Three decades ago, transfusion-related acute lung injury (TRALI) was considered a rare complication of transfusion medicine. Nowadays, the US Food and Drug Administration acknowledge the syndrome as ...the leading cause of transfusion-related mortality. Understanding of the pathogenesis of TRALI has resulted in the design of preventive strategies from a blood-bank perspective. A major breakthrough in efforts to reduce the incidence of TRALI has been to exclude female donors of products with high plasma volume, resulting in a decrease of roughly two-thirds in incidence. However, this strategy has not completely eradicated the complication. In the past few years, research has identified patient-related risk factors for the onset of TRALI, which have empowered physicians to take an individualised approach to patients who need transfusion.
Evidence that extreme rainfall intensity is increasing at the global scale has strengthened considerably in recent years. Research now indicates that the greatest increases are likely to occur in ...short‐duration storms lasting less than a day, potentially leading to an increase in the magnitude and frequency of flash floods. This review examines the evidence for subdaily extreme rainfall intensification due to anthropogenic climate change and describes our current physical understanding of the association between subdaily extreme rainfall intensity and atmospheric temperature. We also examine the nature, quality, and quantity of information needed to allow society to adapt successfully to predicted future changes, and discuss the roles of observational and modeling studies in helping us to better understand the physical processes that can influence subdaily extreme rainfall characteristics. We conclude by describing the types of research required to produce a more thorough understanding of the relationships between local‐scale thermodynamic effects, large‐scale atmospheric circulation, and subdaily extreme rainfall intensity.
Key Points
Significant increases in rainfall intensity are expected at subdaily time scalesDescribes link between subdaily extreme rainfall and atmospheric temperatureDiscusses role of observations and modeling to help understand future change
Adhesion of erythrocytes to endothelial cells lining the vascular wall can cause vaso-occlusive events that impair blood flow which in turn may result in ischemia and tissue damage. Adhesion of ...erythrocytes to vascular endothelial cells has been described in multiple hemolytic disorders, especially in sickle cell disease, but the adhesion of normal erythrocytes to endothelial cells has hardly been described. It was shown that calcium-loaded erythrocytes can adhere to endothelial cells. Because sickle erythrocyte adhesion to ECs can be enhanced by ultra-large von Willebrand factor multimers, we investigated whether calcium loading of erythrocytes could promote binding to endothelial cells via ultra-large von Willebrand factor multimers. We used (immunofluorescent) live-cell imaging of washed erythrocytes perfused over primary endothelial cells at venular flow rate. Using this approach, we show that calcium-loaded erythrocytes strongly adhere to histamine-stimulated primary human endothelial cells. This adhesion is mediated by ultra-large von Willebrand factor multimers. Von Willebrand factor knockdown or ADAMTS13 cleavage abolished the binding of erythrocytes to activated endothelial cells under flow. Platelet depletion did not interfere with erythrocyte binding to von Willebrand factor. Our results reveal platelet-independent adhesion of calcium-loaded erythrocytes to endothelium-derived von Willebrand factor. Erythrocyte adhesion to von Willebrand factor may be particularly relevant for venous thrombosis, which is characterized by the formation of erythrocyte-rich thrombi.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
The joint detection of gravitational waves (GWs) and electromagnetic radiation from the binary neutron star (BNS) merger GW170817 has provided unprecedented insight into a wide range of ...physical processes: heavy element synthesis via the
r
-process; the production of relativistic ejecta; the equation of state of neutron stars and the nature of the merger remnant; the binary coalescence timescale; and a measurement of the Hubble constant via the “standard siren” technique. In detail, all of these results depend on the distance to the host galaxy of the merger event, NGC 4993. In this Letter we measure the surface brightness fluctuation (SBF) distance to NGC 4993 in the F110W and F160W passbands of the Wide Field Camera 3 Infrared Channel (WFC3/IR) on the
Hubble Space Telescope
(
HST
). For the preferred F110W passband we derive a distance modulus of
(
m
−
M
)
=
33.05
±
0.08
±
0.10
mag, or a linear distance
d
= 40.7 ± 1.4 ± 1.9 Mpc (random and systematic errors, respectively); a virtually identical result is obtained from the F160W data. This is the most precise distance to NGC 4993 available to date. Combining our distance measurement with the corrected recession velocity of NGC 4993 implies a Hubble constant
H
0
= 71.9 ± 7.1 km s
−1
Mpc
−1
. A comparison of our result to the GW-inferred value of
H
0
indicates a binary orbital inclination of
i
≳ 137°. The SBF technique can be applied to early-type host galaxies of BNS mergers to ∼100 Mpc with
HST
and possibly as far as ∼300 Mpc with the
James Webb Space Telescope
, thereby helping to break the inherent distance-inclination degeneracy of the GW data at distances where many future BNS mergers are likely to be detected.
