207 research outputs found
Dissolved organic carbon transformations and microbial community response to variations in recharge waters in a shallow carbonate aquifer
- Author
- A Baker
- A Huguet
- AJ Lawaetz
- Alexandre M. Anesio
- B Cottrell
- C Stedmon
- CA Stedmon
- CA Stedmon
- CL Muller
- Darren M. Reynolds
- DF Levia
- DF Levia
- DF Levia
- DM McKnight
- E Graber
- Emma L. Evans
- FF Whitaker
- FF Whitaker
- FF Whitaker
- FF Whitaker
- FF Whitaker
- FF Whitaker
- Fiona F. Whitaker
- G Guggenberger
- GJ Avery
- H Ciglasch
- IC Wilhartitz
- J Helms
- J Hur
- J Jin
- J Weishaar
- JA Korak
- JD Gulley
- JE Birdwell
- JL Carew
- Katherine J. Cooper
- KS Simon
- M Baker
- M Pronk
- M Sanchez
- Miranda Naish
- MS Twardowski
- N Hudson
- P Milne
- PG Coble
- PR Salve
- PSM Santos
- PSM Santos
- R Cant
- S Determann
- SC Pryor
- T Ohno
- T Shabarova
- T Shabarova
- WKL Cammack
- Y Chin
- Y Zhang
- YL Zhang
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- 01/01/2016
- Field of study
© 2016, The Author(s). In carbonate aquifers, dissolved organic carbon from the surface drives heterotrophic metabolism, generating CO2 in the subsurface. Although this has been a proposed mechanism for enhanced dissolution at the water table, respiration rates and their controlling factors have not been widely evaluated. This study investigates the composition and concentration of dissolved organic carbon (DOC) reaching the water table from different recharge pathways on a subtropical carbonate island using a combination of DOC concentration measurements, fluorescence and absorption characterisation. In addition, direct measurements of the microbial response to the differing water types were made. Interactions of rainfall with the vegetation, via throughfall and stemflow, increase the concentration of DOC. The highest DOC concentrations are associated with stemflow, overland recharge and dissolution hole waters which interact with bark lignin and exhibit strong terrestrial-derived characteristics. The groundwater samples exhibit the lowest concentrations of DOC and are comprised of refractory humic-like organic matter. The heterotrophic response seems to be controlled by the concentration of DOC in the sample. The terrestrially sourced humic-like matter in the stemflow and dissolution hole samples was highly labile, thus increasing the amount of biologically produced CO2 to drive dissolution. Based on the calculated respiration rates, microbial activity could enhance carbonate dissolution, increasing porosity generation by a maximum of 1%kyr−1 at the top of the freshwater lens
Carbonate phases rich in magnesium in the Triassic limestones of the eastern part of the Germanic Basin
- Author
- AV Radha
- D Kralj
- D Nürnberg
- DJ Ahn
- E Flügel
- F Zhang
- FF Whitaker
- FT Mackenzie
- GA Pawloski
- GT Faust
- HR Wenk
- J Ji
- J Paquette
- J Szulc
- JO Titiloye
- JW Morse
- JW Morse
- K Ramseyer
- K Stanienda
- K Stanienda
- Katarzyna J. Stanienda
- MA Bertram
- MC Nash
- ME Böttcher
- ME Tucker
- OS Pokrovsky
- P Bayliss
- PL Althoff
- RW Fairbridge
- S Boggs Jr
- S Goffredo
- SJ Tsipursky
- TS Feist-Burkhard
- WA Dollase
- WF Cole
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- Field of study
Similarities and differences in the dolomitization history of two coeval Middle Triassic carbonate platforms, Balaton Highland, Hungary
