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PubMed2003

The use of the 'reverse Cornfield inequality' to assess the sensitivity of a non-significant association to an omitted variable.

Unlike randomized experimental studies, investigators do not have control over the treatment assignment in observational studies. Hence, the treated and control (non-treated) groups may have widely different distributions of unobserved covariates. Thus, if observational data are analysed as if they had arisen from a controlled study, the analyses are subject to potential bias. Sensitivity analysis is a technique for assessing whether the inference drawn from a study could be altered by a moderate 'imbalance', between the distribution of the covariates in different groups. In this paper, we examine the sensitivity analysis of the test of proportions in 2 x 2 tables from a new perspective: 'could a non-significant result have occurred because the treated group has a higher prevalence of an unobserved risk factor?'. The study was motivated by an analysis of the studies concerning with the possible effect of spermicide use on birth defects that were cited in a legal decision.

Analysis of Variance↗

PubMed2001

A cost analysis of endoscopic ultrasound in the evaluation of pancreatic head adenocarcinoma.

OBJECTIVE: Endoscopic ultrasound (EUS)-guided fine needle aspiration (FNA) biopsy of nonperitumoral (NPT) lymph nodes (LN) can be helpful in preoperative staging of pancreatic head adenocarcinoma. The economic impact of this staging strategy has not yet been described. The aim of this study was to apply a decision analysis model to compare the costs of three approaches to the management of nonmetastatic pancreatic head adenocarcinoma: EUS FNA versus CT-guided FNA versus surgery. A cost minimization approach was employed, as viewed from the perspective of the payer. METHODS: A decision analysis model was designed using DATA Version 3.5, taking the entry criteria as "resectable" pancreatic head adenocarcinoma as determined by helical CT. Detection of metastatic NPT LN on FNA signified unresectability and obviated the need for surgery. Baseline probabilities were varied through plausible ranges using sensitivity analysis. Cost inputs were based on Medicare professional plus facility fees. The endpoint was cost of management per patient. RESULTS: EUS FNA was the least costly strategy ($15,938) compared with CT FNA ($16,378) and surgery ($18,723). Sensitivity analysis revealed that EUS FNA remained the least costly option provided the frequency of NPT LN involvement was >4%; below this value, surgery became the least costly. CONCLUSIONS: EUS FNA is the least costly staging strategy in the workup of patients with nonmetastatic pancreatic head adenocarcinoma primarily because of confirmation of NPT LN involvement avoiding unnecessary surgery. These results support performing EUS in patients whose tumors are thought to be resectable on helical CT to enhance NPT LN assessment.

Adenocarcinoma↗

PubMed2002

Life expectancy after endovascular versus open abdominal aortic aneurysm repair: results of a decision analysis model on the basis of data from EUROSTAR.

BACKGROUND/OBJECTIVES: Although endovascular abdominal aortic aneurysm (AAA) repair (ENDO) has decreased operative morbidity risks compared with open AAA repair (OPEN), risks of rupture and reintervention are higher after ENDO. We used decision analysis to examine the effect of these competing risks on quality-adjusted life expectancy (QALE) after ENDO and OPEN. METHODS: We used a Markov decision-analysis model to simulate hypothetic cohorts of patients undergoing ENDO or OPEN. Patients moved through a multistate transition model according to probabilities derived from the literature, the EUROSTAR database (for ENDO) and Medicare claims data (for OPEN). Our primary outcome measure was QALE after surgery. We used sensitivity analysis to determine which factors most influenced this outcome. RESULTS: In the base-case analysis of 70-year-old men, life expectancy after ENDO was 7.09 quality-adjusted life years compared with 7.03 quality-adjusted life years for OPEN, a difference of 3 weeks. Sensitivity analysis showed that at less than age 64 years, OPEN results in greater QALE. However, the difference in QALE was small (<3 months) across the entire range of ages studied (60 to 85 years). The optimal strategy was sensitive to changes in ENDO and OPEN operative mortality rate, rupture rate after ENDO, late conversion to OPEN rate, ENDO revision rate, and OPEN reoperation rate. However, the difference between OPEN and ENDO strategies was small across the plausible range of most of these variables. CONCLUSION: For most patients who are candidates for AAA repair, ENDO and OPEN result in similar QALE. Decision analysis suggests that OPEN may be preferred for younger patients with low operative risk and ENDO may be preferred for older patients with higher operative risk. However, given the similarity in overall outcome, patient preference should be weighed heavily in decision making.

