Showing papers by "Charles University in Prague published in 2010"
TL;DR: The European Working Group on Sarcopenia in Older People (EWGSOP) developed a practical clinical definition and consensus diagnostic criteria for age-related sarcopenia as discussed by the authors.
Abstract: The European Working Group on Sarcopenia in Older People (EWGSOP) developed a practical clinical definition and consensus diagnostic criteria for age-related sarcopenia. EWGSOP included representatives from four participant organisations, i.e. the European Geriatric Medicine Society, the European Society for Clinical Nutrition and Metabolism, the International Association of Gerontology and Geriatrics-European Region and the International Association of Nutrition and Aging. These organisations endorsed the findings in the final document. The group met and addressed the following questions, using the medical literature to build evidence-based answers: (i) What is sarcopenia? (ii) What parameters define sarcopenia? (iii) What variables reflect these parameters, and what measurement tools and cut-off points can be used? (iv) How does sarcopenia relate to cachexia, frailty and sarcopenic obesity? For the diagnosis of sarcopenia, EWGSOP recommends using the presence of both low muscle mass + low muscle function (strength or performance). EWGSOP variously applies these characteristics to further define conceptual stages as 'presarcopenia', 'sarcopenia' and 'severe sarcopenia'. EWGSOP reviewed a wide range of tools that can be used to measure the specific variables of muscle mass, muscle strength and physical performance. Our paper summarises currently available data defining sarcopenia cut-off points by age and gender; suggests an algorithm for sarcopenia case finding in older individuals based on measurements of gait speed, grip strength and muscle mass; and presents a list of suggested primary and secondary outcome domains for research. Once an operational definition of sarcopenia is adopted and included in the mainstream of comprehensive geriatric assessment, the next steps are to define the natural course of sarcopenia and to develop and define effective treatment.
8,440 citations
Umeå University1, University of Rennes2, University of Texas at Austin3, Charles University in Prague4, Hanover College5, University of Aberdeen6, University of Coimbra7, Radboud University Nijmegen8, St Bartholomew's Hospital9, Ludwig Maximilian University of Munich10, University of Eastern Piedmont11, Netherlands Cancer Institute12
TL;DR: The 2014 RCC guideline has been updated by a multidisciplinary panel using the highest methodological standards, and provides the best and most reliable contemporary evidence base for RCC management.
3,100 citations
Instituto Português de Oncologia Francisco Gentil1, National Autonomous University of Mexico2, University of Valencia3, National Cheng Kung University4, University of Buenos Aires5, Universidad Nacional de Asunción6, Makerere University7, University of Chile8, American University of Beirut9, Hacettepe University10, Hospital General San Juan de Dios11, Lagos University Teaching Hospital12, University of Barcelona13, University of the Philippines14, Bangabandhu Sheikh Mujib Medical University15, Prince of Songkla University16, Peking Union Medical College17, Royal Women's Hospital18, Kanazawa University19, Charles University in Prague20, Harvard University21, VU University Amsterdam22, Kuwait University23, Columbia University Medical Center24, University of Crete25, Aristotle University of Thessaloniki26, Central University of Venezuela27, University of Las Palmas de Gran Canaria28, University of Antioquia29, Medical University of Lublin30, Western Galilee Hospital31
TL;DR: HPV types 16, 18, 31, 33, 35, 45, 52, and 58 should be given priority when the cross-protective effects of current vaccines are assessed, and for formulation of recommendations for the use of second-generation polyvalent HPV vaccines, according to this largest assessment of HPV genotypes to date.
Abstract: Summary Background Knowledge about the distribution of human papillomavirus (HPV) genotypes in invasive cervical cancer is crucial to guide the introduction of prophylactic vaccines. We aimed to provide novel and comprehensive data about the worldwide genotype distribution in patients with invasive cervical cancer. Methods Paraffin-embedded samples of histologically confirmed cases of invasive cervical cancer were collected from 38 countries in Europe, North America, central South America, Africa, Asia, and Oceania. Inclusion criteria were a pathological confirmation of a primary invasive cervical cancer of epithelial origin in the tissue sample selected for analysis of HPV DNA, and information about the year of diagnosis. HPV detection was done by use of PCR with SPF-10 broad-spectrum primers followed by DNA enzyme immunoassay and genotyping with a reverse hybridisation line probe assay. Sequence analysis was done to characterise HPV-positive samples with unknown HPV types. Data analyses included algorithms of multiple infections to estimate type-specific relative contributions. Findings 22 661 paraffin-embedded samples were obtained from 14 249 women. 10 575 cases of invasive cervical cancer were included in the study, and 8977 (85%) of these were positive for HPV DNA. The most common HPV types were 16, 18, 31, 33, 35, 45, 52, and 58 with a combined worldwide relative contribution of 8196 of 8977 (91%, 95% CI 90–92). HPV types 16 and 18 were detected in 6357 of 8977 of cases (71%, 70–72) of invasive cervical cancer. HPV types 16, 18, and 45 were detected in 443 of 470 cases (94%, 92–96) of cervical adenocarcinomas. Unknown HPV types that were identified with sequence analysis were 26, 30, 61, 67, 69, 82, and 91 in 103 (1%) of 8977 cases of invasive cervical cancer. Women with invasive cervical cancers related to HPV types 16, 18, or 45 presented at a younger mean age than did those with other HPV types (50·0 years [49·6–50·4], 48·2 years [47·3–49·2], 46·8 years [46·6–48·1], and 55·5 years [54·9–56·1], respectively). Interpretation To our knowledge, this study is the largest assessment of HPV genotypes to date. HPV types 16, 18, 31, 33, 35, 45, 52, and 58 should be given priority when the cross-protective effects of current vaccines are assessed, and for formulation of recommendations for the use of second-generation polyvalent HPV vaccines. Our results also suggest that type-specific high-risk HPV-DNA-based screening tests and protocols should focus on HPV types 16, 18, and 45. Funding Spanish grants from Instituto de Salud Carlos III, Agencia de Gestio d'Ajuts Universitaris i de Recerca, Marato de TV3 Foundation, and unrestricted grants from GlaxoSmithKline Biologicals, Sanofi Pasteur MSD, and Merck.
