Evolution of Hypodensity on Non-Contrast CT in Correlation with Collaterals in Anterior Circulation Stroke with Successful Endovascular Reperfusion

Introduction: The aim of the study was to assess the impact of collaterals on the evolution of hypodensity on non-contrast CT (NCCT) in anterior circulation stroke with reperfusion by mechanical thrombectomy (MT). Methods: We retrospectively included stroke patients with middle cerebral artery occlusion who were reperfused by MT in early and late time window. Artificial intelligence (AI)-based software was used to calculate of hypodensity volumes at baseline NCCT (V1) and at follow-up NCCT 24 h after MT (V2), along with the difference between the two volumes (V2-V1) and the follow-up (V2)/baseline (V1) volume ratio (V2/V1). The same software was used to classify collateral status by using a 4-point scale where the score of zero indicated no collaterals and the score of three represented contrast filling of all collaterals. The volumetric values were correlated with the collateral scores. Results: Collateral scores had significant negative correlation with V1 (p = 0.035), V2, V2− V1 and V2/V1 (p < 0.001). In cases with collateral score = 3, V2 was significantly smaller or absent compared to V1; in those with collateral score 2, V2 was slightly larger than V1, and in those with scores 1 and 0 V2 was significantly larger than V1. These relationships were observed in both early and late time windows. Conclusions: The collateral status determined the evolution of the baseline hypodensity on NCCT in patients with anterior circulation stroke who had MT reperfusion. Damage can be stable or reversible in patients with good collaterals while in those with poor collaterals tissues that initially appear normal will frequently appear as necrotic after 24 h. With good collaterals, it is stable or can be reversible while with poor collaterals, normal looking tissue frequently appears as necrotic in follow-up exam. Hence, acute hypodensity represents different states of the ischemic brain parenchyma.

Late time cosmology in f(R,G)- gravity with interacting fluids

Cosmological models are obtained in a $f(R)$ modified gravity with a coupled Gauss-Bonnet (GB) terms in the gravitational action. The dynamical role of the GB terms is explored with a coupled dilaton field in two different cases (I) $f(R)= R + \gamma R^2- \lambda \left( \frac{R}{3m_s^2} \right)^{\delta}$ where $\gamma$, $\lambda$ and $\delta$ are arbitrary constants and (II) $f(R)=R$ and estimate the constraints on the model parameters. In the first case we choose GB terms coupled with a free scalar field in the presence of interacting fluid and in the second case GB terms coupled with scalar field in a self interacting potential to compare the observed universe. The evolutionary scenario of the universe is obtained adopting a numerical technique as the field equations are highly non-linear. Defining a new density parameter $\Omega_{H}$, a ratio of the dark energy density to the present energy density of the non-relativistic matter, we look for a late accelerating universe. The state finder parameters $\Omega_{H}$, deceleration parameter ($q$), jerk parameter ($j$) are plotted. It is noted that a non-singular universe with oscillating cosmological parameters for a given strength of interactions is admitted in Model-I. The gravitational coupling constant $\lambda$ is playing an important role. The Lagrangian density of $f(R)$ is found to dominate over the GB terms when oscillating phase of dark energy arises. In Model-II, we do not find oscillation of the cosmological parameters as the universe evolves. In the presence of interaction the energy from radiation sector of matter cannot flow to the other two sectors of fluid. The range of values of the strengths of interaction of the fluids are estimated for a stable universe assuming the primordial gravitational wave speed equal to unity.

Ebola Virus GP Activates Endothelial Cells via Host Cytoskeletal Signaling Factors

Ebola virus disease (EVD) is a lethal disease caused by the highly pathogenic Ebola virus (EBOV), and its major symptoms in severe cases include vascular leakage and hemorrhage. These symptoms are caused by abnormal activation and disruption of endothelial cells (ECs) whose mediators include EBOV glycoprotein (GP) without the need for viral replication. However, the detailed molecular mechanisms underlying virus–host interactions remain largely unknown. Here, we show that EBOV-like particles (VLPs) formed by GP, VP40, and NP activate ECs in a GP-dependent manner, as demonstrated by the upregulation of intercellular adhesion molecules-1 (ICAM-1) expression. VLPs-mediated ECs activation showed a different kinetic pattern from that of TNF-α-mediated activation and was associated with apoptotic ECs disruption. In contrast to TNF-α, VLPs induced ICAM-1 overexpression at late time points. Furthermore, screening of host cytoskeletal signaling inhibitors revealed that focal adhesion kinase inhibitors were found to be potent inhibitors of ICAM-1 expression mediated by both TNF-α and VLPs. Our results suggest that EBOV GP stimulates ECs to induce endothelial activation and dysfunction with the involvement of host cytoskeletal signaling factors, which represent potential therapeutic targets for EVD.

