<p>Syftet med detta arbete är att undersöka ergonomins och hälsans förutsättningar på en processindustri i Sverige samt att ta fram förslag på förbättringar och ett träningsprogram för personalen på industrin. För att minska risken för belastningsskador är det viktigt att individen arbetar med ergonomiska arbetsställningar. Om arbetsgivaren förser arbetstagaren med så goda förutsättningar som möjligt att tillämpa ergonomiska arbetsställningar samt erbjuda friskvård kan kostnaderna för sjukfrånvaro sänkas betydligt. </p><p>Metoder som använts är kortare observationer följt av de ergonomiska uträkningarna OWAS och RULA. En interventionsgrupp inom produktionen fick besvara en enkät, som även fylldes i av en kontrollgrupp som bestod av administrationspersonal (kontorspersonal). Utifrån resultatet från interventionsgruppen skapades ett träningsprogram som personalen skulle genomföra under arbetspasset</p><p>Studien visade att företaget är en bra arbetsplats. De flesta trivdes bra eller mycket bra och frekvensen av belastningsskador var låg. Problemen som fanns i interventionsgruppen förekom främst i ländryggen medan problem i kontrollgruppen förekom främst i skuldror och nacke. Personalen försöker arbeta i ergonomiska arbetsställningar, men hälften hade inte fått utbildning i hur de skulle lyfta, bära och förflytta de föremål som arbetsuppgifterna krävde. Observationen visade på vissa riskfyllda arbetsställningar, riskerna verifierades med analyser enligt OWAS och RULA. Enkätundersökningen bekräftade att de risker som identifierades utifrån observationerna skapade verkliga problem. En utvärdering av träningsprogrammet visade att det var genomförbart samt att de flesta tänkt att fortsätta med det.</p><p>Nyckelord: Ergonomi, prevention, hälsa.</p><p>This thesis considers the ergonomics and the health conditions at a Swedish process industry plant. It also includes proposing of improvements in the work environment and the development of a trainingprogram for the employees at the industry. It is important that each individual uses ergonomic work postures in order to minimize the risk of cumulative trauma disorder (CTD). If the employer provides possibilities for use of ergonomic postures and offer health care, the costs for absence due to sickness can be significantly reduced.</p><p>The methods used in this study are field observations followed up with modeling using the ergonomic modeling methods OWAS and RULA. An intervention group, consisting of people working in the production answered a survey. The survey were also answered by a control group consisting of people working in the administration. Based on results from the interventiongroup a traningprogram designed to deal with the specific issues within the group were also developed. The interventiongroup tried this program three times a day at their workplace. </p><p>The overall result showed that the company is a good place to work at. Most of the employees were satisfied with there work situation and the frequency of CTD was low. The problems existing in the interventiongroup were mainly located in lower back area. While in the controlgroup the problems were located in the shoulders and neck. All of the employees tried to use ergonomic postures, but half of the employees did not have any education in how to lift, carry or transport the things their work demanded. The analysis of the work posture observations showed an increased risk of CTD for some of the postures. These results were confirmed using OWAS and RULA methods. The survey results confirmed that problems related to the risks pointed out by the observation analysis also existed in reality. An evaluation of the trainingprogram revealed that it was viable and most of the employees wanted to go on using it. </p><p>Keyword: Ergonomic, prevention, health.</p>

