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A simple low-cost sand catcher has been developed for use in wind-tunnel experiments. It is 500 mm high with a 300 mm by 20 mm inlet opening, and is designed to measure total mass transport directly. The length is 280 mm and its walls slowly expand at an angle of 5·6°. The top view is similar to that of the widely used BSNE sampler. Each sidewall is vented with three ventilation screens. Two sets of experiments were conducted on dune sand and at different wind velocities to investigate to what degree the catcher samples isokinetically, efficiently and non-selectively. The results indicate that the catcher measures sufficiently isokinetically (inlet wind velocity over outside wind velocity >0·9). Catch efficiency was around 0·75 and the degree of non-selectivity was >0·80 for 95 per cent of the particle sizes of the test material. It was also observed that the influence of wind velocity on the tested sampler characteristics was of minor importance so that no specific corrections need to be made for different wind velocities. Copyright © 2003 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Study region: Upper Blue Nile Basin, Ethiopia. Study focus: This study was conducted at the Koga Irrigation Scheme in the upper Blue Nile basin (Ethiopia) to investigate the influence of irrigation activity on the groundwater system. Representative samples of six shallow wells in the irrigated fields and four shallow wells in the adjacent non-irrigated (rain-fed agricultural lands) were selected. Dipmeter and hand GPS (GARMIN 60) were used for the monitoring of water table depth and fixing the location of the wells respectively. Arc GIS 10.5 has been applied for interpolation of water table depth (WTD). Water samples were collected and analyzed in the laboratory following international standards. New hydrological insights for the region: The result shows that irrigation contributed to the water table rises of wells located in the irrigated fields which range from 0.77 m to 0.52 m and water table drops were observed in wells located in the non-irrigated fields. Investigations on the groundwater quality (GWQ) indicated that no significant effect was observed in the irrigated and non-irrigated fields. The study shows that good irrigation water management, continuous follow-up of the groundwater table and its physico-chemical properties are essential for the sustainability of the Koga Irrigation Scheme.

This study assessed farmers’ soil and irrigation water management practices, perceptions, and major constraints at Koga, a large-scale irrigation scheme in Ethiopia. Key informant interviews, structured and semi-structured questionnaires, focus group discussions, and field visits were used for data collection. Soil samples were collected for the assessment of soil properties and a comparison with the respondents’ perception of soil-related constraints. A total of 385 respondents were involved in the questionnaire. All of the respondents had a good perception of soil acidity and its management strategies. Respondents’ perception was in line with the mean soil pH, soil texture, infiltration rate, exchangeable acidity, and soil organic carbon obtained from lab analysis and field tests. Soil acidity, unwise use of water, water scarcity, and lack of market linkages hampered the performance of the Koga irrigation scheme. Yet, respondents had a low awareness of irrigation water management. Farmers never used irrigation scheduling, but apply the same amount of water regardless of the crop type. As a result, low yield and water use efficiency were reported. To reduce soil acidity, an adequate lime supply for farmers with hands-on training on how to apply it would be desirable. Farmers should be aware of how to design effective irrigation scheduling and adopt water-saving management strategies.

Competing Interests: Mathieu Pioche is co-funder of ATRACT device, and also consultant for Olympus, Pentax, Erbe, Boston for training in ESD. Other authors have nothing to disclose

Background and Objectives: Patients with dentofacial deformity (DFD) requiring orthognathic treatment have poor aesthetics, jaw function and psychological well-being, which potentially affect the quality of life. This study aimed to investigate the health-related general, oral and orthognathic quality of life, jaw function and sleep-disordered breathing at different stages of orthognathic surgical treatment., Methods: A total of 120 consecutive patients with DFD were recruited and grouped as pre-orthodontic treatment (group 1), pre-surgery (group 2), 4 months post-surgery (group 3), 24 months post-surgery (group 4) and in addition 30 controls without DFD (group 0). Outcomes were assessed using general health Short Form Survey (SF-36), Oral Health Impact (OHIP-14), Orthognathic Quality of Life Questionnaire (OQLQ), STOP-Bang and Jaw Function Limitation Scale (JFLS) questionnaires. In addition, presence or absence of pain was recorded. Data were tested with analysis of variance, Kruskal-Wallis test, Tukey post hoc test and structural equation modelling (SEM)., Results: Results revealed SF-36 (p = .814) and STOP-Bang (p = .143) total scores did not differ between control and treatment groups. In contrast, OHIP-14, OQLQ and JFLS total scores differed between groups (p = .001). Higher scores were observed in groups 1 (p = .001), 2 (p = .001) and 3 (p = .041) compared to group 0, indicating poor oral health in patients with DFD. Importantly, in group 4, oral health-related quality of life was better, and OHIP-14 (p = .936) and JFLS (p = .572) scores did not differ from controls. OQLQ scores of group 4 were significantly lower than group 1 (p = .001) but higher than group 0 (p = .013). SEM results revealed a significant negative associations of pain with JFLS and OQLQ; OHIP-14 with OQLQ; OHIP-14 with SF-36; and finally STOP-Bang with SF-36. Positive associations were observed between JFLS and OHIP-14; OHIP-14 and OQLQ., Conclusion: Oral health-related quality of life and jaw function appears to be improved 24 months after orthognathic surgery. Pain and limitation in jaw function had a negative association with health-related quality of life., (© 2023 John Wiley & Sons Ltd.)

