Monitoring nutrient¯ows and economic performance in African farming systems (NUTMON) II. Tool development

Abstract Farm-NUTMON is a research tool that integrates the assessment of stocks and¯ows of the macro-nutrients nitrogen, phosphorus and potassium on the one hand and economic farm analysis on the other. The tool is applicable at both the farm and the activity level. It includes a structured questionnaire, a database, and two simple static models (NUTCAL for calculation of nutrient¯ows and the ECCAL for calculation of economic parameters). Finally, a user interface facilitates data entry, data manipulation and extracts data from the database to produce input for both models. Farm-NUTMON allows (i) estimation of the extent to which farmers generate income from soil nutrient mining, (ii) assessment of the impact of changes in farm management techniques on nutrient balance and economic performance at activity level and farm level, and (iii) calculation of the economic impact of exogenous changes on the farm and activity level.

Multivariate analysis reveals shared genetic architecture of brain morphology and human behavior.

Human variation in brain morphology and behavior are related and highly heritable. Yet, it is largely unknown to what extent specific features of brain morphology and behavior are genetically related. Here, we introduce a computationally efficient approach for multivariate genomic-relatedness-based restricted maximum likelihood (MGREML) to estimate the genetic correlation between a large number of phenotypes simultaneously. Using individual-level data (N = 20,190) from the UK Biobank, we provide estimates of the heritability of gray-matter volume in 74 regions of interest (ROIs) in the brain and we map genetic correlations between these ROIs and health-relevant behavioral outcomes, including intelligence. We find four genetically distinct clusters in the brain that are aligned with standard anatomical subdivision in neuroscience. Behavioral traits have distinct genetic correlations with brain morphology which suggests trait-specific relevance of ROIs. These empirical results illustrate how MGREML can be used to estimate internally consistent and high-dimensional genetic correlation matrices in large datasets

Parquet approach to nonlocal vertex functions and electrical conductivity of disordered electrons

A diagrammatic technique for two-particle vertex functions is used to describe systematically the influence of spatial quantum coherence and backscattering effects on transport properties of noninteracting electrons in a random potential. In analogy with many-body theory we construct parquet equations for topologically distinct {\em nonlocal} irreducible vertex functions into which the {\em local} one-particle propagator and two-particle vertex of the coherent-potential approximation (CPA) enter as input. To complete the two-particle parquet equations we use an integral form of the Ward identity and determine the one-particle self-energy from the known irreducible vertex. In this way a conserving approximation with (Herglotz) analytic averaged Green functions is obtained. We use the limit of high spatial dimensions to demonstrate how nonlocal corrections to the $d=\infty$ (CPA) solution emerge. The general parquet construction is applied to the calculation of vertex corrections to the electrical conductivity. With the aid of the high-dimensional asymptotics of the nonlocal irreducible vertex in the electron-hole scattering channel we derive a mean-field approximation for the conductivity with vertex corrections. The impact of vertex corrections onto the electronic transport is assessed quantitatively within the proposed mean-field description on a binary alloy.Comment: REVTeX 19 pages, 9 EPS diagrams, 6 PS figure

Effect evaluation of a two-year complex intervention to reduce loneliness in non-institutionalised elderly Dutch people

Background: Public health policy calls for intervention programmes to reduce loneliness in the ageing population. So far, numerous loneliness interventions have been developed, with effectiveness demonstrated for few of these interventions. The loneliness intervention described in this manuscript distinguishes itself from others by including multiple intervention components and targeting individuals and their environment. Intervention components included a mass media campaign, information meetings, psychosocial group courses, social activities organised by neighbours, and training of intermediaries. The aim of this manuscript is to study the effects of this integrated approach on initial and long-term outcomes. Methods: A quasi-experimental pre-test post-test intervention study was conducted among non-institutionalised elderly people aged 65 years and over to evaluate the effectiveness of the intervention by comparing the intervention community and the control community. Data on outputs, initial and long-term outcomes, and the overall goal were collected by self-administered questionnaires. Data of 858 elderly people were available for the analyses. To assess the effect linear regression analyses with adjustments for age, gender, church attendance, and mental health were used. In addition, the process evaluation provided information about the reach of the intervention components. Results: After two years, 39% of the elderly people were familiar with the intervention programme. The intervention group scored more favourably than the control group on three subscales of the initial outcome, motivation (-4.4%, 95% CI-8.3-0.7), perceived social support (-8.2%, 95% CI-13.6-2.4), and subjective norm (-11.5%, 95% CI-17.4-5.4). However, no overall effects were observed for the long-term outcome, social support, and overall goal, loneliness. Conclusions: Two years after its initiation the reach of the intervention programme was modest. Though no effect of the complex intervention was found on social support and loneliness, more favourable scores on loneliness literacy subscales were induced

Meta-GWAS Accuracy and Power (MetaGAP) Calculator Shows that Hiding Heritability Is Partially Due to Imperfect Genetic Correlations across Studies

Large-scale genome-wide association results are typically obtained from a fixed-effects meta-analysis of GWAS summary statistics from multiple studies spanning different regions and/or time periods. This approach averages the estimated effects of genetic variants across studies. In case genetic effects are heterogeneous across studies, the statistical power of a GWAS and the predictive accuracy of polygenic scores are attenuated, contributing to the so-called ‘missing heritability’. Here, we describe the online Meta-GWAS Accuracy and Power (MetaGAP) calculator (available at www.devlaming.eu) which quantifies this attenuation based on a novel multi-study framework. By means of simulation studies, we show that under a wide range of genetic architectures, the statistical power and predictive accuracy provided by this calculator are accurate. We compare the predictions from the MetaGAP calculator with actual results obtained in the GWAS literature. Specifically, we use genomic-relatedness-matrix restricted maximum likelihood to estimate the SNP heritability and cross-study genetic correlation of height, BMI, years of education, and self-rated health in three large samples. These estimates are used as input parameters for the MetaGAP calculator. Results from the calculator suggest that cross-study heterogeneity has led to attenuation of statistical power and predictive accuracy in recent large-scale GWAS efforts on these traits (e.g., for years of education, we estimate a relative loss of 51–62% in the number of genome-wide significant loci and a relative loss in polygenic score R2of 36–38%). Hence, cross-study heterogeneity contributes to the missing heritability

