Micromachined three-dimensional electrode arrays for in-vitro and in-vivo electrogenic cellular networks

This dissertation presents an investigation of micromachined three-dimensional microelectrode arrays (3-D MEAs) targeted toward in-vitro and in-vivo biomedical applications. Current 3-D MEAs are predominantly silicon-based, fabricated in a planar fashion, and are assembled to achieve a true 3-D form: a technique that cannot be extended to micro-manufacturing. The integrated 3-D MEAs developed in this work are polymer-based and thus offer potential for large-scale, high volume manufacturing. Two different techniques are developed for microfabrication of these MEAs - laser micromachining of a conformally deposited polymer on a non-planar surface to create 3-D molds for metal electrodeposition; and metal transfer micromolding, where functional metal layers are transferred from one polymer to another during the process of micromolding thus eliminating the need for complex and non-repeatable 3-D lithography processes. In-vitro and in-vivo 3-D MEAs are microfabricated using these techniques and are packaged utilizing Printed Circuit Boards (PCB) or other low-cost manufacturing techniques. To demonstrate in-vitro applications, growth of 3-D co-cultures of neurons/astrocytes and tissue-slice electrophysiology with brain tissue of rat pups were implemented. To demonstrate in-vivo application, measurements of nerve conduction were implemented. Microelectrode impedance models, noise models and various process models were evaluated. The results confirmed biocompatibility of the polymers involved, acceptable impedance range and noise of the microelectrodes, and potential to improve upon an archaic clinical diagnostic application utilizing these 3-D MEAs.Ph.D.Committee Chair: Mark G. Allen; Committee Member: Elliot L. Chaikof; Committee Member: Ionnis (John) Papapolymerou; Committee Member: Maysam Ghovanloo; Committee Member: Oliver Bran

An Evaluation of Survival of Cancer Patients Based on Registry Data From Low or Medium Resource Countries

