Showing papers by "Utrecht University published in 2005"
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
TL;DR: Patients with glioblastoma containing a methylated MGMT promoter benefited from temozolomide, whereas those who did not have a methylation of theMGMT promoter did notHave such a benefit and were assigned to only radiotherapy.
Abstract: background Epigenetic silencing of the MGMT (O 6 -methylguanine–DNA methyltransferase) DNArepair gene by promoter methylation compromises DNA repair and has been associated with longer survival in patients with glioblastoma who receive alkylating agents. methods We tested the relationship between MGMT silencing in the tumor and the survival of patients who were enrolled in a randomized trial comparing radiotherapy alone with radiotherapy combined with concomitant and adjuvant treatment with temozolomide. The methylation status of the MGMT promoter was determined by methylation-specific polymerase-chain-reaction analysis. results The MGMT promoter was methylated in 45 percent of 206 assessable cases. Irrespective of treatment, MGMT promoter methylation was an independent favorable prognostic factor (P<0.001 by the log-rank test; hazard ratio, 0.45; 95 percent confidence interval, 0.32 to 0.61). Among patients whose tumor contained a methylated MGMT promoter, a survival benefit was observed in patients treated with temozolomide and radiotherapy; their median survival was 21.7 months (95 percent confidence interval, 17.4 to 30.4), as compared with 15.3 months (95 percent confidence interval, 13.0 to 20.9) among those who were assigned to only radiotherapy (P=0.007 by the log-rank test). In the absence of methylation of the MGMT promoter, there was a smaller and statistically insignificant difference in survival between the treatment groups. conclusions Patients with glioblastoma containing a methylated MGMT promoter benefited from temozolomide, whereas those who did not have a methylated MGMT promoter did not have such a benefit.
6,018 citations
TL;DR: Boschma et al. as discussed by the authors argue that the importance of geographical proximity cannot be assessed in isolation, but should always be examined in relation to other dimensions of proximity that may provide alternative solutions to the problem of coordination.
Abstract: Boschma R. A. (2005) Proximity and innovation: a critical assessment, Regional Studies39, 61-74. A key issue in economic geography is to determine the impact of geographical proximity on interactive learning and innovation. We argue that the importance of geographical proximity cannot be assessed in isolation, but should always be examined in relation to other dimensions of proximity that may provide alternative solutions to the problem of coordination. We claim that geographical proximity per se is neither a necessary nor a sufficient condition for learning to take place. Nevertheless, it facilitates interactive learning, most likely by strengthening the other dimensions of proximity. However, proximity may also have negative impacts on innovation due to the problem of lock-in. Accordingly, not only too little, but also too much proximity may be detrimental to interactive learning and innovation. This may be the case for all five dimensions of proximity discussed in the paper, i.e. cognitive, organizatio...
4,727 citations
01 Jan 2005-Methodology: European Journal of Research Methods for The Behavioral and Social Sciences
TL;DR: In this paper, a simulation study is used to determine the influence of different sample sizes at the group level on the accuracy of the estimates (regression coefficients and variances) and their standard errors.
Abstract: An important problem in multilevel modeling is what constitutes a sufficient sample size for accurate estimation. In multilevel analysis, the major restriction is often the higher-level sample size. In this paper, a simulation study is used to determine the influence of different sample sizes at the group level on the accuracy of the estimates (regression coefficients and variances) and their standard errors. In addition, the influence of other factors, such as the lowest-level sample size and different variance distributions between the levels (different intraclass correlations), is examined. The results show that only a small sample size at level two (meaning a sample of 50 or less) leads to biased estimates of the second-level standard errors. In all of the other simulated conditions the estimates of the regression coefficients, the variance components, and the standard errors are unbiased and accurate.
2,931 citations
TL;DR: In this paper, the most important experimental results from the first three years of nucleus-nucleus collision studies at RHIC were reviewed, with emphasis on results of the STAR experiment.
2,750 citations
TL;DR: It is demonstrated that several job resources play a role in buffering the impact of several job demands on burnout, demonstrating that the interaction between (high) demands and (low) resources produces the highest levels of burnout.