A comparative study of Tam3 and Ac transposition in transgenic tobacco and petunia plants

Transposition of the Anthirrinum majus Tam3 element and the Zea mays Ac element has been monitored in petunia and tobacco plants. Plant vectors were constructed with the transposable elements cloned into the leader sequence of a marker gene. Agrobacterium tumefaciens-mediated leaf disc transformation was used to introduce the transposable element constructs into plant cells. In transgenic plants, excision of the transposable element restores gene expression and results in a clearly distinguishable phenotype. Based on restored expression of the hygromycin phosphotransferase II (HPTII) gene, we established that Tam3 excises in 30% of the transformed petunia plants and in 60% of the transformed tobacco plants. Ac excises from the HPTII gene with comparable frequencies (30%) in both plant species. When the β-glucuronidase (GUS) gene was used to detect transposition of Tam3, a significantly lower excision frequency (13%) was found in both plant species. It could be shown that deletion of parts of the transposable elements Tam3 and Ac, removing either one of the terminal inverted repeats (TIR) or part of the presumptive transposase coding region, abolished the excision from the marker genes. This demonstrates that excision of the transposable element Tam3 in heterologous plant species, as documented for the autonomous element Ac, also depends on both properties. Southern blot hybridization shows the expected excision pattern and the reintegration of Tam3 and Ac elements into the genome of tobacco plants.

Overcoming attenuation bias in regressions using polygenic indices

Measurement error in polygenic indices (PGIs) attenuates the estimation of their effects in regression models. We analyze and compare two approaches addressing this attenuation bias: Obviously Related Instrumental Variables (ORIV) and the PGI Repository Correction (PGI-RC). Through simulations, we show that the PGI-RC performs slightly better than ORIV, unless the prediction sample is very small (N &lt; 1000) or when there is considerable assortative mating. Within families, ORIV is the best choice since the PGI-RC correction factor is generally not available. We verify the empirical validity of the simulations by predicting educational attainment and height in a sample of siblings from the UK Biobank. We show that applying ORIV between families increases the standardized effect of the PGI by 12% (height) and by 22% (educational attainment) compared to a meta-analysis-based PGI, yet estimates remain slightly below the PGI-RC estimates. Furthermore, within-family ORIV regression provides the tightest lower bound for the direct genetic effect, increasing the lower bound for the standardized direct genetic effect on educational attainment from 0.14 to 0.18 (+29%), and for height from 0.54 to 0.61 (+13%) compared to a meta-analysis-based PGI.</p

"Optical conductance fluctuations: diagrammatic analysis in Landauer approach and non-universal effects"

The optical conductance of a multiple scattering medium is the total transmitted light of a diffuse incoming beam. This quantity, very analogous to the electronic conductance, exhibits universal conductance fluctuations. We perform a detailed diagrammatic analysis of these fluctuations. With a Kadanoff-Baym technique all the leading diagrams are systematically generated. A cancellation of the short distance divergencies occurs, that yields a well behaved theory. The analytical form of the fluctuations is calculated and applied to optical systems. Absorption and internal reflections reduce the fluctuations significantly.Comment: 25 pages Revtex 3.0, 18 seperate postscript figure

Genomic analysis of diet composition finds novel loci and associations with health and lifestyle

We conducted genome-wide association study (GWAS) meta-analyses of relative caloric intake from fat, protein, carbohydrates and sugar in over 235,000 individuals. We identified 21 approximately independent lead SNPs. Relative protein intake exhibits the strongest relationships with poor health, including positive genetic associations with obesity, type 2 diabetes, and heart disease ( ≈ 0.15 − 0.5). Relative carbohydrate and sugar intake have negative genetic correlations with waist circumference, waist-hip ratio, and neighborhood poverty (|| ≈ 0.1 − 0.3). Overall, our results show that the relative intake of each macronutrient has a distinct genetic architecture and pattern of genetic correlations suggestive of health implications beyond caloric content

Expression of CD39 Identifies Activated Intratumoral CD8+T Cells in Mismatch Repair Deficient Endometrial Cancer

Identification of human cancer-reactive CD8+ T cells is crucial for the stratification of patients for immunotherapy and determination of immune-therapeutic effects. To date, these T cells have been identified mainly based on cell surface expression of programmed cell death protein 1 (PD-1) or co-expression of CD103 and CD39. A small subset of CD103- CD39+ CD8+ T cells is also present in tumors, but little is known about these T cells. Here, we report that CD103- CD39+ CD8+ T cells from mismatch repair-deficient endometrial tumors are activated and characterized predominantly by expression of TNFRSF9. In vitro, transforming growth factor-beta (TGF-beta) drives the disappearance of this subset, likely through the conversion of CD103- CD39+ cells to a CD103+ phenotype. On the transcriptomic level, T cell activation and induction of CD39 was associated with a number of tissue residence and TGF-beta responsive transcription factors. Altogether, our data suggest CD39+ CD103- CD8+ tumor-infiltrating T cells are recently activated and likely rapidly differentiate towards tissue residence upon exposure to TGF-beta in the tumor micro-environment, explaining their relative paucity in human tumors