Genome-wide association study identifies new multiple sclerosis susceptibility loci on chromosomes 12 and 20

To identify multiple sclerosis (MS) susceptibility loci, we conducted a genome-wide association study (GWAS) in 1,618 cases and used shared data for 3,413 controls. We performed replication in an independent set of 2,256 cases and 2,310 controls, for a total of 3,874 cases and 5,723 controls. We identified risk-associated SNPs on chromosome 12q13-14 (rs703842, P = 5.4 x 10(-11); rs10876994, P = 2.7 x 10(-10); rs12368653, P = 1.0 x 10(-7)) and upstream of CD40 on chromosome 20q13 (rs6074022, P = 1.3 x 10(-7); rs1569723, P = 2.9 x 10(-7)). Both loci are also associated with other autoimmune diseases. We also replicated several known MS associations (HLA-DR15, P = 7.0 x 10(-184); CD58, P = 9.6 x 10(-8); EVI5-RPL5, P = 2.5 x 10(-6); IL2RA, P = 7.4 x 10(-6); CLEC16A, P = 1.1 x 10(-4); IL7R, P = 1.3 x 10(-3); TYK2, P = 3.5 x 10(-3)) and observed a statistical interaction between SNPs in EVI5-RPL5 and HLA-DR15 (P = 0.001).

Predictors of physical and mental health-related quality of life outcomes among myocardial infarction patients

Background Health-related quality of life (HRQoL) is an important outcome for patients diagnosed with coronary heart disease. This report describes predictors of physical and mental HRQoL at six months post-hospitalisation for myocardial infarction. Methods Participants were myocardial infarction patients (n=430) admitted to two tertiary referral centres in Brisbane, Australia who completed a six month coronary heart disease secondary prevention trial (ProActive Heart). Outcome variables were HRQoL (Short Form-36) at six months, including a physical and mental summary score. Baseline predictors included demographics and clinical variables, health behaviours, and psychosocial variables. Stepwise forward multiple linear regression analyses were used to identify significant independent predictors of six month HRQoL. Results Physical HRQoL was lower in participants who: were older (p<0.001); were unemployed (p=0.03); had lower baseline physical and mental HRQoL scores (p<0.001); had lower confidence levels in meeting sufficient physical activity recommendations (p<0.001); had no intention to be physically active in the next six months (p<0.001); and were more sedentary (p=0.001). Mental HRQoL was lower in participants who: were younger (p=0.01); had lower baseline mental HRQoL (p<0.001); were more sedentary (p=0.01) were depressed (p<0.001); and had lower social support (p=0.001). Conclusions This study has clinical implications as identification of indicators of lower physical and mental HRQoL outcomes for myocardial infarction patients allows for targeted counselling or coronary heart disease secondary prevention efforts. Trial registration Australian Clinical Trials Registry, Australian New Zealand Clinical Trials Registry, CTRN12607000595415. Keywords: Myocardial infarction; Secondary prevention; Cardiac rehabilitation; Telephone-delivered; Health-related quality of life; Health coaching; Tele-health

Association of a polymorphism of the angiotensin I-converting enzyme gene with essential hypertension

A polymorphism of the angiotensin I converting enzyme (ACE) gene has recently been reported and analysis of this polymorphism has indicated that it is associated with several cardiovascular diseases. However, the results are still controversial and such association has not yet been established conclusively. To determine whether the ACE gene may be responsible for essential hypertension in a Japanese population, we also compared the distribution of genotypes and the allele frequency of this polymorphism in our findings of a Japanese population with these features in other countries. Eighty-seven hypertensive patients with a family history of essential hypertension and 95 normotensive patients whose parents had no such history were enrolled in the study. Polymorphism of the ACE gene was determined by using the polymerase chain reaction. Homozygotes for this polymorphism had either a 490-bp band (II) or a 190-bp band (DD) and heterozygotes had both bands (ID). In hypertensive subjects, the numbers and frequency of the ACE genotypes were: II, 44 (0.51); ID, 26 (0.30); DD, 17 (0.19). In normotensive subjects these were: II, 35 (0.37); ID, 43 (0.45); DD, 17 (0.18). There were no significant differences between the two groups in derived allele frequencies (chi 2 = 1.41). The difference between the overall allelic frequency in Japan and that reported in several other countries was significant. We did not find any association between ACE gene polymorphism and essential hypertension in Japan. However, there were significant differences in derived allele frequencies between our findings in a Japanese population and those reported from Europe and Australia.

