Showing papers by "University of Bonn published in 2007"

Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma.

Abstract: Background Interferon alfa is widely used for metastatic renal-cell carcinoma but has limited efficacy and tolerability. Temsirolimus, a specific inhibitor of the mammalian target of rapamycin kinase, may benefit patients with this disease. Methods In this multicenter, phase 3 trial, we randomly assigned 626 patients with previously untreated, poor-prognosis metastatic renal-cell carcinoma to receive 25 mg of intravenous temsirolimus weekly, 3 million U of interferon alfa (with an increase to 18 million U) subcutaneously three times weekly, or combination therapy with 15 mg of temsirolimus weekly plus 6 million U of interferon alfa three times weekly. The primary end point was overall survival in comparisons of the temsirolimus group and the combination-therapy group with the interferon group. Results Patients who received temsirolimus alone had longer overall survival (hazard ratio for death, 0.73; 95% confidence interval [CI], 0.58 to 0.92; P=0.008) and progression-free survival (P<0.001) than did patie...

Efficient RANSAC for Point-Cloud Shape Detection

Abstract: In this paper we present an automatic algorithm to detect basic shapes in unorganized point clouds. The algorithm decomposes the point cloud into a concise, hybrid structure of inherent shapes and a set of remaining points. Each detected shape serves as a proxy for a set of corresponding points. Our method is based on random sampling and detects planes, spheres, cylinders, cones and tori. For models with surfaces composed of these basic shapes only, for example, CAD models, we automatically obtain a representation solely consisting of shape proxies. We demonstrate that the algorithm is robust even in the presence of many outliers and a high degree of noise. The proposed method scales well with respect to the size of the input point cloud and the number and size of the shapes within the data. Even point sets with several millions of samples are robustly decomposed within less than a minute. Moreover, the algorithm is conceptually simple and easy to implement. Application areas include measurement of physical parameters, scan registration, surface compression, hybrid rendering, shape classification, meshing, simplification, approximation and reverse engineering.

A Review of Statistical Approaches to Level Set Segmentation: Integrating Color, Texture, Motion and Shape

Abstract: Since their introduction as a means of front propagation and their first application to edge-based segmentation in the early 90's, level set methods have become increasingly popular as a general framework for image segmentation. In this paper, we present a survey of a specific class of region-based level set segmentation methods and clarify how they can all be derived from a common statistical framework. Region-based segmentation schemes aim at partitioning the image domain by progressively fitting statistical models to the intensity, color, texture or motion in each of a set of regions. In contrast to edge-based schemes such as the classical Snakes, region-based methods tend to be less sensitive to noise. For typical images, the respective cost functionals tend to have less local minima which makes them particularly well-suited for local optimization methods such as the level set method. We detail a general statistical formulation for level set segmentation. Subsequently, we clarify how the integration of various low level criteria leads to a set of cost functionals. We point out relations between the different segmentation schemes. In experimental results, we demonstrate how the level set function is driven to partition the image plane into domains of coherent color, texture, dynamic texture or motion. Moreover, the Bayesian formulation allows to introduce prior shape knowledge into the level set method. We briefly review a number of advances in this domain.

Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS): Process, format, and clinimetric testing plan.

Abstract: This article presents the revision process, major innovations, and clinimetric testing program for the Movement Disorder Society (MDS)-sponsored revision of the Unified Parkinson's Disease Rating Scale (UPDRS), known as the MDS-UPDRS. The UPDRS is the most widely used scale for the clinical study of Parkinson's disease (PD). The MDS previously organized a critique of the UPDRS, which cited many strengths, but recommended revision of the scale to accommodate new advances and to resolve problematic areas. An MDS-UPDRS committee prepared the revision using the recommendations of the published critique of the scale. Subcommittees developed new material that was reviewed by the entire committee. A 1-day face-to-face committee meeting was organized to resolve areas of debate and to arrive at a working draft ready for clinimetric testing. The MDS-UPDRS retains the UPDRS structure of four parts with a total summed score, but the parts have been modified to provide a section that integrates nonmotor elements of PD: I, Nonmotor Experiences of Daily Living; II, Motor Experiences of Daily Living; III, Motor Examination; and IV, Motor Complications. All items have five response options with uniform anchors of 0 = normal, 1 = slight, 2 = mild, 3 = moderate, and 4 = severe. Several questions in Part I and all of Part II are written as a patient/caregiver questionnaire, so that the total rater time should remain approximately 30 minutes. Detailed instructions for testing and data acquisition accompany the MDS-UPDRS in order to increase uniform usage. Multiple language editions are planned. A three-part clinimetric program will provide testing of reliability, validity, and responsiveness to interventions. Although the MDS-UPDRS will not be published until it has successfully passed clinimetric testing, explanation of the process, key changes, and clinimetric programs allow clinicians and researchers to understand and participate in the revision process.

