Infrared and infrared emission spectroscopy of gallium oxide α-GaO(OH) nanostructures

Infrared spectroscopy has been used to study nano to micro sized gallium oxyhydroxide α-GaO(OH), prepared using a low temperature hydrothermal route. Rod-like α-GaO(OH) crystals with average length of ~2.5 μm and width of 1.5 μm were prepared when the initial molar ratio of Ga to OH was 1:3. β-Ga2O3 nano and micro-rods were prepared through the calcination of α-GaO(OH) The initial morphology of α-GaO(OH) is retained in the β-Ga2O3 nanorods. The combination of infrared and infrared emission spectroscopy complimented with dynamic thermal analysis were used to characterise the α-GaO(OH) nanotubes and the formation of β-Ga2O3 nanorods. Bands at around 2903 and 2836 cm-1 are assigned to the -OH stretching vibration of α-GaO(OH) nanorods. Infrared bands at around 952 and 1026 cm-1 are assigned to the Ga-OH deformation modes of α-GaO(OH). A significant number of bands are observed in the 620 to 725 cm-1 region and are assigned to GaO stretching vibrations.

Psychosocial outcomes of Hong Kong Chinese diagnosed with acute coronary syndromes: a prospective repeated measures study.

BACKGROUND: Western studies have suggested that emotional stress and distress impacted on the morbidity and mortality in people following acute coronary events. Symptoms of anxiety and depression have been associated with re-infarction and death, prolonged recovery and disability and depression may precipitate the client's low self-esteem. This study examined perceived anxiety, depression and self-esteem of Hong Kong Chinese clients diagnosed with acute coronary syndrome (ACS) over a 6-month period following hospital admission. OBJECTIVES: To examine: DESIGN: A prospective, repeated measures design with measures taken on two occasions over a 6-month period; (1) within the 1st week of hospital admission following the onset of ACS and (2) at 6 months follow up. SETTING AND PARTICIPANTS: Convenient sample of 182 voluntary consented clients admitted with ACS to a major public hospital in Hong Kong who could communicate in Chinese, complete questionnaires, cognitive intact, and were haemodynamically stable and free from acute chest pain at the time of interview. METHODS: Baseline data were obtained within 1 week after hospital admission. The follow-up data was collected 6 months after hospital discharge. The Chinese version of the Hospital Anxiety and Depression Scale (HADS), State Self-esteem Scale (SSES), and Rosenberg's Self-Esteem Scale (RSES) were used to assess anxiety and depression, state self-esteem, and trait self-esteem, respectively. RESULTS: Findings suggested gender differences in clients' perception in anxiety, depression and self-esteem. Improvements in clients' perception of these variables were evident over the 6-month period following their acute coronary events. CONCLUSION: The study confirmed the western notion that psychosocial problems are common among coronary clients and this also applies to Hong Kong Chinese diagnosed with ACS. Further studies to explore effective interventions to address these psychosocial issues are recommended.

Fold back current control and admittance protection scheme for a distribution network containing distributed generators

Islanded operation, protection, reclosing and arc extinguishing are some of the challenging issues related to the connection of converter interfaced distributed generators (DGs) into a distribution network. The isolation of upstream faults in grid connected mode and fault detection in islanded mode using overcurrent devices are difficult. In the event of an arc fault, all DGs must be disconnected in order to extinguish the arc. Otherwise, they will continue to feed the fault, thus sustaining the arc. However, the system reliability can be increased by maximising the DG connectivity to the system: therefore, the system protection scheme must ensure that only the faulted segment is removed from the feeder. This is true even in the case of a radial feeder as the DG can be connected at various points along the feeder. In this paper, a new relay scheme is proposed which, along with a novel current control strategy for converter interfaced DGs, can isolate permanent and temporary arc faults. The proposed protection and control scheme can even coordinate with reclosers. The results are validated through PSCAD/EMTDC simulation and MATLAB calculations.

