The most energetic planetary collisions attain shock pressures that result in abundant melting and vaporization. Accurate predictions of the extent of melting and vaporization require knowledge of ...vast regions of the phase diagrams of the constituent materials. To reach the liquid‐vapor phase boundary of silica, we conducted uniaxial shock‐and‐release experiments, where quartz was shocked to a state sufficient to initiate vaporization upon isentropic decompression (hundreds of GPa). The apparent temperature of the decompressing fluid was measured with a streaked optical pyrometer, and the bulk density was inferred by stagnation onto a standard window. To interpret the observed post‐shock temperatures, we developed a model for the apparent temperature of a material isentropically decompressing through the liquid‐vapor coexistence region. Using published thermodynamic data, we revised the liquid‐vapor boundary for silica and calculated the entropy on the quartz Hugoniot. The silica post‐shock temperature measurements, up to entropies beyond the critical point, are in excellent qualitative agreement with the predictions from the decompressing two‐phase mixture model. Shock‐and‐release experiments provide an accurate measurement of the temperature on the phase boundary for entropies below the critical point, with increasing uncertainties near and above the critical point entropy. Our new criteria for shock‐induced vaporization of quartz are much lower than previous estimates, primarily because of the revised entropy on the Hugoniot. As the thermodynamics of other silicates are expected to be similar to quartz, vaporization is a significant process during high‐velocity planetary collisions.
Key Points
We measured the temperature on the liquid‐vapor curve of silica
We calculated the entropy on the quartz Hugoniot
We provide new criteria for shock‐induced vaporization of silica
Vitamin D deficiency has been implicated as a pathogenic factor in sepsis and intensive therapy unit mortality but has not been assessed as a risk factor for acute respiratory distress syndrome ...(ARDS). Causality of these associations has never been demonstrated.
To determine if ARDS is associated with vitamin D deficiency in a clinical setting and to determine if vitamin D deficiency in experimental models of ARDS influences its severity.
Human, murine and in vitro primary alveolar epithelial cell work were included in this study.
Vitamin D deficiency (plasma 25(OH)D levels <50 nmol/L) was ubiquitous in patients with ARDS and present in the vast majority of patients at risk of developing ARDS following oesophagectomy. In a murine model of intratracheal lipopolysaccharide challenge, dietary-induced vitamin D deficiency resulted in exaggerated alveolar inflammation, epithelial damage and hypoxia. In vitro, vitamin D has trophic effects on primary human alveolar epithelial cells affecting >600 genes. In a clinical setting, pharmacological repletion of vitamin D prior to oesophagectomy reduced the observed changes of in vivo measurements of alveolar capillary damage seen in deficient patients.
Vitamin D deficiency is common in people who develop ARDS. This deficiency of vitamin D appears to contribute to the development of the condition, and approaches to correct vitamin D deficiency in patients at risk of ARDS should be developed.
UKCRN ID 11994.
In the pursuit of improved diagnostic tests for infectious diseases, several classes of molecules have been scrutinized as prospective biomarkers. Small (18–22 nucleotide), non-coding RNA transcripts ...called microRNAs (miRNAs) have emerged as promising candidates with extensive diagnostic potential, due to their role in numerous diseases, previously established methods for quantitation and their stability within biofluids. Despite efforts to identify, characterize and apply miRNA signatures as diagnostic markers in a range of non-infectious diseases, their application in infectious disease has advanced relatively slowly. Here, we outline the benefits that miRNA biomarkers offer to the diagnosis, management, and treatment of infectious diseases. Investigation of these novel biomarkers could advance the use of personalized medicine in infectious disease treatment, which raises important considerations for validating their use as diagnostic or prognostic markers. Finally, we discuss new and emerging miRNA detection platforms, with a focus on rapid, point-of-care testing, to evaluate the benefits and obstacles of miRNA biomarkers for infectious disease.
Non-epithelial gonadal tumours largely comprise sex cord-stromal tumours (SCSTs) and germ cell tumours (GCTs). Specific somatic mutations in DICER1, a microRNA maturation pathway gene, have been ...identified in these tumours. We conducted a study that aimed to confirm, refine and extend the previous observations.
We used Sanger sequencing to sequence the RNase IIIa and IIIb domains of DICER1 in 154 gonadal tumours from 135 females and 19 males, as well as 43 extra-gonadal GCTs from 26 females and 17 males.
We identified heterozygous non-synonymous mutations in the RNase IIIb domain of DICER1 in 14/197 non-epithelial tumours (7.1%). Mutations were found in 9/28 SCSTs (32%), 5/118 gonadal GCTs (4.2%), 0/43 extra-gonadal GCTs and 0/8 miscellaneous tumours. The 14 mutations affected only five residues: E1705, D1709, E1788, D1810 and E1813. In all five patients where matched and constitutional DNA was available, the mutations were only somatic. There were no mutations found in the RNase IIIa domain.
