Virtual countries: Internet domain names and geographical terms

This paper examines the dispute between the Seattle company Virtual Countries Inc. and the Republic of South Africa over the ownership of the domain name address southafrica.com. The first part of the paper deals with the pre-emptive litigation taken by Virtual Countries Inc. in a District Court of the United States. The second part considers the possible arbitration of the dispute under the Uniform Domain Name Dispute Resolution Process of the Internet Corporation for Assigned Names and Numbers (ICANN) and examines the wider implications of this dispute for the jurisdiction and the governance of ICANN. The final section of the paper evaluates the Final Report of the Second WIPO Internet Domain Name Process.

The chromosome 16q region associated with ankylosing spondylitis includes the candidate gene tumour necrosis factor receptor type 1-associated death domain (TRADD)

Objective: To replicate and refine the reported association of ankylosing spondylitis (AS) with two nonsynonymous single nucleotide polymorphisms (nsSNPs) on chromosome 16q22.1. Methods: Firstly, 730 independent UK patients with AS were genotyped for rs9939768 and rs6979 and allele frequencies were compared with 2879 previously typed historic disease controls. Secondly, the two data sets were combined in meta-analyses. Finally, 5 tagging SNPs, located between rs9939768 and rs6979, were analysed in 1604 cases and 1020 controls. Results: The association of rs6979 with AS was replicated, p=0.03, OR=1.14 (95% CI 1.01 to 1.28), and a trend for association with rs9939768 detected, p=0.06, OR=1.25 (95% CI 0.99 to 1.57). Meta-analyses revealed association of both SNPs with AS, p=0.0008, OR=1.31 (95% CI 1.12 to 1.54) and p=0.0009, OR=1.15 (95% CI 1.06 to 1.23) for rs9939768 and rs6979, respectively. New associations with rs9033 and rs868213 (p=0.00002, OR=1.23 (95% CI 1.12 to 1.36) and p=0.00002 OR=1.45 (95% CI 1.22 to 1.72), respectively, were identified. Conclusions: The region on chromosome 16 that has been replicated in the present work is interesting as the highly plausible candidate gene, tumour necrosis factor receptor type 1 (TNFR1)-associated death domain (TRADD), is located between rs9033 and rs868213. It will require additional work to identify the primary genetic association(s) with AS.

Association of sporadic chondrocalcinosis with a -4-basepair G-to-A transition in the 5′-untranslated region of ANKH that promotes enhanced expression of ANKH protein and excess generation of extracellular inorganic pyrophosphate

Objective Certain mutations in ANKH, which encodes a multiple-pass transmembrane protein that regulates inorganic pyrophosphate (PPi) transport, are linked to autosomal-dominant familial chondrocalcinosis. This study investigated the potential for ANKH sequence variants to promote sporadic chondrocalcinosis. Methods ANKH variants identified by genomic sequencing were screened for association with chondrocalcinosis in 128 patients with severe sporadic chondrocalcinosis or pseudogout and in ethnically matched healthy controls. The effects of specific variants on expression of common markers were evaluated by in vitro transcription/translation. The function of these variants was studied in transfected human immortalized CH-8 articular chondrocytes. Results Sporadic chondrocalcinosis was associated with a G-to-A transition in the ANKH 5′-untranslated region (5′-UTR) at 4 bp upstream of the start codon (in homozygotes of the minor allele, genotype relative risk 6.0, P = 0.0006; overall genotype association P = 0.02). This -4-bp transition, as well as 2 mutations previously linked with familial and sporadic chondrocalcinosis (+14 bp C-to-T and C-terminal GAG deletion, respectively), but not the French familial chondrocalcinosis kindred 143-bp T-to-C mutation, increased reticulocyte ANKH transcription/ANKH translation in vitro. Transfection of complementary DNA for both the wild-type ANKH and the -4-bp ANKH protein variant promoted increased extracellular PPi in CH-8 cells, but unexpectedly, these ANKH mutants had divergent effects on the expression of extracellular PPi and the chondrocyte hypertrophy marker, type X collagen. Conclusion A subset of sporadic chondrocalcinosis appears to be heritable via a -4-bp G-to-A ANKH 5′-UTR transition that up-regulates expression of ANKH and extracellular PPi in chondrocyte cells. Distinct ANKH mutations associated with heritable chondrocalcinosis may promote disease by divergent effects on extracellular PPi and chondrocyte hypertrophy, which is likely to mediate differences in the clinical phenotypes and severity of the disease.

