Probability Of Events Research Articles

Carotid-Femoral pulse wave velocity progression in hypertensive patients is associated with subsequent cardiovascular outcomes

Abstract Background Arterial stiffness (Pulse Wave Velocity - PWV) is associated with CV events and mortality. However, little is known on the relationship of its progression (ΔPWV) over time with CV outcomes. Purpose The aim of our study was to evaluate the relationship between PWV progression and all-cause mortality and CV events in hypertensive subjects. Methods We enrolled 402 consecutive hypertensive outpatients. At baseline anamnestic, clinical, BP, laboratory data and PWV were assessed. We performed a PWV follow-up examination at a median time of 3.7±0.5 years. Patients were subsequently followed for a median time of 10.1 (IQR 9.5 -10.5) years recording all-cause mortality and CV events. Results At baseline the mean age was 53.2±13.0 years, SBP and DBP were 141.8±17.5 and 86.8±10.5 mmHg and PWV was 8.5±1.9 m/s. Despite an improvement in BP control (- 9.2±19.5 and -8.0±12.3 for SBP and DBP respectively), at follow-up the population showed a PWV increase (ΔPWV +0.6±1.9 m/s). Progressors (ΔPWV ≥ 0.5 m/s, 204 patients, 50.7%) had a significantly lower survival probability and higher cumulative incidence of composite events, while no differences were seen for CV events (unadjusted analysis). At cox multivariable analysis neither ΔPWV ≥ 0.5 m/s (progressors) nor ΔPWV (as a spline function) were associated with CV events and with all-cause mortality. However, the association with survival probability and cumulative incidence of CV events, as a composite outcome, was significant (HR = 2.32, 95% CI: 1.33 – 4.04, p=0.003). Conclusions In conclusion, our study shows that PWV progression of at least 0.5 m/s is frequent in hypertensive patients and that it is associated with a significantly higher risk of developing CV events or dying (composite outcome).

Third ventilatory threshold in heart failure patients undergoing CPET: a prognostic analysis

Abstract Introduction One crucial element in cardiopulmonary exercise testing (CPET) involves identifying the first and second ventilatory thresholds (VT), VT1 and VT2, which hold known prognostic implications. If the individual can sustain exercise considerably beyond VT2, a third breakpoint (VT3 – Figure A) may emerge, coinciding with heightened hyperventilation to counter metabolic acidosis. Historically, this point has been mainly described among athletes and its meaning is still not entirely clear. We aimed to assess the prognostic value of VT3 in patients with heart failure (HF). Methods Retrospective, single-center study enrolling HF patients undergoing CPET from 2015 to 2021. We evaluated the typical CPET parameters along with the three ventilatory thresholds: VT1, VT2, and the newly introduced VT3. The primary outcome was a composite of cardiovascular death, urgent heart transplant, need for left ventricle assistance device and HF hospitalizations. Results We included 221 patients (82% men, mean age 58±12 years), among whom 69% had ischemic heart failure aetiology. The mean left ventricular ejection fraction (LVEF) was 34±9%, with a mean respiratory exchange ratio 1.15±0.082, mean pVO2 18.5±6.3, and a mean VE/VCO2 slope of 41.3±12.9. VT3 was attained by 43% (n = 94) of the patients. In comparison to those who did not achieve VT3, patients who reached this threshold were younger (56±11 vs 60±12; p = 0.05), had a higher pVO2 (20.5±6.9 vs 17±5.4; p = 0.05), higher RER (1.16±0.86 vs 1.13±0.78; p = 0.05), and lower VE/VCO2 slope (39±10.3 vs 43±14.3; p = 0.05). Regarding the three ventilatory thresholds (VT1, VT2, VT3), 7% (n=17) achieved a maximum of one threshold, 50% (n=110) achieved two thresholds, and 43% (n=94) reached all three thresholds. After a median follow-up of 2,3 years patients with identifiable VT3 had significantly better prognosis (HR 0,434; 95%CI 0,246-0,767; p=0,004) than those without this threshold. Furthermore, the number of identifiable ventilatory thresholds correlated positively with prognosis. In fact, patients with only 2 thresholds have twice the probability of developing an event and those with one or zero identifiable thresholds have a 4-fold increase in the probability of events (Figure C). Conclusion In a cohort of patients with HF, those with identifiable VT3 had a lower incidence of events. This parameter may aid in prognostic stratification in this population. However, this findings warrant further prospective validation.Figure 1

