Showing papers by "Charles University in Prague published in 2013"
Katholieke Universiteit Leuven1, Gdańsk Medical University2, University of Valencia3, Zamorano4, Ghent University5, Charles University in Prague6, University of Glasgow7, University of Naples Federico II8, University Medical Center Utrecht9, Linköping University10, University of Birmingham11, University of Oslo12, Lund University13, Complutense University of Madrid14, University of Erlangen-Nuremberg15, John Radcliffe Hospital16, Tallinn University of Technology17, University of Lausanne18
TL;DR: 2007 Guidelines for the Management of Arterial Hypertension : The Task Force for the management of Arterspertension of the European Society ofhypertension (ESH) and of theEuropean Society of Cardiology (ESC).
Abstract: Because of new evidence on several diagnostic and therapeutic aspects of hypertension, the present guidelines differ in many respects from the previous ones. Some of the most important differences are listed below:
1. Epidemiological data on hypertension and BP control in Europe.
2. Strengthening of the prognostic value of home blood pressure monitoring (HBPM) and of its role for diagnosis and management of hypertension, next to ambulatory blood pressure monitoring (ABPM).
3. Update of the prognostic significance of night-time BP, white-coat hypertension and masked hypertension.
4. Re-emphasis on integration of BP, cardiovascular (CV) risk factors, asymptomatic organ damage (OD) and clinical complications for total CV risk assessment.
5. Update of the prognostic significance of asymptomatic OD, including heart, blood vessels, kidney, eye and brain.
6. Reconsideration of the risk of overweight and target body mass index (BMI) in hypertension.
7. Hypertension in young people.
8. Initiation of antihypertensive treatment. More evidence-based criteria and no drug treatment of high normal BP.
9. Target BP for treatment. More evidence-based criteria and unified target systolic blood pressure (SBP) (<140 mmHg) in both higher and lower CV risk patients.
10. Liberal approach to initial monotherapy, without any all-ranking purpose.
11. Revised schema for priorital two-drug combinations.
12. New therapeutic algorithms for achieving target BP.
13. Extended section on therapeutic strategies in special conditions.
14. Revised recommendations on treatment of hypertension in the elderly.
15. Drug treatment of octogenarians.
16. Special attention to resistant hypertension and new treatment approaches.
17. Increased attention to OD-guided therapy.
18. New approaches to chronic management of hypertensive disease
7,018 citations
University of Tennessee1, Centre national de la recherche scientifique2, International Union for Conservation of Nature and Natural Resources3, Swedish University of Agricultural Sciences4, Missouri Botanical Garden5, University of Paris-Sud6, University of Girona7, Institut national de la recherche agronomique8, Charles University in Prague9, Academy of Sciences of the Czech Republic10, University of Porto11, University of Minho12, Paul Sabatier University13, Spanish National Research Council14
TL;DR: Recent progress in understanding invasion impacts and management is highlighted, and the challenges that the discipline faces in its science and interactions with society are discussed.
Abstract: Study of the impacts of biological invasions, a pervasive component of global change, has generated remarkable understanding of the mechanisms and consequences of the spread of introduced populations. The growing field of invasion science, poised at a crossroads where ecology, social sciences, resource management, and public perception meet, is increasingly exposed to critical scrutiny from several perspectives. Although the rate of biological invasions, elucidation of their consequences, and knowledge about mitigation are growing rapidly, the very need for invasion science is disputed. Here, we highlight recent progress in understanding invasion impacts and management, and discuss the challenges that the discipline faces in its science and interactions with society.
2,346 citations
TL;DR: The aims are to bridge the gap between clinical and tissue-based diagnosis, to improve management and provide a common reference point for future registries and multicentre randomised controlled trials of aetiology-driven treatment in inflammatory heart muscle disease.
Abstract: In this position statement of the ESC Working Group on Myocardial and Pericardial Diseases an expert consensus group reviews the current knowledge on clinical presentation, diagnosis and treatment of myocarditis, and proposes new diagnostic criteria for clinically suspected myocarditis and its distinct biopsy-proven pathogenetic forms. The aims are to bridge the gap between clinical and tissue-based diagnosis, to improve management and provide a common reference point for future registries and multicentre randomised controlled trials of aetiology-driven treatment in inflammatory heart muscle disease.
