Colonic stricture in a boy with cystic fibrosis.

Many problems may arise within the gastrointestinal tract of patients with cystic fibrosis. We report a new cause of subacute intestinal obstruction due to a fibrotic stricture of the ascending colon in a child with cystic fibrosis. Treatment was with a right hemicolectomy. There has been no recurrence after nine months follow-up. Recent similar cases suggest that this new pathology is linked to the use of enteric-coated high-strength pancreatin microspheres.This article is freely available via Open Access. Click on the ‘Additional Link’ above to access the full-text from the publisher’s site

High-strength pancreatic enzyme supplements and large-bowel stricture in cystic fibrosis.

This article is freely available via Open Access. Click on the ‘Additional Link’ above to access the full-text from the publisher’s site

The relationship between cleavage, DNA replication, and gene expression in the mouse 2-cell embryo.

The 2-cell stage of mouse embryogenesis is characterized by two phases of alpha-amanitin-sensitive polypeptide synthetic activity, which appear to mark the first major expression of the embryonic genome, as assessed by examination of in vitro translates of mRNA. Using populations of embryos synchronized to the first cleavage division, we have established that DNA replication takes place over the period 1 to 5.5 h after the first cleavage division; the two bursts of putative transcription take place before and immediately after DNA replication, and the translation products are detectable in each case within 3-4 h. In addition, we have shown that suppression of cytokinesis and the second round of DNA replication does not affect synthesis of the alpha-amanitin-sensitive polypeptides, and that neither DNA replication nor the loss of maternal mRNA that take place during the 2-cell stage are dependent upon synthesis of the alpha-amanitin-sensitive polypeptides.This article is freely available via Open Access. Click on the ‘Additional Link’ above to access the full-text from the publisher’s site

Cochlear implant referral patterns in the UK suggest a postcode lottery with inequitable access for older adults; results of a pilot audit in five Audiology sites

OBJECTIVE: To use a standardised reporting tool to identify potential eligible candidates for cochlear implant (CI) referral and quantify the proportion of adults who had a CI referral discussion after presenting with an audiogram within United Kingdom (UK) audiometric criteria. DESIGN: Retrospective multicentre 6-month audit of Audiology clinic databases. STUDY SAMPLE: A total of 810 adults from five geographically diverse UK Audiology sites. RESULTS: Data were collected in late 2019 after UK CI audiometric candidacy criteria changed; one site collected only 3 months of data. The proportion of potential eligible adults (based only on audiometry) considered for CI referral was 64% (521 out of 810) and varied by site (from 50% to 83%). About 24% of patients (123 out of 521) declined CI referral; this also varied across sites (12-45%). The median age of patients where CI referral was not considered was 80 years - significantly higher than the group where CI referral was considered (73 years). CONCLUSIONS: CI referral is dependent on where adults live, and how old they are. Older adults are significantly less likely to be considered for CI referral by Audiologists. Audiology clinics need more support to empower staff to talk to patients about CI referral.Published version, accepted version (12 month embargo)15 month embargo from date of publicatio

World Health Organization (WHO) International Classification of Functioning, Disability and Health (ICF) Core Set Development for Interstitial Lung Disease

