The microbial contamination of biomedical devices is a leading cause of hospital- acquired infection. A number of strategies aimed at developing device coatings that are refractory to microbial adhesion, colonisation and biofilm formation have been developed, but the problem remains. The incorporation of biocides into biomedical device surface coatings has shown promising results in preventing the establishment of infection. Current controversy over the possibility that extensive use of biocides could potentially lead to antimicrobial resistance has fuelled the search for new actives with good antimicrobial activity and low cytotoxicity, that maintain marked efficacy after prolonged use. This doctoral thesis aims to evaluate the antimicrobial potential of a novel peptide based on human apolipoprotein E receptor binding region (apoEdpL-W). The spectrum of antimicrobial activity and anti-biofilm efficacy of apoEdpL-W was compared to that of common biocides polyhexamethylene biguanide, triclosan, cetrimide and chlorhexidine. The potential to induce bacterial insusceptibility towards these agents after long-term sub-lethal level exposure was assessed. Initial examination against 18 test microorganisms, commonly associated with device infection, showed that apoEdpL-W displayed broad-range antimicrobial and anti-biofilm efficacy. ApoEdpL-W also maintained marked antibacterial activity after incorporation onto various biomaterial polymers, often used in device surface coatings. Alterations in bacterial susceptibility after prolonged exposure to apoEdpL-W, as well as to the other biocides, were often temporary and partially reverted once the bacteria had been grown in the absence of the antimicrobial agent. The adaption of Staphylococcus aureus to the presence of triclosan resulted in the formation of small colony variants (SVCs) with reduced triclosan susceptibility. Analysis of the physiological characteristics of the triclosan induced SCVs revealed the loss of virulence determinants and potentially reduced pathogenic capability, when compared to the parent strain. The biocompatibility index values of the test actives were determined by the parallel assessment of their antibacterial activity and in vitro cytotoxicity. ApoEdpL-W showed good antibacterial efficacy whilst remaining relatively less toxic to mammalian cells than triclosan or chlorhexidine. We studied the interactions of the test antimicrobials with a preformed phospholipid bilayer using the quartz crystal microbalance device and dual polarisation interferometry, to better understand potential mode of action. Analysis revealed that ApoEdpL-W and PHMB induced the highest level of bilayer disruption, of all the antimicrobials tested. These data suggest that apoEdpL-W demonstrates antibacterial activity; biocompatibility and long-term efficacy on a level that compares favourably to that of currently used biocides. The peptide demonstrates good antimicrobial efficacy when incorporated into a range of biomaterial polymers and shows the potential to be developed as an effective coating for the reduction of device associated infections.

Thesis advisor: Charles Murry / This dissertation addresses questions in the pharmaceutical and medical device industries. In the first chapter, I study the welfare effects of price discrimination in the medical device industry. In the second chapter, I document shifts in the marketing and prescription behavior for a drug after it is acquired. In the third chapter I study the reputation spillover effects of a major medical device recall. Chapter 1: Implantable medical device manufacturers are able to directly price discriminate by setting different prices for the same product in different hospitals. I analyze the welfare effects of this form of price discrimination in the case of Implantable Cardioverter Defibrillators (ICDs). I find that if ICD manufacturers were forced to switch to uniform pricing, prices increase on average, which causes a decline in hospital welfare and manufacturer profits. Allowing manufacturers to indirectly price discriminate by strategically delaying the exit of old products to target their elastic consumers can cause an increase in product variety, which can lead to different welfare predictions. If we fail to account for a manufacturer's ability change their product offerings in response to a uniform pricing policy, we can overestimate the effects of uniform pricing on hospital welfare, underestimate the effect of uniform pricing on the take up of older, lower quality products, and we may overestimate or underestimate the effects of uniform pricing on manufacturer profitability. Chapter 2: In this chapter, Motaz Al-Chanati and I document novel evidence of a shift in marketing and prescription behavior for a drug after its acquisition. Network size is highly relevant for this industry, as advertising to physicians (known as detailing) typically involves in-person meetings between sales representatives and physicians. We use 10 drug acquisitions in 2015-2016 to document patterns in the data consistent with firms leveraging their existing physician-sales representative networks to market a drug after they acquire it. We also show that this shift in marketing strategy translates into prescription behavior, i.e. after a drug is acquired, physicians that have prior relationships with the acquiring firm increase their prescriptions of it. Chapter 3: I analyze the effects a major product recall in the implantable medical device industry on the sales of other products manufactured by the recalling firxm. I find that after the recall, consumers substituted away from the recalling firm's other products that were not recalled, and toward the products of the recalling firm's rivals. I also quantify the heterogeneity in the response to this recall based on two consumer characteristics: firm loyalty and exposure. I construct proxies for these characteristics, and I find that while consumers that were more exposed to the recall did not have a significantly different response to it, consumers that were more loyal to the recalling firm had smaller responses to it. / Thesis (PhD) — Boston College, 2022. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Economics.