2,145 citations
15 Apr 2010
TL;DR: Systematic studies of more than 25,000 cancer genomes will reveal the repertoire of oncogenic mutations, uncover traces of the mutagenic influences, define clinically relevant subtypes for prognosis and therapeutic management, and enable the development of new cancer therapies.
Abstract: The International Cancer Genome Consortium (ICGC) was launched to coordinate large-scale cancer genome studies in tumours from 50 different cancer types and/or subtypes that are of clinical and societal importance across the globe. Systematic studies of more than 25,000 cancer genomes at the genomic, epigenomic and transcriptomic levels will reveal the repertoire of oncogenic mutations, uncover traces of the mutagenic influences, define clinically relevant subtypes for prognosis and therapeutic management, and enable the development of new cancer therapies.
2,041 citations
University of Cologne1, Heidelberg University2, University of Mainz3, Praxis4, Ludwig Maximilian University of Munich5, Frankston Hospital6, University of Bologna7, Peter MacCallum Cancer Centre8, Medical University of Vienna9, Charles University in Prague10, University of Ulm11, Hoffmann-La Roche12
TL;DR: Chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab improves progression-free survival and overall survival in patients with chronic lymphocytic leukaemia, and the results suggest that the choice of a specific first-line treatment changes the natural course of chronic lymphocytes.
1,758 citations
Erasmus University Rotterdam1, University of Cambridge2, University of Paris3, University of Copenhagen4, Aarhus University5, Ghent University6, National and Kapodistrian University of Athens7, French Institute of Health and Medical Research8, University of Upper Alsace9, VU University Amsterdam10, Maastricht University11, University of Manchester12, Manchester Royal Infirmary13, University of Brescia14, Charles University in Prague15
TL;DR: In this paper, the authors established reference and normal values for Carotid-femoral pulse wave velocity (PWV), a direct measure of aortic stiffness, based on a large European population.
Abstract: Aims: Carotid-femoral pulse wave velocity (PWV), a direct measure of aortic stiffness, has become increasingly important for total cardiovascular (CV) risk estimation. Its application as a routine tool for clinical patient evaluation has been hampered by the absence of reference values. The aim of the present study is to establish reference and normal values for PWV based on a large European population. Methods and results: We gathered data from 16 867 subjects and patients from 13 different centres across eight European countries, in which PWV and basic clinical parameters were measured. Of these, 11 092 individuals were free from overt CV disease, non-diabetic and untreated by either anti-hypertensive or lipid-lowering drugs and constituted the reference value population, of which the subset with optimal/normal blood pressures (BPs) (n = 1455) is the normal value population. Prior to data pooling, PWV values were converted to a common standard using established conversion formulae. Subjects were categorized by age decade and further subdivided according to BP categories. Pulse wave velocity increased with age and BP category; the increase with age being more pronounced for higher BP categories and the increase with BP being more important for older subjects. The distribution of PWV with age and BP category is described and reference values for PWV are established. Normal values are proposed based on the PWV values observed in the non-hypertensive subpopulation who had no additional CV risk factors. Conclusion: The present study is the first to establish reference and normal values for PWV, combining a sizeable European population after standardizing results for different methods of PWV measurement.
1,435 citations
Medical University of Vienna1, Maastricht University2, Leiden University3, Paris Descartes University4, University of Leeds5, Pierre-and-Marie-Curie University6, Utrecht University7, Humboldt State University8, University of Montpellier9, University of Genoa10, University of Santiago, Chile11, Autonomous University of Madrid12, University of Glasgow13, Charles University in Prague14, Radboud University Nijmegen15, King's College London16, Sapienza University of Rome17, Karolinska Institutet18, Oregon Health & Science University19, Tufts University20, Charité21
TL;DR: In this article, the authors present a set of recommendations for the treatment of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs (DMARDs) and glucocorticoids (GCs) that also account for strategic algorithms and deal with economic aspects.