Global patterns and determinants of vascular plant diversity

Abstract: Plants, with an estimated 300,000 species, provide crucial primary production and ecosystem structure. To date, our quantitative understanding of diversity gradients of megadiverse clades such as plants has been hampered by the paucity of distribution data. Here, we investigate the global-scale species-richness pattern of vascular plants and examine its environmental and potential his- torical determinants. Across 1,032 geographic regions worldwide, potential evapotranspiration, the number of wet days per year, and measurements of topographical and habitat heterogeneity emerge as core predictors of species richness. After accounting for environmental effects, the residual differences across the major floristic kingdoms are minor, with the exception of the uniquely diverse Cape Region, highlighting the important role of historical contingencies. Notably, the South African Cape region contains more than twice as many species as expected by the global environmental model, confirming its uniquely evolved flora. A combined multipredictor model explains 70% of the global variation in species richness and fully accounts for the enigmatic latitudinal gradient in species richness. The models illustrate the geographic interplay of different environmental predictors of species richness. Our findings highlight that different hypotheses about the causes of diversity gradients are not mutually exclusive, but likely act synergistically with water- energy dynamics playing a dominant role. The presented geostatistical approach is likely to prove instrumental for identifying richness patterns of the many other taxa without single-species distribution data that still escape our understanding. biodiversity historical contingency latitudinal gradient macroecology species richness

Seizure prediction: the long and winding road.

Abstract: The sudden and apparently unpredictable nature of seizures is one of the most disabling aspects of the disease epilepsy. A method capable of predicting the occurrence of seizures from the electroencephalogram (EEG) of epilepsy patients would open new therapeutic possibilities. Since the 1970s investigations on the predictability of seizures have advanced from preliminary descriptions of seizure precursors to controlled studies applying prediction algorithms to continuous multi-day EEG recordings. While most of the studies published in the 1990s and around the turn of the millennium yielded rather promising results, more recent evaluations could not reproduce these optimistic findings, thus raising a debate about the validity and reliability of previous investigations. In this review, we will critically discuss the literature on seizure prediction and address some of the problems and pitfalls involved in the designing and testing of seizure-prediction algorithms. We will give an account of the current state of this research field, point towards possible future developments and propose methodological guidelines for future studies on seizure prediction.

Analysis of 81 genes from 64 plastid genomes resolves relationships in angiosperms and identifies genome-scale evolutionary patterns.

Abstract: Angiosperms are the largest and most successful clade of land plants with >250,000 species distributed in nearly every terrestrial habitat. Many phylogenetic studies have been based on DNA sequences of one to several genes, but, despite decades of intensive efforts, relationships among early diverging lineages and several of the major clades remain either incompletely resolved or weakly supported. We performed phylogenetic analyses of 81 plastid genes in 64 sequenced genomes, including 13 new genomes, to estimate relationships among the major angiosperm clades, and the resulting trees are used to examine the evolution of gene and intron content. Phylogenetic trees from multiple methods, including model-based approaches, provide strong support for the position of Amborella as the earliest diverging lineage of flowering plants, followed by Nymphaeales and Austrobaileyales. The plastid genome trees also provide strong support for a sister relationship between eudicots and monocots, and this group is sister to a clade that includes Chloranthales and magnoliids. Resolution of relationships among the major clades of angiosperms provides the necessary framework for addressing numerous evolutionary questions regarding the rapid diversification of angiosperms. Gene and intron content are highly conserved among the early diverging angiosperms and basal eudicots, but 62 independent gene and intron losses are limited to the more derived monocot and eudicot clades. Moreover, a lineage-specific correlation was detected between rates of nucleotide substitutions, indels, and genomic rearrangements.

