Analysis of consciousness for complete locked-in syndrome patients

This thesis presents methods for detecting consciousness in patients with complete locked-in syndrome (CLIS). CLIS patients are unable to speak and have lost all muscle movement. Externally, the internal brain activity of such patients cannot be easily perceived, but CLIS patients are considered to be still conscious and cognitively active. Detecting the current state of consciousness of CLIS patients is non-trivial, and it is difficult to ascertain whether CLIS patients are conscious or not. Thus, it is vital to develop alternative ways to re-establish communication with these patients during periods of awareness, and a possible platform is through brain–computer interface (BCI). Since consciousness is required to use BCI correctly, this study proposes a modus operandi to analyze not only in intracranial electrocorticography (ECoG) signals with greater signal-to-noise ratio (SNR) and higher signal amplitude, but also in non-invasive electroencephalography (EEG) signals. By applying three different time-domain analysis approaches sample entropy, permutation entropy, and Poincaré plot as feature extraction to prevent disease-related reductions of brainwave frequency bands in CLIS patients, and cross-validated to improve the probability of correctly detecting the conscious states of CLIS patients. Due to the lack a of 'ground truth' that could be used as teaching input to correct the outcomes, k-Means and DBSCAN these unsupervised learning methods were used to reveal the presence of different levels of consciousness for individual participation in the experiment first in locked-in state (LIS) patients with ALSFRS-R score of 0. The results of these different methods converge on the specific periods of consciousness of CLIS/LIS patients, coinciding with the period during which CLIS/LIS patients recorded communication with an experimenter. To determine methodological feasibility, the methods were also applied to patients with disorders of consciousness (DOC). The results indicate that the use of sample entropy might be helpful to detect awareness not only in CLIS/LIS patients but also in minimally conscious state (MCS)/unresponsive wakefulness syndrome (UWS) patients, and showed good resolution for both ECoG signals up to 24 hours a day and EEG signals focused on one or two hours at the time of the experiment. This thesis focus on consistent results across multiple channels to avoid compensatory effects of brain injury. Unlike most techniques designed to help clinicians diagnose and understand patients' long-term disease progression or distinguish between different disease types on the clinical scales of consciousness. The aim of this investigation is to develop a reliable brain-computer interface-based communication aid eventually to provide family members with a method for short-term communication with CLIS patients in daily life, and at the same time, this will keep patients' brains active to increase patients' willingness to live and improve their quality of life (QOL)

Consciousness Detection in a Complete Locked-in Syndrome Patient through Multiscale Approach Analysis

Completely locked-in state (CLIS) patients are unable to speak and have lost all muscle movement. From the external view, the internal brain activity of such patients cannot be easily perceived, but CLIS patients are considered to still be conscious and cognitively active. Detecting the current state of consciousness of CLIS patients is non-trivial, and it is difficult to ascertain whether CLIS patients are conscious or not. Thus, it is important to find alternative ways to re-establish communication with these patients during periods of awareness, and one such alternative is through a brain–computer interface (BCI). In this study, multiscale-based methods (multiscale sample entropy, multiscale permutation entropy and multiscale Poincaré plots) were applied to analyze electrocorticogram signals from a CLIS patient to detect the underlying consciousness level. Results from these different methods converge to a specific period of awareness of the CLIS patient in question, coinciding with the period during which the CLIS patient is recorded to have communicated with an experimenter. The aim of the investigation is to propose a methodology that could be used to create reliable communication with CLIS patients

A path to precision cosmology: synergy between four promising late-universe cosmological probes

In the next decades, it is necessary to forge new late-universe cosmological probes to precisely constrain the Hubble constant and the equation of state of dark energy simultaneously. In this work, we show that the four typical late-universe cosmological probes, the 21 cm intensity mapping (IM), fast radio burst (FRB), gravitational wave (GW) standard siren, and strong gravitational lensing (SGL), are expected to be forged into useful tools in solving the Hubble tension and exploring dark energy. We propose that the synergy of them is rather important in cosmology. We simulate the 21 cm IM, FRB, GW, and SGL data based on the hypothetical observations of the Hydrogen Intensity and Real-time Analysis eXperiment (HIRAX), the Square Kilometre Array (SKA), the Einstein Telescope (ET), and the Large Synoptic Survey Telescope (LSST), respectively. We find that the four probes show obviously different parameter degeneracy orientations in cosmological constraints, so any combination of them can break the parameter degeneracies and thus significantly improve the constraint precision. The joint 21 cm IM+FRB+GW+SGL data can provide the constraint errors of $\sigma(\Omega_{\rm m})=0.0022$ and $\sigma(H_0)=0.16\ \rm km\ s^{-1}\ Mpc^{-1}$ in the $\Lambda$CDM model, which meet the standard of precision cosmology, i.e., the constraint precision of parameters is better than 1%. In addition, the joint data give $\sigma(w)=0.020$ in the $w$CDM model, and $\sigma(w_0)=0.066$ and $\sigma(w_a)=0.25$ in the $w_0w_a$CDM model, which are all better than the constraints obtained by the CMB+BAO+SN data. We show that the synergy between the four late-universe cosmological probes has magnificent prospects.Comment: 28 pages, 9 figures; accepted for publication in JCA

El papel del locus de control del jefe entre el guanxi percibido y la conducta de liderazgo en los negocios familiares

