Massive Ellipticals at High Redshift: NICMOS Imaging of Z~1 Radio Galaxies

We present deep, continuum images of eleven high-redshift (0.811 < z < 1.875) 3CR radio galaxies observed with NICMOS. Our images probe the rest-frame optical light where stars are expected to dominate the galaxy luminosity. The rest-frame UV light of eight of these galaxies demonstrates the well-known ``alignment effect''. Most of the radio galaxies have rounder, more symmetric morphologies at rest-frame optical wavelengths. Here we show the most direct evidence that in most cases the stellar hosts are normal elliptical galaxies with de Vaucouleurs law light profiles. For a few galaxies very faint traces of the UV-bright aligned component are also visible in the infrared images. We derive both the effective radius and surface-brightness for nine of eleven sample galaxies by fitting surface-brightness models to them. We find their sizes are similar to those of local FRII radio source hosts and are in general larger than other local galaxies. The derived host galaxy luminosities are very high and lie at the bright end of luminosity functions constructed at similar redshifts. The galaxies in our sample are also brighter than the rest-frame size--surface-brightness locus defined by the low-redshift sources. Passive evolution roughly aligns the z ~ 1 galaxies with the low-redshift samples. The optical host is sometimes centered on a local minimum in the rest-frame UV emission, suggesting the presence of substantial dust obscuration. We also see good evidence of nuclear point sources in three galaxies. Overall, our results are consistent with the hypothesis that these galaxies have already formed the bulk of their stars at redshifts greater than z >~ 2, and that the AGN phenomenon takes place within otherwise normal, perhaps passively evolving, galaxies. (abridged)Comment: 28 pages, 14 figures, accepted to ApJ. Uses AASTEX and emulateapj

Evolution of the use of corticosteroids for the treatment of hospitalised COVID-19 patients in Spain between March and November 2020: SEMI-COVID national registry

Objectives: Since the results of the RECOVERY trial, WHO recommendations about the use of corticosteroids (CTs) in COVID-19 have changed. The aim of the study is to analyse the evolutive use of CTs in Spain during the pandemic to assess the potential influence of new recommendations. Material and methods: A retrospective, descriptive, and observational study was conducted on adults hospitalised due to COVID-19 in Spain who were included in the SEMI-COVID- 19 Registry from March to November 2020. Results: CTs were used in 6053 (36.21%) of the included patients. The patients were older (mean (SD)) (69.6 (14.6) vs. 66.0 (16.8) years; p < 0.001), with hypertension (57.0% vs. 47.7%; p < 0.001), obesity (26.4% vs. 19.3%; p < 0.0001), and multimorbidity prevalence (20.6% vs. 16.1%; p < 0.001). These patients had higher values (mean (95% CI)) of C-reactive protein (CRP) (86 (32.7-160) vs. 49.3 (16-109) mg/dL; p < 0.001), ferritin (791 (393-1534) vs. 470 (236- 996) µg/dL; p < 0.001), D dimer (750 (430-1400) vs. 617 (345-1180) µg/dL; p < 0.001), and lower Sp02/Fi02 (266 (91.1) vs. 301 (101); p < 0.001). Since June 2020, there was an increment in the use of CTs (March vs. September; p < 0.001). Overall, 20% did not receive steroids, and 40% received less than 200 mg accumulated prednisone equivalent dose (APED). Severe patients are treated with higher doses. The mortality benefit was observed in patients with oxygen saturation </=90%. Conclusions: Patients with greater comorbidity, severity, and inflammatory markers were those treated with CTs. In severe patients, there is a trend towards the use of higher doses. The mortality benefit was observed in patients with oxygen saturation </=90%

The trans-ancestral genomic architecture of glycemic traits

Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 x 10(-8)), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution.A trans-ancestry meta-analysis of GWAS of glycemic traits in up to 281,416 individuals identifies 99 novel loci, of which one quarter was found due to the multi-ancestry approach, which also improves fine-mapping of credible variant sets.Diabetes mellitus: pathophysiological changes and therap

BCR-ABL activity and its response to drugs can be determined in CD34⁺ CML stem cells by CrkL phosphorylation status using flow cytometry

In chronic myeloid leukaemia, CD34&lt;sup&gt;+&lt;/sup&gt; stem/progenitor cells appear resistant to imatinib mesylate (IM) &lt;i&gt;in vitro&lt;/i&gt; and &lt;i&gt;in vivo&lt;/i&gt;. To investigate the underlying mechanism(s) of IM resistance, it is essential to quantify Bcr-AbI kinase status at the stem cell level. We developed a flow cytometry method to measure CrkL phosphorylation(P-CrkL) in samples with &lt; 10&lt;sup&gt;4&lt;/sup&gt; cells. The method was first validated in wild-type (K562) and mutant (BAF3) BCR-ABL&lt;sup&gt;+&lt;/sup&gt; as well as BCR-ABL&lt;sup&gt;-&lt;/sup&gt; (HL60) cell lines. In response to increasing IM concentration, there was a linear reduction in P-CrkL, which was Bcr-AbI specific and correlated with known resistance. The results were comparable to those from Western blotting. The method also proved to be reproducible with small samples of normal and Ph&lt;sup&gt;+&lt;/sup&gt; CD34&lt;sup&gt;+&lt;/sup&gt; cells and was able to discriminate between Ph&lt;sup&gt;-&lt;/sup&gt;, sensitive and resistant Ph&lt;sup&gt;+&lt;/sup&gt; cells. This assay should now enable investigators to unravel the mechanism(s) of IM resistance in stem cells

Inactivation of HOXA genes by hypermethylation in myeloid and lymphoid malignancy is frequent and associated with poor prognosis

&lt;p&gt;&lt;b&gt;Purpose:&lt;/b&gt; The HOX genes comprise a large family of homeodomain-containing transcription factors, present in four separate clusters, which are key regulators of embryonic development, hematopoietic differentiation, and leukemogenesis. We aimed to study the role of DNA methylation as an inducer of HOX gene silencing in leukemia.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Experimental Design:&lt;/b&gt; Three hundred and seventy-eight samples Of myeloid and lymphoid leukemia were quantitatively analyzed (by COBRA analysis and pyrosequencing of bisulfite-modified DNA) for methylation of eight HOXA and HOXB cluster genes. The biological significance of the methylation identified was studied by expression analysis and through re-expression of HOXA5 in a chronic myeloid leukemia (CML) blast crisis cell line model.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Results:&lt;/b&gt; Here, we identify frequent hypermethylation and gene inactivation of HOXA and HOXB cluster genes in leukemia. In particular, hypermethylation of HOXA4 and HOXA5 was frequently observed (26-79%) in all types of leukemias studied. HOXA6 hypermethylation was predominantly restricted to lymphoid malignancies, whereas hypermethylation of other HOXA and HOXB genes was only observed in childhood leukemia. HOX gene methylation exhibited clear correlations with important clinical variables, most notably in CML, in which hypermethylation of both HOXA5 (P = 0.00002) and HOXA4 (P = 0.006) was strongly correlated with progression to blast crisis. Furthermore, re-expression of HOXA5 in CML blast crisis cells resulted in the induction of markers of granulocytic differentiation.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Conclusion:&lt;/b&gt; We propose that in addition to the oncogenic role of some HOX family members, other HOX genes are frequent targets for gene inactivation and normally play suppressor roles in leukemia development.&lt;/p&gt