Dengue fever is a re-emerging viral disease commonly occurring in tropical and subtropical areas. The clinical features and abnormal laboratory test results of dengue infection are similar to those ...of other febrile illnesses; hence, its accurate and timely diagnosis for providing appropriate treatment is difficult. Delayed diagnosis may be associated with inappropriate treatment and higher risk of death. Early and correct diagnosis can help improve case management and optimise the use of resources such as hospital staff, beds, and intensive care equipment. The goal of this study was to develop a predictive model to characterise dengue severity based on early clinical and laboratory indicators using data mining and statistical tools.
We retrieved data from a study of febrile illness in children at Angkor Hospital for Children, Cambodia. Of 1225 febrile episodes recorded, 198 patients were confirmed to have dengue. A classification and regression tree (CART) was used to construct a predictive decision tree for severe dengue, while logistic regression analysis was used to independently quantify the significance of each parameter in the decision tree.
A decision tree algorithm using haematocrit, Glasgow Coma Score, urine protein, creatinine, and platelet count predicted severe dengue with a sensitivity, specificity, and accuracy of 60.5%, 65% and 64.1%, respectively.
The decision tree we describe, using five simple clinical and laboratory indicators, can be used to predict severe cases of dengue among paediatric patients on admission. This algorithm is potentially useful for guiding a patient-monitoring plan and outpatient management of fever in resource-poor settings.
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.
The solution‐state interactions of plutonium and berkelium with the octadentate chelator 3,4,3‐LI(1,2‐HOPO) (343‐HOPO) were investigated and characterized by X‐ray absorption spectroscopy, which ...revealed in situ reductive decomposition of the tetravalent species of both actinide metals to yield Pu(III) and Bk(III) coordination complexes. X‐ray absorption near‐edge structure (XANES) measurements were the first indication of in situ synchrotron redox chemistry as the Pu threshold and white‐line position energies for Pu‐343‐HOPO were in good agreement with known diagnostic Pu(III) species, whereas Bk‐343‐HOPO results were found to mirror the XANES behavior of Bk(III)‐DTPA. Extended X‐ray absorption fine structure results revealed An—OHOPO bond distances of 2.498 (5) and 2.415 (2) Å for Pu and Bk, respectively, which match well with bond distances obtained for trivalent actinides and 343‐HOPO via density functional theory calculations. Pu(III)‐ and Bk(III)‐343‐HOPO data also provide initial insight into actinide periodicity as they can be compared with previous results with Am(III)‐, Cm(III)‐, Cf(III)‐, and Es(III)‐343‐HOPO, which indicate there is likely an increase in 5f covalency and heterogeneity across the actinide series.
X‐ray absorption spectroscopy was used to probe the interactions between an octadentate hydroxypyridinone chelator and two transuranic elements in microgram quantities – plutonium and berkelium – within buffered solutions. Despite the precedence for chelation‐driven stabilization of the tetravalent oxidation state of actinides with this ligand, in situ reductive decomposition yielded plutonium(III) and berkelium(III) coordination complexes.
Methylation of the SKA2 (spindle and kinetochore-associated complex subunit 2) gene has recently been identified as a promising biomarker of suicide risk. Based on this finding, we examined ...associations between SKA2 methylation, cortical thickness and psychiatric phenotypes linked to suicide in trauma-exposed veterans. About 200 trauma-exposed white non-Hispanic veterans of the recent conflicts in Iraq and Afghanistan (91% male) underwent clinical assessment and had blood drawn for genotyping and methylation analysis. Of all, 145 participants also had neuroimaging data available. Based on previous research, we examined DNA methylation at the cytosine-guanine locus cg13989295 as well as DNA methylation adjusted for genotype at the methylation-associated single nucleotide polymorphism (rs7208505) in relationship to whole-brain cortical thickness, posttraumatic stress disorder symptoms (PTSD) and depression symptoms. Whole-brain vertex-wise analyses identified three clusters in prefrontal cortex that were associated with genotype-adjusted SKA2 DNA methylation (methylation(adj)). Specifically, DNA methylation(adj) was associated with bilateral reductions of cortical thickness in frontal pole and superior frontal gyrus, and similar effects were found in the right orbitofrontal cortex and right inferior frontal gyrus. PTSD symptom severity was positively correlated with SKA2 DNA methylation(adj) and negatively correlated with cortical thickness in these regions. Mediation analyses showed a significant indirect effect of PTSD on cortical thickness via SKA2 methylation status. Results suggest that DNA methylation(adj) of SKA2 in blood indexes stress-related psychiatric phenotypes and neurobiology, pointing to its potential value as a biomarker of stress exposure and susceptibility.
