Summary
Background
Epidermolysis bullosa acquisita (EBA) is a complex autoimmune bullous disease disease with variable clinical presentations and multiple possible diagnostic tests, making an ...international consensus on the diagnosis of EBA essential.
Objectives
To obtain an international consensus on the clinical and diagnostic criteria for EBA.
Methods
The International Bullous Diseases Group (IBDG) met three times to discuss the clinical and diagnostic criteria for EBA. For the final voting exercise, 22 experts from 14 different countries voted on 50 different items. When > 30% disagreed with a proposal, a discussion was held and re‐voting carried out.
Results
In total, 48 of 50 proposals achieved consensus after discussion. This included nine diagnostic criteria, which are summarized in a flow chart. The IBDG was unable to determine one procedure that would be applicable worldwide. A limitation of the study is that differential diagnosis of bullous systemic lupus erythematosus has not been addressed.
Conclusions
This first international consensus conference established generally agreed‐upon clinical and laboratory criteria defining the clinical classification of and diagnostic testing for EBA. Holding these voting exercises in person with the possibility of discussion prior to voting has advantages in reaching consensus over Delphi exercises with remote voting.
What's already known about this topic?
Currently, there is a lack of consensus on the diagnosis of epidermolysis bullosa acquisita (EBA).
What does this study add?
These recommendations, which have been developed by international experts, provide appropriate pathways for EBA diagnosis: the algorithms may be used to distinguish EBA from other blistering diseases, which affect the epithelial basement membrane zone.
Linked Comment: Yamagami. Br J Dermatol 2018; 179:7.
The impact of black carbon (BC) aerosols on the global radiation balance is not well constrained. Here twelve global aerosol models are used to show that at least 20% of the present uncertainty in ...modeled BC direct radiative forcing (RF) is due to diversity in the simulated vertical profile of BC mass. Results are from phases 1 and 2 of the global aerosol model intercomparison project (AeroCom). Additionally, a significant fraction of the variability is shown to come from high altitudes, as, globally, more than 40% of the total BC RF is exerted above 5 km. BC emission regions and areas with transported BC are found to have differing characteristics. These insights into the importance of the vertical profile of BC lead us to suggest that observational studies are needed to better characterize the global distribution of BC, including in the upper troposphere.
The Zenifim Formation is being considered as a potential disposal formation for a deep borehole nuclear repository concept in Israel. Site selection and repository construction are intended to ensure ...that waste is separated from circulating groundwater, but long-term deformation of the wellbore could potentially create fluid flow pathways. To understand how time-dependent rock strength could affect wellbore stability, we conducted creep tests under low to moderate confining pressures on retrieved core from the Zenifim formation. During creep, samples strain slowly as gradual damage accumulation progressively weakens the samples. Failure eventually occurred through the near-instantaneous formation of a shear fracture. Experimental results were used to calibrate a continuum damage poro-elastic model for sandstones. The calibrated damage-poro-elastic model successfully simulates different types of loading experiments including quasi-static and creep. The state of strain in experiments is close to yield during loading as the yield cap continuously evolves with damage accumulation. For creep tests, most damage occurs during triaxial loading. Minor damage accumulation occurs under constant load until the final stage of creep, where damage accelerates and promotes unstable fracturing.
Context.
The Calar Alto high-Resolution search for M dwarfs with Exo-earths with Near-infrared and optical Echelle Spectrographs (CARMENES) survey is searching for Earth-like planets orbiting M ...dwarfs using the radial velocity method. Studying the stellar activity of the target stars is important to avoid false planet detections and to improve our understanding of the atmospheres of late-type stars.
Aims.
In this work we present measurements of activity indicators at visible and near-infrared wavelengths for 331 M dwarfs observed with CARMENES. Our aim is to identify the activity indicators that are most sensitive and easiest to measure, and the correlations among these indicators. We also wish to characterise their variability.
Methods.
