Lower Confidence Limit Research Articles

Gender and Age Analyses of NIRS/STAI Pearson Correlation Coefficients at Resting State.

According to the valence asymmetry hypothesis, the left/right asymmetry of PFC activity is correlated with specific emotional responses to mental stress and personality traits. In a previous study we measured spontaneous oscillation of oxy-Hb concentrations in the bilateral PFC at rest in normal adults employing two-channel portable NIRS and computed the laterality index at rest (LIR). We investigated the Pearson correlation coefficient between the LIR and anxiety levels evaluated by the State-Trait Anxiety Inventory (STAI) test. We found that subjects with right-dominant activity at rest showed higher STAI scores, while those with left dominant oxy-Hb changes at rest showed lower STAI scores such that the Pearson correlation coefficient between LIR and STAI was positive. This study performed Bootstrap analysis on the data and showed the following statistics of the target correlation coefficient: mean=0.4925 and lower confidence limit=0.177 with confidence level 0.05. Using the KS-test, we demonstrated that the correlation did not depend on age, whereas it did depend on gender.

Risk Assessment of Dietary Exposure to Aflatoxin Contamination in Spices

This study highlights the daily consumption of spices in human diet and the potential of aflatoxin B1 (AFBI) contamination which attributable to the risk of developing liver cancer. All the AFBI contamination data in spices from various studies in Malaysia were considered for calculation of risk assessment by dietary exposure and margin of exposure (MOE). The mean dietary exposure to AFB1 ranges from 0.21-1.32 ng/kg-bw/day (overall mean, 0.59 ng/kgbw/ day), and 12.27 ng/kg-bw/day was the highest reported level of AFBI contamination. The MOEs derived from these dietary exposures at a benchmark dose lower confidence limit (BMDL10) of 0.305 μg/kg-bw/day were 230-1,450 (overall mean, 520). The MOE of less than 10,000 indicates the risk of AFBI contamination in spices should be a high priority for risk management actions. Based on the tolerable daily intake (TDI) in Asia of 0.11-0.19 ng AFB1/kg-bw/day for liver, the overall mean of 0.59 ng/kg-bw/day represents 3-536% of this TDI. Population risk for primary liver cancer attributable to AFB1 contamination in spices were 0.01-0.03 (0.1-0.7%) and 0-0.31 (0-6%) cancers/year/100,000 population, for mean and range of exposures. The risk, which was less than 1 cancer case/year/100,000 population, suggested that Malaysian population is not significantly at risk.

Estimation in discrete reliability growth, a growth model with coefficient condition

This paper considers the well known problem of estimating reliability in discrete reliability growth context with sequence of dichotomous success-failure outcomes. More precisely, the authors generalize the simple order relationship constraint with some coefficients. The authors prove that under some mild conditions, the generalized constraint MLE problem can be transformed to a traditional isotonic problem. The authors also study the lower confidence limit estimation of reliability with sample space ranking method. A simulation is conducted to illustrate the superiority of the proposed method.

Dietary exposure of acrylamide from the fifth Chinese Total Diet Study

The levels of acrylamide in 240 food composite samples from the 5th Chinese Total Diet Study (TDS) were measured using an LC-MS/MS method and the exposure estimates for the general population were evaluated. The samples were collected from 20 provinces in China, covering about two thirds of the Chinese population. Acrylamide was detected in 40.0% of composite samples with the concentrations ranged from 0.8 to 211.8 μg/kg. The average dietary intakes from the 5th Chinese TDS were 0.319 μg kg−1 bw day−1 and an increase with about 70% was observed from the 3rd Chinese TDS in 2000 to the 5th Chinese TDS between 2009 and 2012. The main food group contributors to acrylamide exposure were vegetables (35.2%), cereals (34.3%) and potatoes (15.7%). Based on the benchmark dose lower confidence limit at 10% risk (BMDL10) of 0.31 mg kg−1 bw day−1 for the induction of mammary tumors in rats and 0.18 mg kg−1 bw day−1 for Harderian gland tumors in mice, the margins of exposure (MOEs) were 973 and 565 for Chinese general population, respectively. These MOEs indicate a human health concern.

