Showing papers by "University of Erlangen-Nuremberg published in 2007"

2007 Guidelines for the Management of Arterial Hypertension : The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC).

Abstract: 2007 Guidelines for the Management of Arterial Hypertension : The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC).

Bias in random forest variable importance measures: Illustrations, sources and a solution

Abstract: Variable importance measures for random forests have been receiving increased attention as a means of variable selection in many classification tasks in bioinformatics and related scientific fields, for instance to select a subset of genetic markers relevant for the prediction of a certain disease. We show that random forest variable importance measures are a sensible means for variable selection in many applications, but are not reliable in situations where potential predictor variables vary in their scale of measurement or their number of categories. This is particularly important in genomics and computational biology, where predictors often include variables of different types, for example when predictors include both sequence data and continuous variables such as folding energy, or when amino acid sequence data show different numbers of categories. Simulation studies are presented illustrating that, when random forest variable importance measures are used with data of varying types, the results are misleading because suboptimal predictor variables may be artificially preferred in variable selection. The two mechanisms underlying this deficiency are biased variable selection in the individual classification trees used to build the random forest on one hand, and effects induced by bootstrap sampling with replacement on the other hand. We propose to employ an alternative implementation of random forests, that provides unbiased variable selection in the individual classification trees. When this method is applied using subsampling without replacement, the resulting variable importance measures can be used reliably for variable selection even in situations where the potential predictor variables vary in their scale of measurement or their number of categories. The usage of both random forest algorithms and their variable importance measures in the R system for statistical computing is illustrated and documented thoroughly in an application re-analyzing data from a study on RNA editing. Therefore the suggested method can be applied straightforwardly by scientists in bioinformatics research.

How to diagnose diastolic heart failure: a consensus statement on the diagnosis of heart failure with normal left ventricular ejection fraction by the Heart Failure and Echocardiography Associations of the European Society of Cardiology

Abstract: Diastolic heart failure (DHF) currently accounts for more than 50% of all heart failure patients. DHF is also referred to as heart failure with normal left ventricular (LV) ejection fraction (HFNEF) to indicate that HFNEF could be a precursor of heart failure with reduced LVEF. Because of improved cardiac imaging and because of widespread clinical use of plasma levels of natriuretic peptides, diagnostic criteria for HFNEF needed to be updated. The diagnosis of HFNEF requires the following conditions to be satisfied: (i) signs or symptoms of heart failure; (ii) normal or mildly abnormal systolic LV function; (iii) evidence of diastolic LV dysfunction. Normal or mildly abnormal systolic LV function implies both an LVEF > 50% and an LV end-diastolic volume index (LVEDVI) 16 mmHg or mean pulmonary capillary wedge pressure >12 mmHg) or non-invasively by tissue Doppler (TD) (E/E' > 15). If TD yields an E/E' ratio suggestive of diastolic LV dysfunction (15 > E/E' > 8), additional non-invasive investigations are required for diagnostic evidence of diastolic LV dysfunction. These can consist of blood flow Doppler of mitral valve or pulmonary veins, echo measures of LV mass index or left atrial volume index, electrocardiographic evidence of atrial fibrillation, or plasma levels of natriuretic peptides. If plasma levels of natriuretic peptides are elevated, diagnostic evidence of diastolic LV dysfunction also requires additional non-invasive investigations such as TD, blood flow Doppler of mitral valve or pulmonary veins, echo measures of LV mass index or left atrial volume index, or electrocardiographic evidence of atrial fibrillation. A similar strategy with focus on a high negative predictive value of successive investigations is proposed for the exclusion of HFNEF in patients with breathlessness and no signs of congestion. The updated strategies for the diagnosis and exclusion of HFNEF are useful not only for individual patient management but also for patient recruitment in future clinical trials exploring therapies for HFNEF.

Cytokines in the pathogenesis of rheumatoid arthritis

Abstract: Cytokines regulate a broad range of inflammatory processes that are implicated in the pathogenesis of rheumatoid arthritis. In rheumatoid joints, it is well known that an imbalance between pro- and anti-inflammatory cytokine activities favours the induction of autoimmunity, chronic inflammation and thereby joint damage. However, it remains less clear how cytokines are organized within a hierarchical regulatory network, and therefore which cytokines may be the best targets for clinical intervention a priori. Here, we discuss the crucial effector function of cytokines in the immunological processes that are central to the pathogenesis of rheumatoid arthritis.

