Stochastic modeling and decision making in two healthcare applications: inpatient flow management and influenza pandemics

Delivering health care services in an efficient and effective way has become a great challenge for many countries due to the aging population worldwide, rising health expenses, and increasingly complex healthcare delivery systems. It is widely recognized that models and analytical tools can aid decision-making at various levels of the healthcare delivery process, especially when decisions have to be made under uncertainty. This thesis employs stochastic models to improve decision-making under uncertainty in two specific healthcare settings: inpatient flow management and infectious disease modeling. In Part I of this thesis, we study patient flow from the emergency department (ED) to hospital inpatient wards. This line of research aims to develop insights into effective inpatient flow management to reduce the waiting time for admission to inpatient wards from the ED. Delayed admission to inpatient wards, also known as ED boarding, has been identified as a key contributor to ED overcrowding and is a big challenge for many hospitals. Part I consists of three main chapters. In Chapter 2 we present an extensive empirical study of the inpatient department at our collaborating hospital. Motivated by this empirical study, in Chapter 3 we develop a high fidelity stochastic processing network model to capture inpatient flow with a focus on the transfer process from the ED to the wards. In Chapter 4 we devise a new analytical framework, two-time-scale analysis, to predict time-dependent performance measures for some simplified versions of our proposed model. We explore both exact Markov chain analysis and diffusion approximations. Part I of the thesis makes contributions in three dimensions. First, we identify several novel features that need to be built into our proposed stochastic network model. With these features, our model is able to capture inpatient flow dynamics at hourly resolution and reproduce the empirical time-dependent performance measures, whereas traditional time-varying queueing models fail to do so. These features include unconventional non-i.i.d. (independently and identically distributed) service times, an overflow mechanism, and allocation delays. Second, our two-time-scale framework overcomes a number of challenges faced by existing analytical methods in analyzing models with these novel features. These challenges include time-varying arrivals and extremely long service times. Third, analyzing the developed stochastic network model generates a set of useful managerial insights, which allow hospital managers to (i) identify strategies to reduce the waiting time and (ii) evaluate the trade-off between the benefit of reducing ED congestion and the cost from implementing certain policies. In particular, we identify early discharge policies that can eliminate the excessively long waiting times for patients requesting beds in the morning. In Part II of the thesis, we model the spread of influenza pandemics with a focus on identifying factors that may lead to multiple waves of outbreak. This line of research aims to provide insights and guidelines to public health officials in pandemic preparedness and response. In Chapter 6 we evaluate the impact of seasonality and viral mutation on the course of an influenza pandemic. In Chapter 7 we evaluate the impact of changes in social mixing patterns, particularly mass gatherings and holiday traveling, on the disease spread. In Chapters 6 and 7 we develop agent-based simulation models to capture disease spread across both time and space, where each agent represents an individual with certain socio-demographic characteristics and mixing patterns. The important contribution of our models is that the viral transmission characteristics and social contact patterns, which determine the scale and velocity of the disease spread, are no longer static. Simulating the developed models, we study the effect of the starting season of a pandemic, timing and degree of viral mutation, and duration and scale of mass gatherings and holiday traveling on the disease spread. We identify possible scenarios under which multiple outbreaks can occur during an influenza pandemic. Our study can help public health officials and other decision-makers predict the entire course of an influenza pandemic based on emerging viral characteristics at the initial stage, determine what data to collect, foresee potential multiple waves of attack, and better prepare response plans and intervention strategies, such as postponing or cancelling public gathering events.Ph.D

PO-259 Effect of 30%，50% and 70% VO2 max treadmill exercises on gut microbiome in hypertensive mice

