Pesticide transport simulation by SWAP–PEARL (Soil–Water–Atmosphere–Plant and Pesticide Emission Assessment at Regional and Local scales) models can help to predict pesticide leaching at regional ...scales. For reasons of economic and time efficiency, measurement efforts should be prioritized towards critical parameters. The objective of this research is to perform a Morris screening and Sobol–Jansen sensitivity analysis to SWAP–PEARL models, using a reasonable worst‐case scenario. Three pesticide compounds were analyzed:, bentazon (zero sorption), imidacloprid (moderately sorbed), and compound I (highly sorbed). Initial macropore and pesticide parameter values were varied by ±20% to generate parameter ranges. The outputs analyzed were the concentration in drainage water, the average concentration in groundwater between 1 and 2 m, and the concentration in the soil system at 100‐cm depth. Influential parameters found through the Morris method were analyzed using the Sobol–Jansen method. The results for bentazon indicate that the degradation half‐life (DT50), the bottom depth of the internal catchment (zic), and the proportion of the internal catchment at the soil surface (pic_0) are critical parameters in all the outputs analyzed. For imidacloprid and compound I, the most relevant parameters for drainage output are the Freundlich sorption exponent (Fexp) and zic; for groundwater, the relevant parameters are Fexp, the bottom depth of static macropores (zst), and pic_0; and for soil concentrations at 100‐cm depth, the relevant parameters are Fexp, zic, and pic_0. The Morris and Sobol–Jansen methods produce the same results for the first position in the ranking. Measurement efforts should be performed to update national soil databases, including critical pesticide and macropore parameters.
Summary
Background
Bullous pemphigoid (BP) is the most common autoimmune‐mediated subepidermal blistering skin disease and is associated with significant morbidity and mortality.
Objectives
To ...determine the 3‐year mortality rate, risk factors and causes of death in patients with BP in Singapore, compared with the general population.
Methods
We conducted a retrospective cohort study of all newly diagnosed patients with BP seen at the National Skin Centre from 1 April 2004 to 31 December 2009. Demographic and clinical data on comorbidities and treatment were recorded. Mortality information was obtained from the National Registry of Diseases.
Results
In total 359 patients were included in our study. The 1‐, 2‐, 3‐year mortality rates were 26·7%, 38·4% and 45·7%, respectively. The 3‐year standardized mortality risk for patients with BP was 2·74 (95% confidence interval 2·34–3·19) times higher than for the age‐ and sex‐matched general population. Parkinson disease, heart failure and chronic renal disease were associated with increased mortality, while combination treatment with low‐to‐moderate‐dose corticoste‐roids and immunomodulatory agents such as doxycycline and/or nicotinamide was associated with lower mortality. Overall, infections were the most common cause of death (59·8%), with the main causes of death being pneumonia (42·7%), cardiovascular disease (14·6%) and stroke (11·6%).
Conclusions
This study confirms an increased 3‐year mortality rate for patients with BP in Singapore. Risk factors for increased mortality include medical comorbidities, especially neurological, cardiac and renal diseases. Treatment with combination therapy, including the use of low‐to‐moderate‐dose corticosteroid, appeared to decrease mortality risk in patients with BP.
What's already known about this topic?
Bullous pemphigoid (BP) is the most common subepidermal blistering skin disease and is associated with significant morbidity.
Patients with BP have an increased mortality rate compared with the general population in Western cohorts.
What does this study add?
This is the first comprehensive study to demonstrate increased mortality risk in Asian patients with BP.
Mortality risk factors include Parkinson disease, heart failure and chronic renal disease.
Combination treatment with low‐to‐moderate‐dose corticosteroids and immunomodulatory agents, such as doxycycline and/or nicotinamide, was associated with lower mortality.
Balling defect of the additively manufactured titanium lattice implants easily leads to muscle tissue rejection, which might cause failure of implantation. Electropolishing is widely used in surface ...polishing of complex components and has potential to deal with the balling defect. However, a clad layer could be formed on the surface of titanium alloy after electropolishing, which may affect the biocompatibility of the metal implants. To manufacture lattice structured β-type Ti-Ni-Ta-Zr (TNTZ) for bio-medical applications, it is necessary to investigate the impact of electropolishing on material biocompatibility. In this study, animal experiments were conducted to investigate the in vivo biocompatibility of the as-printed TNTZ alloy with or without electropolishing; and proteomics technology was used to elaborate the results. The following conclusions were drawn: (a) a 30% oxalic acid electropolishing treatment was effective in solving balling defects, and ~21 nm amorphous clad layer would be formed on the surface of the material after polishing; (b) the electropolished TNTZ suggested decreased cell cytotoxicity and improved blood biocompatibility as compared to as-printed TNTZ; (c) the amorphous clad layer could make a barrier to prevent Ta and Zr ions from penetrating into the muscle tissue, and could form a good tissue regeneration at the implantation site during 4 weeks, indicating that the electropolished TNTZ has the potential as implants; and (d) the cells attached to the electropolished TNTZ showed higher antioxidant capacity but less proliferation than attached to as-printed TNTZ.
