Showing papers by "University of Barcelona published in 2009"
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TL;DR: Version 5 implements a number of new features and analytical methods allowing extensive DNA polymorphism analyses on large datasets, including visualizing sliding window results integrated with available genome annotations in the UCSC browser.
Abstract: Motivation: DnaSP is a software package for a comprehensive analysis of DNA polymorphism data. Version 5 implements a number of new features and analytical methods allowing extensive DNA polymorphism analyses on large datasets. Among other features, the newly implemented methods allow for: (i) analyses on multiple data files; (ii) haplotype phasing; (iii) analyses on insertion/deletion polymorphism data; (iv) visualizing sliding window results integrated with available genome annotations in the UCSC browser.
Availability: Freely available to academic users from: http://www.ub.edu/dnasp
Contact: [email protected]
13,511 citations
TL;DR: In this paper, a review of the electrochemical methods used at lab and pilot plant scale to decontaminate synthetic and real effluents containing dyes, considering the period from 2009 to 2013, as an update of our previous review up to 2008.
Abstract: As the environment preservation gradually becomes a matter of major social concern and more strict legislation is being imposed on effluent discharge, more effective processes are required to deal with non-readily biodegradable and toxic pollutants. Synthetic organic dyes in industrial effluents cannot be destroyed in conventional wastewater treatment and consequently, an urgent challenge is the development of new environmentally benign technologies able to mineralize completely these non-biodegradable compounds. This review aims to increase the knowledge on the electrochemical methods used at lab and pilot plant scale to decontaminate synthetic and real effluents containing dyes, considering the period from 2009 to 2013, as an update of our previous review up to 2008. Fundamentals and main applications of electrochemical advanced oxidation processes and the other electrochemical approaches are described. Typical methods such as electrocoagulation, electrochemical reduction, electrochemical oxidation and indirect electro-oxidation with active chlorine species are discussed. Recent advances on electrocatalysis related to the nature of anode material to generate strong heterogeneous OH as mediated oxidant of dyes in electrochemical oxidation are extensively examined. The fast destruction of dyestuffs mediated with electrogenerated active chlorine is analyzed. Electro-Fenton and photo-assisted electrochemical methods like photoelectrocatalysis and photoelectro-Fenton, which destroy dyes by heterogeneous OH and/or homogeneous OH produced in the solution bulk, are described. Current advantages of the exposition of effluents to sunlight in the emerging photo-assisted procedures of solar photoelectrocatalysis and solar photoelectro-Fenton are detailed. The characteristics of novel combined methods involving photocatalysis, adsorption, nanofiltration, microwaves and ultrasounds among others and the use of microbial fuel cells are finally discussed.
3,112 citations
TL;DR: Electro-Fenton (EF) Process 6585 4.2.1.
Abstract: 2.2. Fenton’s Chemistry 6575 2.2.1. Origins 6575 2.2.2. Fenton Process 6575 2.3. Photo-Fenton Process 6577 3. H2O2 Electrogeneration for Water Treatment 6577 3.1. Fundamentals 6578 3.2. Cathode Materials 6579 3.3. Divided Cells 6580 3.4. Undivided Cells 6583 4. Electro-Fenton (EF) Process 6585 4.1. Origins 6585 4.2. Fundamentals of EF for Water Remediation 6586 4.2.1. Cell Configuration 6586 4.2.2. Cathodic Fe2+ Regeneration 6586 4.2.3. Anodic Generation of Heterogeneous Hydroxyl Radical 6587
2,652 citations
TL;DR: It is reported that angiogenesis inhibitors targeting the VEGF pathway demonstrate antitumor effects in mouse models of pancreatic neuroendocrine carcinoma and glioblastoma but concomitantly elicit tumor adaptation and progression to stages of greater malignancy, with heightened invasiveness and in some cases increased lymphatic and distant metastasis.
2,303 citations
TL;DR: Observations suggest that harnessing the anti-inflammatory properties of Treg cells to inhibit elements of the metabolic syndrome may have therapeutic potential.