2,265 citations
University of California, San Diego1, University of Western Ontario2, Katholieke Universiteit Leuven3, University of Chicago4, Icahn School of Medicine at Mount Sinai5, Lille University of Science and Technology6, Charles University in Prague7, University of Alberta8, University of Washington9, University of British Columbia10, Millennium Pharmaceuticals11
TL;DR: Vedolizumab-treated patients with active Crohn's disease were more likely than patients receiving placebo to have a remission, but not a CDAI-100 response, at week 6; patients with a response to induction therapy who continued to receive vedolIZumab (rather than switching to placebo) were morelikely to be in remission at week 52.
Abstract: BackgroundUstekinumab, a monoclonal antibody to the p40 subunit of interleukin-12 and interleukin-23, was evaluated as an intravenous induction therapy in two populations with moderately to severely active Crohn’s disease. Ustekinumab was also evaluated as subcutaneous maintenance therapy. MethodsWe randomly assigned patients to receive a single intravenous dose of ustekinumab (either 130 mg or approximately 6 mg per kilogram of body weight) or placebo in two induction trials. The UNITI-1 trial included 741 patients who met the criteria for primary or secondary nonresponse to tumor necrosis factor (TNF) antagonists or had unacceptable side effects. The UNITI-2 trial included 628 patients in whom conventional therapy failed or unacceptable side effects occurred. Patients who completed these induction trials then participated in IM-UNITI, in which the 397 patients who had a response to ustekinumab were randomly assigned to receive subcutaneous maintenance injections of 90 mg of ustekinumab (either every 8 w...
2,059 citations
Clinical Trial Service Unit1, Glasgow Caledonian University2, Institut Gustave Roussy3, All India Institute of Medical Sciences4, Cairo University5, Monash University6, Queen's University Belfast7, University of Newcastle8, Tehran University of Medical Sciences9, Kaohsiung Medical University10, Tel Aviv Sourasky Medical Center11, Tata Memorial Hospital12, Charles University in Prague13, Cancer Institute14
TL;DR: Treatment allocation seemed to have no effect on breast cancer outcome among 1248 women with ER-negative disease, and an intermediate effect among 4800 women with unknown ER status, and a further reduction in recurrence and mortality, particularly after year 10.
1,637 citations
TL;DR: The European Association of Urology (EAU) guidelines on non-muscle-invasive bladder cancer (NMIBC) were published in 2013 and the levels of evidence and grades of recommendation were assigned.
1,608 citations
Katholieke Universiteit Leuven1, Gdańsk Medical University2, University of Valencia3, Ghent University4, Charles University in Prague5, University of Glasgow6, University of Naples Federico II7, Utrecht University8, Linköping University9, University of Münster10, University of Oslo11, Complutense University of Madrid12, University of Erlangen-Nuremberg13, John Radcliffe Hospital14, Tallinn University of Technology15, University of Lausanne16
TL;DR: The 2013 European Society of Hypertension/European Society of Cardiology (ESH/ESC) guidelines continue to adhere to some fundamental principles that inspired the 2003 and 2007 guidelines, namely to base recommendations on properly conducted studies identified from an ext
Abstract: 1. INTRODUCTION1.1 PrinciplesThe 2013 European Society of Hypertension/European Society of Cardiology (ESH/ESC) guidelines continue to adhere to some fundamental principles that inspired the 2003 and 2007 guidelines, namely to base recommendations on properly conducted studies identified from an ext
1,139 citations
TL;DR: Riociguat significantly improved exercise capacity and pulmonary vascular resistance in patients with chronic thromboembolic pulmonary hypertension.
Abstract: BACKGROUND Riociguat, a member of a new class of compounds (soluble guanylate cyclase stim ulators), has been shown in previous clinical studies to be beneficial in the treat ment of chronic thromboembolic pulmonary hypertension. METHODS In this phase 3, multicenter, randomized, double-blind, placebo-controlled study, we randomly assigned 261 patients with inoperable chronic thromboembolic pul monary hypertension or persistent or recurrent pulmonary hypertension after pul monary endarterectomy to receive placebo or riociguat. The primary end point was the change from baseline to the end of week 16 in the distance walked in 6 minutes. Secondary end points included changes from baseline in pulmonary vascular resis tance, N-terminal pro–brain natriuretic peptide (NT-proBNP) level, World Health Organization (WHO) functional class, time to clinical worsening, Borg dyspnea score, quality-of-life variables, and safety. RESULTS By week 16, the 6-minute walk distance had increased by a mean of 39 m in the riociguat group, as compared with a mean decrease of 6 m in the placebo group (least-squares mean difference, 46 m; 95% confidence interval [CI], 25 to 67; P<0.001). Pulmonary vascular resistance decreased by 226 dyn · sec · cm –5 in the riociguat group and increased by 23 dyn · sec · cm –5 in the placebo group (least-squares mean difference, –246 dyn · sec · cm –5 ; 95% CI, –303 to –190; P<0.001). Riociguat was also associated with significant improvements in the NT-proBNP level (P<0.001) and WHO functional class (P = 0.003). The most common serious adverse events were right ventricular failure (in 3% of patients in each group) and syncope (in 2% of the riociguat group and in 3% of the placebo group). CONCLUSIONS Riociguat significantly improved exercise capacity and pulmonary vascular re sistance in patients with chronic thromboembolic pulmonary hypertension. (Funded by Bayer HealthCare; CHEST-1 and CHEST-2 ClinicalTrials.gov numbers, NCT00855465 and NCT00910429, respectively.)
