Distribution and function of TRP ion channels in primary sensory neurons

It is frequently argued that cannabinoids exert part of their analgesic and anti-inflammatory effects via activation of the cannabinoid CB1 receptor located on TRPV1-expressing primary sensory nerve fibres in peripheral tissues. However, we find no evidence of CB1 receptor immunoreactivity on nerve fibres in rat or mouse hindpaw skin and mesenteric artery. The CB1 receptor agonists anandamide and HU210 also fail to inhibit TRPV1-mediated calcitonin gene-related peptide (CGRP) release from primary sensory neurons in rat hindpaw skin and mesenteric artery. Therefore, this study do not support the general view that the analgesic and anti-inflammatory effects of CB1 receptor agonists are due to direct inhibition of TRPV1-expressing primary sensory nerve terminals in the periphery. Garlic contains a number of organosulphur compounds, including allicin and diallyl disulfide (DADS), some of which may contribute to its pungent and vasodilator properties. Our results show that raw garlic extract, allicin and DADS activate TRPA1 ion channels on primary sensory neurons in culture and nerve fibres in the vascular system. These findings highlight TRPA1 as a novel ion channel in the vascular system and provide novel pharmacological tools for investigating the role of this ion channel. Whether activation of TRPA1 in the vascular system explains the beneficial antihypertensive effect observed by garlic treatment remains to be shown. This study also expands our understanding of how TRPA1 is regulated on a molecular basis, which is of importance for development of novel drug therapies for pain, inflammation and vascular disease. The skin is a major sensory organ that contains a large number of nerves. The TRP ion channels TRPV2 and TRPM8 are expressed in the somatosensory nervous system in animals and are therefore likely to be expressed in humans as well. Fluorescence immunohistochemistry was used to identify these channels and compare their expression and distribution patterns with known neuronal markers of the sensory nervous system in skin from healthy volunteers and from individuals with a mutation in the gene encoding nerve growth factor beta (NGF?) that causes Norrbottnian congenital insensitivity to pain. This study shows for the first time the presence of TRPV2 and TRPM8 in sensory nerves in the human skin. TRPV2 and TRPM8 as well as TRPV1 immunoreactive nerve fibres are present in unmyelinated nerve fibres in epidermis and papillary dermis, in nerve bundles, and around blood vessels and hair follicles. In contrast to TRPV1, TRPV2 and TRPM8 are found mainly in the papillary dermis and seem to be restricted to peptidergic nerve fibres, of which the majority contains the sensory neuropeptides CGRP or SP. There is a substantial loss of nerve fibres containing TRPV1, TRPV2 and TRPM8 in skin from individuals with Norrbottnian congenital insensitivity to pain. Insight into the role of TRPV2 and TRPM8 in human skin may open new avenues for treatment of neuropathic pain and inflammatory skin diseases

Medical Laser-Induced Thermotherapy - Models and Applications

Heat has long been utilised as a therapeutic tool in medicine. Laser-induced thermotherapy aims at achieving the local destruction of lesions, relying on the conversion of the light absorbed by the tissue into heat. In interstitial laser-induced thermotherapy, light is focused into thin optical fibres, which are placed deep into the tumour mass. The objective of this work was to increase the understanding of the physical and biological phenomena governing the response to laser-induced thermotherapy, with special reference to treatment of liver tumours and benign prostatic hyperplasia. Mathematical models were used to calculate the distribution of light absorption and the subsequent temperature distribution in laser-irradiated tissues. The models were used to investigate the influence on the temperature distribution of a number of different factors, such as the design of the laser probe, the number of fibres, the optical properties of the tissue, the duration of irradiation, blood perfusion and boundary conditions. New results concerning transurethral microwave thermotherapy were obtained by incorporating the distribution of absorbed microwaves into the model. Prototypes of new laser applicators for anatomically correct treatment of benign prostatic hyperplasia were developed and tested ex vivo. Experimental work on liver tumours pointed to the importance of eliminating the blood flow in the liver during treatment to reduce convective heat loss. In addition, it was shown that hepatic inflow occlusion during treatment increased the thermal sensitivity of tumour tissue. The dynamic influence of interstitial laser thermotherapy on liver perfusion was investigated using interstitial laser Doppler flowmetry. Vessel damage after the combined treatment of laser-induced heat treatment and photodynamic therapy was studied

