Estimation of lead-time bias and its impact on the outcome of surveillance for the early diagnosis of hepatocellular carcinoma

none27Lead-time is the time by which diagnosis is anticipated by screening/surveillance with respect to the symptomatic detection of a disease. Any screening program, including surveillance for hepatocellular carcinoma (HCC), is subject to lead-time bias. Data regarding lead-time for HCC are lacking. Aims of the present study were to calculate lead-time and to assess its impact on the benefit obtainable from the surveillance of cirrhotic patients.Background & Aims: Lead-time is the time by which diagnosis is anticipated by screening/surveillance with respect to the symptomatic detection of a disease. Any screening program, including surveillance for hepatocellular carcinoma (HCC), is subject to lead-time bias. Data regarding lead-time for HCC are lacking. Aims of the present study were to calculate lead-time and to assess its impact on the benefit obtainable from the surveillance of cirrhotic patients. Methods: One-thousand three-hundred and eighty Child–Pugh class A/B patients from the ITA.LI.CA database, in whom HCC was detected during semiannual surveillance (n = 850), annual surveillance (n = 234) or when patients came when symptomatic (n = 296), were selected. Lead-time was estimated by means of appropriate formulas and Monte Carlo simulation, including 1000 patients for each arm. Results: The 5-year overall survival after HCC diagnosis was 32.7% in semiannually surveilled patients, 25.2% in annually surveilled patients, and 12.2% in symptomatic patients (p <0.001). In a 10-year follow-up perspective, the median lead-time calculated for all surveilled patients was 6.5 months (7.2 for semiannual and 4.1 for annual surveillance). Lead-time bias accounted for most of the surveillance benefit until the third year of follow-up after HCC diagnosis. However, even after lead-time adjustment, semiannual surveillance maintained a survival benefit over symptomatic diagnosis (number of patients needed to screen = 13), as did annual surveillance (18 patients). Conclusions: Lead-time bias is the main determinant of the short-term benefit provided by surveillance for HCC, but this benefit becomes factual in a long-term perspective, confirming the clinical utility of an anticipated diagnosis of HCC.openAlessandro, Cucchetti; Franco, Trevisani; Anna, Pecorelli; Virginia, Erroi; Fabio, Farinati; Francesca, Ciccarese; Gian, Lodovico Rapaccini; Mariella Di, Marco; Eugenio, Caturelli; Edoardo, G. Giannini; Marco, Zoli; Franco, Borzio; Giuseppe, Cabibbo; Martina, Felder; Antonio, Gasbarrini; Rodolfo, Sacco; Francesco, Giuseppe Foschi; Gabriele, Missale; Filomena, Morisco; Gianluca, Svegliati Baroni; Roberto, Virdone; Mauro, Bernardi; Antonio D., Pinna; for the Italian Liver Cancer Group [...; Bolondi, Luigi; Maurizio, Biselli; Piscaglia, Fabio; ...].Alessandro, Cucchetti; Franco, Trevisani; Anna, Pecorelli; Virginia, Erroi; Fabio, Farinati; Francesca, Ciccarese; Gian, Lodovico Rapaccini; Mariella Di, Marco; Eugenio, Caturelli; Edoardo, G. Giannini; Marco, Zoli; Franco, Borzio; Giuseppe, Cabibbo; Martina, Felder; Antonio, Gasbarrini; Rodolfo, Sacco; Francesco, Giuseppe Foschi; Gabriele, Missale; Filomena, Morisco; Gianluca, Svegliati Baroni; Roberto, Virdone; Mauro, Bernardi; Antonio D., Pinna; for the Italian Liver Cancer Group [..; Bolondi, Luigi; Maurizio, Biselli; Piscaglia, Fabio; ..]