1,065 citations
TL;DR: The Electric and Magnetic Field Instrument and Integrated Science (EMFISIS) investigation on the NASA Radiation Belt Storm Probes (now named the Van Allen Probes) mission provides key wave and very low frequency magnetic field measurements to understand radiation belt acceleration, loss, and transport.
Abstract: The Electric and Magnetic Field Instrument and Integrated Science (EMFISIS) investigation on the NASA Radiation Belt Storm Probes (now named the Van Allen Probes) mission provides key wave and very low frequency magnetic field measurements to understand radiation belt acceleration, loss, and transport. The key science objectives and the contribution that EMFISIS makes to providing measurements as well as theory and modeling are described. The key components of the instruments suite, both electronics and sensors, including key functional parameters, calibration, and performance, demonstrate that EMFISIS provides the needed measurements for the science of the RBSP mission. The EMFISIS operational modes and data products, along with online availability and data tools provide the radiation belt science community with one the most complete sets of data ever collected.
1,060 citations
TL;DR: Eleven evidence-based recommendations for the non-pharmacological core management of hip and knee OA were developed, concerning the following nine topics: assessment, general approach, patient information and education, lifestyle changes, exercise, weight loss, assistive technology and adaptations, footwear and work.
Abstract: The objective was to develop evidence -based recommendations and a research and educational agenda for the non-pharmacological management of hip and knee osteoarthritis (OA). The multidisciplinary task force comprised 21 experts: nurses, occupational therapists, physiotherapists, rheumatologists, orthopaedic surgeons, general practitioner, psychologist, dietician, clinical epidemiologist and patient representatives. After a preliminary literature review, a first task force meeting and five Delphi rounds, provisional recommendations were formulated in order to perform a systematic review. A literature search of Medline and eight other databases was performed up to February 2012. Evidence was graded in categories I-IV and agreement with the recommendations was determined through scores from 0 (total disagreement) to 10 (total agreement). Eleven evidence-based recommendations for the non-pharmacological core management of hip and knee OA were developed, concerning the following nine topics: assessment, general approach, patient information and education, lifestyle changes, exercise, weight loss, assistive technology and adaptations, footwear and work. The average level of agreement ranged between 8.0 and 9.1. The proposed research agenda included an overall need for more research into non-pharmacological interventions for hip OA, moderators to optimise individualised treatment, healthy lifestyle with economic evaluation and long-term follow-up, and the prevention and reduction of work disability. Proposed educational activities included the required skills to teach, initiate and establish lifestyle changes. The 11 recommendations provide guidance on the delivery of non-pharmacological interventions to people with hip or knee OA. More research and educational activities are needed, particularly in the area of lifestyle changes.
1,029 citations
TL;DR: The classification working group of the International Society of Urological Pathology consensus conference on renal neoplasia was in charge of making recommendations regarding additions and changes to the current World Health Organization Classification of Renal Tumors, with consensus that 5 entities should be recognized as new distinct epithelial tumors within the classification system.
