Doctors under the microscope: the birth of medical audit

In 1989 a UK government White Paper introduced medical audit as a comprehensive and statutory system of assessment and improvement in quality of care in hospitals. A considerable body of research has described the evolution of medical audit in terms of a struggle between doctors and National Health Service managers over control of quality assurance. In this paper we examine the emergence of medical audit from 1910 to the early 1950s, with a particular focus on the pioneering work of the American surgeons Codman, MacEachern and Ponton. It is contended that medical professionals initially created medical audit in order to articulate a suitable methodology for assessing individual and organisational performance. Rather than a means of protecting the medical profession from public scrutiny, medical auditing was conceived and operationalised as a managerial tool for fostering the active engagement of senior hospital managers and discharging public accountability. These early debates reveal how accounting was implicated in the development of a system for monitoring and improving the work of medical professionals, advancing the quality of hospital care, and was advocated in ways, which included rather than excluded managers

Geochronology of reworked ash and its implications for accommodation space variations in distal foreland basins, McMurray Formation, Alberta, Canada

A bentonite bed consisting of reworked volcanic ash from the Barremian to Aptian lower McMurray Formation is dated using chemical abrasion thermal ionization mass spectrometry (CA-TIMS) on zircon. The bentonite bed is from a cored interval in the McKay Paleovalley in the northern Athabasca Oil Sands Region of Alberta, Canada. Deposition of the lower McMurray Formation took place in the distal portion of the Western Canada Sedimentary Basin early in the Cretaceous-to-Paleocene phase of widespread contractional deformation in the Canadian Cordillera. A 30 g sample of volcanic ash yielded >10,000 very small (<50 µm) zircon grains with the vast majority (~99.7%) being highly abraded and clearly detrital. Twenty-six sharply faceted grains were sufficiently large to be mounted for laser ablation inductively coupled plasma mass spectrometry (LA-ICPMS) analysis, which yielded seven Lower Cretaceous dates. These Lower Cretaceous grains were further analyzed using CA-TIMS. The five youngest CA-TIMS dates agree with a weighted mean of 121.51 ± 0.11 Ma which is conservatively interpreted as a maximum depositional age (MDA). The good agreement between the five zircon dates indicates the MDA is probably the depositional age. This study demonstrates that with careful analysis of zircon populations, high-confidence MDAs can be derived even from reworked ash beds that are dominated overwhelmingly by detrital zircon. The date from this study overlaps a previously published MDA of 121.39 ± 0.27 Ma for the top of the lower McMurray Formation in Firebag Tributary in the northeastern Athabasca Oil Sands Area. The overlapping dates establish a widespread chronostratigraphic surface within the northern Athabasca Oil Sands Area. Both ages are from ash beds preserved in coal seams, suggesting that the coal-bearing interval is a regional marker bed and that the ash beds may form an intraformational datum. Further, the occurrence of the ash beds in the McMurray Formation in close proximity to regional flooding surfaces suggests that tectonic activity in the emerging Canadian Cordillera influenced accommodation space variations in the distal portions of the adjacent foreland basin

Origins of cattle on Chirikof Island, Alaska, elucidated from genome-wide SNP genotypes

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A Bayesian Nonparametric Regression Model With Normalized Weights - A Study of Hippocampal Atrophy in Alzheimer’s Disease

Hippocampal volume is one of the best established biomarkers for Alzheimer’s disease. However, for appropriate use in clinical trials research, the evolution of hippocampal volume needs to be well understood. Recent theoretical models propose a sigmoidal pattern for its evolution. To support this theory, the use of Bayesian nonparametric regression mixture models seems particularly suitable due to the flexibility that models of this type can achieve and the unsatisfactory predictive properties of semiparametric methods. In this article, our aim is to develop an interpretable Bayesian nonparametric regression model which allows inference with combinations of both continuous and discrete covariates, as required for a full analysis of the dataset. Simple arguments regarding the interpretation of Bayesian nonparametric regression mixtures lead naturally to regression weights based on normalized sums. Difficulty in working with the intractable normalizing constant is overcome thanks to recent advances in MCMC methods and the development of a novel auxiliary variable scheme. We apply the new model and MCMC method to study the dynamics of hippocampal volume, and our results provide statistical evidence in support of the theoretical hypothesis

Characterization of the John A. Galt telescope for radio holography with CHIME

The Canadian Hydrogen Intensity Mapping Experiment (CHIME) will measure the 21 cm emission of astrophysical neutral hydrogen to probe large scale structure at redshifts z=0.8-2.5. However, detecting the 21 cm signal beneath substantially brighter foregrounds remains a key challenge. Due to the high dynamic range between 21 cm and foreground emission, an exquisite calibration of instrument systematics, notably the telescope beam, is required to successfully filter out the foregrounds. One technique being used to achieve a high fidelity measurement of the CHIME beam is radio holography, wherein signals from each of CHIME's analog inputs are correlated with the signal from a co-located reference antenna, the 26 m John A. Galt telescope, as the 26 m Galt telescope tracks a bright point source transiting over CHIME. In this work we present an analysis of several of the Galt telescope's properties. We employ driftscan measurements of several bright sources, along with background estimates derived from the 408 MHz Haslam map, to estimate the Galt system temperature. To determine the Galt telescope's beam shape, we perform and analyze a raster scan of the bright radio source Cassiopeia A. Finally, we use early holographic measurements to measure the Galt telescope's geometry with respect to CHIME for the holographic analysis of the CHIME and Galt interferometric data set

