Socioeconomic inequalities in cardiovascular mortality and the role of childhood socioeconomic conditions and adulthood risk factors : a prospective cohort study with 17-years of follow up

Background The mechanisms underlying socioeconomic inequalities in mortality from cardiovascular diseases (CVD) are largely unknown. We studied the contribution of childhood socioeconomic conditions and adulthood risk factors to inequalities in CVD mortality in adulthood. Methods The prospective GLOBE study was carried out in the Netherlands, with baseline data from 1991, and linked with the cause of death register in 2007. At baseline, participants reported on adulthood socioeconomic position (SEP) (own educational level), childhood socioeconomic conditions (occupational level of respondent’s father), and a broad range of adulthood risk factors (health behaviours, material circumstances, psychosocial factors). This present study is based on 5,395 men and 6,306 women, and the data were analysed using Cox regression models and hazard ratios (HR). Results A low adulthood SEP was associated with increased CVD mortality for men (HR 1.84; 95% CI: 1.41-2.39) and women (HR 1.80; 95%CI: 1.04-3.10). Those with poorer childhood socioeconomic conditions were more likely to die from CVD in adulthood, but this reached statistical significance only among men with the poorest childhood socioeconomic circumstances. About half of the investigated adulthood risk factors showed significant associations with CVD mortality among both men and women, namely renting a house, experiencing financial problems, smoking, physical activity and marital status. Alcohol consumption and BMI showed a U-shaped relationship with CVD mortality among women, with the risk being significantly greater for both abstainers and heavy drinkers, and among women who were underweight or obese. Among men, being single or divorced and using sleep/anxiety drugs increased the risk of CVD mortality. In explanatory models, the largest contributor to adulthood CVD inequalities were material conditions for men (42%; 95% CI: −73 to −20) and behavioural factors for women (55%; 95% CI: -191 to −28). Simultaneous adjustment for adulthood risk factors and childhood socioeconomic conditions attenuated the HR for the lowest adulthood SEP to 1.34 (95% CI: 0.99-1.82) for men and 1.19 (95% CI: 0.65-2.15) for women. Conclusions Adulthood material, behavioural and psychosocial factors played a major role in the explanation of adulthood SEP inequalities in CVD mortality. Childhood socioeconomic circumstances made a modest contribution, mainly via their association with adulthood risk factors. Policies and interventions to reduce health inequalities are likely to be most effective when considering the influence of socioeconomic circumstances across the entire life course and in particular, poor material conditions and unhealthy behaviours in adulthood.

Arbitration proceeding – determination of “market price” – subpoena under Commercial Arbitration Act 1990 s 17

AGL Wholesale Gas Ltd v Origin Energy Ltd [2008] QCA 366 involved an appeal against the setting aside of paragraphs of a subpoena issued under s 17 of the Commercial Arbitration Act 1990 (Qld). The Court was satisfied that even if the documents were of “apparent relevance” to the subject matter of the proceedings, it would nevertheless be oppressive to require their production.

Discrete loading of the foot during hurdle drills: A pilot investigation

Introduction: Lower limb function in hurdling is patently asymmetrical. The lead limb undertakes the preparatory and landing steps while the trail limb contends with the hurdle and recovery steps. Discrete loading profiles of these steps will reflect the asymmetrical function and may provide useful insight into injury mechanisms. A pilot study was undertaken to determine the loading profiles of the hurdle, landing and recovery steps of elite male hurdlers. Equivalent data for steps between hurdles, where the running action is more symmetrical, were used for the purpose of comparison, simultaneously minimising the confounding effect of speed. Methodology: In-shoe pressures were recorded (FScan, 200 Hz) for four elite male hurdlers while they completed a routine hurdle drill at a self-selected fast but sub-race speed. The drill comprised of three consecutive hurdles. Data for the hurdle, landing and recovery steps of the first and second hurdles, along with data for the running steps between hurdles 1 and 2, and 2 and 3, were used for the purpose of analysis. Peak pressures within 1cm2 masks were determined for the hallux, first, central and fifth metatarsals (T1, M1, M2–4 and M5 respectively). Peak pressure (kPa) and loading duration (ms) for the hurdle, landing and recovery steps are reported as a percentage of the respective limb-matched values for between-hurdle steps. Results/discussion: For between-hurdle steps, T1, M1 and M2–4 peak pressures were 312/357, 356/306 and 362/368 kPa, lead/trail limbs respectively. For the hurdle, landing and recovery steps, pressures at T1 and M1 increased. For T1 the increases were in the order of 17%, 36% and 8% (hurdle, landing and recovery steps, respectively) while the corresponding increases at M1 were 7%, 54% and 20%. Pressures at M2–4 were similar for all steps, while M5 loaded erratically. For the between-hurdle steps, the loading durations at T1, M1 and M2–4, were 160/162, 170/142 and 190/191 ms, respectively. For the landing step, loading duration decreased for T1, M1and M2–4 (−8%, −19% and −18%, respectively). In the hurdle step, loading duration decreased for the metatarsals but not for T1. Conclusions: The hurdling action leads to regional pressure increases that act for shorter durations in comparison to the between-hurdle running steps. These changes are most notable at the first metatarsal, a common site of foot injury.

