Relation of vertebral deformities to bone density, structure, and strength.

Because they are not reliably discriminated by areal bone mineral density (aBMD) measurements, it is unclear whether minimal vertebral deformities represent early osteoporotic fractures. To address this, we compared 90 postmenopausal women with no deformity (controls) with 142 women with one or more semiquantitative grade 1 (mild) deformities and 51 women with any grade 2-3 (moderate/severe) deformities. aBMD was measured by dual-energy X-ray absorptiometry (DXA), lumbar spine volumetric bone mineral density (vBMD) and geometry by quantitative computed tomography (QCT), bone microstructure by high-resolution peripheral QCT at the radius (HRpQCT), and vertebral compressive strength and load-to-strength ratio by finite-element analysis (FEA) of lumbar spine QCT images. Compared with controls, women with grade 1 deformities had significantly worse values for many bone density, structure, and strength parameters, although deficits all were much worse for the women with grade 2-3 deformities. Likewise, these skeletal parameters were more strongly associated with moderate to severe than with mild deformities by age-adjusted logistic regression. Nonetheless, grade 1 vertebral deformities were significantly associated with four of the five main variable categories assessed: bone density (lumbar spine vBMD), bone geometry (vertebral apparent cortical thickness), bone strength (overall vertebral compressive strength by FEA), and load-to-strength ratio (45-degree forward bending ÷ vertebral compressive strength). Thus significantly impaired bone density, structure, and strength compared with controls indicate that many grade 1 deformities do represent early osteoporotic fractures, with corresponding implications for clinical decision making

Impact of model resolution on tropical cyclone simulation using the HighResMIP–PRIMAVERA multimodel Ensemble

A multimodel, multiresolution set of simulations over the period 1950–2014 using a common forcing protocol from CMIP6 HighResMIP have been completed by six modeling groups. Analysis of tropical cyclone performance using two different tracking algorithms suggests that enhanced resolution toward 25 km typically leads to more frequent and stronger tropical cyclones, together with improvements in spatial distribution and storm structure. Both of these factors reduce typical GCM biases seen at lower resolution. Using single ensemble members of each model, there is little evidence of systematic improvement in interannual variability in either storm frequency or accumulated cyclone energy as compared with observations when resolution is increased. Changes in the relationships between large-scale drivers of climate variability and tropical cyclone variability in the Atlantic Ocean are also not robust to model resolution. However, using a larger ensemble of simulations (of up to 14 members) with one model at different resolutions does show evidence of increased skill at higher resolution. The ensemble mean correlation of Atlantic interannual tropical cyclone variability increases from ~0.5 to ~0.65 when resolution increases from 250 to 100 km. In the northwestern Pacific Ocean the skill keeps increasing with 50-km resolution to 0.7. These calculations also suggest that more than six members are required to adequately distinguish the impact of resolution within the forced signal from the weather noise

Electoral Dioramas: On the Problem of Representation in Voting Advice Applications

Voting Advice Applications (VAAs) are online tools designed to help citizens decide how to vote. They typically offer their users a representation of what is at stake in an election by matching user preferences on issues with those of parties or candidates. While the use of VAAs has boomed in recent years in both established and new democracies, this new phenomenon in the electoral landscape has received little attention from political theorists. The current academic debate is focused on epistemic aspects of the question how a VAA can adequately represent electoral politics. We argue that conceptual and normative presuppositions at play in the background of the tool are at least as important. Even a well-developed VAA does not simply reflect what is at stake in the election by neutrally passing along information. Rather, it structures political information in a way that is informed by the developers’ presuppositions. Yet, these presuppositions remain hidden if we interpret the tool as a mirror that offers the user a reflection of him/herself situated within the political landscape. VAAs should therefore be understood as electoral dioramas, staged according to a contestable picture of politics

Projected future changes in tropical cyclones using the CMIP6 HighResMIP multimodel ensemble

Future changes in tropical cyclone properties are an important component of climate change impacts and risk for many tropical and midlatitude countries. In this study we assess the performance of a multimodel ensemble of climate models, at resolutions ranging from 250 to 25 km. We use a common experimental design including both atmosphere‐only and coupled simulations run over the period 1950–2050, with two tracking algorithms applied uniformly across the models. There are overall improvements in tropical cyclone frequency, spatial distribution, and intensity in models at 25 km resolution, with several of them able to represent very intense storms. Projected tropical cyclone activity by 2050 generally declines in the South Indian Ocean, while changes in other ocean basins are more uncertain and sensitive to both tracking algorithm and imposed forcings. Coupled models with smaller biases suggest a slight increase in average TC 10 m wind speeds by 2050

