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Most of the currently employed methods, such as Gamma method and shear analogy method, to estimate the bending stiffness and bending capacity of cross-laminated timber (CLT) beams, are computationally extensive. In our previous study, a rolling shear analysis (RSA)-based method, which simplifies the calculation, was developed to determine the shearing capacity of CLT beams. In the present study, the authors expand upon the RSA method to determine the apparent stiffness and bending capacity of 3- and 5-layer CLT beams. By considering the shear deformation of cross layers, simplified formulas to determine the apparent bending stiffness of CLT beam was derived. Two schemes to determine the CLT bending capacity were proposed. One is based on the shear stress analysis, and the other is based on the formula specified in Canadian standard, CSA O86, by replacing the effective stiffness with the apparent stiffness. Test results from the authors and the other researchers were adopted to validate the method. The findings showed that the RSA method, using the apparent stiffness obtained from the proposed method along with the bending capacity formula in CSA O86, can provide a simpler and more reliable estimation of the apparent bending stiffness and bending capacity of CLT beams as compared to the Gamma method and shear analogy method. [ABSTRACT FROM AUTHOR]

Despite the longstanding use of nitrous oxide and descriptions of its psychological effects more than a century ago, there is a paucity of neurobiological investigation of associated psychedelic experiences. We measure the brain's functional geometry (through analysis of cortical gradients) and temporal dynamics (through analysis of co-activation patterns) using human resting-state functional magnetic resonance imaging data acquired before and during administration of 35% nitrous oxide. Both analyses demonstrate that nitrous oxide reduces functional differentiation in frontoparietal and somatomotor networks. Importantly, the subjective psychedelic experience induced by nitrous oxide is inversely correlated with the degree of functional differentiation. Thus, like classical psychedelics acting on serotonin receptors, nitrous oxide flattens the functional geometry of the cortex and disrupts temporal dynamics in association with psychoactive effects. Like classical psychedelics, nitrous oxide reduces functional differentiation in human frontoparietal and somatomotor networks, flattening functional brain geometry and disrupting temporal dynamics in association with the psychedelic experience. [ABSTRACT FROM AUTHOR]

The Yarlung Tsangpo, the longest river in the southern Tibetan Plateau (TP), has attracted much research attention aimed at understanding the factors controlling its modern hydrology and possible future discharge in the context of ongoing climate change. However, partly due to the complex regional climatic background, no consistent conclusions have been reached, especially for its upper reaches. Paleohydrological reconstructions of the source region of the Yarlung Tsangpo can potentially improve our understanding of the history of humidity and its response to climatic variability. In this study, we used a 97 cm gravity core from Gongzhu Co to reconstruct the hydrology change during the late Holocene. The core was dated using AMS 14C and Pb/Cs methods, and we used measurements of element contents (determined by high-resolution XRF scanning), grain size, IC/TOC, and magnetic susceptibility to reconstruct hydroclimatic changes in the source of the Yarlung Tsangpo watershed since ∼4000 yr ago. Combined with a modern meteorological data set, we found that PC1 of the XRF data, the Ca/(Fe + Ti) ratio, and EM1 of the grain size data were indicative of changes in humidity. Our records demonstrate a wet interval during ∼4−1.7 ka BP (ka = 1000 yr, BP represents years before 1950 AD), followed by a dry period during since ∼1 ka BP. Comparison with independent regional paleoclimatic records revealed shifts in the dominant factors controlling humidity. The wet interval during ∼4−1.7 ka BP was coeval with a strengthened Westerlies, implying a dominant moisture supply from northern high latitudes. However, the extremely low values of Ca/(Fe + Ti) ratio during ∼4−2.5 ka BP indicate potential glacial freshwater source, which is corroborated by the concurrent high magnetic susceptibility values and increased grain size. The rapid drying trend during ∼1.7−1 ka BP suggests a switch in moisture supply from the Westerlies to the Indian Summer Monsoon (ISM). We attribute the drought conditions after ∼1 ka BP to a weakened ISM, although a Westerlies influence and the potential effect of high temperatures on evaporation cannot be excluded. We suggest that future hydroclimatic research in this region should attempt to distinguish the individual moisture contributions of the ISM and the Westerlies during the last millennium. [ABSTRACT FROM AUTHOR]

