Cyclophosphamide for interstitial lung disease-associated acute respiratory failure:mortality, clinical response and radiological characteristics

BACKGROUND: Treatment for interstitial lung disease (ILD) patients with acute respiratory failure (ARF) is challenging, and literature to guide such treatment is scarce. The reported in-hospital mortality rates of ILD patients with ARF are high (62–66%). Cyclophosphamide is considered a second-line treatment in steroid-refractory ILD-associated ARF. The first aim of this study was to evaluate the in-hospital mortality in patients with ILD-associated ARF treated with cyclophosphamide. The second aim was to compare computed tomographic (CT) patterns and physiological and ventilator parameters between survivors and non-survivors. METHODS: Retrospective analysis of patients with ILD-associated ARF treated with cyclophosphamide between February 2016 and October 2017. Patients were categorized into three subgroups: connective tissue disease (CTD)-associated ILD, other ILD or vasculitis. In-hospital mortality was evaluated in the whole cohort and in these subgroups. Clinical response was determined using physiological and ventilator parameters: Sequential Organ Failure Assessment Score (SOFA), PaO2/FiO2 (P/F) ratio and dynamic compliance (Cdyn) before and after cyclophosphamide treatment. The following CT features were quantified: ground-glass opacification (GGO) proportion, reticulation proportion, overall extent of parenchymal disease and fibrosis coarseness score. RESULTS: Fifteen patients were included. The overall in-hospital mortality rate was 40%. In-hospital mortality rates for CTD-associated ILD, other ILD and vasculitis were 20, 57, and 33%, respectively. The GGO proportion (71% vs 45%) was higher in non-survivors. There were no significant differences in the SOFA score, P/F ratio or Cdyn between survivors and non-survivors. However, in survivors the P/F ratio increased from 129 to 220 mmHg and Cdyn from 75 to 92 mL/cmH2O 3 days after cyclophosphamide treatment. In non-survivors the P/F ratio hardly changed (113–114 mmHg) and Cdyn even decreased (27–20 mL/cmH2O). CONCLUSION: In this study, we found a mortality rate of 40% in patients treated with cyclophosphamide for ILD-associated ARF. Connective tissue disease-associated ILD and vasculitis were associated with a lower risk of death. In non-survivors, the CT GGO proportion was significantly higher. The P/F ratio and Cdyn in survivors increased after 3 days of cyclophosphamide treatment. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12890-021-01615-2

Comorbid conditions explain the association between posttraumatic stress disorder and incident cardiovascular disease

Background Posttraumatic stress disorder ( PTSD ) is associated with risk of cardiovascular disease ( CVD ). Biopsychosocial factors associated with PTSD likely account for some or all of this association. We determined whether 1, or a combination of comorbid conditions explained the association between PTSD and incident CVD . Methods and Results Eligible patients used 1 of 5 Veterans Health Affairs medical centers distributed across the United States. Data were obtained from electronic health records. At index date, 2519 Veterans Health Affairs ( VA ) patients, 30 to 70 years of age, had PTSD diagnoses and 1659 did not. Patients had no CVD diagnoses for 12 months before index date. Patients could enter the cohort between 2008 and 2012 with follow-up until 2015. Age-adjusted Cox proportional hazard models were computed before and after adjusting for comorbidities. Patients were middle aged (mean=50.1 years, SD ±11.0), mostly male (87.0%), and 60% were white. The age-adjusted association between PTSD and incident CVD was significant (hazard ratio=1.41; 95% CI : 1.21-1.63). After adjustment for metabolic conditions, the association between PTSD and incident CVD was attenuated but remained significant (hazard ratio=1.23; 95% CI : 1.06-1.44). After additional adjustment for smoking, sleep disorder, substance use disorder, anxiety disorders, and depression, PTSD was not associated with incident CVD (hazard ratio=0.96; 95% CI : 0.81-1.15). Conclusions PTSD is not an independent risk factor for CVD . Physical and psychiatric conditions and smoking that co-occur with PTSD explain why this patient population has an increased risk of CVD . Careful monitoring may limit exposure to CVD risk factors and subsequent incident CVD

Greenhouse Gas Reduction Pathways: In the UNFCCC Process up to 2025

Meeting the EU objective of limiting global average temperature increase to 2 degrees Celsius above pre-industrial levels requires a peak in global greenhouse gas emissions within the next two decades. This means that early participation of developing countries in global emission control is needed, even under a significant strengthening of the commitments of Annex I countries under the Kyoto Protocol. The study has shown that it is possible to design a set of consistent rules for the attribution of the long-term emission endowments of the different world regions. The gains from participating in global emission trading and from reduced air pollution damage and/or abatement costs does substantially enhance, from a developing country perspective, the attractiveness of an early participation in a regime based on greenhouse gas reduction pathways, provided that the level and the form of their commitment is well designed so as to minimise economic risks

