Showing papers by "University of Copenhagen published in 2008"

A grid of MARCS model atmospheres for late-type stars. I. Methods and general properties

Abstract: Context. In analyses of stellar spectra and colours, and for the analysis of integrated light from galaxies, a homogeneous grid of model atmospheres of late-type stars and corresponding flux spectra is needed. Aims. We construct an extensive grid of spherically-symmetric models (supplemented with plane-parallel ones for the highest surface gravities), built on up-to-date atomic and molecular data, and make it available for public use. Methods. The most recent version of the MARCS program is used. Results. We present a grid of about 104 model atmospheres for stars with 2500K <= T-eff <= 8000 K, -1 <= log g = log (GM/R-2) <= 5 (cgs) with various masses and radii, -5 <= [Me/H] <= + 1, with [alpha/Fe] = 0.0 and 0.4 and different choices of C and N abundances. This includes "CN-cycled" models with C/N=4.07 (solar), 1.5 and 0.5, C/O ranging from 0.09 to (normally) 5.0 to also represent stars of spectral types R, S and N, and with 1.0 <= xi(t) = 5km s(-1). We also list thermodynamic quantities (T, P-g, P-e, rho, partial pressures of molecules, etc.) and provide them on the World Wide Web, as well as calculated fluxes in approximately 108 000 wavelength points. Underlying assumptions in addition to 1D stratification (spherical or plane-parallel) include hydrostatic equilibrium, mixing-length convection and local thermodynamic equilibrium. We discuss a number of general properties of the models, in particular in relation to the effects of changing abundances, of blanketing, and of sphericity. We illustrate positive and negative feedbacks between sphericity and molecular blanketing. We compare the models with those of other available grids and find excellent agreement with planeparallel models of Castelli & Kurucz (if convection is treated consistently) within the overlapping parameter range. Although there are considerable departures from the spherically-symmetric NextGen models, the agreement with more recent PHOENIX models is gratifying. Conclusions. The models of the grid show considerable regularities, but some interesting departures from general patterns occur for the coolest models due to the molecular opacities. We have tested a number of approximate "rules of thumb" concerning effects of blanketing and sphericity and often found them to be astonishingly accurate. Some interesting new phenomena have been discovered and explored, such as the intricate coupling between blanketing and sphericity, and the strong effects of carbon enhancement on metal-poor models. We give further details of line absorption data for molecules, as well as details of models and comparisons with observations in subsequent papers.

Characterizing dissolved organic matter fluorescence with parallel factor analysis: a tutorial

Abstract: A sub-fraction of dissolved organic matter fluoresces when excited with ultraviolet light. This property is used to quantify and characterize changes in dissolved organic matter (DOM) in aquatic environments. Detailed mapping of the fluorescence properties of DOM produces excitation emission matrices (EEM), which are well suited to multi-way data analysis techniques (chemometrics). Techniques such as parallel factor analysis (PARAFAC) are increasingly being applied to characterize DOM fluorescence properties. Here, an introduction to the technique and description of the advantages and pitfalls of its application to DOM fluorescence is presented. Additionally a MATLAB based tutorial and toolbox specific to PARAFAC analysis of DOM fluorescence is presented.

Muscle as an endocrine organ: focus on muscle-derived interleukin-6.

Abstract: Skeletal muscle has recently been identified as an endocrine organ. It has, therefore, been suggested that cytokines and other peptides that are produced, expressed, and released by muscle fibers and exert paracrine, autocrine, or endocrine effects should be classified as "myokines." Recent research demonstrates that skeletal muscles can produce and express cytokines belonging to distinctly different families. However, the first identified and most studied myokine is the gp130 receptor cytokine interleukin-6 (IL-6). IL-6 was discovered as a myokine because of the observation that it increases up to 100-fold in the circulation during physical exercise. Identification of IL-6 production by skeletal muscle during physical activity generated renewed interest in the metabolic role of IL-6 because it created a paradox. On one hand, IL-6 is markedly produced and released in the postexercise period when insulin action is enhanced but, on the other hand, IL-6 has been associated with obesity and reduced insulin action. This review focuses on the myokine IL-6, its regulation by exercise, its signaling pathways in skeletal muscle, and its role in metabolism in both health and disease.

