Pattern-recognition receptors in airway inflammation

Airway inflammation is a defining feature of allergic rhinitis and asthma. Bacterial and viral infections are known to cause exacerbations of both diseases, but knowledge about the mechanisms involved is limited. The pattern-recognition receptors (PRRs) comprise several receptor families which recognize microbial structures or host-derived danger signals, and trigger an immune response. The Toll-like receptors (TLRs) are the best characterized set of receptors, but another family of PRRs, the Nod-like receptors (NLRs), has recently been described. The TLRs and NLRs are found both in leukocytes and structural cells throughout the airways and are becoming increasingly implicated in airway inflammation. This thesis characterizes the presence and functional response of various members of the TLR and NLR families. Lipopolysaccharide (LPS) is found in the cell wall of Gram-negative bacteria and exerts its effects through TLR4. In the first three papers nasal LPS challenge was used as a method to study neutrophil inflammatory responses in the nose. In the first paper we explored if the upper airways could be used as a model for inflammatory events in the lung. LPS-induced neutrophil inflammation in the nose was inhibited and the results compared with findings in a study of similar design on the lower airways. The nasal model was found to mimic the responses seen in the lower airway study, with no signs of systemic activation or adverse effects. This suggests the nasal LPS model to be a safe and convenient method for studying neutrophilic airway inflammation. The nasal model was subsequently used in the second paper to analyze the role of macrophage inflammatory protein (MIP)-1α in LPS-induced local inflammation. The LPS challenge resulted in a neutrophil-mediated secretion of MIP-1α, dependent on the nuclear factor (NF)-κB, protein kinase C (PKC) and p38 mitogen activated protein kinase (MAPK) pathways. LPS also delayed neutrophil apoptosis in vitro, suggesting that the secretion of MIP-1α may be boosted by a prolonged neutrophil survival. This indicates that MIP- 1α plays a role in neutrophilic airway disease. In the third paper we investigated whether symptomatic allergic rhinitis affected the expression of TLR4 in nasal lavage, blood and bone marrow. Provocation with LPS in a milieu of allergic inflammation, caused by allergen challenge, resulted in a release of cytokines like interleukin (IL)-4, IL-5, IL-10, IL-13, Interferon (IFN)-γ and tumor necrosis factor (TNF)-α. No such cytokine release was seen with either allergen or LPS alone, nor when LPS preceded allergen. The systemic up-regulation of TLR4 seen during on-going allergic rhinitis might contribute to the presently seen increase in LPS response. It is therefore tempting to extrapolate these findings to a clinical situation in which a local infection can cause exacerbation or aggravation of allergic symptoms. The systemic up-regulation of TLR4 seen during symptomatic allergic rhinitis might contribute to the observed increase in response when LPS was applied following allergen challenge. The results strengthen the suggestion that a local infection may exacerbate allergic inflammation. The fourth study aimed to visualize the effects of allergen on two major populations of dendritic cells, the myeloid (mDCs) and the plasmacytoid dendritic cells (pDCs), in the nose of patients with allergic rhinitis. Allergen challenge increased the number of pDCsin the nasal sub-epithelium. In vitro studies of pDCs revealed that they could be activated by TNF-α, IL-4 and CpG stimulation, and that TNF-α caused a higher activation among atopic than non-atopic subjects. The data support the notion of mDCs and pDCs as distinct populations with different roles in the allergic process. Further, it suggests that the pDCs observed upon allergen challenge might be of an activated phenotype and play a role in the course of allergic rhinitis. The fifth study focused on the effects of TLR7 stimulation on airway smooth muscle contraction. Guinea pig tracheas were stimulated with the TLR7 agonists R837 and R848 for three days, and the contractile response along with the underlying signal pathways were investigated in a myograph model. TLR7 stimulation was found to reduce airway smooth muscle contraction in an epithelium-independent manner, dependent on p38 MAPK and NF-κB pathways. This indicates that TLR7 stimulation can be part of a protective mechanism against virus infection and that TLR7 deficiency might be a cause of airway disease. Further, it suggests that TLR7 ligands might be a future option for treatment of airway hyperresponsiveness. The sixth study characterized the expression and function of NLRs in neutrophils, with focus on Nucleotide-binding oligomerization domain (NOD)1, NOD2 and NACHTLRR- PYD binding protein (NLRP)3. An expression of NOD2 and NLRP3 protein and mRNA was found in isolated neutrophils. NOD2 activation resulted in IL-8 secretion and a change in neutrophil phenotype, while activation of NLRP3 caused secretion of IL-1β. Both receptors caused an increased neutrophil migration. The findings might reflect a previously unknown pathway for activation of these cells

