The structural MR imaging correlates of cognitive impairment in multiple sclerosis are still debated. This study assessed lesional and atrophy measures of white matter and gray matter involvement in ...patients with MS acquired in 7 European sites to identify the MR imaging variables most closely associated with cognitive dysfunction.
Brain dual-echo, 3D T1-weighted, and double inversion recovery scans were acquired at 3T from 62 patients with relapsing-remitting MS and 65 controls. Patients with at least 2 neuropsychological tests with abnormal findings were considered cognitively impaired. Focal WM and cortical lesions were identified, and volumetric measures from WM, cortical GM, the hippocampus, and deep GM nuclei were obtained. Age- and site-adjusted models were used to compare lesion and volumetric MR imaging variables between patients with MS who were cognitively impaired and cognitively preserved. A multivariate analysis identified MR imaging variables associated with cognitive scores and disability.
Twenty-three patients (38%) were cognitively impaired. Compared with those with who were cognitively preserved, patients with MS with cognitive impairment had higher T2 and T1 lesion volumes and a trend toward a higher number of cortical lesions. Significant brain, cortical GM, hippocampal, deep GM nuclei, and WM atrophy was found in patients with MS with cognitive impairment versus those who were cognitively preserved. Hippocampal and deep GM nuclei atrophy were the best predictors of cognitive impairment, while WM atrophy was the best predictor of disability.
Hippocampal and deep GM nuclei atrophy are key factors associated with cognitive impairment in MS. These MR imaging measures could be applied in a multicenter context, with cognition as clinical outcome.
Fault slip rate is one of the most crucial parameters to characterize earthquake occurrence in fault‐based seismic hazard assessments (SHA). Accordingly, paleoseismic studies have increasingly ...focused on constraining this parameter in active faults worldwide. We present a comprehensive paleoseismic study in the Alhama de Murcia Fault (AMF), one of the most active faults in SE Spain and source of destructing earthquakes such as the 2011 Mw 5.2 Lorca event. Contrasting with previous studies, we integrate paleoseismic data from four fault strands in the AMF and, based on trench slip analysis and numerical dates, we derive slip rate estimates of each strand over the whole transect and assess their time variability. The AMF has a minimum net slip rate between 1.35+0.16/−0.10 and 1.64+0.16/−0.11 mm/yr for the past 18 ± 1 to 15.2 ± 1.1 ka. These results prove the importance of accounting for the complete sections of a geological structure as they are almost twice the previous estimates for a single fault branch. Slip rate variability is identified in the AMF, with cyclic acceleration‐quiescence patterns that could be related to stress field changes driven by fault interaction or synchronicity with neighboring faults (e.g., Carrascoy). We hope that the data presented here motivates their inclusion into forthcoming fault‐based SHAs. In this regard, limitations related to the lack of paleoseismic data for one fault strand, along with poor characterization of the strike component of slip and insufficient age control of the units for another strand are highlighted and need to be accounted for by modelers.
Key Points
Multi‐site paleoseismic surveys allow to improve the estimations of the geological slip rates in the Alhama de Murcia Fault (AMF)
The AMF shows a geological slip rate between 1.35 and 1.64 mm/yr for the past 18–15 ka
Late Quaternary slip rate fluctuations suggest strain rate variations and highlight possible synchronicities with neighboring faults
The objective of this study was to test the effectiveness of ivermectin for the treatment of mouse hepatitis virus (MHV), a type 2 family RNA coronavirus similar to SARS-CoV-2. Female BALB/cJ mice ...were infected with 6,000 PFU of MHV-A59 (group infected, n = 20) or infected and then immediately treated with a single dose of 500 µg/kg ivermectin (group infected + IVM, n = 20) or were not infected and treated with PBS (control group, n = 16). Five days after infection/treatment, the mice were euthanized and the tissues were sampled to assess their general health status and infection levels. Overall, the results demonstrated that viral infection induced typical MHV-caused disease, with the livers showing severe hepatocellular necrosis surrounded by a severe lymphoplasmacytic inflammatory infiltration associated with a high hepatic viral load (52,158 AU), while mice treated with ivermectin showed a better health status with a lower viral load (23,192 AU; p < 0.05), with only a few having histopathological liver damage (p < 0.05). No significant differences were found between the group infected + IVM and control group mice (P = NS). Furthermore, serum transaminase levels (aspartate aminotransferase and alanine aminotransferase) were significantly lower in the treated mice than in the infected animals. In conclusion, ivermectin diminished the MHV viral load and disease in the mice, being a useful model for further understanding this therapy against coronavirus diseases.