Inhibiting Inducible Nitric Oxide Synthase in Enteric Glia Restores Electrogenic Ion Transport in Mice With Colitis

BACKGROUND & AIMS: Disturbances in the control of ion transport lead to epithelial barrier dysfunction in patients with colitis. Enteric glia regulate intestinal barrier function and colonic ion transport. However, it is not clear whether enteric glia are involved in the epithelial hypo-responsiveness. We investigated enteric glial regulation of ion transport in mice with trinitrobenzene sulphonic acid- or dextran sodium sulfate-induced colitis and in Il10(−/−) mice. METHODS: Electrically-evoked ion transport was measured in full-thickness segments of colon from CD1 and Il10(−/−) mice with or without colitis in Ussing chambers. Nitric oxide (NO) production was assessed using amperometry. Bacterial translocation was investigated in the liver, spleen and blood of mice. RESULTS: Electrical stimulation of the colon evoked a tetrodotoxin-sensitive chloride secretion. In mice with colitis, ion transport almost completely disappeared. Inhibiting inducible NO synthase (NOS2), but not neuronal NOS (NOS1), partially restored the evoked secretory response. Blocking glial function with fluoroacetate, which is not a NOS2 inhibitor, also partially restored ion transport. Combined NOS2 inhibition and fluoroacetate administration fully restored secretion. Epithelial responsiveness to vasoactive intestinal peptide was increased after enteric glial function was blocked in mice with colitis. In colons of mice without colitis, NO was produced in the myenteric plexus almost completely via NOS1. NO production was increased in mice with colitis, compared to mice without colitis; a substantial proportion of NOS2 was blocked by fluoroacetate administration. Inhibition of enteric glial function in vivo reduced the severity of trinitrobenzene sulphonic acid -induced colitis and associated bacterial translocation. CONCLUSIONS: Increased production of NOS2 in enteric glia contributes to the dysregulation of intestinal ion transport in mice with colitis. Blocking enteric glial function in these mice restores epithelial barrier function and reduces bacterial translocation

Metabolism of phenol and hydroquinone to reactive products by macrophage peroxidase or purified prostaglandin H synthase.

Macrophages, an important cell-type of the bone marrow stroma, are possible targets of benzene toxicity because they contain relatively large amounts of prostaglandin H synthase (PHS), which is capable of metabolizing phenolic compounds to reactive species. PHS also catalyzes the production of prostaglandins, negative regulators of myelopoiesis. Studies indicate that the phenolic metabolites of benzene are oxidized in bone marrow to reactive products via peroxidases. With respect to macrophages, PHS peroxidase is implicated, as in vivo benzene-induced myelotoxicity is prevented by low doses of nonsteroidal anti-inflammatory agents, drugs that inhibit PHS. Incubations of either 14C-phenol or 14C-hydroquinone with a lysate of macrophages collected from mouse peritoneum (greater than 95% macrophages), resulted in an irreversible binding to protein that was dependent upon H2O2, incubation time, and concentration of radiolabel. Production of protein-bound metabolites from phenol or hydroquinone was inhibited by the peroxidase inhibitor aminotriazole. Protein binding from 14C-phenol also was inhibited by 8 microM hydroquinone, whereas binding from 14C-hydroquinone was stimulated by 5 mM phenol. The nucleophile cysteine inhibited protein binding of both phenol and hydroquinone and increased the formation of radiolabeled water-soluble metabolites. Similar to the macrophage lysate, purified PHS also catalyzed the conversion of phenol to metabolites that bound to protein and DNA; this activation was both H2O2- and arachidonic acid-dependent. These results indicate a role for macrophage peroxidase, possibly PHS peroxidase, in the conversion of phenol and hydroquinone to reactive metabolites and suggest that the macrophage should be considered when assessing the hematopoietic toxicity of benzene

A Detection of Cosmological 21 cm Emission from CHIME in Cross-correlation with eBOSS Measurements of the Lyman-α\alpha Forest

We report the detection of 21 cm emission at an average redshift $\bar{z} = 2.3$ in the cross-correlation of data from the Canadian Hydrogen Intensity Mapping Experiment (CHIME) with measurements of the Lyman-$\alpha$ forest from eBOSS. Data collected by CHIME over 88 days in the $400-500$~MHz frequency band ($1.8 < z < 2.5$) are formed into maps of the sky and high-pass delay filtered to suppress the foreground power, corresponding to removing cosmological scales with $k_\parallel \lesssim 0.13\ \text{Mpc}^{-1}$ at the average redshift. Line-of-sight spectra to the eBOSS background quasar locations are extracted from the CHIME maps and combined with the Lyman-$\alpha$ forest flux transmission spectra to estimate the 21 cm-Lyman-$\alpha$ cross-correlation function. Fitting a simulation-derived template function to this measurement results in a $9\sigma$ detection significance. The coherent accumulation of the signal through cross-correlation is sufficient to enable a detection despite excess variance from foreground residuals $\sim6-10$ times brighter than the expected thermal noise level in the correlation function. These results are the highest-redshift measurement of \tcm emission to date, and set the stage for future 21 cm intensity mapping analyses at $z>1.8$