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.

High-density lipoprotein deficiency and dyslipoproteinemia associated with venous thrombosis in men

Background-Although dyslipoproteinemia is associated with arterial atherothrombosis, little is known about plasma lipoproteins in venous thrombosis patients. Methods and Results-We determined plasma lipoprotein subclass concentrations using nuclear magnetic resonance spectroscopy and antigenic levels of apolipoproteins AI and B in blood samples from 49 male venous thrombosis patients and matched controls aged <55 years. Venous thrombosis patients had significantly lower levels of HDL particles, large HDL particles, HDL cholesterol, and apolipoprotein AI and significantly higher levels of LDL particles and small LDL particles. The quartile-based odds ratios for decreased HDL particle and apolipoprotein AI levels in patients compared with controls were 6.5 and 6.0 (95% CI, 2.3 to 19 and 2.1 to 17), respectively. Odds ratios for apolipoprotein B/apolipoprotein AI ratio and LDL cholesterol/HDL cholesterol ratio were 6.3 and 2.7 (95% CI, 1.9 to 21 and 1.1 to 6.5), respectively. When polymorphisms in genes for hepatic lipase, endothelial lipase, and cholesteryl ester transfer protein were analyzed, patients differed significantly from controls in the allelic frequency for the TaqI B1/B2 polymorphism in cholesteryl ester transfer protein, consistent with the observed pattern of lower HDL and higher LDL. Conclusions-Venous thrombosis in men aged <55 years old is associated with dyslipoproteinemia involving lower levels of HDL particles, elevated levels of small LDL particles, and an elevated ratio of apolipoprotein B/apolipoprotein AI. This dyslipoproteinemia seems associated with a related cholesteryl ester transfer protein genotype difference. © 2005 American Heart Association, Inc.

Women's labor force participation and marriage : the case of Korea

In this paper, we examine the relationship between marital status and female labor force participation in Korea, and argue that marriage remains a major obstacle to young Korean women's employment. We find that an average married woman is much less likely (by 40–60%) to participate in the labor force than a single woman in urban Korea. Further investigation into the participation patterns among married women reveals that labor force participation rate (LFPR) varies with husband's occupation and her own age. Lower LFPR among the young married women is explained by demand-side factors, while relatively higher LFPR among the middle-aged married women is mostly explained by the supply-side factors.

CDKN2A mutation in a non-FAMMM kindred with cancers at multiple sites results in a functionally abnormal protein

The CDKN2A gene encodes p16 (CDKN2A), a cell-cycle inhibitor protein which prevents inappropriate cell cycling and, hence, proliferation. Germ-line mutations in CDKN2A predispose to the familial atypical multiple-mole melanoma (FAMMM) syndrome but also have been seen in rare families in which only 1 or 2 individuals are affected by cutaneous malignant melanoma (CMM). We therefore sequenced exons 1alpha and 2 of CDKN2A using lymphocyte DNA isolated from index cases from 67 families with cancers at multiple sites, where the patterns of cancer did not resemble those attributable to known genes such as hMLH1, hMLH2, BRCA1, BRCA2, TP53 or other cancer susceptibility genes. We found one mutation, a mis-sense mutation resulting in a methionine to isoleucine change at codon 53 (M531) of exon 2. The individual tested had developed 2 CMMs but had no dysplastic nevi and lacked a family history of dysplastic nevi or CMM. Other family members had been diagnosed with oral cancer (2 persons), bladder cancer (1 person) and possibly gall-bladder cancer. While this mutation has been reported in Australian and North American melanoma kindreds, we did not observe it in 618 chromosomes from Scottish and Canadian controls. Functional studies revealed that the CDKN2A variant carrying the M531 change was unable to bind effectively to CDK4, showing that this mutation is of pathological significance. Our results have confirmed that CDKN2A mutations are not limited to FAMMM kindreds but also demonstrate that multi-site cancer families without melanoma are very unlikely to contain CDKN2A mutations.

Molecular classification of cutaneous malignant melanoma by gene expression profiling

The most common human cancers are malignant neoplasms of the skin. Incidence of cutaneous melanoma is rising especially steeply, with minimal progress in non-surgical treatment of advanced disease. Despite significant effort to identify independent predictors of melanoma outcome, no accepted histopathological, molecular or immunohistochemical marker defines subsets of this neoplasm. Accordingly, though melanoma is thought to present with different 'taxonomic' forms, these are considered part of a continuous spectrum rather than discrete entities. Here we report the discovery of a subset of melanomas identified by mathematical analysis of gene expression in a series of samples. Remarkably, many genes underlying the classification of this subset are differentially regulated in invasive melanomas that form primitive tubular networks in vitro, a feature of some highly aggressive metastatic melanomas. Global transcript analysis can identify unrecognized subtypes of cutaneous melanoma and predict experimentally verifiable phenotypic characteristics that may be of importance to disease progression.