More than half (8/15) of Sertoli-Leydig cell tumours (SLCTs) harbour DICER1 mutations in the RNase IIIb domain, while mutations are rarely found in GCTs. Genetic alterations in SLCTs may aid in classification and provide new approaches to therapy.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, SIK, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
ABSTRACT
In the two decades since the first extra‐solar planet was discovered, the detection and characterization of extra‐solar planets has become one of the key endeavours in all of modern science. ...Recently, direct detection techniques such as interferometry or coronagraphy have received growing attention because they reveal the population of exoplanets inaccessible to Doppler or transit techniques, and moreover they allow the faint signal from the planet itself to be investigated. Next‐generation stellar interferometers are increasingly incorporating photonic technologies due to the increase in fidelity of the data generated. Here, we report the design, construction and commissioning of a new high‐contrast imager, the integrated pupil‐remapping interferometer, an instrument we expect will find application in the detection of young faint companions in the nearest star‐forming regions. The laboratory characterization of the instrument demonstrated high‐visibility fringes on all interferometer baselines in addition to stable closure phase signals. We also report the first successful on‐sky experiments with the prototype instrument at the 3.9‐m Anglo‐Australian Telescope. Performance metrics recovered were consistent with ideal device behaviour after accounting for expected levels of decoherence and signal loss from the uncompensated seeing. The prospect of complete Fourier coverage coupled with the current performance metrics means that this photonically enhanced instrument is well positioned to contribute to the science of high‐contrast companions.
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BFBNIB, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
Background
Severe vitamin D deficiency causes osteomalacia, yet trials of vitamin D supplementation in the community have not on average demonstrated benefit to bone mineral density (BMD) or fracture ...risk in adults.
Objective
To determine whether monthly high‐dose vitamin D supplementation influences BMD in the general population and in those with low 25‐hydroxyvitamin D levels.
Methods
Two‐year substudy of a trial in older community‐resident adults. A total of 452 participants were randomized to receive monthly doses of vitamin D3 100 000 IU, or placebo. The primary end‐point was change in lumbar spine BMD. Exploratory analyses to identify thresholds of baseline 25‐hydroxyvitamin D for vitamin D effects on BMD were prespecified.
Results
Intention‐to‐treat analyses showed no significant treatment effect in the lumbar spine (between‐groups difference 0.0071 g cm−2, 95%CI: −0.0012, 0.0154) or total body but BMD loss at both hip sites was significantly attenuated by ~1/2% over 2 years. There was a significant interaction between baseline 25‐hydroxyvitamin D and treatment effect (P = 0.04). With baseline 25‐hydroxyvitamin D ≤ 30 nmol L−1 (n = 46), there were between‐groups BMD changes at the spine and femoral sites of ~2%, significant in the spine and femoral neck, but there was no effect on total body BMD. When baseline 25‐hydroxyvitamin D was >30 nmol L−1, differences were ~1/2% and significant only at the total hip.
Conclusions
This substudy finds no clinically important benefit to BMD from untargeted vitamin D supplementation of older, community‐dwelling adults. Exploratory analyses suggest meaningful benefit in those with baseline 25‐hydroxyvitamin D ≤ 30 nmol L−1. This represents a significant step towards a trial‐based definition of vitamin D deficiency for bone health in older adults.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
We present the results of a search for galaxy clusters in the Subaru–XMM Deep Field (SXDF). We reach a depth for a total cluster flux in the 0.5–2 keV band of 2 × 10−15 erg cm−2 s−1 over one of the ...widest XMM–Newton contiguous raster surveys, covering an area of 1.3 deg2. Cluster candidates are identified through a wavelet detection of extended X-ray emission. The red-sequence technique allows us to identify 57 cluster candidates. We report on the progress with the cluster spectroscopic follow-up and derive their properties based on the X-ray luminosity and cluster scaling relations. In addition, three sources are identified as X-ray counterparts of radio lobes, and in three further sources, an X-ray counterpart of the radio lobes provides a significant fraction of the total flux of the source. In the area covered by near-infrared data, our identification success rate achieves 86 per cent. We detect a number of radio galaxies within our groups, and for a luminosity-limited sample of radio galaxies we compute halo occupation statistics using a marked cluster mass function. We compare the cluster detection statistics in the SXDF with that in the literature and provide the modelling using the concordance cosmology combined with current knowledge of the X-ray cluster properties. The joint cluster log(N) − log(S) is overpredicted by the model, and an agreement can be achieved through a reduction of the concordance σ8 value by 5 per cent. Having considered the dn/dz and the X-ray luminosity function of clusters, we conclude that to pin down the origin of disagreement a much wider (50 deg2) survey is needed.
