Metabolic dysfunction-associated steatotic liver disease and risk of cardiovascular disease.

OBJECTIVE: We explored clinical implications of the new definition of metabolic dysfunction-associated steatotic liver disease (MASLD) by assessing its prevalence and associated cardiovascular disease (CVD) risk. DESIGN: From nationwide health screening data, we identified 9 775 066 adults aged 20-79 who underwent health examination in 2009. Participants were categorised into four mutually exclusive groups: (1) MASLD; (2) MASLD with increased alcohol intake (MetALD); (3) MASLD with other combined aetiology (the three collectively referred to as MASLD/related steatotic liver disease (SLD)); and (4) no MASLD/related SLD. SLD was determined by fatty liver index ≥30. The primary outcome was CVD event, defined as a composite of myocardial infarction, ischaemic stroke, heart failure or cardiovascular death. RESULTS: The prevalence of MASLD, MetALD and MASLD with other combined aetiology was 27.5%, 4.4% and 1.5%, respectively. A total of 8 808 494 participants without prior CVD were followed up for a median of 12.3 years, during which 272 863 CVD events occurred. The cumulative incidence and multivariable-adjusted risk of CVD were higher in participants with MASLD/related SLD than in those without (HR 1.38 (95% CI 1.37 to 1.39)). Multivariable-adjusted HR (95% CI) of CVD events was 1.39 (1.38 to 1.40) for MASLD, 1.28 (1.26 to 1.30) for MetALD and 1.30 (1.26 to 1.34) for MASLD with other combined aetiology compared to the absence of any of these conditions. CVD risk was also higher in participants with metabolic dysfunction-associated fatty liver disease or non-alcoholic fatty liver disease than in those without the respective condition. CONCLUSION: Over one-third of Korean adults have MASLD/related SLD and bear a high CVD risk.

Protective Topical Dual-Sided Nanofibrous Hemostatic Dressing Using Mussel and Silk Proteins with Multifunctionality of Hemostasis and Anti-Bacterial Infiltration.

Topical hemostatic agents are preferred for application to sensitive bleeding sites because of their immediate locoregional effects with less tissue damage. However, the majority of commercial hemostatic agents fail to provide stable tissue adhesion to bleeding wounds or act as physical barriers against contaminants. Hence, it has become necessary to investigate biologically favorable materials that can be applied and left within the body post-surgery. In this study, a dual-sided nanofibrous dressing for topical hemostasis is electrospun using a combination of two protein materials: bioengineered mussel adhesive protein (MAP) and silk fibroin (SF). The wound-adhesive inner layer is fabricated using dihydroxyphenylalanine (DOPA)-containing MAP, which promotes blood clotting by aggregation of hemocytes and activation of platelets. The anti-adhesive outer layer is composed of alcohol-treated hydrophobic SF, which has excellent spinnability and mechanical strength for fabrication. Because both proteins are fully biodegradable in vivo and biocompatible, the dressing would be suitable to be left in the body. Through in vivo evaluation using a rat liver damage model, significantly reduced clotting time and blood loss are confirmed, successfully demonstrating that the proposed dual-sided nanofibrous dressing has the right properties and characteristics as a topical hemostatic agent having dual functionality of hemostasis and physical protection.

Changes in the intrinsic severity of severe acute respiratory syndrome coronavirus 2 according to the emerging variant: a nationwide study from February 2020 to June 2022, including comparison with vaccinated populations.

BACKGROUND: As the population acquires immunity through vaccination and natural infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), understanding the intrinsic severity of coronavirus disease (COVID-19) is becoming challenging. We aimed to evaluate the intrinsic severity regarding circulating variants of SARS-CoV-2 and to compare this between vaccinated and unvaccinated individuals. METHODS: With unvaccinated and initially infected confirmed cases of COVID-19, we estimated the case severity rate (CSR); case fatality rate (CFR); and mortality rate (MR), including severe/critical cases and deaths, stratified by age and compared by vaccination status according to the period regarding the variants of COVID-19 and vaccination. The overall rate was directly standardized with age. RESULTS: The age-standardized CSRs (aCSRs) of the unvaccinated group were 2.12%, 5.51%, and 0.94% in the pre-delta, delta, and omicron period, respectively, and the age-standardized CFRs (aCFRs) were 0.60%, 2.49%, and 0.63% in each period, respectively. The complete vaccination group had lower severity than the unvaccinated group over the entire period showing under 1% for the aCSR and 0.5% for the aCFR. The age-standardized MR of the unvaccinated group was 448 per million people per month people in the omicron period, which was 11 times higher than that of the vaccinated group. In terms of age groups, the CSR and CFR sharply increased with age from the 60 s and showed lower risk reduction in the 80 s when the period changed to the omicron period. CONCLUSIONS: The intrinsic severity of COVID-19 was the highest in the delta period, with over 5% for the aCSR, whereas the completely vaccinated group maintained below 1%. This implies that when the population is vaccinated, the impact of COVID-19 will be limited, even if a new mutation appears. Moreover, considering the decreasing intrinsic severity, the response to COVID-19 should prioritize older individuals at a higher risk of severe disease.