Background and Objective: Patients with dentofacial deformity often present with impaired masticatory function, orofacial pain and temporomandibular disorders (TMD). This study investigates the relationship between TMD, pain, jaw and masticatory function at different stages of orthognathic surgical (OS) treatment., Methods: A total of 120 OS patients were prospectively recruited and grouped as pre-orthodontic (group 1), pre-surgery (group 2), 4-month post-surgery (group 3), 24-month post-surgery (group 4), in addition to 30 controls (group 0). Outcomes were assessed using: Jaw Function Limitation Scale (JFLS), McGill pain questionnaire, DC/TMD instrument, voluntary maximum bite force (MVBF), and masticatory efficiency (ME) using two-coloured chewing gum. Data were analysed using structural equation modelling., Results: The prevalence of non-painful TMD did not differ between groups (p = .827). However, the prevalence of painful TMD differed between groups (p = .001). Among the painful TMDs, the highest prevalence was observed for masseter myalgia in group 2 (p = .031), and importantly group 4 did not differ from group 0 (p = .948). The MPQ score was significantly higher in group 1 (p = .001) compared to group 0, and the JFLS score was significantly higher in groups 1, 2 and 3 compared to group 0. Notably, MPQ (p = .756) and JFLS (p = .572) scores in group 4 were not different from group 0. However, MVBF (p = .996) and ME (p = .991) did not differ between groups 1 and 4. The association of self-reported pain and jaw function with the masticatory function was observed in OS patients., Conclusion: OS was not associated with a negative impact on TMD. Jaw function and pain levels were similar to controls at the 24-month follow-up. The masticatory function was further affected by the surgery and seems to require a longer recovery time. Moreover, it was confirmed that pain and TMD were associated with limitations in jaw function and impacts on masticatory function., (© 2023 The Authors. Journal of Oral Rehabilitation published by John Wiley & Sons Ltd.)

The aim of this study was to retrospectively evaluate pharyngeal airway (PA) changes after bimaxillary surgery (BMS). Preoperative, immediate- and 5-year postoperative cone-beam computed tomography images of subjects who underwent BMS were assessed. The primary outcome variable was the PA volume. The secondary outcome variables were the retropalatal and oropharyngeal volumes, cross-sectional area, minimal hydraulic diameter, soft tissue, skeletal movements and sleep-disordered breathing (SDB). A total of 50 patients were included, 33 female and 17 male, with a mean age of 26.5 years. A significant increase in the PA volume was seen immediately after surgery (40%), and this increase was still present at 5-year follow-up (34%) (P < 0.001). A linear mixed model regression analysis revealed that a mandibular advancement of ≥5 mm (P = 0.025) and every 1-mm upward movement of epiglottis (P = 0.016) was associated with a volume increase of the oropharyngeal compartment. Moreover, ≥5-mm upward movement of hyoid bone (P = 0.034) and every 1-mm increase in minimal hydraulic diameter (P < 0.001) correlated with an increase of the PA volume. A total of 30 subjects reported improvement in the SDB at 5-year follow-up. This study demonstrated that BMS led to an increase in PA dimensions in non-OSA patients, and these changes were still present at 5-year follow-up. BMS seemed to induce clinical improvement in SDB., Competing Interests: Declaration of competing interest All authors have no competing interests to declare., (Copyright © 2022. Published by Elsevier Ltd.)

In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (F ROH ) for >1.4 million individuals, we show that F ROH is significantly associated (p < 0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: F ROH equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44-66%] in the odds of having children. Finally, the effects of F ROH are confirmed within full-sibling pairs, where the variation in F ROH is independent of all environmental confounding.

Rationale: Higher social integration is associated with lower cardiovascular mortality; however, whether it is associated with incident coronary heart disease (CHD), especially in women, and whether associations differ by case fatality are unclear., Objectives: This study sought to examine the associations between social integration and risk of incident CHD in a large female prospective cohort., Methods and Results: Seventy-six thousand three hundred and sixty-two women in the Nurses' Health Study, free of CHD and stroke at baseline (1992), were followed until 2014. Social integration was assessed by a simplified Berkman-Syme Social Network Index every 4 years. End points included nonfatal myocardial infarction and fatal CHD. Two thousand three hundred and seventy-two incident CHD events occurred throughout follow-up. Adjusting for demographic, health/medical risk factors, and depressive symptoms, being socially integrated was significantly associated with lower CHD risk, particularly fatal CHD. The most socially integrated women had a hazard ratio of 0.55 (95% confidence interval, 0.41-0.73) of developing fatal CHD compared with those least socially integrated ( P for trend <0.0001). When additionally adjusting for lifestyle behaviors, findings for fatal CHD were maintained but attenuated ( P for trend =0.02), whereas the significant associations no longer remained for nonfatal myocardial infarction. The inverse associations between social integration and nonfatal myocardial infarction risk were largely explained by health-promoting behaviors, particularly through differences in cigarette smoking; however, the association with fatal CHD risk remained after accounting for these behaviors and, thus, may involve more direct biological mechanisms., Conclusions: Social integration is inversely associated with CHD incidence in women, but is largely explained by lifestyle/behavioral pathways., (© 2017 American Heart Association, Inc.)

