Meta-analysis of 28,141 individuals identifies common variants within five new loci that influence uric acid concentrations

Elevated serum uric acid levels cause gout and are a risk factor for cardiovascular disease and diabetes. To investigate the polygenetic basis of serum uric acid levels, we conducted a meta-analysis of genome-wide association scans from 14 studies totalling 28,141 participants of European descent, resulting in identification of 954 SNPs distributed across nine loci that exceeded the threshold of genome-wide significance, five of which are novel. Overall, the common variants associated with serum uric acid levels fall in the following nine regions: SLC2A9 (p = 5.2x10(-201)), ABCG2 (p = 3.1x10(-26)), SLC17A1 (p = 3.0x10(-14)), SLC22A11 (p = 6.7x10(-14)), SLC22A12 (p = 2.0x10(-9)), SLC16A9 (p = 1.1x10(-8)), GCKR (p = 1.4x10(-9)), LRRC16A (p = 8.5x10(-9)), and near PDZK1 (p = 2.7x10(-9)). Identified variants were analyzed for gender differences. We found that the minor allele for rs734553 in SLC2A9 has greater influence in lowering uric acid levels in women and the minor allele of rs2231142 in ABCG2 elevates uric acid levels more strongly in men compared to women. To further characterize the identified variants, we analyzed their association with a panel of metabolites. rs12356193 within SLC16A9 was associated with DL-carnitine (p = 4.0x10(-26)) and propionyl-L-carnitine (p = 5.0x10(-8)) concentrations, which in turn were associated with serum UA levels (p = 1.4x10(-57) and p = 8.1x10(-54), respectively), forming a triangle between SNP, metabolites, and UA levels. Taken together, these associations highlight additional pathways that are important in the regulation of serum uric acid levels and point toward novel potential targets for pharmacological intervention to prevent or treat hyperuricemia. In addition, these findings strongly support the hypothesis that transport proteins are key in regulating serum uric acid levels.

A high-density association screen of 155 ion transport genes for involvement with common migraine

The clinical overlap between monogenic Familial Hemiplegic Migraine (FHM) and common migraine subtypes, and the fact that all three FHM genes are involved in the transport of ions, suggest that ion transport genes may underlie susceptibility to common forms of migraine. To test this leading hypothesis, we examined common variation in 155 ion transport genes using 5257 single nucleotide polymorphisms (SNPs) in a Finnish sample of 841 unrelated migraine with aura cases and 884 unrelated non-migraine controls. The top signals were then tested for replication in four independent migraine case-control samples from the Netherlands, Germany and Australia, totalling 2835 unrelated migraine cases and 2740 unrelated controls. SNPs within 12 genes (KCNB2, KCNQ3, CLIC5, ATP2C2, CACNA1E, CACNB2, KCNE2, KCNK12, KCNK2, KCNS3, SCN5A and SCN9A) with promising nominal association (0.00041 < P < 0.005) in the Finnish sample were selected for replication. Although no variant remained significant after adjusting for multiple testing nor produced consistent evidence for association across all cohorts, a significant epistatic interaction between KCNB2 SNP rs1431656 (chromosome 8q13.3) and CACNB2 SNP rs7076100 (chromosome 10p12.33) (pointwise P = 0.00002; global P = 0.02) was observed in the Finnish case-control sample. We conclude that common variants of moderate effect size in ion transport genes do not play a major role in susceptibility to common migraine within these European populations, although there is some evidence for epistatic interaction between potassium and calcium channel genes, KCNB2 and CACNB2. Multiple rare variants or trans-regulatory elements of these genes are not ruled out.

Genomewide linkage study in 1,176 affected sister pair families identifies a significant susceptibility locus for endometriosis on chromosome 10q26

Endometriosis is a common gynecological disease that affects up to 10% of women in their reproductive years. It causes pelvic pain, severe dysmenorrhea, and subfertility. The disease is defined as the presence of tissue resembling endometrium in sites outside the uterus. Its cause remains uncertain despite >50 years of hypothesis-driven research, and thus the therapeutic options are limited. Disease predisposition is inherited as a complex genetic trait, which provides an alternative route to understanding the disease. We seek to identify susceptibility loci, using a positional-cloning approach that starts with linkage analysis to identify genomic regions likely to harbor these genes. We conducted a linkage study of 1,176 families (931 from an Australian group and 245 from a U.K. group), each with at least two members--mainly affected sister pairs--with surgically diagnosed disease. We have identified a region of significant linkage on chromosome 10q26 (maximum LOD score [MLS] of 3.09; genomewide P = .047) and another region of suggestive linkage on chromosome 20p13 (MLS = 2.09). Minor peaks (with MLS > 1.0) were found on chromosomes 2, 6, 7, 8, 12, 14, 15, and 17. This is the first report of linkage to a major locus for endometriosis. The findings will facilitate discovery of novel positional genetic variants that influence the risk of developing this debilitating disease. Greater understanding of the aberrant cellular and molecular mechanisms involved in the etiology and pathophysiology of endometriosis should lead to better diagnostic methods and targeted treatments.

