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Showing papers by "University of Western Ontario published in 2005"


Journal ArticleDOI
TL;DR: The addition of temozolomide to radiotherapy for newly diagnosed glioblastoma resulted in a clinically meaningful and statistically significant survival benefit with minimal additional toxicity.
Abstract: methods Patients with newly diagnosed, histologically confirmed glioblastoma were randomly assigned to receive radiotherapy alone (fractionated focal irradiation in daily fractions of 2 Gy given 5 days per week for 6 weeks, for a total of 60 Gy) or radiotherapy plus continuous daily temozolomide (75 mg per square meter of body-surface area per day, 7 days per week from the first to the last day of radiotherapy), followed by six cycles of adjuvant temozolomide (150 to 200 mg per square meter for 5 days during each 28-day cycle). The primary end point was overall survival. results A total of 573 patients from 85 centers underwent randomization. The median age was 56 years, and 84 percent of patients had undergone debulking surgery. At a median follow-up of 28 months, the median survival was 14.6 months with radiotherapy plus temozolomide and 12.1 months with radiotherapy alone. The unadjusted hazard ratio for death in the radiotherapy-plus-temozolomide group was 0.63 (95 percent confidence interval, 0.52 to 0.75; P<0.001 by the log-rank test). The two-year survival rate was 26.5 percent with radiotherapy plus temozolomide and 10.4 percent with radiotherapy alone. Concomitant treatment with radiotherapy plus temozolomide resulted in grade 3 or 4 hematologic toxic effects in 7 percent of patients.

16,653 citations


Journal ArticleDOI
TL;DR: Patients with moderate-to-severe active ulcerative colitis treated with infliximab at weeks 0, 2, and 6 and every eight weeks thereafter were more likely to have a clinical response at weeks 8, 30, and 54 than were those receiving placebo.
Abstract: Background Infliximab, a chimeric monoclonal antibody directed against tumor necrosis factor α, is an established treatment for Crohn's disease but not ulcerative colitis. Methods Two randomized, double-blind, placebo-controlled studies — the Active Ulcerative Colitis Trials 1 and 2 (ACT 1 and ACT 2, respectively) — evaluated the efficacy of infliximab for induction and maintenance therapy in adults with ulcerative colitis. In each study, 364 patients with moderate-to-severe active ulcerative colitis despite treatment with concurrent medications received placebo or infliximab (5 mg or 10 mg per kilogram of body weight) intravenously at weeks 0, 2, and 6 and then every eight weeks through week 46 (in ACT 1) or week 22 (in ACT 2). Patients were followed for 54 weeks in ACT 1 and 30 weeks in ACT 2. Results In ACT 1, 69 percent of patients who received 5 mg of infliximab and 61 percent of those who received 10 mg had a clinical response at week 8, as compared with 37 percent of those who received placebo (P<0...

3,345 citations


Journal ArticleDOI
09 Mar 2005-JAMA
TL;DR: Improvement in practitioner performance was associated with CDSSs that automatically prompted users compared with requiring users to activate the system and studies in which the authors were not the developers, as well as other factors.
Abstract: ContextDevelopers of health care software have attributed improvements in patient care to these applications. As with any health care intervention, such claims require confirmation in clinical trials.ObjectivesTo review controlled trials assessing the effects of computerized clinical decision support systems (CDSSs) and to identify study characteristics predicting benefit.Data SourcesWe updated our earlier reviews by searching the MEDLINE, EMBASE, Cochrane Library, Inspec, and ISI databases and consulting reference lists through September 2004. Authors of 64 primary studies confirmed data or provided additional information.Study SelectionWe included randomized and nonrandomized controlled trials that evaluated the effect of a CDSS compared with care provided without a CDSS on practitioner performance or patient outcomes.Data ExtractionTeams of 2 reviewers independently abstracted data on methods, setting, CDSS and patient characteristics, and outcomes.Data SynthesisOne hundred studies met our inclusion criteria. The number and methodologic quality of studies improved over time. The CDSS improved practitioner performance in 62 (64%) of the 97 studies assessing this outcome, including 4 (40%) of 10 diagnostic systems, 16 (76%) of 21 reminder systems, 23 (62%) of 37 disease management systems, and 19 (66%) of 29 drug-dosing or prescribing systems. Fifty-two trials assessed 1 or more patient outcomes, of which 7 trials (13%) reported improvements. Improved practitioner performance was associated with CDSSs that automatically prompted users compared with requiring users to activate the system (success in 73% of trials vs 47%; P = .02) and studies in which the authors also developed the CDSS software compared with studies in which the authors were not the developers (74% success vs 28%; respectively, P = .001).ConclusionsMany CDSSs improve practitioner performance. To date, the effects on patient outcomes remain understudied and, when studied, inconsistent.

