46 research outputs found
Crosscurrents in 1986 bank performance
Bank profits ; Banks and banking - Ratio analysis ; Federal Reserve District, 7th
Anemia and brain oxygen after severe traumatic brain injury
Purpose: To investigate the relationship between hemoglobin (Hgb) and brain tissue oxygen tension (PbtO2) after severe traumatic brain injury (TBI) and to examine its impact on outcome. Methods: This was a retrospective analysis of a prospective cohort of severe TBI patients whose PbtO2 was monitored. The relationship between Hgb—categorized into four quartiles (≤9; 9-10; 10.1-11; >11g/dl)—and PbtO2 was analyzed using mixed-effects models. Anemia with compromised PbtO2 was defined as episodes of Hgb≤9g/dl with simultaneous PbtO211g/dl as the reference level, and controlling for important physiologic covariates (CPP, PaO2, PaCO2), Hgb≤9g/dl was the only Hgb level that was associated with lower PbtO2 (coefficient −6.53 (95% CI −9.13; −3.94), p<0.001). Anemia with simultaneous PbtO2<20mmHg, but not anemia alone, increased the risk of unfavorable outcome (odds ratio 6.24 (95% CI 1.61; 24.22), p=0.008), controlling for age, GCS, Marshall CT grade, and APACHE II score. Conclusions: In this cohort of severe TBI patients whose PbtO2 was monitored, a Hgb level no greater than 9g/dl was associated with compromised PbtO2. Anemia with simultaneous compromised PbtO2, but not anemia alone, was a risk factor for unfavorable outcome, irrespective of injury severit
Genomic analyses identify recurrent MEF2D fusions in acute lymphoblastic leukemia
Chromosomal rearrangements are initiating events in acute lymphoblastic leukaemia (ALL). Here using RNA sequencing of 560 ALL cases, we identify rearrangements between MEF2D (myocyte enhancer factor 2D) and five genes (BCL9, CSF1R, DAZAP1, HNRNPUL1 and SS18) in 22 B progenitor ALL (B-ALL) cases with a distinct gene expression profile, the most common of which is MEF2DBCL9. Examination of an extended cohort of 1,164 B-ALL cases identified 30 cases with MEF2D rearrangements, which include an additional fusion partner, FOXJ2; thus, MEF2D-rearranged cases comprise 5.3% of cases lacking recurring alterations. MEF2D-rearranged ALL is characterized by a distinct immunophenotype, DNA copy number alterations at the rearrangement sites, older diagnosis age and poor outcome. The rearrangements result in enhanced MEF2D transcriptional activity, lymphoid transformation, activation of HDAC9 expression and sensitive to histone deacetylase inhibitor treatment. Thus, MEF2D-rearranged ALL represents a distinct form of high-risk leukaemia, for which new therapeutic approaches should be considered.This work was supported in part by
the American Lebanese Syrian Associated Charities of St. Jude Children’s Research
Hospital; by a Stand Up to Cancer Innovative Research Grant and St. Baldrick’s
Foundation Scholar Award (to C.G.M.); by a St. Baldrick’s Consortium Award (S.P.H.),
by a Leukemia and Lymphoma Society Specialized Center of Research grant (S.P.H. and
C.G.M.), by a Lady Tata Memorial Trust Award (I.I.), by a Leukemia and Lymphoma
Society Special Fellow Award and Alex’s Lemonade Stand Foundation Young Investigator
Awards (K.R.), by an Alex’s Lemonade Stand Foundation Award (M.L.) and by
National Cancer Institute Grants CA21765 (St Jude Cancer Center Support Grant), U01
CA157937 (C.L.W. and S.P.H.), U24 CA114737 (to Dr Gastier-Foster), NCI Contract
HHSN261200800001E (to Dr Gastier-Foster), U10 CA180820 (ECOG-ACRIN
Operations) and CA180827 (E.P.); U10 CA180861 (C.D.B. and G.M.); U24 CA196171
(The Alliance NCTN Biorepository and Biospecimen Resource); CA145707 (C.L.W. and
C.G.M.); and grants to the COG: U10 CA98543 (Chair’s grant and supplement to
support the COG ALL TARGET project), U10 CA98413 (Statistical Center) and U24
CA114766 (Specimen Banking). This project has been funded in whole or in part with
Federal funds from the National Cancer Institute, National Institutes of Health, under
Contract Number HHSN261200800001E
Investigation of hospital discharge cases and SARS-CoV-2 introduction into Lothian care homes
Background
The first epidemic wave of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in Scotland resulted in high case numbers and mortality in care homes. In Lothian, over one-third of care homes reported an outbreak, while there was limited testing of hospital patients discharged to care homes.
Aim
To investigate patients discharged from hospitals as a source of SARS-CoV-2 introduction into care homes during the first epidemic wave.
Methods
A clinical review was performed for all patients discharges from hospitals to care homes from 1st March 2020 to 31st May 2020. Episodes were ruled out based on coronavirus disease 2019 (COVID-19) test history, clinical assessment at discharge, whole-genome sequencing (WGS) data and an infectious period of 14 days. Clinical samples were processed for WGS, and consensus genomes generated were used for analysis using Cluster Investigation and Virus Epidemiological Tool software. Patient timelines were obtained using electronic hospital records.
Findings
In total, 787 patients discharged from hospitals to care homes were identified. Of these, 776 (99%) were ruled out for subsequent introduction of SARS-CoV-2 into care homes. However, for 10 episodes, the results were inconclusive as there was low genomic diversity in consensus genomes or no sequencing data were available. Only one discharge episode had a genomic, time and location link to positive cases during hospital admission, leading to 10 positive cases in their care home.
Conclusion
The majority of patients discharged from hospitals were ruled out for introduction of SARS-CoV-2 into care homes, highlighting the importance of screening all new admissions when faced with a novel emerging virus and no available vaccine
SARS-CoV-2 Omicron is an immune escape variant with an altered cell entry pathway
Vaccines based on the spike protein of SARS-CoV-2 are a cornerstone of the public health response to COVID-19. The emergence of hypermutated, increasingly transmissible variants of concern (VOCs) threaten this strategy. Omicron (B.1.1.529), the fifth VOC to be described, harbours multiple amino acid mutations in spike, half of which lie within the receptor-binding domain. Here we demonstrate substantial evasion of neutralization by Omicron BA.1 and BA.2 variants in vitro using sera from individuals vaccinated with ChAdOx1, BNT162b2 and mRNA-1273. These data were mirrored by a substantial reduction in real-world vaccine effectiveness that was partially restored by booster vaccination. The Omicron variants BA.1 and BA.2 did not induce cell syncytia in vitro and favoured a TMPRSS2-independent endosomal entry pathway, these phenotypes mapping to distinct regions of the spike protein. Impaired cell fusion was determined by the receptor-binding domain, while endosomal entry mapped to the S2 domain. Such marked changes in antigenicity and replicative biology may underlie the rapid global spread and altered pathogenicity of the Omicron variant
LIN-53, a nucleosome remodeling protein, is a potential interactor with C. elegans cytoplasmic signaling protein MIG-10
The C. elegans protein MIG-10 is a cytoplasmic signaling protein known to facilitate neuronal migrations during development of the worm. LIN-53 is a nucleosome remodeling factor associated with transcriptional repression in C. elegans. Biochemical analyses were performed using co-immunoprecipitation and western blotting techniques to assess the interaction of these two proteins. Preliminary results suggest a potential interaction between LIN-53 and MIG-10. Work is in progress to determine whether lin-53 mutations affect neuronal migrations in C. elegans