Receptor Activator of NF-κB (RANK) Confers Resistance to Chemotherapy in AML and Associates with Dismal Disease Course.

Although treatment options of acute myeloid leukemia (AML) have improved over the recent years, prognosis remains poor. Better understanding of the molecular mechanisms influencing and predicting treatment efficacy may improve disease control and outcome. Here we studied the expression, prognostic relevance and functional role of the tumor necrosis factor receptor (TNFR) family member Receptor Activator of Nuclear Factor (NF)-κB (RANK) in AML. We conducted an experimental ex vivo study using leukemic cells of 54 AML patients. Substantial surface expression of RANK was detected on primary AML cells in 35% of the analyzed patients. We further found that RANK signaling induced the release of cytokines acting as growth and survival factors for the leukemic cells and mediated resistance of AML cells to treatment with doxorubicin and cytarabine, the most commonly used cytostatic compounds in AML treatment. In line, RANK expression correlated with a dismal disease course as revealed by reduced overall survival. Together, our results show that RANK plays a yet unrecognized role in AML pathophysiology and resistance to treatment, and identify RANK as "functional" prognostic marker in AML. Therapeutic modulation of RANK holds promise to improve treatment response in AML patients

Filtration Efficiency of Hospital Face Mask Alternatives Available for Use during the COVID-19 Pandemic

Importance: Procuring respiratory protection for clinicians and other health care workers has become a major challenge of the coronavirus disease 2019 (COVID-19) pandemic and has resulted in nonstandard practices such as the use of expired respirators and various decontamination processes to prolong the useful life of respirators in health care settings. In addition, imported, non-National Institute for Occupational Safety and Health (NIOSH)-approved respirators have been donated or acquired by hospitals as a potential replacement for limited NIOSH-approved N95 respirators. Objective: To assess fitted filtration efficiencies (FFEs) for face mask alternatives used during the COVID-19 pandemic. Design, Setting, and Participants: For this quality-improvement study conducted between April and June 2020, we used the Occupational Safety and Health Administration's Quantitative Fit Testing Protocol for Filtering Facepiece Respirators in a laboratory atmosphere supplemented with sodium chloride particles to assess the FFEs of a variety of respirators worn by a male volunteer and female volunteer. Main Outcomes and Measures: The FFEs of respirators commonly worn by clinicians and other health care workers and available respirator alternatives during the COVID-19 pandemic. Results: Of the 29 different fitted face mask alternatives tested on 1 man and 1 woman, expired N95 respirators with intact elastic straps and respirators subjected to ethylene oxide and hydrogen peroxide sterilization had unchanged FFE (>95%). The performance of N95 respirators in the wrong size had slightly decreased performance (90%-95% FFE). All of the respirators not listed as approved in this evaluation (n = 6) failed to achieve 95% FFE. Neither of the 2 imported respirators authorized for use by the Centers for Disease Control and Prevention that were not NIOSH-approved tested in this study achieved 95% FFE, and the more effective of the 2 functioned at approximately 80% FFE. Surgical and procedural face masks had filtering performance that was lower relative to that of N95 respirators (98.5% overall FFE), with procedural face masks secured with elastic ear loops showing the lowest efficiency (38.1% overall FFE). Conclusions and Relevance: This quality-improvement study evaluating 29 face mask alternatives for use by clinicians interacting with patients during the COVID-19 pandemic found that expired N95 respirators and sterilized, used N95 respirators can be used when new N95 respirators are not available. Other alternatives may provide less effective filtration

Open charm and charmonium production at relativistic energies

We calculate open charm and charmonium production in $Au+Au$ reactions at $\sqrt{s}$ = 200 GeV within the hadron-string dynamics (HSD) transport approach employing open charm cross sections from $pN$ and $\pi N$ reactions that are fitted to results from PYTHIA and scaled in magnitude to the available experimental data. Charmonium dissociation with nucleons and formed mesons to open charm ($D+\bar{D}$ pairs) is included dynamically. The 'comover' dissociation cross sections are described by a simple phase-space model including a single free parameter, i.e. an interaction strength $M_0^2$, that is fitted to the $J/\Psi$ suppression data for $Pb+Pb$ collisions at SPS energies. As a novel feature we implement the backward channels for charmonium reproduction by $D \bar{D}$ channels employing detailed balance. From our dynamical calculations we find that the charmonium recreation is comparable to the dissociation by 'comoving' mesons. This leads to the final result that the total $J/\Psi$ suppression at $\sqrt{s}$ = 200 GeV as a function of centrality is slightly less than the suppression seen at SPS energies by the NA50 Collaboration, where the 'comover' dissociation is substantial and the backward channels play no role. Furthermore, even in case that all directly produced $J/\Psi$ mesons dissociate immediately (or are not formed as a mesonic state), a sizeable amount of charmonia is found asymptotically due to the $D+\bar{D} \to J/\Psi$ + meson channels in central collisions of $Au+Au$ at $\sqrt{s}$ = 200 GeV which, however, is lower than the $J/\Psi$ yield expected from binary scaling of $pp$ collisions.Comment: 42 pages, including 14 eps figures, discussions extended and references added, to be published in Phys. Rev.

