate whether responsiveness to erlotinib and its impact on survival were associated with expression by the tumor of epidermal growth factor receptor (EGFR) and EGFR gene amplification and mutations. Methods EGFR expression was evaluated immunohistochemically in non–small-cell lung cancer specimens from 325 of 731 patients in the trial; 197 samples were analyzed for EGFR mutations; and 221 samples were analyzed for the number of EGFR genes. Results In univariate analyses, survival was longer in the erlotinib group than in the placebo group when EGFR was expressed (hazard ratio for death, 0.68; P=0.02) or there was a high number of copies of EGFR (hazard ratio, 0.44; P=0.008). In multivariate analyses, adenocarcinoma (P=0.01), never having smoked (P<0.001), and expression of EGFR (P=0.03) were a...

Interprofessional teamwork: Professional cultures as barriers

Abstract: Each health care profession has a different culture which includes values, beliefs, attitudes, customs and behaviours. Professional cultures evolved as the different professions developed, reflecting historic factors, as well as social class and gender issues. Educational experiences and the socialization process that occur during the training of each health professional reinforce the common values, problem-solving approaches and language/jargon of each profession. Increasing specialization has lead to even further immersion of the learners into the knowledge and culture of their own professional group. These professional cultures contribute to the challenges of effective interprofessional teamwork. Insight into the educational, systemic and personal factors which contribute to the culture of the professions can help guide the development of innovative educational methodologies to improve interprofessional collaborative practice.

Adjuvant docetaxel for node-positive breast cancer.

Abstract: results At a median follow-up of 55 months, the estimated rates of disease-free survival at five years were 75 percent among the 745 patients randomly assigned to receive TAC and 68 percent among the 746 randomly assigned to receive FAC, representing a 28 percent reduction in the risk of relapse (P=0.001) in the TAC group. The estimated rates of overall survival at five years were 87 percent and 81 percent, respectively. Treatment with TAC resulted in a 30 percent reduction in the risk of death (P=0.008). The incidence of grade 3 or 4 neutropenia was 65.5 percent in the TAC group and 49.3 percent in the FAC group (P<0.001); rates of febrile neutropenia were 24.7 percent and 2.5 percent, respectively (P<0.001). Grade 3 or 4 infections occurred in 3.9 percent of the patients who received TAC and 2.2 percent of those who received FAC (P=0.05); no deaths occurred as a result of infection. Two patients in each group died during treatment. Congestive heart failure and acute myeloid leukemia occurred in less than 2 percent of the patients in each group. Quality-of-life scores decreased during chemotherapy but returned to baseline levels after treatment. conclusions Adjuvant chemotherapy with TAC, as compared with FAC, significantly improves the rates of disease-free and overall survival among women with operable node-positive breast cancer.

Frequency, type and clinical importance of medication history errors at admission to hospital: a systematic review

Abstract: Background: Over a quarter of hospital prescribing errors are attributable to incomplete medication histories being obtained at the time of admission. We undertook a systematic review of studies describing the frequency, type and clinical importance of medication history errors at hospital admission. Methods: We searched MEDLINE, EMBASE and CINAHL for articles published from 1966 through April 2005 and bibliographies of papers subsequently retrieved from the search. We reviewed all published studies with quantitative results that compared prescription medication histories obtained by physicians at the time of hospital admission with comprehensive medication histories. Three reviewers independently abstracted data on methodologic features and results. Results: We identified 22 studies involving a total of 3755 patients (range 33–1053, median 104). Errors in prescription medication histories occurred in up to 67% of cases: 10%– 61% had at least 1 omission error (deletion of a drug used before admission), and 13%– 22% had at least 1 commission error (addition of a drug not used before admission); 60%– 67% had at least 1 omission or commission error. Only 5 studies ( n = 545 patients) explicitly distinguished between unintentional discrepancies and intentional therapeutic changes through discussions with ordering physicians. These studies found that 27%– 54% of patients had at least 1 medication history error and that 19%– 75% of the discrepancies were unintentional. In 6 of the studies ( n = 588 patients), the investigators estimated that 11%–59% of the medication history errors were clinically important. Interpretation: Medication history errors at the time of hospital admission are common and potentially clinically important. Improved physician training, accessible community pharmacy databases and closer teamwork between patients, physicians and pharmacists could reduce the frequency of these errors.

