The forward march of biobanking creates the need for an alternative approach to biobank governance. Biobanking encourages medical advancement by making the conduct of health-related research more efficient, by minimising physical harms to participants, and by facilitating personalised medicine and greater understandings of disease. Nonetheless, its characteristics that distinguish it from general health-related research often give rise to many ethical and social issues. For example, multiple and unexpected uses of biobank resources can render conventional informed consent inadequate for safeguarding participants and maintaining public trust and confidence. Also, because the size of a biobank cohort is normally large, biobanking usually requires considerable management resources and this can mean that biobanks can likely be financially dependent upon for-profit entities. This dependency can cause concern among participants and publics about commercial exploitation. These issues suggest that a new approach to biobank governance is required to address them. Indeed, their complexity and the sheer longevity of biobanking itself also suggest that it is relatively feasible and coherent to address them by focusing on a relationship between participants and biobankers. This involves many aspects of interaction and reflects an element of continuity, which is crucial to biobanking success, as opposed to one-off measures. Consequently, with the aim of addressing issues that arise from biobanking, this thesis offers an analysis of the participant-biobanker relationship that can deal with these issues. Such a relationship constitutes an authentic research relationship in biobanking (“ARR”). Based on this premise, the main research question of my thesis is to ask: What form of research relationship is appropriate for effective and ethical biobanking practices? Three sub-questions are raised to solve this top-level research question. They start with a normative question of why the ARR proposed in this thesis is desirable for biobanking. The next sub-question asks what this ARR should look like from a conceptual perspective. For a practical respect on my proposals, the last sub-question concerns the ways in which the ARR can be fostered in practice. To address these research questions, my thesis first establishes the main characteristics of the proposed ARR as the fundamental notion thereof. These main characteristics are used to answer the first sub-question. For the second sub-question, the thesis suggests that the ARR should be based on the concept of partnership, as opposed to solidarity, mainly because partnership can exhibit the main characteristics of the ARR – as argued – and can also be prescribed in a governance manner. The thesis then uses partnership as a basis for proposing the key features of the ARR, which are deemed to be a conceptual framework for the ARR. To answer the last sub-question, the thesis uses this conceptual framework to propose a partnership model for biobank governance that can be used to develop the ARR in practice. My original contribution is to propose a novel approach to an ARR, and this ARR is based on the concept of partnership. In other words, my thesis argues that the pursuit of the ARR, which looks like a partnership relationship, is an important element of biobanking success. In this respect, my thesis is about a sociologically informed role for partnership in biobank governance. It also provides a nuanced epistemological grounding for a participant-biobanker relationship in both conceptual and practical ways. From a philosophical perspective, my thesis proposes an ethical framework for biobank governance that perceives partnership as a virtuous trait for biobankers and provides rules for acquiring this trait through biobanking practices. Notably, it is argued that this partnership is not – nor need it be – the legal paradigm of partnership, which fundamentally refers to for-profit business association. While law might have a role to play in facilitating the development of the ARR, it cannot prescribe the ARR nor should it attempt to do so.

The aim of this project was to work towards developing a droplet-based microfluidic device which can perform cell lysis, Whole Genome Amplification (WGA) and storage of the amplified DNA. This would provide an automated biobanking device capable of high-throughput sample processing whilst shielding the samples from the sample loss and contamination commonly experienced by conventional, isolated sample handling methods.WGA has been examined using two commercially available WGA kits (GenomiPhi V2 and HY) to produce a continuous flow device that is capable of amplifying both human genomic DNA (gDNA) and bacterial plasmid DNA samples in nanolitre volume droplets. A positive effect of reducing reaction volumes on the amplification of bacterial plasmid DNA was shown by obtaining an increase in yield with decreasing volumes. It was shown, however, that a reduction in the volume of the WGA reaction has a negative impact on the amplification of human gDNA, in terms of both reduced yield and copy number variation (CNV). Furthermore, a novel method for reducing this CNV has been achieved by pooling the products of multiple reaction volumes. Finally, a cell lysis device has been developed which can perform rapid lysis of a human neuroblastoma cell line in continuously flowing droplets through addition of an alkaline solution.These devices provide an advantage over previously developed methods, displaying cell lysis of a human cell line and amplification of both human gDNA and plasmid DNA, while the continuous flow design of the devices allows for both high-throughput processing of samples and the future integration of the devices to form a μTAS biobanking device.