Abstract: Treatment of rheumatoid arthritis (RA) may differ among rheumatologists and currently, clear and consensual international recommendations on RA treatment are not available. In this paper recommendations for the treatment of RA with synthetic and biological disease-modifying antirheumatic drugs (DMARDs) and glucocorticoids (GCs) that also account for strategic algorithms and deal with economic aspects, are described. The recommendations are based on evidence from five systematic literature reviews (SLRs) performed for synthetic DMARDs, biological DMARDs, GCs, treatment strategies and economic issues. The SLR-derived evidence was discussed and summarised as an expert opinion in the course of a Delphi-like process. Levels of evidence, strength of recommendations and levels of agreement were derived. Fifteen recommendations were developed covering an area from general aspects such as remission/low disease activity as treatment aim via the preference for methotrexate monotherapy with or without GCs vis-a-vis combination of synthetic DMARDs to the use of biological agents mainly in patients for whom synthetic DMARDs and tumour necrosis factor inhibitors had failed. Cost effectiveness of the treatments was additionally examined. These recommendations are intended to inform rheumatologists, patients and other stakeholders about a European consensus on the management of RA with DMARDs and GCs as well as strategies to reach optimal outcomes of RA, based on evidence and expert opinion.
1,372 citations
University of North Carolina at Chapel Hill1, University of Texas Health Science Center at Houston2, University of Pavia3, University of Cambridge4, University of Milan5, Stanford University6, Kaiser Permanente7, National Institutes of Health8, University of Washington9, Wake Forest University10, Cedars-Sinai Medical Center11, Group Health Cooperative12, Lund University13, University of Michigan14, National Institute for Health and Welfare15, University of Helsinki16, Boston University17, University of Chicago18, International Agency for Research on Cancer19, Charles University in Prague20, French Institute of Health and Medical Research21, Institut Gustave Roussy22, University of Padua23, University of Glasgow24, Palacký University, Olomouc25, Trinity College, Dublin26, National and Kapodistrian University of Athens27, Newcastle University28, University of Aberdeen29, University of Turin30, Nofer Institute of Occupational Medicine31, Russian Academy32, University of Exeter33, Harvard University34, Massachusetts Institute of Technology35, Broad Institute36, VU University Amsterdam37, Erasmus University Rotterdam38, University of Virginia39, Virginia Commonwealth University40, University of Pennsylvania41, Duke University42, University of Ioannina43, Tufts University44
TL;DR: A meta-analyses of several smoking phenotypes within cohorts of the Tobacco and Genetics Consortium found the strongest association was a synonymous 15q25 SNP in the nicotinic receptor gene CHRNA3, and three loci associated with number of cigarettes smoked per day were identified.
Abstract: Consistent but indirect evidence has implicated genetic factors in smoking behavior1,2. We report meta-analyses of several smoking phenotypes within cohorts of the Tobacco and Genetics Consortium (n = 74,053). We also partnered with the European Network of Genetic and Genomic Epidemiology (ENGAGE) and Oxford-GlaxoSmithKline (Ox-GSK) consortia to follow up the 15 most significant regions (n > 140,000). We identified three loci associated with number of cigarettes smoked per day. The strongest association was a synonymous 15q25 SNP in the nicotinic receptor gene CHRNA3 (rs1051730[A], b = 1.03, standard error (s.e.) = 0.053, beta = 2.8 x 10(-73)). Two 10q25 SNPs (rs1329650[G], b = 0.367, s. e. = 0.059, beta = 5.7 x 10(-10); and rs1028936[A], b = 0.446, s. e. = 0.074, beta = 1.3 x 10(-9)) and one 9q13 SNP in EGLN2 (rs3733829[G], b = 0.333, s. e. = 0.058, P = 1.0 x 10(-8)) also exceeded genome-wide significance for cigarettes per day. For smoking initiation, eight SNPs exceeded genome-wide significance, with the strongest association at a nonsynonymous SNP in BDNF on chromosome 11 (rs6265[C], odds ratio (OR) = 1.06, 95% confidence interval (Cl) 1.04-1.08, P = 1.8 x 10(-8)). One SNP located near DBH on chromosome 9 (rs3025343[G], OR = 1.12, 95% Cl 1.08-1.18, P = 3.6 x 10(-8)) was significantly associated with smoking cessation.
1,104 citations
University of Basel1, Radboud University Nijmegen2, University of Padua3, Complutense University of Madrid4, University of Paris5, University of Zurich6, University of Bari7, Lithuanian University of Health Sciences8, University of Florence9, Russian Academy10, Rambam Health Care Campus11, University of Regensburg12, Charité13, University of the Witwatersrand14, Johns Hopkins University15, University of Coimbra16, University of Verona17, Lund University18, University of Ljubljana19, Utrecht University20, University of Pécs21, Medical University of Vienna22, University of Debrecen23, Sapienza University of Rome24, University of Geneva25, University of Silesia in Katowice26, University College London27, University of Tübingen28, Military Medical Academy29, Lille University of Science and Technology30, University of Michigan31, Iuliu Hațieganu University of Medicine and Pharmacy32, Charles University in Prague33, University of Zagreb34
TL;DR: Disease-related causes, in particular pulmonary fibrosis, PAH and cardiac causes, accounted for the majority of deaths in SSc.
