In stroke patients directly admitted to thrombectomy-capable centers, the value of intravenous thrombolysis (IVT) with alteplase before thrombectomy is time dependent. While early IVT may improve outcomes, delayed IVT administration lowers the likelihood of benefit. To date, no previous cost-effectiveness study has considered onset-to-treatment time. This study evaluated the cost-effectiveness of intravenous (IV) alteplase plus thrombectomy vs thrombectomy alone in patients admitted directly to thrombectomy-capable centers across 16 countries, stratified by onset-to-IVT time. A decision tree integrated with a Markov model estimated costs, quality-adjusted life years (QALYs), and incremental net monetary benefit (INMB) over 15 years. A willingness-to-pay threshold of one gross domestic product per capita was applied for each country. Effectiveness data were derived from individual patient data from 6 trials including patients with anterior circulation large-vessel occlusion eligible for both IVT and thrombectomy who presented directly to thrombectomy-capable centers. Costs were obtained from a literature review. Onset-to-IVT time was categorized as <140, 140-169, 170-199, and ≥200 minutes. One-way sensitivity and probabilistic sensitivity analyses were performed to check robustness of results. Ninety-day functional outcome distributions from 2,268 patients (median age 71 years; 44% female) were used to model cost-effectiveness in a hypothetical cohort of 10,000 patients. Without accounting for onset-to-IVT time, IV alteplase plus thrombectomy seemed cost-effective in 13 countries (INMB: $85-$3,618; 50-65% probability of cost-effectiveness) and not cost-effective in the United States, China, and Vietnam, with modest health gains (0.06-0.08 QALYs per patient). Time-stratified analyses revealed that IVT plus thrombectomy was cost-effective in 16 countries when onset-to-IVT time was <140 minutes (INMB: $615-$30,645; 82%-98% probability) and at 140-169 minutes (INMB: $86-$16,918; 51%-77% probability). However, IV alteplase plus thrombectomy was no longer cost-effective in 8 countries at 170-199 minutes. Universally, the INMB was negative for onset-to-IVT times exceeding 200 minutes. Cost-effectiveness of IV alteplase plus thrombectomy varies per country and onset-to-IVT time. IV alteplase plus thrombectomy is cost-effective when IVT can be administered within 170 minutes from symptom onset. Cost-effectiveness of IV alteplase plus thrombectomy diminishes progressively with longer onset-to-IVT times and becomes detrimental after 200 minutes.

A hyperspectral co-design framework guided by occlusion sensitivity for early mould detection in bamboo.

Causal effects of lung function on brain cortical and subcortical structure: a two-sample univariable and multivariable Mendelian Randomization study.

Real-world applications of integrated traditional Chinese and Western medicine in patients with intermediate coronary lesions: Insights from a multicenter observational cohort study.

Acute Necrotizing Encephalopathy in Children: Meta-Analysis of Observational Studies on the Efficacy of Steroid Treatment.

Mechanistic models in systems biology enable biophysically-backed testing of hypothesised mechanisms. However, determination of their parameter values is highly challenging, and the data available for calibration is frequently qualitative in nature. Acknowledging this, many approaches abandon mechanistic description, avoiding parameterisation and simulating biological network behaviours in a qualitative fashion. Appealing are the methods that capture some of the best of both types of approach, maintaining a qualitative perspective while using mechanistic models that naturally generalise to quantitative data and carry biochemical implications. Here, using a pea branching network model as an exemplar, we demonstrate the conversion of biological hypotheses into simplified, parameter-free mathematical models, elucidating the biophysical assumptions implicitly made by this approach and analysing the exemplar model's behaviour. Using likelihood-free Bayesian calibration, we compare the parameter-free model to the set of plausible calibrations of its parameterised analog, hence demonstrating that almost all of the qualitative conclusions given data - including both suitability of a hypothesised network structure, and sensitivity analysis - are obtained by the parameter-free paradigm. Altogether, our findings highlight the usefulness of parameter-free treatments of quantitative models, and also deepen understanding of branching network function across mutant and grafted plants.

Chronic hepatitis B (CHB) refers to a global infectious disease caused by the hepatitis B virus. The treatment of CHB causes a heavy economic burden to society. To ensure the rational allocation of medical resources in the whole society and achieve the goal of patients' satisfaction and economy, this study aimed to evaluate the economics of de novo combination of tenofovir alafenamide fumarate (TAF) as the first-line nucleos(t)ide analogues (NAs) and peginterferon alfa-2b (PEG-IFNα-2b) versus PEG-IFNα-2b monotherapy of HBeAg-positive CHB in China. The Markov model was used to simulate the transition of HBeAg-positive CHB patients aged 30 in China under various health states using TreeAge Pro 2011 software. The cycle length was 1 year, and the cycle period of the model was 50 years. The model parameters included clinical efficacy, cost, transition probability and discount rate. Cost-effectiveness analysis was conducted through simulation of the total cost and quality adjusted life years (QALYs) of various treatment options through models. Simultaneously, one-way sensitivity analysis, probabilistic sensitivity analysis and scenario analysis were performed. De novo combination of TAF and PEG-IFNα-2b and PEG-IFNα-2b monotherapy resulted in 11.16 and 10.81 QALYs, with total costs of $55559.72 and $57670.23, respectively. De novo combination strategy for HBeAg-positive CHB patients can save costs and obtain more health outcomes. Sensitivity analyses showed the reliability of the results. From the perspective of the whole society, the de novo combination strategy of TAF and PEG-IFNα-2b for patients with HBeAg-positive CHB may be more cost-effective than PEG-IFNα-2b monotherapy.

