Showing papers by "Katholieke Universiteit Leuven published in 2008"

Treatment of Hypertension in Patients 80 Years of Age or Older

Abstract: A b s t r ac t Background Whether the treatment of patients with hypertension who are 80 years of age or older is beneficial is unclear. It has been suggested that antihypertensive therapy may reduce the risk of stroke, despite possibly increasing the risk of death. Methods We randomly assigned 3845 patients from Europe, China, Australasia, and Tunisia who were 80 years of age or older and had a sustained systolic blood pressure of 160 mm Hg or more to receive either the diuretic indapamide (sustained release, 1.5 mg) or matching placebo. The angiotensin-converting-enzyme inhibitor perindopril (2 or 4 mg), or matching placebo, was added if necessary to achieve the target blood pressure of 150/80 mm Hg. The primary end point was fatal or nonfatal stroke. Results The active-treatment group (1933 patients) and the placebo group (1912 patients) were well matched (mean age, 83.6 years; mean blood pressure while sitting, 173.0/90.8 mm Hg); 11.8% had a history of cardiovascular disease. Median follow-up was 1.8 years. At 2 years, the mean blood pressure while sitting was 15.0/6.1 mm Hg lower in the active-treatment group than in the placebo group. In an intention-to- treat analysis, active treatment was associated with a 30% reduction in the rate of fatal or nonfatal stroke (95% confidence interval (CI), −1 to 51; P = 0.06), a 39% reduc- tion in the rate of death from stroke (95% CI, 1 to 62; P = 0.05), a 21% reduction in the rate of death from any cause (95% CI, 4 to 35; P = 0.02), a 23% reduction in the rate of death from cardiovascular causes (95% CI, −1 to 40; P = 0.06), and a 64% re- duction in the rate of heart failure (95% CI, 42 to 78; P<0.001). Fewer serious adverse events were reported in the active-treatment group (358, vs. 448 in the placebo group; P = 0.001). Conclusions The results provide evidence that antihypertensive treatment with indapamide (sus- tained release), with or without perindopril, in persons 80 years of age or older is beneficial. (ClinicalTrials.gov number, NCT00122811.)

Genome-wide association defines more than 30 distinct susceptibility loci for Crohn's disease

Abstract: Several risk factors for Crohn's disease have been identified in recent genome-wide association studies. To advance gene discovery further, we combined data from three studies on Crohn's disease (a total of 3,230 cases and 4,829 controls) and carried out replication in 3,664 independent cases with a mixture of population-based and family-based controls. The results strongly confirm 11 previously reported loci and provide genome-wide significant evidence for 21 additional loci, including the regions containing STAT3, JAK2, ICOSLG, CDKAL1 and ITLN1. The expanded molecular understanding of the basis of this disease offers promise for informed therapeutic development.

Guidelines for the use and interpretation of assays for monitoring autophagy in higher eukaryotes

Abstract: Research in autophagy continues to accelerate,(1) and as a result many new scientists are entering the field Accordingly, it is important to establish a standard set of criteria for monitoring macroautophagy in different organisms Recent reviews have described the range of assays that have been used for this purpose(2,3) There are many useful and convenient methods that can be used to monitor macroautophagy in yeast, but relatively few in other model systems, and there is much confusion regarding acceptable methods to measure macroautophagy in higher eukaryotes A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers of autophagosomes versus those that measure flux through the autophagy pathway; thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from fully functional autophagy that includes delivery to, and degradation within, lysosomes (in most higher eukaryotes) or the vacuole (in plants and fungi) Here, we present a set of guidelines for the selection and interpretation of the methods that can be used by investigators who are attempting to examine macroautophagy and related processes, as well as by reviewers who need to provide realistic and reasonable critiques of papers that investigate these processes This set of guidelines is not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to verify an autophagic response

A 4-Year Trial of Tiotropium in chronic obstructive pulmonary disease

Abstract: In patients with COPD, therapy with tiotropium was associated with improvements in lung function, quality of life, and exacerbations during a 4-year period but did not significantly reduce the rate of decline in FEV1. (ClinicalTrials.gov number, NCT00144339.)