USP15 deubiquitinase safeguards hematopoiesis and genome integrity in hematopoietic stem cells and leukemia cells

Altering ubiquitination by disruption of individual deubiquitinating enzymes (DUBs) has proven to affect hematopoietic stem cell (HSC) maintenance. However, comprehensive knowledge of DUB function during hematopoiesis in vivo is lacking. To accomplish this goal, we systematically inactivated DUBs in mouse hematopoietic progenitors using in vivo small hairpin RNAs (shRNAs) screens. We found that multiple DUBs may be individually required for hematopoiesis and that the ubiquitin-specific protease 15 (USP15) is particularly important for the maintenance of murine hematopoietic stem and progenitor cells in vitro and in vivo. Consistently, Usp15 knockout mice exhibited a reduced HSC pool. The defect was intrinsic to HSCs, as demonstrated by competitive repopulation assays. Importantly, USP15 is highly expressed in normal human hematopoietic cells and leukemias, and USP15 depletion in murine early progenitors and myeloid leukemia cells impaired in vitro expansion and increased genotoxic stress. Our study underscores the importance of DUBs in preserving normal hematopoiesis and uncovers USP15 as a critical DUB in safeguarding genome integrity in HSC and in leukemia cells

The dynamical evolution of very-low mass binaries in open clusters

Very low-mass binaries (VLMBs), with system masses <0.2 Msun appear to have very different properties to stellar binaries. This has led to the suggestion that VLMBs form a distinct and different population. As most stars are born in clusters, dynamical evolution can significantly alter any initial binary population, preferentially destroying wide binaries. In this paper we examine the dynamical evolution of initially different VLMB distributions in clusters to investigate how different the initial and final distributions can be. We find that the majority of the observed VLMB systems, which have separations <20 au, cannot be destroyed in even the densest clusters. Therefore, the distribution of VLMBs with separations <20 au now must have been the birth population (although we note that the observations of this population may be very incomplete). Most VLMBs with separations >100 au can be destroyed in high-density clusters, but are mainly unaffected in low-density clusters. Therefore, the initial VLMB population must contain many more binaries with these separations than now, or such systems must be made by capture during cluster dissolution. M-dwarf binaries are processed in the same way as VLMBs and so the difference in the current field populations either points to fundamentally different birth populations, or significant observational incompleteness in one or both samples.Comment: 11 pages, 10 figues, accepted for publication in MNRA

Variability selected high-redshift quasars on SDSS Stripe 82

The SDSS-III BOSS Quasar survey will attempt to observe z>2.15 quasars at a density of at least 15 per square degree to yield the first measurement of the Baryon Acoustic Oscillations in the Ly-alpha forest. To help reaching this goal, we have developed a method to identify quasars based on their variability in the u g r i z optical bands. The method has been applied to the selection of quasar targets in the SDSS region known as Stripe 82 (the Southern equatorial stripe), where numerous photometric observations are available over a 10-year baseline. This area was observed by BOSS during September and October 2010. Only 8% of the objects selected via variability are not quasars, while 90% of the previously identified high-redshift quasar population is recovered. The method allows for a significant increase in the z>2.15 quasar density over previous strategies based on optical (ugriz) colors, achieving a density of 24.0 deg^{-2} on average down to g~22 over the 220 deg^2 area of Stripe 82. We applied this method to simulated data from the Palomar Transient Factory and from Pan-STARRS, and showed that even with data that have sparser time sampling than what is available in Stripe 82, including variability in future quasar selection strategies would lead to increased target selection efficiency in the z>2.15 redshift range. We also found that Broad Absorption Line quasars are preferentially present in a variability than in a color selection.Comment: 14 pages, 21 figures, accepted for publication in A&

A translucent interstellar cloud at z=2.69: CO, H2 and HD in the line-of-sight to SDSS J123714.60+064759.5

