Hundreds of variants clustered in genomic loci and biological pathways affect human height

Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P < 0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.

Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution

Waist-hip ratio (WHR) is a measure of body fat distribution and a predictor of metabolic consequences independent of overall adiposity. WHR is heritable, but few genetic variants influencing this trait have been identified. We conducted a meta-analysis of 32 genome-wide association studies for WHR adjusted for body mass index (comprising up to 77,167 participants), following up 16 loci in an additional 29 studies (comprising up to 113,636 subjects). We identified 13 new loci in or near RSPO3, VEGFA, TBX15-WARS2, NFE2L3, GRB14, DNM3-PIGC, ITPR2-SSPN, LY86, HOXC13, ADAMTS9, ZNRF3-KREMEN1, NISCH-STAB1 and CPEB4 (P = 1.9 × 10−9 to P = 1.8 × 10−40) and the known signal at LYPLAL1. Seven of these loci exhibited marked sexual dimorphism, all with a stronger effect on WHR in women than men (P for sex difference = 1.9 × 10−3 to P = 1.2 × 10−13). These findings provide evidence for multiple loci that modulate body fat distribution independent of overall adiposity and reveal strong gene-by-sex interactions.

International contact lens prescribing in 2015

We have been collecting data on worldwide contact lens prescribing habits for almost 20 years. Over this time period, we have amassed prospective information about 315,000 contact lens fits in 59 countries. This article marks our 15th report in Contact Lens Spectrum and features a breakdown of more than 23,000 contact lens fits in 34 markets. As in previous years, our international network of coordinators distributed survey forms to eyecare practitioners in their market who then recorded generic information about the first 10 patients fit with contact lenses after receipt. Information is gathered about patient age and gender; whether the contact lenses are prescribed as a new fit or a refit; contact lens material, design, and replacement frequency; number of intended days per week of use; wearing modality; and care system. Contact lens fits are weighted to reflect the number of fits undertaken by each eyecare practitioner. The study data were entered and processed at the University of Manchester and at the University of Waterloo.

Cord blood 25-hydroxyvitamin D and fetal growth in the China-Anhui birth cohort study

We determined the association of cord blood 25-hydroxyvitamin D [25(OH)D] with birth weight and the risk of small for gestational age (SGA). As part of the China-Anhui Birth Cohort (C-ABC) study, we measured cord blood levels of 25(OH)D in 1491 neonates in Hefei, China. The data on maternal sociodemographic characteristics, health status, lifestyle, birth outcomes were prospectively collected. Multiple regression models were used to estimate the association of 25(OH)D levels with birth weight and the risk of SGA. Compared with neonates in the lowest decile of cord blood 25(OH)D levels, neonates in four deciles (the fourth, fifth, sixth and seventh deciles) had significantly increased birth weight and decreased risk of SGA. Multiple linear regression models showed that per 10 nmol/L increase in cord blood 25(OH)D, birth weight increased by 61.0 g (95% CI: 31.9, 89.9) at concentrations less than 40 nmol/L, and then decreased by 68.5 g (95% CI: −110.5, −26.6) at concentrations from 40 to 70 nmol/L. This study provides the first epidemiological evidence that there was an inverted U shaped relationship between neonatal vitamin D status and fetal growth, and the risk of SGA reduced at moderate concentration.

Inductor realisation using a finite gain differential amplifier

A finite gain differential amplifier is used along with a few passive RC elements to simulate an inductor. Methods for obtaining low Q inductance and frequency dependent high QI inductance are described. Sensitivity analysis when the gain varies is also included.

