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Objectives Informing research participants of the results of studies in which they took part is viewed as an ethical imperative. However, there is little guidance in the literature about how to do this. The Fluoxetine Or Control Under Supervision trial randomised 3127 patients with a recent acute stroke to 6 months of fluoxetine or placebo and was published in the Lancet on 5 December 2018. The trial team decided to inform the participants of the results at exactly the same time as the Lancet publication, and also whether they had been allocated fluoxetine or placebo. In this report, we describe how we informed participants of the results.Design In the 6-month and 12-month follow-up questionnaires, we invited participants to provide an email address if they wished to be informed of the results of the trial. We re-opened our trial telephone helpline between 5 December 2018 and 31 March 2019.Setting UK stroke services.Participants 3127 participants were randomised. 2847 returned 6-month follow-up forms and 2703 returned 12-month follow-up forms; the remaining participants had died (380), withdrawn consent or did not respond.Results Of those returning follow-up questionnaires, a total of 1845 email addresses were provided and a further 50 people requested results to be sent by post. Results were sent to all email and postal addresses provided; 309 emails were returned unrecognised. Seventeen people replied, of whom three called the helpline and the rest responded by email.Conclusion It is feasible to disseminate results of large trials to research participants, though only around 60% of those randomised wanted to receive the results. The system we developed was efficient and required very little resource, and could be replicated by trialists in the future.Trial registration number ISRCTN83290762; Post-results.

Campylobacter jejuni is the leading cause of bacterial food borne illness. While helical cell shape is considered important for C. jejuni pathogenesis, this bacterium is capable of adopting other morphologies. To better understand how helical-shaped C. jejuni maintain their shape and thus any associated colonisation, pathogenicity or other advantage, it is first important to identify the genes and proteins involved. So far, two peptidoglycan modifying enzymes Pgp1 and Pgp2 have been shown to be required for C. jejuni helical cell shape. We performed a visual screen of ∼2000 transposon mutants of C. jejuni for cell shape mutants. Whole genome sequence data of the mutants with altered cell shape, directed mutants, wild type stocks and isolated helical and rod-shaped 'wild type' C. jejuni, identified a number of different mutations in pgp1 and pgp2, which result in a change in helical to rod bacterial cell shape. We also identified an isolate with a loss of curvature. In this study, we have identified the genomic change in this isolate, and found that targeted deletion of the gene with the change resulted in bacteria with loss of curvature. Helical cell shape was restored by supplying the gene in trans. We examined the effect of loss of the gene on bacterial motility, adhesion and invasion of tissue culture cells and chicken colonisation, as well as the effect on the muropeptide profile of the peptidoglycan sacculus. Our work identifies another factor involved in helical cell shape., (Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Campylobacter jejuni, the most common cause of bacterial diarrhoeal disease, is normally helical. However, it can also adopt straight rod, elongated helical and coccoid forms. Studying how helical morphology is generated, and how it switches between its different forms, is an important objective for understanding this pathogen. Here, we aimed to determine the genetic factors involved in generating the helical shape of Campylobacter. A C. jejuni transposon (Tn) mutant library was screened for non-helical mutants with inconsistent results. Whole genome sequence variation and morphological trends within this Tn library, and in various C. jejuni wild type strains, were compared and correlated to detect genomic elements associated with helical and rod morphologies. All rod-shaped C. jejuni Tn mutants and all rod-shaped laboratory, clinical and environmental C. jejuni and Campylobacter coli contained genetic changes within the pgp1 or pgp2 genes, which encode peptidoglycan modifying enzymes. We therefore confirm the importance of Pgp1 and Pgp2 in the maintenance of helical shape and extended this to a wide range of C. jejuni and C. coli isolates. Genome sequence analysis revealed variation in the sequence and length of homopolymeric tracts found within these genes, providing a potential mechanism of phase variation of cell shape.

Objective: To describe and compare patterns of physical activity among stroke survivors during their hospital stay and community living with early supported discharge., Design: Observational cohort study of physical activity before and after early supported discharge., Setting: UK National Health Service stroke units and participants' homes., Participants: Forty-one stroke survivors with a mean age of 69 (standard deviation 11) years, and a median Modified Rivermead Mobility Index of 33.5 [interquartile range (IQR) 25.8 to 35.3]., Main Outcome Measures: The primary outcome measures were time spent in sitting/standing/walking and number of steps taken, as recorded by a physical activity monitor., Results: There were statistical differences (P<0.001) for all categories of physical activity. After early supported discharge to the community, participants took more than twice the number of steps {median 474 (IQR 189 to 773) vs. 1193 (IQR 512 to 2856), median difference 636 [95% confidence interval (CI) 262 to 931]} and spent more than double the time in standing [median 51 (IQR 22 to 128) minutes vs. 100 (IQR 51 to 178) minutes, median difference 28 (95% CI 11 to 68)] compared with their hospital stay., Conclusion: Community living with early supported discharge promoted higher levels of physical activity in medically stable stroke survivors. The near-doubling of activity may serve as a guideline for what is achievable during stroke rehabilitation., Clinical Trial Registration: Number UKCRN 15472., (Copyright © 2015 Chartered Society of Physiotherapy. Published by Elsevier Ltd. All rights reserved.)

