Pilotstudie av hästars användning av en ligghall i ett lösdriftssystem

Different types of loose housing systems are becoming more common, primarily with the aim to increase the welfare of the horses. According to Swedish Animal Welfare legislation, horses kept outside all year around must have access to a shelter during the cold season, for protection against cold, rain and wind. The shelter should be equipped with dry and soft bed for the horse to satisfy their need for sleep. This study aimed to investigate how a group of horses used the shelter in a loose housing system called HIT Active Stable, at the Swedish National Equestrian Centre Flyinge. The study was performed during four days in the autumn. The duration of time the horses spent in the shelter was measured, also which location in the shelter the horses preferred to remain and what behaviour they performed. The shelter was divided into four zones to discern which location the horses preferred, how many horses who were within the zone limits and if they were standing or lying down. The four zones were observed once per hour. The behaviours in the shelter were observed every minute in five randomly selected horses. Differences in the use of the shelter during the day and at night were also recorded. The results show that the horses used the shelter about one out of five observations, mainly at night. The front part of the shelter, closest to the exits, was the most attractive place for the horses to remain. The most common behaviour of all the observations was resting behaviour (71%) such as lying on the chest, lying on the side and standing passively. We concluded that these results suggest that having access to a shelter seems to satisfy the horses need to rest.För cirka sex tusen år sedan domesticerades hästen blev en viktig del inom jordbruket (Hartley-Edwards 1994). Hästen stallades senare upp i enskilda boxar eller spiltor för att vara lättillgängliga för människan. Spår av krubbor och spiltor åt kungliga hästar har påträffats så långt tillbaka som för 900-800 f.kr (Chenevix-Trench 1970). Sedan dess har denna typ av hästhållning hängt kvar och har länge varit det vanligaste sättet att hålla häst på (Hartley-Edwards 1994). Majoriteten (85 %) av de cirka 360 000 hästar som fanns i Sverige år 2011 var uppstallade i boxar enligt en rapport från Jordbruksverket (2012). År 2002 hölls cirka 68 % av svenska tävlingshästar ensamma i hagen (Eklund 2008). Enligt Djurskyddsmyndighetens föreskrifter gällande allmänna råd om hästhållning (2 kap 1§) skall hästars behov av social kontakt tillgodoses och då helst genom fysisk kontakt med andra artfränder. Enligt Djurskyddsmyndighetens föreskrifter gällande allmänna råd om hästhållning (5 kap 1§) ska hästar dagligen ges möjlighet att röra sig fritt i sina naturliga gångarter (Jordbruksverket 2007a). Hästens naturliga behov blir därför delvis åsidosatta i den traditionella hästhållningen där hästar hålls ensamma med begränsad rörelsefrihet (Hartmann, Christensen & Keeling 2009). Genom ökad förståelse för hästens behov och välfärd väljer nu fler och fler hästägare att hålla sina hästar i grupp vid utevistelse (Werhahn et al. 2011). Även lösdriftssystem har blivit vanligare under de senare åren (Jordbruksverket 2008). Dessa alternativ mot den traditionella hästhållningen, där hästar hålls i individuella boxar, erbjuder hästar att bättre tillgodose deras naturliga behov vad gäller socialisering, rörelsebehov och ättider (Rose-Meierhöfer et al. 2010). Enligt Djurskyddsmyndighetens föreskrifter gällande allmänna råd om hästhållning (5 kap 10§) ska hästar som hålls ute dygnet runt ha tillgång till en ligghall vid de kalla årstiderna då betestillväxt inte sker för att få skydd mot kyla, nederbörd och vind. Hästen har en relativt liten kroppsyta i förhållande till sin kroppsvikt, vilket gör att den lättare kan hålla värmen vid kallt klimat (Morgan 2007). Hästen reglerar även sin temperatur genom födointag, andningsfrekvens, blodflöde, aktivitet och svettning (Cymbaluk & Christison 1990). Ett skydd mot vind och nederbörd är det viktigaste för att hästen ska kunna hålla en normal kroppstemperatur då den lättare kyls ner vid dessa klimat (Jordbruksverket 2007b). Hästens värmeavgivning sker dels i form