Mechanistic insights into a hydrate contribution to the Paleocene-Eocene carbon cycle perturbation from coupled thermohydraulic simulations

During the Paleocene-Eocene Thermal Maximum (PETM), the carbon isotopic signature (δ13C) of surface carbon-bearing phases decreased abruptly by at least 2.5 to 3.0‰. This carbon isotope excursion (CIE) has been attributed to widespread methane hydrate dissociation in response to rapid ocean warming. We ran a thermohydraulic modeling code to simulate hydrate dissociation due to ocean warming for various PETM scenarios. Our results show that hydrate dissociation in response to such warming can be rapid but suggest that methane release to the ocean is modest and delayed by hundreds to thousands of years after the onset of dissociation, limiting the potential for positive feedback from emission-induced warming. In all of our simulations at least half of the dissociated hydrate methane remains beneath the seabed, suggesting that the pre-PETM hydrate inventory needed to account for all of the CIE is at least double that required for isotopic mass balance

A beam-beam monitoring detector for the MPD experiment at NICA

The Multi-Purpose Detector (MPD) is to be installed at the Nuclotron Ion Collider fAcility (NICA) of the Joint Institute for Nuclear Research (JINR). Its main goal is to study the phase diagram of the strongly interacting matter produced in heavy-ion collisions. These studies, while providing insight into the physics of heavy-ion collisions, are relevant for improving our understanding of the evolution of the early Universe and the formation of neutron stars. In order to extend the MPD trigger capabilities, we propose to include a high granularity beam-beam monitoring detector (BE-BE) to provide a level-0 trigger signal with an expected time resolution of 30 ps. This new detector will improve the determination of the reaction plane by the MPD experiment, a key measurement for flow studies that provides physics insight into the early stages of the reaction. In this work, we use simulated Au+Au collisions at NICA energies to show the potential of such a detector to determine the event plane resolution, providing further redundancy to the detectors originally considered for this purpose namely, the Fast Forward Detector (FFD) and the Hadron Calorimeter (HCAL). We also show our results for the time resolution studies of two prototype cells carried out at the T10 beam line at the CERN PS complex.Comment: 16 pages, 12 figures. Updated to published version with added comments and correction

Transmission of sheep-bovine spongiform encephalopathy to pigs

Experimental transmission of the bovine spongiform encephalopathy (BSE) agent has been successfully reported in pigs inoculated via three simultaneous distinct routes (intracerebral, intraperitoneal and intravenous). Sheep derived BSE (Sh-BSE) is transmitted more efficiently than the original cattle-BSE isolate in a transgenic mouse model expressing porcine prion protein. However, the neuropathology and distribution of Sh-BSE in pigs as natural hosts, and susceptibility to this agent, is unknown. In the present study, seven pigs were intracerebrally inoculated with Sh-BSE prions. One pig was euthanized for analysis in the preclinical disease stage. The remaining six pigs developed neurological signs and histopathology revealed severe spongiform changes accompanied by astrogliosis and microgliosis throughout the central nervous system. Intracellular and neuropil-associated pathological prion protein (PrPSc) deposition was consistently observed in different brain sections and corroborated by Western blot. PrPSc was detected by immunohistochemistry and enzyme immunoassay in the following tissues in at least one animal: lymphoid tissues, peripheral nerves, gastrointestinal tract, skeletal muscle, adrenal gland and pancreas. PrPSc deposition was revealed by immunohistochemistry alone in the retina, optic nerve and kidney. These results demonstrate the efficient transmission of Sh-BSE in pigs and show for the first time that in this species propagation of bovine PrPSc in a wide range of peripheral tissues is possible. These results provide important insight into the distribution and detection of prions in non-ruminant animals

Peripheral neuropathy caused by fenugreek (Trigonella foenum-graecum) straw intoxication in cattle and experimental reproduction in sheep and goats

