Molecular characteristics and chromatin texture features in acute promyelocytic leukemia

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Background: Acute promyelocytic leukemia is a cytogenetically well defined entity. Nevertheless, some features observed at diagnosis are related to a worse outcome of the patients. Methods: In a prospective study, we analyzed peripheral (PB) leukocyte count, immunophenotype, methylation status of CDKN2B, CDKN2A and TP73; FLT3 and NPM1 mutations besides nuclear chromatin texture characteristics of the leukemic cells. We also examined the relation of these features with patient's outcome. Results: Among 19 cases, 4 had a microgranular morphology, 7 presented PB leukocytes >10x10(9)/l, 2 had FLT3-ITD and 3 had FLT3-TKD (all three presenting a methylated CDKN2B). NPM1 mutation was not observed. PB leukocyte count showed an inverse relation with standard deviation of gray levels, contrast, cluster prominence, and chromatin fractal dimension (FD). Cases with FLT3-ITD presented a microgranular morphology, PB leukocytosis and expression of HLA-DR, CD34 and CD11b. Concerning nuclear chromatin texture variables, these cases had a lower entropy, contrast, cluster prominence and FD, but higher local homogeneity, and R(2)45, in keeping with more homogeneously distributed chromatin. In the univariate Cox analysis, a higher leukocyte count, FLT3-ITD mutation, microgranular morphology, methylation of CDKN2B, besides a higher local homogeneity of nuclear chromatin, a lower chromatin entropy and FD were associated to a worse outcome. All these features lost significance when the cases were stratified for FLT3-ITD mutation. Methylation status of CDNK2A and TP73 showed no relation to patient's survival. Conclusion: in APL, patients with FLT3-ITD mutation show different clinical characteristics and have blasts with a more homogeneous chromatin texture. Texture analysis demonstrated that FLTD-ITD was accompanied not only by different cytoplasmic features, but also by a change in chromatin structure in routine cytologic preparations. Yet we were not able to detect chromatin changes by nuclear texture analysis of patients with the FTLD-TKD or methylation of specific genes.7Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)FAPESP [2007/54686-0]CNPq [302277/2009-9, 307270/2010-6, 402022/2010-6

The LUX-ZEPLIN (LZ) Experiment

We describe the design and assembly of the LUX-ZEPLIN experiment, a direct detection search for cosmic WIMP dark matter particles. The centerpiece of the experiment is a large liquid xenon time projection chamber sensitive to low energy nuclear recoils. Rejection of backgrounds is enhanced by a Xe skin veto detector and by a liquid scintillator Outer Detector loaded with gadolinium for efficient neutron capture and tagging. LZ is located in the Davis Cavern at the 4850' level of the Sanford Underground Research Facility in Lead, South Dakota, USA. We describe the major subsystems of the experiment and its key design features and requirements

The impact of surgical delay on resectability of colorectal cancer: An international prospective cohort study

AIM: The SARS-CoV-2 pandemic has provided a unique opportunity to explore the impact of surgical delays on cancer resectability. This study aimed to compare resectability for colorectal cancer patients undergoing delayed versus non-delayed surgery. METHODS: This was an international prospective cohort study of consecutive colorectal cancer patients with a decision for curative surgery (January-April 2020). Surgical delay was defined as an operation taking place more than 4 weeks after treatment decision, in a patient who did not receive neoadjuvant therapy. A subgroup analysis explored the effects of delay in elective patients only. The impact of longer delays was explored in a sensitivity analysis. The primary outcome was complete resection, defined as curative resection with an R0 margin. RESULTS: Overall, 5453 patients from 304 hospitals in 47 countries were included, of whom 6.6% (358/5453) did not receive their planned operation. Of the 4304 operated patients without neoadjuvant therapy, 40.5% (1744/4304) were delayed beyond 4 weeks. Delayed patients were more likely to be older, men, more comorbid, have higher body mass index and have rectal cancer and early stage disease. Delayed patients had higher unadjusted rates of complete resection (93.7% vs. 91.9%, P = 0.032) and lower rates of emergency surgery (4.5% vs. 22.5%, P < 0.001). After adjustment, delay was not associated with a lower rate of complete resection (OR 1.18, 95% CI 0.90-1.55, P = 0.224), which was consistent in elective patients only (OR 0.94, 95% CI 0.69-1.27, P = 0.672). Longer delays were not associated with poorer outcomes. CONCLUSION: One in 15 colorectal cancer patients did not receive their planned operation during the first wave of COVID-19. Surgical delay did not appear to compromise resectability, raising the hypothesis that any reduction in long-term survival attributable to delays is likely to be due to micro-metastatic disease