Stochastic analysis of the VEGF receptor response curve

Recently, an analysis of the response curve of the vascular endothelial growth factor (VEGF) receptor and its application to cancer therapy was described in [T. Alarcón, and K. Page, J. R. Soc. Lond. Interface 4, 283–304 (2007)]. The analysis is significantly extended here by demonstrating that an alternative computational strategy, namely the Krylov FSP algorithm for the direct solution of the chemical master equation, is feasible for the study of the receptor model. The new method allows us to further investigate the hypothesis of symmetry in the stochastic fluctuations of the response. Also, by augmenting the original model with a single reversible reaction we formulate a plausible mechanism capable of realizing a bimodal response, which is reported experimentally but which is not exhibited by the original model. The significance of these findings for mechanisms of tumour resistance to antiangiogenic therapy is discussed.

Body composition and its relationship to metabolic risk factors in Asian children

Obesity is a major public health problem in both developed and developing countries. The body mass index (BMI) is the most common index used to define obesity. The universal application of the same BMI classification across different ethnic groups is being challenged due to the inability of the index to differentiate fat mass (FM) and fat�]free mass (FFM) and the recognized ethnic differences in body composition. A better understanding of the body composition of Asian children from different backgrounds would help to better understand the obesity�]related health risks of people in this region. Moreover, the limitations of the BMI underscore the necessity to use where possible, more accurate measures of body fat assessment in research and clinical settings in addition to BMI, particularly in relation to the monitoring of prevention and treatment efforts. The aim of the first study was to determine the ethnic difference in the relationship between BMI and percent body fat (%BF) in pre�]pubertal Asian children from China, Lebanon, Malaysia, the Philippines, and Thailand. A total of 1039 children aged 8�]10 y were recruited using a non�]random purposive sampling approach aiming to encompass a wide BMI range from the five countries. Percent body fat (%BF) was determined using the deuterium dilution technique to quantify total body water (TBW) and subsequently derive proportions of FM and FFM. The study highlighted the sex and ethnic differences between BMI and %BF in Asian children from different countries. Girls had approximately 4.0% higher %BF compared with boys at a given BMI. Filipino boys tended to have a lower %BF than their Chinese, Lebanese, Malay and Thai counterparts at the same age and BMI level (corrected mean %BF was 25.7�}0.8%, 27.4�}0.4%, 27.1�}0.6%, 27.7�}0.5%, 28.1�}0.5% for Filipino, Chinese, Lebanese, Malay and Thai boys, respectively), although they differed significantly from Thai and Malay boys. Thai girls had approximately 2.0% higher %BF values than Chinese, Lebanese, Filipino and Malay counterparts (however no significant difference was seen among the four ethnic groups) at a given BMI (corrected mean %BF was 31.1�}0.5%, 28.6�}0.4%, 29.2�}0.6%, 29.5�}0.6%, 29.5�}0.5% for Thai, Chinese, Lebanese, Malay and Filipino girls, respectively). However, the ethnic difference in BMI�]%BF relationship varied by BMI. Compared with Caucasians, Asian children had a BMI 3�]6 units lower for a given %BF. More than one third of obese Asian children in the study were not identified using the WHO classification and more than half were not identified using the International Obesity Task Force (IOTF) classification. However, use of the Chinese classification increased the sensitivity by 19.7%, 18.1%, 2.3%, 2.3%, and 11.3% for Chinese, Lebanese, Malay, Filipino and Thai girls, respectively. A further aim of the first study was to determine the ethnic difference in body fat distribution in pre�]pubertal Asian children from China, Lebanon, Malaysia, and Thailand. The skin fold thicknesses, height, weight, waist circumference (WC) and total adiposity (as determined by deuterium dilution technique) of 922 children from the four countries was assessed. Chinese boys and girls had a similar trunk�]to�]extremity skin fold thickness ratio to Thai counterparts and both groups had higher ratios than the Malays and Lebanese at a given total FM. At a given BMI, both Chinese and Thai boys and girls had a higher WC than Malays and Lebanese (corrected mean WC was 68.1�}0.2 cm, 67.8�}0.3 cm, 65.8�}0.4 cm, 64.1�}0.3 cm for Chinese, Thai, Lebanese and Malay boys, respectively; 64.2�}0.2 cm, 65.0�}0.3 cm, 62.9�}0.4 cm, 60.6�}0.3 cm for Chinese, Thai, Lebanese and Malay girls, respectively). Chinese boys and girls had lower trunk fat adjusted subscapular/suprailiac skinfold ratio compared with Lebanese and Malay counterparts. The second study aimed to develop and cross�]validate bioelectrical impedance analysis (BIA) prediction equations of TBW and FFM for Asian pre�]pubertal children from China, Lebanon, Malaysia, the Philippines, and Thailand. Data on height, weight, age, gender, resistance and reactance measured by BIA were collected from 948 Asian children (492 boys and 456 girls) aged 8�]10 y from the five countries. The deuterium dilution technique was used as the criterion method for the estimation of TBW and FFM. The BIA equations were developed from the validation group (630 children randomly selected from the total sample) using stepwise multiple regression analysis and cross�]validated in a separate group (318 children) using the Bland�]Altman approach. Age, gender and ethnicity influenced the relationship between the resistance index (RI = height2/resistance), TBW and FFM. The BIA prediction equation for the estimation of TBW was: TBW (kg) = 0.231�~Height2 (cm)/resistance (ƒ¶) + 0.066�~Height (cm) + 0.188�~Weight (kg) + 0.128�~Age (yr) + 0.500�~Sex (male=1, female=0) . 