Plasma fetuin-A is associated with type 2 diabetes, and AHSG, the gene encoding fetuin-A, has been identified as a susceptibility locus for diabetes and metabolic syndrome. Thus far, unbiased investigations of the genetic determinants of plasma fetuin-A concentrations have not been conducted. We searched for single nucleotide polymorphisms (SNPs) related to fetuin-A concentrations by a genome-wide association study in six population-based studies. We examined the association of fetuin-A levels with ∼ 2.5 million genotyped and imputed SNPs in 9,055 participants of European descent and 2,119 African Americans. In both ethnicities, the strongest associations were centered in a region with a high degree of LD near the AHSG locus. Among 136 genome-wide significant (P < 0.05 × 10-8) SNPs near the AHSG locus, the top SNP was rs4917 (P =1.27 × 10-303), a known coding SNP in exon 6 that is associated with a 0.06 g/l (∼13%) lower fetuin-A level. This variant alone explained 14% of the variation in fetuin-A levels. Analyses conditioned on rs4917 indicated that the strong association with the AHSG locus stems from additional independent associations of multiple variants among European Americans. In conclusion, levels of fetuin-A in plasma are strongly associated with SNPs in its encoding gene, AHSG, but not elsewhere in the genome. Given the strength of the associations observed for multiple independent SNPs, the AHSG gene is an example of a candidate locus suitable for additional investigations including fine mapping to elucidate the biological basis of the findings and further functional experiments to clarify AHSG as a potential therapeutic target., (Published by Oxford University Press 2017. This work is written by US Government employees and is in the public domain in the US.)

Physical activity (PA) may modify the genetic effects that give rise to increased risk of obesity. To identify adiposity loci whose effects are modified by PA, we performed genome-wide interaction meta-analyses of BMI and BMI-adjusted waist circumference and waist-hip ratio from up to 200,452 adults of European (n = 180,423) or other ancestry (n = 20,029). We standardized PA by categorizing it into a dichotomous variable where, on average, 23% of participants were categorized as inactive and 77% as physically active. While we replicate the interaction with PA for the strongest known obesity-risk locus in the FTO gene, of which the effect is attenuated by ~30% in physically active individuals compared to inactive individuals, we do not identify additional loci that are sensitive to PA. In additional genome-wide meta-analyses adjusting for PA and interaction with PA, we identify 11 novel adiposity loci, suggesting that accounting for PA or other environmental factors that contribute to variation in adiposity may facilitate gene discovery.

The Nurses' Health Study (NHS), Nurses' Health Study II (NHSII), Health Professionals Follow Up Study (HPFS) and the Physicians Health Study (PHS) have collected detailed longitudinal data on multiple exposures and traits for approximately 310,000 study participants over the last 35 years. Over 160,000 study participants across the cohorts have donated a DNA sample and to date, 20,691 subjects have been genotyped as part of genome-wide association studies (GWAS) of twelve primary outcomes. However, these studies utilized six different GWAS arrays making it difficult to conduct analyses of secondary phenotypes or share controls across studies. To allow for secondary analyses of these data, we have created three new datasets merged by platform family and performed imputation using a common reference panel, the 1,000 Genomes Phase I release. Here, we describe the methodology behind the data merging and imputation and present imputation quality statistics and association results from two GWAS of secondary phenotypes (body mass index (BMI) and venous thromboembolism (VTE)). We observed the strongest BMI association for the FTO SNP rs55872725 (β = 0.45, p = 3.48x10-22), and using a significance level of p = 0.05, we replicated 19 out of 32 known BMI SNPs. For VTE, we observed the strongest association for the rs2040445 SNP (OR = 2.17, 95% CI: 1.79-2.63, p = 2.70x10-15), located downstream of F5 and also observed significant associations for the known ABO and F11 regions. This pooled resource can be used to maximize power in GWAS of phenotypes collected across the cohorts and for studying gene-environment interactions as well as rare phenotypes and genotypes.

