| 581. |
- Blomgren, J., et al.
(author)
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Putting co-creation into practice : lessons learned from developing a midwife-led quality improvement intervention
- 2023
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In: Global Health Action. - : Taylor and Francis Ltd.. - 1654-9716 .- 1654-9880. ; 16:1
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Journal article (peer-reviewed)abstract
- Background: Integrating evidence-based midwifery practices improves healthcare quality for women and newborns, but an evidence-to-practice gap exists. Co-created quality improvement initiatives led by midwives could bridge this gap, prevent resource waste and ensure intervention relevance. However, how to co-create a midwife-led quality improvement intervention has not been scientifically explored. Objective: The objective of this study is to describe the co-creation process and explore the needs and determinants of a midwife-led quality improvement targeting evidence-based midwifery practices. Methods: A qualitative deductive approach using the Consolidated Framework for Advancing Implementation Science was employed. An analysis matrix based on the framework was developed, and the data were coded according to categories. Data were gathered from interviews, focus group discussions, observations and workshops. New mothers and birth companions (n = 19) were included through convenience sampling. Midwives (n = 26), professional association representatives, educators, policymakers, managers, and doctors (n = 7) were purposely sampled. Results: The co-creation process of the midwife-led Quality Improvement intervention took place in four stages. Firstly, core elements of the intervention were established, featuring a group of midwife champions leading a quality improvement initiative using a train-the-trainers approach. Secondly, the intervention needs, context and determinants were explored, which showed knowledge and skills gaps, a lack of shared goals among staff, and limited resources. However, there was clear relevance, compatibility, and mission alignment for a midwife-led quality improvement at all levels. Thirdly, during co-creation workshops with new mothers and companions, the consensus was to prioritise improved intrapartum support, while workshops with midwives identified enhancing the use of birth positions and perineal protection as key focus areas for the forthcoming Quality Improvement intervention. Lastly, the findings guided intervention strategies, including peer-assisted learning, using existing structures, developing educational material, and building stakeholder relationships. Conclusions: This study provides a practical example of a co-creation process for a midwife-led quality improvement intervention, which can be relevant in different maternity care settings. © 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
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| 582. |
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| 583. |
- Bron, Peter A., et al.
(author)
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Can probiotics modulate human disease by impacting intestinal barrier function?
- 2017
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In: British Journal of Nutrition. - Cambridge, United Kingdom : Cambridge University Press. - 0007-1145 .- 1475-2662. ; 117:1, s. 93-107
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Research review (peer-reviewed)abstract
- Intestinal barrier integrity is a prerequisite for homeostasis of mucosal function, which is balanced to maximise absorptive capacity, while maintaining efficient defensive reactions against chemical and microbial challenges. Evidence is mounting that disruption of epithelial barrier integrity is one of the major aetiological factors associated with several gastrointestinal diseases, including infection by pathogens, obesity and diabetes, necrotising enterocolitis, irritable bowel syndrome and inflammatory bowel disease. The notion that specific probiotic bacterial strains can affect barrier integrity fuelled research in which in vitro cell lines, animal models and clinical trials are used to assess whether probiotics can revert the diseased state back to homeostasis and health. This review catalogues and categorises the lines of evidence available in literature for the role of probiotics in epithelial integrity and, consequently, their beneficial effect for the reduction of gastrointestinal disease symptoms.
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| 584. |
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| 585. |
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| 586. |
- Chen, Hao Yu, et al.