0.316�~Ethnicity (Thai ethnicity=1, others=0) �] 4.574, and for the estimation of FFM: FFM (kg) = 0.299�~Height2 (cm)/resistance (ƒ¶) + 0.086�~Height (cm) + 0.245�~Weight (kg) + 0.260�~Age (yr) + 0.901�~Sex (male=1, female=0) �] 0.415�~Ethnicity (Thai ethnicity=1, others=0) �] 6.952. The R2 was 88.0% (root mean square error, RSME = 1.3 kg), 88.3% (RSME = 1.7 kg) for TBW and FFM equation, respectively. No significant difference between measured and predicted TBW and between measured and predicted FFM for the whole cross�]validation sample was found (bias = �]0.1�}1.4 kg, pure error = 1.4�}2.0 kg for TBW and bias = �]0.2�}1.9 kg, pure error = 1.8�}2.6 kg for FFM). However, the prediction equation for estimation of TBW/FFM tended to overestimate TBW/FFM at lower levels while underestimate at higher levels of TBW/FFM. Accuracy of the general equation for TBW and FFM compared favorably with both BMI�]specific and ethnic�]specific equations. There were significant differences between predicted TBW and FFM from external BIA equations derived from Caucasian populations and measured values in Asian children. There were three specific aims of the third study. The first was to explore the relationship between obesity and metabolic syndrome and abnormalities in Chinese children. A total of 608 boys and 800 girls aged 6�]12 y were recruited from four cities in China. Three definitions of pediatric metabolic syndrome and abnormalities were used, including the International Diabetes Federation (IDF) and National Cholesterol Education Program (NCEP) definition for adults modified by Cook et al. and de Ferranti et al. The prevalence of metabolic syndrome varied with different definitions, was highest using the de Ferranti definition (5.4%, 24.6% and 42.0%, respectively for normal�]weight, overweight and obese children), followed by the Cook definition (1.5%, 8.1%, and 25.1%, respectively), and the IDF definition (0.5%, 1.8% and 8.3%, respectively). Overweight and obese children had a higher risk of developing the metabolic syndrome compared to normal�]weight children (odds ratio varied with different definitions from 3.958 to 6.866 for overweight children, and 12.640�]26.007 for obese children). Overweight and obesity also increased the risk of developing metabolic abnormalities. Central obesity and high triglycerides (TG) were the most common while hyperglycemia was the least frequent in Chinese children regardless of different definitions. The second purpose was to determine the best obesity index for the prediction of cardiovascular (CV) risk factor clustering across a 2�]y follow�]up among BMI, %BF, WC and waist�]to�]height ratio (WHtR) in Chinese children. Height, weight, WC, %BF as determined by BIA, blood pressure, TG, high�]density lipoprotein cholesterol (HDL�]C), and fasting glucose were collected at baseline and 2 years later in 292 boys and 277 girls aged 8�]10 y. The results showed the percentage of children who remained overweight/obese defined on the basis of BMI, WC, WHtR and %BF was 89.7%, 93.5%, 84.5%, and 80.4%, respectively after 2 years. Obesity indices at baseline significantly correlated with TG, HDL�]C, and blood pressure at both baseline and 2 years later with a similar strength of correlations. BMI at baseline explained the greatest variance of later blood pressure. WC at baseline explained the greatest variance of later HDL�]C and glucose, while WHtR at baseline was the main predictor of later TG. Receiver�]operating characteristic (ROC) analysis explored the ability of the four indices to identify the later presence of CV risk. The overweight/obese children defined on the basis of BMI, WC, WHtR or %BF were more likely to develop CV risk 2 years later with relative risk (RR) scores of 3.670, 3.762, 2.767, and 2.804, respectively. The final purpose of the third study was to develop age�] and gender�]specific percentiles of WC and WHtR and cut�]off points of WC and WHtR for the prediction of CV risk in Chinese children. Smoothed percentile curves of WC and WHtR were produced in 2830 boys and 2699 girls aged 6�]12 y randomly selected from southern and northern China using the LMS method. The optimal age�] and gender�]specific thresholds of WC and WHtR for the prediction of cardiovascular risk factors clustering were derived in a sub�]sample (n=1845) by ROC analysis. Age�] and gender�]specific WC and WHtR percentiles were constructed. The WC thresholds were at the 90th and 84th percentiles for Chinese boys and girls, respectively, with sensitivity and specificity ranging from 67.2% to 83.3%. The WHtR thresholds were at the 91st and 94th percentiles for Chinese boys and girls, respectively, with sensitivity and specificity ranging from 78.6% to 88.9%. The cut�]offs of both WC and WHtR were age�] and gender�]dependent. In conclusion, the current thesis quantifies the ethnic differences in the BMI�]%BF relationship and body fat distribution between Asian children from different origins and confirms the necessity to consider ethnic differences in body composition when developing BMI and other obesity index criteria for obesity in Asian children. Moreover, ethnicity is also important in BIA prediction equations. In addition, WC and WHtR percentiles and thresholds for the prediction of CV risk in Chinese children differ from other populations. Although there was no advantage of WC or WHtR over BMI or %BF in the prediction of CV risk, obese children had a higher risk of developing the metabolic syndrome and abnormalities than normal�]weight children regardless of the obesity index used.