Risk of Obstructive Sleep Apnea, Chronic Dizziness, and Sleep Duration.

BACKGROUND: Although it is recommended that obstructive sleep apnea (OSA) be screened for using a validated self-report questionnaire in patients experiencing dizziness, there is still a lack of research on the relationship between high risk of OSA and chronic dizziness. OBJECTIVES: The study aimed to examine the relationship between the high risk of OSA and chronic dizziness and investigate how this relationship is affected by sleep duration. METHODS: This cross-sectional study used data from the 8th Korea National Health and Nutrition Examination Survey (2019-2021). Adults aged 40 years or older were included and divided into two groups using the STOP-Bang Questionnaire (SBQ): a high-risk group for OSA or not. Complex samples logistic regression analyses were performed to examine the odds ratios of chronic dizziness based on the national population estimates. RESULTS: Our findings showed that individuals in the high-risk group for OSA were significantly more likely to experience chronic dizziness. Specifically, among subgroups based on sleep duration, the high-risk group for OSA with a short sleep duration of ≤5 hours demonstrated the highest odds of chronic dizziness, showing a significantly 2.48-fold increased likelihood compared to the non-high risk for OSA with a sleep duration of 5-9 hours. DISCUSSION: The SBQ can be beneficial when other causes do not explain chronic dizziness, helping to rule in the possibility of OSA. Educating individuals suspected of having OSA or who have been diagnosed with OSA about the importance of adequate sleep duration may help reduce the risk of chronic dizziness.

Epidemiology of Respiratory Viruses in Korean Children Before and After the COVID-19 Pandemic: A Prospective Study From National Surveillance System.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic led to a decrease in the seasonal incidence of many respiratory viruses worldwide due to the impact of nonpharmaceutical interventions (NPIs). However, as NPI measures were relaxed, respiratory viral infections re-emerged. We aimed to characterize the epidemiology of respiratory viruses in Korean children during post-COVID-19 pandemic years compared to that before the pandemic. METHODS: A nationwide prospective ongoing surveillance study has been conducted for detection of respiratory viruses between January 2017 and June 2023. We included data on adenovirus (AdV), human bocavirus (HBoV), human coronavirus (HCoV), human metapneumovirus (HMPV), human rhinovirus (HRV), influenza virus (IFV), parainfluenza virus (PIV), and respiratory syncytial virus (RSV), which were detected in children and adolescents younger than 20 years. We analyzed the weekly detection frequency of individual viruses and the age distribution of the affected children. The study period was divided into prepandemic (2017-2019) and postpandemic (2021-2023) periods. RESULTS: A total of 19,589 and 14,068 samples were collected in the pre- and postpandemic periods, respectively. The overall detection rate of any virus throughout the study period was 63.1%, with the lowest occurring in the 2nd half of 2020 (50.6%) and the highest occurring in the 2nd half of 2021 (72.3%). Enveloped viruses (HCoV, HMPV, IFV, PIV, and RSV) almost disappeared, but nonenveloped viruses (AdV, HBoV, and HRV) were detected even during the peak of the COVID-19 pandemic. The codetection rate increased from 15.0% prepandemic to 19.1% postpandemic (P < 0.001). During the postpandemic period, a large out-of-season PIV and HMPV epidemic occurred, but the usual seasonality began to be restored in 2023. The mean age of children with each virus detected in 2023 was significantly greater than that in prepandemic years (P = 0.003 and 0.007 for AdV and HCoV, respectively; P < 0.001 for others). The mean age of children with IFV increased in 2022 (11.1 ± 5.2 years) from prepandemic years (7.9 ± 4.6 years) but decreased to 8.7 ± 4.1 years in 2023. CONCLUSION: With the relaxation of NPI measures, several seasonal respiratory viruses cocirculated with unusual seasonal epidemic patterns and were associated with increasing age of infected children.