No description available.

Thesis (M.A.)--Georgia State University, 2007. / Title from file title page. Lindsey L. Cohen, committee chair;Lisa Armistead, Chris Henrich, committee members. Electronic text (67 p. : ill.) : digital, PDF file. Description based on contents viewed Dec. 13, 2007. Includes bibliographical references (p. 42-49) and index.

Narcolepsy is a chronic neurological disorder caused by the brain’s inability to regulate sleep wake cycles normally [1]. Narcoleptic patients feel overwhelmingly tired and sleepy. They do not have the ability to carry out normal day time activities, such as work or study, hence proper treatment is essential. In order to provide an accurate diagnosis of the sleep disorder, physicians must analyze the sleep stages of the patient. Sleep staging analysis is the process of extracting sleep information with brain signals known as electrophysiological signals. There are three major electrophysiological signals: Electroencephalograms (EEG), Electro-oculograms (EOG), and Electromyograms (EMG). Through the three signals, physicians and technicians can classify the sleep stages. Although all three signals are important, most physicians and researchers agree that 95% of information can be extracted from EEG signal. With the current technology, patients must go to the hospital and sleep there over night to perform the sleep stage studies. Electrodes are placed on their scalp, eyelids and skin for this examination. Often patients feel that it is very inconvenient and time consuming. Moreover, the technicians are prone to make human errors during the classification of the sleep stages. These errors are a result of fatigue that the technicians experience while doing the long process of classification of the sleep stages, and the complexity and ambiguity of the rules to determine the sleep stages. Our research group has worked together to construct a portable device that will provide advice to the narcolepsy patient for activity planning and medication dosage. In addition, it provides fore-warning to the patients prior to an narcoleptic attack. This device will also perform real-time sleep analysis and alertness assessment through processing of electroencephalogram (EEG) signal. The classification accuracy is extremely important to the development of this device. With high accuracy of the classifier, treatment for the patients can be determined more accurately by the physicians. As a result, the main purpose of the research presented in this thesis is to analyze different classification methodology and to optimize the parameters of each technology to obtain the optimal sleep stage classification results. The thesis will also present the description of the portable device and its components used for the development of the prototype.

Narcolepsy is a chronic neurological disorder caused by the brain’s inability to regulate sleep wake cycles normally [1]. Narcoleptic patients feel overwhelmingly tired and sleepy. They do not have the ability to carry out normal day time activities, such as work or study, hence proper treatment is essential. In order to provide an accurate diagnosis of the sleep disorder, physicians must analyze the sleep stages of the patient. Sleep staging analysis is the process of extracting sleep information with brain signals known as electrophysiological signals. There are three major electrophysiological signals: Electroencephalograms (EEG), Electro-oculograms (EOG), and Electromyograms (EMG). Through the three signals, physicians and technicians can classify the sleep stages. Although all three signals are important, most physicians and researchers agree that 95% of information can be extracted from EEG signal. With the current technology, patients must go to the hospital and sleep there over night to perform the sleep stage studies. Electrodes are placed on their scalp, eyelids and skin for this examination. Often patients feel that it is very inconvenient and time consuming. Moreover, the technicians are prone to make human errors during the classification of the sleep stages. These errors are a result of fatigue that the technicians experience while doing the long process of classification of the sleep stages, and the complexity and ambiguity of the rules to determine the sleep stages. Our research group has worked together to construct a portable device that will provide advice to the narcolepsy patient for activity planning and medication dosage. In addition, it provides fore-warning to the patients prior to an narcoleptic attack. This device will also perform real-time sleep analysis and alertness assessment through processing of electroencephalogram (EEG) signal. The classification accuracy is extremely important to the development of this device. With high accuracy of the classifier, treatment for the patients can be determined more accurately by the physicians. As a result, the main purpose of the research presented in this thesis is to analyze different classification methodology and to optimize the parameters of each technology to obtain the optimal sleep stage classification results. The thesis will also present the description of the portable device and its components used for the development of the prototype.