Abstract: This study tested and refined the job demands–resources model, demonstrating that several job resources play a role in buffering the impact of several job demands on burnout. A total of 1,012 employees of a large institute for higher education participated in the study. Four demanding aspects of the job (e.g., work overload, emotional demands) and 4 job resources (e.g., autonomy, performance feedback) were used to test the central hypothesis that the interaction between (high) demands and (low) resources produces the highest levels of burnout (exhaustion, cynicism, reduced professional efficacy). The hypothesis was rejected for (reduced) professional efficacy but confirmed for exhaustion and cynicism regarding 18 out of 32 possible 2-way interactions (i.e., combinations of specific job demands and resources). During the past three decades, many studies have shown that unfavorable job characteristics may have a profound impact on job stress and burnout. For example, research has revealed that work overload, lack of autonomy, emotional demands, lowsocial support, and role ambiguity can all lead to feelings of exhaustion and negative, callous attitudes toward work (for reviews, see Lee & Ashforth, 1996; Schaufeli & Enzmann, 1998). Although these previous studies have produced a long list of possible antecedents of burnout, theoretical progress has been limited. The present study tries to increase our insight in the causes of burnout by extending the job demands–resources (JD-R) model (Bakker, Demerouti, De Boer, & Schaufeli, 2003; Demerouti, Bakker, Nachreiner, & Schaufeli, 2001). The central hypothesis tested is that burnout is the result of an imbalance between job demands and resources, and that several job resources may compensate for the influence of several job demands on burnout. Evidence for this contention would offer organizations a clear tool for competitive advantage, because proof for such moderating effects implies that employee well-being and productivity may be maintained, even when it is difficult to reduce or redesign job demands.
1,903 citations
TL;DR: This work shows that five PIN genes collectively control auxin distribution to regulate cell division and cell expansion in the primary root and reveals an interaction network of auxin transport facilitators and root fate determinants that control patterning and growth of the root primordium.
Abstract: Local accumulation of the plant growth regulator auxin mediates pattern formation in Arabidopsis roots and influences outgrowth and development of lateral root- and shoot-derived primordia. However, it has remained unclear how auxin can simultaneously regulate patterning and organ outgrowth and how its distribution is stabilized in a primordium-specific manner. Here we show that five PIN genes collectively control auxin distribution to regulate cell division and cell expansion in the primary root. Furthermore, the joint action of these genes has an important role in pattern formation by focusing the auxin maximum and restricting the expression domain of PLETHORA (PLT) genes, major determinants for root stem cell specification. In turn, PLT genes are required for PIN gene transcription to stabilize the auxin maximum at the distal root tip. Our data reveal an interaction network of auxin transport facilitators and root fate determinants that control patterning and growth of the root primordium.
1,794 citations
TL;DR: In this paper, the state of the art of hydrolysis-fermentation technologies to produce ethanol from lignocellulosic biomass, as well as developing technologies, are evaluated.
Abstract: The state of the art of hydrolysis-fermentation technologies to produce ethanol from lignocellulosic biomass, as well as developing technologies, is evaluated. Promising conversion concepts for the short-, middle- and long-term are defined. Their technical performance was analysed, and results were used for economic evaluations. The current available technology, which is based on dilute acid hydrolysis, has about 35% efficiency (HHV) from biomass to ethanol. The overall efficiency, with electricity co-produced from the not fermentable lignin, is about 60%. Improvements in pre-treatment and advances in biotechnology, especially through process combinations can bring the ethanol efficiency to 48% and the overall process efficiency to 68%. We estimate current investment costs at 2.1 k€/kW HHV (at 400 MW HHV input, i.e. a nominal 2000 tonne dry/day input). A future technology in a 5 times larger plant (2 GW HHV ) could have investments of 900 k€/kW HHV . A combined effect of higher hydrolysis-fermentation efficiency, lower specific capital investments, increase of scale and cheaper biomass feedstock costs (from 3 to 2 €/GJ HHV ), could bring the ethanol production costs from 22 €/GJ HHV in the next 5 years, to 13 €/GJ over the 10–15 year time scale, and down to 8.7 €/GJ in 20 or more years.
1,683 citations
Macquarie University1, University of Minnesota2, VU University Amsterdam3, University of Oslo4, Centre national de la recherche scientifique5, Tohoku University6, Curtin University7, Landcare Research8, Polish Academy of Sciences9, University of Tokyo10, Utrecht University11, University of Córdoba (Spain)12, University of New South Wales13
TL;DR: Global-scale quantification of relationships between plant traits gives insight into the evolution of the world's vegetation, and is crucial for parameterizing vegetation-climate models.