New England Youth Speeding Project: A pilot study of young drivers and risky driving: Effective strategies for preventing speeding amongst young Australians aged 16-25 years in the New England Region

Young Australian drivers aged 17 – 25 years are overwhelmingly represented in road fatalities where speed is a factor. In the combined LGAs of Armidale Dumaresq, Guyra, Uralla and Walcha in the 5 years 1999-2003 inclusive, 43% of speeding related casualty crashes involved a young driver aged less than 25 years. This is despite the fact that the 17-25 age group account for only 25% of the driving population in this area. Young male drivers account for the majority of these crashes and also tend to have a higher number of driving offences and accrue more penalties for road traffic offences, especially speeding. By analysing data from questionnaires by male and female participants this research project has been able to evaluate road safety advertisements to determine which ones are most effective to young drivers, what features of these advertisements are effective, how males differ from females in their receptiveness and preferences for road safety advertisements and specifically how to target young people especially young men in conveying road safety messages. Finally this research project has identified factors that are important in the production of media road safety advertisements and has made recommendations for how best to convey effective road safety messages to young Australian drivers in rural areas.

Global variation in the effects of ambient temperature on mortality: A systematic evaluation

Background: Studies have examined the effects of temperature on mortality in a single city, country, or region. However, less evidence is available on the variation in the associations between temperature and mortality in multiple countries, analyzed simultaneously. Methods: We obtained daily data on temperature and mortality in 306 communities from 12 countries/regions (Australia, Brazil, Thailand, China, Taiwan, Korea, Japan, Italy, Spain, United Kingdom, United States, and Canada). Two-stage analyses were used to assess the nonlinear and delayed relation between temperature and mortality. In the first stage, a Poisson regression allowing overdispersion with distributed lag nonlinear model was used to estimate the community-specific temperature-mortality relation. In the second stage, a multivariate meta-analysis was used to pool the nonlinear and delayed effects of ambient temperature at the national level, in each country. Results: The temperatures associated with the lowest mortality were around the 75th percentile of temperature in all the countries/regions, ranging from 66th (Taiwan) to 80th (UK) percentiles. The estimated effects of cold and hot temperatures on mortality varied by community and country. Meta-analysis results show that both cold and hot temperatures increased the risk of mortality in all the countries/regions. Cold effects were delayed and lasted for many days, whereas heat effects appeared quickly and did not last long. Conclusions: People have some ability to adapt to their local climate type, but both cold and hot temperatures are still associated with increased risk of mortality. Public health strategies to alleviate the impact of ambient temperatures are important, in particular in the context of climate change.

Incidence and mortality of female breast cancer in the Asia-Pacific region

Objective: To provide an overview of the incidence and mortality of female breast cancer for countries in the Asia-Pacific region. Methods: Statistical information about breast cancer was obtained from publicly available cancer registry and mortality databases (such as GLOBOCAN), and supplemented with data requested from individual cancer registries. Rates were directly age-standardised to the Segi World Standard population and trends were analysed using joinpoint models. Results: Breast cancer was the most common type of cancer among females in the region, accounting for 18% of all cases in 2012, and was the fourth most common cause of cancer-related deaths (9%). Although incidence rates remain much higher in New Zealand and Australia, rapid rises in recent years were observed in several Asian countries. Large increases in breast cancer mortality rates also occurred in many areas, particularly Malaysia and Thailand, in contrast to stabilising trends in Hong Kong and Singapore, while decreases have been recorded in Australia and New Zealand. Mortality trends tended to be more favourable for women aged under 50 compared to those who were 50 years or older. Conclusion: It is anticipated that incidence rates of breast cancer in developing countries throughout the Asia-Pacific region will continue to increase. Early detection and access to optimal treatment are the keys to reducing breast cancer-related mortality, but cultural and economic obstacles persist. Consequently, the challenge is to customise breast cancer control initiatives to the particular needs of each country to ensure the best possible outcomes.