Epidemiology of Equestrian Accidents: a Literature Review

Purpose: This manuscript aimed to present a review of the literature pertaining to horse riding and other horse-related injuries. Method: A review of the literature was performed, searching for appropriate terms with regards to horse accidents, horse riding injuries and protective clothing for the horse riding context. The literature review search returned 151 relevant full-text articles, with 71 of these detailing the overall injury epidemiology of horse-related accidents. Most of these studies were conducted in the USA and used a retrospective review of hospital data methodology. Results: Of the 71 articles investigated, 60 suggested that those most frequently involved in horse-related accidents are young females and 97% of papers investigating injury mechanisms found the most commonly involved was a fall from horseback. It was suggested in multiple studies that these injury events mostly occurred in warm weather conditions, when the horse behaved in an unexpected manner. Injury type and location varied by the primary mechanism of injury; but frequently involved body regions were the head and upper extremities, and the most common injuries observed were fractures and soft tissue injuries. Neurological trauma was reported by all relevant studies to be the most frequent cause of fatality. Conclusion: Some improvements in horse-related accident numbers and outcomes have been observed with the development and introduction of protective devices such as helmets and vests. Yet despite the benefits of helmet and vest usage, there is evidence to suggest helmets do not perform as well as they could. Further work could investigate improvements in safety measures and risk factors associated with fatalities

Ansvar för andra - En studie av grundtankar bakom regler om näringsidkares utsträckta ansvar

Genomgående ämne för denna uppsats är ansvar för andra. I en näringsverksamhet uppkommer flera situationer där det, för näringsidkarens del, kan bli tal om ansvar för någon annan. Ett sådant ansvar, i denna uppsats kallat ”utsträckt ansvar” eller ”kedjeansvar”, innebär att näringsidkaren kan bli ansvarig för någon annans agerande. Uppsatsen ämnar klarlägga huruvida det föreligger gemensamma grundtankar bakom reglerna för näringsidkares utsträckta ansvar. Underlaget utgörs av tre olika lagregler inom skilda områden. Den, för gemene man, mest kända bestämmelsen som reglerar denna typ av ansvar för andra är troligen den i skadeståndslagen, det så kallade principalansvaret i SkstL 3 kap. 1 §. Detta medför en ansvarsförpliktelse hos arbetsgivaren för sina arbetstagares, i tjänsten, vållande handlingar gentemot en tredje man. Vidare beskrivs det utsträckta kontrollansvaret enligt KöpL 27 § och 40 §, där det tas sikte på säljarens ansvar gentemot köparen vid avtalsbrott, orsakat av en av säljaren anlitad person. Den tredje lagregeln som framställs finnes i BrB 10 kap. 5 e § och handlar om en näringsidkares utsträcka ansvar när dennes företrädare har begått mutbrott. Uppsatsen mynnar ut i en djupare förståelse kring tankegången bakom reglerna och bekräftar tanken om att de, till synes, är väldigt olika men tar sikte på att lösa samma problematik, nämligen ansvarsfrågans gränser gällande näringsidkare. En gemensam nämnare som författaren tycks se är att näringsidkaren skall ha ett visst utsträckt ansvar för de han avtalar med, till följd av allmänna principer inom avtalsförhållande. Vid läsning av denna uppsats bör analogier dock dras med försiktighet och författaren vill understryka att jämförelsen reglerna emellan ska förstås utifrån ett grundtanke-perspektiv

Analyses of injuries to equestrians in a Swedish district over a 16-year period

Horse riding is a popular, yet dangerous, sport, and as such, horse-related injuries contribute considerably to the total number of people hospitalized every year. While some investigations have explored this public health issue, many have focused only on hospital registrations or insurance information, while neglecting the cases where the rider may have not required hospitalization. This study investigated the pattern of equestrian injuries in Sweden and examined factors for predicting hospitalized injuries, using visits to hospital, local medical centers, and public dental services. Data were gathered over a 16-year period at all medical facilities within Skaraborg, Sweden, and retrospectively reviewed. There were 7815 horse-related injury events during the study period. The sample of horse-related injuries were largely represented by females (88%) and those aged between 10 and 20\ua0years old. Injuries commonly took place during private/leisure time (90.8%) and in the afternoon. Logistic regression analysis found that older riders were significantly more likely to be admitted to hospital (OR\ua0=\ua01.013), while female riders were less likely to be admitted than males (OR\ua0=\ua00.739). The numbers of people registering at medical facilities due to horse-related injuries are increasing. Therefore, improved intervention measures must be further investigated

