Statistical Sensitivity Analysis Research Articles

Shear-Wave Velocity Model for the Dead Sea Transform from Multimode Inversion of Surface Waves Excited by the February 2023 Southeast Türkiye Earthquake Sequence

Abstract The dispersive nature of surface waves can be used for shear-wave velocity inversion at different scales. We show that four large earthquakes from the 2023 Türkiye earthquake sequence generate visible surface waves recorded by a dense strong-motion network deployed along the Dead Sea Transform (DST) in Israel. Thanks to favorable geometrical conditions and source radiation patterns, we observe both Rayleigh and Love waves that travel predominantly parallel to the network. We can reliably compute the dispersion of three Love-wave modes and two Rayleigh-wave modes. Using these dispersion curves, we invert for a 1D S-wave velocity model of the entire DST, outperforming an existing model. Statistical and kernel sensitivity analysis show high certainty down to a depth of 30 km thanks to the multimode joint inversion in the frequency band of 0.03–0.3 Hz. Using a multiwindow approach, we invert for an along-strike laterally varying velocity model of the DST. Although it is limited to the fundamental Love-wave mode, using the 1D model as a constraint allows us to recover a shallow (10 km) velocity structure in agreement with previous studies of the area. Despite the simplicity of our used approach, it can be used as a basis for more advanced studies.

Bioavailability of Oral Curcumin in Systematic Reviews: A Methodological Study.

Curcumin is a natural compound found in turmeric that exhibits diverse biological activities. However, its poor bioavailability limits its therapeutic application, which has led to the development of various bioavailability-improved formulations. In this methodological study, we analyzed whether systematic reviews on curcumin considered the bioavailability of systemic oral curcumin formulations when synthesizing evidence from human clinical trials. A total of 171 systematic reviews published between 2003 and 2022 were included in the study. From the included studies, we extracted data on study characteristics; type of curcumin; methods; and reporting regarding bioavailability, funding, and conflict of interest. Our results show that systematic reviews rarely consider the variable bioavailability of tested curcumin formulations. Relevant statistical subgroup and/or sensitivity analyses were reported in the methods and results of only 3.5% and 6.4% of reviews, respectively. However, more reviews mentioned bioavailability in their discussion (57%) or conclusion (13%). The detailed analysis of the included systematic reviews suggests that there is broad recognition of product bioavailability as a crucial factor affecting the health effects of curcumin, which is not accompanied by adequate evidence synthesis. Therefore, the results of most systematic reviews on orally administered curcumin should be taken with caution.

The citrate transporter SLC13A5 as a therapeutic target for kidney disease: evidence from Mendelian randomization to inform drug development

BackgroundSolute carrier family 13 member 5 (SLC13A5) is a Na+-coupled citrate co-transporter that mediates entry of extracellular citrate into the cytosol. SLC13A5 inhibition has been proposed as a target for reducing progression of kidney disease. The aim of this study was to leverage the Mendelian randomization paradigm to gain insight into the effects of SLC13A5 inhibition in humans, towards prioritizing and informing clinical development efforts.MethodsThe primary Mendelian randomization analyses investigated the effect of SLC13A5 inhibition on measures of kidney function, including creatinine and cystatin C-based measures of estimated glomerular filtration rate (creatinine-eGFR and cystatin C-eGFR), blood urea nitrogen (BUN), urine albumin-creatinine ratio (uACR), and risk of chronic kidney disease and microalbuminuria. Secondary analyses included a paired plasma and urine metabolome-wide association study, investigation of secondary traits related to SLC13A5 biology, a phenome-wide association study (PheWAS), and a proteome-wide association study. All analyses were compared to the effect of genetically predicted plasma citrate levels using variants selected from across the genome, and statistical sensitivity analyses robust to the inclusion of pleiotropic variants were also performed. Data were obtained from large-scale genetic consortia and biobanks, with sample sizes ranging from 5023 to 1,320,016 individuals.ResultsWe found evidence of associations between genetically proxied SLC13A5 inhibition and higher creatinine-eGFR (p = 0.002), cystatin C-eGFR (p = 0.005), and lower BUN (p = 3 × 10−4). Statistical sensitivity analyses robust to the inclusion of pleiotropic variants suggested that these effects may be a consequence of higher plasma citrate levels. There was no strong evidence of associations of genetically proxied SLC13A5 inhibition with uACR or risk of CKD or microalbuminuria. Secondary analyses identified evidence of associations with higher plasma calcium levels (p = 6 × 10−13) and lower fasting glucose (p = 0.02). PheWAS did not identify any safety concerns.ConclusionsThis Mendelian randomization analysis provides human-centric insight to guide clinical development of an SLC13A5 inhibitor. We identify plasma calcium and citrate as biologically plausible biomarkers of target engagement, and plasma citrate as a potential biomarker of mechanism of action. Our human genetic evidence corroborates evidence from various animal models to support effects of SLC13A5 inhibition on improving kidney function.

