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Percutaneous vertebroplasty is increasingly used for treatment of pain in patients with osteoporotic vertebral compression fractures, but the efficacy, cost-effectiveness, and safety of the procedure remain uncertain. We aimed to clarify whether vertebroplasty has additional value compared with optimum pain treatment in patients with acute vertebral fractures. Patients were recruited to this open-label prospective randomised trial from the radiology departments of six hospitals in the Netherlands and Belgium. Patients were aged 50 years or older, had vertebral compression fractures on spine radiograph (minimum 15% height loss; level of fracture at Th5 or lower; bone oedema on MRI), with back pain for 6 weeks or less, and a visual analogue scale (VAS) score of 5 or more. Patients were randomly allocated to percutaneous vertebroplasty or conservative treatment by computer-generated randomisation codes with a block size of six. Masking was not possible for participants, physicians, and outcome assessors. The primary outcome was pain relief at 1 month and 1 year as measured by VAS score. Analysis was by intention to treat. This study is registered at ClinicalTrials.gov, number NCT00232466. Between Oct 1, 2005, and June 30, 2008, we identified 431 patients who were eligible for randomisation. 229 (53%) patients had spontaneous pain relief during assessment, and 202 patients with persistent pain were randomly allocated to treatment (101 vertebroplasty, 101 conservative treatment). Vertebroplasty resulted in greater pain relief than did conservative treatment; difference in mean VAS score between baseline and 1 month was −5·2 (95% CI −5·88 to −4·72) after vertebroplasty and −2·7 (−3·22 to −1·98) after conservative treatment, and between baseline and 1 year was −5·7 (−6·22 to −4·98) after vertebroplasty and −3·7 (−4·35 to −3·05) after conservative treatment. The difference between groups in reduction of mean VAS score from baseline was 2·6 (95% CI 1·74–3·37, p<0·0001) at 1 month and 2·0 (1·13–2·80, p<0·0001) at 1 year. No serious complications or adverse events were reported. In a subgroup of patients with acute osteoporotic vertebral compression fractures and persistent pain, percutaneous vertebroplasty is effective and safe. Pain relief after vertebroplasty is immediate, is sustained for at least a year, and is significantly greater than that achieved with conservative treatment, at an acceptable cost. ZonMw; COOK Medical.

Diffuse infiltrative invasion is a major cause for the dismal prognosis of glioblastoma multiforme (GBM), but the underlying mechanisms remain incompletely understood. Using human glioma stem cells (GSCs) that recapitulate the invasive propensity of primary GBM, we find that EphA2 critically regulates GBM invasion in vivo . EphA2 was expressed in all seven GSC lines examined, and overexpression of EphA2 enhanced intracranial invasion. The effects required Akt-mediated phosphorylation of EphA2 on serine 897. In vitro the Akt–EphA2 signaling axis is maintained in the absence of ephrin-A ligands and is disrupted upon ligand stimulation. To test whether ephrin-As in tumor microenvironment can regulate GSC invasion, the newly established Efna1;Efna3;Efna4 triple knockout mice (TKO) were used in an ex vivo brain slice invasion assay. We observed significantly increased GSC invasion through the brain slices of TKO mice relative to wild-type (WT) littermates. Mechanistically EphA2 knockdown suppressed stem cell properties of GSCs, causing diminished self-renewal, reduced stem marker expression and decreased tumorigenicity. In a subset of GSCs, the reduced stem cell properties were associated with lower Sox2 expression. Overexpression of EphA2 promoted stem cell properties in a kinase-independent manner and increased Sox2 expression. Disruption of Akt-EphA2 cross-talk attenuated stem cell marker expression and neurosphere formation while having minimal effects on tumorigenesis. Taken together, the results show that EphA2 endows invasiveness of GSCs in vivo in cooperation with Akt and regulates glioma stem cell properties.

Intense femtosecond laser excitation can produce transient states of matter that would otherwise be inaccessible to laboratory investigation. At high excitation densities, the interatomic forces that bind solids and determine many of their properties can be substantially altered. Here, we present the detailed mapping of the carrier density-dependent interatomic potential of bismuth approaching a solid-solid phase transition. Our experiments combine stroboscopic techniques that use a high-brightness linear electron accelerator-based x-ray source with pulse-by-pulse timing reconstruction for femtosecond resolution, allowing quantitative characterization of the interatomic potential energy surface of the highly excited solid.

