38 research outputs found

    Antibodies to leukotoxin A from the periodontal pathogen Aggregatibacter actinomycetemcomitans in patients at an increased risk of rheumatoid arthritis

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    ObjectivesPeriodontitis and underlying bacteria have been linked to the development of rheumatoid arthritis (RA). One suggested pathogen is Aggregatibacter actinomycetemcomitans (A.a.), which expresses leukotoxin A (LtxA) that can citrullinate human proteins, providing a possible trigger for the production of anti-citrullinated protein antibodies (ACPA). In this study, we seek to determine the presence of antibodies toward LtxA in patients at risk of developing RA.MethodsTwo prospective observational patient cohorts (one Swedish and one British) with symptomatic at-risk patients were studied. Anti-LtxA antibodies were analyzed by a cell-based neutralization assay in baseline serum and compared to 100 Swedish blood donors that served as controls.ResultsSerum anti-LtxA levels or positivity did not differ between patients and blood donors. In the British cohort, anti-LtxA was more prevalent among ACPA-positive arthralgia patients compared with ACPA-negative arthralgia cases (24% vs. 13%, p < 0.0001). In the Swedish at-risk cohort, anti-LtxA positive patients were at increased risk of progression to arthritis (hazard ratio (HR) 2.10, 95% CI 1.04–4.20), but this was not confirmed in the UK at-risk cohort (HR 0.99, CI 0.60–1.65).ConclusionSerum anti-LtxA is not elevated before RA diagnosis, and associations with disease progression and ACPA levels differ between populations. Other features of the oral microbiome should be explored in upcoming periodontitis-related RA research

    Управление деятельностью транспортной службы предприятия (на примере КЖРЭУП «Центральное»)

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    BACKGROUND: Drug-induced liver injury (DILI) is one of the most common adverse reactions leading to product withdrawal post-marketing. Recently, genome-wide association studies have identified a number of human leukocyte antigen (HLA) alleles associated with DILI; however, the cellular and chemical mechanisms are not fully understood. METHODS: To study these mechanisms, we established an HLA-typed cell archive from 400 healthy volunteers. In addition, we utilized HLA genotype data from more than four million individuals from publicly accessible repositories such as the Allele Frequency Net Database, Major Histocompatibility Complex Database and Immune Epitope Database to study the HLA alleles associated with DILI. We utilized novel in silico strategies to examine HLA haplotype relationships among the alleles associated with DILI by using bioinformatics tools such as NetMHCpan, PyPop, GraphViz, PHYLIP and TreeView. RESULTS: We demonstrated that many of the alleles that have been associated with liver injury induced by structurally diverse drugs (flucloxacillin, co-amoxiclav, ximelagatran, lapatinib, lumiracoxib) reside on common HLA haplotypes, which were present in populations of diverse ethnicity. CONCLUSIONS: Our bioinformatic analysis indicates that there may be a connection between the different HLA alleles associated with DILI caused by therapeutically and structurally different drugs, possibly through peptide binding of one of the HLA alleles that defines the causal haplotype. Further functional work, together with next-generation sequencing techniques, will be needed to define the causal alleles associated with DILI

    Fcγ-receptors in systemic autoimmune conditions : lessons from murine mercury-induced autoimmunity