Are motivational deficits part of the behavioural phenotype of Down syndrome?

Motivational deficits are generally accepted to be part of the behavioural phenotype associated with Down syndrome (DS). A motivational profile comprising low or inconsistent levels of task persistence, avoidance of challenging activities and over-dependence on adult direction has been described. However, comparisons are usually made between children with DS and those who are developing typically, without the inclusion of samples with intellectual disability (ID) from aetiologies other than DS. Such comparisons are needed to determine the extent to which motivational deficits are specific to DS, as opposed to being a feature of ID generally. Methods: The current study collected data about the personality-motivation profiles of children in three groups matched for mental age. They consisted of 80 typically developing (TD)3–7 year old children, 62 children with DS aged 7–15 years, and 54 children with moderate ID aged 7–15 years. Parents completed the 37-item EZ-Personality Questionnaire (EZPQ; Zigler et al., 2002), a measure of personality-motivational functioning. Results: There were significant differences between TD children and those with ID on all EZPQ scales. In most respects children with DS did not differ significantly from others with moderate ID, although they were rated as having greater expectancy of success and fewer negative reactions. Conclusion: The finding that children with DS are less motivated than TD children of the same mental age is consistent with previous studies in which parents have rated motivation. It seems, however, that motivation difficulties are associated with ID more generally, rather than being specific to those with DS. The study raises questions about phenotypic versus experiential effects on motivation for children with ID.

Anthropogenic landscape change promotes asymmetric dispersal and limits regional patch occupancy in a spatially structured bird population

