Showing papers by "University of Barcelona published in 2008"
University of Barcelona1, University of Pisa2, University of Duisburg-Essen3, Auckland City Hospital4, University of São Paulo5, European University6, Icahn School of Medicine at Mount Sinai7, Goethe University Frankfurt8, University of Bologna9, Hannover Medical School10, University of Mainz11, Aix-Marseille University12, Université catholique de Louvain13, University of Düsseldorf14, Bayer15, Bayer Corporation16
TL;DR: In patients with advanced hepatocellular carcinoma, median survival and the time to radiologic progression were nearly 3 months longer for patients treated with sorafenib than for those given placebo.
Abstract: Background No effective systemic therapy exists for patients with advanced hepatocellular carcinoma. A preliminary study suggested that sorafenib, an oral multikinase inhibitor of the vascular endothelial growth factor receptor, the platelet-derived growth factor receptor, and Raf may be effective in hepatocellular carcinoma. Methods In this multicenter, phase 3, double-blind, placebo-controlled trial, we randomly assigned 602 patients with advanced hepatocellular carcinoma who had not received previous systemic treatment to receive either sorafenib (at a dose of 400 mg twice daily) or placebo. Primary outcomes were overall survival and the time to symptomatic progression. Secondary outcomes included the time to radiologic progression and safety. Results At the second planned interim analysis, 321 deaths had occurred, and the study was stopped. Median overall survival was 10.7 months in the sorafenib group and 7.9 months in the placebo group (hazard ratio in the sorafenib group, 0.69; 95% confidence interval, 0.55 to 0.87; P<0.001). There was no significant difference between the two groups in the median time to symptomatic progression (4.1 months vs. 4.9 months, respectively, P=0.77). The median time to radiologic progression was 5.5 months in the sorafenib group and 2.8 months in the placebo group (P<0.001). Seven patients in the sorafenib group (2%) and two patients in the placebo group (1%) had a partial response; no patients had a complete response. Diarrhea, weight loss, hand-foot skin reaction, and hypophosphatemia were more frequent in the sorafenib group. Conclusions In patients with advanced hepatocellular carcinoma, median survival and the time to radiologic progression were nearly 3 months longer for patients treated with sorafenib than for those given placebo.
10,074 citations
TL;DR: The advances in the comprehension of synchronization phenomena when oscillating elements are constrained to interact in a complex network topology are reported and the new emergent features coming out from the interplay between the structure and the function of the underlying pattern of connections are overviewed.
2,953 citations
TL;DR: A new set of covalent atomic radii has been deduced from crystallographic data for most of the elements with atomic numbers up to 96 and shows a well behaved periodic dependence that allows us to interpolate a few radii for elements for which structural data is lacking.
Abstract: A new set of covalent atomic radii has been deduced from crystallographic data for most of the elements with atomic numbers up to 96. The proposed radii show a well behaved periodic dependence that allows us to interpolate a few radii for elements for which structural data is lacking, notably the noble gases. The proposed set of radii therefore fills most of the gaps and solves some inconsistencies in currently used covalent radii. The transition metal and lanthanide contractions as well as the differences in covalent atomic radii between low spin and high spin configurations in transition metals are illustrated by the proposed radii set.
2,948 citations
Daniel J. Klionsky1, Hagai Abeliovich2, Patrizia Agostinis3, Devendra K. Agrawal4 +232 more•Institutions (137)
TL;DR: A set of guidelines for the selection and interpretation of the methods that can be used by investigators who are attempting to examine macroautophagy and related processes, as well as by reviewers who need to provide realistic and reasonable critiques of papers that investigate these processes are presented.
Abstract: Research in autophagy continues to accelerate,(1) and as a result many new scientists are entering the field Accordingly, it is important to establish a standard set of criteria for monitoring macroautophagy in different organisms Recent reviews have described the range of assays that have been used for this purpose(2,3) There are many useful and convenient methods that can be used to monitor macroautophagy in yeast, but relatively few in other model systems, and there is much confusion regarding acceptable methods to measure macroautophagy in higher eukaryotes A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers of autophagosomes versus those that measure flux through the autophagy pathway; thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from fully functional autophagy that includes delivery to, and degradation within, lysosomes (in most higher eukaryotes) or the vacuole (in plants and fungi) Here, we present a set of guidelines for the selection and interpretation of the methods that can be used by investigators who are attempting to examine macroautophagy and related processes, as well as by reviewers who need to provide realistic and reasonable critiques of papers that investigate these processes This set of guidelines is not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to verify an autophagic response
2,310 citations
TL;DR: The LHCb experiment is dedicated to precision measurements of CP violation and rare decays of B hadrons at the Large Hadron Collider (LHC) at CERN (Geneva).