2,875 citations


Journal ArticleDOI
TL;DR: When analyzed in a large number of electrophysiology laboratories worldwide, catheter ablation of AF shows to be effective in ≈80% of patients after 1.3 procedures per patient, with ≈70% of them not requiring further antiarrhythmic drugs during intermediate follow-up.
Abstract: Background— The purpose of this study was to provide an updated worldwide report on the methods, efficacy, and safety of catheter ablation of atrial fibrillation (AF). Methods and Results— A questi...

2,626 citations


Journal ArticleDOI
TL;DR: In this article, a study of Canadian firms in the oil and gas, mining, and forestry industries from 1986 to 1995 showed that both resource-based and institutional factors influence corporate sustainable development.
Abstract: This study operationalizes corporate sustainable development and examines its organizational determinants. Data for this project pertain to Canadian firms in the oil and gas, mining, and forestry industries from 1986 to 1995. I find that both resource-based and institutional factors influence corporate sustainable development. By exploring time-related effects, I also find that media pressures were important in early periods and resource-based opportunities endured over time. This finding challenges the assumption that firms first adopt innovations in response to technical rewards which are later institutionalized. These counter-intuitive results may be attributable to the unique characteristics of the dependent variable, corporate sustainable development. They raise important questions and directions for future research. Copyright © 2004 John Wiley & Sons, Ltd.

2,209 citations


ReportDOI
TL;DR: In this paper, the authors formalize the concepts of self-productivity and complementarity of human capital investments and use them to explain the evidence on skill formation, and provide a theoretical framework for interpreting the evidence from a vast empirical literature, for guiding the next generation of empirical studies, and for formulating policy.
Abstract: This paper presents economic models of child development that capture the essence of recent findings from the empirical literature on skill formation. The goal of this essay is to provide a theoretical framework for interpreting the evidence from a vast empirical literature, for guiding the next generation of empirical studies, and for formulating policy. Central to our analysis is the concept that childhood has more than one stage. We formalize the concepts of self-productivity and complementarity of human capital investments and use them to explain the evidence on skill formation. Together, they explain why skill begets skill through a multiplier process. Skill formation is a life cycle process. It starts in the womb and goes on throughout life. Families play a role in this process that is far more important than the role of schools. There are multiple skills and multiple abilities that are important for adult success. Abilities are both inherited and created, and the traditional debate about nature versus nurture is scientiÞcally obsolete. Human capital investment exhibits both self-productivity and complementarity. Skill attainment at one stage of the life cycle raises skill attainment at later stages of the life cycle (self-productivity). Early investment facilitates the productivity of later investment (complementarity). Early investments are not productive if they are not followed up by later investments (another aspect of complementarity). This complementarity explains why there is no equity-efficiency trade-off for early investment. The returns to investing early in the life cycle are high. Remediation of inadequate early investments is difficult and very costly as a consequence of both self-productivity and complementarity.

1,585 citations


Journal ArticleDOI
TL;DR: It is shown theoretically and empirically that AUC is a better measure (defined precisely) than accuracy and reevaluate well-established claims in machine learning based on accuracy using AUC and obtain interesting and surprising new results.
Abstract: The area under the ROC (receiver operating characteristics) curve, or simply AUC, has been traditionally used in medical diagnosis since the 1970s. It has recently been proposed as an alternative single-number measure for evaluating the predictive ability of learning algorithms. However, no formal arguments were given as to why AUC should be preferred over accuracy. We establish formal criteria for comparing two different measures for learning algorithms and we show theoretically and empirically that AUC is a better measure (defined precisely) than accuracy. We then reevaluate well-established claims in machine learning based on accuracy using AUC and obtain interesting and surprising new results. For example, it has been well-established and accepted that Naive Bayes and decision trees are very similar in predictive accuracy. We show, however, that Naive Bayes is significantly better than decision trees in AUC. The conclusions drawn in this paper may make a significant impact on machine learning and data mining applications.

1,528 citations


Journal ArticleDOI
TL;DR: The results suggest that implicit and explicit measures are generally related but that higher order inferences and lack of conceptual correspondence can reduce the influence of automatic associations on explicit self-reports.
Abstract: Theoretically, low correlations between implicit and explicit measures can be due to (a) motivational biases in explicit self reports, (b) lack of introspective access to implicitly assessed representations, (c) factors influencing the retrieval of information from memory, (d) method-related characteristics of the two measures, or (e) complete independence of the underlying constructs. The present study addressed these questions from a meta-analytic perspective, investigating the correlation between the Implicit Association Test (IAT) and explicit self-report measures. Based on a sample of 126 studies, the mean effect size was .24, with approximately half of the variability across correlations attributable to moderator variables. Correlations systematically increased as a function of (a) increasing spontaneity of self-reports and (b) increasing conceptual correspondence between measures. These results suggest that implicit and explicit measures are generally related but that higher order inferences and lack of conceptual correspondence can reduce the influence of automatic associations on explicit self-reports.