Abstract: The classification working group of the International Society of Urological Pathology consensus conference on renal neoplasia was in charge of making recommendations regarding additions and changes to the current World Health Organization Classification of Renal Tumors (2004). Members of the group performed an exhaustive literature review, assessed the results of the preconference survey and participated in the consensus conference discussion and polling activities. On the basis of the above inputs, there was consensus that 5 entities should be recognized as new distinct epithelial tumors within the classification system: tubulocystic renal cell carcinoma (RCC), acquired cystic disease-associated RCC, clear cell (tubulo) papillary RCC, the MiT family translocation RCCs (in particular t(6;11) RCC), and hereditary leiomyomatosis RCC syndrome-associated RCC. In addition, there are 3 rare carcinomas that were considered as emerging or provisional new entities: thyroid-like follicular RCC; succinate dehydrogenase B deficiency-associated RCC; and ALK translocation RCC. Further reports of these entities are required to better understand the nature and behavior of these highly unusual tumors. There were a number of new concepts and suggested modifications to the existing World Health Organization 2004 categories. Within the clear cell RCC group, it was agreed upon that multicystic clear cell RCC is best considered as a neoplasm of low malignant potential. There was agreement that subtyping of papillary RCC is of value and that the oncocytic variant of papillary RCC should not be considered as a distinct entity. The hybrid oncocytic chromophobe tumor, which is an indolent tumor that occurs in 3 settings, namely Birt-Hogg-Dube Syndrome, renal oncocytosis, and as a sporadic neoplasm, was placed, for the time being, within the chromophobe RCC category. Recent advances related to collecting duct carcinoma, renal medullary carcinoma, and mucinous spindle cell and tubular RCC were elucidated. Outside of the epithelial category, advances in our understanding of angiomyolipoma, including the epithelioid and epithelial cystic variants, were considered. In addition, the apparent relationship between cystic nephroma and mixed epithelial and stromal tumor was discussed, with the consensus that these tumors form a spectrum of neoplasia. Finally, it was thought that the synovial sarcoma should be removed from the mixed epithelial and mesenchymal category and placed within the sarcoma group. The new classification is to be referred to as the International Society of Urological Pathology Vancouver Classification of Renal Neoplasia.
TL;DR: The Cherenkov Telescope Array (CTA) as discussed by the authors is a very high-energy (VHE) gamma ray observatory with an international collaboration with more than 1000 members from 27 countries in Europe, Asia, Africa and North and South America.
TL;DR: Cangrelor significantly reduced the rate of ischemic events, including stent thrombosis, during PCI, with no significant increase in severe bleeding.
Abstract: Background The intensity of antiplatelet therapy during percutaneous coronary intervention (PCI) is an important determinant of PCI-related ischemic complications. Cangrelor is a potent intravenous adenosine diphosphate (ADP)–receptor antagonist that acts rapidly and has quickly reversible effects. Methods In a double-blind, placebo-controlled trial, we randomly assigned 11,145 patients who were undergoing either urgent or elective PCI and were receiving guideline-recommended therapy to receive a bolus and infusion of cangrelor or to receive a loading dose of 600 mg or 300 mg of clopidogrel. The primary efficacy end point was a composite of death, myocardial infarction, ischemia-driven revascularization, or stent thrombosis at 48 hours after randomization; the key secondary end point was stent thrombosis at 48 hours. The primary safety end point was severe bleeding at 48 hours. Results The rate of the primary efficacy end point was 4.7% in the cangrelor group and 5.9% in the clopidogrel group (adjusted od...
TL;DR: It is shown that not only are the search queries and the prices connected but there also exists a pronounced asymmetry between the effect of an increased interest in the currency while being above or below its trend value.
Abstract: Digital currencies have emerged as a new fascinating phenomenon in the financial markets. Recent events on the most popular of the digital currencies – BitCoin – have risen crucial questions about behavior of its exchange rates and they offer a field to study dynamics of the market which consists practically only of speculative traders with no fundamentalists as there is no fundamental value to the currency. In the paper, we connect two phenomena of the latest years – digital currencies, namely BitCoin, and search queries on Google Trends and Wikipedia – and study their relationship. We show that not only are the search queries and the prices connected but there also exists a pronounced asymmetry between the effect of an increased interest in the currency while being above or below its trend value.
TL;DR: In this paper, the results of the four LEP experiments were combined to determine fundamental properties of the W boson and the electroweak theory, including the branching fraction of W and the trilinear gauge-boson self-couplings.
TL;DR: In this article, a detailed description of the analysis used by the CMS Collaboration in the search for the standard model Higgs boson in pp collisions at the LHC, which led to the observation of a new boson.
Abstract: A detailed description is reported of the analysis used by the CMS Collaboration in the search for the standard model Higgs boson in pp collisions at the LHC, which led to the observation of a new boson. The data sample corresponds to integrated luminosities up to 5.1 inverse femtobarns at sqrt(s) = 7 TeV, and up to 5.3 inverse femtobarns at sqrt(s) = 8 TeV. The results for five Higgs boson decay modes gamma gamma, ZZ, WW, tau tau, and bb, which show a combined local significance of 5 standard deviations near 125 GeV, are reviewed. A fit to the invariant mass of the two high resolution channels, gamma gamma and ZZ to 4 ell, gives a mass estimate of 125.3 +/- 0.4 (stat) +/- 0.5 (syst) GeV. The measurements are interpreted in the context of the standard model Lagrangian for the scalar Higgs field interacting with fermions and vector bosons. The measured values of the corresponding couplings are compared to the standard model predictions. The hypothesis of custodial symmetry is tested through the measurement of the ratio of the couplings to the W and Z bosons. All the results are consistent, within their uncertainties, with the expectations for a standard model Higgs boson.