The "Fourth Mission": The Time Commitment of Anesthesiology Faculty for Management Is Comparable to Their Time Commitments to Education, Research, and Indirect Patient Care.

Academic anesthesia departments have management responsibilities (e.g., coordinating sedation, directing the operating rooms [ORs], informatics, ongoing professional performance evaluation, staff scheduling, and workroom inventory management). For each of the 64 faculty, a survey sampled 10 weekdays and 4 weekend days of professional activity over N=56 days. Faculty time in managerial activities was 126% of time spent on education, 107% of time spent in research, and 112% of time spent on mandatory indirect clinical support (e.g., fire safety training). The 95% lower confidence limits calculated using Fieller's theorem were 107%, 89%, and 91%, respectively. Corresponding bootstrap limits were 107%, 89%, and 90%, respectively. Thus, although our College of Medicine tripartite mission includes clinical care, education, and research, administrative activities constitute a "fourth mission" of our department.

Development of an inhalation unit risk factor for isoprene

A unit risk factor (URF) was developed for isoprene based on evaluation of three animal studies with adequate data to perform dose–response modeling (NTP, 1994, 1999; Placke et al., 1996). Ultimately, the URF of 6.2E-08 per ppb (2.2E-08 per μg/m3) was based on the 95% lower confidence limit on the effective concentration corresponding to 10% extra risk for liver carcinoma in male B6C3F1 mice after incorporating appropriate adjustment factors for species differences in target tissue metabolite concentrations and inhalation dosimetry. The corresponding lifetime air concentration at the 1 in 100,000 no significant excess risk level is 160 ppb (450 μg/m3). This concentration is almost 4400 times lower than the lowest exposure level associated with statistically increased liver carcinoma in B6C3F1 mice in the key study (700 ppm in Placke et al., 1996) and is above typical isoprene breath concentrations reported in the scientific literature. Continuous lifetime environmental exposure to the 1 in 100,000 excess risk level of 160 ppb would be expected to raise the human blood isoprene area under the curve (AUC) less than one-third of the standard deviation of the endogenous mean blood AUC. The mean for ambient air monitoring sites in Texas (2005–2014) is approximately 0.13 ppb.

Case Sequencing of Diagnostic Imaging Studies Performed Under General Anesthesia or Monitored Anesthesia Care During Nights and Weekends.

General anesthesia or monitored anesthesia care sometimes is provided in nonoperating room (OR) locations during nights and weekends (e.g., for magnetic resonance imaging [MRI] or computerized tomography [CT]). Rational and consistent scheduling and sequencing decisions for these diagnostic imaging procedures, including coordination with OR cases, cannot be done without knowing how long each case can wait to be started without risking a worsening of the patient's condition. We reviewed the medical records of the 81 patients who underwent diagnostic imaging procedures (78 = MRI, 3 = CT scan) under general anesthesia or monitored anesthesia care either on weekends or between 6 pm and 6 am at the University of Iowa Hospitals between March 2012 and February 2014. For 77.8% of patients, the indications could have changed clinical management within 4 hours (N = 63/81). Among the 63 imaging studies with potential immediate impact, there was documentation of results having been communicated to the treating team within 4 hours of the completion of imaging for 39 of the patients. Among the 39 patients, 15 promptly received medications or underwent procedures based on the imaging results. Thus, 15 of the 81 patients had a change in care (18.5%, 95% lower confidence limit = 11.2%). Our results are important since we showed previously that it is not possible to make rational and consistent decisions in case sequencing without knowing how long each case (including diagnostic imaging procedures) can wait to be started without a change in the patient's risk. The scheduled surgical procedure itself provides sufficient information to assess safe waiting times to start add-on cases (e.g., appendectomy). In contrast, MRI provides no context as to how potential findings will influence treatment. Our results show that the assumption cannot reasonably be made when sequencing cases that all imaging studies can or cannot wait longer than pending surgical procedures. Our results show that, for evidence-based OR management decision-making, information to decide appropriate waiting should be obtained electronically or verbally for each imaging study.