Syftet med detta arbete är att undersöka ergonomins och hälsans förutsättningar på en processindustri i Sverige samt att ta fram förslag på förbättringar och ett träningsprogram för personalen på industrin. För att minska risken för belastningsskador är det viktigt att individen arbetar med ergonomiska arbetsställningar. Om arbetsgivaren förser arbetstagaren med så goda förutsättningar som möjligt att tillämpa ergonomiska arbetsställningar samt erbjuda friskvård kan kostnaderna för sjukfrånvaro sänkas betydligt. Metoder som använts är kortare observationer följt av de ergonomiska uträkningarna OWAS och RULA. En interventionsgrupp inom produktionen fick besvara en enkät, som även fylldes i av en kontrollgrupp som bestod av administrationspersonal (kontorspersonal). Utifrån resultatet från interventionsgruppen skapades ett träningsprogram som personalen skulle genomföra under arbetspasset Studien visade att företaget är en bra arbetsplats. De flesta trivdes bra eller mycket bra och frekvensen av belastningsskador var låg. Problemen som fanns i interventionsgruppen förekom främst i ländryggen medan problem i kontrollgruppen förekom främst i skuldror och nacke. Personalen försöker arbeta i ergonomiska arbetsställningar, men hälften hade inte fått utbildning i hur de skulle lyfta, bära och förflytta de föremål som arbetsuppgifterna krävde. Observationen visade på vissa riskfyllda arbetsställningar, riskerna verifierades med analyser enligt OWAS och RULA. Enkätundersökningen bekräftade att de risker som identifierades utifrån observationerna skapade verkliga problem. En utvärdering av träningsprogrammet visade att det var genomförbart samt att de flesta tänkt att fortsätta med det. Nyckelord: Ergonomi, prevention, hälsa. This thesis considers the ergonomics and the health conditions at a Swedish process industry plant. It also includes proposing of improvements in the work environment and the development of a trainingprogram for the employees at the industry. It is important that each individual uses ergonomic work postures in order to minimize the risk of cumulative trauma disorder (CTD). If the employer provides possibilities for use of ergonomic postures and offer health care, the costs for absence due to sickness can be significantly reduced. The methods used in this study are field observations followed up with modeling using the ergonomic modeling methods OWAS and RULA. An intervention group, consisting of people working in the production answered a survey. The survey were also answered by a control group consisting of people working in the administration. Based on results from the interventiongroup a traningprogram designed to deal with the specific issues within the group were also developed. The interventiongroup tried this program three times a day at their workplace. The overall result showed that the company is a good place to work at. Most of the employees were satisfied with there work situation and the frequency of CTD was low. The problems existing in the interventiongroup were mainly located in lower back area. While in the controlgroup the problems were located in the shoulders and neck. All of the employees tried to use ergonomic postures, but half of the employees did not have any education in how to lift, carry or transport the things their work demanded. The analysis of the work posture observations showed an increased risk of CTD for some of the postures. These results were confirmed using OWAS and RULA methods. The survey results confirmed that problems related to the risks pointed out by the observation analysis also existed in reality. An evaluation of the trainingprogram revealed that it was viable and most of the employees wanted to go on using it. Keyword: Ergonomic, prevention, health.

Diss. Uppsala : Uppsala universitet, 2007.

Neurologically related injuries cause a similar number of deaths ascancer, and brain damage is the second commonest cause of death in theworld and probably the leading cause of permanent disability. Thedevastating effects of most cases of brain damage could be avoided if itwere detected and medical treatment initiated in time. The passiveelectrical properties of biological tissue have been investigated for almost acentury and electrical bioimpedance studies in neurology have beenperformed for more than 50 years. Even considering the extensive effortsdedicated to investigating potential applications of electrical bioimpedancefor brain monitoring, especially in the last 20 years, and the specificallyacute need for such non-invasive and efficient diagnosis support tools,Electrical Bioimpedance technology has not made the expectedbreakthrough into clinical application yet. In order to reach this stage inthe age of evidence-based medicine, the first essential step is todemonstrate the biophysical basis of the method under study. The presentresearch work confirms that the cell swelling accompanying thehypoxic/ischemic injury mechanism modifies the electrical properties ofbrain tissue, and shows that by measuring the complex electricalbioimpedance it is possible to detect the changes resulting from braindamage. For the development of a successful monitoring method, after thevital biophysical validation it is critical to have available the properelectrical bioimpedance technology and to implement an efficient protocolof use. Electronic instrumentation is needed for broadband spectroscopymeasurements of complex electrical bioimpedance; the selection of theelectrode setup is crucial to obtain clinically relevant measurements, andthe proper biosignal analysis and processing is the core of the diagnosissupport system. This work has focused on all these aspects since they arefundamental for providing the solid medico-technological backgroundnecessary to enable the clinical usage of Electrical Bioimpedance forcerebral monitoring.