Broad phylogenomic sampling improves resolution of the animal tree of life

Abstract: Long-held ideas regarding the evolutionary relationships among animals have recently been upended by sometimes controversial hypotheses based largely on insights from molecular data. These new hypotheses include a clade of moulting animals (Ecdysozoa) and the close relationship of the lophophorates to molluscs and annelids (Lophotrochozoa). Many relationships remain disputed, including those that are required to polarize key features of character evolution, and support for deep nodes is often low. Phylogenomic approaches, which use data from many genes, have shown promise for resolving deep animal relationships, but are hindered by a lack of data from many important groups. Here we report a total of 39.9 Mb of expressed sequence tags from 29 animals belonging to 21 phyla, including 11 phyla previously lacking genomic or expressed-sequence-tag data. Analysed in combination with existing sequences, our data reinforce several previously identified clades that split deeply in the animal tree (including Protostomia, Ecdysozoa and Lophotrochozoa), unambiguously resolve multiple long-standing issues for which there was strong conflicting support in earlier studies with less data (such as velvet worms rather than tardigrades as the sister group of arthropods), and provide molecular support for the monophyly of molluscs, a group long recognized by morphologists. In addition, we find strong support for several new hypotheses. These include a clade that unites annelids (including sipunculans and echiurans) with nemerteans, phoronids and brachiopods, molluscs as sister to that assemblage, and the placement of ctenophores as the earliest diverging extant multicellular animals. A single origin of spiral cleavage (with subsequent losses) is inferred from well-supported nodes. Many relationships between a stable subset of taxa find strong support, and a diminishing number of lineages remain recalcitrant to placement on the tree.

Large recurrent microdeletions associated with schizophrenia

Abstract: Reduced fecundity, associated with severe mental disorders, places negative selection pressure on risk alleles and may explain, in part, why common variants have not been found that confer risk of disorders such as autism, schizophrenia and mental retardation. Thus, rare variants may account for a larger fraction of the overall genetic risk than previously assumed. In contrast to rare single nucleotide mutations, rare copy number variations (CNVs) can be detected using genome-wide single nucleotide polymorphism arrays. This has led to the identification of CNVs associated with mental retardation and autism. In a genome-wide search for CNVs associating with schizophrenia, we used a population-based sample to identify de novo CNVs by analysing 9,878 transmissions from parents to offspring. The 66 de novo CNVs identified were tested for association in a sample of 1,433 schizophrenia cases and 33,250 controls. Three deletions at 1q21.1, 15q11.2 and 15q13.3 showing nominal association with schizophrenia in the first sample (phase I) were followed up in a second sample of 3,285 cases and 7,951 controls (phase II). All three deletions significantly associate with schizophrenia and related psychoses in the combined sample. The identification of these rare, recurrent risk variants, having occurred independently in multiple founders and being subject to negative selection, is important in itself. CNV analysis may also point the way to the identification of additional and more prevalent risk variants in genes and pathways involved in schizophrenia.