Genetic improvement of giant freshwater prawn in Vietnam

The giant freshwater prawn (Macrobrachium rosenbergii) or GFP is one of the most important freshwater crustacean species in the inland aquaculture sector of many tropical and subtropical countries. Since the 1990’s, there has been rapid global expansion of freshwater prawn farming, especially in Asian countries, with an average annual rate of increase of 48% between 1999 and 2001 (New, 2005). In Vietnam, GFP is cultured in a variety of culture systems, typically in integrated or rotational rice-prawn culture (Phuong et al., 2006) and has become one of the most common farmed aquatic species in the country, due to its ability to grow rapidly and to attract high market price and high demand. Despite potential for expanded production, sustainability of freshwater prawn farming in the region is currently threatened by low production efficiency and vulnerability of farmed stocks to disease. Commercial large scale and small scale GFP farms in Vietnam have experienced relatively low stock productivity, large size and weight variation, a low proportion of edible meat (large head to body ratio), scarcity of good quality seed stock. The current situation highlights the need for a systematic stock improvement program for GFP in Vietnam aimed at improving economically important traits in this species. This study reports on the breeding program for fast growth employing combined (between and within) family selection in giant freshwater prawn in Vietnam. The base population was synthesized using a complete diallel cross including 9 crosses from two local stocks (DN and MK strains) and a third exotic stock (Malaysian strain - MY). In the next three selection generations, matings were conducted between genetically unrelated brood stock to produce full-sib and (paternal) half-sib families. All families were produced and reared separately until juveniles in each family were tagged as a batch using visible implant elastomer (VIE) at a body size of approximately 2 g. After tags were verified, 60 to 120 juveniles chosen randomly from each family were released into two common earthen ponds of 3,500 m2 pond for a grow-out period of 16 to 18 weeks. Selection applied at harvest on body weight was a combined (between and within) family selection approach. 81, 89, 96 and 114 families were produced for the Selection line in the F0, F1, F2 and F3 generations, respectively. In addition to the Selection line, 17 to 42 families were produced for the Control group in each generation. Results reported here are based on a data set consisting of 18,387 body and 1,730 carcass records, as well as full pedigree information collected over four generations. Variance and covariance components were estimated by restricted maximum likelihood fitting a multi-trait animal model. Experiments assessed performance of VIE tags in juvenile GFP of different size classes and individuals tagged with different numbers of tags showed that juvenile GFP at 2 g were of suitable size for VIE tags with no negative effects evident on growth or survival. Tag retention rates were above 97.8% and tag readability rates were 100% with a correct assignment rate of 95% through to mature animal size of up to 170 g. Across generations, estimates of heritability for body traits (body weight, body length, cephalothorax length, abdominal length, cephalothorax width and abdominal width) and carcass weight traits (abdominal weight, skeleton-off weight and telson-off weight) were moderate and ranged from 0.14 to 0.19 and 0.17 to 0.21, respectively. Body trait heritabilities estimated for females were significantly higher than for males whereas carcass weight trait heritabilities estimated for females and males were not significantly different (P > 0.05). Maternal and common environmental effects for body traits accounted for 4 to 5% of the total variance and were greater in females (7 to 10%) than in males (4 to 5%). Genetic correlations among body traits were generally high in both sexes. Genetic correlations between body and carcass weight traits were also high in the mixed sexes. Average selection response (% per generation) for body weight (transformed to square root) estimated as the difference between the Selection and the Control group was 7.4% calculated from least squares means (LSMs), 7.0% from estimated breeding values (EBVs) and 4.4% calculated from EBVs between two consecutive generations. Favourable correlated selection responses (estimated from LSMs) were detected for other body traits (12.1%, 14.5%, 10.4%, 15.5% and 13.3% for body length, cephalothorax length, abdominal length, cephalothorax width and abdominal width, respectively) over three selection generations. Data in the second selection generation showed positive correlated responses for carcass weight traits (8.8%, 8.6% and 8.8% for abdominal weight, skeleton-off weight and telson-off weight, respectively). Data in the third selection generation showed that heritability for body traits were moderate and ranged from 0.06 to 0.11 and 0.11 to 0.22 at weeks 10 and 18, respectively. Body trait heritabilities estimated at week 10 were not significantly lower than at week 18. Genetic correlations between body traits within age and genetic correlations for body traits between ages were generally high. Overall our results suggest that growth rate responds well to the application of family selection and carcass weight traits can also be improved in parallel, using this approach. Moreover, selection for high growth rate in GFP can be undertaken successfully before full market size has been reached. The outcome of this study was production of an improved culture strain of GFP for the Vietnamese culture industry that will be trialed in real farm production environments to confirm the genetic gains identified in the experimental stock improvement program.