Evolution of asymptotic giant branch stars II. Optical to far-infrared isochrones with improved TP-AGB models

Abstract: We present a large set of theoretical isochrones, whose distinctive features mostly reside on the greatly-improved treatment of the thermally-pulsing asymptotic giant branch (TP-AGB) phase. Essentially, we have coupled the TP-AGB tracks described in Paper I, at their stages of pre-flash quiescent H-shell burning, with the evolutionary tracks for the previous evolutionary phases from Girardi et al. (2000, AA the bell-shaped sequences in the Hertzsprung-Russell (HR) diagram for stars with hot-bottom burning; the changes of pulsation mode between fundamental and first overtone; the sudden changes of mean mass-loss rates as the surface chemistry changes from M- to C-type; etc. Theoretical isochrones are then converted to about 20 different photometric systems - including traditional ground-based systems, and those of recent major wide-field surveys such as SDSS, OGLE, DENIS, 2MASS, UKIDSS, etc., - by means of synthetic photometry applied to an updated library of stellar spectra, suitably extended to include C-type stars. Finally, we correct the predicted photometry for the effect of circumstellar dust during the mass-losing stages of the AGB evolution, which allows us to improve the results for the optical-to-infrared systems, and to simulate mid- and far-IR systems such as those of Spitzer and AKARI. We illustrate the most striking properties of these isochrones by means of basic comparisons with observational data for the Milky Way disc and the Magellanic Clouds. Access to the data is provided both via a web repository of static tables (http://stev.oapd.inaf.it/ dustyAGB07 and CDS), and via an interactive web interface (http://stev.oapd. inaf. it/cmd), which provides tables for any intermediate value of age and metallicity, for several photometric systems, and for different choices of dust properties.

Stromal gene signatures in large-B-cell lymphomas

Abstract: Background The addition of rituximab to combination chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), or R-CHOP, has significantly improved the survival of patients with diffuse large-B-cell lymphoma. Whether gene-expression signatures correlate with survival after treatment of diffuse large-B-cell lymphoma is unclear. Methods We profiled gene expression in pretreatment biopsy specimens from 181 patients with diffuse large-B-cell lymphoma who received CHOP and 233 patients with this disease who received R-CHOP. A multivariate gene-expression–based survival-predictor model derived from a training group was tested in a validation group. Results A multivariate model created from three gene-expression signatures — termed “germinal-center B-cell,” “stromal-1,” and “stromal-2” — predicted survival both in patients who received CHOP and patients who received R-CHOP. The prognostically favorable stromal-1 signature reflected extracellular-matrix deposition and histiocytic infilt...

Vitamin D and Human Health: Lessons from Vitamin D Receptor Null Mice

Abstract: The vitamin D endocrine system is essential for calcium and bone homeostasis. The precise mode of action and the full spectrum of activities of the vitamin D hormone, 1,25-dihydroxyvitamin D [1,25-(OH)2D], can now be better evaluated by critical analysis of mice with engineered deletion of the vitamin D receptor (VDR). Absence of a functional VDR or the key activating enzyme, 25-OHD-1α-hydroxylase (CYP27B1), in mice creates a bone and growth plate phenotype that mimics humans with the same congenital disease or severe vitamin D deficiency. The intestine is the key target for the VDR because high calcium intake, or selective VDR rescue in the intestine, restores a normal bone and growth plate phenotype. The VDR is nearly ubiquitously expressed, and almost all cells respond to 1,25-(OH)2D exposure; about 3% of the mouse or human genome is regulated, directly and/or indirectly, by the vitamin D endocrine system, suggesting a more widespread function. VDR-deficient mice, but not vitamin D- or 1α-hydroxylase-deficient mice, and man develop total alopecia, indicating that the function of the VDR and its ligand is not fully overlapping. The immune system of VDR- or vitamin D-deficient mice is grossly normal but shows increased sensitivity to autoimmune diseases such as inflammatory bowel disease or type 1 diabetes after exposure to predisposing factors. VDR-deficient mice do not have a spontaneous increase in cancer but are more prone to oncogene- or chemocarcinogen-induced tumors. They also develop high renin hypertension, cardiac hypertrophy, and increased thrombogenicity. Vitamin D deficiency in humans is associated with increased prevalence of diseases, as predicted by the VDR null phenotype. Prospective vitamin D supplementation studies with multiple noncalcemic endpoints are needed to define the benefits of an optimal vitamin D status.

The LEDA Traitbase: A database of life-history traits of the Northwest European flora

Abstract: Summary 1. An international group of scientists has built an open internet data base of life-history traits of the Northwest European flora (the LEDA-Traitbase) that can be used as a data source for fundamental research on plant biodiversity and coexistence, macro-ecological patterns and plant functional responses. 2. The species-trait matrix comprises referenced information under the control of an editorial board, for ca. 3000 species of the Northwest European flora, combining existing information and additional measurements. The data base currently contains data on 26 plant traits that describe three key features of plant dynamics: persistence, regeneration and dispersal. The LEDA-Traitbase is freely available at www.leda-traitbase.org. 3. We present the structure of the data base and an overview of the trait information available. 4. Synthesis. The LEDA Traitbase is useful for large-scale analyses of functional responses of communities to environmental change, effects of community trait composition on ecosystem properties and patterns of rarity and invasiveness, as well as linkages between traits as expressions of fundamental trade-offs in plants.