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BFBNIB, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
Background
We recently reported that the administration of zoledronate every 18 months to osteopenic older women reduces the incidence of fractures.
Objective
Here, we present a more detailed ...analysis of that trial to determine whether baseline clinical characteristics impact on the anti‐fracture efficacy of this intervention.
Methods
This is a prospective, randomized, placebo‐controlled, double‐blind trial in osteopenic postmenopausal women aged ≥ 65 years, to determine the anti‐fracture efficacy of zoledronate. 2000 women were recruited using electoral rolls and randomized to receive 4 infusions of either zoledronate 5 mg or normal saline, at 18‐month intervals. Each participant was followed for 6 years. Calcium supplements were not supplied.
Results
Fragility fractures (either vertebral or nonvertebral) occurred in 190 women in the placebo group (227 fractures) and in 122 women in the zoledronate group (131 fractures), odds ratio (OR) 0.59 (95%CI 0.46, 0.76; P < 0.0001). There were no significant interactions between baseline variables (age, anthropometry, BMI, dietary calcium intake, baseline fracture status, recent falls history, bone mineral density, calculated fracture risk) and the treatment effect. In particular, the reduction in fractures appeared to be independent of baseline fracture risk, and numbers needed to treat (NNT) to prevent one woman fracturing were not significantly different across baseline fracture risk tertiles.
Conclusions
The present analyses indicate that the decrease in fracture numbers is broadly consistent across this cohort. The lack of relationship between NNTs and baseline fracture risk calls into question the need for BMD measurement and precise fracture risk assessment before initiating treatment in older postmenopausal women.
Zoledronate prevented fractures in osteopenic women aged >65 years, and this was independent of baseline characteristics such as age, history of fractures and falls, and calculated fracture risk.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Hendra and Nipah viruses (genus Henipavirus, family Paramyxoviridae) are highly pathogenic bat-borne viruses. The need for high biocontainment when studying henipaviruses has hindered the development ...of therapeutics and knowledge of the viral infection cycle. We have performed a genome-wide siRNA screen at biosafety level 4 that identified 585 human proteins required for henipavirus infection. The host protein with the largest impact was fibrillarin, a nucleolar methyltransferase that was also required by measles, mumps and respiratory syncytial viruses for infection. While not required for cell entry, henipavirus RNA and protein syntheses were greatly impaired in cells lacking fibrillarin, indicating a crucial role in the RNA replication phase of infection. During infection, the Hendra virus matrix protein co-localized with fibrillarin in cell nucleoli, and co-associated as a complex in pulldown studies, while its nuclear import was unaffected in fibrillarin-depleted cells. Mutagenesis studies showed that the methyltransferase activity of fibrillarin was required for henipavirus infection, suggesting that this enzyme could be targeted therapeutically to combat henipavirus infections.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Electroplated hard chromium (EPHC) is used in many industries as a wear and corrosion resistant coating. However, the long term viability of the electroplating process is at risk due to legislation ...regarding the toxic chemicals used. The physical vapour deposition (PVD) process has been shown to produce chromium and chromium-based coatings that could be a possible alternative for EPHC in some applications. This study investigates the microstructure and properties of two PVD chromium coatings as a possible alternative to EPHC to provide resistance to galling. Two PVD deposition processes are investigated, namely electron beam PVD (EBPVD) and unbalanced magnetron sputtering (UMS). Galling wear tests were performed according to ASTM G98-17. The results show that the two PVD coatings are of similar hardness, surface roughness and exhibit similar scratch behaviour. However, the galling wear resistance of the coating deposited by UMS is approximately ten times that of the EBPVD coating, and similar to that of the EPHC. X-ray diffraction reveals that the EBPVD chromium coating has a strong preferred orientation of the {200} planes parallel to the coating surface whilst in the UMS PVD coating, preferred orientations of the {110} and {211} planes parallel to the surface are observed. The EPHC does not exhibit relative peak intensities which conform to the International Centre for Diffraction Data (ICDD) powder diffraction pattern consistent with chromium. The crystal orientation of the PVD chromium coatings appears to play a significant role in influencing galling resistance.
•The crystal orientation of PVD chromium coatings plays a significant role in their tribological behaviour.•Hardness alone cannot be used as a predictor of galling resistance of coated components against 316 steel.•Unbalanced magnetron sputtered PVD chromium is a possible candidate as an alternative to conventional electroplated chromium.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
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