Marked association of a RFLP for the low density lipoprotein receptor gene with obesity in essential hypertensives

RFLPs at the low density lipoprotein receptor locus (LDLR) display marked linkage disequilibrium between each other. Cross-sectional analysis of a bi-alleleic ApaLI RFLP of LDLR showed that the 9.4- and 6.6-kb alleles were present in similar frequency between a group of 84 Caucasian essential hypertensive (HT) and a group of 96 normotensive subjects whose parents each had a similar blood pressure status at age > or = 50. After subdividing HTs into lean and obese, however, the frequency of the 6.6-kb allele in the 27 HTs with BMI > or = 26 kg/m2 was 0.63, compared with 0.39 for HTs with BMI < 26 (chi 2 = 8.8; P = 0.004). The difference in genotype frequencies was even more striking (chi 2 = 23; P = 0.00008), with a virtual absence of 9.4-kb homozygotes in the obese HT group (1 vs 22). Genetic variation at LDLR (19p13.2) is thus associated with obesity in HT.

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.

Cross-sectional study of a microsatellite marker in the low densitity lipoprotein receptor gene in obese normotensives

1. The low density lipoprotein receptor is an important regulator of serum cholesterol which may have implications for the development of both hypertension and obesity. In this study, genotypes for a low density lipoprotein receptor gene (LDLR) dinucleotide polymorphism were determined in both lean and obese normotensive populations. 2. In previous cross-sectional association studies an ApaLI and a HincII polymorphism for LDLR were shown to be associated with obesity in essential hypertensives. However, these polymorphisms did not show an association with obesity in normotensives. 3. In contrast, this study reports that preliminary results for an LDLR microsatellite marker, located more towards the 3' end of the gene, show a significant association with obesity in the normotensive population studied. These results indicate that LDLR could play an important role in the development of obesity, which might be independent of hypertension.

More naturalness, less control: The effect of natural mapping on the co-located player experience

In the past years, there has been a surge in game controllers that allow players to play in a more physical, more natural way. In this paper we present an experimental study of the effect of gaming using these naturally mapped controllers on the player experience in a social setting. Results support the hypothesis that more naturally mapped controllers augment spatial presence. Furthermore, the results suggest that gaming with more naturally mapped controllers augment social presence for female players, but not for male players. However, gaming via naturally mapped controllers decreases perceived control and actual performance. Hence, users with high performance expectations might not benefit from gaming via naturally mapped controllers.

Impact of rain on daily bus ridership : a Brisbane case study

Weather is one of the most significant elements affecting transit ridership on a daily basis. Until now, there has been limited focus in the literature investigating this issue. Adverse weather conditions impact travellers in choosing travel mode and route, travel schedule, and trip making itself. This paper explores the relationship between adverse weather and transit ridership by analysing the correlation between daily bus ridership and daily precipitation for a three-year period from 2010 to 2012. It is observed from the analysis that wet weather has varying impacts on daily bus ridership. Overall, rainfall negatively affects the daily bus ridership in this region. Morning peak-hours and weekend ridership were found more sensitive to rain than entire day’s ridership and weekdays. The study also found a negative correlation between the morning-peak precipitation level and the daily bus ridership, which suggests that a small amount of morning peak-hours rain reduces a significant amount bus ridership for the whole day. The analysis also confirms that summer rain has the most significant effect on ridership compared with the other three seasons. The study findings will contribute to enhancing the fundamental understanding of traveller behaviours, particularly mode choice behaviour under adverse weather conditions.

HLA-DRB1 associations with disease susceptibility and clinical course in Australians with multiple sclerosis

Human leucocyte antigen (HLA)-DRB1*1501 and other class II alleles influence susceptibility to multiple sclerosis (MS), but their contribution if any to the clinical course of MS remains uncertain. Here, we have investigated DRB1 alleles in a large sample of 1230 Australian MS cases, with some enrichment for subjects with primary progressive (PPMS) disease (n = 246) and 1210 healthy controls. Using logistic regression, we found that DRB1*1501 was strongly associated with risk (P = 7 x 10-45), as expected, and after adjusting for DRB1*1501, a predisposing effect was also observed for DRB1*03 (P = 5 x 10-7). Individuals homozygous for either DRB1*15 or DRB1*03 were considerably more at risk of MS than heterozygotes and non-carriers. Both the DRB1*04 and the DRB1*01/DRB1*15 genotype combination, respectively, protected against PPMS in comparison to subjects with relapsing disease. Together, these data provide further evidence of heterogeneity at the DRB1 locus and confirm the importance of HLA variants in the phenotypic expression of MS.

