705 research outputs found
Orlicz-Sobolev nematic elastomers
We extend the existence theorems in Barchiesi et al. (2017), for models of nematic
elastomers and magnetoelasticity, to a larger class in the scale of Orlicz spaces.
These models consider both an elastic term where a polyconvex energy density is
composed with an unknown state variable defined in the deformed configuration,
and a functional corresponding to the nematic energy (or the exchange and
magnetostatic energies in magnetoelasticity) where the energy density is integrated
over the deformed configuration. In order to obtain the desired compactness and
lower semicontinuity, we show that the regularity requirement that maps create
no new surface can still be imposed when the gradients are in an Orlicz class with
an integrability just above the space dimension minus one
A Remarkably Stable Phosphorylated Form of Ca 2+ -ATPase Prepared from Ca 2+ -loaded and Fluorescein Isothiocyanate-labeled Sarcoplasmic Reticulum Vesicles
After the nucleotide binding domain in sarcoplasmic reticulum Ca2+-ATPase has been derivatized with fluorescein isothiocyanate at Lys-515, ATPase phosphorylation in the presence of a calcium gradient, with Ca2+ on the lumenal side but without Ca2+ on the cytosolic side, results in the formation of a species that exhibits exceptionally low probe fluorescence (Pick, U. (1981) FEBS Lett. 123, 131-136). We show here that, as long as the free calcium concentration on the cytosolic side is kept in the nanomolar range, this low fluorescence species is remarkably stable, even when the calcium gradient is subsequently dissipated by ionophore. This species is a Ca2+-free phosphorylated species. The kinetics of Ca2+ binding to it indicates that its transport sites are exposed to the cytosolic side of the membrane and retain a high affinity for Ca2+. Thus, in the ATPase catalytic cycle, an intrinsically transient phosphorylated species with transport sites occupied but not yet occluded must also have been stabilized by fluorescein isothiocyanate (FITC), possibly mimicking ADP. The low fluorescence mainly results from a change in FITC absorption. The Ca2+-free low fluorescence FITC-ATPase species remains stable after addition of thapsigargin in the absence or presence of decavanadate, or after solubilization with dodecylmaltoside. The remarkable stability of this phosphoenzyme species and the changes in FITC spectroscopic properties are discussed in terms of a putative FITC-mediated link between the nucleotide binding domain and the phosphorylation domain in Ca2+-ATPase, and the possible formation of a transition state-like conformation with a compact cytosolic head. These findings might open a path toward structural characterization of a stable phosphorylated form of Ca2+-ATPase for the first time, and thus to further insights into the pump's mechanism
A variational model for fracture and debonding of thin films under in-plane loadings
We study fracture and debonding of a thin stiff film bonded to a rigid substrate through a thin compliant layer, introducing a two-dimensional variational fracture model in brittle elasticity. Fractures are naturally distinguished between transverse cracks in the film (curves in 2D) and debonded surfaces (2D planar regions). In order to study the mechanical response of such systems under increasing loads, we formulate a dimension-reduced, rate-independent, irreversible evolution law accounting for both transverse fracture and debonding. We propose a numerical implementation based on a regularized formulation of the fracture problem via a gradient damage functional, and provide an illustration of its capabilities exploring complex crack patterns, showing a qualitative comparison with geometrically involved real life examples. Moreover, we justify the underlying dimension-reduced model in the setting of scalar-valued displacement fields by a rigorous asymptotic analysis using Γ-convergence, starting from the three-dimensional variational fracture (free-discontinuity) problem under precise scaling hypotheses on material and geometric parameters. © 2014 Elsevier Ltd
Risk of Invasive Fungal Infections in Patients with Chronic Lymphocytic Leukemia treated with Bruton Tyrosine Kinase Inhibitors – A Case-Control Propensity Score Matched Analysis