Objective Gut microbiome has a significant impact on human health through the interaction with host and environment, which is closely related to a series of chronic diseases. The diversity of gut microbiome and its metabolic disorder are the risk factor of hypertension. The changes of gut microbiome structure and abundance are closely related to the pathogenesis of hypertension, in which Bifidobacterium and lactic acid bacteria can bind with the hypotensive substances to show the hypotensive therapy. However, the diet and exercise have great impact on the structure and function of gut microbiome, and of which aerobic exercise could increase the ratio of gut beneficial bacteria to harmful bacteria effectively. The effect of treadmill exercise on gut microbiome of hypertensive mice was studied in this paper, which provided a theoretical basis for the prevention and treatment of hypertension by gut microbiome. Methods SPF Kunming mice were fed with 8% high salt diet for 6 weeks to make the hypertension model. Compared with the blood pressure of mice before the formal experiment, The standard was that the blood pressure of the experimental mice was increased by SBP >15% or DBP > 5%, which was indicated the model of hypertension was established successfully. The motion slope and velocity of the maximum oxygen uptake of 30%, 50%, and 70% were measured respectively. The mice were divided into 4 groups randomly according to their body weight, 10 mice/group. The 30% VO2 max, 50% VO2 max, and 70% VO2 max were exercised for 6 weeks as well as the control group. The mice were divided into cages and fed in accordance with the national standard rodent diet. The blood pressure of mice was measured weekly by tail pressure method (Tail-cuff).The abundance of Bifidobacterium, Bacteroides, Lactobacillus and Enterobacter in the gut microbiome of mice feces were tested by 16S sequencing every two weeks. The ratio of Firmicute / Bacteroides (F/B ratio) was also measured by sequencing as a parameter to reflect the disorder of gut microbiome. The ratio of Firmicutes / Bacteroides is almost equal 1, and the present study found that the F/B increased significantly in the hypertensive group. Real-time PCR was used to detect the changes of plasma inflammatory factors IL-1β, IL-6 and TNF-ɑ. The previous study had shown that the intestinal disorders can lead to an increase in pathogenic bacteria, further leading to the inflammation. Finally, the experimental data were analyzed by independent sample t-test. Results (1) After six weeks of exercise intervention, the blood pressure (132.87mm Hg±5.23mm Hg) of the exercise group was significantly lower than the control group (99.57mm Hg±7.47mm Hg), especially in the 50%VO2 max mice. (2) Compared with the rest group, the abundance of gut microbiome in the exercise group was increased, among which the number of Bifidobacteria, Lactobacillus, and Bacteroides were increased significantly, of which 50% of VO2 max group increased most significantly, and the number of Enterobacter was less than the control group (p<0.05). (3) Compared with the control group, the ratio of F/B in the exercise groups were lower than the control group, but the 50% VO2 max group was decreased most obviously (p < 0.05). (4) Compared with the control group, the plasma levels of IL-1β, IL-6 and TNF-ɑ in exercise groups were significantly lower than the control group (p < 0.05). Conclusions  (1) The aerobic exercise could change the abundance and structure of gut microbiome in hypertensive mice, increase the beneficial bacteria Bifidobacteria and lactobacillus in the intestinal tract of mice, and reduce the ratio of Firmicutes/Bacteroides, improving the gut microbiome disorder. (2) The aerobic exercise could alleviate the inflammatory reaction of the body by regulating the structure of gut microbiome of hypertensive mice, improving the blood pressure of mice; (3) 50%VO2 max was the most significant exercise intensity to improve the abundance and structure of gut microbiome in hypertensive mice. &nbsp

PO-128 Effects of 30%, 50%, 70%VO2 max treadmill exercises on gut microbiome of atherosclerotic mice