av strålning via hästens kroppsyta till omgivningen, dels genom att svett och annan fuktighet avdunstar från kroppen, genom värmeledning mellan underlaget och kroppsytan samt genom strömning från kroppsytan till omgivningen genom vind (Michanek & Ventorp 2001). En ligghall ger hästen möjlighet att själv reglera sin värmeavgivning. Det genom dess väggar och tak ger ett skydd mot bland annat vind och regn, som motverkar strömning och konvektion, samt minskar ledningsförlusten mot liggytan genom en torr ströbädd (Morgan 2007). En studie gjordes under ett helt år på gotlandsruss permanent hållna på lösdrift. Studien visade att ligghallen användes nästan dubbelt så mycket när växtligheten var som minst jämfört mot resterande del av året (Näslund 2016). En annan studie gjordes under vinterhalvåret på islandshästar också permanent hållna på lösdrift. Den studien visade att ligghallen användes signifikant mer vid stark vind (>10 m/s) och stark vind i samband med regn eller snö (Mejdell & Bøe 2005). I Snoeks et al. (2015) studie över klimatets påverkan av ligghallsanvändningen i ett lösdriftssystem, visade att vind i kombination med regn ökade användandet av ligghallen signifikant mer oavsett temperatur. Även en studie av Michanek & Ventorp (1996) som gjordes i Skåne under vintertid på två ungston visade på att regn och kraftig vind ökade användningen av ligghallen. En annan studie visade att hästar använde ligghallen mer vid snöfall, regn, hård vindstyrka och lägre temperaturer. Samma studie visade även att ligghallen används mer av ston än valacker (Heleski & Murtazashvili 2010). Enligt Djurskyddsmyndighetens föreskrifter gällande allmänna råd om hästhållning (5 kap 10§) ska ligghallen även vara utrustad med en torr och ren liggplats för att hästen ska kunna tillgodose sitt sömnbehov. Hästens behov av sömn är betydligt mindre än exempelvis människans. Studier på hästar i fritt tillstånd visar att hästar ligger ner betydligt mindre än människan (Duncan 1985; Boyd et al. 1988). En studie visade att vuxna hästar vilar cirka 5-6 timmar per dygn, men sover endast cirka 3-4 timmar av denna tid. Vidare visade studien att hästen har ett behov av REM-sömn (Rapid Eye Movement) som kräver att hästen ligger ner med stöd för huvudet och kan inte kompenseras med annan typ av sömn. Samma studie visade att hästens sömn är uppdelad under dygnet, vanligtvis mellan fem och sju perioder per dygn som varar cirka 30 till 40 minuter (Dallaire 1986). Hästen vilar till största del under natten (Duncan, 1985; Dallaire 1986). Den kan vila stående, liggande på bröstet eller liggande på sidan och har alltid en eller flera flockmedlemmar som håller vakt under tiden (Rifa 1989). Dallaires studie (1986) visade även att tryggheten spelar stor roll för om hästen vill lägga sig ner eller inte då det kan det ta flera dagar för en häst i vilt tillstånd beroende på hur trygg den kände sig i sin omgivning. En annan faktor som kan påverka hästens vilja att lägga sig är underlaget. Hunter och Houpt (1989) studerade om ponnyer föredrog att ligga ned på strödda eller icke strödda ytor. Resultatet visade att ingen ponny observerades liggande på den icke strödda ytan. Andra studier visade att hästar ligger signifikant mer på halm än på spån (Greening et al. 2013;Pedersen Riemann, Søndergaard & Ladewigs 2004) Medjell & Bøes studie (2005) visade att hästarna använde ligghallen dagligen. Av alla observationer spenderade de 30,3 % inne i ligghallen. Hästarna låg ned cirka en tredjedel av observationerna i ligghallen och observerades mycket sällan liggandes utomhus. I Autios studie (2008) var ligghallsanvändningen totalt 43 % av alla observationer. Michanek & Ventorps studie (1996) visade att de spenderade 30,8 % av observationerna i ligghallen. Fler studier visade att hästar använde ligghallen mer under nattetid än dagtid och har även observerats liggandes procentuellt mer under nattetid än dagtid (Michanek & Ventorp 1996; Autio 2008). Det har också visats att vila förekommit framförallt i ligghallarna, även om vilobeteenden också förekommit utanför ligghallarna (Autio 2008). Ett tidigare examensarbete studerade fyra hästars användning av ligghall och visade att de upprätthöll sig i ligghallen 19 % av observationerna (Brosäter & Peterhoff 2013)

