The Feasibility, Tolerability, Safety, and Accuracy of Low-radiation Dynamic Computed Tomography Myocardial Perfusion Imaging With Regadenoson Compared With Single-photon Emission Computed Tomography

Objectives: Computed tomography (CT) myocardial perfusion imaging (CT-MPI) with hyperemia induced by regadenoson was evaluated for the detection of myocardial ischemia, safety, relative radiation exposure, and patient experience compared with single-photon emission computed tomography (SPECT) imaging. Materials and Methods: Twenty-four patients (66.5 y, 29% male) who had undergone clinically indicated SPECT imaging and provided written informed consent were included in this phase II, IRB-approved, and FDA-approved clinical trial. All patients underwent coronary CT angiography and CT-MPI with hyperemia induced by the intravenous administration of regadenoson (0.4 mg/5 mL). Patient experience and findings on CT-MPI images were compared to SPECT imaging. Results: Patient experience and safety were similar between CT-MPI and SPECT procedures and no serious adverse events due to the administration of regadenoson occurred. SPECT resulted in a higher number of mild adverse events than CT-MPI. Patient radiation exposure was similar during the combined coronary computed tomography angiography and CT-MPI (4.4 [2.7] mSv) and SPECT imaging (5.6 [1.7] mSv) (P-value 0.401) procedures. Using SPECT as the reference standard, CT-MPI analysis showed a sensitivity of 58.3% (95% confidence interval [CI]: 27.7-84.8), a specificity of 100% (95% CI: 73.5-100), and an accuracy of 79.1% (95% CI: 57.9-92.87). Low apparent sensitivity occurred when the SPECT defects were small and highly suspicious for artifacts. Conclusions: This study demonstrated that CT-MPI is safe, well tolerated, and can be performed with comparable radiation exposure to SPECT. CT-MPI has the benefit of providing both complete anatomic coronary evaluation and assessment of myocardial perfusion

The Surgical Infection Society revised guidelines on the management of intra-abdominal infection

Background: Previous evidence-based guidelines on the management of intra-abdominal infection (IAI) were published by the Surgical Infection Society (SIS) in 1992, 2002, and 2010. At the time the most recent guideline was released, the plan was to update the guideline every five years to ensure the timeliness and appropriateness of the recommendations. Methods: Based on the previous guidelines, the task force outlined a number of topics related to the treatment of patients with IAI and then developed key questions on these various topics. All questions were approached using general and specific literature searches, focusing on articles and other information published since 2008. These publications and additional materials published before 2008 were reviewed by the task force as a whole or by individual subgroups as to relevance to individual questions. Recommendations were developed by a process of iterative consensus, with all task force members voting to accept or reject each recommendation. Grading was based on the GRADE (Grades of Recommendation Assessment, Development, and Evaluation) system; the quality of the evidence was graded as high, moderate, or weak, and the strength of the recommendation was graded as strong or weak. Review of the document was performed by members of the SIS who were not on the task force. After responses were made to all critiques, the document was approved as an official guideline of the SIS by the Executive Council. Results: This guideline summarizes the current recommendations developed by the task force on the treatment of patients who have IAI. Evidence-based recommendations have been made regarding risk assessment in individual patients; source control; the timing, selection, and duration of antimicrobial therapy; and suggested approaches to patients who fail initial therapy. Additional recommendations related to the treatment of pediatric patients with IAI have been included. Summary: The current recommendations of the SIS regarding the treatment of patients with IAI are provided in this guideline

The problematic relationship between knowing how and knowing that in secondary art education

This is a postprint of an article whose final and definitive form has been published in the Oxford Review of Education© 2005 Copyright Taylor & Francis; Oxford Review of Education is available online at http://www.informaworld.comThis article explores and attempts to rectify current conceptual confusion found in secondary art education in the UK between procedural knowledge or 'knowing how' and declarative knowledge or 'knowing that'. The paper argues that current practice confuses procedural knowledge with declarative knowledge. A corollary is that assessment evidence for 'knowing how', which is shown or demonstrated, is confused with assessment evidence for 'knowing that', which requires spoken or written forms of reporting. The confusion is replicated in the national examination, the General Certificate of Secondary Education, taken by students at the age of 16. The article traces this confusion to three dualisms: the Cartesian dualisms of mind and body, an individual mind and the distributed mind of culture, and the more recent mind-in-brain hemisphere dualism. The article advocates a Wittgensteinian embodied, socio-cultural view of mind as a way of solving the current conceptual confusion that prevails in art education in the UK