We present extensive photometry at ultraviolet (UV), optical, and near-infrared (NIR) wavelengths, as well as dense sampling of optical spectra, for the normal Type Ia supernova (SN Ia) 2005cf. The ...optical photometry, performed at eight different telescopes, shows a 1σ scatter of lsim0.03 mag after proper corrections for the instrument responses. From the well-sampled light curves, we find that SN 2005cf reached a B-band maximum at 13.63 ± 0.02 mag, with an observed luminosity decline rate Δm 15(B) = 1.05 ± 0.03 mag. The correlations between the decline rate and various color indexes, recalibrated on the basis of an expanded SN Ia sample, yield a consistent estimate for the host-galaxy reddening of SN 2005cf, E(B – V)host = 0.10 ± 0.03 mag. The UV photometry was obtained with the Hubble Space Telescope and the Swift Ultraviolet/Optical Telescope, and the results match each other to within 0.1-0.2 mag. The UV light curves show similar evolution to the broadband U, with an exception in the 2000-2500 Å spectral range (corresponding to the F220W/uvm2 filters), where the light curve appears broader and much fainter than that on either side (likely owing to the intrinsic spectral evolution). Combining the UV data with the ground-based optical and NIR data, we establish the generic UV-optical-NIR bolometric light curve for SN 2005cf and derive the bolometric corrections in the absence of UV and/or NIR data. The overall spectral evolution of SN 2005cf is similar to that of a normal SN Ia, but with variety in the strength and profile of the main feature lines. The spectra at early times displayed strong, high-velocity (HV) features in the Ca II H&K doublet and NIR triplet, which were distinctly detached from the photosphere (v ≈ 10,000 km s–1) at a velocity ranging from 20,000 to 25,000 km s–1. One interesting feature is the flat-bottomed absorption observed near 6000 Å in the earliest spectrum, which rapidly evolved into a triangular shape and then became a normal Si II λ6355 absorption profile at about one week before maximum brightness. This premaximum spectral evolution is perhaps due to the blending of the Si IIλ6355 at photospheric velocity and another HV absorption component (e.g., an Si II shell at a velocity ~18,000 km s–1) in the outer ejecta, and may be common in other normal SNe Ia. The possible origin of the HV absorption features is briefly discussed.
Polymerase chain reaction (PCR) assessment of clonal T-cell receptor (TCR) and immunoglobulin (Ig) gene rearrangements is an important diagnostic tool in mature T-cell neoplasms. However, lack of ...standardized primers and PCR protocols has hampered comparability of data in previous clonality studies. To obtain reference values for Ig/TCR rearrangement patterns, 19 European laboratories investigated 188 T-cell malignancies belonging to five World Health Organization-defined entities. The TCR/Ig spectrum of each sample was analyzed in duplicate in two different laboratories using the standardized BIOMED-2 PCR multiplex tubes accompanied by international pathology panel review. TCR clonality was detected in 99% (143/145) of all definite cases of T-cell prolymphocytic leukemia, T-cell large granular lymphocytic leukemia, peripheral T-cell lymphoma (unspecified) and angioimmunoblastic T-cell lymphoma (AILT), whereas nine of 43 anaplastic large cell lymphomas did not show clonal TCR rearrangements. Combined use of TCRB and TCRG genes revealed two or more clonal signals in 95% of all TCR clonal cases. Ig clonality was mostly restricted to AILT. Our study indicates that the BIOMED-2 multiplex PCR tubes provide a powerful strategy for clonality assessment in T-cell malignancies assisting the firm diagnosis of T-cell neoplasms. The detected TCR gene rearrangements can also be used as PCR targets for monitoring of minimal residual disease.