Abstract: Summary • Global-scale quantification of relationships between plant traits gives insight into the evolution of the world’s vegetation, and is crucial for parameterizing vegetation‐ climate models. • A database was compiled, comprising data for hundreds to thousands of species for the core ‘leaf economics’ traits leaf lifespan, leaf mass per area, photosynthetic capacity, dark respiration, and leaf nitrogen and phosphorus concentrations, as well as leaf potassium, photosynthetic N-use efficiency (PNUE), and leaf N : P ratio. • While mean trait values differed between plant functional types, the range found within groups was often larger than differences among them. Future vegetation‐ climate models could incorporate this knowledge. • The core leaf traits were intercorrelated, both globally and within plant functional types, forming a ‘leaf economics spectrum’. While these relationships are very general, they are not universal, as significant heterogeneity exists between relationships fitted to individual sites. Much, but not all, heterogeneity can be explained by variation in sample size alone. PNUE can also be considered as part of this trait spectrum, whereas leaf K and N : P ratios are only loosely related.
1,606 citations
TL;DR: The findings suggest that cortical function becomes fine-tuned with development, followed by association areas involved in top-down control of behavior in brain regions associated with more basic functions mature first.
1,369 citations
University of California, San Diego1, Vanderbilt University Medical Center2, Georgia Institute of Technology3, Anschutz Medical Campus4, Duke University5, University of Texas Southwestern Medical Center6, Ochanomizu University7, University of Tokyo8, University of Graz9, Utrecht University10, University of California, Irvine11
TL;DR: A comprehensive classification of lipids with a common platform that is compatible with informatics requirements has been developed to deal with the massive amounts of data that will be generated by the lipid community.
TL;DR: A multilocus sequence typing (MLST) scheme was developed for Klebsiella pneumoniae and provided unambiguous data useful for the epidemiology of K. pneumoniae isolates.
Abstract: A multilocus sequence typing (MLST) scheme was developed for Klebsiella pneumoniae. Sequences of seven housekeeping genes were obtained for 67 K. pneumoniae strains, including 19 ceftazidime- and ciprofloxacin-resistant isolates. Forty distinct allelic profiles were identified. MLST data were validated against ribotyping and showed high (96%) discriminatory power. The MLST approach provides unambiguous data useful for the epidemiology of K. pneumoniae isolates.
TL;DR: Defects in the mitotic checkpoint generate aneuploidy and might facilitate tumorigenesis, but more severe disabling of checkpoint signalling is a possible anticancer strategy.
Abstract: Abnormal chromosome content — also known as aneuploidy — is the most common characteristic of human solid tumours. It has therefore been proposed that aneuploidy contributes to, or even drives, tumour development. The mitotic checkpoint guards against chromosome mis-segregation by delaying cell-cycle progression through mitosis until all chromosomes have successfully made spindle-microtubule attachments. Defects in the mitotic checkpoint generate aneuploidy and might facilitate tumorigenesis, but more severe disabling of checkpoint signalling is a possible anticancer strategy.
TL;DR: Although some inconsistencies remain, the results in general support a fetal programming hypothesis and programs to reduce maternal stress in pregnancy are warranted.
TL;DR: Geochemical data from five new South Atlantic deep-sea sections indicate that a large mass of carbon dissolved in the ocean at the Paleocene-Eocene boundary and that permanent sequestration of this carbon occurred through silicate weathering feedback.
Abstract: The Paleocene-Eocene thermal maximum (PETM) has been attributed to the rapid release of ∼2000 × 10 9 metric tons of carbon in the form of methane. In theory, oxidation and ocean absorption of this carbon should have lowered deep-sea pH, thereby triggering a rapid ( 100,000 years). These findings indicate that a large mass of carbon (»2000 × 10 9 metric tons of carbon) dissolved in the ocean at the Paleocene-Eocene boundary and that permanent sequestration of this carbon occurred through silicate weathering feedback.
TL;DR: A temperature history for different parts of the world from 169 glacier length records is constructed using a first-order theory of glacier dynamics, which related changes in glacier length to changes in temperature.
