Thesis (Ph. D. in Electrical and Medical Engineering)--Harvard-MIT Program in Health Sciences and Technology, 2013.. / Cataloged from PDF version of thesis. / Includes bibliographical references (p. 64-72). / Mucus is a biological hydrogel which lines the wet (non-keratinized) epithelia of the body. Mucus provides a gateway between the cells of the epithelium and the outside world, and is postulated to provide a selective filtering function which is critical to physiological functioning and has been implicated in diseases. Currently, much of the mechanisms and criteria of this selective filtering function is not well understood. In this thesis, we contribute novel microfluidic devices to characterize the selective permeability properties of the mucus barrier. Microfluidics provides the engineering ability to create channels with precise geometries, fluid flow capability, and allow chemical concentration gradients. Our devices mimic the physiological environment of the mucosa and enable improved measurements of the mucus layer selective permeability. The first microfluidic device mimics the acid barrier function of the stomach mucus layer. This device reproduces on-chip the secretion of mucus by the gastric mucosa into an acidic stomach lumen. We use this device to demonstrate that the secretion of mucins, the glycoprotein structural component of mucus, contributes significantly to the acid barrier function by continuously binding H'. The second microfluidic device probes the permeability of the mucus barrier to nanoscale peptides, as a model for drug molecules and in vivo signaling molecules. The device enabled the creation of a mucus layer next to a flowing aqueous layer, mimicking the in vivo mucus layer and lumen of the gastrointestinal, respiratory, and female reproductive tracts. Peptides added to the aqueous flow diffused across the mucus barrier interface into the mucus layer. This device demonstrated that the mucus barrier provides selective permeability to nanoscale peptides based on electrostatic interactions, and suggest novel surface functionalization strategies for drug carriers to improve mucosal drug delivery. Taken together, this thesis provides new microfluidic tools to probe the selective permeability function of the mucus barrier. Using the microfluidic tools, we show new mechanistic understanding of this barrier. / by Leon Daliang Li. / Ph.D.in Electrical and Medical Engineering

Thesis (M.B.A.)--Massachusetts Institute of Technology, Sloan School of Management, 2013. / Cataloged from PDF version of thesis. / Includes bibliographical references (p. 22-24). / There has recently been a dramatic increase in demand for healthcare innovation. In this thesis we present a framework for analyzing a digital health innovation ecosystem in the US. Our framework consists of four key activities: innovation generation, entrepreneurial team formation, early company incubation, and validation of the core innovation. Throughout the paper we analyze the existing literature around innovation in order to motivate the design of the framework. The framework is applied to three key innovation ecosystems in the US; Silicon Valley, Boston, and New York as a way to illustrate how this tool can be used to analyze digital health ecosystems in order to understand what key areas exist for improvement. We end the thesis with a discussion of the various programmatic ideas that might be used to bolster each category as well as a discussion of adapting this type of ecosystem development to the natural capacity of a region. / by Elliot Cohen. / M.B.A.

Thesis: S.M. in Engineering and Management, Massachusetts Institute of Technology, School of Engineering, System Design and Management Program, Engineering and Management Program, 2014. / Cataloged from PDF version of thesis. / Includes bibliographical references (pages 74-80). / A 2007 congressional mandate to the U.S. Department of Defense (DOD) concerned instituting a center to address the ever increasing invisible wounds of the Iraq and Afghanistan wars and impact to the Military Health System (MHS) by way of its excellence. The National Intrepid Center of Excellence (NICoE), constructed through private donations secured by the Intrepid Fallen Heroes Fund (IFHF), was established for targeting the comorbid traumatic brain injury (TBI) and psychological health (PH) conditions of these wars. There are three prongs of the NICoE's mission: the first involves the clinical care of services members through diagnosis and treatment, the second education, and the third research, which informs the other two prongs. Interdisciplinary and patient- and family-centric, the clinical