Chromosome 17 and the inducible nitric oxide synthase gene in human essential hypertension

Essential hypertension is a common multifactorial trait that results in a significantly increased risk for heart attack and stroke. The condition has a genetic basis, although at present the number of genes is unknown. In order to identify such genes, we are utilising a linkage scanning approach using microsatellite markers and affected sibships. Here we provide evidence for the location of at least one hypertension susceptibility locus on chromosome 17. Analysis of 177 affected sibpairs gave evidence for significant excess allele sharing to D17S949 (SPLINK: P=0.0029; MAPMAKER SIBS: P=0.0033; ASPEX: P=0.0061; GENEHUNTER: P=0.0096; ANALYZE (SIBPAIR): P=0.0025) on 17q22–24, with significant allele sharing also indicated for an additional marker, D17S799 (SPLINK: P=0.025; MAPMAKER SIBS: P= 0.025) located close to the centromere. Since these two genomic regions are well separated, our results indicate that there may be more than one chromosome 17 locus affecting human blood pressure. Moreover, further investigation of this chromosome, utilizing a polymorphism within the promoter of the iNOS candidate gene, NOS2A, revealed both increased allele sharing among sibpairs (SPLINK: P=0.02; ASPEX: P=0.00004) and positive association (P= 0.034) of NOS2A to essential hypertension. Hence these results indicate that chromosome 17 and, more specifically, the NOS2A gene may play a role in human essential hypertension.

The duration of Chlamydia muridarum genital tract infection and associated chronic pathological changes are reduced in IL-17 knockout mice but protection is not increased further by immunization

IL-17 is believed to be important for protection against extracellular pathogens, where clearance is dependent on neutrophil recruitment and local activation of epithelial cell defences. However, the role of IL-17 in protection against intracellular pathogens such as Chlamydia is less clear. We have compared (i) the course of natural genital tract C. muridarum infection, (ii) the development of oviduct pathology and (iii) the development of vaccine-induced immunity against infection in wild type (WT) BALB/c and IL-17 knockout mice (IL-17-/-) to determine if IL-17-mediated immunity is implicated in the development of infection-induced pathology and/or protection. Both the magnitude and duration of genital infection was significantly reduced in IL-17-/- mice compared to BALB/c. Similarly, hydrosalpinx was also greatly reduced in IL-17-/- mice and this correlated with reduced neutrophil and macrophage infiltration of oviduct tissues. Matrix metalloproteinase (MMP) 9 and MMP2 were increased in WT oviducts compared to IL-17-/- animals at day 7 post-infection. In contrast, oviducts from IL-17-/- mice contained higher MMP9 and MMP2 at day 21. Infection also elicited higher levels of Chlamydia-neutralizing antibody in serum of IL-17-/- mice than WT mice. Following intranasal immunization with C. muridarum Major Outer Membrane Protein (MOMP) and cholera toxin plus CpG adjuvants, significantly higher levels of chlamydial MOMP-specific IgG and IgA were found in serum and vaginal washes of IL-17-/- mice. T cell proliferation and IFNγ production by splenocytes was greater in WT animals following in vitro re-stimulation, however vaccination was only effective at reducing infection in WT, not IL-17-/- mice. Intranasal or transcutaneous immunization protected WT but not IL-17-/- mice against hydrosalpinx development. Our data show that in the absence of IL-17, the severity of C. muridarum genital infection and associated oviduct pathology are significantly attenuated, however neither infection or pathology can be reduced further by vaccination protocols that effectively protect WT mice.

