| 1. |
- Jung, Christian, et al.
(författare)
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A comparison of very old patients admitted to intensive care unit after acute versus elective surgery or intervention
- 2019
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Ingår i: Journal of critical care. - : W B SAUNDERS CO-ELSEVIER INC. - 0883-9441 .- 1557-8615. ; 52, s. 141-148
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Tidskriftsartikel (refereegranskat)abstract
- Background: We aimed to evaluate differences in outcome between patients admitted to intensive care unit (ICU) after elective versus acute surgery in a multinational cohort of very old patients (80 years; VIP). Predictors of mortality, with special emphasis on frailty, were assessed.Methods: In total, 5063 VIPs were induded in this analysis, 922 were admitted after elective surgery or intervention, 4141 acutely, with 402 after acute surgery. Differences were calculated using Mann-Whitney-U test and Wilcoxon test. Univariate and multivariable logistic regression were used to assess associations with mortality.Results: Compared patients admitted after acute surgery, patients admitted after elective surgery suffered less often from frailty as defined as CFS (28% vs 46%; p < 0.001), evidenced lower SOFA scores (4 +/- 5 vs 7 +/- 7; p < 0.001). Presence of frailty (CFS >4) was associated with significantly increased mortality both in elective surgery patients (7% vs 12%; p = 0.01), in acute surgery (7% vs 12%; p = 0.02).Conclusions: VIPs admitted to ICU after elective surgery evidenced favorable outcome over patients after acute surgery even after correction for relevant confounders. Frailty might be used to guide clinicians in risk stratification in both patients admitted after elective and acute surgery.
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| 2. |
- Bak-Coleman, Joseph B., et al.
(författare)
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Stewardship of global collective behavior
- 2021
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 118:27
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Tidskriftsartikel (refereegranskat)abstract
- Collective behavior provides a framework for understanding how the actions and properties of groups emerge from the way individuals generate and share information. In humans, information flows were initially shaped by natural selection yet are increasingly structured by emerging communication technologies. Our larger, more complex social networks now transfer high-fidelity information over vast distances at low cost. The digital age and the rise of social media have accelerated changes to our social systems, with poorly understood functional consequences. This gap in our knowledge represents a principal challenge to scientific progress, democracy, and actions to address global crises. We argue that the study of collective behavior must rise to a crisis discipline just as medicine, conservation, and climate science have, with a focus on providing actionable insight to policymakers and regulators for the stewardship of social systems.
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| 5. |
- Blumen, Sergiu C, et al.
(författare)
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Aggressive familial ALS with unusual brain MRI and a SOD1 gene mutation.
- 2010
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Ingår i: Amyotrophic Lateral Sclerosis and other Motor Neuron Disorders. - : Informa Healthcare. - 1466-0822 .- 1743-4483. ; 11:1-2, s. 228-231
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Tidskriftsartikel (refereegranskat)abstract
- We studied two sisters with rapidly progressing ALS starting at the ages of 46 and 48 years and leading to death after 14 months. Both fulfilled the El Escorial criteria for definite ALS and had marked upper motor neuron (UMN) predominance. Brain MRI, on fluid attenuation recovery (FLAIR) mode, showed outstanding hyperintensities of the precentral gyrus, centrum semiovale, corona radiata and along the corticospinal pathways in the brainstem. Screening for the SOD1 gene disclosed, at codon 140, a base substitution of adenine for thymine (GGT>CCA) known as the A140A 'silent' mutation since it does not change the amino acid (alanine) encoded for at that position. The severe UMN involvement and the fast progression of the disease may correlate with the MRI findings. It is also possible that the A140A mutation is not incidental; the mutated mRNA might be cytotoxic.
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| 6. |
- Henmyr, Viktor, et al.
(författare)
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Characterization of genetic variation in TLR8 in relation to allergic rhinitis
- 2015
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Ingår i: Allergy. European Journal of Allergy and Clinical Immunology. - : Wiley-Blackwell. - 0105-4538 .- 1398-9995.
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: A previous investigation of all 10 TLR-genes for associations with allergic rhinitis (AR) detected a number of significant SNPs in the TLR8 locus. The associations indicated that an accumulation of rare variants could explain the signal. The present study therefore searches for rare variants in the TLR8 region and also investigates the reproducibility of previous SNP associations.METHODS: The TLR8 gene was re-sequenced in 288 AR patients from Malmö and the data was compared with publically available data. Seven previously AR-associated SNPs from TLR8 were analyzed for AR-associations in 422 AR patients and 859 controls from the BAMSE cohort. The associations detected in present and previous studies were compared.RESULTS: Sequencing detected 13 polymorphisms (3 promotor, 10 coding) among 288 AR patients. Four of the coding polymorphisms were rare (MAF <1%) and three of those were novel. Two coding polymorphisms were benign missense mutations and the rest were synonymous. Comparison with 1000Genomes and Exome Aggregation Consortium data revealed no accumulation of rare variants in the AR cases. The AR-association tests made using the BAMSE cohort yielded 5 P-values < 0.05. Tests of IgE-levels yielded 4 significant SNP associations to birch pollen. Comparing results between different populations revealed opposing risk alleles, different gender effects and response to different allergens in the different populations.CONCLUSIONS: Rare variants in TLR8 are not associated with AR. Comparison of present and previous association studies reveal contradictory results for common variants. Thus, no associations exist between genetic variation in TLR8 and AR. This article is protected by copyright. All rights reserved.
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| 7. |
- Lemonnier, Nathanaël, et al.
