| 1. |
- Munke, Anna, et al.
(författare)
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Data Descriptor : Coherent diffraction of single Rice Dwarf virus particles using hard X-rays at the Linac Coherent Light Source
- 2016
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Ingår i: Scientific Data. - : Nature Publishing Group. - 2052-4463. ; 3
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Tidskriftsartikel (refereegranskat)abstract
- Single particle diffractive imaging data from Rice Dwarf Virus (RDV) were recorded using the Coherent X-ray Imaging (CXI) instrument at the Linac Coherent Light Source (LCLS). RDV was chosen as it is a wellcharacterized model system, useful for proof-of-principle experiments, system optimization and algorithm development. RDV, an icosahedral virus of about 70 nm in diameter, was aerosolized and injected into the approximately 0.1 mu m diameter focused hard X-ray beam at the CXI instrument of LCLS. Diffraction patterns from RDV with signal to 5.9 angstrom ngstrom were recorded. The diffraction data are available through the Coherent X-ray Imaging Data Bank (CXIDB) as a resource for algorithm development, the contents of which are described here.
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| 2. |
- Andreasson, Anna N., et al.
(författare)
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Prediction pathways for innate immune pathology, IBS, anxiety and depression in a general population (The POPCOL Study)
- 2013
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Ingår i: Brain, behavior, and immunity. - : Elsevier BV. - 0889-1591 .- 1090-2139. ; 32, s. e46-e46
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- The aim of this study was to ascertain whether low grade innate inflammation contributes to a pathway of depression and anxiety via irritable bowel syndrome (IBS). We evaluated innate immune cell counts in colonic mucosa in normal subjects and those with IBS (Rome III) from a population based study in which 745 randomly selected subjects had a colonoscopy (mean age 51 years;57% women). Intraepithelial lymphocytes (IELs) per 100 enterocytes and eosinophils (eos) per five non-overlapping high power fields (HPF) were counted in 90 controls and 100 cases; immunocytochemistry (CD117) was performed for mast cells per 5HPF in 80 controls and 81 cases. IELs, mast cells and eos were individually summed over 5 sites (terminal ileum, caecum, transverse colon, sigmoid colon and rectum). Anxiety and depression scores were calculated from HADS. A causal model path model which hypothesises immune cells being associated with IBS which, in turn, is associated with elevated anxiety and depression was tested using path analysis implemented in the MPlus software. All hypothesised paths reached statistical significance (p < .05) supporting the individual hypothesized pathways. The overall model fit was reasonable although imperfect. In conclusion, a significant contribution of innate immune inflammatory load leading to anxiety and depression via IBS was found. Whether therapy directed to decreasing this inflammatory load also lifts depression and anxiety should be further explored.
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| 3. |
- Bielecki, Johan, 1982, et al.
(författare)
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Electrospray sample injection for single-particle imaging with x-ray lasers
- 2019
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Ingår i: Science advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 5:5
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Tidskriftsartikel (refereegranskat)abstract
- The possibility of imaging single proteins constitutes an exciting challenge for x-ray lasers. Despite encouraging results on large particles, imaging small particles has proven to be difficult for two reasons: not quite high enough pulse intensity from currently available x-ray lasers and, as we demonstrate here, contamination of the aerosolized molecules by nonvolatile contaminants in the solution. The amount of contamination on the sample depends on the initial droplet size during aerosolization. Here, we show that, with our electrospray injector, we can decrease the size of aerosol droplets and demonstrate virtually contaminant-free sample delivery of organelles, small virions, and proteins. The results presented here, together with the increased performance of next-generation x-ray lasers, constitute an important stepping stone toward the ultimate goal of protein structure determination from imaging at room temperature and high temporal resolution.
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| 4. |
- Schafmayer, Clemens, et al.
(författare)
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Genome-wide association analysis of diverticular disease points towards neuromuscular, connective tissue and epithelial pathomechanisms
- 2019
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Ingår i: Gut. - : BMJ. - 0017-5749 .- 1468-3288. ; 68:5, s. 854-865
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Tidskriftsartikel (refereegranskat)abstract
- Objective Diverticular disease is a common complex disorder characterised by mucosal outpouchings of the colonic wall that manifests through complications such as diverticulitis, perforation and bleeding. We report the to date largest genome-wide association study (GWAS) to identify genetic risk factors for diverticular disease. Design Discovery GWAS analysis was performed on UK Biobank imputed genotypes using 31 964 cases and 419 135 controls of European descent. Associations were replicated in a European sample of 3893 cases and 2829 diverticula-free controls and evaluated for risk contribution to diverticulitis and uncomplicated diverticulosis. Transcripts at top 20 replicating loci were analysed by real-time quatitative PCR in preparations of the mucosal, submucosal and muscular layer of colon. The localisation of expressed protein at selected loci was investigated by immunohistochemistry. Results We discovered 48 risk loci, of which 12 are novel, with genome-wide significance and consistent OR in the replication sample. Nominal replication (p< 0.05) was observed for 27 loci, and additional 8 in meta-analysis with a population-based cohort. The most significant novel risk variant rs9960286 is located near CTAGE1 with a p value of 2.3x10-10 and 0.002 (OR allelic = 1.14 (95% CI 1.05 to 1.24)) in the replication analysis. Four loci showed stronger effects for diverticulitis, PHGR1 (OR 1.32, 95% CI 1.12 to 1.56), FAM155A-2 (OR 1.21, 95% CI 1.04 to 1.42), CALCB (OR 1.17, 95% CI 1.03 to 1.33) and S100A10 (OR 1.17, 95% CI 1.03 to 1.33). Conclusion I n silico analyses point to diverticulosis primarily as a disorder of intestinal neuromuscular function and of impaired connective fibre support, while an additional diverticulitis risk might be conferred by epithelial dysfunction.