Syöpätaakka kasvaa maailmanlaajuisesti. Erityisesti kehitysmaat ovat huonosti varautuneita tähän muutokseen mm. kehittymättömistä seurantajärjestelmistä johtuen. Monialainen kansainvälinen yhteistyö on tarpeen kehittyneitten ja kehittyvien maitten välillä. Järjestelmällinen syöpäilmaantuvuuden ja -kuolleisuuden raportointi on vuosikymmeniä vanhaa. Sen sijaan eloonjäämistiedot ovat puutteelliset erityisesti kehitysmaissa, joten eloonjäämistutkimuksen edellytyksenä ovat erilliset tutkimukset aineistoista analyysiin. Eloonjäämistutkimus mittaa syöpädiagnoosin jälkeistä elinaikaa. Väestöpohjaisten eloonjäämistietojen avulla arvioidaan syöväntorjunnan voimavarojen, kuten seulontojen ja hoitojen, jakautumista, saatavuutta ja kehityssuuntia. Kehittyvien maitten eloonjäämistietoja on ruvennut satunnaisesti pulpahtelemaan tieteellisessä kirjallisuudessa ja ensimmäisiä vertailuja kehittyvien ja kehittyneiden maitten välillä tehdään paraikaa. Väitöskirja tarjoaa metodisen arvioketjun eloonjäämistutkimuksen suorituksesta tilastoanalyysiin. havaintoaineistona on enemmän kuin 25. syöpärekisterin syöpäilmoitukset ja tapausseuranta. Rekisterit edustavat varakkaista väestöistä kehitysmaaväestöihin. Pääasiallisen aineiston muodostaa Maailman Terveysjärjestön (WHO) Kansainvälisen Syöväntutkimuskeskuksen (IARC) SURVCAN-tietokanta. Syöpäpotilaitten seuranta on eloonjäämistutkimuksen edellytys ja seurannan laatu vaihtelee suuresti. Se voi johtua kuolemansyy- ja muitten väestötietojärjestelmien puutteista, jotka ovat erityisesti kehitysmaille tyypillisiä. Niitten pelkkä rutiinihyödyntäminen johtaa kuolemantapausten aliarvioimiseen, eli virheellisesti liian suuriin eloonjäämislukuihin. Syöpärekisterit ovatkin kehittäneet aktiivisen rekisteröintijärjestelmän, eli rekisterihenkilökunta tekee rekisteri-ilmoitukset itse vierailemalla säännöllisesti alueen terveydenhuoltoyksiköissä. Sillä pyritään minimoimaan seurannasta kadonneitten potilaitten osuutta. Mikäli kato pysyy korkeana ja korreloi ennustetekijöihin perinteiset aktuaarimenetelmät antavat virheellisiä eloonjäämislukuja. Väitöskirjassa esitetään analyysimenetelmä, jolla harhaa voidaan pienentää. Rekisteriaineistojen analyysi osoitti, että eloonjäämislukujen aktuaariarviot poikkesivat 22-47 prosenttiyksikköä passiivisen seurannan ja aktiiviseksi oletetun seurannan välillä. Kadon analyysikorjauksen vaikutus oli pieni 1-4 prosenttiyksikköä väestöpohjaisten rekisterien aineistoissa ja suurempi 2-7 prosenttiyksikköä sairaala-aineistoissa. Erityisesti kehittyvien maitten eloonjäämistutkimuksissa tulee arvioida seurannan aikaisen kadon vaikutusta ennen kuin tuloksia käytetään hoito- tai muihin vertailuihin tai voimavarojen arviointiin ja suunnitteluun. Korjaavina toimenpiteinä ovat seurantajärjestelmän parantaminen aktiiviseksi ja katoharhaa korjaavien menetelmien käyttö tavanomaisten aktuaarimenetelmien sijaan.Cancer is a growing global health issue and many low or medium resource countries are ill-prepared to deal with the ever-increasing cancer burden owing to lack of well-developed surveillance systems. This needs an inter-disciplinary approach through international collaborations between low, middle and high income countries. Systematic reporting of cancer incidence and to some extent, cancer mortality, has been done periodically for many decades now. Unlike in well-developed countries, cancer survival however, is not routinely reported from low or medium resource countries. It required special and concerted efforts from multiple quarters to get reliable survival statistics. Cancer survival generally refers to the lifetime of a person after the diagnosis. Population-based cancer survival data are essential for evaluating the development and distribution of and accessibility to cancer health services like treatment or screening. Since data from low or medium resource countries are beginning to surface in intermittent intervals, so have comparisons between well-developed and less-developed countries. This dissertation provides a stepwise methodological evaluation right from the conduct of survival study to the estimation of survival probability through empirical data from more than 25 registries in several low or medium resource countries with variable gross national income values. This is inevitable for a balanced interpretation of survival differences. The main material for study came from the SURVCAN database of the multinational study by the International Agency for Research on Cancer, Lyon, France, and is supplemented by several materials from India and Thailand. The impact of variation in patient follow-up on survival statistics is undisputed. It could be due to inappropriate methods employed for getting vital status information: lack of active methods of follow up in the presence of sub-optimal mortality ascertainment or high magnitude of loss to follow up by ineffective active follow up. In both instances, it is shown by empirical data that application of standard methodology results in systematic bias in the estimate of survival. If the losses are high and result in non-random censoring due to correlation with outcome, say death, it is a clear indicator to improve the follow up by vigorous active methods and to deviate from standard life table estimation of survival and resort to estimation of survival by differential loss-adjustment procedures explained through its determinants. The magnitude of bias varied between 1-4 percent units for population-based 5-year absolute survival and was larger between 2-7 percent units even for 3-year overall survival for hospital-based studies, for different cancers. In a registry data environment that warranted the employment of active methods of follow up and the real losses to follow up did not exceed one in five cases, the bias induced in actuarial survival under different assumptions of vital status of cases due to inappropriate choice of follow up methods revealed the following: if only passive methods were employed, say for convenience or out of constraints, without any active follow up component, the bias induced in 5-year absolute survival estimates varied between 22-47 percent units for different cancers; when predominantly passive methods of follow up were employed with necessary active component, the bias ranged between 3-10 percent units; when follow up methods were totally by active methods but losses to follow up cases were excluded from analysis, the bias induced varied between 2-8 percent units for different cancers. This provides an objective index of bias resulting in over-estimation or under-estimation of survival in a low or medium resource country setting. In these circumstances, age-standardized survival rates might adjust for the potential confounders and survival data by important prognostic factors like extent of disease may still appear plausible or consistent. But a systematic evaluation of bias in estimating survival due to methodological problems and its suitable correction are mandatory before survival differences could be attributed to the varied development of treatment resources and/or disease characteristics in low or medium resources settings

Correlation study between total calcium, ionized calcium, serum albumin and their significance with Vitamin D.

