We compare two approaches in their ability to solve for optimal Ramsey policies in heterogeneous-agent models, considering the optimal provision of a public good. First, the “transition” approach ...makes the problem tractable by assuming a constant path for the planner's instruments. Second, the “truncation” approach uses a Lagrangian technique, solving the Ramsey problem of a finite state space model that approximates the full model. The truncation approach is shown to compute quantitatively accurate estimates of the actual values of the planner's instruments, whereas a time-inconsistency issue is found to affect the transition approach.
ON MONOTONE RECURSIVE PREFERENCES Bommier, Antoine; Kochov, Asen; Le Grand, François
Econometrica,
September 2017, Letnik:
85, Številka:
5
Journal Article
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Odprti dostop
We explore the set of preferences defined over temporal lotteries in an infinite horizon setting. We provide utility representations for all preferences that are both recursive and monotone. Our ...results indicate that the class of monotone recursive preferences includes Uzawa-Epstein preferences and risk-sensitive preferences, but leaves aside several of the recursive models suggested by Epstein and Zin (1989) and Weil (1990). Our representation result is derived in great generality using Lundberg's (1982, 1985) work on functional equations.
We determine an optimal protocol for temozolomide using population variability and dynamic optimization techniques inspired by artificial intelligence. We use a Pharmacokinetics/Pharmacodynamics ...(PK/PD) model based on Faivre and coauthors (Faivre, et al., 2013) for the pharmacokinetics of temozolomide, as well as the pharmacodynamics of its efficacy. For toxicity, which is measured by the nadir of the normalized absolute neutrophil count, we formalize the myelosuppression effect of temozolomide with the physiological model of Panetta and coauthors (Panetta, et al., 2003). We apply the model to a population with variability as given in Panetta and coauthors (Panetta, et al., 2003). Our optimization algorithm is a variant in the class of Monte-Carlo tree search algorithms. We do not impose periodicity constraint on our solution. We set the objective of tumor size minimization while not allowing more severe toxicity levels than the standard Maximum Tolerated Dose (MTD) regimen. The protocol we propose achieves higher efficacy in the sense that -compared to the usual MTD regimen- it divides the tumor size by approximately 7.66 after 336 days -the 95% confidence interval being 7.36-7.97. The toxicity is similar to MTD. Overall, our protocol, obtained with a very flexible method, gives significant results for the present case of temozolomide and calls for further research mixing operational research or artificial intelligence and clinical research in oncology.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
We present a truncation theory of idiosyncratic histories for heterogeneous‐agent models. This method allows us to solve for optimal Ramsey policies in such models with aggregate shocks. The method ...can be applied to a large variety of settings, with occasionally binding credit constraints. We use this theory to characterize the optimal level of unemployment insurance over the business cycle in a production economy. We find that the optimal policy is countercyclical.
The use of oocytes obtained from younger donors for IVF followed by embryo transfer represents an opportunity to accelerate genetic gain by reducing generation time. In this study, we investigated ...the relationship between donor age and the in vitro developmental competence of oocytes obtained from Holstein females (aged 5–18 months) after FSH stimulation and coasting. The follicle size patterns showed a significantly higher total number of small follicles (5–6 mm) from donors aged 5 to 10 months and a higher total number of medium-sized follicles (7–10 mm) in donors aged 6 to 7 months. Our analysis also revealed that the total number of follicles was significantly higher (P < 0.05) in donors aged 5 to 8 months and tended to be higher (P = 0.053) in nine-month-old donors. However, oocytes obtained from donors aged 5 to 10 months yielded fewer embryos reaching the morula and blastocyst stages. In summary, our results demonstrate that a higher number of oocytes can be obtained from younger animals but lower developmental competence negates this gain.
Understanding of developmental haemostasis is critical to ensure optimal prevention, diagnosis, and treatment of haemorrhagic and thrombotic diseases in children. As coagulation test results are ...known to be dependent on the reagents/analysers used, it is recommended for each laboratory to define the age-dependent reference ranges by using its own technical condition. That study was carried out in seven centers to establish age-specific reference ranges using the same reagents and analyser. Plasma samples were obtained from 1437 paediatric patients from the following age groups: 15 days-4 weeks (n=36), 1-5 months (n=320), 6-12 months (n=176), 1-5 years (n=507), 6-10 years (n=132) and 11-17 years (n=262). Indication of coagulation testing was pre-operative screening for non-acute diseases in most cases. PT values were similar in the different age groups to those in adults, whereas longer aPTTs were demonstrated in the younger children. Plasma levels of all clotting factors, except for FV, were significantly decreased (p<0.0001) in the youngest children, adult values being usually reached before the end of the first year. The same applied to antithrombin, protein C/S, and plasminogen. In contrast, FVIII and VWF levels were elevated in the youngest children and returned to adult values within six months. The same applied to D-dimer levels, which were found elevated, particularly until six months of life, until puberty. These data suggest that most coagulation test results are highly dependent on age, mainly during the first year of life, and that age-specific reference ranges must be used to ensure proper evaluation of coagulation in children.