Evaluation of Cloth Masks and Modified Procedure Masks as Personal Protective Equipment for the Public During the COVID-19 Pandemic

Importance: During the coronavirus disease 2019 (COVID-19) pandemic, the general public has been advised to wear masks or improvised face coverings to limit transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, there has been considerable confusion and disagreement regarding the degree to which masks protect the wearer from airborne particles. Objectives: To evaluate the fitted filtration efficiency (FFE) of various consumer-grade and improvised face masks, as well as several popular modifications of medical procedure masks that are intended to improve mask fit or comfort. Design, Setting, and Participants: For this study conducted in a research laboratory between June and August 2020, 7 consumer-grade masks and 5 medical procedure mask modifications were fitted on an adult male volunteer, and FFE measurements were collected during a series of repeated movements of the torso, head, and facial muscles as outlined by the US Occupational Safety and Health Administration Quantitative Fit Testing Protocol. The consumer-grade masks tested included (1) a 2-layer woven nylon mask with ear loops that was tested with an optional aluminum nose bridge and nonwoven filter insert in place, (2) a cotton bandana folded diagonally once (ie, "bandit" style) or in a (3) multilayer rectangle according to the instructions presented by the US Surgeon General, (4) a single-layer woven polyester/nylon mask with ties, (5) a nonwoven polypropylene mask with fixed ear loops, (6) a single-layer woven polyester gaiter/neck cover balaclava bandana, and (7) a 3-layer woven cotton mask with ear loops. Medical procedure mask modifications included (1) tying the mask's ear loops and tucking in the side pleats, (2) fastening ear loops behind the head with 3-dimensional-printed ear guards, (3) fastening ear loops behind the head with a claw-type hair clip, (4) enhancing the mask/face seal with rubber bands over the mask, and (5) enhancing the mask/face seal with a band of nylon hosiery over the fitted mask. Main Outcomes and Measures: The primary study outcome was the measured FFE of common consumer-grade and improvised face masks, as well as several popular modifications of medical procedure masks. Results: The mean (SD) FFE of consumer grade masks tested on 1 adult male with no beard ranged from 79.0% (4.3%) to 26.5% (10.5%), with the 2-layer woven nylon mask having the highest FFE. Unmodified medical procedure masks with ear loops had a mean (SD) FFE of 38.5% (11.2%). All modifications evaluated in this study increased procedure mask FFE (range [SD], 60.3% [11.1%] to 80.2% [3.1%]), with a nylon hosiery sleeve placed over the procedure mask producing the greatest improvement. Conclusions and Relevance: While modifications to improve medical procedure mask fit can enhance the filtering capability and reduce inhalation of airborne particles, this study demonstrates that the FFEs of consumer-grade masks available to the public are, in many cases, nearly equivalent to or better than their non-N95 respirator medical mask counterparts

Impact of safety-engineered devices on the incidence of occupational blood and body fluid exposures among healthcare personnel in an Academic Facility, 2000-2014

background. Legislative actions and advanced technologies, particularly dissemination of safety-engineered devices, have aided in protecting healthcare personnel from occupational blood and body fluid exposures (BBFE). objective. To investigate the trends in BBFE among healthcare personnel over 15 years and the impact of safety-engineered devices on the incidence of percutaneous injuries as well as features of injuries associated with these devices. methods. Retrospective cohort study at University of North Carolina Hospitals, a tertiary care academic facility. Data on BBFE in healthcare personnel were extracted from Occupational Health Service records (2000'2014). Exposures associated with safety-engineered and conventional devices were compared. Generalized linear models were applied to measure the annual incidence rate difference by exposure type over time. results. A total of 4,300 BBFE, including 3,318 percutaneous injuries (77%), were reported. The incidence rate for overall BBFE was significantly reduced during 2000'2014 (incidence rate difference, 1.72; P=.0003). The incidence rate for percutaneous injuries was also dramatically reduced during 2001'2006 (incidence rate difference, 1.37; P= .0079) but was less changed during 2006'2014. Percutaneous injuries associated with safety-engineered devices accounted for 27% of all BBFE. BBFE was most commonly due to injecting through skin, placing intravenous catheters, and blood drawing. conclusions. Our study revealed significant overall reduction in BBFE and percutaneous injuries likely due in part to the impact of safetyengineered devices but also identified that a considerable proportion of percutaneous injuries is now associated with these devices. Additional prevention strategies are needed to further reduce percutaneous injuries and improve design of safety-engineered devices

