Showing papers by "Utrecht University published in 2002"

The Measurement of Engagement and Burnout: A Two Sample Confirmatory Factor Analytic Approach

Abstract: This study examines the factorial structure of a new instrument to measure engagement, the hypothesized `opposite' of burnout in a sample of university students (N=314) and employees (N=619). In addition, the factorial structure of the Maslach-Burnout Inventory-General Survey (MBI-GS) is assessed and the relationship between engagement and burnout is examined. Simultaneous confirmatory factor analyses in both samples confirmed the original three-factor structure of the MBI-GS (exhaustion, cynicism, and professional efficacy) as well as the hypothesized three-factor structure of engagement (vigor, dedication, and absorption). Contrary to expectations, a model with two higher-order factors – ‘burnout’ and ‘engagement’ – did not show a superior fit to the data. Instead, our analyses revealed an alternative model with two latent factors including: (1) exhaustion and cynicism (‘core of burnout’); (2) all three engagement scales plus efficacy. Both latent factors are negatively related and share between 22% and 38% of their variances in both samples. Despite the fact that slightly different versions of the MBI-GS and the engagement questionnaire had to be used in both samples the results were remarkably similar across samples, which illustrates the robustness of our findings.

A purposeful approach to the constant comparative method in the analysis of qualitative interviews

Abstract: The constant comparative method (CCM) together with theoretical sampling constitutethe core of qualitative analysis in the grounded theory approach and in other types ofqualitative research. Since the application of the method remains rather unclear, researchers do not know how to `go about' the CCM in their research practice. This study contributes to a purposeful approach of the CCM in order to systematize the analysis process and to increase the traceability and verification of the analyses. The step by step approach is derived from and illustrated with an empirical study into the experience of multiple sclerosis (MS) by patients and their spousal care providers. In this study five different steps were distinguished on the basis of four criteria: (1) the data involved and the overall analysis activities, (2) the aim, (3) the results and (4) the questions asked. It is concluded that systematization of qualitative analysis results from the researcher using a sound plan for conducting CCM regarding these four aspects.

Antiphospholipid syndrome: Clinical and immunologic manifestations and patterns of disease expression in a cohort of 1,000 patients

Abstract: Objective. To analyze the clinical and immunologic manifestations of antiphospholipid syndrome (APS) in a large cohort of patients and to define patterns of disease expression. Methods. The clinical and serologic features of APS (Sapporo preliminary criteria) in 1,000 patients from 13 European countries were analyzed using a computerized database. Results. The cohort consisted of 820 female patients (82.0%) and 180 male patients (18.0%) with a mean +/- SD age of 42 +/- 14 years at study entry. "Primary" APS was present in 53.1% of the patients; APS was associated with systemic lupus erythematosus (SLE) in 36.2%, with lupus-like syndrome in 5.0%, and with other diseases in 5.9%. A variety of thrombotic manifestations affecting the majority of organs were recorded. A catastrophic APS occurred in 0.8% of the patients. Patients with APS associated with SLE had more episodes of arthritis and livedo reticularis, and more frequently exhibited thrombocytopenia and leukopenia. Female patients had a higher frequency of arthritis, livedo reticularis, and migraine. Male patients had a higher frequency of myocardial infarction, epilepsy, and arterial thrombosis in the lower legs and feet. In 28 patients (2.8%), disease onset occurred before age 15; these patients had more episodes of chorea and jugular vein thrombosis than the remaining patients. In 127 patients (12.7%), disease onset occurred after age 50; most of these patients were men. These patients had a higher frequency of stroke and angina pectoris, but a lower frequency of livedo reticularis, than the remaining patients. Conclusion. APS may affect any organ of the body and display a broad spectrum of manifestations. An association with SLE, the patient's sex, and the patient's age at disease onset can modify the disease expression and define specific subsets of APS.

European prospective investigation into cancer and nutrition (EPIC): study populations and data collection