Trigonella foenum-graecum (fenugreek) is a legume widely used as a food supplement in humans and less frequently in ruminants. Toxicity has been described sporadically in ruminants grazing mature fenugreek plants or stubble; however, the pathological features are unclear. This report describes a natural outbreak of intoxication in cattle fed fenugreek straw and the experimental reproduction using 8 sheep and 8 goats. Affected cattle presented clinical signs approximately 1 month after consuming the straw and 100 of 400 cattle (25%) were affected, of which 60 of 100 (60%) died or were euthanized. Clinical signs were characterized by proprioceptive positioning defects with abnormal postures and weakness of hindlimbs. Forelimbs were also affected in severely affected animals, and cattle became recumbent. Locomotion was characterized by trembling, and some cattle showed high-stepping movements of their forelimbs and knuckled over in their fetlocks. Experimental intoxication induced clinical signs only in sheep and were similar to cattle, although with signs starting in the forelegs. Gross and microscopic lesions were similar in spontaneous and experimental intoxications. Macroscopic changes corresponded with muscular hemorrhages and edema, mainly surrounding the peripheral nerves. Microscopic examination only demonstrated lesions in the distal peripheral nerves, which included edema, hemorrhages, and Wallerian degeneration. Neurofilament immunohistochemistry revealed altered axon labeling and S100 showed a decrease in myelin intensity and loss of its typical compact arrangement around axons. Biochemical and hematological abnormalities included elevated levels of muscle and liver enzymes and thrombocytopenia. These findings indicate that fenugreek straw induces peripheral neuropathy in cattle and sheep, but not in goats

Leishmania spp. epidemiology of canine leishmaniasis in the Yucatan Peninsula

Canine Leishmaniasis is widespread in various Mexican states, where different species of Leishmania have been isolated from dogs. In the present study, we describe the detection of L. braziliensis, L. infantum, and L. mexicana in serum of dogs from the states of Yucatan and Quintana Roo in the Yucatan Peninsula (Mexico). A total of 412 sera were analyzed by ELISA using the total extract of the parasite and the iron superoxide dismutase excreted by different trypanosomatids as antigens. We found the prevalence of L. braziliensis to be 7.52%, L. infantum to be 6.07%, and L. mexicana to be 20.63%, in the dog population studied. The results obtained with ELISA using iron superoxide dismutase as the antigen were confirmed by western blot analysis with its greater sensitivity, and the agreement between the two techniques was very high

Association of body mass index with clinical outcomes in patients with atrial fibrillation: a report from the FANTASIIA Registry

[Abstract] Background. Obesity and atrial fibrillation (AF) frequently coexist and independently increase mortality. We sought to assess the association between obesity and adverse events in patients receiving oral anticoagulants for AF. Methods and Results. Consecutive AF outpatients receiving anticoagulant agents (both vitamin K antagonists and direct oral anticoagulants) were recruited into the FANTASIIA (Atrial fibrillation: influence of the level and type of anticoagulation on the incidence of ischemic and hemorrhagic stroke) registry. This observational, multicenter, and prospective registry of AF patients analyzes the quality of anticoagulation, incidence of events, and differences between oral anticoagulant therapies. We analyzed baseline patient characteristics according to body mass index, normal: <25 kg/m2, overweight: 25–30 kg/m2, and obese: ≥30 kg/m2), assessing all‐cause mortality, stroke, major bleeding and major adverse cardiovascular events (a composite of ischemic stroke, myocardial infarction, and total mortality) at 3 years’ follow‐up. In this secondary prespecified substudy, the association of weight on prognosis was evaluated. We recruited 1956 patients (56% men, mean age 73.8±9.4 years): 358 (18.3%) had normal body mass index, 871 (44.5%) were overweight, and 727 (37.2%) were obese. Obese patients were younger (P<0.01) and had more comorbidities. Mean time in the therapeutic range was similar across body mass index categories (P=0.42). After a median follow‐up of 1070 days, 255 patients died (13%), 45 had a stroke (2.3%), 146 a major bleeding episode (7.5%) and 168 a major adverse cardiovascular event (8.6%). Event rates were similar between groups for total mortality (P=0.29), stroke (P=0.90), major bleeding (P=0.31), and major adverse cardiovascular events (P=0.24). On multivariate Cox analysis, body mass index was not independently associated with all‐cause mortality, cardiovascular mortality, stroke, major bleeding, or major adverse cardiovascular events. Conclusions. In this prospective cohort of patients anticoagulated for AF, obesity was highly prevalent and was associated with more comorbidities, but not with poor prognosis