Relative peripheral hyperopia does not predict development and progression of myopia in children

Purpose To test the hypothesis that relative peripheral hyperopia predicts development and progression of myopia. Methods Refraction along the horizontal visual field was measured under cycloplegia at visual field angles of 0°, ±15°, and ±30° at baseline, 1 and 2 years in over 1700 initially 7-year-old Chinese children, and at baseline and 1 year in over 1000 initially 14-year olds. One refraction classification for central refraction was “nonmyopia, myopia” (nM, M), consisting of nM greater than −0.50 diopters (D; spherical equivalent) and M less than or equal to −0.50 D. A second classification was “hyperopia, emmetropia, low myopia, and moderate/high myopia” (H, E, LM, MM) with H greater than or equal to +1.00 D, E, −0.49 to +0.99 D, LM, −2.99 to −0.50 D, and MM less than or equal to −3.00 D. Subclassifications were made on the basis of development and progression of myopia over the 2 years. Changes in central refraction over time were determined for different groups, and relative peripheral refraction over time was compared between different subgroups. Results Simple linear regression of central refraction as a function of relative peripheral refraction did not predict myopia progression as relative peripheral refraction became more hyperopic: relative peripheral hyperopia and relative peripheral myopia predicted significant myopia progression for 0% and 35% of group/visual field angle combinations, respectively. Subgroups who developed myopia did not have more initial relative peripheral hyperopia than subgroups who did not develop myopia. Conclusions Relative peripheral hyperopia does not predict development nor progression of myopia in children. This calls into question the efficacy of treatments that aim to slow progression of myopia in children by “treating” relative peripheral hyperopia.

Ambidextrous leadership and team innovation

Purpose The purpose of this paper is to report the first empirical test of the recently proposed ambidexterity theory of leadership for innovation (Rosing et al., 2011). This theory proposes that the interaction between two complementary leadership behaviors – opening and closing – predicts team innovation, such that team innovation is highest when both opening and closing leadership behaviors are high. Design/methodology/approach Multi-source survey data came from 33 team leaders of architectural and interior design firms and 90 of their employees. Findings Results supported the interaction hypothesis, even after controlling for leaders’ transformational leadership behavior and general team success. Research limitations/implications The relatively small sample size and the cross-sectional design are potential limitations of the study. The findings provide initial support for the central hypothesis of the ambidexterity theory of leadership for innovation. Practical implications The results suggest that organizations could train team leaders’ ambidextrous leadership behaviors to increase team innovation. Social implications Identifying ways to facilitate organizational innovation is important, as it contributes to employment and company growth as well as individual and societal well-being. Originality/value This multi-source study contributes to the literatures on leadership and innovation in organizations by showing that ambidextrous leadership behaviors predict team innovation above and beyond transformational leadership behavior.

Assessing the effectiveness of High Intensity Interval Training (HIIT) for smoking cessation in women: HIIT to quit study protocol

Background: Smoking and physical inactivity are major risk factors for heart disease. Linking strategies that promote improvements in fitness and assist quitting smoking has potential to address both these risk factors simultaneously. The objective of this study is to compare the effects of two exercise interventions (high intensity interval training (HIIT) and lifestyle physical activity) on smoking cessation in female smokers. Method/design: This study will use a randomised controlled trial design. Participants: Women aged 18–55 years who smoke ≥ 5 cigarettes/day, and want to quit smoking. Intervention: all participants will receive usual care for quitting smoking. Group 1 - will complete two gym-based supervised HIIT sessions/week and one home-based HIIT session/week. At each training session participants will be asked to complete four 4-min (4 × 4 min) intervals at approximately 90 % of maximum heart rate interspersed with 3- min recovery periods. Group 2 - participants will receive a resource pack and pedometer, and will be asked to use the 10,000 steps log book to record steps and other physical activities. The aim will be to increase daily steps to 10,000 steps/day. Analysis will be intention to treat and measures will include smoking cessation, withdrawal and cravings, fitness, physical activity, and well-being. Discussion: The study builds on previous research suggesting that exercise intensity may influence the efficacy of exercise as a smoking cessation intervention. The hypothesis is that HIIT will improve fitness and assist women to quit smoking.

