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The 1D power spectrum P 1D of the Ly α forest provides important information about cosmological and astrophysical parameters, including constraints on warm dark matter models, the sum of the masses of the three neutrino species, and the thermal state of the intergalactic medium. We present the first measurement of P 1D with the quadratic maximum likelihood estimator (QMLE) from the Dark Energy Spectroscopic Instrument (DESI) survey early data sample. This early sample of 54 600 quasars is already comparable in size to the largest previous studies, and we conduct a thorough investigation of numerous instrumental and analysis systematic errors to evaluate their impact on DESI data with QMLE. We demonstrate the excellent performance of the spectroscopic pipeline noise estimation and the impressive accuracy of the spectrograph resolution matrix with 2D image simulations of raw DESI images that we processed with the DESI spectroscopic pipeline. We also study metal line contamination and noise calibration systematics with quasar spectra on the red side of the Ly α emission line. In a companion paper, we present a similar analysis based on the Fast Fourier Transform estimate of the power spectrum. We conclude with a comparison of these two approaches and discuss the key sources of systematic error that we need to address with the upcoming DESI Year 1 analysis. [ABSTRACT FROM AUTHOR]

We estimate the redshift-dependent, anisotropic clustering signal in the Dark Energy Spectroscopic Instrument (DESI) Year 1 Survey created by tidal alignments of Luminous Red Galaxies (LRGs) and a selection-induced galaxy orientation bias. To this end, we measured the correlation between LRG shapes and the tidal field with DESI's Year 1 redshifts, as traced by LRGs and Emission-Line Galaxies. We also estimate the galaxy orientation bias of LRGs caused by DESI's aperture-based selection, and find it to increase by a factor of seven between redshifts 0.4−1.1 due to redder, fainter galaxies falling closer to DESI's imaging selection cuts. These effects combine to dampen measurements of the quadrupole of the correlation function (ξ2) caused by structure growth on scales of 10–80 h −1 Mpc by about 0.15 per cent for low redshifts (0.4 < z < 0.6) and 0.8 per cent for high (0.8 < z < 1.1), a significant fraction of DESI's error budget. We provide estimates of the ξ2 signal created by intrinsic alignments that can be used to correct this effect, which is necessary to meet DESI's forecasted precision on measuring the growth rate of structure. While imaging quality varies across DESI's footprint, we find no significant difference in this effect between imaging regions in the Legacy Imaging Survey. [ABSTRACT FROM AUTHOR]

We present the one-dimensional Ly α forest power spectrum measurement using the first data provided by the Dark Energy Spectroscopic Instrument (DESI). The data sample comprises 26 330 quasar spectra, at redshift z > 2.1, contained in the DESI Early Data Release and the first 2 months of the main survey. We employ a Fast Fourier Transform (FFT) estimator and compare the resulting power spectrum to an alternative likelihood-based method in a companion paper. We investigate methodological and instrumental contaminants associated with the new DESI instrument, applying techniques similar to previous Sloan Digital Sky Survey (SDSS) measurements. We use synthetic data based on lognormal approximation to validate and correct our measurement. We compare our resulting power spectrum with previous SDSS and high-resolution measurements. With relatively small number statistics, we successfully perform the FFT measurement, which is already competitive in terms of the scale range. At the end of the DESI survey, we expect a five times larger Ly α forest sample than SDSS, providing an unprecedented precise one-dimensional power spectrum measurement. [ABSTRACT FROM AUTHOR]

Accurate quasar classifications and redshift measurements are increasingly important to precision cosmology experiments. Broad absorption line (BAL) features are present in 15–20 per cent of all quasars, and these features can introduce systematic redshift errors, and in extreme cases produce misclassifications. We quantitatively investigate the impact of BAL features on quasar classifications and redshift measurements with synthetic spectra that were designed to match observations by the Dark Energy Spectroscopic Instrument (DESI) survey. Over the course of 5 yr, DESI aims to measure spectra for 40 million galaxies and quasars, including nearly three million quasars. Our synthetic quasar spectra match the signal-to-noise ratio and redshift distributions of the first year of DESI observations, and include the same synthetic quasar spectra both with and without BAL features. We demonstrate that masking the locations of the BAL features decreases the redshift errors by about 1 per cent and reduces the number of catastrophic redshift errors by about 80 per cent. We conclude that identifying and masking BAL troughs should be a standard part of the redshift determination step for DESI and other large-scale spectroscopic surveys of quasars. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 59-year-old man who had an unusual case of an Epstein-Barr virus (EBV)-associated monotypic posttransplant lymphoproliferative disorder with plasmacytic features in leukemic phase.

