Absence of bias against smokers in access to coronary revascularization after cardiac catheterization

Objective. Many consider smoking to be a personal choice for which individuals should be held accountable. We assessed whether there is any evidence of bias against smokers in cardiac care decision-making by determining whether smokers were as likely as non-smokers to undergo revascularization procedures after cardiac catheterization. Design. Prospective cohort study. Subjects and setting. All patients undergoing cardiac catheterization in Alberta, Canada. Main measures. Patients were categorized as current smokers, former smokers, or never smokers, and then compared for their risk-adjusted likelihood of undergoing revascularization procedures (percutaneous coronary intervention or coronary artery bypass grafting) after cardiac catheterization. Results. Among 20406 patients undergoing catheterization, 25.4% were current smokers at the time of catheterization, 36.6% were former smokers, and 38.0% had never smoked. When compared with never smokers (reference group), the hazard ratio for undergoing any revascularization procedure after catheterization was 0.98 (95% CI 0.93-1.03) for current smokers and 0.98 (0.94-1.03) for former smokers. The hazard ratio for undergoing coronary artery bypass grafting was 1.09 (1.00-1.19) for current smokers and 1.00 (0.93-1.08) for former smokers. For percutaneous coronary intervention, the hazard ratios were 0.93 (0.87-0.99) for current smokers and 1.00 (0.94-1.06) for former smokers. Conclusion. Despite potential for discrimination on the basis of smoking status, current and former smokers undergoing cardiac catheterization in Alberta, Canada were as likely to undergo revascularization procedures as catheterization patients who had never smoke

The clustering of polarity reversals of the geomagnetic field

Often in nature the temporal distribution of inhomogeneous stochastic point processes can be modeled as a realization of renewal Poisson processes with a variable rate. Here we investigate one of the classical examples, namely the temporal distribution of polarity reversals of the geomagnetic field. In spite of the commonly used underlying hypothesis, we show that this process strongly departs from a Poisson statistics, the origin of this failure stemming from the presence of temporal clustering. We find that a Levy statistics is able to reproduce paleomagnetic data, thus suggesting the presence of long-range correlations in the underlying dynamo process.Comment: 4 pages, in press on PRL (31 march 2006?

Accuracy of city postal code coordinates as a proxy for location of residence

BACKGROUND: Health studies sometimes rely on postal code location as a proxy for the location of residence. This study compares the postal code location to that of the street address using a database from the Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease (APPROACH(©)). Cardiac catheterization cases in an urban Canadian City were used for calendar year 1999. We determined location in meters for both the address (using the City of Calgary Street Network File in ArcView 3.2) and postal code location (using Statistic Canada's Postal Code Conversion File). RESULTS: The distance between the two estimates of location for each case were measured and it was found that 87.9% of the postal code locations were within 200 meters of the true address location (straight line distances) and 96.5% were within 500 meters of the address location (straight line distances). CONCLUSIONS: We conclude that postal code locations are a reasonably accurate proxy for address location. However, there may be research questions for which a more accurate description of location is required

Kinetics of fragmentation-annihilation processes

We investigate the kinetics of systems in which particles of one species undergo binary fragmentation and pair annihilation. In the latter, nonlinear process, fragments react at collision to produce an inert species, causing loss of mass. We analyse these systems in the reaction-limited regime by solving a continuous model within the mean-field approximation. The rate of fragmentation, for a particle of mass $x$ to break into fragments of masses $y$ and $x-y$, has the form $x^{\lambda-1}$ ($\lambda>0$), and the annihilation rate is constant and independent of the masses of the reactants. We find that the asymptotic regime is characterized by the annihilation of small-mass clusters. The results are compared with those for a model with linear mass-loss (i.e.\ with a sink). We also study more complex models, in which the processes of fragmentation and annihilation are controlled by mutually-reacting catalysts. Both pair- and linear-annihilation are considered. Depending on the specific model and initial densities of the catalysts, the time-decay of the cluster-density can now be very unconventional and even non-universal. The interplay between the intervening processes and the existence of a scaling regime are determined by the asymptotic behaviour of the average-mass and of the mass-density, which may either decay indefinitely or tend to a constant value. We discuss further developments of this class of models and their potential applications.Comment: 16 pages(LaTeX), submitted to Phys. Rev.