Graphical Abstract
Oesophageal adenocarcinoma (EAC) incidence is rapidly increasing in Western countries. A better understanding of EAC underpins efforts to improve early detection and treatment outcomes. While large ...EAC exome sequencing efforts to date have found recurrent loss-of-function mutations, oncogenic driving events have been underrepresented. Here we use a combination of whole-genome sequencing (WGS) and single-nucleotide polymorphism-array profiling to show that genomic catastrophes are frequent in EAC, with almost a third (32%, n=40/123) undergoing chromothriptic events. WGS of 22 EAC cases show that catastrophes may lead to oncogene amplification through chromothripsis-derived double-minute chromosome formation (MYC and MDM2) or breakage-fusion-bridge (KRAS, MDM2 and RFC3). Telomere shortening is more prominent in EACs bearing localized complex rearrangements. Mutational signature analysis also confirms that extreme genomic instability in EAC can be driven by somatic BRCA2 mutations. These findings suggest that genomic catastrophes have a significant role in the malignant transformation of EAC.
•Population prevalence of gestational hypercalcemia was 1.7 % in the third trimester.•Hyperparathyroidism and vitamin D toxicity were excluded as main causes.•No cases with profiles suggestive of ...mutations in the CYP24A1 gene were found.•Hypercalcemic women had a relatively high serum 1,25(OH)2D concentration despite an appropriately suppressed PTH.
Gestational hypercalcemia is associated with an increased risk of maternal, fetal and neonatal morbidity and mortality. Hypercalcemia may develop during pregnancy in individuals who were previously asymptomatic. The increased sensitivity during pregnancy may be related to physiological, gestational alterations in vitamin D and calcium metabolism and may be influenced by gene variants. The prevalence is unknown.
We investigated the prevalence of hypercalcemia in trimester 3 (T3) in a population representative prospective cohort study (n = 1832) in South-West Sweden. Women with serum albumin (Alb) adjusted calcium (CaAlb) ≥ 2.65 mmol/L in T3 (n = 30) were matched to normo-calcemic controls, and markers of calcium and vitamin D metabolism were investigated in trimester 1 (T1) and T3. Serum concentrations of Ca, phosphate (P), Magnesium (Mg), Alb and creatinine (Cr), parathyroid hormone (PTH; T3 only), vitamin D metabolites (total 25(OH)D, 1,25(OH)2D, 24,25(OH)2D, and free 25(OH)D) were analysed in T1 and T3. CaAlb (Payne; inter-laboratory difference: UEA = 0.15 + 0.9*UGOT; UEA 2.54 = UGOT 2.65) and estimated glomerular filtration rate (eGFR; modified 4-variable MDRD) and vitamin D metabolites ratios (VMR) were calculated. Normally and non-normally distributed data were presented as mean (SD) or median (95 %CI). Group differences in relationships between vitamin D metabolites and with PTH were investigated with multiple regression analyses.
Hypercalcemia in T3 was found in 1.7 % of women. PTH concentrations suggestive of primary hyperparathyroidism was found in 1 woman and none had 25(OH)D or 24,25(OH)2D concentrations in the toxicity range or suggestive of mutations in the CYP24A1 gene. CaAlb was significantly higher in hypercalcemic cases compared to controls in T1 (2.44 (2.30–2.80) vs 2.37 (2.25–2.49) mmol/L) and T3 (2.63 (2.52–2.78) vs 2.46 (2.31–2.58) mmol/L). Serum P was higher among cases than controls in T3 (1.12 (0.16) vs 1.07 (0.18) mmol/L) but not in T1 (1.12 (0.18) and 1.12 (0.16) mmol/L). PTH in T3 was lower in cases (1.6 (1.6–2.8) vs 2.3 (2.1–2.8) pmol/L) but 1,25(OH)2D concentrations were similar. There were no significant group differences in serum 25(OH)D, free 25(OH)D, 24,25(OH)2D, Mg, Alb, Cr and eGFR. Regression analyses did not show significant differences between cases and controls in relationships between vitamin D metabolites and with PTH, except for the free 25(OH)D-PTH relationship and a higher free:total 25(OH)D ratio in cases at T1.