Process Capability Assessment for Asymmetric Tolerances with Consideration of Gauge Measurement Errors

In recent years, the issue of process capability assessment in the presence of gauge measurement errors (GME) for cases with symmetric tolerances was investigated enthusiastically. However, even processes with symmetric tolerances are very common in practical situations, cases of asymmetric tolerances also occur in manufacturing industries. In this article, a novel approach, called the generalized confidence interval (GCI) approach, is applied to assess the capabilities of processes with asymmetric tolerances in the presence of the GME. To examine the performance of the proposed approach, an exhaustive simulation was conducted. The conclusion is that the proposed approach appears quite satisfactorily for assessing process performance with asymmetric tolerances in the presence of GME in terms of the coverage rate (CR) and the average value of the generalized lower confidence limits.

Levels and daily intake of lead (Pb) and six essential elements in gari samples from Ondo State, Southwest Nigeria: A potential risk factor of health status

Gari, a staple food in most West African countries is a processed product of cassava plant. It supplies about 70% of the daily calorie intake in these countries. In this study, levels of lead (Pb), zinc (Zn), manganese (Mn), cobalt (Co), copper (Cu), calcium (Ca) and iron (Fe) in gari samples that were collected from four major Nigerian cities: Akure, Ondo, Isua and Ore – all located in Ondo State, Southwest, Nigeria were determined. The estimated daily intakes (EDI) of these elements were determined and compared to the recommended dietary intake limits or requirements. The mean concentrations of Pb in gari samples was 0.16±0.09mg/kg while for essential elements the concentrations were 4.13±0.95, 0.00497±0.00078, 12.98±1.48, 1.01±0.47, 512.6±9.12 and 23.22±2.32mg/kg for Zn, Mn, Co, Cu, Ca and Fe, respectively. The mean estimated dietary intakes were 0.0333±0.00443, 0.88±0.21, 1.06±0.36, 0.00278±0.00068, 0.22±0.04, 109.7±4.22 and 4.97±1.07mg/day for Pb, Zn, Mn, Co, Cu, Ca and Fe respectively. The estimated mean Pb dietary intake from gari consumption alone was almost the same as the benchmark dose lower confidence limit (BMDL) for Pb, thus inferring that dietary route is a potential source of Pb contamination for gari consumers in Southwest Nigerian. Also, the data from this study indicated that gari is a good source of some essential elements like Mn, Co, and Cu but not exceptionally rich in Zn, Fe and Ca. It is therefore recommended that gari diets should be complemented with other food substances like beef, vegetables and low fat cheese that are good sources of the deficient elements.

Low-Sodium Versus Standard-Sodium Peritoneal Dialysis Solution in Hypertensive Patients: A Randomized Controlled Trial