Purpose: Previously, we mapped the disease locus in the beagle model of autosomal recessive primary open angle glaucoma (POAG) to a 4-Mb interval on chromosome 20, and identified a Gly661Arg variant in ADAMTS10 as the candidate disease-causing variant. The purpose of this study was to test the hypothesis that the Gly661Arg variant of ADAMTS10 causes glaucoma by genotyping dogs of various breeds affected and unaffected by primary glaucoma., Methods: Dogs of various breeds, affected or unaffected with primary glaucoma, were genotyped for the Gly661Arg variant of ADAMTS10, as well as 7 other nonsynonymous single nucleotide polymorphisms (SNPs) in other genes in the beagle POAG locus that segregate with disease. Alternate allele frequencies were calculated with 95% confidence intervals and comparisons made to expected allele frequency relative to disease prevalence or between cases and controls., Results: For the nonsynonymous SNPs other than the ADAMTS10 variant, control dogs were identified that were homozygous for the alternative alleles, ruling out those variants as causative. None of the nonsynonymous SNPs were found associated with primary glaucoma in American cocker spaniels. The Gly661Arg variant of ADAMTS10 was the only variant with minor allele frequency consistent with the prevalence of primary glaucoma in the general beagle population. The only dog found homozygous for the Gly661Arg variant of ADAMTS10 was an affected beagle, unrelated to the POAG colony., Conclusions: These findings support the Gly661Arg mutation of ADAMTS10 as the likely cause of POAG in beagles.

Objective: To evaluate the incidence and risk factors associated with development of postoperative glaucoma in the Labrador Retriever following routine phacoemulsification., Methods: Medical records from Labradors and a randomly selected population of non-Labradors were retrospectively evaluated. Signalment, diabetic status, cataract stage, gonioscopic findings, presence of preoperative lens-induced uveitis, development of postoperative hypertension (POH), postoperative glaucoma and postoperative visual status were recorded for each patient. Survival curves were developed using the Cox proportional hazards model., Results: Forty-two Labradors (66 eyes) and 199 non-Labradors (314 eyes) were included. The incidence of POH was significantly higher in Labradors (33%) than non-Labradors (18%). Labradors were at significantly increased risk of postoperative glaucoma and blindness compared to non-Labradors. Estimated probabilities of postoperative glaucoma in Labradors were 23%, 25%, 30% and 35% at weeks 4, 26, 52 and 104, respectively, compared with 5%, 6%, 7% and 9% at weeks 4, 26, 52 and 104, respectively, in non-Labradors. Estimated probabilities of postoperative blindness in Labradors were 5%, 9%, 15% and 27% at weeks 4, 26, 52 and 104, respectively, compared with 2%, 3%, 5% and 10% at weeks 4, 26, 52 and 104, respectively, in non-Labradors. Risk factors for the development of glaucoma in Labradors included increasing age and development of POH. No statistically significant risk factors for the development of glaucoma were identified in non-Labradors., Conclusions: Labradors are at increased risk of glaucoma and blindness following phacoemulsification compared with non-Labradors. POH and increasing age represent risk factors for the development of postoperative glaucoma in Labradors., (© 2011 American College of Veterinary Ophthalmologists.)

Benthic species of algae and cyanobacteria (i.e., those that grow on surfaces), may provide potential advantages over planktonic species for some commercial-scale biotechnological applications. A multitude of different designs of photobioreactor (PBR) are available for growing planktonic species but to date there has been little research on PBR for benthic algae or cyanobacteria. One notable advantage of some benthic cyanobacterial species is that during their growth cycle they become positively buoyant, detach from the growth surface and form floating mats. This 'self-harvesting' capability could be advantageous in commercial PBRs as it would greatly reduce dewatering costs. In this study we compared the growth rates and efficiency of 'self-harvesting' among three species of benthic cyanobacteria; Phormidium autumnale; Phormidium murrayi and Planktothrix sp.. Phormidium autumnale produced the greatest biomass and formed cohesive mats once detached. Using this strain and an optimised MLA media, a variety of geometries of benthic PBRs (bPBRs) were trialed. The geometry and composition of growth surface had a marked effect on cyanobacterial growth. The highest biomass was achieved in a bPBR comprising of a vertical polyethylene bag with loops of silicone tubing to provide additional growth surfaces. The productivity achieved in this bPBR was a similar order of magnitude as planktonic species, with the additional advantage that towards the end of the exponential phase the bulk of the biomass detached forming a dense mat at the surface of the medium.