Calcium is an essential but controversial nutrient: there is no consensus on the level of human calcium requirement or the significance of calcium deficiency. Apart from providing rigidity to the skeleton, an alternate metabolic form of calcium viz., ionized calcium plays a key role in the biochemical and metabolic functions. The protection of this critical concentration by parathyroid hormone and vitamin D reflects the vital role that calcium plays in the neuromuscular system in regulation of the heart, in enzyme-mediated reactions and in many other metabolic processes. The objective of this study was to examine and establish the relationship between Total Calcium, Ionized Calcium and Serum Albumin and the significance of these factors with Vitamin D. For the samples, biochemical assay using electro-chemiluminescence technique (for Vitamin D) was used; Total Calcium and Serum Albumin were analyzed using manual dye-binding methods and the readings were acquired using a semi automatic analyzer. Appropriate statistical methods were used to conclude that, a very good correlation exists between Total calcium to VitaminD3 to that of Ionized Calcium to Vitamin D3 (

The International Collaboration for Research methods Development in Oncology (CReDO) workshops: shaping the future of global oncology research

Low-income and middle-income countries (LMICs) have a disproportionately high burden of cancer and cancer mortality. The unique barriers to optimum cancer care in these regions necessitate context-specific research. The conduct of research in LMICs has several challenges, not least of which is a paucity of formal training in research methods. Building capacity by training early career researchers is essential to improve research output and cancer outcomes in LMICs. The International Collaboration for Research methods Development in Oncology (CReDO) workshop is an initiative by the Tata Memorial Centre and the National Cancer Grid of India to address gaps in research training and increase capacity in oncology research. Since 2015, there have been five CReDO workshops, which have trained more than 250 oncologists from India and other countries in clinical research methods and protocol development. Participants from all oncology and allied fields were represented at these workshops. Protocols developed included clinical trials, comparative effectiveness studies, health services research, and observational studies, and many of these protocols were particularly relevant to cancer management in LMICs. A follow-up of these participants in 2020 elicited an 88% response rate and showed that 42% of participants had made progress with their CReDO protocols, and 73% had initiated other research protocols and published papers. In this Policy Review, we describe the challenges to research in LMICs, as well as the evolution, structure, and impact of CReDO and other similar workshops on global oncology research

Nations within a nation: variations in epidemiological transition across the states of India, 1990–2016 in the Global Burden of Disease Study

18% of the world's population lives in India, and many states of India have populations similar to those of large countries. Action to effectively improve population health in India requires availability of reliable and comprehensive state-level estimates of disease burden and risk factors over time. Such comprehensive estimates have not been available so far for all major diseases and risk factors. Thus, we aimed to estimate the disease burden and risk factors in every state of India as part of the Global Burden of Disease (GBD) Study 2016

An Evaluation of Survival of Cancer Patients Based on Registry Data From Low or Medium Resource Countries