MRI evaluation of the contralateral breast in women with recently diagnosed breast cancer

Abstract: Even after careful clinical and mammographic evaluation, cancer is found in the contralateral breast in up to 10% of women who have received treatment for unilateral breast cancer. We conducted a study to determine whether magnetic resonance imaging (MRI) could improve on clinical breast examination and mammography in detecting contralateral breast cancer soon after the initial diagnosis of unilateral breast cancer. Methods A total of 969 women with a recent diagnosis of unilateral breast cancer and no abnormalities on mammographic and clinical examination of the contralateral breast underwent breast MRI. The diagnosis of MRI-detected cancer was confirmed by means of biopsy within 12 months after study entry. The absence of breast cancer was determined by means of biopsy, the absence of positive findings on repeat imaging and clinical examination, or both at 1 year of follow-up. Results MRI detected clinically and mammographically occult breast cancer in the contralateral breast in 30 of 969 women who were enrolled in the study (3.1%). The sensitivity of MRI in the contralateral breast was 91%, and the specificity was 88%. The negative predictive value of MRI was 99%. A biopsy was performed on the basis of a positive MRI finding in 121 of the 969 women (12.5%), 30 of whom had specimens that were positive for cancer (24.8%); 18 of the 30 specimens were positive for invasive cancer. The mean diameter of the invasive tumors detected was 10.9 mm. The additional number of cancers detected was not influenced by breast density, menopausal status, or the histologic features of the primary tumor. Conclusions MRI can detect cancer in the contralateral breast that is missed by mammography and clinical examination at the time of the initial breast-cancer diagnosis. (ClinicalTrials. gov number, NCT00058058.)

Long-term survival with glioblastoma multiforme

Abstract: The median survival of glioblastoma patients is approximately 12 months. However, 3-5% of the patients survives for more than 3 years and are referred to as long-term survivors. The clinical and molecular factors that contribute to long-term survival are still unknown. To identify specific parameters that might be associated with this phenomenon, we performed a detailed clinical and molecular analysis of 55 primary glioblastoma long-term survivors recruited at the six clinical centres of the German Glioma Network and one associated centre. An evaluation form was developed and used to document demographic, clinical and treatment-associated parameters. In addition, environmental risk factors, associated diseases and occupational risks were assessed. These patients were characterized by young age at diagnosis and a good initial Karnofsky performance score (KPS). None of the evaluated socioeconomic, environmental and occupational factors were associated with long-term survival. Molecular analyses revealed MGMT hypermethylation in 28 of 36 tumours (74%) investigated. TP53 mutations were found in 9 of 31 tumours (29%) and EGFR amplification in 10 of 38 tumours (26%). Only 2 of 32 tumours (6%) carried combined 1p and 19q deletions. Comparison of these data with results from an independent series of 141 consecutive unselected glioblastoma patients registered in the German Glioma Network revealed significantly more frequent MGMT hypermethylation in the long-term survivor group. Taken together, our findings underline the association of glioblastoma long-term survival with prognostically favourable clinical factors, in particular young age and good initial performance score, as well as MGMT promoter hypermethylation.

Comparison of quantification methods to measure fire-derived (black/elemental) carbon in soils and sediments using reference materials from soil, water, sediment and the atmosphere

Abstract: Black carbon (BC), the product of incomplete combustion of fossil fuels and biomass (called elemental carbon (EC) in atmospheric sciences), was quantified in 12 different materials by 17 laboratories from different disciplines, using seven different methods. The materials were divided into three classes: (1) potentially interfering materials, (2) laboratory-produced BC-rich materials, and (3) BC-containing environmental matrices (from soil, water, sediment, and atmosphere). This is the first comprehensive intercomparison of this type (multimethod, multilab, and multisample), focusing mainly on methods used for soil and sediment BC studies. Results for the potentially interfering materials (which by definition contained no fire-derived organic carbon) highlighted situations where individual methods may overestimate BC concentrations. Results for the BC-rich materials (one soot and two chars) showed that some of the methods identified most of the carbon in all three materials as BC, whereas other methods identified only soot carbon as BC. The different methods also gave widely different BC contents for the environmental matrices. However, these variations could be understood in the light of the findings for the other two groups of materials, i.e., that some methods incorrectly identify non-BC carbon as BC, and that the detection efficiency of each technique varies across the BC continuum. We found that atmospheric BC quantification methods are not ideal for soil and sediment studies as in their methodology these incorporate the definition of BC as light-absorbing material irrespective of its origin, leading to biases when applied to terrestrial and sedimentary materials. This study shows that any attempt to merge data generated via different methods must consider the different, operationally defined analytical windows of the BC continuum detected by each technique, as well as the limitations and potential biases of each technique. A major goal of this ring trial was to provide a basis on which to choose between the different BC quantification methods in soil and sediment studies. In this paper we summarize the advantages and disadvantages of each method. In future studies, we strongly recommend the evaluation of all methods analyzing for BC in soils and sediments against the set of BC reference materials analyzed here.