Gloger's rule is usually interpreted as predicting darker coloured animals in warmer and more humid/vegetated regions. The relative importance of temperature and rainfall or vegetation is however unclear, and often only one variable is tested at a time, mainly through proxies. Here, I assess the predictions of Gloger's rule for interspecific achromatic plumage variation (dark to light variation) for an entire avifauna (551 species of Australian landbirds). I tested the effects of climatic variables (temperature and rainfall) and vegetation structure on plumage reflectance at species and assemblage level (100 × 100 km cells), controlling for phylogenetic relatedness and spatial autocorrelation. To assess the robustness of these results I compared observed results with those of a null distribution of effects obtained from repeatedly simulating random plumage reflectance evolution on the phylogeny. At both the species and assemblage level, darker coloured birds were found in wetter and colder regions and in more densely vegetated habitats. Simulations confirm results at the species level and the effect of temperature at the assemblage level, but rainfall and vegetation effects at the assemblage level fall within the distribution of simulated effects and should be interpreted with care. Interspecific colour variation in Australian birds supports Gloger's rule for rainfall/vegetation, but shows the opposite pattern for temperature. Darker colours in wet and vegetated environments are consistent with the role of melanin pigmentation in preventing feather degradation by bacteria, but also with background‐matching for camouflage. Darker plumage might be beneficial in colder regions or detrimental in warmer regions if it affects thermoregulation, a selective force often only assumed to be of importance for ectotherms. The data highlight the need to test the generality of biogeographic rules across levels and at broad scale. Experimental work is needed to confirm the mechanisms linking plumage achromatic variation to climate.

In this work, we propose a strategy for high-throughput design and development of compositionally complex alloys combining theoretical and experimental alloy screening. This methodology was applied for the exploration of the (Co 2 CrFeNi 2 ) 1- x - y Ti x Al y subsystem of so-called high entropy superalloys in the Al–Co–Cr–Fe–Ni–Ti alloy system. Alloy design was guided by thermodynamic calculations based on the CALPHAD approach. The evolution of the microstructure with increasing Al and Ti content was analyzed in the as-built, homogenized and age-hardened conditions by means of scanning electron microscopy, energy-dispersive X-ray spectroscopy and electron backscattered diffraction. Additionally, the evolution of the sample hardness with increasing Al and Ti contents was determined for all conditions. Based on the experimental results, the reliability of the CALPHAD calculations was assessed. Generally, a good agreement between calculations and experiments is achieved in the homogenized state. In the aged conditions, the CALPHAD predictions of the precipitation processes are partly inaccurate and need improvement. Optimal Al and Ti concentrations are derived for age hardening through L1 2 and combined L1 2  + B2 precipitations.

Anthropogenic environmental impacts can disrupt the sensory environment of animals and affect important processes from mate choice to predator avoidance. Currently, these effects are best understood for auditory and chemosensory modalities, and recent reviews highlight their importance for conservation. We examined how anthropogenic changes to the visual environment (ambient light, transmission, and backgrounds) affect visual communication and camouflage and considered the implications of these effects for conservation. Human changes to the visual environment can increase prédation risk by affecting camouflage effectiveness, lead to maladaptive patterns of mate choice, and disrupt mutualistic interactions between pollinators and plants. Implications for conservation are particularly evident for disrupted camouflage due to its tight links with survival. The conservation importance of impaired visual communication is less documented. The effects of anthropogenic changes on visual communication and camouflage may be severe when they affect critical processes such as pollination or species recognition. However, when impaired mate choice does not lead to hybridization, the conservation consequences are less clear. We suggest that the demographic effects of human impacts on visual communication and camouflage will be particularly strong when human-induced modifications to the visual environment are evolutionarily novel (i.e., very different from natural variation); affected species and populations have low levels of intraspecific (genotypic and phenotypic) variation and behavioral, sensory, or physiological plasticity; and the processes affected are directly related to survival (camouflage), species recognition, or number of offspring produced, rather than offspring quality or attractiveness. Our findings suggest that anthropogenic effects on the visual environment may be of similar importance relative to conservation as anthropogenic effects on other sensory modalities. Los impactos ambientales antropogénicos pueden perturbar el ambiente sensorial de los animales y afectar procesos importantes, desde selección de pareja hasta evitación de depredadores. Actualmente, estos efectos están mejor entendidos para las modalidades audiosensoriales y quimiosensoriales, y las revisiones recientes resaltan su importancia para la conservación. Examinamos cómo los cambios antropogénicos al ambiente visual (luz de ambiente, trasmisión, fondos) afectan la comunicación visual y el camuflaje y consideramos las implicaciones de estos efectos para la conservación. Los cambios humanos al ambiente visual pueden incrementar el riesgo de depredación al afectar la efectividad del camuflaje, llevar a patrones mal-adaptativos de selección de pareja y perturbar las interacciones mutualistas entre los polinizadores y las plantas. Las implicaciones para la conservación son particularmente evidentes para el camuflaje perturbado debido a su fuerte vínculo con la supervivencia. La importancia de la conservación de la comunicación visual disminuida está menos documentada. Los efectos de los cambios antropogénicos sobre la comunicación visual y el camuflaje pueden ser graves cuando afectan los procesos críticos, como la polinización o el reconocimiento de especie. Sin embargo, cuando la selección afectada de pareja no resulta en la hibridación, las consecuencias para la conservación quedan menos claras. Sugerimos que los efectos demográficos de los impactos humanos sobre la comunicación visual y el camuflaje serán particularmente fuertes cuando las modificaciones al ambiente visual inducidas por humanos sean evolutivamente novedosas (es decir, muy diferentes a la variación natural); cuando las especies y poblaciones afectadas tengan niveles bajos de variación intraespecífica (genotípica y fenotípica) y plasticidad conductual, sensorial o fisiológica; y cuando los procesos afectados estén directamente relacionados con la supervivencia (camuflaje), reconocimiento de especie o número de descendientes producidos, en lugar de la calidad o lo atractivo de los descendientes. Nuestros hallazgos sugieren que los efectos antropogénicos sobre el ambiente visual pueden ser de importancia similar en relación con la conservación como lo son los efectos antropogénicos sobre otras modalidades sensoriales.