- Author
- A Spadafora
- AG Fischer
- AM Alonso-Zarza
- AM Alonso-Zarza
- AM Alonso-Zarza
- B Jones
- C Spötl
- C Spötl
- C Vasconcelos
- Ch Korte
- D Chen
- D Wright
- DA Budd
- DF Sibley
- DT Wright
- FF Whitaker
- FH Nader
- GD Jones
- HS Chafetz
- J Haas
- J Haas
- J Haas
- J Haas
- J Haas
- J Rosenbaum
- JA McKenzie
- JAD Dickson
- János Haas
- K Bazargani-Guiliani
- M Sánchez-Román
- Orsolya Győri
- PA Scholle
- PW Choquette
- Q Fu
- R Cuia Di
- R Riding
- R Riding
- SJ Mazzullo
- Sándor Kele
- T Budai
- T Budai
- T Budai
- T Budai
- T Budai
- Tamás Budai
- TRR Bontognali
- TRR Bontognali
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- 23/02/2014
- Field of study
Dolomitization of platform carbonates is commonly the result of multiphase processes. Documentation of the complex dolomitization history is difficult if completely dolomitized sections are studied. Two Middle Anisian sections representing two coeval carbonate platforms were investigated and compared in the present study. Both sections are made up of meter-scale peritidal–lagoonal cycles with significant pedogenic overprint. One of the sections contains non-dolomitized, partially dolomitized, and completely dolomitized intervals, whereas the other is completely dolomitized. Based on investigations of the partially dolomitized section, penecontemporaneous dolomite formation and/or very early post-depositional dolomitization were identified in various lithofacies types. In shallow subtidal facies, porphyrotopic dolomite was found preferentially in microbial micritic fabrics. Microbially induced dolomite precipitation and/or progressive replacement of carbonate sediments could be interpreted for stromatolites. Cryptocrystalline to very finely crystalline dolomite, probably of pedogenic origin, was encountered in paleosoil horizons. Fabric-destructive dolomite commonly found below these horizons was likely formed via reflux of evaporated seawater. As a result of the different paleogeographic settings of the two platforms, their shallow-burial conditions were significantly different. One of the studied sections was located at the basinward platform margin where pervasive fabric-retentive dolomitization took place in a shallow-burial setting, probably via thermal convection. In contrast, in the area of the other, smaller platform shallow-water carbonates were covered by basinal deposits, preventing fluid circulation and accordingly pervasive shallow-burial dolomitization. In the intermediate to deep burial zone, recrystallization of partially dolomitized limestone and occlusion of newly opened fractures and pores by coarsely crystalline dolomite took place
Measurement of the inclusive and dijet cross-sections of b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector
- Author
- Aad G
- Abbott B
- Abdallah J
- Abdelalim AA
- Abdesselam A
- Abdinov O
- Abi B
- Abolins M
- Abramowicz H
- Abreu H
- Acerbi E
- Acharya BS
- Ackers M
- Adams DL
- Addy TN
- Adelman J
- Aderholz M
- Adomeit S
- Adragna P
- Adye T
- Aefsky S
- Aguilar-Saavedra JA
- Aharrouche M
- Ahlen SP
- Ahles F
- Ahmad A
- Ahsan M
- Aielli G
- Akdogan T
- Akesson TPA
- Akimoto G
- Akimov AV
- Alam MA
- Alam MS
- Albrand S
- Aleksa M
- Aleksandrov IN
- Aleppo M
- Alessandria F
- Alexa C
- Alexander G
- Alexandre G
- Alexopoulos T
- Alhroob M