A human MAP kinase interactome.

Mitogen-activated protein kinase (MAPK) pathways form the backbone of signal transduction in the mammalian cell. Here we applied a systematic experimental and computational approach to map 2,269 interactions between human MAPK-related proteins and other cellular machinery and to assemble these data into functional modules. Multiple lines of evidence including conservation with yeast supported a core network of 641 interactions. Using small interfering RNA knockdowns, we observed that approximately one-third of MAPK-interacting proteins modulated MAPK-mediated signaling. We uncovered the Na-H exchanger NHE1 as a potential MAPK scaffold, found links between HSP90 chaperones and MAPK pathways and identified MUC12 as the human analog to the yeast signaling mucin Msb2. This study makes available a large resource of MAPK interactions and clone libraries, and it illustrates a methodology for probing signaling networks based on functional refinement of experimentally derived protein-interaction maps

FGF8 isoform b expression in human prostate cancer.

Overexpression of fibroblast growth factor 8 (FGF8) mRNA has been previously described in prostate cancer. Of its four isoforms, FGF8b is thought to be the most important in carcinogenesis. We hypothesised that immunodetection of FGF8b in archival prostate cancer specimens is of potential prognostic value. Using a selected cohort of prostate tumours from transurethral (n=30) and radical prostatectomies (n=59), an optimised protocol for FGF8b immunoreactivity was used to corroborate expression with clinical parameters. No expression was observed in benign prostates (n=10). In prostate cancer, immunoreactivity was localised to the malignant epithelium with weak signals in the adjacent stroma. Expression of FGF8b in stage T1 and T2 cancers were 40 and 67%, respectively. In contrast, FGF8b expression was present in 94% of T3 and 100% of T4 cancers. By histological grade, FGF8b was found in 41% of low-grade cancers (Gleason score 4-6), 60% of intermediate-grade cancers (Gleason score 7 and 92% of high-grade cancers (Gleason score 8-10). The intensity of expression was significantly associated with stage (P=0.0004) and grade (P<0.0001) of disease. We further hypothesised that FGF8b overexpression resulted from enhanced transcription and translation rather than from abnormalities involving the FGF8 gene locus. This was tested by means of fluorescent in situ hybridisation in 20 cancer specimens to map the FGF8 gene locus. FGF8 gene copy number in benign and malignant nuclei was found to be similar (2.33+/-0.57 and 2.0+/-0.81, respectively P=0.51). Based on these findings, we propose a multicentre study on cohorts of patients to further evaluate FGF8b as a potential prognostic marker in prostate cancer

The Alberta Heart Failure Etiology and Analysis Research Team (HEART) study

Background Nationally, symptomatic heart failure affects 1.5-2% of Canadians, incurs $3 billion in hospital costs annually and the global burden is expected to double in the next 1–2 decades. The current one-year mortality rate after diagnosis of heart failure remains high at >25%. Consequently, new therapeutic strategies need to be developed for this debilitating condition. Methods/Design The objective of the Alberta HEART program (http://albertaheartresearch.ca) is to develop novel diagnostic, therapeutic and prognostic approaches to patients with heart failure with preserved ejection fraction. We hypothesize that novel imaging techniques and biomarkers will aid in describing heart failure with preserved ejection fraction. Furthermore, the development of new diagnostic criteria will allow us to: 1) better define risk factors associated with heart failure with preserved ejection fraction; 2) elucidate clinical, cellular and molecular mechanisms involved with the development and progression of heart failure with preserved ejection fraction; 3) design and test new therapeutic strategies for patients with heart failure with preserved ejection fraction. Additionally, Alberta HEART provides training and education for enhancing translational medicine, knowledge translation and clinical practice in heart failure. This is a prospective observational cohort study of patients with, or at risk for, heart failure. Patients will have sequential testing including quality of life and clinical outcomes over 12 months. After that time, study participants will be passively followed via linkage to external administrative databases. Clinical outcomes of interest include death, hospitalization, emergency department visits, physician resource use and/or heart transplant. Patients will be followed for a total of 5 years. Discussion Alberta HEART has the primary objective to define new diagnostic criteria for patients with heart failure with preserved ejection fraction. New criteria will allow for targeted therapies, diagnostic tests and further understanding of the patients, both at-risk for and with heart failure

