Inflammatory bowel disease:The genetic background and beyond

Inflammatoire darm ziekten (IBD) zoals de ziekte van Crohn (CD) en colitis ulcerosa (CU) zijn deels erfelijk en deels omgevingsbepaalde ziekten en worden gekenmerkt door een chronisch recidiverende ontsteking van de darm. Waarschijnlijk zijn een verstoorde immuunreactie op normale darmflora samen met een verminderde darmwand integriteit onderliggend aan deze soms zeer ernstige en hardnekkige ziekte. Meer inzicht in de pathogenese is derhalve essentieel. Door het DNA te screenen op risico gebieden, zijn er tot op heden 163 gebieden gevonden geassocieerd met een verhoogd ziekte risico. Hiermee kan 15-25% van de totale erfelijkheid verklaard worden. In dit proefschrift worden een aantal potentiële bronnen van de ontbrekende erfelijkheid onderzocht. Er zouden meer risico gebieden kunnen zijn voor IBD. Wij analyseerden een aantal strategisch gekozen gebieden en vonden twee nieuwe risico gebieden voor IBD, en we vonden een omgekeerde associatie voor een specifiek gen voor CD en CU. Verder kan er mogelijk meer van de erfelijkheid verklaard worden met bekende risico gebieden. Mogelijk heeft dezelfde genetisch code een ander effect op ziekte risico als deze van vader of moeder wordt geërfd. Wij testten de overlappende IBD risico gebieden en vonden hier weinig aanwijzingen voor. Daarnaast werd onderzocht wat de effecten van de hoeveelheid risico gebieden is op cel niveau in afweer cellen. Deze relatie hebben wij niet kunnen vinden, wel vonden we een verschil tussen gezonde mensen en patiënten. Wij hebben bijgedragen aan de identificatie van nieuwe risico gebieden op het DNA voor inflammatoire darmziekten en potentiële bronnen voor de ontbrekende erfelijkheid onderzocht

Gait quality assessed by trunk accelerometry after total knee arthroplasty and its association with patient related outcome measures

Background: With an increasingly younger population and more active patients, assessment of functional outcome is more important than ever in patients undergoing total knee arthroplasty. Accelerometers have been used successfully to objectively evaluate gait quality in other fields. The aim of this study was to assess gait quality with accelerometers before and after surgery, and to assess added value of resulting parameters to patient reported outcome measures scores. Methods: Sixty-five patients (mean age 65 years (range 41–75)) who underwent primary total knee arthroplasty were evaluated using a tri-axial trunk accelerometer preoperatively and 1 year after surgery. Gait quality parameters derived from the accelerometry data were evaluated in three dimensions at both time points. Factor analysis was performed on all outcome variables and changes from before to 1 year after surgery in the most representative variable for each factor were studied. Findings: Factor analysis identified three separate gait quality factors, with questionnaire and gait quality parameters loading on different factors. Both gait quality factor scores and questionnaire factor scores improved significantly 1 year after surgery. As expected based on the factor analysis, only weak to moderate associations were found between patient reported outcome measures and gait quality before surgery, after surgery and in change scores. Interpretation: The independence of patient reported outcome measures and gait quality parameters measured with trunk accelerometry indicates that gait quality parameters provide additional information on functional outcome after total knee arthroplasty. Providing caretakers with objectively measurable targets using accelerometry could help improve outcome of these patients

The quest for genetic risk factors for Crohn's disease in the post-GWAS era

Multiple genome-wide association studies (GWASs) and two large scale meta-analyses have been performed for Crohn's disease and have identified 71 susceptibility loci. These findings have contributed greatly to our current understanding of the disease pathogenesis. Yet, these loci only explain approximately 23% of the disease heritability. One of the future challenges in this post-GWAS era is to identify potential sources of the remaining heritability. Such sources may include common variants with limited effect size, rare variants with higher effect sizes, structural variations, or even more complicated mechanisms such as epistatic, gene-environment and epigenetic interactions. Here, we outline potential sources of this hidden heritability, focusing on Crohn's disease and the currently available data. We also discuss future strategies to determine more about the heritability; these strategies include expanding current GWAS, fine-mapping, whole genome sequencing or exome sequencing, and using family-based approaches. Despite the current limitations, such strategies may help to transfer research achievements into clinical practice and guide the improvement of preventive and therapeutic measures

The Early Royal Society and Visual Culture

Recent studies have fruitfully examined the intersection between early modern science and visual culture by elucidating the functions of images in shaping and disseminating scientific knowledge. Given its rich archival sources, it is possible to extend this line of research in the case of the Royal Society to an examination of attitudes towards images as artefacts –manufactured objects worth commissioning, collecting and studying. Drawing on existing scholarship and material from the Royal Society Archives, I discuss Fellows’ interests in prints, drawings, varnishes, colorants, images made out of unusual materials, and methods of identifying the painter from a painting. Knowledge of production processes of images was important to members of the Royal Society, not only as connoisseurs and collectors, but also as those interested in a Baconian mastery of material processes, including a “history of trades”. Their antiquarian interests led to discussion of painters’ styles, and they gradually developed a visual memorial to an institution through portraits and other visual records.AH/M001938/1 (AHRC

Correction to: Putting genome-wide sequencing in neonates into perspective

The original version of this Article contained an error in the spelling of the author Pleuntje J. van der Sluijs, which was incorrectly given as Eline (P. J.) van der Sluijs. This has now been corrected in both the PDF and HTML versions of the Article