Collagen is the primary component of the extracellular matrix in the human body. It has proved challenging to fabricate collagen scaffolds capable of replicating the structure and function of tissues ...and organs. We present a method to 3D-bioprint collagen using freeform reversible embedding of suspended hydrogels (FRESH) to engineer components of the human heart at various scales, from capillaries to the full organ. Control of pH-driven gelation provides 20-micrometer filament resolution, a porous microstructure that enables rapid cellular infiltration and microvascularization, and mechanical strength for fabrication and perfusion of multiscale vasculature and tri-leaflet valves. We found that FRESH 3D-bioprinted hearts accurately reproduce patient-specific anatomical structure as determined by micro-computed tomography. Cardiac ventricles printed with human cardiomyocytes showed synchronized contractions, directional action potential propagation, and wall thickening up to 14% during peak systole.
Following the 1986 Chernobyl accident, 116,000 people were permanently evacuated from the 4,200 km2 Chernobyl exclusion zone 1. There is continuing scientific and public debate surrounding the fate ...of wildlife that remained in the abandoned area. Several previous studies of the Chernobyl exclusion zone (e.g. 2,3) indicated major radiation effects and pronounced reductions in wildlife populations at dose rates well below those thought 4,5 to cause significant impacts. In contrast, our long-term empirical data showed no evidence of a negative influence of radiation on mammal abundance. Relative abundances of elk, roe deer, red deer and wild boar within the Chernobyl exclusion zone are similar to those in four (uncontaminated) nature reserves in the region and wolf abundance is more than 7 times higher. Additionally, our earlier helicopter survey data show rising trends in elk, roe deer and wild boar abundances from one to ten years post-accident. These results demonstrate for the first time that, regardless of potential radiation effects on individual animals, the Chernobyl exclusion zone supports an abundant mammal community after nearly three decades of chronic radiation exposures.
Deryabina et al. report that numbers of large mammals in the exclusion zone around the wrecked Chernobyl reactor are as high or higher than in surrounding non-contaminated areas.
The atmospheric component of the new Hadley Centre Global Environmental Model (HadGEM1) is described and an assessment of its mean climatology presented. HadGEM1 includes substantially improved ...representations of physical processes, increased functionality, and higher resolution than its predecessor, the Third Hadley Centre Coupled Ocean–Atmosphere General Circulation Model (HadCM3). Major developments are the use of semi-Lagrangian instead of Eulerian advection for both dynamical and tracer fields; new boundary layer, gravity wave drag, microphysics, and sea ice schemes; and major changes to the convection, land surface (including tiled surface characteristics), and cloud schemes. There is better coupling between the atmosphere, land, ocean, and sea ice subcomponents and the model includes an interactive aerosol scheme, representing both the first and second indirect effects. Particular focus has been placed on improving the processes (such as clouds and aerosol) that are most uncertain in projections of climate change.
These developments lead to a significantly more realistic simulation of the processes represented, the most notable improvements being in the hydrological cycle, cloud radiative properties, the boundary layer, the tropopause structure, and the representation of tracers.
Summary
Background
Cutaneous immune‐related adverse events (cirAEs) are a common side‐effect of immune checkpoint inhibitors (ICIs). However, prior work examining these toxicities in detail has ...considered only the fraction of events evaluated by dermatologists. Associations between dermatology referral, cirAE treatment and survival outcomes remain underexplored across care settings.
Objectives
To comprehensively categorize cirAE patterns among all patients treated with immunotherapy at our institution, and to evaluate: (i) the effect of dermatology referral on cirAE treatment and (ii) the impact of cirAE treatment on survival.
Methods
This was a retrospective cohort analysis of patients with cancer who initiated ICI therapy between 1 January 2016 and 8 March 2019 and developed one or more cirAEs, as screened for using International Classification of Diseases 10th revision codes and confirmed via manual chart review (n = 358). All relevant information documented prior to 31 March 2020 was included.
Results
CirAEs evaluated by dermatologists were significantly more likely to be treated than cirAEs that were not referred (odds ratio 6·08, P < 0·001). Patients who received any cirAE treatment had improved progression‐free survival hazard ratio (HR) 0·59, P = 0·001 and overall survival (HR 0·58, P = 0·007) compared with those who did not.
Conclusions
CirAEs evaluated by dermatologists were significantly more likely to be treated than cirAEs that were not referred, and patients who received any treatment for a cirAE had improved survival outcomes.
What is already known about this topic?
Cutaneous immune‐related adverse events (cirAEs) are common among patients on immune checkpoint inhibitor (ICI) therapy, occurring in up to one‐third of ICI monotherapy recipients.