Analysis of the association between vestibular schwannoma and hearing status using a newly developed radiomics technique.

PURPOSE: Vestibular schwannoma is a benign tumor originating from Schwann cells surrounding the eighth cranial nerve and can cause hearing loss, tinnitus, balance problems, and facial nerve disorders. Because of the slow growth of the tumor, predicting the hearing function of patients with vestibular schwannoma's is important to obtain information that would be useful for deciding the treatment modality. This study aimed to analyze the association between magnetic resonance imaging features and hearing status using a new radiomics technique. METHODS: We retrospectively analyzed 115 magnetic resonance images and hearing results from 73 patients with vestibular schwannoma. A total of 70 radiomics features from each tumor volume were calculated using T1-weighted magnetic resonance imaging. Radiomics features were classified as histogram-based, shape-based, texture-based, and filter-based. The least absolute shrinkage and selection operator method was used to select the radiomics features among the 70 features that best predicted the hearing test. To ensure the stability of the selected features, the least absolute shrinkage and selection operator method was repeated 10 times. Finally, features set five or more times were selected as radiomics signatures. RESULTS: The radiomics signatures selected using the least absolute shrinkage and selection operator method were: minimum, variance, maximum 3D diameter, size zone variance, log skewness, skewness slope, and kurtosis slope. In random forest, the mean performance was 0.66 (0.63-0.77), and the most important feature was Log skewness. CONCLUSIONS: Newly developed radiomics features are associated with hearing status in patients with vestibular schwannoma and could provide information when deciding the treatment modality.

Enhancing Human Cutaneous Wound Healing through Targeted Suppression of Large Conductance Ca2+-Activated K+ Channels.

The modulation of K+ channels plays a crucial role in cell migration and proliferation, but the effect of K+ channels on human cutaneous wound healing (CWH) remains underexplored. This study aimed to determine the necessity of modulating K+ channel activity and expression for human CWH. The use of 25 mM KCl as a K+ channel blocker markedly improved wound healing in vitro (in keratinocytes and fibroblasts) and in vivo (in rat and porcine models). K+ channel blockers, such as quinine and tetraethylammonium, aided in vitro wound healing, while Ba2+ was the exception and did not show similar effects. Single-channel recordings revealed that the Ba2+-insensitive large conductance Ca2+-activated K+ (BKCa) channel was predominantly present in human keratinocytes. NS1619, an opener of the BKCa channel, hindered wound healing processes like proliferation, migration, and filopodia formation. Conversely, charybdotoxin and iberiotoxin, which are BKCa channel blockers, dramatically enhanced these processes. The downregulation of BKCa also improved CWH, whereas its overexpression impeded these healing processes. These findings underscore the facilitative effect of BKCa channel suppression on CWH, proposing BKCa channels as potential molecular targets for enhancing human cutaneous wound healing.

Information Geometry Theoretic Measures for Characterizing Neural Information Processing from Simulated EEG Signals.

In this work, we explore information geometry theoretic measures for characterizing neural information processing from EEG signals simulated by stochastic nonlinear coupled oscillator models for both healthy subjects and Alzheimer's disease (AD) patients with both eyes-closed and eyes-open conditions. In particular, we employ information rates to quantify the time evolution of probability density functions of simulated EEG signals, and employ causal information rates to quantify one signal's instantaneous influence on another signal's information rate. These two measures help us find significant and interesting distinctions between healthy subjects and AD patients when they open or close their eyes. These distinctions may be further related to differences in neural information processing activities of the corresponding brain regions, and to differences in connectivities among these brain regions. Our results show that information rate and causal information rate are superior to their more traditional or established information-theoretic counterparts, i.e., differential entropy and transfer entropy, respectively. Since these novel, information geometry theoretic measures can be applied to experimental EEG signals in a model-free manner, and they are capable of quantifying non-stationary time-varying effects, nonlinearity, and non-Gaussian stochasticity presented in real-world EEG signals, we believe that they can form an important and powerful tool-set for both understanding neural information processing in the brain and the diagnosis of neurological disorders, such as Alzheimer's disease as presented in this work.