Alloying gold with copper makes for a highly selective visible-light photocatalyst for the reduction of nitroaromatics to anilines

Finely control of product selectivity is an essential issue in organic chemical production. In the synthesis of functionalized anilines via reduction of the corresponding nitroarenes, the challenge is to selectively reduce only the nitro group in the presence of other reducible functional groups in nitroarene molecules at a high reaction rate. Normally, the nitroarene is reduced stepwise through a series of intermediates that remain as byproducts, increasing the aniline synthesis cost. Here we report that alloying small amounts of copper into gold nanoparticles can alter the reaction pathway of the catalytic reduction under visible-light irradiation at ambient temperature, allowing nitroaromatics to be transformed directly to anilines in a highly selective manner. The reasons for the high efficiency of the photocatalytic reduction under these comparatively benign conditions as well as the light-excited reaction mechanisms are discussed. This photocatalytic process avoids byproducts, exhibits a high reaction rate and excellent substituent tolerance, and can be used for the synthesis of many useful functionalized anilines under environmentally benign conditions. Switching of the reaction pathway simply by tailoring the bimetallic alloy NPs of the photocatalysts is effective for engineering of product chemoselectivity.

Modelling Cued-Target Recall using Quantum Inspired Models of Target Activation

This article presents and evaluates Quantum Inspired models of Target Activation using Cued-Target Recall Memory Modelling over multiple sources of Free Association data. Two components were evaluated: Whether Quantum Inspired models of Target Activation would provide a better framework than their classical psychological counterparts and how robust these models are across the different sources of Free Association data. In previous work, a formal model of cued-target recall did not exist and as such Target Activation was unable to be assessed directly. Further to that, the data source used was suspected of suffering from temporal and geographical bias. As a consequence, Target Activation was measured against cued-target recall data as an approximation of performance. Since then, a formal model of cued-target recall (PIER3) has been developed [10] with alternative sources of data also becoming available. This allowed us to directly model target activation in cued-target recall with human cued-target recall pairs and use multiply sources of Free Association Data. Featural Characteristics known to be important to Target Activation were measured for each of the data sources to identify any major differences that may explain variations in performance for each of the models. Each of the activation models were used in the PIER3 memory model for each of the data sources and was benchmarked against cued-target recall pairs provided by the University of South Florida (USF). Two methods where used to evaluate performance. The first involved measuring the divergence between the sets of results using the Kullback Leibler (KL) divergence with the second utilizing a previous statistical analysis of the errors [9]. Of the three sources of data, two were sourced from human subjects being the USF Free Association Norms and the University of Leuven (UL) Free Association Networks. The third was sourced from a new method put forward by Galea and Bruza, 2015 in which pseudo Free Association Networks (Corpus Based Association Networks - CANs) are built using co-occurrence statistics on large text corpus. It was found that the Quantum Inspired Models of Target Activation not only outperformed the classical psychological model but was more robust across a variety of data sources.

Trial of the Primary Care Practice Improvement Tool: Building organisational performance in Australian general practice and primary health care

Objective: To nationally trial the Primary Care Practice Improvement Tool (PC-PIT), an organisational performance improvement tool previously co-created with Australian primary care practices to increase their focus on relevant quality improvement (QI) activities. Design: The study was conducted from March to December 2015 with volunteer general practices from a range of Australian primary care settings. We used a mixed-methods approach in two parts. Part 1 involved staff in Australian primary care practices assessing how they perceived their practice met (or did not meet) each of the 13 PC-PIT elements of high-performing practices, using a 1–5 Likert scale. In Part 2, two external raters conducted an independent practice visit to independently and objectively assess the subjective practice assessment from Part 1 against objective indicators for the 13 elements, using the same 1–5 Likert scale. Concordance between the raters was determined by comparing their ratings. In-depth interviews conducted during the independent practice visits explored practice managers’ experiences and perceived support and resource needs to undertake organisational improvement in practice. Results: Data were available for 34 general practices participating in Part 1. For Part 2, independent practice visits and the inter-rater comparison were conducted for a purposeful sample of 19 of the 34 practices. Overall concordance between the two raters for each of the assessed elements was excellent. Three practice types across a continuum of higher- to lower-scoring practices were identified, with each using the PC-PIT in a unique way. During the in-depth interviews, practice managers identified benefits of having additional QI tools that relate to the PC-PIT elements. Conclusions: The PC-PIT is an organisational performance tool that is acceptable, valid and relevant to our range of partners and the end users (general practices). Work is continuing with our partners and end users to embed the PC-PIT in existing organisational improvement programs.