2007 ESH-ESC Practice Guidelines for the Management of Arterial Hypertension: ESH-ESC Task Force on the Management of Arterial Hypertension.

Abstract: Authors/Task Force Members: Giuseppe Mancia, Co-Chairperson (Italy), Guy De Backer, Co-Chairperson (Belgium), Anna Dominiczak (UK), Renata Cifkova (Czech Republic), Robert Fagard (Belgium), Giuseppe Germano (Italy), Guido Grassi (Italy), Anthony M. Heagerty (UK), Sverre E. Kjeldsen (Norway), Stephane Laurent (France), Krzysztof Narkiewicz (Poland), Luis Ruilope (Spain), Andrzej Rynkiewicz (Poland), Roland E. Schmieder (Germany), Harry A.J. Struijker Boudier (Netherlands), Alberto Zanchetti (Italy)

Halogen bonding: the σ-hole

Abstract: Halogen bonding refers to the non-covalent interactions of halogen atoms X in some molecules, RX, with negative sites on others. It can be explained by the presence of a region of positive electrostatic potential, the sigma-hole, on the outermost portion of the halogen's surface, centered on the R-X axis. We have carried out a natural bond order B3LYP analysis of the molecules CF(3)X, with X = F, Cl, Br and I. It shows that the Cl, Br and I atoms in these molecules closely approximate the [Formula: see text] configuration, where the z-axis is along the R-X bond. The three unshared pairs of electrons produce a belt of negative electrostatic potential around the central part of X, leaving the outermost region positive, the sigma-hole. This is not found in the case of fluorine, for which the combination of its high electronegativity plus significant sp-hybridization causes an influx of electronic charge that neutralizes the sigma-hole. These factors become progressively less important in proceeding to Cl, Br and I, and their effects are also counteracted by the presence of electron-withdrawing substituents in the remainder of the molecule. Thus a sigma-hole is observed for the Cl in CF(3)Cl, but not in CH(3)Cl.

2007 Guidelines for the management of arterial hypertension

Abstract: For several years the European Society of Hypertension (ESH) and the European Society of Cardiology (ESC) decided not to produce their own guidelines on the diagnosis and treatment of hypertension but to endorse the guidelines on hypertension issued by the World Health Organization (WHO) and International Society of Hypertension (ISH)1,2 with some adaptation to reflect the situation in Europe. However, in 2003 the decision was taken to publish ESH/ESC specific guidelines3 based on the fact that, because the WHO/ISH Guidelines address countries widely varying in the extent of their health care and availability of economic resource, they contain diagnostic and therapeutic recommendations that may be not totally appropriate for European countries. In Europe care provisions may often allow a more in-depth diagnostic assessment of cardiovascular risk and organ damage of hypertensive individuals as well as a wider choice of antihypertensive treatment. The 2003 ESH/ESC Guidelines3 were well received by the clinical world and have been the most widely quoted paper in the medical literature in the last two years.4 However, since 2003 considerable additional evidence on important issues related to diagnostic and treatment approaches to hypertension has become available and therefore updating of the previous guidelines has been found advisable. In preparing the new guidelines the Committee established by the ESH and ESC has agreed to adhere to the principles informing the 2003 Guidelines, namely 1) to try to offer the best available and most balanced recommendation to all health care providers involved in the management of hypertension, 2) to address this aim again by an extensive and critical review of the data accompanied by a series of boxes where specific recommendations are given, as well as by a concise set of practice recommendations to be published soon thereafter as already done in 2003; …

Early decompressive surgery in malignant infarction of the middle cerebral artery: a pooled analysis of three randomised controlled trials