(author)
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Association of FADS1/2 Locus Variants and Polyunsaturated Fatty Acids With Aortic Stenosis
- 2020
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In: JAMA cardiology. - : American Medical Association (AMA). - 2380-6583 .- 2380-6591. ; 5:6, s. 694-702
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Journal article (peer-reviewed)abstract
- Importance: Aortic stenosis (AS) has no approved medical treatment. Identifying etiological pathways for AS could identify pharmacological targets.Objective: To identify novel genetic loci and pathways associated with AS.Design, Setting, and Participants: This genome-wide association study used a case-control design to evaluate 44 703 participants (3469 cases of AS) of self-reported European ancestry from the Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort (from January 1, 1996, to December 31, 2015). Replication was performed in 7 other cohorts totaling 256 926 participants (5926 cases of AS), with additional analyses performed in 6942 participants from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. Follow-up biomarker analyses with aortic valve calcium (AVC) were also performed. Data were analyzed from May 1, 2017, to December 5, 2019.Exposures: Genetic variants (615 643 variants) and polyunsaturated fatty acids (ω-6 and ω-3) measured in blood samples.Main Outcomes and Measures: Aortic stenosis and aortic valve replacement defined by electronic health records, surgical records, or echocardiography and the presence of AVC measured by computed tomography.Results: The mean (SD) age of the 44 703 GERA participants was 69.7 (8.4) years, and 22 019 (49.3%) were men. The rs174547 variant at the FADS1/2 locus was associated with AS (odds ratio [OR] per C allele, 0.88; 95% CI, 0.83-0.93; P = 3.0 × 10-6), with genome-wide significance after meta-analysis with 7 replication cohorts totaling 312 118 individuals (9395 cases of AS) (OR, 0.91; 95% CI, 0.88-0.94; P = 2.5 × 10-8). A consistent association with AVC was also observed (OR, 0.91; 95% CI, 0.83-0.99; P = .03). A higher ratio of arachidonic acid to linoleic acid was associated with AVC (OR per SD of the natural logarithm, 1.19; 95% CI, 1.09-1.30; P = 6.6 × 10-5). In mendelian randomization, increased FADS1 liver expression and arachidonic acid were associated with AS (OR per unit of normalized expression, 1.31 [95% CI, 1.17-1.48; P = 7.4 × 10-6]; OR per 5-percentage point increase in arachidonic acid for AVC, 1.23 [95% CI, 1.01-1.49; P = .04]; OR per 5-percentage point increase in arachidonic acid for AS, 1.08 [95% CI, 1.04-1.13; P = 4.1 × 10-4]).Conclusions and Relevance: Variation at the FADS1/2 locus was associated with AS and AVC. Findings from biomarker measurements and mendelian randomization appear to link ω-6 fatty acid biosynthesis to AS, which may represent a therapeutic target.
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| 587. |
- Chen, H. Y., et al.
(author)
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Genome-wide association meta-analysis in 652,134 participants identifies 9 novel susceptibility loci for aortic stenosis
- 2020
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In: European Heart Journal. - : Oxford University Press. - 0195-668X .- 1522-9645. ; 41:Suppl 2, s. 1862-1862
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Journal article (other academic/artistic)abstract
- Background: Aortic stenosis (AS) is the most common form of incident valvular heart disease. While valve replacement is effective, the absence of an approved medical therapy provides no alternatives to patients with contraindications or mild disease. An improved understanding of the genetics of AS could identify targets for pharmacological intervention.Methods: An inverse variance-weighted, fixed effects meta-analysis of the association of 11,591,806 variants with AS was undertaken using data from 10 European cohorts totalling 652,134 participants (13,758 cases of AS). We queried publicly available datasets to characterize the functional consequences of genome-wide significant variants, conducted a phenome-wide association study to assess their association with other outcomes, and constructed polygenic risk scores to examine their association with AS. We also performed gene- and gene-set enrichment analyses, estimated genetic correlation with cardiovascular traits, and assessed whether five lipid or immunological biomarkers were causally associated with AS using Mendelian randomization.Results: Eighteen independent variants at 16 loci attained genome-wide significance in the meta-analysis, including variants at all seven previously reported loci. Many of the significant variants were intronic or intergenic, and the phenome-wide association study revealed extensive pleiotropy with apolipoprotein B, C-reactive protein, and other cardiovascular and immunological traits. A weighted polygenic risk score composed of the 18 variants was strongly associated with AS (adjusted OR per SD, 1.38; 95% CI, 1.33 to 1.44; p=4.6×10–57), and improved the discriminatory ability for AS when added to a model that contained clinical risk factors (difference in the area under the curve p=2.0×10–11). Gene-based approaches indicated higher IL6R expression in the blood among AS cases compared to controls (p=3.1×10–6), and the association of LDLR with AS (p=2.3×10–10). Gene set analyses revealed that genes bound by the transcription factor TCF7 or micro-RNAs miR-21, miR-219, miR-491, and miR-19 were differentially expressed in the liver depending on AS status (p≤5.7×10–4), suggesting disease development may be mediated by tissue-specific transcriptional and post-transcriptional regulation. Mendelian randomization supported a causal association of five lipid and immunological biomarkers with AS, including low-density lipoprotein cholesterol (OR per mmol/L, 1.61; 95% CI, 1.48 to 1.75; p=1.3×10–30).Conclusions: Evidence from large-scale genetic analyses indicate that lipid metabolism, inflammation, and calcification are key contributors to AS.
