This paper addresses the problem of integrating phenomenal consciousness with physical laws by seeking to identify and define its function. The central claim is that the hard problem is caused by the same epistemic paradox that makes quantum and classical physics mutually incompatible: the measure-theoretic limit. It is logically impossible to explain the mechanism by which state transitions occur within continuous time except by using approximations, because the mathematics requires point-equivalent instants of zero duration, which cannot exist ontologically when time is continuous. Classical and quantum physics use mutually incompatible frameworks to model causality and overcome this dt→0 limit. It is argued here that consciousness functions as an ontological workaround for this and all problems related to temporally extended information in continuous time, including sensory qualia. The temporal uncertainty principle (TUP) defines consciousness as a superposition of two contradictory temporal perspectives, synchronous and diachronic, within a single "now". These perspectives interact recursively to reduce uncertainty to a point where further reduction is logically and physically impossible. This mechanism prevents computational paralysis when the system confronts unresolvable causal boundaries, and enables the generation of novel concepts and adaptive behaviours. The bi-directional electromagnetic model (BIDEM) postulates how the brain can achieve this mechanism within a general resonance theory (GRT) framework. By demonstrating how phase-amplitude coupling integrates two dimensionally orthogonal substrates, BIDEM enables diachronic information to act within simultaneously experienced instants. The model yields testable predictions for cross-frequency EM interactions and introduces a "simultaneity barrier" as the basis for an objective Turing test of artificial consciousness.
In this paper, we develop a hybrid dynamical system to model mosquito population suppression incorporating both time and state-dependent switching. The time-dependent switching arises from a mismatch between the sexual lifespan of sterile mosquitoes and the sampling period, while the state-dependent switching is governed by the relation between the state of wild mosquitoes at sampling instants and the epidemiological threshold. We investigate the long-term dynamics of the hybrid system with sampling period exceeding the sexual lifespan. The wild population is shown to converge to a pseudo-equilibrium when the epidemiological threshold exceeds this equilibrium value. For the other situation, we establish sufficient conditions for the existence of a unique (pseudo)-harmonic solution and analyze its stability. Using Poincaré mapping, we further derive explicit existence criteria for subharmonic solutions and rigorously prove their global asymptotic stability. Finally, some numerical examples are provided to illustrate our theoretical findings and to deliver practical insights for release strategy development.
This research delves into the passivity-based pinning synchronization problem for switched directed networks (SDNs) within the context of a sampled-data-based event-triggered (SDET) communication environment. An improved state-dependent switching strategy (SDSS) using sampled measurements alongside a novel time-dependent Lyapunov-Krasovskii functional (LKF) approach is constructed. Subsequently, a relaxed passivity analysis framework is then presented, ensuring that the resultant synchronization error system (SES) remains passive, and that the examined SDNs achieve asymptotic synchronization in the absence of external inputs. Unlike conventional strategies, the proposed switching protocol depends exclusively on system states at discrete sampling instants and effectively utilizes historical state data, yielding a less conservative theoretical framework for passivity synthesis in SDNs. Furthermore, the resulting synchronization criterion is independent of the number of network nodes, rendering it suitable for SDNs with large size. Ultimately, two examples involving relevant application in image encryption and decryption are provided to verify the effectiveness and applicability of the proposed scheme, and highlight the distinct advantage of switching behaviors in enhancing encryption confidentiality.
This article investigates the problem of dissipativity-based output feedback control for networked sampled-data systems under actuator failures and consecutive denial-of-service (DoS) attacks. Two distinct sampling periods are considered, each governed by constant occurrence probabilities following a Bernoulli distribution. The communication channel from the sampler to the controller is vulnerable to malicious DoS attacks, with both the maximum number of consecutive occurrences and the attacking rate taken into account. On this basis, a mathematical model is built to characterize the interval between two sequential update instants at the controller side, whose randomness is captured by the probabilistic distributions of the stochastic sampling and consecutive attacks. By developing a sampled-data output feedback controller, an equivalent discrete-time closed-loop system is constructed. Then, two alternative control synthesis conditions are suggested for solving the controller, which can ensure the stochastic stability and strict dissipativity of the system. Finally, simulations are performed on two examples to illustrate the effectiveness of the proposed method.