ABSTRACT
The merger of two or more galaxies can enhance the inflow of material from galactic scales into the close environments of active galactic nuclei (AGNs), obscuring and feeding the ...supermassive black hole (SMBH). Both recent simulations and observations of AGN in mergers have confirmed that mergers are related to strong nuclear obscuration. However, it is still unclear how AGN obscuration evolves in the last phases of the merger process. We study a sample of 60 luminous and ultra-luminous IR galaxies (U/LIRGs) from the GOALS sample observed by NuSTAR. We find that the fraction of AGNs that are Compton thick (CT; $N_{\rm H}\ge 10^{24}\rm \, cm^{-2}$) peaks at $74_{-19}^{+14}{{\ \rm per\ cent}}$ at a late merger stage, prior to coalescence, when the nuclei have projected separations (dsep) of 0.4–6 kpc. A similar peak is also observed in the median NH $(1.6\pm 0.5)\times 10^{24}\rm \, cm^{-2}$. The vast majority ($85^{+7}_{-9}{{\ \rm per\ cent}}$) of the AGNs in the final merger stages (dsep ≲ 10 kpc) are heavily obscured ($N_{\rm H}\ge 10^{23}\rm \, cm^{-2}$), and the median NH of the accreting SMBHs in our sample is systematically higher than that of local hard X-ray-selected AGN, regardless of the merger stage. This implies that these objects have very obscured nuclear environments, with the $N_{\rm H}\ge 10^{23}\rm \, cm^{-2}$ gas almost completely covering the AGN in late mergers. CT AGNs tend to have systematically higher absorption-corrected X-ray luminosities than less obscured sources. This could either be due to an evolutionary effect, with more obscured sources accreting more rapidly because they have more gas available in their surroundings, or to a selection bias. The latter scenario would imply that we are still missing a large fraction of heavily obscured, lower luminosity ($L_{2-10}\lesssim 10^{43}\rm \, erg\, s^{-1}$) AGNs in U/LIRGs.
Oxidative stress can play a key role in Cd-induced dysfunctions. Quercetin is a potent oxygen free radicals scavenger and a metal chelator. Our aim was to study the effect of quercetin on Cd-induced ...kidney damage and oxidative stress as well as its mechanism of action. Wistar rats were distributed in four experimental groups: control rats; Cd; quercetin and Cd
+
quercetin. Renal toxicity was evaluated by measuring urinary excretion of proteins, albumin, glucose and enzymes markers of tubular necrosis, as well as plasma concentration of creatinine. Plasma TBARS concentration and activity of antioxidant enzymes in kidney were also measured. Renal cell damage was assessed by electron microscopy. Animals that received both Cd and quercetin showed a better renal function than those receiving Cd alone. Cd-induced tubular lesions were markedly reduced in rats that also received quercetin. Cd-induced increase in plasma TBARS was prevented by the administration of quercetin. Total plasma antioxidants and renal superoxide dismutase and glutathione-reductase activities were higher in the group that received Cd and quercetin than in rats that received Cd alone. Quercetin administration does not modify the renal content or the urinary excretion of Cd. In conclusion, quercetin treatment prevents renal tubular damage and increased oxidative stress induced by chronic Cd administration, most probably throughout its antioxidant properties.
The growing development of technologies and processes for resource treatment and recovery is offering endless possibilities for creating new plant-wide configurations or modifying existing ones. ...However, the configurations’ complexity, the interrelation between technologies and the influent characteristics turn decision-making into a complex or unobvious process. In this frame, the Plant-Wide Modelling (PWM) library presented in this paper allows a thorough, comprehensive and refined analysis of different plant configurations that are basic aspects in decision-making from an energy and resource recovery perspective. In order to demonstrate the potential of the library and the need to run simulation analyses, this paper carries out a comparative analysis of WWTPs, from a techno-economic point of view. The selected layouts were (1) a conventional WWTP based on a modified version of the Benchmark Simulation Model No. 2, (2) an upgraded or retrofitted WWTP, and (3) a new Wastewater Resource Recovery Facilities (WRRF) concept denominated as C/N/P decoupling WWTP. The study was based on a preliminary analysis of the organic matter and nutrient energy use and recovery options, a comprehensive mass and energy flux distribution analysis in each configuration in order to compare and identify areas for improvement, and a cost analysis of each plant for different influent COD/TN/TP ratios. Analysing the plants from a standpoint of resources and energy utilization, a low utilization of the energy content of the components could be observed in all configurations. In the conventional plant, the COD used to produce biogas was around 29%, the upgraded plant was around 36%, and 34% in the C/N/P decoupling WWTP. With regard to the self-sufficiency of plants, achieving self-sufficiency was not possible in the conventional plant, in the upgraded plant it depended on the influent C/N ratio, and in the C/N/P decoupling WWTP layout self-sufficiency was feasible for almost all influents, especially at high COD concentrations. The plant layouts proposed in this paper are just a sample of the possibilities offered by current technologies. Even so, the library presented here is generic and can be used to construct any other plant layout, provided that a model is available.
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•Comparative analysis of evolutionary WWTP, from a techno-economic point of view.•Analysis of organic matter and nutrient energy use and recovery options.•Comparative analysis of COD and nutrient flux distributions in evolutionary plants.•Analysis of the costs distributions in WWTPs for different influent COD/N/P ratios.•Simulations based on the Plant-wide modelling methodology.