Objective  To observe the dynamic changes of gut microbiome in mice before and after different intensities of treadmill exercises, and to explore the effects of different intensities of treadmill exercises on gut microbiome of atherosclerotic (AS) mice. Methods  The 50 male ApoE-/- mice aged 8 weeks were randomly divided into 2 groups, 10 mice in the general feeding group and the other 40 mice in the AS group, which were fed with normal and high-fat diet for 4 weeks respectively. Weight and blood test were taken before and after 4 weeks feeding. The serum Triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein (HDL) levels were examined by blood test in ApoE-/- mice model, and atherosclerotic disease degeneration score of adult mice was used to determine the success of modeling after 4 weeks feeding. Then two mice selected from the normal and high-fat group respectively selected to test the maximum oxygen uptake (VO2 max) by the reformative Bedford method, and the running platform speed and slope corresponding to 30%, 50% and 70%VO2 max were determined. The 40 AS mice were randomly divided into the model blank group, the low-intensity exercise group, the medium-intensity exercise group and the high-intensity exercise group according to their weight for 4 weeks of exercises, respectively. The low-intensity exercise group was 30% VO2 max, with a slope of 10 degrees and a speed of 10 m/min. The medium intensity exercise group was 50% VO2 max with a slope of 10 degrees and a speed of 15 m/min. The high-intensity exercise group was 70% VO2 max with a slope of 10 degrees and a speed of 20 m/min. The exercises were performed for 4 weeks, 5 days a week, 20 minutes a day. The fresh feces were collected from 5 groups of mice before and after 4 weeks treadmill exercises. The number of gut Lactobacillus, Bacteroides, Firmicutes, Bifidobacterium, Verrucomicrobiaceae, Akkermansia , Escherichia coli, Collinsella and Clostridium in AS mice were analyzed by 16s sequencing.  Results 1. The TG, TC and LDL-C were significantly increased in the blood serum of the mice after the modeling, and the HDL-C was decreased, and the atherosclerotic disease degeneration score was significantly increased in the adult mice, and the modeling was successful. 2. The different intensity treadmill exercises can increase the number of gut probiotics in mice and decrease the number of harmful bacteria. The beneficial bacteria in gut tract of AS mice with moderate intensity of 50% VO2max was observed in the experiment: Bacteroides, Bifidobacterium and Verrucomicrobiaceae, Akkermansia were significantly increased, P<0.05. The harmful bacteria:Lactobacillus, Escherichia coli, Collinsella and Clostridium were significantly decreased, P<0.05. The ratio of Firmicutes / Bacteroidetes was increased. Conclusions  1. High-fat diet can lead to AS in ApoE-/- mice. 2. The different intensity treadmill exercises can reduce the weight of AS mice. 3. The number and abundance of probiotics of gut microbiome of AS mice could be promoted by different intensity treadmill exercises, among which the medium intensity aerobic exercise can significantly increase the number of beneficial bacteria such Bacteroidetes, Bifidobacteria, Verrucomicrobiaceae and Akkermansia, meanwhile, the structure of gut microbiome in AS mice was improved as well

A universal strategy for metal oxide anchored and binder-free carbon matrix electrode : a supercapacitor case with superior rate performance and high mass loading

Financial support from China Fund KU Leuven (ISP/13/02SJT) is acknowledged. J. Luo acknowledges the Research Foundation - Flanders (FWO) for FWO Postdoctoral Fellowship (12F5514N), a Research Grant (Project number: 1529816N) and a travel grant (V410316N) for a Visiting Professorship in Technical University of Denmark. X. Zhang is grateful to the China Scholarship Council. We thank Prof. Dirk De Vos (KU Leuven) for technical discussions, Prof. Lei Li (Shanghai Jiao Tong University) for providing nickel foams and Prof. Qingfeng Li (Technical University of Denmark) for assistance in TEM measurements. Appendix ADespite the significant advances in preparing carbon-metal oxide composite electrodes, strategies for seamless interconnecting of these two materials without using binders are still scarce. Herein we design a novel method for in situ synthesis of porous 2D-layered carbon-metal oxide composite electrode. Firstly, 2D-layered Ni-Co mixed metal-organic frameworks (MOFs) are deposited directly on nickel foam by anodic electrodeposition. Subsequent pyrolysis and activation procedure lead to the formation of carbon-metal oxides composite electrodes. Even with an ultrahigh mass loading of 13.4 mg cm, the as-prepared electrodes exhibit a superior rate performance of 93% (from 1 to 20 mA cm), high capacitance (2098 mF cm at a current density of 1 mA cm), low resistance and excellent cycling stability, making them promising candidates for practical supercapacitor application. As a proof of concept, several MOF derived electrodes with different metal sources have also been prepared successfully via the same route, demonstrating the versatility of the proposed method for the preparation of binder-free carbon-metal oxide composite electrodes for electrochemical devices

Role of tungsten doping on the surface states in BiVO4 photoanodes for water oxidation: tuning the electron trapping process

The nanostructured BiVO4 photoanodes were prepared by electrospinning and were further characterized by XRD, SEM, and XPS, confirming the bulk and surface modification of the electrodes attained by W addition. The role of surface states (SS) during water oxidation for the as-prepared photoanodes was investigated by using electrochemical, photoelectrochemical, and impedance spectroscopy measurements. An optimum 2% doping is observed in voltammetric measurements with the highest photocurrent density at 1.23 VRHE under back side illumination. It has been found that a high PEC performance requires an optimum ratio of density of surface states (NSS) with respect to the charge donor density (Nd), to give both good conductivity and enough surface reactive sites. The optimum doping (2%) shows the highest Nd and SS concentration, which leads to the high film conductivity and reactive sites. The reason for SS acting as reaction sites (i-SS) is suggested to be the reversible redox process of V5+/V4+ in semiconductor bulk to form water oxidation intermediates through the electron trapping process. Otherwise, the irreversible surface reductive reaction of VO2+ to VO2+ though the electron trapping process raises the surface recombination. W doping does have an effect on the surface properties of the BiVO4 electrode. It can tune the electron trapping process to obtain a high concentration of i-SS and less surface recombination. This work gives a further understanding for the enhancement of PEC performance caused by W doping in the field of charge transfer at the semiconductor/electrolyte interface.Peer ReviewedPostprint (author's final draft