Abstract: The LHCb experiment is dedicated to precision measurements of CP violation and rare decays of B hadrons at the Large Hadron Collider (LHC) at CERN (Geneva). The initial configuration and expected performance of the detector and associated systems, as established by test beam measurements and simulation studies, is described.
2,286 citations
National Institutes of Health1, University of Nebraska Medical Center2, University of British Columbia3, University of Oslo4, Katholieke Universiteit Leuven5, University of Barcelona6, Oregon Health & Science University7, University of Arizona8, Cleveland Clinic9, University of Rochester10, University of Würzburg11, Bosch12, St Bartholomew's Hospital13
TL;DR: Survival after treatment of diffuse large-B-cell lymphoma is influenced by differences in immune cells, fibrosis, and angiogenesis in the tumor microenvironment, and a multivariate model created from three gene-expression signatures predicted survival both in patients who received CHOP and patients who receive R-CHOP.
Abstract: Background The addition of rituximab to combination chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), or R-CHOP, has significantly improved the survival of patients with diffuse large-B-cell lymphoma. Whether gene-expression signatures correlate with survival after treatment of diffuse large-B-cell lymphoma is unclear. Methods We profiled gene expression in pretreatment biopsy specimens from 181 patients with diffuse large-B-cell lymphoma who received CHOP and 233 patients with this disease who received R-CHOP. A multivariate gene-expression–based survival-predictor model derived from a training group was tested in a validation group. Results A multivariate model created from three gene-expression signatures — termed “germinal-center B-cell,” “stromal-1,” and “stromal-2” — predicted survival both in patients who received CHOP and patients who received R-CHOP. The prognostically favorable stromal-1 signature reflected extracellular-matrix deposition and histiocytic infilt...
1,577 citations
Joint Genome Institute1, University of Oxford2, University of St Andrews3, University of California, Berkeley4, Washington University in St. Louis5, University of Lausanne6, Swiss Institute of Bioinformatics7, Kyoto University8, California Institute of Technology9, National Institute for Medical Research10, University of Barcelona11, Children's Hospital Oakland12, Genetic Information Research Institute13, National Institute of Genetics14, Stanford University15, National Institute of Informatics16, University of California, San Diego17
TL;DR: Whole-genome comparisons illuminate the murky relationships among the three chordate groups (tunicates, lancelets and vertebrates), and allow not only reconstruction of the gene complement of the last common chordate ancestor but also partial reconstruction of its genomic organization.
Abstract: Lancelets ('amphioxus') are the modern survivors of an ancient chordate lineage, with a fossil record dating back to the Cambrian period. Here we describe the structure and gene content of the highly polymorphic approximately 520-megabase genome of the Florida lancelet Branchiostoma floridae, and analyse it in the context of chordate evolution. Whole-genome comparisons illuminate the murky relationships among the three chordate groups (tunicates, lancelets and vertebrates), and allow not only reconstruction of the gene complement of the last common chordate ancestor but also partial reconstruction of its genomic organization, as well as a description of two genome-wide duplications and subsequent reorganizations in the vertebrate lineage. These genome-scale events shaped the vertebrate genome and provided additional genetic variation for exploitation during vertebrate evolution.
1,513 citations
Humboldt University of Berlin1, University of California, Berkeley2, Lawrence Berkeley National Laboratory3, University of Lisbon4, DSM5, University of Paris6, Harvard University7, University of Toronto8, Hamilton College9, Carnegie Institution for Science10, American Astronomical Society11, California Institute of Technology12, Centra13, University of California, Santa Cruz14, University of Arizona15, University of Illinois at Urbana–Champaign16, Dublin City University17, Stockholm University18, Université Paris-Saclay19, University of Oxford20, Fermilab21, Vanderbilt University22, European Southern Observatory23, University of Barcelona24, Southwestern College25, Rensselaer Polytechnic Institute26, Louisiana State University27, Western Kentucky University28, Texas A&M University29, University of Cambridge30
TL;DR: A new compilation of Type Ia supernovae (SNe Ia), a new data set of low-redshift nearby-Hubble-flow SNe, and new analysis procedures to work with these heterogeneous compilations is presented in this article.