We present the analysis of a sub-DLA system (log N(H^0)=20.0+/-0.15, z_abs=2.69) toward SDSS J123714+064759 (z_em=2.78). Using the VLT/UVES and X-shooter spectrographs, we detect H2, HD and CO molecules in absorption with log N(H2,HD,CO)=(19.21,14.48,14.17). The overall metallicity of the system is super-solar ([Zn/H]=+0.34) and iron is highly depleted ([Fe/Zn]=-1.39), revealing metal-rich and dusty gas. The strongest H2 component does not coincide with the centre of the HI absorption. This implies that the molecular fraction in this component, f=2N(H2)/(2N(H2)+N(H^0)), is larger than the mean molecular fraction =1/4 in the system. This is supported by the detection of Cl^0 associated with this H2-component having N(Cl^0)/N(Cl^+)>0.4. Since Cl^0 is tied up to H2 by charge exchange reactions, this means that the molecular fraction in this component is not far from unity. The size of the molecular cloud is probably smaller than 1pc. Both the CO/H2=10^-5 and CO/C^0~1 ratios for f>0.24 indicate that the cloud classifies as translucent, i.e., a regime where carbon is found both in atomic and molecular form. The corresponding extinction, Av=0.14, albeit lower than the definition of a translucent sightline (based on extinction properties), is high for the observed H^0 column density. This means that intervening clouds with similar local properties but with larger column densities could be missed by current magnitude-limited QSO surveys. The excitation of CO is dominated by radiative interaction with the Cosmic Microwave Background Radiation (CMBR) and we derive Tex(CO)=10.5+0.8-0.6 K when TCMBR(z=2.69)=10.05 K is expected. The astration factor of deuterium -with respect to the primordial D/H ratio- is only about 3. This can be the consequence of accretion of unprocessed gas from the intergalactic medium onto the associated galaxy. [abridged]Comment: 17 pages, 21 figures, 8 tables, accepted for publication in A&

Search for cold gas in strong MgII absorbers at 0.5<z<1.5: nature and evolution of 21-cm absorbers

We report 4 new detections of 21-cm absorption from a systematic search of 21-cm absorption in a sample of 17 strong (Wr(MgII 2796)>1A) intervening MgII absorbers at 0.5<z<1.5. We also present 20-cm milliarcsecond scale maps of 40 quasars having 42 intervening strong MgII absorbers for which we have searched for 21-cm absorption. Combining 21-cm absorption measurements for 50 strong MgII systems from our surveys with the measurements from literature, we obtain a sample of 85 strong MgII absorbers at 0.5<z<1 and 1.1<z<1.5. We present detailed analysis of this sample, taking into account the effect of the varying 21-cm optical depth sensitivity and covering factor associated with the different quasar sight lines. We find that the 21-cm detection rate is higher towards the quasars with flat or inverted spectral index at cm wavelengths. About 70% of 21-cm detections are towards the quasars with linear size, LS<100 pc. The 21-cm absorption lines having velocity widths, DeltaV>100 km/s are mainly seen towards the quasars with extended radio morphology at arcsecond scales. However, we do not find any correlation between the integrated 21-cm optical depth or DeltaV with the LS measured from the milliarcsecond scale images. All this can be understood if the absorbing gas is patchy with a typical correlation length of ~30-100 pc. We show that within the measurement uncertainty, the 21-cm detection rate in strong MgII systems is constant over 0.5<z<1.5, i.e., over ~30% of the total age of universe. We show that the detection rate can be underestimated by up to a factor 2 if 21-cm optical depths are not corrected for the partial coverage estimated using milliarcsecond scale maps. Since stellar feedback processes are expected to diminish the filling factor of cold neutral medium over 0.5<z<1, this lack of evolution in the 21-cm detection rate in strong MgII absorbers is intriguing. [abridged]Comment: 28 pages, 14 figures, 9 tables, accepted for publication in Astronomy and Astrophysic

The formation of very wide binaries during the star cluster dissolution phase

Over the past few decades, numerous wide (>1000 au) binaries in the Galactic field and halo have been discovered. Their existence cannot be explained by the process of star formation or by dynamical interactions in the field, and their origin has long been a mystery. We explain the origin of these wide binaries by formation during the dissolution phase of young star clusters: an initially unbound pair of stars may form a binary when their distance in phase-space is small. Using N-body simulations, we find that the resulting wide binary fraction in the semi-major axis range 1000 au - 0.1 pc for individual clusters is 1-30%, depending on the initial conditions. The existence of numerous wide binaries in the field is consistent with observational evidence that most clusters start out with a large degree of substructure. The wide binary fraction decreases strongly with increasing cluster mass, and the semi-major axis of the newly formed binaries is determined by the initial cluster size. The resulting eccentricity distribution is thermal, and the mass ratio distribution is consistent with gravitationally-focused random pairing. As a large fraction of the stars form in primordial binaries, we predict that a large number of the observed 'wide binaries' are in fact triple or quadruple systems. By integrating over the initial cluster mass distribution, we predict a binary fraction of a few per cent in the semi-major axis range 1000 au - 0.1 pc in the Galactic field, which is smaller than the observed wide binary fraction. However, this discrepancy may be solved when we consider a broad range of cluster morphologies.Comment: 14 pages, 12 figures, accepted by MNRA