Background and Objectives: Advanced esophageal squamous cell carcinoma (ESCC) is a prevalent and highly malignant tumor with a poor prognosis. Recently, the RATIONALE-306 trial demonstrated that tislelizumab combined with chemotherapy provided overall survival benefits for these patients. This study aimed to assess the cost-effectiveness of this treatment approach in Chinese patients with advanced ESCC from the perspective of healthcare system. Methods: A Markov model was constructed to assess the economic and health benefits associated with tislelizumab plus chemotherapy over a 10-year lifetime horizon, utilizing data from the RATIONALE-306 trial. The analysis encompassed the calculation of several key parameters, including the incremental cost-effectiveness ratio (ICER), total cost, incremental cost, total effectiveness, and incremental effectiveness. Tislelizumab was considered cost-effective if the ICER obtained was below the willingness-to-pay (WTP) threshold of US$38,223 per quality-adjusted life-year (QALY); otherwise, it would be deemed not cost-effective. To ensure the robustness of the findings, the results were subjected to one-way sensitivity analysis and probabilistic sensitivity analysis (PSA). Results: In the base-case analysis, the incremental effectiveness and cost associated with tislelizumab plus chemotherapy, compared to chemotherapy alone, were determined to be 0.40 QALY and US$7604, respectively. This resulted in an ICER of US$18,846 per QALY, which is below the WTP threshold of US$38,223 per QALY. Furthermore, the results from the one-way sensitivity analysis and PSA indicated robustness of the findings. Conclusion: Our lifetime simulation study demonstrated that, in the case of advanced ESCC, the combination of tislelizumab and chemotherapy offers increased effectiveness compared to chemotherapy alone, albeit at a higher cost. Moreover, considering the current WTP threshold in China, the addition of tislelizumab to chemotherapy is considered a cost-effective approach. [ABSTRACT FROM AUTHOR]

Complete locked-in syndrome (CLIS) resulting from late-stage amyotrophic lateral sclerosis (ALS) is characterised by loss of motor function and eye movements. The absence of behavioural indicators of consciousness makes the search for neuronal correlates as possible biomarkers clinically and ethically urgent. EEG-based measures of brain dynamics such as power-law exponent (PLE) and Lempel-Ziv complexity (LZC) have been shown to have explanatory power for consciousness and may provide such neuronal indices for patients with CLIS. Here, we validated PLE and LZC (calculated in a dynamic way) as benchmarks of a wide range of arousal states across different reference states of consciousness (e.g., awake, sleep stages, ketamine, sevoflurane). We show a tendency toward high PLE and low LZC, with high intra-subject fluctuations and inter-subject variability in a cohort of CLIS patients with values graded along different arousal states as in our reference data sets. In conclusion, changes in brain dynamics indicate altered arousal in CLIS. Specifically, PLE and LZC are potentially relevant biomarkers to identify or diagnose the arousal level in CLIS and to determine the optimal time point for treatment, including communication attempts. EEG-based dynamics associated with different arousal states are used to identify indices associated with complete locked-in syndrome, which could aid treatments and communication aids [ABSTRACT FROM AUTHOR]

Scale-free physiological processes are ubiquitous in the human organism. Resting-state functional MRI studies observed the loss of scale-free dynamics under anesthesia. In contrast, the modulation of scale-free dynamics during task-related activity remains an open question. We investigate scale-free dynamics in the cerebral cortex's unimodal periphery and transmodal core topography in rest and task states during three conscious levels (awake, sedation, and anesthesia) complemented by computational modelling (Stuart-Landau model). The empirical findings demonstrate that the loss of the brain's intrinsic scale-free dynamics in the core-periphery topography during anesthesia, where pink noise transforms into white noise, disrupts the brain's neuronal alignment with the task's temporal structure. The computational model shows that the stimuli's scale-free dynamics, namely pink noise distinguishes from brown and white noise, also modulate task-related activity. Together, we provide evidence for two mechanisms of consciousness, temporo-spatial nestedness and alignment, suggested by the Temporo-Spatial Theory of Consciousness (TTC). Summary: Investigation of scale-free brain dynamics via rest-task modulation across awake, sedative, and anesthetic states of consciousness shows that brain dynamics lose alignment to the task's temporal structure in anesthesia as in wakefulness. [ABSTRACT FROM AUTHOR]