Att välja grundläggande karttjänst : utveckling av jämförelsemodell och testverktyg för utvärdering

Sammanfattning: Många verksamheter använder karttjänster för att lösa problem och underlätta beslutsfattande. Allt fler upptäcker fördelarna med detta och integrerar karttjänster i verksamhetssystem. Dessa tjänster utvecklas från grundläggande karttjänster som kan ha betydande skillnader mellan sig vilket gör valet av tjänst till en viktig fråga. Eftersom karttjänsterna är olika och uppbyggda av en mängd mindre beståndsdelar blir jämförelsen av karttjänsterna tidsödande om alla komponenter ska utvärderas mot varandra. Som stöd vid val av karttjänst utvecklades inom examensarbetet en jämförelsemodell. Modellen kan användas för att underlätta urvalsarbetet genom att strukturera de beståndsdelar som bygger upp en karttjänst för att tydliggöra skillnader mellan dem. Under litteraturstudier upptäcktes hur olika och komplexa verksamheters kravbilder på en kartjänst kan vara. En karttjänst är uppbyggd av en mängd beståndsdelar, olika parametrar är viktiga för olika verksamheter. För att inte proritera bort parametrar som i vissa situationer kan vara av värde strukturerades de under sju kategorier för att öka överblicken. För att spegla att verksamheter har olika behov kan användare justera vikter efter en kravspecifikation så att tyngdpunkten läggs på viktiga kategorier. Modellen anpassas efter användarens krav och användarbarheten ökar. För att underlätta användningen av jämförelsemodellen utvecklades ett testverktyg anpassat efter modellen. I verktyget kan användare ställa in vikter för att anpassa verktyget efter de egna behoven. Det finns test för de flesta kategorierna där användaren får en uppfattning om karttjänsternas för- och nackdelar då de utvärderas sida vid sida. Användaren betygsätter sedan respektive kategori. När utvärderingen är klar visas ett resultat där vikter och betyg presenteras. För att förbättra modell samt testverktyg utfördes användartester och två större pilotfall. I pilotstudien konstruerades verklighetstrogna testfall vilka användes för att utvärdera modell och verktyg. Den slutsats som framkommit är att ett användningsområde för en generell jämförelsemodell samt testverktyg finns. De prototyper som framtagits under examensarbetet behöver dock utvecklas för att fungera framgångsrikt.Summary: Many organizations use map services in their daily work to solve problems and enhance decision making processes. The number of organizations who enjoy the benefits of map services and integrate them into their system is increasing. To choose a certain map service is an important decision since the differences between them can be significant. The service is dependent on many minor components which all affect the outcome of the integrated system. To simplify the procedure of choosing a fundamental map service, a general model was defined. The benchmarking model is used to ease the selection process by structuring the features that constitute a map service and clarifying the differences between them. An existing structure was sought to inspire and help define the benchmarking model. Studies of GIS related organizations and map services were also conducted, and the knowledge was used for choosing the components of the model. Requirement specifications of map services for organizations can be complex and varied. Parameters for map services are measured differently depending on needs and business focus. Therefore, parameters in the model were structured under seven categories to create an overview. The benchmarking model can be adjusted with weights for each category to put emphasis on the most important requirements. This way the model can be kept general while being specific for its users. A testing tool was implemented in the form of a web application, designed to evaluate and complement the model. The tool is an implementation of the benchmarking model and gives the user a deeper knowledge and understanding of the model. While using the testing tool, a user may configure the tool to better suit the individual priorities. This is done by adjusting weights for each category. Some of the categories have hands on tests where both map services are presented together and commands chosen by the user are carried out simultaneously. These tests help the user grade the different categories which are finally presented along with the weights in a result page. User tests and a pilot study helped to detect minor faults in the model and the application during the working process. For the pilot study two users cases were designed to test the model in different situations close to reality. The conclusion of the master thesis is that a benchmarking model in collaboration with a testing tool can be useful in the decision making process of integrating a map service. However, the prototypes that have been developed necessitates improvement to operate successfully

