Showing papers by "Erasmus University Rotterdam published in 2004"

Docetaxel plus Prednisone or Mitoxantrone plus Prednisone for Advanced Prostate Cancer

Abstract: As compared with the men in the mitoxantrone group, men in the group given docetaxel every three weeks had a hazard ratio for death of 0.76 (95 percent confidence interval, 0.62 to 0.94; P = 0.009 by the stratified log-rank test) and those given weekly docetaxel had a hazard ratio for death of 0.91 (95 percent confidence interval, 0.75 to 1.11; P=0.36). The median survival was 16.5 months in the mitoxantrone group, 18.9 months in the group given docetaxel every 3 weeks, and 17.4 months in the group given weekly docetaxel. Among these three groups, 32 percent, 45 percent, and 48 percent of men, respectively, had at least a 50 percent decrease in the serum PSA level (P<0.001 for both comparisons with mitoxantrone); 22 percent, 35 percent (P=0.01), and 31 percent (P=0.08) had predefined reductions in pain; and 13 percent, 22 percent (P=0.009), and 23 percent (P=0.005) had improvements in the quality of life. Adverse events were also more common in the groups that received docetaxel. conclusions When given with prednisone, treatment with docetaxel every three weeks led to superior survival and improved rates of response in terms of pain, serum PSA level, and quality of life, as compared with mitoxantrone plus prednisone.

Mild cognitive impairment--beyond controversies, towards a consensus: report of the International Working Group on Mild Cognitive Impairment.

Abstract: The First Key Symposium was held in Stockholm, Sweden, 2-5 September 2003. The aim of the symposium was to integrate clinical and epidemiological perspectives on the topic of Mild Cognitive Impairment (MCI). A multidisciplinary, international group of experts discussed the current status and future directions of MCI, with regard to clinical presentation, cognitive and functional assessment, and the role of neuroimaging, biomarkers and genetics. Agreement on new perspectives, as well as recommendations for management and future research were discussed by the international working group. The specific recommendations for the general MCI criteria include the following: (i) the person is neither normal nor demented; (ii) there is evidence of cognitive deterioration shown by either objectively measured decline over time and/or subjective report of decline by self and/or informant in conjunction with objective cognitive deficits; and (iii) activities of daily living are preserved and complex instrumental functions are either intact or minimally impaired.

Prevalence of age-related macular degeneration in the United States.

Abstract: Objective: To estimate the prevalence and distribution of age-related macular degeneration (AMD) in the United States by age, race/ethnicity, and gender.Methods: Summary prevalence estimates of drusen 125 pin or larger, neovascular AMD, and geographic atrophy were prepared separately for black and white persons in 5-year age intervals starting at 40 years. The estimated rates were based on a meta-analysis of recent population-based studies in the United States, Australia, and Europe. These rates were applied to 2000 US Census data and to projected US population figures for 2020 to estimate the number of the US population with drusen and AMD.Results: The overall prevalence of neovascular AMD and/or geographic atrophy in the US population 40 years and older is estimated to be 1.47% (95% confidence interval, 1.38%-1.55%), with 1.75 million citizens having AMD. The prevalence of AMD increased dramatically with age, with more than 15% of the white women older than 80 years having neovascular AMD and/or geographic atrophy. More than 7 million individuals had drusen measuring 125 pin or larger and were, therefore, at substantial risk of developing AMD. Owing to the rapidly aging population, the number of persons having AMD will increase by 50% to 2.95 million in 2020. Age-related macular degeneration was far more prevalent among white than among black persons.Conclusion: Age-related macular degeneration affects more than 1.75 million individuals in the United States. Owing to the rapid aging of the US population, this number will increase to almost 3 million by 2020.

Work group diversity and group performance: an integrative model and research agenda.

Abstract: Research on the relationship between work group diversity and performance has yielded inconsistent results. To address this problem, the authors propose the categorization-elaboration model (CEM), which reconceptualizes and integrates information/decision making and social categorization perspectives on work-group diversity and performance. The CEM incorporates mediator and moderator variables that typically have been ignored in diversity research and incorporates the view that information/decision making and social categorization processes interact such that intergroup biases flowing from social categorization disrupt the elaboration (in-depth processing) of task-relevant information and perspectives. In addition, the authors propose that attempts to link the positive and negative effects of diversity to specific types of diversity should be abandoned in favor of the assumption that all dimensions of diversity may have positive as well as negative effects. The ways in which these propositions may set the agenda for future research in diversity are discussed.