Background: Prior reports have suggested a possible increase in the frequency of invasive fungal infections (IFIs) with use of a Bruton tyrosine kinase inhibitors (BTKi) for treatment of chronic lymphoid malignancies such as chronic lymphocytic leukemia (CLL), but precise estimates are lacking. We aim to characterize the prevalence of IFIs among patients with CLL, for whom BTKi are now the first line recommended therapy. Methods: We queried TriNetX, a global research network database, to identify adult patients with CLL using the ICD-10 codes (C91.1) and laboratory results. We performed a case-control propensity score-matched analysis to determine IFIs events by BTKi use. We adjusted for age, sex, ethnicity, and clinical risk factors associated with an increased risk of IFIs. Results: Among 5,358 matched patients with CLL, we found an incidence of 4.6% of IFIs in patients on a BTKi vs. 3.5% among patients with CLL not on a BTKi at five years. Approximately 1% of patients with CLL developed an IFI while on a BTKi within this period. Our adjusted IFI event analysis found an elevated rate of Pneumocytis jirovecii pneumonia (PJP) (0.5% vs. 0.3%, p = 0.02) and invasive candidiasis (3.5% vs 2.7%, p = 0.012) with the use of a BTKi. The number needed to harm for patients taking a BTKi was 120 and 358 for invasive candidiasis and PJP, respectively. Conclusions: We found an adjusted elevated rate of PJP and invasive candidiasis with BTKi use. The rates are however low with a high number needed to harm. Additional studies stratifying other IFIs with specific BTKi are required to identify at-risk patients and preventive, cost-effective interventions
Charged Annular Disks and Reissner-Nordstr\"{o}m Type Black Holes from Extremal Dust
We present the first analytical superposition of a charged black hole with an
annular disk of extremal dust. In order to obtain the solutions, we first solve
the Einstein-Maxwell field equations for sources that represent disk-like
configurations of matter in confomastatic spacetimes by assuming a functional
dependence among the metric function, the electric potential and an auxiliary
function,which is taken as a solution of the Laplace equation. We then employ
the Lord Kelvin Inversion Method applied to models of finite extension in order
to obtain annular disks. The structures obtained extend to infinity, but their
total masses are finite and all the energy conditions are satisfied. Finally,
we observe that the extremal Reissner-Nordstr\"{o}m black hole can be embedded
into the center of the disks by adding a boundary term in the inversion.Comment: 17 revtex pages, 8 eps figure
Linear and machine learning modelling for spatiotemporal disease predictions: Force-of-Infection of Chagas disease
Q1Q1Background:
Chagas disease is a long-lasting disease with a prolonged asymptomatic period. Cumulative indices of infection such as prevalence do not shed light on the current epidemiological situation, as they integrate infection over long periods. Instead, metrics such as the Force-of-Infection (FoI) provide information about the rate at which susceptible people become infected and permit sharper inference about temporal changes in infection rates. FoI is estimated by fitting (catalytic) models to available age-stratified serological (ground-truth) data. Predictive FoI modelling frameworks are then used to understand spatial and temporal trends indicative of heterogeneity in transmission and changes effected by control interventions. Ideally, these frameworks should be able to propagate uncertainty and handle spatiotemporal issues.
Methodology/principal findings:
We compare three methods in their ability to propagate uncertainty and provide reliable estimates of FoI for Chagas disease in Colombia as a case study: two Machine Learning (ML) methods (Boosted Regression Trees (BRT) and Random Forest (RF)), and a Linear Model (LM) framework that we had developed previously. Our analyses show consistent results between the three modelling methods under scrutiny. The predictors (explanatory variables) selected, as well as the location of the most uncertain FoI values, were coherent across frameworks. RF was faster than BRT and LM, and provided estimates with fewer extreme values when extrapolating to areas where no ground-truth data were available. However, BRT and RF were less efficient at propagating uncertainty.
Conclusions/significance:
The choice of FoI predictive models will depend on the objectives of the analysis. ML methods will help characterise the mean behaviour of the estimates, while LM will provide insight into the uncertainty surrounding such estimates. Our approach can be extended to the modelling of FoI patterns in other Chagas disease-endemic countries and to other infectious diseases for which serosurveys are regularly conducted for surveillance.https://orcid.org/0000-0002-8165-3198Revista Internacional - IndexadaA1N
Estudio de peso y rendimiento en canal de las razas Sanmartinera, Cebú y sus cruces en los Llanos Orientales.