Model Selection and Model Averaging

Abstract: Given a data set, you can fit thousands of models at the push of a button, but how do you choose the best? With so many candidate models, overfitting is a real danger. Is the monkey who typed Hamlet actually a good writer? Choosing a model is central to all statistical work with data. We have seen rapid advances in model fitting and in the theoretical understanding of model selection, yet this book is the first to synthesize research and practice from this active field. Model choice criteria are explained, discussed and compared, including the AIC, BIC, DIC and FIC. The uncertainties involved with model selection are tackled, with discussions of frequentist and Bayesian methods; model averaging schemes are presented. Real-data examples are complemented by derivations providing deeper insight into the methodology, and instructive exercises build familiarity with the methods. The companion website features Data sets and R code.

The genome of the model beetle and pest Tribolium castaneum.

Abstract: Tribolium castaneum is a member of the most species-rich eukaryotic order, a powerful model organism for the study of generalized insect development, and an important pest of stored agricultural products. We describe its genome sequence here. This omnivorous beetle has evolved the ability to interact with a diverse chemical environment, as shown by large expansions in odorant and gustatory receptors, as well as P450 and other detoxification enzymes. Development in Tribolium is more representative of other insects than is Drosophila, a fact reflected in gene content and function. For example, Tribolium has retained more ancestral genes involved in cell-cell communication than Drosophila, some being expressed in the growth zone crucial for axial elongation in short-germ development. Systemic RNA interference in T. castaneum functions differently from that in Caenorhabditis elegans, but nevertheless offers similar power for the elucidation of gene function and identification of targets for selective insect control.

Jatropha bio-diesel production and use

Abstract: The interest in using Jatropha curcas L. (JCL) as a feedstock for the production of bio-diesel is rapidly growing. The properties of the crop and its oil have persuaded investors, policy makers and clean development mechanism (CDM) project developers to consider JCL as a substitute for fossil fuels to reduce greenhouse gas emissions. However, JCL is still a wild plant of which basic agronomic properties are not thoroughly understood and the environmental effects have not been investigated yet. Gray literature reports are very optimistic on simultaneous wasteland reclamation capability and oil yields, further fueling the Jatropha bio-diesel hype. In this paper, we give an overview of the currently available information on the different process steps of the production process of bio-diesel from JCL, being cultivation and production of seeds, extraction of the oil, conversion to and the use of the bio-diesel and the by-products. Based on this collection of data and information the best available practice, the shortcomings and the potential environmental risks and benefits are discussed for each production step. The review concludes with a call for general precaution and for science to be applied. (C) 2008 Elsevier Ltd. All rights reserved.

Local Invariant Feature Detectors: A Survey

Abstract: In this survey, we give an overview of invariant interest point detectors, how they evolvd over time, how they work, and what their respective strengths and weaknesses are. We begin with defining the properties of the ideal local feature detector. This is followed by an overview of the literature over the past four decades organized in different categories of feature extraction methods. We then provide a more detailed analysis of a selection of methods which had a particularly significant impact on the research field. We conclude with a summary and promising future research directions.

Benchmarking Classification Models for Software Defect Prediction: A Proposed Framework and Novel Findings

Abstract: Software defect prediction strives to improve software quality and testing efficiency by constructing predictive classification models from code attributes to enable a timely identification of fault-prone modules. Several classification models have been evaluated for this task. However, due to inconsistent findings regarding the superiority of one classifier over another and the usefulness of metric-based classification in general, more research is needed to improve convergence across studies and further advance confidence in experimental results. We consider three potential sources for bias: comparing classifiers over one or a small number of proprietary data sets, relying on accuracy indicators that are conceptually inappropriate for software defect prediction and cross-study comparisons, and, finally, limited use of statistical testing procedures to secure empirical findings. To remedy these problems, a framework for comparative software defect prediction experiments is proposed and applied in a large-scale empirical comparison of 22 classifiers over 10 public domain data sets from the NASA Metrics Data repository. Overall, an appealing degree of predictive accuracy is observed, which supports the view that metric-based classification is useful. However, our results indicate that the importance of the particular classification algorithm may be less than previously assumed since no significant performance differences could be detected among the top 17 classifiers.

Loss of microRNA cluster miR-29a/b-1 in sporadic Alzheimer's disease correlates with increased BACE1/beta-secretase expression.

