Scalable Robust Kidney Exchange

In barter exchanges, participants directly trade their endowed goods in a constrained economic setting without money. Transactions in barter exchanges are often facilitated via a central clearinghouse that must match participants even in the face of uncertainty---over participants, existence and quality of potential trades, and so on. Leveraging robust combinatorial optimization techniques, we address uncertainty in kidney exchange, a real-world barter market where patients swap (in)compatible paired donors. We provide two scalable robust methods to handle two distinct types of uncertainty in kidney exchange---over the quality and the existence of a potential match. The latter case directly addresses a weakness in all stochastic-optimization-based methods to the kidney exchange clearing problem, which all necessarily require explicit estimates of the probability of a transaction existing---a still-unsolved problem in this nascent market. We also propose a novel, scalable kidney exchange formulation that eliminates the need for an exponential-time constraint generation process in competing formulations, maintains provable optimality, and serves as a subsolver for our robust approach. For each type of uncertainty we demonstrate the benefits of robustness on real data from a large, fielded kidney exchange in the United States. We conclude by drawing parallels between robustness and notions of fairness in the kidney exchange setting.Comment: Presented at AAAI1

Essays in Econometrics and Dynamic Kidney Exchange

Thesis advisor: Stefan HoderleinThis dissertation is divided into two parts. Part I - Dynamic Kidney Exchange In recent years, kidney paired donation (KPD) has an emerged as an attractive alternative for end-stage renal disease patients with incompatible living donors. However, we argue that the matching algorithm currently used by organ clearinghouses is inefficient, in the sense that a larger number of patients may be reached if kidney transplant centers take into consideration how their pool of patients and donors will evolve over time. In our work Two Novel Algorithms for Dynamic Kidney Exchange, we explore this claim and propose new computational algorithms to increase the cardinality of matchings in a discrete-time dynamic kidney exchange model with Poisson entries and Geometric deaths. Our algorithms are classified into direct prediction methods and multi-armed bandit methods. In the direct prediction method, we use machine learning estimator to produce a probability that each patient-donor pair should be matched today, as op- posed to being left for a future matching. The estimators are trained on offline optimal solutions. In contrast, in multi-armed bandit methods, we use simulations to evaluate the desirability of different matchings. Since the amount of different matchings is enormous, multi-armed bandits (MAB) are employed to decrease order to decrease the computational burden. Our methods are evaluated using simulations in a variety of simulation configurations. We find that the performance of at least one of our methods, based on multi-armed bandit algorithms, is able to uniformly dominate the myopic method that is used by kidney transplants in practice. We restrict our experiments to pairwise kidney exchange, but the methods described here are easily extensible, computational constraints permitting. Part II - Econometrics In our econometric paper Heterogenous Production Functions, Panel Data, and Productivity, we present methods for identification of moments and nonparametric marginal distributions of endogenous random coefficient models in fixed-T linear panel data models. Our identification strategy is constructive, immediately leading to relatively simple estimators that can be shown to be consistent and asymptotically normal. Because our strategy makes use of special properties of “small” (measure-zero) subpopulations, our estimators are irregularly identified: they can be shown to be consistent and asymptotically Normal, but converge at rates slower than root-n. We provide an illustration of our methods by estimating first and second moments of random Cobb-Douglas coefficients in production functions, using Indian plant-level microdata.Thesis (PhD) — Boston College, 2018.Submitted to: Boston College. Graduate School of Arts and Sciences.Discipline: Economics

Tissue and sex especifities in the Ca2+ handling by isolated mitochondria : evaluations under conditions avoiding the permeability transition