The definition of the muscle insertion surface (MIS) is often simplified in micro-finite element (micro-FE) models despite its potential impact on the predictions of mechanical properties that are relevant to bone adaptation. This study investigated the effect of MIS size on local strain energy density (SED) in the mouse tibia. Micro-FE models of six mouse tibiae were developed from micro-CT images, and loading conditions were derived from musculoskeletal simulations of trotting gait. For the seven muscles with the highest contributions to tibial loading, three MIS configurations were tested: full anatomical surface, 50% reduced surface, and a single-node application. A total of 198 micro-FE models were run, both for individual muscle applications and multi-muscle configurations at key instants of the stance phase. SED values were compared across MIS conditions using the mean absolute difference, normalised by the median, mean, or 95th percentile of the SED. Significant differences in SED were observed between MIS configurations, with the largest effects near the MIS and boundary conditions. The effect of MIS modification on SED values was heterogeneous across the different muscles, highlighting the importance of anatomical features. Even with multiple muscle loading, SED differences exceeded 20% in most comparisons. These results demonstrate that simplifications of the MIS, especially to single-node applications, can considerably alter local SED predictions and are likely to compromise the accuracy of bone adaptation models. Accurate representation of the MIS is therefore essential for reliable mechanoregulation analysis and should be prioritised in multiscale models of skeletal loading.
Physical-layer key generation (PLKG) is a technique that produces symmetric encryption keys by exploiting the inherent characteristics of wireless channels. It offers advantages including high physical-layer security, elimination of pre-shared keys, dynamic upgradability, and resistance to quantum attacks, making PLKG a promising security solution for next-generation (6G) networks. However, satellite communication channels exhibit high dynamics and long propagation delays. Characteristics such as large Doppler shifts, short coherence times, and orbital predictability pose severe challenges to PLKG, including reciprocity degradation, low key generation rate (KGR), and susceptibility to channel-prediction attacks. This work proposes a delay-Doppler domain time-hopping key generation scheme (KE-DD-TH) based on Orthogonal Time Frequency Space (OTFS) modulation for high-speed links between Low-Earth-Orbit (LEO)/Medium-Earth-Orbit (MEO) satellites and ground terminals in Ka/Ku bands. The scheme performs non-uniform sampling on the DD domain grid of OTFS symbols using an ephemeris-driven pseudo-random time-hopping sequence generated by cascaded linear feedback shift registers (LFSRs) and a nonlinear matrix transformation. Both legitimate parties estimate the channel only at time-hopping instants and multiply two adjacent estimates to construct an "equivalent channel" matrix, yielding a random source with high entropy, high reciprocity, and low predictability. The eavesdropper's key disagreement rate (KDR) remains close to 0.5 under all signal-to-noise ratio (SNR) conditions, corresponding to the ideal random-guessing baseline. This indicates that Eve obtains negligible mutual information, i.e., I(KA;KE)≈0. By contrast, the conventional KE-DD scheme allows Eve's KDR to degrade to 0.014 at 30 dB SNR, indicating near-complete key recovery. The generated keys pass all 12 randomness tests of the NIST SP 800-22 statistical test suite.
Strain resilient nanocomposite conductors with self-healing ability are vital for skin-mounted devices and system-level bioelectronics, especially for wireless systems that require extremely low surface resistance and high stability of electromagnetic wave transmission. However, nanocomposite conductors inherently suffer from a trade-off between conductivity and flexible deformability or self-healing ability. Herein, a strain resilient and self-healing conductor (with ultralow sheet resistance of 10.8 mΩ/sq) is fabricated based on a well-designed polymer binder. It not only maintains outstanding stretchability (a break at elongation over 700%) and electrical stability during repeated stretching (1000 cycles) but also exhibits self-healing performance. On this basis, a flexible antenna with outstanding electromagnetic performance (realized gain of 5.25 dBi, nearly equivalent to that of copper-based devices), excellent self-healing ability is realized for wireless e-skin which can support instant communication exceeding 70 m. This approach overcomes the trade-off between high conductivity and excellent mechanical property in nanocomposite conductor and paves the way for completely self-healing flexible antenna towards wireless e-skins.
