The aim of this study is to identify the variables that affect stress redistribution in the strata underneath supercritical longwall panels. To do this, Wilson’s equations for the vertical stress ...distribution in the vicinity of a single longwall panel after it has been mined have been used in conjunction with finite element modelling to evaluate vertical stresses in the underlying strata. Key findings of the study are that the abutment angle has a significantly greater effect on the magnitude of the relative changes in vertical stress in the strata below a pillar than the overburden depth; anisotropic deformation behaviour of the rock mass results in strong ‘columnisation’ of the vertical stresses in the strata below the first mined seam; and the final vertical stress induced into the strata surrounding the second seam is larger in magnitude when narrow pillars are used in the first mined seam in conjunction with a large value of the ratio of overburden depth to interburden depth. For the particular cases considered in this study, increasing the abutment angle by 20° tripled the predicted change in vertical stress at a depth of 25m below the overlying seam. Furthermore, replacing the isotropic elastic material with a transversely isotropic elastic material increased the vertical stress at the depth of 25m below the overlying seam by 74%.
► Numerical methods are used to evaluate stresses under supercritical longwalls. ► Abutment angle of first mined seam significantly affects the maximum vertical stress. ► Multi-seam mining stability depends on pillar width as well as the OB/IB ratio. ► Larger vertical stresses at depth are observed for transversely isotropic rocks. ► The coal friction angle and UCS have little effect on the vertical stress changes.
Febrile illnesses are pre-eminent contributors to morbidity and mortality among children in South-East Asia but the causes are poorly understood. We determined the causes of fever in children ...hospitalised in Siem Reap province, Cambodia.
A one-year prospective study of febrile children admitted to Angkor Hospital for Children, Siem Reap. Demographic, clinical, laboratory and outcome data were comprehensively analysed. Between October 12(th) 2009 and October 12(th) 2010 there were 1225 episodes of febrile illness in 1180 children. Median (IQR) age was 2.0 (0.8-6.4) years, with 850 (69%) episodes in children <5 years. Common microbiological diagnoses were dengue virus (16.2%), scrub typhus (7.8%), and Japanese encephalitis virus (5.8%). 76 (6.3%) episodes had culture-proven bloodstream infection, including Salmonella enterica serovar Typhi (22 isolates, 1.8%), Streptococcus pneumoniae (13, 1.1%), Escherichia coli (8, 0.7%), Haemophilus influenzae (7, 0.6%), Staphylococcus aureus (6, 0.5%) and Burkholderia pseudomallei (6, 0.5%). There were 69 deaths (5.6%), including those due to clinically diagnosed pneumonia (19), dengue virus (5), and melioidosis (4). 10 of 69 (14.5%) deaths were associated with culture-proven bloodstream infection in logistic regression analyses (odds ratio for mortality 3.4, 95% CI 1.6-6.9). Antimicrobial resistance was prevalent, particularly in S. enterica Typhi, (where 90% of isolates were resistant to ciprofloxacin, and 86% were multi-drug resistant). Comorbid undernutrition was present in 44% of episodes and a major risk factor for acute mortality (OR 2.1, 95% CI 1.1-4.2), as were HIV infection and cardiac disease.
We identified a microbiological cause of fever in almost 50% of episodes in this large study of community-acquired febrile illness in hospitalized children in Cambodia. The range of pathogens, antimicrobial susceptibility, and co-morbidities associated with mortality described will be of use in the development of rational guidelines for infectious disease treatment and control in Cambodia and South-East Asia.
The INT/WFC Photometric H... Survey of the Northern Galactic Plane (IPHAS) is a 1800 deg... imaging survey covering Galactic latitudes |b| < 5... and longitudes ... = 30...-215... in the r, i, and Hα ...filters using the Wide Field Camera (WFC) on the 2.5-m Isaac Newton Telescope (INT) in La Palma. We present the first quality-controlled and globally calibrated source catalogue derived from the survey, providing single-epoch photometry for 219 million unique sources across 92 per cent of the footprint. The observations were carried out between 2003 and 2012 at a median seeing of 1.1 arcsec (sampled at 0.33 arcsec pixel...) and to a mean 5... depth of 21.2 (r), 20.0 (i), and 20.3 (Hα) in the Vega magnitude system. We explain the data reduction and quality control procedures, describe and test the global re-calibration, and detail the construction of the new catalogue. We show that the new calibration is accurate to 0.03 mag (root mean square) and recommend a series of quality criteria to select accurate data from the catalogue. Finally, we demonstrate the ability of the catalogue's unique (r - Hα,...r - i) diagram to (i) characterize stellar populations and extinction regimes towards different Galactic sightlines and (ii) select and quantify Hα emission-line objects. IPHAS is the first survey to offer comprehensive CCD photometry of point sources across the Galactic plane at visible wavelengths, providing the much-needed counterpart to recent infrared surveys. (ProQuest: ... denotes formulae/symbols omitted.)