<p>The optimal way to detect and treat cancer is to target cancer cells exclusively without affecting the surrounding tissue. One promising approach is to use radiolabelled molecules to target receptors that are overexpressed in cancer cells. Since the epidermal growth factor receptor (EGFR) family is overexpressed in many types of cancer, it is an attractive target for both diagnostic and therapeutic applications.</p><p>This thesis can be divided into two parts. In part one (paper I), studies were conducted to modulate radionuclide uptake in tumour cells. The results showed that it was possible to modulate the cellular uptake of ¹²⁵I delivered by trastuzumab (targeting HER2) by adding EGF (targeting EGFR).</p><p>In part two (papers II-V) a high affinity EGFR-targeting affibody molecule (Z_EGFR:955)₂ was selected and analysed both <i>in vitro</i> and <i>in vivo</i>. In papers II, III and V, the results obtained when using (Z_EGFR:955)₂ were compared with those obtained with the two EGFR-binding molecules, EGF and cetuximab. These studies demonstrated that the affibody molecule bound specifically to EGFR (probably to subdomain III) with high affinity (~50 nM in biosensor analysis and ~1 nM in cellular studies) and produced intracellular signalling changes similar to those with cetuximab. In paper IV, <i>in vivo</i> studies were made, demonstrating that [¹¹¹In](Z_EGFR:955)₂ gave a tumour-specific ¹¹¹In uptake of 3.8±1.4% of injected dose per gram tumour tissue, 4 h post-injection. The tumours could be easily visualized with a gamma camera at this time-point. </p><p>The results of these studies indicated that the affibody molecule (Z_EGFR:955)₂ is a possible candidate for radionuclide-based imaging of EGFR-expressing tumours. The biological effects of (Z_EGFR:955)₂ might be of interest for therapy applications.</p>

<p>To further develop cancer therapy, targeted delivery of cell killing agents directly to tumor cells is an interesting approach. This thesis describes the development of PEG-stabilized liposome conjugates targeting either epidermal growth factor receptor (EGFR) using its natural ligand EGF, or human epidermal growth factor receptor 2 (HER-2) using the antibody trastuzumab. Both receptors are known to be overexpressed on a variety of tumors. The liposomes were loaded with the boronated compounds water soluble boronated acridine (WSA) or water soluble boronated phenantridine (WSP), compounds primarily developed for boron neutron capture therapy, BNCT. </p><p>The liposome conjugates bound specifically to their receptors in cell culture. Because the WSA conjugates exhibited the most favorable boron uptake this compound was chosen for further study. The WSA-loaded liposome conjugates was internalized, an important characteristic for BNCT, and had a long retention inside the cells. The cellular localization of WSA, studied using fluorescence was found to be mainly cytoplasmic. </p><p>To increase the boron uptake studies comparing different incubation methods was performed. It was shown for both EGF and trastuzumab targeted liposomes the uptake could be increased over 10 times by changing from incubation in monolayer culture to incubation in cell suspension in roller flasks. With this treatment the boron concentrations reached after 24 h incubation time was 90 ppm for EGF-liposomes and 132 ppm for trastuzumab-liposomes, levels that are clinically interesting. </p><p>To study the cell-killing efficacy of the liposome-conjugates an experimental BNCT study was performed using EGF-liposome-WSA on cultured glioma cells. About half the number of thermal neutron was needed to inactivate 90% of the cells if the cells had been incubated with EGF-liposome-WSA compared to control cells. When comparing the survival to dose it was shown that to inactivate 90% of the cells 2.9 Gy was needed for EGF-liposome-WSA and neutrons compared to 5.6 Gy with ¹³⁷Cs gamma. </p><p>The biodistribution of EGF-liposomes was also studied in mice. It was compared to EGF and it was found that the addition of a PEG-stabilized liposome to EGF significantly reduced EGF uptake in liver and kidneys, the circulation time in blood was prolonged as well. The reduced liver uptake might be due to inability of the 100 nm liposomes to pass the sinusoidal fenestrations of the liver and bind to the EGFR-rich hepatocytes. The reduced liver uptake potentates the use of EGF-liposome conjugates for systemic injection.</p>