Risk-taking Factors in a Dynamic Approach

The most common definition of risk is quantified by the probability of an adverse event occurring and the value of the adverse consequence. Theoretically, the decision to take a risk can also be based essentially on these two pieces of information. In addition, according to traditional risk-taking models, the perception of risk, the psychological characteristics of the decision-makers and their relevant experience are also important. In the case of mathematical-statistical-psychological models, little emphasis is placed on the fact that risk is in fact the inability to completely control the activity in question. The causes of this incompleteness are based on the shortcomings in the relevant capabilities of the economic agent. Economic agents have different capabilities, so they rarely face the same risks, even for almost identical activities. Just as the requirements and circumstances of the activity are constantly changing, so are the capabilities of the economic agent. Consequently, the size of the capability gap of an economic agent is also constantly changing. This should be taken into account in risk-taking decisions and their revision. The paper attempts to model this dynamic risk-taking mechanism and to show how different risk-taking strategies may be pursued by economic agents in certain baseline situations.

Is genetic information helpful in predicting recurrent events in young patients after acute coronary syndrome?

Abstract Coronary Artery Disease (CAD) shares environmental and genetic factors. Young patients with acute coronary syndrome (ACS) carry a poor long-term prognosis. The clinical utility of genetic information in predicting CAD events remains unknown. Aim Evaluate the clinical utility of a multiplicative Genetic Risk Score (mGRS) to predict lifelong residual risk in CAD patients below 55 years with few risk factors. Methods 475 non-diabetic patients with LDL cholesterol levels below 100mg/dL at the first admission who suffered a prior MI at age ≤55 years were followed prospectively for a mean of 5.6±5.3 years. A mGRS was performed with nine variants associated with CAD but not with traditional risk factors (TRF): CDKN2B-AS1 (rs1333049 and rs4977574), TCF21 (rs12190287), PHACTR1 (rs1332844), MIA3 (rs17465637), ADAMTS7 (rs3825807), ZC3HC1 (rs11556924), SMAD3 (rs17228212) and GJA4 (rs618675). The mGRS was subdivided into terciles. Using Cox regression analysis, the predictive and discriminative score ability for events was evaluated. C-statistic discriminated cardiovascular events occurrence. Whether mGRS was included in the TRF model, Net Reclassification Improvement (NRI), or Integrated Discrimination Improvement (IDI) reclassified patients. Kaplan-Meier method estimated survival curves. Results There were 153 patients with at least one cardiovascular event. The bivariate analysis showed the strongest correlation with second and third mGRS tercile, multivessel disease, left ventricular dysfunction, and inflammation. Multivariate Cox regression HR adjusted for events was 1.44 (p=0.103) for the intermediate and 2.00 (p=0.001) for the high-risk tercile. The mGRS inclusion improved C-statistic (∆C-index=0.010; p=0.004), NRI (35.4%; p<0.0001) and IDI (2.7%; p=0.0005). Conclusions Our 9-SNP mGRS better identified and reclassified younger CAD patients with a high probability of cardiovascular events, improving clinical decision-making and reducing costs for therapeutic strategies.

