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Causal relationship between obesity and vitamin D status: bi-directional mendelian randomization analysis of multiple cohorts

BACKGROUND: Obesity is associated with vitamin D deficiency, and both are areas of active public health concern. We explored the causality and direction of the relationship between body mass index (BMI) and 25-hydroxyvitamin D [25(OH)D] using genetic markers as instrumental variables (IVs) in bi-directional Mendelian randomization (MR) analysis. METHODS AND FINDINGS: We used information from 21 adult cohorts (up to 42,024 participants) with 12 BMI-related SNPs (combined in an allelic score) to produce an instrument for BMI and four SNPs associated with 25(OH)D (combined in two allelic scores, separately for genes encoding its synthesis or metabolism) as an instrument for vitamin D. Regression estimates for the IVs (allele scores) were generated within-study and pooled by meta-analysis to generate summary effects. Associations between vitamin D scores and BMI were confirmed in the Genetic Investigation of Anthropometric Traits (GIANT) consortium (n = 123,864). Each 1 kg/m(2) higher BMI was associated with 1.15% lower 25(OH)D (p = 6.52×10⁻²⁷). The BMI allele score was associated both with BMI (p = 6.30×10⁻⁶²) and 25(OH)D (-0.06% [95% CI -0.10 to -0.02], p = 0.004) in the cohorts that underwent meta-analysis. The two vitamin D allele scores were strongly associated with 25(OH)D (p≤8.07×10⁻⁵⁷ for both scores) but not with BMI (synthesis score, p = 0.88; metabolism score, p = 0.08) in the meta-analysis. A 10% higher genetically instrumented BMI was associated with 4.2% lower 25(OH)D concentrations (IV ratio: -4.2 [95% CI -7.1 to -1.3], p = 0.005). No association was seen for genetically instrumented 25(OH)D with BMI, a finding that was confirmed using data from the GIANT consortium (p≥0.57 for both vitamin D scores). CONCLUSIONS: On the basis of a bi-directional genetic approach that limits confounding, our study suggests that a higher BMI leads to lower 25(OH)D, while any effects of lower 25(OH)D increasing BMI are likely to be small. Population level interventions to reduce BMI are expected to decrease the prevalence of vitamin D deficiency.

Challenges of operational river forecasting

Skillful and timely streamflow forecasts are critically important to water managers and emergency protection services. To provide these forecasts, hydrologists must predict the behavior of complex coupled human–natural systems using incomplete and uncertain information and imperfect models. Moreover, operational predictions often integrate anecdotal information and unmodeled factors. Forecasting agencies face four key challenges: 1) making the most of available data, 2) making accurate predictions using models, 3) turning hydrometeorological forecasts into effective warnings, and 4) administering an operational service. Each challenge presents a variety of research opportunities, including the development of automated quality-control algorithms for the myriad of data used in operational streamflow forecasts, data assimilation, and ensemble forecasting techniques that allow for forecaster input, methods for using human-generated weather forecasts quantitatively, and quantification of human interference in the hydrologic cycle. Furthermore, much can be done to improve the communication of probabilistic forecasts and to design a forecasting paradigm that effectively combines increasingly sophisticated forecasting technology with subjective forecaster expertise. These areas are described in detail to share a real-world perspective and focus for ongoing research endeavors.

Defining the role of common variation in the genomic and biological architecture of adult human height

Using genome-wide data from 253,288 individuals, we identified 697 variants at genome-wide significance that together explained one-fifth of the heritability for adult height. By testing different numbers of variants in independent studies, we show that the most strongly associated ∼2,000, ∼3,700 and ∼9,500 SNPs explained ∼21%, ∼24% and ∼29% of phenotypic variance. Furthermore, all common variants together captured 60% of heritability. The 697 variants clustered in 423 loci were enriched for genes, pathways and tissue types known to be involved in growth and together implicated genes and pathways not highlighted in earlier efforts, such as signaling by fibroblast growth factors, WNT/β-catenin and chondroitin sulfate-related genes. We identified several genes and pathways not previously connected with human skeletal growth, including mTOR, osteoglycin and binding of hyaluronic acid. Our results indicate a genetic architecture for human height that is characterized by a very large but finite number (thousands) of causal variants.2014

An orchestrated gene expression component of neuronal programmed cell death revealed by cDNA array analysis

Programmed cell death (PCD) during neuronal development and disease has been shown to require de novo RNA synthesis. However, the time course and regulation of target genes is poorly understood. By using a brain-biased array of over 7,500 cDNAs, we profiled this gene expression component of PCD in cerebellar granule neurons challenged separately by potassium withdrawal, combined potassium and serum withdrawal, and kainic acid administration. We found that hundreds of genes were significantly regulated in discreet waves including known genes whose protein products are involved in PCD. A restricted set of genes was regulated by all models, providing evidence that signals inducing PCD can regulate large assemblages of genes (of which a restricted subset may be shared in multiple pathways).