abstract: Exposure of blood plasma/serum (P/S) to thawed conditions, greater than -30°C, can produce biomolecular changes that misleadingly impact measurements of clinical markers within archived samples. Reported here is a low sample-volume, dilute-and-shoot, intact protein mass spectrometric assay of albumin proteoforms called “ΔS-Cys-Albumin” that quantifies cumulative exposure of archived P/S samples to thawed conditions. The assay uses the fact that S-cysteinylation (oxidation) of albumin in P/S increases to a maximum value when exposed to temperatures greater than -30°C. The multi-reaction rate law that governs this albumin S-cysteinylation formation in P/S was determined and was shown to predict the rate of formation of S-cysteinylated albumin in P/S samples—a step that enables back-calculation of the time at which unknown P/S specimens have been exposed to room temperature. To emphasize the capability of this assay, a blind challenge demonstrated the ability of ΔS-Cys-Albumin to detect exposure of individual and grouped P/S samples to unfavorable storage conditions. The assay was also capable of detecting an anomaly in a case study of nominally pristine serum samples collected under NIH-sponsorship, demonstrating that empirical evidence is required to guarantee accurate knowledge of archived P/S biospecimen storage history. The ex vivo glycation of human serum albumin was also investigated showing that P/S samples stored above their freezing point leads to significant increases in glycated albumin. These increases were found to occur within hours at room temperature, and within days at -20 °C. These increases continued over a period of 1-2 weeks at room temperature and over 200 days at -20 °C, ultimately resulting in a doubling of glycated albumin in both healthy and diabetic patients. It was also shown that samples stored at lower surface area-to-volume ratios or incubated under a nitrogen atmosphere experienced less rapid glucose adduction of albumin—suggesting a role for oxidative glycation in the ex vivo glycation of albumin. / Dissertation/Thesis / Doctoral Dissertation Biochemistry 2018

No description available.

Philosophiae Doctor - PhD / A laboratory information management system (LIMS) is central to the informatics infrastructure that underlies biobanking activities. To date, a wide range of commercial and open source LIMS are available. The decision to opt for one LIMS over another is often influenced by the needs of the biobank clients and researchers, as well as available financial resources. However, to find a LIMS that incorporates all possible requirements of a biobank may often be a complicated endeavour. The need to implement biobank standard operation procedures as well as stimulate the use of standards for biobank data representation motivated the development of Baobab LIMS, an open source LIMS for Biobanking. Baobab LIMS comprises modules for biospecimen kit assembly, shipping of biospecimen kits, storage management, analysis requests, reporting, and invoicing. Baobab LIMS is based on the Plone web-content management framework, a server-client-based system, whereby the end user is able to access the system securely through the internet on a standard web browser, thereby eliminating the need for standalone installations on all machines. The Baobab LIMS components were tested and evaluated in three human biobanks. The testing of the LIMS modules aided in the mapping of the biobanks requirements to the LIMS functionalities, and furthermore, it helped to reveal new user suggestions, such as the enhancement of the online documentation. The user suggestions are demonstrated to be important for both LIMS strengthen and biobank sustainability. Ultimately, the practical LIMS evaluations showed the ability of Boabab LIMS to be used in the management of human biobanks operations of relatively different biobanking workflows.

Since the decoding of the human genome project concluded in 2003, rapid technological advances in the area of human genetics including genetic testing and bio banking have accelerated. Public discussion of genetic testing and biobanking are the focus of this thesis. Genetic profiling and predictive tests aim to establish the causal conditions for disorders such as Fragile X, cystic fibrosis and Huntington's disease. Biobanking involves the storage of genetic material for genetic research and can also include genealogical research. The complex and varied relationships that Maori (indigenous peoples of New Zealand) in different social locations have with western science (and human genetics in particular) is at the heart of this thesis. The thesis explores the responses of three differently located Maori social groups to the challenges posed by genetic testing and biobanking. Focus/contact group discussion with Maori members of the Church of Jesus Christ of Latter Day Saints, a group of rongoa or traditional Maori health practitioners, and a group of Maori lawyers illustrate both diversity in the ways in which Maori respond to the issues posed by human genetics, and connections among them as they draw on Maori ontologies and epistemologies. In the analyses of these discussions which constitute the core of this thesis, Maori can be seen juggling alternative frames of reference and negotiating between knowledge systems. The thesis does not purport to provide an overview of Maori responses to genetic testing. Instead it uses discussion among three groups of research participants to illustrate the relevance of temporal and relational knowledge in local situations. A range of social science and Te Ao Maori conceptual tools are used to analyse conversations among research participants. These tools include discussion of power/knowledge and governmentality, actor network theory, sociological discussions of agency as well as concepts of whakapapa, kaitiaki, mauri, and mana motuhake. My goal is to illustrate both connection and heterogeneity in Maori responses to the challenges posed by genetic testing and bio banking.