Aged↗

PubMed1985

A biomechanical model of the lumbosacral joint during lifting activities.

A biomechanical model of the lumbosacral region was constructed for the purpose of systematically studying the combined stresses and strains on the local ligaments, muscles and disc tissue during sagittal plane two-handed lifting. The model was validated in two ways. The first validation was a comparison of experimental study results with model predictions. In general predictions compared very reasonably with observed values of several authors with the exception of strain predictions on the articular ligaments. Second, a sensitivity analysis was performed over a wide range of lifting tasks. The predicted stress/strain values followed anticipated patterns and were of reasonable magnitudes. On the basis of the results of the sensitivity analysis it was concluded that typical lifting tasks can lead to excessive disc compressive forces, muscle moment generation requirements, and possibly lumbodorsal fascia strains. Conversely, annulus rupture of a healthy disc due to overstrain appears very unlikely.

Biomechanical Phenomena↗

PubMed1999

rhDNase therapy for the treatment of cystic fibrosis patients with mild to moderate lung disease.

OBJECTIVE: To assess the cost-effectiveness of rhDNase (Pulmozyme(R)) for patients with cystic fibrosis (CF) aged 5 years or more, with mild to moderate lung disease. The review addresses four questions: a) does rhDNase therapy work in the short term?, b) does rhDNase therapy work more effectively in certain groups of patients?, c) does rhDNase therapy work in the long term? and d) what is the cost-effectiveness of rhDNase therapy? METHODS: A structured rapid review with modelling and cost-effectiveness calculations. Electronic searches were carried out to identify randomised controlled trials (RCTs), systematic reviews, epidemiological and economic information. Databases searched included Cochrane Library, Medline, Healthstar, Embase, PreMedline and NHS Economic Evaluation Database (NHS EED). Exclusion criteria were trials of very short duration (14 days or less) and those which looked at CF patients with severe lung disease. Open label extensions providing information on longer term outcomes were included. RESULTS: Nine published RCTs were identified, although only one met the inclusion criteria. This large RCT was of good methodological quality, and shows that treatment with rhDNase over a 6-month period improves lung function, and decreases the risk of respiratory exacerbations. Expert opinion suggests that there are identifiable subgroups of patients showing improvement, little or no change, and deterioration after treatment with rhDNase. However, the best supporting evidence for this comes from a retrospective case series, showing that response to rhDNase is highly variable, and that early improvement was a good predictive marker for long-term benefit. Evidence for the long-term impact of rhDNase is not yet available from any RCTs. A simplified model was therefore developed to estimate the decline in lung function for patients treated with rhDNase, compared with those who were not treated. From this model it appears that the continued use of rhDNase over the lifetime of a CF patient might extend their life expectancy by 2 years. If treatment is limited to a subgroup of patients with moderate lung disease who respond to treatment, the continued use of rhDNase might extend their life expectancy by 7 years. Using the model, the discounted cost per life year gained for all patients is estimated at approximately pound52 500, with a range of between approximately pound25 000-57 000 from sensitivity analysis. For the subgroup of patients, the discounted cost per life year gained is estimated at approximately pound16 000, with a range of between approximately pound18 000-36 600 from sensitivity analysis. CONCLUSIONS: Although there is short-term evidence that the use of rhDNase improves lung function and decreases the risk of respiratory exacerbations, at present there is no evidence from RCTs to indicate whether this effect is sustained over a longer time period, or whether rhDNase is associated with a reduction in mortality. RCTs to date have been of insufficient duration to answer important questions about long term outcomes, particularly the effects of rhDNase on lung function, respiratory exacerbations and mortality. Further long-term research is needed, with economic analysis to evaluate the long term cost-effectiveness of rhDNase. Research is also needed to identify, in advance, which patients would benefit most from this expensive treatment.

