En svensk kodifikationsstrid? En komparativ studie av det svenska civillagförslaget år 1826

Användandet av s.k. kodifikationer som lagstiftningsmodell växte i popularitet som tydligast från och med upplysningstiden. Kodifikationen ämnar ge en fullständig, systematisk och tydlig bild av lagen. Modellen användes av flertalet framväxande nationalstater i 1800-talets Europa, där kodifikationen förstärkte och legitimerade centralstyret. I Sverige uppmärksammades behovet av en reformerad civillagstiftning i samband med författandet av RF 1809. Den existerande lagen från år 1734 ansågs vara obsolet och bristfällig. I teorin skulle en kodifikation kunna råda bot på dessa svagheter och enligt den framväxande liberalismen markera övergången till ett individfokuserat samhälle. En liknande otillfredsställdhet med rättsläget fanns i de tyska staterna, som var splittrade efter tysk-romerska rikets fall. År 1814 ägde den s.k. kodifikationsstriden rum, där idén om en alltysk lag mötte kraftigt motstånd från konservatismen, som lyckades hejda förslaget under flera decennier. De konservativa strömningarna gav upphov till ett eko i Sverige. Syftet med uppsatsen är att undersöka om den svenska debatten kring det civillagförslag som skrevs kan beskrivas som en svensk kodifikationsstrid. Vid debattiden var liberalismen och konservatismen varandras motsatser i frågan om det framtida samhället, vilket avspeglades på civillagförslaget och dess remissyttrande. Den liberala lagkommittén verkade genom sitt borgerliga lagförslag för avskaffandet av ståndssamhället genom att emancipera individen från staten och söka realisera konstitutionens upplysningsanda, vilket från den laggranskande Högsta domstolen med konservatism, av rädsla för en radikal samhällsordning med ett försvagat bondestånd genom ståndsupplösningen. 1734 års lag bestod i slutändan på bekostnad av normativ och jämlik lag i en era av förändring, där kontinuitet nog ironiskt blev den stora vinnaren.The usage of the legislative model codification grew in popularity from the enlightenment on. The codification aims to present a complete, clear and systematic view of the law. The model was used by several emerging national states in 19th century Europe, where the codification was used to strengthen and legitimize the central power. In Sweden, the pressing need for a reformed civil law was recognized when the new constitution was written in 1809. The existing civil law from 1734 was seen as obsolete and inadequate. In theory, a codification could remedy these weaknesses and for the developing liberalism mark the transition to a new society with the individual in focus. In the German states, which were divided after the fall of the Holy Roman Empire, a similar dissatisfaction with the legal position existed. In 1814, the so-called Codification War took place there, where the idea of a unifying German law was opposed by the conservatism, which managed to repress the proposal for decades. The conservative tides gave rise to a strong conservatism in Sweden. The purpose of the essay is to investigate whether the Swedish debate about the civil law proposal which was written can be described as a Swedish Codification War. At the time of the debate, liberalism and conservatism were strong opponents, which mirrored on the civil law proposal respectively the comments on official report from the Supreme Court. The liberal law committee acted through its bourgeois law proposal for the abolition of the estate society, by emancipating the individual from the state and seeking to realize the enlightened spirit of the new constitution, which was responded with conservatism from the law reviewing Supreme Court, in fear of a radical social order, with a weakened farmer estate through the disintegration of the estates. In the end, the law of 1734 persisted, at the expense of a normative and equal law, in times of changes, where ironically continuity was the big winner

A pleiotropic missense variant in SLC39A8 is associated with Crohn's disease and human gut microbiome composition

Genome-wide association studies have identified 200 inflammatory bowel disease (IBD) loci, but the genetic architecture of Crohn's disease (CD) and ulcerative colitis remain incompletely defined. Here, we aimed to identify novel associations between IBD and functional genetic variants using the Illumina ExomeChip (San Diego, CA)

Environmental factors in a population-based inception cohort of inflammatory bowel disease patients in Europe--an ECCO-EpiCom study.

To access publisher's full text version of this article click on the hyperlink at the bottom of the pageThe incidence of inflammatory bowel disease (IBD) is increasing in Eastern Europe possibly due to changes in environmental factors towards a more "westernised" standard of living. The aim of this study was to investigate differences in exposure to environmental factors prior to diagnosis in Eastern and Western European IBD patients.The EpiCom cohort is a population-based, prospective inception cohort of 1560 unselected IBD patients from 31 European countries covering a background population of 10.1 million. At the time of diagnosis patients were asked to complete an 87-item questionnaire concerning environmental factors.A total of 1182 patients (76%) answered the questionnaire, 444 (38%) had Crohn's disease (CD), 627 (53%) ulcerative colitis (UC), and 111 (9%) IBD unclassified. No geographic differences regarding smoking status, caffeine intake, use of oral contraceptives, or number of first-degree relatives with IBD were found. Sugar intake was higher in CD and UC patients from Eastern Europe than in Western Europe while fibre intake was lower (p<0.01). Daily consumption of fast food as well as appendectomy before the age of 20 was more frequent in Eastern European than in Western European UC patients (p<0.01). Eastern European CD and UC patients had received more vaccinations and experienced fewer childhood infections than Western European patients (p<0.01).In this European population-based inception cohort of unselected IBD patients, Eastern and Western European patients differed in environmental factors prior to diagnosis. Eastern European patients exhibited higher occurrences of suspected risk factors for IBD included in the Western lifestyle.Danish Colitis Crohn Patients Organisation (CCF) Vibeke Binder and Povl Riis Foundation Scientific Council at Herlev Hospital Sigrid Rignnor Moran Foundation, Aage and Johanne Louis-Hansens Foundation Munkholm Foundation C.C. Klestrup and Henriette Klestrup Foundation Knud and Dagny Gad Andresens Foundation Else and Mogens Wedell-Wedellsborgs Foundation Direktor Jacob Madsen and Olga Madsen's Foundation, Scan Ve