care offered is cutting-edge, as well as the research conducted, which is on the forefront of efforts to understand comorbid TBI and PH conditions. The clinical care prong is in the process of being replicated to the NICoE's satellite centers at home bases across the U.S., which have already or will be established. This thesis involves characterizing the NICoE from Enterprise Architecting and Sustainability Pillars frameworks, as well as their interrelationships, to gain holistic understanding of the NICoE as an enterprise in service to the MHS and society in general, which is not evidenced in the literature. This understanding, along with information pertaining to the satellite centers and additional research, is used to recommend guidance in the form of heuristics to the NICoE for its replication to the centers. / by Christine Meier. / S.M. in Engineering and Management

Cette thèse est axée sur le domaine de la communication optique sans fil en intérieur pour la surveillance de la santé basée sur des capteurs corporels. L’état de l'art des communications optique sans fil dans les domaines infrarouge, visible et UV ainsi que l'analyse des systèmes liés à la santé utilisant cette technologie ont été fournis. Cela a permis de définir les objectifs et l'orientation de cette thèse. Nous avons étudié l'utilisation de la technologie infrarouge pour la transmission de données entre un capteur porté par un patient et des récepteurs situés aux coins d'un panneau d'éclairage central au plafond de l'environnement. Un lien en visible a été utilisé pour la transmission de données du luminaire vers le patient portant un smartphone équipé d'un décodeur. Les principaux défis étaient la robustesse des liens infrarouge et visible en ce qui concerne la mobilité du patient et l'impact du corps de l'utilisateur en raison de l'emplacement du capteur. Les simulations de canaux réalisées grâce à la technique de Ray-Tracing associée à la méthode de Monte-Carlo ont permis de déterminer le gain de canal qui est le paramètre principal représentant la performance. En raison de la mobilité du patient, l'analyse a été réalisée de manière statistique et en tenant compte de différents emplacements du capteur sur le corps, de la cheville à l'épaule. Les paramètres physiques et géométriques optimaux relatifs aux émetteurs et aux récepteurs afin de garantir les meilleures performances ont été déduites. Il a été démontré qu’il est essentiel de modéliser la présence du corps pour les deux liaisons montante et descendante. Les performances globales du système ont mis en évidence le potentiel des transmissions sans fil entièrement optiques pour la surveillance médicale basée sur des capteurs corporels. Cela a été en partie confirmé par des expérimentations menées à partir de prototypes de capteur communicant en infrarouge et de produits commerciaux pour la liaison en visible. / This thesis is focused on the field of indoor optical wireless communication for health monitoring based on body sensors. The state of the art of optical wireless in the infrared, visible and UV domains as well as the analysis of health related systems using this technology have been provided. This helped to define the objectives and orientations of this thesis. We have studied the use of infrared technology for data transmission between a sensor worn by a patient and receivers located at the corners of a central lighting panel at the ceiling of the environment. A link in visible was used for the transmission of data from the luminaire to the patient carrying a smartphone equipped with a decoder. The main challenges were the robustness of the infrared and visible links with regard to patient mobility and the impact of the user's body due to the location of the sensor. The channel simulations performed using the Ray-Tracing technique associated with the Monte-Carlo method allowed determining the channel gain, which is the main parameter representing the performance. Due to the patient mobility, the analysis was performed statistically and taking into account different locations of the sensor on the body, from the ankle to the shoulder. The optimal physical and geometrical parameters for transmitters and receivers to ensure the best performance have been deduced. It has been shown that it is essential to model the presence of the body for both uplink and downlink. The overall performance of the system has highlighted the potential of fully optical wireless transmissions for medical surveillance based on body sensors. This has been partly confirmed by experiments carried out from infrared communicating sensor prototypes and commercial products for the visible link.