A nearby multiplanet system
Exoplanets can interact gravitationally with other objects orbiting the same star, affecting their evolution and stability. Studying these effects requires locating ...systems with multiple planets. Monitoring the nearby red dwarf star GJ 887, Jeffers
et al.
detected periodic radial velocity signals, indicating the presence of two planets on orbits with periods of about 9 and 22 days and a further candidate planet (see the Perspective by Davies). The inclinations of the orbits are unknown, so only minimum masses could be determined, but those were consistent with both planets being super-Earths—more massive than Earth but less than Neptune. This system is only 3.3 parsecs from the Sun, which should facilitate follow-up with other techniques.
Science
, this issue p.
1477
; see also p.
1432
Two super-Earth exoplanets orbit GJ 887, a red dwarf star located only 3.3 parsecs from the Sun.
The closet exoplanets to the Sun provide opportunities for detailed characterization of planets outside the Solar System. We report the discovery, using radial velocity measurements, of a compact multiplanet system of super-Earth exoplanets orbiting the nearby red dwarf star GJ 887. The two planets have orbital periods of 9.3 and 21.8 days. Assuming an Earth-like albedo, the equilibrium temperature of the 21.8-day planet is ~350 kelvin. The planets are interior to, but close to the inner edge of, the liquid-water habitable zone. We also detect an unconfirmed signal with a period of ~50 days, which could correspond to a third super-Earth in a more temperate orbit. Our observations show that GJ 887 has photometric variability below 500 parts per million, which is unusually quiet for a red dwarf.
Polymerase chain reaction (PCR) assessment of clonal immunoglobulin (Ig) and T-cell receptor (TCR) gene rearrangements is an important diagnostic tool in mature B-cell neoplasms. However, lack of ...standardized PCR protocols resulting in a high level of false negativity has hampered comparability of data in previous clonality studies. In order to address these problems, 22 European laboratories investigated the Ig/TCR rearrangement patterns as well as t(14;18) and t(11;14) translocations of 369 B-cell malignancies belonging to five WHO-defined entities using the standardized BIOMED-2 multiplex PCR tubes accompanied by international pathology panel review. B-cell clonality was detected by combined use of the IGH and IGK multiplex PCR assays in all 260 definitive cases of B-cell chronic lymphocytic leukemia (n=56), mantle cell lymphoma (n=54), marginal zone lymphoma (n=41) and follicular lymphoma (n=109). Two of 109 cases of diffuse large B-cell lymphoma showed no detectable clonal marker. The use of these techniques to assign cell lineage should be treated with caution as additional clonal TCR gene rearrangements were frequently detected in all disease categories. Our study indicates that the BIOMED-2 multiplex PCR assays provide a powerful strategy for clonality assessment in B-cell malignancies resulting in high Ig clonality detection rates particularly when IGH and IGK strategies are combined.
Aims
. We present the design and pre-launch performance of the Solar Orbiter Heliospheric Imager (SoloHI) which is an instrument prepared for inclusion in the ESA/NASA Solar Orbiter mission, ...currently scheduled for launch in 2020.
Methods
. The goal of this paper is to provide details of the SoloHI instrument concept, design, and pre-flight performance to give the potential user of the data a better understanding of how the observations are collected and the sources that contribute to the signal.
Results
. The paper discusses the science objectives, including the SoloHI-specific aspects, before presenting the design concepts, which include the optics, mechanical, thermal, electrical, and ground processing. Finally, a list of planned data products is also presented.
Conclusions
. The performance measurements of the various instrument parameters meet or exceed the requirements derived from the mission science objectives. SoloHI is poised to take its place as a vital contributor to the science success of the Solar Orbiter mission.
Objective:In a multicentre study to explore the effects of licofelone as a disease-modifying osteoarthritis drug in comparison with naproxen in patients with knee osteoarthritis (OA), using MRI and ...x-ray examination.Methods:Patients with knee OA (n = 355) were randomised to receive either licofelone (200 mg twice a day) or naproxen (500 mg twice a day). MRI and x-ray examinations were performed at baseline, 6 months (MRI only), 12 and 24 months. MRI was used to assess quantitatively changes in cartilage volume, and x-ray examinations (Lyon–Schuss) to measure changes in the mean and minimum joint space width (JSW) in the medial compartment. Questionnaires probing symptoms were completed. Data were presented as intention to treat (ITT) and according to protocol (ATP).Results:Cartilage volume loss in the global joint and medial and lateral compartments was significantly less in the licofelone than in the naproxen group for ITT at 12 and 24 months and for ATP at all times except in the medial compartment. Patients with medial meniscal extrusion had a greater loss of cartilage volume. In these patients, licofelone markedly reduced the cartilage loss for both ITT and ATP at 12 and 24 months. Although licofelone showed less reduction in the JSW than naproxen, this did not reach significance. All clinical variables were improved at 24 months (p<0.001) for both groups, with a good safety profile.Conclusion:Licofelone and naproxen were equally effective in reducing OA symptoms; however, licofelone significantly reduced cartilage volume loss over time, thus having a protective effect in patients with knee OA. This study proves the superiority of quantitative MRI over x-ray examinations in a multicentre clinical trial.