Abstract: The European Prospective Investigation into Cancer and Nutrition (EPIC) is an ongoing multi-centre prospective cohort study designed to investigate the relationship between nutrition and cancer, with the potential for studying other diseases as well. The study currently includes 519 978 participants (366 521 women and 153 457 men, mostly aged 35-70 years) in 23 centres located in 10 European countries, to be followed for cancer incidence and cause-specific mortality for several decades. At enrollment, which took place between 1992 and 2000 at each of the different centres, information was collected through a non-dietary questionnaire on lifestyle variables and through a dietary questionnaire addressing usual diet. Anthropometric measurements were performed and blood samples taken, from which plasma, serum, red cells and buffy coat fractions were separated and aliquoted for long-term storage, mostly in liquid nitrogen. To calibrate dietary measurements, a standardised, computer-assisted 24-hour dietary recall was implemented at each centre on stratified random samples of the participants, for a total of 36 900 subjects. EPIC represents the largest single resource available today world-wide for prospective investigations on the aetiology of cancers (and other diseases) that can integrate questionnaire data on lifestyle and diet, biomarkers of diet and of endogenous metabolism (e.g. hormones and growth factors) and genetic polymorphisms. First results of case-control studies nested within the cohort are expected early in 2003. The present paper provides a description of the EPIC study, with the aim of simplifying reference to it in future papers reporting substantive or methodological studies carried out in the EPIC cohort.

Identification of genes that are associated with DNA repeats in prokaryotes.

Abstract: Using in silico analysis we studied a novel family of repetitive DNA sequences that is present among both domains of the prokaryotes (Archaea and Bacteria), but absent from eukaryotes or viruses. This family is characterized by direct repeats, varying in size from 21 to 37 bp, interspaced by similarly sized non-repetitive sequences. To appreciate their characteri-stic structure, we will refer to this family as the clustered regularly interspaced short palindromic repeats (CRISPR). In most species with two or more CRISPR loci, these loci were flanked on one side by a common leader sequence of 300-500 b. The direct repeats and the leader sequences were conserved within a species, but dissimilar between species. The presence of multiple chromosomal CRISPR loci suggests that CRISPRs are mobile elements. Four CRISPR-associated (cas) genes were identified in CRISPR-containing prokaryotes that were absent from CRISPR-negative prokaryotes. The cas genes were invariably located adjacent to a CRISPR locus, indicating that the cas genes and CRISPR loci have a functional relationship. The cas3 gene showed motifs characteristic for helicases of the superfamily 2, and the cas4 gene showed motifs of the RecB family of exonucleases, suggesting that these genes are involved in DNA metabolism or gene expression. The spatial coherence of CRISPR and cas genes may stimulate new research on the genesis and biological role of these repeats and genes.

Forkhead transcription factor FOXO3a protects quiescent cells from oxidative stress

Abstract: Reactive oxygen species are required for cell proliferation but can also induce apoptosis1. In proliferating cells this paradox is solved by the activation of protein kinase B (PKB; also known as c-Akt), which protects cells from apoptosis2. By contrast, it is unknown how quiescent cells that lack PKB activity are protected against cell death induced by reactive oxygen species. Here we show that the PKB-regulated Forkhead transcription factor FOXO3a (also known as FKHR-L1) protects quiescent cells from oxidative stress by directly increasing their quantities of manganese superoxide dismutase (MnSOD) messenger RNA and protein. This increase in protection from reactive oxygen species antagonizes apoptosis caused by glucose deprivation. In quiescent cells that lack the protective mechanism of PKB-mediated signalling, an alternative mechanism is induced as a consequence of PKB inactivity. This mechanism entails the activation of Forkhead transcription factors, the transcriptional activation of MnSOD and the subsequent reduction of reactive oxygen species. Increased resistance to oxidative stress is associated with longevity. The model of Forkhead involvement in regulating longevity stems from genetic analysis in Caenorhabditis elegans3,4,5,6, and we conclude that this model also extends to mammalian systems.

Serum anti-mullerian hormone levels: a novel measure of ovarian reserve

Abstract: BACKGROUND: Anti-Mullerian hormone (AMH) is produced by the granulosa cells of preantral and small antral follicles and its levels can be assessed in serum. Since the number of ovarian follicles declines with increasing age, AMH levels might be used as a marker for ovarian ageing. Therefore, we studied the relationship between AMH levels and ovarian response during ovarian stimulation for IVF. METHODS: A total of 130 patients undergoing their first IVF treatment cycle using a long protocol with GnRH agonist was prospectively included. Blood withdrawal was performed and the number of antral follicles was assessed by ultrasound on day 3 of a spontaneous cycle. Poor response and the number of oocytes were used as primary outcome measures. In a random subset of 23 patients a GnRH agonist stimulation test was performed to investigate whether a rise in FSH and LH would affect AMH levels. RESULTS: The data of 119 patients were analysed. Serum AMH levels were highly correlated with the number of antral follicles (r 0.77; P < 0.01) and the number of oocytes retrieved (r 0.57, P < 0.01). A negative association was found between AMH levels and poor ovarian response (fewer than 4 oocytes or cycle cancellation; OR 0.82, 95% CI 0.75-0.90, P < 0.01). Inclusion of inhibin B and FSH concentrations to AMH in a multivariate model improved the prediction of ovarian response. The post GnRH agonist rise in FSH and LH levels did not influence AMH values. CONCLUSIONS: Poor response in IVF, indicative of a diminished ovarian reserve, is associated with reduced baseline serum AMH concentrations. In line with recent observations it appears that AMH can be used as a marker for ovarian ageing.