- Aliev M
- Alimonti G
- Alison J
- Aliyev M
- Allport PP
- Allwood-Spiers SE
- Almenar CC
- Almond J
- Aloisio A
- Alon R
- Alonso A
- Alonso J
- Alviggi MG
- Amako K
- Amaral P
- Amelung C
- Ammosov VV
- Amorim A
- Amoros G
- Amram N
- Anastopoulos C
- Andari N
- Andeen T
- Anders CF
- Anderson KJ
- Andreazza A
- Andrei V
- Andrieux M-L
- Anduaga XS
- Angerami A
- Anghinolfi F
- Anh TV
- Anjos N
- Annovi A
- Antonaki A
- Antonelli M
- Antonelli S
- Antos J
- Anulli F
- Aoun S
- Apolle R
- Arabidze G
- Aracena I
- Arai Y
- Arce ATH
- Archambault JP
- Arfaoui S
- Arguin J-F
- Arik E
- Arik M
- Armbruster AJ
- Arms KE
- Armstrong SR
- Arnaez O
- Arnault C
- Artamonov A
- Artoni G
- Arutinov D
- Asai S
- Asfandiyarov R
- Ask S
- Asman B
- Asquith L
- Assamagan K
- Astbury A
- Astvatsatourov A
- Atoian G
- Aubert B
- Auerbach B
- Auge E
- Augsten K
- Aurousseau M
- Austin N
- Avramidou R
- Axen D
- Ay C
- Azuelos G
- Azuma Y
- Baak MA
- Baccaglioni G
- Bacci C
- Bach AM
- Bachacou H
- Bachas K
- Bachy G
- Backes M
- Badescu E
- Bagnaia P
- Bahinipati S
- Bai Y
- Bailey DC
- Bain T
- Baines JT
- Baker OK
- Baker S
- Banas E
- Banerjee P
- Banerjee S
- Banfi D
- Bangert A
- Bansal V
- Bansil HS
- Barak L
- Baranov SP
- Barashkou A
- Barber T
- Barberio EL
- Barberis D
- Barbero M
- Bardin DY
- Barillari T
- Barisonzi M
- Barklow T
- Barlow N
- Barnett BM
- Barnett RM
- Baroncelli A
- Barr AJ
- Barreiro F
- Barrera CO
- Barrillon P
- Bartoldus R
- Barton AE
- Bartsch D
- Bates RL
- Batkova L
- Batley JR
- Battaglia A
- Battistin M
- Battistoni G
- Bauer F
- Bawa HS
- Beare B
- Beau T
- Beauchemin PH
- Beccherle R
- Bechtle P
- Beck HP
- Beckingham M
- Becks KH
- Beddall A
- Beddall AJ
- Bednyakov VA
- Bee C
- Begel M
- Behera PK
- Beimforde M
- Belanger-Champagne C
- Belenguer MJ
- Belhorma B
- Bell PJ
- Bell WH
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- Bellagamba L
- Bellina F
- Bellomo G
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- Belloni A
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- Benchouk C
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- Benhammou Y
- Benjamin DP
- Benoit M
- Bensinger JR
- Benslama K
- Bentvelsen S
- Berge D
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- Berghaus F
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- Bobbink GJ
- Bobrovnikov VB
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- Bogdanchikov A
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- Fiolhais MCN
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- Flammer J
- Flechl M
- Fleck I
- Fleckner J
- Fleischmann P
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- Zhemchugov A
- Zheng S
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- Zieminska D
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- Zimmermann S
- Zimmermann S
- Ziolkowski M
- Zitoun R
- Zivkovic L
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- zur Nedden M
- Zutshi V
- Zwalinski L
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- 31/12/2010
- Field of study
The inclusive and dijet production cross-sections have been measured for jets
containing b-hadrons (b-jets) in proton-proton collisions at a centre-of-mass
energy of sqrt(s) = 7 TeV, using the ATLAS detector at the LHC. The
measurements use data corresponding to an integrated luminosity of 34 pb^-1.
