357 research outputs found
A benchmarking study of two trauma centres highlighting limitations when standardising mortality for comorbidity
<p>Abstract</p> <p>Introduction</p> <p>A continuous process of trauma centre evaluation is essential to ensure the development and progression of trauma care at regional, national and international levels. Evaluation may be by comparison between pooled datasets or by direct benchmarking between centres. This study attempts to benchmark mortality at two trauma centres standardising this for multiple case-mix factors, which includes the prevalence of individual background pre-existing diseases within the study population.</p> <p>Methods</p> <p>Trauma patients with an Injury Severity Score (ISS) >15 admitted to the two centres in 2001 and 2002 were included in the study with the exception of those who died in the emergency department. Patient characteristics were analysed in terms of 18 case-mix factors including Glasgow Coma Scale on arrival, Injury Severity Score and the presence or absence of 9 co-morbidity types, and patient outcome was compared based on in-hospital mortality before and after standardisation.</p> <p>Results</p> <p>Crude mortality was greater at UHNS (18.2 vs 14.5%) with a non-significant odds ratio of 1.31 prior to adjusting for case-mix (P = 0.171). Adjustment for case mix using logistic regression analysis altered the odds ratio to 1.64, which was not significant (P = 0.069).</p> <p>Discussion</p> <p>This study did not demonstrate any significant difference in the outcome of patients treated at either hospital during the study period. More importantly it has raised several important methodological issues pertinent to researchers undertaking registry based benchmarking studies. Data at the two registries was collected by personnel with differing backgrounds, in formats that were not completely compatible and was collected for patients that met different admissions criteria. The inclusion of a meaningful analysis of pre-existing disease was limited by the availability of robust data and sample size. We suggest greater communication between trauma research coordinators to ensure equivalent data collection and facilitate future benchmarking studies.</p
Giving up on consciousness as the ghost in the machine
Consciousness as used here, refers to the private, subjective experience of being
aware of our perceptions, thoughts, feelings, actions, memories (psychological contents)
including the intimate experience of a unified self with the capacity to generate and
control actions and psychological contents. This compelling, intuitive consciousnesscentric account has, and continues to shape folk and scientific accounts of psychology
and human behavior. Over the last 30 years, research from the cognitive neurosciences
has challenged this intuitive social construct account when providing a neurocognitive
architecture for a human psychology. Growing evidence suggests that the executive
functions typically attributed to the experience of consciousness are carried out
competently, backstage and outside subjective awareness by a myriad of fast, efficient
non-conscious brain systems. While it remains unclear how and where the experience
of consciousness is generated in the brain, we suggested that the traditional intuitive
explanation that consciousness is causally efficacious is wrong-headed when providing a
cognitive neuroscientific account of human psychology. Notwithstanding the compelling
1st-person experience (inside view) that convinces us that subjective awareness is the
mental curator of our actions and thoughts, we argue that the best framework for
building a scientific account is to be consistent with the biophysical causal dependency
of prior neural processes. From a 3rd person perspective, (outside view), we propose
that subjective awareness lacking causal influence, is (no more) than our experience of
being aware, our awareness of our psychological content, knowing that we are aware,
and the belief that that such experiences are evidence of an agentive capacity shared
by others. While the human mind can be described as comprising both conscious
and nonconscious aspects, both ultimately depend on neural process in the brain. In
arguing for the counter-intuitive epiphenomenal perspective, we suggest that a scientific
approach considers all mental aspects of mind including consciousness in terms of
their underlying, preceding (causal) biological changes, in the realization that most brain
processes are not accompanied by any discernible change in subjective awareness
Evaluating the Presence of In-Vehicle Devices on Driver Performance: Methodological Issues
A central concern of Intelligent Transportation Systems (ITS) is the effect of in-vehicle devices (e.g. cell phones, navigation systems, radios) on driver performance and safety. As diverse and innovative technologies are designed and implemented for in-vehicle use, questions regarding the presence and use of these devices assume progressively greater importance. Concern for the safety of advanced driver training and require us to develop and validate reliable and effective procedures for assessing such effects. This work examines a number of candidate procedures, in particular the evaluation of cognitive workload as a strategy by which such goals might be achieved
STORMTOOLS: Coastal Environmental Risk Index (CERI)
One of the challenges facing coastal zone managers and municipal planners is the development of an objective, quantitative assessment of the risk to structures, infrastructure, and public safety that coastal communities face from storm surge in the presence of changing climatic conditions, particularly sea level rise and coastal erosion. Here we use state of the art modeling tool (ADCIRC and STWAVE) to predict storm surge and wave, combined with shoreline change maps (erosion), and damage functions to construct a Coastal Environmental Risk Index (CERI). Access to the state emergency data base (E-911) provides information on structure characteristics and the ability to perform analyses for individual structures. CERI has been designed as an on line Geographic Information System (GIS) based tool, and hence is fully compatible with current flooding maps, including those from FEMA. The basic framework and associated GIS methods can be readily applied to any coastal area. The approach can be used by local and state planners to objectively evaluate different policy options for effectiveness and cost/benefit. In this study, CERI is applied to RI two communities; Charlestown representing a typical coastal barrier system directly exposed to ocean waves and high erosion rates, with predominantly low density single family residences and Warwick located within Narragansett Bay, with more limited wave exposure, lower erosion rates, and higher residential housing density. Results of these applications are highlighted herein