Peritoneal dialysis (PD) solutions with reduced sodium content may have advantages for hypertensive patients; however, they have lower osmolarity and solvent drag, so the achieved Kt/Vurea may be lower. Furthermore, the increased transperitoneal membrane sodium gradient can influence sodium balance with consequences for blood pressure (BP) control. Prospective, randomized, double-blind clinical trial to prove the noninferiority of total weekly Kt/Vurea with low-sodium versus standard-sodium PD solution, with the lower confidence limit above the clinically accepted difference of -0.5. Hypertensive patients (≥ 1 antihypertensive drug, including diuretics, or office systolic BP ≥ 130 mmHg) on continuous ambulatory PD therapy from 17 sites. 108 patients were randomly assigned (1:1) to 6-month treatments with either low-sodium (125 mmol/L of sodium; 1.5%, 2.3%, or 4.25% glucose; osmolarity, 338-491 mOsm/L) or standard-sodium (134 mmol/L of sodium; 1.5%, 2.3%, or 4.25% glucose; osmolarity, 356-509 mOsm/L) PD solution. Primary end point: weekly total Kt/Vurea; secondary outcomes: BP control, safety, and tolerability. Total Kt/Vurea was determined from 24-hour dialysate and urine collection; BP, by office measurement. Total Kt/Vurea after 12 weeks was 2.53 ± 0.89 in the low-sodium group (n = 40) and 2.97 ± 1.58 in the control group (n = 42). The noninferiority of total Kt/Vurea could not be confirmed. There was no difference for peritoneal Kt/Vurea (1.70 ± 0.38 with low sodium, 1.77 ± 0.44 with standard sodium), but there was a difference in renal Kt/Vurea (0.83 ± 0.80 with low sodium, 1.20 ± 1.54 with standard sodium). Mean daily sodium removal with dialysate at week 12 was 1.188 g higher in the low-sodium group (P < 0.001). BP changed marginally with standard-sodium solution, but decreased with low-sodium PD solution, resulting in less antihypertensive medication. Broader variability of study population than anticipated, particularly regarding residual kidney function. The noninferiority of the low-sodium PD solution for total Kt/Vurea could not be proved; however, it showed beneficial clinical effects on sodium removal and BP.

The causal effect of education on HIV stigma in Uganda: Evidence from a natural experiment

RationaleHIV is highly stigmatized in sub-Saharan Africa. This is an important public health problem because HIV stigma has many adverse effects that threaten to undermine efforts to control the HIV epidemic. ObjectiveThe implementation of a universal primary education policy in Uganda in 1997 provided us with a natural experiment to test the hypothesis that education is causally related to HIV stigma. MethodsFor this analysis, we pooled publicly available, population-based data from the 2011 Uganda Demographic and Health Survey and the 2011 Uganda AIDS Indicator Survey. The primary outcomes of interest were negative attitudes toward persons with HIV, elicited using four questions about anticipated stigma and social distance. ResultsStandard least squares estimates suggested a statistically significant, negative association between years of schooling and HIV stigma (each P < 0.001, with t-statistics ranging from 4.9 to 14.7). We then used a natural experiment design, exploiting differences in birth cohort exposure to universal primary education as an instrumental variable. Participants who were <13 years old at the time of the policy change had 1.36 additional years of schooling compared to those who were ≥13 years old. Adjusting for linear age trends before and after the discontinuity, two-stage least squares estimates suggested no statistically significant causal effect of education on HIV stigma (P-values ranged from 0.21 to 0.69). Three of the four estimated regression coefficients were positive, and in all cases the lower confidence limits convincingly excluded the possibility of large negative effect sizes. These instrumental variables estimates have a causal interpretation and were not overturned by several robustness checks. ConclusionWe conclude that, for young adults in Uganda, additional years of education in the formal schooling system driven by a universal primary school intervention have not had a causal effect on reducing negative attitudes toward persons with HIV.

Estimation of the benchmark dose of urinary cadmium as the reference level for renal dysfunction: a large sample study in five cadmium polluted areas in China