Variants in CHEK2 other than 1100delC do not make a major contribution to breast cancer susceptibility

We recently reported that a sequence variant in the cell-cycle-checkpoint kinase CHEK2 (CHEK2 1100delC) is a low-penetrance breast cancer-susceptibility allele in noncarriers of BRCA1 or BRCA2 mutations. To investigate whether other CHEK2 variants confer susceptibility to breast cancer, we screened the full CHEK2 coding sequence in BRCA1/2-negative breast cancer cases from 89 pedigrees with three or more cases of breast cancer. We identified one novel germline variant, R117G, in two separate families. To evaluate the possible association of R117G and two germline variants repo

Measurement of the W+W-gamma Cross Section and Direct Limits on Anomalous Quartic Gauge Boson Couplings at LEP

The process e+e- -> W+W-gamma is analysed using the data collected with the L3 detector at LEP at a centre-of-mass energy of 188.6GeV, corresponding to an integrated luminosity of 176.8pb^-1. Based on a sample of 42 selected W+W- candidates containing an isolated hard photon, the W+W-gamma cross section, defined within phase-space cuts, is measured to be: sigma_WWgamma = 290 +/- 80 +/- 16 fb, consistent with the Standard Model expectation. Including the process e+e- -> nu nu gamma gamma, limits are derived on anomalous contributions to the Standard Model quartic vertices W+W- gamma gamma and W+W-Z gamma at 95% CL: -0.043 GeV^-2 < a_0/Lambda^2 < 0.043 GeV^-2 0.08 GeV^-2 < a_c/Lambda^2 < 0.13 GeV^-2 0.41 GeV^-2 < a_n/Lambda^2 < 0.37 GeV^-2

Production of Single W Bosons at \sqrt{s}=189 GeV and Measurement of WWgamma Gauge Couplings

Single W boson production in electron-positron collisions is studied with the L3 detector at LEP. The data sample collected at a centre-of-mass energy of \sqrt{s} = 188.7GeV corresponds to an integrated luminosity of 176.4pb^-1. Events with a single energetic lepton or two acoplanar hadronic jets are selected. Within phase-space cuts, the total cross-section is measured to be 0.53 +/- 0.12 +/- 0.03 pb, consistent with the Standard Model expectation. Including our single W boson results obtained at lower \sqrt{s}, the WWgamma gauge couplings kappa_gamma and lambda_gamma are determined to be kappa_gamma = 0.93 +/- 0.16 +/- 0.09 and lambda_gamma = -0.31 +0.68 -0.19 +/- 0.13

Search for an invisibly decaying Higgs boson in e^+e^- collisions at \sqrt{s} = 183 - 189 GeV

A search for a Higgs boson decaying into invisible particles is performed using the data collected at LEP by the L3 experiment at centre-of-mass energies of 183 GeV and 189 GeV. The integrated luminosities are respectively 55.3 pb^-1 and 176.4 pb^-1. The observed candidates are consistent with the expectations from Standard Model processes. In the hypothesis that the production cross section of this Higgs boson equals the Standard Model one and the branching ratio into invisible particles is 100%, a lower mass limit of 89.2 GeV is set at 95% confidence level

On the dispersion of solid particles in a liquid agitated by a bubble swarm

This article deals with the dispersion of solid particles in a liquid agitated by a homogeneous swarm of bubbles. The scale of interest lies between the plant scale (of the order of the tank) and the microscale (less than the bubble diameter). The strategy consists in simulating both the twophase flow of deforming bubbles and the motion of solid particles. The evolution of the spatial distribution of particles together with the encounter and entrainment phenomena is studied as a function of the void fraction and the relative size and mass of particles. The influence of the shape of the bubble and of the model of forces that govern the motion of particles is also considered