To further develop cancer therapy, targeted delivery of cell killing agents directly to tumor cells is an interesting approach. This thesis describes the development of PEG-stabilized liposome conjugates targeting either epidermal growth factor receptor (EGFR) using its natural ligand EGF, or human epidermal growth factor receptor 2 (HER-2) using the antibody trastuzumab. Both receptors are known to be overexpressed on a variety of tumors. The liposomes were loaded with the boronated compounds water soluble boronated acridine (WSA) or water soluble boronated phenantridine (WSP), compounds primarily developed for boron neutron capture therapy, BNCT. The liposome conjugates bound specifically to their receptors in cell culture. Because the WSA conjugates exhibited the most favorable boron uptake this compound was chosen for further study. The WSA-loaded liposome conjugates was internalized, an important characteristic for BNCT, and had a long retention inside the cells. The cellular localization of WSA, studied using fluorescence was found to be mainly cytoplasmic. To increase the boron uptake studies comparing different incubation methods was performed. It was shown for both EGF and trastuzumab targeted liposomes the uptake could be increased over 10 times by changing from incubation in monolayer culture to incubation in cell suspension in roller flasks. With this treatment the boron concentrations reached after 24 h incubation time was 90 ppm for EGF-liposomes and 132 ppm for trastuzumab-liposomes, levels that are clinically interesting. To study the cell-killing efficacy of the liposome-conjugates an experimental BNCT study was performed using EGF-liposome-WSA on cultured glioma cells. About half the number of thermal neutron was needed to inactivate 90% of the cells if the cells had been incubated with EGF-liposome-WSA compared to control cells. When comparing the survival to dose it was shown that to inactivate 90% of the cells 2.9 Gy was needed for EGF-liposome-WSA and neutrons compared to 5.6 Gy with 137Cs gamma. The biodistribution of EGF-liposomes was also studied in mice. It was compared to EGF and it was found that the addition of a PEG-stabilized liposome to EGF significantly reduced EGF uptake in liver and kidneys, the circulation time in blood was prolonged as well. The reduced liver uptake might be due to inability of the 100 nm liposomes to pass the sinusoidal fenestrations of the liver and bind to the EGFR-rich hepatocytes. The reduced liver uptake potentates the use of EGF-liposome conjugates for systemic injection.

The optimal way to detect and treat cancer is to target cancer cells exclusively without affecting the surrounding tissue. One promising approach is to use radiolabelled molecules to target receptors that are overexpressed in cancer cells. Since the epidermal growth factor receptor (EGFR) family is overexpressed in many types of cancer, it is an attractive target for both diagnostic and therapeutic applications. This thesis can be divided into two parts. In part one (paper I), studies were conducted to modulate radionuclide uptake in tumour cells. The results showed that it was possible to modulate the cellular uptake of 125I delivered by trastuzumab (targeting HER2) by adding EGF (targeting EGFR). In part two (papers II-V) a high affinity EGFR-targeting affibody molecule (ZEGFR:955)2 was selected and analysed both in vitro and in vivo. In papers II, III and V, the results obtained when using (ZEGFR:955)2 were compared with those obtained with the two EGFR-binding molecules, EGF and cetuximab. These studies demonstrated that the affibody molecule bound specifically to EGFR (probably to subdomain III) with high affinity (~50 nM in biosensor analysis and ~1 nM in cellular studies) and produced intracellular signalling changes similar to those with cetuximab. In paper IV, in vivo studies were made, demonstrating that [111In](ZEGFR:955)2 gave a tumour-specific 111In uptake of 3.8±1.4% of injected dose per gram tumour tissue, 4 h post-injection. The tumours could be easily visualized with a gamma camera at this time-point. The results of these studies indicated that the affibody molecule (ZEGFR:955)2 is a possible candidate for radionuclide-based imaging of EGFR-expressing tumours. The biological effects of (ZEGFR:955)2 might be of interest for therapy applications.