TL;DR: In this review, attention is paid to metallothioneins as small, cysteine-rich and heavy metal-binding proteins, which participate in an array of protective stress responses, which plays a key role in regulation of zinc levels and distribution in the intracellular space.
Abstract: Free radicals are chemical particles containing one or more unpaired electrons, which may be part of the molecule. They cause the molecule to become highly reactive. The free radicals are also known to play a dual role in biological systems, as they can be either beneficial or harmful for living systems. It is clear that there are numerous mechanisms participating on the protection of a cell against free radicals. In this review, our attention is paid to metallothioneins (MTs) as small, cysteine-rich and heavy metal-binding proteins, which participate in an array of protective stress responses. The mechanism of the reaction of metallothioneins with oxidants and electrophilic compounds is discussed. Numerous reports indicate that MT protects cells from exposure to oxidants and electrophiles, which react readily with sulfhydryl groups. Moreover, MT plays a key role in regulation of zinc levels and distribution in the intracellular space. The connections between zinc, MT and cancer are highlighted.
TL;DR: In a study of Y(4260) → π+ π- J/φ decays, a structure is observed in the M(π(±)J/ψ) mass spectrum with 5.2σ significance that can be interpreted as a new charged charmoniumlike state.
Abstract: The cross section for ee+ e- → π+ π- J/ψ between 3.8 and 5.5 GeV is measured with a 967 fb(-1) data sample collected by the Belle detector at or near the Υ(nS) (n = 1,2,…,5) resonances. The Y(4260) state is observed, and its resonance parameters are determined. In addition, an excess of π+ π- J/ψ production around 4 GeV is observed. This feature can be described by a Breit-Wigner parametrization with properties that are consistent with the Y(4008) state that was previously reported by Belle. In a study of Y(4260) → π+ π- J/ψ decays, a structure is observed in the M(π(±)J/ψ) mass spectrum with 5.2σ significance, with mass M = (3894.5 ± 6.6 ± 4.5) MeV/c2 and width Γ = (63 ± 24 ± 26) MeV/c2, where the errors are statistical and systematic, respectively. This structure can be interpreted as a new charged charmoniumlike state.
Brown University1, Université catholique de Louvain2, Scott & White Hospital3, University of Pittsburgh4, University of Paris5, François Rabelais University6, Tufts University7, Mercy Health Partners8, Charles University in Prague9, München Klinik Bogenhausen10, China Medical University (Taiwan)11, Ghent University12, Keio University13, University of Miami14, University of Nebraska Medical Center15, Eisai16, Memorial Hospital of Rhode Island17, Université libre de Bruxelles18
TL;DR: Among patients with severe sepsis, the use of eritoran, compared with placebo, did not result in reduced 28-day mortality, and no significant differences were observed in any of the prespecified subgroups.
Abstract: Importance Eritoran is a synthetic lipid A antagonist that blocks lipopolysaccharide (LPS) from binding at the cell surface MD2-TLR4 receptor. LPS is a major component of the outer membrane of gram-negative bacteria and is a potent activator of the acute inflammatory response. Objective To determine if eritoran, a TLR4 antagonist, would significantly reduce sepsis-induced mortality. Design, Setting, and Participants We performed a randomized, double-blind, placebo-controlled, multinational phase 3 trial in 197 intensive care units. Patients were enrolled from June 2006 to September 2010 and final follow-up was completed in September 2011. Interventions Patients with severe sepsis (n = 1961) were randomized and treated within 12 hours of onset of first organ dysfunction in a 2:1 ratio with a 6-day course of either eritoran tetrasodium (105 mg total) or placebo, with n = 1304 and n = 657 patients, respectively. Main Outcome Measures The primary end point was 28-day all-cause mortality. The secondary end points were all-cause mortality at 3, 6, and 12 months after beginning treatment. Results Baseline characteristics of the 2 study groups were similar. In the modified intent-to-treat analysis (randomized patients who received at least 1 dose) there was no significant difference in the primary end point of 28-day all-cause mortality with 28.1% (366/1304) in the eritoran group vs 26.9% (177/657) in the placebo group (P = .59; hazard ratio, 1.05; 95% CI, 0.88-1.26; difference in mortality rate, −1.1; 95% CI, −5.3 to 3.1) or in the key secondary end point of 1-year all-cause mortality with 44.1% (290/657) in the eritoran group vs 43.3% (565/1304) in the placebo group, Kaplan-Meier analysis of time to death by 1 year, P = .79 (hazard ratio, 0.98; 0.85-1.13). No significant differences were observed in any of the prespecified subgroups. Adverse events, including secondary infection rates, did not differ between study groups. Conclusions and Relevance Among patients with severe sepsis, the use of eritoran, compared with placebo, did not result in reduced 28-day mortality. Trial Registration clinicaltrials.gov Identifier: NCT00334828
TL;DR: In this paper, the spin and parity quantum numbers of the Higgs boson were studied based on the collision data collected by the ATLAS experiment at the LHC, and the results showed that the standard model spin-parity J(...
