High-density lipoprotein and the risk of recurrent venous thromboembolism

BACKGROUND - High-density lipoprotein (HDL) protects against arterial atherothrombosis, but it is unknown whether it protects against recurrent venous thromboembolism. METHODS AND RESULTS - We studied 772 patients after a first spontaneous venous thromboembolism (average follow-up 48 months) and recorded the end point of symptomatic recurrent venous thromboembolism, which developed in 100 of the 772 patients. The relationship between plasma lipoprotein parameters and recurrence was evaluated. Plasma apolipoproteins AI and B were measured by immunoassays for all subjects. Compared with those without recurrence, patients with recurrence had lower mean (±SD) levels of apolipoprotein AI (1.12±0.22 versus 1.23±0.27 mg/mL, P<0.001) but similar apolipoprotein B levels. The relative risk of recurrence was 0.87 (95% CI, 0.80 to 0.94) for each increase of 0.1 mg/mL in plasma apolipoprotein AI. Compared with patients with apolipoprotein AI levels in the lowest tertile (<1.07 mg/mL), the relative risk of recurrence was 0.46 (95% CI, 0.27 to 0.77) for the highest-tertile patients (apolipoprotein AI >1.30 mg/mL) and 0.78 (95% CI, 0.50 to 1.22) for midtertile patients (apolipoprotein AI of 1.07 to 1.30 mg/mL). Using nuclear magnetic resonance, we determined the levels of 10 major lipoprotein subclasses and HDL cholesterol for 71 patients with recurrence and 142 matched patients without recurrence. We found a strong trend for association between recurrence and low levels of HDL particles and HDL cholesterol. CONCLUSIONS - Patients with high levels of apolipoprotein AI and HDL have a decreased risk of recurrent venous thromboembolism. © 2007 American Heart Association, Inc.

DNA technology for the detection of common genetic variants that predispose to thrombophilia

With the identification of common single locus point mutations as risk factors for thrombophilia, many DNA testing methodologies have been described for detecting these variations. Traditionally, functional or immunological testing methods have been used to investigate quantitative anticoagulant deficiencies. However, with the emergence of the genetic variations, factor V Leiden, prothrombin 20210 and, to a lesser extent, the methylene tetrahydrofolate reductase (MTHFR677) and factor V HR2 haplotype, traditional testing methodologies have proved to be less useful and instead DNA technology is more commonly employed in diagnostics. This review considers many of the DNA techniques that have proved to be useful in the detection of common genetic variants that predispose to thrombophilia. Techniques involving gel analysis are used to detect the presence or absence of restriction sites, electrophoretic mobility shifts, as in single strand conformation polymorphism or denaturing gradient gel electrophoresis, and product formation in allele-specific amplification. Such techniques may be sensitive, but are unwielding and often need to be validated objectively. In order to overcome some of the limitations of gel analysis, especially when dealing with larger sample numbers, many alternative detection formats, such as closed tube systems, microplates and microarrays (minisequencing, real-time polymerase chain reaction, and oligonucleotide ligation assays) have been developed. In addition, many of the emerging technologies take advantage of colourimetric or fluorescence detection (including energy transfer) that allows qualitative and quantitative interpretation of results. With the large variety of DNA technologies available, the choice of methodology will depend on several factors including cost and the need for speed, simplicity and robustness. © 2000 Lippincott Williams & Wilkins.

Use of first nucleotide change technology to determine the frequency of factor V Leiden in a population of Australian blood donors

Activated protein C resistance (APCR), the most common risk factor for venous thrombosis, is the result of a G to A base substitution at nucleotide 1691 (R506Q) in the factor V gene. Current techniques to detect the factor V Leiden mutation, such as determination of restriction length polymorphisms, do not have the capacity to screen large numbers of samples in a rapid, cost- effective test. The aim of this study was to apply the first nucleotide change (FNC) technology, to the detection of the factor V Leiden mutation. After preliminary amplification of genomic DNA by polymerase chain reaction (PCR), an allele-specific primer was hybridised to the PCR product and extended using fluorescent terminating dideoxynucleotides which were detected by colorimetric assay. Using this ELISA-based assay, the prevalence of the factor V Leiden mutation was determined in an Australian blood donor population (n = 500). A total of 18 heterozygotes were identified (3.6%) and all of these were confirmed with conventional MnlI restriction digest. No homozygotes for the variant allele were detected. We conclude from this study that the frequency of 3.6% is compatible with others published for Caucasian populations. In addition, the FNC technology shows promise as the basis for a rapid, automated DNA based test for factor V Leiden.

The impact of rhetoric and reality on community anticipation of risk in the development of multi-purpose services (MPS) : A grounded theory study

better health service.Conclusion:This research provides an insight into the perceptions of the rhetoric and reality of community member involvement in the process of developing multi-purpose services. It revealed a grounded theory in which fear and trust were intrinsic to a process of changing from a traditional hospital service to the acceptance of a new model of health care provided at a multi-purpose service.

Age and gender comparisons of driving while sleepy : behaviours and risk perceptions

To assist road safety professionals in developing effective strategies to combat the risk associated with driving while fatigued, a survey was administered to 1000 Australian drivers. Participants reported their past behaviours in regards to driving while sleepy and their perceptions of risk associated with driving fatigued as compared to speeding and driving under the influence of alcohol. Although participants appeared to be aware of the substantial risk associated with driving while sleepy, many drivers reported that they frequently drive when sleepy. Age and gender comparisons, revealed that risk taking behaviour in regards to driving while sleepy is occurring across all age groups and in both male and female drivers. Overall young to middle age drivers and male drivers reported the highest frequency of driving while sleepy and reported the lowest perceived personal risk in regards to driving while sleepy.