That Blackfella Bloodsucka Dance!

"That Blackfella Bloodsucka Dance!" A novel in which a part-blood Aboriginal Australian becomes a full-blood vampire (see the above pdf for the first 50 pages FREE!). Synopsis. In this bold and cheeky meditation on religion, middle-aged muscleman, uncertain Catholic and wanna-be academic Sterling de Bortoli is a self-described Octaroon: a one eighth Aboriginal Australian. Neither black nor white this part-blood Blackfella struggles with concepts of identity, moving between the two worlds but not really belonging to either. Thus he pursues a frustrated, anarchic, homeless existence in Canberra and Melbourne, until, through the influence of the Anti-Christ, his Dark Lord Maria, he travels to Islamic Morocco. It's a land completely foreign to his Dreamtime totem, and it's where de Bortoli learns to be a full-blood vampire ... a monster who never says sorry. ISBN: 978-3-8454-4518-2 Available in hard copy and E-book.

Modeling fault among motorcyclists involved in crashes

Singapore crash statistics from 2001 to 2006 show that the motorcyclist fatality and injury rates per registered vehicle are higher than those of other motor vehicles by 13 and 7 times respectively. The crash involvement rate of motorcyclists as victims of other road users is also about 43%. The objective of this study is to identify the factors that contribute to the fault of motorcyclists involved in crashes. This is done by using the binary logit model to differentiate between at-fault and not-at-fault cases and the analysis is further categorized by the location of the crashes, i.e., at intersections, on expressways and at non-intersections. A number of explanatory variables representing roadway characteristics, environmental factors, motorcycle descriptions, and rider demographics have been evaluated. Time trend effect shows that not-at-fault crash involvement of motorcyclists has increased with time. The likelihood of night time crashes has also increased for not-at-fault crashes at intersections and expressways. The presence of surveillance cameras is effective in reducing not-at-fault crashes at intersections. Wet road surfaces increase at-fault crash involvement at non-intersections. At intersections, not-at-fault crash involvement is more likely on single lane roads or on median lane of multi-lane roads, while on expressways at-fault crash involvement is more likely on the median lane. Roads with higher speed limit have higher at-fault crash involvement and this is also true on expressways. Motorcycles with pillion passengers or with higher engine capacity have higher likelihood of being at-fault in crashes on expressways. Motorcyclists are more likely to be at-fault in collisions involving pedestrians and this effect is higher at night. In multi-vehicle crashes, motorcyclists are more likely to be victims than at fault. Young and older riders are more likely to be at-fault in crashes than middle-aged group of riders. The findings of this study will help to develop more targeted countermeasures to improve motorcycle safety and more cost-effective safety awareness program in motorcyclist training.

Developing targeted countermeasures to improve motorcycle safety

The fatality and injury rate of motorcyclists per registered vehicle are higher than those of other motor vehicles by 13 and 7 times respectively. The crash involvement rate of motorcyclists as a victim party is 58% at intersections and as an offending party is 67% at expressways. Previous research efforts showed that the motorcycle safety programs are not very effective in improving motorcycle safety. This is perhaps due to inefficient design of safety program as specific causal factors may not be well explored. The objective of this study is to propose more sophisticated countermeasures and awareness programs for improving motorcycle safety after analyzing specific causal factors for motorcycle crashes at intersections and expressways. Methodologically this study applies the binary logistic model to explore the at-fault or not-at-fault crash involvement of motorcyclists at those locations. A number of explanatory variables representing roadway characteristics, environmental factors, motorcycle descriptions, and rider demographics have been evaluated. Results shows that the night time crash occurrence, presence of red light camera, lane position, rider age, licence class, and multivehicle collision significantly affect the fault of motorcyclists involved in crashes at intersections. On the other hand, the night time crash occurrence, lane position, speed limit, rider age, licence class, engine capacity, riding with pillion passenger, foreign registered motorcycles, and multivehicle collision has been found to be significant at expressways. Legislate to wear reflective clothes and using reflective markings on the motorcycles and helmets are suggested as an effective countermeasure for reducing their vulnerability. The red light cameras at intersections reduce the vulnerability of motorcycles and hence motorcycle flow and motorcycle crashes should be considered during installation of red light cameras. At signalized intersections, motorcyclists may be taught to follow correct movement and queuing rather than weaving through the traffic as it leads them to become victims of other motorists. The riding simulators in the training centers can be useful to demonstrate the proper movement and queuing at junctions. Riding with pillion passenger and excess speed at expressways are found to significantly influence the at at-fault crash involvement of the motorcyclists. Hence the motorcyclists should be advised to concentrate more on riding while riding with pillion passenger and encouraged to avoid excess speed at expressways. Very young and very older group of riders are found to be at-fault than middle aged groups. Hence this group of riders should be targeted for safety improvement. This can be done by arranging safety talks and programs in motorcycling clubs in colleges and universities as well as community riding clubs with high proportion of elderly riders. It is recommended that the driving centers may use the findings of this study to include in licensure program to make motorcyclists more aware of the different factors which expose the motorcyclists to crash risks so that more defensive riding may be needed.