The effects of high temperature on cardiovascular admissions in the most populous tropical city in Vietnam

This study examined the short-term effects of temperature on cardiovascular hospital admissions (CHA) in the largest tropical city in Southern Vietnam. We applied Poisson time-series regression models with Distributed Lag Non-Linear Model (DLNM) to examine the temperature-CHA association while adjusting for seasonal and long-term trends, day of the week, holidays, and humidity. The threshold temperature and added effects of heat waves were also evaluated. The exposure-response curve of temperature-CHA reveals a J-shape relationship with a threshold temperature of 29.6 °C. The delayed effects temperature-CHA lasted for a week (0–5 days). The overall risk of CHA increased 12.9% (RR, 1.129; 95%CI, 0.972–1.311) during heatwave events, which were defined as temperature ≥ the 99th percentile for ≥2 consecutive days. The modification roles of gender and age were inconsistent and non-significant in this study. An additional prevention program that reduces the risk of cardiovascular disease in relation to high temperatures should be developed.

Estimating daily and diurnal variations of illicit drug use in Hong Kong: A pilot study of using wastewater analysis in an Asian metropolitan city

The measurement of illicit drug metabolites in raw wastewater is increasingly being adopted as an approach to objectively monitor population-level drug use, and is an effective complement to traditional epidemiological methods. As such, it has been widely applied in western countries. In this study, we utilised this approach to assess drug use patterns over nine days during April 2011 in Hong Kong. Raw wastewater samples were collected from the largest wastewater treatment plant serving a community of approximately 3.5 million people and analysed for excreted drug residues including cocaine, ketamine, methamphetamine, 3,4-methylenedioxymethamphetamine (MDMA) and key metabolites using liquid chromatography coupled with tandem mass spectrometry. The overall drug use pattern determined by wastewater analysis was consistent with that have seen amongst people coming into contact with services in relation to substance use; among our target drugs, ketamine (estimated consumption: 1400–1600 mg/day/1000 people) was the predominant drug followed by methamphetamine (180–200 mg/day/1000 people), cocaine (160–180 mg/day/1000 people) and MDMA (not detected). The levels of these drugs were relatively steady throughout the monitoring period. Analysing samples at higher temporal resolution provided data on diurnal variations of drug residue loads. Elevated ratios of cocaine to benzoylecgonine were identified unexpectedly in three samples during the evening and night, providing evidence for potential dumping events of cocaine. This study provides the first application of wastewater analysis to quantitatively evaluate daily drug use in an Asian metropolitan community. Our data reinforces the benefit of wastewater monitoring to health and law enforcement authorities for strategic planning and evaluation of drug intervention strategies.

Violence against children in the Asia Pacific region: the situation is becoming clearer [Editorial]

Up to the year 2000, there was very little scientific evidence in this region about the scale of child maltreatment, its effects on children, families, and society, and the resultant economic burden. Since then, many agencies large and small, government and nongovernment, and universitybased researchers have worked independently with diverse groups of people to measure violence, neglect and other childhood adversities and to understand the harmful consequences...

The burden of child maltreatment in the East Asia and Pacific region

This study estimated the health and economic burden of child maltreatment in the East Asia and Pacific region, addressing a significant gap in the current evidence base. Systematic reviews and meta-analyses were conducted to estimate the prevalence of child physical abuse, sexual abuse, emotional abuse, neglect, and witnessing parental violence. Population Attributable Fractions were calculated and Disability-Adjusted Life Years (DALYs) lost from physical and mental health outcomes and health risk behaviors attributable to child maltreatment were estimated using the most recent comparable Global Burden of Disease data. DALY losses were converted into monetary value by assuming that one DALY is equal to the sub-region’s per capita GDP. The estimated economic value of DALYs lost to violence against children as a percentage of GDP ranged from 1.24% to 3.46% across sub-regions defined by the World Health Organization. The estimated economic value of DALYs (in constant 2000 US$) lost to child maltreatment in the EAP region totaled US $151 billion, accounting for 1.88% of the region’s GDP. Updated to 2012 dollars, the estimated economic burden totaled US $194 billion. In sensitivity analysis, the aggregate costs as a percentage of GDP range from 1.36% to 2.52%. The economic burden of child maltreatment in the East Asia and Pacific region is substantial, indicating the importance of preventing and responding to child maltreatment in this region. More comprehensive research into the impact of multiple types of childhood adversity on a wider range of putative health outcomes is needed to guide policy and programs for child protection in the region, and globally.