The current status of breast MR imaging. Part I. Choice of technique, image interpretation, diagnostic accuracy, and transfer to clinical practice.

Abstract: Compared with mammography and breast ultrasonography, contrast material–enhanced magnetic resonance (MR) imaging is a breast imaging technique that offers not only information on lesion cross-sectional morphology but also on functional lesion features such as tissue perfusion and enhancement kinetics. After an enthusiastic start to clinical breast MR imaging in the early 1990s, a variety of difficulties and obstacles were identified that hampered the transfer of the modality into clinical practice, including a lack of standardization regarding image acquisition and interpretation guidelines, a lack of MR-compatible interventional materials, and a lack of evidence regarding its diagnostic accuracy—particularly specificity and positive predictive value, as well as sensitivity for ductal carcinoma in situ. This article is the first of two on the current status of breast MR imaging. The pathophysiologic basis of breast MR and the effects on acquisition technique and diagnostic accuracy, the diverging demands ...

Why your model parameter confidences might be too optimistic - unbiased estimation of the inverse covariance matrix

Abstract: Aims. The maximum-likelihood method is the standard approach to obtain model fits to observational data and the corresponding confidence regions. We investigate possible sources of bias in the log- likelihood function and its subsequent analysis, focusing on estimators of the inverse covariance matrix. Furthermore, we study under which circumstances the estimated covariance matrix is invertible. Methods. We perform Monte-Carlo simulations to investigate the behaviour of estimators for the inverse covariance matrix, depending on the number of independent data sets and the number of variables of the data vectors. Results. We find that the inverse of the maximum-likelihood estimator of the covariance is biased, the amount of bias depending on the ratio of the number of bins (data vector variables), p, to the number of data sets, n. This bias inevitably leads to an ‐ in extreme cases catastro phic ‐ underestimation of the size of confidence regions. We repor t on a method to remove this bias for the idealised case of Gaussian noise and statistically independent data vectors. Moreover, we demonstrate that marginalisation over parameters introduces a bias into the marginalised log-likelihood function. Measures of the sizes of confidenc e regions suffer from the same problem. Furthermore, we give an analytic proof for the fact that the estimated covariance matrix is singular if p> n.

Distinct Pathways of Antigen Uptake and Intracellular Routing in CD4 and CD8 T Cell Activation

Abstract: The mechanisms that allow antigen-presenting cells (APCs) to selectively present extracellular antigen to CD8+ effector T cells (cross-presentation) or to CD4+ T helper cells are not fully resolved. We demonstrated that APCs use distinct endocytosis mechanisms to simultaneously introduce soluble antigen into separate intracellular compartments, which were dedicated to presentation to CD8+ or CD4+ T cells. Specifically, the mannose receptor supplied an early endosomal compartment distinct from lysosomes, which was committed to cross-presentation. These findings imply that antigen does not require intracellular diversion to access the cross-presentation pathway, because it can enter the pathway already during endocytosis.