Syöpätaakka kasvaa maailmanlaajuisesti. Erityisesti kehitysmaat ovat huonosti varautuneita tähän muutokseen mm. kehittymättömistä seurantajärjestelmistä johtuen. Monialainen kansainvälinen yhteistyö on tarpeen kehittyneitten ja kehittyvien maitten välillä. Järjestelmällinen syöpäilmaantuvuuden ja -kuolleisuuden raportointi on vuosikymmeniä vanhaa. Sen sijaan eloonjäämistiedot ovat puutteelliset erityisesti kehitysmaissa, joten eloonjäämistutkimuksen edellytyksenä ovat erilliset tutkimukset aineistoista analyysiin. Eloonjäämistutkimus mittaa syöpädiagnoosin jälkeistä elinaikaa. Väestöpohjaisten eloonjäämistietojen avulla arvioidaan syöväntorjunnan voimavarojen, kuten seulontojen ja hoitojen, jakautumista, saatavuutta ja kehityssuuntia. Kehittyvien maitten eloonjäämistietoja on ruvennut satunnaisesti pulpahtelemaan tieteellisessä kirjallisuudessa ja ensimmäisiä vertailuja kehittyvien ja kehittyneiden maitten välillä tehdään paraikaa. Väitöskirja tarjoaa metodisen arvioketjun eloonjäämistutkimuksen suorituksesta tilastoanalyysiin. havaintoaineistona on enemmän kuin 25. syöpärekisterin syöpäilmoitukset ja tapausseuranta. Rekisterit edustavat varakkaista väestöistä kehitysmaaväestöihin. Pääasiallisen aineiston muodostaa Maailman Terveysjärjestön (WHO) Kansainvälisen Syöväntutkimuskeskuksen (IARC) SURVCAN-tietokanta. Syöpäpotilaitten seuranta on eloonjäämistutkimuksen edellytys ja seurannan laatu vaihtelee suuresti. Se voi johtua kuolemansyy- ja muitten väestötietojärjestelmien puutteista, jotka ovat erityisesti kehitysmaille tyypillisiä. Niitten pelkkä rutiinihyödyntäminen johtaa kuolemantapausten aliarvioimiseen, eli virheellisesti liian suuriin eloonjäämislukuihin. Syöpärekisterit ovatkin kehittäneet aktiivisen rekisteröintijärjestelmän, eli rekisterihenkilökunta tekee rekisteri-ilmoitukset itse vierailemalla säännöllisesti alueen terveydenhuoltoyksiköissä. Sillä pyritään minimoimaan seurannasta kadonneitten potilaitten osuutta. Mikäli kato pysyy korkeana ja korreloi ennustetekijöihin perinteiset aktuaarimenetelmät antavat virheellisiä eloonjäämislukuja. Väitöskirjassa esitetään analyysimenetelmä, jolla harhaa voidaan pienentää. Rekisteriaineistojen analyysi osoitti, että eloonjäämislukujen aktuaariarviot poikkesivat 22-47 prosenttiyksikköä passiivisen seurannan ja aktiiviseksi oletetun seurannan välillä. Kadon analyysikorjauksen vaikutus oli pieni 1-4 prosenttiyksikköä väestöpohjaisten rekisterien aineistoissa ja suurempi 2-7 prosenttiyksikköä sairaala-aineistoissa. Erityisesti kehittyvien maitten eloonjäämistutkimuksissa tulee arvioida seurannan aikaisen kadon vaikutusta ennen kuin tuloksia käytetään hoito- tai muihin vertailuihin tai voimavarojen arviointiin ja suunnitteluun. Korjaavina toimenpiteinä ovat seurantajärjestelmän parantaminen aktiiviseksi ja katoharhaa korjaavien menetelmien käyttö tavanomaisten aktuaarimenetelmien sijaan.Cancer is a growing global health issue and many low or medium resource countries are ill-prepared to deal with the ever-increasing cancer burden owing to lack of well-developed surveillance systems. This needs an inter-disciplinary approach through international collaborations between low, middle and high income countries. Systematic reporting of cancer incidence and to some extent, cancer mortality, has been done periodically for many decades now. Unlike in well-developed countries, cancer survival however, is not routinely reported from low or medium resource countries. It required special and concerted efforts from multiple quarters to get reliable survival statistics. Cancer survival generally refers to the lifetime of a person after the diagnosis. Population-based cancer survival data are essential for evaluating the development and distribution of and accessibility to cancer health services like treatment or screening. Since data from low or medium resource countries are beginning to surface in intermittent intervals, so have comparisons between well-developed and less-developed countries. This dissertation provides a stepwise methodological evaluation right from the conduct of survival study to the estimation of survival probability through empirical data from more than 25 registries in several low or medium resource countries with variable gross national income values. This is inevitable for a balanced interpretation of survival differences. The main material for study came from the SURVCAN database of the multinational study by the International Agency for Research on Cancer, Lyon, France, and is supplemented by several materials from India and Thailand. The impact of variation in patient follow-up on survival statistics is undisputed. It could be due to inappropriate methods employed for getting vital status information: lack of active methods of follow up in the presence of sub-optimal mortality ascertainment or high magnitude of loss to follow up by ineffective active follow up. In both instances, it is shown by empirical data that application of standard methodology results in systematic bias in the estimate of survival. If the losses are high and result in non-random censoring due to correlation with outcome, say death, it is a clear indicator to improve the follow up by vigorous active methods and to deviate from standard life table estimation of survival and resort to estimation of survival by differential loss-adjustment procedures explained through its determinants. The magnitude of bias varied between 1-4 percent units for population-based 5-year absolute survival and was larger between 2-7 percent units even for 3-year overall survival for hospital-based studies, for different cancers. In a registry data environment that warranted the employment of active methods of follow up and the real losses to follow up did not exceed one in five cases, the bias induced in actuarial survival under different assumptions of vital status of cases due to inappropriate choice of follow up methods revealed the following: if only passive methods were employed, say for convenience or out of constraints, without any active follow up component, the bias induced in 5-year absolute survival estimates varied between 22-47 percent units for different cancers; when predominantly passive methods of follow up were employed with necessary active component, the bias ranged between 3-10 percent units; when follow up methods were totally by active methods but losses to follow up cases were excluded from analysis, the bias induced varied between 2-8 percent units for different cancers. This provides an objective index of bias resulting in over-estimation or under-estimation of survival in a low or medium resource country setting. In these circumstances, age-standardized survival rates might adjust for the potential confounders and survival data by important prognostic factors like extent of disease may still appear plausible or consistent. But a systematic evaluation of bias in estimating survival due to methodological problems and its suitable correction are mandatory before survival differences could be attributed to the varied development of treatment resources and/or disease characteristics in low or medium resources settings