1,509 citations


Journal ArticleDOI
TL;DR: An overview of common methods of formulating R0 and surrogate threshold parameters from deterministic, non-structured models and the recent use of R0 in assessing emerging diseases, such as severe acute respiratory syndrome and avian influenza, a number of recent livestock diseases, and vector-borne diseases malaria, dengue and West Nile virus are surveyed.
Abstract: The basic reproductive ratio, R0, is defined as the expected number of secondary infections arising from a single individual during his or her entire infectious period, in a population of susceptibles. This concept is fundamental to the study of epidemiology and within-host pathogen dynamics. Most importantly, R0 often serves as a threshold parameter that predicts whether an infection will spread. Related parameters which share this threshold behaviour, however, may or may not give the true value of R0. In this paper we give a brief overview of common methods of formulating R0 and surrogate threshold parameters from deterministic, non-structured models. We also review common means of estimating R0 from epidemiological data. Finally, we survey the recent use of R0 in assessing emerging diseases, such as severe acute respiratory syndrome and avian influenza, a number of recent livestock diseases, and vector-borne diseases malaria, dengue and West Nile virus.

1,080 citations


Journal ArticleDOI
01 Jan 2005-Ecology
TL;DR: This paper found no evidence of nonlinear relationships between body mass and body size and showed that residuals from reduced major axis (RMA) and major axis regression performed better than residuals of ordinary least squares (OLS) regression as indices of body condition.
Abstract: Body condition can have important fitness consequences, but measuring body condition of live animals from wild populations has been the subject of much recent debate. Using the residuals from a regression of body mass on a linear measure of body size is one of the most common methods of measuring condition and has been used in many vertebrate taxa. Recently, the use of this method has been criticized because assumptions are likely violated. We tested several assumptions regarding the use of this method with body composition and morphometric data from five species of small mammals and with statistical simulations. We tested the assumptions that the relationship between body mass and body size is linear, and that the proportion of mass associated with energy reserves is independent of body size. In addition, we tested whether the residuals from reduced major axis (RMA) regression or major axis (MA) regression performed better than the residuals from ordinary least squares (OLS) regression as indices of body condition. We found no evidence of nonlinear relationships between body mass and body size. Relative energy reserves (fat and lean dry mass) were generally independent or weakly dependent on body size. Residuals from MA and RMA regression consistently explained less variation in body composition than OLS regression. Using statistical simulations, we compared the effects of violations of the assumption that true condition and residual indices are independent of body size on the OLS, MA, and RMA procedures and found that OLS performed better than the RMA and MA procedures. Despite recent criticisms of residuals from mass-size OLS regressions, these indices of body condition appear to satisfy critical assumptions. Although some caution is warranted when using residuals, especially when both inter- individual variation in body size and measurement error are high, we found no reason to reject OLS residuals as legitimate indices of body condition.

997 citations


Journal ArticleDOI
TL;DR: Infliximab is effective in both an induction and maintenance regimen for the treatment of moderate-to-severe psoriasis, with a high percentage of patients achieving sustained PASI 75 and PASi 90 improvement through 1 year.

Journal ArticleDOI
TL;DR: A set of feature norms collected from approximately 725 participants for 541 living (dog) and nonliving (chair) basic-level concepts, the largest such set of norms developed to date are described, making these norms available to facilitate other research, while obviating the need to repeat the labor-intensive methods involved in collecting and analyzing such norms.
Abstract: Semantic features have provided insight into numerous behavioral phenomena concerning concepts, categorization, and semantic memory in adults, children, and neuropsychological populations. Numerous theories and models in these areas are based on representations and computations involving semantic features. Consequently, empirically derived semantic feature production norms have played, and continue to play, a highly useful role in these domains. This article describes a set of feature norms collected from approximately 725 participants for 541 living (dog) and nonliving (chair) basic-level concepts, the largest such set of norms developed to date. This article describes the norms and numerous statistics associated with them. Our aim is to make these norms available to facilitate other research, while obviating the need to repeat the labor-intensive methods involved in collecting and analyzing such norms. The full set of norms may be downloaded from www.psychonomic.org/archive.

