Purpose
Contemporary trauma resuscitation prioritizes control of bleeding and uses major haemorrhage protocols (MHPs) to prevent and treat coagulopathy. We aimed to determine whether augmenting MHPs ...with Viscoelastic Haemostatic Assays (VHA) would improve outcomes compared to Conventional Coagulation Tests (CCTs).
Methods
This was a multi-centre, randomized controlled trial comparing outcomes in trauma patients who received empiric MHPs, augmented by either VHA or CCT-guided interventions. Primary outcome was the proportion of subjects who, at 24 h after injury, were alive and free of massive transfusion (10 or more red cell transfusions). Secondary outcomes included 28-day mortality. Pre-specified subgroups included patients with severe traumatic brain injury (TBI).
Results
Of 396 patients in the intention to treat analysis, 201 were allocated to VHA and 195 to CCT-guided therapy. At 24 h, there was no difference in the proportion of patients who were alive and free of massive transfusion (VHA: 67%, CCT: 64%, OR 1.15, 95% CI 0.76–1.73). 28-day mortality was not different overall (VHA: 25%, CCT: 28%, OR 0.84, 95% CI 0.54–1.31), nor were there differences in other secondary outcomes or serious adverse events. In pre-specified subgroups, there were no differences in primary outcomes. In the pre-specified subgroup of 74 patients with TBI, 64% were alive and free of massive transfusion at 24 h compared to 46% in the CCT arm (OR 2.12, 95% CI 0.84–5.34).
Conclusion
There was no difference in overall outcomes between VHA- and CCT-augmented-major haemorrhage protocols.
Abstract
The Type Ia supernova (SN Ia) LSQ14fmg exhibits exaggerated properties that may help to reveal the origin of the “super-Chandrasekhar” (or 03fg-like) group. The optical spectrum is typical ...of a 03fg-like SN Ia, but the light curves are unlike those of any SNe Ia observed. The light curves of LSQ14fmg rise extremely slowly. At −23 rest-frame days relative to
B
-band maximum, LSQ14fmg is already brighter than
mag before host extinction correction. The observed color curves show a flat evolution from the earliest observation to approximately 1 week after maximum. The near-infrared light curves peak brighter than −20.5 mag in the
J
and
H
bands, far more luminous than any 03fg-like SNe Ia with near-infrared observations. At 1 month past maximum, the optical light curves decline rapidly. The early, slow rise and flat color evolution are interpreted to result from an additional excess flux from a power source other than the radioactive decay of the synthesized
56
Ni. The excess flux matches the interaction with a typical superwind of an asymptotic giant branch (AGB) star in density structure, mass-loss rate, and duration. The rapid decline starting at around 1 month past
B
-band maximum may be an indication of rapid cooling by active carbon monoxide (CO) formation, which requires a low-temperature and high-density environment. These peculiarities point to an AGB progenitor near the end of its evolution and the core degenerate scenario as the likely explosion mechanism for LSQ14fmg.
Abstract
We present our analysis of the Type II supernova DLT16am (SN 2016ija). The object was discovered during the ongoing
(DLT40) one-day cadence supernova search at
in the “edge-on” nearby (
) ...galaxy NGC 1532. The subsequent prompt and high-cadenced spectroscopic and photometric follow-up revealed a highly extinguished transient, with
, consistent with a standard extinction law with
R
V
= 3.1 and a bright (
) absolute peak magnitude. A comparison of the photometric features with those of large samples of SNe II reveals a fast rise for the derived luminosity and a relatively short plateau phase, with a slope of
, consistent with the photometric properties typical of those of fast-declining SNe II. Despite the large uncertainties on the distance and the extinction in the direction of DLT16am, the measured photospheric expansion velocity and the derived absolute
V
-band magnitude at
after the explosion match the existing luminosity–velocity relation for SNe II.
In his News In Depth story “Mystery oil spill threatens marine sanctuary in Brazil” (8 November 2019, p. 672), H. Escobar highlights important ecosystems that have been affected by the spill. ...However, he did not mention the Brazilian rhodolith beds—the most extensive, abundant, and diverse biogenic carbonate habitats in the South Atlantic (1). The oil spill severely threatens these ecosystems, which comprise a staggering 2 x 1011 tons of carbonatic bank (2), stretch from 5°N to 27°S along the Brazilian coast, and cover a seabed potential area of 229,000 km2 (1).Brazil's rhodolith beds are recognized as an oasis of diversity (3). Although they harbor species of great economic and ecological value, they remain unprotected. The oil pollution will likely cause major socio-environmental and economic losses, similar to those caused by the Deepwater Horizon incident in the Gulf of Mexico (4). The contamination will compromise the region's food security as well as biodiversity conservation and efficient management. Moreover, the ongoing oil spill could have global consequences given the potential biogeochemical role of rhodolith beds in the oceanic carbon balance (1, 5). Thus, this event must not be downplayed or concealed, as has been attempted in the case of Brazilian mining accidents (6) and Amazon deforestation and fires (7). We advocate urgent action to evaluate and mitigate the oil spill and to remediate and restore areas on the oil slick route. Brazil must follow in the footsteps of Australia and Europe (8) and prioritize rhodolith bed conservation.