Epidemiology of sepsis in Germany: results from a national prospective multicenter study

Abstract: To determine the prevalence and mortality of ICU patients with severe sepsis in Germany, with consideration of hospital size. Prospective, observational, cross-sectional 1-day point-prevalence study. 454 ICUs from a representative nationwide sample of 310 hospitals stratified by size. Data were collected via 1-day on-site audits by trained external study physicians. Visits were randomly distributed over 1 year (2003). Inflammatory response of all ICU patients was assessed using the ACCP/SCCM consensus conference criteria. Patients with severe sepsis were followed up after 3 months for hospital mortality and length of ICU stay. Main outcome measures were prevalence and mortality. A total of 3,877 patients were screened. Prevalence was 12.4% (95% CI, 10.9–13.8%) for sepsis and 11.0% (95% CI, 9.7–12.2%) for severe sepsis including septic shock. The ICU and hospital mortality of patients with severe sepsis was 48.4 and 55.2%, respectively, without significant differences between hospital size. Prevalence and mean length of ICU stay of patients with severe sepsis were significantly higher in larger hospitals and universities (≤ 200 beds: 6% and 11.5 days, universities: 19% and 19.2 days, respectively). The expected number of newly diagnosed cases with severe sepsis in Germany amounts to 76–110 per 100,000 adult inhabitants. To allow better comparison between countries, future epidemiological studies should use standardized study methodologies with respect to sepsis definitions, hospital size, and daily and monthly variability.

Social Comparison Affects Reward-Related Brain Activity in the Human Ventral Striatum

Abstract: Whether social comparison affects individual well-being is of central importance for understanding behavior in any social environment. Traditional economic theories focus on the role of absolute rewards, whereas behavioral evidence suggests that social comparisons influence well-being and decisions. We investigated the impact of social comparisons on reward-related brain activity using functional magnetic resonance imaging (fMRI). While being scanned in two adjacent MRI scanners, pairs of subjects had to simultaneously perform a simple estimation task that entailed monetary rewards for correct answers. We show that a variation in the comparison subject's payment affects blood oxygenation level-dependent responses in the ventral striatum. Our results provide neurophysiological evidence for the importance of social comparison on reward processing in the human brain.

Fog Research: A Review of Past Achievements and Future Perspectives

Abstract: The scientific community that includes meteorologists, physical scientists, engineers, medical doctors, biologists, and environmentalists has shown interest in a better understanding of fog for years because of its effects on, directly or indirectly, the daily life of human beings. The total economic losses associated with the impact of the presence of fog on aviation, marine and land transportation can be comparable to those of tornadoes or, in some cases, winter storms and hurricanes. The number of articles including the word ``fog'' in Journals of American Meteorological Society alone was found to be about 4700, indicating that there is substantial interest in this subject. In spite of this extensive body of work, our ability to accurately forecast/nowcast fog remains limited due to our incomplete understanding of the fog processes over various time and space scales. Fog processes involve droplet microphysics, aerosol chemistry, radiation, turbulence, large/small-scale dynamics, and surface conditions (e.g., partaining to the presence of ice, snow, liquid, plants, and various types of soil). This review paper summarizes past achievements related to the understanding of fog formation, development and decay, and in this respect, the analysis of observations and the development of forecasting models and remote sensing methods are discussed in detail. Finally, future perspectives for fog-related research are highlighted.

Guidelines for the clinical management of Lynch syndrome (hereditary non-polyposis cancer)

Abstract: Lynch syndrome (hereditary non-polyposis colorectal cancer) is characterised by the development of colorectal cancer, endometrial cancer and various other cancers, and is caused by a mutation in one of the mismatch repair genes: MLH1, MSH2, MSH6 or PMS2. The discovery of these genes, 15 years ago, has led to the identification of large numbers of affected families. In April 2006, a workshop was organised by a group of European experts in hereditary gastrointestinal cancer (the Mallorca-group), aiming to establish guidelines for the clinical management of Lynch syndrome. 21 experts from nine European countries participated in this workshop. Prior to the meeting, various participants prepared the key management issues of debate according to the latest publications. A systematic literature search using Pubmed and the Cochrane Database of Systematic Reviews reference lists of retrieved articles and manual searches of relevant articles was performed. During the workshop, all recommendations were discussed in detail. Because most of the studies that form the basis for the recommendations were descriptive and/or retrospective in nature, many of them were based on expert opinion. The guidelines described in this manuscript may be helpful for the appropriate management of families with Lynch syndrome. Prospective controlled studies should be undertaken to improve further the care of these families.