Journal ArticleDOI
01 May 2005-Brain
TL;DR: Although there is substantial variation in outcome definition and methodology among the studies, consistent patterns of results emerge for various surgical interventions after adjusting for sources of heterogeneity.
Abstract: Summary Assessment of long-term outcomes is essential in brain surgery for epilepsy, which is an irreversible intervention for a chronic condition. Excellent short-term results of resective epilepsy surgery have been established, but less is known about long-term outcomes. We performed a systematic review and meta-analysis of the evidence on this topic. To provide evidence-based estimates of longterm results of various types of epilepsy surgery and to identify sources of variation in results of published studies, we searched Medline, Index Medicus, the Cochrane database, bibliographies of reviews, original articles and book chapters to identify articles published since 1991 that contained >20 patients of any age, undergoing resective or non-resective epilepsy surgery, and followed for a mean/median of >5 years. Two reviewers independently assessed study eligibility and extracted data, resolving disagreements through discussion. Seventy-six articles fulfilled our eligibility criteria, of which 71 reported on resective surgery (93%) and five (7%) on non-resective surgery. There were no randomized trials and only six studies had a control group. Some articles contributed more than one study, yielding 83 studies of which 78 dealt with resective surgery and five with non-resective surgery. Forty studies (51%) of resective surgery referred to temporal lobe surgery, 25 (32%) to grouped temporal and extratemporal surgery, seven (9%) to frontal surgery, two (3%) to grouped extratemporal surgery, two (3%) to hemispherectomy, and one (1%) each to parietal and occipital surgery. In the non-resective category, three studies reported outcomes after callosotomy and two after multiple subpial transections. The median proportion of long-term seizure-free patients was 66% with temporal lobe resections, 46% with occipital and parietal resections, and 27% with frontal lobe resections. In the long term, only 35% of patients with callosotomy were free of most disabling seizures, and 16% with multiple subpial transections remained free of all seizures. The year of operation, duration of follow-up and outcome classification system were most strongly associated with outcomes. Almost all long-term outcome studies describe patient cohorts without controls. Although there is substantial variation in outcome definition and methodology among the studies, consistent patterns of results emerge for various surgical interventions after adjusting for sources of heterogeneity. The long-term (>5 years) seizure free rate following temporal lobe resective surgery was similar to that reported in short-term controlled studies. On the other hand, long-term seizure freedom was consistently lower after extratemporal surgery and palliative procedures.

Journal ArticleDOI
TL;DR: Induction therapy with natalizumab for Crohn's disease resulted in small, nonsignificant improvements in response and remission rates, which will need to be weighed against the risk of serious adverse events.
Abstract: BackgroundNatalizumab, a humanized monoclonal antibody against α4 integrin, inhibits leukocyte adhesion and migration into inflamed tissue. MethodsWe conducted two controlled trials to evaluate natalizumab as induction and maintenance therapy in patients with active Crohn's disease. In the first trial, 905 patients were randomly assigned to receive 300 mg of natalizumab or placebo at weeks 0, 4, and 8. The primary outcome was response, defined by a decrease in the Crohn's Disease Activity Index (CDAI) score of at least 70 points, at week 10. In the second trial, 339 patients who had a response to natalizumab in the first trial were randomly reassigned to receive 300 mg of natalizumab or placebo every four weeks through week 56. The primary outcome was a sustained response through week 36. A secondary outcome in both trials was disease remission (a CDAI score of less than 150). ResultsIn the first trial, the natalizumab and placebo groups had similar rates of response (56 percent and 49 percent, respective...

Journal ArticleDOI
TL;DR: In this article, the authors present a theoretical analysis of the follower's role in the charismatic leadership process, distinguishing between two types of charismatic relationships and present general propositions about how followers' self-concepts may determine the type of charismatic relationship they form with the leader.
Abstract: We present a theoretical analysis of the follower's role in the charismatic leadership process. Specifically, we distinguish between two types of charismatic relationships—personalized and socialized—and present general propositions about how followers' self-concepts may determine the type of charismatic relationship they form with the leader. We then develop more specific propositions about the follower's role in various stages of the charismatic relationship process, and we conclude by outlining the implications of the propositions and suggesting further opportunities for theoretical extension.