Texture-modified meat and carrot products for elderly people with dysphagia: preference in relation to health and oral status

Background : Reduced taste and smell, chewing problems and swallowing dysfunction are common among elderly people and affect perception, food choice and the ability to eat. Objective : To study the preference for texture-modified carrot and meat products in elderly people aiming to meet the needs of people with impaired chewing and/or swallowing. Design : Data were collected using questionnaires focusing on health, oral status and preference for the products. Altogether, 108 elderly people in ordinary housing (OH) and 50 living in special housing (SH) in Malmouml (SH-M) and Goumlteborg (SH-G) participated. Results : 19% had a body mass index ≤22, predominantly in SH (24%). Stroke was reported by 20% of the subjects in SH. Among those with subjectively experienced difficulties in swallowing (12%), 58% reported coughing, 21% a gurgly voice in association with food intake and 50% obstruction during swallowing. Only 20% with subjective swallowing difficulties had been specifically examined regarding this problem. All the tested products were easy to masticate and swallow. Compared with OH, people in SH-M found the meat products easier to masticate and swallow. Compared with OH, subjects in SH found the carrot products easier to masticate Conclusions : There is a need to develop tasty texture-modified nutritious food products for people with mastication and/or swallowing problems. Possible factors for differences in preference between groups, in this study OH and SH, may be related to health status in general and specifically mastication and swallowing functions

Momsplikt för ideella föreningar - En studie om hur nya krav på redovisning kan komma att påverka ideella föreningar.

Examensarbetets titel: Momsplikt för ideella föreningar - En studie om hur nya krav på redovisning kan komma att påverka ideella föreningar. Seminariedatum: 4 juni 2014 Ämne/kurs: FEKH69, Examensarbete i redovisning på kandidatnivå, 15 hög-skolepoäng Författare: Karin Ekman, Michaela Johnsson & Carin Wikstrand Handledare: Ola Mattisson Syfte: Att ur ett företagsekonomiskt perspektiv beskriva och analysera hur ideella föreningars redovisning kan komma att påverkas vid ett införande av momsplikt, samt att analysera detta ur ett intressent-perspektiv. Metod: Studien utgår ifrån det insamlade empiriska materialet, vilket se-dan tolkas i förhållande till redan befintliga teorier. Studien är av kvalitativ karaktär och har genomförts med hjälp av personliga intervjuer. Teoretiska perspektiv: De teoretiska utgångspunkterna för analys av empirin är intressent-teori samt institutionell teori (isomorfism). Empiri: Intervjuunderlaget består av sex ekonomiansvariga i ideella föreningar, representerade av studentnationer. Utöver dessa har vi intervjuat två rättsliga experter på Skatteverket samt en skattekonsult på EY. Resultat: Rent praktiskt innebär ett införande av momsplikt att redovisning-en utvidgas till att innefatta redovisning av ingående och utgående moms. Resultatet i studien pekar mot att ett införande av moms-plikt kommer innebära ökade svårigheter för de redovisningsansvariga i ideella föreningar. Den största svårigheten torde vara momshanteringen vid blandad verksamhet. Detta kan i sin tur på-verka intressenterna i olika omfattning, exempelvis kan viljan att arbeta i en ideell förening minska på grund av ökat ansvar.Title: Value Added Tax for non-profit associations – a study of how new accounting requirements will affect non-profit associations. Seminar date: 4th of June 2014 Course: FEKH69, Business Administration: Degree Project in Accounting, Undergraduate Level, 15 ECTS‐credits Authors: Karin Ekman, Michaela Johnsson & Carin Wikstrand Advisor: Ola Mattisson Purpose: Our purpose is to, through a business perspective, describe and analyse how the accounting in non-profit associations will be af-fected by a VAT requirement. Furthermore we analyse the subject through a stakeholder perspective. Methodology: The study is based on our empirical material which has been ana-lysed relative our theories. The study is qualitative and conducted through interviews. Theoretical perspectives: The theories, which are used, are the stakeholder theory and the institutional theory. Empirical foundation: We have conducted interviews with six non-profit associations, represented by student organisations. Further we have interviewed three experts, two from Skatteverket and one from EY. Conclusions: In practical terms a VAT-requirement will mean that the account-ing will include more areas. A VAT-requirement for the non-profit associations would most likely result in difficulties for the finan-cial accountants in these organisations. The major difficulty is to manage VAT when the organisation operates in a variety of areas. From a stakeholder perspective this could mean that the desire to work in a non-profit association decline because of an increased responsibility

