The effect of endovascular thrombectomy that is performed more than 6 hours after the onset of ischemic stroke is uncertain. Patients with a clinical deficit that is disproportionately severe ...relative to the infarct volume may benefit from late thrombectomy.
We enrolled patients with occlusion of the intracranial internal carotid artery or proximal middle cerebral artery who had last been known to be well 6 to 24 hours earlier and who had a mismatch between the severity of the clinical deficit and the infarct volume, with mismatch criteria defined according to age (<80 years or ≥80 years). Patients were randomly assigned to thrombectomy plus standard care (the thrombectomy group) or to standard care alone (the control group). The coprimary end points were the mean score for disability on the utility-weighted modified Rankin scale (which ranges from 0 death to 10 no symptoms or disability) and the rate of functional independence (a score of 0, 1, or 2 on the modified Rankin scale, which ranges from 0 to 6, with higher scores indicating more severe disability) at 90 days.
A total of 206 patients were enrolled; 107 were assigned to the thrombectomy group and 99 to the control group. At 31 months, enrollment in the trial was stopped because of the results of a prespecified interim analysis. The mean score on the utility-weighted modified Rankin scale at 90 days was 5.5 in the thrombectomy group as compared with 3.4 in the control group (adjusted difference Bayesian analysis, 2.0 points; 95% credible interval, 1.1 to 3.0; posterior probability of superiority, >0.999), and the rate of functional independence at 90 days was 49% in the thrombectomy group as compared with 13% in the control group (adjusted difference, 33 percentage points; 95% credible interval, 24 to 44; posterior probability of superiority, >0.999). The rate of symptomatic intracranial hemorrhage did not differ significantly between the two groups (6% in the thrombectomy group and 3% in the control group, P=0.50), nor did 90-day mortality (19% and 18%, respectively; P=1.00).
Among patients with acute stroke who had last been known to be well 6 to 24 hours earlier and who had a mismatch between clinical deficit and infarct, outcomes for disability at 90 days were better with thrombectomy plus standard care than with standard care alone. (Funded by Stryker Neurovascular; DAWN ClinicalTrials.gov number, NCT02142283 .).
The majority of individuals with amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) exhibit neuronal cytoplasmic inclusions rich in the RNA binding protein TDP43. Even so, the ...relation between the RNA binding properties of TDP43 and neurodegeneration remains obscure. Here, we show that engineered mutations disrupting a salt bridge between the RNA recognition motifs of TDP43 interfere with RNA binding and eliminate the recognition of native TDP43 substrates. The same mutations dramatically destabilize TDP43, alter its subcellular localization, and abrogate TDP43-dependent neurodegeneration. Worms harboring homologous TDP-1 mutations phenocopy knockout strains, confirming the necessity of salt bridge residues for TDP43 function. Moreover, the accumulation of functional TDP43, but not RNA binding-deficient variants, disproportionately affects transcripts encoding ribosome and oxidative phosphorylation components. These studies demonstrate the significance of the salt bridge in sustaining TDP43 stability and RNA binding properties, factors that are crucial for neurodegeneration arising from TDP43 deposition in ALS and FTD.
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•The Arg151/Asp247 salt bridge dictates TDP43 RNA binding affinity and specificity•Disrupting the salt bridge results in TDP43 destabilization and mislocalization•Both reduced RNA binding and protein instability mitigate TDP43-mediated toxicity•Active TDP43 accumulation selectively affects ribosomal and mitochondrial RNAs
Flores et al. uncover essential roles for an intramolecular salt bridge in the function of TDP43, an RNA binding protein implicated in neurodegenerative diseases. Salt bridge interruption attenuates TDP43 RNA binding affinity and specificity, destabilizes the protein, and prevents TDP43-mediated neurotoxicity arising from misprocessing of ribosomal and mitochondrial transcripts.
Nanonetworks consist of nano-sized communicating devices which are able to perform simple tasks at the nanoscale. The limited capabilities of individual nanomachines and the Terahertz (THz) band ...channel behavior lead to error-prone wireless links. In this paper, a cross-layer analysis of error-control strategies for nanonetworks in the THz band is presented. A mathematical framework is developed and used to analyze the tradeoffs between Bit Error Rate, Packet Error Rate, energy consumption and latency, for five different error-control strategies, namely, Automatic Repeat reQuest (ARQ), Forward Error Correction (FEC), two types of Error Prevention Codes (EPC) and a hybrid EPC. The cross-layer effects between the physical and the link layers as well as the impact of the nanomachine capabilities in both layers are taken into account. At the physical layer, nanomachines are considered to communicate by following a time-spread on-off keying modulation based on the transmission of femtosecond-long pulses. At the link layer, nanomachines are considered to access the channel in an uncoordinated fashion, by leveraging the possibility to interleave pulse-based transmissions from different nodes. Throughout the analysis, accurate path loss, noise and multi-user interference models, validated by means of electromagnetic simulation, are utilized. In addition, the energy consumption and latency introduced by a hardware implementation of each error control technique, as well as, the additional constraints imposed by the use of energy-harvesting mechanisms to power the nanomachines, are taken into account. The results show that, despite their simplicity, EPCs outperform traditional ARQ and FEC schemes, in terms of error correcting capabilities, which results in further energy savings and reduced latency.