Epilepsy, a chronic neurological disorder has an estimated prevalence of between 0.4% and 1.0% globally, and 1% in South Africa. Epilepsy has multiple underlying causes including head injuries, vascular insults, hippocampal sclerosis, cortical dysgenesis, drug or alcohol abuse and infectious diseases, such as neurocysticercosis and HIV/AIDS. Causes in South Africa are likely to be infectious due to the high HIV and tuberculosis prevalence. The condition has substantial individual and societal economic impacts, with economic costs ranging from the direct and indirect costs of treatment and loss of productivity due to illness. Primary treatment of epilepsy in the South African public sector is through pharmacotherapy, with monotherapy being preferred to polytherapy. No cost-effectiveness studies on the first-line treatment of epilepsy have been conducted in the South African context or in similar contexts using the combination of drugs in this analysis which are levetiracetam, lamotrigine, carbamazepine, phenytoin and valproate. The current first-line epilepsy treatment in South Africa is lamotrigine, phenytoin or carbamazepine. Levetiracetam is under consideration for use as a first-line treatment due to the reported minimal serious side effects, its ease of use, linear pharmacokinetics and reduced interaction with other drugs. The study was model-based and conducted from the providers’ perspective, specifically in the South African public health sector. It compared levetiracetam, lamotrigine, carbamazepine, phenytoin and valproate as first-line treatment in focal seizures (International Classification of Diseases (ICD)-10 code: G40.2) and generalized tonic-clonic seizures (ICD-10 code: G40.3). The population considered for the analysis was patients with newly diagnosed epilepsy expected to utilize services in the public health sector. The analysis consisted of a costeffectiveness analysis and a budget impact analysis. The budget impact analysis was conducted for the first year of treatment for each of the treatment strategies, while the cost-effectiveness analysis was conducted for a five-year period. Both a decision-tree representing the first six months of treatment and a Markov model representing the rest of the treatment period were used for the cost-effectiveness analysis. The methodology for the cost-effectiveness analysis was based on the International Decision Support Initiative (IDSI) reference case. Costs were expressed as South African Rands, 2018 value and effects were expressed as Quality Adjusted Life Years (QALYs). Results were expressed as Incremental Cost-Effectiveness Ratios (ICERs) and sensitivity analyses were performed to cater for uncertainty. The use of levetiracetam along with the use of phenytoin, valproate and carbamazepine in the treatment of newly diagnosed epilepsy was found to be dominated by treatment using lamotrigine. Treatment with lamotrigine over a five-year period was found to be the least costly option and had the highest number of QALYs gained. The estimated cost of treating one case of epilepsy was R1 252 higher using levetiracetam compared to using lamotrigine. Levetiracetam had 0,02 QALYs lower than those of lamotrigine. Phenytoin, carbamazepine and valproate were found to have the same effect size of 3,97 QALYs. Sensitivity analyses were conducted using some levetiracetam-related costs and quality of life values. Both the levetiracetam-related costs used in the sensitivity analyses showed that lower cost values were associated with less negative ICER values (i.e. levetiracetam became comparatively more cost-effective as the levetiracetam-related costs became lower). There were no trends observed regarding the impact of the quality of life measures and the probability of remaining controlled on levetiracetam on the ICER values obtained. The pharmaceutical costs of treating newly diagnosed epilepsy with levetiracetam were found to be higher in comparison to those of comparators. For a 100% treatment coverage, the cost of treatment with lamotrigine, the other second-generation AED under analysis was about R19 million cheaper compared to treatment with levetiracetam over a one-year period. Treatment with carbamazepine was found to be the cheapest option, costing about R20 million less than treatment with levetiracetam. On inclusion of other health systems costs associated with seizure and side-effect treatment levetiracetam was still found to be the costliest treatment option while lamotrigine became the least costly option. The effect sizes of all the treatments under analysis were similar, with a difference of 0,04 QALYs being observed between the most effective and the least effective treatment option. This led to costs being the main driver of the resulting ICER values. Approximately a 93% price reduction is required for levetiracetam to be more cost-effective than lamotrigine. The model results for the cost-effectiveness analysis agree with the findings from the study conducted to inform the National Institute for Health and Clinical Excellence (NICE) treatment guidelines in the United Kingdom, which found that levetiracetam was not cost-effective. Lamotrigine is recommended for the treatment of both partial and generalized tonic-clonic seizures by the Health Technology Assessment Agencies in the United Kingdom and Scotland. It is the only drug recommended for the treatment of both indications, with carbamazepine being recommended for the treatment of partial seizures and valproate for the treatment of generalized tonic-clonic seizures. Levetiracetam was found to not be a cost-effective treatment option for both generalized tonicclonic seizures and partial seizures in the South African public health sector context, even when accounting for the titration period and the drug prevalence of Steven Johnson Syndrome associated with some of the comparators. Lamotrigine is therefore recommended for use as the first-line treatment of epilepsy in the South African public health sector.