Adolescent↗

PubMed2025

Anoikis classification of lung squamous cell carcinoma reveals correlation with clinical prognosis and immune characteristics.

BACKGROUND: Anoikis is a new mode of cell death that has been shown to correlate significantly with tumors. However, the clinical prognostic significance of anoikis in lung squamous cell carcinoma (LUSC) remains poorly studied. METHODS: The differentially expressed ARGs and candidate genes were selected by the differential analysis to construct a predictive model. Independent prognostic gene was determined by Cox and LASSO analysis and we used the HCC95 and NCI H520 cell line to verify the gene function. We used the data from TCGA, GEO, GeneCards, and Harmonizome databases to analyze the immune microenvironment, functional enrichment, and drug sensitivity analysis. RESULTS: We identified 717 differentially expressed and selected 3 ARGs (FADD, SNAI1, and BAG4) to construct a predictive model. We found that SNAI1 is an independent prognostic gene and confirmed that knocking out the SNAI1 inhibited the HCC95/NCI H520 cell proliferation. We used single-sample gene-set enrichment analysis (ssGSEA) to evaluate the immune infiltration based on the 3 ARG expression levels. We constructed a risk score and provided a visual representation of the prophetic implications of the ARGs-based signature through a nomogram. We found 15 susceptible drugs in the high-risk group and 15 sensitive drugs in the low-risk group by the drug sensitivity analysis. CONCLUSION: We used ARGs to construct a prognosis model for LUSC that can accurately predict the prognosis of LUSC patients. ARGs, especially SNAI1, play an essential role in developing LUSC. These findings could provide individualized treatment plans and new research ideas for LUSC patients.

Humans↗

PubMed1995

A quality-adjusted survival meta-analysis of adjuvant chemotherapy for premenopausal breast cancer. International Breast Cancer Study Group.

The purpose of this paper is to develop and apply a meta-analysis methodology, that does not require patient-level data, for comparing treatments in terms of quality-of-life-adjusted survival. As a motivating example, we considered adjuvant chemotherapy for breast cancer. This therapy has been shown to offer an improvement in recurrence-free and overall survival, especially for younger women, but its acute toxic effects discourage some physicians from prescribing it. To determine whether the benefit of adjuvant chemotherapy treatment outweighs its costs in terms of toxic effects, we performed a meta-analysis of quality-adjusted survival based on data from 1229 patients, 49 years of age or younger, randomized in eight clinical trials that compared chemotherapy versus no adjuvant systemic therapy. We conducted the meta-analysis by performing a quality-adjusted survival analysis known as a Q-TWiST analysis on each trial. A Q-TWiST analysis allows one to make treatment comparisons that incorporate differences in quality of life associated with various health states. In this analysis, we define as health states the periods of time patients spend: (i) with subjective toxic effects of chemotherapy; (ii) without symptoms of recurrence and toxicity, and (iii) following disease recurrence. We assigned weights to each health state which reflect their relative value in terms of quality of life and allowed them to vary in a sensitivity analysis. We then combined the individual trial results in a meta-analysis, using a multivariate regression model, in such a way that we could easily perform an overall sensitivity analysis. Individual patient-level data are not required to perform this meta-analysis methodology if the individual Q-TWiST analysis results for each trial are available.

Adult↗

PubMed2005

A method to automate probabilistic sensitivity analyses of misclassified binary variables.

BACKGROUND: Misclassification bias is present in most studies, yet uncertainty about its magnitude or direction is rarely quantified. METHODS: The authors present a method for probabilistic sensitivity analysis to quantify likely effects of misclassification of a dichotomous outcome, exposure or covariate. This method involves reconstructing the data that would have been observed had the misclassified variable been correctly classified, given the sensitivity and specificity of classification. The accompanying SAS macro implements the method and allows users to specify ranges of sensitivity and specificity of misclassification parameters to yield simulation intervals that incorporate both systematic and random error. RESULTS: The authors illustrate the method and the accompanying SAS macro code by applying it to a study of the relation between occupational resin exposure and lung-cancer deaths. The authors compare the results using this method with the conventional result, which accounts for random error only, and with the original sensitivity analysis results. CONCLUSION: By accounting for plausible degrees of misclassification, investigators can present study results in a way that incorporates uncertainty about the bias due to misclassification, and so avoid misleadingly precise-looking results.