Regadenoson stress echocardiography: a road ahead

Abstract Introduction Drugs used in stress echocardiography (SE) have important limitations due to side effects and contraindications. Since its approval in 2008, Regadenoson has seen a significant increase in usage. This is largely attributed to its good safety profile and diagnostic accuracy, making it the preferred drug for stress tests in many European centers. However, despite its expanding use and major advantages, current guidelines don't place it as the first choice for SE, probably because the reported experience with this drug remains limited. The aim of the present study was to assess the safety and short-medium term prognosis of patients who underwent Regadenoson SE. Methods Retrospective observational study. Patients who underwent Regadenoson SE between 2017 and 2023 were included. Safety was assessed by monitoring immediate adverse effects following Regadenoson infusion and the need for using an antidote (Aminophylline). A positive test result was defined by the occurrence of any of the following: wall motion abnormalities, left ventricle dilatation, electrocardiographic changes or symptoms of ischemia. During the follow up, we registered the incidence of ischaemic events (admission for unstable angina, acute myocardial infarction (AMI) or cardiovascular (CV) death) and other CV events such as admission for heart failure (HF) and stroke. Additionally, we evaluated patients in both groups who underwent coronary angiography (by computerized tomography or coronary catheterization) during the follow up period. The groups with negative SE (NSE) and positive SE (PSE) were compared. Results The total number of patients was 344, with a median follow up of 29 months. Basal population characteristics and events by group (NSE and PSE) are shown in Figure 1. We needed to use the antidote in only one case, because of ventricular bigeminism, with no other major adverse effects reported. SE was positive in 37 (11%) patients. In this group, patients were more likely to present ischaemic events (16% vs. 3%, p<0.01) and admissions for HF (24% vs. 5%, p <0.01), compared to the NSE one. In those who underwent coronary angiography, revascularization was needed in 14 patients of the PSE group, and only in 7 of the NSE group (38% vs 2%, p < 0.05). The indications for these last cases were persistent angina in 5 patients (2 of them with history of coronary artery disease) and revascularization following an AMI in 2 patients. (Figure 2). Conclusions The probability of an ischaemic event after a negative Regadenoson SE remains very low, unlike positive studies. Regadenoson SE showed to be both safe in assessing ischemic cardiomyopathy and very useful for its prognostic value. These findings encourage its expanding use in the stress echo lab.

Subclinical myocardial fibrosis is almost ubiquitous in the hearts of older British persons: 'MyoFit46' cardiovascular sub-study of the NSHD

Abstract Background Unprecedented numbers are now surviving to older age, but little is known about the burden or pattern of myocardial fibrosis in the asymptomatic elderly population. Previous 1.5 Tesla (T) cardiovascular magnetic resonance (CMR) studies found a prevalence of unexpected infarct-pattern late gadolinium enhancement (LGE) of 17-20% above 75 years but less is known about non-infarct pattern scar in this group. We investigated the prevalence, patterns, and clinical predictors of left ventricular (LV) scar in a large asymptomatic older age cohort. Methods CMR with a single 3T magnet was performed on participants all born in the same week in March 1946, as part of the longest running continued surveillance birth cohort: the National Survey of Health and Development. LV short-axis stack LGE imaging was performed using a free-breathing motion-corrected balanced steady-state free precession sequence with phase-sensitive inversion-recovery. Two blinded observers independently recorded the prevalence, extent, and pattern of LGE per participant. Logistic regression was used to study the association between clinicodemographic parameters and LGE. Results 460 participants were prospectively recruited of which 406 completed CMR with LGE imaging (77.8 ± 0.1 years, 44% male). 341 (84%) demonstrated LGE affecting a mean of 2.1±1.2 myocardial segments per participant (Figure 1). The commonest pattern of LGE was inferior right ventricular insertion point (RVIP), observed in 66.9%. Other patterns included (Figure 2): Linear mid-wall (19.6%) of which 38% were located in the inferior/lateral walls; subepicardial (12.1%); subendocardial infarct-pattern (8.8%); patchy/diffuse (1.6%); embolic LGE (0.6%). Sub-analysis was performed comparing those without significant unexpected fibrosis (LGE–) vs those with focal fibrosis (LGE+, excluding RVIP and those participants with a known history of prior myocardial infarction). LGE+ participants were more likely to be female (71.7% vs 49.1%, p<0.001) or diabetic (11.3% vs 5.1%, p=0.05), had a higher body surface area (BSA, 1.9 vs 1.8 m2, p<0.001), weight (80.1 vs 72.8 kg, p<0.001), LV indexed end systolic volume (24.2 vs 20.4 ml/m2, p=0.001) and LV indexed mass (59.2 vs 55.4 g/m2, p<0.001), and a lower LV ejection fraction (67.9 vs 71.8%, p<0.001) In multivariable logistic regression: BSA, LV indexed mass, LV ejection fraction and diabetic status were independently associated with LGE+ status (odds ratios [95% confidence intervals]: 9.4 [0.7–3.8]; 1.0 [0.01–0.05]; 0.9 [-0.08--0.02]; and 2.5 [0.03–1.7] respectively, p<0.05). Conclusion Advanced PSIR MOCO LGE imaging at 3T reveals that the majority (84%) of asymptomatic British persons above the age of 75 harbour unexpected ‘subclinical’ focal fibrosis, with a substantial proportion of these scars consistent with probable historical myocarditis events. Further work will now explore the life-course determinants of this scar burden in the older age human heart.

