An optimization of hematopoietic stem and progenitor cell isolation for scientific and clinical purposes by the application of a new parameter determining the hematopoietic graft efficacy.

The transplantation of hematopoietic stem and progenitor cells (HSPC) is an established lifesaving therapy. Bone marrow (BM), harvested from heparinized cadaveric organ donors, peripheral blood (PB) and cord blood (CB), are important sources of hematopoietic stem cells. HSPCs, which are used for transplantation purposes, are routinely evaluated in terms of number of mononuclear cells (MNCs), CD34+ MNCs count and viability. The efficacy of grafting is determined additionally in clonogenic tests in vitro. These tests deliver important information about the number of HSPCs and their proliferative potential. Unfortunately, they do not give a possibility to evaluate the functional HSPC chemotactic reactivity in the SDF-1 gradient, which is probably the key phenomenon for HSPC homing after transplantation procedure. Thus, the aim of our study was to optimize HSPC isolation according to their chemotactic reactivity in SDF-1 gradient. Using multiparameter cell sorter (FACS Aria, BD) we examined the HSPCs attracted by SDF-1 on a single cell level. The population of cells which participated in the chemotactic process was highly enriched in CXCR4+lin-AC133+CD45+ cells (referred as hematopoietic stem cells) and to our surprise in CXCR4+lin-AC133+CD45- cells (referred as pluripotent stem cells) in quantitative amounts. Since reactivity of HSPCs may depend on various factors involved in the protocol of their isolation and short-term storage, we tested the most commonly used anticoagulants (ACD, CPDA-1, EDTA and Heparin) and culture media (DME, IMDM, RPMI). HSPCs, harvested from CB, PB and BM, were subsequently investigated for clonogenic growth of CFU-GM in methylcellulose cultures and for the level of apoptosis by employing annexin V staining. Evaluating clonogenic potential, ability of chemotactic reactivity in SDF-1 gradient and intensification of apoptosis of HSPC as the most safe anticoagulant and medium were selected. This study has proved that chemotactic reactivity of HSPCs is a new but very important parameter which should be included in the procedure of their isolation

Spherically symmetric Einstein-Maxwell theory and loop quantum gravity corrections

Effects of inverse triad corrections and (point) holonomy corrections, occuring in loop quantum gravity, are considered on the properties of Reissner-Nordstr\"om black holes. The version of inverse triad corrections with unmodified constraint algebra reveals the possibility of occurrence of three horizons (over a finite range of mass) and also shows a mass threshold beyond which the inner horizon disappears. For the version with modified constraint algebra, coordinate transformations are no longer a good symmetry. The covariance property of spacetime is regained by using a \emph{quantum} notion of mapping from phase space to spacetime. The resulting quantum effects in both versions of these corrections can be associated with renormalization of either mass, charge or wave function. In neither of the versions, Newton's constant is renormalized. (Point) Holonomy corrections are shown to preclude the undeformed version of constraint algebra as also a static solution, though time-independent solutions exist. A possible reason for difficulty in constructing a covariant metric for these corrections is highlighted. Furthermore, the deformed algebra with holonomy corrections is shown to imply signature change.Comment: 38 pages, 9 figures, matches published versio

Turning big bang into big bounce: II. Quantum dynamics

We analyze the big bounce transition of the quantum FRW model in the setting of the nonstandard loop quantum cosmology (LQC). Elementary observables are used to quantize composite observables. The spectrum of the energy density operator is bounded and continuous. The spectrum of the volume operator is bounded from below and discrete. It has equally distant levels defining a quantum of the volume. The discreteness may imply a foamy structure of spacetime at semiclassical level which may be detected in astro-cosmo observations. The nonstandard LQC method has a free parameter that should be fixed in some way to specify the big bounce transition.Comment: 14 pages, no figures, version accepted for publication in Class. Quant. Gra

