Systemic sclerosis (SSc) is an autoimmune disease that shows one of the highest mortality rates among rheumatic diseases. We perform a large genome-wide association study (GWAS), and meta-analysis ...with previous GWASs, in 26,679 individuals and identify 27 independent genome-wide associated signals, including 13 new risk loci. The novel associations nearly double the number of genome-wide hits reported for SSc thus far. We define 95% credible sets of less than 5 likely causal variants in 12 loci. Additionally, we identify specific SSc subtype-associated signals. Functional analysis of high-priority variants shows the potential function of SSc signals, with the identification of 43 robust target genes through HiChIP. Our results point towards molecular pathways potentially involved in vasculopathy and fibrosis, two main hallmarks in SSc, and highlight the spectrum of critical cell types for the disease. This work supports a better understanding of the genetic basis of SSc and provides directions for future functional experiments.
Summary
COVID‐19 is an infectious disease caused by severe acute respiratory coronavirus 2 (SARS‐CoV‐2). Vesicular skin rashes have been reported as associated with COVID‐19, but there is little ...information about this cutaneous manifestation. We designed a prospective observational study of patients diagnosed with COVID‐19 who had vesicular lesions. Clinical characterization of skin findings was conducted by dermatologists. When possible, histological analysis and detection of SARS‐CoV‐2 in the content of the vesicles was performed. In total, 24 patients were included. A disseminated pattern was found in 18 patients (75%), and a localized pattern was found in 6 (25%). Median duration of the skin rash was 10 days. Of the 24 patients, 19 (79.2%) developed the skin rash after the onset of COVID‐19 symptoms. Histological examination in two patients was consistent with viral infection, SARS‐CoV‐2 was not detected in four patients. This single‐centre study shows the clinical characteristics of vesicular skin rashes in patients with COVID‐19.
Seven mixed sewage sludges from different wastewater treatment plants, which have an anaerobic digester in operation, were evaluated in order to clarify the literature uncertainty with regard to the ...sewage sludge characterisation and biodegradability. Moreover, a methodology is provided to determine the Anaerobic Digestion Model No. 1 parameters, coefficients and initial state variables as well as a discussion about the accuracy of the first order solubilisation constant, which was obtained through biomethane potential test. The results of the biomethane potential tests showed ultimate methane potentials from 188 to 214 mL CH4 g−1 CODfed, COD removals between 58 and 65% and two homogeneous groups for the first order solubilisation constant: (i) the lowest rate group from 0.23 to 0.35 day−1 and (ii) the highest rate group from 0.27 to 0.43 day−1. However, no statistically significant relationship between the ultimate methane potential or the disintegration constant and the sewage sludge characterisation was found. Next, a methodology based on the sludge characterisation before and after the biomethane potential test was developed to calculate the biodegradable fraction, the composite concentration and stoichiometric coefficients and the soluble COD of the sewage sludge; required parameters for the implementation of the Anaerobic Digestion Model No. 1. The comparison of the experimental and the simulation results proved the consistency of the developed methodology. Nevertheless, an underestimation of the first order solubilisation constant was detected when the experimental results were simulated with the solubilisation constant obtained from the linear regression experimental data fitting. The latter phenomenon could be related to the accumulation of intermediary compounds during the biomethane potential assay.
•No relationship between sludge characterisation and solubilisation constant was found.•Solubilisation rate underestimation was related to soluble compounds accumulation.•A methodology to provide ADM1 parameters, coefficients and variables was developed.
The prediction of supercooled cloud drops in the atmosphere is a basic tool for aviation safety, owing to their contact with and instant freezing on sensitive locations of the aircraft. One of the ...main disadvantages for predicting atmospheric icing conditions is the acquisition of observational data. In this study, we used in‐cloud microphysics measurements taken during 10 flights of a C‐212 research aircraft under winter conditions, during which we encountered 37 regions containing supercooled liquid water. To investigate the capability of the Weather Research and Forecasting model to detect regions containing supercooled cloud drops, we propose a multiphysics ensemble approach. We used four microphysics and two planetary boundary layer schemes. The Morrison parameterization yielded superior results, whereas the planetary boundary layer schemes were essential in evaluating the presence of liquid water content. The Goddard microphysics scheme best detected the presence of ice water content but tended to underestimate liquid water content.