Abstract: Although the role of APP and PSEN genes in genetic Alzheimer's disease (AD) cases is well established, fairly little is known about the molecular mechanisms affecting A generation in sporadic AD. Deficiency in A clearance is certainly a possibility, but increased expression of proteins like APP or BACE1/-secretase may also be associated with the disease. We therefore investigated changes in microRNA (miRNA) expression profiles of sporadic AD patients and found that several miRNAs potentially involved in the regulation of APP and BACE1 expression appeared to be decreased in diseased brain. We show here that miR-29a, -29b-1, and -9 can regulate BACE1 expression in vitro. The miR-29a/b-1 cluster was signifi- cantly (and AD-dementia-specific) decreased in AD patients dis- playing abnormally high BACE1 protein. Similar correlations be- tween expression of this cluster and BACE1 were found during brain development and in primary neuronal cultures. Finally, we provide evidence for a potential causal relationship between miR-29a/b-1 expression and A generation in a cell culture model. We propose that loss of specific miRNAs can contribute to in- creased BACE1 and A levels in sporadic AD. neurodegeneration amyloid noncoding RNA

Review on solving the inverse problem in EEG source analysis

Abstract: In this primer, we give a review of the inverse problem for EEG source localization. This is intended for the researchers new in the field to get insight in the state-of-the-art techniques used to find approximate solutions of the brain sources giving rise to a scalp potential recording. Furthermore, a review of the performance results of the different techniques is provided to compare these different inverse solutions. The authors also include the results of a Monte-Carlo analysis which they performed to compare four non parametric algorithms and hence contribute to what is presently recorded in the literature. An extensive list of references to the work of other researchers is also provided. This paper starts off with a mathematical description of the inverse problem and proceeds to discuss the two main categories of methods which were developed to solve the EEG inverse problem, mainly the non parametric and parametric methods. The main difference between the two is to whether a fixed number of dipoles is assumed a priori or not. Various techniques falling within these categories are described including minimum norm estimates and their generalizations, LORETA, sLORETA, VARETA, S-MAP, ST-MAP, Backus-Gilbert, LAURA, Shrinking LORETA FOCUSS (SLF), SSLOFO and ALF for non parametric methods and beamforming techniques, BESA, subspace techniques such as MUSIC and methods derived from it, FINES, simulated annealing and computational intelligence algorithms for parametric methods. From a review of the performance of these techniques as documented in the literature, one could conclude that in most cases the LORETA solution gives satisfactory results. In situations involving clusters of dipoles, higher resolution algorithms such as MUSIC or FINES are however preferred. Imposing reliable biophysical and psychological constraints, as done by LAURA has given superior results. The Monte-Carlo analysis performed, comparing WMN, LORETA, sLORETA and SLF, for different noise levels and different simulated source depths has shown that for single source localization, regularized sLORETA gives the best solution in terms of both localization error and ghost sources. Furthermore the computationally intensive solution given by SLF was not found to give any additional benefits under such simulated conditions.

Human metabolic phenotype diversity and its association with diet and blood pressure

Abstract: Metabolic phenotypes are the products of interactions among a variety of factors-dietary, other lifestyle/environmental, gut microbial and genetic. We use a large-scale exploratory analytical approach to investigate metabolic phenotype variation across and within four human populations, based on 1H NMR spectroscopy. Metabolites discriminating across populations are then linked to data for individuals on blood pressure, a major risk factor for coronary heart disease and stroke (leading causes of mortality worldwide). We analyse spectra from two 24-hour urine specimens for each of 4,630 participants from the INTERMAP epidemiological study, involving 17 population samples aged 40-59 in China, Japan, UK and USA. We show that urinary metabolite excretion patterns for East Asian and western population samples, with contrasting diets, diet-related major risk factors, and coronary heart disease/stroke rates, are significantly differentiated (P < 10(-16)), as are Chinese/Japanese metabolic phenotypes, and subgroups with differences in dietary vegetable/animal protein and blood pressure. Among discriminatory metabolites, we quantify four and show association (P < 0.05 to P < 0.0001) of mean 24-hour urinary formate excretion with blood pressure in multiple regression analyses for individuals. Mean 24-hour urinary excretion of alanine (direct) and hippurate (inverse), reflecting diet and gut microbial activities, are also associated with blood pressure of individuals. Metabolic phenotyping applied to high-quality epidemiological data offers the potential to develop an area of aetiopathogenetic knowledge involving discovery of novel biomarkers related to cardiovascular disease risk.