Societies are plagued by growing healthcare expenditures and budgetary constraints. The strategy for solving the issue has been heavily debated, with proposed solutions such as Valuebased healthcare (VBHC), Public-Private Partnerships (PPP) and improved medical treatments. A novel concept that aims to improve medical treatment is strategic biobanking. Strategic biobanking is the act of saving biological samples and clinical data for future research. Access to strategic samples can speed up future clinical trials and studies, provide researchers with more useful research material, enable more thorough analyses of biomarkers, facilitate faster drug development, and increase the power of both retrospective analyses and precision medicine. This thesis studies the shared value effects of a strategic biobanking PPP by drawing on the theoretical fields of VBHC, PPP and Creating Shared Value (CSV). Specifically, the effects of hospital organisational structure, regulatory framework and public interest on strategic biobanking PPPs was studied. The research was carried out through a single holistic case study of Karolinska University Hospital in Stockholm, Sweden and multiple pharmaceutical companies, and data was collected through semi-structured interviews. Data analysis was carried out in accordance with the grounded theory framework. The researchers find that regulatory structure can limit the options when crafting the business model and the industry value proposition for a strategic biobanking PPP. Some strategies on how to deal with these restraints are outlined. Furthermore, the research highlights the importance of longitudinal data-sets and how a hospital organised according to the VBHC principles is more suitable for implementation of longitudinal sampling routines. Finally, the research shows that that the concept of CSV can act as guidance for private partner decision making to increase public interest. By adopting principles of transparency regarding financial incentives and motivations, an industry partner can garner increased trust with the general public as well as their public partner. The shared value effects are pronounced, and the study finds that a strategic biobanking PPP moves the boundary for what is scientifically possible for all stakeholders in the healthcare domain. / Samhällen plågas av skenande sjukvårdskostnader och budgetåtstramningar. Vilken strategi som kan lösa problemet har debatterats flitigt. Lösningar så som Value-based Healthcare (VBHC), Public-Private Partnerships (PPPs) och mer avancerad vård har alla föreslagits som alternativ. Ett nytt koncept som ämnar att förbättra sjukvården är strategisk biobankning. Strategisk biobankning innebär att spara biologiska prover och klinisk data inför framtiden. Detta kan snabba på framtida kliniska prövningar och studier, förse forskare med mer användbart forskningsmaterial, möjliggöra mer grundliga analyser av biomarkörer, snabbare utveckling av mediciner, samt öka potensen hos både retrospektiva studier och precision medicine. Denna uppsats studerar gemensamma värdeeffekter hos ett PPP inom strategisk biobanking genom att använda sig av de teoretiska fälten VBHC, PPP och Creating Shared Value (CSV). Mer specifikt studeras hur PPP inom strategisk biobankning påverkas av sjukhusets organisationsstruktur, rådande regelverk och allmänintresse. Forskningen utfördes genom en enkel, holistisk, fallstudie av Karolinska Universitetssjukhuset i Stockholm, Sverige. Data samlades genom semi-strukturerade intervjuer och analyserades senare enligt ramverket för Grounded Theory. Forskarna finner även att rådande regelverk begränsar möjligheten för utveckling av affärsmodell och värdeerbjudande gentemot privata partners. Några strategier för att hantera dessa begränsningar tas upp i uppsatsen. Vidare belyses vikten av longitudinella dataset, och att ett sjukhus vars organisation är strukturerad enligt VBHC-principer är mer lämpligt för implementation av longitudinell provsamling. Slutligen finner forskarna att privata CSV-conceptet utgör bra vägledning för privata partners för att skapa allmänintresse. Genom att anamma principer som premierar transparans gentemot sina ekonomiska och strategiska incitament så kan förtroende byggas gentemot allmänheten. De gemensamma värdeeffekterna är tydliga, och forskarna finner att tillgång till en strategisk biobank flyttar gränsen för vad som är vetenskapligt möjligt för alla aktörer i det sjukvårdsrelaterade ekosystemet.