Intestinal microbiota and the innate immune system – a crosstalk in Crohn’s disease pathogenesis

Crohn’s disease (CD) is a chronic, relapsing inflammatory disorder that can occur anywhere along the gastrointestinal tract. The precise etiology of CD is still unclear but it is widely accepted that a complex series of interactions between susceptibility genes, the immune system and environmental factors are implicated in the onset and perpetuation of the disease. Increasing evidence from experimental and clinical studies implies the intestinal microbiota in disease pathogenesis, thereby supporting the hypothesis that chronic intestinal inflammation arises from an abnormal immune response against the microorganisms of the intestinal flora in genetically susceptible individuals. Given that CD patients display changes in their gut microbiota composition, collectively termed “dysbiosis,” the question raises whether the altered microbiota composition is a cause of disease or rather a consequence of the inflammatory state of the intestinal environment. This review will focus on the crosstalk between the gut microbiota and the innate immune system during intestinal inflammation, thereby unraveling the role of the microbiota in CD pathogenesis

Current understanding of the human microbiome

Author Posting. © The Author(s), 2018. This is the author's version of the work. It is posted here by permission of Nature Publishing Group for personal use, not for redistribution. The definitive version was published in Nature Medicine 24 (2018): 392–400, doi:10.1038/nm.4517.Our understanding of the link between the human microbiome and disease, including obesity, inflammatory bowel disease, arthritis and autism, is rapidly expanding. Improvements in the throughput and accuracy of DNA sequencing of the genomes of microbial communities associated with human samples, complemented by analysis of transcriptomes, proteomes, metabolomes and immunomes, and mechanistic experiments in model systems, have vastly improved our ability to understand the structure and function of the microbiome in both diseased and healthy states. However, many challenges remain. In this Review, we focus on studies in humans to describe these challenges, and propose strategies that leverage existing knowledge to move rapidly from correlation to causation, and ultimately to translation.Many of the studies described here in our laboratories were supported by the NIH, NSF, DOE, and the Alfred P. Sloan Foundation.2018-10-1

Accelerating earlier access to anti-TNF-α agents with biosimilar medicines in the management of inflammatory bowel disease

Data indicate that earlier initiation of anti-tumor necrosis factor alpha (anti-TNF-α) biologic medicines may prevent progression to irreversible bowel damage and improve outcomes for patients with inflammatory bowel disease (IBD), particularly Crohn\u27s disease. However, the high cost of such therapies may restrict access and prevent timely treatment of IBD. Biosimilar anti-TNF-α medicines may represent a valuable opportunity for cost savings and optimized patient outcomes by improving access to advanced therapies and allowing earlier anti-TNF-α treatment initiation. Biosimilar anti-TNF-α medicines have been shown to offer consistent therapeutic outcomes to their reference medicines, yet despite entering the IBD treatment armamentarium over 10 years ago, their implementation in clinical practice remains suboptimal. Factors limiting the \u27real\u27 use of biosimilar anti-TNF-α medicines may include an ongoing lack of understanding and acceptance of biosimilars by both healthcare professionals (HCPs) and patients, as well as systemic factors such as formulary decisions outside of the control of the prescriber. In this review, an expert panel of gastroenterologists discusses HCP-level considerations to improve biosimilar anti-TNF-α utilization in IBD in order to support early anti-TNF-α initiation and maximize patient outcomes

Fetal and early life antibiotics exposure and very early onset inflammatory bowel disease – a population-based study