Immunity against a Chlamydia infection and disease may be determined by a balance of IL-17 signaling

Most vaccines developed against Chlamydia using animal models provide partial protection against a genital tract infection. However, protection against the oviduct pathology associated with infertility is highly variable and often has no defining immunological correlate. When comparing two adjuvants (CTA1-DD and a combination of Cholera toxin plus CpG- oligodeoxynucleotide–CT/CpG) combined with the chlamydial major outer membrane protein (MOMP) antigen and delivered via the intranasal (IN), sublingual (SL) or transcutaneous (TC) routes, we identified two vaccine groups with contrasting outcomes following infection. SL immunization with MOMP/CTA1-DD induced a 70% reduction in the incidence of oviduct pathology, without significantly altering the course of infection. Conversely, IN immunization with MOMP/CT/CpG prevented an ascending infection, but not the oviduct pathology. This anomaly presented a unique opportunity to study the mechanisms by which vaccines can prevent oviduct pathology, other than by controlling the infection. The IL-17 signaling in the oviducts was found to associate with both the enhancement of immunity to infection and the development of oviduct pathology. This conflicting role of IL-17 may provide some explanation for the discordance in protection between infection and disease and suggests that controlling immunopathology, as opposed to the rapid eradication of the infection, may be essential for an effective human chlamydial vaccine that prevents infertility.

Dispositional resistance to change : measurement equivalence and the link to personal values across 17 nations

The concept of dispositional resistance to change has been introduced in a series of exploratory and confirmatory analyses through which the validity of the Resistance to Change (RTC) Scale has been established (S. Oreg, 2003). However, the vast majority of participants with whom the scale was validated were from the United States. The purpose of the present work was to examine the meaningfulness of the construct and the validity of the scale across nations. Measurement equivalence analyses of data from 17 countries, representing 13 languages and 4 continents, confirmed the cross-national validity of the scale. Equivalent patterns of relationships between personal values and RTC across samples extend the nomological net of the construct and provide further evidence that dispositional resistance to change holds equivalent meanings across nations.

The heat shock protein 90 inhibitor, 17-allylamino-17- demethoxygeldanamycin, enhances osteoclast formation and potentiates bone metastasis of a human breast cancer cell line

Breast cancer metastasis to the bone occurs frequently, causing numerous complications including severe pain, fracture, hypercalcemia, and paralysis. Despite its prevalence and severity, few effective therapies exist. To address this, we examined whether the heat shock protein 90 (Hsp90) inhibitor, 17-allylamino-17-demethoxygeldanamycin (17-AAG), would be efficacious in inhibiting breast cancer metastasis to bone. Utilizing the human breast cancer subline, MDA-MB-231SA, previously in vivo selected for its enhanced ability to generate osteolytic bone lesions, we determined that 17-AAG potently inhibited its in vitro proliferation and migration. Moreover, 17-AAG significantly reduced MDA-MB-231SA tumor growth in the mammary-fat pad of nude mice. Despite these findings, 17-AAG enhanced the incidence of bone metastasis and osteolytic lesions following intracardiac inoculation in the nude mouse. Consistent with these findings, 17-AAG enhanced osteoclast formation 2- to 4-fold in mouse bone marrow/osteoblast cocultures, receptor activator of nuclear factor κB ligand (BANKL)-stimulated bone marrow, and RAW264.7 cell models of in vitro osteoclastogenesis. Moreover, the drug enhanced osteoclastogenesis in human cord blood progenitor cells, demonstrating that its effects were not limited to mouse models. In addition to 17-AAG, other Hsp90 inhibitors, such as radicicol and herbimycin A, also enhanced osteoclastogenesis. A pro-osteolytic action of 17-AAG independent of tumor presence was also determined in vivo, in which 17-AAG-treated tumor-naive mice had reduced trabecular bone volume with an associated increase in osteoclast number. Thus, HSP90 inhibitors can stimulate osteoclast formation, which may underlie the increased incidence of osteolysis and skeletal tumor incidence causedby 17-AAG in vivo. These data suggest an important contraindication to the Hsp90 targeted cancer therapy currently undergoing clinical trial.