Bias↗

PubMed2004

A cost-utility analysis of secondary prophylaxis for variceal hemorrhage.

BACKGROUND: Secondary prophylaxis for esophageal variceal hemorrhage (VH) is recommended, but there has never been a cost-utility analysis of its implementation. OBJECTIVE: The objective was to compare the cost utility of various strategies for the secondary prophylaxis of VH including (a) observation alone, (b) medical therapy (MED), (c) endoscopic band ligation (EBL), (d) endoscopic band ligation plus medical therapy (EBL + M), and (e) transjugular intrahepatic portosystemic shunt (TIPS), and to examine the effect of adherence on these strategies. METHODS: A Markov model was developed for all five strategies, and included surveillance, risk of hepatic encephalopathy, complications, and nonadherence. DATA SOURCES: Published literature and the Health Care Financing Administration. TARGET POPULATION: People with cirrhosis and a history of controlled VH. TIME HORIZON: Three years. PERSPECTIVE: Third-party payer. OUTCOME MEASURES: Incremental cost-effectiveness ratios for quality-adjusted life-years (QALYs) gained. RESULTS OF BASE-CASE ANALYSIS: Combination EBL + M was the optimal strategy, dominating all other strategies including observation, meaning that it was more effective and less expensive than the others. In addition, EBL alone dominated observation and TIPS in terms of QALYs, and MED alone dominated the strategy of observation in terms of QALYs. RESULTS OF SENSITIVITY ANALYSIS: Important variables affecting the optimal strategy were the odds ratio (OR) of VH with EBL compared to MED, the OR of VH with EBL + M compared to EBL, and patients' preferences regarding taking the medication as reflected in the associated toll exacted on the health state utility. Variations in these parameters within the range of clinical plausibility allowed EBL or MED to become the optimal strategy. TIPS was the optimal strategy only if adherence rates for all strategies were less than 12%. RESULTS OF MONTE CARLO ANALYSIS: Neither observation nor TIPS was ever the optimal strategy, and EBL + M was optimal in 62% of cases. If the variables identified in the sensitivity analysis were controlled, then EBL + M was optimal in 95% of cases. CONCLUSIONS: TIPS should be reserved only for patients with very poor adherence. Otherwise, patients are best served by medications, EBL, or a combination of both, depending on the comparative rates of rebleeding with each and patients' preferences regarding medical therapy. The redundancy of combination band ligation plus medical therapy can improve outcomes, particularly in the setting of poor patient adherence.

Adolescent↗

PubMed2003

The appropriate rate of breast conserving surgery: an evidence-based estimate.

PURPOSE: The objective of the present study was to estimate the proportion of incident cases of breast cancer that should receive breast conserving surgery (BCS), using an evidence-based approach. METHODS: An extensive search of the literature was undertaken to identify eligibility criteria for BCS. The eligibility criteria for BCS were combined with the information about case mix and patient preference to estimate the need for BCS. An epidemiological approach was then used to estimate the incidence of each eligibility criterion for BCS in a typical North American population of breast cancer patients. The effect of sampling error on the estimated appropriate rate of BCS was calculated, and the effect of systematic error using alternative sources of information, was estimated by sensitivity analysis. RESULTS: The analysis showed that 69.6% of breast cancer cases are eligible for BCS, and that 48.0 +/- 6.0% of breast cancer patients are both eligible for BCS and prefer it to mastectomy. Based on sensitivity analysis, the plausible range of the appropriate rate was 42.1% to 49.43%. The proportion of breast cancer cases in which BCS was appropriate was stage dependent; 63.0 +/- 11.5% in ductal carcinoma in-situ; 57.0 +/- 9.9% in stage I; 52.2 +/- 9.4% in stage II, and 27.2 +/- 5.2% in stage III. CONCLUSIONS: This model suggests that BCS is appropriate in 48% of all breast cancer patients. This information may be useful in auditing surgical practice, and may serve as a basis for planning of ancillary services, including radiotherapy.