BackgroundItai-itai disease primarily results from cadmium (Cd) exposure and is known as one of the four major pollution diseases in Japan. Cd pollution is more serious in several areas of China than in Japan. However, there is still a lack of information regarding the threshold level of Cd exposure for the adverse health effects in the general Chinese population. This study aims to evaluate the reference value of urinary Cd (UCd) for renal dysfunction in a Chinese population as the benchmark dose lower confidence limit (BMDL) based on a large sample survey.MethodsA total of 6103 participants who lived in five Cd polluted areas of China participated in this study. We analyzed UCd levels as a biomarker of exposure and urinary β2-microglobulin (Uβ2-MG) levels as a renal tubular effect biomarker. The BMD studies were performed using BMD software. The benchmark response (BMR) was defined as a 10 % additional risk above the background.ResultsThere was a positive correlation between the UCd levels and the prevalence of Uβ2-MG. The BMD of UCd for Uβ2-MG was estimated for each province. The findings showed that the BMD levels were related to the participants’ geographic region, which may be partially due to the large differences in Cd exposure level, ethnic group, lifestyle and diet of the sample population in these study areas. The reference level of UCd for the renal effects was further evaluated by combining the five sets of data from all 6103 subjects. The overall BMDLs of UCd for Uβ2-MG with an excess risk of 10 % were 2.00 μg/g creatinine (μg/g cr) in males and 1.69 μg/g cr in females, which were significantly lower than the World Health Organization (WHO) threshold level of 5 μg/g cr for Cd-related renal effects.ConclusionsThe selection of the sample population and geographic region affected the BMDL evaluation. Based on the findings of this survey of a large sample population, the UCd BMDLs for Uβ2-MG in males with BMRs at 10 % were 2.00 μg/g cr. The BMD was slightly lower in females, which indicated that females may be relatively more sensitive to Cd exposure than males.

Confidence bounds for nonlinear dose-response relationships.

An important aim of drug trials is to characterize the dose-response relationship of a new compound. Such a relationship can often be described by a parametric (nonlinear) function that is monotone in dose. If such a model is fitted, it is useful to know the uncertainty of the fitted curve. It is well known that Wald confidence intervals are based on linear approximations and are often unsatisfactory in nonlinear models. Apart from incorrect coverage rates, they can be unreasonable in the sense that the lower confidence limit of the difference to placebo can be negative, even when an overall test shows a significant positive effect. Bootstrap confidence intervals solve many of the problems of the Wald confidence intervals but are computationally intensive and prone to undercoverage for small sample sizes. In this work, we propose a profile likelihood approach to compute confidence intervals for the dose-response curve. These confidence bounds have better coverage than Wald intervals and are more precise and generally faster than bootstrap methods. Moreover, if monotonicity is assumed, the profile likelihood approach takes this automatically into account. The approach is illustrated using a public dataset and simulations based on the Emax and sigmoid Emax models.

Study on probability plot correlation coefficient of the log-Weibull distribution

The log-Weibull distribution is a variant of the three-parameter Weibull distribution. The probability plot of a distribution model is desired since it can help to decide on whether the model is appropriate for fitting a given dataset and can provide the initial estimate of the model parameters. The decision on the appropriateness of a distribution is somehow subjective. This paper presents a probability plot of the log-Weibull distribution (LWPP). The distribution of the probability plot correlation coefficient is studied. From this distribution, a lower confidence limit is determined for determining whether the probability plot correlation coefficient derived from a given data set is large enough. The appropriateness and usefulness of this study are illustrated by two real-world examples.

Benchmark Dose for Urinary Cadmium based on a Marker of Renal Dysfunction: A Meta-Analysis.

BackgroundLow doses of cadmium can cause adverse health effects. Benchmark dose (BMD) and the one-sided 95% lower confidence limit of BMD (BMDL) to derive points of departure for urinary cadmium exposure have been estimated in several previous studies, but the methods to derive BMD and the estimated BMDs differ.ObjectivesWe aimed to find the associated factors that affect BMD calculation in the general population, and to estimate the summary BMD for urinary cadmium using reported BMDs.MethodsA meta-regression was performed and the pooled BMD/BMDL was estimated using studies reporting a BMD and BMDL, weighted by sample size, that were calculated from individual data based on markers of renal dysfunction.ResultsBMDs were highly heterogeneous across studies. Meta-regression analysis showed that a significant predictor of BMD was the cut-off point which denotes an abnormal level. Using the 95th percentile as a cut off, BMD5/BMDL5 estimates for 5% benchmark responses (BMR) of β2-microglobulinuria (β2-MG) estimated was 6.18/4.88 μg/g creatinine in conventional quantal analysis and 3.56/3.13 μg/g creatinine in the hybrid approach, and BMD5/BMDL5 estimates for 5% BMR of N-acetyl-β-d-glucosaminidase (NAG) was 10.31/7.61 μg/g creatinine in quantal analysis and 3.21/2.24 g/g creatinine in the hybrid approach. However, the meta-regression showed that BMD and BMDL were significantly associated with the cut-off point, but BMD calculation method did not significantly affect the results. The urinary cadmium BMDL5 of β2-MG was 1.9 μg/g creatinine in the lowest cut-off point group.ConclusionThe BMD was significantly associated with the cut-off point defining the abnormal level of renal dysfunction markers.