TL;DR: In this paper, two-particle angular correlations for charged particles emitted in pPb collisions at a nucleon-nucleon center-of-mass energy of 5.02 TeV are presented.
Charité1, Linköping University2, Athens State University3, French Institute of Health and Medical Research4, Medical University of Łódź5, University Clinical Hospital Mostar6, University of Lisbon7, University of Graz8, Alexandria University9, Charles University in Prague10, Lithuanian University of Health Sciences11, Semmelweis University12, University of Brescia13
TL;DR: To evaluate how recommendations of European guidelines regarding pharmacological and non‐pharmacological treatments for heart failure are adopted in clinical practice, a large number of patients with HF are receiving treatment according to these guidelines.
Abstract: AimsTo evaluate how recommendations of European guidelines regarding pharmacological and non-pharmacological treatments for heart failure (HF) are adopted in clinical practice.Methods and resultsThe ESC-HF Long-Term Registry is a prospective, observational study conducted in 211 Cardiology Centres of 21 European and Mediterranean countries, members of the European Society of Cardiology (ESC). From May 2011 to April 2013, a total of 12 440 patients were enrolled, 40.5% with acute HF and 59.5% with chronic HF. Intravenous treatments for acute HF were heterogeneously administered, irrespective of guideline recommendations. In chronic HF, with reduced EF, renin-angiotensin system (RAS) blockers, beta-blockers, and mineralocorticoid antagonists (MRAs) were used in 92.2, 92.7, and 67.0% of patients, respectively. When reasons for non-adherence were considered, the real rate of undertreatment accounted for 3.2, 2.3, and 5.4% of the cases, respectively. About 30% of patients received the target dosage of these drugs, but a documented reason for not achieving the target dosage was reported in almost two-thirds of them. The more relevant reasons for non-implantation of a device, when clinically indicated, were related to doctor uncertainties on the indication, patient refusal, or logistical/cost issues.ConclusionThis pan-European registry shows that, while in patients with acute HF, a large heterogeneity of treatments exists, drug treatment of chronic HF can be considered largely adherent to recommendations of current guidelines, when the reasons for non-adherence are taken into account. Observations regarding the real possibility to adhere fully to current guidelines in daily clinical practice should be seriously considered when clinical practice guidelines have to be written. © 2013 Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2013. For permissions please email: journals.permissions@oup.com
TL;DR: Among patients with NSTE acute coronary syndromes who were scheduled to undergo catheterization, pretreatment with prasugrel did not reduce the rate of major ischemic events up to 30 days but increased the rates of major bleeding complications.
