Severe bronchopulmonary dysplasia improved by noninvasive positive pressure ventilation: a case report

<p>Abstract</p> <p>Introduction</p> <p>This is the first report to describe the feasibility and effectiveness of noninvasive positive pressure ventilation in the secondary treatment of bronchopulmonary dysplasia.</p> <p>Case presentation</p> <p>A former male preterm of Caucasian ethnicity delivered at 29 weeks gestation developed severe bronchopulmonary dysplasia. At the age of six months he was in permanent tachypnea and dyspnea and in need of 100% oxygen with a flow of 2.0 L/minute via a nasal cannula. Intermittent nocturnal noninvasive positive pressure ventilation was then administered for seven hours daily. The ventilator was set at a positive end-expiratory pressure of 6 cmH₂O, with pressure support of 4 cmH₂O, trigger at 1.4 mL/second, and a maximum inspiratory time of 0.7 seconds. Over the course of seven weeks, the patient's maximum daytime fraction of inspired oxygen via nasal cannula decreased from 1.0 to 0.75, his respiratory rate from 64 breaths/minute to 50 breaths/minute and carbon dioxide from 58 mmHg to 44 mmHg.</p> <p>Conclusion</p> <p>Noninvasive positive pressure ventilation may be a novel therapeutic option for established severe bronchopulmonary dysplasia. In the case presented, noninvasive positive pressure ventilation achieved sustained improvement in ventilation and thus prepared our patient for safe home oxygen therapy.</p

Loss of Kat2A Enhances Transcriptional Noise and Depletes Acute Myeloid Leukemia Stem-Like Cells

Acute Myeloid Leukemia (AML) is an aggressive hematological malignancy with abnormal progenitor self-renewal and defective myelo-monocytic differentiation. Its pathogenesis comprises subversion of transcriptional regulation, through mutation and by hijacking normal chromatin regulation. Kat2a is a histone acetyltransferase central to promoter activity that we recently associated with stability of pluripotency networks, and identified as a genetic vulnerability in AML. Through combined chromatin profiling and single-cell transcriptomics, we demonstrate that Kat2a contributes to leukemia propagation through homogeneity of transcriptional programs and preservation of leukemia stem-like cells. Kat2a loss reduces transcriptional bursting frequency in a subset of gene promoters, generating enhanced variability of transcript levels but minimal effects on mean gene expression. Destabilization of target programs shifts cellular equilibrium out of self-renewal towards differentiation. We propose that control of transcriptional variability is central to leukemia stem-like cell propagation, and establish a paradigm exploitable in different tumors and at distinct stages of cancer evolution.This work was funded by a Kay Kendall Leukaemia Fund Intermediate Fellowship (KKL888) and by a Leuka John Goldman Fellowship for Future Science (2017) to C.P.. S.P. is funded through a Cambridge-DBT Lectureship; R.K. was funded by an Isaac Newton Trust (INT) Research Grant and a Wellcome Trust ISSF/INT/University of Cambridge Joint Research Grant to C.P.; S.G. is funded by a Lady Tata Memorial Trust PhD Studentship, a Trinity Henry Barlow Trust Scholarship, and the Cambridge Trust; K.Z. received funding from AIRC (Italian Association for Cancer Research) and is the current recipient of a European Commission Horizon 2020 Marie Sklodowska Curie Post-Doctoral Fellowship

A hot and fast ultra-stripped supernova that likely formed a compact neutron star binary.

Compact neutron star binary systems are produced from binary massive stars through stellar evolution involving up to two supernova explosions. The final stages in the formation of these systems have not been directly observed. We report the discovery of iPTF 14gqr (SN 2014ft), a type Ic supernova with a fast-evolving light curve indicating an extremely low ejecta mass (≈0.2 solar masses) and low kinetic energy (≈2 × 1050 ergs). Early photometry and spectroscopy reveal evidence of shock cooling of an extended helium-rich envelope, likely ejected in an intense pre-explosion mass-loss episode of the progenitor. Taken together, we interpret iPTF 14gqr as evidence for ultra-stripped supernovae that form neutron stars in compact binary systems

The Koala: A Fast Blue Optical Transient with Luminous Radio Emission from a Starburst Dwarf Galaxy at z=0.27