Purpose: Keratoconjunctivitis sicca (KCS) is characterized by inflammation and decreased production of tears containing increased levels of cytokines. The release occurs in the setting of conjunctival and lacrimal gland inflammation, potentially mediated by the interaction between lymphocyte function-associated antigen (LFA)-1, a cell surface protein found on lymphocytes, and its cognate ligand intercellular adhesion molecule (ICAM)-1. SAR 1118 is a novel LFA-1 antagonist and may be an effective therapeutic agent for the treatment of KCS. The following studies were performed to assess the in vitro activity of SAR 1118 and to evaluate the clinical efficacy of topical SAR 1118 for the treatment of idiopathic canine KCS., Method: Pharmacodynamics were assessed by measuring the ability of SAR 1118 to inhibit Jurkat T-cell binding with recombinant human ICAM-1 and to inhibit cytokine release from human peripheral blood mononuclear cells (PBMCs) stimulated by staphylococcal enterotoxin B. For the assessment of clinical efficacy, 10 dogs diagnosed with idiopathic KCS were treated with SAR 1118 1% topical ophthalmic solution three times daily for 12 weeks. Schirmer's tear test (STT) was used to measure tear production., Results: SAR 1118 demonstrated concentration-dependent inhibition of Jurkat T-cell attachment, inhibition of lymphocyte activation, and release of inflammatory cytokines, particularly the Th1, Th2, and Th17 T-cell cytokines IFN-γ, IL-2, and IL-17F, respectively. Mean STT values increased from 3.4 mm during week 1 to 5.8 mm at week 12 (P < 0.025). No SAR 1118-related adverse events were observed., Conclusions: SAR 1118 appears to be an effective anti-inflammatory treatment for KCS. Additional studies are warranted to establish the efficacy of SAR 1118 for the treatment of KCS in humans.

A clinical syndrome comprising the formation of thin-walled cysts within the posterior chamber, proteinaceous exudation, and pigment dispersion, which typically culminates in glaucoma is recognized in the Golden Retriever breed. Although not uncommon, this syndrome has been relatively infrequently documented in the literature, particularly from a histological standpoint. Fifteen globes from Golden Retrievers presented to Eye Care for Animals between 2003 and 2009 were evaluated by routine hematoxylin and eosin (H&E) as well as immunohistochemical staining. Alcian blue, periodic acid Schiff (PAS), Masson's trichrome, Cytokeratin, Vimentin, Neuron Specific Enolase (NSE), S-100, and smooth muscle actin staining were performed. The thin-walled cysts stained positive with Vimentin, NSE, and S-100 in 15/15 globes, consistent with a ciliary body epithelial cellular origin. No globes demonstrated goniodysgenesis. All 15 globes exhibited free pigment within the trabecular meshwork. Little to no inflammatory infiltrate was noted in 15/15 eyes. These findings suggest that the term 'uveitis' may be an inappropriate description of this syndrome.

A 13-year-old Golden Retriever was referred for evaluation of generalized corneal edema, dyscoria, and suspected glaucoma affecting the right eye. The dog exhibited no signs of systemic illness, but had a history of a melanoma of the nail bed of the first digit of the right hind limb, excised 1 year previously. Ophthalmologic examination revealed diffuse corneal edema, mild anterior uveitis, glaucoma and a mass within the right iris. Enucleation was performed and histopathologic evaluation of the globe revealed the iris to be infiltrated with an anaplastic melanoma, suspected to represent a metastasis of the original nail bed tumor.

The neuromuscular disease myotonic dystrophy (DM) is caused by microsatellite repeat expansions at two different genomic loci. Mutant DM transcripts are retained in the nucleus together with the muscleblind (Mbnl) proteins, and these abnormal RNAs somehow interfere with pre-mRNA splicing regulation. Here, we show that disruption of the mouse Mbnl1 gene leads to muscle, eye, and RNA splicing abnormalities that are characteristic of DM disease. Our results support the hypothesis that manifestations of DM can result from sequestration of specific RNA binding proteins by a repetitive element expansion in a mutant RNA.

A one-year-old male domestic short haired cat was referred because of an area of keratitis that had developed adjacent to a particularly large unilateral eyelid coloboma. The defect was repaired using an undescribed three-stage surgical technique, which is essentially a combination of existing techniques and consists of using the lower lid to re-construct the upper lid and replacing the resultant lower lid defect with a full thickness graft from the upper lip. This technique is described and the results illustrated by photographs. A good functional and cosmetic result was achieved.