Explaining the relationships between job characteristics, burnout, and engagement: The role of basic psychological need satisfaction

Abstract: Within the Job Demands-Resources model, the presence of job demands (e.g., work pressure) and the absence of job resources (e.g., social support) relate to burnout through a psychological energetic process, whereas the presence of job resources associates with work engagement through a motivational process. Although various mechanisms have been suggested to understand these processes, empirical evidence for these mechanisms is scarce within the JD-R framework. This study examines the role of basic need satisfaction, as defined within Self-Determination Theory, in the relationships between job demands, job resources, and employees’ exhaustion and vigour, the main components of burnout and engagement, respectively. Structural equation modelling in a heterogeneous sample of 745 employees of the Dutch-speaking part of Belgium confirmed that satisfaction of basic psychological needs partially explained the relationships from job demands to exhaustion and from job resources to vigour. It fully accounted for the relationship between job resources and exhaustion. We conclude that the current study adds to the research pointing at need satisfaction as a promising underlying mechanism for employees’ thriving at work.

The Myoblast Autologous Grafting in Ischemic Cardiomyopathy (MAGIC) Trial: First Randomized Placebo-Controlled Study of Myoblast Transplantation

Abstract: Background— Phase I clinical studies have demonstrated the feasibility of implanting autologous skeletal myoblasts in postinfarction scars. However, they have failed to determine whether this procedure was functionally effective and arrhythmogenic. Methods and Results— This multicenter, randomized, placebo-controlled, double-blind study included patients with left ventricular (LV) dysfunction (ejection fraction ≤35%), myocardial infarction, and indication for coronary surgery. Each patient received either cells grown from a skeletal muscle biopsy or a placebo solution injected in and around the scar. All patients received an implantable cardioverter-defibrillator. The primary efficacy end points were the 6-month changes in global and regional LV function assessed by echocardiography. The safety end points comprised a composite index of major cardiac adverse events and ventricular arrhythmias. Ninety-seven patients received myoblasts (400 or 800 million; n=33 and n=34, respectively) or the placebo (n=30). ...

Genes and Molecules of Lactobacilli Supporting Probiotic Action

Abstract: Summary: Lactobacilli have been crucial for the production of fermented products for centuries. They are also members of the mutualistic microbiota present in the human gastrointestinal and urogenital tract. Recently, increasing attention has been given to their probiotic, health-promoting capacities. Many human intervention studies demonstrating health effects have been published. However, as not all studies resulted in positive outcomes, scientific interest arose regarding the precise mechanisms of action of probiotics. Many reported mechanistic studies have addressed mainly the host responses, with less attention being focused on the specificities of the bacterial partners, notwithstanding the completion of Lactobacillus genome sequencing projects, and increasing possibilities of genomics-based and dedicated mutant analyses. In this emerging and highly interdisciplinary field, microbiologists are facing the challenge of molecular characterization of probiotic traits. This review addresses the advances in the understanding of the probiotic-host interaction with a focus on the molecular microbiology of lactobacilli. Insight into the molecules and genes involved should contribute to a more judicious application of probiotic lactobacilli and to improved screening of novel potential probiotics.

An introduction to phase-field modeling of microstructure evolution

Abstract: The phase-field method has become an important and extremely versatile technique for simulating microstructure evolution at the mesoscale. Thanks to the diffuse-interface approach, it allows us to study the evolution of arbitrary complex grain morphologies without any presumption on their shape or mutual distribution. It is also straightforward to account for different thermodynamic driving forces for microstructure evolution, such as bulk and interfacial energy, elastic energy and electric or magnetic energy, and the effect of different transport processes, such as mass diffusion, heat conduction and convection. The purpose of the paper is to give an introduction to the phase-field modeling technique. The concept of diffuse interfaces, the phase-field variables, the thermodynamic driving force for microstructure evolution and the kinetic phase-field equations are introduced. Furthermore, common techniques for parameter determination and numerical solution of the equations are discussed. To show the variety in phase-field models, different model formulations are exploited, depending on which is most common or most illustrative.

An Efficient Dense and Scale-Invariant Spatio-Temporal Interest Point Detector

Abstract: Over the years, several spatio-temporal interest point detectors have been proposed. While some detectors can only extract a sparse set of scale-invariant features, others allow for the detection of a larger amount of features at user-defined scales. This paper presents for the first time spatio-temporal interest points that are at the same time scale-invariant (both spatially and temporally) and densely cover the video content. Moreover, as opposed to earlier work, the features can be computed efficiently. Applying scale-space theory, we show that this can be achieved by using the determinant of the Hessian as the saliency measure. Computations are speeded-up further through the use of approximative box-filter operations on an integral video structure. A quantitative evaluation and experimental results on action recognition show the strengths of the proposed detector in terms of repeatability, accuracy and speed, in comparison with previously proposed detectors.