The article discusses the Acute Leukemia French Association (ALFA)-0701 study which analyzes the positive impact of the level of blast CD33 expression to gemtuzumab ozogamicin (GO) in patients with acute myeloid leukemia. The in vitro result which shows the clear relationship between CD33 expression and GO efficacy and the evaluation of CD33 expression as a continuous covariable and highest response rates were reported for patients with CD33 expression in phase 2 study are mentioned.

Keywords: early assessment; flow cytometry; measurable residual disease; multiple myeloma; outcome EN early assessment flow cytometry measurable residual disease multiple myeloma outcome e82 e85 4 06/14/22 20220615 NES 220615 Multiple myeloma (MM) treatment has evolved remarkably with the introduction of new agents such as proteasome inhibitors, immunomodulatory drugs (IMIDS) and therapeutic antibodies. The level of minimal residual disease in the bone marrow of patients with multiple myeloma before high-dose therapy and autologous blood stem cell transplantation is an independent predictive parameter. The 26 patients with persistent positive MRD had worse PFS compared to the negative MRD post- and pre-ASCT cases (24 months vs 45 months vs 68 months, I p i < 0.0001). [Extracted from the article]

Our specialized population-based registry has allowed us to explore changes in incidence and survival by subtype over the last 30 years. Between 1980 and 2009, 4790 cases of lymphoid malignancies were registered using the International Classification of Diseases for Oncology. The incidence rate of lymphoid malignancies was 20.5 per 100 000 inhabitants per year, and ranged from 0.1 to 4 according to subtype. Five-year net survival was 65%, and ranged from 41 % to 93% according to subtype. We observed an increase in 5-year net survival between the periods 1980-1989 and 2000-2009 (58% vs. 70%). This was observed in most but not all subtypes. Our long-standing population-based registry allowed us to measure differences in trends according to the subtype of lymphoid malignancy. Incidence rates steadily increased in quite frequent entities, and poor survival probability for most entities indicates that they should be the next objective in therapeutic research programs. [ABSTRACT FROM AUTHOR]

Lymphoid neoplasms are a heterogeneous group of lymphoid neoplastic diseases with multiple presentations, and varying prognoses. They are especially frequent in older patients (OPs) and the atypism of this frail elderly population can make the diagnostic process even more difficult. Blood lymphocyte immunophenotyping (BLI) is essential in rapid noninvasive diagnosis orientation and guides complementary investigations. To our knowledge, BLI prescription has never been evaluated in OPs. We hypothesized that, when there is a suspicion of lymphoid neoplasm in the geriatric population, a BLI is performed in view of various clinical or biological abnormalities. This study aimed to: (1) describe the characteristics of hospitalized OPs having undergone BLI for suspected lymphoid neoplasm, (2) identify the causes leading to BLI prescription, and (3) identify the most profitable criteria for BLI prescription. This was a descriptive retrospective study on 151 OPs aged ≥75 years who underwent BLI over a 2-year period. Regarding BLI prescriptions, eight had lymphocytosis, constituting the "lymphocytosis group" (LG+), while the 143 others had BLI prescribed for reasons other than lymphocytosis (LG−), mainly general weakness and anemia. In the LG−, we compared OPs with positive and negative BLI results. The criteria found to be profitable for BLI prescription were lymphadenopathy, splenomegaly, lymphocytosis, and thrombocytopenia. BLI identified circulating lymphoid neoplasms (positive BLI) in 21/151 OPs, mainly marginal zone lymphoma and chronic lymphocytic leukemia. In polymorbid OPs, as per our study population, the diagnostic and therapeutic complexity explained in part the sole use of indirect and minimally invasive diagnostic techniques such as BLI. [ABSTRACT FROM AUTHOR]