This paper presents a positive and normative study of a world financial market when sovereign countries can default on their debt. We construct a tractable model that enables us to study sovereign ...default in general equilibrium. The amount of safe assets is thus endogenous and determined by international risk-sharing. We characterize the equilibrium structure and we show that the market equilibrium can generate multiple equilibria. In addition, the market equilibrium is not constrained-efficient because countries do not fully internalize the value of their debt being used as liquidity. We prove that a world fund issuing a safe asset increases aggregate welfare. The fund's relationship with the IMF's Special Drawing Rights is discussed.
•We construct a tractable model to study sovereign default in general equilibrium.•We show that the market equilibrium can generate multiple equilibria.•The market equilibrium is not constrained-efficient due to market incompleteness.•A world fund issuing a safe asset increases aggregate welfare.•The fund's relationship with the IMF's Special Drawing Rights is discussed.
•We propose a methodology borrowed from IA for treatment protocol optimization.•We apply our method to the administration of anti-VEGF and unlicensed dendritic cells.•We show that optimized protocols ...enable to significantly reduce total drug use.•Optimized protocols also allow tumor eradication even with late diagnosis.
Purpose: We determine an optimal injection pattern for anti-vascular endothelial growth factor (VEGF) and for the combination of anti-VEGF and unlicensed dendritic cells.
Methods: We rely on the mathematical model of Soto-Ortiz and Finley (2016) for the interactions between the tumor growth, angiogenesis and immune system reactions. Our optimization algorithm belongs to the class of Monte-Carlo tree search algorithms. The objective consists in finding the minimal total drug doses for which an injection pattern yields tumor eradication.
Results: Our results are twofold. First, optimized injection protocols enable to significantly reduce the total drug dose for tumor elimination. For instance, for an early diagnosis date, a total dose equal to 58% of the standard anti-VEGF dose enables to eliminate the tumor. In the case of drug combination, associating 25% of the total standard anti-VEGF dose to 10% of the dendritic cell total standard dose eradicates tumor. Our second result is that administering a dose equal to the maximal standard dose allows for later diagnosis date compared to standard protocol. For instance, in the case of anti-VEGF injection, the optimal protocol postpones the maximal diagnosis date by more than one month.
Conclusions. Overall, our optimization based on artificial intelligence delivers significant gains in total drug administration or in the length of the therapeutic window. Our method is flexible and could be adapted to other drug combinations.
•We propose an innovative methodology for characterizing optimal chemotherapy protocols.•Toxicity of MC protocols can be reduced without affecting their efficacy.•Toxicity of some MTD protocols ...cannot be reduced without affecting their efficacy.
Purpose. We compare the Maximum Tolerated Dose (MTD) and Metronomic Chemotherapy (MC) protocols for temozolomide administration. We develop an innovative methodology for characterizing optimal chemotherapy regimens.
Methods.We use a PK/PD model based on Faivre et al. (2013) for the pharmacokinetics of temozolomide, as well as the pharmacodynamics of its efficacy. For toxicity, which is measured by the nadir of the normalized absolute neutrophil count, we formalize the myelosuppression effect of temozolomide with the physiological model of Panetta et al. (2003b). We introduce a multi-criteria tool for comparing protocols along their efficacy and toxicity dimensions.
Results.We show that the toxicity of the MC regimen proposed by Faivre et al. (2013) can greatly be reduced without affecting its efficacy, while the standard MTD protocol efficacy cannot be improved without impairing its toxicity. We also show that for any acceptable toxicity level, the optimal protocol remains closely related to standard MTD.
Conclusions.Overall, our new method enables a rich comparison between protocols along multiple dimensions. We can rank protocols for temozolomide administration. It is a first step toward building optimal individual protocols.
•We use MTCS algorithms to optimize drug regimen in oncology.•We show how adding Bayesian updating allows to dynamically personalize treatment.•Optimal personalized protocols achieve very sizable ...decrease in tumor size.•These better efficacy results are obtained with no toxicity increase.
Using artificial intelligence techniques, we compute optimal personalized protocols for temozolomide administration in a population of patients with variability.
Our optimizations are based on a Pharmacokinetics/Pharmacodynamics (PK/PD) model with population variability for temozolomide, inspired by Faivre et al. 10 and Panetta et al. 25,26. The patient pharmacokinetic parameters can only be partially observed at admission and are progressively learned by Bayesian inference during treatment. For every patient, we seek to minimize tumor size while avoiding severe toxicity, i.e. maintaining an acceptable toxicity level. The optimization algorithm we rely on borrows from the field of artificial intelligence.
Optimal personalized protocols (OPP) achieve a sizable decrease in tumor size at the population level but also patient-wise. The tumor size is on average 67.2 g lighter than with the standard maximum-tolerated dose protocol (MTD) after 336 days (12 MTD cycles). The corresponding 90% confidence interval for average tumor size reduction amounts to 58.6–82.7 g. When treated with OPP, less patients experience severe toxicity in comparison to MTD.
We quantify in-silico the benefits offered by personalized oncology in the case of temozolomide administration. To do so, we compute optimal personalized protocols for a population of heterogeneous patients using artificial intelligence techniques. At each treatment day, the protocol is updated by taking into account the feedback obtained from patient's reaction to the drug administration. Personalized protocols greatly differ from each other, and from the standard MTD protocol. Benefits of personalization are very sizable: tumor sizes are much smaller on average and also patient-wise, while severe toxicity is made less frequent.
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