This article reports on a search for dark matter pair production in association with bottom or top quarks in
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p
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collisions collected at
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TeV by the ATLAS detector at the LHC. ...Events with large missing transverse momentum are selected when produced in association with high-momentum jets of which one or more are identified as jets containing
b
-quarks. Final states with top quarks are selected by requiring a high jet multiplicity and in some cases a single lepton. The data are found to be consistent with the Standard Model expectations and limits are set on the mass scale of effective field theories that describe scalar and tensor interactions between dark matter and Standard Model particles. Limits on the dark-matter–nucleon cross-section for spin-independent and spin-dependent interactions are also provided. These limits are particularly strong for low-mass dark matter. Using a simplified model, constraints are set on the mass of dark matter and of a coloured mediator suitable to explain a possible signal of annihilating dark matter.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Introduction
Peripheral blood is the standard tissue source for germline genetic testing in most scenarios. In patients with hematologic malignancies, however, peripheral blood frequently contains ...tumor- or clonal hematopoiesis-related acquired genetic variants, often occurring in genes that can also cause inherited cancer susceptibility if present in the germline. Thus, an alternative tissue source is necessary. Cultured skin fibroblasts have been used as a potentially ideal alternative because they are free from blood contamination and provide ample DNA yields, advantages that other alternatives such as saliva or nail clippings lack. However, optimal culture methods, expected time from biopsy to sufficient DNA yield, culture failure rate, and limitations of this technique, including the possibility of variants being acquired solely due to the culturing process, are not yet known.
Methods
We conducted a retrospective cohort study of subjects with cytopenias or hematologic malignancies who underwent skin biopsy and fibroblast culture for germline genetic testing from April 2014 to June 2018. Skin biopsy culture technical data, including time from biopsy to culture set-up, shipment from an outside institution, culture failure, and biopsy size, were abstracted from tissue culture logs. Patient demographics, comorbidities, medication history, and hematologic diagnosis and treatment were abstracted from medical records. Next generation sequencing data from targeted capture of 144 inherited cancer and bone marrow failure predisposition genes obtained for clinical genetic testing purposes were analyzed to identify variants at both germline (40-60%) and subclonal (10-40%) variant allele frequencies (VAF). Pathogenicity was interpreted according to ACMG/AMP guidelines. Fisher's exact tests and logistic regression models were used to assess associations with culture failure. T-tests and linear regression models were used to assess factors associated with mean time to confluency.
Results
In total, we studied 350 samples from unique patients, including 61 (24%) who carried one or more pathogenic or likely pathogenic cancer susceptibility gene variant(s). Overall, 16 of the 350 (5%) biopsies failed to grow in culture. The median time from skin biopsy to sufficient growth to extract DNA for genetic testing was 27 days (IQR 22-29 days). Culture failure was significantly more likely in samples with a delay in culture initiation for 24 hours post biopsy (OR=4.32; p<0.01), and a pathogenic germline variant in a gene associated with telomere maintenance (OR=64.50; p<0.01). Factors associated with an increased mean time to sufficient growth included prior allogeneic stem cell transplant (32.1 days versus 27.2 days; p<0.01) and prior intravenous (IV) steroid exposure (29.9 days versus 26.4 days; p<0.01). Among samples cultured successfully, carriers of any pathogenic germline variant had a significantly decreased mean time to sufficient growth (25.4 days versus 28.6 days; p<0.01). A pathogenic or likely pathogenic subclonal variant was identified in 11 (4%) subjects at a median VAF of 20%. Among eight of these with additional tissue available, the presence of the variant was confirmed in four (50%). In individual cases, we found evidence of loss of a pathogenic variant in the hematopoietic malignancy. In one patient with a pathogenic variant with a 50% VAF in the original skin culture, the variant was not present in a skin culture from a second, fresh skin biopsy done due to discordant phenotype.
Conclusions
Culturing of skin fibroblasts for germline genetic testing in patients with hematologic disorders has a high success rate, especially when cultures are initiated within 24 hours of collection, and adds on average 27 days to genetic testing turnaround time. From patients with a hereditary syndrome, most skin biopsies will culture with the exception of individuals with a short telomere syndrome. For this subset, a direct skin biopsy without culture may be necessary. Subclonal variants at VAFs relevant to interpretation of a germline test were found in 4% of cases. Half were confirmed in an alternative tissue. Etiology of the subclonal variants, whether acquired during the culturing process or due to mosaicism or sequencing biases was not always clear. Careful assessment of the clinical phenotype in interpreting and applying germline genetic results to patient care will always be warranted.