LNA-mediated microRNA silencing in non-human primates

Abstract: microRNAs (miRNAs) are small regulatory RNAs that are important in development and disease and therefore represent a potential new class of targets for therapeutic intervention. Despite recent progress in silencing of miRNAs in rodents, the development of effective and safe approaches for sequence-specific antagonism of miRNAs in vivo remains a significant scientific and therapeutic challenge. Moreover, there are no reports of miRNA antagonism in primates. Here we show that the simple systemic delivery of a unconjugated, PBS-formulated locked-nucleic-acid-modified oligonucleotide (LNA-antimiR) effectively antagonizes the liver-expressed miR-122 in non-human primates. Acute administration by intravenous injections of 3 or 10 mg kg(-1) LNA-antimiR to African green monkeys resulted in uptake of the LNA-antimiR in the cytoplasm of primate hepatocytes and formation of stable heteroduplexes between the LNA-antimiR and miR-122. This was accompanied by depletion of mature miR-122 and dose-dependent lowering of plasma cholesterol. Efficient silencing of miR-122 was achieved in primates by three doses of 10 mg kg(-1) LNA-antimiR, leading to a long-lasting and reversible decrease in total plasma cholesterol without any evidence for LNA-associated toxicities or histopathological changes in the study animals. Our findings demonstrate the utility of systemically administered LNA-antimiRs in exploring miRNA function in rodents and primates, and support the potential of these compounds as a new class of therapeutics for disease-associated miRNAs.

Inflammatory and coagulation biomarkers and mortality in patients with HIV infection.

Abstract: Background In the Strategies for Management of Anti-Retroviral Therapy trial, all-cause mortality was higher for participants randomized to intermittent, CD4-guided antiretroviral treatment (ART) (drug conservation [DC]) than continuous ART (viral suppression [VS]). We hypothesized that increased HIV-RNA levels following ART interruption induced activation of tissue factor pathways, thrombosis, and fibrinolysis.

Rhythm control versus rate control for atrial fibrillation and heart failure

Abstract: Methods We conducted a multicenter, randomized trial comparing the maintenance of sinus rhythm (rhythm control) with control of the ventricular rate (rate control) in patients with a left ventricular ejection fraction of 35% or less, symptoms of congestive heart failure, and a history of atrial fibrillation. The primary outcome was the time to death from cardiovascular causes. Results A total of 1376 patients were enrolled (682 in the rhythm-control group and 694 in the rate-control group) and were followed for a mean of 37 months. Of these patients, 182 (27%) in the rhythm-control group died from cardiovascular causes, as compared with 175 (25%) in the rate-control group (hazard ratio in the rhythm-control group, 1.06; 95% confidence interval, 0.86 to 1.30; P = 0.59 by the log-rank test). Secondary outcomes were similar in the two groups, including death from any cause (32% in the rhythm-control group and 33% in the rate-control group), stroke (3% and 4%, respectively), worsening heart failure (28% and 31%), and the composite of death from cardiovascular causes, stroke, or worsening heart failure (43% and 46%). There were also no significant differences favoring either strategy in any predefined subgroup. Conclusions In patients with atrial fibrillation and congestive heart failure, a routine strategy of rhythm control does not reduce the rate of death from cardiovascular causes, as compared with a rate-control strategy. (ClinicalTrials.gov number, NCT00597077.)

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.

The ALICE experiment at the CERN LHC

Abstract: ALICE (A Large Ion Collider Experiment) is a general-purpose, heavy-ion detector at the CERN LHC which focuses on QCD, the strong-interaction sector of the Standard Model. It is designed to address the physics of strongly interacting matter and the quark-gluon plasma at extreme values of energy density and temperature in nucleus-nucleus collisions. Besides running with Pb ions, the physics programme includes collisions with lighter ions, lower energy running and dedicated proton-nucleus runs. ALICE will also take data with proton beams at the top LHC energy to collect reference data for the heavy-ion programme and to address several QCD topics for which ALICE is complementary to the other LHC detectors. The ALICE detector has been built by a collaboration including currently over 1000 physicists and engineers from 105 Institutes in 30 countries. Its overall dimensions are 161626 m3 with a total weight of approximately 10 000 t. The experiment consists of 18 different detector systems each with its own specific technology choice and design constraints, driven both by the physics requirements and the experimental conditions expected at LHC. The most stringent design constraint is to cope with the extreme particle multiplicity anticipated in central Pb-Pb collisions. The different subsystems were optimized to provide high-momentum resolution as well as excellent Particle Identification (PID) over a broad range in momentum, up to the highest multiplicities predicted for LHC. This will allow for comprehensive studies of hadrons, electrons, muons, and photons produced in the collision of heavy nuclei. Most detector systems are scheduled to be installed and ready for data taking by mid-2008 when the LHC is scheduled to start operation, with the exception of parts of the Photon Spectrometer (PHOS), Transition Radiation Detector (TRD) and Electro Magnetic Calorimeter (EMCal). These detectors will be completed for the high-luminosity ion run expected in 2010. This paper describes in detail the detector components as installed for the first data taking in the summer of 2008.