Using the job demands-resources model to predict burnout and performance

Abstract: The job demands-resources (JD-R) model was used to examine the relationship between job characteristics, burnout, and (other-ratings of) performance (N = 146). We hypothesized that job demands (e.g., work pressure and emotional demands) would be the most important antecedents of the exhaustion component of burnout, which, in turn, would predict in-role performance (hypothesis 1). In contrast, job resources (e.g., autonomy and social support) were hypothesized to be the most important predictors of extra-role performance, through their relationship with the disengagement component of burnout (hypothesis 2). In addition, we predicted that job resources would buffer the relationship between job demands and exhaustion (hypothesis 3), and that exhaustion would be positively related to disengagement (hypothesis 4). The results of structural equation modeling analyses provided strong support for hypotheses 1, 2, and 4, but rejected hypothesis 3. These findings support the JD-R model's claim that job demands and job resources initiate two psychological processes, which eventually affect organizational outcomes. © 2004 Wiley Periodicals, Inc.

Streptococcus pneumoniae colonisation: the key to pneumococcal disease.

Abstract: Streptococcus pneumoniae is an important pathogen causing invasive diseases such as sepsis, meningitis, and pneumonia. The burden of disease is highest in the youngest and oldest sections of the population in both more and less developed countries. The treatment of pneumococcal infections is complicated by the worldwide emergence in pneumococci of resistance to penicillin and other antibiotics. Pneumococcal disease is preceded by asymptomatic colonisation, which is especially high in children. The current seven-valent conjugate vaccine is highly effective against invasive disease caused by the vaccine-type strains. However, vaccine coverage is limited, and replacement by non-vaccine serotypes resulting in disease is a serious threat for the near future. Therefore, the search for new vaccine candidates that elicit protection against a broader range of pneumococcal strains is important. Several surface-associated protein vaccines are currently under investigation. Another important issue is whether the aim should be to prevent pneumococcal disease by eradication of nasopharyngeal colonisation, or to prevent bacterial invasion leaving colonisation relatively unaffected and hence preventing the occurrence of replacement colonisation and disease. To illustrate the importance of pneumococcal colonisation in relation to pneumococcal disease and prevention of disease, we discuss the mechanism and epidemiology of colonisation, the complexity of relations within and between species, and the consequences of the different preventive strategies for pneumococcal colonisation.

Mapping the Antigenic and Genetic Evolution of Influenza Virus

Abstract: The antigenic evolution of influenza A (H3N2) virus was quantified and visualized from its introduction into humans in 1968 to 2003. Although there was remarkable correspondence between antigenic and genetic evolution, significant differences were observed: Antigenic evolution was more punctuated than genetic evolution, and genetic change sometimes had a disproportionately large antigenic effect. The method readily allows monitoring of antigenic differences among vaccine and circulating strains and thus estimation of the effects of vaccination. Further, this approach offers a route to predicting the relative success of emerging strains, which could be achieved by quantifying the combined effects of population level immune escape and viral fitness on strain evolution.

Efficacy of MRI and Mammography for Breast-Cancer Screening in Women with a Familial or Genetic Predisposition

Abstract: background The value of regular surveillance for breast cancer in women with a genetic or familial predisposition to breast cancer is currently unproven. We compared the efficacy of magnetic resonance imaging (MRI) with that of mammography for screening in this group of high-risk women. methods Women who had a cumulative lifetime risk of breast cancer of 15 percent or more were screened every six months with a clinical breast examination and once a year by mammography and MRI, with independent readings. The characteristics of the cancers that were detected were compared with the characteristics of those in two different agematched control groups. results We screened 1909 eligible women, including 358 carriers of germ-line mutations. Within a median follow-up period of 2.9 years, 51 tumors (44 invasive cancers, 6 ductal carcinomas in situ, and 1 lymphoma) and 1 lobular carcinoma in situ were detected. The sensitivity of clinical breast examination, mammography, and MRI for detecting invasive breast cancer was 17.9 percent, 33.3 percent, and 79.5 percent, respectively, and the specificity was 98.1 percent, 95.0 percent, and 89.8 percent, respectively. The overall discriminating capacity of MRI was significantly better than that of mammography (P<0.05). The proportion of invasive tumors that were 10 mm or less in diameter was significantly greater in our surveillance group (43.2 percent) than in either control group (14.0 percent [P<0.001] and 12.5 percent [P = 0.04], respectively). The combined incidence of positive axillary nodes and micrometastases in invasive cancers in our study was 21.4 percent, as compared with 52.4 percent (P<0.001) and 56.4 percent (P=0.001) in the two control groups. conclusions MRI appears to be more sensitive than mammography in detecting tumors in women with an inherited susceptibility to breast cancer.