Evalúa el ganado Sanmartinero, Cebú y sus cruces con Charolais, en ganancia de peso, producción de carne y rendimiento en canal. Se utilizaron 18 novillos divididos en 6 grupos de 3 animales cada uno, asÃ: Sanmartinero (SM) y Cebú (C) como razas puras, y Sm x C, C x Sm filial 2 (C x Sm F2), Sm x C F2 y Ch x C x Sm como cruces. Al destete los animales cruzados ganaron 160 gr mas por dÃa que los puros, en el postdestete los puros ganaron mas peso por dÃa que los cruzados. Los pesos promedios al finalizar la ceba en pasto braquiaria fueron: 436, 400, 483, 457, 431 y 468 kg y los pesos al presacrificio después de 24 horas de ayuno fueron: 399, 369, 448, 418, 395 y 429 kg para el Sm, C, Sm x C, C x Sm F2, Sm x C F2 y Ch x C x Sm, respectivamente. En el mismo orden de razas se obtuvieron los siguientes resultados: pesos promedios de las canales: 221, 216, 253, 243, 223 y 245 kg, rendimientos en canal: 55, 58, 56, 56, 56 y 57 por ciento, rendimientos en canal en base al peso vacÃo, sustrayendo el contenido intestinal: 61, 62, 60, 60, 62 y 62 por ciento. Se encontraron diferencias significativas para el peso de las canales entre puros y cruzados. El porcentaje promedio de la merma de los grupos postrefrigeración en 24 horas a 6 grados centÃgrados fue de 1.76 por ciento. En la evaluación de expendio, se presentaron diferencias significativas para el peso de los cortes de primera, segunda y tercera entre los puros y cruzadosGanado de doble propósito-Ganaderia doble proposit
Epidemiological trends and clinical outcomes of cryptococcosis in a medically insured population in the United States: a claims-based analysis from 2017 to 2019
Background: Emerging risk factors highlight the need for an updated understanding of cryptococcosis in the United States. Objective: Describe the epidemiological trends and clinical outcomes of cryptococcosis in three patient groups: people with HIV (PWH), non-HIV-infected and non-transplant (NHNT) patients, and patients with a history of solid organ transplantation. Methods: We utilized data from the Merative Medicaid Database to identify individuals aged 18 and above with cryptococcosis based on the International Classification of Diseases, Tenth Revision diagnosis codes from January 2017 to December 2019. Patients were stratified into PWH, NHNT patients, and transplant recipients according to Infectious Diseases Society of America guidelines. Baseline characteristics, types of cryptococcosis, hospitalization details, and in-hospital mortality rates were compared across groups. Results: Among 703 patients, 59.7% were PWH, 35.6% were NHNT, and 4.7% were transplant recipients. PWH were more likely to be younger, male, identify as Black, and have fewer comorbidities than patients in the NHNT and transplant groups. Notably, 24% of NHNT patients lacked comorbidities. Central nervous system, pulmonary, and disseminated cryptococcosis were most common overall (60%, 14%, and 11%, respectively). The incidence of cryptococcosis fluctuated throughout the study period. PWH accounted for over 50% of cases from June 2017 to June 2019, but this proportion decreased to 47% from July to December 2019. Among the 52% of patients requiring hospitalization, 61% were PWH and 35% were NHNT patients. PWH had longer hospital stays. In-hospital mortality at 90days was significantly higher in NHNT patients (22%) compared to PWH (7%) and transplant recipients (0%). One-year mortality remained lowest among PWH (8%) compared to NHNT patients (22%) and transplant recipients (13%). Conclusion: In this study, most cases of cryptococcosis were PWH. Interestingly, while the incidence remained relatively stable in PWH, it slightly increased in those without HIV by the end of the study period. Mortality was highest in NHNT patients
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