Abstract: Obesity is accompanied by chronic, low-grade inflammation of adipose tissue, which promotes insulin resistance and type-2 diabetes. These findings raise the question of how fat inflammation can escape the powerful armamentarium of cells and molecules normally responsible for guarding against a runaway immune response. CD4(+) Foxp3(+) T regulatory (T(reg)) cells with a unique phenotype were highly enriched in the abdominal fat of normal mice, but their numbers were strikingly and specifically reduced at this site in insulin-resistant models of obesity. Loss-of-function and gain-of-function experiments revealed that these T(reg) cells influenced the inflammatory state of adipose tissue and, thus, insulin resistance. Cytokines differentially synthesized by fat-resident regulatory and conventional T cells directly affected the synthesis of inflammatory mediators and glucose uptake by cultured adipocytes. These observations suggest that harnessing the anti-inflammatory properties of T(reg) cells to inhibit elements of the metabolic syndrome may have therapeutic potential.
1,823 citations
TL;DR: It is argued that when both PI and Psi occur, participants will respond realistically to the virtual reality.
Abstract: In this paper, I address the question as to why participants tend to respond realistically to situations and events portrayed within an immersive virtual reality system. The idea is put forward, based on the experience of a large number of experimental studies, that there are two orthogonal components that contribute to this realistic response. The first is ‘being there’, often called ‘presence’, the qualia of having a sensation of being in a real place. We call this place illusion (PI). Second, plausibility illusion (Psi) refers to the illusion that the scenario being depicted is actually occurring. In the case of both PI and Psi the participant knows for sure that they are not ‘there’ and that the events are not occurring. PI is constrained by the sensorimotor contingencies afforded by the virtual reality system. Psi is determined by the extent to which the system can produce events that directly relate to the participant, the overall credibility of the scenario being depicted in comparison with expectations. We argue that when both PI and Psi occur, participants will respond realistically to the virtual reality.
1,456 citations
TL;DR: Liraglutide once a day provided significantly greater improvements in glycaemic control than did exenatide twice a day, and was generally better tolerated, suggesting that liragLutide might be a treatment option for type 2 diabetes, especially when weight loss and risk of hypoglycaemia are major considerations.
1,414 citations
TL;DR: In this paper, a scaled mass index (SMI) based on the central principle of scaling has been proposed to measure the relative size of energy reserves and other body components of an animal.
Abstract: Body condition is assumed to influence an animal’s health and fitness. Various non-destructive methods based on body mass and a measure of body length have been used as condition indices (CIs), but the dominant method amongst ecologists is currently the calculation of residuals from an ordinary least squares (OLS) regression of body mass against length. Recent studies of energy reserves in small mammals and starlings claimed to validate this method, although we argue that they did not include the most appropriate tests since they compared the CI with the absolute size of energy reserves. We present a novel CI (the ‘scaled mass index’) based on the central principle of scaling, with important methodological, biological and conceptual advantages. Through a reanalysis of data from small mammals, starlings and snakes, we show that the scaled mass index is a better indicator of the relative size of energy reserves and other body components than OLS residuals, performing better in all seven species and in 19 out of 20 analyses. We also present an empirical and theoretical comparison of the scaled mass index and OLS residuals as CIs. We argue that the scaled mass index is a useful new tool for ecologists.
1,358 citations
TL;DR: Although the data are inconclusive about any possible effect on myocardial infarction, rosiglitazone does not increase the risk of overall cardiovascular morbidity or mortality compared with standard glucose-lowering drugs.
1,308 citations
University of Porto1, The Catholic University of America2, Sheba Medical Center3, Rambam Health Care Campus4, University of Palermo5, Boston Children's Hospital6, University College Dublin7, University of Barcelona8, Western General Hospital9, Guy's and St Thomas' NHS Foundation Trust10, McMaster University11, Université de Montréal12, Mount Sinai Hospital13
TL;DR: The treatment of inflammatory bowel disease has been revolutionised over the past decade by the increasing use of immunomodulators, mainly azathioprine/6-mercaptopurine and methotrexate, together with the advent of biological therapy.
1,150 citations
TL;DR: This review summarizes current views on the pathogenesis of myoglobin-induced kidney injury as well as on its prevention and treatment.
Abstract: The causes of acute rhabdomyolysis include trauma, drugs, toxins, and certain infections. Acute kidney injury is a dangerous complication of severe rhabdomyolysis. This review summarizes current views on the pathogenesis of myoglobin-induced kidney injury as well as on its prevention and treatment.
TL;DR: These unexpected findings demonstrate that although the leader cell may have a pivotal role in local cell guidance, physical forces that it generates are but a small part of a global tug-of-war involving cells well back from the leading edge.