Myocarditis prognostic score: a new risk assessment tool in patients with myocarditis

Abstract Background Myocarditis is an inflammatory disease of the myocardium with multiple causes and evolutions. The aim of our study was to design a prognostic multiparametric score in patients with myocarditis, to identify those at higher risk of adverse cardiovascular events (AE). Methods A prospective study was performed enrolling 98 patients with myocarditis: 72 M, 26 F; median age 27 [IQR 20–40]. Patients were divided into 2 groups: complicated (CM) and uncomplicated myocarditis (UM). Six months after hospital admission, cardiac magnetic resonance (CMR) and cardiological consultation were repeated. AE (death, hospitalization for heart failure, heart transplant, ICD implantation, heart failure development) were evaluated at 6 months and after 3 years. Results We found 67 UM and 31 CM. AE were significantly higher in patients with complicated myocarditis. We found a significant correlation between AE and reduced left ventricular ejection fraction (LVEF) at hospital admission, increased GLS, septal LGE at CMR, longer persistence time of increased troponin, LGE extension progression or persistence 6-month CMR. A myocarditis prognostic score was developed on the basis of these parameters. A score ≥ 5 showed higher sensitivity (100%) and specificity (87%) - AUC 1, to identify AE in patients with myocarditis. A score between 3 and 4 showed high sensitivity but low specificity. A score ≤ 2 was associated with low probability of events. Conclusion Our study confirms the high probability of AE in patients with CM and it suggests a myocarditis prognostic score to identify patients at higher risk of AE.

Scarcity induces conflict in Puerto Rican fisheries

Abstract Small-scale fisheries provide vital food security for coastal communities worldwide, yet they face numerous challenges. In particular, fisheries conflicts arise when a marine resource is contested or disputed between a minimum of two actors. Despite the potentially large impacts of fisheries conflicts on marine-based economies, it is difficult to quantify the impact of conflict on fisheries production or on long-standing cooperative relationships that can be vital to the long-term sustainability of a given fishery. Previous work addressing fisheries conflicts has had a limited focus on quantitative measurements of how changes in fishing effort can influence how communities fall into conflict or make concerted efforts to cooperate. To address this knowledge gap, instances of conflict and cooperation amongst fishers in Puerto Rico were documented and categorized into different intensity levels. A linear probability model was then developed to estimate the probability of a conflict event occurring in a specific region, month, and year from 2012 to 2017. The model includes catch per unit effort as a predictor variable and controls for environmental factors. We found that an increase in catch per trip from the previous month has a negative and significant relationship with the probability of a conflict event. This result provides quantitative evidence for the supply-induced scarcity hypothesis, highlighting the importance of managing fisheries sustainably, to avoid future fisheries conflicts.