Intuitive interaction and older people

Older people often struggle with using contemporary products and interfaces. They show slower, less intuitive interaction with more errors. This paper reports on a large project designed to investigate why older people have these difficulties and what strategies could be used to mitigate them. The project team found that older people are less familiar with products that they own than younger ones, while both older and middle aged people are less familiar with products that they do not own than younger ones. Age related cognitive decline is also related to slower and less intuitive performance with contemporary products and interfaces. Therefore, the reasons behind the problems that older people demonstrate with contemporary technologies involve a mix of familiarity and capability. Redundancy applied to an interface in the form of symbols and words is helpful for middle aged and younger old people but the oldest age group performed better with a words only interface. Also, older people showed faster and more intuitive use with a flat interface than a nested one, although there was no difference in errors. Further work is ongoing in order to establish ways in which these findings can be usefully applied in the design process.

Video-based road commentary training improves hazard perception of young drivers in a dual task

This study used a video-based hazard perception dual task to compare the hazard perception skills of young drivers with middle aged, more experienced drivers and to determine if these skills can be improved with video-based road commentary training. The primary task required the participants to detect and verbally identify immediate hazard on video-based traffic scenarios while concurrently performing a secondary tracking task, simulating the steering of real driving. The results showed that the young drivers perceived fewer immediate hazards (mean = 75.2%, n = 24, 19 females) than the more experienced drivers (mean = 87.5%, n = 8, all females), and had longer hazard perception times, but performed better in the secondary tracking task. After the road commentary training, the mean percentage of hazards detected and identified by the young drivers improved to the level of the experienced drivers and was significantly higher than that of an age and driving experience matched control group. The results will be discussed in the context of psychological theories of hazard perception and in relation to road commentary as an evidence-based training intervention that seems to improve many aspects of unsafe driving behaviour in young drivers.

Advice to consult a general medical practitioner in Western Australia : Could it be cancer?

Background: Many people will consult a medical practitioner about lower bowel symptoms, and the demand for access to general practitioners (GPs) is growing. We do not know if people recognise the symptoms of lower bowel cancer when advising others about the need to consult a doctor. A structured vignette survey was conducted in Western Australia. Method: Participants were recruited from the waiting rooms at five general practices. Respondents were invited to complete self-administered questionnaires containing nine vignettes chosen at random from a pool of 64 based on six clinical variables. Twenty-seven vignettes described high-risk bowel cancer scenarios. Respondents were asked if they would recommend a medical consultation for the case described and whether they believed the scenario was a cancer presentation. Logistic regression was used to estimate the independent effects of each variable on the respondent's judgement. Two-hundred and sixty-eight completed responses were collected over eight weeks. Results: The majority (61%) of respondents were female, aged 40 years and older. A history of rectal bleeding, six weeks of symptoms, and weight loss independently increased the odds of recommending a consultation with a medical practitioner by a factor of 7.64, 4.11 and 1.86, respectively. Most cases that were identified as cancer (75.2%) would not be classified as such on current research evidence. Factors that predict recognition of cancer presentations include rectal bleeding, weight loss and diarrhoea.