Gaussian state for the bouncing quantum cosmology

We present results concerning propagation of the Gaussian state across the cosmological quantum bounce. The reduced phase space quantization of loop quantum cosmology is applied to the Friedman-Robertson-Walker universe with a free massless scalar field. Evolution of quantum moments of the canonical variables is investigated. The covariance turns out to be a monotonic function so it may be used as an evolution parameter having quantum origin. We show that for the Gaussian state the Universe is least quantum at the bounce. We propose explanation of this counter-intuitive feature using the entropy of squeezing. The obtained time dependence of entropy is in agreement with qualitative predictions based on von Neumann entropy for mixed states. We show that, for the considered Gaussian state, semiclassicality is preserved across the bounce, so there is no cosmic forgetfulness.Comment: 7 pages, 7 figures; matches version published in Phys. Rev.

Evolution in bouncing quantum cosmology

We present the method of describing an evolution in quantum cosmology in the framework of the reduced phase space quantization of loop cosmology. We apply our method to the flat Friedman-Robertson-Walker model coupled to a massless scalar field. We identify the physical quantum Hamiltonian that is positive-definite and generates globally an unitary evolution of considered quantum system. We examine properties of expectation values of physical observables in the process of the quantum big bounce transition. The dispersion of evolved observables are studied for the Gaussian state. Calculated relative fluctuations enable an examination of the semi-classicality conditions and possible occurrence of the cosmic forgetfulness. Preliminary estimations based on the cosmological data suggest that there was no cosmic amnesia. Presented results are analytical, and numerical computations are only used for the visualization purposes. Our method may be generalized to sophisticated cosmological models including the Bianchi type universes.Comment: 28 pages, 7 figures. Matches version published in Class. Quantum Gra

Loop Quantum Cosmology: A Status Report

The goal of this article is to provide an overview of the current state of the art in loop quantum cosmology for three sets of audiences: young researchers interested in entering this area; the quantum gravity community in general; and, cosmologists who wish to apply loop quantum cosmology to probe modifications in the standard paradigm of the early universe. An effort has been made to streamline the material so that, as described at the end of section I, each of these communities can read only the sections they are most interested in, without a loss of continuity.Comment: 138 pages, 15 figures. Invited Topical Review, To appear in Classical and Quantum Gravity. Typos corrected, clarifications and references adde

Loop quantum gravity: the first twenty five years

This is a review paper invited by the journal "Classical ad Quantum Gravity" for a "Cluster Issue" on approaches to quantum gravity. I give a synthetic presentation of loop gravity. I spell-out the aims of the theory and compare the results obtained with the initial hopes that motivated the early interest in this research direction. I give my own perspective on the status of the program and attempt of a critical evaluation of its successes and limits.Comment: 24 pages, 3 figure

Quantum gravity phenomenology at the dawn of the multi-messenger era—A review

The exploration of the universe has recently entered a new era thanks to the multi-messenger paradigm, characterized by a continuous increase in the quantity and quality of experimental data that is obtained by the detection of the various cosmic messengers (photons, neutrinos, cosmic rays and gravitational waves) from numerous origins. They give us information about their sources in the universe and the properties of the intergalactic medium. Moreover, multi-messenger astronomy opens up the possibility to search for phenomenological signatures of quantum gravity. On the one hand, the most energetic events allow us to test our physical theories at energy regimes which are not directly accessible in accelerators; on the other hand, tiny effects in the propagation of very high energy particles could be amplified by cosmological distances. After decades of merely theoretical investigations, the possibility of obtaining phenomenological indications of Planck-scale effects is a revolutionary step in the quest for a quantum theory of gravity, but it requires cooperation between different communities of physicists (both theoretical and experimental). This review, prepared within the COST Action CA18108 “Quantum gravity phenomenology in the multi-messenger approach”, is aimed at promoting this cooperation by giving a state-of-the art account of the interdisciplinary expertise that is needed in the effective search of quantum gravity footprints in the production, propagation and detection of cosmic messengers.publishedVersio

Temporal changes in the epidemiology, management, and outcome from acute respiratory distress syndrome in European intensive care units: a comparison of two large cohorts