Breast Neoplasms↗

PubMed2006

Consumer-phase Salmonella enterica serovar enteritidis risk assessment for egg-containing food products.

We describe a one-dimensional probabilistic model of the role of domestic food handling behaviors on salmonellosis risk associated with the consumption of eggs and egg-containing foods. Six categories of egg-containing foods were defined based on the amount of egg contained in the food, whether eggs are pooled, and the degree of cooking practiced by consumers. We used bootstrap simulation to quantify uncertainty in risk estimates due to sampling error, and sensitivity analysis to identify key sources of variability and uncertainty in the model. Because of typical model characteristics such as nonlinearity, interaction between inputs, thresholds, and saturation points, Sobol's method, a novel sensitivity analysis approach, was used to identify key sources of variability. Based on the mean probability of illness, examples of foods from the food categories ranked from most to least risk of illness were: (1) home-made salad dressings/ice cream; (2) fried eggs/boiled eggs; (3) omelettes; and (4) baked foods/breads. For food categories that may include uncooked eggs (e.g., home-made salad dressings/ice cream), consumer handling conditions such as storage time and temperature after food preparation were the key sources of variability. In contrast, for food categories associated with undercooked eggs (e.g., fried/soft-boiled eggs), the initial level of Salmonella contamination and the log10 reduction due to cooking were the key sources of variability. Important sources of uncertainty varied with both the risk percentile and the food category under consideration. This work adds to previous risk assessments focused on egg production and storage practices, and provides a science-based approach to inform consumer risk communications regarding safe egg handling practices.

Bacteriophage Typing↗

PubMed2001

A physiologically based pharmacokinetic analysis of capecitabine, a triple prodrug of 5-FU, in humans: the mechanism for tumor-selective accumulation of 5-FU.

PURPOSE: To identify the factors governing the dose-limiting toxicity in the gastrointestine (GI) and the antitumor activity after oral administration of capecitabine, a triple prodrug of 5-FU, in humans. METHOD: The enzyme kinetic parameters for each of the four enzymes involved in the activation of capecitabine to 5-FU and its elimination were measured experimentally in vitro to construct a physiologically based pharmacokinetic model. Sensitivity analysis for each parameter was performed to identify the parameters affecting tissue 5-FU concentrations. RESULTS: The sensitivity analysis demonstrated that (i) the dihydropyrimidine dehydrogenase (DPD) activity in the liver largely determines the 5-FU AUC in the systemic circulation, (ii) the exposure of tumor tissue to 5-FU depends mainly on the activity of both thymidine phosphorylase (dThdPase) and DPD in the tumor tissues, as well as the blood flow rate in tumor tissues with saturation of DPD activity resulting in 5-FU accumulation, and (iii) the metabolic enzyme activity in the GI and the DPD activity in liver are the major determinants influencing exposure to 5-FU in the GI. The therapeutic index of capecitabine was found to be at least 17 times greater than that of other 5-FU-related anticancer agents, including doxifluridine, the prodrug of 5-FU, and 5-FU over their respective clinical dose ranges. CONCLUSIONS: It was revealed that the most important factors that determine the selective production of 5-FU in tumor tissue after capecitabine administration are tumor-specific activation by dThdPase, the nonlinear elimination of 5-FU by DPD in tumor tissue, and the blood flow rate in tumors.

Antimetabolites, Antineoplastic↗

PubMedDate not supplied

[Costs of accidental punctures in hospital health personnel].