Mitochondria have emerged as key actors of innate and adaptive immunity. Mitophagy has a pivotal role in cell homeostasis, but its contribution to macrophage functions and host defense remains to be delineated. Here, we showed that lipopolysaccharide (LPS) in combination with IFN-γ inhibited PINK1-dependent mitophagy in macrophages through a STAT1-dependent activation of the inflammatory caspases 1 and 11. In addition, we demonstrated that the inhibition of mitophagy triggered classical macrophage activation in a mitochondrial ROS-dependent manner. In a murine model of polymicrobial infection (cecal ligature and puncture), adoptive transfer of Pink1-deficient bone marrow or pharmacological inhibition of mitophagy promoted macrophage activation, which favored bactericidal clearance and led to a better survival rate. Reciprocally, mitochondrial uncouplers that promote mitophagy reversed LPS/IFN-γ-mediated activation of macrophages and led to immunoparalysis with impaired bacterial clearance and lowered survival. In critically ill patients, we showed that mitophagy was inhibited in blood monocytes of patients with sepsis as compared with nonseptic patients. Overall, this work demonstrates that the inhibition of mitophagy is a physiological mechanism that contributes to the activation of myeloid cells and improves the outcome of sepsis. [ABSTRACT FROM AUTHOR]

We present a measurement of baryonic acoustic oscillations (BAOs) from Lyα absorption and quasars at an effective redshift using the complete extended Baryonic Oscillation Spectroscopic Survey (eBOSS). The 16th and final eBOSS data release (SDSS DR16) contains all data from eBOSS and its predecessor, the Baryonic Oscillation Spectroscopic Survey (BOSS), providing 210,005 quasars with zq > 2.10 that are used to measure Lyα absorption. We measure the BAO scale both in the autocorrelation of Lyα absorption and in its cross-correlation with 341,468 quasars with redshift zq > 1.77. Apart from the statistical gain from new quasars and deeper observations, the main improvements over previous work come from more accurate modeling of physical and instrumental correlations and the use of new sets of mock data. Combining the BAO measurement from the auto- and cross-correlation yields the constraints of the two ratios and , where the error bars are statistical. These results are within 1.5σ of the prediction of the flat-ΛCDM cosmology of Planck (2016). The analysis code, picca , the catalog of the flux transmission field measurements, and the Δχ2 surfaces are publicly available. [ABSTRACT FROM AUTHOR]

We evaluate the impact of imaging systematics on the clustering of luminous red galaxies (LRG), emission-line galaxies (ELG), and quasars (QSO) targeted for the upcoming Dark Energy Spectroscopic Instrument (DESI) survey. Using Data Release 7 of the DECam Legacy Survey, we study the effects of astrophysical foregrounds, stellar contamination, differences between north galactic cap and south galactic cap measurements, and variations in imaging depth, stellar density, galactic extinction, seeing, airmass, sky brightness, and exposure time before presenting survey masks and weights to mitigate these effects. With our sanitized samples in hand, we conduct a preliminary analysis of the clustering amplitude and evolution of the DESI main targets. From measurements of the angular correlation functions, we determine power law fits |$r_0 = 7.78 \pm 0.26\, h^{-1}$| Mpc, γ  = 1.98 ± 0.02 for LRGs and |$r_0 = 5.45 \pm 0.1\, h^{-1}$| Mpc, γ  = 1.54 ± 0.01 for ELGs. Additionally, from the angular power spectra, we measure the linear biases and model the scale-dependent biases in the weakly non-linear regime. Both sets of clustering measurements show good agreement with survey requirements for LRGs and ELGs, attesting that these samples will enable DESI to achieve precise cosmological constraints. We also present clustering as a function of magnitude, use cross-correlations with external spectroscopy to infer dN/dz and measure clustering as a function of luminosity, and probe higher order clustering statistics through counts-in-cells moments. [ABSTRACT FROM AUTHOR]