A daily diary study on ambidextrous leadership and self-reported employee innovation

Ambidextrous leadership involves a combination of behaviours that stimulate employee exploration (‘opening behaviour’) and behaviours that facilitate exploitation of ideas (‘closing behaviour’). We hypothesized that the interaction between leaders’ daily opening and closing behaviours (i.e., ambidextrous leadership) predicts employees’ daily self-reported innovative performance. Results based on diary data provided by 113 employees across five work days supported this hypothesis: daily self-reported innovative performance was highest when both daily opening and closing behaviours were high.

An insight into the adoption of accountable-eHealth systems: n empirical research model based on the Australian context

This paper provides a first look at the acceptance of Accountable-eHealth (AeH) systems–a new genre of eHealth systems designed to manage information privacy concerns that hinder the proliferation of eHealth. The underlying concept of AeH systems is appropriate use of information through after-the-fact accountability for intentional misuse of information by healthcare professionals. An online questionnaire survey was utilised for data collection from three educational institutions in Queensland, Australia. A total of 23 hypotheses relating to 9 constructs were tested using a structural equation modelling technique. The moderation effects on the hypotheses were also tested based on six moderation factors to understand their role on the designed research model. A total of 334 valid responses were received. The cohort consisted of medical, nursing and other health related students studying at various levels in both undergraduate and postgraduate courses. Hypothesis testing provided sufficient data to accept 7 hypotheses. The empirical research model developed was capable of predicting 47.3% of healthcare professionals’ perceived intention to use AeH systems. All six moderation factors showed significant influence on the research model. A validation of this model with a wider survey cohort is recommended as a future study.

Correlación entre la personalidad y los factores de la Teoría del Comportamiento Planeado (TCP) en adolescentes escolarizados de 11-19 años del Caribe Colombiano

The increasing rate of pregnancies in teenagers and the high incident of the infections of sexual transmission (HIV/ AIDS, for example), these are health related issues (and especially the sexual and reproductive health), which have received great attention on the part of investigators and of the public opinion in general. Recently, there has been evidenced that teenagers carry out very easily risk sexual behaviors, and those who have not presented the above mentioned behaviors also show high levels of intention to carry out them. There is the hypothesis that besides cognitive variables such as attitudes, subjective norms, perceived behavioral control and intention, the personality of the young persons is an aspect that plays an important paper in their sexual and reproductive health. Significant correlations were found between the variales of the TPB and the personality traits; the results suggest that the direction of these correlations is associated with the specific type of behavior or situation that is assessed. Keywords: personality, theory of planned behavior, adolescents, reproductive sexuality.

Computational methods for Bayesian model choice

In this note, we shortly survey some recent approaches on the approximation of the Bayes factor used in Bayesian hypothesis testing and in Bayesian model choice. In particular, we reassess importance sampling, harmonic mean sampling, and nested sampling from a unified perspective.

The effect of ongoing blood loss on human serum concentrations of perfluorinated acids

Perfluorinated alkyl acids (PFAAs) have been detected in serum at low concentrations in background populations. Higher concentrations haven been observed in adult males compared to females, with a possible explanation that menstruation offers females an additional elimination route. In this study, we examined the significance of blood loss as an elimination route of PFAAs. Pooled serum samples were collected from individuals undergoing a medical procedure involving ongoing blood withdrawal called venesection. Concentrations from male venesection patients were approximately 40% lower than males in the general population for perfluorohexane sulfonate (PFHxS), perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA). A simple pharmacokinetic model was used to test the hypothesis that blood loss could explain why adult males have higher concentrations of PFAAs than females, and why males undergoing venesections had lower concentrations compared to males in the general population. The model application generally supported these hypotheses showing that venesection might reduce blood serum concentrations by 37% (PFOA) and 53% (PFOS) compared to the observed difference of 44% and 37%. Menstruation was modeled to show a 22% reduction in PFOA serum concentrations compared to a 24% difference in concentrations between males and females in the background population. Uncertainties in the modeling and the data are identified and discussed.

Hyperferritinemia -cataract syndrome: Long-term ophthalmic observations in an Italian family

Background Hyperferritinemia-cataract syndrome (HCS) is a rare Mendelian condition characterized by bilateral cataract and high levels of serum ferritin in the absence of iron overload. Methods HCS was diagnosed in three adult siblings. In two of them it was possible to assess lens changes initially in 1995 and again in 2013. Serum ferritin, iron, transferrin concentrations and transferrin saturation percentage were also measured, and the Iron Responsive Element (IRE) region of the L-ferritin gene (FTL) was studied. Results Serum ferritin concentrations were considerably elevated while serum iron, transferrin and transferrin saturation levels were within the normal range in each sibling. Cataract changes in our patients were consistent with those previously reported in the literature. Progression of the cataract, an aspect of few studies in this syndrome, appeared to be quite limited in extent. The heterozygous +32G to T (-168G>T) substitution in the IRE of the FTL gene was detected in this family. Conclusions Ophthalmic and biochemical studies together with genetic testing confirmed HCS in three family members. Although the disorder has been extensively described in recent years, little is known regarding cataract evolution over time. In our cases, lens evaluations encompassed many years, identified bilateral cataract of typical morphology and supported the hypothesis that this unique clinical feature of the disease tends to be slowly progressive in nature, at least in adults.