Tree mortality can fundamentally affect soils, which in turn shape forest regeneration and dynamics. Here, we quantify the dynamics of soil volumes associated with tree mortality, parsing effects by mode of tree death (broken vs uprooted) and species. The concept of ecosystem biogeomorphic succession was also tested. We used repeated tree censuses carried out in ten European and North American forests, differing in species composition, climate, and disturbance regimes. Development of more than 172,000 individual trees was recorded over periods of up to 48 years, during which more than one-third of the trees died. Biogeomorphic impact of deaths was modeled using allometry and field measurements. Tree uprooting-related soil volumes accounted annually for 0.01–13.5 m3ha−1, reaching maximum values on sites with infrequent strong windstorms (European mountains). The redistribution of soils related to trees that died standing ranged annually between 0.17 and 20.7 m3ha−1 and were highest in the presence of non-stand-replacing fire (Yosemite National Park, USA). Comparison of the results with known long-term erosion rates suggests that on certain sites over the last few millennia, tree uprooting may represent a significant driver of landscape erosion. Despite the key role of severe disturbances, the data showed potential for future increases in the intensity of biogeomorphic processes. The high biogeomorphic potential in some USA sites that has not yet been realized can be activated by external changes in the disturbance regime. Forests in Central Europe, on the other hand, are more sensitive to changes in biogeomorphic processes due to species turnover.

The TOTEM collaboration at the CERN LHC has measured the differential cross-section of elastic proton–proton scattering at s=8TeV in the squared four-momentum transfer range 0.2GeV2<|t|<1.9GeV2. This interval includes the structure with a diffractive minimum (“dip”) and a secondary maximum (“bump”) that has also been observed at all other LHC energies, where measurements were made. A detailed characterisation of this structure for s=8TeV yields the positions, |t|dip=(0.521±0.007)GeV2 and |t|bump=(0.695±0.026)GeV2, as well as the cross-section values, dσ/dtdip=(15.1±2.5)μb/GeV2 and dσ/dtbump=(29.7±1.8)μb/GeV2, for the dip and the bump, respectively.

Summary Sexual dichromatism (SD) often reflects intense sexual selection on males. It has been hypothesized that sexual selection should favour the elaboration of those male colours that honestly signal quality and that such colours should therefore show higher SD. Costliness of colours is expected to vary according to their production mechanism (pigment type, feather microstructure and combinations thereof). Carotenoid‐based colours, due to their dietary origin and competing functions of carotenoid pigments, are the best documented costly colours, while endogenous pigments and structural colours are expected to be less costly. However, how SD varies with colour‐producing mechanism has not been systematically addressed. Here, we test the link between SD and mechanisms of colour production across nearly all Australian passerines (n = 302) and parrots (n = 48), using reflectance spectrometry and visual models. We quantified SD [chromatic (hue and saturation) and achromatic (light to dark)] for individual plumage patches as well as for the whole plumage. We then compared whether these SD estimates vary for plumage produced by different mechanisms of colour production. Not unexpectedly, individual plumage patches were most sexually dichromatic when males and females have different mechanisms of colour production. In most cases however, both sexes share the same mechanism. Among these, red carotenoid‐based plumage in passerines showed the highest SD, while in passerines as well as in parrots, melanin‐based plumage and white plumage have the lowest levels of SD. Average SD within species is weakly predicted by the proportion of the plumage produced by different mechanisms. This effect is strongest for red carotenoids, but equally so for males and females. In contrast, effects of structural and pheomelanin‐based colours are different between sexes, highlighting the links between high SD and the evolution of different mechanisms of colour production in males and females. While our analysis showed that colours based on red carotenoids have higher levels of SD, the differences were small, and most mechanisms of colour production were able to produce a similar range of SD. These results do not support the hypothesis that sexual selection should preferentially lead to the elaboration of some types of colours over others. A lay summary is available for this article. Lay Summary

One of the critical aspects of masonry failure is the shear capacity of the composite brick-mortar assemblage. In the last four decades, an increasing effort has been devoted to study the shear behavior of masonry structures. Different test approaches have been used to determine the shear strength of masonry, including laboratory tests and in-place measurements. In this paper, a close view of the test method used for the in-place measurement of masonry shear strength is taken, using an innovative approach based on image correlation techniques. A series of in-place shear tests were conducted at one of the masonry infilled reinforced concrete (RC) frames tested at the University of Colorado Boulder, Boulder, CO, within the framework of a comprehensive NSF-NEESR-SG project at the University of California San Diego, San Diego, CA. Initial cohesion and friction angles were determined for the infill wall, and the lack of uniformity along the shear failure planes was investigated with the aid of finite elements and digital image correlations.