The Association of qSOFA, SOFA, and SIRS with Mortality in Emergency Department Pneumonia

Objective: To determine the association between 30-day mortality with Systemic Inflammatory Response Syndrome (SIRS), Sequential Organ Failure Assessment (SOFA), and quick SOFA (qSOFA) in emergency department patients with pneumonia. Secondary outcomes included the association of sepsis scores with hospital admission and direct ICU admission. Methods: This is a secondary analysis of a pneumonia population conducted in the emergency department of 3 tertiary care medical centers and 4 community hospitals. Adult immunocompetent patients diagnosed with pneumonia were included from 3 twelve-month periods spanning December 2009 to October 2015. We generated area under the receiver operating characteristic curve (AUC) values for each sepsis score for our primary outcome of 30-day mortality and secondarily for hospital admission and direct ICU admission. We also created logistic regression models to assess associations of individual score components to the outcomes. Results:We studied 6931 patients with mean (SD) age 58 (20) years, and 30 day all-cause mortality rate 7%. Hospital and ICU admission rate was 63% and 16% respectively. Sepsis by SIRS was present in 70% of patients. Only respiratory rate and white blood count of the SIRS criteria were associated with 30-day mortality (OR=2.42 [1.94, 3.03] and 2.06 [1.68, 2.54] respectively, both p Conclusions: In emergency department patients with pneumonia, qSOFA outperformed SIRS in relation to 30-day mortality. Secondary outcomes also showed better performance of qSOFA in hospital and ICU admission compared to SIRS. SOFA performed better than qSOFA and SIRS for all outcomes except ICU admission

Early aberrant angiogenesis due to elastic fiber fragmentation in aortic valve disease

Elastic fiber fragmentation (EFF) is a hallmark of aortic valve disease (AVD), and neovascularization has been identified as a late finding related to inflammation. We sought to characterize the relationship between early EFF and aberrant angiogenesis. To examine disease progression, regional anatomy and pathology of aortic valve tissue were assessed using histochemistry, immunohistochemistry, and electron microscopy from early-onset (\u3c40 yo) and late-onset (≥40 yo) non-syndromic AVD specimens. To assess the effects of EFF on early AVD processes, valve tissue from Williams and Marfan syndrome patients was also analyzed. Bicuspid aortic valve was more common in early-onset AVD, and cardiovascular comorbidities were more common in late-onset AVD. Early-onset AVD specimens demonstrated angiogenesis without inflammation or atherosclerosis. A distinct pattern of elastic fiber components surrounded early-onset AVD neovessels, including increased emilin-1 and decreased fibulin-5. Different types of EFF were present in Williams syndrome (WS) and Marfan syndrome (MFS) aortic valves; WS but not MFS aortic valves demonstrated angiogenesis. Aberrant angiogenesis occurs in early-onset AVD in the absence of inflammation, implicating EFF. Elucidation of underlying mechanisms may inform the development of new pharmacologic treatments

Differential Expression of Extracellular Matrix-Mediated Pathways in Single-Suture Craniosynostosis

Craniosynostosis is a disease defined by premature fusion of one or more cranial sutures. The mechanistic pathology of single-suture craniosynostosis is complex and while a number of genetic biomarkers and environmental predispositions have been identified, in many cases the causes remain controversial and inconclusive. In this study, gene expression data from 199 patients with isolated sagittal (n = 100), unilateral coronal (n = 50), and metopic (n = 49) synostosis are compared against both a control population (n = 50), as well as each other. After controlling for variables contributing to potential bias, FGF7, SFRP4, and VCAM1 emerged as genes associated with single-suture craniosynostosis due to their significantly large changes in gene expression compared to the control population. Pathway analysis implicated focal adhesion and extracellular matrix (ECM)-receptor interaction as differentially regulated gene networks when comparing all cases of single-suture synostosis and controls. Lastly, overall gene expression was found to be highly conserved between coronal and metopic cases, as evidenced by the fact that WNT2 and IGFBP2 were the only genes differentially regulated to a significantly large extent in a direct comparison. The identification of genes and gene networks associated with Fgf/Igf/Wnt signaling and ECM-mediated focal adhesion not only support the involvement of biomarkers previously reported to be related to craniosynostosis, but also introduce novel transcripts and pathways that may play critical roles in its pathogenesis