Association of Body Mass Index With Clinical Outcomes in Patients With Atrial Fibrillation: A Report From the FANTASIIA Registry

Background Obesity and atrial fibrillation (AF) frequently coexist and independently increase mortality. We sought to assess the association between obesity and adverse events in patients receiving oral anticoagulants for AF. Methods and Results Consecutive AF outpatients receiving anticoagulant agents (both vitamin K antagonists and direct oral anticoagulants) were recruited into the FANTASIIA (Atrial fibrillation: influence of the level and type of anticoagulation on the incidence of ischemic and hemorrhagic stroke) registry. This observational, multicenter, and prospective registry of AF patients analyzes the quality of anticoagulation, incidence of events, and differences between oral anticoagulant therapies. We analyzed baseline patient characteristics according to body mass index, normal: <25 kg/m2, overweight: 25-30 kg/m2, and obese: ≥30 kg/m2), assessing all‐cause mortality, stroke, major bleeding and major adverse cardiovascular events (a composite of ischemic stroke, myocardial infarction, and total mortality) at 3 years' follow‐up. In this secondary prespecified substudy, the association of weight on prognosis was evaluated. We recruited 1956 patients (56% men, mean age 73.8±9.4 years): 358 (18.3%) had normal body mass index, 871 (44.5%) were overweight, and 727 (37.2%) were obese. Obese patients were younger (P<0.01) and had more comorbidities. Mean time in the therapeutic range was similar across body mass index categories (P=0.42). After a median follow‐up of 1070 days, 255 patients died (13%), 45 had a stroke (2.3%), 146 a major bleeding episode (7.5%) and 168 a major adverse cardiovascular event (8.6%). Event rates were similar between groups for total mortality (P=0.29), stroke (P=0.90), major bleeding (P=0.31), and major adverse cardiovascular events (P=0.24). On multivariate Cox analysis, body mass index was not independently associated with all‐cause mortality, cardiovascular mortality, stroke, major bleeding, or major adverse cardiovascular events. Conclusions In this prospective cohort of patients anticoagulated for AF, obesity was highly prevalent and was associated with more comorbidities, but not with poor prognosis

Homozygous R136S mutation in PRNP gene causes inherited early onset prion disease

Altres ajuts: Fundació la Marató de TV3/201821-31Background: More than 40 pathogenic heterozygous PRNP mutations causing inherited prion diseases have been identified to date. Recessive inherited prion disease has not been described to date. Methods: We describe the clinical and neuropathological data of inherited early-onset prion disease caused by the rare PRNP homozygous mutation R136S. In vitro PrP propagation studies were performed using recombinant-adapted protein misfolding cyclic amplification technique. Brain material from two R136S homozygous patients was intracranially inoculated in TgMet129 and TgVal129 transgenic mice to assess the transmissibility of this rare inherited form of prion disease. Results: The index case presented symptoms of early-onset dementia beginning at the age of 49 and died at the age of 53. Neuropathological evaluation of the proband revealed abundant multicentric PrP plaques and Western blotting revealed a ~ 8 kDa protease-resistant, unglycosylated PrP fragment, consistent with a Gerstmann-Sträussler-Scheinker phenotype. Her youngest sibling suffered from progressive cognitive decline, motor impairment, and myoclonus with onset in her late 30s and died at the age of 48. Genetic analysis revealed the presence of the R136S mutation in homozygosis in the two affected subjects linked to homozygous methionine at codon 129. One sibling carrying the heterozygous R136S mutation, linked to homozygous methionine at codon 129, is still asymptomatic at the age of 74. The inoculation of human brain homogenates from our index case and an independent case from a Portuguese family with the same mutation in transgenic mice expressing human PrP and in vitro propagation of PrP studies failed to show disease transmissibility. Conclusion: In conclusion, biallelic R136S substitution is a rare variant that produces inherited early-onset human prion disease with a Gerstmann-Sträussler-Scheinker neuropathological and molecular signature. Even if the R136S variant is predicted to be "probably damaging", heterozygous carriers are protected, at least from an early onset providing evidence for a potentially recessive pattern of inheritance in human prion diseases