Abstract: We present a new compilation of Type Ia supernovae (SNe Ia), a new data set of low-redshift nearby-Hubble-flow SNe, and new analysis procedures to work with these heterogeneous compilations This "Union" compilation of 414 SNe Ia, which reduces to 307 SNe after selection cuts, includes the recent large samples of SNe Ia from the Supernova Legacy Survey and ESSENCE Survey, the older data sets, as well as the recently extended data set of distant supernovae observed with the Hubble Space Telescope (HST) A single, consistent, and blind analysis procedure is used for all the various SN Ia subsamples, and a new procedure is implemented that consistently weights the heterogeneous data sets and rejects outliers We present the latest results from this Union compilation and discuss the cosmological constraints from this new compilation and its combination with other cosmological measurements (CMB and BAO) The constraint we obtain from supernovae on the dark energy density is ΩΛ = 0713+ 0027−0029(stat)+ 0036−0039(sys) , for a flat, ΛCDM universe Assuming a constant equation of state parameter, w, the combined constraints from SNe, BAO, and CMB give w = − 0969+ 0059−0063(stat)+ 0063−0066(sys) While our results are consistent with a cosmological constant, we obtain only relatively weak constraints on a w that varies with redshift In particular, the current SN data do not yet significantly constrain w at z > 1 With the addition of our new nearby Hubble-flow SNe Ia, these resulting cosmological constraints are currently the tightest available
1,420 citations
TL;DR: The results show that a cellular, tissue-engineered airway with mechanical properties that allow normal functioning, and which is free from the risks of rejection, is produced, suggesting that autologous cells combined with appropriate biomaterials might provide successful treatment for patients with serious clinical disorders.
1,355 citations
University College London1, Imperial College London2, University of London3, Erasmus University Rotterdam4, French Institute of Health and Medical Research5, Albert Einstein College of Medicine6, Norwegian University of Science and Technology7, University of Washington8, University of Barcelona9, New York State Department of Health10, Monash University11, University of Toronto12, Mayo Clinic13, Mater Misericordiae University Hospital14, UCL Institute of Neurology15, University of Tübingen16
TL;DR: Mutations in LRRK2 are a clinically relevant cause of PD that merit testing in patients with hereditary PD and in subgroups of patients with PD, but this knowledge should be applied with caution in the diagnosis and counselling of patients.
Abstract: Summary Background Mutations in LRRK2 , the gene that encodes leucine-rich repeat kinase 2, are a cause of Parkinson's disease (PD). The International LRRK2 Consortium was established to answer three key clinical questions: can LRRK2 -associated PD be distinguished from idiopathic PD; which mutations in LRRK2 are pathogenic; and what is the age-specific cumulative risk of PD for individuals who inherit or are at risk of inheriting a deleterious mutation in LRRK2 ? Methods Researchers from 21 centres across the world collaborated on this study. The frequency of the common LRRK2 Gly2019Ser mutation was estimated on the basis of data from 24 populations worldwide, and the penetrance of the mutation was defined in 1045 people with mutations in LRRK2 from 133 families. The LRRK2 phenotype was defined on the basis of 59 motor and non-motor symptoms in 356 patients with LRRK2 -associated PD and compared with the symptoms of 543 patients with pathologically proven idiopathic PD. Findings Six mutations met the consortium's criteria for being proven pathogenic. The frequency of the common LRRK2 Gly2019Ser mutation was 1% of patients with sporadic PD and 4% of patients with hereditary PD; the frequency was highest in the middle east and higher in southern Europe than in northern Europe. The risk of PD for a person who inherits the LRRK2 Gly2019Ser mutation was 28% at age 59 years, 51% at 69 years, and 74% at 79 years. The motor symptoms (eg, disease severity, rate of progression, occurrence of falls, and dyskinesia) and non-motor symptoms (eg, cognition and olfaction) of LRRK2 -associated PD were more benign than those of idiopathic PD. Interpretation Mutations in LRRK2 are a clinically relevant cause of PD that merit testing in patients with hereditary PD and in subgroups of patients with PD. However, this knowledge should be applied with caution in the diagnosis and counselling of patients. Funding UK Medical Research Council; UK Parkinson's Disease Society; UK Brain Research Trust; Internationaal Parkinson Fonds; Volkswagen Foundation; National Institutes of Health: National Institute of Neurological Disorders and Stroke and National Institute of Aging; Udall Parkinson's Disease Centre of Excellence; Pacific Alzheimer Research Foundation Centre; Italian Telethon Foundation; Fondazione Grigioni per il Morbo di Parkinson; Michael J Fox Foundation for Parkinson's Research; Safra Global Genetics Consortium; US Department of Veterans Affairs; French Agence Nationale de la Recherche.
1,310 citations
Johns Hopkins University1, University of Barcelona2, Mayo Clinic3, Maastricht University4, Washington University in St. Louis5, St Mary's Hospital6, Beaumont Hospital7, University of Bordeaux8, University of Oklahoma9, University of Pennsylvania10, Northwestern University11, University of Michigan12, Cleveland Clinic13, Harvard University14, University of California, Los Angeles15
TL;DR: In this article, the authors combine geophysics, microbial ecology and organic geochemistry to show geophysical opportunity and microbial capacity to enhance the net heterotrophy in streams, rivers and estuaries.