Abstract: I constructed a temperature history for different parts of the world from 169 glacier length records. Using a first-order theory of glacier dynamics, I related changes in glacier length to changes in temperature. The derived temperature histories are fully independent of proxy and instrumental data used in earlier reconstructions. Moderate global warming started in the middle of the 19th century. The reconstructed warming in the first half of the 20th century is 0.5 kelvin. This warming was notably coherent over the globe. The warming signals from glaciers at low and high elevations appear to be very similar.
TL;DR: In the literature at the interface of rural livelihood improvement and conservation of natural forests, two overarching issues stand out: (1) how and to what extent use of forest resources do and can contribute to poverty alleviation and (2) How and to how extent poverty mitigation and forest conservation are and can be made convergent rather than divergent goals as discussed by the authors.
TL;DR: Modelling shows that more than half of Hawaiian magmas formed during the past 1 Myr came from a deep olivine-bearing source, and the proportion of recycled (oceanic) crust varies from 30 per cent near the plume centre to insignificant levels at the plumes edge.
Abstract: More than 50 per cent of the Earth's upper mantle consists of olivine and it is generally thought that mantle-derived melts are generated in equilibrium with this mineral. Here, however, we show that the unusually high nickel and silicon contents of most parental Hawaiian magmas are inconsistent with a deep olivine-bearing source, because this mineral together with pyroxene buffers both nickel and silicon at lower levels. This can be resolved if the olivine of the mantle peridotite is consumed by reaction with melts derived from recycled oceanic crust, to form a secondary pyroxenitic source. Our modelling shows that more than half of Hawaiian magmas formed during the past 1 Myr came from this source. In addition, we estimate that the proportion of recycled (oceanic) crust varies from 30 per cent near the plume centre to insignificant levels at the plume edge. These results are also consistent with volcano volumes, magma volume flux and seismological observations.
TL;DR: This study shows that SA, JA, and ET play a primary role in the orchestration of the plant's defense response, but other regulatory mechanisms, such as pathway cross-talk or additional attacker-induced signals, eventually shape the highly complex attacker-specific defense response.
Abstract: Plant defenses against pathogens and insects are regulated differentially by cross-communicating signaling pathways in which salicylic acid (SA), jasmonic acid (JA), and ethylene (ET) play key roles. To understand how plants integrate pathogen- and insect-induced signals into specific defense responses, we monitored the dynamics of SA, JA, and ET signaling in Arabidopsis after attack by a set of microbial pathogens and herbivorous insects with different modes of attack. Arabidopsis plants were exposed to a pathogenic leaf bacterium (Pseudomonas syringae pv. tomato), a pathogenic leaf fungus (Alternaria brassicicola), tissuechewing caterpillars (Pieris rapae), cell-content-feeding thrips (Frankliniella occidentalis), or phloem-feeding aphids (Myzus persicae). Monitoring the signal signature in each plant-attacker combination showed that the kinetics of SA, JA, and ET production varies greatly in both quantity and timing. Analysis of global gene expression profiles demonstrated that the signal signature characteristic of each Arabidopsis-attacker combination is orchestrated into a surprisingly complex set of transcriptional alterations in which, in all cases, stress-related genes are overrepresented. Comparison of the transcript profiles revealed that consistent changes induced by pathogens and insects with very different modes of attack can show considerable overlap. Of all consistent changes induced by A. brassicicola, Pieris rapae, and F. occidentalis, more than 50% also were induced consistently by P. syringae. Notably, although these four attackers all stimulated JA biosynthesis, the majority of the changes in JA-responsive gene expression were attacker specific. All together, our study shows that SA, JA, and ET play a primary role in the orchestration of the plant’s defense response, but other regulatory mechanisms, such as pathway cross-talk or additional attacker-induced signals, eventually shape the highly complex attacker-specific defense response.
TL;DR: The electrostatic interaction between oppositely charged particles can be tuned such that large ionic colloidal crystals form readily, with the approach to controlling opposite-charge interactions facilitating the production of binary crystals of micrometre-sized particles, which could find use as advanced materials for photonic applications.