Impact of airfoil collar on scour reduction around the bridge pier

This paper investigates the effectiveness of four different airfoil collars (bc1, bc2,bc3, and bc4) in reducing scour around the bridge pier. A total of 69 experiments are conducted under two threshold velocities with two pier diameters of 0.05 and 0.06 m and four airfoil collars placed at four locations from the uniform sediment bed. This study investigates the scour hole profiles and their depth, effect of flow intensity, collar diameter, and location on scour depth, and computes the protection efficiencies. The results show that the collar effectively reduces the scour depth. When the collar is located at bed level (i.e., y = 0, where y is water depth from the bed), y/4, y/2, and 3 y/4 above the bed level, the protection efficacies are found to be ranging between the percentages 65–100%, 40–53%, 23–38%, and 8–29% for bc1, bc2,bc3, and bc4, respectively. An empirical relationship is proposed for variation of scour depth with respect to time. Statistical sensitivity analyses are performed and found that the most and least sensitive parameters are h/y and Tc, where h and Tc are the collar's location from the water surface and dimensionless time, respectively.

Interventions to treat patients with blood blister-like aneurysms of the internal carotid artery: a protocol for a network meta-analysis

IntroductionBlood blister-like aneurysm (BBA) is a special type of intracranial aneurysm with relatively low morbidity and high mortality. Various microsurgical techniques and endovascular approaches have been reported, but the optimal...

Comparing perioperative and oncological outcomes of transanal and laparoscopic total mesorectal excision for rectal cancer: a meta-analysis of randomized controlled trials and prospective studies.

Meta-analysis of the results of transanal total mesorectal excision (taTME) and laparoscopic TME (laTME) regarding perioperative and oncological outcomes have been conducted. Due to the lack of high-quality randomized controlled trials (RCTs) and prospective studies in the included literature, the conclusions are unreliable. This study included RCTs and prospective studies for analysis to obtain more reliable conclusions. Systematic searches of the PubMed, Embase, and Cochrane Library databases were conducted up to June 2023. To assess the quality, the Cochrane quality assessment tool and the Newcastle-Ottawa Scale were employed. The perioperative and oncological outcomes were then analyzed. The I2 statistic was used to evaluate statistical heterogeneity and sensitivity analyses was conducted. A total of 22 studies, comprising 5056 patients, were included in the analysis, of which 6 were RCTs and 16 were prospective studies. The conversion rate in the taTME group was significantly lower than that in the laTME group (OR 0.14, 95% CI 0.09 to 0.22, P < 0.01), and the circumferential resection margin (CRM) was longer (MD 0.99mm, 95% CI 0.66 to 1.32mm, P < 0.01), with a lower rate of positive CRM involvement (OR 0.68, 95% CI 0.47 to 0.97, P = 0.03). No statistically significant differences were found in terms of the operation time, intraoperative blood loss, complications, anastomotic leakage, uroschesis, obstruction, secondary operation, hospital stay, urethral injury, readmission, mortality rate within 30days, mesorectal resection quality, number of harvested lymph nodes, distal resection margin (DRM), positive DRM, local recurrence, and distance recurrence (P > 0.05). According to the findings of this meta-analysis, which is based on RCTs and prospective studies, taTME appears to have an advantage over laTME in terms of conversion rate and CRM involvement.

Genetically determined blood pressure, antihypertensive medications, and risk of intracranial aneurysms and aneurysmal subarachnoid hemorrhage: A Mendelian randomization study.