Godley:UptoDate, Inc.: Honoraria; Invitae, Inc.: Membership on an entity's Board of Directors or advisory committees. Segal:BMS: Consultancy, Research Funding; AbbVie: Consultancy; Merck: Consultancy; Astra Zeneca: Consultancy. Churpek:UpToDate, Inc: Honoraria.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The RD52 dual-readout calorimeter is a longitudinally unsegmented instrument intended for the detection of both electromagnetically and hadronically interacting particles with unprecedented ...precision. In this paper, the identification of the showering particles and, in particular, the identification of electrons and gamma s with this instrument are investigated. The techniques used for this purpose include differences in the shower development observed with scintillation light and Cherenkov radiation, the radial shower profile of the particles and the time structure (including the starting point) of the calorimeter signals. It turns out that, at 60 GeV, electrons can be correctly identified in 99.8% of the cases, by means of criteria that eliminate 99.8% of the hadrons.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The Epinephrine Roundtable took place on July 27, 2008, during the 25th Annual Meeting of the Wilderness Medical Society (WMS) in Snowmass, CO. The WMS convened this roundtable to explore areas of ...consensus and uncertainty in the field treatment of anaphylaxis. Panelists were selected on the basis of their relevant academic or professional experience. There is a paucity of data that address the treatment of anaphylaxis in the wilderness. Anaphylaxis is a rare disease, with a sudden onset and drastic course that does not lend itself to study in randomized, controlled trials. Therefore, the panel endorsed the following position based on the limited available evidence and review of published articles, as well as expert consensus. The position represents the consensus of the panelists and is endorsed by the WMS. In 2014, the authors reviewed relevant articles published since the Epinephrine Roundtable. The following is an updated version of the original guidelines published in Wilderness & Environmental Medicine 2010;21(4):185–187.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The small-angle performance of a dual-readout fiber calorimeter Cardini, A.; Cascella, M.; Choi, S. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
02/2016, Volume:
808, Issue:
C
Journal Article
Peer reviewed
Open access
The performance of the RD52 dual-readout calorimeter is measured for very small angles of incidence between the 20GeV electron beam particles and the direction of the fibers that form the active ...elements of this calorimeter. The calorimeter response is observed to be independent of the angle of incidence for both the scintillating and the Čerenkov fibers, whereas significant differences are found between the angular dependence of the energy resolution measured with these two types of fibers. The experimental results are on crucial points at variance with the predictions of GEANT4 Monte Carlo simulations.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The ATLAS experiment at the Large Hadron Collider has a broad physics programme ranging from precision measurements to direct searches for new particles and new interactions, requiring ever larger ...and ever more accurate datasets of simulated Monte Carlo events. Detector simulation with
Geant4
is accurate but requires significant CPU resources. Over the past decade, ATLAS has developed and utilized tools that replace the most CPU-intensive component of the simulation—the calorimeter shower simulation—with faster simulation methods. Here, AtlFast3, the next generation of high-accuracy fast simulation in ATLAS, is introduced. AtlFast3 combines parameterized approaches with machine-learning techniques and is deployed to meet current and future computing challenges, and simulation needs of the ATLAS experiment. With highly accurate performance and significantly improved modelling of substructure within jets, AtlFast3 can simulate large numbers of events for a wide range of physics processes.
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EMUNI, FZAB, GEOZS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
An updated search is performed for gluino, top squark, or bottom squark R-hadrons that have come to rest within the ATLAS calorimeter, and decay at some later time to hadronic jets and a neutralino, ...using 5.0 and 22.9 fb super(-1) of pp collisions at 7 and 8 TeV, respectively. Candidate decay events are triggered in selected empty bunch crossings of the LHC in order to remove pp collision backgrounds. Selections based on jet shape and muon system activity are applied to discriminate signal events from cosmic ray and beam-halo muon backgrounds. In the absence of an excess of events, improved limits are set on gluino, stop, and sbottom masses for different decays, lifetimes, and neutralino masses. With a neutralino of mass 100 GeV, the analysis excludes gluinos with mass below 832 GeV (with an expected lower limit of 731 GeV), for a gluino lifetime between 10 mu s and 1000 s in the generic R-hadron model with equal branching ratios for decays to (ProQuest: Formulae and/or non-USASCII text omitted) and (ProQuest: Formulae and/or non-USASCII text omitted). Under the same assumptions for the neutralino mass and squark lifetime, top squarks and bottom squarks in the Regge R-hadron model are excluded with masses below 379 and 344 GeV, respectively.
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