The use of kidneys donated after circulatory death (DCD) remains controversial due to concerns with regard to high incidences of early graft loss, delayed graft function (DGF), and impaired graft ...survival. As these concerns are mainly based on data from historical cohorts, they are prone to time-related effects and may therefore not apply to the current timeframe. To assess the impact of time on outcomes, we performed a time-dependent comparative analysis of outcomes of DCD and donation after brain death (DBD) kidney transplantations. Data of all 11,415 deceased-donor kidney transplantations performed in The Netherlands between 1990-2018 were collected. Based on the incidences of early graft loss, two eras were defined (1998-2008 n = 3,499 and 2008-2018 n = 3,781), and potential time-related effects on outcomes evaluated. Multivariate analyses were applied to examine associations between donor type and outcomes. Interaction tests were used to explore presence of effect modification. Results show clear time-related effects on posttransplant outcomes. The 1998-2008 interval showed compromised outcomes for DCD procedures (higher incidences of DGF and early graft loss, impaired 1-year renal function, and inferior graft survival), whereas DBD and DCD outcome equivalence was observed for the 2008-2018 interval. This occurred despite persistently high incidences of DGF in DCD grafts, and more adverse recipient and donor risk profiles (recipients were 6 years older and the KDRI increased from 1.23 to 1.39 and from 1.35 to 1.49 for DBD and DCD donors). In contrast, the median cold ischaemic period decreased from 20 to 15 hours. This national study shows major improvements in outcomes of transplanted DCD kidneys over time. The time-dependent shift underpins that kidney transplantation has come of age and DCD results are nowadays comparable to DBD transplants. It also calls for careful interpretation of conclusions based on historical cohorts, and emphasises that retrospective studies should correct for time-related effects.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
We report on measurements of the all-particle cosmic ray energy spectrum and composition in the PeV to EeV energy range using 3 years of data from the IceCube Neutrino Observatory. The IceTop ...detector measures cosmic ray induced air showers on the surface of the ice, from which the energy spectrum of cosmic rays is determined by making additional assumptions about the mass composition. A separate measurement is performed when IceTop data are analyzed in coincidence with the high-energy muon energy loss information from the deep in-ice IceCube detector. In this measurement, both the spectrum and the mass composition of the primary cosmic rays are simultaneously reconstructed using a neural network trained on observables from both detectors. The performance and relative advantages of these two distinct analyses are discussed, including the systematic uncertainties and the dependence on the hadronic interaction models, and both all-particle spectra as well as individual spectra for elemental groups are presented.
Oligomeric species populated during the aggregation of the Aβ42 peptide have been identified as potent cytotoxins linked to Alzheimer's disease, but the fundamental molecular pathways that control ...their dynamics have yet to be elucidated. By developing a general approach that combines theory, experiment and simulation, we reveal, in molecular detail, the mechanisms of Aβ42 oligomer dynamics during amyloid fibril formation. Even though all mature amyloid fibrils must originate as oligomers, we found that most Aβ42 oligomers dissociate into their monomeric precursors without forming new fibrils. Only a minority of oligomers converts into fibrillar structures. Moreover, the heterogeneous ensemble of oligomeric species interconverts on timescales comparable to those of aggregation. Our results identify fundamentally new steps that could be targeted by therapeutic interventions designed to combat protein misfolding diseases.
Proteins are effector molecules that mediate the functions of genes
and modulate comorbidities
, behaviors and drug treatments
. They represent an enormous potential resource for personalized, ...systemic and data-driven diagnosis, prevention, monitoring and treatment. However, the concept of using plasma proteins for individualized health assessment across many health conditions simultaneously has not been tested. Here, we show that plasma protein expression patterns strongly encode for multiple different health states, future disease risks and lifestyle behaviors. We developed and validated protein-phenotype models for 11 different health indicators: liver fat, kidney filtration, percentage body fat, visceral fat mass, lean body mass, cardiopulmonary fitness, physical activity, alcohol consumption, cigarette smoking, diabetes risk and primary cardiovascular event risk. The analyses were prospectively planned, documented and executed at scale on archived samples and clinical data, with a total of ~85 million protein measurements in 16,894 participants. Our proof-of-concept study demonstrates that protein expression patterns reliably encode for many different health issues, and that large-scale protein scanning
coupled with machine learning is viable for the development and future simultaneous delivery of multiple measures of health. We anticipate that, with further validation and the addition of more protein-phenotype models, this approach could enable a single-source, individualized so-called liquid health check.
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