The b-jets are identified using either a lifetime-based method, where secondary
decay vertices of b-hadrons in jets are reconstructed using information from
the tracking detectors, or a muon-based method where the presence of a muon is
used to identify semileptonic decays of b-hadrons inside jets. The inclusive
b-jet cross-section is measured as a function of transverse momentum in the
range 20 < pT < 400 GeV and rapidity in the range |y| < 2.1. The bbbar-dijet
cross-section is measured as a function of the dijet invariant mass in the
range 110 < m_jj < 760 GeV, the azimuthal angle difference between the two jets
and the angular variable chi in two dijet mass regions. The results are
compared with next-to-leading-order QCD predictions. Good agreement is observed
between the measured cross-sections and the predictions obtained using POWHEG +
Pythia. MC@NLO + Herwig shows good agreement with the measured bbbar-dijet
cross-section. However, it does not reproduce the measured inclusive
cross-section well, particularly for central b-jets with large transverse
momenta.Comment: 10 pages plus author list (21 pages total), 8 figures, 1 table, final
version published in European Physical Journal
Jet energy measurement with the ATLAS detector in proton-proton collisions at root s=7 TeV
- Author
- Aad G
- Abbott B
- Abdallah J
- Abdelalim AA
- Abdesselam A
- Abdinov O
- Abi B
- Abolins M
- Abramowicz H
- Abreu H
- Acerbi E
- Acharya BS
- Adams DL
- Addy TN
- Adelman J
- Aderholz M
- Adomeit S
- Adragna P
- Adye T
- Aefsky S
- Aguilar-Saavedra JA
- Aharrouche M
- Ahlen SP
- Ahles F
- Ahmad A
- Ahsan M
- Aielli G
- Akdogana T
- Akesson TPA
- Akimoto G
- Akimov AV
- Akiyama A
- Aktas A
- Alam MA
- Alam MS
- Albert J
- Albrand S
- Aleksa M
- Aleksandrov IN
- Alessandria F
- Alexa C
- Alexander G
- Alexandre G
- Alexopoulos T
- Alhroob M
- Aliev M
- Alimonti G
- Alison J
- Aliyev M
- Allport PP
- Allwood-Spiers SE
- Almenar CC
- Almond J
- Aloisio A
- Alon R
- Alonso A
- Alviggi MG
- Amako K
- Amaral P
- Amelung C
- Ammosov VV
- Amorim A
- Amoros G
- Amram N
- Anastopoulos C
- Ancu LS
- Andari N
- Andeen T
- Anders CF
- Anders G
- Anderson KJ
- Andreazza A
- Andrei V
- Andrieux M-L
- Anduaga XS
- Angerami A
- Anghinolfi F
- Anh TV
- Anjos N
- Annovi A
- Antonaki A
- Antonelli M
- Antonov A
- Antos J
- Anulli F
- Aoun S
- Apolle R
- Arabidze G
- Aracena I
- Arai Y
- Aranda CP
- Arce ATH
- Archambault JP
- Arfaoui S
- Arguin J-F
- Arik E
- Arik M
- Armbruster AJ
- Arnaez O
- Arnault C
- Artamonov A
- Artoni G
- Arutinov D
- Asai S
- Asfandiyarov R
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- Asman B
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- Assamagan K
- Astbury A
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- Atoian G
- Aubert B
- Auge E
- Augsten K
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- Avolio G
- Avramidou R
- Axen D
- Ay C
- Azuelos G
- Azuma Y
- Baak MA
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- Bacci C
- Bach AM
- Bachacou H
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- Bachy G
- Backes M
- Backhaus M
- Badescu E
- Bagnaia P
- Bahinipati S
- Bai Y
- Bailey DC
- Bain T
- Baines JT
- Baker MD
- Baker OK
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- Banfi D
- Bangert A
- Bansal V
- Bansil HS
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- Barber T
- Barberio EL
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- Bardin DY
- Barillari T
- Barisonzi M
- Barklow T
- Barlow N
- Barnett BM
- Barnett RM
- Baroncelli A
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- Barr AJ
- Barreiro F
- Barrera CO
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- Bartoldus R
- Barton AE
- Bartsch D
- Bartsch V
- Bates RL
- Batkova L
- Batley JR
- Battaglia A
- Battistin M
- Battistoni G
- Bauer F
- Bawa HS
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- Beauchemin PH
- Beccherle R
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- Beddall A
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- Beltramello O
- Ben Ami S