Abstract: Objectives To determine the causes and predictors of mortality in systemic sclerosis (SSc). Methods Patients with SSc (n=5860) fulfilling the American College of Rheumatology criteria and prospectively followed in the EULAR Scleroderma Trials and Research (EUSTAR) cohort were analysed. EUSTAR centres completed a structured questionnaire on cause of death and comorbidities. Kaplan-Meier and Cox proportional hazards models were used to analyse survival in SSc subgroups and to identify predictors of mortality. Results Questionnaires were obtained on 234 of 284 fatalities. 55% of deaths were attributed directly to SSc and 41% to non-SSc causes; in 4% the cause of death was not assigned. Of the SSc-related deaths, 35% were attributed to pulmonary fibrosis, 26% to pulmonary arterial hypertension (PAH) and 26% to cardiac causes (mainly heart failure and arrhythmias). Among the non-SSc-related causes, infections (33%) and malignancies (31%) were followed by cardiovascular causes (29%). Of the non-SSc-related fatalities, 25% died of causes in which SSc-related complications may have participated (pneumonia, sepsis and gastrointestinal haemorrhage). Independent risk factors for mortality and their HR were: proteinuria (HR 3.34), the presence of PAH based on echocardiography (HR 2.02), pulmonary restriction (forced vital capacity below 80% of normal, HR 1.64), dyspnoea above New York Heart Association class II (HR 1.61), diffusing capacity of the lung (HR 1.20 per 10% decrease), patient age at onset of Raynaud's phenomenon (HR 1.30 per 10 years) and the modified Rodnan skin score (HR 1.20 per 10 score points). Conclusion Disease-related causes, in particular pulmonary fibrosis, PAH and cardiac causes, accounted for the majority of deaths in SSc.
1,010 citations
J. Craig Venter Institute1, Alfred Wegener Institute for Polar and Marine Research2, École Normale Supérieure3, San Diego State University4, Fraunhofer Society5, Charles University in Prague6, Scottish Association for Marine Science7, Kobe University8, University of Mainz9, University of Arizona10, University of Tennessee Health Science Center11, California State University, Los Angeles12
TL;DR: The Ectocarpus genome sequence represents an important step towards developing this organism as a model species, providing the possibility to combine genomic and genetic approaches to explore these and other aspects of brown algal biology further.
Abstract: Brown algae (Phaeophyceae) are complex photosynthetic organisms with a very different evolutionary history to green plants, to which they are only distantly related. These seaweeds are the dominant species in rocky coastal ecosystems and they exhibit many interesting adaptations to these, often harsh, environments. Brown algae are also one of only a small number of eukaryotic lineages that have evolved complex multicellularity (Fig. 1). We report the 214 million base pair (Mbp) genome sequence of the filamentous seaweed Ectocarpus siliculosus (Dillwyn) Lyngbye, a model organism for brown algae closely related to the kelps (Fig. 1). Genome features such as the presence of an extended set of light-harvesting and pigment biosynthesis genes and new metabolic processes such as halide metabolism help explain the ability of this organism to cope with the highly variable tidal environment. The evolution of multicellularity in this lineage is correlated with the presence of a rich array of signal transduction genes. Of particular interest is the presence of a family of receptor kinases, as the independent evolution of related molecules has been linked with the emergence of multicellularity in both the animal and green plant lineages. The Ectocarpus genome sequence represents an important step towards developing this organism as a model species, providing the possibility to combine genomic and genetic approaches to explore these and other aspects of brown algal biology further
809 citations
TL;DR: The results strongly support the concept that MASC and AciCC are different entities.
Abstract: We present a series of 16 salivary gland tumors with histomorphologic and immunohistochemical features reminiscent of secretory carcinoma of the breast. This is a hitherto undescribed and distinctive salivary gland neoplasm, with features resembling both salivary acinic cell carcinoma (AciCC) and low-grade cystadenocarcinoma, and displaying strong similarities to breast secretory carcinoma. Microscopically, the tumors have a lobulated growth pattern and are composed of microcystic and glandular spaces with abundant eosinophilic homogenous or bubbly secretory material positive for periodic acid-Schiff, mucicarmine, MUC1, MUC4, and mammaglobin. The neoplasms also show strong vimentin, S-100 protein, and STAT5a positivity. For this tumor, we propose a designation mammary analogue secretory carcinoma of salivary glands (MASC). The 16 patients comprised 9 men and 7 women, with a mean age of 46 years (range 21 to 75). Thirteen cases occurred in the parotid gland, and one each in the minor salivary glands of the buccal mucosa, upper lip, and palate. The mean size of the tumors was 2.1 cm (range 0.7 to 5.5 cm). The duration of symptoms was recorded in 11 cases and ranged from 2 months to 30 years. Clinical follow-up was available in 13 cases, and ranged from 3 months to 10 years. Four patients suffered local recurrences. Two patients died, 1 of them owing to multiple local recurrences with extension to the temporal bone, and another owing to metastatic dissemination to cervical lymph nodes, pleura, pericardium, and lungs. We have shown a t(12;15) (p13;q25) ETV6-NTRK3 translocation in all but one case of MASC suitable for analysis. One case was not analyzable and another was not available for testing. This translocation was not found in any conventional salivary AciCC (12 cases), nor in other tumor types including pleomorphic adenoma (1 case) and low-grade cribriform cystadenocarcinoma (1 case), whereas ETV6-NTRK3 gene rearrangements were proven in all 3 tested cases of mammary secretory carcinoma. Thus, our results strongly support the concept that MASC and AciCC are different entities.
TL;DR: In this article, the authors used the ATLAS detector to detect dijet asymmetry in the collisions of lead ions at the Large Hadron Collider and found that the transverse energies of dijets in opposite hemispheres become systematically more unbalanced with increasing event centrality, leading to a large number of events which contain highly asymmetric di jets.