Expected Performance of the ATLAS Experiment - Detector, Trigger and Physics

A detailed study is presented of the expected performance of the ATLAS detector. The reconstruction of tracks, leptons, photons, missing energy and jets is investigated, together with the performance of b-tagging and the trigger. The physics potential for a variety of interesting physics processes, within the Standard Model and beyond, is examined. The study comprises a series of notes based on simulations of the detector and physics processes, with particular emphasis given to the data expected from the first years of operation of the LHC at CERN.

Kotimaisen tuorekalan tuoreuden arviointi laatuindeksimenetelmällä QIM®

Kalateollisuus ja kalakauppa tarvitsisivat menetelmän, jolla kalan säilyvyyttä voitaisiin arvioida reaaliaikaisesti ja luotettavasti. Laatuindeksimenetelmä QIM® (engl. Quality Index Method) on käytössä jo useassa Euroopan maassa useille eri kalalajeille. QIM® pyrkii lajikohtaisesti ennustamaan aistinvaraisten ominaisuuksien muutoksien perusteella jäljellä olevaa säilyvyysaikaa. Työn tavoitteena oli luoda QIM® meressä kasvatetulle siialle. Tämä on ensimmäinen suomalaiselle kalalle tehtävä QIM®, ja tavoitteena on saada meressä kasvatetun siian QIM® myös viralliseen QIM®-käsikirjaan. Tutkimus tehtiin Elintarviketurvallisuusvirasto Eviralle. Tutkittavat kalat Evira osti Kalatukku E. Eriksson Oy:ltä. QIM®-tuloksen tueksi tutkittiin yhden erän pH ja indikoitiin pilaantuminen myös mikrobiologisesti. Luotiin myös kasvatetun siian profiili (arvioijia 13). Itse tutkimusosassa kaksi profiiliraatia (n = 9) ja QIM®-raati (n = 5) arvioivat raa’an ja kypsän kalan. Tulos varmistettiin myös aistinvaraisella kalan laadunarviointimenetelmällä (Evira 8001). QIM®-raati loi QIM®-luonnoksen ja luonnoksen toimivuutta testattiin. Kiinteänä osana työn toteutusta oli myös eri vaiheiden muutosten valokuvaus. Tämän tutkimuksen mukaan luotu QIM®-luonnos on toimiva pohja validoitaessaa QIM®-menetelmää siialle. Voidaan myös todeta, että QIM® soveltuu meressä kasvatetulle siialle. Kypsän kalan aistinvaraisella laadunarviointimenetelmällä (Evira 8001) analysoitiin säilytysajankohta, jolloin kypsästä kalasta voitiin todeta kalan kauppakelvottomuus – tätä pidettiin ajanhetkenä, jolloin raa’an kalan tutkiminen voitiin lopettaa. Tutkimuksessa käytetty mikrobiologinen menetelmä ”Mikrobien lukumäärän määrittäminen” (Evira 3420/1) korreloi QIM®-tuloksen kanssa; kalanäyte oli tässä tutkimuksessa niin mikrobiologisesti arvioituna kuin laatuindeksinkin mukaan käyttökelvotonta viidentenätoista päivänä. Tutkittujen kalojen pH-arvoja ei voitu verrata laatuindeksiin, sillä tässä tutkimuksessa mitattujen pH-arvojen tuloksista ei voitu päätellä pilaantumisen etenemistä. Kun QIM® meressä kasvatetulle siialle on validoitu (Evira), valmista meressä kasvatetun siian QI-menetelmää voidaan hyödyntää jatkossa Suomen kalateollisuudessa ja -markkinoilla. Olisi hyvä, jos QIM® luotaisiin myös muille Suomen yleisimmille kauppakaloille, jotta pakkauksiin merkityt viimeiset käyttöpäivät perustuisivat yhteen yhteiseen menetelmään ja näin viimeisellä käyttöpäivällä olisi tieteellinen pohja.