In conclusion, most common causes of hypercalcemia were excluded in the majority of women. Hypercalcemic women had a relatively high serum 1,25(OH)2D concentration despite an appropriately suppressed PTH, suggestive of abnormal gestational adaptions.
Long noncoding RNAs (lncRNAs) are emerging as new players in gene regulation and are associated with the development of cancers. To investigate the important role and mechanism of lncRNAs in the ...progression of gastric cancer, we screened lncRNAs in gastric cancer tissues and corresponding adjacent tissues, and assessed the effects on gastric cancer. Here, we report that BC032469, a novel lncRNA, expressed highly in gastric cancer tissues, and the upregulation was clinically associated with larger tumor size, poor differentiation and shorter survival of gastric cancer patients. Downregulation of BC032469 resulted in a significant inhibition of proliferation in vitro and in vivo. Mechanistically, BC032469 could directly bind to miR-1207-5p and effectively functioned as a sponge for miR-1207-5p to modulate the derepression of hTERT. Thus, BC032469 may function as a ceRNA to impair miR-1207-5p-dependent hTERT downregulation, suggesting that it may be clinically valuable as a poor prognostic biomarker of gastric cancer.
The Magnetospheric Multiscale (MMS) spacecraft encounter an electron diffusion region (EDR) of asymmetric magnetic reconnection at Earth's magnetopause. The EDR is characterized by agyrotropic ...electron velocity distributions on both sides of the neutral line. Various types of plasma waves are produced by the magnetic reconnection in and near the EDR. Here we report large-amplitude electron Bernstein waves (EBWs) at the electron-scale boundary of the Hall current reversal. The finite gyroradius effect of the outflow electrons generates the crescent-shaped agyrotropic electron distributions, which drive the EBWs. The EBWs propagate toward the central EDR. The amplitude of the EBWs is sufficiently large to thermalize and diffuse electrons around the EDR. The EBWs contribute to the cross-field diffusion of the electron-scale boundary of the Hall current reversal near the EDR.
DEAP-3600 is a single-phase liquid argon (LAr) direct-detection dark matter experiment, operating 2 km underground at SNOLAB (Sudbury, Canada). The detector consists of 3279 kg of LAr contained in a ...spherical acrylic vessel. This paper reports on the analysis of a 758 tonne·day exposure taken over a period of 231 live-days during the first year of operation. No candidate signal events are observed in the WIMP-search region of interest, which results in the leading limit on the WIMP-nucleon spin-independent cross section on a LAr target of 3.9×10−45 cm2 (1.5×10−44 cm2) for a 100 GeV/c2 (1 TeV/c2) WIMP mass at 90% C.L. In addition to a detailed background model, this analysis demonstrates the best pulse-shape discrimination in LAr at threshold, employs a Bayesian photoelectron-counting technique to improve the energy resolution and discrimination efficiency, and utilizes two position reconstruction algorithms based on the charge and photon detection time distributions observed in each photomultiplier tube.
To better understand rapid enhancements of the seed populations (hundreds of keV electrons) in the heart of the Earth's outer radiation belt (L* ~ 3.5–5.0) during different geomagnetic activities, we ...investigate three enhancement events measured by Van Allen Probes in detail. Observations of the fluxes and the pitch angle distributions of energetic electrons are analyzed to determine rapid enhancements of the seed populations. Our study shows that three specified processes associated with substorm electron injections can lead to rapid enhancements of the seed populations, and the electron energy increases up to 342 keV. In the first process, substorm electron injections accompanied by the transient and intense substorm electric fields can directly lead to rapid enhancements of the seed populations in the heart of the outer radiation belt. In the second process, the substorm injected electrons are first trapped in the outer radiation belt and subsequently transported into L* < 4.5 by the convection electric field. In the third process, the lower energy electrons are first injected at L* ~ 5.3 and then undergo drift resonance with ultralow‐frequency waves. These accelerated electrons by ultralow‐frequency waves are further transported into L* < 4.5 due to the convection electric field. This process is consistent with the radial diffusion. Our results suggest that these specified processes are important for understanding the dynamics of the seed populations in the heart of the outer radiation belt.
Key Points
Three specified different processes can lead to rapid enhancements of the seed populations in the heart of the Earth's outer radiation belt
The resonant acceleration associated with ULF waves is important for enhancements of the seed populations in L* ~ 3.5–5.0
These specified processes are important for understanding the dynamics of the seed populations in L* ~ 3.5–5.0
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