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    In this thesis we investigated the role of activating (FcγRI, FcγRIII) and inhibitory (FcγRIIB) Fcγ-receptors on systemic autoimmunity using two mouse strains, DBA/1 (H-2q) and BALB/c mice (H-2d), susceptible to induction of autoimmunity by mercury (Hg). Fc-receptors for IgG (FcγR) link cellular and humoral immune responses, control the balance between activating and inhibitory immune responses and are important in the development of several autoimmune diseases. Mercury induces a T cell-dependent autoimmune condition, Hg-induced autoimmunity (HgIA) in genetically (H-2s,q,f,t2) susceptible mice characterized in its fullblown type by lymphoproliferation, hypergammaglobulinemia, systemic immune-complex (IC) deposits and antinucleolar antibodies (ANoA). All manifestations in HgIA are dependent on the presence of IFN-γ. Hg-treated BALB/c mice lacking activating FcγRs (FcγRI, FcγIII and FcεRI) showed significantly higher levels of both IgG1- and IgG2a-CIC whereas renal mesangial and vessel wall IC deposits were severely delayed and reduced/abolished, compared to mice without mutations (wild type, wt). Wt mice developed modest levels of IgG1- and IgG2a-CIC followed by a distinct formation of IC deposits in the renal glomerular mesangium, as well in renal and splenic vessel walls. Compared to wt mice, the mice lacking the inhibitory FcγRIIB showed similar titres of IC deposits in the renal mesangium, whereas vessel wall IC deposits were reduced. DBA/1 mice deficient for the FcRγ-chain (lack of the activating receptors FcγRI, FcγIII and FcεRI) or FcγRIII and treated with Hg showed a delayed and attenuated IgG1, IgG2a and IgG2b ANoA response compared to wt mice. Increasing the Hg dose or prolonging the treatment time could not override the attenuated ANoA response seen in FcγRIII mice. Female Hg-treated FcγRIIB mice showed a significant increase of IgG2b ANoA development compared to wt mice. The total serum IgG1 response due to treatment with Hg was attenuated in both BALB/c mice lacking the Fcγ-chain, and in DBA/1 mice lacking either the Fcγ- chain or specifically the FcγRIII compared to wt mice. This indicates that FcγRIII is the receptor important for the in HgIA characteristic serum IgG1 response. On the other hand, Hg-treated FcγRIIB deficient BALB/c and DBA/1 mice showed an increase of both serum IgG1 and IgE compared to wt mice. The cytokine profile in DBA/1 wt mice treated with Hg revealed a more marked Th1 profile compared to FcγRIII deficient mice. In contrast, the total Th2 and Th17 profile increased in both wt and FcγRIII deficient mice. However, during Hg treatment IL-21 mRNA expression was significantly reduced in FcγRIII deficient mice compared with wt mice. The increased Th1 profile in the wt mice could not be attributed to an increase of IFN-γ secretion from the major IFN-γ cell source, NK cells. We conclude that FcγRIII are important for the formation of IC deposits as shown by the delayed and reduced formation of IC deposits and the high levels of CIC in mice lacking FcγRIII. The expression of FcγRIII is also of importance for the rapidity and final strength of the ANoA response probably due to a reduced expression of Th1 cytokines and inflammatory factors. The ANoA response is modestly counter-regulated by FcγRIIB. The increase of serum IgG1 in HgIA is dependent on FcγRIII which is likely to be mediated by the low expression of IL- 21 in mice deficient for FcγRIII. In contrast, lack of FcγRIIB increases both the serum IgG1 and IgE response

    Påverkar geotracking detaljhandelns hyror i CBD?