A sample size planning approach that considers both statistical significance and clinical significance.

BackgroundThe CONSORT statement requires clinical trials to report confidence intervals, which help to assess the precision and clinical importance of the treatment effect. Conventional sample size calculations for clinical trials, however, only consider issues of statistical significance (that is, significance level and power).MethodA more consistent approach is proposed whereby sample size planning also incorporates information on clinical significance as indicated by the boundaries of the confidence limits of the treatment effect.ResultsThe probabilities of declaring a “definitive-positive” or “definitive-negative” result (as defined by Guyatt et al., CMAJ 152(2):169-173, 1995) are controlled by calculating the sample size such that the lower confidence limit under H1 and the upper confidence limit under H0 are bounded by relevant cut-offs. Adjustments to the traditional sample size can be directly derived for the comparison of two normally distributed means in a test of nonequality, while simulations are used to estimate the sample size for evaluating the hazards ratio in a proportional-hazards model.ConclusionsThis sample size planning approach allows for an assessment of the potential clinical importance and precision of the treatment effect in a clinical trial in addition to considerations of statistical power and type I error.

Precision of measurements with arbitrary confidence levels when samples are counted equal to or longer than blanks by computer codes.

Past computer solutions for confidence intervals, both in paired counting and when the sample is counted an integer number of times more than the blank, are extended to computing the precision of the measurement. The blank count and the contribution of the sample to the gross count are assumed to be Poisson distributed. While the standard deviation and the probability density function of the net count are readily computed, the name and properties of the probability density function are unknown. Hence, the uncertainty of the net count is unknown. However, both the upper and lower confidence limits, at a given confidence level, can be computed. In general, the difference between the upper limit and the observed net count is greater than the difference between the observed net count and the lower confidence limit. So the bound on the uncertainty is taken to be the difference between the upper confidence limit and the observed net count. Then the precision can be taken to be the bound on the uncertainty divided by the observed net count (relative bound on the uncertainty).

Testosterone-induced micronuclei and increased nuclear division rate in L929 cell line expressing the androgen receptor

Data on the possible genotoxic effects of testosterone are limited: in particular, the potential clastogenic and/or aneugenic effects have not yet been properly investigated. An in vitro micronucleus (MN) assay was performed on L929 cells exposed to testosterone at doses of 10, 15, 20, 30, and 40μg/mL. Significantly increased MN frequencies were detected at doses of 20, 30, and 40μg/mL after 24h and 48h of incubation. The nuclear division index was higher after 48h than 24h of incubation. A benchmark dose (BMD) calculation was used to estimate the 1% extra risk level for MN and increased tetranucleated cells. The calculated 1% extra risk level for MN at 24h was 12.01μg/mL, with a 95% lower confidence limit (BMDL) at 8.98μg/mL; the corresponding BMD and BMDL at 48h were 17.35μg/mL and 10.69μg/mL, respectively. The BMD for tetranucleated cells at 24h was 14.86μg/mL, with a BMDL of 7.75μg/mL; the corresponding values at 48h were 0.50μg/mL for BMD and 0.87μg/mL for BMD. These findings suggest that the intensity of the mitogenic effect of testosterone increases upon prolonged exposure. The results of our study show that testosterone acts both as a mitogenic and genotoxic agent in L929 cells.