The Yo-Yo intermittent recovery test : a useful tool for evaluation of physical performance in intermittent sports.

Abstract: The two Yo-Yo intermittent recovery (IR) tests evaluate an individual's ability to repeatedly perform intense exercise. The Yo-Yo IR level 1 (Yo-Yo IR1) test focuses on the capacity to carry out intermittent exercise leading to a maximal activation of the aerobic system, whereas Yo-Yo IR level 2 (Yo-Yo IR2) determines an individual's ability to recover from repeated exercise with a high contribution from the anaerobic system. Evaluations of elite athletes in various sports involving intermittent exercise showed that the higher the level of competition the better an athlete performs in the Yo-Yo IR tests. Performance in the Yo-Yo IR tests for young athletes increases with rising age. The Yo-Yo IR tests have shown to be a more sensitive measure of changes in performance than maximum oxygen uptake. The Yo-Yo IR tests provide a simple and valid way to obtain important information of an individual's capacity to perform repeated intense exercise and to examine changes in performance.

Hard-X-ray dark-field imaging using a grating interferometer

Abstract: Imaging with visible light today uses numerous contrast mechanisms, including bright- and dark-field contrast, phase-contrast schemes and confocal and fluorescence-based methods. X-ray imaging, on the other hand, has only recently seen the development of an analogous variety of contrast modalities. Although X-ray phase-contrast imaging could successfully be implemented at a relatively early stage with several techniques, dark-field imaging, or more generally scattering-based imaging, with hard X-rays and good signal-to-noise ratio, in practice still remains a challenging task even at highly brilliant synchrotron sources. In this letter, we report a new approach on the basis of a grating interferometer that can efficiently yield dark-field scatter images of high quality, even with conventional X-ray tube sources. Because the image contrast is formed through the mechanism of small-angle scattering, it provides complementary and otherwise inaccessible structural information about the specimen at the micrometre and submicrometre length scale. Our approach is fully compatible with conventional transmission radiography and a recently developed hard-X-ray phase-contrast imaging scheme. Applications to X-ray medical imaging, industrial non-destructive testing and security screening are discussed.

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

Very fast prediction and rationalization of pKa values for protein-ligand complexes.

Abstract: The PROPKA method for the prediction of the pK(a) values of ionizable residues in proteins is extended to include the effect of non-proteinaceous ligands on protein pK(a) values as well as predict the change in pK(a) values of ionizable groups on the ligand itself. This new version of PROPKA (PROPKA 2.0) is, as much as possible, developed by adapting the empirical rules underlying PROPKA 1.0 to ligand functional groups. Thus, the speed of PROPKA is retained, so that the pK(a) values of all ionizable groups are computed in a matter of seconds for most proteins. This adaptation is validated by comparing PROPKA 2.0 predictions to experimental data for 26 protein-ligand complexes including trypsin, thrombin, three pepsins, HIV-1 protease, chymotrypsin, xylanase, hydroxynitrile lyase, and dihydrofolate reductase. For trypsin and thrombin, large protonation state changes (|n| > 0.5) have been observed experimentally for 4 out of 14 ligand complexes. PROPKA 2.0 and Klebe's PEOE approach (Czodrowski P et al. J Mol Biol 2007;367:1347-1356) both identify three of the four large protonation state changes. The protonation state changes due to plasmepsin II, cathepsin D and endothiapepsin binding to pepstatin are predicted to within 0.4 proton units at pH 6.5 and 7.0, respectively. The PROPKA 2.0 results indicate that structural changes due to ligand binding contribute significantly to the proton uptake/release, as do residues far away from the binding site, primarily due to the change in the local environment of a particular residue and hence the change in the local hydrogen bonding network. Overall the results suggest that PROPKA 2.0 provides a good description of the protein-ligand interactions that have an important effect on the pK(a) values of titratable groups, thereby permitting fast and accurate determination of the protonation states of key residues and ligand functional groups within the binding or active site of a protein.

