65 research outputs found
Quantitative hypermorphic FAM111A alleles cause autosomal recessive Kenny-Caffey syndrome type 2 and osteocraniostenosis
No full textKenny-Caffey syndrome (KCS) is a rare genetic disorder characterized by extreme short stature, cortical thickening and medullary stenosis of tubular bones, facial dysmorphism, abnormal T-cell function, and hypoparathyroidism. Biallelic loss-of-function variants in TBCE cause autosomal recessive type 1 KCS (KCS1). By contrast, heterozygous missense variants in a restricted region of the FAM111A gene have been identified in autosomal dominant type 2 KCS (KCS2) and a more severe lethal phenotype, osteocraniostenosis (OCS) that have recently been shown to confer a gain-of-function. In this study, we describe two unrelated children with KCS and OCS who were homozygous for different FAM111A variant alleles that result in replacement of the same residue, Tyr414 (c.1241A>G, p.Y414C and c.1240T>A, p.Y414N), in the mature FAM111A protein. Their heterozygous relatives are asymptomatic. Functional studies of recombinant FAM111AY414C demonstrated normal dimerization and a mild gain-of-function effect. This study provides evidence that both biallelic and monoallelic variants of FAM111A with varying degrees of activation can lead to dominant or recessive KCS2 and OCS.Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made.Journal content freely available via Open Access. Some content may be unavailable due to publisher embargo. Click on the 'Additional link' above to access the full-text
How Safety Culture Surveys Influence the Quality and Safety of Healthcare Organisations
No full textObjectives
Safety culture surveys have been widely used in healthcare for more than two decades predominantly as a tool for measuring the level of safety culture (as defined as the beliefs and attitudes that staff express about how their organisation ought to work and how it does in fact work). However, there is the potential for the survey process itself to influence the safety culture and working practices in departments and organisations. The objective of this study was to identify the mechanism by which these changes might occur.
Design, setting and participants
Mixed methods combining qualitative semi-structured interviews and quantitative scores from patient safety surveys.
This evaluation was conducted across general practice, community and acute hospitals in two NHS regions in England; South West and Greater Manchester. The study was undertaken between 2015 and 2018 during the implementation of a series of Patient Safety Collaboratives. Safety, Communication, Operational Reliability, and Engagement (SCORE) surveys were administered in 15 units, followed by a staff debriefing and a second SCORE survey. Semi-structured interviews were conducted with clinicians (n=61). Results from the first and second surveys were compared in order to test for differences in responses. Sixty-one semistructured interviews were conducted across participating units and thematically analysed.
Analysis and results
Results from the first and second surveys were compared using chi-squared and Fisher’s exact tests. Sixtyone semi-structured interviews were conducted across participating units and thematically analysed.
There was little change in responses between the first and second SCORE surveys. Within general practice there was some improvement in responses in three survey domains; however, these differences were not conclusive. The qualitative interview data demonstrated a beneficial effect on safety culture. Staff stated that the survey debriefings created a new safe space where problems could be discussed and improvement plans created.
Conclusions
Safety culture surveys can improve safety culture within departments if they are followed by a process that includes debriefing the staff and working with them to develop improvement plans
Peritoneal morphological and functional changes associated with platelet-derived growth factor B
No full textBackground:
Morphological changes associated with long-term peritoneal dialysis (PD) include increased vascular surface area due to angiogenesis, submesothelial fibrosis and epithelial mesenchymal transition. Platelet-derived growth factor (PDGF) has been associated with all of these phenomena, and is a prototypical & response to injury & growth factor.
Methods: Rats received an intraperitoneal injection of adenoviral vector expressing PDGF-B. At sacrifice, we analysed the structure and function of the peritoneal membrane. Gene expression in the peritoneal tissue was assessed for changes suggestive of epithelial mesenchymal transition.