Background: Genome-wide association studies (GWAS) have made little progress in identifying variants linked to depression. We hypothesized that examining depressive symptoms and considering gene-environment interaction (GxE) might improve efficiency for gene discovery. We therefore conducted a GWAS and genome-wide by environment interaction study (GWEIS) of depressive symptoms., Methods: Using data from the SHARe cohort of the Women's Health Initiative, comprising African Americans (n = 7,179) and Hispanics/Latinas (n = 3,138), we examined genetic main effects and GxE with stressful life events and social support. We also conducted a heritability analysis using genome-wide complex trait analysis (GCTA). Replication was attempted in four independent cohorts., Results: No SNPs achieved genome-wide significance for main effects in either discovery sample. The top signals in African Americans were rs73531535 (located 20 kb from GPR139, P = 5.75 × 10(-8) ) and rs75407252 (intronic to CACNA2D3, P = 6.99 × 10(-7) ). In Hispanics/Latinas, the top signals were rs2532087 (located 27 kb from CD38, P = 2.44 × 10(-7) ) and rs4542757 (intronic to DCC, P = 7.31 × 10(-7) ). In the GEWIS with stressful life events, one interaction signal was genome-wide significant in African Americans (rs4652467; P = 4.10 × 10(-10) ; located 14 kb from CEP350). This interaction was not observed in a smaller replication cohort. Although heritability estimates for depressive symptoms and stressful life events were each less than 10%, they were strongly genetically correlated (rG = 0.95), suggesting that common variation underlying self-reported depressive symptoms and stressful life event exposure, though modest on their own, were highly overlapping in this sample., Conclusions: Our results underscore the need for larger samples, more GEWIS, and greater investigation into genetic and environmental determinants of depressive symptoms in minorities., (© 2016 Wiley Periodicals, Inc.)

The Patagonian subregion belongs to the Andean region, and is comprised of two provinces: Central Patagonia and Subandean Patagonia. It extends from central Mendoza, widening through Neuquén, Río Negro, Chubut, and Santa Cruz, to northern Tierra del Fuego, and reaches Chile (Morrone 2006). The knowledge of terrestrial Heteroptera in this region is poor and is limited to a few contributions (e.g. Berg 1979, Breddin 1898, Pennington 1920, Faúndez & Carvajal 2011, Faundez 2015).

Background: Mendelian Randomization (MR) studies have reported that type 2 diabetes (T2D) was not associated with Alzheimer disease (AD). We adopted a modified, mechanism-specific MR design to explore this surprising result., Methods: Using inverse-variance weighted MR analysis, we evaluated the association between T2D and AD using data from 39 single nucleotide polymorphisms (SNPs) significantly associated with T2D in DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) and the corresponding associations of each SNP with AD risk obtained from the International Genomics of Alzheimer's Project (IGAP, n=17,008 AD cases and n=37,154 controls). We evaluated mechanism-specific genetic subscores, including β-cell function, insulin sensitivity, and adiposity, and repeated analyses in 8501 Health and Retirement Study participants for replication and model validation., Results: In IGAP, the overall T2D polygenic score did not predict AD [odds ratio (OR) for the T2D polygenic score=1.01; 95% confidence interval (CI), 0.96, 1.06] but the insulin sensitivity polygenic score predicted higher AD risk (OR=1.17; 95% CI, 1.02, 1.34). In the Health and Retirement Study, polygenic scores were associated with T2D risk; the associations between insulin sensitivity genetic polygenic score and cognitive phenotypes were not statistically significant., Conclusions: Evidence from polygenic scores suggests that insulin sensitivity specifically may affect AD risk, more than T2D overall.

Usual sleep duration is a heritable trait correlated with psychiatric morbidity, cardiometabolic disease and mortality, although little is known about the genetic variants influencing this trait. A genome-wide association study (GWAS) of usual sleep duration was conducted using 18 population-based cohorts totaling 47 180 individuals of European ancestry. Genome-wide significant association was identified at two loci. The strongest is located on chromosome 2, in an intergenic region 35- to 80-kb upstream from the thyroid-specific transcription factor PAX8 (lowest P=1.1 × 10(-9)). This finding was replicated in an African-American sample of 4771 individuals (lowest P=9.3 × 10(-4)). The strongest combined association was at rs1823125 (P=1.5 × 10(-10), minor allele frequency 0.26 in the discovery sample, 0.12 in the replication sample), with each copy of the minor allele associated with a sleep duration 3.1 min longer per night. The alleles associated with longer sleep duration were associated in previous GWAS with a more favorable metabolic profile and a lower risk of attention deficit hyperactivity disorder. Understanding the mechanisms underlying these associations may help elucidate biological mechanisms influencing sleep duration and its association with psychiatric, metabolic and cardiovascular disease.