Abstract: It has been thought that sheets of cells move by traction forces exerted by the cells at the leading edge of the sheet. Using traction microscopy to create a map of physical forces, it is now shown that in fact it is cells many rows from the front that do most of the work. Fundamental biological processes including morphogenesis, tissue repair and tumour metastasis require collective cell motions1,2,3, and to drive these motions cells exert traction forces on their surroundings4. Current understanding emphasizes that these traction forces arise mainly in ‘leader cells’ at the front edge of the advancing cell sheet5,6,7,8,9. Our data are contrary to that assumption and show for the first time by direct measurement that traction forces driving collective cell migration arise predominately many cell rows behind the leading front edge and extend across enormous distances. Traction fluctuations are anomalous, moreover, exhibiting broad non-Gaussian distributions characterized by exponential tails10,11,12. Taken together, these unexpected findings demonstrate that although the leader cell may have a pivotal role in local cell guidance, physical forces that it generates are but a small part of a global tug-of-war involving cells well back from the leading edge.
TL;DR: Use of noninvasive techniques for diagnosis, new methods and strategies for prevention, and, finally, the efficacy of monotherapy and de-escalation in the treatment of VAP are discussed.
Abstract: Purpose of reviewVentilator-associated pneumonia (VAP) is the main nosocomial infection in patients receiving mechanical ventilation. Despite numerous advances in the understanding of this disorder, the incidence rate continues in an unacceptable range. In this review, we discuss some important find
TL;DR: This review summarizes what is understood about naturally acquired and experimentally induced immunity against malaria with the help of evolving insights provided by biotechnology and places these insights in the context of historical, clinical, and epidemiological observations.
Abstract: Naturally acquired immunity to falciparum malaria protects millions of people routinely exposed to Plasmodium falciparum infection from severe disease and death. There is no clear concept about how this protection works. There is no general agreement about the rate of onset of acquired immunity or what constitutes the key determinants of protection; much less is there a consensus regarding the mechanism(s) of protection. This review summarizes what is understood about naturally acquired and experimentally induced immunity against malaria with the help of evolving insights provided by biotechnology and places these insights in the context of historical, clinical, and epidemiological observations. We advocate that naturally acquired immunity should be appreciated as being virtually 100% effective against severe disease and death among heavily exposed adults. Even the immunity that occurs in exposed infants may exceed 90% effectiveness. The induction of an adult-like immune status among high-risk infants in sub-Saharan Africa would greatly diminish disease and death caused by P. falciparum. The mechanism of naturally acquired immunity that occurs among adults living in areas of hyper- to holoendemicity should be understood with a view toward duplicating such protection in infants and young children in areas of endemicity.
TL;DR: Fpocket provides a rapid, open source and stable basis for further developments related to protein pocket detection, efficient pocket descriptor extraction, or drugablity prediction purposes.
Abstract: Virtual screening methods start to be well established as effective approaches to identify hits, candidates and leads for drug discovery research. Among those, structure based virtual screening (SBVS) approaches aim at docking collections of small compounds in the target structure to identify potent compounds. For SBVS, the identification of candidate pockets in protein structures is a key feature, and the recent years have seen increasing interest in developing methods for pocket and cavity detection on protein surfaces.
University of Milano-Bicocca1, University of Paris2, University of Brescia3, University of Bologna4, University of Lausanne5, Queen Mary University of London6, Ghent University7, University of Barcelona8, University of Glasgow9, Istanbul University10, Katholieke Universiteit Leuven11, Hannover Medical School12, University of Manchester13, University of Oslo14, Joseph Fourier University15, Gdańsk Medical University16, University of Copenhagen17, University of Münster18, University of Valencia19, Complutense University of Madrid20, University of Erlangen-Nuremberg21, Maastricht University22, University of Amsterdam23, University of Milan24
TL;DR: The objective of this study was to establish a baseline for the design of a systematic literature review of this type of treatment for high blood pressure using a simple, straightforward, and scalable procedure.