Abstract
Supernova (SN) 2016bdu is an unusual transient resembling SN 2009ip. SN 2009ip-like events are characterized by a long-lasting phase of erratic variability that ends with two luminous ...outbursts a few weeks apart. The second outburst is significantly more luminous (about 3 mag) than the first. In the case of SN 2016bdu, the first outburst (Event A) reached an absolute magnitude Mr ≈ −15.3 mag, while the second one (Event B) occurred over one month later and reached Mr ≈ −18 mag. By inspecting archival data, a faint source at the position of SN 2016bdu is several times in the past few years. We interpret these detections as signatures of a phase of erratic variability, similar to that experienced by SN 2009ip between 2008 and mid-2012, and resembling the currently observed variability of the luminous blue variable SN 2000ch in NGC 3432. Spectroscopic monitoring of SN 2016bdu during the second peak initially shows features typical of an SN IIn. One month after the Event B maximum, the spectra develop broad Balmer lines with P Cygni profiles and broad metal features. At these late phases, the spectra resemble those of a typical Type II SN. All members of this SN 2009ip-like group are remarkably similar to the Type IIn SN 2005gl. For this object, the claim of a terminal SN explosion is supported by the disappearance of the progenitor star. While the similarity with SN 2005gl supports a genuine SN explosion scenario for SN 2009ip-like events, the unequivocal detection of nucleosynthesized elements in their nebular spectra is still missing.
Prophylactic human papillomavirus (HPV) vaccines have to provide sustained protection. We assessed efficacy, immunogenicity, and safety of the HPV-16/18 AS04-adjuvanted vaccine up to 6.4 years.
Women ...aged 15-25 years, with normal cervical cytology, who were HPV-16/18 seronegative and oncogenic HPV DNA-negative (14 types) at screening participated in a double-blind, randomised, placebo-controlled initial study (n=1113; 560 vaccine group vs 553 placebo group) and follow-up study (n=776; 393 vs 383). 27 sites in three countries participated in the follow-up study. Cervical samples were tested every 6 months for HPV DNA. Management of abnormal cytologies was prespecified, and HPV-16/18 antibody titres were assessed. The primary objective was to assess long-term vaccine efficacy in the prevention of incident cervical infection with HPV 16 or HPV 18, or both. We report the analyses up to 6.4 years of this follow-up study and combined with the initial study. For the primary endpoint, the efficacy analysis was done in the according-to-protocol (ATP) cohort; the analysis of cervical intraepithelial neoplasia grade 2 and above (CIN2+) was done in the total vaccinated cohort (TVC). The study is registered with ClinicalTrials.gov, number NCT00120848.
For the combined analysis of the initial and follow-up studies, the ATP efficacy cohort included 465 women in the vaccine group and 454 in the placebo group; the TVC included 560 women in the vaccine group and 553 in the placebo group. Vaccine efficacy against incident infection with HPV 16/18 was 95.3% (95% CI 87.4-98.7) and against 12-month persistent infection was 100% (81.8-100). Vaccine efficacy against CIN2+ was 100% (51.3-100) for lesions associated with HPV-16/18 and 71.9% (20.6-91.9) for lesions independent of HPV DNA. Antibody concentrations by ELISA remained 12-fold or more higher than after natural infection (both antigens). Safety outcomes were similar between groups: during the follow-up study, 30 (8%) participants reported a serious adverse event in the vaccine group versus 37 (10%) in the placebo group. None was judged related or possibly related to vaccination, and no deaths occurred.
Our findings show excellent long-term efficacy, high and sustained immunogenicity, and favourable safety of the HPV-16/18 AS04-adjuvanted vaccine up to 6.4 years.
GlaxoSmithKline Biologicals (Belgium).