Between overt and covert research: concealment and disclosure in an ethnographic study of commercial hospitality
This article examines the ways in which problems of concealment emerged in an ethnographic study of a suburban bar and considers how disclosure of the research aims, the recruitment of informants, and elicitation of information was negotiated throughout the fieldwork. The case study demonstrates how the social context and the relationships with specific informants determined overtness or covertness in the research. It is argued that the existing literature on covert research and covert methods provides an inappropriate frame of reference with which to understand concealment in fieldwork. The article illustrates why concealment is sometimes necessary, and often unavoidable, and concludes that the criticisms leveled against covert methods should not stop the fieldworker from engaging in research that involves covertness
3C. 3-Ketosteroid receptors (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database
Steroid hormone receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on Nuclear Hormone Receptors [65, 193]) are nuclear hormone receptors of the NR3 class, with endogenous agonists that may be divided into 3-hydroxysteroids (estrone and 17β-estradiol) and 3-ketosteroids (dihydrotestosterone [DHT], aldosterone, cortisol, corticosterone, progesterone and testosterone)
3C. 3-Ketosteroid receptors in GtoPdb v.2021.3
Steroid hormone receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on Nuclear Hormone Receptors [74, 215, 3]) are nuclear hormone receptors of the NR3 class, with endogenous agonists that may be divided into 3-hydroxysteroids (estrone and 17β-estradiol) and 3-ketosteroids (dihydrotestosterone [DHT], aldosterone, cortisol, corticosterone, progesterone and testosterone). For rodent GR and MR, the physiological ligand is corticosterone rather than cortisol
3C. 3-Ketosteroid receptors in GtoPdb v.2023.1
Steroid hormone receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on Nuclear Hormone Receptors [75, 218, 3]) are nuclear hormone receptors of the NR3 class, with endogenous agonists that may be divided into 3-hydroxysteroids (estrone and 17β-estradiol) and 3-ketosteroids (dihydrotestosterone [DHT], aldosterone, cortisol, corticosterone, progesterone and testosterone). For rodent GR and MR, the physiological ligand is corticosterone rather than cortisol
Inhibition of aminoglycoside 6\u3csup\u3e′\u3c/sup\u3e-n-acetyltransferase type ib (Aac(6\u3csup\u3e′\u3c/sup\u3e )-ib): Structure–activity relationship of substituted pyrrolidine pentamine derivatives as inhibitors
The aminoglycoside 6′-N-acetyltransferase type Ib (AAC(6′ )-Ib) is a common cause of resistance to amikacin and other aminoglycosides in Gram-negatives. Utilization of mixture-based combinatorial libraries and application of the positional scanning strategy identified an inhibitor of AAC(6′ )-Ib. This inhibitor’s chemical structure consists of a pyrrolidine pentamine scaffold substituted at four locations (R1, R3, R4, and R5). The substituents are two S-phenyl groups (R1 and R4), an S-hydroxymethyl group (R3), and a 3-phenylbutyl group (R5). Another location, R2, does not have a substitution, but it is named because its stereochemistry was modified in some compounds utilized in this study. Structure–activity relationship (SAR) analysis using derivatives with different functionalities, modified stereochemistry, and truncations was carried out by assessing the effect of the addition of each compound at 8 µM to 16 µg/mL amikacin-containing media and performing checkerboard assays varying the concentrations of the inhibitor analogs and the antibiotic. The results show that: (1) the aromatic functionalities at R1 and R4 are essential, but the stereochemistry is essential only at R4; (2) the stereochemical conformation at R2 is critical; (3) the hydroxyl moiety at R3 as well as stereoconformation are required for full inhibitory activity; (4) the phenyl functionality at R5 is not essential and can be replaced by aliphatic groups; (5) the location of the phenyl group on the butyl carbon chain at R5 is not essential; (6) the length of the aliphatic chain at R5 is not critical; and (7) all truncations of the scaffold resulted in inactive compounds. Molecular docking revealed that all compounds preferentially bind to the kanamycin C binding cavity, and binding affinity correlates with the experimental data for most of the compounds evaluated. The SAR results in this study will serve as the basis for the design of new analogs in an effort to improve their ability to induce phenotypic conversion to susceptibility in amikacin-resistant pathogens
Structural Integrity of the -Carboxyglutamic Acid Domain of Human Blood Coagulation Factor IXa Is Required for Its Binding to Cofactor VIIIa
This report describes the analysis of a novel mutant human factor IX protein from a patient with hemophilia B (factor IX activity adenine transition) in exon 2 at nucleotide 6409 which results in a glycine --> arginine substitution at amino acid 12 in the gamma-carboxyglutamic acid rich (Gla) domain of the mature protein. Factor IX was isolated by immunoaffinity chromatography from plasma obtained from the proband. The purified protein is indistinguishable from normal factor IX by polyacrylamide gel electrophoresis. Characterization of the variant in purified component assays reveals that it is activated normally by its physiologic activator factor XIa, but its phospholipid-dependent activation by the factor VIIa-tissue factor complex is diminished. In the presence of phospholipid and 5 mM Ca2+, the activities of variant and normal plasma-derived factor IX are similar; however, in the presence of activated factor VIIIa (intrinsic tenase complex), the normal augmentation of the cleavage of the specific substrate of factor IX, factor X, is not observed. The determination of the association constants for normal and variant factor IXa with factor VIIIa shows that the affinity of the activated variant factor IX for the cofactor factor VIIIa is 172-fold lower than normal. Competition studies using active site-inactivated factor IXas in the intrinsic tenase complex confirm that the defect in the variant protein is in its binding to factor VIIIa. We conclude that the structural integrity of the Gla domain of human factor IX is critical for the normal binding of factor IXa to factor VIIIa in the intrinsic tenase complex. In addition, a glycine at amino acid 12 is necessary for normal activation of factor IX by the factor VIIa-tissue factor complex
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