Design and Validation of a Tool for Neurite Tracing and Analysis in Fluorescence Microscopy Images

Abstract: Background: For the investigation of the molecular mechanisms involved in neurite outgrowth and differentiation, accurate and reproducible segmentation and quantification of neuronal processes are a prerequisite. To facilitate this task, we developed a semiautomatic neurite tracing technique. This article describes the design and validation of the technique. Methods: The technique was compared to fully manual delineation. Four observers repeatedly traced selected neurites in 20 fluorescence microscopy images of cells in culture, using both methods. Accuracy and reproducibility were determined by comparing the tracings to high-resolution reference tracings, using two error measures. Labor intensiveness was measured in numbers of mouse clicks required. The significance of the results was determined by a Student t-test and by analysis of variance. Results: Both methods slightly underestimated the true neurite length, but the differences were not unanimously significant. The average deviation from the true neurite centerline was a factor 2.6 smaller with the developed technique compared to fully manual tracing. Intraobserver variability in the respective measures was reduced by a factor 6.0 and 23.2. Interobserver variability was reduced by a factor 2.4 and 8.8, respectively, and labor intensiveness by a factor 3.3. Conclusions: Providing similar accuracy in measuring neurite length, significantly improved accuracy in neurite centerline extraction, and significantly improved reproducibility and reduced labor intensiveness, the developed technique may replace fully manual tracing methods.

Prognostically useful gene-expression profiles in acute myeloid leukemia.

Abstract: background In patients with acute myeloid leukemia (AML) a combination of methods must be used to classify the disease, make therapeutic decisions, and determine the prognosis. However, this combined approach provides correct therapeutic and prognostic information in only 50 percent of cases. methods We determined the gene-expression profiles in samples of peripheral blood or bone marrow from 285 patients with AML using Affymetrix U133A GeneChips containing approximately 13,000 unique genes or expression-signature tags. Data analyses were carried out with Omniviz, significance analysis of microarrays, and prediction analysis of microarrays software. Statistical analyses were performed to determine the prognostic significance of cases of AML with specific molecular signatures. results Unsupervised cluster analyses identified 16 groups of patients with AML on the basis of molecular signatures. We identified the genes that defined these clusters and determined the minimal numbers of genes needed to identify prognostically important clusters with a high degree of accuracy. The clustering was driven by the presence of chromosomal lesions (e.g., t(8;21), t(15;17), and inv(16)), particular genetic mutations ( CEBPA ), and abnormal oncogene expression ( EVI1 ). We identified several novel clusters, some consisting of specimens with normal karyotypes. A unique cluster with a distinctive gene-expression signature included cases of AML with a poor treatment outcome. conclusions Gene-expression profiling allows a comprehensive classification of AML that includes previously identified genetically defined subgroups and a novel cluster with an adverse prognosis.

Biological, physiological, pathophysiological, and pharmacological aspects of ghrelin.

Abstract: Ghrelin is a peptide predominantly produced by the stomach. Ghrelin displays strong GH-releasing activity. This activity is mediated by the activation of the so-called GH secretagogue receptor type 1a. This receptor had been shown to be specific for a family of synthetic, peptidyl and nonpeptidyl GH secretagogues. Apart from a potent GH-releasing action, ghrelin has other activities including stimulation of lactotroph and corticotroph function, influence on the pituitary gonadal axis, stimulation of appetite, control of energy balance, influence on sleep and behavior, control of gastric motility and acid secretion, and influence on pancreatic exocrine and endocrine function as well as on glucose metabolism. Cardiovascular actions and modulation of proliferation of neoplastic cells, as well as of the immune system, are other actions of ghrelin. Therefore, we consider ghrelin a gastrointestinal peptide contributing to the regulation of diverse functions of the gut-brain axis. So, there is indeed a possibility that ghrelin analogs, acting as either agonists or antagonists, might have clinical impact.

