Accelerating food safety and quality control: The use of antibody engineering techniques in the detec-tion of low-molecular weight food contaminants

The increased awareness and evolved consumer habits have set more demanding standards for the quality and safety control of food products. The production of foodstuffs which fulfill these standards can be hampered by different low-molecular weight contaminants. Such compounds can consist of, for example residues of antibiotics in animal use or mycotoxins. The extremely small size of the compounds has hindered the development of analytical methods suitable for routine use, and the methods currently in use require expensive instrumentation and qualified personnel to operate them. There is a need for new, cost-efficient and simple assay concepts which can be used for field testing and are capable of processing large sample quantities rapidly. Immunoassays have been considered as the golden standard for such rapid on-site screening methods. The introduction of directed antibody engineering and in vitro display technologies has facilitated the development of novel antibody based methods for the detection of low-molecular weight food contaminants. The primary aim of this study was to generate and engineer antibodies against low-molecular weight compounds found in various foodstuffs. The three antigen groups selected as targets of antibody development cause food safety and quality defects in wide range of products: 1) fluoroquinolones: a family of synthetic broad-spectrum antibacterial drugs used to treat wide range of human and animal infections, 2) deoxynivalenol: type B trichothecene mycotoxin, a widely recognized problem for crops and animal feeds globally, and 3) skatole, or 3-methyindole is one of the two compounds responsible for boar taint, found in the meat of monogastric animals. This study describes the generation and engineering of antibodies with versatile binding properties against low-molecular weight food contaminants, and the consecutive development of immunoassays for the detection of the respective compounds.

Utilization of Meat and bone meal for energy production

At the end of the 1990s the stock breeding in the Europe was suffering from the animal disease epidemics such as Bovine spongiform encephalopathy (BSE) and foot –and mouth disease. The European Union (EU) tackled to this problem by tightening the legislation of animal by-products. At this point, rendering and fat producing industries faces new challenges, which they have to cope with in a way of trying to find alternatives to their products (animal fats and meat and bone meal). One of the most promising alternatives to utilize these products was to use them in energy production purposes. The purpose of the Thesis was to examine the utilization possibilities of Meat and bone meal (MBM) for energy production. The first part of the Thesis consists of theory part. The theory part includes evaluation of basic properties of MBM as a fertilizer and as a fuel, legislative evaluation and evaluation of different burning techniques. The second part of the Thesis consists of burning tests in Energy laboratory of LUT with different mixtures of peat and MBM. The purpose of the burning tests was to identify co-firing possibilities of peat and MBM and emission- and ash properties for peat and MBM.

Use of preclinical and early clinical data for dose selection of a selective estrogen receptor modulator toremifene in treatment of breast cancer

In development of human medicines, it is important to predict early and accurately enough the disease and patient population to be treated as well as the effective and safe dose range of the studied medicine. This is pursued by using preclinical research models, clinical pharmacology and early clinical studies with small sample sizes. When successful, this enables effective development of medicines and reduces unnecessary exposure of healthy subjects and patients to ineffectice or harmfull doses of experimental compounds. Toremifene is a selective estrogen receptor modulator (SERM) used for treatment of breast cancer. Its development was initiated in 1980s when selection of treatment indications and doses were based on research in cell and animal models and on noncomparative clinical studies including small number of patients. Since the early development phase, the treatment indication, the patient population and the dose range were confirmed in large comparative clinical studies in patients. Based on the currently available large and long term clinical study data the aim of this study was to investigate how the early phase studies were able to predict the treatment indication, patient population and the dose range of the SERM. As a conclusion and based on the estrogen receptor mediated mechanism of action early studies were able to predict the treatment indication, target patient population and a dose range to be studied in confirmatory clinical studies. However, comparative clinical studies are needed to optimize dose selection of the SERM in treatment of breast cancer.

Repair of segmental bone defects with fiber-reinforced composite: a study of material development and an animal model on rabbits