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

Performance of missing transverse momentum reconstruction with the ATLAS detector using proton–proton collisions at √s = 13 TeV

The performance of the missing transverse momentum (EmissT) reconstruction with the ATLAS detector is evaluated using data collected in proton–proton collisions at the LHC at a centre-of-mass energy of 13 TeV in 2015. To reconstruct EmissT, fully calibrated electrons, muons, photons, hadronically decaying τ -leptons, and jets reconstructed from calorimeter energy deposits and charged-particle tracks are used. These are combined with the soft hadronic activity measured by reconstructed charged-particle tracks not associated with the hard objects. Possible double counting of contributions from reconstructed charged-particle tracks from the inner detector, energy deposits in the calorimeter, and reconstructed muons from the muon spectrometer is avoided by applying a signal ambiguity resolution procedure which rejects already used signals when combining the various EmissT contributions. The individual terms as well as the overall reconstructed EmissT are evaluated with various performance metrics for scale (linearity), resolution, and sensitivity to the data-taking conditions. The method developed to determine the systematic uncertainties of the EmissT scale and resolution is discussed. Results are shown based on the full 2015 data sample corresponding to an integrated luminosity of 3.2 fb−1

Measurement of the t¯tZ and t¯tW cross sections in proton-proton collisions at √s=13 TeV with the ATLAS detector

A measurement of the associated production of a top-quark pair (t¯t) with a vector boson (W, Z) in proton-proton collisions at a center-of-mass energy of 13 TeV is presented, using 36.1  fb−1 of integrated luminosity collected by the ATLAS detector at the Large Hadron Collider. Events are selected in channels with two same- or opposite-sign leptons (electrons or muons), three leptons or four leptons, and each channel is further divided into multiple regions to maximize the sensitivity of the measurement. The t¯tZ and t¯tW production cross sections are simultaneously measured using a combined fit to all regions. The best-fit values of the production cross sections are σt¯tZ=0.95±0.08stat±0.10syst pb and σt¯tW=0.87±0.13stat±0.14syst pb in agreement with the Standard Model predictions. The measurement of the t¯tZ cross section is used to set constraints on effective field theory operators which modify the t¯tZ vertex

Combined measurement of differential and total cross sections in the H → γγ and the H → ZZ* → 4ℓ decay channels at s=13 TeV with the ATLAS detector

A combined measurement of differential and inclusive total cross sections of Higgs boson production is performed using 36.1 fb−1 of 13 TeV proton–proton collision data produced by the LHC and recorded by the ATLAS detector in 2015 and 2016. Cross sections are obtained from measured H→γγ and H→ZZ*(→4ℓ event yields, which are combined taking into account detector efficiencies, resolution, acceptances and branching fractions. The total Higgs boson production cross section is measured to be 57.0−5.9 +6.0 (stat.) −3.3 +4.0 (syst.) pb, in agreement with the Standard Model prediction. Differential cross-section measurements are presented for the Higgs boson transverse momentum distribution, Higgs boson rapidity, number of jets produced together with the Higgs boson, and the transverse momentum of the leading jet. The results from the two decay channels are found to be compatible, and their combination agrees with the Standard Model predictions

Search for High-Mass Resonances Decaying to τν in pp Collisions at √s=13 TeV with the ATLAS Detector

A search for high-mass resonances decaying to τν using proton-proton collisions at √s=13 TeV produced by the Large Hadron Collider is presented. Only τ-lepton decays with hadrons in the final state are considered. The data were recorded with the ATLAS detector and correspond to an integrated luminosity of 36.1 fb−1. No statistically significant excess above the standard model expectation is observed; model-independent upper limits are set on the visible τν production cross section. Heavy W′ bosons with masses less than 3.7 TeV in the sequential standard model and masses less than 2.2–3.8 TeV depending on the coupling in the nonuniversal G(221) model are excluded at the 95% credibility level