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- Benchekroun D
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- Benhammou Y
- Benjamin DP
- Benoit M
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- Bhimji W
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- Biebel O
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- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- 01/03/2013
- Field of study
The jet energy scale and its systematic uncertainty are determined for jets measured with the ATLAS detector at the LHC in proton-proton collision data at a centre-of-mass energy of √s = 7TeV corresponding to an integrated luminosity of 38 pb-1. Jets are reconstructed with the anti-kt algorithm with distance parameters R=0. 4 or R=0. 6. Jet energy and angle corrections are determined from Monte Carlo simulations to calibrate jets with transverse momenta pT≥20 GeV and pseudorapidities {pipe}η{pipe}<4. 5. The jet energy systematic uncertainty is estimated using the single isolated hadron response measured in situ and in test-beams, exploiting the transverse momentum balance between central and forward jets in events with dijet topologies and studying systematic variations in Monte Carlo simulations. The jet energy uncertainty is less than 2. 5 % in the central calorimeter region ({pipe}η{pipe}<0. 8) for jets with 60≤pT<800 GeV, and is maximally 14 % for pT<30 GeV in the most forward region 3. 2≤{pipe}η{pipe}<4. 5. The jet energy is validated for jet transverse momenta up to 1 TeV to the level of a few percent using several in situ techniques by comparing a well-known reference such as the recoiling photon pT, the sum of the transverse momenta of tracks associated to the jet, or a system of low-pT jets recoiling against a high-pT jet. More sophisticated jet calibration schemes are presented based on calorimeter cell energy density weighting or hadronic properties of jets, aiming for an improved jet energy resolution and a reduced flavour dependence of the jet response. The systematic uncertainty of the jet energy determined from a combination of in situ techniques is consistent with the one derived from single hadron response measurements over a wide kinematic range. The nominal corrections and uncertainties are derived for isolated jets in an inclusive sample of high-pT jets. Special cases such as event topologies with close-by jets, or selections of samples with an enhanced content of jets originating from light quarks, heavy quarks or gluons are also discussed and the corresponding uncertainties are determined. © 2013 CERN for the benefit of the ATLAS collaboration
Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease
- Author
- A Abbate
- A Abhyankar
- A Adams
- A Agafina
- A Akyea-Djamson
- A Alan
- A Alfieri
- A Alfrey
- A Alvarisqueta
- A Amos
- A Anadiotis
- A Anneveldt
- A Antolick
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- Wilhoit G
- Wilkins M
- Wilkinson S
- William M
- Willingham K
- Willmerdinger M
- Willner C
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- Winkelmann B
- Winkler J
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- Xu Zj
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- Yakushin S
- Yamada T
- Yamaguchi E
- Yamamoto H
- Yamamoto T
- Yamane M
- Yan J
- Yanase T
- Yanev T
- Yang Cc
- Yang K
- Yang P
- Yao Z
- Yaoqing H
- Yarows S
- Yasuoka S
- Yasutake M
- Yigit Z
- Yilmaz Mb
- Yim Kh
- Yim S
- Yokoyama M
- Yong H
- Yoshida M
- Yoshimoto E
- Yossen M
- Young A
- Younis L
- Youssef G
- Yuan Z
- Yunoki C
- Yupanqui H
- Z Zhai
- Z Zilahi
- Zadionchenko V
- Zadra R
- Zagozen P
- Zaidman C
- Zalazar L
- Zaman A
- Zangroniz P
- Zarate J
- Zareczky P
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- Zdrenghea D
- Zebrack J
- Zena N
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- Zhang W
- Zhang Y
- Zhao R
- Zhou H
- Zidova M
- Zielinski M
- Zieve F
- Zineldine A.
- Zirlik A
- Zucchetti C
- Publication venue
- 'Massachusetts Medical Society'
- Publication date
- 01/01/2017
- Field of study
Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.