Entrance to and advancement within the Swedish medical labour market for physicians with a medical degree from outside the European Union

Background Many physicians who migrate wish to continue practicing medicine in their destination country. However, they may meet barriers and obstacles that prolong the process of entering and advancing within the destination country’s medical labour market. Migrant physicians’ competences are needed, and if fully utilised, it will be beneficial for them, the patients, the medical workforce, and for society. Aim The aim was to explore the entrance to and the advancement within the Swedish medical labour market for physicians with a medical degree from outside of the EU/EEA. Method The study participants were mainly physicians who had enrolled in a complementary programme for physicians with a medical degree from outside the EU/EEA and Switzerland. Both qualitative and quantitative methods were used. Study I included semi-structured interviews with 24 physicians. Study II was a cross-sectional study that included questionnaire data from 283 respondents. Study III included test data from physicians with a medical degree from outside the EU/EEA who had taken a licensing exam 2013–2019 (n = 564), and 14 semi-structured interviews. Study IV included questionnaire data from 101 respondents, and four semi-structured interviews. Interview transcripts and questionnaire free-text answers were thematically analysed. For Study II, the statistical data were descriptively analysed. For Study III, linear and logistic regression analysis were used. In Study IV, descriptive and inferential statistical analyses were performed on the data. To understand and discuss how MPs enter and advance within the medical labour market in Sweden, Bourdieu’s concepts of the social field, symbolic capital and doxa were used as a lens. As a complement to Bourdieu’s theory, self-determination theory (SDT) was used. Results In Study I, several conceptions about working in rural and remote areas in Sweden were identified. These regarded the themes finding work, work content and tasks, and living. Conceptions about working in a certain type of area gave rise to conceptions about what it would be like to live in the same area. The participants’ conceptions derived from their own and from others’ experiences; and conceptions influenced study participants’ motivation of where to work, negatively or positively. In Study II, 88% of the respondents held a position as a physician when answering the questionnaire, but they were in varying stages of their careers from one another; as they also had begun the complementary programme at different times. The respondents had mainly found their first job after the programme via spontaneous job applications, during internships or via friends or other programme participants. Barriers and facilitating aspects as well as the different strategies they used were explored. During their job-seeking process, the respondents reported experiencing discrimination or having their competences undervalued. To increase job prospects, the respondents had, for example, worked as assistant nurses or medical assistants before beginning the complementary programme. Respondents had developed their language by using different resources. Due to high labour market conditions, respondents had moved or changed specialty to increase job prospects. Study III revealed that age was a predictor for succeeding on the licensing exam, and that the complementary programme seemed to reduce the negative age effect for participants aged 45 years or older. In the qualitative material, perceived influential aspects for succeeding or failing on the exam related to the two themes preparations and biographical aspects, and to the exam and exam situation. Study IV explored aspects that influenced choices of employment and specialty, and found that the most important aspects related to choosing employment were the ability to combine work with family, and possibilities for developing competences. The majority of the respondents had specialised in general medicine, and women were more likely to specialise in general medicine than men. Influencers on the interviewees’ motivation and choice to specialise in general medicine related to the themes of job opportunities, positive experiences from PHC, working conditions and family conditions. Conclusions Barriers and limiting circumstances may derive from the micro and meso levels, and influence on a micro level; however, individuals still have agency. They can influence their paths to the labour market and advance within it through certain strategies and/or facilitating aspects. Many barriers and facilitating aspects corresponded to one another and were two sides of the same proverbial coin. The social context and environment influenced the study participants’ choices regarding where to work and in which specialty. Aspects relating to work life and private life collaborated to influence motivation and choices. As a group, these MPs could be interpreted as being hierarchically positioned lower in the Swedish medical field than physicians who trained in the country. However, on an individual level, this may not hold true, as the group is heterogeneous in terms of gender, ethnicity, country of origin, country for medical education, and age. Influential aspects on the macro, meso and micro levels may change over time