Abstract: Summary Background Malignant infarction of the middle cerebral artery (MCA) is associated with an 80% mortality rate. Non-randomised studies have suggested that decompressive surgery reduces this mortality without increasing the number of severely disabled survivors. To obtain sufficient data as soon as possible to reliably estimate the effects of decompressive surgery, results from three European randomised controlled trials (DECIMAL, DESTINY, HAMLET) were pooled. The trials were ongoing when the pooled analysis was planned. Methods Individual data for patients aged between 18 years and 60 years, with space-occupying MCA infarction, included in one of the three trials, and treated within 48 h after stroke onset were pooled for analysis. The protocol was designed prospectively when the trials were still recruiting patients and outcomes were defined without knowledge of the results of the individual trials. The primary outcome measure was the score on the modified Rankin scale (mRS) at 1 year dichotomised between favourable (0–4) and unfavourable (5 and death) outcome. Secondary outcome measures included case fatality rate at 1 year and a dichotomisation of the mRS between 0–3 and 4 to death. Data analysis was done by an independent data monitoring committee. Findings 93 patients were included in the pooled analysis. More patients in the decompressive-surgery group than in the control group had an mRS≤4 (75% vs 24%; pooled absolute risk reduction 51% [95% CI 34–69]), an mRS≤3 (43% vs 21%; 23% [5–41]), and survived (78% vs 29%; 50% [33–67]), indicating numbers needed to treat of two for survival with mRS≤4, four for survival with mRS≤3, and two for survival irrespective of functional outcome. The effect of surgery was highly consistent across the three trials. Interpretation In patients with malignant MCA infarction, decompressive surgery undertaken within 48 h of stroke onset reduces mortality and increases the number of patients with a favourable functional outcome. The decision to perform decompressive surgery should, however, be made on an individual basis in every patient.

Ultralow-power organic complementary circuits

Abstract: Organic transistors and circuits show great promise for the realization of futuristic roll-up displays, adaptive sensors for humanoid robots and ubiquitous radio-frequency identification tags. But today's organic circuits require operating voltages of 15 to 30 volts (10 to 20 batteries' worth), and they draw enough power to drain those batteries in a day. To overcome this major hurdle, Hagen Klauk et al. have developed a method of fabricating organic circuits that run on a single 1.5-volt battery for several years. The key to the method is the use of a layer of an insulating organic material just one molecule thick; although the layer is very thin, it leaks only a small amount of current, while it provides for a large capacitance. Two different types of organic semiconductors are used to fabricate transistors, logic gates and ring oscillators. A report of the development of organic electronic circuits, which require only a single 1.5V battery and last for several years. The main ingredient is the use of a single layer of an insulating organic material. Although the layer is very thin, it leaks only small amount of current, while providing for a large capacitance. The prospect of using low-temperature processable organic semiconductors to implement transistors, circuits, displays and sensors on arbitrary substrates, such as glass or plastics, offers enormous potential for a wide range of electronic products1. Of particular interest are portable devices that can be powered by small batteries or by near-field radio-frequency coupling. The main problem with existing approaches is the large power consumption of conventional organic circuits, which makes battery-powered applications problematic, if not impossible. Here we demonstrate an organic circuit with very low power consumption that uses a self-assembled monolayer gate dielectric and two different air-stable molecular semiconductors (pentacene and hexadecafluorocopperphthalocyanine, F16CuPc). The monolayer dielectric is grown on patterned metal gates at room temperature and is optimized to provide a large gate capacitance and low gate leakage currents. By combining low-voltage p-channel and n-channel organic thin-film transistors in a complementary circuit design, the static currents are reduced to below 100 pA per logic gate. We have fabricated complementary inverters, NAND gates, and ring oscillators that operate with supply voltages between 1.5 and 3 V and have a static power consumption of less than 1 nW per logic gate. These organic circuits are thus well suited for battery-powered systems such as portable display devices2 and large-surface sensor networks3 as well as for radio-frequency identification tags with extended operating range4.

Normative data for the "Sniffin' Sticks" including tests of odor identification, odor discrimination, and olfactory thresholds: an upgrade based on a group of more than 3,000 subjects.