Measuring risk and blameworthiness in the sentencing of criminal defendants : an exploratory study in Western Australia's Higher Courts

The focal concern perspective dominates quantitative explorations of judicial sentencing. A critical argument underlying this perspective is the role of judicial assessments of risk and blameworthiness. Prior research has not generally explored how these two concepts fit together. This study provides an empirical test of the focal concerns perspective by examining the latent structure among the measures traditionally used in sentencing research, and investigates the extent to which focal concerns can be applied in a non-US jurisdiction. Using factor analysis (as suggested by prior research), we find evidence of distinct factors of risk and blameworthiness, with separate and independent effects on sentencing outcomes. We also identify the need for further development of the focal concerns perspective, especially around the role of perceptual shorthand.

Risk of falls, injurious falls, and other injuries resulting from visual impairment among older adults with age-related macular degeneration

Purpose: Age-related macular degeneration (AMD) is the leading cause of irreversible visual impairment among older adults. This study explored the relationship between AMD, falls risk and other injuries and identified visual risk factors for these adverse events. Methods: Participants included 76 community-dwelling individuals with a range of severity of AMD (mean age, 77.0±6.9 years). Baseline assessment included binocular visual acuity, contrast sensitivity and merged visual fields. Participants completed monthly falls and injury diaries for one year following the baseline assessment. Results: Overall, 74% of participants reported having either a fall, injurious fall or other injury. Fifty-four percent of participants reported a fall and 30% reported more than one fall; of the 102 falls reported, 63% resulted in an injury. Most occurred outdoors (52%), between late morning and late afternoon (61%) and when navigating on level ground (62%). The most common non-fall injuries were lacerations (36%) and collisions with an object (35%). Reduced contrast sensitivity and visual acuity were associated with increased fall rate, after controlling for age, gender, cognitive function, cataract severity and self-reported physical function. Reduced contrast sensitivity was the only significant predictor of falls and other injuries. Conclusion: Among older adults with AMD, increased visual impairment was significantly associated with an increased incidence of falls and other injuries. Reduced contrast sensitivity was significantly associated with increased rates of falls, injurious falls and injuries, while reduced visual acuity was only associated with increased falls risk. These findings have important implications for the assessment of visually impaired older adults.

Unlicensed drivers : are they high risk?

- Road safety implications of unlicensed driving - Present results from three studies examining: the crash involvement of unlicensed drivers; the impact of licence disqualification on offending; characteristics of unlicensed driving offenders - Countermeasure implications - Discussion of high-risk groups and innovative countermeasure options

Convexity, Classification, and Risk Bounds

Many of the classification algorithms developed in the machine learning literature, including the support vector machine and boosting, can be viewed as minimum contrast methods that minimize a convex surrogate of the 0–1 loss function. The convexity makes these algorithms computationally efficient. The use of a surrogate, however, has statistical consequences that must be balanced against the computational virtues of convexity. To study these issues, we provide a general quantitative relationship between the risk as assessed using the 0–1 loss and the risk as assessed using any nonnegative surrogate loss function. We show that this relationship gives nontrivial upper bounds on excess risk under the weakest possible condition on the loss function—that it satisfies a pointwise form of Fisher consistency for classification. The relationship is based on a simple variational transformation of the loss function that is easy to compute in many applications. We also present a refined version of this result in the case of low noise, and show that in this case, strictly convex loss functions lead to faster rates of convergence of the risk than would be implied by standard uniform convergence arguments. Finally, we present applications of our results to the estimation of convergence rates in function classes that are scaled convex hulls of a finite-dimensional base class, with a variety of commonly used loss functions.

Rademacher and Gaussian complexities: Risk bounds and structural results

We investigate the use of certain data-dependent estimates of the complexity of a function class, called Rademacher and Gaussian complexities. In a decision theoretic setting, we prove general risk bounds in terms of these complexities. We consider function classes that can be expressed as combinations of functions from basis classes and show how the Rademacher and Gaussian complexities of such a function class can be bounded in terms of the complexity of the basis classes. We give examples of the application of these techniques in finding data-dependent risk bounds for decision trees, neural networks and support vector machines.

Common variation in the fibroblast growth factor receptor 2 gene is not associated with endometriosis risk

BACKGROUND Endometriosis is a polygenic disease with a complex and multifactorial aetiology that affects 8-10% of women of reproductive age. Epidemiological data support a link between endometriosis and cancers of the reproductive tract. Fibroblast growth factor receptor 2 (FGFR2) has recently been implicated in both endometrial and breast cancer. Our previous studies on endometriosis identified significant linkage to a novel susceptibility locus on chromosome 10q26 and the FGFR2 gene maps within this linkage region. We therefore hypothesized that variation in FGFR2 may contribute to the risk of endometriosis. METHODS We genotyped 13 single nucleotide polymorphisms (SNPs) densely covering a 27 kb region within intron 2 of FGFR2 including two SNPs (rs2981582 and rs1219648) significantly associated with breast cancer and a total 40 tagSNPs across 150 kb of the FGFR2 gene. SNPs were genotyped in 958 endometriosis cases and 959 unrelated controls. RESULTS We found no evidence for association between endometriosis and FGFR2 intron 2 SNPs or SNP haplotypes and no evidence for association between endometriosis and variation across the FGFR2 gene. CONCLUSIONS Common variation in the breast-cancer implicated intron 2 and other highly plausible causative candidate regions of FGFR2 do not appear to be a major contributor to endometriosis susceptibility in our large Australian sample.