Abstract: Abbreviations ACE: angiotensin-converting enzyme; BP: blood pressure; DBP: diastolic blood pressure; eGFR: estimated glomerular filtration rate; ESC: European Society of Cardiology; ESH: European Society of Hypertension; ET: endothelin; IMT: carotid intima-media thickness; JNC: Joint National Commit
Columbia University1, University of Miami2, University of North Carolina at Chapel Hill3, SUNY Downstate Medical Center4, University College London5, Cambridge University Hospitals NHS Foundation Trust6, University of California, San Francisco7, University of California, Los Angeles8, University of Alabama at Birmingham9, Rio de Janeiro State University10, University of Guadalajara11, University of Düsseldorf12, New York University13, University of Barcelona14, Shanghai Jiao Tong University15, University of Lisbon16, Stellenbosch University17, Guy's and St Thomas' NHS Foundation Trust18, Oregon Health & Science University19, University of Padua20, University of Leeds21, North Shore-LIJ Health System22, Northwestern University23, Medical University of South Carolina24, University of Birmingham25, Sun Yat-sen University26, Lille University of Science and Technology27, Charité28, Rutgers University29, Federal University of São Paulo30, University of Debrecen31, Imperial College London32, Emory University33, University of Liège34, University of Pittsburgh35, University of Paris36, University of the Witwatersrand37, California State University, Long Beach38, Royal Melbourne Hospital39, University of Texas Southwestern Medical Center40, Autonomous University of Barcelona41, Pennsylvania State University42, Johns Hopkins University43, University of Szeged44, Duke University45, University of Colorado Denver46, Harvard University47, University of Cape Town48, University of Malaya49, Peking Union Medical College50
TL;DR: Although most patients in both treatment groups experienced clinical improvement, the study did not meet its primary objective of showing that MMF was superior to IVC as induction treatment for lupus nephritis.
Abstract: Recent studies have suggested that mycophenolate mofetil (MMF) may offer advantages over intravenous cyclophosphamide (IVC) for the treatment of lupus nephritis, but these therapies have not been compared in an international randomized, controlled trial. Here, we report the comparison of MMF and IVC as induction treatment for active lupus nephritis in a multinational, two-phase (induction and maintenance) study. We randomly assigned 370 patients with classes III through V lupus nephritis to open-label MMF (target dosage 3 g/d) or IVC (0.5 to 1.0 g/m(2) in monthly pulses) in a 24-wk induction study. Both groups received prednisone, tapered from a maximum starting dosage of 60 mg/d. The primary end point was a prespecified decrease in urine protein/creatinine ratio and stabilization or improvement in serum creatinine. Secondary end points included complete renal remission, systemic disease activity and damage, and safety. Overall, we did not detect a significantly different response rate between the two groups: 104 (56.2%) of 185 patients responded to MMF compared with 98 (53.0%) of 185 to IVC. Secondary end points were also similar between treatment groups. There were nine deaths in the MMF group and five in the IVC group. We did not detect significant differences between the MMF and IVC groups with regard to rates of adverse events, serious adverse events, or infections. Although most patients in both treatment groups experienced clinical improvement, the study did not meet its primary objective of showing that MMF was superior to IVC as induction treatment for lupus nephritis.
University of Oxford1, University of Paris2, University of Barcelona3, Southend University Hospital NHS Foundation Trust4, University of Zurich5, University of Groningen6, Boston University7, Norfolk and Norwich University Hospital8, Lund University9, Food and Drug Administration10, Istanbul University11
TL;DR: On the basis of evidence and expert consensus, recommendations have been made for the evaluation, investigation, treatment and monitoring of patients with small and medium vessel vasculitis for use in everyday clinical practice.
Abstract: Objectives: To develop European League Against Rheumatism (EULAR) recommendations for the management of small and medium vessel vasculitis. Methods: An expert group (consisting of 10 rheumatologists, 3 nephrologists, 2 immunologists, 2 internists representing 8 European countries and the USA, a clinical epidemiologist and a representative from a drug regulatory agency) identified 10 topics for a systematic literature search using a modified Delphi technique. In accordance with standardised EULAR operating procedures, recommendations were derived for the management of small and medium vessel vasculitis. In the absence of evidence, recommendations were formulated on the basis of a consensus opinion. Results: In all, 15 recommendations were made for the management of small and medium vessel vasculitis. The strength of recommendations was restricted by low quality of evidence and by EULAR standardised operating procedures. Conclusions: On the basis of evidence and expert consensus, recommendations have been made for the evaluation, investigation, treatment and monitoring of patients with small and medium vessel vasculitis for use in everyday clinical practice.
TL;DR: The magnetocaloric effects of Ni-Mn-based Heusler alloys are surveyed and their relation with the magnetic shape-memory and magnetic superelasticity reported in these materials are discussed.