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    In Sweden, there is practically free rental setting in the retail market. While there is an indirect tenancy regulation that protects the tenant, it does not prevent the establishment of market rents.Rent levels are generally highest in the central business district (CBD), following a rental pattern that confirms the monocentric urban model. It is also confirmed in the classic works of Von Thünen, Alonso, Mills, and Muth, that strong links exist between price and centrality. Stockholm's inner city is a typical example of this. The purpose of this thesis is to investigate whether geotracking can be used as an indicator of a prime location. Since the monocentric model claims that rents levels should be highest in the most central parts of a city, geotracking will be investigated as a tool for measuring the degree of centrality. The geotracking variable is based on the number of passing pedestrians outside retail premises, while rent levels are collected by leasing contracts. Geotracking serves as anexplanatory variable in the hedonic model where rent levels work as the dependent variable.This thesis assumes that a more central location, within the CBD, has a higher number of passers by than a less central one. This is a quantitative research-based study on walking data from Footfall, as well as market information provided Cushman & Wakefield. Footfall is a tool within Datscha that quantifies peoples movement patterns by tracking them through the mobile phone network. During this study, over 370 leases will be examined, of which approximately 250 contracts will be used in a regression analysis. All premises are located in the central parts of Stockholm. The relationship between rent levels and pedestrian traffic will be analysed in a traditional hedonic price equation with linear regression analysis. Through Footfall, the average number of passersby is collected for each address between March 2019, up until March 2020. The study results in a positive, and statistically significant, relationship between the number of passers by and rents for retail. In other words, rent levels increase as pedestrian traffic past the premises increase. However, the statistical relationship is weak. In the past, numerous studies on the relationship between location, rent, and property prices have been carried out. However,to our knowledge, there are no earlier studies of significance where Footfall- data has been usedfor academic purposes, until now.I Sverige är det så gott som fri hyressättning på butikhyresmarknaden. Det finns en indirekt hyresreglering som skyddar hyresgästen, men som inte hindrar etablering av marknadshyra. Hyresnivåerna är i allmänhet högst i CBD (stadskärnan) och i huvudsak enligt ett hyresmönster som kallas monocentrisk stadsmodell. Detta styrks även i studier från klassiska verk så som Von Thünen, Alonso, Mills och Muth, där starka kopplingar mellan pris och centralitet redovisas. Ett tydligt exempel är Stockholms innerstad. Syftet med denna studie är att undersöka huruvida geotracking kan användas som en indikator för centraliteten av ett läge. Då den monocentriska stadsmodellen fastslår att hyresnivåerna bör vara högst i de mest centrala delarna av en stad, kommer geotracking undersökas som ett verktyg för att mäta graden av centralitet vidare inom just CBD. Variabeln för geotracking baseras på antalet förbipasserande fotgängare utanför detaljhandelslokaler medans hyresnivåerna samlas in från hyresavtal. Geotracking fungerar som en förklarande variabel iden hedoniska modellen, där hyresnivåer fungerar som den beroende variabeln. Rapporten bygger på antagandet att ett mer centralt läge inom CBD har ett högre antal förbipasserande än ett mindre centralt. Detta är en kvantitativ forskningsbaserad studie på promenaddata från Datscha (Footfall), samt marknadsinformation tillhandahållen av Cushman & Wakefield. Footfall ägs av Datscha och ärett verktyg som kvantifierar människors rörelsemönster. Under denna studie kommer över 370 hyresavtal att granskas, varav cirka 250 kontrakt kommer att användas i en regressionsanalys.Samtliga lokaler är lokaliserade i Stockholms innerstad. Förhållandet mellan hyresnivåer och fotgängstrafik kommer att analyseras i en traditionell hedonisk prisekvation med linjärregressionsanalys. Genom Footfall hämtas det genomsnittliga antalet förbipasserande för varje adress mellan mars 2019 fram till mars 2020.Studien Studien resulterar i ett positivt och statistiskt signifikant samband mellan antalet förbipasserande och hyror för detaljhandeln. Med andra ord, hyresnivåerna ökar när fotgängstrafiken förbi lokaler ökar. Sambandet är dock statistiskt svagt. Tidigare har det gjorts undersökningar på förhållandet mellan plats, hyror och fastighetspriser

    Is it economically ben eficial to restore the surrounding areas in the Million Programme?

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    I denna kandidatuppsats har vi undersökt vår frågeställning ifall det är långsiktigt ekonomiskgynnsamt att rusta upp och renovera närområden i miljonprogram med utgångspunkt ifaktorer inom social hållbarhet. Detta har gjorts genom en kvalitativ analys baserad påintervjuer av fastighetsägare och byggbolag samt tidigare studier och teoretiskautgångspunkter. Till dessa valdes viktiga faktorer ut. För att kunna svara på vår frågeställningbehövdes de faktorer som fåtts från teoretiska utgångspunkter, tidigare studier samt intervjuerdelas upp i kategorier. Dessa valdes ut ifrån Östgötamodellen och sattes som grund, mednågra mindre justeringar. Östgötamodellens sista kategori byttes ut från “Kön, ålder och arv”till “Transparens och delaktighet”. De faktorer som inte kunde tilldelas en kategori sattes som“Icke tilldelad”.Efter indelningen i kategorier analyserades likheter och skillnader i fokus och vid jämförelsenmellan teoretiska utgångspunkter, intervjuer och tidigare studier kunde ett glapp mellanfastighetsägare och byggbolagens beslutsfattande organ uppfattas. Detta skulle kunna vara enanledning till varför social hållbarhet inte legat i fokus och inte prioriterats tidigare. Dockskulle detta behöva utvärderas mer för att kunna säkerställas.För att få företagen att satsa på sociala investeringar och upprustning av närområdet kringmiljonprogram, i större utsträckning, behövs långsiktigt ekonomiskt gynnsamhet bevisas.Först då kan det finnas intresse från företagens beslutande organ att även titta på den socialahållbarhetens kategorier vid avgörandet i huruvida ett projekt borde genomföras eller inte.Detta är svårt att visa på idag då många av projekten som skulle kunna generera denna typ avdata i framtiden är i startgropen, och resultat från projekten har helt enkelt inte utvärderats än.In this bachelor thesis, we have investigated if it is economically beneficial to restore thesurrounding areas in the Million Programme based on factors of social sustainability. Aqualitative analysis has been made based on interviews with property owners, constructioncompanies, previous studies and selected factors of various theoretical concepts. To answerour question, the factors were divided into different categories. The categories were selectedfrom Östgötamodellen, with some minor adjustments. The last category of Östgötamodellen,“Gender, Age and Heritage”, was replaced by “Transparency and Participation”. The factorswithout a particular assigned category were set as “unallocated”After categorising the factors of social sustainability, similarities and differences in focuswere analysed. In the comparison between theoretical concepts, interviews and previousstudies, a gap between property owners and the decisions that are made within theconstruction companies were highlighted. That might be a reason why social sustainabilityhas not been prioritised before. This could merely be a matter of speculations and thereforeneeds to be evaluated further.In order to get companies to invest in social initiatives and restore the surrounding areaswithin the Million Programme; the long-term economic benefits must be proven. If this canbe achieved, there may be a change in how the decisions are made when evaluating whether aproject should be implemented or not. Due to the fact that a lot of the projects are relativelynew and have not been evaluated yet, it is difficult to prove if these projects can generateeconomic benefits in the future