Anti‐Müllerian hormone expression pattern in the human ovary: potential implications for initial and cyclic follicle recruitment

Abstract: Anti-Mullerian hormone (AMH) is a member of the transforming growth factor-b superfamily, which plays an important role in both ovarian primordial follicle recruitment and dominant follicle selection in mice. However, the role of AMH in folliculo- genesis in humans has not been investigated in detail. In the present study, AMH expression was assessed using immunohisto- chemistry in ovarian sections, obtained from healthy regularly cycling women. To this end, a novel monoclonal antibody to human AMH was developed. AMH expression was not observed in primordial follicles, whereas 74% of the primary follicles showed at least a weak signal in the granulosa cells. The highest level of AMH expression was present in the granulosa cells of secondary, preantral and small antral follicles <4 mm in diameter. In larger (4-8 mm) antral follicles, AMH expression grad- ually disappeared. In conclusion, in the human AMH expression follows a similar pattern as compared to the mouse and rat, suggesting an important role of AMH in folliculogenesis.

Subpopulations of mouse blood monocytes differ in maturation stage and inflammatory response.

Abstract: Blood monocytes are well-characterized precursors for macrophages and dendritic cells. Subsets of human monocytes with differential representation in various disease states are well known. In contrast, mouse monocyte subsets have been characterized minimally. In this study we identify three subpopulations of mouse monocytes that can be distinguished by differential expression of Ly-6C, CD43, CD11c, MBR, and CD62L. The subsets share the characteristics of extensive phagocytosis, similar expression of M-CSF receptor (CD115), and development into macrophages upon M-CSF stimulation. By eliminating blood monocytes with dichloromethylene-bisphosphonate-loaded liposomes and monitoring their repopulation, we showed a developmental relationship between the subsets. Monocytes were maximally depleted 18 h after liposome application and subsequently reappeared in the circulation. These cells were exclusively of the Ly-6C(high) subset, resembling bone marrow monocytes. Serial flow cytometric analyses of newly released Ly-6C(high) monocytes showed that Ly-6C expression on these cells was down-regulated while in circulation. Under inflammatory conditions elicited either by acute infection with Listeria monocytogenes or chronic infection with Leishmania major, there was a significant increase in immature Ly-6C(high) monocytes, resembling the inflammatory left shift of granulocytes. In addition, acute peritoneal inflammation recruited preferentially Ly-6C(med-high) monocytes. Taken together, these data identify distinct subpopulations of mouse blood monocytes that differ in maturation stage and capacity to become recruited to inflammatory sites.

Physical activity, including walking, and cognitive function in older women.

Abstract: ContextPhysical activity may help maintain cognitive function in older adults.ObjectiveTo examine the relation of long-term regular physical activity, including walking, to cognitive function.DesignWomen reported participation in leisure-time physical activities on biennial mailed questionnaires beginning in 1986. We assessed long-term activity by averaging energy expenditures from questionnaires in 1986 through participants' baseline cognitive assessments (1995 to 2001). We used linear regression to estimate adjusted mean differences in baseline cognitive performance and cognitive decline over 2 years, across levels of physical activity and walking.Setting and ParticipantsNurses' Health Study, including 18 766 US women aged 70 to 81 years.Main Outcome MeasureValidated telephone assessments of cognition administered twice approximately 2 years apart (1995 to 2001 and 1997 to 2003), including tests of general cognition, verbal memory, category fluency, and attention.ResultsHigher levels of activity were associated with better cognitive performance. On a global score combining results of all 6 tests, women in the second through fifth quintiles of energy expenditure scored an average of 0.06, 0.06, 0.09, and 0.10 standard units higher than women in the lowest quintile (P for trend <.001). Compared with women in the lowest physical activity quintile, we found a 20% lower risk of cognitive impairment for women in the highest quintile of activity. Among women performing the equivalent of walking at an easy pace for at least 1.5 h/wk, mean global scores were 0.06 to 0.07 units higher compared with walking less than 40 min/wk (P≤.003). We also observed less cognitive decline among women who were more active, especially those in the 2 highest quintiles of energy expenditure. Women in the fourth and fifth quintiles had mean changes in global scores that were 0.04 (95% confidence interval, 0.02-0.10) and 0.06 (95% confidence interval, 0.02-0.11) standard units better than those in the lowest quintile.ConclusionLong-term regular physical activity, including walking, is associated with significantly better cognitive function and less cognitive decline in older women.