Hypersensitivity of DJ-1-deficient mice to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrindine (MPTP) and oxidative stress

Abstract: Mutations of the DJ-1 (PARK7) gene are linked to familial Parkinson's disease. We used gene targeting to generate DJ-1-deficient mice that were viable, fertile, and showed no gross anatomical or neuronal abnormalities. Dopaminergic neuron numbers in the substantia nigra and fiber densities and dopamine levels in the striatum were normal. However, DJ-1-/- mice showed hypolocomotion when subjected to amphetamine challenge and increased striatal denervation and dopaminergic neuron loss induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrindine. DJ-1-/-embryonic cortical neurons showed increased sensitivity to oxidative, but not nonoxidative, insults. Restoration of DJ-1 expression to DJ-1-/- mice or cells via adenoviral vector delivery mitigated all phenotypes. WT mice that received adenoviral delivery of DJ-1 resisted 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrindine-induced striatal damage, and neurons overexpressing DJ-1 were protected from oxidative stress in vitro. Thus, DJ-1 protects against neuronal oxidative stress, and loss of DJ-1 may lead to Parkinson's disease by conferring hypersensitivity to dopaminergic insults.

Sirt1 regulates insulin secretion by repressing UCP2 in pancreatic beta cells.

Abstract: Sir2 and insulin/IGF-1 are the major pathways that impinge upon aging in lower organisms. In Caenorhabditis elegans a possible genetic link between Sir2 and the insulin/IGF-1 pathway has been reported. Here we investigate such a link in mammals. We show that Sirt1 positively regulates insulin secretion in pancreatic beta cells. Sirt1 represses the uncoupling protein (UCP) gene UCP2 by binding directly to the UCP2 promoter. In beta cell lines in which Sirt1 is reduced by SiRNA, UCP2 levels are elevated and insulin secretion is blunted. The up-regulation of UCP2 is associated with a failure of cells to increase ATP levels after glucose stimulation. Knockdown of UCP2 restores the ability to secrete insulin in cells with reduced Sirt1, showing that UCP2 causes the defect in glucose-stimulated insulin secretion. Food deprivation induces UCP2 in mouse pancreas, which may occur via a reduction in NAD (a derivative of niacin) levels in the pancreas and down-regulation of Sirt1. Sirt1 knockout mice display constitutively high UCP2 expression. Our findings show that Sirt1 regulates UCP2 in beta cells to affect insulin secretion.

Residential Radon and Risk of Lung Cancer: A Combined Analysis of 7 North American Case-Control Studies

Abstract: Background:Underground miners exposed to high levels of radon have an excess risk of lung cancer. Residential exposure to radon is at much lower levels, and the risk of lung cancer with residential exposure is less clear. We conducted a systematic analysis of pooled data from all North American resi

The Structure of Goal Contents Across 15 Cultures.

Abstract: The authors investigated the structure of goal contents in a group of 1,854 undergraduates from 15 cultures around the world. Results suggested that the 11 types of goals the authors assessed were consistently organized in a circumplex fashion across the 15 cultures. The circumplex was well described by positioning 2 primary dimensions underlying the goals: intrinsic (e.g., self-acceptance, affiliation) versus extrinsic (e.g., financial success, image) and self-transcendent (e.g., spirituality) versus physical (e.g., hedonism). The circumplex model of goal contents was also quite similar in both wealthier and poorer nations, although there were some slight cross-cultural variations. The relevance of these results for several theories of motivation and personality are discussed.

Glucosamine therapy for treating osteoarthritis.