Abstract: "Sniffin' Sticks" is a test of nasal chemosensory function that is based on pen-like odor dispensing devices, introduced some 10 years ago by Kobal and co-workers. It consists of tests for odor threshold, discrimination, and identification. Previous work established its test-retest reliability and validity. Results of the test are presented as "TDI score", the sum of results obtained for threshold, discrimination, and identification measures. While normative data have been established they are based on a relatively small number of subjects, especially with regard to subjects older than 55 years where data from only 30 healthy subjects have been used. The present study aimed to remedy this situation. Now data are available from 3,282 subjects as compared to data from 738 subjects published previously. Disregarding sex-related differences, the TDI score at the tenth percentile was 24.9 in subjects younger than 15 years, 30.3 for ages from 16 to 35 years, 27.3 for ages from 36 to 55 years, and 19.6 for subjects older than 55 years. Because the tenth percentile has been defined to separate hyposmia from normosmia, these data can be used as a guide to estimate individual olfactory ability in relation to subject's age. Absolute hyposmia was defined as the tenth percentile score of 16-35 year old subjects. Other than previous reports the present norms are also sex-differentiated with women outperforming men in the three olfactory tests. Further, the present data suggest specific changes of individual olfactory functions in relation to age, with odor thresholds declining most dramatically compared to odor discrimination and odor identification.

TiO2 nanotubes: Self-organized electrochemical formation, properties and applications

Abstract: The present paper gives an overview and review on self-organized TiO2 nanotube layers and other transition metal oxide tubular structures grown by controlled anodic oxidation of a metal substrate We describe mechanistic aspects of the tube growth and discuss the electrochemical conditions that need to be fulfilled in order to synthesize these layers Key properties of these highly ordered, high aspect ratio tubular layers are discussed In the past few years, a wide range of functional applications of the layers have been explored ranging from photocatalysis, solar energy conversion, electrochromic effects over using the material as a template or catalyst support to applications in the biomedical field A comprehensive view on state of the art is provided

Dickkopf-1 is a master regulator of joint remodeling

Abstract: Degenerative and inflammatory joint diseases lead to a destruction of the joint architecture. Whereas degenerative osteoarthritis results in the formation of new bone, rheumatoid arthritis leads to bone resorption. The molecular basis of these different patterns of joint disease is unknown. By inhibiting Dickkopf-1 (DKK-1), a regulatory molecule of the Wnt pathway, we were able to reverse the bone-destructive pattern of a mouse model of rheumatoid arthritis to the bone-forming pattern of osteoarthritis. In this way, no overall bone erosion resulted, although bony nodules, so-called osteophytes, did form. We identified tumor necrosis factor-a (TNF) as a key inducer of DKK-1 in the mouse inflammatory arthritis model and in human rheumatoid arthritis. These results suggest that the Wnt pathway is a key regulator of joint remodeling. Affliction of joints is the hallmark of rheumatic disease. In addition to pain, both degenerative and inflammatory rheumatic diseases lead to a profound remodeling of the joint architecture, which causes functional disability and progressive crippling. This structural damage is largely responsible for the high socioeconomic burden of rheumatic disease, and definition of its molecular mechanism is therefore of key interest 1 .

Nanosize and Vitality: TiO2 Nanotube Diameter Directs Cell Fate

Abstract: We generated, on titanium surfaces, self-assembled layers of vertically oriented TiO2 nanotubes with defined diameters between 15 and 100 nm and show that adhesion, spreading, growth, and differentiation of mesenchymal stem cells are critically dependent on the tube diameter. A spacing less than 30 nm with a maximum at 15 nm provided an effective length scale for accelerated integrin clustering/focal contact formation and strongly enhances cellular activities compared to smooth TiO2 surfaces. Cell adhesion and spreading were severely impaired on nanotube layers with a tube diameter larger than 50 nm, resulting in dramatically reduced cellular activity and a high extent of programmed cell death. Thus, on a TiO2 nanotube surface, a lateral spacing geometry with openings of 30−50 nm represents a critical borderline for cell fate.

Quasiparticle dynamics in graphene

Abstract: The effectively massless, relativistic behaviour of graphene’s charge carriers—known as Dirac fermions—is a result of its unique electronic structure, characterized by conical valence and conduction bands that meet at a single point in momentum space (at the Dirac crossing energy). The study of many-body interactions amongst the charge carriers in graphene and related systems such as carbon nanotubes, fullerenes and graphite is of interest owing to their contribution to superconductivity and other exotic ground states in these systems. Here we show, using angle-resolved photoemission spectroscopy, that electron–plasmon coupling plays an unusually strong role in renormalizing the bands around the Dirac crossing energy—analogous to mass renormalization by electron–boson coupling in ordinary metals. Our results show that electron–electron, electron–plasmon and electron–phonon coupling must be considered on an equal footing in attempts to understand the dynamics of quasiparticles in graphene and related systems.