Observational studies suggest that different classes of antihypertensive drugs may have different effects on the occurrence of intracranial aneurysms (IA) and subarachnoid hemorrhage (SAH). However, the reported results in previous studies are inconsistent, and randomized data are absent. We performed a two-sample Mendelian randomization (MR) analysis to study the causal effects of genetically determined blood pressure (BP) and genetic proxies for antihypertensive drug classes on the risk of IA and SAH. Genetic instruments and outcome data were obtained from independent genome-wide association studies (GWAS) or published data, which were exclusively restricted to European ancestry. Causal relationships were identified using inverse-variance weighted MR analyses and a series of statistical sensitivity analyses. The FinnGen consortium was used for repeated analysis to verify results obtained from the above GWAS. Two-sample MR analysis showed that genetically determined Systolic BP, Dystolic BP, and Pulse Pressure were related to a higher risk of IA and SAH. Based on identified single nucleotide polymorphisms (SNPs) that influence the effect of calcium channel blockers (CCB, 42 SNPs), beta-blockers (BB, 8 SNPs), angiotensin-converting enzyme inhibitors (ACEI, 2 SNPs), angiotensin receptor blockers (ARB, 1 SNPs), and thiazides (5 SNPs), genetically determined effect of CCBs was associated with a higher risk of IA (OR, 1.07 [95% CI, 1.03-1.10], p = 5.02 × 10-5) and SAH (OR, 1.06 [95% CI, 1.03-1.09], p = 1.84 × 10-3). No associations were found between other antihypertensive drugs and the risk of IA or SAH. The effect of CCBs on SAH was confirmed in FinnGenconsortium samples (OR, 1.04 [95% CI, 1.00-1.08], p = 0.042). This MR analysis supports the role of elevated blood pressure in the occurrence of intracranial aneurysms and subarachnoid hemorrhage. However, genetic proxies for calcium channel blockers were associated with an increased risk of intracranial aneurysms and subarachnoid hemorrhage. Further studies are required to confirm these findings and investigate the underlying mechanisms.

The Effectiveness of Virtual Simulation in Knowledge of Nurses: A Protocol for Systematic Review and Meta-Analysis of Randomized Controlled Trials

Abstract:&#x0D; Background: Nursing education is evolving with technological advancements, including the adoption of virtual simulation. This protocol outlines a systematic review and meta-analysis aimed at evaluating the effectiveness of virtual simulation in improving nurses' knowledge.&#x0D; Methods: The study adheres to PRISMA guidelines and is registered in PROSPERO (registration number CRD42022352907). Eligible studies encompass randomized controlled trials (RCTs) that examine virtual simulation's impact on registered nurses, student nurses, or nursing professionals. The intervention involves various virtual simulation tools (virtual reality, augmented reality, serious games) compared against traditional methods or control groups. The primary outcome is improved nursing knowledge, measured through validated assessment tools. Methodological quality will be assessed using the Cochrane Risk of Bias tool.&#x0D; Results: Electronic databases (PubMed, Scopus, Web of Science, PsycINFO) will be systematically searched for eligible studies. The search strategy combines controlled vocabulary terms and keywords to ensure comprehensive retrieval. Two reviewers will independently screen titles, abstracts, and full texts. Data extraction will be standardized to collect study details, participant characteristics, intervention specifics, outcome measures, and findings related to knowledge enhancement.&#x0D; Analysis: Quantitative synthesis (meta-analysis) will be conducted if sufficient homogeneity exists among the included studies. Heterogeneity will be assessed using statistical tests, with subgroup and sensitivity analyses for further exploration. The GRADE approach will assess evidence quality and recommendation strength, considering bias risk, heterogeneity, indirectness, precision, and publication bias.&#x0D; Conclusion: The systematic review aims to provide evidence-based insights into the impact of virtual simulation on nurses' knowledge enhancement. By synthesizing data from RCTs, the study intends to guide educational practices and policy decisions for optimizing nursing education through innovative methods.