Background: Obesity and anxiety are often linked but the direction of effects is not clear., Method: Using genetic instrumental variable (IV) analyses in 5911 female participants from the Nurses' Health Study (NHS, initiated 1976) and 3697 male participants from the Health Professional Follow-up Study (HPFS, initiated 1986), we aimed to determine whether obesity increases symptoms of phobic anxiety. As instrumental variables we used the fat mass and obesity-associated (FTO) gene, the melanocortin 4 receptor (MC4R) gene and a genetic risk score (GRS) based on 32 single nucleotide polymorphisms (SNPs) that significantly predict body mass index (BMI). 'Functional' GRSs corresponding with specific biological pathways that shape BMI (adipogenesis, appetite and cardiopulmonary) were considered. The main outcome was phobic anxiety measured by the Crown Crisp Index (CCI) in 2004 in the NHS and in 2000 in the HPFS., Results: In observational analysis, a 1-unit higher BMI was associated with higher phobic anxiety symptoms [women: β = 0.05, 95% confidence interval (CI) 0.030-0.068; men: β = 0.04, 95% CI 0.016-0.071). IV analyses showed that BMI was associated with higher phobic anxiety symptoms in the FTO-instrumented analysis (p = 0.005) but not in the GRS-instrumented analysis (p = 0.256). Functional GRSs showed heterogeneous, non-significant effects of BMI on phobic anxiety symptoms., Conclusions: Our findings do not provide conclusive evidence in favor of the hypothesis that higher BMI leads to higher levels of phobic anxiety, but rather suggest that genes that influence obesity, in particular FTO, may have direct effects on phobic anxiety, and hence that obesity and phobic anxiety may share common genetic determinants.

We give critical attention to the assumptions underlying Mendelian randomization analysis and their biological plausibility. Several scenarios violating the Mendelian randomization assumptions are described, including settings with inadequate phenotype definition, the setting of time-varying exposures, the presence of gene-environment interaction, the existence of measurement error, the possibility of reverse causation, and the presence of linkage disequilibrium. Data analysis examples are given, illustrating that the inappropriate use of instrumental variable techniques when the Mendelian randomization assumptions are violated can lead to biases of enormous magnitude. To help address some of the strong assumptions being made, three possible approaches are suggested. First, the original proposal of Katan (Lancet. 1986;1:507-508) for Mendelian randomization was not to use instrumental variable techniques to obtain estimates but merely to examine genotype-outcome associations to test for the presence of an effect of the exposure on the outcome. We show that this more modest goal and approach can circumvent many, though not all, the potential biases described. Second, we discuss the use of sensitivity analysis in evaluating the consequences of violations in the assumptions and in attempting to correct for those violations. Third, we suggest that a focus on negative, rather than positive, Mendelian randomization results may turn out to be more reliable.

Background: According to the Federal Institution of Health Insurance, ENT doctors perform more skin prick tests for the diagnosis of allergic rhinitis (AR) than other medical specialties in Belgium. However, immunotherapy (IT) is not practiced by all. This study aims to obtain insight into IT practice by ENT doctors, the type of IT performed and the reasons not to perform IT., Methodology: A questionnaire was sent to all registered ENT doctors of Belgium (n=648), involving questions on type and duration of ENT practice, geography and gender. In addition, the questionnaire informed about diagnosis of AR, indication for IT, type of IT performed, and reasons not to perform IT and referral pattern., Results: The response rate among ENT doctors was 54%, with 7% of responders being excluded as they do not diagnose AR. 81% of Belgian ENT doctors make the indication for IT in AR patients, with 19% neglecting the indication for IT in AR patients. The two main reasons for not indicating IT are lack of expertise and the perception of high costs associated with IT. 70% of ENT specialists are practicing IT themselves, with sublingual IT being mostly performed. Interestingly, IT is mostly frequently performed by those ENT doctors with long-standing ENT practice, in private practice and in Wallonia., Conclusion: Despite the high prevalence of AR in ENT practice, IT is most frequently performed by ENT doctors with longstanding practice, working in private practice and/or in the French speaking part of Belgium. Among the different types of IT, sublingual IT is the most frequently performed means of IT by ENT doctors.

Context: Anxiety disorders are common, with a lifetime prevalence of 20% in the U.S., and are responsible for substantial burdens of disability, missed work days and health care utilization. To date, no causal genetic variants have been identified for anxiety, anxiety disorders, or related traits., Objective: To investigate whether a phobic anxiety symptom score was associated with 3 alternative polygenic risk scores, derived from external genome-wide association studies of anxiety, an internally estimated agnostic polygenic score, or previously identified candidate genes., Design: Longitudinal follow-up study. Using linear and logistic regression we investigated whether phobic anxiety was associated with polygenic risk scores derived from internal, leave-one out genome-wide association studies, from 31 candidate genes, and from out-of-sample genome-wide association weights previously shown to predict depression and anxiety in another cohort., Setting and Participants: Study participants (n = 11,127) were individuals from the Nurses' Health Study and Health Professionals Follow-up Study., Main Outcome Measure: Anxiety symptoms were assessed via the 8-item phobic anxiety scale of the Crown Crisp Index at two time points, from which a continuous phenotype score was derived., Results: We found no genome-wide significant associations with phobic anxiety. Phobic anxiety was also not associated with a polygenic risk score derived from the genome-wide association study beta weights using liberal p-value thresholds; with a previously published genome-wide polygenic score; or with a candidate gene risk score based on 31 genes previously hypothesized to predict anxiety., Conclusion: There is a substantial gap between twin-study heritability estimates of anxiety disorders ranging between 20-40% and heritability explained by genome-wide association results. New approaches such as improved genome imputations, application of gene expression and biological pathways information, and incorporating social or environmental modifiers of genetic risks may be necessary to identify significant genetic predictors of anxiety.