(författare)
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A novel whole blood gene expression signature for asthma, dermatitis, and rhinitis multimorbidity in children and adolescents
- 2020
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Ingår i: Allergy. European Journal of Allergy and Clinical Immunology. - : WILEY. - 0105-4538 .- 1398-9995. ; 75:12, s. 3248-3260
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Tidskriftsartikel (refereegranskat)abstract
- Background: Allergic diseases often occur in combination (multimorbidity). Human blood transcriptome studies have not addressed multimorbidity. Large-scale gene expression data were combined to retrieve biomarkers and signaling pathways to disentangle allergic multimorbidity phenotypes.Methods: Integrated transcriptomic analysis was conducted in 1233 participants with a discovery phase using gene expression data (Human Transcriptome Array 2.0) from whole blood of 786 children from three European birth cohorts (MeDALL), and a replication phase using RNA Sequencing data from an independent cohort (EVA-PR, n = 447). Allergic diseases (asthma, atopic dermatitis, rhinitis) were considered as single disease or multimorbidity (at least two diseases), and compared with no disease.Results: Fifty genes were differentially expressed in allergic diseases. Thirty-two were not previously described in allergy. Eight genes were consistently overexpressed in all types of multimorbidity for asthma, dermatitis, and rhinitis (CLC, EMR4P, IL5RA, FRRS1, HRH4, SLC29A1, SIGLEC8, IL1RL1). All genes were replicated the in EVA-PR cohort. RT-qPCR validated the overexpression of selected genes. In MeDALL, 27 genes were differentially expressed in rhinitis alone, but none was significant for asthma or dermatitis alone. The multimorbidity signature was enriched in eosinophil-associated immune response and signal transduction. Protein-protein interaction network analysis identified IL5/JAK/STAT and IL33/ST2/IRAK/TRAF as key signaling pathways in multimorbid diseases. Synergistic effect of multimorbidity on gene expression levels was found.Conclusion: A signature of eight genes identifies multimorbidity for asthma, rhinitis, and dermatitis. Our results have clinical and mechanistic implications, and suggest that multimorbidity should be considered differently than allergic diseases occurring alone.
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| 8. |
- Madsen, Lynette D, et al.
(författare)
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Texture of Al thin films deposited by magnetron sputtering onto epitaxial W(001)
- 2000
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Ingår i: Journal of Applied Physics. - : AIP Publishing. - 0021-8979 .- 1089-7550. ; 87:1, s. 168-171
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Tidskriftsartikel (refereegranskat)abstract
- Highly textured epitaxial metallizations will be required for the next generation of devices with the main driving force being a reduction in electromigration. Herein a model system of 190 nm of Al on a 140 nm layer of W grown on MgO less than 00l greater than substrates was studied. The W layer was less than 00l greater than oriented and rotated 45 degrees with respect to the MgO substrate to minimize the misfit; the remaining strain was accommodated by dislocations, evident in transmission electron microscopy images. From high-resolution x-ray diffraction (XRD) measurements, the out-of-plane lattice parameter was determined to be 3.175 Angstrom, and the in-plane parameter was 3.153 Angstrom, i.e., the W film sustained a strain resulting in a tetragonal distortion of the lattice. XRD pole figures showed that the Al had four fold symmetry and two dominant orientations, less than 016 greater than and less than 3 9 11 greater than, which were twinned with multiple placements on the epitaxial W layer. The driving force for the tilted less than 001 greater than and less than 011 greater than orientations of Al on W is due to strain minimization through lattice matching. These results show that less than 00l greater than Al deposited at ambient conditions onto W is difficult to achieve and implies that electromigration difficulties are inherent.
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| 9. |
- Rosvall, Martin, 1978-, et al.
(författare)
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The map equation
- 2009
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Ingår i: The European Physical Journal Special Topics. - : Springer Science and Business Media LLC. - 1951-6355 .- 1951-6401. ; 178:1, s. 13-23
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Tidskriftsartikel (refereegranskat)abstract
- Many real-world networks are so large that we must simplify their structure before we can extract useful information about the systems they represent. As the tools for doing these simplifications proliferate within the network literature, researchers would benefit from some guidelines about which of the so-called community detection algorithms are most appropriate for the structures they are studying and the questions they are asking. Here we show that different methods highlight different aspects of a network's structure and that the the sort of information that we seek to extract about the system must guide us in our decision. For example, many community detection algorithms, including the popular modularity maximization approach, infer module assignments from an underlying model of the network formation process. However, we are not always as interested in how a system's network structure was formed, as we are in how a network's extant structure influences the system's behavior. To see how structure influences current behavior, we will recognize that links in a network induce movement across the network and result in system-wide interdependence. In doing so, we explicitly acknowledge that most networks carry flow. To highlight and simplify the network structure with respect to this flow, we use the map equation. We present an intuitive derivation of this flow-based and information-theoretic method and provide an interactive on-line application that anyone can use to explore the mechanics of the map equation. We also describe an algorithm and provide source code to efficiently decompose large weighted and directed networks based on the map equation.
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| 10. |
- Yngve, Ulrika, et al.
(författare)
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Triazolopyrimidinones as gamma-secretase modulators : structure-activity relationship, modulator profile, and in vivo profiling
- 2013
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Ingår i: MedChemComm. - : Royal Society of Chemistry (RSC). - 2040-2503 .- 2040-2511. ; 4:2, s. 422-431
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Tidskriftsartikel (refereegranskat)abstract
- The structure-activity relationship for a series of potent g-secretase modulators based on the 6,7-dihydro4H-[1,2,4]triazolo[1,5-a]pyrimidin-5-one scaffold is described. Furthermore, we report details regarding the modulator profile on A beta processing, as well as in vivo efficacy, for the optimized compounds.
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