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| 5. |
- Walter, Susanna, et al.
(författare)
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Abdominal pain is associated with anxiety and depression scores in a sample of the general adult population with no signs of organic gastrointestinal disease
- 2013
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Ingår i: Neurogastroenterology and Motility. - : Wiley-Blackwell. - 1350-1925 .- 1365-2982. ; 25:9, s. 741-E576
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Tidskriftsartikel (refereegranskat)abstract
- Background Abdominal pain is common in the community, but only a subset meet diagnostic criteria for irritable bowel syndrome (IBS). Although anxiety and depression have been linked to IBS, the role of mood disturbances in the remainder with symptoms remains unclear. We aimed to study the associations between abdominal pain, anxiety, depression, and quality of life in the general population who were free of organic colonic disease by colonoscopy. Methods Two hundred and seventy-two randomly selected subjects from the general population, mean age 54 years (27-71), were clinically evaluated, had a colonoscopy and laboratory investigations to exclude organic gastrointestinal (GI) disease. All subjects completed GI symptom diaries for 1 week, the Rome II modular questionnaire, the Hospital Anxiety and Depression Scale, and Short Form 36. Key Results Twenty-two subjects were excluded due to organic disease; 1532 daily symptom records were available for analysis in the remainder. Thirty-four percent (n = 83) recorded at least one episode of abdominal pain on the diary. Twelve percent fulfilled Rome II criteria for IBS. Both anxiety and depression scores were higher in subjects who reported abdominal pain vs those who did not (P andlt; 0.0005 and P andlt; 0.0005). Anxiety and depression scores independently from IBS diagnosis (Rome II) predicted pain reporting and also correlated positively with pain burden. Quality of life scores were generally lower in subjects with abdominal pain. Conclusions andamp; Inferences Anxiety and depression are linked to functional abdominal pain, not only in subjects with IBS but also in otherwise healthy people with milder, subtle GI symptoms.
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| 6. |
- Andreasson, Anna N., et al.
(författare)
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Contemplate your symptoms and re-evaluate your health
- 2015
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Ingår i: Brain, behavior, and immunity. - : Elsevier BV. - 0889-1591 .- 1090-2139. ; 49, s. e38-e39
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Tidskriftsartikel (refereegranskat)abstract
- Bodily signals and how these are interpreted affect self-ratings of health. It is thus reasonable that appraisals of health are affected by imminent exposures and disease primes. We aimed to investigate whether self-ratings of health are affected by a symptom rating and if changes are substantiated in persons who report more symptoms. We used data from 813 persons who completed a questionnaire daily for 21 consecutive days. The questionnaire included a one-item self-rating of health (“pre-SRH”; 1 = excellent, 7 = very poor), a subsequent 26-item rating of physical and mental symptoms and thereafter a second (identical) self-rating of health (“post-SRH”). Paired t-tests were used to test for differences between pre-SRH and post-SRH. Mixed effect regression models were used to calculate the interaction effect of pre-SRH and symptom score on post-SRH adjusted for gender, age and if the person had been working that day (13545 observations). SRH worsened significantly (p <<.0001) after the symptom rating, from 2.72 pre-SRH (95%CI:−2.70–2.74) to 2.77 post-SRH (95%CI:2.75–2.79). There was a significant interaction between pre-SRH and symptoms on post-SRH so that persons who reported more symptoms changed their post-SRH rating to a higher degree than those who reported fewer symptoms, irrespective of their subjective health status. The results support the notion that subjective health perception is affected by focus of attention, and that the effect depends on level of symptoms.
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| 7. |
- Andreasson, Anna N., et al.