Boosting Photoelectrochemical Water Oxidation of Hematite in Acidic Electrolytes by Surface State Modification

State-of-the-art water-oxidation catalysts (WOCs) in acidic electrolytes usually contain expensive noble metals such as ruthenium and iridium. However, they too expensive to be implemented broadly in semiconductor photoanodes for photoelectrochemical (PEC) water splitting devices. Here, an Earth-abundant CoFe Prussian blue analogue (CoFe-PBA) is incorporated with core-shell FeO/FeTiO type II heterojunction nanowires as composite photoanodes for PEC water splitting. Those deliver a high photocurrent of 1.25 mA cm at 1.23 V versus reversible reference electrode in acidic electrolytes (pH = 1). The enhancement arises from the synergic behavior between the successive decoration of the hematite surface with nanolayers of FeTiO and then, CoFe-PBA. The underlying physical mechanism of performance enhancement through formation of the FeO/FeTiO/CoFe-PBA heterostructure reveals that the surface states' electronic levels of hematite are modified such that an interfacial charge transfer becomes kinetically favorable. These findings open new pathways for the future design of cheap and efficient hematite-based photoanodes in acidic electrolytes

The impact of mass gatherings and holiday traveling on the course of an influenza pandemic: a computational model

<p>Abstract</p> <p>Background</p> <p>During the 2009 H1N1 influenza pandemic, concerns arose about the potential negative effects of mass public gatherings and travel on the course of the pandemic. Better understanding the potential effects of temporal changes in social mixing patterns could help public officials determine if and when to cancel large public gatherings or enforce regional travel restrictions, advisories, or surveillance during an epidemic.</p> <p>Methods</p> <p>We develop a computer simulation model using detailed data from the state of Georgia to explore how various changes in social mixing and contact patterns, representing mass gatherings and holiday traveling, may affect the course of an influenza pandemic. Various scenarios with different combinations of the length of the mass gatherings or traveling period (range: 0.5 to 5 days), the proportion of the population attending the mass gathering events or on travel (range: 1% to 50%), and the initial reproduction numbers R₀(1.3, 1.5, 1.8) are explored.</p> <p>Results</p> <p>Mass gatherings that occur within 10 days before the epidemic peak can result in as high as a 10% relative increase in the peak prevalence and the total attack rate, and may have even worse impacts on local communities and travelers' families. Holiday traveling can lead to a second epidemic peak under certain scenarios. Conversely, mass traveling or gatherings may have little effect when occurring much earlier or later than the epidemic peak, e.g., more than 40 days earlier or 20 days later than the peak when the initial R₀= 1.5.</p> <p>Conclusions</p> <p>Our results suggest that monitoring, postponing, or cancelling large public gatherings may be warranted close to the epidemic peak but not earlier or later during the epidemic. Influenza activity should also be closely monitored for a potential second peak if holiday traveling occurs when prevalence is high.</p

Clonal evolution in liver cancer at single-cell and single-variant resolution.

Genetic heterogeneity of tumor is closely related to its clonal evolution, phenotypic diversity and treatment resistance, and such heterogeneity has only been characterized at single-cell sub-chromosomal scale in liver cancer. Here we reconstructed the single-variant resolution clonal evolution in human liver cancer based on single-cell mutational profiles. The results indicated that key genetic events occurred early during tumorigenesis, and an early metastasis followed by independent evolution was observed in primary liver tumor and intrahepatic metastatic portal vein tumor thrombus. By parallel single-cell RNA-Seq, the transcriptomic phenotype of HCC was found to be related with genetic heterogeneity. For the first time we reconstructed the single-cell and single-variant clonal evolution in human liver cancer, and dissection of both genetic and phenotypic heterogeneity will facilitate better understanding of their relationship