Abstract: Rivers may be efficient environments for metabolizing terrestrial organic carbon that was previously thought to be recalcitrant, owing to pockets that provide geophysical opportunities by retaining material for longer, and to the adaptation of microbial communities, which has enabled them to exploit the energy that escapes upstream ecosystems. Metabolism of terrestrial organic carbon in freshwater ecosystems is responsible for a large amount of carbon dioxide outgassing to the atmosphere, in contradiction to the conventional wisdom that terrestrial organic carbon is recalcitrant and contributes little to the support of aquatic metabolism. Here, we combine recent findings from geophysics, microbial ecology and organic geochemistry to show geophysical opportunity and microbial capacity to enhance the net heterotrophy in streams, rivers and estuaries. We identify hydrological storage and retention zones that extend the residence time of organic carbon during downstream transport as geophysical opportunities for microorganisms to develop as attached biofilms or suspended aggregates, and to metabolize organic carbon for energy and growth. We consider fluvial networks as meta-ecosystems to include the acclimation of microbial communities in downstream ecosystems that enable them to exploit energy that escapes from upstream ecosystems, thereby increasing the overall energy utilization at the network level.
TL;DR: In 409 patients with assessable metaphases, cytogenetic abnormalities were associated with shorter survival, but their independent contribution to prognosis was restricted to patients in the intermediate-risk groups.
TL;DR: To overcome the complexity of genomic aberrations in HCC, combination therapies will be critical and a molecular classification of HCC based on genome‐wide investigations and identification of patient subclasses according to drug responsiveness will lead to a more personalized medicine.
TL;DR: High-resolution, genome-wide copy number analysis coupled with gene-expression profiling provides genetic evidence that the DLBCL subtypes are distinct diseases that use different oncogenic pathways.
Abstract: Gene-expression profiling has been used to define 3 molecular subtypes of diffuse large B-cell lymphoma (DLBCL), termed germinal center B-cell-like (GCB) DLBCL, activated B-cell-like (ABC) DLBCL, and primary mediastinal B-cell lymphoma (PMBL). To investigate whether these DLBCL subtypes arise by distinct pathogenetic mechanisms, we analyzed 203 DLBCL biopsy samples by high-resolution, genome-wide copy number analysis coupled with gene-expression profiling. Of 272 recurrent chromosomal aberrations that were associated with gene-expression alterations, 30 were used differentially by the DLBCL subtypes (P < 0.006). An amplicon on chromosome 19 was detected in 26% of ABC DLBCLs but in only 3% of GCB DLBCLs and PMBLs. A highly up-regulated gene in this amplicon was SPIB, which encodes an ETS family transcription factor. Knockdown of SPIB by RNA interference was toxic to ABC DLBCL cell lines but not to GCB DLBCL, PMBL, or myeloma cell lines, strongly implicating SPIB as an oncogene involved in the pathogenesis of ABC DLBCL. Deletion of the INK4a/ARF tumor suppressor locus and trisomy 3 also occurred almost exclusively in ABC DLBCLs and was associated with inferior outcome within this subtype. FOXP1 emerged as a potential oncogene in ABC DLBCL that was up-regulated by trisomy 3 and by more focal high-level amplifications. In GCB DLBCL, amplification of the oncogenic mir-17-92 microRNA cluster and deletion of the tumor suppressor PTEN were recurrent, but these events did not occur in ABC DLBCL. Together, these data provide genetic evidence that the DLBCL subtypes are distinct diseases that use different oncogenic pathways.
TL;DR: The results show that bilingualism exerts an influence in the attainment of efficient attentional mechanisms by young adults that are supposed to be at the peak of their attentional capabilities.
TL;DR: A consensus on a new definition, criteria for diagnosis and recommendations on HRS treatment was reached at the 56th Meeting of the American Association for the Study of Liver Diseases (AASLD) as mentioned in this paper.
Abstract: 34 and the only effective treatment is liver transplantation. During the 56th Meeting of the American Association for the Study of Liver Diseases, the International Ascites Club held a Focused Study Group (FSG) on HRS for the purpose of reporting the results of an international workshop and to reach a consensus on a new definition, criteria for diagnosis and recommendations on HRS treatment. A similar workshop was held in Chicago in 1994 in which standardised nomenclature and diagnostic criteria for refractory ascites and HRS were established. 5 The introduction of innovative treatments and improvements in our understanding of the pathogenesis of HRS during the previous decade led to an increasing need to undertake a new consensus meeting. This paper reports the scientific rationale behind the new definitions and recommendations.