Minimum Wage Channels of Adjustment

Industrial Relations, forthcoming Abstract: The effects of minimum wage increases in 2007-2009 are analyzed using a sample of restaurants from Georgia/Alabama. Store-level payroll records provide precise measures of compliance costs. Examined are multiple adjustment channels. Exploiting variation in compliance costs across restaurants, we find employment and hours responses to be variable and in most cases statistically insignificant. Channels of adjustment to wage increases and to changes in non-labor costs include prices, profits, wage compression, turnover, and performance standards

First measurement of the cross-correlation of CMB lensing and galaxy lensing

We measure the cross-correlation of cosmic microwave background (CMB) lensing convergence maps derived from Atacama Cosmology Telescope data with galaxy lensing convergence maps as measured by the Canada-France-Hawaii Telescope Stripe 82 Survey. The CMB-galaxy lensing cross power spectrum is measured for the first time with a significance of 4.2σ, which corresponds to a 12% constraint on the amplitude of density fluctuations at redshifts ∼0.9. With upcoming improved lensing data, this novel type of measurement will become a powerful cosmological probe, providing a precise measurement of the mass distribution at intermediate redshifts and serving as a calibrator for systematic biases in weak lensing measurements

First Measurement of the Cross-Correlation of CMB Lensing and Galaxy Lensing

We measure the cross-correlation of cosmic microwave background lensing convergence maps derived from Atacama Cosmology Telescope data with galaxy lensing convergence maps as measured by the Canada-France-Hawaii Telescope Stripe 82 Survey. The CMB-galaxy lensing cross power spectrum is measured for the first time with a significance of 3.2, which corresponds to a 16% constraint on the amplitude of density fluctuations at redshifts ~ 0.9. With upcoming improved lensing data, this novel type of measurement will become a powerful cosmological probe, providing a precise measurement of the mass distribution at intermediate redshifts and serving as a calibrator for systematic biases in weak lensing measurements

Structure-Guided Evolution of Potent and Selective CHK1 Inhibitors through Scaffold Morphing

Pyrazolopyridine inhibitors with low micromolar potency for CHK1 and good selectivity against CHK2 were previously identified by fragment-based screening. The optimization of the pyrazolopyridines to a series of potent and CHK1-selective isoquinolines demonstrates how fragment-growing and scaffold morphing strategies arising from a structure-based understanding of CHK1 inhibitor binding can be combined to successfully progress fragment-derived hit matter to compounds with activity in vivo. The challenges of improving CHK1 potency and selectivity, addressing synthetic tractability, and achieving novelty in the crowded kinase inhibitor chemical space were tackled by multiple scaffold morphing steps, which progressed through tricyclic pyrimido[2,3-b]azaindoles to N-(pyrazin-2-yl)pyrimidin-4-amines and ultimately to imidazo[4,5-c]pyridines and isoquinolines. A potent and highly selective isoquinoline CHK1 inhibitor (SAR-020106) was identified, which potentiated the efficacies of irinotecan and gemcitabine in SW620 human colon carcinoma xenografts in nude mice

Adjunctive Dexamethasone Affects the Expression of Genes Related to Inflammation, Neurogenesis and Apoptosis in Infant Rat Pneumococcal Meningitis