Determinants of uptake of whole-body skin self-examination in older men

Early detection through whole-body Skin Self-Examination (wbSSE) may decrease mortality from melanoma. Using the Health Action Process Approach (HAPA) or Health Belief Model (HBM) we aimed to assess determinants of uptake of wbSSE in 410 men 50 years of older who participated in the control group of a randomized trial. Overall, the HAPA was a significantly better predictor of wbSSE compared to the HBM (p < .001). The construct of self-efficacy in the HBM was a significant predictor of future wbSSE (p = .001), while neither perceived threat (p = .584) nor outcome expectations (p = .220) were. In contrast, self-efficacy, perceived threat, and outcome expectations predicted intention to perform SSE, which predicted behavior (p = .015). The HAPA construct volitional self-efficacy was also associated with wbSSE (p = .046). The use of the HAPA model for future SSE interventions for this population is warranted.

Genotypes of the MTHFR C677T and MTRR A66G genes act independently to reduce migraine disability in response to vitamin supplementation

BACKGROUND: Migraine is a chronic disabling neurovascular condition that may in part be caused by endothelial and cerebrovascular disruption induced by hyperhomocysteinaemia. We have previously provided evidence indicating that reduction of homocysteine by vitamin supplementation can reduce the occurrence of migraine in women. The current study examined the genotypic effects of methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) gene variants on the occurrence of migraine in response to vitamin supplementation. METHODS: This was a 6-month randomized, double-blinded placebo-controlled trial of daily vitamin B supplementation (B(6), B(9) and B(12)) on reduction of homocysteine and of the occurrence of migraine in 206 female patients diagnosed with migraine with aura. RESULTS: Vitamin supplementation significantly reduced homocysteine levels (P<0.001), severity of headache in migraine (P=0.017) and high migraine disability (P=0.022) in migraineurs compared with the placebo effect (P>0.1). When the vitamin-treated group was stratified by genotype, the C allele carriers of the MTHFR C677T variant showed a higher reduction in homocysteine levels (P<0.001), severity of pain in migraine (P=0.01) and percentage of high migraine disability (P=0.009) compared with those with the TT genotypes. Similarly, the A allele carriers of the MTRR A66G variants showed a higher level of reduction in homocysteine levels (P<0.001), severity of pain in migraine (P=0.002) and percentage of high migraine disability (P=0.006) compared with those with the GG genotypes. Genotypic analysis for both genes combined indicated that the treatment effect modification of the MTRR variant was independent of the MTHFR variant. CONCLUSION: This provided further evidence that vitamin supplementation is effective in reducing migraine and also that both MTHFR and MTRR gene variants are acting independently to influence treatment response in female migraineurs.

G-protein β3 subunit gene (GNB3) variant in causation of essential hypertension

Essential hypertensives display enhanced signal transduction through pertussis toxin-sensitive G proteins. The T allele of a C825T variant in exon 10 of the G protein β3 subunit gene (GNB3) induces formation of a splice variant (Gβ3-s) with enhanced activity. The T allele of GNB3 was shown recently to be associated with hypertension in unselected German patients (frequency=0.31 versus 0.25 in control). To confirm and extend this finding in a different setting, we performed an association study in Australian white hypertensives. This involved an extensively examined cohort of 110 hypertensives, each of whom were the offspring of 2 hypertensive parents, and 189 normotensives whose parents were both normotensive beyond age 50 years. Genotyping was performed by polymerase chain reaction and digestion with BseDI, which either cut (C allele) or did not cut (T allele) the 268-bp polymerase chain reaction product. T allele frequency in the hypertensive group was 0.43 compared with 0.25 in the normotensive group (χ2=22; P=0.00002; odds ratio=2.3; 95% CI=1.7 to 3.3). The T allele tracked with higher pretreatment blood pressure: diastolic=105±7, 109±16, and 128±28 mm Hg (mean±SD) for CC, CT, and 7T, respectively (P=0.001 by 1-way ANOVA). Blood pressures were higher in female hypertensives with a T allele (P=0.006 for systolic and 0.0003 for diastolic by ANOVA) than they were in male hypertensives. In conclusion, the present study of a group with strong family history supports a role for a genetically determined, physiologically active splice variant of the G protein β3 subunit gene in the causation of essential hypertension.

Examination of the role of nitric oxide synthase and renal kallikrein as candidate genes for essential hypertension

Nitric oxide synthase and renal kallikrein are both involved in blood pressure regulation. Genes for these enzymes may, therefore, be considered candidates for hypertension pathogenesis. 2. In the present study, genotypes for nitric oxide synthase and renal kallikrein microsatellite markers were determined in a cross-sectional association analysis of hypertensive patients and normotensive control subjects. 3. Results from this study did not indicate an association of either of the candidate gene polymorphisms with essential hypertension. Hence, findings for this study do not support a role for these genes in human hypertension.