Background: Mortality rates for patients with ARDS remain high. We assessed temporal changes in the epidemiology and management of ARDS patients requiring invasive mechanical ventilation in European ICUs. We also investigated the association between ventilatory settings and outcome in these patients. Methods: This was a post hoc analysis of two cohorts of adult ICU patients admitted between May 1–15, 2002 (SOAP study, n = 3147), and May 8–18, 2012 (ICON audit, n = 4601 admitted to ICUs in the same 24 countries as the SOAP study). ARDS was defined retrospectively using the Berlin definitions. Values of tidal volume, PEEP, plateau pressure, and FiO2 corresponding to the most abnormal value of arterial PO2 were recorded prospectively every 24 h. In both studies, patients were followed for outcome until death, hospital discharge or for 60 days. Results: The frequency of ARDS requiring mechanical ventilation during the ICU stay was similar in SOAP and ICON (327[10.4%] vs. 494[10.7%], p = 0.793). The diagnosis of ARDS was established at a median of 3 (IQ: 1–7) days after admission in SOAP and 2 (1–6) days in ICON. Within 24 h of diagnosis, ARDS was mild in 244 (29.7%), moderate in 388 (47.3%), and severe in 189 (23.0%) patients. In patients with ARDS, tidal volumes were lower in the later (ICON) than in the earlier (SOAP) cohort. Plateau and driving pressures were also lower in ICON than in SOAP. ICU (134[41.1%] vs 179[36.9%]) and hospital (151[46.2%] vs 212[44.4%]) mortality rates in patients with ARDS were similar in SOAP and ICON. High plateau pressure (> 29 cmH2O) and driving pressure (> 14 cmH2O) on the first day of mechanical ventilation but not tidal volume (> 8 ml/kg predicted body weight [PBW]) were independently associated with a higher risk of in-hospital death. Conclusion: The frequency of and outcome from ARDS remained relatively stable between 2002 and 2012. Plateau pressure > 29 cmH2O and driving pressure > 14 cmH2O on the first day of mechanical ventilation but not tidal volume > 8 ml/kg PBW were independently associated with a higher risk of death. These data highlight the continued burden of ARDS and provide hypothesis-generating data for the design of future studies

The clinical relevance of oliguria in the critically ill patient : Analysis of a large observational database

Funding Information: Marc Leone reports receiving consulting fees from Amomed and Aguettant; lecture fees from MSD, Pfizer, Octapharma, 3 M, Aspen, Orion; travel support from LFB; and grant support from PHRC IR and his institution. JLV is the Editor-in-Chief of Critical Care. The other authors declare that they have no relevant financial interests. Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Urine output is widely used as one of the criteria for the diagnosis and staging of acute renal failure, but few studies have specifically assessed the role of oliguria as a marker of acute renal failure or outcomes in general intensive care unit (ICU) patients. Using a large multinational database, we therefore evaluated the occurrence of oliguria (defined as a urine output 16 years) patients in the ICON audit who had a urine output measurement on the day of admission were included. To investigate the association between oliguria and mortality, we used a multilevel analysis. Results: Of the 8292 patients included, 2050 (24.7%) were oliguric during the first 24 h of admission. Patients with oliguria on admission who had at least one additional 24-h urine output recorded during their ICU stay (n = 1349) were divided into three groups: transient - oliguria resolved within 48 h after the admission day (n = 390 [28.9%]), prolonged - oliguria resolved > 48 h after the admission day (n = 141 [10.5%]), and permanent - oliguria persisting for the whole ICU stay or again present at the end of the ICU stay (n = 818 [60.6%]). ICU and hospital mortality rates were higher in patients with oliguria than in those without, except for patients with transient oliguria who had significantly lower mortality rates than non-oliguric patients. In multilevel analysis, the need for RRT was associated with a significantly higher risk of death (OR = 1.51 [95% CI 1.19-1.91], p = 0.001), but the presence of oliguria on admission was not (OR = 1.14 [95% CI 0.97-1.34], p = 0.103). Conclusions: Oliguria is common in ICU patients and may have a relatively benign nature if only transient. The duration of oliguria and need for RRT are associated with worse outcome.publishersversionPeer reviewe