(författare)
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Development and preliminary validation of the Sickness Questionnaire (SicknessQ)
- 2013
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Ingår i: Brain, behavior, and immunity. - : Elsevier BV. - 0889-1591 .- 1090-2139. ; 32
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Tidskriftsartikel (refereegranskat)abstract
- The lack of questionnaires to measure subjective feelings of being sick made us develope the Sickness Questionnaire (SicknessQ) for assessment of sickness behavior in people. The objective of the present investigation was to test its internal consistency, criteria validity, and sensitivity to capture the sickness response in an experimental setting. An initial pool of items was developed based on previous research. The statistical properties of SicknessQ was assessed in 172 men and women primary care patients with acute complaints and involved three steps: (1) principal component analyses to reduce the number of items and to identify latent factor structures, (2) tests of internal consistencies of subscales, and (3) hierarchical regression analyses to test criteria validity of the subscales. Subsequently, sensitivity to change was tested in a placebo controlled experiment in which 31 blinded healthy men and women were injected with endotoxin (LPS) to provoke sickness behavior. Principal components analysis suggested a 3-factor solution with a total of 11 items measuring fatigue (5 items), pain (4 items) and emotion (2 items). The total scale as well as each of the three separate factors were significantly changed 90 min after endotoxin injection as compared to baseline (p’s < .01). In all, the new 11-item SicknessQ is highly sensitive to a mild systemic inflammation. Further studies are planned to test its usefulness and prognostic value in clinical settings.
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| 8. |
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| 9. |
- Ethier, J-F., et al.
(författare)
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Clinical Data Integration Model : Core Interoperability Ontology for Research Using Primary Care Data
- 2015
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Ingår i: Methods of Information in Medicine. - 0026-1270 .- 2511-705X. ; 54:1, s. 16-23
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: This article is part of the Focus Theme of Methods of Information in Medicine on "Managing Interoperability and Complexity in Health Systems". Background: Primary care data is the single richest source of routine health care data. However its use, both in research and clinical work, often requires data from multiple clinical sites, clinical trials databases and registries. Data integration and interoperability are therefore of utmost importance. Objectives: TRANSFoRm's general approach relies on a unified interoperability frame-work, described in a previous paper. We developed a core ontology for an interoperability framework based on data mediation. This article presents how such an ontology, the Clinical Data Integration Model (CDIM), can be designed to support, in conjunction with appropriate terminologies, biomedical data federation within TRANSFoRm, an EU FP7 project that aims to develop the digital infrastructure for a learning healthcare system in European Primary Care. Methods: TRANSFoRm utilizes a unified structural /terminological interoperability framework, based on the local-as-view mediation paradigm. Such an approach mandates the global information model to describe the domain of interest independently of the data sources to be explored. Following a requirement analysis process, no ontology focusing on primary care research was identified and, thus we designed a realist ontology based on Basic Formal Ontology to support our framework in collaboration with various terminologies used in primary care. Results: The resulting ontology has 549 classes and 82 object properties and is used to support data integration for TRANSFoRm's use cases. Concepts identified by researchers were successfully expressed in queries using CDIM and pertinent terminologies. As an example, we illustrate how, in TRANSFoRm, the Query Formulation Workbench can capture eligibility criteria in a computable representation, which is based on CDIM. Conclusion: A unified mediation approach to semantic interoperability provides a flexible and extensible framework for all types of interaction between health record systems and research systems. CDIM, as core ontology of such an approach, enables simplicity and consistency of design across the heterogeneous software landscape and can support the specific needs of EHR-driven phenotyping research using primary care data.
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| 10. |
- Lekander, Mats, et al.
(författare)
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Intrinsic functional connectivity of insular cortex and symptoms of sickness during acute experimental inflammation
- 2016
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Ingår i: Brain, behavior, and immunity. - : Elsevier BV. - 0889-1591 .- 1090-2139. ; 56, s. 34-41
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Tidskriftsartikel (refereegranskat)abstract
- Task-based fMRI has been used to study the effects of experimental inflammation on the human brain, but it remains unknown whether intrinsic connectivity in the brain at rest changes during a sickness response. Here, we investigated the effect of experimental inflammation on connectivity between areas relevant for monitoring of bodily states, motivation, and subjective symptoms of sickness. In a double blind randomized controlled trial, 52 healthy volunteers were injected with 0.6 ng/kg LPS (lipopolysaccharide) or placebo, and participated in a resting state fMRI experiment after approximately 2h 45 minutes. Resting state fMRI data were available from 48 participants, of which 28 received LPS and 20 received placebo. Bilateral anterior and bilateral posterior insula sections were used as seed regions and connectivity with bilateral orbitofrontal and cingulate (anterior and middle) cortices was investigated. Back pain, headache and global sickness increased significantly after as compared to before LPS, while a non-significant trend was shown for increased nausea. Compared to placebo, LPS was followed by increased connectivity between left anterior insula and left midcingulate cortex. This connectivity was significantly correlated to increase in back pain after LPS and tended to be related to increased global sickness, but was not related to increased headache or nausea. LPS did not affect the connectivity from other insular seeds. In conclusion, the finding of increased functional connectivity between left anterior insula and middle cingulate cortex suggests a potential neurophysiological mechanism that can be further tested to understand the subjective feeling of malaise and discomfort during a sickness response.
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