Early Aberrant Angiogenesis Due to Elastic Fiber Fragmentation in Aortic Valve Disease

Elastic fiber fragmentation (EFF) is a hallmark of aortic valve disease (AVD), and neovascularization has been identified as a late finding related to inflammation. We sought to characterize the relationship between early EFF and aberrant angiogenesis. To examine disease progression, regional anatomy and pathology of aortic valve tissue were assessed using histochemistry, immunohistochemistry, and electron microscopy from early-onset (<40 yo) and late-onset (≥40 yo) non-syndromic AVD specimens. To assess the effects of EFF on early AVD processes, valve tissue from Williams and Marfan syndrome patients was also analyzed. Bicuspid aortic valve was more common in early-onset AVD, and cardiovascular comorbidities were more common in late-onset AVD. Early-onset AVD specimens demonstrated angiogenesis without inflammation or atherosclerosis. A distinct pattern of elastic fiber components surrounded early-onset AVD neovessels, including increased emilin-1 and decreased fibulin-5. Different types of EFF were present in Williams syndrome (WS) and Marfan syndrome (MFS) aortic valves; WS but not MFS aortic valves demonstrated angiogenesis. Aberrant angiogenesis occurs in early-onset AVD in the absence of inflammation, implicating EFF. Elucidation of underlying mechanisms may inform the development of new pharmacologic treatments

Exome Sequencing Identifies a Recurrent De Novo ZSWIM6 Mutation Associated with Acromelic Frontonasal Dysostosis

Acromelic frontonasal dysostosis (AFND) is a rare disorder characterized by distinct craniofacial, brain, and limb malformations, including frontonasal dysplasia, interhemispheric lipoma, agenesis of the corpus callosum, tibial hemimelia, preaxial polydactyly of the feet, and intellectual disability. Exome sequencing of one trio and two unrelated probands revealed the same heterozygous variant (c.3487C>T [p. Arg1163Trp]) in a highly conserved protein domain of ZSWIM6; this variant has not been seen in the 1000 Genomes data, dbSNP, or the Exome Sequencing Project. Sanger validation of the three trios confirmed that the variant was de novo and was also present in a fourth isolated proband. In situ hybridization of early zebrafish embryos at 24 hr postfertilization (hpf) demonstrated telencephalic expression of zswim6 and onset of midbrain, hindbrain, and retinal expression at 48 hpf. Immunohistochemistry of later-stage mouse embryos demonstrated tissue-specific expression in the derivatives of all three germ layers. qRT-PCR expression analysis of osteoblast and fibroblast cell lines available from two probands was suggestive of Hedgehog pathway activation, indicating that the ZSWIM6 mutation associated with AFND may lead to the craniofacial, brain and limb malformations through the disruption of Hedgehog signaling

Argonne National Laboratory Reports

Quarterly report of the Argonne National Laboratory Chemical Engineering Division regarding activities related to properties and handling of radioactive materials, operation of nuclear reactors, and other relevant research

William Walker: social activism and Belfast labourism, 1870-1918

This thesis examines the social and political activism of the Belfast labour movement though one of its leaders, William Walker (1870 - 1918). It reassesses his place in Irish historiography which often dismissed him despite his acknowledged prominence in early twentieth century Ireland. The thesis argues that Walker has been narrowly defined as a political activist and makes the case for broadening the understanding of him through his social activism. [...]. The thesis conclused by arguing that Walker deserves greater recogniition for his courage, sense of dury and commitment to improving working-class conditions [abridged abstract]