Abstract: Colloidal suspensions are widely used to study processes such as melting, freezing1,2,3 and glass transitions4,5. This is because they display the same phase behaviour as atoms or molecules, with the nano- to micrometre size of the colloidal particles making it possible to observe them directly in real space3,4. Another attractive feature is that different types of colloidal interactions, such as long-range repulsive1,3, short-range attractive5, hard-sphere-like2,3,4 and dipolar3, can be realized and give rise to equilibrium phases. However, spherically symmetric, long-range attractions (that is, ionic interactions) have so far always resulted in irreversible colloidal aggregation6. Here we show that the electrostatic interaction between oppositely charged particles can be tuned such that large ionic colloidal crystals form readily, with our theory and simulations confirming the stability of these structures. We find that in contrast to atomic systems, the stoichiometry of our colloidal crystals is not dictated by charge neutrality; this allows us to obtain a remarkable diversity of new binary structures. An external electric field melts the crystals, confirming that the constituent particles are indeed oppositely charged. Colloidal model systems can thus be used to study the phase behaviour of ionic species. We also expect that our approach to controlling opposite-charge interactions will facilitate the production of binary crystals of micrometre-sized particles, which could find use as advanced materials for photonic applications7.
TL;DR: A review of the systemic acute phase reaction with major cytokines involved, and the hepatic metabolic changes, negative and positive acute phase proteins (APPs) with function and associated pathology is given, it appears that APPs represent appropriate analytes for assessment of animal health.
Abstract: A review of the systemic acute phase reaction with major cytokines involved, and the hepatic metabolic changes, negative and positive acute phase proteins (APPs) with function and associated pathology is given. It appears that APPs represent appropriate analytes for assessment of animal health. Whereas they represent non-specific markers as biological effect reactants, they can be used for assessing nutritional deficits and reactive processes, especially when positive and negative acute phase variables are combined in an index. When such acute phase index is applied to separate healthy animals from animals with some disease, much better results are obtained than with single analytes and statistically acceptable results for culling individual animals may be reached. Unfortunately at present no cheap, comprehensive and easy to use system is available for assessing various acute phase proteins in serum or blood samples at the same time. Protein microarray or fluid phase microchip technology may satisfy this need; and permit simultaneous analysis of numerous analytes in the same small volume sample and enable integration of information derived from systemic reactivity and nutrition with disease specific variables. Applying such technology may help to solve health problems in various countries not only in animal husbandry but also in human populations.
TL;DR: A review of 45 studies on the Effort-Reward Imbalance (ERI) Model published from 1986 to 2003 showed that the extrinsic ERI hypothesis has gained considerable empirical support.
TL;DR: Patients with DM1 and DM2 are at increased risk for lower respiratory tract infection, urinary tract infections, and skin and mucous membrane infection, and risks increased with recurrences of common infections.
Abstract: Background. Clinical data on the association of diabetes mellitus with common infections are virtually lacking, not conclusive, and often biased. We intended to determine the relative risks of common infections in patients with type 1 and type 2 diabetes mellitus (DM1 and DM2, respectively). Methods. In a 12-month prospective cohort study conducted as part of the Second Dutch National Survey of General Practice, we compared 705 adult patients who had DM1 and 6712 adult patients who had DM2 with 18,911 control patients who had hypertension without diabetes. Outcome measures were medically attended episodes of infection of the respiratory tract, urinary tract, and skin and mucous membranes. We applied multivariable and polytomous logistic regression analysis to determine independent risks of infections and their recurrences in patients with diabetes, compared with control patients. Results. Upper respiratory infections were equally common among patients with diabetes and control patients. Patients with diabetes had a greater risk of lower respiratory tract infection (for patients with DM1: adjusted odds ratio [AOR], 1.42 [95% confidence interval {CI}, 0.96-2.08]; for patients with DM2: AOR, 1.32 [95% CI, 1.13-1.53]), urinary tract infection (for patients with DM1: AOR, 1.96 [95% CI, 1.49-2.58]; for patients with DM2: AOR, 1.24 [95% CI, 1.10-1.39]), bacterial skin and mucous membrane infection (for patients with DM1: AOR, 1.59 [95% CI, 1.12-2.24]; for patients with DM2: AOR, 1.33 [95% CI, 1.15-1.54]), and mycotic skin and mucous membrane infection (for patients with DM1: AOR, 1.34 [95% CI, 0.97-1.84]; for patients with DM2: AOR, 1.44 [95% CI, 1.27-1.63]). Risks increased with recurrences of common infections. Conclusions. Patients with DM1 and DM2 are at increased risk for lower respiratory tract infection, urinary tract infection, and skin and mucous membrane infection. Studies are warranted into management of such infections in patients with diabetes.