Micro-holographic methods for sub-micrometer grating fabrication in fused silica with UV femtosecond laser

The optical layouts incorporating binary phase diffractive grating and a standard micro-objective were used for femtosecond microfabrication of periodical structures in fused silica. Two beams, generated in Talbot type interferometer, interfered on a surface and in the bulk of the sample. The method suggested allows better control over the transverse size of the grating pitch, and thus control the reflection strength of the waveguide or fibre grating. We present the examples of direct inscription of the sub-micrometer periodical structures using a 267 nm femtosecond laser radiation.

Micro-holographic methods for sub-micrometer grating fabrication in fused silica with UV femtosecond laser

The optical layouts incorporating binary phase diffractive grating and a standard micro-objective were used for femtosecond microfabrication of periodical structures in fused silica. Two beams, generated in Talbot type interferometer, interfered on a surface and in the bulk of the sample. The method suggested allows better control over the transverse size of the grating pitch, and thus control the reflection strength of the waveguide or fibre grating. We present the examples of direct inscription of the sub-micrometer periodical structures using a 267 nm femtosecond laser radiation.

Account book of Andrew Croswell, 1794-1802

Andrew Croswell kept this account book while an undergraduate at Harvard College. It contains entries from 1794, the year he entered, until his graduation in 1798. There is also one entry on the back cover apparently made in 1802. The entries, divided by school term, are very detailed. Croswell indicates the cost of the following, among many other expenses and purchases: transportation, most often to Hingham and Plymouth; payment for "passing the bridge"; candles; hiring a horse; wood and having it cut; laundry; quills and pencils; paper and ink; razors, haircuts, hair ribbons; a trunk; clothing and cloth for trousers; furniture; tickets to the theater; door locks; a bowl and spoon; "batts and balls" and "other necessaries"; tobacco; toothbrushes; shoe and boot repair; fruit; wine, brandy and rum; cheese; coffee and tea; butter; lemons; sugar; and wafers. There are also entries for college-related costs, including the payment of quarter bills, buttery bills, Hasty Pudding Club dues, and a fee to the President of Harvard College related to Croswell's graduation. There are also entries pertaining to the cost of celebrating various special occasions, including Election Day, Christmas Eve, "Independent Day," and George Washington's birthday.

A dictionary of arts, manufactures and mines; containing a clear exposition of their principles and practice. Illustrated with nearly sixteen hundred engravings on wood. Reprinted entirely from the last corrected and greatly enl. English ed.

Accompanied by "Supplement" 1096 p.

A treatise on wood engraving, historical and practical. With upwards of three hundred illustrations engraved on wood,

Mode of access: Internet.

The life and times of Anthony Wood, antiquary, of Oxford, 1632-1695, described by himself:

Vols. 1-2 have series title on cover only.

Effect of early release from intense competition within high density natural regeneration on the properties of the juvenile and mature wood of 40-year-old Sitka spruce (Picea sitchensis (Bong.) Carr.)

Peer reviewed

WOOD DENSITY VARIATION AND TREE RING DEMARCATION IN Gmelina arborea TREES USING X-RAY DENSITOMETRY

Due to its relationship with other properties, wood density is the main wood quality parameter. Modern, accurate methods - such as X-ray densitometry - are applied to determine the spatial distribution of density in wood sections and to evaluate wood quality. The objectives of this study were to determinate the influence of growing conditions on wood density variation and tree ring demarcation of gmelina trees from fast growing plantations in Costa Rica. The wood density was determined by X-ray densitometry method. Wood samples were cut from gmelina trees and were exposed to low X-rays. The radiographic films were developed and scanned using a 256 gray scale with 1000 dpi resolution and the wood density was determined by CRAD and CERD software. The results showed tree-ring boundaries were distinctly delimited in trees growing in site with rainfall lower than 25 10 mm/year. It was demonstrated that tree age, climatic conditions and management of plantation affects wood density and its variability. The specific effect of variables on wood density was quantified by for multiple regression method. It was determined that tree year explained 25.8% of the total variation of density and 19.9% were caused by climatic condition where the tree growing. Wood density was less affected by the intensity of forest management with 5.9% of total variation.