TL;DR: It is demonstrated that CARD11 is a bona fide oncogenein DLBCL, providing a genetic rationale for the development of pharmacological inhibitors of the CARD11 pathway forDLBCL therapy.
Abstract: Diffuse large B cell lymphoma (DLBCL) is the most common form of non-Hodgkin's lymphoma. In the least curable (ABC) subtype of DLBCL, survival of the malignant cells is dependent on constitutive activation of the nuclear factor-kappaB (NF-kappaB) signaling pathway. In normal B cells, antigen receptor-induced NF-kappaB activation requires CARD11, a cytoplasmic scaffolding protein. To determine whether CARD11 contributes to tumorigenesis, we sequenced the CARD11 gene in human DLBCL tumors. We detected missense mutations in 7 of 73 ABC DLBCL biopsies (9.6%), all within exons encoding the coiled-coil domain. Experimental introduction of CARD11 coiled-coil domain mutants into lymphoma cell lines resulted in constitutive NF-kappaB activation and enhanced NF-kappaB activity upon antigen receptor stimulation. These results demonstrate that CARD11 is a bona fide oncogenein DLBCL, providing a genetic rationale for the development of pharmacological inhibitors of the CARD11 pathway for DLBCL therapy.
New York University1, J. Craig Venter Institute2, University of South Florida3, University of Maryland, Baltimore4, University of Maryland, College Park5, World Health Organization6, Burnet Institute7, University of Pennsylvania8, University of Barcelona9, Walter and Eliza Hall Institute of Medical Research10, Hood College11, Heidelberg University12, University of Queensland13, Emory University14, Macquarie University15, University of Melbourne16, University of São Paulo17, Centers for Disease Control and Prevention18
TL;DR: The synteny and isochore structure of P. vivax chromosomes are described, and it is shown that the parasite resembles other malaria parasites in gene content and metabolic potential, but possesses novel gene families and potential alternative invasion pathways not recognized previously.
Abstract: The human malaria parasite Plasmodium vivax is responsible for 25-40% of the approximately 515 million annual cases of malaria worldwide. Although seldom fatal, the parasite elicits severe and incapacitating clinical symptoms and often causes relapses months after a primary infection has cleared. Despite its importance as a major human pathogen, P. vivax is little studied because it cannot be propagated continuously in the laboratory except in non-human primates. We sequenced the genome of P. vivax to shed light on its distinctive biological features, and as a means to drive development of new drugs and vaccines. Here we describe the synteny and isochore structure of P. vivax chromosomes, and show that the parasite resembles other malaria parasites in gene content and metabolic potential, but possesses novel gene families and potential alternative invasion pathways not recognized previously. Completion of the P. vivax genome provides the scientific community with a valuable resource that can be used to advance investigation into this neglected species.
Journal Article•
TL;DR: European position paper on rhinosinusitis and nasal polyps 2007）是由欧洲变态反应和临床免疫学会
Abstract: 欧洲鼻-鼻窦炎鼻息肉诊疗意见书2007（European position paper on rhinosinusitis and nasal polyps 2007，EPOS 2007）是由欧洲变态反应和临床免疫学会在EPOS 2005的基础上修改而成的一个针对鼻窦炎鼻息肉的循征性诊疗意见书，发表在2007年鼻科学杂志上，同时该文被WHO发表的专业指导文献“完整的呼吸道（inter airway）”作为鼻-鼻窦炎和鼻息肉诊断和治疗的主要索引依据。其目的和主要内容为：①更新鼻-鼻窦炎和鼻息肉的部分概念；②对现有的诊断和治疗方案进行循证性系统评估；③提供临床诊断和阶梯性治疗的详细步骤和处理策略；③规范疗效评估方法。本袖珍版是在EPOS 2007全文的基础上对其主要内容进行高度概括，取其精华。由中山大学附属第一医院耳鼻咽喉科医院史剑波等教授翻译成中文（译者对袖珍版内容做了部分删节，如删节了“为基层和非耳鼻咽喉专科医生提供的成人急性鼻-鼻窦炎循证处理策略”，“为基层和非耳鼻咽喉专科医生提供的成人伴有和不伴有鼻息肉的慢性鼻-鼻窦炎循证处理策略”），并于2007年11月在桂林召开的全国慢性鼻-鼻窦炎诊治专家论坛上进行解读和讨论。刊出本文的目的是为了让国内读者及时了解欧洲对鼻-鼻窦炎鼻息肉诊断和治疗的最新进展，据此进一步规范国内对鼻-鼻窦炎鼻息肉的临床诊疗。此文的翻译和在本刊刊登已得到本“意见书”原作者Fokkens和Lund教授的授权。
University of Turin1, Mayo Clinic2, National and Kapodistrian University of Athens3, Harvard University4, University of Arkansas for Medical Sciences5, Wayne State University6, University of Bologna7, Cross Cancer Institute8, University of Tübingen9, Royal Prince Alfred Hospital10, Charité11, Catholic Medical Center12, University of Barcelona13, Lund University14, Cornell University15, Norwegian University of Science and Technology16, St James's University Hospital17, Emory University18, The Royal Marsden NHS Foundation Trust19, Cedars-Sinai Medical Center20, Erasmus University Rotterdam21, Cleveland Clinic22
TL;DR: This manuscript summarizes the available evidence and recommends a prophylaxis strategy according to a risk-assessment model for venous thromboembolism (VTE), and recommends low-molecular-weight heparin (LMWH), warfarin or aspirin.