Despite the increasing integration of digital technologies into dental education, the pedagogical value of digital cephalometric training remains unclear. This training may also influence professional self-confidence. This study evaluated a digital cephalometric training model and explored the determinants of student self-assessment. In this quasi-experimental study, students identified 20 landmarks before and after training, using digital cephalometric software. After training, students completed a 6-dimensional questionnaire using a 5-point Likert scale. Paired t tests were used to compare pretraining and posttraining accuracy, and Pearson's correlation and multiple linear regression were used to examine associations among the dimensions and predictors of self-assessment. Digital training significantly improved the accuracy of all 20 landmarks, with the greatest gains for traditionally difficult points (eg, nasion and pterygomaxillary fissure). Students valued instant feedback, autonomous learning, and a blended digital-traditional model. Despite objective skill improvements, a confidence gap emerged: self-assessment scores were relatively low, and regression analysis showed that self-assessed confidence was not predicted by positive digital learning experiences but by endorsement of the value of traditional methods in fostering professional thinking. Digital cephalometric training effectively enhanced landmark identification skills relevant to orthodontic diagnosis; however, educators must address the disconnect between objective competence and subjective confidence. Integrating new technologies with foundational professional values using traditional approaches may better support students' professional confidence.
The rapid development of digital tools for medical education and training has expanded the possibilities for flexible and personalized learning, but it has also created challenges in choosing the best tools to meet specific learning needs. This article presents a functional framework that assists educators and learners in selecting tools based on their needs and the learning context. By categorizing tools into synchronous and asynchronous types, we aim to simplify the decision-making process and optimize educational experiences. Synchronous learning tools like YouTube Live, PathCast, Zoom and Microsoft Teams support real-time participation and promote communication, collaboration and responsiveness in the learning environment. These tools are especially useful for live streaming, Q&A, and discussions where instant feedback can support learning outcomes. Asynchronous learning tools such as YouTube, Canvas, Elicit and Quizlet, give learners the flexibility to learn material at their own pace, encouraging independent learning and memorization. Asynchronous platforms allow for pausing, reviewing and repeating material as needed, making them ideal for complex courses that require effective repetition. Hybrid models, especially the flipped classroom approach, blend these modes effectively. Tools like Edpuzzle and Nearpod make it possible to create interactive lessons and exercises in the classroom. The integration of innovative technology in medical education is not solely about adopting new tools but also about promoting adaptability and a culture of continuous learning. Blending synchronous and asynchronous tools with a human-centered approach, can build flexible, responsive learning environments that empower educators and learners to make informed choices, creating adaptive and effective learning environments that meet diverse needs.
Durable tough underwater tissue adhesion presents a big challenge due to the inherent materials science trade-off between robust interfacial bonding and cohesion strength. Inspired by the synergistic adhesion mechanisms of mussel foot proteins and barnacle cement proteins, we designed and synthesized a novel adhesive via UV-initiated copolymerization of four acrylate monomers: a long-chain alkyl catechol derivative (Cd), its phenolic analogue (Cs), hydroxyethyl acrylate (HEA), and dimethylaminoethyl methacrylate (DMA). Its adhesion is water-triggered, fast (<1 min), tough (underwater tissue adhesion strength: ∼388 kPa; interfacial toughness: ∼530 J/m2), due to the strong interfacial interactions at the adhesive/adherend interface, and the good energy dissipation capacity from the high cohesive mechanical properties (stress: 724 kPa, strain: 395%, and toughness: 864 kJ/m3). Moreover, its adhesion strength to underwater tissue is durable for up to 14 d, attributable to its non-swelling properties (water adsorption ratio is just ∼4%). It can effectively close tissue incisions and facilitate wound healing. This study elucidates the influence of catechol groups, cationic moiety, and hydrophobic segments on underwater adhesion, and therefore develops a non-swellable wet tissue adhesive for better serving the clinical needs.