Safety assessment of sapropterin dihydrochloride: real-world adverse event analysis based on the FDA adverse event reporting system (FAERS)

ObjectiveSapropterin dihydrochloride is the first drug for the therapy of phenylketonuria, which is a rare disease that occurs one of 10,000–15,000 newborns. As a result, detailed and comprehensive reports on the safety of sapropterin in large, real-world populations are required. The purpose of this study is to undertake a complete analysis of sapropterin’s adverse events (AEs) using the FDA Adverse Event Reporting System (FAERS) database.MethodsWe retrieved reports of adverse events with sapropterin as the principal suspect from FAERS between the first quarter of 2008 and the first quarter of 2024. The Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), and Bayesian Confidence Propagation Neural Network (BCPNN) were utilized to detect AE signals.ResultsThe study collected 4,953 suspected AE cases from the FAERS database, with sapropterin as the major suspect. A total of 130 positive signals were obtained utilizing the ROR, PRP, and BCPNN. The FAERS database revealed that common clinical AEs of sapropterin included vomiting, upper respiratory infection, rhinorrhea, and a reduction in amino acid concentrations. Furthermore, we detected probable unexpected adverse events (AEs) using disproportionality analysis, including gastroesophageal reflux disease, flatulence, influenza, ear infection, viral infection, pharyngitis streptococcal, spontaneous abortion, and nephrolithiasis.ConclusionBy analyzing huge amounts of real-world data from the FAERS database, we found potential novel AEs of sapropterin using disproportionate analysis. It is advantageous for healthcare professionals and pharmacists to focus on efficiently managing sapropterin’s high-risk adverse events, improving drug levels in clinical settings, and ensuring patient medication safety.

Development of a prognostic model for predicting long-term visual acuity after cataract surgery in children with bilateral congenital cataracts: a single centre retrospective, observational study

BackgroundTo evaluate factors influencing best corrected visual acuity (BCVA) in paediatric patients with bilateral congenital cataracts (CC) after cataract extraction and intraocular lens (IOL) implantation, as well as develop a robust model for predicting long-term visual acuity.MethodsThis retrospective study followed 194 paediatric patients with bilateral CC from January 2008 to December 2021. The endpoint event was defined as a final BCVA < 0.22 Log MAR at the last follow-up, which indicated good outcome. The probability of reaching this endpoint event was modelled using Cox proportional hazards regression analysis and internally validated through 200 iteration of 5-fold cross-validation.ResultsA prognostic model for long-term visual acuity in bilateral CC after surgical treatment was established as follows: ln h(t) = −0.009 × “age at cataract extraction” − 0.015 × “age at IOL implantation” − 2.934 × “without nystagmus at last follow − up” + ln h0(0), in which h0(t) represents the baseline risk equation that can be any non-negative equation for time (t); h(t) represents the probability of the endpoint event occurring at time (t) without any endpoint event occurring before it. The model was visualized using a nomogram and contour plot to facilitate clinical practice. The model demonstrated reasonably accurate discrimination with an area under the receiver operating characteristic curve of 0.712 (95% confidence interval [CI]: 0.589–0.835) and a C-index of 0.797 (95% CI: 0.683–0.911). According to the model, children with bilateral CC had a higher likelihood of achieving a good outcome (BCVA < 0.22 Log MAR) if they underwent cataract extraction before the age of six months (hazard ratio [HR] 1.80, 95% CI: 0.92–3.70), received IOL implantation before the age of thirty-one months (HR 3.70, 95% CI: 1.77–7.80), and presented without nystagmus during their last follow-up visit (HR 11.20, 95% CI: 3.96–31.80).ConclusionsThis long-term visual acuity prognostic model demonstrates adequate performance for individualized prediction and assists in clinical decision-making. The risk stratification index guides optimal timing for surgery.