We present a measurement of the baryon acoustic oscillation (BAO) scale at redshift z = 2.35 from the three-dimensional correlation of Lyman-α (Lyα) forest absorption and quasars. The study uses 266 590 quasars in the redshift range 1.77 <  z <  3.5 from the Sloan Digital Sky Survey (SDSS) Data Release 14 (DR14). The sample includes the first two years of observations by the SDSS-IV extended Baryon Oscillation Spectroscopic Survey (eBOSS), providing new quasars and re-observations of BOSS quasars for improved statistical precision. Statistics are further improved by including Lyα absorption occurring in the Lyβ wavelength band of the spectra. From the measured BAO peak position along and across the line of sight, we determined the Hubble distance DH and the comoving angular diameter distance DM relative to the sound horizon at the drag epoch rd: DH(z = 2.35)/rd = 9.20 ± 0.36 and DM(z = 2.35)/rd = 36.3 ± 1.8. These results are consistent at 1.5σ with the prediction of the best-fit spatially-flat cosmological model with the cosmological constant reported for the Planck (2016) analysis of cosmic microwave background anisotropies. Combined with the Lyα auto-correlation measurement presented in a companion paper, the BAO measurements at z = 2.34 are within 1.7σ of the predictions of this model. [ABSTRACT FROM AUTHOR]

We measure the imprint of primordial baryon acoustic oscillations (BAOs) in the correlation function of Lyα absorption in quasar spectra from the Baryon Oscillation Spectroscopic Survey (BOSS) and the extended BOSS (eBOSS) in Data Release 14 (DR14) of the Sloan Digital Sky Survey (SDSS)-IV. In addition to 179 965 spectra with absorption in the Lyman-α (Lyα) region, we use Lyα absorption in the Lyman-β region of 56 154 spectra for the first time. We measure the Hubble distance, DH, and the comoving angular diameter distance, DM, relative to the sound horizon at the drag epoch rd at an effective redshift z = 2.34. Using a physical model of the correlation function outside the BAO peak, we find DH(2.34)/rd = 8.86 ± 0.29 and DM(2.34)/rd = 37.41 ± 1.86, within 1σ from the flat-ΛCDM model consistent with CMB anisotropy measurements. With the addition of polynomial "broadband" terms, the results remain within one standard deviation of the CMB-inspired model. Combined with the quasar-Lyα cross-correlation measurement presented in a companion paper, the BAO measurements at z = 2.35 are within 1.7σ of the predictions of this model. [ABSTRACT FROM AUTHOR]

Cohen syndrome (CS) is a rare genetic disorder due to mutations in VPS13B gene. Among various clinical and biological features, CS patients suffer from inconsistent neutropenia, which is associated with recurrent but minor infections. We demonstrate here that this neutropenia results from an exaggerate rate of neutrophil apoptosis. Besides this increased cell death, which occurs in the absence of any endoplasmic reticulum stress or defect in neutrophil elastase (ELANE) expression or localization, all neutrophil functions appeared to be normal. We showed a disorganization of the Golgi apparatus in CS neutrophils precursors, that correlates with an altered glycosylation of ICAM-1 in these cells, as evidenced by a migration shift of the protein. Furthermore, a striking decrease in the expression of SERPINB1 gene, which encodes a critical component of neutrophil survival, was detected in CS neutrophils. These abnormalities may account for the excessive apoptosis of neutrophils leading to neutropenia in CS. Key messages: Cohen syndrome patients' neutrophils display normal morphology and functions. Cohen syndrome patients' neutrophils have an increased rate of spontaneous apoptosis compared to healthy donors' neutrophils. No ER stress or defective ELA2 expression or glycosylation was observed in Cohen syndrome patients' neutrophils. SerpinB1 expression is significantly decreased in Cohen syndrome neutrophils as well as in VPS13B-deficient cells. [ABSTRACT FROM AUTHOR]

Thrombotic manifestations are a hallmark of many auto-immune diseases (AID), specially of warm autoimmune hemolytic anemia (wAIHA), as 15 to 33% of adults with wAIHA experience venous thromboembolic events (VTE). However, beyond the presence of positive antiphospholipid antibodies and splenectomy, risk factors for developing a VTE during wAIHA have not been clearly identified. The aim of this retrospective study was to characterize VTEs during wAIHA and to identify risk factors for VTE. Forty-eight patients with wAIHA were included, among whom 26 (54%) had secondary wAIHA. Eleven (23%) patients presented at least one VTE, that occurred during an active phase of the disease for 10/11 patients (90%). The frequency of VTE was not different between primary and secondary AIHA (23.7 vs. 19.2%; p = 0.5). The Padua prediction score based on traditional risk factors was not different between patients with and without VTE. On multivariate analysis, total bilirubin ≥ 40 μmol/L [odds ratio (OR) = 7.4; p = 0.02] and leucocyte count above 7x109/L (OR = 15.7; p = 0.02) were significantly associated with a higher risk of thrombosis. Antiphospholipid antibodies were screened in 9 out the 11 patients who presented a VTE and were negative. Thus, the frequency of VTE is high (23%) during wAIHA and VTE preferentially occur within the first weeks of diagnosis. As no clinically relevant predictive factors of VTE could be identified, the systematic use of a prophylactic anticoagulation should be recommended in case of active hemolysis and its maintenance after hospital discharge should be considered. The benefit of a systematic screening for VTE and its procedure remain to be determined. [ABSTRACT FROM AUTHOR]