A 60 000 year Greenland stratigraphic ice core chronology

Abstract: . The Greenland Ice Core Chronology 2005 (GICC05) is a time scale based on annual layer counting of high-resolution records from Greenland ice cores. Whereas the Holocene part of the time scale is based on various records from the DYE-3, the GRIP, and the NorthGRIP ice cores, the glacial part is solely based on NorthGRIP records. Here we present an 18 ka extension of the time scale such that GICC05 continuously covers the past 60 ka. The new section of the time scale places the onset of Greenland Interstadial 12 (GI-12) at 46.9±1.0 ka b2k (before year AD 2000), the North Atlantic Ash Zone II layer in GI-15 at 55.4±1.2 ka b2k, and the onset of GI-17 at 59.4±1.3 ka b2k. The error estimates are derived from the accumulated number of uncertain annual layers. In the 40–60 ka interval, the new time scale has a discrepancy with the Meese-Sowers GISP2 time scale of up to 2.4 ka. Assuming that the Greenland climatic events are synchronous with those seen in the Chinese Hulu Cave speleothem record, GICC05 compares well to the time scale of that record with absolute age differences of less than 800 years throughout the 60 ka period. The new time scale is generally in close agreement with other independently dated records and reference horizons, such as the Laschamp geomagnetic excursion, the French Villars Cave and the Austrian Kleegruben Cave speleothem records, suggesting high accuracy of both event durations and absolute age estimates.

Complementary Feeding: A Commentary by the ESPGHAN Committee on Nutrition

Abstract: This position paper on complementary feeding summarizes evidence for health effects of complementary foods. It focuses on healthy infants in Europe. After reviewing current knowledge and practices, we have formulated these conclusions: Exclusive or full breast-feeding for about 6 months is a desirable goal. Complementary feeding (ie, solid foods and liquids other than breast milk or infant formula and follow-on formula) should not be introduced before 17 weeks and not later than 26 weeks. There is no convincing scientific evidence that avoidance or delayed introduction of potentially allergenic foods, such as fish and eggs, reduces allergies, either in infants considered at increased risk for the development of allergy or in those not considered to be at increased risk. During the complementary feeding period, >90% of the iron requirements of a breast-fed infant must be met by complementary foods, which should provide sufficient bioavailable iron. Cow's milk is a poor source of iron and should not be used as the main drink before 12 months, although small volumes may be added to complementary foods. It is prudent to avoid both early ( or=7 months) introduction of gluten, and to introduce gluten gradually while the infant is still breast-fed, inasmuch as this may reduce the risk of celiac disease, type 1 diabetes mellitus, and wheat allergy. Infants and young children receiving a vegetarian diet should receive a sufficient amount ( approximately 500 mL) of breast milk or formula and dairy products. Infants and young children should not be fed a vegan diet.

An Omnibus Test for Univariate and Multivariate Normality

Abstract: We suggest a convenient version of the omnibus test for normality, using skewness and kurtosis based on Shenton and Bowman [Journal of the American Statistical Association (1977) Vol. 72, pp. 206–211], which controls well for size, for samples as low as 10 observations. A multivariate version is introduced. Size and power are investigated in comparison with four other tests for multivariate normality. The first power experiments consider the whole skewness–kurtosis plane; the second use a bivariate distribution which has normal marginals. It is concluded that the proposed test has the best size and power properties of the tests considered.