Equitable healthcare access for mobile, informally employed populations remains elusive in many developing contexts. We examine the impact of the first phase of China's cross-regional instant reimbursement (CRIR) reform-a province-level reform-on enrollment in health insurance and healthcare utilization. Informed by a theoretical model, we implement a triple-differences design leveraging CRIR's staggered rollout to identify causal effects. Results show that CRIR substantially increased local UEBMI enrollment (by 8%) and healthcare visits (by 14%), while reducing out-of-pocket spending (by 22%). These gains stem from lower administrative frictions and strengthened financial protection. Low-income, less-educated, and more informally employed migrants benefit the most, underscoring the reform's role in promoting inclusive development. Our findings highlight the importance of portable social insurance in improving healthcare access for mobile populations and offer insights for similar reforms in other developing settings.
Advanced underwater adhesives with injectability and robustness show great promise in enhancing surgical success and improving patient outcomes. However, the development of hemostatic adhesives that are quick-acting, highly adhesive, long- lasting, and biocompatible remains a challenge when addressing hemorrhage. To tackle the problem, here, a novel idea is presented to develop a robust injectable hydrogel adhesive through continuous structural inheritance strategy made from a combination of biopolymers and crosslinked poly(acrylic acid). The sequential crosslinking strategy can make strong and tough interfaces with wet tissues to achieve fast and repeatable adhesion and outperform commercial hemostatic agents. The chemically-physically crosslinked hybrid nanocomposite underwater adhesive, characterized by its robustness and injectability, has shown promising results as an effective and safe sealant for improving the treatment of bleeding tissues in animal models such as rats, rabbits, and pigs. It is anticipated that our research introduces a novel strategy for developing desirable and promising adhesive hemostat candidates for diverse biological tissues in clinics.
Microwave imaging is a promising non-ionizing technique for bedside follow-up of intracranial hemorrhage, but dynamic monitoring remains challenging under limited multistatic sampling because weak inter-frame changes can be obscured by measurement variability, model mismatch, and the high cost of frame-by-frame nonlinear inversion. To address this problem, this paper proposes a state-referenced truncated singular-value decomposition (SR-TSVD) framework for dynamic microwave monitoring of hemorrhagic evolution. The method maintains an internal gate state and reconstructs only the state-referenced increment at each monitoring instant. A row-whitened TSVD inversion is introduced to reduce channel dominance effects and improve robustness to route-dependent imbalance, while a residual-driven gate-refresh mechanism updates the internal state only when the current linearization background becomes insufficiently accurate. The proposed method was validated through two-dimensional numerical experiments and hardware phantom measurements. The numerical study examined different lesion evolution scenarios and analyzed the effects of antenna count, frequency diversity, and measurement noise. The hardware study showed that the method preserves the main dynamic evolution in a real measurement system and remains more stable than baseline linear methods under sparse array conditions. These results indicate that SR-TSVD provides an effective and computationally practical framework for repeated bedside microwave monitoring of intracranial hemorrhage.
The breast peritumor microenvironment (pTME) is increasingly recognized as a mediator of breast cancer progression and treatment resistance. However, how tumor compressive forces (i.e., solid stresses) influence it remains unclear. Using instant fluorescence lifetime imaging microscopy (FLIM), we show that in vitro compression metabolically reprograms stromal cells found in the breast pTME. Namely, compression shifts fibroblasts and differentiated adipocytes toward a more glycolytic state, but promotes increased oxidative phosphorylation in undifferentiated adipocytes. Through RNA-sequencing, we confirmed that compression downregulates oxidative phosphorylation and upregulates glycolysis in fibroblasts. Furthermore, we demonstrate that compression induces mitochondrial dysregulation in undifferentiated adipocytes, driven partly by upregulated mitophagy and disrupted fission/fusion dynamics. The analysis of human breast cancer samples confirms these stromal cell types recapitulate these distinct metabolic states, consistent with in vitro findings. By elucidating tumor-host mechano-metabolic interactions, these results will inform the development of innovative treatment strategies to improve survival.