Streptococcus pneumoniae is the most common pathogen causing non-epidemic bacterial meningitis worldwide. The immune response and inflammatory processes contribute to the pathophysiology. Hence, the anti-inflammatory dexamethasone is advocated as adjuvant treatment although its clinical efficacy remains a question at issue. In experimental models of pneumococcal meningitis, dexamethasone increased neuronal damage in the dentate gyrus. Here, we investigated expressional changes in the hippocampus and cortex at 72 h after infection when dexamethasone was given to infant rats with pneumococcal meningitis. Nursing Wistar rats were intracisternally infected with Streptococcus pneumoniae to induce experimental meningitis or were sham-infected with pyrogen-free saline. Besides antibiotics, animals were either treated with dexamethasone or saline. Expressional changes were assessed by the use of GeneChip® Rat Exon 1.0 ST Arrays and quantitative real-time PCR. Protein levels of brain-derived neurotrophic factor, cytokines and chemokines were evaluated in immunoassays using Luminex xMAP® technology. In infected animals, 213 and 264 genes were significantly regulated by dexamethasone in the hippocampus and cortex respectively. Separately for the cortex and the hippocampus, Gene Ontology analysis identified clusters of biological processes which were assigned to the predefined categories “inflammation”, “growth”, “apoptosis” and others. Dexamethasone affected the expression of genes and protein levels of chemokines reflecting diminished activation of microglia. Dexamethasone-induced changes of genes related to apoptosis suggest the downregulation of the Akt-survival pathway and the induction of caspase-independent apoptosis. Signalling of pro-neurogenic pathways such as transforming growth factor pathway was reduced by dexamethasone resulting in a lack of pro-survival triggers. The anti-inflammatory properties of dexamethasone were observed on gene and protein level in experimental pneumococcal meningitis. Further dexamethasone-induced expressional changes reflect an increase of pro-apoptotic signals and a decrease of pro-neurogenic processes. The findings may help to identify potential mechanisms leading to apoptosis by dexamethasone in experimental pneumococcal meningitis

An immune dysfunction score for stratification of patients with acute infection based on whole-blood gene expression

Dysregulated host responses to infection can lead to organ dysfunction and sepsis, causing millions of global deaths each year. To alleviate this burden, improved prognostication and biomarkers of response are urgently needed. We investigated the use of whole-blood transcriptomics for stratification of patients with severe infection by integrating data from 3149 samples from patients with sepsis due to community-acquired pneumonia or fecal peritonitis admitted to intensive care and healthy individuals into a gene expression reference map. We used this map to derive a quantitative sepsis response signature (SRSq) score reflective of immune dysfunction and predictive of clinical outcomes, which can be estimated using a 7- or 12-gene signature. Last, we built a machine learning framework, SepstratifieR, to deploy SRSq in adult and pediatric bacterial and viral sepsis, H1N1 influenza, and COVID-19, demonstrating clinically relevant stratification across diseases and revealing some of the physiological alterations linking immune dysregulation to mortality. Our method enables early identification of individuals with dysfunctional immune profiles, bringing us closer to precision medicine in infection

Atacama Cosmology Telescope: Component-separated maps of CMB temperature and the thermal Sunyaev-Zel’dovich effect

Optimal analyses of many signals in the cosmic microwave background (CMB) require map-level extraction of individual components in the microwave sky, rather than measurements at the power spectrum level alone. To date, nearly all map-level component separation in CMB analyses has been performed exclusively using satellite data. In this paper, we implement a component separation method based on the internal linear combination (ILC) approach which we have designed to optimally account for the anisotropic noise (in the 2D Fourier domain) often found in ground-based CMB experiments. Using this method, we combine multifrequency data from the Planck satellite and the Atacama Cosmology Telescope Polarimeter (ACTPol) to construct the first wide-area (≈2100 sq. deg.), arcminute-resolution component-separated maps of the CMB temperature anisotropy and the thermal Sunyaev-Zel’dovich (tSZ) effect sourced by the inverse-Compton scattering of CMB photons off hot, ionized gas. Our ILC pipeline allows for explicit deprojection of various contaminating signals, including a modified blackbody approximation of the cosmic infrared background (CIB) spectral energy distribution. The cleaned CMB maps will be a useful resource for CMB lensing reconstruction, kinematic SZ cross-correlations, and primordial non-Gaussianity studies. The tSZ maps will be used to study the pressure profiles of galaxies, groups, and clusters through cross-correlations with halo catalogs, with dust contamination controlled via CIB deprojection. The data products described in this paper are available on LAMBDA