Rolling shear, an inherent property of cross-laminated timber (CLT) due to the weak shear strength of cross layers, is always the determinant of load-bearing capacity for short-span CLT members subjected to out-of-plane bending. Many analytical models were developed to calculate the shear capacity of CLT members. Because of the difficulty to precisely model the complicated shear failure mechanisms, however, no model was universally accepted. This paper aims to study the appropriacy of the commonly used analytical models, namely, composite beam theory, shear analogy method, Gamma method, and simple beam theory, by tests and analytical calculations. A composite beam theory-based simplified method was proposed. Three-point loading tests for the short-span CLT panels with 3 and 5 layers were conducted, and the shear capacities of the test specimens were calculated using the above-mentioned analytical methods. Shear strength and modulus of cross layers of the test specimens, which were used as the inputs for calculating the shear capacities, were tested by modified planar shear method. By comparing the calculation results obtained from different analytical models and the test results as well, it can be concluded that: (1) composite beam theory, shear analogy method, and the proposed simplified method give almost the same calculation results, therefore, the proposed simplified method can be used as the replacement for the other models; (2) Gamma method is more appropriate for calculating the shear capacity in case the input shear strength is determined by planar shear test; (3) the simple beam theory that is used in CSA O86 provides significantly lower shear capacity predictions than those obtained by the other methods. [ABSTRACT FROM AUTHOR]

Consciousness is a multidimensional phenomenon, but key dimensions such as awareness and wakefulness have been described conceptually rather than neurobiologically. We hypothesize that dimensions of consciousness are encoded in multiple neurofunctional dimensions of the brain. We analyze cortical gradients, which are continua of the brain's overarching functional geometry, to characterize these neurofunctional dimensions. We demonstrate that disruptions of human consciousness – due to pharmacological, neuropathological, or psychiatric causes – are associated with a degradation of one or more of the major cortical gradients depending on the state. Network-specific reconfigurations within the multidimensional cortical gradient space are associated with behavioral unresponsiveness of various etiologies, and these spatial reconfigurations correlate with a temporal disruption of structured transitions of dynamic brain states. In this work, we therefore provide a unifying neurofunctional framework for multiple dimensions of human consciousness in both health and disease. Dimensions of consciousness such as wakefulness or awareness are well established but have not been mapped to the brain. Here, the authors show that dimensions of consciousness are encoded in the functional geometry of the cortex. [ABSTRACT FROM AUTHOR]

Smoke exposure during pregnancy has detrimental effects upon numerous fetal and neonatal outcomes. Nicotine (the main component of tobacco) has been suggested to affect placental development. During placental development, efficient invasion by trophoblasts is required for establishment of the fetus–maternal circulation. In this study we explored the regulation of trophoblast invasion by nicotine. An immortalized first trimester extravillous trophoblast cell line (HTR-8/SVneo cells) was used for all the experiments, which were treated by nicotine, methyllycaconitine, and C-X-C motif chemokine ligand 12 (CXCL12). Total RNA and protein were used to study the expressions of nicotinic acetylcholine receptors (nAChRs), and transwell assay was used to study invasiveness. Changes of RNA expression due to nicotine treatment were detected by RNA sequence. Level of CXCL12 mRNA was verified by quantitative PCR. We showed that HTR-8/SVneo expressed subunits α2–4, α7, α9, β1, and β2 of nAChRs. Nicotine downregulated CXCL12 expression and inhibited trophoblast invasion. Methyllycaconitine, as an antagonist of the α7 homopolymer, blocked the inhibitory effect of nicotine. CXCL12 could rescue the nicotine-induced inhibitory effect on invasion of HTR-8/SVneo cells. These results suggest that the α7 subunit of the nAChR has important roles in modulating trophoblast invasion through CXCL12. [ABSTRACT FROM AUTHOR]

Due to an error in production, the article should have indicated that Jing Chen and Min Qiu are co-first authors, as displayed here. [ABSTRACT FROM AUTHOR]