Minimum Information Variability in Linear Langevin Systems via Model Predictive Control.

Controlling the time evolution of a probability distribution that describes the dynamics of a given complex system is a challenging problem. Achieving success in this endeavour will benefit multiple practical scenarios, e.g., controlling mesoscopic systems. Here, we propose a control approach blending the model predictive control technique with insights from information geometry theory. Focusing on linear Langevin systems, we use model predictive control online optimisation capabilities to determine the system inputs that minimise deviations from the geodesic of the information length over time, ensuring dynamics with minimum "geometric information variability". We validate our methodology through numerical experimentation on the Ornstein-Uhlenbeck process and Kramers equation, demonstrating its feasibility. Furthermore, in the context of the Ornstein-Uhlenbeck process, we analyse the impact on the entropy production and entropy rate, providing a physical understanding of the effects of minimum information variability control.

Alkaline-sensitive two-pore domain potassium channels form functional heteromers in pancreatic ß-cells.

Two-pore domain K+ channels (K2P channels), active as dimers, produce inhibitory currents regulated by a variety of stimuli. Among them, TWIK1-related alkalinization-activated K+ channel 1 (TALK1), TWIK1-related alkalinization-activated K+ channel 2 (TALK2), and TWIK1-related acid-sensitive K+ channel 2 (TASK2) form a subfamily of structurally related K2P channels stimulated by extracellular alkalosis. The human genes encoding these proteins are clustered at chromosomal region 6p21 and coexpressed in multiple tissues, including the pancreas. The question whether these channels form functional heteromers remained open. By analyzing single-cell transcriptomic data, we show that these channels are coexpressed in insulin-secreting pancreatic ß-cells. Using in situ proximity ligation assay and electrophysiology, we show that they form functional heterodimers both upon heterologous expression and under native conditions in human pancreatic ß-cells. We demonstrate that heteromerization of TALK2 with TALK1 or with TASK2 endows TALK2 with sensitivity to extracellular alkalosis in the physiological range. We further show that the association of TASK2 with TALK1 and TALK2 increases their unitary conductance. These results provide a new example of heteromerization in the K2P channel family expanding the range of the potential physiological and pathophysiological roles of TALK1/TALK2/TASK2 channels, not only in insulin-secreting cells but also in the many other tissues in which they are coexpressed.

Virulence-associated type III secretion systems in Gram-negative bacteria.

Virulence-associated bacterial type III secretion systems are multiprotein molecular machines that promote the pathogenicity of bacteria towards eukaryotic host cells. These machines form needle-like structures, named injectisomes, that span both bacterial and host membranes, forming a direct conduit for the delivery of bacterial proteins into host cells. Once within the host, these bacterial effector proteins are capable of manipulating a multitude of host cell functions. In recent years, the knowledge of assembly, structure and function of these machines has grown substantially and is presented and discussed in this review.

A stochastic model of edge-localized modes in magnetically confined plasmas.

Magnetically confined plasmas are far from equilibrium and pose considerable challenges in statistical analysis. We discuss a non-perturbative statistical method, namely a time-dependent probability density function (PDF) approach that is potentially useful for analysing time-varying, large, or non-Gaussian fluctuations and bursty events associated with instabilities in the low-to-high confinement transition and the H-mode. Specifically, we present a stochastic Langevin model of edge-localized modes (ELMs) by including stochastic noise terms in a previous ODE ELM model. We calculate exact time-dependent PDFs by numerically solving the Fokker-Planck equation and characterize time-varying statistical properties of ELMs for different energy fluxes and noise amplitudes. The stochastic noise is shown to introduce phase-mixing and plays a significant role in mitigating extreme bursts of large ELMs. Furthermore, based on time-dependent PDFs, we provide a path-dependent information geometric theory of the ELM dynamics and demonstrate its utility in capturing self-regulatory relaxation oscillations, bursts and a sudden change in the system. This article is part of a discussion meeting issue 'H-mode transition and pedestal studies in fusion plasmas'.

H-mode transition and pedestal studies.