A short purification process for quantitative isolation of PrP(Sc) from naturally occurring and experimental transmissible spongiform encephalopathies

BACKGROUND: Transmissible spongiform encephalopathies (TSEs) are neurodegenerative diseases affecting both humans and animals. They are associated with post-translational conversion of the normal cellular prion protein (PrP(C)) into a heat- and protease-resistant abnormal isoform (PrP(Sc)). Detection of PrP(Sc) in individuals is widely utilized for the diagnosis of prion diseases. METHODS: TSE brain tissue samples have been processed in order to quantitatively isolate PrP(Sc). The protocol includes an initial homogenization, digestion with proteinase K and salt precipitation. RESULTS: Here we show that over 97 percent of the PrP(Sc) present can be precipitated from infected brain material using this simple salting-out procedure for proteins. No chemically harsh conditions are used during the process in order to conserve the native quality of the isolated protein. CONCLUSION: The resulting PrP(Sc)-enriched preparation should provide a suitable substrate for analyzing the structure of the prion agent and for scavenging for other molecules with which it may associate. In comparison with most methods that exist today, the one described in this study is rapid, cost-effective and does not demand expensive laboratory equipment

Comparison of distance measures in spatial analytical modeling for health service planning

<p>Abstract</p> <p>Background</p> <p>Several methodological approaches have been used to estimate distance in health service research. In this study, focusing on cardiac catheterization services, Euclidean, Manhattan, and the less widely known Minkowski distance metrics are used to estimate distances from patient residence to hospital. Distance metrics typically produce less accurate estimates than actual measurements, but each metric provides a single model of travel over a given network. Therefore, distance metrics, unlike actual measurements, can be directly used in spatial analytical modeling. Euclidean distance is most often used, but unlikely the most appropriate metric. Minkowski distance is a more promising method. Distances estimated with each metric are contrasted with road distance and travel time measurements, and an optimized Minkowski distance is implemented in spatial analytical modeling.</p> <p>Methods</p> <p>Road distance and travel time are calculated from the postal code of residence of each patient undergoing cardiac catheterization to the pertinent hospital. The Minkowski metric is optimized, to approximate travel time and road distance, respectively. Distance estimates and distance measurements are then compared using descriptive statistics and visual mapping methods. The optimized Minkowski metric is implemented, via the spatial weight matrix, in a spatial regression model identifying socio-economic factors significantly associated with cardiac catheterization.</p> <p>Results</p> <p>The Minkowski coefficient that best approximates road distance is 1.54; 1.31 best approximates travel time. The latter is also a good predictor of road distance, thus providing the best single model of travel from patient's residence to hospital. The Euclidean metric and the optimal Minkowski metric are alternatively implemented in the regression model, and the results compared. The Minkowski method produces more reliable results than the traditional Euclidean metric.</p> <p>Conclusion</p> <p>Road distance and travel time measurements are the most accurate estimates, but cannot be directly implemented in spatial analytical modeling. Euclidean distance tends to underestimate road distance and travel time; Manhattan distance tends to overestimate both. The optimized Minkowski distance partially overcomes their shortcomings; it provides a single model of travel over the network. The method is flexible, suitable for analytical modeling, and more accurate than the traditional metrics; its use ultimately increases the reliability of spatial analytical models.</p