Increased Mortality after Dronedarone Therapy for Severe Heart Failure

Abstract: BACKGROUND: Dronedarone is a novel antiarrhythmic drug with electrophysiological properties that are similar to those of amiodarone, but it does not contain iodine and thus does not cause iodine-re ...

Bone Marrow-Derived Macrophages (BMM): Isolation and Applications

Abstract: INTRODUCTIONBone marrow-derived macrophages (BMM) are primary macrophage cells, derived from bone marrow cells in vitro in the presence of growth factors. Macrophage colony-stimulating factor (M-CSF) is a lineage-specific growth factor that is responsible for the proliferation and differentiation of committed myeloid progenitors into cells of the macrophage/monocyte lineage. Mice lacking functional M-CSF are deficient in macrophages and osteoclasts and suffer from osteopetrosis. In this protocol, bone marrow cells are grown in culture dishes in the presence of M-CSF, which is secreted by L929 cells and is used in the form of L929-conditioned medium. Under these conditions, the bone marrow monocyte/macrophage progenitors will proliferate and differentiate into a homogenous population of mature BMMs. The efficiency of the differentiation is assessed using fluorescence-activated cell sorting (FACS) analysis of Mac-1 and 4/80 surface antigen expression. Once differentiated, the BMMs are suitable for numerous types of experimental manipulations, including morphological, gene expression, and physiological studies. For example, phagocytic cells such as macrophages have a unique ability to ingest microbes. We describe a test for the phagocytic efficiency of BMMs by exposing them to fluorescently labeled yeast zymosan bioparticles. Also, a method to deliver DNA or small interfering RNAs (siRNAs) into these hard-to-transfect cells is described. Finally, the proliferation of the BMMs is assayed using carboxyfluorescein succinimidyl ester (CFSE), a fluorescein derivative that partitions equally between daughter cells after cell division.

Definition, assessment and treatment of wheezing disorders in preschool children: An evidence-based approach

Abstract: There is poor agreement on definitions of different phenotypes of preschool wheezing disorders. The present Task Force proposes to use the terms episodic (viral) wheeze to describe children who wheeze intermittently and are well between episodes, and multiple-trigger wheeze for children who wheeze both during and outside discrete episodes. Investigations are only needed when in doubt about the diagnosis. Based on the limited evidence available, inhaled short-acting beta(2)-agonists by metered-dose inhaler/spacer combination are recommended for symptomatic relief. Educating parents regarding causative factors and treatment is useful. Exposure to tobacco smoke should be avoided; allergen avoidance may be considered when sensitisation has been established. Maintenance treatment with inhaled corticosteroids is recommended for multiple-trigger wheeze; benefits are often small. Montelukast is recommended for the treatment of episodic (viral) wheeze and can be started when symptoms of a viral cold develop. Given the large overlap in phenotypes, and the fact that patients can move from one phenotype to another, inhaled corticosteroids and montelukast may be considered on a trial basis in almost any preschool child with recurrent wheeze, but should be discontinued if there is no clear clinical benefit. Large well-designed randomised controlled trials with clear descriptions of patients are needed to improve the present recommendations on the treatment of these common syndromes.

Why chronic wounds will not heal: a novel hypothesis.

Abstract: The present paper presents a hypothesis aimed at explaining why venous leg ulcers, pressure ulcers, and diabetic foot ulcers develop into a chronic state. We propose that the lack of proper wound healing is at least in part caused by inefficient eradication of infecting, opportunistic pathogens, a situation reminiscent of chronic Pseudomonas aeruginosa infections found in patients suffering from cystic fibrosis (CF). We have analyzed sections from chronic wounds by fluorescence in situ hybridization and found distinct microcolonies--the basal structures of bacterial biofilms. Several researchers have previously reported that another important hallmark of biofilm formation is development of increased tolerance to various antimicrobial measures and treatments. Furthermore, the immune response to infecting bacteria in the cystic fibrosis lung is dominated by polymorphonuclear neutrophils (PMNs), and we have recently shown that in vitro biofilms of P. aeruginosa produce a shielding mechanism that offers protection from the phagocytic activity of PMNs. We hypothesize that the presence of P. aeruginosa in biofilms, and the lack of concomitant elimination by attended PMNs, are the main causes of inefficient eradication by antibiotic treatment and antimicrobial activity of the innate immune system, respectively.