1. Local extinctions in habitat patches and asymmetric dispersal between patches are key processes structuring animal populations in heterogeneous environments. Effective landscape conservation requires an understanding of how habitat loss and fragmentation influence demographic processes within populations and movement between populations. 2. We used patch occupancy surveys and molecular data for a rainforest bird, the logrunner (Orthonyx temminckii), to determine (i) the effects of landscape change and patch structure on local extinction; (ii) the asymmetry of emigration and immigration rates; (iii) the relative influence of local and between-population landscapes on asymmetric emigration and immigration; and (iv) the relative contributions of habitat loss and habitat fragmentation to asymmetric emigration and immigration. 3. Whether or not a patch was occupied by logrunners was primarily determined by the isolation of that patch. After controlling for patch isolation, patch occupancy declined in landscapes experiencing high levels of rainforest loss over the last 100 years. Habitat loss and fragmentation over the last century was more important than the current pattern of patch isolation alone, which suggested that immigration from neighbouring patches was unable to prevent local extinction in highly modified landscapes. 4. We discovered that dispersal between logrunner populations is highly asymmetric. Emigration rates were 39% lower when local landscapes were fragmented, but emigration was not limited by the structure of the between-population landscapes. In contrast, immigration was 37% greater when local landscapes were fragmented and was lower when the between-population landscapes were fragmented. Rainforest fragmentation influenced asymmetric dispersal to a greater extent than did rainforest loss, and a 60% reduction in mean patch area was capable of switching a population from being a net exporter to a net importer of dispersing logrunners. 5. The synergistic effects of landscape change on species occurrence and asymmetric dispersal have important implications for conservation. Conservation measures that maintain large patch sizes in the landscape may promote asymmetric dispersal from intact to fragmented landscapes and allow rainforest bird populations to persist in fragmented and degraded landscapes. These sink populations could form the kernel of source populations given sufficient habitat restoration. However, the success of this rescue effect will depend on the quality of the between-population landscapes.

Infrared and Raman spectroscopic characterization of the borate mineral hydroboracite CaMg[B3O4(OH)3]2⋅3H2O : implications for the molecular structure

We have studied the mineral hydroboracite CaMg[B3O4(OH)3]2∙3H2O using electron microscopy and vibrational spectroscopy. Both tetrahedral and trigonal boron units are observed. The nominal resolution of the Raman spectrometer is of the order of 2 cm-1 and as such is sufficient enough to identify separate bands for the stretching bands of the two boron isotopes. The Raman band at 1039 cm-1 is assigned to BO stretching vibration. Raman bands at 1144, 1157, 1229, 1318 cm-1 are attributed to the BOH in-plane bending modes. Raman bands at 825 and 925 cm-1 are attributed to the antisymmetric stretching modes of tetrahedral boron. The sharp Raman peak at 925 cm-1 is from the 11-B component such a mode, then it should have a smaller 10-B satellite near (1.03)x(925) = 952 cm-1, and indeed a small peak at 955 is observed. Four sharp Raman bands observed at 3371, 3507, 3563 and 3632 cm-1 are attributed to the stretching vibrations of hydroxyl units. The broad Raman bands at 3076, 3138, 3255, 3384 and 3551 cm-1 are assigned to water stretching vibrations. Infrared bands at 3367, 3505, 3559 and 3631 cm-1are assigned to the stretching vibration of the hydroxyl units. Broad infrared bands at 3072 and 3254 cm-1 are assigned to water stretching vibrations. Infrared bands at 1318, 1349, 1371, 1383 cm-1 are assigned to the antisymmetric stretching vibrations of trigonal boron

Determinants and treatment of hypertension in South Africans: The first demographic and health survey

Objectives: To identify the groups of patients with high prevalence and poor control of hypertension in South Africa. Methods: In the first national Demographic and Health Survey, 12 952 randomly selected South Africans, aged 15 years and older were surveyed. Trained interviewers completed questionnaires on socio-demographic characteristics, lifestyle and the management of hypertension. This cross-sectional survey also included blood pressure, height and weight measurements. Logistic regression analyses identified the determinants of hypertension and the treatment status in this dataset. Results: A high risk of hypertension was associated with less than tertiary education, older age groups, overweight and obese people, using alcohol in excess, and a family history of stroke and hypertension. Rural Africans had the lowest risk of hypertension, which was significantly higher in obese African women than in women with normal body mass index. Improved hypertension control was found in the wealthy, women, older persons, being Asian, and having medical insurance. Conclusions: Rural African people had lower hypertension prevalence rates than the other groups. The poorer, younger men, without health insurance had the worst level of hypertension control.