In Argentina, five genera and 14 species are recorded in the subfamilies Prostemmatinae and Nabinae: Hoplistoscelis sordidus Reuter, Lasiomerus constrictus Champion, Metatropiphorus alvarengai Reuter, Nabis argentinus Meyer-Dür, Nabis (Tropiconabis) capsiformis Germar, Nabis faminei Stål, Nabis paranensis Harris, Nabis punctipennis Blanchard, Nabis roripes Stål, Nabis setricus Harris, Nabis tandilensis Berg, Pagasa (Pagasa) costalis Reuter, Pagasa (Lampropagasa) fuscipennis Reuter and Pagasa (Pagasa) signatipennis Reuter.

African Americans are disproportionately affected by type 2 diabetes (T2DM) yet few studies have examined T2DM using genome-wide association approaches in this ethnicity. The aim of this study was to identify genes associated with T2DM in the African American population. We performed a Genome Wide Association Study (GWAS) using the Affymetrix 6.0 array in 965 African-American cases with T2DM and end-stage renal disease (T2DM-ESRD) and 1029 population-based controls. The most significant SNPs (n = 550 independent loci) were genotyped in a replication cohort and 122 SNPs (n = 98 independent loci) were further tested through genotyping three additional validation cohorts followed by meta-analysis in all five cohorts totaling 3,132 cases and 3,317 controls. Twelve SNPs had evidence of association in the GWAS (P<0.0071), were directionally consistent in the Replication cohort and were associated with T2DM in subjects without nephropathy (P<0.05). Meta-analysis in all cases and controls revealed a single SNP reaching genome-wide significance (P<2.5×10(-8)). SNP rs7560163 (P = 7.0×10(-9), OR (95% CI) = 0.75 (0.67-0.84)) is located intergenically between RND3 and RBM43. Four additional loci (rs7542900, rs4659485, rs2722769 and rs7107217) were associated with T2DM (P<0.05) and reached more nominal levels of significance (P<2.5×10(-5)) in the overall analysis and may represent novel loci that contribute to T2DM. We have identified novel T2DM-susceptibility variants in the African-American population. Notably, T2DM risk was associated with the major allele and implies an interesting genetic architecture in this population. These results suggest that multiple loci underlie T2DM susceptibility in the African-American population and that these loci are distinct from those identified in other ethnic populations.

Circulating levels of adiponectin, a hormone produced predominantly by adipocytes, are highly heritable and are inversely associated with type 2 diabetes mellitus (T2D) and other metabolic traits. We conducted a meta-analysis of genome-wide association studies in 39,883 individuals of European ancestry to identify genes associated with metabolic disease. We identified 8 novel loci associated with adiponectin levels and confirmed 2 previously reported loci (P = 4.5×10(-8)-1.2×10(-43)). Using a novel method to combine data across ethnicities (N = 4,232 African Americans, N = 1,776 Asians, and N = 29,347 Europeans), we identified two additional novel loci. Expression analyses of 436 human adipocyte samples revealed that mRNA levels of 18 genes at candidate regions were associated with adiponectin concentrations after accounting for multiple testing (p<3×10(-4)). We next developed a multi-SNP genotypic risk score to test the association of adiponectin decreasing risk alleles on metabolic traits and diseases using consortia-level meta-analytic data. This risk score was associated with increased risk of T2D (p = 4.3×10(-3), n = 22,044), increased triglycerides (p = 2.6×10(-14), n = 93,440), increased waist-to-hip ratio (p = 1.8×10(-5), n = 77,167), increased glucose two hours post oral glucose tolerance testing (p = 4.4×10(-3), n = 15,234), increased fasting insulin (p = 0.015, n = 48,238), but with lower in HDL-cholesterol concentrations (p = 4.5×10(-13), n = 96,748) and decreased BMI (p = 1.4×10(-4), n = 121,335). These findings identify novel genetic determinants of adiponectin levels, which, taken together, influence risk of T2D and markers of insulin resistance., Competing Interests: DM Waterworth, X Yuan, and VE Mooser are full-time employees of GlaxoSmithKline. P Vollenweider received grant money from GlaxoSmithKline to fund the CoLaus study. The other authors declare no competing financial interests.