Methods for controlling and evaluating residual confounding in the association analysis of observational study with a multicenter database

The observational research based on big data in healthcare has attracted increasing attention, with the control and evaluation of residual confounding being the critical issue that needs to be solved urgently. This review summarized the methods for statistical adjustment and sensitivity analysis of residual confounding in the association analysis with a multicenter database. Based on individual-level data, the residual confounding can be adjusted in each subcenter using methods such as regression discontinuity design, while the pooled estimate can be obtained as a weighted average. Based on the center-level results, the Bayesian Meta-analysis method can adjust the pooled estimates. The sensitivity analysis of residual confounding can also be carried out using center-level data to calculate the E-value, p^(q), T^(r, q) and G^r,q. The abovementioned methods should be selected reasonably according to the requirements for practical applications, advantages, and disadvantages. For example, the use of subcenter individual data for residual confounding adjustment usually needs strict study design and frequent coordination; the Bayesian Meta-analysis is based on some strong assumptions; the interpretation of the results in the sensitivity analysis, such as E-value requires professional judgment to assess the risk of residual confounding. Therefore, the methods for controlling and evaluating residual confounding in association analysis based on multicenter databases still need further development and improvement.

The interactions between host genome and gut microbiome increase the risk of psychiatric disorders: Mendelian randomization and biological annotation

BackgroundThe correlation between human gut microbiota and psychiatric diseases has long been recognized. Based on the heritability of the microbiome, genome-wide association studies on human genome and gut microbiome (mbGWAS) have revealed important host-microbiome interactions. However, establishing causal relationships between specific gut microbiome features and psychological conditions remains challenging due to insufficient sample sizes of previous studies of mbGWAS. MethodsCross-cohort meta-analysis (via METAL) and multi-trait analysis (via MTAG) were used to enhance the statistical power of mbGWAS for identifying genetic variants and genes. Using two large mbGWAS studies (7,738 and 5,959 participants respectively) and12 disease-specific studies from the Psychiatric Genomics Consortium (PGC), we performed bidirectional two-sample mendelian randomization (MR) analyses between microbial features and psychiatric diseases (up to 500,199 individuals). Additionally, we conducted downstream gene- and gene-set-based analyses to investigate the shared biology linking gut microbiota and psychiatric diseases. ResultsMETAL and MTAG conducted in mbGWAS could boost power for gene prioritization and MR analysis. Increases in the number of lead SNPs and mapped genes were witnessed in 13/15 species and 5/10 genera after using METAL, and MTAG analysis gained an increase in sample size equivalent to expanding the original samples from 7% to 63%. Following METAL use, we identified a positive association between Bacteroides faecis and ADHD (OR, 1.09; 95 %CI, 1.02–1.16; P = 0.008). Bacteroides eggerthii and Bacteroides thetaiotaomicron were observed to be positively associated with PTSD (OR, 1.11; 95 %CI, 1.03–1.20; P = 0.007; OR, 1.11; 95 %CI, 1.01–1.23; P = 0.03). These findings remained stable across statistical models and sensitivity analyses. No genetic liabilities to psychiatric diseases may alter the abundance of gut microorganisms.Using biological annotation, we identified that those genes contributing to microbiomes (e.g., GRIN2A and RBFOX1) are expressed and enriched in human brain tissues. ConclusionsOur statistical genetics strategy helps to enhance the power of mbGWAS, and our genetic findings offer new insights into biological pleiotropy and causal relationship between microbiota and psychiatric diseases.

Comparison of surgical strategies in patients with chronic subdural haematoma: a protocol for a network meta-analysis

IntroductionChronic subdural haematoma (CSDH) is one of the most common neurosurgical emergencies, especially in the elderly population. Surgery is the mainstay of treatment for CSDH. Some studies have suggested that...

A study on the collapse characteristics of loess based on energy spectrum superposition method

Mineral types form the basis for studying the structural stability of loess, and identifying mineral types at the microscopic scale has always been a difficult task. Identifying mineral types at the microscopic scale is very helpful in understanding the differential role that different minerals play in the structural stability of loess, and it can also clarify the specific mineral changes that occur during the process of humidification and dehumidification. Using an innovative energy spectrum superposition method, this article combines backscattered electron imaging and X-ray energy spectrum analysis results to achieve direct identification of the eight main minerals in loess, including quartz, illite, and chlorite, within SEM images. The mineral identification results provide a basis for statistical analysis of mineral water sensitivity and morphological changes under wetting conditions. The results demonstrate that chlorite and hematite, which account for no more than 23% of the loess composition, play a crucial role in binding. Furthermore, these minerals exhibit significant hydrolysis phenomena. Particularly, the intense decomposition of chlorite leads to the displacement of non-binding quartz and feldspar particles, thereby altering the pore structure of loess. These findings are of great significance in understanding the multi-level collapsibility of loess.