Identifying risk factors and protective factors for venous leg ulcer recurrence using a theoretical approach : a longitudinal study

Background The high recurrence rate of chronic venous leg ulcers has a significant impact on an individual’s quality of life and healthcare costs. Objectives This study aimed to identify risk and protective factors for recurrence of venous leg ulcers using a theoretical approach by applying a framework of self and family management of chronic conditions to underpin the study. Design Secondary analysis of combined data collected from three previous prospective longitudinal studies. Setting The contributing studies’ participants were recruited from two metropolitan hospital outpatient wound clinics and three community-based wound clinics. Participants Data were available on a sample of 250 adults, with a leg ulcer of primarily venous aetiology, who were followed after ulcer healing for a median follow-up time of 17 months after healing (range: 3 to 36 months). Methods Data from the three studies were combined. The original participant data were collected through medical records and self-reported questionnaires upon healing and every 3 months thereafter. A Cox proportion-hazards regression analysis was undertaken to determine the influential factors on leg ulcer recurrence based on the proposed conceptual framework. Results The median time to recurrence was 42 weeks (95% CI 31.9–52.0), with an incidence of 22% (54 of 250 participants) recurrence within three months of healing, 39% (91 of 235 participants) for those who were followed for six months, 57% (111 of 193) by 12 months, 73% (53 of 72) by two years and 78% (41 of 52) of those who were followed up for three years. A Cox proportional-hazards regression model revealed that the risk factors for recurrence included a history of deep vein thrombosis (HR 1.7, 95% CI 1.07–2.67, p=0.024), history of multiple previous leg ulcers (HR 4.4, 95% CI 1.84–10.5, p=0.001), and longer duration (in weeks) of previous ulcer (HR 1.01, 95% CI 1.003–1.01, p<0.001); while the protective factors were elevating legs for at least 30 minutes per day (HR 0.33, 95% CI 0.19–0.56, p<0.001), higher levels of self-efficacy (HR 0.95, 95% CI 0.92–0.99, p=0.016), and walking around for at least three hours/day (HR 0.66, 95% CI 0.44–0.98, p=0.040). Conclusions Results from this study provide a comprehensive examination of risk and protective factors associated with leg ulcer recurrence based on the chronic disease self and family management framework. These results in turn provide essential steps towards developing and testing interventions to promote optimal prevention strategies for venous leg ulcer recurrence.

Robust conservation decision-making

Decision-making for conservation is conducted within the margins of limited funding. Furthermore, to allocate these scarce resources we make assumptions about the relationship between management impact and expenditure. The structure of these relationships, however, is rarely known with certainty. We present a summary of work investigating the impact of model uncertainty on robust decision-making in conservation and how this is affected by available conservation funding. We show that achieving robustness in conservation decisions can require a triage approach, and emphasize the need for managers to consider triage not as surrendering but as rational decision making to ensure species persistence in light of the urgency of the conservation problems, uncertainty, and the poor state of conservation funding. We illustrate this theory by a specific application to allocation of funding to reduce poaching impact on the Sumatran tiger Panthera tigris sumatrae in Kerinci Seblat National Park, Indonesia. To conserve our environment, conservation managers must make decisions in the face of substantial uncertainty. Further, they must deal with the fact that limitations in budgets and temporal constraints have led to a lack of knowledge on the systems we are trying to preserve and on the benefits of the actions we have available (Balmford & Cowling 2006). Given this paucity of decision-informing data there is a considerable need to assess the impact of uncertainty on the benefit of management options (Regan et al. 2005). Although models of management impact can improve decision making (e.g.Tenhumberg et al. 2004), they typically rely on assumptions around which there is substantial uncertainty. Ignoring this 'model uncertainty', can lead to inferior decision-making (Regan et al. 2005), and potentially, the loss of the species we are trying to protect. Current methods used in ecology allow model uncertainty to be incorporated into the model selection process (Burnham & Anderson 2002; Link & Barker 2006), but do not enable decision-makers to assess how this uncertainty would change a decision. This is the basis of information-gap decision theory (info-gap); finding strategies most robust to model uncertainty (Ben-Haim 2006). Info-gap has permitted conservation biology to make the leap from recognizing uncertainty to explicitly incorporating severe uncertainty into decision-making. In this paper we present a summary of McDonald-Madden et al (2008a) who use an info-gap framework to address the impact of uncertainty in the functional representations of biological systems on conservation decision-making. Furthermore, we highlight the importance of two key elements limiting conservation decision-making - funding and knowledge - and how they interact to influence the best management strategy for a threatened species. Copyright © ASCE 2011.

