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Summary Background Antibiotic-associated diarrhoea (AAD) is a side-effect of antibiotic consumption and probiotics have been shown to reduce AAD. Methods A multicentre, double-blind, placebo-controlled, randomized trial was conducted to evaluate the role of Lactobacillus casei DN114001 (combined as a drink with two regular yoghurt bacterial strains) in reducing AAD and Clostridioides difficile infection in patients aged over 55 years. The primary outcome was the incidence of AAD during 2 weeks of follow-up. Results A total of 1127 patients (mean age ± standard deviation: 73.6 ± 10.5) were randomized to the active group (N = 549) or placebo group (N = 577). Both groups were followed up as per protocol. The proportion of patients experiencing AAD during follow-up was 19.3% (106/549) in the probiotic group vs 17.9% (103/577) in the placebo group (unadjusted odds ratio 1.10, 95% confidence interval 0.82–1.49, P = 0.53). Conclusions No significant evidence was found of a beneficial effect of the specific probiotic formulation in preventing AAD in this elderly population drawn from a number of different UK hospitals. However, in the UK and in many other healthcare systems there have, in recent years, been many changes in antibiotic stewardship policies, an overall decrease in incidence in C. difficile infection, as well as an increased awareness of infection prevention, and modifications in nursing practice. In light of these factors, it is impossible to conclude definitively from the current trial that the study-specific probiotic formulation has no role in preventing AAD, and it is our view that further trials may be indicated, controlling for these variables.

Supernatants from apple cutin-induced cultures of the light leaf spot pathogen Pyrenopeziza brassicae were shown to contain a single esterase with a pI of approx. 4.4 and a MW of 21 kDa. Analysis of the hydrolysis products derived from enzymatic cleavage of 3 H labelled cutin by TLC demonstrated that these supernatants had cutinolytic activity. Treatment with the serine esterase inhibitors ebelactones A and B resulted in 50% inhibition of the P. brassicae esterase activity at concentrations of 4 and 0.4 μ g ml −1 , respectively. It is therefore concluded that following induction in vitro with apple cutin, P. brassicae produces a single extracellular esterase with cutinolytic activity. A putative cutinase gene was cloned by heterologous Southern hybridization of P. brassicae genomic DNA using the Botrytis cinerea cutinase gene as a probe. The ORF (706 bp) is predicted to encode a polypeptide of 203 amino acids with a molecular weight of 20.379 kDa and a pI of 4.38. This polypeptide shows high levels of homology with the cutinases of B. cinerea and of other fungi, and contains the conserved histidine, aspartic acid and serine catalytic triad. Expression of the putative cutinase gene was shown to correlate with induction of esterase activity in vitro . SEM analysis of Brassica napus leaves infected with P. brassicae confirmed that direct penetration of the host surface occurs with no evidence of appressorial formation. The ebelactones A (100 μ g ml −1 ) and B (10 μ g ml −1 ) had no effect on germination of P. brassicae conidia in vitro ; however, a marked decrease in pathogenicity of P. brassicae was observed on B. napus plants treated with 100 μ g ml −1 ebelactone A or 10 μ g ml −1 ebelactone B. In these plants, failed penetration was observed and the number of acervular conidiomata was greatly reduced. These results suggest a functional role for fungal cutinolytic activity in pathogenicity of P. brassicae on B. napus.

Background Sjogren’s syndrome (SS) is a multi-system autoimmune disorder known to affect the CNS. Studies have reported that 7%>100% patients experience neuropsychological manifestations including cognitive impairment, depression and anxiety (1,2). Depression has been shown to predict physician attendance and work status in SS (3). The relationship between cognitive and behavioural dysfunction is yet to be established in this disease group. Objectives To determine the relationship between self- reported cognitive symptoms and measures of depression and anxiety in primary Sjogren’s syndrome Methods As part of an ongoing cognitive and quantitative neuroimaging study in 30 Sjogren’s syndrome patients and 20 matched healthy controls, data on subjective cognitive dysfunction and measures of anxiety and depression have been collected in 27 primary SS patients and 14 age-, sex- and education-matched controls. Presence and severity of anxiety and depression was assessed using the self-administered Hospital Anxiety and Depression Scale (HADS). Self-reported cognitive symptoms, including failures in memory, perception and motor lapses were assessed using the Cognitive Failures Questionnaire (CFQ). Correlation between these variables was measured using two-tailed Pearson coefficient calculation. Results Mean total HADS values for the SS and control group were 16.54 (95% confidence interval (CI) 13.67 to 19.41)and 8.29 (95% confidence interval 5.09 to 11.49) respectively. On the subscales for anxiety and depression, the mean depression score for patients was 6.78 (95% CI 5.09-8.52) and controls was 2.50 (95% CI 1.13-3.87). The mean anxiety score was 9.74 (95% CI 8.21-11.27) and 5.79 (95% CI 3.58-8) respectively. 44% (12/27) of patients and 7% (1/14) of controls had abnormal anxiety scores. 14% (4/27) of patients had abnormal depression scores whereas only one control had a borderline score. Bivariate correlation analysis revealed significant correlation between total cognitive failures score and total HAD, anxiety and depression subscale scores in the patient group (r=0.70, 0.62, 0.56 respectively, p=0.01) but not in the control group. Conclusions Primary SS patients report a significantly increased level of subjective cognitive failure symptoms as assessed by the CFQ as well as significantly increased anxiety and depression measures. In keeping with previous study of subjective cognitive evaluation in affective disorders, the total CFQ score correlated with anxiety and depression scores in our patient group. While the increased reporting of cognitive failures in our patient group may relate to significantly increased affective disturbances, ongoing studies of objective cognitive test scores and biological correlates are necessary to explore the exact nature of this relationship. References Soliotis, F.C., C.P. Mavragani, and H.M. Moutsopoulos, Central nervous system involvement in Sjogren’s syndrome. Ann Rheum Dis, 2004. 63(6): p. 616-20. Valtysdottir, S.T., et al., Psychological well-being in patients with primary Sjogren’s syndrome. Clin Exp Rheumatol, 2000. 18(5): p. 597-600. Westhoff, G., T. Dorner, and A. Zink, Fatigue and depression predict physician visits and work disability in women with primary Sjogren’s syndrome: results from a cohort study. Rheumatology (Oxford), 2011. Disclosure of Interest K. Davies: None Declared, R. Trimble Grant/Research support from: Funded by the Headley Trust, Sainsbury’s Family Charitable Trusts, R. Haynes: None Declared, N. Dowell: None Declared, J. Rusted: None Declared, D. Chan: None Declared

This article reports the first phase of an investigation into the quantification of software reliability. Following an extensive literature search the current approaches are critically reviewed. The difficulties in interpretation attached to quantifications in probabilistic terms are highlighted. The notion of software credibility is proposed as a means of condensing quality assurance techniques into a measure of reliability suitable for use in general reliability assessments.

Summary The Bala rocks which lie between Rhayader and Abergwesyn form an isolated inlier termed the Rhiwnant Inlier. The rocks of this country, which are chiefly shales and mudstones, include also large masses of conglomerate, especially within the Lower Birkhill. The unconformity at the base of the Upper Birkhill and the overlap at the base of the Gala proved to occur in the Rhayader area are not visible in the country to the west. With the kind permission of Dr. Herbert Lapworth I have included the area between the Elan Valley and Rhayader mapped by him.