OBJECTIVES: The aim of this study was to calculate the average cost of each hepatitis B, C and HIV follow-up carried out in the health personnel that have suffered an exposure to blood and body fluids and to estimate the cost for each of the different types of sources as well as to identify the items that account for the main part of the cost. METHODS: A cost analysis was carried out. The post-exposure programme was modelled in a decision tree combining probabilities (percentage of each type of source in dependence of its positivity for the three viruses and immunization state of the health personnel against hepatitis B) and monetary costs (pesetas from 1994). Costs included: salaries, laboratory, chemist, energy, cleaning, telephone, medical and office equipment, amortization and lost productivity. A sensitivity analysis was carried out with the real fulfillment of the programme. RESULTS: The average cost was 39,564 ptas. (29,750 ptas. applying the sensitivity analysis), with a range from 86,864 ptas. (source positive for the three viruses and injured subject not immunized) to 23,074 ptas. (source negative for the three viruses). If the source was hepatitis B positive, the average cost was 86,093 ptas. when the injured subject was not immunized and 53,232 ptas. if he was immunized. Serologic tests account for the main part of the cost (range from 72.8% to 87.7%). CONCLUSIONS: High cost suggests an appropriate risk evaluation in order to avoid unnecessary follow-ups. The model used allows to know the cost of each potentially avoided episode and it could be used for any hospital in order to make an economical evaluation of new preventive devices.

Accidents, Occupational↗

PubMed2002

Cost analysis of magnetic resonance cholangiography in the management of inoperable hilar biliary obstruction.

OBJECTIVE: Palliation of patients with Klatskin tumors involving both hepatic ducts is usually performed with bilateral biliary stent placement. Magnetic resonance cholangiopancreatography (MRCP) offers the ability to visualize the hepatic ducts without injection of contrast, thereby reducing the patient's risk of developing postprocedure bacterial cholangitis. We used decision analysis techniques to quantitate the cost-effectiveness of MRCP before stent placement versus routine placement of bilateral biliary stents in the setting of inoperable malignant hilar obstruction. In addition to determining which strategy was most economical, we used sensitivity analysis to identify the critical factors defining relative costs. METHODS: A decision analysis model was designed comparing MRCP with subsequent unilateral biliary stent placement and double biliary stent placement approaches for palliation of jaundice in a patient with inoperable malignant hilar obstruction, as viewed from the societal perspective. Baseline probabilities, obtained from the published literature, were varied through plausible ranges using sensitivity analysis. Charges were based on Medicare professional plus facility fees or diagnosis-related group rates for out- and inpatients, respectively. RESULTS: MRCP with subsequent directed unilateral stent placement was the least costly approach ($3806) compared with bilateral stent placement ($4275), provided the bilateral biliary stent complication rate was >3%. Bilateral stent placement needed to confer a survival advantage of at least 7 days over unilateral stent placement to become the more cost-effective approach. CONCLUSIONS: The use of MRCP to guide biliary stent placement in a patient with inoperable hilar obstruction reduces the overall cost of treatment. The uncertainty of any survival advantage that bilateral biliary stent placement confers over unilateral stent placement makes cost-effectiveness difficult to assess.

Cholangiography↗

PubMedDate not supplied

Determining the cost-effectiveness of mass screening for cervical cancer using common analytic models.

OBJECTIVE: To estimate the cost per life-year saved (cost-effectiveness ratio [CER]) for cervical cancer and to evaluate the influence of the decreased incidence upon the cost per life-year saved. STUDY DESIGN: We established hypothetical cohorts at 10-year intervals between 30 and 79 years of age, each of which consisted of 100,000 asymptomatic female subjects, and estimated the cost and effect of single mass screening for cervical cancer. To investigate the influence on CER, we performed a sensitivity analysis of each item, including the consultation rate for further examination, prevalence rate and cost of medical treatment. RESULTS: The estimated CER per one expected life-year of survival was lowest for subjects in their 30s and highest for those in their 70s. The difference between the two was more than five-fold. Sensitivity analysis was rarely affected by changes in the cost of medical treatment and the prevalence rate, but the effectiveness rate could be fairly affected by the consultation rate for closer examination. CONCLUSION: Mass screening for cervical cancer is acceptable in terms of economic effectiveness. Moreover, mass screening for cervical cancer could decrease the morbidity rate for scores of years thereafter.