Orientadores: Tiago Rezende Figueira, Roger Frigério CastilhoDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências MédicasResumo: Algumas das características das mitocôndrias, incluindo as suas funções de transporte de Ca2+, podem apresentar dimorfismo sexual e especificidades teciduais. No entanto, as mensurações do transporte de Ca2+ em mitocôndrias isoladas estão sujeitas a artefatos secundários a abertura do poro de transição de permeabilidade mitocondrial (PTP) induzido pelo acúmulo excessivo de Ca2+ nesta organela. Neste estudo, o objetivo inicial foi avaliar se a inibição do PTP pela ciclosporina A (CsA) afeta a mensuração de diversas variáveis que descrevem o transporte de Ca2+por mitocôndrias isoladas de fígado de rato. Os resultados obtidos indicam que as concentrações de estado estável do Ca2+ externo a mitocôndria e as taxas deefluxo mitocondrial de Ca2+através de trocadores seletivos foram superestimados em até 4 vezes quando o PTP não foi inibido farmacologicamente pela CsA. O objetivo subsequente foi analisar o transporte de Ca2+ em mitocôndrias isoladas de fígado, de músculo esquelético, de coração e de cérebro de ratos machos e fêmeas sob condições experimentais específicas (i.e. meio de incubação contendo inibidores TPM, substratos energéticos ligados a NAD e níveis relevantes de Ca2+, Mg2+e Na+). Os dados indicaram que a taxa de influxo de Ca2+em mitocôndrias de fígado foi ~4 vezes superior a dos outros tecidos, as quais foram semelhantes entre si. Em contrapartida, as taxas de efluxo de Ca2+ apresentaram uma maior diversidade entre tecidos, especialmente na presença de Na+. Curiosamente, o efluxo de Ca2+na ausência de Na+foi significativamente mais elevado nas mitocôndrias cardíacas (~4nmol/mg/min) em relação às taxas observadas nos outros tecidos, contrariando a concepção de que o efluxo de Ca2+de mitocôndrias de coração é dependente, quase que exclusivamente, de um trocador que requer Na+. A especificidade em relação ao sexo só foi observada em dois índices relacionados a homeostase mitocondrial de Ca2+(i.e. cinética geral normalizada da captação de Ca2+ e a concentração de estado estável do Ca2+ externo a mitocôndria) em mitocôndrias isoladas de coração (mais lentos ou maiores na fêmea) e na respiração estimulada por ADP em mitocôndrias de fígado (~20% maior na fêmea). O presente estudo demonstrou a importância metodológica de se prevenir a abertura do PTP para a análise das propriedades e da variabilidade fisiológica do transporte de Ca2+por mitocôndrias isoladas. Adicionalmente, concluímos que sob as condições experimentais aqui utilizadas, o efluxo de Ca2+ mitocondrial apresenta grandes especificidades teciduais e que alguns achados desafiam conceitos estabelecidos em estudos anteriores sob condições arguivelmente menos controladasAbstract: The characteristics of mitochondria, including their Ca2+ transport functions, may exhibit tissue specificity and sex dimorphism. Because the measurements of the Ca2+ handling by isolated mitochondria may be biased by dysfunction secondary to Ca2+-induced mitochondrial permeability transition (MPT) pore opening, this study evaluates the extent to which MPT inhibition by cyclosporine-A affects the measurement of Ca2+ transport in isolated rat liver mitochondria. The results indicate that the steady-state levels of external Ca2+ and the rates of mitochondrial Ca2+ efflux through the selective pathways can be overestimated by up to 4-fold if MPT pore opening is not prevented. Then, we analyzed the Ca2+ transport in isolated mitochondria from the liver, skeletal muscle, heart and brain of male and female rats under incubation conditions containing MPT inhibitors, NAD-linked substrates and relevant levels of free Ca2+, Mg2+ and Na+. Except for the liver mitochondria displaying values4-fold higher, the Ca2+ influx rates were similar among the other tissues. In contrast, the Ca2+ efflux rates exhibited more tissue diversity, especially in the presence of Na+. Interestingly, the Na+-independent Ca2+ efflux was highest in the heart mitochondria (~4 nmol/mg/min), thus challenging the view that heart mitochondrial Ca2+ efflux relies almost exclusively on a Na+-dependent pathway. Sex specificity was only observed in two kinetic indexes (i.e. the normalized overall kinetics of Ca2+ uptake and the steady-state levels of external Ca2+) of heart mitochondrial Ca2+ homeostasis (slower or higher in female)and in the ADP-stimulated respiration of liver mitochondria (~20% higher in females). The present study shows the methodological importance of preventing MPT when measuring the properties and the physiological variability of the Ca2+ handling by isolated mitochondria. Moreover, we conclude that mitochondrial Ca2+ efflux exhibits great tissue specificity under our conditions, which may challenge some concepts raised in previous studies that employed experimental conditions that are arguably not well controlledMestradoFisiopatologia MédicaMestra em Ciência

A hybrid algorithm for Bayesian network structure learning with application to multi-label learning

We present a novel hybrid algorithm for Bayesian network structure learning, called H2PC. It first reconstructs the skeleton of a Bayesian network and then performs a Bayesian-scoring greedy hill-climbing search to orient the edges. The algorithm is based on divide-and-conquer constraint-based subroutines to learn the local structure around a target variable. We conduct two series of experimental comparisons of H2PC against Max-Min Hill-Climbing (MMHC), which is currently the most powerful state-of-the-art algorithm for Bayesian network structure learning. First, we use eight well-known Bayesian network benchmarks with various data sizes to assess the quality of the learned structure returned by the algorithms. Our extensive experiments show that H2PC outperforms MMHC in terms of goodness of fit to new data and quality of the network structure with respect to the true dependence structure of the data. Second, we investigate H2PC's ability to solve the multi-label learning problem. We provide theoretical results to characterize and identify graphically the so-called minimal label powersets that appear as irreducible factors in the joint distribution under the faithfulness condition. The multi-label learning problem is then decomposed into a series of multi-class classification problems, where each multi-class variable encodes a label powerset. H2PC is shown to compare favorably to MMHC in terms of global classification accuracy over ten multi-label data sets covering different application domains. Overall, our experiments support the conclusions that local structural learning with H2PC in the form of local neighborhood induction is a theoretically well-motivated and empirically effective learning framework that is well suited to multi-label learning. The source code (in R) of H2PC as well as all data sets used for the empirical tests are publicly available.Comment: arXiv admin note: text overlap with arXiv:1101.5184 by other author