Background: The World Health Organization (WHO) introduced the International Classification of Functioning, Disability, and Health (ICF) as a scientific method of disability data collection comprised of >1,200 categories describing the spectrum of impairment types (functional, symptoms-based and anatomical) under the bio-psycho-social model with consideration of environmental and personal factors (pf). ICF Core Sets and ICF Checklists are streamlined disease-specific resources for clinical use, service provision, and for use in health economics and health policy. ICF can disclose strengths and weaknesses across multiple patient-reported outcome measures (PROMs) and help consolidate best-fitting question-items from multiple PROMs. Interstitial lung diseases (ILDs), are generally progressive, with restrictive physiology sometimes occurring in the context of multi-organ autoimmunity/inflammatory conditions such as connective tissue diseases (CTDs). In spite of significant associated morbidity and potential disability, ILD has yet to be linked to the ICF. Methods: Each instrument and their question-items within the consensus-recommended core sets for clinical trials in ILD were deconstructed to single concept units, and then linked per updated ICF linkage rules. Inter-linker agreement was established. Three additional subsequently validated measures were also included. Results: One-hundred-eleven ICF categories were identified for ten PROMs and three traditional objective measures that were amenable to ICF linkage. The proportion of agreement ranged from 0.79 (95% CI: 0.62, 0.91) to 0.93 (0.76, 0.99) with the overall proportion of inter-linker agreement being very high 0.86 (0.82, 0.89) for the initial instruments, with 94-100% for the three additional PROMs. Thirty-four new 'Personal Factors' emerged to capture disease-specific qualities not elsewhere described in ICF, e.g. 'pf_embarrassed by cough' or 'pf_panic/afraid when can't get a breath'. Conclusion: This first known effort in ICF linkage of ILD has provided important revelations on the current utility of the ICF in lung disease. Results have indicated areas for meaningful assessment of ICF descriptors for lung impairment. The mapping across PROMs provides insight into possibilities of developing more streamline and precise instrumentation. Finally, familiarity with the ICF in ILD may enable clinicians to experience a smoother transition with the imminent harmonization of ICD and ICF, ICD-11.Published version, accepted versionThe article is available via Open Access. Click on the 'Additional link' above to access the full-text

FOSL2 truncating variants in the last exon cause a neurodevelopmental disorder with scalp and enamel defects

PURPOSE: We aimed to investigate the molecular basis of a novel recognizable neurodevelopmental syndrome with scalp and enamel anomalies caused by truncating variants in the last exon of the gene FOSL2, encoding a subunit of the AP-1 complex. METHODS: Exome sequencing was used to identify genetic variants in all cases, recruited through Matchmaker exchange. Gene expression in blood was analyzed using reverse transcription polymerase chain reaction. In vitro coimmunoprecipitation and proteasome inhibition assays in transfected HEK293 cells were performed to explore protein and AP-1 complex stability. RESULTS: We identified 11 individuals from 10 families with mostly de novo truncating FOSL2 variants sharing a strikingly similar phenotype characterized by prenatal growth retardation, localized cutis scalp aplasia with or without skull defects, neurodevelopmental delay with autism spectrum disorder, enamel hypoplasia, and congenital cataracts. Mutant FOSL2 messenger RNAs escaped nonsense-mediated messenger RNA decay. Truncated FOSL2 interacts with c-JUN, thus mutated AP-1 complexes could be formed. CONCLUSION: Truncating variants in the last exon of FOSL2 associate a distinct clinical phenotype by altering the regulatory degradation of the AP-1 complex. These findings reveal a new role for FOSL2 in human pathology.Accepted version (6 month embargo), submitted versionRD&E staff can access the full-text of this article by clicking on the 'Additional Link' above and logging in with NHS OpenAthens if prompted

UK trainees' perceptions of leadership and leadership development

PURPOSE: This paper reports on trainees' perceptions of leadership and leadership development, to inform the support that may be provided to them. It draws on a formative evaluation of the new role of clinical leadership mentor (CLM), introduced by Health Education England South-West in 2018. CLMs are responsible for 'overseeing the process and progress of leadership development among the trainees within their Trust/Local Education Provider'. METHODS: The evaluation was a formative evaluation, based on interviews with CLMs, trainees and trainers and a survey of trainees and trainers. Recruitment was through 8 of the 19 CLMs in the South West. A report for each participating CLM was available to support the development of their individual role. In exploring trainees' perceptions of leadership and leadership development, this paper draws on data from trainees: 112 survey returns which included over 7000 words of free text data and 13 interviews. FINDINGS: Our findings suggest a more nuanced understanding of leadership in medical trainees than was previously reported in the literature, and a wider acceptance of their leadership role. We highlight the problem of considering postgraduate doctors as a homogeneous group, particularly with reference to specialty. We also highlight that the organisational context for leadership development can be supportive or non-supportive. Leadership learning through genuine leadership experience with appropriate support from trainers and the wider Trust offers opportunities for both trainees and Trusts. PRACTICAL IMPLICATIONS: Trainees are accepting of their roles as leaders. The value of leadership learning through genuine leadership experience was highlighted. Improving the environment for leadership development offers Trusts and trainees opportunities for genuine service improvement.Published version, accepted versionFull Text unavailable for 1 year from time of publication