Strong Linkage Between Observed Daily Precipitation Extremes and Anthropogenic Emissions Across the Contiguous United States

AbstractThe results of probabilistic event attribution studies depend on the choice of the extreme value statistics used in the analysis, particularly with the arbitrariness in the selection of appropriate thresholds to define extremes. We bypass this issue by using the Extended Generalized Pareto Distribution (ExtGPD), which jointly models low precipitation with a generalized Pareto distribution and extremes with a different Pareto tail, to conduct daily precipitation attribution across the contiguous United States (CONUS). We apply the ExtGPD to 12 general circulation models from the Coupled Model Intercomparison Project Phase 6 and compare counterfactual scenarios with and without anthropogenic emissions. Observed precipitation by the Climate Prediction Center is used for evaluating the GCMs. We find that greenhouse gases rather than natural variability can explain the observed magnitude of extreme daily precipitation, especially in the temperate regions. Our results highlight an unambiguous linkage of anthropogenic emissions to daily precipitation extremes across CONUS.

Government green procurement and corporate ESG performance

This study utilizes data from China's A-share listed companies from 2009 to 2022 and manually collects government green procurement lists published on the Chinese government procurement website. By matching this data with listed companies, we employ a multi-period Difference-in-Differences (DID) model to examine the impact of a firm's inclusion in government green procurement lists on its Environmental, Social, and Governance (ESG) performance. We find that government green procurement significantly improves firms' ESG performance. In the mechanism analysis, we find that executive green perceptions and media and analyst attention amplify the positive impact of government green procurement on firms' ESG performance. Through the heterogeneity analysis, we find that government green procurement promotes ESG performance more significantly when the listed company is a state-owned enterprise, and this promotion is more obvious in central state-owned enterprises. In addition, we find that government green procurement enhances ESG performance more significantly when the company is located in a region with higher levels of market integration. Further research find that government green procurement effectively inhibit “greenwashing” behavior and reduce the probability of negative events. Our findings provide important micro-empirical evidence for understanding the effects of market-based policy instruments on corporate ESG performance and contribute positively to the practice of improving corporate governance capabilities.

An integrated approach for multi-objective differential algorithm based event constrained optimal power flow for power system resiliency enhancement

ABSTRACT Due to climatic changes, the probability of occurrence and the intensity of extreme weather events increase day by day which leads to power outages. The probability of failure events is calculated using Monte Carlo simulation technique which is used to identify the most frequent failure events. The least eigenvalues of the inverse reduced Jacobian matrix decide the sensitive buses for load shedding using V-Q sensitivity analysis. This work presents the multi-objective differential evolution (MODE) algorithm for solving resilient constrained optimal power flow (RCOPF) in a deregulated power system. The control variables namely the real power of generators in a base case and under event, generator bus voltage magnitude, the real and reactive power demand of the selected load buses, tap settings and capacitor bank ratings. This algorithm is validated in IEEE 30 bus test system and the Indian 62 bus utility test system to show the effectiveness in four different cases including tie lines and distributed generation.

Tolerance of Oncogene-Induced Replication Stress: A Fuel for Genomic Instability.

Activation of oncogenes disturbs a wide variety of cellular processes and induces physiological dysregulation of DNA replication, widely referred to as replication stress (RS). Oncogene-induced RS can cause replication forks to stall or collapse, thereby leading to DNA damage. While the DNA damage response (DDR) can provoke an anti-tumor barrier to prevent the development of cancer, a small subset of cells triggers replication stress tolerance (RST), allowing precancerous cells to survive, thereby promoting clonal expansion and genomic instability (GIN). Genomic instability (GIN) is a hallmark of cancer, driving genetic alterations ranging from nucleotide changes to aneuploidy. These alterations increase the probability of oncogenic events and create a heterogeneous cell population with an enhanced ability to evolve. This review explores how major oncogenes such as RAS, cyclin E, and MYC induce RS through diverse mechanisms. Additionally, we delve into the strategies employed by normal and cancer cells to tolerate RS and promote GIN. Understanding the intricate relationship between oncogene activation, RS, and GIN is crucial to better understand how cancer cells emerge and to develop potential cancer therapies that target these vulnerabilities.