Abstract: What is osteoarthritis and glucosamine? Osteoarthritis (OA) is the most common form of arthritis that can affect the hands, hips, shoulders and knees. In OA, the cartilage that protects the ends of the bones breaks down and causes pain and swelling. Drug and non-drug treatments are used to relieve pain and/or swelling. Glucosamine can be found naturally in the body and is used by the body as one of the building blocks of cartilage. Glucosamine can also be taken as a pill as a supplement to the diet, or sometimes as an injection. It can come in combination with other supplements (such as chondroitin), or by itself in the form of glucosamine hydrochloride or sulphate. The usual dose recommended on packages is 1500 mg per day or 500 mg three times a day. In Europe, glucosamine is prescribed by health care providers. But in North America, people can buy glucosamine supplements without a prescription. This means that, in North America, glucosamine is not regulated and the pills may or may not truly contain the amount described on the label. Best estimate of what happens after about 6 months Pain: The high quality studies showed that pain improved about the same whether people took glucosamine or fake pills. If all of the studies are examined (including low quality and old studies), then glucosamine improved pain more than fake pills. People who took fake pills had a pain score of 7 points on a 0 to 100 scale. Pain may improve by 10 more points with glucosamine than with fake pills. Studies testing only the Rotta brand of glucosamine (including low quality and older studies) showed that glucosamine improved pain more than fake pills. People who took fake pills had a pain score of 6 points on a 0 to 20 scale. People who took the Rotta brand of glucosamine rated their pain 3 points lower than people who did not take glucosamine. Function: The high quality studies show that glucosamine improved function more than fake pills when measured by one type of scale, but improved the same amount as fake pills when measured by another scale. Studies testing only the Rotta brand of glucosamine (including low quality and older studies) showed that glucosamine improved function more than fake pills. People who took fake pills had a function score of 22 points on a 0 to 68 scale. People who took the Rotta brand of glucosamine had their ability to function improve by 2 points compared to people who did not take glucosamine. There was no difference in the number of people who had side effects. Side effects mainly included stomach upset and other joint pain.

The metabolically healthy but obese individual presents a favorable inflammation profile.

Abstract: 4.8 vs. 45.5 4.4%; not significant), MHO individuals had significantly lower levels of visceral fat, fasting insulin, plasma triglycerides, high-sensitivity C-reactive protein (CRP), and -1 antitrypsin levels and higher levels of high-density lipoprotein cholesterol than at risk individuals (P 0.05). Stepwise regression analysis showed that CRP, fasting triglycerides, and the lean body mass index explained 19.5, 8.5, and 4.0%, respectively, of the variance observed in glucose disposal (total r 2 0.320; P 0.001) Conclusion: Results of the present study indicate that postmenopausal women displaying the MHO phenotype also have a favorable inflammation profile as shown by lower CRP and -1 antitrypsin levels compared with insulin-resistant women. This suggests that a lower inflammation state, as attested by low CRP levels, could play a role in the protective profile of the MHO individual, and this may be associated metabolically to a lower risk for cardiovascular disease. (J Clin Endocrinol Metab 90: 4145–4150, 2005)

A Meta‐analysis for Exploring the Diverse Causes and Effects of Stress in Teachers

Abstract: This study provides a correlational meta ‐ analysis of 65 independently written or published studies on teacher stress between 1998 and 2003. We measured the relationships between teacher stress and numerous other constructs including coping, burnout, emotional responses, personality mediators, personal support, environmental structure, and background characteristics. A theoretical ‐ empirical model of construct relationships investigated across studies was developed and n = 2,527 correlational effect sizes were used to estimate the empirical relationships between the operationalized theoretical constructs. Results showed that the strongest association of teacher stressors exists with negatively oriented emotional responses confirming the central role of teachers’ coping mechanisms, personality mediators, and burnout potential according to our model of the stress cycle. Key words: stress, coping, teacher burn ‐ out, teacher emotional response Cette recherche fournit une meta ‐ analyse correlationnelle de 65 etudes, redigees ou publiees entre 1998 et 2003, sur le stress chez les enseignants. Les auteurs ont mesure les relations entre le stress des enseignants et de nombreux autres construits, dont l’adaptation au stress, l’epuisement professionnel, les reactions emotionnelles, les personality mediators, le soutien personnel, la structure du milieu et les antecedents. Un modele theorico ‐ empirique des relations entre les construits a ete elabore et des valeurs d’effets correlationnels de n = 2527 ont ete utilisees pour determiner les relations empiriques entre les construits theoriques operationalises. Les resultats demontrent que, pour les facteurs de stress chez les enseignants, l’association la plus importante se trouve du cote des reactions emotionnelles negatives, ce qui confirme le role cle des mecanismes d’adaptation au stress des enseignants, des personality mediators et du potentiel d’epuisement professionnel selon le modele du cycle du stress qui a ete utilise. Mots cles : stress, adaptation au stress, meta ‐ analyse, enseignants.