International Agency for Research on Cancer1, Medical Research Council2, Aarhus University3, Aalborg University4, French Institute of Health and Medical Research5, National and Kapodistrian University of Athens6, University of Naples Federico II7, University of Turin8, Imperial College London9, Utrecht University10, University of Tromsø11, Lund University12, Umeå University13, University of Cambridge14, University of Oxford15
TL;DR: It is confirmed that colorectal cancer risk is positively associated with high consumption of red and processed meat and support an inverse association with fish intake.
Abstract: Background: Current evidence suggests that high red meat intake is associated with increased colorectal cancer risk. High fi sh intake may be associated with a decreased risk, but the existing evidence is less convincing. Methods: We prospectively followed 478 040 men and women from 10 European countries who were free of cancer at enrollment between 1992 and 1998. Information on diet and lifestyle was collected at baseline. After a mean follow-up of 4.8 years, 1329 incident colorectal cancers were documented. We examined the relationship between intakes of red and processed meat, poultry, and fi sh and colorectal cancer risk using a proportional hazards model adjusted for age, sex, energy (nonfat and fat sources), height, weight, workrelated physical activity, smoking status, dietary fi ber and folate, and alcohol consumption, stratifi ed by center. A calibration substudy based on 36 994 subjects was used to correct hazard ratios (HRs) and 95% confi dence intervals (CIs) for diet measurement errors. All statistical tests were two-sided. Results: Colorectal cancer risk was positively associated with intake of red and processed meat (highest [>160 g/day] versus lowest [ 80 g/day versus <10 g/day, HR = 0.69, 95 % CI = 0.54 to 0.88; P trend <.001), but was not related to poultry intake. Correcting for measurement error strengthened the associations between colorectal cancer and red and processed meat intake (per 100-g increase HR = 1.25, 95% CI =1.09 to 1.41, P trend = .001 and HR = 1.55, 95% CI = 1.19 to 2.02, P trend = .001 before and after calibration, respectively) and for fi sh (per 100 g increase HR = 0.70, 95% CI = 0.57 to 0.87, P trend <.001 and HR = 0.46, 95% CI = 0.27 to 0.77, P trend = .003; before and after correction, respectively). In this study population, the absolute risk of development of colorectal cancer within 10 years for a study subject aged 50 years was 1.71% for the highest category of red and processed meat intake and 1.28% for the lowest category of intake and was 1.86% for subjects in the lowest category of fi sh intake and 1.28% for subjects in the highest category of fi sh intake. Conclusions: Our data confi rm that colorectal cancer risk is positively associated with high consumption of red and processed meat and support an inverse association with fi sh intake. [J Natl Cancer Inst 2005;97:906–16]
TL;DR: It is concluded that special consideration should be given to studying and regulating coarse particles separately from fine particles, suggesting that coarse PM may lead to adverse responses in the lungs triggering processes leading to hospital admissions.
Abstract: Studies on health effects of airborne particulate matter (PM) have traditionally focused on particles ,10 mm in diameter (PM10) or particles ,2.5 mm in diameter (PM2.5). The coarse fraction of PM10, particles .2.5 mm, has only been studied recently. These particles have different sources and composition compared with PM2.5. This paper is based on a systematic review of studies that have analysed fine and coarse PM jointly and examines the epidemiological evidence for effects of coarse particles on health. Time series studies relating ambient PM to mortality have in some places provided evidence of an independent effect of coarse PM on daily mortality, but in most urban areas, the evidence is stronger for fine particles. The few long-term studies of effects of coarse PM on survival do not provide any evidence of association. In studies of chronic obstructive pulmonary disease, asthma and respiratory admissions, coarse PM has a stronger or as strong short-term effect as fine PM, suggesting that coarse PM may lead to adverse responses in the lungs triggering processes leading to hospital admissions. There is also support for an association between coarse PM and cardiovascular admissions. It is concluded that special consideration should be given to studying and regulating coarse particles separately from fine particles.
TL;DR: A major pathway by which amino acids control mTOR signaling is distinct from that of insulin and that, instead of signaling through components of the insulin/class 1PI3K pathway, amino acids mediate mTOR activation by signaling through class 3 PI3K, hVps34.