A critical review on performance of buried pipeline subjected to pipe bursting and earthquake induced permanent ground deformation

The primary means of transportation for various substances including water, oil and natural gas are the nation’s pipelines. From the geotechnical perspective, one of the prime reasons for buried pipeline failure is the impact of ground deformation either resulting from the earthquake (viz. landslide, lateral spreading, fault movement), or from nearby pipe bursting operation. Failure of a pipeline can lead to an explosion, environmental contamination, fire, financial loss, and risk to living beings. Hence, it is crucial to design the buried pipeline considering the impact of potential earth movement. In this regard, the current review article highlighted the impact of seismic landslide and other possible patterns of ground deformation on buried pipeline along with the effect of pipe bursting induced ground movement on surrounding pipeline particularly focusing on analytical works. In addition, a statistical sensitivity analysis is also performed to identify the most influencing pipe-soil input design parameters.

FACE VALIDATION IN LARGE-SCALE SIMULATION PROJECTS

Face validation is an informal type of validation, usually applied in the early stages of a simulation project or model development process. Face validation is used to determine the reasonableness of a model or simulation when advanced validation methods such as statistical analysis or sensitivity analysis are not applicable. In large-scale simulation projects such as warfare simulation applications, which consist of a large number and variety of models that cannot be evaluated independently and contain high levels of uncertainty, face validation should be utilized, but no standard method for face validation can be proposed. In this paper, we review the literature and practical applications of face validation. We propose a process to improve the effectiveness of face validation. The proposed process is expected to help to realize a measurable, concrete and practical face validation, especially in large-scale projects involving high-fidelity complex models and constructive simulations.

Factors associated with interstitial lung disease in patients with rheumatoid arthritis: A systematic review and meta-analysis.

Interstitial lung disease (ILD) is frequent in patients with rheumatoid arthritis (RA) and is a potentially life-threatening complication with significant morbidity and mortality. This meta-analysis aims to systematically determine the factors associated with the development of rheumatoid arthritis-related interstitial lung disease (RA-ILD). All primary studies which reported the factors associated with of RA-ILD were eligible for the review except case reports. The Cochrane Library, PubMed, Embase, Web of Science, Chinese Biological Medicine Database (CBM), China National Knowledge Infrastructure (CNKI), and WANFANG electronic databases were searched through to December 30, 2022, for studies investigating the factors associated with RA-ILD. The methodological quality assessment of the eligible studies was performed using the Newcastle-Ottawa Scale (NOS). 2 reviewers extracted relevant data independently. Then, weighed mean differences (WMDs) or pooled odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were obtained for the relationships between the factors and RA-ILD. The statistical meta-analysis, subgroup and sensitivity analyses were performed using the Review Manager 5.3, and publication bias with Egger's test were performed using the Stata12.0 software. A total of 22 articles were screened for a meta-analysis which involved 1887 RA-ILD patients and 8066 RA without ILD patients. Some identified factors that were associated with an increased risk of RA-ILD included male sex (OR = 1.92, 95% CI: 1.54-2.39; P < 0.00001), older age (WMD = 5.77 years, 95% CI: 3.50-8.04; P < 0.00001), longer duration of RA (WMD = 0.80 years, 95% CI 0.12-1.47; P = 0.02), older age at onset of RA (WMD = 6.41 years, 95% CI: 3.17-9.64; P = 0.0001), smoking (OR = 1.69, 95% CI: 1.30-2.18; P < 0.0001). Five factors of laboratory items associated with the development of RA-ILD were evaluated in the meta-analysis. Compared with RA without ILD patients, positive rheumatoid factor (RF) (OR = 1.72, 95% CI: 1.47-2.01; P < 0.00001) and positive anti-citrullinated protein antibodies (ACPA) (OR = 1.58, 95% CI: 1.31-1.90; P < 0.00001) increased the risk of RA-ILD. Meanwhile, RF titer (WMD = 183.62 (IU/mL), 95% CI: 66.94-300.30; P = 0.002) and ACPA titer (WMD = 194.18 (IU/mL), 95% CI: 115.89-272.47; P < 0.00001) were significantly associated with increased risk of RA-ILD. Elevated erythrocyte sedimentation rate (ESR) (WMD = 7.41 (mm/h), 95% CI: 2.21-12.61; P = 0.005) and C-reactive protein (CRP) (WMD = 4.98 (mg/L), 95% CI: 0.76-9.20; P = 0.02) were also significantly associated with the development of the RA-ILD, whereas antinuclear antibody (ANA) positive status was not significantly associated with increased risk of RA-ILD (OR = 1.27, 95% CI: 1.00-1.60; P = 0.05). This meta-analysis showed that male gender, older age, longer duration of RA, older age at onset of RA, smoking, positive RF, positive ACPA, elevated RF titer, elevated ACPA titer, higher ESR and higher CRP were associated with RA-ILD.