Biodiversity loss is an important issue for New Zealand: for the domestic environment, economy and society, but also for New Zealand as a member of the international community. Biodiversity offset banking is making an important contribution to addressing such issues in a number of countries around the world. Developing the ability to participate and take advantage of possible benefits requires comprehensively understanding both the fundamental principles and varying concepts, and supports the analysis necessary for New Zealand to progress towards offset banking. New Zealand can learn much from observing and investigating overseas models and use them as valuable templates. California and New South Wales provide examples of potential policies and frameworks (both economic and social) to establish and operate successful offset banking systems. Discussions of offset banking, both in theory and practice, frequently concern the potential failings of the system. These issues can be conceptualised as various forms of risk. Considering offset banking as sustainable development, this thesis addresses such risks to reflect the tripartite biological, financial and social framework of sustainable development. Biologically, risk is in the potential biodiversity outcomes are inadequate, unexpected or undesirable. Scientific uncertainty underlies this, both inherently and from the limits of current scientific disciplines. Through expanding scientific knowledge and experience, measures for reducing or accommodating the risk of uncertainty are emerging. Financial risk represents concerns that individual banks may lack the monetary support to achieve the specific biodiversity conservation required for the site. Also the system of interacting banks, bankers and traders may fail to produce financial outcomes that support effective and efficient biodiversity conservation over the breath of the scheme. Social risk lies in the potential that societies’ individuals conduct themselves in ways that conflict with achieving biodiversity conservation through malfeasance or negligence. Additionally, there is social risk that an offset banking system fails to respond appropriately to broader society and human, such as equity and intergenerational justice. Here, deliberating these risks is primary to appreciating how design elements and emergent properties minimize risks. Given comprehensive understanding, components of a system can be designed and allow informed policy, regulations and rules to offer successful risk mitigation. For this reason policy, rules and regulations observed within California and New South Wales helps to discuss this and establish guidance for New Zealand offset banking design to draw upon. Californian systems are achieving promising conservation and continued growth; New South Wales’ Biobanking scheme is robustly designed and in its early stages. Each contrasts in design and carries varying criticisms. California has been observed as potentially shortcoming biologically, whereas New South Wales Biobanking has been questioned based on the strength and character of its economic underpinnings. In addition to these considerations, New Zealand has significant societal perspectives to incorporate given current popular, socio-democratic conservation modus operandi. Identifying the three forms of risk present highlights the importance of allocating appropriate consideration and expertise to the biological, economic and social components of offset banking. Successful sustainable development, biodiversity conservation and risk mitigation may be achieved through designing mechanisms, regulations and governing policy for offset banking. New Zealand may therefore expand the success and application of current offsetting by taking guidance from examples and analysis presented here.

Limited breeding success in captive breeding programs has necessitated the development of assisted reproductive technologies (ART) to preserve and increase genetic variation and population numbers of both captive and wild amphibian groups. ART has been shown to be successful in numerous anuran species, and current studies focus on the application of ART in ex-situ populations. The focus of this project is to show that linking in-situ and ex-situ amphibian populations through sperm cryopreservation, genome banking, and in-vitro fertilization is possible, with the goal of increasing gene diversity throughout groups in order to produce self-sustaining, wild populations in the future. Specific objectives include developing a sperm-cryopreservation methodology using sperm from the model species Anaxyrus fowleri, applying this protocol to the cryopreservation of spermatozoa from two other threatened anurans to determine protocol transmissibility, and linking in-situ and ex-situ populations of an endangered species using cryopreserved sperm form wild males to produce viable offspring.

Amidst the amphibian extinction crisis, in situ and ex situ amphibian species conservation initiatives utilize assisted reproductive technologies for optimal genetic management of captive and wild populations. Development of effective, simple, low-cost methods for obtaining gametes for artificial fertilization, sperm biobanking, or natural breeding alleviates obstacles for institutions or programs to apply reproductive technologies. Objectives herein include investigating the efficacy of alternative hormones for inducing spermiation, an alternative hormone administration route for inducing ovulation, exploring the physiological effects of hormone therapy, and utilizing sperm from deceased animals for biobanking.