Abstract: By using the ATLAS detector, observations have been made of a centrality-dependent dijet asymmetry in the collisions of lead ions at the Large Hadron Collider. In a sample of lead-lead events with a per-nucleon center of mass energy of 2.76 TeV, selected with a minimum bias trigger, jets are reconstructed in fine-grained, longitudinally segmented electromagnetic and hadronic calorimeters. The transverse energies of dijets in opposite hemispheres are observed to become systematically more unbalanced with increasing event centrality leading to a large number of events which contain highly asymmetric dijets. This is the first observation of an enhancement of events with such large dijet asymmetries, not observed in proton-proton collisions, which may point to an interpretation in terms of strong jet energy loss in a hot, dense medium.
TL;DR: In this article, a combination of the inclusive deep inelastic cross sections measured by the H1 and ZEUS Collaborations in neutral and charged current unpolarised e(+/-)p scattering at HERA during the period 1994-2000 is presented.
Abstract: A combination is presented of the inclusive deep inelastic cross sections measured by the H1 and ZEUS Collaborations in neutral and charged current unpolarised e(+/-)p scattering at HERA during the period 1994-2000. The data span six orders of magnitude in negative four-momentum-transfer squared, Q(2), and in Bjorken x. The combination method used takes the correlations of systematic uncertainties into account, resulting in an improved accuracy. The combined data are the sole input in a NLO QCD analysis which determines a new set of parton distributions, HERAPDF1.0, with small experimental uncertainties. This set includes an estimate of the model and parametrisation uncertainties of the fit result.
TL;DR: Most North, West, and Central European countries used p-PCI for the majority of their STEMI patients, and the lack of organized p- PCI networks was associated with fewer patients overall receiving some form of reperfusion therapy.
Abstract: Aims Patient access to reperfusion therapy and the use of primary percutaneous coronary intervention (p-PCI) or thrombolysis (TL) varies considerably between European countries. The aim of this study was to obtain a realistic contemporary picture of how patients with ST elevation myocardial infarction (STEMI) are treated in different European countries.
Methods and results The chairpersons of the national working groups/societies of interventional cardiology in European countries and selected experts known to be involved in the national registries joined the writing group upon invitation. Data were collected about the country and any existing national STEMI or PCI registries, about STEMI epidemiology, and treatment in each given country and about PCI and p-PCI centres and procedures in each country. Results from the national and/or regional registries in 30 countries were included in this analysis. The annual incidence of hospital admission for any acute myocardial infarction (AMI) varied between 90–312/100 thousand/year, the incidence of STEMI alone ranging from 44 to 142. Primary PCI was the dominant reperfusion strategy in 16 countries and TL in 8 countries. The use of a p-PCI strategy varied between 5 and 92% (of all STEMI patients) and the use of TL between 0 and 55%. Any reperfusion treatment (p-PCI or TL) was used in 37–93% of STEMI patients. Significantly less reperfusion therapy was used in those countries where TL was the dominant strategy. The number of p-PCI procedures per million per year varied among countries between 20 and 970. The mean population served by a single p-PCI centre varied between 0.3 and 7.4 million inhabitants. In those countries offering p-PCI services to the majority of their STEMI patients, this population varied between 0.3 and 1.1 million per centre. In-hospital mortality of all consecutive STEMI patients varied between 4.2 and 13.5%, for patients treated by TL between 3.5 and 14% and for patients treated by p-PCI between 2.7 and 8%. The time reported from symptom onset to the first medical contact (FMC) varied between 60 and 210 min, FMC-needle time for TL between 30 and 110 min, and FMC-balloon time for p-PCI between 60 and 177 min.
Conclusion Most North, West, and Central European countries used p-PCI for the majority of their STEMI patients. The lack of organized p-PCI networks was associated with fewer patients overall receiving some form of reperfusion therapy.
TL;DR: Final analysis of AVAiL confirms the efficacy of bevacizumab when combined with cisplatin–gemcitabine, and the PFS benefit did not translate into a significant OS benefit, possibly due to high use of efficacious second-line therapies.
TL;DR: Therapy for SIBO must be complex, addressing all causes, symptoms and complications, and fully individualised, it should include treatment of the underlying disease, nutritional support and cyclical gastro-intestinal selective antibiotics.
Abstract: Human intestinal microbiota create a complex polymicrobial ecology. This is characterised by its high population density, wide diversity and complexity of interaction. Any dysbalance of this complex intestinal microbiome, both qualitative and quantitative, might have serious health consequence for a macro-organism, including small intestinal bacterial overgrowth syndrome (SIBO). SIBO is defined as an increase in the number and/or alteration in the type of bacteria in the upper gastrointestinal tract. There are several endogenous defence mechanisms for preventing bacterial overgrowth: gastric acid secretion, intestinal motility, intact ileo-caecal valve, immunoglobulins within intestinal secretion and bacteriostatic properties of pancreatic and biliary secretion. Aetiology of SIBO is usually complex, associated with disorders of protective antibacterial mechanisms (e.g. achlorhydria, pancreatic exocrine insufficiency, immunodeficiency syndromes), anatomical abnormalities (e.g. small intestinal obstruction, diverticula, fistulae, surgical blind loop, previous ileo-caecal resections) and/or motility disorders (e.g. scleroderma, autonomic neuropathy in diabetes mellitus, post-radiation enteropathy, small intestinal pseudo-obstruction). In some patients more than one factor may be involved. Symptoms related to SIBO are bloating, diarrhoea, malabsorption, weight loss and malnutrition. The gold standard for diagnosing SIBO is still microbial investigation of jejunal aspirates. Non-invasive hydrogen and methane breath tests are most commonly used for the diagnosis of SIBO using glucose or lactulose. Therapy for SIBO must be complex, addressing all causes, symptoms and complications, and fully individualised. It should include treatment of the underlying disease, nutritional support and cyclical gastro-intestinal selective antibiotics. Prognosis is usually serious, determined mostly by the underlying disease that led to SIBO.