Genetic case-control association studies often include data on clinical covariates, such as body mass index (BMI), smoking status, or age, that may modify the underlying genetic risk of case or control samples. For example, in type 2 diabetes, odds ratios for established variants estimated from low-BMI cases are larger than those estimated from high-BMI cases. An unanswered question is how to use this information to maximize statistical power in case-control studies that ascertain individuals on the basis of phenotype (case-control ascertainment) or phenotype and clinical covariates (case-control-covariate ascertainment). While current approaches improve power in studies with random ascertainment, they often lose power under case-control ascertainment and fail to capture available power increases under case-control-covariate ascertainment. We show that an informed conditioning approach, based on the liability threshold model with parameters informed by external epidemiological information, fully accounts for disease prevalence and non-random ascertainment of phenotype as well as covariates and provides a substantial increase in power while maintaining a properly controlled false-positive rate. Our method outperforms standard case-control association tests with or without covariates, tests of gene x covariate interaction, and previously proposed tests for dealing with covariates in ascertained data, with especially large improvements in the case of case-control-covariate ascertainment. We investigate empirical case-control studies of type 2 diabetes, prostate cancer, lung cancer, breast cancer, rheumatoid arthritis, age-related macular degeneration, and end-stage kidney disease over a total of 89,726 samples. In these datasets, informed conditioning outperforms logistic regression for 115 of the 157 known associated variants investigated (P-value = 1 × 10(-9)). The improvement varied across diseases with a 16% median increase in χ(2) test statistics and a commensurate increase in power. This suggests that applying our method to existing and future association studies of these diseases may identify novel disease loci., Competing Interests: The authors have declared that no competing interests exist.

By combining genome-wide association data from 8,130 individuals with type 2 diabetes (T2D) and 38,987 controls of European descent and following up previously unidentified meta-analysis signals in a further 34,412 cases and 59,925 controls, we identified 12 new T2D association signals with combined P<5x10(-8). These include a second independent signal at the KCNQ1 locus; the first report, to our knowledge, of an X-chromosomal association (near DUSP9); and a further instance of overlap between loci implicated in monogenic and multifactorial forms of diabetes (at HNF1A). The identified loci affect both beta-cell function and insulin action, and, overall, T2D association signals show evidence of enrichment for genes involved in cell cycle regulation. We also show that a high proportion of T2D susceptibility loci harbor independent association signals influencing apparently unrelated complex traits.

Glucose levels 2 h after an oral glucose challenge are a clinical measure of glucose tolerance used in the diagnosis of type 2 diabetes. We report a meta-analysis of nine genome-wide association studies (n = 15,234 nondiabetic individuals) and a follow-up of 29 independent loci (n = 6,958-30,620). We identify variants at the GIPR locus associated with 2-h glucose level (rs10423928, beta (s.e.m.) = 0.09 (0.01) mmol/l per A allele, P = 2.0 x 10(-15)). The GIPR A-allele carriers also showed decreased insulin secretion (n = 22,492; insulinogenic index, P = 1.0 x 10(-17); ratio of insulin to glucose area under the curve, P = 1.3 x 10(-16)) and diminished incretin effect (n = 804; P = 4.3 x 10(-4)). We also identified variants at ADCY5 (rs2877716, P = 4.2 x 10(-16)), VPS13C (rs17271305, P = 4.1 x 10(-8)), GCKR (rs1260326, P = 7.1 x 10(-11)) and TCF7L2 (rs7903146, P = 4.2 x 10(-10)) associated with 2-h glucose. Of the three newly implicated loci (GIPR, ADCY5 and VPS13C), only ADCY5 was found to be associated with type 2 diabetes in collaborating studies (n = 35,869 cases, 89,798 controls, OR = 1.12, 95% CI 1.09-1.15, P = 4.8 x 10(-18)).

Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes.

Introduction: Early Class III treatment with reverse-pull headgear generally results in maxillary skeletal protraction but is frequently also accompanied by unfavorable dentoalveolar effects. An alternative treatment with intermaxillary elastics from a temporary anchorage device might permit equivalent favorable skeletal changes without the unwanted dentoalveolar effects., Methods: Six consecutive patients (3 boys, 3 girls; ages, 10-13 years 3 months) with Class III occlusion and maxillary deficiency were treated by using intermaxillary elastics to titanium miniplates. Cone-beam computed tomography scans taken before and after treatment were used to create 3-dimensional volumetric models that were superimposed on nongrowing structures in the anterior cranial base to determine anatomic changes during treatment., Results: The effect of the intermaxillary elastic forces was throughout the nasomaxillary structures. All 6 patients showed improvements in the skeletal relationship, primarily through maxillary advancement with little effect on the dentoalveolar units or change in mandibular position., Conclusions: The use of intermaxillary forces applied to temporary anchorage devices appears to be a promising treatment method.

Background and Objectives: Venous thromboembolism (VTE) is a complex disorder influenced by numerous risk factors, and occurs frequently in at-risk hospitalized patients. Because appropriate prevention with thromboprophylaxis is underused, we wanted to create an electronic tool to provide a simple risk assessment and suggest appropriate prophylaxis., Design and Methods: To develop the risk matrix, iterative rating of odds ratios was performed for 60 predisposing VTE risk factors, using analytical methods that account for multiple risk factors in a single patient and their non-independence. For exposing risk factors, a single score was assigned to each set of factors, both medical (25 items) and surgical conditions (144 items). A CART regression model was used to integrate the risk scales into a 4-level measure of overall risk. The validity of the level of risk and the appropriateness of 11 different prophylactic approaches was assessed using the RAND/UCLA appropriateness method and validated by expert opinion ratings (n=1998) on sample case scenarios (n=108)., Results: Correlation between the level of risk calculated by the risk matrix and that offered by expert opinion for individual surgical and medical clinical cases was high (65% and 70%, respectively). The matrix over-estimated the level of risk, compared with that offered by expert opinion, in 28% and 20% of surgical and medical cases, respectively, but the appropriate prophylaxis suggested was no different. Between-expert agreement on the appropriateness of the prophylaxis recommendations was high (90-94% of indications)., Interpretation and Conclusions: This computer-based electronic tool for individualized assessment of venous thromboembolic risk successfully identified both the perceived risk of thrombosis and the appropriate prophylactic approach for medical and surgical patients.