    Is it economically ben eficial to restore the surrounding areas in the Million Programme?

    No full text
    I denna kandidatuppsats har vi undersökt vår frågeställning ifall det är långsiktigt ekonomiskgynnsamt att rusta upp och renovera närområden i miljonprogram med utgångspunkt ifaktorer inom social hållbarhet. Detta har gjorts genom en kvalitativ analys baserad påintervjuer av fastighetsägare och byggbolag samt tidigare studier och teoretiskautgångspunkter. Till dessa valdes viktiga faktorer ut. För att kunna svara på vår frågeställningbehövdes de faktorer som fåtts från teoretiska utgångspunkter, tidigare studier samt intervjuerdelas upp i kategorier. Dessa valdes ut ifrån Östgötamodellen och sattes som grund, mednågra mindre justeringar. Östgötamodellens sista kategori byttes ut från “Kön, ålder och arv”till “Transparens och delaktighet”. De faktorer som inte kunde tilldelas en kategori sattes som“Icke tilldelad”.Efter indelningen i kategorier analyserades likheter och skillnader i fokus och vid jämförelsenmellan teoretiska utgångspunkter, intervjuer och tidigare studier kunde ett glapp mellanfastighetsägare och byggbolagens beslutsfattande organ uppfattas. Detta skulle kunna vara enanledning till varför social hållbarhet inte legat i fokus och inte prioriterats tidigare. Dockskulle detta behöva utvärderas mer för att kunna säkerställas.För att få företagen att satsa på sociala investeringar och upprustning av närområdet kringmiljonprogram, i större utsträckning, behövs långsiktigt ekonomiskt gynnsamhet bevisas.Först då kan det finnas intresse från företagens beslutande organ att även titta på den socialahållbarhetens kategorier vid avgörandet i huruvida ett projekt borde genomföras eller inte.Detta är svårt att visa på idag då många av projekten som skulle kunna generera denna typ avdata i framtiden är i startgropen, och resultat från projekten har helt enkelt inte utvärderats än.In this bachelor thesis, we have investigated if it is economically beneficial to restore thesurrounding areas in the Million Programme based on factors of social sustainability. Aqualitative analysis has been made based on interviews with property owners, constructioncompanies, previous studies and selected factors of various theoretical concepts. To answerour question, the factors were divided into different categories. The categories were selectedfrom Östgötamodellen, with some minor adjustments. The last category of Östgötamodellen,“Gender, Age and Heritage”, was replaced by “Transparency and Participation”. The factorswithout a particular assigned category were set as “unallocated”After categorising the factors of social sustainability, similarities and differences in focuswere analysed. In the comparison between theoretical concepts, interviews and previousstudies, a gap between property owners and the decisions that are made within theconstruction companies were highlighted. That might be a reason why social sustainabilityhas not been prioritised before. This could merely be a matter of speculations and thereforeneeds to be evaluated further.In order to get companies to invest in social initiatives and restore the surrounding areaswithin the Million Programme; the long-term economic benefits must be proven. If this canbe achieved, there may be a change in how the decisions are made when evaluating whether aproject should be implemented or not. Due to the fact that a lot of the projects are relativelynew and have not been evaluated yet, it is difficult to prove if these projects can generateeconomic benefits in the future

    Påverkar geotracking detaljhandelns hyror i CBD?