Gas exchange with a reflecting system for inhalational anaesthesia

In order to reduce comsumption of inhalational anaesthetsics during high flow anaesthesia a system open in regard to oxygen, nitogen and nitrous oxide, but closed to inhalational anaesthetics, was developed. This was achieved by a reflecting filter for inhalational anaesthetics made of active carbon. The principle has been developed into the commersially available Anesthetic Conserving Device (ACD, AnaConDa®).The ACD is a modified heat- and moisture exchanger (HME) containing av bacterial and viral filter as well as a carbon filter. The ACD can be used during surgery for administering the inhalational agents isoflurane and sevoflurane as an alternative to low-flow anaesthesia systems. It can also be used in intensive care units to administer sedation using isoflurane or sevoflurane to critically ill patients. The thesis is based on four papers. In paper I it is shown that that the wash-in kinetics for sevoflurane delivered by the ACD is similar to a vaporiser. With the ACD, end-tidal sevoflurane accurately reflects arterial sevoflurane tension whereas inspired tension may be underesteimated. Despite an increase in tidal volume of patients in a group with an ACD corresponding to the larger internal volume of the device compared to a conventional HME, the PaCO2 was considerably higher in this group. In paper II CO2 exchange and airway dead space is compared using an HME, ACD without reflecting filter and ACD with reflecting filter in a laboratory set-up. It is shown that the ACD binds CO2 resulting in a dead space effect 180 ml in excess of its internal volume. This is due to adsorption of CO2 in the ACD during expiration and return of CO2 during the following inspiration. In paper III the ACD is used without inhalational anaesthetics in patients as well as in a laboratory set-up with varying temperature and humidity. It is confirmed that an ACD used in humans as well as in a test lung increases the dead space effect and CO2 rebreathing to a greater extent than can be explained by its internal volume. This is caused by adsorption of CO2 in the ACD during expiration and release of CO2 during inspiration. It is also shown that rebreathing of CO2 is attenuated but not abolished by humidity. In paper IV the ACD is used with sevoflurane in humans and in a laboratory set-up. It is shown that sevoflurane attenuates but does not abolish rebreathing of CO2, thereby reducing the dead space effect of the ACD. In conlusion, the ACD causes a dead space effect larger than its internal volume due to CO2 rebreathing. This may influence the clinical use of the ACD

Standardization of Environmental Management and Sustainability Reporting

Abstract Title Standardization of Environmental Management and Sustainability Reporting Seminar Date May 29th 2013 Course BUSN68 Degree Project - Accounting and Management Control; BUSN69 Degree Project - Accounting and Auditing, 15 ECTS Authors Johanna Geijer and Linda Sturesson Advisors Per Magnus Andersson and Stefan Yard Keywords Standardization, Environmental Management, Sustainability Reporting, ISO 14001, GRI Purpose The purpose of this thesis is to increase the understanding of why companies choose to standardize environmental management and sustainability reporting instead of using a unique solution. Theoretical Framework The presented theoretical framework of this thesis built on exogenous and endogenous theories consisting of legitimacy theory, stakeholder theory, institutional theory, the resource based view and positive accounting theory. Besides this benefits and implications of standardization will be given account for. Methodology The methodology undertaken is generally based on a qualitative research approach through case studies. A quantitative approach will also be used for the conducted pilot survey and information found in sustainability reports. Complementary to this an expert interview has also been completed. Empirical Foundation The empirical findings imply that the mostly used strategy amongst the investigated corporations is the use of both ISO 14001 and GRI. Such well-established standards also seem to create a foundation for continuous improvements within corporations. Case studies furthermore highlight requirements from customers, investors and owners as an important factor. Conclusions This study indicates that corporations choose to standardize their environmental management and sustainability reporting in search of legitimacy and because of stakeholder demands. Furthermore standards can also become normative making them essential for economic survival. Benefits such as improved comparability and efficiency as well as increased awareness also influence corporations to standardize this area. The study also confirmed that purchase and certification costs of standard deter marginal users to standardize

Centralization of inventory management for spare parts

Background Arriva DK currently has a decentralized organization where each depot is responsible for the inventory control of their spare parts. This type of organization often presents challenges when it comes to control and management. Arriva DK suffers from high order costs due to lack of coordination between the depots and the suppliers. To address these issues Arriva wants to introduce a central warehouse. Purpose The aim of the thesis is to optimize inventory management by creating simulation models that from a cost perspective explore the effects of introducing a central warehouse for spare parts. To provide Arriva DK with simulation models of the supply chain and inventory management, both with – and without a central warehouse. Method The thesis is built on Hillier and Lieberman’s Operations research method. Data used in the thesis consist of both primary and secondary quantitative and qualitative data. Literature studies have also been done and are the basis for the theory. Two simulation models were built. The first model represents an optimized decentralized situation that uses joint replenishment. The second model represents a system with a central warehouse, which also uses joint replenishment. Thereafter the models were compared to determine if an investment in a centralized system is profitable. Conclusions The results from the simulation study showed that the total cost for the CW-model is higher than the DC-model in all scenarios. Both the holding- and order cost will be higher with a central warehouse. The major advantage of using a central warehouse is that the number of orders to the suppliers will be reduced by more than 50%. This along with the suppliers only have to deliver to one location will result in price reductions on the products. Even with small discounts, will a central warehouse be profitable since the procurement cost represents such a large part of the total cost