Insights into phase transition kinetics from colloid science

Abstract: Colloids display intriguing transitions between gas, liquid, solid and liquid crystalline phases. Such phase transitions are ubiquitous in nature and have been studied for decades. However, the predictions of phase diagrams are not always realized; systems often become undercooled, supersaturated, or trapped in gel-like states. In many cases the end products strongly depend on the starting position in the phase diagram and discrepancies between predictions and actual observations are due to the intricacies of the dynamics of phase transitions. Colloid science aims to understand the underlying mechanisms of these transitions. Important advances have been made, for example, with new imaging techniques that allow direct observation of individual colloidal particles undergoing phase transitions, revealing some of the secrets of the complex pathways involved.

Global air pollution crossroads over the Mediterranean

Abstract: The Mediterranean Intensive Oxidant Study, performed in the summer of 2001, uncovered air pollution layers from the surface to an altitude of 15 kilometers. In the boundary layer, air pollution standards are exceeded throughout the region, caused by West and East European pollution from the north. Aerosol particles also reduce solar radiation penetration to the surface, which can suppress precipitation. In the middle troposphere, Asian and to a lesser extent North American pollution is transported from the west. Additional Asian pollution from the east, transported from the monsoon in the upper troposphere, crosses the Mediterranean tropopause, which pollutes the lower stratosphere at middle latitudes.

Hostile attribution of intent and aggressive behavior: a meta-analysis.

Abstract: A meta-analytic review was conducted to explain divergent findings on the relation between children's aggressive behavior and hostile attribution of intent to peers. Forty-one studies with 6,017 participants were included in the analysis. Ten studies concerned representative samples from the general population, 24 studies compared nonaggressive to extremely aggressive nonreferred samples, and 7 studies compared nonreferred samples with children referred for aggressive behavior problems. A robust significant association between hostile attribution of intent and aggressive behavior was found. Effect sizes differed considerably between studies. Larger effects were associated with more severe aggressive behavior, rejection by peers as one of the selection criteria, inclusion of 8- to-12-year-old participants, and absence of control for intelligence. Video and picture presentation of stimuli were associated with smaller effect sizes than was audio presentation. Staging of actual social interactions was associated with the largest effects. The importance of understanding moderators of effect size for theory development is stressed.

Exploration of the possibilities for production of Fischer Tropsch liquids and power via biomass gasification

Abstract: This paper reviews the technical feasibility and economics of biomass integrated gasification–Fischer Tropsch (BIG-FT) processes in general, identifies most promising system configurations and identifies key R&D issues essential for the commercialisation of BIG-FT technology. The FT synthesis produces hydrocarbons of different length from a gas mixture of H2 and CO. The large hydrocarbons can be hydrocracked to form mainly diesel of excellent quality. The fraction of short hydrocarbons is used in a combined cycle with the remainder of the syngas. Overall LHV energy efficiencies, 1 calculated with the flowsheet modelling tool Aspenplus, are 33–40% for atmospheric gasification systems and 42–50% for pressurised gasification systems. Investment costs of such systems ( 367 MW th ) are MUS$ 280–450, 2 depending on the system configuration. In the short term, production costs of FT-liquids will be about US$ 16/GJ. In the longer term, with large-scale production, higher CO conversion and higher C5+ selectivity in the FT process, production costs of FT-liquids could drop to US$ 9/GJ. These perspectives for this route and use of biomass-derived FT-fuels in the transport sector are promising. Research and development should be aimed at the development of large-scale (pressurised) biomass gasification-based systems and special attention must be given to the gas cleaning section.