Background: In this study, we primarily sought to assess the ability of flow cytometry to predict early clinical deterioration and overall survival in patients with sepsis admitted in the ED and ICU.Methods: Patients admitted for community-acquired acute sepsis from 11 hospital centers were eligible. Early (day 7) and late (day 28) deaths were notified. Levels of CD64pos granulocytes, CD16pos monocytes, CD16dim immature granulocytes (IGs), and T and B lymphocytes were assessed by flow cytometry using an identical, cross-validated, robust, and simple consensus standardized protocol in each center.Results: Among 1,062 patients screened, 781 patients with confirmed sepsis were studied (age, 67 ± 48 years; Simplified Acute Physiology Score II, 36 ± 17; Sequential Organ Failure Assessment, 5 ± 4). Patients were divided into three groups (sepsis, severe sepsis, and septic shock) on day 0 and on day 2. On day 0, patients with sepsis exhibited increased levels of CD64pos granulocytes, CD16pos monocytes, and IGs with T-cell lymphopenia. Clinical severity was associated with higher percentages of IGs and deeper T-cell lymphopenia. IG percentages tended to be higher in patients whose clinical status worsened on day 2 (35.1 ± 35.6 vs 43.5 ± 35.2, P = .07). Increased IG percentages were also related to occurrence of new organ failures on day 2. Increased IG percentages, especially when associated with T-cell lymphopenia, were independently associated with early (P < .01) and late (P < .01) death.Conclusions: Increased circulating IGs at the acute phase of sepsis are linked to clinical worsening, especially when associated with T-cell lymphopenia. Early flow cytometry could help clinicians to target patients at high risk of clinical deterioration.Trial Registry: ClinicalTrials.gov; No.: NCT01995448; URL: www.clinicaltrials.gov. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: To investigate the efficacy, safety, and cost of a pomalidomide‐dexamethasone regimen in patients with relapsed and refractory multiple myeloma (RRMM). Methods: All patients (n = 63) treated with pomalidomide‐dexamethasone for RRMM in our university hospital between August 2013 and October 2015 were included. Results: Pomalidomide was discontinued early due to progression (before the 4th cycle) in 17 (27%) patients. No case was discontinued for intolerance. The only independent factor that predicted early pomalidomide discontinuation was time from diagnosis to pomalidomide initiation <3 years. Overall response rate was 51% including complete response in 8%, very good partial response in 25%, and partial response in 19% patients. Thirteen (33%) patients showed stable disease. Median overall survival was 6.4 months in the 17 patients who discontinued pomalidomide early vs 26.8 months in the 14 patients with stable disease vs not achieved in the 32 responders (log‐rank; P < 10−3). The most common grade ≥3 adverse events were neutropenia (14%) and infections (25%). The incremental cost‐effectiveness ratio of pomalidomide‐dexamethasone compared with dexamethasone alone was estimated at €39 911 per life‐year gained. Conclusions: The study demonstrated that pomalidomide‐dexamethasone regimen has a long‐term favorable safety‐efficacy profile in RRMM patients. The survival benefit is substantial even in patients with stable disease. [ABSTRACT FROM AUTHOR]