Recommended Standard of Cerebrospinal Fluid Analysis in the Diagnosis of Multiple Sclerosis: A Consensus Statement

Abstract: New criteria for the diagnosis of multiple sclerosis (MS) were published as the result of an internationally formed committee. To increase the specificity of diagnosis and to minimize the number of false diagnoses, the committee recommended the use of both clinical and paraclinical criteria, the latter involving information obtained from magnetic resonance imaging, evoked potentials, and cerebrospinal fluid (CSF) analysis. Although rigorous magnetic resonance imaging requirements were provided, the "new criteria paper" fell short in terms of guidelines as to how the CSF analysis should be performed and simply equated the IgG index with isoelectric focusing, without any justification. The spectrum of parameters analyzed and methods, for CSF analysis differ worldwide and often yield variable results in terms of sensitivity, specificity, accuracy, and reliability, with no decided "optimal" CSF test for the diagnosis of MS. To address this question specifically, an international panel of experts in MS and CSF diagnostic techniques was convened and the result was this article, representing a consensus of all the participants. These recommendations for establishing a standard for the evaluation of CSF in patients suspected of having MS should greatly complement the new criteria in ensuring that a correct diagnosis of MS is being made.

A Cube Model for Competency Development: Implications for Psychology Educators and Regulators

Abstract: This article provides a conceptual framework for training in professional psychology focused on the construct of competency. The authors present a 3-dimensional competency model delineating the domains of knowledge, skills, attitudes, and values that serve as the foundation required of all psychologists, the domains of functional competencies that broadly define what psychologists do, and the stages of professional development from doctoral education to lifelong learning through continuing education. The goal in presenting this model is to provide a conceptual frame of reference for those responsible for psychology education, credentialing, and regulation.

Studying Software Engineers: Data Collection Techniques for Software Field Studies

Abstract: Software engineering is an intensively people-oriented activity, yet too little is known about how designers, maintainers, requirements analysts and all other types of software engineers perform their work. In order to improve software engineering tools and practice, it is therefore essential to conduct field studies, i.e. to study real practitioners as they solve real problems. To do so effectively, however, requires an understanding of the techniques most suited to each type of field study task. In this paper, we provide a taxonomy of techniques, focusing on those for data collection. The taxonomy is organized according to the degree of human intervention each requires. For each technique, we provide examples from the literature, an analysis of some of its advantages and disadvantages, and a discussion of how to use it effectively. We also briefly talk about field study design in general, and data analysis.

A solution to the 2-pyridyl organometallic cross-coupling problem: regioselective catalytic direct arylation of pyridine N-oxides.

Abstract: Direct arylation reactions of pyridine N-oxides occur in excellent yield with complete selectivity for the 2-position with a wide range of aryl bromides. This reactivity permits the use of inexpensive, commercially available, and bench-stable pyridine N-oxides as replacements for problematic 2-metallapyridines in palladium-catalyzed cross-coupling reactions.

Adverse drug events occurring following hospital discharge.

Abstract: OBJECTIVE: To describe the incidence of adverse drug events (ADEs), preventable ADEs, and ameliorable ADEs occurring after hospital discharge and their associated risk factors.

Comparison of the Canadian CT Head Rule and the New Orleans Criteria in Patients With Minor Head Injury

Abstract: ContextCurrent use of cranial computed tomography (CT) for minor head injury is increasing rapidly, highly variable, and inefficient. The Canadian CT Head Rule (CCHR) and New Orleans Criteria (NOC) are previously developed clinical decision rules to guide CT use for patients with minor head injury and with Glasgow Coma Scale (GCS) scores of 13 to 15 for the CCHR and a score of 15 for the NOC. However, uncertainty about the clinical performance of these rules exists.ObjectiveTo compare the clinical performance of these 2 decision rules for detecting the need for neurosurgical intervention and clinically important brain injury.Design, Setting, and PatientsIn a prospective cohort study (June 2000-December 2002) that included 9 emergency departments in large Canadian community and university hospitals, the CCHR was evaluated in a convenience sample of 2707 adults who presented to the emergency department with blunt head trauma resulting in witnessed loss of consciousness, disorientation, or definite amnesia and a GCS score of 13 to 15. The CCHR and NOC were compared in a subgroup of 1822 adults with minor head injury and GCS score of 15.Main Outcome MeasuresNeurosurgical intervention and clinically important brain injury evaluated by CT and a structured follow-up telephone interview.ResultsAmong 1822 patients with GCS score of 15, 8 (0.4%) required neurosurgical intervention and 97 (5.3%) had clinically important brain injury. The NOC and the CCHR both had 100% sensitivity but the CCHR was more specific (76.3% vs 12.1%, P<.001) for predicting need for neurosurgical intervention. For clinically important brain injury, the CCHR and the NOC had similar sensitivity (100% vs 100%; 95% confidence interval [CI], 96%-100%) but the CCHR was more specific (50.6% vs 12.7%, P<.001), and would result in lower CT rates (52.1% vs 88.0%, P<.001). The κ values for physician interpretation of the rules, CCHR vs NOC, were 0.85 vs 0.47. Physicians misinterpreted the rules as not requiring imaging for 4.0% of patients according to CCHR and 5.5% according to NOC (P = .04). Among all 2707 patients with a GCS score of 13 to 15, the CCHR had sensitivities of 100% (95% CI, 91%-100%) for 41 patients requiring neurosurgical intervention and 100% (95% CI, 98%-100%) for 231 patients with clinically important brain injury.ConclusionFor patients with minor head injury and GCS score of 15, the CCHR and the NOC have equivalent high sensitivities for need for neurosurgical intervention and clinically important brain injury, but the CCHR has higher specificity for important clinical outcomes than does the NOC, and its use may result in reduced imaging rates.