Physical activity and physical fitness in African-American girls with and without obesity

Lack of physical activity and low levels of physical fitness are thought to be contributing factors to the high prevalence of obesity in African-American girls, To examine this hypothesis, we compared habitual physical activity and physical fitness in 54 African-American girls with obesity and 96 African-American girls without obesity residing in rural South Carolina, Participation in vigorous (greater than or equal to 6 METs) (VPA) or moderate and vigorous physical activity (greater than or equal to 4 METs) (MVPA) was assessed on three consecutive days using the Previous Day Physical Activity Recall, Cardiorespiratory fitness was assessed using the PWC 170 cycle ergometer test, Upper body strength was determined at two sites via isometric cable tensiometer tests, Relative to their counterparts without obesity, girls with obesity reported significantly fewer 30-minute blocks of VPA (0.90 +/- 0.14 vs. 1.3 +/- 0.14) and MVPA (1.2 +/- 0.18 vs. 1.7 +/- 0.16) (p<0.01), Within the entire sample, VPA and MVPA were inversely associated with body mass index (r=-0.17 and r=-0.19) and triceps skinfold thickness (r=-0.19 and r=-0.22) (p<0.05), In the PWC 170 test and isometric strength tests, girls with obesity demonstrated absolute scores that were similar to, or greater than, those of girls without obesity; however, when scores were expressed relative to bodyweight, girls with obesity demonstrated significantly lower values (p<0.05). The results support the hypothesis that lack of physical activity and low physical fitness are important contributing factors in the development and/or maintenance of obesity in African-American girls.

Methodology to predict the safety performance of rural multilane highways [Final Report for NCHRP Project 17-29]

The objective of this research is to develop a methodology that predicts the safety performance of various elements considered in the planning, design, and operation of nonlimited- access rural multilane highways.

Copyright and creativity: An ongoing debate in the creative industries

This paper critically analyzes the divergent perspectives on how copyright and intellectual property laws impact creativity, innovation, and the creative industries. One perspective defines the creative industries based on copyright as the means by which revenues are generated from innovation and the dissemination of new ideas. At the same time, it has been argued that copyright and intellectual property regimes fetter creativity and innovation, and that this has become even more marked in the context of digital media convergence and the networked global creative economy. These issues have resonated in debates around the creative industries, particularly since the initial DCMS mapping study in the UK in 1998 defined creative industries as combining individual creativity and exploitable forms of intellectual property. The issue of competing claims for the relationship between copyright and the creative industries has also arisen in Australia, with a report by the Australian Law Reform Commission entitled Copyright and the Digital Economy. This paper will consider the competing claims surrounding copyright and the creative industries, and the implications for policy-makers internationally.

Enrichment of circulating interleukin-17-secreting interleukin-23 receptor-positive γ/δ T cells in patients with active ankylosing spondylitis

Objective Ankylosing spondylitis (AS) is a common inflammatory arthritis affecting primarily the axial skeleton. IL23R is genetically associated with AS. This study was undertaken to investigate and characterize the role of interleukin-23 (IL-23) signaling in AS pathogenesis. Methods The study population consisted of patients with active AS (n = 17), patients with psoriatic arthritis (n = 8), patients with rheumatoid arthritis, (n = 9), and healthy subjects (n = 20). IL-23 receptor (IL-23R) expression in T cells was determined in each subject group, and expression levels were compared. Results The proportion of IL-23R-expressing T cells in the periphery was 2-fold higher in AS patients than in healthy controls, specifically driven by a 3-fold increase in IL-23R-positive γ/δ T cells in AS patients. The proportions of CD4+ and CD8+ cells that were positive for IL-17 were unchanged. This increased IL-23R expression on γ/δ T cells was also associated with enhanced IL-17 secretion, with no observable IL-17 production from IL-23R-negative γ/δ T cells in AS patients. Furthermore, γ/δ T cells from AS patients were heavily skewed toward IL-17 production in response to stimulation with IL-23 and/or anti-CD3/CD28. Conclusion Recently, mouse models have shown IL-17-secreting γ/δ T cells to be pathogenic in infection and autoimmunity. Our data provide the first description of a potentially pathogenic role of these cells in a human autoimmune disease. Since IL-23 is a maturation and growth factor for IL-17-producing cells, increased IL-23R expression may regulate the function of this putative pathogenic γ/δ T cell population.