In this thesis, we design novel implantable antennas for medical implant communication systems and it could operate with the metamaterial which is the artificial electromagnetic (EM) cover layer. The metamaterial based matching layer placed on the surface of the body can improve the performance of the implantable antenna. First, we propose two layers and three layers antenna design. The three layers antenna features high tolerance, high gain, low-profile and miniaturization. The antenna achieves gain −21.7 dBi and efficiency 0.2%. Compared with other literatures of implanted antenna design, the proposed three layers antenna reveals the best gain with similar dimensions. Furthermore, its frequency response is insensitive to the change of the implanted environment. The conception of impedance matching is applied to further improve the gain of the proposed antenna. The matching layers are realized by utilizing the metamaterial and it is placed between the body and the air. In this case, the gain of the three¡Vlayer antenna can be enhanced by 1.23¡V5.2 dB. Furthermore, we propose a size reduction technique to reduce the thickness of the matching layer. The miniature matching layers can increase the gain of the three¡Vlayer antenna by 1.64 dB and 2.63 dB with the dimension of 40¡Ñ40¡Ñ4mm³ and 60¡Ñ60¡Ñ4mm³ respectively. Finally, we propose a co¡Vdesign method of the antenna and metamaterial. The antenna will resonate after placing metamaterial on the surface of the body. So that we can control the antenna whether to transmit power or not by the circuit design in the biomedical device to detect the return loss of the antenna.

Up to date, the biggest challenge of Taiwan¡¦s medical device industry is that the major market was occupied by international companies which directly hold the research and development, manufacture and selling. In addition, the medical devices have the properties in producing few products with diverse forms, research and development with complicating technology and high threshold in the application of product license. As the domestic market in Taiwan is quite small, small and medium-sized enterprises are the mainscales of Enterprises' Operating Capacity here. The chosen of joint venture of two enterprises through strategic cooperation may be one solution to survive in such ecology and play their good in order to create the core value supporting the goal of sustainability for business management. According to the policy considerations, the biotechnology and medical treatment industry are as the important issue in ECFA agreement between Taiwan and mainland China in 2010. All together, there are hundreds and thousands of opportunities for merger, acquisitions and strategic alliance within this industyin the foreseeable future. This study was based on the study case of the 32-years-old Excelsior. It began with dialysis market-oriented industry and then branched out into all the medical equipment industry. Through strategic co-operation, it expanded to become a medical integration platform providing services regarding to comprehensive roles from trade to hospital management. It accommodates the full range of downstream applications for Medical Engineering Services, Pharmaceutical warehousing and logistics, Procurement and supply, and health care management. Although the Excelsior has been to China ten years ago, it fails to succeed and returns back. In 2011, Excelsior makes the joining venture cooperates with the biggest pharmaceutic distributor in China, Sinopharm focuses on four major medicalterritory that are dialysis, medical cosmetic, dentistry and health-check, and approaches the 5000 billion market in Health-Care-Reform offered by the 12th-Five year-plan of China. However, this time it attempts a come back to become the most valuable of the integrated medical and health industry in Asia. Through study on the history and outcome of joining venture between Excelsior and Sinopharm in the field of medical device industry, this thesis addresses factors that will affect business innovation integrated and product line expression. Through studying the case of Excelsior on its background, history of Strategic cooperation¡B integrated product line¡Bfinancial management and experience of success or failure in the past may provide the reference for the development of Taiwan medical device industry.