The cytosolic protease dipeptidyl peptidase 3 (DPP3) is released into the circulation upon profound cellular stress. In the bloodstream, circulating DPP3 (cDPP3) rapidly degrades several important mediators of vascular tone. The cDPP3-antagonizing antibody Procizumab (PCZ) improved outcome in animal models of shock. This study aimed to establish the safety and tolerability of PCZ across relevant animal species. In the first study, mice received vehicle (n = 72), 37.5 (n = 114), 75 (n = 114), or 150 (n = 126) mg/kg of PCZ intravenously on days 1, 2, 13, and 14. In the second study, cynomolgus monkeys received vehicle (n = 10), 40 (n = 6), 120 (n = 6), or 350 (n = 10) mg/kg of PCZ intravenously on days 1, 2, 13 and 14. Toxicokinetic analyses demonstrated instant and dose-dependent peak concentrations. PCZ was eliminated relatively fast compared to other monoclonal antibodies and administration resulted in an instant reduction of cDPP3 enzyme activity, confirming the intended pharmacodynamic mechanism-of-action. Apart from fully reversible, non-dose-dependent increases of enzymes aspartate aminotransferase, alanine aminotransferase, and creatinine kinase in monkeys, and decreased rarefaction of the cytoplasm of hepatocytes in treated mice compared to the control group, toxicologic analyses showed no test item-related effects. In both studies, no mortality, moribund condition or any other adverse histopathological findings were attributed to PCZ therapy. These findings demonstrate that intravenous, repeated administration of high doses of PCZ was well tolerated in mice and cynomolgus monkeys. Results of this study were followed by a Phase 1 safety assessment of PCZ in humans, with single-administration clinical doses of 3, 6, and 12 mg/kg (NCT06331884).
Description This painting depicts young Asclepius under the guidance of Chiron, the wise centaur renowned for his knowledge of healing and medicine. In Greek mythology, Asclepius was entrusted to Chiron after Apollo recognized his potential. Within the nurturing environment of Chiron's home, Asclepius absorbed lessons on the use of medicinal herbs, wound treatment, and the foundational principles of care, skills that would eventually elevate him to become the Greek God of Medicine. The herbs symbolize hands-on learning and the practical foundation of healing, while the book signifies the accumulation and sharing of knowledge, showing how medical innovation progresses through study, collaboration, and the passing of wisdom. It's not just the transfer of knowledge, but the intentionality and patience in Chiron's teaching, mirrored in Asclepius's focused and reverent attention. This scene illustrates the timeless impact of mentorship and deliberate instruction. It shows that mastery is not instant but cultivated through observation, practice, and careful guidance. The relationship between teacher and student is depicted as a partnership in growth, emphasizing that the development of skill and wisdom requires patience, trust, and attentive presence. Medicine is not merely a collection of facts, but a craft honed through experience and human connection. The painting captures the essence of how knowledge is passed from teacher to student, highlighting the enduring importance of mentorship in shaping not only skill, but character and empathy.
The aim of this study was to evaluate the association between retail food environments and consumption of ultra-processed foods in children. A cross-sectional study was conducted with 206 children aged 6-36 months who were followed up in primary health care. Consumption of ultra-processed foods was investigated using the intake marker form. Food deserts and swamps were identified using the Brazilian methodology proposed by the Food and Nutrition Security Intersectoral Chamber, and the density of healthy and unhealthy food outlets per 10,000 inhabitants was calculated. The associations between food environments and consumption of ultra-processed foods were estimated using binary logistic regression, yielding odds ratios (OR) and respective 95% confidence intervals (95%CI) from a generalized estimating equations model. Ultra-processed foods were part of the diet in 60.18% of the children, with sweetened beverages being the most prevalent (42.22%). Living in sectors classified as food swamps was positively and independently associated with consumption of instant noodles, packaged snacks, or crackers (OR 2.71; 95%CI 1.19-6.16) and stuffed cookies/sweets/candies (OR 2.50; 95%CI 1.03-6.12). Children living in food swamps were more likely to consume ultra-processed foods. The results indicate the need to promote environments that favor healthy food choices among families and children through adequate nutrition, nutrition education, and policies that regulate access to and the advertising of unhealthy foods. Avaliar a associação entre ambientes de varejo alimentar e consumo de alimentos ultraprocessados em crianças. Estudo transversal com 206 crianças de 6 a 36 meses de idade acompanhadas na Atenção Primária à Saúde. O consumo de alimentos ultraprocessados foi investigado por meio do formulário de marcadores de ingestão. Desertos e pântanos alimentares foram identificados com base na metodologia brasileira proposta pela Câmara Intersetorial de Segurança Alimentar e Nutricional; ainda, calculou-se a densidade de estabelecimentos de alimentos saudáveis e não saudáveis por 10 mil habitantes. As associações entre ambientes alimentares e consumo de alimentos ultraprocessados foram estimadas por meio de regressão logística binária, apresentando Odds Ratio (OR) e respectivos Intervalos de Confiança de 95% (IC95%), com base no modelo de equações de estimativa generalizadas. Alimentos ultraprocessados faziam parte da dieta de 60,18% das crianças, sendo as bebidas adoçadas as mais prevalentes (42,22%). Residir em setores classificados como pântanos alimentares associou-se positiva e independentemente ao consumo de macarrão instantâneo, salgadinhos de pacote ou biscoitos salgados (OR 2,71; IC95% 1,19–6,16) e biscoito recheado, doces ou guloseimas (OR 2,50; IC95% 1,03–6,12). As crianças que viviam em pântanos alimentares eram mais propensas a consumir alimentos ultraprocessados. Os resultados indicam a necessidade de promover ambientes que favoreçam escolhas alimentares saudáveis entre famílias e crianças, por meio de alimentação adequada, educação nutricional e políticas que regulem acesso e publicidade de alimentos não saudáveis.