La presente tesi, attraverso l’utilizzo di diverse fonti di dati, sia longitudinali che trasversali, contribuisce alla letteratura esistente in materia di lavoro precario, invecchiamento e discriminazione di genere, fornendo evidenza empirica riguardo le conseguenze in termini di salute e benessere della precarietà, del pensionamento e della leadership femminile nel mercato del lavoro. Il primo capitolo esamina la relazione esistente fra insicurezza sul lavoro, prospettive di reimpiego e disagio psicologico, utilizzando dati cross-country provenienti dalle European Working Conditions Surveys del 2010. Il secondo capitolo è dedicato alla stima dell’effetto causale del pensionamento sull’utilizzo dei servizi sanitari in 10 paesi Europei nel periodo 2004-2013. In particolare, il capitolo approfondisce il tema della riduzione del costo opportunità del tempo libero dopo il pensionamento, che può dare luogo ad aumenti improvvisi nell’utilizzo dei servizi sanitari. Il terzo capitolo, infine, studia la relazione esistente tra leadership femminile, pratiche organizzative a livello aziendale e discriminazione di genere per 30 paesi Europei, considerati nel periodo 1995-2010. / The present dissertation, using both longitudinal and cross-sectional data from different sources, contributes to existing literature on precarious employment, aging and gender discrimination providing empirical evidence on the health and wellbeing outcomes of work-related insecurity, retirement and female leadership across European countries. Chapter 1 examines the relationship among perceived job insecurity, employability and psychological distress in Europe, using cross-country data from the 2010 European Working Conditions Surveys. Chapter 2, using SHARE data (from 2004 to 2013) for 10 European countries, is devoted to the analysis of the (causal) effect of retirement on health care utilization. In particular, it explores the existence of a discontinuous change in health investment at the time of retirement, as suggested by the theory, asking whether this ``puzzling'' jump is associated with the drop in the opportunity cost of time induced by retirement. Chapter 3 investigates the association between female leadership, work organization practices and perceived gender discrimination within firms, using EWCS data for 30 European countries for the period 1995-2010.

La tesi si compone di tre capitoli. Il primo capitolo è una rassegna critica che intende spiegare come mai la riforma del sistema sanitario in Cina non funziona come ci si aspettava. Comparando il caso cinese con le con le riforme avvenute in Messico e Vietnam, vengono individuate alcune ragioni metodologiche sia di policy design che di valutazione d’impatto. Il secondo capitolo propone una fusione tra la letteratura sulla spesa medica e la letteratura inerente alla misurazione multidimensionale della povertà. Viene così analizzato l’impatto della spesa medica non-rimborsabile sul benessere generale. Il nostro studio suggerisce che, nelle aree rurali dei paesi in via di sviluppo, specialmente lì dove il sistema sanitario è agli esordi, le famiglie tendono ad essere messe in condizione di povertà più per colpa di problematiche legate agli aspetti sanitari che per una vera e propria scarsità monetaria. Ne segue che il design e le valutazioni delle politiche di welfare dovrebbero avere un respiro più ampio e non focalizzarsi soltanto sulla povertà in termini di reddito. L’ultimo capitolo è un tentativo di valutare gli impatti di un esperimento sociale ‘block-randomized’ in Cina. E’ stata utilizzata la metodologia Difference-in-Difference per stimare l’average treatment effect con un insieme di variabili relative alle spese mediche non-rimborsabili. I risultati dimostrano come i poveri possano beneficiare di più da questo tipo di interventi. / The thesis consists three chapters. The first one, a critical review, aims at explaining why health care system reform in China does not work as expected. By comparing the case of China with the cases of Mexico and Vietnam, we try to find the explanation from the policy design and evaluation methodology. The second chapter proposes to combine catastrophic health expenditure literature with multidimensional poverty literature to analyze the impact of out-of-pocket health expenditure on overall well-being. Our study suggests that, in the rural area of developing countries, especially where health care system is in its infancy, households may be driven into poverty by health-related deprivation more than monetary deprivation. Therefore, policy-makers should evaluate and design welfare policy from a broader perspective other than only focusing on addressing the monetary poverty. The last chapter attempts to evaluate the impacts of a block-randomized social experiment in rural China, which implemented the provider payment intervention on outpatient services. Difference-in-difference methods are employed to estimate the average treatment effect with a set of outcome variables related to out-of-pocket health expenditure. We find that the poor may benefit more from the interventions.