Background: Expression of SRY [sex-determining region Y]-box11 (SOX11) is specific to mantle cell lymphoma (MCL) and contributes, in conjunction with immunoglobulin variable heavy chain gene mutation status, to the identification of two forms of this disease. Methods: The aim of this report was firstly, to design an easy and suitable RT-qPCR method to quantify SOX11 mRNA expression in mantle cell lymphoma and other B cell malignancies with the proper reference gene; secondly, to define the best threshold of relative quantity of SOX11 mRNA in order to reach the best compromise between sensitivity and specificity. Results: For best discrimination of MCL and non-MCL groups we determined an area under the curve (AUC) of 0.9750 and a threshold of 1.76 with 100% sensitivity and 88% specificity. AUC and threshold values of respectively 0.91/1.346 [87% sensitivity, 80% specificity] and 0.9525/1.7120 [100% sensitivity, 88% specificity] for GAPDH and RPLP0 respectively denote that the RPLP0 reference gene alone is sufficient for PCR housekeeping gene. Conclusion: This work describes an RT-qPCR assay for SOX11 expression in order to better characterize MCL at diagnosis. Further studies on larger cohorts are needed to evaluate this molecular tool, especially for the follow-up of minimal residual disease. [ABSTRACT FROM AUTHOR]

Calreticulin (CALR) mutations have recently been reported in 70–84% of JAK2V617F-negative myeloproliferative neoplasms (MPN), and this detection has become necessary to improve the diagnosis of MPN. In a large single-centre cohort of 298 patients suffering from Essential Thrombocythemia (ET), the JAK2V617F, CALR and MPL mutations were noted in 179 (60%), 56 (18.5%) and 13 (4.5%) respectively. For the detection of the CALR mutations, three methods were compared in parallel: high-resolution melting-curve analysis (HRM), product-sizing analysis and Sanger sequencing. The sensitivity for the HRM, product-sizing analysis and Sanger sequencing was 96.4%, 98.2% and 89.3% respectively, whereas the specificity was 96.3%, 100% and 100%. In our cohort, the product-sizing analysis was the most sensitive method and was the easiest to interpret, while the HRM was sometimes difficult to interpret. In contrast, when large series of samples were tested, HRM provided results more quickly than did the other methods, which required more time. Finally, the sequencing method, which is the reference method, had the lowest sensitivity but can be used to describe the type of mutation precisely. Altogether, our results suggest that in routine laboratory practice, product-sizing analysis is globally similar to HRM for the detection of CALR mutations, and that both may be used as first-line screening tests. If the results are positive, Sanger sequencing can be used to confirm the mutation and to determine its type. Product-sizing analysis provides sensitive and specific results, moreover, with the quantitative measurement of CALR, which might be useful to monitor specific treatments. [ABSTRACT FROM AUTHOR]

An amendment to this paper has been published and can be accessed via the original article. [ABSTRACT FROM AUTHOR]

Background: Although immune modulation is a promising therapeutic avenue in coronavirus disease 2019 (COVID-19), the most relevant targets remain to be found. COVID-19 has peculiar characteristics and outcomes, suggesting a unique immunopathogenesis.Methods: Thirty-six immunocompetent non-COVID-19 and 27 COVID-19 patients with severe pneumonia were prospectively enrolled in a single center, most requiring intensive care. Clinical and biological characteristics (including T cell phenotype and function and plasma concentrations of 30 cytokines) and outcomes were compared.Results: At similar baseline respiratory severity, COVID-19 patients required mechanical ventilation for significantly longer than non-COVID-19 patients (15 [7-22] vs. 4 (0-15) days; p = 0.0049). COVID-19 patients had lower levels of most classical inflammatory cytokines (G-CSF, CCL20, IL-1β, IL-2, IL-6, IL-8, IL-15, TNF-α, TGF-β), but higher plasma concentrations of CXCL10, GM-CSF and CCL5, compared to non-COVID-19 patients. COVID-19 patients displayed similar T-cell exhaustion to non-COVID-19 patients, but with a more unbalanced inflammatory/anti-inflammatory cytokine response (IL-6/IL-10 and TNF-α/IL-10 ratios). Principal component analysis identified two main patterns, with a clear distinction between non-COVID-19 and COVID-19 patients. Multivariate regression analysis confirmed that GM-CSF, CXCL10 and IL-10 levels were independently associated with the duration of mechanical ventilation.Conclusion: We identified a unique cytokine response, with higher plasma GM-CSF and CXCL10 in COVID-19 patients that were independently associated with the longer duration of mechanical ventilation. These cytokines could represent the dysregulated immune response in severe COVID-19, as well as promising therapeutic targets. ClinicalTrials.gov: NCT03505281. [ABSTRACT FROM AUTHOR]