We present ZTF18abvkwla (the "Koala"), a fast blue optical transient discovered in the Zwicky Transient Facility (ZTF) One-Day Cadence (1DC) Survey. ZTF18abvkwla has a number of features in common with the groundbreaking transient AT 2018cow: blue colors at peak ($g-r\approx -0.5$ mag), a short rise time from half-max of under two days, a decay time to half-max of only three days, a high optical luminosity (${M}_{g,\mathrm{peak}}\approx -20.6$ mag), a hot (gsim40,000 K) featureless spectrum at peak light, and a luminous radio counterpart. At late times (${\rm{\Delta }}t\gt 80\,\mathrm{days}$), the radio luminosity of ZTF18abvkwla ($\nu {L}_{\nu }\gtrsim {10}^{40}\,\mathrm{erg}\,{{\rm{s}}}^{-1}$ at 10 $\mathrm{GHz}$, observer-frame) is most similar to that of long-duration gamma-ray bursts (GRBs). The host galaxy is a dwarf starburst galaxy ($M\approx 5\times {10}^{8}\,{M}_{\odot }$, $\mathrm{SFR}\approx 7\,{M}_{\odot }\,{\mathrm{yr}}^{-1}$) that is moderately metal-enriched ($\mathrm{log}[{\rm{O}}/{\rm{H}}]\approx 8.5$), similar to the hosts of GRBs and superluminous supernovae. As in AT2018cow, the radio and optical emission in ZTF18abvkwla likely arise from two separate components: the radio from fast-moving ejecta (${\rm{\Gamma }}\beta c\gt 0.38c$) and the optical from shock-interaction with confined dense material (<0.07 M ⊙ in $\sim {10}^{15}\,\mathrm{cm}$). Compiling transients in the literature with ${t}_{\mathrm{rise}}\lt 5\,\mathrm{days}$ and ${M}_{\mathrm{peak}}\lt -20$ mag, we find that a significant number are engine-powered, and suggest that the high peak optical luminosity is directly related to the presence of this engine. From 18 months of the 1DC survey, we find that transients in this rise-luminosity phase space are at least two to three orders of magnitude less common than CC SNe. Finally, we discuss strategies for identifying such events with future facilities like the Large Synoptic Survey Telescope, as well as prospects for detecting accompanying X-ray and radio emission

Identification of Novel Pathogenicity Loci in Clostridium perfringens Strains That Cause Avian Necrotic Enteritis

Type A Clostridium perfringens causes poultry necrotic enteritis (NE), an enteric disease of considerable economic importance, yet can also exist as a member of the normal intestinal microbiota. A recently discovered pore-forming toxin, NetB, is associated with pathogenesis in most, but not all, NE isolates. This finding suggested that NE-causing strains may possess other virulence gene(s) not present in commensal type A isolates. We used high-throughput sequencing (HTS) technologies to generate draft genome sequences of seven unrelated C. perfringens poultry NE isolates and one isolate from a healthy bird, and identified additional novel NE-associated genes by comparison with nine publicly available reference genomes. Thirty-one open reading frames (ORFs) were unique to all NE strains and formed the basis for three highly conserved NE-associated loci that we designated NELoc-1 (42 kb), NELoc-2 (11.2 kb) and NELoc-3 (5.6 kb). The largest locus, NELoc-1, consisted of netB and 36 additional genes, including those predicted to encode two leukocidins, an internalin-like protein and a ricin-domain protein. Pulsed-field gel electrophoresis (PFGE) and Southern blotting revealed that the NE strains each carried 2 to 5 large plasmids, and that NELoc-1 and -3 were localized on distinct plasmids of sizes ∼85 and ∼70 kb, respectively. Sequencing of the regions flanking these loci revealed similarity to previously characterized conjugative plasmids of C. perfringens. These results provide significant insight into the pathogenetic basis of poultry NE and are the first to demonstrate that netB resides in a large, plasmid-encoded locus. Our findings strongly suggest that poultry NE is caused by several novel virulence factors, whose genes are clustered on discrete pathogenicity loci, some of which are plasmid-borne

Confined dense circumstellar material surrounding a regular type II supernova

With the advent of new wide-field, high-cadence optical transient surveys, our understanding of the diversity of core-collapse supernovae has grown tremendously in the last decade. However, the pre-supernova evolution of massive stars, which sets the physical backdrop to these violent events, is theoretically not well understood and difficult to probe observationally. Here we report the discovery of the supernova iPTF 13dqy = SN 2013fs a mere ∼3 h after explosion. Our rapid follow-up observations, which include multiwavelength photometry and extremely early (beginning at ∼6 h post-explosion) spectra, map the distribution of material in the immediate environment (≲1015 cm) of the exploding star and establish that it was surrounded by circumstellar material (CSM) that was ejected during the final ∼1 yr prior to explosion at a high rate, around 10-3 solar masses per year. The complete disappearance of flash-ionized emission lines within the first several days requires that the dense CSM be confined to within ≲1015 cm, consistent with radio non-detections at 70–100 days. The observations indicate that iPTF 13dqy was a regular type II supernova; thus, the finding that the probable red supergiant progenitor of this common explosion ejected material at a highly elevated rate just prior to its demise suggests that pre-supernova instabilities may be common among exploding massive stars. © 2017 Nature Publishing Grou