Data to understand the inventiveness and technology transfer process for medical devices in India is lacking and majority of medical devices are imported. The presence of a medical school in a university system is expected to enhance healthcare inventiveness. Universities with medical schools have 2.5 times more R&D expenditure and productivity than universities without medical schools. Therefore, the presence or absence of medical schools in universities serves as interesting samples for technology transfer analysis. This thesis focuses on medical device inventiveness and technology transfer office efficiencies of American universities. Three sample sets are used. The first is data from 1242 US universities, of which 734 had medical schools, and their Technology Transfer Office (TTO) productivity from years 1999-2008. The second consisted of 5693 medical device patents filed at USPTO by universities worldwide during years 1999-2008, including US universities. The third consisted of 32 cochlear implant university based patents from 7 primary patent classes in USPTO. Universities involved in medical device research (MDU) and universities not involved in medical device research (NMDU) are compared in our study to understand differences in their technology transfer activities. Initially, Social network analysis is used to understand the interrelatedness of technologies in university based research using patent classes. Degree, betweenness and closeness centrality of 32 cochlear implant patents (out of 345 overall filed patents in USPTO including corporate filings), showed the importance of universities’ R&D contribution to the overall evolution of cochlear implant technology. Dynamics in terms of emergence and disappearance of technologies (represented by US patent classes in years 1977 to 2012), are identified. Our study highlights that universities' research focus within medical device research is confined to few technology classes like surgery, drugs and body treating compositions for therapeutic purposes and image analysis. In these technology areas, universities share of patent holding is found to be more compared to other medical device technologies. Multivariate OLS and binary logistic regressions are used to understand university characteristics that influences amount of patenting by universities. Our study attempts to delineate and highlight university characteristics that may influence amount of patenting in general, i.e., across all technologies and specifically those university characteristics that may influence more patenting in medical device technologies. Our study establishes that university characteristic variables like age, public/private ownership and research productivity influences amount of patenting by universities in general, across all technologies. However, additional university characteristics like presence of medical school and expenditure on legal fees are found influencing amount of patenting in medical device technologies by universities. Data Envelopment Analysis (DEA) is used in our attempt to understand the efficiency of universities in transferring their technologies to industries. Interesting insights are obtained on observing slack obtained during DEA. Our study highlights that some universities may have to reduce their research expenditure in large scales and number of employees working in their technology transfer offices in large scales compared to other universities in order to improve their efficiency in technology transfer process. Our study establishes that in order to improve technology transfer efficiencies, MDUs with higher research expenditure may have to reduce their research expenditure in large volumes compared to universities with lesser research expenditures. However, these MDUs may not be required to greatly reduce their technology transfer employees as compared to universities with lesser research expenditures, in order to improve their technology transfer efficiencies. Moreover, MDUs generating more number of invention disclosures and receiving more faculty awards annually can increase their patenting, licensing and startups in smaller volumes, in order to improve their technology transfer efficiencies, as compared to universities generating lesser invention disclosures and receiving lesser faculty awards, which can increase their patenting and licensing in larger volumes.

The present day world has been experiencing rapid technological advancement on the one hand and increasing number of diseases afflicting the human beings on the other. To deal with the later, medical devices are innovated and introduced in to the market (making use of the technological advancements), on a continuous basis across the world. However, taking an innovated medical device to the market poses innumerable challenges and therefore, these have to be clinically trialled before its launch to ensure safety and efficacy. Of late, India has emerged as one of the preferred destinations to carry out clinical studies due to numerous advantages, primarily its diverse human gene pool and cost-competitiveness. However, there is very little understanding on the landscape of medical devices clinically trialled in India. It is to throw light on this critical issue with respect to the selection of participants in the clinical trial process, selection of locations and determination of trial duration that the present study has been carried out. In addition, the role of patents associated with the introduction of new medical devices in relation to the key challenges is examined. Furthermore, we studied the characteristics of clinical trials by industry and non-industry sponsors and between cardiovascular and other disease related trials. The present study has been carried out based on secondary data covering 108 medical device clinical trial registrations accessed from Clinical Trial Registry of India (CTRI) database pertaining to the period 2008-2014. At the outset, the pattern of trials related to the most prominent diseases such as cardiology and cardiovascular diseases and those which are invasive and non-invasive are examined. Our findings indicate that almost 50% of the trials are related to diseases of cardiology, cardiovascular diseases and those which are invasive in nature. For studying the patenting aspect, we proposed a conceptual grouping of sponsors as Incumbent, Potential Entrant and Supporter, based on their patent holdings in the domestic market and in PCT (Patent Cooperation Treaty) filings. Patents owned by Primary Sponsor (PS) showed significant variations in their clinical trial characteristics particularly the invasiveness of device, disease type, locations and participants. Three quantitative models are developed to identify the factors that influence the selection of number of participants, locations and time taken to execute medical device clinical trials using multivariate statistical techniques. The results of the three conceptual models on number of participants, locations and trial duration showed invasiveness of device and disease type playing significant roles in all the three models. The number of PCTs owned by PS was found to be influential in selecting the number of locations and participants but not the patents owned in IPO (Indian Patent Office). We also observed significant differences between industry and non-industry sponsors in terms of their clinical trial characteristics. The findings of the study formed the basis to understand the medical device clinical trial landscape and other pertinent issues in the Indian context, which enabled us to derive appropriate inferences and policy implications.