Optimizing Equitable Resource Allocation in Parallel Any-Scale Queues with Service Abandonment and its Application to Liver Transplant

We study the problem of equitably and efficiently allocating an arriving resource to multiple queues with customer abandonment. The problem is motivated by the cadaveric liver allocation system of the United States, which includes a large number of small-scale (in terms of yearly arrival intensities) patient waitlists with the possibility of patients abandoning (due to death) until the required service is completed (matched donor liver arrives). We model each waitlist as a GI/MI/1+GI queue, in which a virtual server receives a donor liver for the patient at the top of the waitlist, and patients may abandon while waiting or during service. To evaluate the performance of each queue, we develop a finite approximation technique as an alternative to fluid or diffusion approximations, which are inaccurate unless the queue's arrival intensity is large. This finite approximation for hundreds of queues is used within an optimization model to optimally allocate donor livers to each waitlist. A piecewise linear approximation of the optimization model is shown to provide the desired accuracy. Computational results show that solutions obtained in this way provide greater flexibility, and improve system performance when compared to solutions from the fluid models. Importantly, we find that appropriately increasing the proportion of livers allocated to waitlists with small scales or high mortality risks improves the allocation equity. This suggests a proportionately greater allocation of organs to smaller transplant centers and/or those with more vulnerable populations in an allocation policy. While our motivation is from liver allocation, the solution approach developed in this paper is applicable in other operational contexts with similar modeling frameworks.Comment: 48 Page

Minimally Invasive Urological Procedures and Related Technological Developments

The landscape of minimally invasive urological intervention is changing. A lot of new innovations and technological developments have happened over the last 3 decades. Laparoscopy and robotic surgery have revolutionised kidney and prostate cancer treatment, with more minimally invasive procedures now being carried out than ever before. At the same time, technological advancements and the use of laser have changed the face of endourology. Several new innovative treatments are now commonplace for benign prostate enlargement (BPE). Management of prostate cancer now involves procedures such as robotic prostatectomy, brachytherapy, radiotherapy, cryotherapy and HIFU. Robotic partial nephrectomy and cryotherapy have changed the face of renal cancer. En-bloc resection of bladder cancer is challenging the traditional management of non-muscle invasive bladder cancer and becoming commonplace, while robotic cystectomy is also gaining popularity for muscle invasive bladder cancer. Newer surgical intervention related to BPE includes laser (holmium, thulium and green light), water-based treatment (Rezum, Aquablation) and other minimally invasive procedures such as prostate artery embolisation (PAE) and Urolift. Endourological procedures have incorporated newer laser types and settings such as moses technology, disposable ureteroscopes (URS) and minimisation of percutaneous nephrolithotomy (PCNL) instruments. All these technological innovations and improvements have led to shorter hospital stay, reduced cost, potential reduction in complications and improvement in the quality of life (QoL)

Sub Maximal Ergospirometry Parameters in Untrained Non-Frail Octogenarian Subjects

This research received resources from the Vicerrectoria for Research, Development and Innovation of the University of Santiago de Chile. Dicyt, codigo 022087CB_DAS, categoria Dicyt Asociativo.Background and Objectives: The prevalence of chronic diseases increases with age, and in octogenarian elderly, a cardiorespiratory test with gas analysis is more effective in determining the risk of mortality than applying the conventional risk factors. Materials and Methods: 25 untrained non-frail octogenarian subjects (four men) performed a submaximal test with gas analysis, which was stopped after the second ventilatory threshold (VT2) was reached. The variables analyzed were oxygen consumption at the first threshold (VO2 VT1); ventilatory class (VE/VCO2); oxygen uptake efficiency slope (OUES); cardiorespiratory optimal point (COP); oxygen pulse difference between VT2 and VT1 (diff. VO2/HR VT2-VT1). Results: the variables were classified categorically based on cut-off points present in the literature, where the variable with the highest percentage of altered cases was dif. VO2/HR VT2-VT1 at 48%; followed by VO2 VT1 at 40%, OUES at 36%, COP at 32%, and VE/VCO2 at 24%. Chi-square analysis between the measured parameters defined that normal and altered variables were related to each other, except for the variable VE/VCO2 and OUES. Conclusions: it was found that the main altered variable was the oxygen pulse and the least altered variable was VCO2/VCO2; there was only a statistically significant difference in a pair of OUES vs. VE/VCO2 variables.Vicerrectoria for Research, Development and Innovation of the University of Santiago de Chile. Dicyt, categoria Dicyt Asociativo 022087CB_DA