Objective Earlier studies on antibiotics exposure and development of IBD (Crohn’s disease (CD) and ulcerative colitis (UC)) may have been biased by familial factors and gastroenteritis. We aimed to estimate the association between antibiotics during pregnancy or infantile age and very early onset (VEO) IBD. Design In this cohort study of 827 239 children born in Sweden between 2006 and 2013, we examined the link between exposure to systemic antibiotics and VEO-IBD (diagnosis <6 years of age), using Cox proportional hazard regression models. Information on antibiotics and IBD was retrieved from the nationwide population-based Swedish Prescribed Drug Register and the National Patient Register. We specifically examined potential confounding from parental IBD and gastroenteritis. Results Children exposed to antibiotics during pregnancy were at increased risk of IBD compared with general population controls (adjusted HR (aHR) 1.93; 95% CI 1.06 to 3.50). Corresponding aHRs were 2.48 (95% CI 1.01 to 6.08) for CD and 1.25 (95% CI 0.47 to 3.26) for UC, respectively. For antibiotics in infantile age, the aHR for IBD was 1.11 (95% CI 0.57 to 2.15); for CD 0.72 (95% CI 0.27 to 1.92) and 1.23 (95% CI 0.45 to 3.39) for UC. Excluding children with gastroenteritis 12 months prior to the first IBD diagnosis retained similar aHR for antibiotics during pregnancy and CD, while the association no longer remained significant for IBD. Conclusion We found that exposure to antibiotics during pregnancy, but not in infantile age, is associated with an increased risk of VEO-IBD regardless of gastroenteritis. The risk increase for exposure in pregnancy may be due to changes in the microbiota.Financial support was provided from the Swedish Research Council through the Swedish Initiative for Research on Microdata in the Social And Medical Sciences (SIMSAM) framework grant no 340-2013-5867, grants provided by the Stockholm County Council (ALF-projects), the Swedish Heart-Lung Foundation and the Swedish Asthma and Allergy Association’s Research Foundation.Accepte

Unmet Medical Needs in Ulcerative Colitis: An Expert Group Consensus

BACKGROUND The authors aimed to conduct an extensive literature review and consensus meeting to identify unmet needs in ulcerative colitis (UC) and ways to overcome them. UC is a relapsing and remitting inflammatory bowel disease with varied, and changing, incidence rates worldwide. UC has an unpredictable disease course and is associated with a high health economic burden. During 2016 and 2017, a panel of experts was convened to identify, discuss and address areas of unmet need in UC. METHODS PubMed and Cochrane Library databases were searched for relevant articles describing studies performed in patients with UC. These findings were used to generate a set of statements relating to unmet needs in UC. Consensus on these statements was then sought from a panel of 9 expert gastroenterologists using a modified Delphi review process that consisted of anonymous surveys followed by live meetings. RESULTS In 2 literature reviews, over 5,000 unique records were identified and a total of 138 articles were fully reviewed. These were used to consider 26 areas of unmet need, which were explored in 2 face-to-face meetings, in which the statements were debated and amended, resulting in consensus on 30 final statements. The unmet needs identified were categorised into 7 areas: impact of UC on patients' daily life; importance of early diagnosis and treatment; drawbacks of existing treatments; urgent need for new treatments; and disease-, practice- or patient-focused unmet needs. CONCLUSIONS These expert group meetings found a number of areas of unmet needs in UC, which is an important first step in tackling them in the future. Future research and development should be focused in these areas for the management of patients with UC

Exposure to air pollution increases susceptibility to ulcerative colitis through epigenetic alterations in CXCR2 and MHC class III region

Summary Background This study aims to confirm the associations of air pollution with ulcerative colitis (UC) and Crohn's disease (CD); to explore interactions with genetics and lifestyle; and to characterize potential epigenetic mechanisms. Methods We identified over 450,000 individuals from the UK Biobank and investigated the relationship between air pollution and incident inflammatory bowel disease (IBD). Cox regression was utilized to calculate hazard ratios (HRs), while also exploring potential interactions with genetics and lifestyle factors. Additionally, we conducted epigenetic Mendelian randomization (MR) analyses to examine the association between air pollution-related DNA methylation and UC. Finally, our findings were validated through genome-wide DNA methylation analysis of UC, as well as co-localization and gene expression analyses. Findings Higher exposures to NOx (HR = 1.20, 95% CI 1.05–1.38), NO2 (HR = 1.19, 95% CI = 1.03–1.36), PM2.5 (HR = 1.19, 95% CI = 1.05–1.36) and combined air pollution score (HR = 1.26, 95% CI = 1.11–1.45) were associated with incident UC but not CD. Interactions with genetic risk score and lifestyle were observed. In MR analysis, we found five and 22 methylated CpG sites related to PM2.5 and NO2 exposure to be significantly associated with UC. DNA methylation alterations at CXCR2 and sites within the MHC class III region, were validated in genome-wide DNA methylation analysis, co-localization analysis and analysis of colonic tissue. Interpretation We report a potential causal association between air pollution and UC, modified by lifestyle and genetic influences. Biological pathways implicated include epigenetic alterations in key genetic loci, including CXCR2 and susceptible loci within MHC class III region. Funding Xue Li was supported by the Natural Science Fund for Distinguished Young Scholars of Zhejiang Province (LR22H260001) and the National Nature Science Foundation of China (No. 82204019). ET was supported by the CRUK Career Development Fellowship (C31250/A22804) and the Research Foundation Flanders (FWO). JW was supported by Belgium by a PhD Fellowship strategic basic research (SB) grant (1S06023N). JKN was supported by the National Science Center, Poland (No. 2020/39/D/NZ5/02720). The IBD Character was supported by the European Union's Seventh Framework Programme [FP7] grant IBD Character (No. 2858546)