Genetically Elevated C-Reactive Protein and Ischemic Vascular Disease

Abstract: Background Elevated levels of C-reactive protein (CRP) are associated with increased risks of ischemic heart disease and ischemic cerebrovascular disease. We tested whether this is a causal association. Methods We studied 10,276 persons from a general population cohort, including 1786 in whom ischemic heart disease developed and 741 in whom ischemic cerebrovascular disease developed. We examined another 31,992 persons from a cross-sectional general population study, of whom 2521 had ischemic heart disease and 1483 had ischemic cerebrovascular disease. Finally, we compared 2238 patients with ischemic heart disease with 4474 control subjects and 612 patients with ischemic cerebrovascular disease with 1224 control subjects. We measured levels of high-sensitivity CRP and conducted genotyping for four CRP polymorphisms and two apolipoprotein E polymorphisms. Results The risk of ischemic heart disease and ischemic cerebrovascular disease was increased by a factor of 1.6 and 1.3, respectively, in persons who had CRP levels above 3 mg per liter, as compared with persons who had CRP levels below 1 mg per liter. Genotype combinations of the four CRP polymorphisms were associated with an increase in CRP levels of up to 64%, resulting in a theoretically predicted increased risk of up to 32% for ischemic heart disease and up to 25% for ischemic cerebrovascular disease. However, these genotype combinations were not associated with an increased risk of ischemic vascular disease. In contrast, apolipoprotein E genotypes were associated with both elevated cholesterol levels and an increased risk of ischemic heart disease. Conclusions Polymorphisms in the CRP gene are associated with marked increases in CRP levels and thus with a theoretically predicted increase in the risk of ischemic vascular disease. However, these polymorphisms are not in themselves associated with an increased risk of ischemic vascular disease.

Guidelines and good clinical practice recommendations for contrast enhanced ultrasound (CEUS) - Update 2008

Abstract: EFSUMB study group M. Claudon1, D. Cosgrove2, T. Albrecht3, L. Bolondi4, M. Bosio5, F. Calliada6, J.-M. Correas7, K. Darge8, C. Dietrich9, M. D'On ofrio10, D. H. Evans11, C. Filice12, L. Greiner13, K. Jäger14, N. de. Jong15, E. Leen16, R. Lencioni17, D. Lindsell18, A. Martegani19, S. Meairs20, C. Nolsøe21, F. Piscaglia22, P. Ricci23, G. Seidel24, B. Skjoldbye25, L. Solbiati26, L. Thorelius27, F. Tranquart28, H. P. Weskott29, T. Whittingham30

The same sequence variant on 9p21 associates with myocardial infarction, abdominal aortic aneurysm and intracranial aneurysm

Abstract: Recently, two common sequence variants on 9p21, tagged by rs10757278-G and rs10811661-T, were reported to be associated with coronary artery disease (CAD)(1-4) and type 2 diabetes (T2D)(5-7), respectively. We proceeded to further investigate the contributions of these variants to arterial diseases and T2D. Here we report that rs10757278-G is associated with, in addition to CAD, abdominal aortic aneurysm (AAA; odds ratio (OR) 1.31, P = 1.2 x 10(-12)) and intracranial aneurysm (OR = 1.29, P = 2.5 x 10(-6)), but not with T2D. This variant is the first to be described that affects the risk of AAA and intracranial aneurysm in many populations. The association of rs10811661-T to T2D replicates in our samples, but the variant does not associate with any of the five arterial diseases examined. These findings extend our insight into the role of the sequence variant tagged by rs10757278-G and show that it is not confined to atherosclerotic diseases.