Extrinsic optical scattering loss in photonic crystal waveguides: role of fabrication disorder and photon group velocity.

Abstract: Formulas are presented that provide clear physical insight into the phenomenon of extrinsic optical scattering loss in photonic crystal waveguides due to random fabrication imperfections such as surface roughness and disorder. Using a photon Green-function-tensor formalism, we derive explicit expressions for the backscattered and total transmission losses. Detailed calculations for planar photonic crystals yield extrinsic loss values in overall agreement with experimental measurements, including the full dispersion characteristics. We also report that loss in photonic crystal waveguides scales inversely with group velocity, at least, thereby raising serious questions about future low-loss applications based on operating frequencies that approach the photonic band edge.

Factor analytic models: viewing the structure of an assessment instrument from three perspectives.

Abstract: The overarching purpose of this article is to present a nonmathematical introduction to the application of confirmatory factor analysis (CFA) within the framework of structural equation modeling as it applies to psychological assessment instruments. In the interest of clarity and ease of understanding, I model exploratory factor analysis (EFA) structure in addition to first- and second-order CFA structures. All factor analytic structures are based on the same measuring instrument, the Beck Depression Inventory–II (BDI–II; Beck, Steer, & Brown, 1996). Following a "walk" through the general process of CFA modeling, I identify several common misconceptions and improper application practices with respect to both EFA and CFA and tender caveats with a view to preventing further proliferation of these pervasive practices.

Fraïssé Limits, Ramsey Theory, and topological dynamics of automorphism groups

Abstract: (A) In this paper we study some connections between the Fraisse theory of amalgamation classes and ultrahomogeneous structures, Ramsey theory, and topological dynamics of automorphism groups of countable structures. A prime concern of topological dynamics is the study of continuous actions of (Hausdorff) topological groups G on (Hausdorff) compact spaces X.

On adaptive Markov chain Monte Carlo algorithms

Abstract: We look at adaptive Markov chain Monte Carlo algorithms that generate stochastic processes based on sequences of transition kernels, where each transition kernel is allowed to depend on the history of the process. We show under certain conditions that the stochastic process generated is ergodic, with appropriate stationary distribution. We use this result to analyse an adaptive version of the random walk Metropolis algorithm where the scale parameter σ is sequentially adapted using a Robbins-Monro type algorithm in order to find the optimal scale parameter σopt. We close with a simulation example.

Latent Motivational Change in an Academic Setting: A 3-Year Longitudinal Study

Abstract: This research examined changes in intrinsic and extrinsic motivation during the transition from junior to senior high school as well as the impact of motivational changes on various educational consequences (i.e., dropout intentions, absenteeism, homework frequency, and educational aspirations). A total of 646 participants completed a questionnaire in 8th, 9th, and 10th grade.Using the true intraindividual change modeling technique (R.Steyer, I.Partchev, & M.J.Shanahan, 2000), the authors reached results revealing that students’ intrinsic motivation and extrinsic motivation decreased gradually from 8th to 10th grade.Furthermore, less educational adjustment was observed for students experiencing a decline in external regulation during the transitional year and students experiencing a decline in intrinsic motivation and identified regulation during the year after the transition.