The special and historical relationship network in Chinese societies is based on blood ties or family emotional connection, in which family business appears the best representative. With the specialty of corporate structure, power and leadership between superiors and subordinates are the critical issues for research, where managers’ personality is particularly emphasized. We combine guanxi in Chinese societies, power, influence tactics, and locus of control in the research model, 147 family business in Taiwan are proceeded the questionnaire survey, and 332 valid copies are retrieved. With hierarchical regression analysis, the findings show the close relations between managers’ power, perceived guanxi and leadership behavior, in which managers’ locus of control play a critical role. It is therefore suggested that the assignation of managers in such type of enterprises should be more cautious; in addition to the communication with the subordinates, the fitness with personality and competence should be concerned in order to maintain the favorable work efficiency and the relations between superiors and subordinates.La histórica y especial red de relaciones de la sociedad china se basa en lazos de sangre o en conexiones familiares emocionales de las que los negocios familiares son la mejor representación. Junto con la especialización de las estructuras corporativas, la cuestión clave de esta investigación será el poder y el liderazgo de los jefes sobre los subordinados, poniendo el énfasis en la personalidad del jefe. En el modelo de investigación –administración de un cuestionario a 147 negocios familiares de Taiwán, de los que 332 fueron válidos- combinamos el “guanxi” de las sociedades chinas, el poder, las tácticas para tener influencia y el locus de control. Mediante análisis jerárquicos de regresión los resultados muestran la estrecha relación que se da entre el poder de los jefes, el “guanxi” percibido y la conducta de liderazgo, en la que el locusde control de los jefes desempeña un papel destacado. Por eso se recomienda que la designación de jefes en esas empresas sea más cuidadosa. Además de la comunicación con los subordinados, debe prestarse atención a la adecuación entre personalidad y la competencia para mantener una eficiencia laboral y unas relaciones entre jefes y subordinados favorables

EBV-positive Hodgkin lymphoma is associated with suppression of p21cip1/waf1 and a worse prognosis

<p>Abstract</p> <p>Background</p> <p>About 30-50% of Hodgkin lymphomas (HLs) harbor the Epstein-Barr virus (EBV), but the impact of EBV infection on clinical outcomes has been unclear. EBV-encoded small RNAs (<it>EBER</it>s) are presented in all EBV-infected cells, but their functions are still less understood.</p> <p>Results</p> <p><it>EBER1 </it>was transfected into two HL cell lines, KMH2 and L428, and microarrays were used to screen for <it>EBER1</it>-induced changes. We found that <it>EBER1 </it>suppressed <it>p21</it>^cip1/waf1transcription in HL cell lines. In addition, positive regulators of <it>p21</it>^cip1/waf1transcription, such as p53, EGR1, and STAT1, were decreased. Suppression of <it>p21</it>^cip1/waf1in the <it>EBER1</it>⁺HL cell lines was associated with increased resistance to histone deacetylase inhibitors or proteasome inhibitors, drugs known to cause apoptosis by increasing p21^cip1/waf1levels. On biopsy specimens, EBV⁺HLs had weaker expression of both p21^cip1/waf1and active caspase 3. Clinically, suppression of p21^cip1/waf1in EBV⁺HLs was associated with a worse 2-year disease-free survival rate (45% for EBV⁺HLs <it>vs</it>. 77% for EBV^-HLs, <it>p </it>= 0.002).</p> <p>Conclusion</p> <p>Although the underlying mechanisms are still relatively unclear, <it>EBER1 </it>inhibits <it>p21</it>^cip1/waf1transcription and prevents apoptosis through down-regulation of p53, EGR1, and STAT1. The anti-apoptotic activity of <it>EBER1 </it>may be important in the rescue of Reed-Sternberg cells from drug-induced apoptosis and in the clinical behaviors of EBV⁺HLs.</p

Different Influences on Tacrolimus Pharmacokinetics by Coadministrations of Zhi Ke and Zhi Shi in Rats

Tacrolimus, an immunosuppressant with narrow therapeutic window, has been used widely in transplant patients. Grapefruit juice and pomelo have been reported to increase the blood levels of tacrolimus. Zhi Ke and Zhi Shi, the ripe peels and unripe fruits of Citrus aurantium which is chemotaxonomically related to grapefruit and pomelo, are in wide use in clinical Chinese medicine. To investigate the possible interaction of these two Citrus herbs with tacrolimus, male Sprague-Dawley rats were orally given tacrolimus (1.5 mg/kg) with and without Zhi Ke and Zhi Shi decoctions in a cross-over design. Blood samples were withdrawn via cardiopuncture at specific time and quantitated by a microparticle enzyme immunoassay. In addition, to explore the mechanism of interaction, LS 180 cell line was used for the transport study of rhodamine 123, a typical substrate of P-glycoprotein (P-gp). The results showed that Zhi Shi significantly decreased the Cmax and AUC0−t of tacrolimus by 72.4% and 72.0%, respectively, whereas Zhi Ke did not affect tacrolimus pharmacokinetics. LS 180 cell line study indicated that Zhi Shi increased the efflux activity of P-gp, enabling us to explain the decreased oral bioavailability of tacrolimus caused by Zhi Shi. Hence, we suggest that Zhi Shi be contraindicated for transplant patients treated with tacrolimus to reduce the risk of allograft rejection