The Repair of segmental defects in load-bearing long bones is a challenging task because of the diversity of the load affecting the area; axial, bending, shearing and torsional forces all come together to test the stability/integrity of the bone. The natural biomechanical requirements for bone restorative materials include strength to withstand heavy loads, and adaptivity to conform into a biological environment without disturbing or damaging it. Fiber-reinforced composite (FRC) materials have shown promise, as metals and ceramics have been too rigid, and polymers alone are lacking in strength which is needed for restoration. The versatility of the fiber-reinforced composites also allows tailoring of the composite to meet the multitude of bone properties in the skeleton. The attachment and incorporation of a bone substitute to bone has been advanced by different surface modification methods. Most often this is achieved by the creation of surface texture, which allows bone growth, onto the substitute, creating a mechanical interlocking. Another method is to alter the chemical properties of the surface to create bonding with the bone – for example with a hydroxyapatite (HA) or a bioactive glass (BG) coating. A novel fiber-reinforced composite implant material with a porous surface was developed for bone substitution purposes in load-bearing applications. The material’s biomechanical properties were tailored with unidirectional fiber reinforcement to match the strength of cortical bone. To advance bone growth onto the material, an optimal surface porosity was created by a dissolution process, and an addition of bioactive glass to the material was explored. The effects of dissolution and orientation of the fiber reinforcement were also evaluated for bone-bonding purposes. The Biological response to the implant material was evaluated in a cell culture study to assure the safety of the materials combined. To test the material’s properties in a clinical setting, an animal model was used. A critical-size bone defect in a rabbit’s tibia was used to test the material in a load-bearing application, with short- and long-term follow-up, and a histological evaluation of the incorporation to the host bone. The biomechanical results of the study showed that the material is durable and the tailoring of the properties can be reproduced reliably. The Biological response - ex vivo - to the created surface structure favours the attachment and growth of bone cells, with the additional benefit of bioactive glass appearing on the surface. No toxic reactions to possible agents leaching from the material could be detected in the cell culture study when compared to a nontoxic control material. The mechanical interlocking was enhanced - as expected - with the porosity, whereas the reinforcing fibers protruding from the surface of the implant gave additional strength when tested in a bone-bonding model. Animal experiments verified that the material is capable of withstanding load-bearing conditions in prolonged use without breaking of the material or creating stress shielding effects to the host bone. A Histological examination verified the enhanced incorporation to host bone with an abundance of bone growth onto and over the material. This was achieved with minimal tissue reactions to a foreign body. An FRC implant with surface porosity displays potential in the field of reconstructive surgery, especially regarding large bone defects with high demands on strength and shape retention in load-bearing areas or flat bones such as facial / cranial bones. The benefits of modifying the strength of the material and adjusting the surface properties with fiber reinforcement and bone-bonding additives to meet the requirements of different bone qualities are still to be fully discovered.

Building climate justice : an analysis of how the nexus between climate change and human rights shapes public policy agendas and alternatives

This thesis provides an analysis of how the nexus between climate change and human rights shapes public policy agendas and alternatives. It draws upon seminal work conducted by John Kingdon, whose landmark publication “Agendas, alternatives, and public policy” described how separate streams of problems, solutions, and politics converge to move an issue onto the public policy agenda toward potential government action. Building on Kingdon’s framework, this research explores how human rights contribute to surfacing the problem of climate change; developing alternative approaches to tackling climate change; and improving the political environment necessary for addressing climate change with sufficient ambition. The study reveals that climate change undermines the realization of human rights and that human rights can be effective tools in building climate resilience. This analysis was developed using a mixed methods approach and drawing upon substantial literature review, the researcher’s own participation in international climate policy design; elite interviews with thought leaders dealing with climate change and human rights; and regular inputs from focus groups comprised of practitioners drawn from the fields of climate change, development and human rights. This is a journal based thesis with a total of six articles submitted for evaluation, published in peer‐reviewed publications, over a five year period. Denna avhandling analyserar hur klimatfrågan och mänskliga rättigheter i samverkan formar den politiska agendan och det politiskt möjliga. Den bygger på banbrytande forskning av John Kingdon, vars publikation “Agendas, alternatives, and public policy” beskriver hur en fråga blir politiskt viktig och lyfts upp på den politiska agendan. Med utgångspunkt i Kingdons ramverk, utforskar avhandlingen hur mänskliga rättigheter bidrar till att blottlägga klimatfrågan som problem; utveckla alternativa metoder för att angripa och hantera klimatfrågan; samt skapa ett politiskt klimat nödvändigt för att på ett ambitiöst sätt kunna angripa klimatfrågan. Studien visar att klimatförändringar undergräver mänskliga rättigheterna men att arbete med mänskliga rättigheter kan vara ett effektivt verktyg för att stå emot och hantera effekterna av klimatförändringar. Analysen har genomförts med hjälp av en rad olika metoder vilka inkluderar litteraturstudier, författarens egna observationer under klimatförhandlingar; intervjuer med ledande tänkare inom klimatfrågan och mänskliga rättigheter; samt data insamlad genom fokusgrupper bestående av yrkesverksamma inom klimat, utveckling och mänskliga rättigheter. Avhandlingen är baserad på totalt sex artiklar som publicerats i fackgranskade tidskrifter under en femårsperiod.