Prostaglandin (PG)E2is a potent mediator of pain and inflammation, and high levels of this lipid mediator are observed in numerous disease states. The inhibition of PGE2production to control pain and ...to treat diseases such as rheumatoid arthritis to date has depended on nonsteroidal antiinflammatory agents such as aspirin. However, these agents inhibit the synthesis of all prostanoids. To produce biologically active PGE2, PGE synthases catalyze the isomerization of PGH2into PGE2. Recently, several PGE synthases have been identified and cloned, but their role in inflammation is not clear. To study the physiological role of the individual PGE synthases, we have generated by targeted homologous recombination a mouse line deficient in microsomal PGE synthase 1 (mPGES1) on the inbred DBA/1lacJ background. mPGES1-deficient (mPGES1-/-) mice are viable and fertile and develop normally compared with wild-type controls. However, mPGES1-/-mice displayed a marked reduction in inflammatory responses compared with mPGES1+/+mice in multiple assays. Here, we identify mPGES1 as the PGE synthase that contributes to the pathogenesis of collagen-induced arthritis, a disease model of human rheumatoid arthritis. We also show that mPGES1 is responsible for the production of PGE2that mediates acute pain during an inflammatory response. These findings suggest that mPGES1 provides a target for the treatment of inflammatory diseases and pain associated with inflammatory states.
The deformation characteristics of soil subjected to vacuum pressure are discussed and an approximate method is proposed for calculating settlement and lateral displacement of the ground induced by ...vacuum consolidation. Laboratory oedometer test results indicate that if the vacuum pressure alone is larger than the lateral stress required to maintain an at-rest (no horizontal strain) condition, there will be inward lateral displacement and the vacuum pressure will induce generally less settlement than a surcharge load of the same magnitude. In the case of field vacuum consolidation, the confining stress acting on a soil element can be regarded as consisting of two parts: Due to vacuum pressure and earth pressure. Assuming a value of the lateral earth pressure coefficient acting in the ground under vacuum consolidation
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, somewhere between the active and at-rest values, an equation defining the depth—below which there will be no significant inward lateral displacement—is derived. Further, assuming that the volumetric strain induced by vacuum consolidation is the same as the one-dimensional consolidation induced by application of a surcharge load of the same magnitude, an approximate method is proposed for calculating the ground settlement and inward lateral displacement induced by vacuum consolidation. This method has been applied to two case histories reported in the literature, and it is shown that the field-measured data are simulated reasonably well, suggesting that the method may be useful for the design of vacuum consolidation projects.
•A clay-bearing layer is detected within the sulfate-rich deposits of Meridiani Planum.•Landscape formation such as karst emplacement seems mineralogy-driven.•The regional mineralogy and geology is ...best explained by surficial and groundwater processes.
The area of Meridiani Planum on Mars became of particular interest after the detection of coarse-grained, gray hematite, which led to the choice of this region as final landing site for the Mars Exploration Rover Opportunity. Multiple additional minerals have since been detected in the region, both from orbit and in situ. The present paper reassesses in detail the mineralogy and geomorphology of the area (between 3.5°S to 6.5°N latitude and 8.0°W to 8.0°E longitude) using visible and near-infrared hyperspectral data, merged with high spatial resolution images into a Geographic Information System. Fe/Mg-rich phyllosilicates, as well as several types of sulfates are identified within the kilometer of sedimentary deposits constituting the etched terrains and the overlying hematite-rich plains. The mineralogical stratigraphy of the etched terrains is characterized by a sulfate-rich unit, enriched in Fe/Mg-rich clays in its uppermost part. This clay-rich horizon is capped by another sulfate-rich unit, of different composition, associated with hematite detections and constituting the material of the hematite plains unit. The clay-bearing unit, which directly underlies the hematite plains, may be exposed in the rim of Endeavour Crater and could correspond to the material that is currently being analyzed by Opportunity. Diverse landforms including karsts and pan features are observed at the surface of the hydrated etched terrains and indicate past surface water and potential groundwater aquifers. Our analysis reveals that both surficial water and groundwater processes are required to explain the diversity of morphologies and mineralogies observed in the area. Although orbital detections are consistent with the hematite and sulfate detections made in situ by Opportunity in the hematite plains, they also show the presence of a clay-rich horizon at depth, overlying another, thicker, possibly chemically distinct, sulfate-rich unit within the etched terrains. Therefore we conclude that the very acidic conditions that prevailed during the formation of the topmost sulfate-rich unit, as observed in Meridiani Planum and in the hematite plains by the rover Opportunity, are not representative of the entire history of the etched terrains. In contrast, most hydrated minerals in Meridiani Planum likely formed at more neutral pH, at the beginning of the Hesperian. The overall sulfate/clay/sulfate sequence is similar to the one observed in Gale Crater, the landing site of the Mars Science Laboratory rover.
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