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| 588. |
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| 589. |
- Cooil, Simon P., et al.
(author)
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In Situ Patterning of Ultrasharp Dopant Profiles in Silicon
- 2017
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In: ACS Nano. - : American Chemical Society (ACS). - 1936-0851 .- 1936-086X. ; 11:2, s. 1683-1688
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Journal article (peer-reviewed)abstract
- We develop a method for patterning a buried two-dimensional electron gas (2DEG) in silicon using low kinetic energy electron stimulated desorption (LEESD) of a monohydride resist mask. A buried 2DEG forms as a result of placing a dense and narrow profile of phosphorus dopants beneath the silicon surface; a so-called δ -layer. Such 2D dopant profiles have previously been studied theoretically, and by angle-resolved photoemission spectroscopy, and have been shown to host a 2DEG with properties desirable for atomic-scale devices and quantum computation applications. Here we outline a patterning method based on low kinetic energy electron beam lithography, combined with in situ characterization, and demonstrate the formation of patterned features with dopant concentrations sufficient to create localized 2DEG states.
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| 590. |
- Cserni, G, et al.
(author)
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Consistency in recognizing microinvasion in breast carcinomas is improved by immunohistochemistry for myoepithelial markers.
- 2016
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In: Virchows Archiv: an international journal of pathology. - : Springer Science and Business Media LLC. - 1432-2307. ; 468:4, s. 473-481
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Journal article (peer-reviewed)abstract
- Microinvasion is the smallest morphologically identifiable stage of invasion. Its presence and distinction from in situ carcinoma may have therapeutic implications, and clinical staging also requires the recognition of this phenomenon. Microinvasion is established on the basis of several morphological criteria, which may be difficult and not perfectly reproducible among pathologists. The aim of this study was to assess the consistency of diagnosing microinvasion in the breast on traditional haematoxylin and eosin (HE) stained slides and to evaluate whether immunohistochemistry (IHC) for myoepithelial markers could improve this. Digital images were generated from representative areas of 50 cases stained with HE and IHC for myoepithelial markers. Cases were specifically selected from the spectrum of in situ to microinvasive cancers. Twenty-eight dedicated breast pathologists assessed these cases at different magnifications through a web-based platform in two rounds: first HE only and after a washout period by both HE and IHC. Consistency in the recognition of microinvasion significantly improved with the use of IHC. Concordance rates increased from 0.85 to 0.96, kappa from 0.5 to 0.85, the number of cases with 100 % agreement rose from 9/50 to 25/50 with IHC and the certainty of diagnosis also increased. The use of IHC markedly improves the consistency of identifying microinvasion. This corroborates previous recommendations to use IHC for myoepithelial markers to clarify cases where uncertainty exists about the presence of microinvasion. Microinvasive carcinoma is a rare entity, and seeking a second opinion may avoid overdiagnosis.
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