Abstract: Magnetic Heusler alloys which undergo a martensitic transition display interesting functional properties. In the present review, we survey the magnetocaloric effects of Ni-Mn-based Heusler alloys and discuss their relation with the magnetic shape-memory and magnetic superelasticity reported in these materials. We show that all these effects are a consequence of a strong coupling between structure and magnetism which enables a magnetic field to rearrange martensitic variants as well as to provide the possibility to induce the martensitic transition. These two features are respectively controlled by the magnetic anisotropy of the martensitic phase and by the difference in magnetic moments between the structural phases. The relevance of each of these contributions to the magnetocaloric properties is analysed.
TL;DR: The results of the present meta-analysis indicate that child sexual abuse is a serious problem in the countries analysed, and an overall international figure is established in order to establish an Overall international figure.
TL;DR: Findings in the field of mitochondrial dynamics in mammalian cells and their implication in human pathologies have established mitochondrial dynamics as a consolidated area in cellular physiology.
Abstract: The meaning of the word mitochondrion (from the Greek mitos, meaning thread, and chondros, grain) illustrates that the heterogeneity of mitochondrial morphology has been known since the first descriptions of this organelle. Such a heterogeneous morphology is explained by the dynamic nature of mitochondria. Mitochondrial dynamics is a concept that includes the movement of mitochondria along the cytoskeleton, the regulation of mitochondrial architecture (morphology and distribution), and connectivity mediated by tethering and fusion/fission events. The relevance of these events in mitochondrial and cell physiology has been partially unraveled after the identification of the genes responsible for mitochondrial fusion and fission. Furthermore, during the last decade, it has been identified that mutations in two mitochondrial fusion genes (MFN2 and OPA1) cause prevalent neurodegenerative diseases (Charcot-Marie Tooth type 2A and Kjer disease/autosomal dominant optic atrophy). In addition, other diseases such as type 2 diabetes or vascular proliferative disorders show impaired MFN2 expression. Altogether, these findings have established mitochondrial dynamics as a consolidated area in cellular physiology. Here we review the most significant findings in the field of mitochondrial dynamics in mammalian cells and their implication in human pathologies.
TL;DR: The identification of those athletes at increased risk may be a salient first step before designing and implementing specific pre-season and in-season training programs aimed to modify the identified risk factors and to decrease ACL injury rates.
Abstract: Soccer is the most commonly played sport in the world, with an estimated 265 million active soccer players by 2006. Inherent to this sport is the higher risk of injury to the anterior cruciate ligament (ACL) relative to other sports. ACL injury causes the most time lost from competition in soccer which has influenced a strong research focus to determine the risk factors for injury. This research emphasis has afforded a rapid influx of literature defining potential modifiable and non-modifiable risk factors that increase the risk of injury. The purpose of the current review is to sequence the most recent literature that reports potential mechanisms and risk factors for non-contact ACL injury in soccer players. Most ACL tears in soccer players are non-contact in nature. Common playing situations precluding a non-contact ACL injury include: change of direction or cutting maneuvers combined with deceleration, landing from a jump in or near full extension, and pivoting with knee near full extension and a planted foot. The most common non-contact ACL injury mechanism include a deceleration task with high knee internal extension torque (with or without perturbation) combined with dynamic valgus rotation with the body weight shifted over the injured leg and the plantar surface of the foot fixed flat on the playing surface. Potential extrinsic non-contact ACL injury risk factors include: dry weather and surface, and artificial surface instead of natural grass. Commonly purported intrinsic risk factors include: generalized and specific knee joint laxity, small and narrow intercondylar notch width (ratio of notch width to the diameter and cross sectional area of the ACL), pre-ovulatory phase of menstrual cycle in females not using oral contraceptives, decreased relative (to quadriceps) hamstring strength and recruitment, muscular fatigue by altering neuromuscular control, decreased “core” strength and proprioception, low trunk, hip, and knee flexion angles, and high dorsiflexion of the ankle when performing sport tasks, lateral trunk displacement and hip adduction combined with increased knee abduction moments (dynamic knee valgus), and increased hip internal rotation and tibial external rotation with or without foot pronation. The identified mechanisms and risk factors for non-contact ACL injuries have been mainly studied in female soccer players; thus, further research in male players is warranted. Non-contact ACL injuries in soccer players likely has a multi-factorial etiology. The identification of those athletes at increased risk may be a salient first step before designing and implementing specific pre-season and in-season training programs aimed to modify the identified risk factors and to decrease ACL injury rates. Current evidence indicates that this crucial step to prevent ACL injury is the only option to effectively prevent the sequelae of osteoarthritis associated with this traumatic injury.