TL;DR: In this article, the authors present a zodiacal cloud model based on the orbital properties and lifetimes of comets and asteroids, and on the dynamical evolution of dust after ejection.
Abstract: The zodiacal cloud is a thick circumsolar disk of small debris particles produced by asteroid collisions and comets. Their relative contribution and how particles of different sizes dynamically evolve to produce the observed phenomena of light scattering, thermal emission, and meteoroid impacts are unknown. Until now, zodiacal cloud models have been phenomenological in nature, composed of ad hoc components with properties not understood from basic physical processes. Here, we present a zodiacal cloud model based on the orbital properties and lifetimes of comets and asteroids, and on the dynamical evolution of dust after ejection. The model is quantitatively constrained by Infrared Astronomical Satellite (IRAS) observations of thermal emission, but also qualitatively consistent with other zodiacal cloud observations, with meteor observations, with spacecraft impact experiments, and with properties of recovered micrometeorites (MMs). We find that particles produced by Jupiterfamily comets (JFCs) are scattered by Jupiter before they are able to orbitally decouple from the planet and drift down to 1 AU. Therefore, the inclination distribution of JFC particles is broader than that of their source comets and leads to good fits to the broad latitudinal distribution of fluxes observed by IRAS. We find that 85%–95% of the observed mid-infrared emission is produced by particles from JFCs and 100 μm undergo a further collisional cascade with smaller fragments being progressively more affected by Poynting–Robertson (PR) drag. Upon reaching D 10 4 times brighter during the Late Heavy Bombardment (LHB) epoch ≈3.8 Gyr ago, when the outer planets scattered numerous comets into the inner solar system. The bright debris disks with a large 24 μm excess observed around mature stars may be an indication of massive cometary populations existing in those systems. We estimate that at least ∼10 22 , ∼2 × 10 21 , and ∼2 × 10 20 go f
TL;DR: In this article, a meta-regression analysis of 64 outcomes from 37 empirical studies was carried out to uncover the underlying factors, which can influence the observed variation in the empirical results, and the results suggest both that the empirical method used matters for the nexus and that the likelihood of finding a negative link between environmental and financial performance significantly increases when using simple correlation coefficients instead of more advanced econometric analysis.
TL;DR: Ways in which plants cope with cold stress are described, and the current state of the art with respect to both the model plant Arabidopsis thaliana and crop plants in the area of gene expression and metabolic pathways during low-temperature stress are discussed.
Abstract: As sessile organisms, plants are unable to escape from the many abiotic and biotic factors that cause a departure from optimal conditions of growth and development. Low temperature represents one of the most harmful abiotic stresses affecting temperate plants. These species have adapted to seasonal variations in temperature by adjusting their metabolism during autumn, increasing their content of a range of cryo-protective compounds to maximise their cold tolerance. Some of these molecules are synthesised de novo. The down-regulation of some gene products represents an additional important regulatory mechanism. Ways in which plants cope with cold stress are described, and the current state of the art with respect to both the model plant Arabidopsis thaliana and crop plants in the area of gene expression and metabolic pathways during low-temperature stress are discussed.
TL;DR: This work considers data analysis approaches to testing associations between a phenotype and collections of rare variants in a defined genomic region or set of regions and determines their properties and power in different contexts.
Abstract: The limitations of genome-wide association (GWA) studies that focus on the phenotypic influence of common genetic variants have motivated human geneticists to consider the contribution of rare variants to phenotypic expression. The increasing availability of high-throughput sequencing technologies has enabled studies of rare variants but these methods will not be sufficient for their success as appropriate analytical methods are also needed. We consider data analysis approaches to testing associations between a phenotype and collections of rare variants in a defined genomic region or set of regions. Ultimately, although a wide variety of analytical approaches exist, more work is needed to refine them and determine their properties and power in different contexts.
TL;DR: The aim of this revised international guideline was to present a peer‐reviewed evidence‐based statement for the guidance of practice for clinical neurologists, geriatricians, psychiatrists, and other specialist physicians responsible for the care of patients with AD.
Abstract: The aim of this revised international guideline was to present
a peer-reviewed evidence-based statement for the guidance of
practice for clinical neurologists, geriatricians,
psychiatrists, and other specialist physicians responsible for
the care of patients with AD. Mild cognitive impairment and
non- Alzheimer dementias are not included in this guideline.
Methods: The task force working group reviewed evidence from
original research articles, meta-analysis, and systematic
reviews, published before May 2009. The evidence was classified
and consensus recommendations graded (A, B, or C) according to
the EFNS guidance. Where there was a lack of evidence, but
clear consensus, good practice points were provided. Results:
The recommendations for clinical diagnosis, blood tests,
neuropsychology, neuroimaging, electroencephalography,
cerebrospinal fluid (CSF) analysis, genetic testing, disclosure
of diagnosis, treatment of AD, behavioural and psychological
symptoms in dementia, legal issues, counselling and support for
caregivers were all revised as compared with the previous EFNS
guideline. Conclusion: A number of new recommendations and good
practice points are made, namely in CSF, neuropsychology,
neuroimaging and reviewing non-evidence based therapies. The
assessment, interpretation, and treatment of symptoms,
disability, needs, and caregiver stress during the course of AD
require the contribution of many different professionals. These
professionals should adhere to these guideline to improve the
diagnosis and management of AD.