Denna kandidatuppsats har i syfte att granska de olika teknologierna för biomakt som gestaltas inom psykiatrivården i Sverige. Metoden som kommer att användas för analysen är fallstudier vilket kommer att användas tillsammans med teorier om biomakt. Den teoretiker som främst förekommer är Michel Foucault, men teorin kommer att kompletteras med fler filosofer och forskare. Analysen kommer att ha en avgränsning vid tre stycken diagnoser; schizofreni, bipolär sjukdom och borderline. I granskningen kommer teorierna och metoden användas för att identifiera vilka olika behandlingsformer som används för patienterna samt vilka teknologier för makt som förekommer i behandlingarna. Resultatet för analysen visar att de huvudsakliga behandlingsformerna för diagnoserna är läkemedel och kognitiv beteendeterapi vilka gestaltar två olika former av biomakt, både regulativ makt och disciplinär makt / The purpose of this bachelor thesis is to examine the different kinds of technologies of biopower that exist within the Swedish psychiatric institution. The method of use is case studies, that will be used in conjunction with theories about biopower. The theorist that is primarily used is Michel Foucault, however the theories about biopower will be further complemented by more philosophers and researchers. The analysis will be limited to three diagnoses; schizophrenia, bipolar disorder and borderline. The theories and methodology will be used in order to identify the different therapies used for the patients as well as the technologies of power that occur in the treatments. The result of the analysis shows that the main forms of treatment for the diagnoses are drugs and cognitive behavioral therapy which consist of two different forms of biopower, both regulatory power and disciplinary power.

<p>This thesis describes recombinant proteins that have been generated by rational and combinatorial protein engineering strategies for use in subunit vaccine delivery and tumor targeting.</p><p>In a first series of studies, recombinant methods for incorporating immunogens into an adjuvant formulation, e.g. immunostimulating complexes (iscoms), were evaluated. Protein immunogens, which are not typically immunogenic in themselves, are normally administered with an adjuvant to improve their immunogenicity. To accomplish iscom incorporation of a <i>Toxoplasma gondii</i> surface antigen through hydrophobic interaction, lipids were added either <i>in vivo</i> via <i>E. coli</i> expression, or <i>in vitro</i> via interaction of an introduced hexahistidyl (His6) peptide and a chelating lipid. The possibility of exploiting the strong interaction between biotin and streptavidin was also explored, in order to couple a<i> Neospora caninum</i> surface antigen to iscom matrix, i.e. iscom particles without any antigen. Subsequent analyses confirmed that the immunogens were successfully incorporated into iscoms by the investigated strategies. In addition, immunization of mice with the recombinant Neospora antigen NcSRS2, associated with iscoms through the biotin-streptavidin interaction, induced specific antibodies to native NcSRS2 and reduced clinical symptoms following challenge infection. The systems described in this thesis might offer convenient and efficient methods for incorporating recombinant immunogens into adjuvant formulations that might be considered for the generation of future recombinant subunit vaccines.</p><p>In a second series of studies, Affibody® (affibody) ligands directed to the extracellular domain of human epidermal growth factor receptor 2 (HER2/neu), which is known to be overexpressed in ∼ 20-30% of breast cancers, were isolated by phage display <i>in vitro</i> selection from a combinatorial protein library based on the 58 amino acid residue staphylococcal protein A-derived Z domain. Biosensor analyses demonstrated that one of the variants from the phage selection, denoted His₆-Z_HER2/neu:4, selectively bound with nanomolar affinity (KD ≈ 50 nM) to the extracellular domain of HER2/neu (HER2-ECD) at a different site than the monoclonal antibody trastuzumab. In order to exploit avidity effects, a bivalent affibody ligand was constructed by head-to-tail dimerization, resulting in a 15.6 kDa affibody ligand, termed His₆-(Z_HER2/neu:4)₂, that was shown to have an improved apparent affinity to HER2-ECD (KD ≈ 3 nM) compared to the monovalent affibody. Moreover, radiolabeled monovalent and bivalent affibody ligands showed specific binding in vitro to native HER2/neu molecules expressed in human cancer cells. Biodistribution studies in mice carrying SKOV-3 xenografted tumors revealed that significant amounts of radioactivity were specifically targeted to the tumors <i>in vivo</i>, and the tumors could easily be visualized with a gamma camera. These results suggest that affibody ligands would be interesting candidates for specific tumor targeting in clinical applications, such as <i>in vivo</i> imaging and radiotherapy.</p>