The Influence of Fault Geometrical Complexity on Surface Rupture Length

AbstractPropagating earthquakes must overcome geometrical complexity on fault networks to grow into large, surface rupturing events. We map step‐overs, bends, gaps, splays, and strands of length scales ∼100–500 m from the surface ruptures of 31 strike‐slip earthquakes, recording whether ruptures propagated past the feature. We find that step‐overs and bends can arrest rupture and develop a statistical model for passing probability as a function of geometry for each group. Step‐overs wider than 1.2 km, single bends larger than 32°, and double bends larger than 38° are breached by rupture half of the time. ∼20% of the ruptures terminate on straight segments. We examine how the distribution of geometrical complexity influences surface rupture length, inferring an exponential relationship between rupture length and event probability. Our findings support that geometrical complexity helps limit the size of large events and provide insights into the competition between energy supply and dissipation during rupture propagation.

Double-loop importance sampling for McKean–Vlasov stochastic differential equation

This paper investigates Monte Carlo (MC) methods to estimate probabilities of rare events associated with the solution to the d-dimensional McKean–Vlasov stochastic differential equation (MV-SDE). MV-SDEs are usually approximated using a stochastic interacting P-particle system, which is a set of P coupled d-dimensional stochastic differential equations (SDEs). Importance sampling (IS) is a common technique for reducing high relative variance of MC estimators of rare-event probabilities. We first derive a zero-variance IS change of measure for the quantity of interest by using stochastic optimal control theory. However, when this change of measure is applied to stochastic particle systems, it yields a P×d\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$P \ imes d$$\\end{document}-dimensional partial differential control equation (PDE), which is computationally expensive to solve. To address this issue, we use the decoupling approach introduced in (dos Reis et al. 2023), generating a d-dimensional control PDE for a zero-variance estimator of the decoupled SDE. Based on this approach, we develop a computationally efficient double loop MC (DLMC) estimator. We conduct a comprehensive numerical error and work analysis of the DLMC estimator. As a result, we show optimal complexity of OTOLr-4\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\mathcal {O}\\left( \ extrm{TOL}_{\ extrm{r}}^{-4}\\right) $$\\end{document} with a significantly reduced constant to achieve a prescribed relative error tolerance TOLr\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\ extrm{TOL}_{\ extrm{r}}$$\\end{document}. Subsequently, we propose an adaptive DLMC method combined with IS to numerically estimate rare-event probabilities, substantially reducing relative variance and computational runtimes required to achieve a given TOLr\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\ extrm{TOL}_{\ extrm{r}}$$\\end{document} compared with standard MC estimators in the absence of IS. Numerical experiments are performed on the Kuramoto model from statistical physics.

Evaluation of the effectiveness and safety of Korean red ginseng extract as immune-enhancer in Vietnamese adults: A randomized placebo-controlled trial

Purpose: To investigate the safety and immune-enhancing effect of Korean red ginseng (KRG) extract in Vietnamese adults. Methods: Participants in this randomized, placebo-controlled double-blinded study were administered either 960 mg of KRG extract (n = 51) or placebo capsules (n = 50) for 12 weeks at Hanoi Medical University, Vietnam. The KRG extract was standardized to contain 5.27 mg of 3 ginsenosides (Rg1, Rb1, and Rg3) per gram. Blood samples for assessment of treatment effectiveness were collected from the subjects on days 21 and 84. Immune cytokines were quantified using enzyme-linked immunosorbent assay (ELISA). Blood samples for safety assessment, hematological and biochemical variables, and urinalysis were performed at the beginning and end of the intervention (days 21 and 84, respectively). Results: The KRG group showed a significant increase in lymph T cell % at the end of the 12-week intervention (p &lt; 0.001). There were significant decreases in numbers of white blood cells (WBC) and natural killer (NK) cells in both groups. However, there were no significant differences in populations of WBC and NK cells between the 2 groups. Serum concentrations of cytokines, i.e., TNF-α, β, γ; IFN- α, γ; IL-1β and 4β were decreased in the KRG group when compared to baseline values. There were no probable or definite adverse events (AEs) related to KRG. A total of 9 participants (4 in KRG group and 5 in placebo group) tested positive for COVID-19 during the trial. Conclusion: The KRG extract-induced increase in population of T-cells and reductions in cytokine levels following a 12-week exposure may be beneficial for COVID-19 patients.