Key Points
In‐cloud microphysics measurements were taken using aircraft under winter conditions
The Weather Research and Forecasting model was evaluating for icing forecast with multiphysics ensemble approach
The Morrison microphysics scheme yielded superior results, and the PBL schemes were essential in evaluating the liquid water content
Background
Few reported studies compare drug survival in moderate‐to‐severe psoriasis vulgaris.
Objectives
To describe and compare drug survival of systemic drugs, including biologic agents ...(infliximab, etanercept, adalimumab and ustekinumab) and classical drugs (acitretin, ciclosporin and methotrexate) in moderate‐to‐severe psoriasis.
Methods
This was a multicenter, prospective, cohort study of patients receiving systemic therapies between 2008 and 2013 in 12 hospitals in Spain. Baseline data and drug discontinuation were collected. Drug survival is presented using Kaplan–Meier survival curves. We compared adjusted risk ratios of serious adverse events (AEs) with results of survival analysis for AEs.
Results
A total of 1956 patients were included for analysis (1240 exposed to biologics during follow‐up and 1076 to classic therapies). Median follow‐up time was 3.3 years (0.0–5.1 years). There were 2209 discontinuations out of 3640 therapy cycles started. The main reason for discontinuation was lack of efficacy (36.4%) and remission (27.2%). Biologics showed a higher drug survival than classics and the pattern of survival results for all outcomes (positive or negative) were very similar. Adjusted risk ratios of serious AEs did not agree with results of survival analysis.
Limitations
A limitation is that this is an observational study with potential selection bias.
Conclusion
Survival as a proxy measure of drug safety in psoriasis is inadequate.
We present the results of prompt optical follow-up of the electromagnetic counterpart of the gravitational-wave event GW170817 by the Transient Optical Robotic Observatory of the South Collaboration. ...We detected highly significant dimming in the light curves of the counterpart ( mag, mag, mag) over the course of only 80 minutes of observations obtained ∼35 hr after the trigger with the T80-South telescope. A second epoch of observations, obtained ∼59 hr after the event with the EABA 1.5 m telescope, confirms the fast fading nature of the transient. The observed colors of the counterpart suggest that this event was a "blue kilonova" relatively free of lanthanides.
Summary
Background
To date, genetic studies of hypersensitivity reactions to non‐steroidal anti‐inflammatory drugs (NSAIDs) have been carried out mainly in aspirin‐induced asthma and to a lesser ...extent in chronic urticaria, with no studies in patients with acute urticaria (AU), the most common entity induced by these drugs.
Objective
In this work, we analysed the association of common variants of 15 relevant genes encoding both enzymes and receptors from the arachidonic acid (AA) pathway with NSAID‐induced AU.
Methods
Patients were recruited in several Allergy Services that are integrated into the Spanish network RIRAAF, and diagnosed of AU induced by cross‐intolerance (CRI) to NSAIDs. Genotyping was carried out by TaqMan allelic discrimination assays.
Results
A total of 486 patients with AU induced by CRI to NSAIDs and 536 unrelated controls were included in this large Spanish case‐control study. Seven variants from 31 tested in six genes were associated in a discovery study population from Malaga (0.0003 ≤ p‐value ≤ 0.041). A follow‐up analysis in an independent sample from Madrid replicated three of the SNPs from the ALOX15 (rs7220870), PTGDR (rs8004654) and CYSLTR1 (rs320095) genes (1.055x10‐6≤meta‐analysis p‐value ≤ 0.003).
Conclusions and Clinical Relevance
Genetic variants of the AA pathway may play an important role in NSAID‐induced AU. These data may help understand the mechanism underlying this disease.