Abstract: BACKGROUND: Although P2Y12 antagonists are effective in patients with non-ST-segment elevation (NSTE) acute coronary syndromes, the effect of the timing of administration--before or after coronary angiography--is not known. We evaluated the effect of administering the P2Y12 antagonist prasugrel at the time of diagnosis versus administering it after the coronary angiography if percutaneous coronary intervention (PCI) was indicated. METHODS: We enrolled 4033 patients with NSTE acute coronary syndromes and a positive troponin level who were scheduled to undergo coronary angiography within 2 to 48 hours after randomization. Patients were randomly assigned to receive prasugrel (a 30-mg loading dose) before the angiography (pretreatment group) or placebo (control group). When PCI was indicated, an additional 30 mg of prasugrel was given in the pretreatment group at the time of PCI and 60 mg of prasugrel was given in the control group. RESULTS: The rate of the primary efficacy end point, a composite of death from cardiovascular causes, myocardial infarction, stroke, urgent revascularization, or glycoprotein IIb/IIIa inhibitor rescue therapy (glycoprotein IIb/IIIa bailout) through day 7, did not differ significantly between the two groups (hazard ratio with pretreatment, 1.02; 95% confidence interval [CI], 0.84 to 1.25; P=0.81). The rate of the key safety end point of all Thrombolysis in Myocardial Infarction (TIMI) major bleeding episodes, whether related or not related to coronary-artery bypass grafting (CABG), through day 7 was increased with pretreatment (hazard ratio, 1.90; 95% CI, 1.19 to 3.02; P=0.006). The rates of TIMI major bleeding and life-threatening bleeding not related to CABG were increased by a factor of 3 and 6, respectively. Pretreatment did not reduce the rate of the primary outcome among patients undergoing PCI (69% of the patients) but increased the rate of TIMI major bleeding at 7 days. All the results were confirmed at 30 days and in prespecified subgroups. CONCLUSIONS: Among patients with NSTE acute coronary syndromes who were scheduled to undergo catheterization, pretreatment with prasugrel did not reduce the rate of major ischemic events up to 30 days but increased the rate of major bleeding complications. (Funded by Daiichi Sankyo and Eli Lilly; ACCOAST ClinicalTrials.gov number, NCT01015287.).
TL;DR: In this article, the production properties and couplings of the recently discovered Higgs boson using the decays into boson pairs were measured using the complete pp collision data sample recorded by the ATLAS experiment at the CERN Large Hadron Collider at centre-of-mass energies of 7 TeV and 8 TeV, corresponding to an integrated luminosity of about 25/fb.
TL;DR: In this article, the luminosity calibration for the ATLAS detector at the LHC during pp collisions at root s = 7 TeV in 2010 and 2011 is presented, and a luminosity uncertainty of delta L/L = +/- 3.5 % is obtained.
Abstract: The luminosity calibration for the ATLAS detector at the LHC during pp collisions at root s = 7 TeV in 2010 and 2011 is presented. Evaluation of the luminosity scale is performed using several luminosity-sensitive detectors, and comparisons are made of the long-term stability and accuracy of this calibration applied to the pp collisions at root s = 7 TeV. A luminosity uncertainty of delta L/L = +/- 3.5 % is obtained for the 47 pb(-1) of data delivered to ATLAS in 2010, and an uncertainty of delta L/L = +/- 1.8 % is obtained for the 5.5 fb(-1) delivered in 2011.
TL;DR: This review summarizes literature data on mechanisms involved in the immobilization process and presents results from laboratory and field experiments, including the subsequent influence on higher plants and aided phytostabilization, evaluating the stability of the oxide-based amendments in the treated soils and their efficiency in the long-term.
TL;DR: Recent work has identified cell‐type‐specific inhibitory and excitatory interactions, the dichotomy between neuronal firing and the non‐local measurement of local field potentials distant to that firing, and the reflection of the neuronal dark matter problem in non‐firing neurons active in seizures.
Abstract: Epilepsy has been historically seen as a functional brain disorder associated with excessive synchronization of large neuronal populations leading to a hypersynchronous state. Recent evidence showed that epileptiform phenomena, particularly seizures, result from complex interactions between neuronal networks characterized by heterogeneity of neuronal firing and dynamical evolution of synchronization. Desynchronization is often observed preceding seizures or during their early stages; in contrast, high levels of synchronization observed towards the end of seizures may facilitate termination. In this review we discuss cellular and network mechanisms responsible for such complex changes in synchronization. Recent work has identified cell-type-specific inhibitory and excitatory interactions, the dichotomy between neuronal firing and the non-local measurement of local field potentials distant to that firing, and the reflection of the neuronal dark matter problem in non-firing neurons active in seizures. These recent advances have challenged long-established views and are leading to a more rigorous and realistic understanding of the pathophysiology of epilepsy.
TL;DR: Two-particle correlations in relative azimuthal angle and pseudorapidity are measured using the ATLAS detector at the LHC and the resultant Δø correlation is approximately symmetric about π/2, and is consistent with a dominant cos2Δø modulation for all ΣE(T)(Pb) ranges and particle p(T).