TL;DR: In this article, the authors reported a measurement of the flux of cosmic rays with unprecedented precision and statistics using the Pierre Auger Observatory based on fluorescence observations in coincidence with at least one surface detector.
01 Jan 2010
TL;DR: In this article, the authors present formulas relevant for time series analysis: 31.1. Predictions in Time Series, 31.2. Decomposition of (economic) Time Series and 31.3. Estimation of Correlation and Spectral Characteristics.
Abstract: Chapter 31 contains formulas relevant for time series analysis: 31.1. Predictions in Time Series, 31.2. Decomposition of (Economic) Time Series, 31.3. Estimation of Correlation and Spectral Characteristics, 31.4. Linear Time Series, 31.5 Nonlinear and Financial Time Series, 31.6 Multivariate Time Series, 31.7. Kalman Filter.
Nagoya University1, Budker Institute of Nuclear Physics2, Novosibirsk State University3, École Polytechnique Fédérale de Lausanne4, University of Sydney5, Panjab University, Chandigarh6, Nara Women's University7, Polish Academy of Sciences8, University of Maribor9, Fu Jen Catholic University10, National Taiwan University11, National Central University12, Hanyang University13, Yonsei University14, Sungkyunkwan University15, Max Planck Society16, University of Cincinnati17, Karlsruhe Institute of Technology18, University of Ljubljana19, Korea University20, Tohoku Gakuin University21, Kyungpook National University22, University of Tokyo23, Niigata University24, Seoul National University25, Graduate University for Advanced Studies26, Charles University in Prague27, Tokyo Metropolitan University28, University of Giessen29, University of Science and Technology of China30, Osaka City University31, Tokyo University of Agriculture and Technology32, Toho University33, Kanagawa University34, Virginia Tech35, Austrian Academy of Sciences36, University of Melbourne37, National United University38
TL;DR: In this paper, a search for lepton-flavor-violating τ decays into three leptons (electrons or muons) using 782 fb-1 of data collected with the Belle detector at the KEKB asymmetric-energy e+ e- collider is presented.
TL;DR: In this article, the authors describe the methodology and data used to determine greenhouse gas (GHG) emissions attributable to ten cities or city-regions: Los Angeles County, Denver City and County, Greater Toronto, New York City, Greater London, Geneva Canton, Greater Prague, Barcelona, Cape Town and Bangkok.
TL;DR: There is good evidence for the efficacy of biological agents in patients with RA and safety data confirm an increased risk of bacterial infection and TB with TNFi compared with conventional DMARDs.
Abstract: Objectives To review the evidence for the efficacy and safety of biological agents in patients with rheumatoid arthritis (RA) to provide data to develop treatment recommendations by the European League Against Rheumatism (EULAR) Task Force. Methods Medline, Embase and Cochrane databases were searched for relevant articles on infliximab (IFX), etanercept (ETN), adalimumab (ADA), certolizumab-pegol (CZP), golimumab (GLM), anakinra (ANA), abatacept (ABT), rituximab (RTX) and tocilizumab (TCZ) published between 1962 and February 2009; published abstracts from the 2007–2008 American College of Rheumatology (ACR) and EULAR conference were obtained. Results 87 articles and 40 abstracts were identified. In methotrexate (MTX) naive patients, biological therapy with IFX, ETN, ADA, GLM or ABT has been shown to improve clinical outcomes (level of evidence 1B). In MTX/other synthetic disease-modifying antirheumatic drug (DMARD) failures all nine biological agents confer benefit (1B), with lower efficacy noted for ANA. RTX, ABT, TCZ and GLM demonstrate efficacy in tumour necrosis factor inhibitor (TNFi) failures (1B). Less evidence exists for switching between IFX, ETN and ADA (3B). Biological and MTX combination therapy is more efficacious than a biological agent alone (1B). A safety review shows no increased malignancy risk compared with conventional DMARDs (3B). TNFi are generally associated with an increased risk of serious bacterial infection, particularly within the first 6 months of treatment initiation; increased tuberculosis (TB) rates with TNFi are highest with the monoclonal antibodies (3B). Conclusions There is good evidence for the efficacy of biological agents in patients with RA. Safety data confirm an increased risk of bacterial infection and TB with TNFi compared with conventional DMARDs.
Harvard University1, National and Kapodistrian University of Athens2, Rabin Medical Center3, Charles University in Prague4, Sapienza University of Rome5, University of Turin6, Medical University of Lublin7, Johnson & Johnson8, Johnson & Johnson Pharmaceutical Research and Development9, Peking University10, University of Salamanca11
TL;DR: VMP significantly prolongs OS versus MP after lengthy follow-up and extensive subsequent antimyeloma therapy, and appears more beneficial than first treating with conventional agents and saving bortezomib- and other novel agent-based treatment until relapse.