Optimization of LTE UE Gateway for Uplink video transmission

Long Term Evolution (LTE) is the next step evolution of Third Generation Partnership Project (3GPP) for providing a technology that supports high speed up-link and down-link data rates. The term Internet of Things is a buzzword, where objects, commonly termed as things collect information and communicate them with the use of radio technologies. These objects can be anything; starting from a temperature sensor to a surveillance camera. This thesis work is based on optimizing the data transmission from a Video Camera (sensor) through a LTE User Equipment (UE) that act as a gateway to eNodeB. The idea behind this work is to reduce the energy consumption of the UE gateway through proxy based traffic shaping mechanism termed as bundling. Our measurement results show that through the method of streaming with bundling, the UE can reduce its energy consumption from 44% to 60% for video bit rate of 500 kbps. We analysed the energy consumption for 250, 500, 750 and 1000 kbps video bit rates with varying environmental scenarios such as increase in Round Trip Time (RTT), Packet Loss in the Internet, UE mobility, and background traffic scenarios and found out that video streaming with bundling is the energy efficient approach for data transmission in LTE

Low-Power, Multimodal Laser Micromachining of Materials for Applications in sub-5 µm Shadow Masks and sub-10 µm Interdigitated Electrodes (IDEs) Fabrication

Laser micromachining is a direct write microfabrication technology that has several advantages over traditional micro/nanofabrication techniques. In this paper, we present a comprehensive characterization of a QuikLaze 50ST2 multimodal laser micromachining tool by determining the ablation characteristics of six (6) different materials and demonstrating two applications. Both the thermodynamic theoretical and experimental ablation characteristics of stainless steel (SS) and aluminum are examined at 1064 nm, silicon and polydimethylsiloxane (PDMS) at 532 nm, and Kapton® and polyethylene terephthalate at 355 nm. We found that the experimental data aligned well with the theoretical analysis. Additionally, two applications of this multimodal laser micromachining technology are demonstrated: shadow masking down to approximately 1.5 µm feature sizes and interdigitated electrode (IDE) fabrication down to 7 µm electrode gap width