Abstract: Two-particle correlations in relative azimuthal angle (Delta phi) and pseudorapidity (Delta eta) are measured in root S-NN = 5.02 TeV p + Pb collisions using the ATLAS detector at the LHC. The measurements are performed using approximately 1 mu b(-1) of data as a function of transverse momentum (p(T)) and the transverse energy (Sigma E-T(Pb)) summed over 3.1 < eta < 4.9 in the direction of the Pb beam. The correlation function, constructed from charged particles, exhibits a long-range (2 < vertical bar Delta eta vertical bar < 5) "near-side" (Delta phi similar to 0) correlation that grows rapidly with increasing Sigma E-T(Pb). A long-range "away-side" (Delta phi similar to pi) correlation, obtained by subtracting the expected contributions from recoiling dijets and other sources estimated using events with small Sigma E-T(Pb), is found to match the near-side correlation in magnitude, shape (in Delta eta and Delta phi) and Sigma E-T(Pb) dependence. The resultant Delta phi correlation is approximately symmetric about pi/2, and is consistent with a dominant cos2 Delta phi modulation for all Sigma E-T(Pb) ranges and particle p(T).
International Agency for Research on Cancer1, National Health Service2, University of Oxford3, Imperial College London4, University of Surrey5, Royal Surrey County Hospital6, Erasmus University Rotterdam7, Leeds Teaching Hospitals NHS Trust8, University of Dundee9, Stavanger University Hospital10, University of Zagreb11, Mario Negri Institute for Pharmacological Research12, Karolinska Institutet13, German Cancer Research Center14, University of Oslo15, Queen Mary University of London16, Peking Union Medical College17, American Cancer Society18, University of Amsterdam19, FH Joanneum20, University of Burgundy21, University of Ljubljana22, University of Vermont23, National Cancer Research Institute24, University of Caen Lower Normandy25, Catholic University of Korea26, St George's Hospital27, University of Latvia28, Oregon Health & Science University29, University of Copenhagen30, GlaxoSmithKline31, Centers for Disease Control and Prevention32, University of North Carolina at Chapel Hill33, Ruhr University Bochum34, Institute of Oncology Ljubljana35, Cancer Care Ontario36, University of Toronto37, University of Coimbra38, University of Chicago39, University Hospitals Coventry and Warwickshire NHS Trust40, Charles University in Prague41, Katholieke Universiteit Leuven42, University of Miami43, Niigata University44, Memorial Sloan Kettering Cancer Center45, Flinders University46
TL;DR: An overview of the principles, recommendations and standards in the guidelines for quality assurance in CRC screening and diagnosis are presented in journal format in an open-access Supplement of Endoscopy.
Abstract: Population-based screening for early detection and treatment of colorectal cancer (CRC) and precursor lesions, using evidence-based methods, can be effective in populations with a significant burden of the disease provided the services are of high quality. Multidisciplinary, evidence-based guidelines for quality assurance in CRC screening and diagnosis have been developed by experts in a project co-financed by the European Union. The 450-page guidelines were published in book format by the European Commission in 2010. They include 10 chapters and over 250 recommendations, individually graded according to the strength of the recommendation and the supporting evidence. Adoption of the recommendations can improve and maintain the quality and effectiveness of an entire screening process, including identification and invitation of the target population, diagnosis and management of the disease and appropriate surveillance in people with detected lesions. To make the principles, recommendations and standards in the guidelines known to a wider professional and scientific community and to facilitate their use in the scientific literature, the original content is presented in journal format in an open-access Supplement of Endoscopy. The editors have prepared the present overview to inform readers of the comprehensive scope and content of the guidelines.
TL;DR: Exome sequencing of zona glomerulosa–like APAs identifies nine with somatic mutations in either ATP1A1, encoding the Na+/K+ ATPase α1 subunit, or CACNA1D, encoding Cav1.3, which caused inward leak currents under physiological conditions and induced a shift of voltage-dependent gating to more negative voltages, suppressed inactivation or increased currents.
Abstract: At least 5% of individuals with hypertension have adrenal aldosterone-producing adenomas (APAs). Gain-of-function mutations in KCNJ5 and apparent loss-of-function mutations in ATP1A1 and ATP2A3 were reported to occur in APAs. We find that KCNJ5 mutations are common in APAs resembling cortisol-secreting cells of the adrenal zona fasciculata but are absent in a subset of APAs resembling the aldosterone-secreting cells of the adrenal zona glomerulosa. We performed exome sequencing of ten zona glomerulosa-like APAs and identified nine with somatic mutations in either ATP1A1, encoding the Na(+)/K(+) ATPase α1 subunit, or CACNA1D, encoding Cav1.3. The ATP1A1 mutations all caused inward leak currents under physiological conditions, and the CACNA1D mutations induced a shift of voltage-dependent gating to more negative voltages, suppressed inactivation or increased currents. Many APAs with these mutations were <1 cm in diameter and had been overlooked on conventional adrenal imaging. Recognition of the distinct genotype and phenotype for this subset of APAs could facilitate diagnosis.