Using a spectral subtraction technique, we measured pseudo-equivalent widths of the He
I
D
3
, H
α
, He
I
λ
10833 Å, and Pa
β
lines, the Na
I
D doublet, and the Ca
II
infrared triplet, which have a chromospheric component in active M dwarfs. In addition, we measured an index of the strength of two TiO and two VO bands, which are formed in the photosphere. We also searched for periodicities in these activity indicators for all sample stars using generalised Lomb-Scargle periodograms.
Results.
We find that the most slowly rotating stars of each spectral subtype have the strongest H
α
absorption. H
α
is correlated most strongly with He
I
D
3
, whereas Na
I
D and the Ca
II
infrared triplet are also correlated with H
α
. He
I
λ
10833 Å and Pa
β
show no clear correlations with the other indicators. The TiO bands show an activity effect that does not appear in the VO bands. We find that the relative variations of H
α
and He
I
D
3
are smaller for stars with higher activity levels, while this anti-correlation is weaker for Na
I
D and the Ca
II
infrared triplet, and is absent for He
I
λ
10833 Å and Pa
β
. Periodic variation with the rotation period most commonly appears in the TiO bands, H
α
, and in the Ca
II
infrared triplet.
To obtain quantitative data on the progression of the most common spinocerebellar ataxias (SCAs) and identify factors that influence their progression, we initiated the EUROSCA natural history study, ...a multicentric longitudinal cohort study of 526 patients with SCA1, SCA2, SCA3, or SCA6. We report the results of the 1- and 2-year follow-up visits.
As the primary outcome measure we used the Scale for the Assessment and Rating of Ataxia (SARA, 0-40), and as a secondary measure the Inventory of Non-Ataxia Symptoms (INAS, 0-16) count.
The annual increase of the SARA score was greatest in SCA1 (2.18 ± 0.17, mean ± SE) followed by SCA3 (1.61 ± 0.12) and SCA2 (1.40 ± 0.11). SARA progression in SCA6 was slowest and nonlinear (first year: 0.35 ± 0.34, second year: 1.44 ± 0.34). Analysis of the INAS count yielded similar results. Larger expanded repeats and earlier age at onset were associated with faster SARA progression in SCA1 and SCA2. In SCA1, repeat length of the expanded allele had a similar effect on INAS progression. In SCA3, SARA progression was influenced by the disease duration at inclusion, and INAS progression was faster in females.
Our study gives a comprehensive quantitative account of disease progression in SCA1, SCA2, SCA3, and SCA6 and identifies factors that specifically affect disease progression.
Abstract
SN 2023emq is a fast-evolving transient initially classified as a rare Type Icn supernova (SN), interacting with a H- and He-free circumstellar medium (CSM) around maximum light. Subsequent ...spectroscopy revealed the unambiguous emergence of narrow He lines, confidently placing SN 2023emq in the more common Type Ibn class. Photometrically, SN 2023emq has several uncommon properties regardless of its class, including its extreme initial decay (faster than >90% of Type Ibn/Icn SNe) and sharp transition in the decline rate from 0.20 to 0.07 mag day
−1
at +20 days. The bolometric light curve can be modeled as CSM interaction with 0.32
M
⊙
of ejecta and 0.12
M
⊙
of CSM, with 0.006
M
⊙
of nickel, as expected of fast, interacting SNe. Furthermore, broadband polarimetry at +8.7 days (
P
= 0.55% ± 0.30%) is consistent with spherical symmetry. A discovery of a transitional Type Icn/Ibn SN would be unprecedented and would give valuable insights into the nature of mass loss suffered by the progenitor just before death, but we favor an interpretation that SN 2023emq is a Type Ibn SN that exhibited flash-ionized features in the earliest spectrum, as the features are not an exact match with other Type Icn SNe to date. However, the feature at 5700 Å, in the region of C
iii
and N
ii
emission, is significantly stronger in SN 2023emq than in the few other flash-ionized Type Ibn SNe, and if it is related to C
iii
, it possibly implies a continuum of properties between the two classes.