Developmental immunotoxicity testing of 4-methyl anisole

The developmental immunotoxicity of 4-methyl anisole (4MA) was investigated in the rat. Four study designs were used, with either premating or post-weaning onset of exposure, continued to postnatal day 50, and with or without additional oral gavage of pups from postnatal day 10 onward. Reduced litter size (benchmark dose lower confidence limit (BMDL) 80mg/kg bw/day) was the most sensitive developmental parameter, with pup relative organ weight effects observed at similar BMDLs, in the absence of maternal toxicity. Eosinophil numbers were reduced at lower doses (BMDL 16mg/kg bw/day). KLH challenge resulted in increased IL-13 and TNF-α responses, and variably reduced IgG production (BMDL 27mg/kg bw/day). T4 levels were reduced by 11% at maximum with a BMDL of 73mg/kg bw/day. Differences between exposure cohorts were limited and were considered to be without biological significance. This study shows that 4MA induces developmental immunotoxicity at doses below those inducing developmental and general toxicity. These observations being independent of the study designs applied suggest that the post-weaning period, included in all designs, is the most relevant sensitive period for inducing 4MA mediated developmental immunotoxicity. Moreover, this study stresses the importance of including developmental immunotoxicity testing by default in regulatory toxicology.

Mechanistic Modeling of the Effects of Acidosis on Thrombin Generation.

Acidosis, a frequent complication of trauma and complex surgery, results from tissue hypoperfusion and IV resuscitation with acidic fluids. While acidosis is known to inhibit the function of distinct enzymatic reactions, its cumulative effect on the blood coagulation system is not fully understood. Here, we use computational modeling to test the hypothesis that acidosis delays and reduces the amount of thrombin generation in human blood plasma. Moreover, we investigate the sensitivity of different thrombin generation parameters to acidosis, both at the individual and population level. We used a kinetic model to simulate and analyze the generation of thrombin and thrombin-antithrombin complexes (TAT), which were the end points of this study. Large groups of temporal thrombin and TAT trajectories were simulated and used to calculate quantitative parameters, such as clotting time (CT), thrombin peak time, maximum slope of the thrombin curve, thrombin peak height, area under the thrombin trajectory (AUC), and prothrombin time. The resulting samples of parameter values at different pH levels were compared to assess the acidosis-induced effects. To investigate intersubject variability, we parameterized the computational model using the data on clotting factor composition for 472 subjects from the Leiden Thrombophilia Study. To compare acidosis-induced relative parameter changes in individual ("virtual") subjects, we estimated the probabilities of relative change patterns by counting the pattern occurrences in our virtual subjects. Distribution overlaps for thrombin generation parameters at distinct pH levels were quantified using the Bhattacharyya coefficient. Acidosis in the range of pH 6.9 to 7.3 progressively increased CT, thrombin peak time, AUC, and prothrombin time, while decreasing maximum slope of the thrombin curve and thrombin peak height (P < 10). Acidosis delayed the onset and decreased the amount of TAT generation (P < 10). As a measure of intrasubject variability, maximum slope of the thrombin curve and CT displayed the largest and second-largest acidosis-induced relative changes, and AUC displayed the smallest relative changes among all thrombin generation parameters in our virtual subject group (1-sided 95% lower confidence limit on the fraction of subjects displaying the patterns, 0.99). As a measure of intersubject variability, the overlaps between the maximum slope of the thrombin curve distributions at acidotic pH levels with the maximum slope of the thrombin curve distribution at physiological pH level systematically exceeded analogous distribution overlaps for CT, thrombin peak time, and prothrombin time. Acidosis affected all quantitative parameters of thrombin and TAT generation. While maximum slope of the thrombin curve showed the highest sensitivity to acidosis at the individual-subject level, it may be outperformed by CT, thrombin peak time, and prothrombin time as an indicator of acidosis at the subject-group level.