Quantifying the heart failure epidemic: prevalence, incidence rate, lifetime risk and prognosis of heart failure The Rotterdam Study.

Abstract: Aims To determine the prevalence, incidence rate, lifetime risk and prognosis of heart failure. Methods and Results The Rotterdam Study is a prospective population-based cohort study in 7983 participants aged ⩾55. Heart failure was defined according to criteria of the European Society of Cardiology. Prevalence was higher in men and increased with age from 0.9% in subjects aged 55–64 to 17.4% in those aged ⩾85. Incidence rate of heart failure was 14.4/1000 person-years (95% CI 13.4–15.5) and was higher in men (17.6/1000 man-years, 95% CI 15.8–19.5) than in women (12.5/1000 woman-years, 95% CI 11.3–13.8). Incidence rate increased with age from 1.4/1000 person-years in those aged 55–59 to 47.4/1000 person-years in those aged ⩾90. Lifetime risk was 33% for men and 29% for women at the age of 55. Survival after incident heart failure was 86% at 30 days, 63% at 1 year, 51% at 2 years and 35% at 5 years of follow-up. Conclusion Prevalence and incidence rates of heart failure are high. In individuals aged 55, almost 1 in 3 will develop heart failure during their remaining lifespan. Heart failure continues to be a fatal disease, with only 35% surviving 5 years after the first diagnosis.

Avian influenza A virus (H7N7) associated with human conjunctivitis and a fatal case of acute respiratory distress syndrome

Abstract: Highly pathogenic avian influenza A viruses of subtypes H5 and H7 are the causative agents of fowl plague in poultry. Influenza A viruses of subtype H5N1 also caused severe respiratory disease in humans in Hong Kong in 1997 and 2003, including at least seven fatal cases, posing a serious human pandemic threat. Between the end of February and the end of May 2003, a fowl plague outbreak occurred in The Netherlands. A highly pathogenic avian influenza A virus of subtype H7N7, closely related to low pathogenic virus isolates obtained from wild ducks, was isolated from chickens. The same virus was detected subsequently in 86 humans who handled affected poultry and in three of their family members. Of these 89 patients, 78 presented with conjunctivitis, 5 presented with conjunctivitis and influenza-like illness, 2 presented with influenza-like illness, and 4 did not fit the case definitions. Influenza-like illnesses were generally mild, but a fatal case of pneumonia in combination with acute respiratory distress syndrome occurred also. Most virus isolates obtained from humans, including probable secondary cases, had not accumulated significant mutations. However, the virus isolated from the fatal case displayed 14 amino acid substitutions, some of which may be associated with enhanced disease in this case. Because H7N7 viruses have caused disease in mammals, including horses, seals, and humans, on several occasions in the past, they may be unusual in their zoonotic potential and, thus, form a pandemic threat to humans.

Prevalence and incidence of shoulder pain in the general population; a systematic review.

Abstract: Objective: To investigate the incidence and prevalence of shoulder complaints in the general population.Method: A systematic review of the literature was conducted. Medline, Embase, and Cinahl were searched for relevant studies.Results: Eighteen studies on prevalence and one study on incidence met the inclusion criteria. Incidence figures of 0.9–2.5% were found for different age groups. Prevalence figures differed from 6.9 to 26% for point prevalence, 18.6–31% for 1‐month prevalence, 4.7–46.7% for 1‐year prevalence and 6.7–66.7% for lifetime prevalence. Prevalence rates decreased when the case definition was restricted, in terms of duration of pain or the presence of limited movements, and increased when the location for pain was enlarged.Conclusion: The reported prevalence figures on shoulder complaints diverged strongly. Health professionals and policymakers who estimate the amount of medical care needed and related costs should be aware of the variations in prevalence rate and the underlying reasons fo...

