Predicting oral anticoagulant response using a pharmacodynamic model

We developed a pharmacokinetic and pharmacodynamic model of warfarin absorption, metabolism, and anticoagulant action appropriate for guiding anticoagulant therapy. The model requires only two independently adjustable parameters to describe warfarin's effect on individual patients. For any given individual, these parameters are rapidly and inexpensively identified using a computer program based on the model. Test data were generated by superimposing Gaussian noise on dose-response curves calculated with the model. Then the computer program was applied to the test data. Future prothrombin complex activities (PCA's) and maintenance doses were predicted accurately early in the course of drug administration. In addition, the program accurately predicted PCA response in two groups of normal volunteers.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44006/1/10439_2006_Article_BF02363455.pd

Genetics of coronary artery calcification among African Americans, a meta-analysis

Background: Coronary heart disease (CHD) is the major cause of death in the United States. Coronary artery calcification (CAC) scores are independent predictors of CHD. African Americans (AA) have higher rates of CHD but are less well-studied in genomic studies. We assembled the largest AA data resource currently available with measured CAC to identify associated genetic variants.Methods: We analyzed log transformed CAC quantity (ln(CAC + 1)), for association with ~2.5 million single nucleotide polymorphisms (SNPs) and performed an inverse-variance weighted meta-analysis on results for 5,823 AA from 8 studies. Heritability was calculated using family studies. The most significant SNPs among AAs were evaluated in European Ancestry (EA) CAC data; conversely, the significance of published SNPs for CAC/CHD in EA was queried within our AA meta-analysis.Results: Heritability of CAC was lower in AA (~30%) than previously reported for EA (~50%). No SNP reached genome wide significance (p < 5E-08). Of 67 SNPs with p < 1E-05 in AA there was no evidence of association in EA CAC data. Four SNPs in regions previously implicated in CAC/CHD (at 9p21 and PHACTR1) in EA reached

Employment discrimination in Northern Ireland and the Good Friday Agreement

The paper analyses employment differences between Northern Ireland's Catholics and Protestants and examines whether the Good Friday Agreement signed in 1998 was followed by an improvement in the relative position of Catholics.

Long-term maintenance of arytenoid cartilage abduction and stability during exercise after laryngoplasty in 33 horses

&lt;b&gt;Objectives&lt;/b&gt; To (1) assess long-term maintenance of arytenoid cartilage abduction (ACA) after laryngoplasty (LP); and (2) correlate the residual grade of ACA and postoperative abductory loss with arytenoid cartilage stability (ACS) during exercise.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Study Design&lt;/b&gt; Case series.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Animals&lt;/b&gt; Horses re-examined after laryngoplasty (n = 33).&lt;p&gt;&lt;/p&gt; &lt;b&gt;Methods&lt;/b&gt; Of 89 LP horses (2005–2010), 33 had historic ACA data available and upper airway endoscopy at rest and during over-ground exercise (mean, 33 months; range, 4–71 months) after surgery. ACA grade at 1 and 6 weeks postoperatively were correlated to long-term ACA grade. Effects of long-term ACA grade and magnitude of postoperative abductory loss on ACS during exercise were investigated.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Results&lt;/b&gt; Median ACA grade at 1 week (n = 33) was 2, reducing to grade 3 by week 6 (n = 16). Grade 3 abduction was maintained in the long-term. Correlation between ACA at 1 week and the long-term was poor (ρ = .43, P = .1), but there was good correlation between week 6 and long-term (ρ = .89, P &lt; .001). Arytenoid cartilage instability was observed during exercise in 7/33 of horses, and not significantly associated with the ACA grade (P = .50), or the number of grades of ACA lost (P = .64).&lt;p&gt;&lt;/p&gt; &lt;b&gt;Conclusions&lt;/b&gt; Limited abductory loss occurs after 6 weeks postoperatively. Resting ACA grade was not a useful predictor of ACS during exercise.&lt;p&gt;&lt;/p&gt

Measuring effects on intima media thickness: An evaluation of Rosuvastatin in subclinical atherosclerosis - The rationale and methodology of the METEOR study

Background: Increased carotid intima media thickness (IMT) is associated with established coronary heart disease (CHD) and is a marker of atherosclerosis. Statins are an effective treatment for dyslipidaemia, and have been shown to retard progression or promote carotid IMT regression in patients at high risk of CHD. Rosuvastatin is a highly efficacious statin, and the Measuring Effects on intima media Thickness: an Evaluation Of Rosuvastatin ( METEOR) study is designed to assess the impact of rosuvastatin on carotid IMT progression in low risk subjects with signs of subclinical atherosclerosis. Methods: In this randomised, parallel-group study, asymptomatic subjects at low risk of cardiovascular disease, but with evidence of atherosclerosis ( defined as carotid IMT greater than or equal to 1.2 mm and <3.5 mm), will receive rosuvastatin ( 40 mg/day) or placebo for 104 weeks. The study will enrol 840 European and US subjects randomised 5: 2 between rosuvastatin and placebo. The primary end point will be the change in carotid IMT from baseline to study end, measured using B-mode ultrasonography. Other efficacy end points include changes in the serum lipid profile and C-reactive protein. Safety parameters will also be assessed. Conclusion: The METEOR study will evaluate whether long-term rosuvastatin treatment promotes regression, or slows progression, of subclinical atherosclerosis in asymptomatic subjects at low risk of cardiovascular disease

Born in Britain: how are native ethnic minorities faring in the British labour market?

In spite of the 40 years that have passed since legislation was first introduced to combat racial discrimination, British-born ethnic minorities fare little better than their immigrant parents in the UK labour market