Association between occupational exposure to mineral oil and rheumatoid arthritis: results from the Swedish EIRA case–control study

The aim of the present study was to investigate the association between exposure to mineral oil and the risk of developing rheumatoid arthritis (RA), and in addition to perform a separate analysis on the major subphenotypes for the disease; namely, rheumatoid factor (RF)-positive RA, RF-negative RA, anticitrulline-positive RA and anticitrulline-negative RA, respectively. A population-based case–control study of incident cases of RA was performed among the population aged 18–70 years in a defined area of Sweden during May 1996–December 2003. A case was defined as an individual from the study base who for the first time received a diagnosis of RA according to the American College of Rheumatology criteria of 1987. Controls were randomly selected from the study base with consideration taken for age, gender and residential area. Cases (n = 1,419) and controls (n = 1,674) answered an extensive questionnaire regarding lifestyle factors and occupational exposures, including different types of mineral oils. Sera from cases and controls were investigated for RF and anticitrulline antibodies. Among men, exposure to any mineral oil was associated with a 30% increased relative risk of developing RA (relative risk = 1.3, 95% confidence interval = 1.0–1.7). When cases were subdivided into RF-positive RA and RF-negative RA, an increased risk was only observed for RF-positive RA (relative risk = 1.4, 95% confidence interval 1.0–2.0). When RA cases were subdivided according to the presence of anticitrulline antibodies, an increased risk associated with exposure to any mineral oil was observed only for anticitrulline-positive RA (relative risk = 1.6, 95% confidence interval = 1.1–2.2). Analysis of the interaction between oil exposure and the presence of HLA-DR shared epitope genes regarding the incidence of RA indicated that the increased risk associated with exposure to mineral oil was not related to the presence of shared epitope genotypes. In conclusion, our study shows that exposure to mineral oil is associated with an increased risk to develop RF-positive RA and anticitrulline-positive RA, respectively. The findings are of particular interest since the same mineral oils can induce polyarthritis in rats

Proliferation and differentiation potential of chondrocytes from osteoarthritic patients

Autologous chondrocyte transplantation (ACT) has been shown, in long-term follow-up studies, to be a promising treatment for the repair of isolated cartilage lesions. The method is based on an implantation of in vitro expanded chondrocytes originating from a small cartilage biopsy harvested from a non-weight-bearing area within the joint. In patients with osteoarthritis (OA), there is a need for the resurfacing of large areas, which could potentially be made by using a scaffold in combination with culture-expanded cells. As a first step towards a cell-based therapy for OA, we therefore investigated the expansion and redifferentiation potential in vitro of chondrocytes isolated from patients undergoing total knee replacement. The results demonstrate that OA chondrocytes have a good proliferation potential and are able to redifferentiate in a three-dimensional pellet model. During the redifferentiation, the OA cells expressed increasing amounts of DNA and proteoglycans, and at day 14 the cells from all donors contained type II collagen-rich matrix. The accumulation of proteoglycans was in comparable amounts to those from ACT donors, whereas total collagen was significantly lower in all of the redifferentiated OA chondrocytes. When the OA chondrocytes were loaded into a scaffold based on hyaluronic acid, they bound to the scaffold and produced cartilage-specific matrix proteins. Thus, autologous chondrocytes are a potential source for the biological treatment of OA patients but the limited collagen synthesis of the OA chondrocytes needs to be further explained

Text Annotation Handbook: A Practical Guide for Machine Learning Projects

This handbook is a hands-on guide on how to approach text annotation tasks. It provides a gentle introduction to the topic, an overview of theoretical concepts as well as practical advice. The topics covered are mostly technical, but business, ethical and regulatory issues are also touched upon. The focus lies on readability and conciseness rather than completeness and scientific rigor. Experience with annotation and knowledge of machine learning are useful but not required. The document may serve as a primer or reference book for a wide range of professions such as team leaders, project managers, IT architects, software developers and machine learning engineers.Comment: 30 pages, white pape

Genetic and environmental determinants for disease risk in subsets of rheumatoid arthritis defined by the anticitrullinated protein/peptide antibody fine specificity profile

OBJECTIVES: To increase understanding of the aetiology and pathogenesis of rheumatoid arthritis (RA), genetic and environmental risk factors for RA subsets, defined by the presence or absence of different anticitrullinated protein/peptide antibodies (ACPAs) targeting citrullinated peptides from α-enolase, vimentin, fibrinogen and collagen type II, were investigated. METHODS: 1985 patients with RA and 2252 matched controls from the EIRA case-control cohort were used in the study. Serum samples were assayed by ELISA for the presence of anticyclic citrullinated peptides (anti-CCP) antibodies and four different ACPA fine specificities. Cross-reactivity between ACPAs was examined by peptide absorption experiments. Genotyping was performed for HLA-DRB1 shared epitope (SE) alleles and the PTPN22 gene, while information regarding smoking was obtained by questionnaire. The association of genetic and environmental risk factors with different subsets of RA was calculated by logistic regression analysis. RESULTS: Limited cross-reactivity was observed between different ACPA fine specificities. In total, 17 RA subsets could be identified based on their different ACPA fine specificity profiles. Large differences in association with genetic and environmental determinants were observed between subsets. The strongest association of HLA-DRB1 SE, PTPN22 and smoking was identified for the RA subset which was defined by the presence of antibodies to citrullinated α-enolase and vimentin. CONCLUSION: This study provides the most comprehensive picture to date of how HLA-DRB1 SE, PTPN22 and smoking are associated with the presence of specific ACPA reactivities rather than anti-CCP levels. The new data will form a basis for molecular studies aimed at understanding disease development in serologically distinct subsets of RA.The Swedish Research CouncilVinnovaKing Gustaf V's 80-year foundationGums&Joints (FP7-Health-2010-261460)MasterSwitch (FP6-Health-2007-2.4.5-12)The Swedish Rheumatic FoundationThe Swedish Council for Working Life and Social ResearchThe IMI program BTCure (115142-2)Publishe