Limitations on Contract Termination Rights—Franchise Cancellations

Chemokines may contribute to the systemic inflammation that is linked to the increased risk of co-morbidities in patients with psoriasis. The aim of this study was to investigate circulating chemokines in patients with psoriasis and their relationship to disease severity. Analysis of plasma levels of chemokines in patients with psoriasis before narrowband ultraviolet B (UVB) therapy revealed increased expression of Th1-associated CXCL9 and -10, Th2-associated CCL17 and CCL22, and Th17-associated CCL20. CCL20 correlated with disease severity. UVB therapy reduced skin symptoms, but did not affect the chemokine levels in plasma. Anti-CD3 and anti-CD28-mediated activation of peripheral blood mononuclear cells (PBMCs) caused a higher secretion of Th2 cytokine interleukin (IL)-13 by PBMCs from patients with psoriasis than from healthy controls. The sustained high expression of inflammatory chemokines is a potential link to systemic inflammation in psoriasis. UVB therapy may be a more effective treatment of local rather than systemic inflammation

A shotgun metagenomic investigation of the microbiota of udder cleft dermatitis in comparison to healthy skin in dairy cows

Udder cleft dermatitis (UCD) is a skin condition affecting the fore udder attachment of dairy cows. UCD may be defined as mild (eczematous skin changes) or severe (open wounds, large skin changes). Our aims were to compare the microbiota of mild and severe UCD lesions with the microbiota of healthy skin from the fore udder attachment of control cows, and to investigate whether mastitis-causing pathogens are present in UCD lesions. Samples were obtained from cows in six dairy herds. In total, 36 UCD samples categorized as mild (n = 17) or severe (n = 19) and 13 control samples were sequenced using a shotgun metagenomic approach and the reads were taxonomically classified based on their k-mer content. The Wilcoxon rank sum test was used to compare the abundance of different taxa between different sample types, as well as to compare the bacterial diversity between samples. A high proportion of bacteria was seen in all samples. Control samples had a higher proportion of archaeal reads, whereas most samples had low proportions of fungi, protozoa and viruses. The bacterial microbiota differed between controls and mild and severe UCD samples in both composition and diversity. Subgroups of UCD samples were visible, characterized by increased proportion of one or a few bacterial genera or species, e.g. Corynebacterium, Staphylococcus, Brevibacterium luteolum, Trueperella pyogenes and Fusobacterium necrophorum. Bifidobacterium spp. were more common in controls compared to UCD samples. The bacterial diversity was higher in controls compared to UCD samples. Bacteria commonly associated with mastitis were uncommon. In conclusion, a dysbiosis of the microbiota of mild and severe UCD samples was seen, characterized by decreased diversity and an increased proportion of certain bacteria. There was no evidence of a specific pathogen causing UCD or that UCD lesions are important reservoirs for mastitis-causing bacteria

A Review of the Carbon Footprint of Cu and Zn Production from Primary and Secondary Sources

Copper (Cu) and zinc (Zn) with their unique properties are central for economic growth, quality of life, and the creation of new jobs. The base-metal producing sector is, however, under growing public pressure in respect to energy and water requirements and needs to meet several challenges, including increased demand and lower ore grades, which are generally associated with larger resource use. The development of technologies for metal production from secondary sources is often motivated by increased sustainability, and this paper aims to provide further insights about one specific aspect of sustainability—namely, climate change. The paper presents a review of carbon footprints (CF) for Cu and Zn produced from primary and secondary raw materials by analyzing data taken from scientific literature and the Ecoinvent database. Comparisons are carried out based on the source of data selected as a reference case. The data available in the literature indicate that secondary production of Cu and Zn has the potential to be more beneficial compared to primary production regarding the impact on climate change. However, the technologies used today for the production of both metals from secondary sources are still immature, and more research on this topic is needed. The general variation of data suggests that the standardization of a comparison is needed when assessing the environmental benefits of production in line with the principles of waste valorization, the zero waste approach, and circular econom