Abstract: The incidence of venous thromboembolism (VTE) is more than 1%omicron annually in the general population and increases further in cancer patients. The risk of VTE is higher in multiple myeloma (MM) patients who receive thalidomide or lenalidomide, especially in combination with dexamethasone or chemotherapy. Various VTE prophylaxis strategies, such as low-molecular-Weight heparin (LMWH), warfarin or aspirin, have been investigated in small, uncontrolled clinical studies. This manuscript summarizes the available evidence and recommends a prophylaxis strategy according to a risk-assessment model. Individual risk factors for thrombosis associated with thalidomide/lenalidomide-based therapy include age, history of VTE, central venous catheter, comorbidities (infections, diabetes, cardiac disease), immobilization, surgery and inherited thrombophilia. Myeloma-related risk factors include diagnosis and hyperviscosity. VTE is very high in patients who receive high-dose dexamethasone, doxorubicin or multiagent chemotherapy in combination with thalidomide or lenalidomide, but not with bortezomib. The panel recommends aspirin for patients with <= 1 risk factor for VTE. LMWH (equivalent to enoxaparin 40 mg per day) is recommended for those with two or more individual/myeloma-related risk factors. LMWH is also recommended for all patients receiving concurrent high-dose dexamethasone or doxorubicin. Full-dose warfarin targeting a therapeutic INR of 2-3 is an alternative to LMWH, although there are limited data in the literature with this strategy. In the absence of clear data from randomized studies as a foundation for recommendations, many of the following proposed strategies are the results of common sense or derive from the extrapolation of data from many studies not specifically designed to answer these questions. Further investigation is needed to define the best VTE prophylaxis.
University of Rome Tor Vergata1, University of Edinburgh2, University of Michigan3, Leiden University4, King's College London5, Imperial College London6, University of Genoa7, St. Elizabeth's Medical Center8, University of London9, Dartmouth College10, National Jewish Health11, University of Barcelona12, Sapienza University of Rome13, University Hospitals Coventry and Warwickshire NHS Trust14, University of Florence15, Erasmus University Rotterdam16, University of Washington17, University College London18, Maastricht University19
TL;DR: The American Thoracic Society/European Respiratory Society jointly created a Task Force on “Outcomes for COPD pharmacological trials: from lung function to biomarkers” to inform the chronic obstructive pulmonary disease research community about the possible use and limitations of current outcomes and markers.
Abstract: The American Thoracic Society/European Respiratory Society jointly created a Task Force on "Outcomes for COPD pharmacological trials: from lung function to biomarkers" to inform the chronic obstructive pulmonary disease research community about the possible use and limitations of current outcomes and markers when evaluating the impact of a pharmacological therapy. Based on their review of the published literature, the following document has been prepared with individual sections that address specific outcomes and markers, and a final section that summarises their recommendations.
TL;DR: In this paper, mass mortality of at least 25 rocky benthic macro-invertebrate species (mainly gorgonians and sponges) was observed in the entire Northwestern (NW) Mediterranean region, affecting several thousand kilometers of coastline.
Abstract: Late in summer 2003, extensive mass mortality of at least 25 rocky benthic macro-invertebrate species (mainly gorgonians and sponges) was observed in the entire Northwestern (NW) Mediterranean region, affecting several thousand kilometers of coastline. We were able to characterize the mortality event by studying six areas covering the main regions of the NW Mediterranean basin. The degree of impact on each study area was quantified at 49 sites by estimating the proportion of colonies affected in populations of several gorgonian species compared with reference data obtained in years without mortality signs. According to these data, the western areas (Catalan coast and Balearic Islands) were the least affected, while the central areas (Provence coast and Corsica-Sardinia) showed a moderate impact. The northernmost and eastern areas (Gulf of Genoa and Gulf of Naples) displayed the highest impact, with almost 80% of gorgonian colonies affected. The heat wave of 2003 in Europe caused an anomalous warming of seawater, which reached the highest temperatures ever recorded in the studied regions, between 1 and 3 °C above the climatic values (mean and maximum). Because this exceptional warming was observed in the depth ranges most affected by the mortality, it seems likely that the 2003 anomalous temperature played a key role in the observed mortality event. A correlation analysis between temperature conditions and degree of impact seems to support this hypothesis. Under the present climate warming trend, new mass mortality events may occur in the near future, possibly driving a major biodiversity crisis in the Mediterranean Sea.