Comparison Study of FNAC Using the Milan System Cytopathology versus Definitive Histology for the Diagnosis of Salivary Gland Tumors

Introduction: Salivary gland tumors (SGT) represent 6 to 8 percent of head and neck tumors. The cytologic diagnosis of SGT is performed by fine-needle aspiration cytology (FNAC) with variable sensitivity and specificity. The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) categorizes the cytological results and provides the risk of malignancy (ROM). The aim of our study was to evaluate the cytological findings with the definitive pathological findings to assess the sensitivity, specificity, and diagnostic accuracy of FNAC in SGT according to MSRSGC classification. Method: An observational, retrospective, single-center study was carried out at a tertiary referral hospital over a period of 10 years. Patients that underwent FNAC for major SGT and that have undergone surgery to remove the tumor were included. A histopathological follow-up was performed on the surgically excised lesions. Results from the FNAC were categorized into one of the six MSRSGC categories. The sensitivity, specificity, positive and negative predictive values, and diagnostic accuracy of FNAC for determining benign and malignant cases were calculated. Results: A total of 417 cases were analyzed. The cytological prediction of ROM was 10% in nondiagnostic, 12.12% in non-neoplastic, 3.58% in neoplasm benign group, 60% in AUS and SUMP groups, and 100% in suspicious and malignant group. The statistical analysis of sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy for determining benign cases was 99%, 55%, 94%, 93%, and 94%, respectively, and for determining malignant neoplasm was 54%, 99%, 93%, 94%, and 94%, respectively. Conclusion: In our hands, MSRSGC is highly sensitive for benign tumors and highly specific for malignant tumors. The low sensitivity to differentiate malignant from benign cases makes it necessary to apply an adequate anamnesis, physical examination, and imaging tests to consider surgical treatment in most cases.

Statistical prediction and sensitivity analysis of kinetic rate constants for efficient thermal valorization of plastic waste into combustible oil and gases

Sensitivity analyses of rate constants for chemical kinetics of the pyrolysis reaction are essential for the efficient valorization of plastic waste into combustible liquids and gases. Finding the role of individual rate constants can provide important information on the process conditions, quality, and quantity of the pyrolysis products. The reaction temperature and time can also be reduced through these analyses. For sensitivity analysis, one possible approach is to estimate the kinetic parameters using MLRM (multiple linear regression model) in SPSS. To date, no research reports on this research gap are documented in the published literature. In this study, MLRM is applied to kinetic rate constants, which slightly differ from experimental data. The experimental and statistically predicted rate constants varied up to 200% from their original values to perform sensitivity analysis using MATLAB software. The product yield was examined after 60 min of thermal pyrolysis at a fixed temperature of 420 °C. The predicted rate constant “k(8)” with a slight difference of 0.02 and 0.04 from the experiment revealed 85% oil yield and 40% light wax after 60 min of operation. The heavy wax was missing from the products under these conditions. This rate constant can be utilized to maximize the commercial-scale extraction of liquids and light waxes from thermal pyrolysis of plastics.