The value of human and social capital investments for the business performance of startups

Abstract: We investigate the manifold posed question: To what extent does investment in human and social capital, besides the effect of talent, enhance entrepreneurial performance? We distinguish between three different performance measures: survival, profits, and generated employment. On the basis of the empirical analysis of a rich Dutch longitudinal data set of firm founders, we conclude that specific investments indeed affect the three performance measures substantially and significantly. Specific attention is paid to the unobserved talent bias. Moreover, the effect of the emergence of so called "knowledge industries" is explored.

Essential Role of Lung Plasmacytoid Dendritic Cells in Preventing Asthmatic Reactions to Harmless Inhaled Antigen

Abstract: Tolerance is the usual outcome of inhalation of harmless antigen, yet T helper (Th) type 2 cell sensitization to inhaled allergens induced by dendritic cells (DCs) is common in atopic asthma. Here, we show that both myeloid (m) and plasmacytoid (p) DCs take up inhaled antigen in the lung and present it in an immunogenic or tolerogenic form to draining node T cells. Strikingly, depletion of pDCs during inhalation of normally inert antigen led to immunoglobulin E sensitization, airway eosinophilia, goblet cell hyperplasia, and Th2 cell cytokine production, cardinal features of asthma. Furthermore, adoptive transfer of pDCs before sensitization prevented disease in a mouse asthma model. On a functional level, pDCs did not induce T cell division but suppressed the generation of effector T cells induced by mDCs. These studies show that pDCs provide intrinsic protection against inflammatory responses to harmless antigen. Therapies exploiting pDC function might be clinically effective in preventing the development of asthma.

A comparison of the EQ-5D and SF-6D across seven patient groups.

Abstract: As the number of preference-based instruments grows, it becomes increasingly important to compare different preference-based measures of health in order to inform an important debate on the choice of instrument. This paper presents a comparison of two of them, the EQ-5D and the SF-6D (recently developed from the SF-36) across seven patient/population groups (chronic obstructive airways disease, osteoarthritis, irritable bowel syndrome, lower back pain, leg ulcers, post menopausal women and elderly). The mean SF-6D index value was found to exceed the EQ-5D by 0.045 and the intraclass correlation coefficient between them was 0.51. Whilst this convergence lends some support for the validity of these measures, the modest difference at the aggregate level masks more significant differences in agreement across the patient groups and over severity of illness, with the SF-6D having a smaller range and lower variance in values. There is evidence for floor effects in the SF-6D and ceiling effects in the EQ-5D. These discrepancies arise from differences in their health state classifications and the methods used to value them. Further research is required to fully understand the respective roles of the descriptive systems and the valuation methods and to examine the implications for estimates of the impact of health care interventions.

Leadership, self, and identity: A review and research agenda

Abstract: This article reviews empirical research on the role of follower self-conception in leader-ship effectiveness. and specifies an agenda for future research in this area. The review shows that several aspects of follower self-conception (i.e., self-construal, self-efficacy, self-esteem, and self-consistency) may be affected by leadership. and may mediate the effects of leadership on follower behavior. There also is consistent evidence that follower self-construal moderates the impact of leadership on follower attitudes and behavior. Two key themes for future research are defined. First, future research should focus on the development of theory about the role of relational self-construal in the leadership process. Second, it seems particularly valuable to develop theory about the interplay of different aspects of follower self-conception in leadership effectiveness. including the interactive effects of these aspects of self Working backwards from these theoretical models of follower self-conception, specific leader behavior relevant to these aspects of self should then be identified. (C) 2004 Elsevier Inc. All rights reserved.

Lung cancer: intragenic ERBB2 kinase mutations in tumours.

Abstract: The protein-kinase family is the most frequently mutated gene family found in human cancer and faulty kinase enzymes are being investigated as promising targets for the design of antitumour therapies. We have sequenced the gene encoding the transmembrane protein tyrosine kinase ERBB2 (also known as HER2 or Neu) from 120 primary lung tumours and identified 4% that have mutations within the kinase domain; in the adenocarcinoma subtype of lung cancer, 10% of cases had mutations. ERBB2 inhibitors, which have so far proved to be ineffective in treating lung cancer, should now be clinically re-evaluated in the specific subset of patients with lung cancer whose tumours carry ERBB2 mutations.