A framework for how logistics service providers should handle returns as a warehouse operation for e-commerce companies

Title: A framework for how logistics service providers should handle returns as a warehouse operation for pure e-commerce companies Authors: Louise Meurling and Matilda Sturesson Supervisor: Joakim Kembro, Division of Engineering Logistics at LTH Problem description: Managing the reverse logistics process in a warehouse is a central part of the activities for companies operating in e-commerce. Companies can outsource the return handling to a Logistics Service Provider (LSP) in order to focus on their core competences. The theory of today is based on the assumption that a physical point of contact is included in the chain. Therefore, there is a need to extend the theory into the context of e-commerce. Purpose: The purpose of this thesis is to create a framework for how LSPs should handle returns in the warehouse, from the point of receiving until put back in storage, for customers in the e-commerce business. Research questions: How should a LSP handle returns in the warehouse for customers of e-commerce? What are the barriers of the return handling in a warehouse and how can LSPs overcome these? How do the different characteristics of products and customers of a LSP change the handling of returns? How can the return handling in a warehouse of a LSP contribute to greater value for the customers acting in the e-commerce business? Methodology: A flexible design methodology has been used in this thesis together with a multiple case study based on two cases at PostNord TPL´s facility in Helsingborg. Interviews, observations, and historical data have been collected and analysed in an intra case analysis and a cross-case analysis in order to answer the research questions and modify the reverse logistics framework to the context of e-commerce. Conclusions: A framework for how LSPs should handle returns in a warehouse is extended based on theory to the context of e-commerce. Several barriers of the return handling for LSPs have been identified. These are: limited sharing of forecasts, limited visibility, customer requirements, heterogenous decision making, and the changing business of e-commerce. It can be concluded that the product and customer characteristics impact the handling of returns to a large extent. To be able to contribute to greater value for the customers, the LSP should offer a fast, efficient, and less costly reverse logistics process than if they would perform it in-house. Keywords: Warehouse activities, inbound logistics, reverse logistics process, returns, return handling, e-commerce, logistics service provide

Theoretical analysis of transurethral laser-induced thermo-therapy for treatment of benign prostatic hyperplasia. Evaluation of a water-cooled applicator

A mathematical model for predicting the temperature rise in transurethral laser-induced thermo-therapy for benign prostatic hyperplasia was developed. In the model an optical line source emitting light from an Nd:YAG laser isotropically was placed in the urethra. Water cooling of the urethral epithelium was modelled using a two-tube system. The relationship between the difference in outlet and inlet water temperatures and the highest tissue temperature level reached was theoretically investigated. It was found that the water temperature difference was linearly dependent on the steady-state maximum tissue temperature. The theoretical calculations suggest that the water-cooled applicator can be used to measure the maximum tissue temperature. With temperature control, the prostatic tissue temperature can be prevented from exceeding the boiling point of water, excluding tissue carbonization. The model was also used to evaluate the influence of a number of different parameters on the damaged tissue volume. Increasing the urethral lumen radius by a factor of two by means of inserting different sized tubes was found to augment the tissue volume raised to therapeutic temperatures by up to 50%. The calculations showed that cooling of the urethral epithelium can result in an increase in the damaged volume by 80% as compared to not applying any cooling. The temperature of the cooling water was found to influence the tissue temperature only to a small extent

Collaboration for Innovation - a study in the Öresund Region

We have made a thesis about Collaboration for Innovation in the Öresund region from a Swedish perspective. The thesis is taking both regional and corporate aspects into consideration when studying this subject. The empiric material is based upon several interviews with persons having knowledge about our subject as well as a web survey including 49 companies situated in the Öresund region. We have been able to divide our findings into two kinds of problems: Structure- and Process problems. The analyze is partialy based upon the Triple- and Penta-Helix models