Measurement of the cross-section for b-jets produced in association with a Z boson at root s=7 TeV with the ATLAS detector ATLAS Collaboration
- Author
- Aad G
- Abbott B
- Abdallah J
- Abdelalim AA
- Abdesselam A
- Abdinov O
- Abi B
- Abolins M
- Abramowicz H
- Abreu H
- Acerbi E
- Acharya BS
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- Aefsky S
- Aguilar-Saavedra JA
- Aharrouche M
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- Akesson TPA
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- Zolnierowski Y
- Zsenei A
- zur Nedden M
- Zutshi V
- Zwalinski L
- Publication venue
- 'Elsevier BV'
- Publication date
- 01/01/2011
- Field of study
A measurement is presented of the inclusive cross-section for b-jet production in association with a Z boson in pp collisions at a centre-of-mass energy of root s = 7 TeV. The analysis uses the data sample collected by the ATLAS experiment in 2010, corresponding to an integrated luminosity of approximately 36 pb(-1). The event selection requires a Z boson decaying into high P-T electrons or muons, and at least one b-jet, identified by its displaced vertex, with transverse momentum p(T) > 25 GeV and rapidity vertical bar y vertical bar < 2.1. After subtraction of background processes, the yield is extracted from the vertex mass distribution of the candidate b-jets. The ratio of this cross-section to the inclusive Z cross-section (the average number of b-jets per Z event) is also measured. Both results are found to be in good agreement with perturbative QCD predictions at next-to-leading order
Effects of alirocumab on types of myocardial infarction: insights from the ODYSSEY OUTCOMES trial
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- Abbas J
- Abbate A
- Abdullakutty J
- Abhyanakar AD
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- Zuniga JDH
- Zurakowski A
- Zuran I
- Zweiker R
- Publication venue
- 'Oxford University Press (OUP)'
- Publication date
- 01/01/2019
- Field of study
Aims The third Universal Definition of Myocardial Infarction (MI) Task Force classified MIs into five types: Type 1, spontaneous; Type 2, related to oxygen supply/demand imbalance; Type 3, fatal without ascertainment of cardiac biomarkers; Type 4, related to percutaneous coronary intervention; and Type 5, related to coronary artery bypass surgery. Low-density lipoprotein cholesterol (LDL-C) reduction with statins and proprotein convertase subtilisin–kexin Type 9 (PCSK9) inhibitors reduces risk of MI, but less is known about effects on types of MI. ODYSSEY OUTCOMES compared the PCSK9 inhibitor alirocumab with placebo in 18 924 patients with recent acute coronary syndrome (ACS) and elevated LDL-C (≥1.8 mmol/L) despite intensive statin therapy. In a pre-specified analysis, we assessed the effects of alirocumab on types of MI. Methods and results Median follow-up was 2.8 years. Myocardial infarction types were prospectively adjudicated and classified. Of 1860 total MIs, 1223 (65.8%) were adjudicated as Type 1, 386 (20.8%) as Type 2, and 244 (13.1%) as Type 4. Few events were Type 3 (n = 2) or Type 5 (n = 5). Alirocumab reduced first MIs [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.77–0.95; P = 0.003], with reductions in both Type 1 (HR 0.87, 95% CI 0.77–0.99; P = 0.032) and Type 2 (0.77, 0.61–0.97; P = 0.025), but not Type 4 MI. Conclusion After ACS, alirocumab added to intensive statin therapy favourably impacted on Type 1 and 2 MIs. The data indicate for the first time that a lipid-lowering therapy can attenuate the risk of Type 2 MI. Low-density lipoprotein cholesterol reduction below levels achievable with statins is an effective preventive strategy for both MI types.For complete list of authors see http://dx.doi.org/10.1093/eurheartj/ehz299</p
Pan-cancer analysis of whole genomes
- Author
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- abn Wong
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- abp Kazanov
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- ac Hu