In order for the collaborations to be fruitful and sustainable between organisations and open source software (OSS) ecosystems, maintainers need to understand if, and how it is possible to evaluate OSS ecosystem health in an effective manner. Understanding how OSS maintainers characterise ecosystem health and how they evaluate these health characteristics using digital evaluation tools is interesting to analyse since it could give insight in how ecosystem health in practice is evaluated, which health aspects can be evaluated with the help of digital tools, and what barriers exists in the evaluation processes. This qualitative study is based on semi-structured interviews and was conducted in order to answer two research questions regarding this topic. The answers which were produced by the semi-structured interviews were transcribed and coded to later be analysed where conclusions could be drawn. The research attempts to broaden the academic perspective on how ecosystem maintainers view health and how health evaluation digital tools can help maintainers understand the state of their ecosystem health, and what barriers exist. It became clear during the research that answering how ecosystem health is to be characterized is incredibly difficult since the answer might differ in many ways depending on the nature of the project, where the project is in its life cycle, and who is asking the questions. Two views surrounding the definition of ecosystem health are presented, one revolving around longevity and the other revolving around an ecosystem life cycle perspective. Furthermore, Diversity, Governance, Activity and Licensing seem to be the health characteristics maintainers find to be the most important for ecosystem health evaluation. Out of these, tools such as the ones offered by CHAOSS, seem somewhat geared towards assessing Activity, Licensing and Diversity. Saving time and finding trends when evaluating health are examples of how tools help maintainers however, barriers exist for maintainers in smaller or younger projects who have not practiced health evaluation for a very long time. Finally, another barrier is the amount of additional context and human judgment which is needed when using tools for the health evaluation. / För att samarbetet mellan organisationer och öppen källkod (OSS) ekosystem ska vara gynnsamma och hållbara, måste ekosystemsunderhållare förstå om och hur det är möjligt att utvärdera OSS-ekosystemhälsa på ett effektivt sätt. Att förstå hur OSS-underhållare karaktäriserar ekosystemhälsa och hur de utvärderar dessa hälsoegenskaper med hjälp av digitala utvärderingsverktyg är intressant att analysera eftersom det skulle kunna ge insikt i hur ekosystemhälsa i praktiken utvärderas, vilka hälsoaspekter som kan utvärderas med hjälp av digitala verktyg, och vilka hinder som finns i utvärderingsprocesserna. Denna kvalitativa studie är baserad på semistrukturerade intervjuer och genomfördes för att besvara två forskningsfrågor inom detta ämne. Svaren som producerades av de semistrukturerade intervjuerna transkriberades och kodades för att senare analyseras där slutsatser kunde dras. Forskningen försöker vidga det akademiska perspektivet på hur ekosystemsunderhållare ser på hälsa och hur hälsoutvärderingsverktyg kan hjälpa underhållare att förstå hälsotillståndet för deras ekosystem, men också vilka hinder som finns i processerna. Det blev tydligt under forskningen att det är otroligt svårt att svara på hur ekosystemhälsa ska karakteriseras eftersom svaret kan skilja sig åt på många sätt beroende på projektets karaktär, var projektet befinner sig i sin livscykel och vem som ställer frågorna. Två synpunkter kring definitionen av ekosystemhälsa tas upp, en som kretsar kring livslängd, och den andra som kretsar kring ett ekosystemlivscykelperspektiv. Dessutom verkar Mångfald, Styrning, Aktivitet och Licensiering vara de hälsoegenskaper som underhållare anser vara de viktigaste för hälsoutvärdering av ekosystem. Av dessa verkar verktyg som de som erbjuds av CHAOSS något inriktade på att bedöma Aktivitet, licensiering och mångfald. Att spara tid och hitta trender när man utvärderar hälsa är exempel på hur verktyg hjälper underhållare, men hinder finns för underhållare i mindre eller yngre projekt som inte har praktiserat hälsoutvärdering under en längre period. Slutligen är en annan barriär den mängden ytterligare kontext och mänskligt omdöme som behövs när man använder verktyg för hälsoutvärderingen.

