Human - Technology - Organization (HTO) is a well-established, general unifying concept in the Swedish Accident Investigation Authority (SHK) that represents an approach, knowledge and use of various tools regarding interactions between people, technology and organizational factors. The HTO-perspective is well described in literature but there are few studies on how SHKs staff experiences working according to this method in their investigations. The aim of this study was therefore to describe their HTO-perspective, examine how it is used in the investigations at SHK and describe the investigators experience of working with the HTO-perspective as well as the method's usefulness compared to old methods in accident investigations. A literature study has been conducted in the areas of HTO, Theory of planned behavior (TPB) and safety culture. TPB and safety culture are described in this paper since they highlight the different aspects of a HTO-perspective. The hypothesis was answered by using semi-structured interviews. The interviews were analyzed by a content analysis and themes were identified. Furthermore the material from the interviews was subsequently structured through a Strength – Weakness – Opportunities – Threats analysis (SWOT), i.e. the informants' view on the HTO-perspective was structured based on the strengths, weaknesses, opportunities and threats SHKs staff experience that the method has in the investigative work. The informants consisted of two investigators at SHK who 3have worked with accident investigations for a long time in various roles. The results yielded that the investigators had a positive attitude towards conducting investigations according to the HTO-perspective because they feel that this perspective provides them with cross-competence. A flaw is though that the perspective lacks a structured approach. As a result of this, the investigators own experiences and expertise play a major role in the quality of the investigation. As the study's aim is met and the informants are considered to be experts the validity requirements are also fulfilled.

A. A study of Stichodactyla helianthus toxin’s potential to penetrate the buccal mucosa Introduction:  Buccal mucosa is an alternative route for drug administration and has advantages over other conventional routes by avoiding both enzymes in the gastro intestinal system and the hepatic first passage mechanism. Stichodactyla helianthus toxin (ShK) is a peptide toxin that blocks potassium channels in T lymphocytes and could be a future treatment for autoimmune diseases when finding a suitable way of administration. Aim:  The purpose of this part of the study was to develop a robust and reproducible assay for identification and quantification of ShK. The method was then employed for a proof of principle study; determining the concentration of ShK following an in vitro permeability experiment, to evaluate the potential of ShK penetrating the buccal mucosa in porcine tissue.  Materials and Methods:  An HPLC method was developed and validated. A piece of porcine buccal mucosa was used as a membrane because of its similarities with human buccal mucosa, and cinched in between a modified Ussing Chamber consisting of a donor and a receptor chamber. Samples were withdrawn from the receptor chamber to determine the amount of ShK that had penetrated the membrane. Results: The HPLC method developed for quantification of ShK demonstrated high accuracy and precision. No concentrations of ShK were able to be quantified from the receptor chambers. Conclusions:  A robust assay for quantification of ShK was developed but the results from the experiment indicated that ShK could not penetrate the buccal mucosa membrane. B. An investigation of the permeability alterations in the blood-brain barrier associated with Alzheimer’s disease   Introduction:  The blood brain barrier (BBB) protects the brain from potential dangerous substances by different barrier properties such as tight junctions and efflux transporters such as P-glycoprotein. Previous studies have showed that the barrier functions may be altered in Alzheimer’s disease and thereby increase the exposure to substances that are normally excluded from the brain parenchyma. This could be an issue regarding safety and toxicity of medications used among Alzheimer patients. Aim:  The aim of this part of the study was to investigate the difference in brain uptake of verapamil, digoxin, loperamide, propanolol, diazepam and sucrose between 3xTg-AD mice and wild type control mice. Materials and Methods: Female 3xTg-AD mice and control mice of the age 11.5-13.5 months were used. In Situ brain perfusion with radiolabeled substances (n=5-12) was performed and the brain uptake ratio of the substances was compared and statistically analyzed.  Results: No difference in the vascular volume was found when comparing 3xTg-AD with control mice. The ratio of diazepam was observed to be higher in the cortex and propranolol higher in the hippocampus, of 3xTg-AD mice. The uptake ratio of verapamil was higher in both the hippocampus and cortex of 3xTg-AD mice whereas digoxin appeared to be lower in the cortex of 3xTg-AD mice. There was no difference in uptake ratio of loperamide between 3xTg-AD and control mice. Conclusions:  This study in addition to previously executed studies in our laboratory, showed that the membrane thickness is age dependent in 3xTg-AD and that further studies needs to be conducted on the expression of P-glycoprotein in the BBB in 3xTg-AD and control mice.