    No full text
    In Sweden, there is practically free rental setting in the retail market. While there is an indirect tenancy regulation that protects the tenant, it does not prevent the establishment of market rents.Rent levels are generally highest in the central business district (CBD), following a rental pattern that confirms the monocentric urban model. It is also confirmed in the classic works of Von Thünen, Alonso, Mills, and Muth, that strong links exist between price and centrality. Stockholm's inner city is a typical example of this. The purpose of this thesis is to investigate whether geotracking can be used as an indicator of a prime location. Since the monocentric model claims that rents levels should be highest in the most central parts of a city, geotracking will be investigated as a tool for measuring the degree of centrality. The geotracking variable is based on the number of passing pedestrians outside retail premises, while rent levels are collected by leasing contracts. Geotracking serves as anexplanatory variable in the hedonic model where rent levels work as the dependent variable.This thesis assumes that a more central location, within the CBD, has a higher number of passers by than a less central one. This is a quantitative research-based study on walking data from Footfall, as well as market information provided Cushman & Wakefield. Footfall is a tool within Datscha that quantifies peoples movement patterns by tracking them through the mobile phone network. During this study, over 370 leases will be examined, of which approximately 250 contracts will be used in a regression analysis. All premises are located in the central parts of Stockholm. The relationship between rent levels and pedestrian traffic will be analysed in a traditional hedonic price equation with linear regression analysis. Through Footfall, the average number of passersby is collected for each address between March 2019, up until March 2020. The study results in a positive, and statistically significant, relationship between the number of passers by and rents for retail. In other words, rent levels increase as pedestrian traffic past the premises increase. However, the statistical relationship is weak. In the past, numerous studies on the relationship between location, rent, and property prices have been carried out. However,to our knowledge, there are no earlier studies of significance where Footfall- data has been usedfor academic purposes, until now.I Sverige är det så gott som fri hyressättning på butikhyresmarknaden. Det finns en indirekt hyresreglering som skyddar hyresgästen, men som inte hindrar etablering av marknadshyra. Hyresnivåerna är i allmänhet högst i CBD (stadskärnan) och i huvudsak enligt ett hyresmönster som kallas monocentrisk stadsmodell. Detta styrks även i studier från klassiska verk så som Von Thünen, Alonso, Mills och Muth, där starka kopplingar mellan pris och centralitet redovisas. Ett tydligt exempel är Stockholms innerstad. Syftet med denna studie är att undersöka huruvida geotracking kan användas som en indikator för centraliteten av ett läge. Då den monocentriska stadsmodellen fastslår att hyresnivåerna bör vara högst i de mest centrala delarna av en stad, kommer geotracking undersökas som ett verktyg för att mäta graden av centralitet vidare inom just CBD. Variabeln för geotracking baseras på antalet förbipasserande fotgängare utanför detaljhandelslokaler medans hyresnivåerna samlas in från hyresavtal. Geotracking fungerar som en förklarande variabel iden hedoniska modellen, där hyresnivåer fungerar som den beroende variabeln. Rapporten bygger på antagandet att ett mer centralt läge inom CBD har ett högre antal förbipasserande än ett mindre centralt. Detta är en kvantitativ forskningsbaserad studie på promenaddata från Datscha (Footfall), samt marknadsinformation tillhandahållen av Cushman & Wakefield. Footfall ägs av Datscha och ärett verktyg som kvantifierar människors rörelsemönster. Under denna studie kommer över 370 hyresavtal att granskas, varav cirka 250 kontrakt kommer att användas i en regressionsanalys.Samtliga lokaler är lokaliserade i Stockholms innerstad. Förhållandet mellan hyresnivåer och fotgängstrafik kommer att analyseras i en traditionell hedonisk prisekvation med linjärregressionsanalys. Genom Footfall hämtas det genomsnittliga antalet förbipasserande för varje adress mellan mars 2019 fram till mars 2020.Studien Studien resulterar i ett positivt och statistiskt signifikant samband mellan antalet förbipasserande och hyror för detaljhandeln. Med andra ord, hyresnivåerna ökar när fotgängstrafiken förbi lokaler ökar. Sambandet är dock statistiskt svagt. Tidigare har det gjorts undersökningar på förhållandet mellan plats, hyror och fastighetspriser
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