Associations of ATR and CHEK1 Single Nucleotide Polymorphisms with Breast Cancer

DNA damage and replication checkpoints mediated by the ATR-CHEK1 pathway are key to the maintenance of genome stability, and both ATR and CHEK1 have been proposed as potential breast cancer susceptibility genes. Many novel variants recently identified by the large resequencing projects have not yet been thoroughly tested in genome-wide association studies for breast cancer susceptibility. We therefore used a tagging SNP (tagSNP) approach based on recent SNP data available from the 1000 genomes projects, to investigate the roles of ATR and CHEK1 in breast cancer risk and survival. ATR and CHEK1 tagSNPs were genotyped in the Sheffield Breast Cancer Study (SBCS; 1011 cases and 1024 controls) using Illumina GoldenGate assays. Untyped SNPs were imputed using IMPUTE2, and associations between genotype and breast cancer risk and survival were evaluated using logistic and Cox proportional hazard regression models respectively on a per allele basis. Significant associations were further examined in a meta-analysis of published data or confirmed in the Utah Breast Cancer Study (UBCS). The most significant associations for breast cancer risk in SBCS came from rs6805118 in ATR (p=7.6x10-5) and rs2155388 in CHEK1 (p=3.1x10-6), but neither remained significant after meta-analysis with other studies. However, meta-analysis of published data revealed a weak association between the ATR SNP rs1802904 (minor allele frequency is 12%) and breast cancer risk, with a summary odds ratio (confidence interval) of 0.90 (0.83-0.98) [p=0.0185] for the minor allele. Further replication of this SNP in larger studies is warranted since it is located in the target region of 2 microRNAs. No evidence of any survival effects of ATR or CHEK1 SNPs were identified. We conclude that common alleles of ATR and CHEK1 are not implicated in breast cancer risk or survival, but we cannot exclude effects of rare alleles and of common alleles with very small effect sizes

Proteome Analysis of Borrelia burgdorferi Response to Environmental Change

We examined global changes in protein expression in the B31 strain of Borrelia burgdorferi, in response to two environmental cues (pH and temperature) chosen for their reported similarity to those encountered at different stages of the organism's life cycle. Multidimensional nano-liquid chromatographic separations coupled with tandem mass spectrometry were used to examine the array of proteins (i.e., the proteome) of B. burgdorferi for different pH and temperature culture conditions. Changes in pH and temperature elicited in vitro adaptations of this spirochete known to cause Lyme disease and led to alterations in protein expression that are associated with increased microbial pathogenesis. We identified 1,031 proteins that represent 59% of the annotated genome of B. burgdorferi and elucidated a core proteome of 414 proteins that were present in all environmental conditions investigated. Observed changes in protein abundances indicated varied replicon usage, as well as proteome functional distributions between the in vitro cell culture conditions. Surprisingly, the pH and temperature conditions that mimicked B. burgdorferi residing in the gut of a fed tick showed a marked reduction in protein diversity. Additionally, the results provide us with leading candidates for exploring how B. burgdorferi adapts to and is able to survive in a wide variety of environmental conditions and lay a foundation for planned in situ studies of B. burgdorferi isolated from the tick midgut and infected animals

The Case for Probe-class NASA Astrophysics Missions

Astrophysics spans an enormous range of questions on scales from individual planets to the entire cosmos. To address the richness of 21st century astrophysics requires a corresponding richness of telescopes spanning all bands and all messengers. Much scientific benefit comes from having the multi-wavelength capability available at the same time. Most of these bands,or measurement sensitivities, require space-based missions. Historically, NASA has addressed this need for breadth with a small number of flagship-class missions and a larger number of Explorer missions. While the Explorer program continues to flourish, there is a large gap between Explorers and strategic missions. A fortunate combination of new astrophysics technologies with new, high capacity, low dollar-per-kg to orbit launchers, and new satellite buses allow for cheaper missions with capabilities approaching strategic mission levels. NASA has recognized these developments by calling for Probe-class mission ideas for mission studies, spanning most of the electromagnetic spectrum from GeV gamma-rays to the far infrared, and the new messengers of neutrinos and ultra-high energy cosmic rays. The key insight from the Probes exercise is that order-of-magnitude advances in science performance metrics are possible across the board for initial total cost estimates in the range 500M-1B dollars