The high confinement mode (H-mode) is the widely adopted standard operation scenario for the path to fusion in toroidal confinement devices. Since its discovery in 1982, the H-mode and access to the H-mode (the low to high and high to low transitions) remain two of the most actively researched areas in magnetically confined fusion programmes across the world. Significant progress has been made in the understanding of the intricate H-mode phase dynamics in recent years, from improvement in experimental diagnostic capability, theoretical development and modelling. The 'H-mode transition and pedestal studies' Special Issue provides a timely overview of recent progress in the study of H-modes covering experimental studies, further theoretical inquiry and computational modelling. This article is part of a discussion meeting issue 'H-mode transition and pedestal studies in fusion plasmas'.

H-mode dithering phase studies on ST40.

The dithering H-mode phase, characterized by oscillations, is generally observed at input power values close to the L-H transition power threshold and low plasma collisionalities (low electron density and/or high plasma temperature). Measurements to characterize the dithering phase are presented for the low aspect ratio, high magnetic field tokamak, ST40. The dithering phase oscillation frequency is observed between 400 and 800 Hz and demonstrates an inverse relationship with core plasma density. Dithering phase H-modes are documented across a nonlinear, low-density power threshold operational space, with signature low- and high-density branches. The minimum power threshold for dithering H-mode access is measured at a core, line average electron density of 4.7(±0.5) × 1019 m-3, close to a predicted value of 4.1(±0.4) × 1019 m-3 from multi-machine studies. ASTRA calculated values of power coupled to the ion species, at the dithering H-mode transition, exhibit a similar nonlinear dependence on density. This analysis points to the important contribution of the ion thermal channel to the L-H phase transition. The low-frequency plasma density and D-alpha dithers appear to be accompanied by sudden bursts of magnetohydrodynamic (MHD) activity. A simple model is tested to demonstrate a possible scenario of self-regulation among turbulence, zonal flows, pressure (density) gradient and MHD activities. This article is part of a discussion meeting issue 'H-mode transition and pedestal studies in fusion plasmas'.

How Ethical Ideology Influences Mask-Wearing Intention in a Pandemic: The Mediating Role of Moral Norms and Threat to Freedom.

The present study examined how two types of ethical ideologies (idealism, and relativism) influenced behavioral intention to wear a mask during the COVID-19 pandemic through two appraisals (moral norms, and threat to freedom) of a mask-wearing issue. A total of 823 responses were collected through a cross-sectional survey, and 776 responses were used for testing hypotheses. The study found that idealism has a significant indirect effect on behavioral intention through increased moral norms and decreased threat to freedom. Also, the study revealed that relativism has a significant indirect effect on behavioral intention through increased threat to freedom.

The Impact of Entry Restrictions on the Spread of Severe Acute Respiratory Syndrome Coronavirus Variants Between 2021 and 2022.

To contain the surge of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the South Korean government has implemented non-pharmacological interventions as well as border restrictions. The efficacy of entry restrictions should be evaluated to facilitate their preparation for new variants of SARS-CoV-2. This study explored the impact of border policy changes on overseas entrants and local cases of SARS-CoV-2 variants. Data from the Korea Disease Control and Prevention Agency randomly collected between April 11, 2021 and August 20, 2022 were evaluated using the Granger causality model. The results showed that the outbreak gap of delta variants between international and domestic cases was 10 weeks, while that of omicron variants was approximately 2 weeks, meaning that the quarantine policy helped contain delta variants rather than more transmissible variants. It is recommended that countries implement quarantine policies based on particular purposes accounting for the specific features of different variants to avoid potential negative impacts on the economy.

Comparative Computational Analysis of Spike Protein Structural Stability in SARS-CoV-2 Omicron Subvariants.

The continuous emergence of new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with multiple spike (S) protein mutations pose serious threats to current coronavirus disease 2019 (COVID-19) therapies. A comprehensive understanding of the structural stability of SARS-CoV-2 variants is vital for the development of effective therapeutic strategies as it can offer valuable insights into their potential impact on viral infectivity. S protein mediates a virus' attachment to host cells by binding to angiotensin-converting enzyme 2 (ACE2) through its receptor-binding domain (RBD), and mutations in this protein can affect its stability and binding affinity. We analyzed S protein structural stability in various Omicron subvariants computationally. Notably, the S protein sequences analyzed in this work were obtained directly from our own sample collection. We evaluated the binding free energy between S protein and ACE2 in several complex forms. Additionally, we measured distances between the RBD of each chain in S protein to analyze conformational changes. Unlike most of the prior studies, we analyzed full-length S protein-ACE2 complexes instead of only RBD-ACE2 complexes. Omicron subvariants including BA.1, BA.2, BA.2.12.1, BA.4/BA.5, BA.2.75, BA.2.75_K147E, BA.4.6 and BA.4.6_N658S showed enhanced stability compared to wild type, potentially due to distinct S protein mutations. Among them, BA.2.75 and BA.4.6_N658S exhibited the highest and lowest level of stability, respectively.