TL;DR: The physiological basis of crop yield and its response to stresses is highlighted, with special emphasis on drought, and ways to improve the efficiency of crop breeding through a better physiological understanding by both conventional and molecular methods are discussed.
Abstract: The need to accelerate breeding for increased yield potential and better adaptation to drought and other abiotic stresses is an issue of increasing urgency. As the population continues to grow rapidly, the pressure on resources (mainly untouched land and water) is also increasing, and potential climate change poses further challenges. We discuss ways to improve the efficiency of crop breeding through a better physiological understanding by both conventional and molecular methods. Thus the review highlights the physiological basis of crop yield and its response to stresses, with special emphasis on drought. This is not just because physiology forms the basis of proper phenotyping, one of the pillars of breeding, but because a full understanding of physiology is also needed, for example, to design the traits targeted by molecular breeding approaches such as marker-assisted selection (MAS) or plant transformation or the way these traits are evaluated. Most of the information in this review deals with cereals...
Stony Brook University1, University of New South Wales2, Georgetown University3, University of North Carolina at Chapel Hill4, Federal University of Rio de Janeiro5, Rockefeller University6, University of Toronto7, Emory University8, University of Barcelona9, University of Bonn10, Pierre-and-Marie-Curie University11, University of Paris12, Vita-Salute San Raffaele University13, Autonomous University of Barcelona14, Merck & Co.15
TL;DR: In HIV-infected patients with limited treatment options, raltegravir plus optimization background therapy provided better viral suppression than optimized background therapy alone for at least 48 weeks.
Abstract: Results In the combined studies, 699 of 703 randomized patients (462 and 237 in the raltegravir and placebo groups, respectively) received the study drug. Seventeen of the 699 patients (2.4%) discontinued the study before week 16. Discontinuation was related to the study treatment in 13 of these 17 patients: 7 of the 462 raltegravir recipients (1.5%) and 6 of the 237 placebo recipients (2.5%). The results of the two studies were consistent. At week 16, counting noncompletion as treatment failure, 355 of 458 raltegravir recipients (77.5%) had HIV-1 RNA levels below 400 copies per milliliter, as compared with 99 of 236 placebo recipients (41.9%, P<0.001). Suppression of HIV-1 RNA to a level below 50 copies per milliliter was achieved at week 16 in 61.8% of the raltegravir recipients, as compared with 34.7% of placebo recipients, and at week 48 in 62.1% as compared with 32.9% (P<0.001 for both comparisons). Without adjustment for the length of follow-up, cancers were detect ed in 3.5% of raltegravir recipients and in 1.7% of placebo recipients. The overall frequencies of drug-related adverse events were similar in the raltegravir and placebo groups. Conclusions In HIV-infected patients with limited treatment options, raltegravir plus optimized background therapy provided better viral suppression than optimized background therapy alone for at least 48 weeks. (ClinicalTrials.gov numbers, NCT00293267 and NCT00293254.)
TL;DR: In this article, a review of studies on post-fire plant regeneration and soil losses in the Mediterranean basin is presented, which suggests that although many Mediterranean ecosystems are highly resilient to fire, some are fire-sensitive (e.g. pine woodlands).
Abstract: Evolutionary and paleoecological studies suggest that fires are natural in the Mediterranean basin. However, the important increase in the number of fires and area burned during the 20th century has created the perception that fires are disasters. In the present paper, we review to what extent fires are generating ecological disasters in the Mediterranean basin, in view of current fire regimes and the long-term human pressure on the landscapes. Specifically, we review studies on post-fire plant regeneration and soil losses. The review suggests that although many Mediterranean ecosystems are highly resilient to fire (shrublands and oak forest), some are fire-sensitive (e.g. pine woodlands). Observed erosion rates are, in some cases, relatively high, especially in high fire severity conditions. The sensitive ecosystems (in the sense of showing strong post-fire vegetation changes and soil losses) are mostly of human origin (e.g. extensive pine plantations in old fields). Thus, although many Mediterranean basin plants have traits to cope with fire, a large number of the ecosystems currently found in this region are strongly altered, and may suffer disasters. Post-fire disasters are not the rule, but they may be important under conditions of previous human disturbances.