Sensitivity analysis is the process of attributing the variability of model outputs to uncertainties in input parameters and assumptions. Why is this technique important? Which methods and concepts should be prioritized in teaching it? And what instructional strategies are best suited to different audiences? This work seeks to address these questions by drawing on the experience gained from 12 summer schools conducted by the authors since 1999, along with numerous specialized training courses delivered to academia, research organizations, and international institutions. We aim to distill these experiences into practical guidance for teaching sensitivity analysis, offering both methodological foundations and pedagogical strategies to support educators and futurepractitioners.

The Doyle–Fuller–Newman model is arguably the most ubiquitous electrochemical model in lithium-ion battery research. Since it is a highly nonlinear model, its input–output relations are still poorly understood. Researchers therefore often employ sensitivity analyses to elucidate relative parametric importance for certain use cases. However, some methods are ill-suited for the complexity of the model and appropriate methods often face the downside of only being applicable to scalar quantities of interest. We implement a novel framework for global sensitivity analysis of time-dependent model outputs and apply it to a drive cycle simulation. We conduct a full and a subgroup sensitivity analysis to resolve lowly sensitive parameters and explore the model error when unimportant parameters are set to arbitrary values. Our findings suggest that the method identifies insensitive parameters whose variations cause only small deviations in the voltage response of the model. By providing the methodology, we hope research questions related to parametric sensitivity for time-dependent quantities of interest, such as voltage responses, can be addressed more easily and adequately in simulative battery research and beyond. • Time-dependent global sensitivity analysis of 24 parameters of the Doyer–Fuller–Newman model for drive cycle simulations. • Use of an innovative history-aware approach, which aggregates the parameters’ effects over time to obtain accurate results. • Investigation of the model error introduced by arbitrarily valued insensitive parameters and discussion of ramifications in the context of battery model parametrization. • Open-source implementation of novel algorithms for variance-based sensitivity analysis of time-dependent model outputs.

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are widely used for metabolic disorders, but emerging safety concerns include alopecia and reproductive or endocrine-related adverse events (AEs). This study investigated the association between specific GLP-1 RAs and these endocrine-related AEs using a large-scale pharmacovigilance database. This study analysed the U.S. FDA Adverse Event Reporting System (FAERS) data (Q2 2022-Q2 2025) for six GLP-1 Ras (exenatide, lixisenatide, liraglutide, dulaglutide, semaglutide, and tirzepatide) to identify alopecia- and reproductive or endocrine-related a AEs. Disproportionality analyses were conducted using crude and adjusted reporting odds ratios (cROR and aROR) from logistic regression controlling for potential confounding factors. Sensitivity analyses with positive and negative controls were used to validate the signal robustness. A total of 1276 alopecia-related and 759 reproductive or endocrine-related cases were identified. Semaglutide showed significant positive associations with alopecia (aROR 1.23 [1.11-1.35]) and reproductive/hormonal disorders, including polycystic ovary syndrome (aROR 6.59 [3.73-11.64]) and menstrual abnormalities. In contrast, dulaglutide and tirzepatide demonstrated negative associations for several reproductive outcomes (e.g.,dysmenorrhoea, amenorrhoea, heavy menstrual bleeding), indicating lower reporting odds in this dataset. Sensitivity analyses using control drugs confirmed the consistency and specificity of these findings. This real-world pharmacovigilance study identified agent-specific differences in the endocrine and dermatologic safety profiles of GLP-1 RAs. While semaglutide exhibited disproportionate reporting for alopecia and hormonal imbalance, dulaglutide and tirzepatide showed lower or non-significant disproportionality signals for these events. These results highlight the need for personalised agent selection and continued pharmacovigilance to optimise long-term patient safety.

Risk of Glaucoma in Patients With Idiopathic Noninfectious Uveitis: A Multi-Institutional Real-World Retrospective Cohort Study.