Journal ArticleDOI
TL;DR: The Atmospheric Chemistry Experiment (ACE) is a Canadian satellite mission for remote sensing of the Earth's atmosphere that was launched into low Earth circular orbit (altitude 650 km, inclination 74°) on 12 Aug. 2003.
Abstract: SCISAT-1, also known as the Atmospheric Chemistry Experiment (ACE), is a Canadian satellite mission for remote sensing of the Earth's atmosphere. It was launched into low Earth circular orbit (altitude 650 km, inclination 74°) on 12 Aug. 2003. The primary ACE instrument is a high spectral resolution (0.02 cm-1) Fourier Transform Spectrometer (FTS) operating from 2.2 to 13.3 μm (750-4400 cm-1). The satellite also features a dual spectrophotometer known as MAESTRO with wavelength coverage of 285-1030 nm and spectral resolution of 1-2 nm. A pair of filtered CMOS detector arrays records images of the Sun at 0.525 and 1.02 μm. Working primarily in solar occultation, the satellite provides altitude profile information (typically 10-100 km) for temperature, pressure, and the volume mixing ratios for several dozen molecules of atmospheric interest, as well as atmospheric extinction profiles over the latitudes 85°N to 85°S. This paper presents a mission overview and some of the first scientific results. Copyright 2005 by the American Geophysical Union.

Proceedings ArticleDOI
15 May 2005
TL;DR: It is concluded that, based on the data available thus far, the use of mutation operators is yielding trustworthy results (generated mutants are similar to real faults); Mutants appear however to be different from hand-seeded faults that seem to be harder to detect than real faults.
Abstract: The empirical assessment of test techniques plays an important role in software testing research. One common practice is to instrument faults, either manually or by using mutation operators. The latter allows the systematic, repeatable seeding of large numbers of faults; however, we do not know whether empirical results obtained this way lead to valid, representative conclusions. This paper investigates this important question based on a number of programs with comprehensive pools of test cases and known faults. It is concluded that, based on the data available thus far, the use of mutation operators is yielding trustworthy results (generated mutants are similar to real faults). Mutants appear however to be different from hand-seeded faults that seem to be harder to detect than real faults.

Journal ArticleDOI
TL;DR: All health care professionals need to understand the principles of EBP, recognise EBP in action, implement evidence-based policies, and have a critical attitude to their own practice and to evidence.
Abstract: A variety of definitions of evidence-based practice (EBP) exist. However, definitions are in themselves insufficient to explain the underlying processes of EBP and to differentiate between an evidence-based process and evidence-based outcome. There is a need for a clear statement of what Evidence-Based Practice (EBP) means, a description of the skills required to practise in an evidence-based manner and a curriculum that outlines the minimum requirements for training health professionals in EBP. This consensus statement is based on current literature and incorporating the experience of delegates attending the 2003 Conference of Evidence-Based Health Care Teachers and Developers ("Signposting the future of EBHC"). Evidence-Based Practice has evolved in both scope and definition. Evidence-Based Practice (EBP) requires that decisions about health care are based on the best available, current, valid and relevant evidence. These decisions should be made by those receiving care, informed by the tacit and explicit knowledge of those providing care, within the context of available resources. Health care professionals must be able to gain, assess, apply and integrate new knowledge and have the ability to adapt to changing circumstances throughout their professional life. Curricula to deliver these aptitudes need to be grounded in the five-step model of EBP, and informed by ongoing research. Core assessment tools for each of the steps should continue to be developed, validated, and made freely available. All health care professionals need to understand the principles of EBP, recognise EBP in action, implement evidence-based policies, and have a critical attitude to their own practice and to evidence. Without these skills, professionals and organisations will find it difficult to provide 'best practice'.

Proceedings ArticleDOI
15 May 2005
TL;DR: It is concluded that, based on the data available thus far, the use of mutation operators is yielding trustworthy results (generated mutants are similar to real faults); Mutants appear however to be different from hand-seeded faults that seem to be harder to detect than real faults.
Abstract: The empirical assessment of test techniques plays an important role in software testing research. One common practice is to instrument faults, either manually or by using mutation operators. The latter allows the systematic, repeatable seeding of large numbers of faults; however, we do not know whether empirical results obtained this way lead to valid, representative conclusions. This paper investigates this important question based on a number of programs with comprehensive pools of test cases and known faults. It is concluded that, based on the data available thus far, the use of mutation operators is yielding trustworthy results (generated mutants are similar to real faults). Mutants appear however to be different from hand-seeded faults that seem to be harder to detect than real faults.