Abstract: During the evolution of metazoans and the rise of systemic hormonal regulation, the insulin-controlled class 1 phosphatidylinositol 3OH-kinase (PI3K) pathway was merged with the primordial amino acid-driven mammalian target of rapamycin (mTOR) pathway to control the growth and development of the organism. Insulin regulates mTOR function through a recently described canonical signaling pathway, which is initiated by the activation of class 1 PI3K. However, how the amino acid input is integrated with that of the insulin signaling pathway is unclear. Here we used a number of molecular, biochemical, and pharmacological approaches to address this issue. Unexpectedly, we found that a major pathway by which amino acids control mTOR signaling is distinct from that of insulin and that, instead of signaling through components of the insulin/class 1 PI3K pathway, amino acids mediate mTOR activation by signaling through class 3 PI3K, hVps34.
TL;DR: In this article, a more fundamental form of reflection is needed, referred to as core reflection, which concurs with the recent emphasis in psychology on attending to people's strengths rather than their deficiencies.
Abstract: Reflection is currently a key concept in teacher education. The reflection process is often described in terms of a cyclical model. In the present article, we explain how such a model can be used for supporting student teachers’ reflection on practical situations they are confronted with, and on their behaviour, skills and beliefs in such situations. In some cases, however, more fundamental issues appear to influence teachers’ practical functioning. For example, their self‐concept can have a decisive influence on the way they function, or they may do what is expected of them, and yet not feel truly involved. In such cases, a more fundamental form of reflection is needed, which in this article we refer to as ‘core reflection’. The focus on core reflection concurs with the recent emphasis in psychology on attending to people’s strengths rather than their deficiencies.
TL;DR: In this article, the authors review recent developments in Kα and Kβ spectroscopy and show how the chemical sensitivity of the fluorescence lines can be exploited for selective X-ray absorption studies.
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26 Dec 2005TL;DR: In times of crisis, communities and members of organizations expect their leaders to minimize the impact of the crisis at the level of the organization as mentioned in this paper, which is a defining feature of contemporary governance.
Abstract: Crisis management has become a defining feature of contemporary governance. In times of crisis, communities and members of organizations expect their leaders to minimize the impact of the crisis at ...
TL;DR: In this article, the authors found that olanzapine-treated patients have less change over time in whole brain gray matter volumes and lateral ventricle volumes than haloperidol-treatment patients and that gray matter changes are associated with changes in psychopathology and neurocognition.
Abstract: Background Pathomorphologic brain changes occurring as early as first-episode schizophrenia have been extensively described. Longitudinal studies have demonstrated that these changes may be progressive and associated with clinical outcome. This raises the possibility that antipsychotics might alter such pathomorphologic progression in early-stage schizophrenia. Objective To test a priori hypotheses that olanzapine-treated patients have less change over time in whole brain gray matter volumes and lateral ventricle volumes than haloperidol-treated patientsandthat gray matter and lateral ventricle volume changes are associated with changes in psychopathology and neurocognition. Design Longitudinal, randomized, controlled, multisite, double-blind study. Patients treated and followed up for up to 104 weeks. Neurocognitive and magnetic resonance imaging (MRI) assessments performed at weeks 0 (baseline), 12, 24, 52, and 104. Mixed-models analyses with time-dependent covariates evaluated treatment effects on MRI end points and explored relationships between MRI, psychopathologic, and neurocognitive outcomes. Setting Fourteen academic medical centers (United States, 11; Canada, 1; Netherlands, 1; England, 1). Participants Patients with first-episode psychosis (DSM-IV) and healthy volunteers. Interventions Random allocation to a conventional antipsychotic, haloperidol (2-20 mg/d), or an atypical antipsychotic, olanzapine (5-20 mg/d). Main Outcome Measures Brain volume changes assessed by MRI. Results Of 263 randomized patients, 161 had baseline and at least 1 postbaseline MRI evaluation. Haloperidol-treated patients exhibited significant decreases in gray matter volume, whereas olanzapine-treated patients did not. A matched sample of healthy volunteers (n = 58) examined contemporaneously showed no change in gray matter volume. Conclusions Patients with first-episode psychosis exhibited a significant between-treatment difference in MRI volume changes. Haloperidol was associated with significant reductions in gray matter volume, whereas olanzapine was not. Post hoc analyses suggested that treatment effects on brain volume and psychopathology of schizophrenia may be associated. The differential treatment effects on brain morphology could be due to haloperidol-associated toxicity or greater therapeutic effects of olanzapine.