Genome-wide association study of intraocular pressure identifies the GLCCI1/ICA1 region as a glaucoma susceptibility locus

To discover quantitative trait loci for intraocular pressure, amajor risk factor for glaucoma and the only modifiable one,weperformed agenome-wide association studyonadiscoverycohort of2175individualsfromSydney, Australia. We found a novel association between intraocular pressure and a common variant at 7p21 near to GLCCI1 and ICA1. The findings in this region were confirmed through two UK replication cohorts totalling 4866 individuals (rs59072263, Pcombined = 1.10 × 10-8). A copy of the G allele at this SNP is associated with an increase in mean IOP of 0.45 mmHg (95%CI = 0.30-0.61 mmHg). These results lend support to the implication of vesicle trafficking and glucocorticoid inducibility pathways in the determination of intraocular pressure and in the pathogenesis of primary open-angle glaucoma.

Common variants in the HLA-DRB1-HLA-DQA1 HLA class II region are associated with susceptibility to visceral leishmaniasis

To identify susceptibility loci for visceral leishmaniasis, we undertook genome-wide association studies in two populations: 989 cases and 1,089 controls from India and 357 cases in 308 Brazilian families (1,970 individuals). The HLA-DRB1-HLA-DQA1 locus was the only region to show strong evidence of association in both populations. Replication at this region was undertaken in a second Indian population comprising 941 cases and 990 controls, and combined analysis across the three cohorts for rs9271858 at this locus showed P combined = 2.76 × 10 -17 and odds ratio (OR) = 1.41, 95% confidence interval (CI) = 1.30-1.52. A conditional analysis provided evidence for multiple associations within the HLA-DRB1-HLA-DQA1 region, and a model in which risk differed between three groups of haplotypes better explained the signal and was significant in the Indian discovery and replication cohorts. In conclusion, the HLA-DRB1-HLA-DQA1 HLA class II region contributes to visceral leishmaniasis susceptibility in India and Brazil, suggesting shared genetic risk factors for visceral leishmaniasis that cross the epidemiological divides of geography and parasite species. © 2013 Nature America, Inc. All rights reserved.

Common variants in the region around Osterix are associated with bone mineral density and growth in childhood

Peak bone mass achieved in adolescence is a determinant of bone mass in later life. In order to identify genetic variants affecting bone mineral density (BMD), we performed a genome-wide association study of BMD and related traits in 1518 children from the Avon Longitudinal Study of Parents and Children (ALSPAC). We compared results with a scan of 134 adults with high or low hip BMD. We identified associations with BMD in an area of chromosome 12 containing the Osterix (SP7) locus, a transcription factor responsible for regulating osteoblast differentiation (ALSPAC: P = 5.8 × 10-4; Australia: P = 3.7 × 10-4). This region has previously shown evidence of association with adult hip and lumbar spine BMD in an Icelandic population, as well as nominal association in a UK population. A meta-analysis of these existing studies revealed strong association between SNPs in the Osterix region and adult lumbar spine BMD (P = 9.9 × 10-11). In light of these findings, we genotyped a further 3692 individuals from ALSPAC who had whole body BMD and confirmed the association in children as well (P = 5.4 × 10-5). Moreover, all SNPs were related to height in ALSPAC children, but not weight or body mass index, and when height was included as a covariate in the regression equation, the association with total body BMD was attenuated. We conclude that genetic variants in the region of Osterix are associated with BMD in children and adults probably through primary effects on growth.

Genome-wide association study of ulcerative colitis identifies three new susceptibility loci, including the HNF4A region

Ulcerative colitis is a common form of inflammatory bowel disease with a complex etiology. As part of the Wellcome Trust Case Control Consortium 2, we performed a genome-wide association scan for ulcerative colitis in 2,361 cases and 5,417 controls. Loci showing evidence of association at P 1 × 10 5 were followed up by genotyping in an independent set of 2,321 cases and 4,818 controls. We find genome-wide significant evidence of association at three new loci, each containing at least one biologically relevant candidate gene, on chromosomes 20q13 (HNF4A; P = 3.2 × 10 17), 16q22 (CDH1 and CDH3; P = 2.8 × 10 8) and 7q31 (LAMB1; P = 3.0 × 10 8). Of note, CDH1 has recently been associated with susceptibility to colorectal cancer, an established complication of longstanding ulcerative colitis. The new associations suggest that changes in the integrity of the intestinal epithelial barrier may contribute to the pathogenesis of ulcerative colitis. © 2009 Nature America, Inc. All rights reserved.