Thesis: Ph. D., Massachusetts Institute of Technology, Department of Economics, 2018. / Cataloged from PDF version of thesis. / Includes bibliographical references (pages 147-156). / This thesis consists of three chapters on the economics of health and healthcare. The first and third chapters explore geographic variation in health outcomes within the United States. The second chapter focuses on empirical methods for obtaining causal estimates of treatment effects with an application to healthcare settings. In the first chapter I study geographic variation in health care utilization under two different insurance systems: traditional Medicare and employer-provided private insurance. For each system, I use patient migration as a source of identification combined with empirical Bayes methods to construct optimal linear forecasts for the causal effects of place on utilization. These place effects measure the causal differences in treatment intensity across areas. I find similar levels of variation in the causal place effects for the publicly and privately insured patients, with a correlation of .39 across the two systems. These findings emphasize that insurance systems are affecting the forces that drive the causal component of geographic variation in utilization. In the second chapter, Liyang Sun and I explore event studies, a model for estimating treatment effects using variation in the timing of treatment. Researchers often run fixed effects regressions for event studies that implicitly assume treatment effects are constant across cohorts first treated at different times. In this paper we show that these regressions produce causally uninterpretable estimands when treatment effects vary across cohorts. We propose alternative estimators that identify convex averages of the cohort-specific treatment effects, hence allowing for causal interpretation even under heterogeneous treatment effects. We illustrate the shortcomings of fixed effects estimators in comparison to our proposed estimators through an empirical application on the economic consequences of hospitalization. In the third chapter, Raj Chetty, Michael Stepner, Shelby Lin, Benjamin Scuderi, Nicholas Turner, Augustin Begeron, David Cutler and I use newly available administrative data to quantify the relationship between income and mortality in the United States. Although it is well known that there are significant differences in health and longevity between income groups, debate remains about the magnitudes and determinants of these differences. We use new data from 1.4 billion anonymous earnings and mortality records to construct more precise estimates of the relationship between income and life expectancy at the national level than was feasible in prior work. We then construct new local area (county and metro area) estimates of life expectancy by income group and identify factors that are associated with higher levels of life expectancy for low-income individuals. Our study yields four sets of results. First, higher income was associated with greater longevity throughout the income distribution. The gap in life expectancy between the richest 1% and poorest 1% of individuals was 14.6 years for men and 10.1 years for women. Second, inequality in life expectancy increased over time. Between 2001 and 2014, life expectancy increased by 2.34 years for men and 2.91 years for women in the top 5% of the income distribution, but increased by only 0.32 years for men and 0.04 years for women in the bottom 5%. Third, life expectancy varied substantially across local areas. For individuals in the bottom income quartile, life expectancy differed by approximately 4.5 years between areas with the highest and lowest longevity. Changes in life expectancy between 2001 and 2014 ranged from gains of more than 4 years to losses of more than 2 years across areas. Fourth, geographic differences in life expectancy for individuals in the lowest income quartile were significantly correlated with health behaviors such as smoking, but were not significantly correlated with access to medical care, physical environmental factors, income inequality, or labor market conditions. Life expectancy for low income individuals was positively correlated with the local area fraction of immigrants, fraction of college graduates, and local government expenditures. Additional information on this project is available at https: //healthinequality. org/. / by Sarah Marie Abraham. / Ph. D.

Thesis (S.M.)--Massachusetts Institute of Technology, Engineering Systems Division, 2013. / Cataloged from PDF version of thesis. / Includes bibliographical references (p. 106-110). / Effective use of data is believed to be the key to address systemic inefficiencies in health innovation and delivery, and to significantly enhance value creation for patients and all stakeholders. However, there is no definition for health data. Rather, data in health is an assortment of observations and reports varying from science to clinical notes and reimbursement claims that emerge from practice rather than design. What is health data? In this thesis we try to answer that question by looking at the system of health almost exclusively as a system that generates, transforms, and interprets data. We overview the different meanings data has throughout the health system, we analyze systematically the inefficiencies and trends as they emerge from data, and propose a new architecture for the system of health in which data is not present by accident. The result of this thesis is a new architecture for the system of health that is consistent with its present state but also consistent with a future learning system and a redefinition of value in health care that is patient and information centric. / by Melissa Beth Rosen Ceruolo. / S.M.