Childhood Trauma Associated With Smaller Hippocampal Volume in Women With Major Depression

Abstract: Objective: Smaller hippocampal volume has been reported only in some but not all studies of unipolar major depressive disorder. Severe stress early in life has also been associated with smaller hippocampal volume and with persistent changes in the hypothalamic-pituitary-adrenal axis. However, prior hippocampal morphometric studies in depressed patients have neither reported nor controlled for a history of early childhood trauma. In this study, the volumes of the hippocampus and of control brain regions were measured in depressed women with and without childhood abuse and in healthy nonabused comparison subjects. Method: Study participants were 32 women with current unipolar major depressive disorder—21 with a history of prepubertal physical and/or sexual abuse and 11 without a history of prepubertal abuse—and 14 healthy nonabused female volunteers. The volumes of the whole hippocampus, temporal lobe, and whole brain were measured on coronal MRI scans by a single rater who was blind to the subjects’ diagnoses. Results: The depressed subjects with childhood abuse had an 18% smaller mean left hippocampal volume than the nonabused depressed subjects and a 15% smaller mean left hippocampal volume than the healthy subjects. Right hippocampal volume was similar across the three groups. The right and left hippocampal volumes in the depressed women without abuse were similar to those in the healthy subjects. Conclusions: A smaller hippocampal volume in adult women with major depressive disorder was observed exclusively in those who had a history of severe and prolonged physical and/or sexual abuse in childhood. An unreported history of childhood abuse in depressed subjects could in part explain the inconsistencies in hippocampal volume findings in prior studies in major depressive disorder.

The biogenesis and functions of exosomes.

Abstract: Exosomes are membrane vesicles with a diameter of 40-100 nm that are secreted by many cell types into the extracellular milieu. They correspond to the internal vesicles of an endosomal compartment, the multivesicular body and are released upon exocytic fusion of this organelle with the plasma membrane. Intracellularly, they are formed by inward budding of the endosomal membrane in a process that sequesters particular proteins and lipids. The unique composition of exosomes may confer specific functions on them upon secretion. Although their physiological role in vivo is far from being unraveled, it is apparent that they function in a multitude of processes, including intercellular communication during the immune response. Exosomes may have evolved early in the evolution of multicellular organisms and also seem to be important for tissue developmental processes.

The performance paradox in the public sector

Abstract: Administrative reform has led to a strong increase in the use of performance assessment instruments in the public sector. However, this has also led to several unintended consequences, such as the performance paradox, tunnel vision, and “analysis paralysis.” These unintended consequences can reduce the quality of the knowledge about actual levels of performance or even negatively affect performance. Examples can be found in all policy sectors. The authors argue that certain characteristics of the public sector–such as ambiguous policy objectives, discretionary authority of street–level bureaucrats, simultaneous production and consumption of services, and the disjunction of costs and revenues–increase the risk of a performance paradox, either unintentionally or deliberately. Performance assessment should therefore take the special characteristics of the public sector into account and develop systems that can handle contested and multiple performance indicators, striking a balance in the degree of “measure ...

A novel Epac-specific cAMP analogue demonstrates independent regulation of Rap1 and ERK.

Abstract: cAMP is involved in a wide variety of cellular processes that were thought to be mediated by protein kinase A (PKA)1. However, cAMP also directly regulates Epac1 and Epac2, guanine nucleotide-exchange factors (GEFs) for the small GTPases Rap1 and Rap2 (refs 2,3). Unfortunately, there is an absence of tools to discriminate between PKA- and Epac-mediated effects. Therefore, through rational drug design we have developed a novel cAMP analogue, 8-(4-chloro-phenylthio)-2′-O-methyladenosine-3′,5′-cyclic monophosphate (8CPT-2Me-cAMP), which activates Epac, but not PKA, both in vitro and in vivo. Using this analogue, we tested the widespread model that Rap1 mediates cAMP-induced regulation of the extracellular signal-regulated kinase (ERK)4,5. However, both in cell lines in which cAMP inhibits growth-factor-induced ERK activation and in which cAMP activates ERK, 8CPT-2Me-cAMP did not affect ERK activity. Moreover, in cell lines in which cAMP activates ERK, inhibition of PKA and Ras, but not Rap1, abolished cAMP-mediated ERK activation. We conclude that cAMP-induced regulation of ERK and activation of Rap1 are independent processes.

Analysis of the Plasmodium falciparum proteome by high-accuracy mass spectrometry

Abstract: The annotated genomes of organisms define a 'blueprint' of their possible gene products. Post-genome analyses attempt to confirm and modify the annotation and impose a sense of the spatial, temporal and developmental usage of genetic information by the organism. Here we describe a large-scale, high-accuracy (average deviation less than 0.02 Da at 1,000 Da) mass spectrometric proteome analysis of selected stages of the human malaria parasite Plasmodium falciparum. The analysis revealed 1,289 proteins of which 714 proteins were identified in asexual blood stages, 931 in gametocytes and 645 in gametes. The last two groups provide insights into the biology of the sexual stages of the parasite, and include conserved, stage-specific, secreted and membrane-associated proteins. A subset of these proteins contain domains that indicate a role in cell-cell interactions, and therefore can be evaluated as potential components of a malaria vaccine formulation. We also report a set of peptides with significant matches in the parasite genome but not in the protein set predicted by computational methods.