Systemic hypertension and obstructive sleep apnea (OSA) are closely linked conditions that substantially increase the risk of cardiovascular disease (CVD). Left ventricular end-diastolic volume (LVEDV) is a crucial echocardiographic marker of cardiac remodeling; however, its prognostic value in patients with concomitant systemic hypertension and OSA remains poorly defined. This study aimed to examine the association between LVEDV and the incidence of CVD in this high-risk population. This retrospective cohort study included patients with confirmed systemic hypertension and OSA, who were stratified into tertiles based on baseline LVEDV. Multivariable Cox proportional hazards models, adjusted for demographic factors, comorbid conditions, and OSA severity, were used to evaluate CVD risk. Sensitivity and stratified analyses were conducted to assess the robustness of the findings. A total of 1914 patients (mean age 48.7±10.2 years) were followed for a median of 83 months, during which 186 incident CVD events were documented. The incidence of CVD increased progressively across LVEDV tertiles. In fully adjusted analyses, patients in the highest tertile (T3: >81mL) showed a significantly higher risk of CVD compared with those in the lowest tertile (T1: <70mL) (hazard ratio [HR]=1.86; 95% confidence interval [CI]: 1.30-2.67; P=0.001). Although a higher risk was observed for the intermediate tertile (T2: 70-81mL), this association did not reach statistical significance (HR=1.29; 95% CI: 0.88-1.88; P=0.19). These associations remained stable across sensitivity and stratified analyses. Elevated LVEDV is independently associated with an increased risk of CVD in patients with coexisting systemic hypertension and OSA. These findings support LVEDV as a novel and readily obtainable echocardiographic biomarker for cardiovascular risk stratification in this population. Routine assessment of LVEDV may enable earlier identification of individuals at heightened risk and inform timely preventive strategies in patients with OSA-related systemic hypertension.

TwinAI: A digital twin and graph reinforcement learning framework for real-time management of water distribution networks

Spatial random field applications of soil properties integrated with finite element modeling tools are substantial in civil engineering to delineate stochastic characteristics of system responses that reflect real site conditions due to uncertainty. This research combines a random finite element model of a homogeneous hypothetical embankment dam’s hydraulic conductivity in the x and y directions and a stochastic upstream reservoir head on the upstream boundary. Statistical parameters of random hydraulic conductivities (mean, coefficient of variation, and horizontal–vertical scale of fluctuation) and probability distribution characteristics of stochastic boundary conditions are derived from available literature. The Karhunen–Loève expansion method is utilized in random field generation. Seepage fluxes and hydraulic gradients through the embankment dam are computed by Monte Carlo simulations. Sensitivity analyses are conducted to interpret the influences of correlation distances and coefficient of variation (COV) on the seepage flow through the embankment dam. Fully stochastic analyses of seepage also provide ranges of exceedance probability to evaluate piping risk conditions rather than assessing a single probability value. Results demonstrate that the effects of autocorrelation have minor importance when compared to COVs in both directions. It is of particular importance to compare fully stochastic seepage analysis for various scenarios and deterministic analysis to perform reliability-based design for decision-making processes.

Background incidence rates and observed-to-expected ratios of adverse events of special interest after covid-19 mRNA vaccination during pregnancy in France: a nationwide population-based study.

Lymphocyte-based inflammatory biomarkers during the postpartum period and postpartum depression symptoms in U.S. women.

Techno-economic assessment of the sorption enhanced methanation: Levelized cost of methane, performance indicators and sensitivity analysis

Comparative life cycle assessment of paper and cardboard based packaging solutions for e-commerce: A case study on a book application.

Effect of desktop virtual patient simulation on clinical reasoning skills of nursing students: A systematic review and meta-analysis.

Lung cancer is a heterogeneous and complex disease requiring multidisciplinary input for optimal management planning, with guidelines recommending that all patients be discussed in a multidisciplinary setting. Multidisciplinary meeting (MDM) discussion aims to enhance evidence-based management, improve treatment access, and optimize complex management plans. We aimed to assess the extent and impacts of MDM discussion in patients with lung cancer described by the Victorian Lung Cancer Registry from 2011 to 2023 in Victoria, Australia. We identified MDM-presented and nonpresented patients and assessed the impacts of MDM presentation. OR and survival hazard ratios were assessed using Cox proportional regression analysis. Survival analysis was determined using the Kaplan-Meier product-limit method. Sensitivity analyses were conducted using landmark analysis and propensity score matching methods. A total of 18,597 patients were included, of whom 67% had evidence of presentation to a lung cancer MDM, with MDM presentation increasing from 59.1% to 80.6% during the study period. MDM presentation was associated with higher levels of provision of guideline-concordant treatment in NSCLC (56.2% versus 44.5%, p < 0.001), and lower levels of no treatment (10.0% versus 21.4%, p < 0.001). Modifiable factors that could increase MDM presentation include referral of patients of older age, stage IV disease, SCLC, and diagnosis at a private or regional hospital. Propensity-matched survival analysis in NSCLC revealed a median survival of 1.1 years for MDM-presented versus 0.86 years for nonpresented individuals, providing a 12% reduction in mortality hazard (hazard ratio 0.88 [0.82-0.95], p < 0.001). During the period of activity of the Victorian Lung Cancer Registry, MDM presentation increased from 59.1% to 80.6%. Management outcomes in MDM-presented patients identified multiple underserved cohorts and revealed considerable increases in treatment modalities and guideline-concordant treatment in NSCLC in this observational study, with an associated 12% improvement in survival advantage overall.