Deriving Thresholds of Object-Oriented Metrics to Predict Defect-Proneness of Classes: A Large-Scale Meta-Analysis

Many studies have explored the methods of deriving thresholds of object-oriented (i.e. OO) metrics. Unsupervised methods are mainly based on the distributions of metric values, while supervised methods principally rest on the relationships between metric values and defect-proneness of classes. The objective of this study is to empirically examine whether there are effective threshold values of OO metrics by analyzing existing threshold derivation methods with a large-scale meta-analysis. Based on five representative threshold derivation methods (i.e. VARL, ROC, BPP, MFM, and MGM) and 3268 releases from 65 Java projects, we first employ statistical meta-analysis and sensitivity analysis techniques to derive thresholds for 62 OO metrics on the training data. Then, we investigate the predictive performance of five candidate thresholds for each metric on the validation data to explore which of these candidate thresholds can be served as the threshold. Finally, we evaluate their predictive performance on the test data. The experimental results show that 26 of 62 metrics have the threshold effect and the derived thresholds by meta-analysis achieve promising results of GM values and significantly outperform almost all five representative (baseline) thresholds.

Modeling identifies variability in SARS-CoV-2 uptake and eclipse phase by infected cells as principal drivers of extreme variability in nasal viral load in the 48 h post infection

The SARS-CoV-2 coronavirus continues to evolve with scores of mutations of the spike, membrane, envelope, and nucleocapsid structural proteins that impact pathogenesis. Infection data from nasal swabs, nasal PCR assays, upper respiratory samples, ex vivo cell cultures and nasal epithelial organoids reveal extreme variabilities in SARS-CoV-2 RNA titers within and between the variants. Some variabilities are naturally prone to clinical testing protocols and experimental controls. Here we focus on nasal viral load sensitivity arising from the timing of sample collection relative to onset of infection and from heterogeneity in the kinetics of cellular infection, uptake, replication, and shedding of viral RNA copies. The sources of between-variant variability are likely due to SARS-CoV-2 structural protein mutations, whereas within-variant population variability is likely due to heterogeneity in cellular response to that particular variant. With the physiologically faithful, agent-based mechanistic model of inhaled exposure and infection from (Chen et al., 2022), we perform statistical sensitivity analyses of the progression of nasal viral titers in the first 0–48 h post infection, focusing on three kinetic mechanisms. Model simulations reveal shorter latency times of infected cells (including cellular uptake, viral RNA replication, until the onset of viral RNA shedding) exponentially accelerate nasal viral load. Further, the rate of infectious RNA copies shed per day has a proportional influence on nasal viral load. Finally, there is a very weak, negative correlation of viral load with the probability of infection per virus-cell encounter, the model proxy for spike-receptor binding affinity.

Predicting and validating the load-settlement behavior of large-scale geosynthetic-reinforced soil abutments using hybrid intelligent modeling

Settlement prediction of geosynthetic-reinforced soil (GRS) abutments under service loading conditions is an arduous and challenging task for practicing geotechnical/civil engineers. Hence, in this paper, a novel hybrid artificial intelligence (AI)-based model was developed by the combination of artificial neural network (ANN) and Harris hawks’ optimisation (HHO), that is, ANN-HHO, to predict the settlement of the GRS abutments. Five other robust intelligent models such as support vector regression (SVR), Gaussian process regression (GPR), relevance vector machine (RVM), sequential minimal optimisation regression (SMOR), and least-median square regression (LMSR) were constructed and compared to the ANN-HHO model. The predictive strength, relalibility and robustness of the model were evaluated based on rigorous statistical testing, ranking criteria, multi-criteria approach, uncertainity analysis and sensitivity analysis (SA). Moreover, the predictive veracity of the model was also substantiated against several large-scale independent experimental studies on GRS abutments reported in the scientific literature. The acquired findings demonstrated that the ANN-HHO model predicted the settlement of GRS abutments with reasonable accuracy and yielded superior performance in comparison to counterpart models. Therefore, it becomes one of predictive tools employed by geotechnical/civil engineers in preliminary decision-making when investigating the in-service performance of GRS abutments. Finally, the model has been converted into a simple mathematical formulation for easy hand calculations, and it is proved cost-effective and less time-consuming in comparison to experimental tests and numerical simulations.