Results: Over-expression of PDGF in the rat peritoneum led to significant angiogenesis, cellular proliferation and submesothelial thickening. Although PDGF induced expression of transforming growth factor beta, there was a lack of activation of this growth factor, and we believe that this explains the lack of significant collagen accumulation observed by a hydroxyproline assay. Despite evidence of angiogenesis and subsequent increased solute transport, we observed only a transient, non-significant impact on ultrafiltration function. This suggests that increased vascular surface area is necessary, but not sufficient, to produce ultrafiltration dysfunction. There was no evidence of epithelial mesenchymal transition observed either in regulation of associated genes such as Snail or E-Cadherin or in the lack of dual-labelled epithelial and mesenchymal cells on immunofluorescence. Mesothelial cells exposed to PDGF-B demonstrated increased collagen gene expression.
Conclusions: PDGF-B induced angiogenesis without fibrosis in the peritoneum. The lack of significant ultrafiltration dysfunction and epithelial mesenchymal transition, as observed in patients on PD, suggests that PDGF-B may play a role, but is not the integral component, in response to peritoneal injury.
</p
Editor’s Note
No full textIn this issue of Newport History, Gary Scharnhorst examines Bret Harte, an elusive literary figure who made a brief but lasting impact on Newport society and letters. Harte established his reputation as a writer in California with western tales like The Luck of Roaring Camp and The Heathen Chinee. He moved to Newport in 1871 in an attempt to remake himself into a respectable author and poet on the East Coast. One notable, though criticized, poem emerged from his tenure here: A Newport Romance. In On the Carbon-14 Analyses of Mortar from the Newport Tower: Theoretical Considerations, Andre J. De Bethune claims that the process of dating mortar through carbon-14 testing has inherent flaws. Until these questions can be resolved, according to Bethune, a pre-Columbian origin for the Newport Tower cannot be excluded. Finally, From the Collections examines the use of family history newsletters in genealogical research
Editor’s Note
No full textIn this issue of Newport History, Gary Scharnhorst examines Bret Harte, an elusive literary figure who made a brief but lasting impact on Newport society and letters. Harte established his reputation as a writer in California with western tales like The Luck of Roaring Camp and The Heathen Chinee. He moved to Newport in 1871 in an attempt to remake himself into a respectable author and poet on the East Coast. One notable, though criticized, poem emerged from his tenure here: A Newport Romance. In On the Carbon-14 Analyses of Mortar from the Newport Tower: Theoretical Considerations, Andre J. De Bethune claims that the process of dating mortar through carbon-14 testing has inherent flaws. Until these questions can be resolved, according to Bethune, a pre-Columbian origin for the Newport Tower cannot be excluded. Finally, From the Collections examines the use of family history newsletters in genealogical research
CDC Buryu oilseed flax
No full textCDC Buryu, a late maturing oilseed flax (Linum usitatissimum L.), was registered in 2016 by the Crop Development Centre, University of Saskatchewan, Saskatoon, Saskatchewan. This cultivar had yield (106%) comparable to CDC Bethune and a maturity rating equal to Flanders in all soil zones of the Northern Prairies. The yield advantage over CDC Bethune was greater (>8%) in the Brown soil and Black soil zones of the Northern Prairies. It had medium oil content, oil quality, and seed size and good lodging resistance. It is immune to North American rust (race 371) caused by Melampsora lini and moderately resistant to wilt caused by Fusarium oxysporum f. sp. Lini and powdery mildew caused by Oidium lini.The presentation of the authors' names and (or) special characters in the title of the pdf file of the accepted manuscript may differ slightly from what is displayed on the item page. The information in the pdf file of the accepted manuscript reflects the original submission by the author
Response to ‘Can the quality of colonic surgery be improved by standardization of surgical technique with complete mesocolic excision?’
No full textRD&E staff can access the full-text of this article via OpenAthens. Click on the 'Additional Link' above to access the full-text and log in with NHS OpenAthens if prompted
Comment on: Randomized controlled trial of plain English and visual abstracts for disseminating surgical research via social media
No full textpre-print, post-print (12 month embargo)This article is freely available via Open Access. Click on the publisher URL to access it via the publisher's site
- …