Large seals fabricated from small segments reduce procurement lead time

Large diameter seals are fabricated from narrow strip stock welded in segments to form a complete ring. This technique could be used to reduce the cost of critical, large diameter seals in the heating and ventilating industry, petrochemical industry, and marine fabrication industry

Pricing in a duopoly with a lead time advantage

We analyze the price competition between two suppliers offering two different lead times and two different prices to a buyer. The buyer chooses its inventory replenishment policy in order to minimize its infinite-horizon average cost. In essence, the fast and expensive supplier is used only in emergencies, while the slow and cheap supplier receives the bulk of the orders. Thus, despite a higher price, the fast supplier is able to capture a part of the buyer's orders. We analyze the price competition between the asymmetric suppliers, where the market share of each supplier is derived from the buyer's inventory problem. We find equilibria that differ significantly from the Bertrand price-only competition. In particular, for some cost parameters, the fast supplier is able to charge a premium for faster delivery, and stay in business even with a higher production cost. We obtain in some cases closed-form formulas for the price difference in equilibrium. Hence, our results show that high cost suppliers may not be driven out of business if they can offer fast delivery.offshoring; dual sourcing;

Clips: a capacity and lead time integrated procedure for scheduling.

We propose a general procedure to address real life job shop scheduling problems. The shop typically produces a variety of products, each with its own arrival stream, its own route through the shop and a given customer due date. The procedure first determines the manufacturing lot sizes for each product. The objective is to minimize the expected lead time and therefore we model the production environment as a queueing network. Given these lead times, release dates are set dynamically. This in turn creates a time window for every manufacturing order in which the various operations have to be sequenced. The sequencing logic is based on a Extended Shifting Bottleneck Procedure. These three major decisions are next incorporated into a four phase hierarchical operational implementation scheme. A small numerical example is used to illustrate the methodology. The final objective however is to develop a procedure that is useful for large, real life shops. We therefore report on a real life application.Model; Models; Applications; Product; Scheduling;

Effect of flow forecasting quality on benefits of reservoir operation - a case study for the Geheyan reservoir (China)

This paper presents a methodology to determine the effect of flow forecasting quality on the benefits of reservoir operation. The benefits are calculated in terms of the electricity generated, and the quality of the flow forecasting is defined in terms of lead time and accuracy of the forecasts. In order to determine such an effect, an optimization model for reservoir operation was developed which consists of two sub-models: a long-term (monthly) and a short-term (daily) optimization sub-model. A methodology was developed to couple these two sub-models, so that both short-term benefits (time span in the order of the flow forecasting lead time) and long-term benefits (one year) were considered and balanced. Both sub-models use Discretized Dynamic Programming (DDP) as their optimization algorithms. The Geheyan reservoir on the Qingjiang River in China was taken as case study. Observed (from the 1997 hydrological year) and forecasted flow series were used to calculate the benefits. Forecasted flow series were created by adding noises to the observed series. Different magnitudes of noise reflected different levels of forecasting accuracies. The results reveal, first of all, a threshold lead time of 33 days, beyond which further extension of the forecasting lead time will not lead to a significant increase in benefits. Secondly, for lead times shorter than 33 days, a longer lead time will generally lead to a higher benefit. Thirdly, a perfect inflow forecasting with a lead time of 4 days will realize 87% of the theoretical maximum electricity generated in one year. Fourthly, for a certain lead time, more accurate forecasting leads to higher benefits. For inflow forecasting with a fixed lead time of 4 days and different forecasting accuracies, the benefits can increase by 5 to 9% compared to the actual operation results. It is concluded that the definition of the appropriate lead time will depend mainly on the physical conditions of the basin and on the characteristics of the reservoir. The derived threshold lead time (33 days) gives a theoretical upper limit for the extension of forecasting lead time. Criteria for the appropriate forecasting accuracy for a specific feasible lead-time should be defined from the benefit-accuracy relationship, starting from setting a preferred benefit level, in terms of percentage of the theoretical maximum. Inflow forecasting with a higher accuracy does not always increase the benefits, because these also depend on the operation strategies of the reservoir.\u