We present comprehensive observations and analysis of the energetic H-stripped SN 2016coi (a.k.a. ASASSN-16fp), spanning the γ-ray through optical and radio wavelengths, acquired within the first ...hours to ∼420 days post explosion. Our observational campaign confirms the identification of He in the supernova (SN) ejecta, which we interpret to be caused by a larger mixing of Ni into the outer ejecta layers. By modeling the broad bolometric light curve, we derive a large ejecta-mass-to-kinetic-energy ratio (Mej ∼ 4-7 M , Ek ∼ (7-8) × 1051 erg). The small Ca ii λλ7291,7324 to O i λλ6300,6364 ratio (∼0.2) observed in our late-time optical spectra is suggestive of a large progenitor core mass at the time of collapse. We find that SN 2016coi is a luminous source of X-rays (LX > 1039 erg s−1 in the first ∼100 days post explosion) and radio emission (L8.5 GHz ∼ 7 × 1027 erg s−1 Hz−1 at peak). These values are in line with those of relativistic SNe (2009bb, 2012ap). However, for SN 2016coi, we infer substantial pre-explosion progenitor mass loss with a rate ∼ (1-2) × and a sub-relativistic shock velocity vsh ∼ 0.15c, which is in stark contrast with relativistic SNe and similar to normal SNe. Finally, we find no evidence for a SN-associated shock breakout γ-ray pulse with energy Eγ > 2 × 1046 erg. While we cannot exclude the presence of a companion in a binary system, taken together, our findings are consistent with a massive single-star progenitor that experienced large mass loss in the years leading up to core collapse, but was unable to achieve complete stripping of its outer layers before explosion.
G Protein Signaling Modulator-3 (GPSM3) is a leukocyte-specific regulator of G protein-coupled receptors (GPCRs), which binds inactivated Gαi·GDP subunits and precludes their reassociation with Gβγ ...subunits. GPSM3 deficiency protects mice from inflammatory arthritis and, in humans, GPSM3 single-nucleotide polymorphisms (SNPs) are inversely associated with the risk of rheumatoid arthritis development; recently, these polymorphisms were linked to one particular SNP (rs204989) that decreases GPSM3 transcript abundance. However, the precise role of GPSM3 in leukocyte biology is unknown. Here, we show that GPSM3 is induced in the human promyelocytic leukemia NB4 cell line following retinoic acid treatment, which differentiates this cell line into a model of neutrophil physiology (NB4*). Reducing GPSM3 expression in NB4* cells, akin to the effect ascribed to the rs204989 C>T transition, disrupts cellular migration toward leukotriene B4 (LTB4) and (to a lesser extent) interleukin-8 (a.k.a. IL-8 or CXCL8), but not migration toward formylated peptides (fMLP). As the chemoattractants LTB4 and CXCL8 are involved in recruitment of neutrophils to the arthritic joint, our results suggest that the arthritis-protective GPSM3 SNP rs204989 may act to decrease neutrophil chemoattractant responsiveness.
Hydrogen-poor superluminous supernovae (SLSNe-I) have been predominantly found in low-metallicity, star-forming dwarf galaxies. Here we identify Gaia17biu/SN 2017egm as an SLSN-I occurring in a ..."normal" spiral galaxy (NGC 3191) in terms of stellar mass (several times 1010 M ) and metallicity (roughly solar). At redshift z = 0.031, Gaia17biu is also the lowest-redshift SLSN-I to date, and the absence of a larger population of SLSNe-I in dwarf galaxies of similar redshift suggests that metallicity is likely less important to the production of SLSNe-I than previously believed. With the smallest distance and highest apparent brightness for an SLSN-I, we are able to study Gaia17biu in unprecedented detail. Its pre-peak near-ultraviolet to optical color is similar to that of Gaia16apd and among the bluest observed for an SLSN-I, while its peak luminosity (Mg = −21 mag) is substantially lower than that of Gaia16apd. Thanks to the high signal-to-noise ratios of our spectra, we identify several new spectroscopic features that may help to probe the properties of these enigmatic explosions. We detect polarization at the ∼0.5% level that is not strongly dependent on wavelength, suggesting a modest, global departure from spherical symmetry. In addition, we put the tightest upper limit yet on the radio luminosity of an SLSN-I with <5.4 × 1026 erg s−1 Hz−1 at 10 GHz, which is almost a factor of 40 better than previous upper limits and one of the few measured at an early stage in the evolution of an SLSN-I. This limit largely rules out an association of this SLSN-I with known populations of gamma-ray-burst-like central engines.
The BRPF (Bromodomain and PHD Finger-containing) protein family are important scaffolding proteins for assembly of MYST histone acetyltransferase complexes. A selective benzimidazolone BRPF1 ...inhibitor showing micromolar activity in a cellular target engagement assay was recently described. Herein, we report the optimization of this series leading to the identification of a superior BRPF1 inhibitor suitable for in vivo studies.
PDF