Journal ArticleDOI
TL;DR: The authors examined three psychological aspects of identity formation (style, status, and process) in relation to personal agency associated with the individualization process and found that higher levels of agency are positively related to exploration and flexible commitment, unrelated to conformity, and negatively related to avoidance.
Abstract: The study of emerging adulthood—the prolonged transition to adulthood extending into the 20s—is a rapidly growing area of research. Although identity issues are prominent during this period, the role of personal agency and individualization in the identity formation process during these years is not well understood. This study examines three psychological aspects of identity formation (style, status, and process) in relation to personal agency associated with the individualization process. Structural equation modeling analyses suggest that higher levels of agency are positively related to exploration and flexible commitment, unrelated to conformity, and negatively related to avoidance. Cluster analysis was used to examine and support a theorized polarity between developmental and default forms of individualization. Replicated across three U.S. ethnic groups, the results suggest that emerging adults utilize agentic capacities to varying degrees, and that the degree of agency utilized is directly related to...

ReportDOI
TL;DR: In this paper, the authors consider the economic interpretation of these analyses and how the availability of repeated cross-section and panel data improves the ability of analysts to estimate the rate of return, and propose a nonparametric approach for estimating marginal internal rates of return that takes into account tuition, income taxes and forms of uncertainty.
Abstract: Numerous studies regress log earnings on schooling and report estimated coefficients as "Mincer rates of return" A more recent literature uses instrumental variables This chapter considers the economic interpretation of these analyses and how the availability of repeated cross section and panel data improves the ability of analysts to estimate the rate of return We consider under what conditions the Mincer model estimates an ex post rate of return We test and reject the model on six cross sections of US Census data We present a general nonparametric approach for estimating marginal internal rates of return that takes into account tuition, income taxes and forms of uncertainty We also contrast estimates based on a single cross-section of data, using the synthetic cohort approach, with estimates based on repeated cross-sections following actual cohorts Cohort-based models fitted on repeated cross section data provide more reliable estimates of ex post returns Accounting for uncertainty affects estimates of rates of return Accounting for sequential revelation of information calls into question the validity of the internal rate of return as a tool for policy analysis An alternative approach to computing economic rates of return that accounts for sequential revelation of information is proposed and the evidence is summarized We distinguish ex ante from ex post returns New panel data methods for estimating the uncertainty and psychic costs facing agents are reviewed We report recent evidence that demonstrates that there are large psychic costs of schooling This helps to explain why persons do not attend school even though the financial rewards for doing so are high We present methods for computing distributions of returns ex ante and ex post We review the literature on instrumental variable estimation The link of the estimates to the economics is not strong The traditional instruments are weak, and this literature has not produced decisive empirical estimates We exposit new methods that interpret the economic content of different instruments within a unified framework

Journal ArticleDOI
TL;DR: Methods and procedures are described to assist scientists new to the field in designing and conducting experiments to investigate sex differences in research involving both laboratory animals and humans.
Abstract: Female and male brains differ. Differences begin early during development due to a combination of genetic and hormonal events and continue throughout the lifespan of an individual. Although researchers from a myriad of disciplines are beginning to appreciate the importance of considering sex differences in the design and interpretation of their studies, this is an area that is full of potential pitfalls. A female's reproductive status and ovarian cycle have to be taken into account when studying sex differences in health and disease susceptibility, in the pharmacological effects of drugs, and in the study of brain and behavior. To investigate sex differences in brain and behavior there is a logical series of questions that should be answered in a comprehensive investigation of any trait. First, it is important to determine that there is a sex difference in the trait in intact males and females, taking into consideration the reproductive cycle of the female. Then, one must consider whether the sex difference is attributable to the actions of gonadal steroids at the time of testing and/or is sexually differentiated permanently by the action of gonadal steroids during development. To answer these questions requires knowledge of how to assess and/or manipulate the hormonal condition of the subjects in the experiment appropriately. This article describes methods and procedures to assist scientists new to the field in designing and conducting experiments to investigate sex differences in research involving both laboratory animals and humans.

Journal ArticleDOI
TL;DR: In this paper, a review of over 150 studies shows that there is a clear consistency between spiritual values and practices and effective leadership, and that the following practices have been emphasized in many spiritual teachings: showing respect for others, demonstrating fair treatment, expressing caring and concern, listening responsively, recognizing the contributions of others, and engaging in reflective practice.
Abstract: This review of over 150 studies shows that there is a clear consistency between spiritual values and practices and effective leadership. Values that have long been considered spiritual ideals, such as integrity, honesty, and humility, have been demonstrated to have an effect on leadership success. Similarly, practices traditionally associated with spirituality as demonstrated in daily life have also been shown to be connected to leadership effectiveness. All of the following practices have been emphasized in many spiritual teachings, and they have also been found to be crucial leadership skills: showing respect for others, demonstrating fair treatment, expressing caring and concern, listening responsively, recognizing the contributions of others, and engaging in reflective practice.