In eukaryotic cells the histone methylase SUV39H1 and the methyl-lysine binding protein HP1 functionally interact to repress transcription at heterochromatic sites. Lysine 9 of histone H3 is ...methylated by SUV39H1 (ref. 2), creating a binding site for the chromo domain of HP1 (refs 3, 4). Here we show that SUV39H1 and HP1 are both involved in the repressive functions of the retinoblastoma (Rb) protein. Rb associates with SUV39H1 and HP1 in vivo by means of its pocket domain. SUV39H1 cooperates with Rb to repress the cyclin E promoter, and in fibroblasts that are disrupted for SUV39, the activity of the cyclin E and cyclin A2 genes are specifically elevated. Chromatin immunoprecipitations show that Rb is necessary to direct methylation of histone H3, and is necessary for binding of HP1 to the cyclin E promoter. These results indicate that the SUV39H1-HP1 complex is not only involved in heterochromatic silencing but also has a role in repression of euchromatic genes by Rb and perhaps other co-repressor proteins.
...we evaluated omicron nAbT in four patients with a history of breakthrough delta infection after two vaccine doses. The exact correlates of immune protection against VOC remain undefined; however, ...multiple studies have shown that higher nAbT correlate with reduced risk of symptomatic infection.10,11 Finally, we did not evaluate vaccine-induced cellular responses to omicron as we had for other VOCs.2 We note that emerging reports suggest T-cell responses against omicron remain comparable to ancestral variants in the general population without cancer.12,13 In conclusion, we show that most of the patients with cancer in the CAPTURE cohort lacked detectable nAbT against omicron following two vaccine doses, independent of the vaccine type. CS is funded by CRUK (TRACERx, PEACE and CRUK Cancer Immunotherapy Catalyst Network), the CRUK Lung Cancer Centre of Excellence (C11496/A30025), the Rosetrees Trust, Butterfield and Stoneygate Trusts, the Novo Nordisk Foundation (ID16584), a Royal Society Professorship Enhancement award (RP/EA/180007), the National Institute of Health Research (NIHR) Biomedical Research Centre at University College London Hospitals, the CRUK University College London Centre, the Experimental Cancer Medicine Centre and the Breast Cancer Research Foundation (BCRF 20-157). ST is funded by Cancer Research UK (A29911); the Francis Crick Institute, which receives its core funding from Cancer Research UK (FC10988), the UK Medical Research Council (FC10988), and the Wellcome Trust (FC10988); the NIHR Biomedical Research Centre at the Royal Marsden Hospital and Institute of Cancer Research (grant reference number A109), the Royal Marsden Cancer Charity, The Rosetrees Trust (A2204), Ventana Medical Systems (grant reference numbers 10467 and 10530), the National Institute of Health (U01 CA247439) and Melanoma Research Alliance (686061).
We present precise photospheric parameters of 282 M dwarfs determined from fitting the most recent version of PHOENIX models to high-resolution CARMENES spectra in the visible (0.52–0.96
μ
m) and NIR ...wavelength range (0.96–1.71
μ
m). With its aim to search for habitable planets around M dwarfs, several planets of different masses have been detected. The characterization of the target sample is important for the ability to derive and constrain the physical properties of any planetary systems that are detected. As a continuation of previous work in this context, we derived the fundamental stellar parameters effective temperature, surface gravity, and metallicity of the CARMENES M-dwarf targets from PHOENIX model fits using a
χ
2
method. We calculated updated PHOENIX stellar atmosphere models that include a new equation of state to especially account for spectral features of low-temperature stellar atmospheres as well as new atomic and molecular line lists. We show the importance of selecting magnetically insensitive lines for fitting to avoid effects of stellar activity in the line profiles. For the first time, we directly compare stellar parameters derived from multiwavelength range spectra, simultaneously observed for the same star. In comparison with literature values we show that fundamental parameters derived from visible spectra and visible and NIR spectra combined are in better agreement than those derived from the same spectra in the NIR alone.
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