Self‐Healing Materials

Abstract: Self-healing materials are able to partially or completely heal damage inflicted on them, e.g., crack formation; it is anticipated that the original functionality can be restored. This article covers the design and generic principles of self-healing materials through a wide range of different material classes including metals, ceramics, concrete, and polymers. Recent key developments and future challenges in the field of self-healing materials are summarised, and generic, fundamental material-independent principles and mechanism are discussed and evaluated.

Agency and communion from the perspective of self versus others.

Abstract: On the basis of previous research, the authors hypothesize that (a) person descriptive terms can be organized into the broad dimensions of agency and communion of which communion is the primary one; (b) the main distinction between these dimensions pertains to their profitability for the self (agency) vs. for other persons (communion); hence, agency is more desirable and important in the self-perspective, and communion is more desirable and important in the other-perspective; (c) self–other outcome dependency increases importance of another person’s agency. Study 1 showed that a large number of trait names can be reduced to these broad dimensions, that communion comprises more item variance, and that agency is predicted by self-profitability and communion by other-profitability. Studies 2 and 3 showed that agency is more relevant and desired for self, and communion is more relevant and desired for others. Study 4 showed that agency is more important in a close friend than an unrelated peer, and this difference is completely mediated by the perceived outcome dependency.

Hypoxia promotes fibrogenesis in vivo via HIF-1 stimulation of epithelial-to-mesenchymal transition

Abstract: Hypoxia has been proposed as an important microenvironmental factor in the development of tissue fibrosis; however, the underlying mechanisms are not well defined. To examine the role of hypoxia-inducible factor–1 (HIF-1), a key mediator of cellular adaptation to hypoxia, in the development of fibrosis in mice, we inactivated Hif-1α in primary renal epithelial cells and in proximal tubules of kidneys subjected to unilateral ureteral obstruction (UUO) using Cre-loxP–mediated gene targeting. We found that Hif-1α enhanced epithelial-to-mesenchymal transition (EMT) in vitro and induced epithelial cell migration through upregulation of lysyl oxidase genes. Genetic ablation of epithelial Hif-1α inhibited the development of tubulointerstitial fibrosis in UUO kidneys, which was associated with decreased interstitial collagen deposition, decreased inflammatory cell infiltration, and a reduction in the number of fibroblast-specific protein–1–expressing (FSP-1–expressing) interstitial cells. Furthermore, we demonstrate that increased renal HIF-1α expression is associated with tubulointerstitial injury in patients with chronic kidney disease. Thus, we provide clinical and genetic evidence that activation of HIF-1 signaling in renal epithelial cells is associated with the development of chronic renal disease and may promote fibrogenesis by increasing expression of extracellular matrix–modifying factors and lysyl oxidase genes and by facilitating EMT.

An Exceptional Very High Energy Gamma-Ray Flare of PKS 2155-304

Abstract: The high-frequency peaked BL Lac PKS 2155-304 at redshift z=0.116 is a well-known VHE (>100 GeV) gamma-ray emitter. Since 2002 its VHE flux has been monitored using the H.E.S.S. stereoscopic array of imaging atmospheric-Cherenkov telescopes in Namibia. During the July 2006 dark period, the average VHE flux was measured to be more than ten times typical values observed from the object. This article focuses solely on an extreme gamma-ray outburst detected in the early hours of July 28, 2006 (MJD 53944). The average flux observed during this outburst is I(>200 GeV) = (1.72$\pm$$0.05_{\rm stat}$$\pm$$0.34_{\rm syst}$) $\times$ 10$^{-9}$ cm$^{-2}$ s$^{-1}$, corresponding to ~7 times the flux, I(>200 GeV), observed from the Crab Nebula. Peak fluxes are measured with one-minute time scale resolution at more than twice this average value. Variability is seen up to ~600 s in the Fourier power spectrum, and well-resolved bursts varying on time scales of ~200 seconds are observed. There are no strong indications for spectral variability within the data. Assuming the emission region has a size comparable to the Schwarzschild radius of a ~10$^9 M_\odot$ black hole, Doppler factors greater than 100 are required to accommodate the observed variability time scales.