Purpose: Most patients with colorectal liver metastases present to general surgeons and oncologists without a specialist interest in their management. Since treatment strategy is frequently dependent on the response to earlier treatments, our aim was to create a therapeutic decision model identifying appropriate procedure sequences., Methods: We used the RAND Corporation/University of California, Los Angeles Appropriateness Method (RAM) assessing strategies of resection, local ablation and chemotherapy. After a comprehensive literature review, an expert panel rated appropriateness of each treatment option for a total of 1,872 ratings decisions in 252 cases. A decision model was constructed, consensus measured and results validated using 48 virtual cases, and 34 real cases with known outcomes., Results: Consensus was achieved with overall agreement rates of 93.4 to 99.1%. Absolute resection contraindications included unresectable extrahepatic disease, more than 70% liver involvement, liver failure, and being surgically unfit. Factors not influencing treatment strategy were age, primary tumor stage, timing of metastases detection, past blood transfusion, liver resection type, pre-resection carcinoembryonic antigen (CEA), and previous hepatectomy. Immediate resection was appropriate with adequate radiologically-defined resection margins and no portal adenopathy; other factors included presence of < or = 4 or > 4 metastases and unilobar or bilobar involvement. Resection was appropriate postchemotherapy, independent of tumor response in the case of < or = 4 metastases and unilobar liver involvement. Resection was appropriate only for > 4 metastases or bilobar liver involvement, after tumor shrinkage with chemotherapy. When possible, resection was preferred to local ablation., Conclusion: The results were incorporated into a decision matrix, creating a computer program (OncoSurge). This model identifies individual patient resectability, recommending optimal treatment strategies. It may also be used for medical education.

Mini-implants are increasingly used for orthodontic anchorage. Using a mini-implant as anchorage in uprighting a mandibular molar, the need for other orthodontic appliances is minimal. Furthermore, the treatment is not evoking any risk of disturbing the occlusion, since other teeth are not loaded. Depending on a good control of the applied forces and the extrusion of the molar during uprighting, the orthodontic treatment can be simple and not burdening the patient.

From 1999 until 2001, 3625 food samples were examined for the presence of Escherichia coli O157. Samples were from bovine origin (ground beef, n=549; carcasses, n=2452), calves (carcasses, n=147), chicken (breast, n=203; carcasses, n=71) and pigs (carcasses, n=85; trimmings, n=118). Vidas ECO detected 451 (12%) samples positive, but from only 27 (0.74%) samples was E. coli O157 isolated. One strain was isolated from bovine ground beef (0.18%), one from a pig carcass (1.17%) and all others were isolated from bovine carcasses (1.02%). All strains possessed the attaching-and-effacing gene, the enterohemorrhagic plasmid and verotoxin (VT) genes, except the strain isolated from the pig carcass that was therefore eliminated. Six of the strains were urease-positive. Strains were typed by two DNA fingerprinting methods: random amplification of polymorphic DNA (RAPD) and pulsed field gel electrophoresis (PFGE). PFGE revealed a similarity of 71.05%, while RAPD was 77.36% similar. None of the typing methods were able to classify all urease-positive strains to one pattern. Strains in the same PFGE cluster did not belong to one RAPD cluster. This paper highlights that Belgian fresh meat at retail level can be contaminated with E. coli O157 and that two different typing methods divide strains into different types.

Campylobacter spp. are a frequent cause of diarrhoea in man, originating mostly from poultry. It has been suggested that the veterinary use of antibiotics is largely responsible for resistance in human isolates, particularly to quinolones. During a 6 month period from June to December 1998, 677 Campylobacter isolates were obtained from healthy poultry and pigs. Samples were taken at Belgian slaughterhouses. Species identification was performed by biochemical tests, multiplex PCR and SDS-PAGE of whole-cell proteins. The in vitro susceptibility to six antimicrobial drugs was determined by the agar dilution method. Campylobacter jejuni was found more often in poultry than Campylobacter coli (79% C. jejuni versus 21% C. coli). In pigs the situation was reversed (6 versus 94%). Erythromycin resistance was significantly higher (P < 0.05) in C. coli, particularly in C. coli isolated from pigs (67.2%). Alarmingly high rates of resistance to ciprofloxacin were also noted, particularly for C. coli from broilers (62.1%). The latter indicates that resistance of Campylobacter in humans could derive from animals.