Journal ArticleDOI
TL;DR: The C282y mutation is most common in whites, and most C282Y homozygotes have elevations in serum ferritin levels and transferrin saturation values in nonwhites.
Abstract: background Iron overload and hemochromatosis are common, treatable conditions. HFE genotypes, levels of serum ferritin, transferrin saturation values, and self-reported medical history were studied in a multiethnic primary care population. methods Participants were recruited from primary care practices and blood-drawing laboratories. Blood samples were tested for transferrin saturation, serum ferritin, and C282Y and H63D mutations of the HFE gene. Before genetic screening, participants were asked whether they had a history of medical conditions related to iron overload. results Of the 99,711 participants, 299 were homozygous for the C282Y mutation. The estimated prevalence of C282Y homozygotes was higher in non-Hispanic whites (0.44 percent) than in Native Americans (0.11 percent), Hispanics (0.027 percent), blacks (0.014 percent), Pacific Islanders (0.012 percent), or Asians (0.000039 percent). Among participants who were homozygous for the C282Y mutation but in whom iron overload had not been diagnosed (227 participants), serum ferritin levels were greater than 300 µ g per liter in 78 of 89 men (88 percent) and greater than 200 µ g per liter in 79 of 138 women (57 percent). Pacific Islanders and Asians had the highest geometric mean levels of serum ferritin and mean transferrin saturation despite having the lowest prevalence of C282Y homozygotes. There were 364 participants in whom iron overload had not been diagnosed (29 C282Y homozygotes) who had a serum ferritin level greater than 1000 µ g per liter. Among men, C282Y homozygotes and compound heterozygotes were more likely to report a history of liver disease than were participants without HFE mutations. conclusions The C282Y mutation is most common in whites, and most C282Y homozygotes have elevations in serum ferritin levels and transferrin saturation. The C282Y mutation does not account for high mean serum ferritin levels and transferrin saturation values in nonwhites.

Journal ArticleDOI
TL;DR: There is as yet no evidence that the antifracture efficacy of PTH will be superior to the bisphosphonates, whereas cost-utility estimates suggest that teriparatide is significantly more expensive.
Abstract: All therapies currently recommended for the management of osteoporosis act mainly to inhibit bone resorption and reduce bone remodeling. PTH and its analog, teriparatide [recombinant human PTH(1-34)], represent a new class of anabolic therapies for the treatment of severe osteoporosis, having the potential to improve skeletal microarchitecture. Significant reductions in both vertebral and appendicular fracture rates have been demonstrated in the phase III trial of teriparatide, involving elderly women with at least one prevalent vertebral fracture before the onset of therapy. However, there is as yet no evidence that the antifracture efficacy of PTH will be superior to the bisphosphonates, whereas cost-utility estimates suggest that teriparatide is significantly more expensive. Teriparatide should be considered as treatment for postmenopausal women and men with severe osteoporosis, as well as for patients with established glucocorticoid-induced osteoporosis who require long-term steroid treatment. Teriparatide should also be considered for the management of individuals at particularly high risk for fractures, including subjects who are younger than age 65 and who have particularly low bone mineral density measurements (T scores < or = 3.5). Teriparatide therapy is not recommended for more than 2 yr, based, in part, on the induction of osteosarcoma in a rat model of carcinogenicity. Total daily calcium intake from both supplements and dietary sources should be limited to 1500 mg together with adequate vitamin D intake (< or =1000 U/d). Monitoring of serum calcium may be safely limited to measurement after 1 month of treatment; mild hypercalcemia may be treated by withdrawing dietary calcium supplements, reducing the dosing frequency of PTH, or both. At present, concurrent therapy with antiresorptive therapy, particularly bisphosphonates, should be avoided, although sequential therapy with such agents may consolidate the beneficial effects upon the skeleton after PTH is discontinued.

Journal ArticleDOI
TL;DR: Perceptions of daily relationship-based conflicts negatively impacted the perceived satisfaction/closeness and relationship futures of highly anxious individuals, whereas perceptions of greater daily support had positive effects.
Abstract: Guided by attachment theory, a 2-part study was conducted to test how perceptions of relationship-based conflict and support are associated with relationship satisfaction/closeness and future quality. Dating partners completed diaries for 14 days (Part 1) and then were videotaped while discussing a major problem that occurred during the diary study (Part 2). Part 1 reveals that more anxiously attached individuals perceived more conflict with their dating partners and reported a tendency for conflicts to escalate in severity. Perceptions of daily relationship-based conflicts negatively impacted the perceived satisfaction/closeness and relationship futures of highly anxious individuals, whereas perceptions of greater daily support had positive effects. Part 2 reveals that highly anxious individuals appeared more distressed and escalated the severity of conflicts (rated by observers) and reported feeling more distressed. The authors discuss the unique features of attachment anxiety and how changing perceptions of relationship satisfaction/closeness and stability could erode commitment over time. Romantic relationships sometimes seem similar to roller coaster rides in which partners experience breathtaking emotional highs rapidly followed by heartbreaking lows. For many people, these countervailing moments of joy and despair are experienced infrequently and mainly in stressful situations. For some individuals, however, these roller coaster episodes occur on a regular basis during everyday interactions with their romantic partners. Recent research indicates that perceptions of daily relationship events strongly color how individuals construe their romantic partners’ underlying motives and intentions and that these construals can