The solution chemistry of a chelator developed for 227Th targeted alpha therapy was probed. The compound of interest is an octadentate ligand comprising four N-methyl-3-hydroxy-pyridine-2-one ...metal-binding units, two tertiary amine groups, and one carboxylate arm appended for bioconjugation. The seven pK a values of the ligand and the stability constants of complexes formed with Th(IV), Hf(IV), Zr(IV), Gd(III), Eu(III), Al(III), and Fe(III) were determined. The ligand exhibits extreme thermodynamic selectivity toward tetravalent metal ions with a ca. 20 orders of magnitude difference between the formation constant of the Th(IV) species formed at physiological pH, namely ThL−, and that of its Eu(III) analogue. Likewise, log β110 values of 41.7 ± 0.3 and 26.9 ± 0.3 (T = 25 °C) were measured for ThL− and FeIIIL2–, respectively, highlighting the high affinity and selectivity of the ligand for Th ions over potentially competing endogenous metals. Single crystal X-ray analysis of the Fe(III) complex revealed a dinuclear 2:2 metal:chelator complex crystallizing in the space group P1̅. The formation of this dimeric species is likely favored by several intramolecular hydrogen bonds and the protonation state of the chelator in acidic media. LIII edge EXAFS data on the Th(IV) complexes of both the ligand and a monoclonal antibody conjugate revealed the expected mononuclear 1:1 metal:chelator coordination environment. This was also confirmed by high resolution mass spectrometry. Finally, kinetic experiments demonstrated that labeling the bioconjugated ligand with Th(IV) could be achieved and completed after 1 h at room temperature, reinforcing the high suitability of this chelator for 227Th targeted alpha therapy.
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy associated with <5% 5-year survival, in which standard chemotherapeutics have limited benefit. The disease is associated with ...significant intra- and peritumoral inflammation and failure of protective immunosurveillance. Indeed, inflammatory signals are implicated in both tumour initiation and tumour progression. The major pathways regulating PDAC-associated inflammation are now being explored. Activation of leukocytes, and upregulation of cytokine and chemokine signalling pathways, both have been shown to modulate PDAC progression. Therefore, targeting inflammatory pathways may be of benefit as part of a multi-target approach to PDAC therapy. This review explores the pathways known to modulate inflammation at different stages of tumour development, drawing conclusions on their potential as therapeutic targets in PDAC.
The uncertainties and sources of variation in projected impacts of climate change on agriculture and terrestrial ecosystems depend not only on the emission scenarios and climate models used for ...projecting future climates, but also on the impact models used, and the local soil and climatic conditions of the managed or unmanaged ecosystems under study. We addressed these uncertainties by applying different impact models at site, regional and continental scales, and by separating the variation in simulated relative changes in ecosystem performance into the different sources of uncertainty and variation using analyses of variance. The crop and ecosystem models used output from a range of global and regional climate models (GCMs and RCMs) projecting climate change over Europe between 1961-1990 and 2071-2100 under the IPCC SRES scenarios. The projected impacts on productivity of crops and ecosystems included the direct effects of increased CO₂ concentration on photosynthesis. The variation in simulated results attributed to differences between the climate models were, in all cases, smaller than the variation attributed to either emission scenarios or local conditions. The methods used for applying the climate model outputs played a larger role than the choice of the GCM or RCM. The thermal suitability for grain maize cultivation in Europe was estimated to expand by 30-50% across all SRES emissions scenarios. Strong increases in net primary productivity (NPP) (35-54%) were projected in northern European ecosystems as a result of a longer growing season and higher CO₂ concentrations. Changing water balance dominated the projected responses of southern European ecosystems, with NPP declining or increasing only slightly relative to present-day conditions. Both site and continental scale models showed large increases in yield of rain-fed winter wheat for northern Europe, with smaller increases or even decreases in southern Europe. Site-based, regional and continental scale models showed large spatial variations in the response of nitrate leaching from winter wheat cultivation to projected climate change due to strong interactions with soils and climate. The variation in simulated impacts was smaller between scenarios based on RCMs nested within the same GCM than between scenarios based on different GCMs or between emission scenarios.
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