Evidence from molecules and morphology expands Podonomopsis Brundin (Diptera: Chironomidae: Podonominae) to include ‘genus Chile'

The informal taxon ‘genus Chile’ of Brundin, based solely on pupal exuviae of a podonomine Chironomidae, has remained inadequately known for half a century. New collections reveal life associations, and provide molecular data to hypothesise a precise phylogenetic placement in the austral Podonominae. A densely sampled molecular phylogeny based on two nuclear and one mitochondrial DNA markers shows ‘genus Chile’ to be the sister group to Podonomopsis Brundin, 1966. Within Podonomopsis a clade of South American species is sister to all Australian species. We discuss how to rank such a sister group taxon and treat ‘genus Chile’ as a new subgenus Araucanopsis, subg. nov. with the new species, Podonomopsis (Araucanopsis) avelasse, sp. nov. from Chile and Argentina as genotype of the monotypic subgenus. We describe P. (A.) avelasse in all stages and provide an expanded diagnosis and description of Podonomopsis to include Araucanopsis. A dated biogeographic hypothesis (chronogram) infers the most recent common ancestor (tmcra) of expanded Podonomopsis at 95 million years ago (Mya) (68–122 Mya 95% highest posterior density), ‘core’ Podonomopsis at 83 Mya (58–108) and Australian Podonomopsis at 65 Mya (44–87). All dates are before the South America–Australia geological separation through Antarctica, supporting previous conclusions that the taxon distribution is ‘Gondwanan’ in origin. Podonomopsis, even as expanded here, remains unknown from New Zealand or elsewhere on extant Zealandia.

Applicability of pebble matrix filtration for the pre-treatment of surface waters containing high turbidity and NOM

Purification of drinking water is routinely achieved by use of conventional coagulants and disinfection procedures. However, there are instances such as flood events when the level of turbidity reaches extreme levels while NOM may be an issue throughout the year. Consequently, there is a need to develop technologies which can effectively treat water of high turbidity during flood events and natural organic matter (NOM) content year round. It was our hypothesis that pebble matrix filtration potentially offered a relatively cheap, simple and reliable means to clarify such challenging water samples. Therefore, a laboratory scale pebble matrix filter (PMF) column was used to evaluate the turbidity and natural organic matter (NOM) pre-treatment performance in relation to 2013 Brisbane River flood water. Since the high turbidity was only a seasonal and short term problem, the general applicability of pebble matrix filters for NOM removal was also investigated. A 1.0 m deep bed of pebbles (the matrix) partly in-filled with either sand or crushed glass was tested, upon which was situated a layer of granular activated carbon (GAC). Turbidity was measured as a surrogate for suspended solids (SS), whereas, total organic carbon (TOC) and UV Absorbance at 254 nm were measured as surrogate parameters for NOM. Experiments using natural flood water showed that without the addition of any chemical coagulants, PMF columns achieved at least 50% turbidity reduction when the source water contained moderate hardness levels. For harder water samples, above 85% turbidity reduction was obtained. The ability to remove 50% turbidity without chemical coagulants may represent significant cost savings to water treatment plants and added environmental benefits accrue due to less sludge formation. A TOC reduction of 35-47% and UV-254 nm reduction of 24-38% was also observed. In addition to turbidity removal during flood periods, the ability to remove NOM using the pebble matrix filter throughout the year may have the benefit of reducing disinfection by-products (DBP) formation potential and coagulant demand at water treatment plants. Final head losses were remarkably low, reaching only 11 cm at a filtration velocity of 0.70 m/h.

Following fashion: Visible progressiveness and the social construction of firm value

A central tenet underlying studies on management fashions is that the diffusion of novel forms, models and techniques is driven by an institutional norm of progress, which is the societal expectation that managers will continuously use 'new and improved' management practices. We add to the literature on management fashions by arguing that, if the display of progressiveness in the manner of managing and organizing is expected of organizations, firms that are visibly progressive would be evaluated more positively by organizational audiences following this institutional prescription. Using article counts of co-occurrences of firms and various fashionable management practices in Wall Street Journal, we hypothesize positive effects of such associations on security analysts' evaluations of these firms. Results support this hypothesis. Our study enriches the management fashion literature by highlighting the consequential relevance of organizational adherence to the norm of progress.