Summary
The C‐MAC® comprises a Macintosh blade connected to a video unit. The familiarity of the Macintosh blade, and the ability to use the C‐MAC as a direct or indirect laryngoscope, may be ...advantageous. We wished to compare the C‐MAC with Macintosh, Glidescope® and Airtraq® laryngoscopes in easy and simulated difficult laryngoscopy. Thirty‐one experienced anaesthetists performed tracheal intubation in an easy and difficult laryngoscopy scenario. The duration of intubation attempts, success rates, number of intubation attempts and of optimisation manoeuvres, the severity of dental compression, and difficulty of device use were recorded. In easy laryngoscopy, the duration of tracheal intubation attempts were similar with the C‐MAC, Macintosh and Airtraq laryngoscopes; the Glidescope performed less well. The C‐MAC and Airtraq provided the best glottic views, but the C‐MAC was rated as the easiest device to use. In difficult laryngo‐scopy the C‐MAC demonstrated the shortest tracheal intubation times. The Airtraq provided the best glottic view, with the Macintosh providing the worst view. The C‐MAC was the easiest device to use.
Cognitive radio sensor networks (CRSNs) have been proposed to serve as a reliable, robust, and efficient communications infrastructure that can address both the existing and future energy management ...requirements of the smart grid. The existing and envisioned applications of CRSN-based smart grid include substation automation, overhead transmission line monitoring, home energy management, advanced metering infrastructure, wide-area situational awareness, demand response, outage management, distribution automation, asset management. To realize these applications,in this paper, honey bee mating optimization-based routing and cooperative channel assignment algorithms have been proposed. The developed framework significantly decreases the probability of packet loss and preserves high link quality among sensor nodes in harsh smart grid spectrum environments. The proposed approach performance has been evaluated in terms of packet delivery ratio, delay, and energy consumption demonstrating that it has successfully addressed the QoS requirements of most of the SG applications presented.
Service quality (SQ) and customer satisfaction as perceived by 1037 passengers on intercity train services in Bangladesh were examined using structural equation modeling to explain the overall SQ of ...intercity train service. This study presents two structural equation models to reveal the influence of the observed variables on the SQ of intercity train service in the context of a developing country. Out of the two models, the best one is selected based on statistical parameters and resemblance with real life expectations. The framework of the models is based on eighteen observed variables; among them five were considered as endogenous and rest of the thirteen as exogenous variables. The number of latent variables used in the models is one, which is confirmed by the factor analysis. Out of the eighteen observed variables, ‘Overall security’, ‘Female harassment’, ‘Fitness of compartment’ and ‘Waiting place condition’ are found to be the variables which predominantly influence SQ. Moreover, the effect of heterogeneity among users on the performance of the best model is investigated. All the study findings match the real life scenario of a developing country. Acknowledging limited resources of a developing country, the present study provides a guideline to the railway operator for making the intercity train service more attractive for both prospective and existing users.
Functional near-infrared spectroscopy (fNIRS) has evolved as a neuro-imaging modality over the course of the past two decades. The removal of superfluous information accompanying the optical signal, ...however, remains a challenge. A comprehensive analysis of each step is necessary to ensure the extraction of actual information from measured fNIRS waveforms. A slight change in shape could alter the features required for fNIRS-BCI applications. In the present study, the effect of the differential path-length factor (DPF) values on the characteristics of the hemodynamic response function (HRF) was investigated. Results were compiled for both simulated data sets and healthy human subjects over a range of DPF values from three to eight. Different sets of activation durations and stimuli were used to generate the simulated signals for further analysis. These signals were split into optical densities under a constrained environment utilizing known values of DPF. Later, different values of DPF were used to analyze the variations of actual HRF. The results, as summarized into four categories, suggest that the DPF can change the main and post-stimuli responses in addition to other interferences. Six healthy subjects participated in this study. Their observed optical brain time-series were fed into an iterative optimization problem in order to estimate the best possible fit of HRF and physiological noises present in the measured signals with free parameters. A series of solutions was derived for different values of DPF in order to analyze the variations of HRF. It was observed that DPF change is responsible for HRF creep from actual values as well as changes in HRF characteristics.
The Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that originated in Chinese city of Wuhan has caused around 906,092 deaths and 28,040,853 confirmed cases worldwide ...(https://covid19.who.int/, 11 September 2020). In a life-threatening situation, where there is no specific and licensed anti-COVID-19 vaccine or medicine available; the repurposed drug might act as a silver bullet. Currently, more than 211 vaccines, 80 antibodies, 31 antiviral drugs, 35 cell-based, 6 RNA-based and 131 other drugs are in clinical trials. It is therefore utter need of the hour to develop an effective drug that can be used for the treatment of COVID-19 before a vaccine can be developed. One of the best-characterized and attractive drug targets among coronaviruses is the main protease (3CLpro). Therefore, the current study focuses on the molecular docking analysis of TAT-peptide47–57 (GRKKRRQRRRP)-conjugated repurposed drugs (i.e., lopinavir, ritonavir, favipiravir, and hydroxychloroquine) with SARS-CoV-2 main protease (3CLpro) to discover potential efficacy of TAT-peptide (TP) - conjugated repurposing drugs against SARS-CoV-2. The molecular docking results validated that TP-conjugated ritonavir, lopinavir, favipiravir, and hydroxychloroquine have superior and significantly enhanced interactions with the target SARS-CoV-2 main protease. In-silico approach employed in this study suggests that the combination of the drug with TP is an excelling alternative to develop a novel drug for the treatment of SARS-CoV-2 infected patients. The development of TP based delivery of repurposing drugs might be an excellent approach to enhance the efficacy of the existing drugs for the treatment of COVID-19. The predictions from the results obtained provide invaluable information that can be utilized for the choice of candidate drugs for in vitro, in vivo and clinical trials. The outcome from this work prove crucial for exploring and developing novel cost-effective and biocompatible TP conjugated anti-SARS-CoV-2 therapeutic agents in immediate future.
Bis(hexylmethyldithio-/diselenocarbamato)cadmium(II)/zinc(II) (M(E2CNMe n Hex)2 M = Zn, Cd; E = S, Se) have been used as single-source precursors for the preparation of TOPO-capped CdS, CdSe, ZnS, ...and ZnSe nanoparticles. The precursors are stable for long periods of time and pyrolyse cleanly to give high yields of nanocrystals. The nanoparticles were of high quality, close to monodispersed, and showed quantum confinement with characteristic close to band edge luminescence in their emission spectra. The broad diffraction in the XRD pattern and diffuse diffraction rings of the SAED pattern are typical of nanometric size particles. The TEM micrographs showed well-defined, close to spherical particles and the lattice fringes in the HRTEM images confirmed the crystalline nature. The presence of a strong phosphorus peak in the EDAX spectra is indicative of TOPO or TOPE (E = S or Se) bound to the surface.
The prevalence of burnout and depressive symptoms is high among physician trainees.
What is the burden of burnout and depressive symptoms among fellows training in pulmonary and critical care ...medicine (PCCM) and what are associated individual fellow, program, and institutional characteristics?
We conducted a cross-sectional electronic survey of fellows enrolled in pulmonary, PCCM, and critical care medicine training programs in the United States to assess burnout and depressive symptoms. Burnout symptoms were measured using the Maslach Burnout Index two-item measure. The two-item Primary Care Evaluation of Mental Disorders Procedure was used to screen for depressive symptoms. For each of the two outcomes (burnout and depressive symptoms), we constructed three multivariate logistic regression models to assess individual fellow characteristics, program structure, and institutional polices associated with either burnout or depressive symptoms.
Five hundred two of the 976 fellows who received the survey completed it-including both outcome measures-giving a response rate of 51%. Fifty percent of fellows showed positive results for either burnout or depressive symptoms, with 41% showing positive results for depressive symptoms, 32% showing positive results for burnout, and 23% showing positive results for both. Reporting a coverage system in the case of personal illness or emergency (adjusted OR aOR, 0.44; 95% CI, 0.26-0.73) and access to mental health services (aOR, 0.14; 95% CI, 0.04-0.47) were associated with lower odds of burnout. Financial concern was associated with higher odds of depressive symptoms (aOR, 1.13; 95% CI, 1.05-1.22). Working more than 70 hours in an average clinical week and the burdens of electronic health record (EHR) documentation were associated with a higher odds of both burnout and depressive symptoms.
Given the high prevalence of burnout and depressive symptoms among fellows training in PCCM, an urgent need exists to identify solutions that address this public health crisis. Strategies such as providing an easily accessible coverage system, access to mental health resources, reducing EHR burden, addressing work hours, and addressing financial concerns among trainees may help to reduce burnout or depressive symptoms and should be studied further by the graduate medical education community.
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