Adult↗

PubMed2001

[Assessment of paclitaxel treatment of non-small-cell lung cancer].

BACKGROUND: Our goal was to assess the effectiveness of paclitaxel therapy in patients with non-small-cell lung cancer (NSCLC) by means of a meta-analysis of published clinical trials. MATERIAL AND METHOD: We carried out a search of controlled and randomized clinical trials which evaluated treatment with paclitaxel in patients with NSCLC from January 1996 to April 2001, regardless of any other associated therapy and without restrictions in the publication language. We also performed a sensitivity analysis and an analysis of sample heterogeneity. RESULTS: Six randomized and controlled studies fulfilled the inclusion criteria. Results from the analysis of effectiveness favoured significantly treatment with paclitaxel (OR 95% total responders: 1.42 [1.16-1.74]; p = 0.07). These results remained unchanged with the sensitivity analysis. Analysis of survival after 1 year of treatment was not significant (OR 95% 0.96 [0.79-1.17]; p = 0.2) CONCLUSIONS: Paclitaxel in patients with NSCLC offers a therapeutic advantage over other chemotherapy regimes with an overall OR of 1.42. However, this therapy does not appear to offer a significant survival advantage after 1 year.

Antineoplastic Agents, Phytogenic↗

PubMed1991

Drugs, sex and HIV: a mathematical model for New York City.

A data-based mathematical model was formulated to assess the epidemiological consequences of heterosexual, intravenous drug use (IVDU) and perinatal transmission in New York City (NYC). The model was analysed to clarify the relationship between heterosexual and IVDU transmission and to provide qualitative and quantitative insights into the HIV epidemic in NYC. The results demonstrated the significance of the dynamic interaction of heterosexual and IVDU transmission. Scenario analysis of the model was used to suggest a new explanation for the stabilization of the seroprevalence level that has been observed in the NYC IVDU community; the proposed explanation does not rely upon any IVDU or sexual behavioural changes. Gender-specific risks of heterosexual transmission in IVDUs were also explored by scenario analysis. The results showed that the effect of the heterosexual transmission risk factor on increasing the risk of HIV infection depends upon the level of IVDU. The model was used to predict future numbers of adult and pediatric AIDS cases; a sensitivity analysis of the model showed that the confidence intervals on these prediction estimates were extremely wide. This prediction variability was due to the uncertainty in estimating the values of the models' thirty variables (twenty biological-behavioural transmission parameters and the initial sizes of ten subgroups). However, the sensitivity analysis revealed that only a few key variables were significant in contributing to the AIDS case prediction variability; partial rank correlation coefficients were calculated and used to identify and to rank the importance of these key variables. The results suggest that long-term precise estimates of the future number of AIDS cases will only be possible once the values of these key variables have been evaluated accurately.

Female↗

PubMed2004

Stochastic modelling of landfill leachate and biogas production incorporating waste heterogeneity. Model formulation and uncertainty analysis.

A mathematical model simulating the hydrological and biochemical processes occurring in landfilled waste is presented and demonstrated. The model combines biochemical and hydrological models into an integrated representation of the landfill environment. Waste decomposition is modelled using traditional biochemical waste decomposition pathways combined with a simplified methodology for representing the rate of decomposition. Water flow through the waste is represented using a statistical velocity model capable of representing the effects of waste heterogeneity on leachate flow through the waste. Given the limitations in data capture from landfill sites, significant emphasis is placed on improving parameter identification and reducing parameter requirements. A sensitivity analysis is performed, highlighting the model's response to changes in input variables. A model test run is also presented, demonstrating the model capabilities. A parameter perturbation model sensitivity analysis was also performed. This has been able to show that although the model is sensitive to certain key parameters, its overall intuitive response provides a good basis for making reasonable predictions of the future state of the landfill system. Finally, due to the high uncertainty associated with landfill data, a tool for handling input data uncertainty is incorporated in the model's structure. It is concluded that the model can be used as a reasonable tool for modelling landfill processes and that further work should be undertaken to assess the model's performance.

Biodegradation, Environmental↗