Non-fried buckwheat instant noodles are known to be low-fat and low-glycemic-index products but suffer from poor dough processing and poor rehydration. The study aims to improve the rehydration and flavor of non-fried buckwheat noodles by co-fermenting yeast and lactic acid bacteria (Lactobacillus bulgaricus and Streptococcus thermophilus). Non-fried buckwheat instant noodles were evaluated for rehydration, cooking tolerance, texture, digestibility, microstructure, and volatile aroma compounds. Co-fermentation significantly reduced rehydrating time by 15.20% from 342 to 290 s. With mixed culture, the sample with 1% yeast and 0.075% lactic acid bacteria provided excellent cooking tolerance and a good rehydration rate. It also had a low expected glycemic index (45.96-50.74) in digestion assays. The scanning electron microscope showed uniformly distributed pores and a dense gluten network with 1% yeast addition. Electronic nose data indicated that the groups of samples had similar odor characteristics. The gas chromatography-mass spectrometry, combined with principal component analysis and optimal aroma response values, suggested that key aroma compounds (trans-2-nonenal, decanal, 2-pentylfuran, and geranyl acetone) contributed to the unique flavor of non-fried buckwheat noodles. The co-fermentation with yeast and lactic acid bacteria improved the gluten network and quality of non-buckwheat noodles, particularly enriching their volatile compounds. The optimal formulation was 1% yeast with 0.75% lactic acid bacteria. PRACTICAL APPLICATIONS: Compound bacteria fermentation improved the quality of buckwheat instant noodles. Rehydration time was shortened due to the formation of a porous structure. More volatile flavor substances were produced during fermentation. The eGI value was held in 45.96-50.74.
The causal relationship between instant coffee consumption and carpal tunnel syndrome (CTS) remains unclear. This study aimed to investigate the potential causal association between instant coffee consumption and CTS using data from large-scale genome-wide association studies, thereby providing genetic epidemiological evidence on this association. This study selected single nucleotide polymorphisms strongly associated with instant coffee consumption as instrumental variables. A 2-sample Mendelian randomization (MR) design was used. Three MR analysis methods were used: inverse variance weighted, MR-Egger regression, and weighted median to assess potential causal relationships. Cochran's Q test was used to evaluate heterogeneity in the data. Summary statistics were derived from 1,80,764 individuals for instant coffee consumption and 4,80,201 individuals for CTS, all of European ancestry, to minimize bias from population stratification. Sensitivity analyses were performed using the leave-one-out method to validate the robustness of the results. The inverse variance weighted results showed that the odds ratio of CTS with respect to instant coffee consumption was 3.41 (95% confidence interval: 1.65-7.04, P = .0009), suggesting a significant positive causal relationship between instant coffee consumption and CTS. Sensitivity analyses did not reveal significant heterogeneity and horizontal pleiotropy (P > .05). This study suggested a potential positive causal association between instant coffee consumption and CTS using the 2-sample MR approach, although the findings should be considered preliminary and hypothesis-generating.