The impact of the QBO vertical structure on June extreme high temperatures in South Asia

Using observation data and numerical simulations, we have demonstrated that the stratospheric Quasi-Biennial Oscillation (QBO) can predict extreme high temperatures (EHTs) in South Asia in June. The vertical structure of the QBO plays a crucial role in this prediction. When the QBO in June shows easterlies (westerlies) at 50 hPa and westerlies (easterlies) at 70 hPa, more (fewer) EHT events occur. This likely results from the QBO’s vertical structure causing positive (negative) temperature anomalies in the lower stratosphere and negative (positive) static stability anomalies near the tropical tropopause. These anomalies enhance (weaken) convective activity over the equatorial Indian Ocean, leading to anomalous circulation with ascending (descending) air over the equatorial Indian Ocean and descending (ascending) air over northern and central South Asia. This suppresses (promotes) convection over northern and central South Asia, affecting cloud formation and precipitation. Consequently, more (less) solar radiation reaches the region, along with weaker (stronger) evaporative cooling effects, warming (cooling) the surface and creating a background state conducive to (against) EHT events. Additionally, the opposite zonal winds at 30 hPa and 50 hPa in April may serve as a reference factor for predicting the probability of EHT events in northern and central South Asia. This study provides a potential approach for forecasting tropospheric extreme weather events based on stratospheric signals.

Venturing Travelers vs. Home Stayers Under Extreme Risk

ABSTRACT This study explores risk-taking during a pandemic, a severe risk condition similar to terrorism and natural disasters. It examines differences in sociodemographics and psychographics between individuals who traveled during the COVID-19 Pandemic and those who stayed home. Conducted as an online survey in 2022, the study used a randomized experiment. T-tests revealed significant differences in only two sociodemographics and two risk-taking factors of probability neglect and proximity-to-self, but not in personality traits of risk-taking, thrill-seeking, or self-confidence. Travelers were more likely to have young children and higher income while non-travelers scored higher in neglecting the probability of bad events happening to them, potentially because they avoided travel as they perceived a high likelihood of bad events happening while traveling.

Prediction by Young Autistic Children from Visual and Spoken Input.

Recent theoretical accounts suggest that differences in the processing of probabilistic events underlie the core and associated traits of autism spectrum disorder (ASD). These theories hypothesize that autistic individuals are differentially impacted by disruptions in probabilistic input relative to neurotypical peers. According to this view, autistic individuals assign disproportionate weight to prediction errors such that novel input is overweighted relative to the aggregation of prior input; this is referred to as 'hyperplasticity' of learning. Prediction among autistic individuals has primarily been examined in nonverbal, visual contexts with older children and adults. The present study examined 32 autistic and 32 cognitively-matched neurotypical (NT) children's ability to generate predictions and adjust to changes in predictive relationships in auditory stimuli using two eye gaze tasks. In both studies, children were trained and tested on an auditory-visual cue which predicted the location of a reward stimulus. In Experiment 1 the cue was non-linguistic (instrumental sound) whereas in Experiment 2 the cue was linguistically-relevant (speaker gender). In both experiments, the cue-reward contingency was switched after the first block of trials, and predictive behavior was evaluated across a second block of trials. Results: Analyses of children's looking behavior revealed similar performance in both groups on the non-linguistic task (Exp. 1). In the linguistically-relevant task (Exp. 2), predictive looking was less disrupted by the contingency switch for autistic children than NT children. Results suggest that autistic children may demonstrate hyperplastic learning in linguistically-relevant contexts, relative to NT peers.