Novel risk loci for rheumatoid arthritis in Han Chinese and congruence with risk variants in Europeans

Objective To investigate differences in genetic risk factors for rheumatoid arthritis (RA) in Han Chinese as compared with Europeans. Methods A genome-wide association study was conducted in China with 952 patients and 943 controls, and 32 variants were followed up in 2,132 patients and 2,553 controls. A transpopulation meta-analysis with results from a large European RA study was also performed to compare the genetic architecture across the 2 ethnic remote populations. Results Three non-major histocompatibility complex (non-MHC) loci were identified at the genome-wide significance level, the effect sizes of which were larger in anti-citrullinated protein antibody (ACPA)-positive patients than in ACPA-negative patients. These included 2 novel variants, rs12617656, located in an intron of DPP4 (odds ratio [OR] 1.56, P = 1.6 × 10 -21), and rs12379034, located in the coding region of CDK5RAP2 (OR 1.49, P = 1.1 × 10-16), as well as a variant at the known CCR6 locus, rs1854853 (OR 0.71, P = 6.5 × 10-15). The analysis of ACPA-positive patients versus ACPA-negative patients revealed that rs12617656 at the DPP4 locus showed a strong interaction effect with ACPAs (P = 5.3 × 10-18), and such an interaction was also observed for rs7748270 at the MHC locus (P = 5.9 × 10-8). The transpopulation meta-analysis showed genome-wide overlap and enrichment in association signals across the 2 populations, as confirmed by prediction analysis. Conclusion This study has expanded the list of alleles that confer risk of RA, provided new insight into the pathogenesis of RA, and added empirical evidence to the emerging polygenic nature of complex trait variation driven by common genetic variants. Copyright © 2014 by the American College of Rheumatology.

No evidence for genetic association with the let-7 microRNA-binding site or other common KRAS variants in risk of endometriosis

STUDY QUESTION Is there a contribution of the minor allele at the KRAS single nucleotide polymorphism (SNP) rs61764370 in the let-7 microRNA-binding site to endometriosis risk? SUMMARY ANSWER We found no evidence for association between endometriosis risk and rs61764370 or any other SNPs in KRAS. WHAT IS KNOWN ALREADY The rs61764370 SNP in the 3' untranslated region of the KRAS gene is predicted to disrupt a complementary binding site (LCS6) for the let-7 microRNA, and was recently reported to be at a high frequency (31%) in 132 women of varying ancestry with endometriosis compared with frequencies in a database of population controls (up to 7.6% depending on ancestry), suggesting a strong effect of this KRAS SNP in the aetiology of endometriosis. STUDY DESIGN, SIZE AND DURATION This was a case-control study with a total of 11 206 subjects. The study was performed between February 2012 and July 2012. PARTICIPANTS/MATERIALS, SETTINGAND METHODS We first investigated a possible association between common markers in KRAS and endometriosis risk from our genome-wide association (GWA) data in 3194 surgically confirmed endometriosis cases and 7060 controls of European ancestry. Although rs61764370 was not genotyped on the GWA arrays, five SNPs typed in the study were highly correlated with this variant. The rs61764370 and two SNPs highly correlated with rs61764370 were then genotyped in 933 endometriosis cases and 952 controls using the Sequenom MassARRAY platform. MAIN RESULTS AND THE ROLE OF CHANCE There was no evidence for an association between rs61764370 and endometriosis risk P = 0.411 and odds ratio = 1.10 (95% confidence intervals: 0.88-1.36). We also found no evidence for an association between the highly correlated SNP rs17387019 and endometriosis. Their minor allele frequencies in cases and controls were of 0.087-0.091 similar to the population frequency reported previously for this variant in controls. Analyses of endometriosis cases with revised American Fertility Society stage III/IV disease also showed no evidence for an association between these SNPs and endometriosis risk. LIMITATIONS AND REASONS FOR CAUTION The GWA and genotyped data sets were not independent since individuals and cases from some families overlap. Controls in our GWA study were not screened for endometriosis. WIDER IMPLICATIONS OF THE FINDINGS The key SNP, rs61764370, was genotyped in a subset of samples. Our results do not support the suggestion that carrying the minor allele at rs61764370 contributes to a significant number of endometriosis cases and rs61764370 is, therefore, unlikely to be a useful marker of endometriosis risk. STUDY FUNDING/COMPETING INTEREST(S) The research was funded by grants from the Australian National Health and Medical Research Council and Wellcome Trust. None of the authors has competing interests for the study.