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- ac Schlesner
- ad Zhang
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- Zeps
- zf Ghossein
- Zhang
- Zhang
- Zhang
- Zhang
- Zhang
- Zhang
- Zhang H. b
- Zhao
- Zheng
- Zhou
- Zhou
- Zhu
- Zhu
- zi zj
- zm Jayaseelan
- Zou
- Zou
- zt Kim
- zw Lewis
- Ó. A. th
- Ø. sk
- Publication venue
- Publication date
- 11/12/2019
- Field of study
Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe
Effect of alirocumab on mortality after acute coronary syndromes. An analysis of the ODYSSEY OUTCOMES randomized clinical trial
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- Abbas J
- Abbate A
- Abdullakutty J
- Abdullkutty J
- Abhyanakar AD
- Aboyans V
- Abrantes JAM
- Abu-Fadel M
- Acevedo M
- Adamkova V
- Adamo A
- Adhyapak S
- Agarwal H
- Aggarwal R
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- Agnetti V
- Aguirre A
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- Ahremark U
- Ahuad Guerrero RA
- Aidar Ayoub JC
- Airaksinen JK
- Aitken D
- Akatova E
- Akhter F
- Ako J
- Akright L
- Akyea-Djamson A
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- Al-Windy NYY
- Alan D
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- Alexandru TM
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- Publication venue
- 'Ovid Technologies (Wolters Kluwer Health)'
- Publication date
- 04/01/2019
- Field of study
Background: Previous trials of PCSK9 (proprotein convertase subtilisin-kexin type 9) inhibitors demonstrated reductions in major adverse cardiovascular events, but not death. We assessed the effects of alirocumab on death after index acute coronary syndrome. Methods: ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) was a double-blind, randomized comparison of alirocumab or placebo in 18 924 patients who had an ACS 1 to 12 months previously and elevated atherogenic lipoproteins despite intensive statin therapy. Alirocumab dose was blindly titrated to target achieved low-density lipoprotein cholesterol (LDL-C) between 25 and 50 mg/dL. We examined the effects of treatment on all-cause death and its components, cardiovascular and noncardiovascular death, with log-rank testing. Joint semiparametric models tested associations between nonfatal cardiovascular events and cardiovascular or noncardiovascular death. Results: Median follow-up was 2.8 years. Death occurred in 334 (3.5%) and 392 (4.1%) patients, respectively, in the alirocumab and placebo groups (hazard ratio [HR], 0.85; 95% CI, 0.73 to 0.98; P=0.03, nominal P value). This resulted from nonsignificantly fewer cardiovascular (240 [2.5%] vs 271 [2.9%]; HR, 0.88; 95% CI, 0.74 to 1.05; P=0.15) and noncardiovascular (94 [1.0%] vs 121 [1.3%]; HR, 0.77; 95% CI, 0.59 to 1.01; P=0.06) deaths with alirocumab. In a prespecified analysis of 8242 patients eligible for ≥3 years follow-up, alirocumab reduced death (HR, 0.78; 95% CI, 0.65 to 0.94; P=0.01). Patients with nonfatal cardiovascular events were at increased risk for cardiovascular and noncardiovascular deaths (P<0.0001 for the associations). Alirocumab reduced total nonfatal cardiovascular events (P<0.001) and thereby may have attenuated the number of cardiovascular and noncardiovascular deaths. A post hoc analysis found that, compared to patients with lower LDL-C, patients with baseline LDL-C ≥100 mg/dL (2.59 mmol/L) had a greater absolute risk of death and a larger mortality benefit from alirocumab (HR, 0.71; 95% CI, 0.56 to 0.90; Pinteraction=0.007). In the alirocumab group, all-cause death declined wit h achieved LDL-C at 4 months of treatment, to a level of approximately 30 mg/dL (adjusted P=0.017 for linear trend). Conclusions: Alirocumab added to intensive statin therapy has the potential to reduce death after acute coronary syndrome, particularly if treatment is maintained for ≥3 years, if baseline LDL-C is ≥100 mg/dL, or if achieved LDL-C is low. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01663402
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