One of the requirements of the recently approved EU-BSS (European Basic Safety Standards Directive, EURATOM, 2013) is the design and implementation of national radon action plans in the member states ...(Annex XVIII). Such plans require radon surveys. The analysis of indoor radon data is supported by the existing knowledge about geogenic radiation. With this aim, we used the terrestrial gamma dose rate data from the MARNA project. In addition, we considered other criterion regarding the surface of Spain, population, permeability of rocks, uranium and radium contain in soils because currently no data are available related to soil radon gas concentration and permeability in Spain. Given that, a Spanish radon map was produced which will be part of the European Indoor Radon Map and a component of the European Atlas of Natural Radiation. The map indicates geographical areas with high probability of finding high indoor radon concentrations. This information will support legislation regarding prevention of radon entry both in dwellings and workplaces. In addition, the map will serve as a tool for the development of strategies at all levels: individual dwellings, local, regional and national administration.
•The last version of the Spanish indoor radon map accounts with 9211 measurements.•Several criteria has been designed to plan a measurements campaign based on known correlations.•Lithostratigraphy is a good criterion for radon mapping (national scale). Local scales need others.•Radon map is an active tool which will evolve progressively by adding new data.
Summary
Background
Cutaneous squamous cell carcinoma (CSCC) is the second most frequent cancer in humans after basal cell carcinoma, and its incidence is dramatically rising. CSCC is rarely ...problematic, but given its high frequency, the absolute number of complicated cases is also high. It is necessary to identify molecular markers in order to recognize those CSCCs with poor prognosis. There is controversy concerning the role of epidermal growth factor receptor (EGFR) as a marker of prognosis in CSCC. In addition, EGFR‐targeted therapies have emerged in recent years and a better understanding of the role of EGFR in CSCC may be of help for some patients in predicting prognosis and guiding curative management.
Objectives
To evaluate the role of EGFR as a prognostic factor in CSCC.
Methods
We evaluated clinical and histopathological features, including events of poor clinical evolution, in a series of 94 cases of CSCC. We also analysed EGFR expression by immunohistochemistry, fluorescent in situ hybridization and quantitative polymerase chain reaction.
Results
We detected EGFR in 85 cases (90%), with overexpression in 33 cases (35%), and aberrant EGFR expression in the cytoplasm in 50 cases (53%). EGFR overexpression in the primary tumours was associated with lymph node progression, tumour–nodes–metastasis stage progression and proliferation (Ki‐67 staining) in CSCC. EGFR overexpression and poor grade of differentiation were the strongest independent variables defining lymph node metastasis and progression in CSCC in a logistic regression model.
Conclusions
We demonstrate that EGFR overexpression has prognostic implications associated with lymph node metastasis and progression in CSCC.
What's already known about this topic?
Cutaneous squamous cell carcinoma (CSCC) is the second most frequent cancer in humans and sometimes exhibits a poor outcome.
Epidermal growth factor receptor (EGFR) activation in keratinocytes induces cellular proliferation, increases cell survival and induces resistance to apoptosis.
While the expression of EGFR has been extensively studied in CSCC, there is some controversy surrounding its prognostic significance.
What does this study add?
Based on the results of our study, EGFR overexpression appears to have prognostic implications associated with lymph node metastasis and progression in CSCC.
There was no association between the level of EGFR protein, detected by immunohistochemistry, and the level of EGFR RNA.
What is the translational message?
We provide evidence that EGFR expression is a molecular marker for poor clinical outcome in cases of CSCC.
EGFR‐targeted therapies might be helpful in selected patients with metastatic CSCC.
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Linked Comment: Griewank. Br J Dermatol 2017; 176:1126–1127
The synergistic effects of using several supplementary cementitious materials (SCMs), such as Blast Furnace Slags plus Limestone Filler or Fly Ashes, depend on the OPC composition. When using an OPC ...which is poor in C3A and alkalis in ternary formulations, a similar initial strength gain to that of a plain OPC is detected and at longer hydration ages, the formation of monocarboaluminate, hemicarbonate and hydrotalcite instead of monosulphate can be seen. If an OPC with a higher C3A content and alkalis is used with SCMs, the higher availability of Al causes the early formation of monocarboaluminate and a lower initial strength gain. At longer hydration times, in ternary blends with both OPCs, the mechanical strengths are higher and the C-S-H gels formed are richer in Al and poorer in C/S ratio with a subsequent lowering of the alkali content in the pore solution when compared to that in plain OPC.
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