Binary and Millisecond Pulsars at the New Millennium

We review the properties and applications of binary and millisecond pulsars. Our knowledge of these exciting objects has greatly increased in recent years, mainly due to successful surveys which have brought the known pulsar population to over 1300. There are now 56 binary and millisecond pulsars in the Galactic disk and a further 47 in globular clusters. This review is concerned primarily with the results and spin-offs from these surveys which are of particular interest to the relativity community.Comment: 59 pages, 26 figures, 5 tables. Accepted for publication in Living Reviews in Relativity (http://www.livingreviews.org

A prospective cohort study of postoperative complications in the management of perforated peptic ulcer

BACKGROUND: With dwindling rates of postoperative mortality in perforated peptic ulcer that is attributable to H(2)-receptor blocker usage, there is a need to shift the focus towards the prevention of postoperative morbidity. Further, the simultaneous contribution of several putative clinical predictors to this postoperative morbidity is not fully appreciated. Our objective was to assess the predictors of the risk, rate and number of postoperative complications in surgically treated patients of perforated peptic ulcer. METHODS: In a prospective cohort study of 96 subjects presenting as perforated peptic ulcer and treated using Graham's omentoplatsy patch or gastrojejunostomy (with total truncal vagotomy), we assessed the association of clinical predictors with three domains of postoperative complications: the risk of developing a complication, the rate of developing the first complication and the risk of developing higher number of complications. We used multiple regression methods – logistic regression, Cox proportional hazards regression and Poisson regression, respectively – to examine the association of the predictors with these three domains. RESULTS: We observed that the risk of developing a postoperative complication was significantly influenced by the presence of a concomitant medical illness [odds ratio (OR) = 8.9, p = 0.001], abdominal distension (3.8, 0.048) and a need of blood transfusion (OR = 8.2, p = 0.027). Using Poisson regression, it was observed that the risk for a higher number of complications was influenced by the same three factors [relative risk (RR) = 2.6, p = 0.015; RR = 4.6, p < 0.001; and RR = 2.4, p = 0.002; respectively]. However, the rate of development of complications was influenced by a history suggestive of shock [relative hazards (RH) = 3.4, p = 0.002] and A(- )blood group (RH = 4.7, p = 0.04). CONCLUSION: Abdominal distension, presence of a concomitant medical illness and a history suggestive of shock at the time of admission warrant a closer and alacritous postoperative management in patients of perforated peptic ulcer

SN 2018fif: The explosion of a large red supergiant discovered in its infancy by the Zwicky transient facility

High-cadence transient surveys are able to capture supernovae closer to their first light than ever before. Applying analytical models to such early emission, we can constrain the progenitor stars’ properties. In this paper, we present observations of SN 2018fif (ZTF 18abokyfk). The supernova was discovered close to first light and monitored by the Zwicky Transient Facility (ZTF) and the Neil Gehrels Swift Observatory. Early spectroscopic observations suggest that the progenitor of SN 2018fif was surrounded by relatively small amounts of circumstellar material compared to all previous cases. This particularity, coupled with the high-cadence multiple-band coverage, makes it a good candidate to investigate using shock-cooling models. We employ the SOPRANOS code, an implementation of the model by Sapir &amp; Waxman and its extension to early times by Morag et al. Compared with previous implementations, SOPRANOS has the advantage of including a careful account of the limited temporal validity domain of the shock-cooling model as well as allowing usage of the entirety of the early UV data. We find that the progenitor of SN 2018fif was a large red supergiant with a radius of R = 744.0-+128.0183.0 R☉ and an ejected mass of Mej = 9.3-+5.80.4 M☉. Our model also gives information on the explosion epoch, the progenitor’s inner structure, the shock velocity, and the extinction. The distribution of radii is double-peaked, with smaller radii corresponding to lower values of the extinction, earlier recombination times, and a better match to the early UV data. If these correlations persist in future objects, denser spectroscopic monitoring constraining the time of recombination, as well as accurate UV observations (e.g., with ULTRASAT), will help break the extinction/radius degeneracy and independently determine both