TL;DR: The most important control schemes for the parallel operation of UPS systems, including active load-sharing techniques and droop control approaches, are depicted.
Abstract: In the last years, the use of distributed uninterruptible power supply (UPS) systems has been growing into the market, becoming an alternative to large conventional UPS systems. In addition, with the increasing interest in renewable energy integration and distributed generation, distributed UPS systems can be a suitable solution for storage energy in micro grids. This paper depicts the most important control schemes for the parallel operation of UPS systems. Active load-sharing techniques and droop control approaches are described. The recent improvements and variants of these control techniques are presented.
TL;DR: The results show that subjects can rapidly master the authors' asynchronous EEG-based BCI to control a wheelchair and can autonomously operate the BCI over long periods of time without the need for adaptive algorithms externally tuned by a human operator to minimize the impact of EEG non-stationarities.
University of Edinburgh1, University of Cambridge2, University of Kiel3, University of Greifswald4, German Cancer Research Center5, University of Barcelona6, Cancer Research UK7, Technion – Israel Institute of Technology8, University of Michigan9, University of Tokyo10, University of Ottawa11, Ontario Institute for Cancer Research12, Cancer Care Ontario13, University of Toronto14, McGill University15
TL;DR: Findings extend the understanding of the role of common genetic variation in CRC etiology by identifying a previously unreported association, rs3802842 on 11q23, and carrying all six possible risk alleles yielded OR = 2.6 (95% CI = 1.75–3.89) for CRC.
Abstract: In a genome-wide association study to identify loci associated with colorectal cancer (CRC) risk, we genotyped 555,510 SNPs in 1,012 early-onset Scottish CRC cases and 1,012 controls (phase 1). In phase 2, we genotyped the 15,008 highest-ranked SNPs in 2,057 Scottish cases and 2,111 controls. We then genotyped the five highest-ranked SNPs from the joint phase 1 and 2 analysis in 14,500 cases and 13,294 controls from seven populations, and identified a previously unreported association, rs3802842 on 11q23 (OR = 1.1; P = 5.8 x 10(-10)), showing population differences in risk. We also replicated and fine-mapped associations at 8q24 (rs7014346; OR = 1.19; P = 8.6 x 10(-26)) and 18q21 (rs4939827; OR = 1.2; P = 7.8 x 10(-28)). Risk was greater for rectal than for colon cancer for rs3802842 (P < 0.008) and rs4939827 (P < 0.009). Carrying all six possible risk alleles yielded OR = 2.6 (95% CI = 1.75-3.89) for CRC. These findings extend our understanding of the role of common genetic variation in CRC etiology.
University of Silesia in Katowice1, South Tees Hospitals NHS Trust2, Charles University in Prague3, Aarhus University4, University of Barcelona5, Hospital Italiano de Buenos Aires6, University of Alberta7, University of Pennsylvania8, Pierre-and-Marie-Curie University9, University of Freiburg10, Eli Lilly and Company11, Scripps Research Institute12
TL;DR: Neither facilitation of PCI with reteplase plus abcximab nor facilitation with abciximab alone significantly improved the clinical outcomes, as compared with ab ciximabs given at the time of PCI, in patients with ST-segment elevation myocardial infarction.
Abstract: In this international, double-blind, placebo-controlled study, we randomly assigned patients with ST-segment elevation myocardial infarction who presented 6 hours or less after the onset of symptoms to receive combination-facilitated PCI, abciximabfacilitated PCI, or primary PCI. All patients received unfractionated heparin or enoxaparin before PCI and a 12-hour infusion of abciximab after PCI. The primary end point was the composite of death from all causes, ventricular fibrillation occurring more than 48 hours after randomization, cardiogenic shock, and congestive heart failure during the first 90 days after randomization. Results A total of 2452 patients were randomly assigned to a treatment group. Significantly more patients had early ST-segment resolution with combination-facilitated PCI (43.9%) than with abciximab-facilitated PCI (33.1%) or primary PCI (31.0%; P = 0.01 and P = 0.003, respectively). The primary end point occurred in 9.8%, 10.5%, and 10.7% of the patients in the combination-facilitated PCI group, abciximab-facilitated PCI group, and primary-PCI group, respectively (P = 0.55); 90-day mortality rates were 5.2%, 5.5%, and 4.5%, respectively (P = 0.49). Conclusions Neither facilitation of PCI with reteplase plus abciximab nor facilitation with abciximab alone significantly improved the clinical outcomes, as compared with abciximab given at the time of PCI, in patients with ST-segment elevation myocardial infarction. (ClinicalTrials.gov number, NCT00046228.)