TL;DR: This review discusses recently identified information about renal failure in cirrhosis and clinical interventions that may assist in the prevention and management of this complication.
Abstract: Renal failure, a challenging complication of cirrhosis, is one of the most important risk factors for liver transplantation. In recent years, substantial progress has been made toward understanding the pathogenesis and natural history of renal failure in cirrhosis. This review discusses recently identified information about renal failure in cirrhosis and clinical interventions that may assist in the prevention and management of this complication.
University of Barcelona1, Guy's and St Thomas' NHS Foundation Trust2, Sheba Medical Center3, University of Copenhagen4, University of Debrecen5, University of Milan6, Utrecht University7, Sofia Medical University8, University of Pisa9, Université catholique de Louvain10, Dresden University of Technology11, Pierre-and-Marie-Curie University12
TL;DR: Patients with APS still develop significant morbidity and mortality despite current treatment, and it is imperative to increase the efforts in determining optimal prognostic markers and therapeutic measures to prevent these complications.
Abstract: Objectives: To identify the main causes of morbidity and mortality in patients with antiphospholipid syndrome (APS) during a 5-year period and to determine clinical and immunological parameters with prognostic significance. Methods: The clinical and immunological features of a cohort of 1000 patients with APS from 13 European countries who had been followed up from 1999 to 2004 were analysed. Results: 200 (20%) patients developed APS-related manifestations during the 5-year study period. Recurrent thrombotic events appeared in 166 (16.6%) patients and the most common were strokes (2.4% of the total cohort), transient ischaemic attacks (2.3%), deep vein thromboses (2.1%) and pulmonary embolism (2.1%). When the thrombotic events occurred, 90 patients were receiving oral anticoagulants and 49 were using aspirin. 31/420 (7.4%) patients receiving oral anticoagulants presented with haemorrhage. 3/121 (2.5%) women with only obstetric APS manifestations at the start of the study developed a new thrombotic event. A total of 77 women (9.4% of the female patients) had one or more pregnancies and 63 (81.8% of pregnant patients) had one or more live births. The most common fetal complications were early pregnancy loss (17.1% of pregnancies) and premature birth (35% of live births). 53 (5.3% of the total cohort) patients died. The most common causes of death were bacterial infection (21% of deaths), myocardial infarction (19%) and stroke (13%). No clinical or immunological predictor of thrombotic events, pregnancy morbidity or mortality was detected. Conclusion: Patients with APS still develop significant morbidity and mortality despite current treatment (oral anticoagulants or antiaggregants, or both).
TL;DR: The clinical and immunological features of a novel autoantigen related to limbic encephalitis and the effect of patients' antibodies on neuronal cultures are reported.
Abstract: Background
Limbic encephalitis (LE) frequently associates with antibodies to cell surface antigens. Characterization of these antigens is important because it facilitates the diagnosis of those disorders that are treatment-responsive. We report a novel antigen of LE and the effect of patients' antibodies on neuronal cultures.
TL;DR: The results reveal that when the task at hand recruits a good deal of monitoring resources, bilinguals outperform monolinguals and suggests that bilingualism may affect the monitoring processes involved in executive control.
Johns Hopkins University1, Paris Descartes University2, University of Barcelona3, University of Colorado Denver4, University of Pennsylvania5, University of Chicago6, University of Alberta Hospital7, University of Cambridge8, Vanderbilt University Medical Center9, Stanford University10, University of Giessen11, Virginia Commonwealth University12, University of California, San Diego13, University of Paris-Sud14
TL;DR: An overview of specific inflammatory pathways involving cells, chemokines and cytokines, cellular dysfunctions, growth factors, and viral proteins is provided, highlighting their potential role in pulmonary vascular remodeling and the possibility of future targeted therapy.