Despite the prevalence of cirAEs, the relationships between dermatology referral, cirAE treatment and survival outcomes remain underexplored.
What does this study add?
CirAEs evaluated by dermatologists were significantly more likely to be treated than cirAEs that were not referred, and patients who received treatment had improved survival.
Our findings underscore the vital role of dermatologists in oncological care and suggest that closer collaboration between oncologists and dermatologists may be valuable in supporting comprehensive cirAE treatment.
Additionally, our findings suggest that cirAE treatment may serve as a potentially important marker for survival in patients with cancer.
Linked Comment: S. Walsh. Br J Dermatol 2021; 185:486.
The importance of using a general circulation model that includes a well-resolved stratosphere for climate simulations, and particularly the influence this has on surface climate, is investigated. ...High top model simulations are run with the Met Office Unified Model for the Coupled Model Intercomparison Project Phase 5 (CMIP5). These simulations are compared to equivalent simulations run using a low top model differing only in vertical extent and vertical resolution above 15 km. The period 1960–2002 is analyzed and compared to observations and the European Centre for Medium-Range Weather Forecasts (ECMWF) reanalysis dataset. Long-term climatology, variability, and trends in surface temperature and sea ice, along with the variability of the annular mode index, are found to be insensitive to the addition of a well-resolved stratosphere. The inclusion of a well-resolved stratosphere, however, does improve the impact of atmospheric teleconnections on surface climate, in particular the response to El Niño–Southern Oscillation, the quasi-biennial oscillation, and midwinter stratospheric sudden warmings (i.e., zonal mean wind reversals in the middle stratosphere). Thus, including a well-represented stratosphere could improve climate simulation on intraseasonal to interannual time scales.
The performance of the atmospheric component of the new Hadley Centre Global Environmental Model (HadGEM1) is assessed in terms of its ability to represent a selection of key aspects of variability ...in the Tropics and extratropics. These include midlatitude storm tracks and blocking activity, synoptic variability over Europe, and the North Atlantic Oscillation together with tropical convection, the Madden–Julian oscillation, and the Asian summer monsoon.
Comparisons with the previous model, the Third Hadley Centre Coupled Ocean–Atmosphere GCM (HadCM3), demonstrate that there has been a considerable increase in the transient eddy kinetic energy (EKE), bringing HadGEM1 into closer agreement with current reanalyses. This increase in EKE results from the increased horizontal resolution and, in combination with the improved physical parameterizations, leads to improvements in the representation of Northern Hemisphere storm tracks and blocking. The simulation of synoptic weather regimes over Europe is also greatly improved compared to HadCM3, again due to both increased resolution and other model developments.
The variability of convection in the equatorial region is generally stronger and closer to observations than in HadCM3. There is, however, still limited convective variance coincident with several of the observed equatorial wave modes. Simulation of the Madden–Julian oscillation is improved in HadGEM1: both the activity and interannual variability are increased and the eastward propagation, although slower than observed, is much better simulated. While some aspects of the climatology of the Asian summer monsoon are improved in HadGEM1, the upper-level winds are too weak and the simulation of precipitation deteriorates. The dominant modes of monsoon interannual variability are similar in the two models, although in HadCM3 this is linked to SST forcing, while in HadGEM1 internal variability dominates.
Overall, analysis of the phenomena considered here indicates that HadGEM1 performs well and, in many important respects, improves upon HadCM3. Together with the improved representation of the mean climate, this improvement in the simulation of atmospheric variability suggests that HadGEM1 provides a sound basis for future studies of climate and climate change.
Abstract
The climatology of a stratosphere-resolving version of the Met Office’s climate model is studied and validated against ECMWF reanalysis data. Ensemble integrations are carried out at two ...different horizontal resolutions. Along with a realistic climatology and annual cycle in zonal mean zonal wind and temperature, several physical effects are noted in the model. The time of final warming of the winter polar vortex is found to descend monotonically in the Southern Hemisphere, as would be expected for purely radiative forcing. In the Northern Hemisphere, however, the time of final warming is driven largely by dynamical effects in the lower stratosphere and radiative effects in the upper stratosphere, leading to the earliest transition to westward winds being seen in the midstratosphere. A realistic annual cycle in stratospheric water vapor concentrations—the tropical “tape recorder”—is captured. Tropical variability in the zonal mean zonal wind is found to be in better agreement with the reanalysis for the model run at higher horizontal resolution because the simulated quasi-biennial oscillation has a more realistic amplitude. Unexpectedly, variability in the extratropics becomes less realistic under increased resolution because of reduced resolved wave drag and increased orographic gravity wave drag. Overall, the differences in climatology between the simulations at high and moderate horizontal resolution are found to be small.
PDF