Stability in real food webs: weak links in long loops.

Abstract: Increasing evidence that the strengths of interactions among populations in biological communities form patterns that are crucial for system stability requires clarification of the precise form of these patterns, how they come about, and why they influence stability. We show that in real food webs, interaction strengths are organized in trophic loops in such a way that long loops contain relatively many weak links. We show and explain mathematically that this patterning enhances stability, because it reduces maximum "loop weight" and thus reduces the amount of intraspecific interaction needed for matrix stability. The patterns are brought about by biomass pyramids, a feature common to most ecosystems. Incorporation of biomass pyramids in 104 food-web descriptions reveals that the low weight of the long loops stabilizes complex food webs. Loop-weight analysis could be a useful tool for exploring the structure and organization of complex communities.

Non-eosinophilic asthma: importance and possible mechanisms

Abstract: There is increasing evidence that inflammatory mechanisms other than eosinophilic inflammation may be involved in producing the final common pathway of enhanced bronchial reactivity and reversible airflow obstruction that characterises asthma. A review of the literature has shown that, at most, only 50% of asthma cases are attributable to eosinophilic airway inflammation. It is hypothesised that a major proportion of asthma is based on neutrophilic airway inflammation, possibly triggered by environmental exposure to bacterial endotoxin, particulate air pollution, and ozone, as well as viral infections. If there are indeed two (or more) subtypes of asthma, and if non-eosinophilic (neutrophil mediated) asthma is relatively common, this would have major consequences for the treatment and prevention of asthma since most treatment and prevention strategies are now almost entirely focused on allergic/eosinophilic asthma and allergen avoidance measures, respectively. It is therefore important to study the aetiology of asthma further, including the underlying inflammatory profiles.

Self-organization of vegetation in arid ecosystems

Abstract: Scientists are still searching for possible unifying mechanisms to explain this range of spatial patterns (Tongway and Ludwig 2001), and an important question of this research is whether this range is the result of preexisting environmental heterogeneity, the result of spatial selforganization, or both (Klausmeier 1999; Couteron and Lejeune 2001; HilleRisLambers et al. 2001; Von Hardenberg et al. 2001). Here, we contribute to the ongoing debate about vegetation pattern formation in arid ecosystems by presenting novel, spatially explicit model analyses and results, extending on the work of HilleRisLambers et al. (2001). Our results show that these different vegetation patterns observed in arid ecosystems might all be the result of spatial self-organization, caused by one single mechanism: water infiltrates faster into vegetated ground than into bare soil, leading to net displacement of surface water to vegetated patches. This model differs from earlier model results (Klausmeier 1999; Couteron and Lejeune 2001; HilleRisLambers et al. 2001; Von Hardenberg et al. 2001) primarily in two ways: it is fully mechanistic, and it treats the lateral flow of water above and below the soil as separate, not independent, variables. Although the current model greatly simplifies the biophysics of arid systems, it can reproduce the whole range of distinctive vegetation patterns as observed in arid ecosystems, indicating that the proposed mechanism might be generally applicable. We further show that self-organized vegetation patterns can persist far into regions of high aridity, where plants would become extinct if homogeneously distributed, pointing to the importance of this mechanism for maintaining productivity of arid ecosystems (Noy-Meir 1973). Our analyses are based on the model first developed in HilleRisLambers et al. (2001)

A neural basis for the development of inhibitory control

Abstract: The present study explores the neural basis of the development of inhibitory control by combining functional neuroimaging with a parametric manipulation of a go-nogo paradigm. We demonstrate how the maturation of ventral fronto-striatal circuitry underlies the development of this ability. We used event-related fMRI to examine the effect of interference on neural processes involved in inhibitory control in children and adults. Nogo trials were preceded by either 1, 3 or 5 go trials and then compared to one another. Both children and adults showed an increase in errors with increasing interference. Successful response inhibition was associated with stronger activation of prefrontal and parietal regions for children than for adults. In adults, activation in ventral prefrontal regions increased with increasing interference from go trials. Unlike adults, the circuitry appeared to be maximally activated in children when suppressing a behavioral response regardless of the number of preceding responses. Furthermore, activation in ventral fronto-striatal regions correlated with both age and performance. These findings suggest that immature cognition is more susceptible to interference and this is paralleled by maturational differences in underlying fronto-striatal circuitry.