ABSTRACT Recent intensive Swift monitoring of the Seyfert 1 galaxy NGC 5548 yielded 282 usable epochs over 125 days across six UV/optical bands and the X-rays. This is the densest extended active ...galactic nucleus (AGN) UV/optical continuum sampling ever obtained, with a mean sampling rate <0.5 day. Approximately daily Hubble Space Telescope UV sampling was also obtained. The UV/optical light curves show strong correlations ( ) and the clearest measurement to date of interband lags. These lags are well-fit by a wavelength dependence, with a normalization that indicates an unexpectedly large disk radius of lt-day at 1367 , assuming a simple face-on model. The U band shows a marginally larger lag than expected from the fit and surrounding bands, which could be due to Balmer continuum emission from the broad-line region as suggested by Korista and Goad. The UV/X-ray correlation is weaker ( ) and less consistent over time. This indicates that while Swift is beginning to measure UV/optical lags in general agreement with accretion disk theory (although the derived size is larger than predicted), the relationship with X-ray variability is less well understood. Combining this accretion disk size estimate with those from quasar microlensing studies suggests that AGN disk sizes scale approximately linearly with central black hole mass over a wide range of masses.
•FEA tend to overestimate the elastic response of structural timber connections.•The stiffness contact defines the pressure-overclosure relationship of contact areas•The proposed stiffness contact ...improves the joint behaviour obtained by FEM.•The stiffness contact parameter is defined only based on geometrical parameters•Larger contact areas have a lower value of stiffness contact
Finite element models tend to overestimate the actual elastic response of structural timber connections. The paper shows how such overprediction relates to the modelling of the contact between fasteners and timber. The use of a control parameter called stiffness contact is proposed. After an experimental campaign, a method to determine it, based only on the geometry of a rectangular contact area, is proposed. The modeling adequacy is demonstrated by applying it to dowel embedment and moment resistant wood joint tests. The obtained results show good agreement with the experimental test series.
Background: Cognitive impairment is frequent in multiple sclerosis (MS) and lacks effective treatment. Cognitive rehabilitation is widely applied in neurorehabilitation settings. Functional magnetic ...resonance imaging (fMRI) may help in investigating changes in brain activity and provide a tool to assess the efficacy of rehabilitation.
Aim: To investigate the effect on brain activity as measured by fMRI of a cognitive rehabilitation programme in patients with MS and cognitive impairment.
Method: Fifteen patients with MS and cognitive impairment and five healthy subjects were recruited. Neuropsychological assessments were performed in patients with MS at study entry and after rehabilitation to assess cognitive changes. fMRI scans were performed at week −5 (baseline), week 0 (immediately before rehabilitation) and week 5 (immediately after rehabilitation). The fMRI paradigm was the Paced Auditory Serial Addition Test (PASAT). The cognitive rehabilitation programme was composed of 15 computer-aided drill and practice sessions and five non-computer-aided cognitive stimulation group sessions (over 5 weeks). Strict guidelines ensured comparability of all rehabilitation interventions.
Results: Patients had increased brain fMRI activity after rehabilitation in several cerebellar areas when compared with healthy subjects. After rehabilitation, patients had significantly improved their performance on the backward version of the Digit Span Test (p = 0.007) and on a composite score of neuropsychological outcomes (p = 0.009).
Conclusion: The results of the present study indicate that this cognitive rehabilitation programme increases brain activity in the cerebellum of cognitively impaired patients with MS. The role of fMRI in the assessment of neurorehabilitation schemes warrants further investigation.
Simultaneous determination of fertility hormones in saliva using disposable immunosensing platforms and a custom designed field-portable dual potentiostat.
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•Simultaneous determination ...of progesterone and luteinizing hormone in saliva samples.•Disposable immunoplatforms and custom designed field-portable dual potentiostat.•LODs of 1.7 pg mL−1 and 0.10 mIU mL-1 for P4 and LH, respectively, in less than 1 h.•Accurate determination of both target hormones in saliva samples.
This work describes a new electroanalytical device for the simultaneous and reliable determination of two fertility relevant hormones (luteinizing hormone, LH, and progesterone, P4) in saliva. The device is constructed using a custom designed and field-portable potentiostat where dual disposable immunosensing platform are connected. The immunosensors are based on sandwich-type and competitive immunoassays implemented onto magnetic microbeads (MBs) functionalized with Neutravidin and Protein G for the determination of LH and P4, respectively. Amperometric detection performed at −0.20 V vs the Ag pseudo-reference electrode using the H2O2/hydroquinone (HQ) system was employed as the transduction technique after placing the MBs with immunocomplexes for each target hormone on the appropriate working electrode of screen-printed dual carbon electrodes (SPdCEs). The method exhibits high sensitivity and selectivity for the target hormones providing detection limits of 1.7 pg mL−1 and 0.10 mIU mL−1 for P4 and LH, respectively, with a 1 h test time. The applicability of the method was confirmed by determining both hormones in saliva samples from different volunteers providing results comparable to those obtained using amperometric transduction with a commercial potentiostat and with ELISA methodologies involving the same immunoreagents for each target hormone.
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