Direct observation of second-order atom tunnelling

Abstract: Tunnelling of material particles through a classically impenetrable barrier constitutes one of the hallmark effects of quantum physics. When interactions between the particles compete with their mobility through a tunnel junction, intriguing dynamical behaviour can arise because the particles do not tunnel independently. In single-electron or Bloch transistors, for example, the tunnelling of an electron or Cooper pair can be enabled or suppressed by the presence of a second charge carrier due to Coulomb blockade. Here we report direct, time-resolved observations of the correlated tunnelling of two interacting ultracold atoms through a barrier in a double-well potential. For the regime in which the interactions between the atoms are weak and tunnel coupling dominates, individual atoms can tunnel independently, similar to the case of a normal Josephson junction. However, when strong repulsive interactions are present, two atoms located on one side of the barrier cannot separate, but are observed to tunnel together as a pair in a second-order co-tunnelling process. By recording both the atom position and phase coherence over time, we fully characterize the tunnelling process for a single atom as well as the correlated dynamics of a pair of atoms for weak and strong interactions. In addition, we identify a conditional tunnelling regime in which a single atom can only tunnel in the presence of a second particle, acting as a single atom switch. Such second-order tunnelling events, which are the dominating dynamical effect in the strongly interacting regime, have not been previously observed with ultracold atoms. Similar second-order processes form the basis of superexchange interactions between atoms on neighbouring lattice sites of a periodic potential, a central component of proposals for realizing quantum magnetism.

National (Dis)identification and Ethnic and Religious Identity: A Study Among Turkish-Dutch Muslims

Abstract: National (dis)identification is examined in three studies among Turkish-Dutch Muslim participants In explaining national (dis)identification, the first study focuses on ethnic identity, the second on ethnic and religious identity, and the third on three dimensions of religious identity Many participants show low commitment to the nation, and many indicate national disidentification In addition, there is very strong ethnic and religious identification Ethnic and Muslim identifications relate negatively to Dutch identification and, in Study 3, to stronger Dutch disidentification Furthermore, perceived group rejection is associated with increased ethnic minority and religious identification but also with decreased national Dutch identification In addition, in Studies 1 and 2 the effect of perceived rejection on Dutch identification is (partly) mediated by minority group identification The findings are discussed in relation to social psychological thinking about group identification, dual identities, and the importance of religion for intergroup relations

Does efficiency sensing unify diffusion and quorum sensing

Abstract: Quorum sensing faces evolutionary problems from non-producing or over-producing cheaters Such problems are circumvented in diffusion sensing, an alternative explanation for quorum sensing However, both explanations face the problems of signalling in complex environments such as the rhizosphere where, for example, the spatial distribution of cells can be more important for sensing than cell density, which we show by mathematical modelling We argue that these conflicting concepts can be unified by a new hypothesis, efficiency sensing, and that some of the problems associated with signalling in complex environments, as well as the problem of maintaining honesty in signalling, can be avoided when the signalling cells grow in microcolonies

Hemodynamic monitoring in shock and implications for management. International Consensus Conference, Paris, France, 27-28 April 2006.

Abstract: Objective Shock is a severe syndrome resulting in multiple organ dysfunction and a high mortality rate. The goal of this consensus statement is to provide recommendations regarding the monitoring and management of the critically ill patient with shock.

Genetically determined differences in learning from errors

Abstract: The role of dopamine in monitoring negative action outcomes and feedback-based learning was tested in a neuroimaging study in humans grouped according to the dopamine D2 receptor gene polymorphism DRD2-TAQ-IA. In a probabilistic learning task, A1-allele carriers with reduced dopamine D2 receptor densities learned to avoid actions with negative consequences less efficiently. Their posterior medial frontal cortex (pMFC), involved in feedback monitoring, responded less to negative feedback than others' did. Dynamically changing interactions between pMFC and hippocampus found to underlie feedback-based learning were reduced in A1-allele carriers. This demonstrates that learning from errors requires dopaminergic signaling. Dopamine D2 receptor reduction seems to decrease sensitivity to negative action consequences, which may explain an increased risk of developing addictive behaviors in A1-allele carriers.

A comprehensive set of simulations studying the influence of gas expulsion on star cluster evolution

Abstract: We have carried out a large set of N-body simulations studying the effect of residual-gas expulsion on the survival rate, and final properties of star clusters. We have varied the star formation efficiency (SFE), gas expulsion time-scale and strength of the external tidal field, obtaining a three-dimensional grid of models which can be used to predict the evolution of individual star clusters or whole star cluster systems by interpolating between our runs. The complete data of these simulations are made available on the internet.