The mini-JPAS: A study of the wavelength dependence of the photon response nonuniformity of the JPAS-pathfinder camera

Understanding the origins of small-scale flats of CCDs and their wavelength-dependent variations plays an important role in high-precision photometric, astrometric, and shape measurements of astronomical objects. Based on the unique flat data of 47 narrowband filters provided by JPAS-Pathfinder, we analyze the variations of small-scale flats as a function of wavelength. We find moderate variations (from about 1.0% at 390 nm to 0.3% at 890 nm) of small-scale flats among different filters, increasing toward shorter wavelengths. Small-scale flats of two filters close in central wavelengths are strongly correlated. We then use a simple physical model to reproduce the observed variations to a precision of about ±0.14% by considering the variations of charge collection efficiencies, effective areas, and thicknesses between CCD pixels. We find that the wavelength-dependent variations of the small-scale flats of the JPAS-Pathfinder camera originate from inhomogeneities of the quantum efficiency (particularly charge collection efficiency), as well as the effective area and thickness of CCD pixels. The former dominates the variations in short wavelengths, while the latter two dominate at longer wavelengths. The effects on proper flat-fielding, as well as on photometric/flux calibrations for photometric/slitless spectroscopic surveys, are discussed, particularly in blue filters/wavelengths. We also find that different model parameters are sensitive to flats of different wavelengths, depending on the relations between the electron absorption depth, photon absorption length, and CCD thickness. In order to model the wavelength-dependent variations of small-scale flats, a small number (around 10) of small-scale flats with well-selected wavelengths are sufficient to reconstruct small-scale flats in other wavelengths. © 2021. The American Astronomical Society. All rights reserved.he PRNU model adopted in this work was developed as part of Mr. Baocun Chen's undergraduate thesis work under the supervision of H.Z. This work is supported by the National Natural Science Foundation of China through projects NSFC 12173007 and 11603002, the National Key Basic R&D Program of China via 2019YFA0405503, and Beijing Normal University grant No. 310232102. We acknowledge the science research grants from the China Manned Space Project with Nos. CMS-CSST-2021-A08 and CMS-CSST2021-A09. Based on observations made with the JST/T250 telescope and JPCam at the Observatorio Astrofisico de Javalambre (OAJ) in Teruel, owned, managed, and operated by the Centro de Estudios de Fisica del Cosmos de Aragon (CEFCA). We acknowledge the OAJ Data Processing and Archiving Unit (UPAD) for reducing and calibrating the OAJ data used in this work. Funding for the JPAS Project has been provided by the Governments of Spain and Aragon through the Fondo de Inversion de Teruel, European FEDER funding, and the Spanish Ministry of Science, Innovation and Universities, as well as by the Brazilian agencies FINEP, FAPESP, and FAPERJ and the National Observatory of Brazil. Additional funding was also provided by the Tartu Observatory and the JPAS Chinese Astronomical Consortium. With funding from the Spanish government through the Severo Ochoa Centre of Excellence accreditation SEV-2017-0709