Extended-Time Conductivity Testing of Proppants Used for Multi-Stage Horizontal Completions

The American Petroleum Institute Recommended Practice 19-D (2018) is the current industry standard for conductivity testing of proppants used in hydraulic fracturing. Similar to previous standards from both the API and ISO, it continues the practice of measuring a "reference" long-term conductivity after 50-hours of time at a given stress. The fracture design engineer is then left to estimate a damage factor to apply over the life of the well completion based on correlations or experience. This study takes four standard proppants used for multi-stage horizontal well completions in North America and presents test data over 250-days of "extended-time" at 7,500 psi of effective stress. The API RP 19-D procedure was followed for all testing, but extended for 250-days duration for the four proppant types: 40/70 mesh mono-crystalline "White" sand, 40/70 mesh multi-crystalline "Brown" sand, 100 mesh "Brown" sand, and 40/70 mesh Light Weight Ceramic (LWC). The 7,500 psi stress condition was chosen to replicate initial stress conditions for a 10,000 feet deep well with a 0.75 psi/ft fracture gradient - typical of unconventional resource plays such as the Bakken formation of North Dakota or the Delaware Basin in west Texas. Results presented provide a measure of the amount of damage occurring in the proppant pack due to time at stress. To the authors’ knowledge, there has never been any extended-time conductivity data published for multiple proppant types over the timeframe completed in this study - despite the obvious need for this understanding to optimize the stimulation design over the full life of the well. Results for the four proppant types are presented as conductivity curves as a function of time for the 250-days of testing. Pack degradation is shown to follow a semi-log decline. Late time continued degradation for all materials is extrapolated over the life of a typical well (40 years), and compared to extended-time particle size distribution and crush data to explain the results observed. Extended-time data such as this 250-day study have never been published on proppants such as these despite the fact that fracture conductivity has a major impact on the productive life of a well and the ultimate recovery of hydrocarbons from the formation. The data presented should be of great interest to any engineer involved with completion designs, or reservoir engineers assessing the productive life and ultimate recovery in the formation since economic optimization is primarily driven by the interplay of fracture length/area with extended-time in-situ fracture conductivity.

Best Practices in DFIT Interpretation: Comparative Analysis of 62 DFITs from Nine Different Shale Plays

In URTeC-123-2019, a group of operators and service companies presented a step-by-step procedure for interpretation of diagnostic fracture injection tests (DFITs). The procedure has now been applied on a wide variety of data across North and South America. This paper statistically summarizes results from 62 of these DFITs, contributed by ten operators spanning nine different shale plays. URTeC-123-2019 made several novel claims, which are tested and validated in this paper. We find that: (1) a ‘compliance method’ closure signature is apparent in the significant majority of DFITs; (2) in horizontal wells, early time pressure drop due to near-wellbore/midfield tortuosity is substantial and varies greatly, from 500 to 6000+ psi; (3) in vertical wells, early-time pressure drop is far weaker; this supports the interpretation that early- time pressure drop in horizontal wells is caused by near-wellbore/midfield tortuosity from transverse fracture propagation; (4) the (not recommended) tangent method of estimating closure yields Shmin estimates that are 100-1000+ psi lower than the estimate from the (recommended) compliance method; the implied net pressure values are 2.5x higher on average and up to 5-6x higher; (5) as predicted by theory, the difference between the tangent and compliance stress and net pressure estimates increases in formations with greater difference between Shmin and pore pressure; (6) the h-function and G-function methods allow permeability to be estimated from truncated data that never reaches late-time impulse flow; comparison shows that they give results that are close to the permeability estimates from impulse linear flow; (7) false radial flow signatures occur in the significant majority of gas shale DFITs, and are rare in oil shale DFITs; (8) if false radial signatures are used to estimate permeability, they tend to overestimate permeability, often by 100x or more; (9) the holistic-method permeability correlation overestimates permeability by 10-1000x; (10) in tests that do not reach late-time impulse transients, it is reasonable to make an approximate pore pressure estimate by extrapolating the pressure from the peak in t*dP/dt using a scaling of t^(-1/2) in oil shales and t^(3/4) in gas shales. The findings have direct practical implications for operators. Accurate permeability estimates are needed for calculating effective fracture length and for optimizing well spacing and frac design. Accurate stress estimation is fundamental to hydraulic fracture design and other geomechanics applications.

Generalized model of interacting dark energy and dark matter: Phase portrait analysis for evolving universe

The main aim of this work is to give a suitable explanation of present accelerating universe through an acceptable interactive dynamical cosmological model. A three-fluid cosmological model is introduced in the background of Friedmann–Lemaître–Robertson-Walker asymptotically flat spacetime. This model consists of interactive dark matter and dark energy with baryonic matter, taken as perfect fluid, satisfying barotropic equation of state. We consider dust as the candidate of dark matter. A scalar field [Formula: see text] represents dark energy with potential [Formula: see text]. Einstein’s field equations are utilized to construct a three-dimensional interactive autonomous system by choosing suitable interaction between dark energy and dark matter. We take the interaction kernel as [Formula: see text], where [Formula: see text] indicates the density of dark energy, [Formula: see text] is the interacting constant and [Formula: see text] is Hubble parameter. In order to explain the stability of this system, we obtain some suitable critical points. We analyze stability of obtained critical points to show the different phases of universe and cosmological implications. Surprisingly, we find some stable critical points which represent late-time dark energy-dominated era when a model parameter [Formula: see text] is equal to [Formula: see text]. We introduce a two-dimensional interactive autonomous system and after phase portrait analysis of it, we get several stable points which represent dark energy-dominated era and late-time cosmic acceleration simultaneously. Here, we also demonstrate the variation in interaction at vicinity of phantom barrier [Formula: see text]. From our work, we can also predict the future phase evolution of the universe.