Dependence of giant magnetoresistance on oxygen stoichiometry and magnetization in polycrystalline La0.67Ba0.33MnOz

We have studied resistivity, magnetization, and magnetoresistance in polycrystalline La0.67Ba0.33MnOz by reducing the oxygen stoichiometry from z=2.99 to 2.80. As the oxygen content decreases, the resistivity of La0.67Ba0.33 MnOz increases and the magnetic transition temperature shifts to lower temperature. A large magnetoresistance effect was observed over a wide temperature range for all samples except the insulating z=2.80 sample. The similarity between our results on oxygen-deficient polycrystalline La0.67 Ba0.33MnOz and films previously reported to have a very large intrinsic magnetoresistance is discussed. At low temperature the magnetoresistance was observed to be strongly dependent on the magnetization. A possible mechanism for this effect is discussed.

土壤传热特性的实验研究(Experimental Study of Soil Heat Diffusivity)

发展了测定实验室土样热扩散率的方法,介绍了研制的实验装置和建议的操作程序。给出的实验结果表明土壤热扩散率随土壤空隙率、含水量和温度等许多参数而变化。

3D Anisotropic Elastoplastic-Damage Model and its Application in Simulating the Behavior of Rock Materials

A 3D anisotropic elastoplastic-damage model was presented based on continuum damage mechanics theory. In this model, the tensor decomposition technique is employed. Combined with the plastic yield rule and damage evolution, the stress tensor in incremental format is obtained. The derivate eigenmodes in the proposed model are assumed to be related with the uniaxial behavior of the rock material. Each eigenmode has a corresponding damage variable due to the fact that damage is a function of the magnitude of the eigenstrain. Within an eigenmodes, different damage evolution can be used for tensile and compressive loadings. This model was also developed into finite element code in explicit format, and the code was integrated into the well-known computational environment ABAQUS using the ABAQUS/Explicit Solver. Numerical simulation of an uniaxial compressive test for a rock sample is used to examine the performance of the proposed model, and the progressive failure process of the rock sample is unveiled.

Mechanism on Progressive Failure of a Faulted Rock Slope Due to Slip-Weakening

Slip-weakening is one of the characteristics of geological materials under certain loadings. Non-uniform rock structure may exist in the vicinity of the slip surface for a rock slope. Some portion of the slip surface may be penetrated but the other not. For the latter case, the crack or the fault surface will undergo shear deformation before it becomes a successive surface under a certain loading. As the slipped portion advances,slip-weakening occurs over a distance behind the crack tip. In the weakening zone, the shear strength will decrease from its peak value to residual friction level. The stress will redistribute along the surface of crack and in the weakening zone. Thus the changed local stress concentration leads the crack to extend and the ratio of penetration of the slip surface to increase. From the view of large-scale for the whole slip surface, the shear strength will decrease due to the damage of interior rock structure, and the faulted rock behaves as a softening material. Such a kind of mechanism performs in a large number of practical landslides in the zones experienced strong earthquakes. It should be noted that the mechanism mentioned above is different from that of the breakage of structural clay,in which the geological material is regarded as a medium containing structural lumps and structural bands. In this paper, the softening behavior of a faulted rock should be regarded as a comprehensive result of the whole complicated process including slip-weakening, redistribution of stress, extension of crack tip, and the penetration of the slip surface. This process is accompanied by progressive failure and abrupt structural damage. The size of slip-weakening zone is related to the undergoing strain. Once the relative slide is initiated (local or integrated), the effect of slip-weakening will behave in a certain length behind the crack tip until the formation of the whole slip surface.