Corticotroph Aggressive Pituitary Tumors and Carcinomas Frequently Harbor ATRX Mutations

Context: Aggressive pituitary tumors (APTs) are characterized by unusually rapid growth and lack of response to standard treatment. About 1% to 2% develop metastases being classified as pituitary carcinomas (PCs). For unknown reasons, the corticotroph tumors are overrepresented among APTs and PCs. Mutations in the alpha thalassemia/mental retardation syndrome X-linked (ATRX) gene, regulating chromatin remodeling and telomere maintenance, have been implicated in the development of several cancer types, including neuroendocrine tumors. Objective: To study ATRX protein expression and mutational status of the ATRX gene in APTs and PCs. Design: We investigated ATRX protein expression by using immunohistochemistry in 30 APTs and 18 PCs, mostly of Pit-1 and T-Pit cell lineage. In tumors lacking ATRX immunolabeling, mutational status of the ATRX gene was explored. Results: Nine of the 48 tumors (19%) demonstrated lack of ATRX immunolabelling with a higher proportion in patients with PCs (5/18; 28%) than in those with APTs (4/30;13%). Lack of ATRX was most common in the corticotroph tumors, 7/22 (32%), versus tumors of the Pit-1 lineage, 2/24 (8%). Loss-of-function ATRX mutations were found in all 9 ATRX immunonegative cases: nonsense mutations (n = 4), frameshift deletions (n = 4), and large deletions affecting 22-28 of the 36 exons (n = 3). More than 1 ATRX gene defect was identified in 2 PCs. Conclusion: ATRX mutations occur in a subset of APTs and are more common in corticotroph tumors. The findings provide a rationale for performing ATRX immunohistochemistry to identify patients at risk of developing aggressive and potentially metastatic pituitary tumors.Peer reviewe

Genome-wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes.

OBJECTIVE: Proinsulin is a precursor of mature insulin and C-peptide. Higher circulating proinsulin levels are associated with impaired β-cell function, raised glucose levels, insulin resistance, and type 2 diabetes (T2D). Studies of the insulin processing pathway could provide new insights about T2D pathophysiology. RESEARCH DESIGN AND METHODS: We have conducted a meta-analysis of genome-wide association tests of ∼2.5 million genotyped or imputed single nucleotide polymorphisms (SNPs) and fasting proinsulin levels in 10,701 nondiabetic adults of European ancestry, with follow-up of 23 loci in up to 16,378 individuals, using additive genetic models adjusted for age, sex, fasting insulin, and study-specific covariates. RESULTS: Nine SNPs at eight loci were associated with proinsulin levels (P < 5 × 10(-8)). Two loci (LARP6 and SGSM2) have not been previously related to metabolic traits, one (MADD) has been associated with fasting glucose, one (PCSK1) has been implicated in obesity, and four (TCF7L2, SLC30A8, VPS13C/C2CD4A/B, and ARAP1, formerly CENTD2) increase T2D risk. The proinsulin-raising allele of ARAP1 was associated with a lower fasting glucose (P = 1.7 × 10(-4)), improved β-cell function (P = 1.1 × 10(-5)), and lower risk of T2D (odds ratio 0.88; P = 7.8 × 10(-6)). Notably, PCSK1 encodes the protein prohormone convertase 1/3, the first enzyme in the insulin processing pathway. A genotype score composed of the nine proinsulin-raising alleles was not associated with coronary disease in two large case-control datasets. CONCLUSIONS: We have identified nine genetic variants associated with fasting proinsulin. Our findings illuminate the biology underlying glucose homeostasis and T2D development in humans and argue against a direct role of proinsulin in coronary artery disease pathogenesis