RNAseq reveals extensive metabolic disruptions in the sensitive SF-295 cell line treated with schweinfurthins

The schweinfurthin family of natural compounds exhibit a unique and potent differential cytotoxicity against a number of cancer cell lines and may reduce tumor growth in vivo. In some cell lines, such as SF-295 glioma cells, schweinfurthins elicit cytotoxicity at nanomolar concentrations. However, other cell lines, like A549 lung cancer cells, are resistant to schweinfurthin treatment up to micromolar concentrations. At this time, the precise mechanism of action and target for these compounds is unknown. Here, we employ RNA sequencing of cells treated with 50 nM schweinfurthin analog TTI-3066 for 6 and 24 h to elucidate potential mechanisms and pathways which may contribute to schweinfurthin sensitivity and resistance. The data was analyzed via an interaction model to observe differential behaviors between sensitive SF-295 and resistant A549 cell lines. We show that metabolic and stress-response pathways were differentially regulated in the sensitive SF-295 cell line as compared with the resistant A549 cell line. In contrast, A549 cell had significant alterations in response genes involved in translation and protein metabolism. Overall, there was a significant interaction effect for translational proteins, RNA metabolism, protein metabolism, and metabolic genes. Members of the Hedgehog pathway were differentially regulated in the resistant A549 cell line at both early and late time points, suggesting a potential mechanism of resistance. Indeed, when cotreated with the Smoothened inhibitor cyclopamine, A549 cells became more sensitive to schweinfurthin treatment. This study therefore identifies a key interplay with the Hedgehog pathway that modulates sensitivity to the schweinfurthin class of compounds.

Late Time Acceleration of the Universe from Quantum Gravity

We show that the accelerating expansion phase of the universe can emerge from the group field theory formalism, a candidate theory of quantum gravity. The cosmological evolution can be extracted from condensate states using mean field approximation, in a form of modified FLRW equations. By introducing an effective equation of state w, we can reveal the relevant features of the evolution, and show that with proper choice of parameters, w will approach to &minus;1, corresponds to the behaviour of cosmological constant, results in a late time acceleration and leads to de Sitter spacetime asymptotically.

Sex-Related Differences in Outcomes After Endovascular Treatment of Patients With Late-Window Stroke

Background and Purpose: Sex-related differences exist in many aspects of acute stroke and were mainly investigated in the early time window with conflicting results. However, data regarding sex disparities in late presenters are scarce. Therefore, we sought to investigate differences in outcomes between women and men treated with endovascular treatment in the late time window. Methods: Analyses were based on the SOLSTICE Consortium (Selection of Late-Window Stroke for Thrombectomy by Imaging Collateral Extent), which was an individual-patient level analysis of seven trials and registries. Baseline characteristics, 90-day functional independence (modified Rankin Scale score ≤2), mortality, and symptomatic intracranial hemorrhage were compared between women and men. Effect of sex on the association of age and successful reperfusion (final Thrombolysis in Cerebral Infarction 2b–3) with outcomes was assessed using multivariable logistic regression adjusted for age, National Institutes of Health Stroke Scale score, Alberta Stroke Program Early CT Score, time from onset to puncture, occlusion location, intravenous thrombolysis, and successful reperfusion, with interaction terms. Results: Among 608 patients treated with endovascular treatment, 50.5% were women. Women were older than men (median age of 72 versus 68 years, P =0.02) and had a lower prevalence of tandem occlusions (14.0% versus 22.9%, P =0.005). Workflow times were similar between sexes. Adjusted outcomes did not differ between women and men. Functional independence at 90 days was achieved by 127 out of 292 women (43.5%) and 135 out of 291 men (46.4%). Mortality at 90 days (54 [18.5%] versus 48 [16.5%]) and symptomatic intracranial hemorrhage (37 [13.3%] versus 33 [11.6%]) were similar between women and men. There was no sex-by-age interaction on functional outcomes. However, men had higher likelihood of mortality ( P interaction =0.003) and symptomatic intracranial hemorrhage ( P interaction =0.017) with advancing age. Sex did not influence the relation between successful reperfusion and outcomes. Conclusions: In this multicenter analysis of late patients treated with endovascular treatment, sex was not associated with functional outcome. However, sex influenced the association between age and safety outcomes, with men experiencing worse outcomes with advancing age.