Journal ArticleDOI
TL;DR: The observation that hESC lines maintained in vitro develop genetic and epigenetic alterations implies that periodic monitoring of these lines will be required before they are used in in vivo applications and that some late-passage hESS lines may be unusable for therapeutic purposes.
Abstract: Cultured human embryonic stem cell (hESC) lines are an invaluable resource because they provide a uniform and stable genetic system for functional analyses and therapeutic applications. Nevertheless, these dividing cells, like other cells, probably undergo spontaneous mutation at a rate of 10(-9) per nucleotide. Because each mutant has only a few progeny, the overall biological properties of the cell culture are not altered unless a mutation provides a survival or growth advantage. Clonal evolution that leads to emergence of a dominant mutant genotype may potentially affect cellular phenotype as well. We assessed the genomic fidelity of paired early- and late-passage hESC lines in the course of tissue culture. Relative to early-passage lines, eight of nine late-passage hESC lines had one or more genomic alterations commonly observed in human cancers, including aberrations in copy number (45%), mitochondrial DNA sequence (22%) and gene promoter methylation (90%), although the latter was essentially restricted to 2 of 14 promoters examined. The observation that hESC lines maintained in vitro develop genetic and epigenetic alterations implies that periodic monitoring of these lines will be required before they are used in in vivo applications and that some late-passage hESC lines may be unusable for therapeutic purposes.

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TL;DR: This paper builds on the principles and insights from improvisational theater to unpack the nature of collective improvisation and to consider what it takes to do it well and to innovate, and provides initial evidence suggesting that the improvisational skill can be learned by organizational members through training.
Abstract: This paper builds on the principles and insights from improvisational theater to unpack the nature of collective improvisation and to consider what it takes to do it well and to innovate. Furthermore, we discuss the role of training in enhancing the incidence and effectiveness of improvisation. We propose that two common misconceptions about improvisation have hindered managers' understanding of how to develop the improvisational skill. First, the spontaneous facet of improvisation tends to be overemphasized, and second, there is a general assumption that improvisation always leads to positive performance. Our goal is to clear up the conceptual confusion about improvisation by laying out the various aspects of preparation that are required for effective improvisation. In our theoretical model, we delineate how the improvisational theater principles of "practice," "collaboration," "agree, accept, and add," "be present in the moment," and "draw on reincorporation and ready-mades" can be used to understand what it takes to improvise well in work teams and to create a context favoring these efforts. Our findings support a contingent view of the impact of improvisation on innovative performance. Improvisation is not inherently good or bad; however, improvisation has a positive effect on team innovation when combined with team and contextual moderating factors. We also provide initial evidence suggesting that the improvisational skill can be learned by organizational members through training. Our results shed light on the opportunities provided by training in improvisation and on the challenges of creating behavioral change going beyond the individual to the team and, ultimately, to the organization.

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TL;DR: In this article, the authors propose that parenting, with its nurturance, passion, or even neglect or abuse, offers a particularly fruitful metaphor for examining entrepreneurship that may better resonate with entrepreneurs themselves than does current theory.

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TL;DR: In this article, the authors offer a reconceptualization of employee cynicism and present the results of two studies to test the hypotheses that cynicism about an organizational change is distinguishable from skepticism about the change, more general forms of cynicism (disposition and management), and trust in management, and change-specific cynicism and skepticism relate differently to personal and situational variables.
Abstract: We offer a reconceptualization of employee cynicism and present the results of two studies to test the hypotheses that (a) cynicism about an organizational change is distinguishable from skepticism about the change, more general forms of cynicism (disposition and management), and trust in management, (b) change-specific cynicism and skepticism relate differently to personal and situational “antecedent” variables, and (c) change-specific cynicism accounts for variance in employees’ intention to resist change not explained by skepticism, trust, and more general forms of cynicism. Study 1 was conducted with employees (N=65) from several organizations undergoing various changes, and Study 2 with employees (N=701) from a single organization undergoing restructuring and culture change. Results were generally consistent with prediction. Implications for future research and for the management of change are discussed.