Abstract: Purpose The purpose of this study was to confirm overall survival (OS) and other clinical benefits with bortezomib, melphalan, and prednisone (VMP) versus melphalan and prednisone (MP) in the phase III VISTA (Velcade as Initial Standard Therapy in Multiple Myeloma) trial after prolonged follow-up, and evaluate the impact of subsequent therapies. Patients and Methods Previously untreated symptomatic patients with myeloma ineligible for high-dose therapy received up to nine 6-week cycles of VMP (n 344) or MP (n 338). Results With a median follow-up of 36.7 months, there was a 35% reduced risk of death with VMP versus MP (hazard ratio, 0.653; P .001); median OS was not reached with VMP versus 43 months with MP; 3-year OS rates were 68.5% versus 54.0%. Response rates to subsequent thalidomide(41% v 53%) and lenalidomide-based therapies (59% v 52%) appeared similar after VMP or MP; response rates to subsequent bortezomib-based therapy were 47% versus 59%. Among patients treated with VMP (n 178) and MP (n 233), median survival from start of subsequent therapy was 30.2 and 21.9 months, respectively, and there was no difference in survival from salvage among patients who received subsequent bortezomib, thalidomide, or lenalidomide. Rates of adverse events were higher with VMP versus MP during cycles 1 to 4, but similar during cycles 5 to 9. With VMP, 79% of peripheral neuropathy events improved within a median of 1.9 months; 60% completely resolved within a median of 5.7 months. Conclusion VMP significantly prolongs OS versus MP after lengthy follow-up and extensive subsequent antimyeloma therapy. First-line bortezomib use does not induce more resistant relapse. VMP used upfront appears more beneficial than first treating with conventional agents and saving bortezomib- and other novel agent– based treatment until relapse. J Clin Oncol 28:2259-2266. © 2010 by American Society of Clinical Oncology
TL;DR: In this study, fluid optimization guided by SVV during major abdominal surgery is associated with better intraoperative hemodynamic stability, decrease in serum lactate at the end of surgery and lower incidence of postoperative organ complications.
Abstract: Stroke volume variation (SVV) is a good and easily obtainable predictor of fluid responsiveness, which can be used to guide fluid therapy in mechanically ventilated patients. During major abdominal surgery, inappropriate fluid management may result in occult organ hypoperfusion or fluid overload in patients with compromised cardiovascular reserves and thus increase postoperative morbidity. The aim of our study was to evaluate the influence of SVV guided fluid optimization on organ functions and postoperative morbidity in high risk patients undergoing major abdominal surgery. Patients undergoing elective intraabdominal surgery were randomly assigned to a Control group (n = 60) with routine intraoperative care and a Vigileo group (n = 60), where fluid management was guided by SVV (Vigileo/FloTrac system). The aim was to maintain the SVV below 10% using colloid boluses of 3 ml/kg. The laboratory parameters of organ hypoperfusion in perioperative period, the number of infectious and organ complications on day 30 after the operation, and the hospital and ICU length of stay and mortality were evaluated. The local ethics committee approved the study. The patients in the Vigileo group received more colloid (1425 ml [1000-1500] vs. 1000 ml [540-1250]; P = 0.0028) intraoperatively and a lower number of hypotensive events were observed (2[1-2] Vigileo vs. 3.5[2-6] in Control; P = 0.0001). Lactate levels at the end of surgery were lower in Vigileo (1.78 ± 0.83 mmol/l vs. 2.25 ± 1.12 mmol/l; P = 0.0252). Fewer Vigileo patients developed complications (18 (30%) vs. 35 (58.3%) patients; P = 0.0033) and the overall number of complications was also reduced (34 vs. 77 complications in Vigileo and Control respectively; P = 0.0066). A difference in hospital length of stay was found only in per protocol analysis of patients receiving optimization (9 [8-12] vs. 10 [8-19] days; P = 0.0421). No difference in mortality (1 (1.7%) vs. 2 (3.3%); P = 1.0) and ICU length of stay (3 [2-5] vs. 3 [0.5-5]; P = 0.789) was found. In this study, fluid optimization guided by SVV during major abdominal surgery is associated with better intraoperative hemodynamic stability, decrease in serum lactate at the end of surgery and lower incidence of postoperative organ complications. Current Controlled Trials ISRCTN95085011.
TL;DR: In this paper, anisotropy was measured by the fraction of arrival directions that are less than 3.1 degrees from the position of an active galactic nucleus within 75 Mpc (using the Veron-Cetty and Veron 12th catalog).
TL;DR: In this article, the evolution of the nuclear ground-state shapes across the NxZ plane is discussed, and specific data indicating sudden structural changes in various isotopic and isotonic chains of medium-mass and heavy even-even nuclei, as well as diverse theoretical aspects of the models used to describe these changes.
Abstract: Signatures of criticality in the evolution of the nuclear ground-state shapes across the NxZ plane are discussed. Attention is paid to specific data indicating sudden structural changes in various isotopic and isotonic chains of medium-mass and heavy even-even nuclei, as well as to diverse theoretical aspects of the models used to describe these changes. The interacting boson model and the geometric collective model, in particular, are discussed in detail, the former providing global predictions for the evolution of collective observables in nuclei between closed shells and the latter yielding a parameter-efficient description of nuclei at the critical points of shape transitions. Some issues related to the mechanism of first- and second-order quantum phase transitions in general many-body systems are also outlined.