Microstructure of an artificial grain boundary weak link in an YBa2Cu3O(7-δ) thin film grown on a (100)(110), [001]-tilt Y-ZrO2 bicrystal

The microstructure of an artificial grain boundary in an YBa2Cu3O7-δ (YBCO) thin film grown on a (100)(110), [001]-tilt yttria-stabilized-zirconia (YSZ) bicrystal substrate has been studied using transmission electron microscopy (TEM). The orientation relationship between the YBCO film and the YSZ substrate was [001]YBCO∥[001]YSZ and [110]YBCO∥[100]YSZ for each half of the bicrystal film. However, the exact boundary geometry of the bicrystal substrate was not transferred to the film. The substrate boundary was straight while the film boundary was wavy. In several cases there was bending of the lattice confined within a distance of a few basal-plane lattice spacings from the boundary plane and microfaceting. No intergranular secondary phase was observed but about 25% of the boundary was covered by c-axis-tilted YBCO grains and a-axis-oriented grains, both of which were typically adjacent to CuO grains or surrounded by a thin Cu-rich amorphous layer.

Microstructure and properties of artificial grain boundaries in epitaxial YBA2Cu3O7-δ thin films grown on [001] tilt YZrO2 bicrystals

The microstructure of artificial grain boundaries in YBa2Cu3O7-δ (YBCO) thin films grown on [001] tilt YZrO2 (YSZ) bicrystal substrates has been characterized using transmission electron microscopy and atomic force microscopy. Despite a relatively straight morphology of the substrate boundaries, the film boundaries were wavy. The waviness was a result of the combined effects of grooving at the substrate boundaries prior to the film deposition and an island-growth mechanism for YBCO on YSZ substrates. The dihedral angle of the groove walls varied with the misorientation angle and depended on the symmetry of the substrate boundary. The amplitudes of the film boundary waviness compared well with the widths of the grooves. In addition, the grooves induced local bending of the YBCO lattice planes and additional tilt components perpendicular to the c-axis close to the film boundaries. © 1995.

Properties of artificial grain boundary weak links grown on Y-ZrO 2 bicrystals

Weak links were fabricated by pulsed laser deposition of YBa 2Cu3Ox thin films on Y-ZrO2 bicrystal substrates. They were formed by transferring the bicrystal boundary into the epitaxial film during the film growth. Their properties were determined by the misorientation angle ( theta ) between the two halves of the bicrystal. The transport properties of the weak links were studied as a function of theta and an exponential dependence of the weak link critical current density was observed for angles up to 45 degrees . Clear Josephson effects with good microwave and magnetic field response were observed.

Weak links and dc SQUIDS on artificial nonsymmetric grain boundaries in YBa2Cu3O7-δ

We have studied weak links and dc-SQUIDs made from pulsed laser deposited YBa2Cu3O7-δ thin films on Y-ZrO 2 bicrystal substrates. The transport properties of the weak links were studied as a function of the misorientation angle (θ) between the two halves of the bicrystal and an exponential dependence of the weak link critical current density was observed for angles up to 40°at 77 K. Josephson effects with clear microwave and magnetic field responses were observed. An optimum dc-SQUID performance at 77 K was obtained for θ=32°. At this temperature, we achieved a periodic magnetic field response with a modulation depth of 12 μV.

YBa2Cu3O7/NdGaO3/YBa 2Cu3O7 trilayers by modified off-axis sputtering

High-quality epitaxial YBa2Cu3O7-δ (YBCO) thin films were achieved by a modified off-axis sputtering technique with high deposition rates (3.3 nm/min). The film quality and the deposition rate depended crucially on the target-to-substrate separation. Epitaxial YBCO/NdGaO3(NGO)/YBCO trilayers were successfully grown onto SrTiO3, Y-ZrO2, and LaAlO3 substrates by dc and rf sputtering. The epitaxial relations were found to be [001] YBCO//[001]NGO, [100]YBCO, or [010] YBCO//[110]NGO and [001]YBCO//[110] NGO, [100]YBCO, or [010]YBCO//[001] NGO, where the latter orientation relationship was dominating. Subsequent top YBCO layers grew c axis oriented independently of the two epitaxial orientations of the NGO. The orientation relationships between YBCO and NGO were the same. Auger electron depth profiles and transmission electron microscopy indicated that the interdiffusion at the interface between the YBCO and NGO layers was not strong even at 740°C. The superconducting transition temperatures of the top and bottom YBCO layers were about the same as that of YBCO single layers, i.e., 87-90 K. Scanning electron microscopy of the surface morphologies of the YBCO and the NGO showed that a smaller substrate-target distance resulted in smoother films.