Effects of solar UV radiation on aquatic ecosystems and interactions with climate change

Abstract: Recent results continue to show the general consensus that ozone-related increases in UV-B radiation can negatively influence many aquatic species and aquatic ecosystems (e.g., lakes, rivers, marshes, oceans). Solar UV radiation penetrates to ecological significant depths in aquatic systems and can affect both marine and freshwater systems from major biomass producers (phytoplankton) to consumers (e.g., zooplankton, fish, etc.) higher in the food web. Many factors influence the depth of penetration of radiation into natural waters including dissolved organic compounds whose concentration and chemical composition are likely to be influenced by future climate and UV radiation variability. There is also considerable evidence that aquatic species utilize many mechanisms for photoprotection against excessive radiation. Often, these protective mechanisms pose conflicting selection pressures on species making UV radiation an additional stressor on the organism. It is at the ecosystem level where assessments of anthropogenic climate change and UV-related effects are interrelated and where much recent research has been directed. Several studies suggest that the influence of UV-B at the ecosystem level may be more pronounced on community and trophic level structure, and hence on subsequent biogeochemical cycles, than on biomass levels per se.

Biconvex sets and optimization with biconvex functions: a survey and extensions

Abstract: The problem of optimizing a biconvex function over a given (bi)convex or compact set frequently occurs in theory as well as in industrial applications, for example, in the field of multifacility location or medical image registration. Thereby, a function \(f:X\times Y\to{\mathbb{R}}\) is called biconvex, if f(x,y) is convex in y for fixed x∈X, and f(x,y) is convex in x for fixed y∈Y. This paper presents a survey of existing results concerning the theory of biconvex sets and biconvex functions and gives some extensions. In particular, we focus on biconvex minimization problems and survey methods and algorithms for the constrained as well as for the unconstrained case. Furthermore, we state new theoretical results for the maximum of a biconvex function over biconvex sets.

Self-organized, free-standing TiO2 nanotube membrane for flow-through photocatalytic applications.

Abstract: In the present work we show a simple and robust fabrication process of a dense and free-standing membrane consisting of vertically oriented, both-side-open TiO2 nanotubes. This membrane structure allows direct, size-selective, flow-through photocatalytic reactions with a very high efficiency.

Interlayer Interaction and Electronic Screening in Multilayer Graphene Investigated with Angle-Resolved Photoemission Spectroscopy

Abstract: The unusual transport properties of graphene are the direct consequence of a peculiar bandstructure near the Dirac point. We determine the shape of the {pi} bands and their characteristic splitting, and find the transition from two-dimensional to bulk character for 1 to 4 layers of graphene by angle-resolved photoemission. By detailed measurements of the {pi} bands we derive the stacking order, layer-dependent electron potential, screening length and strength of interlayer interaction by comparison with tight binding calculations, yielding a comprehensive description of multilayer graphene's electronic structure.

European citizens' use of E-health services: A study of seven countries

Abstract: European citizens are increasingly being offered Internet health services. This study investigated patterns of health-related Internet use, its consequences, and citizens' expectations about their doctors' provision of e-health services. Representative samples were obtained from the general populations in Norway, Denmark, Germany, Greece, Poland, Portugal and Latvia. The total sample consisted of 7934 respondents. Interviews were conducted by telephone. 44 % of the total sample, 71 % of the Internet users, had used the Internet for health purposes. Factors that positively affected the use of Internet for health purposes were youth, higher education, white-collar or no paid job, visits to the GP during the past year, long-term illness or disabilities, and a subjective assessment of one's own health as good. Women were the most active health users among those who were online. One in four of the respondents used the Internet to prepare for or follow up doctors' appointments. Feeling reassured after using the Internet for health purposes was twice as common as experiencing anxieties. When choosing a new doctor, more than a third of the sample rated the provision of e-health services as important. The users of Internet health services differ from the general population when it comes to health and demographic variables. The most common way to use the Internet in health matters is to read information, second comes using the net to decide whether to see a doctor and to prepare for and follow up on doctors' appointments. Hence, health-related use of the Internet does affect patients' use of other health services, but it would appear to supplement rather than to replace other health services.

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.