State-level nursing home in-service dementia training requirements and inappropriate psychotropic medication use.

BACKGROUND: Although non-pharmacological interventions, which are staff intensive, are recommended for behavioral symptoms of dementia, psychotropics are often prescribed in nursing homes (NHs), with insufficient nurse staffing levels and dementia care training. Since 2017, deficiency citations can be assigned for inappropriate psychotropics use (F-758 tag). Some states require in-service dementia training above federal minimums, but it is unknown whether extra dementia training requirements were related to fewer F-758 citations for residents with dementia and whether nurse staffing influenced the relationship between receiving F-758 citations and having additional state-level dementia training requirements. PURPOSE: To relate F-758 citation occurrence to extra in-service dementia training regulations and to explore how the relationships are affected by nurse staffing levels. METHOD: Generalized linear mixed models were used to examine F-758 citation occurrence in relation to state-level in-service dementia training regulations. Stratification was also conducted to compare the effects in NHs with low versus high nurse staffing. FINDINGS: Requiring in-service dementia training with extra hours was inversely related to receiving F-758 tags. That relationship was also noted in NHs with lower registered nurse and certified nurse assistant staffing. DISCUSSION: In-service dementia training may be helpful in reducing inappropriate psychotropics use, particularly in facilities with lower nurse staffing.

Effects of Stochastic Noises on Limit-Cycle Oscillations and Power Losses in Fusion Plasmas and Information Geometry.

We investigate the effects of different stochastic noises on the dynamics of the edge-localised modes (ELMs) in magnetically confined fusion plasmas by using a time-dependent PDF method, path-dependent information geometry (information rate, information length), and entropy-related measures (entropy production, mutual information). The oscillation quenching occurs due to either stochastic particle or magnetic perturbations, although particle perturbation is more effective in this amplitude diminishment compared with magnetic perturbations. On the other hand, magnetic perturbations are more effective at altering the oscillation period; the stochastic noise acts to increase the frequency of explosive oscillations (large ELMs) while decreasing the frequency of more regular oscillations (small ELMs). These stochastic noises significantly reduce power and energy losses caused by ELMs and play a key role in reproducing the observed experimental scaling relation of the ELM power loss with the input power. Furthermore, the maximum power loss is closely linked to the maximum entropy production rate, involving irreversible energy dissipation in non-equilibrium. Notably, over one ELM cycle, the information rate appears to keep almost a constant value, indicative of a geodesic. The information rate is also shown to be useful for characterising the statistical properties of ELMs, such as distinguishing between explosive and regular oscillations and the regulation between the pressure gradient and magnetic fluctuations.

Stochastic Dynamics of Fusion Low-to-High Confinement Mode (L-H) Transition: Correlation and Causal Analyses Using Information Geometry.

We investigate the stochastic dynamics of the prey-predator model of the Low-to-High confinement mode (L-H) transition in magnetically confined fusion plasmas. By considering stochastic noise in the turbulence and zonal flows as well as constant and time-varying input power Q, we perform multiple stochastic simulations of over a million trajectories using GPU computing. Due to stochastic noise, some trajectories undergo the L-H transition while others do not, leading to a mixture of H-mode and dithering at a given time and/or input power. One of the consequences of this is that H-mode characteristics appear at a smaller input power QQc as a second peak. The coexisting H-mode and dithering near Q=Qc leads to a prominent bimodal PDF with a gradual L-H transition rather than a sudden transition at Q=Qc and uncertainty in the input power. Also, a time-dependent input power leads to increased variability (dispersion) in stochastic trajectories and a more prominent bimodal PDF. We provide an interpretation of the results using information geometry to elucidate self-regulation between zonal flows, turbulence, and information causality rate to unravel causal relations involved in the L-H transition.