University of Manchester1, University of Leeds2, University of Washington3, Leeds Teaching Hospitals NHS Trust4, Université libre de Bruxelles5, Mater Dei Hospital6, Boston Children's Hospital7, University of Paris8, University of Göttingen9, Mount Sinai St. Luke's and Mount Sinai Roosevelt10, University of Barcelona11, Radboud University Nijmegen12, University of Oslo13, Royal Children's Hospital14, VU University Amsterdam15, Katholieke Universiteit Leuven16, University of São Paulo17, Rabin Medical Center18, University of British Columbia19, Technion – Israel Institute of Technology20, Baylor College of Medicine21, University of Melbourne22, Children's National Medical Center23, Ealing Hospital24, Imperial College London25
TL;DR: Mutations in SAMHD1 are described as the cause of Aicardi-Goutières syndrome at the AGS5 locus and data is presented to show that SAM HD1 may act as a negative regulator of the cell-intrinsic antiviral response.
Abstract: Aicardi-Goutieres syndrome is a mendelian mimic of congenital infection and also shows overlap with systemic lupus erythematosus at both a clinical and biochemical level The recent identification of mutations in TREX1 and genes encoding the RNASEH2 complex and studies of the function of TREX1 in DNA metabolism have defined a previously unknown mechanism for the initiation of autoimmunity by interferon-stimulatory nucleic acid Here we describe mutations in SAMHD1 as the cause of AGS at the AGS5 locus and present data to show that SAMHD1 may act as a negative regulator of the cell-intrinsic antiviral response
TL;DR: This Review critically examines what is known about P vivax, focusing on identifying the crucial gaps that create obstacles to the elimination of this parasite in human populations.
Abstract: Summary Plasmodium vivax is geographically the most widely distributed cause of malaria in people, with up to 2·5 billion people at risk and an estimated 80 million to 300 million clinical cases every year—including severe disease and death. Despite this large burden of disease, P vivax is overlooked and left in the shadow of the enormous problem caused by Plasmodium falciparum in sub-Saharan Africa. The technological advances enabling the sequencing of the P vivax genome and a recent call for worldwide malaria eradication have together placed new emphasis on the importance of addressing P vivax as a major public health problem. However, because of this parasite's biology, it is especially difficult to interrupt the transmission of P vivax , and experts agree that the available methods for preventing and treating infections with P vivax are inadequate. It is thus imperative that the development of new methods and strategies become a priority. Advancing the development of such methods needs renewed emphasis on understanding the biology, pathogenesis, and epidemiology of P vivax . This Review critically examines what is known about P vivax , focusing on identifying the crucial gaps that create obstacles to the elimination of this parasite in human populations.
University of Nebraska Medical Center1, Carlos III Health Institute2, University of Oxford3, University of Oslo4, Oregon Health & Science University5, National Institutes of Health6, University of British Columbia7, University of Würzburg8, Bosch9, University of Arizona10, University of Barcelona11, Emory University12
TL;DR: A new algorithm using GCET1, CD10, BCL6, MUM1, and FOXP1 was derived that closely approximated the GEP classification with 93% concordance and will facilitate risk stratification of DLBCL patients and futureDLBCL research using archival materials.
Abstract: Purpose: Hans and coworkers previously developed an immunohistochemical algorithm with ∼80% concordance with the gene expression profiling (GEP) classification of diffuse large B-cell lymphoma (DLBCL) into the germinal center B-cell–like (GCB) and activated B-cell–like (ABC) subtypes. Since then, new antibodies specific to germinal center B-cells have been developed, which might improve the performance of an immunostain algorithm. Experimental Design: We studied 84 cases of cyclophosphamide-doxorubicin-vincristine-prednisone (CHOP)–treated DLBCL (47 GCB, 37 ABC) with GCET1, CD10, BCL6, MUM1, FOXP1, BCL2, MTA3, and cyclin D2 immunostains, and compared different combinations of the immunostaining results with the GEP classification. A perturbation analysis was also applied to eliminate the possible effects of interobserver or intraobserver variations. A separate set of 63 DLBCL cases treated with rituximab plus CHOP (37 GCB, 26 ABC) was used to validate the new algorithm. Results: A new algorithm using GCET1, CD10, BCL6, MUM1, and FOXP1 was derived that closely approximated the GEP classification with 93% concordance. Perturbation analysis indicated that the algorithm was robust within the range of observer variance. The new algorithm predicted 3-year overall survival of the validation set [GCB (87%) versus ABC (44%); P Conclusion: Our new algorithm is significantly more accurate than the Hans9 algorithm and will facilitate risk stratification of DLBCL patients and future DLBCL research using archival materials. (Clin Cancer Res 2009;15(17):5494–502)