Effective elements of cognitive behaviour therapy for psychosis: results of a novel type of subgroup analysis based on principal stratification

Background. Meta-analyses show that cognitive behaviour therapy for psychosis (CBT-P) improves distressing positive symptoms. However, it is a complex intervention involving a range of techniques. No previous study has assessed the delivery of the different elements of treatment and their effect on outcome. Our aim was to assess the differential effect of type of treatment delivered on the effectiveness of CBT-P, using novel statistical methodology. Method. The Psychological Prevention of Relapse in Psychosis (PRP) trial was a multi-centre randomized controlled trial (RCT) that compared CBT-P with treatment as usual (TAU). Therapy was manualized, and detailed evaluations of therapy delivery and client engagement were made. Follow-up assessments were made at 12 and 24 months. In a planned analysis, we applied principal stratification (involving structural equation modelling with finite mixtures) to estimate intention-to-treat (ITT) effects for subgroups of participants, defined by qualitative and quantitative differences in receipt of therapy, while maintaining the constraints of randomization. Results. Consistent delivery of full therapy, including specific cognitive and behavioural techniques, was associated with clinically and statistically significant increases in months in remission, and decreases in psychotic and affective symptoms. Delivery of partial therapy involving engagement and assessment was not effective. Conclusions. Our analyses suggest that CBT-P is of significant benefit on multiple outcomes to patients able to engage in the full range of therapy procedures. The novel statistical methods illustrated in this report have general application to the evaluation of heterogeneity in the effects of treatment.

Improving aircraft maintenance, repair, and overhaul: A novel text mining approach

Aircraft Maintenance, Repair and Overhaul (MRO) feedback commonly includes an engineer’s complex text-based inspection report. Capturing and normalizing the content of these textual descriptions is vital to cost and quality benchmarking, and provides information to facilitate continuous improvement of MRO process and analytics. As data analysis and mining tools requires highly normalized data, raw textual data is inadequate. This paper offers a textual-mining solution to efficiently analyse bulk textual feedback data. Despite replacement of the same parts and/or sub-parts, the actual service cost for the same repair is often distinctly different from similar previously jobs. Regular expression algorithms were incorporated with an aircraft MRO glossary dictionary in order to help provide additional information concerning the reason for cost variation. Professional terms and conventions were included within the dictionary to avoid ambiguity and improve the outcome of the result. Testing results show that most descriptive inspection reports can be appropriately interpreted, allowing extraction of highly normalized data. This additional normalized data strongly supports data analysis and data mining, whilst also increasing the accuracy of future quotation costing. This solution has been effectively used by a large aircraft MRO agency with positive results.

Boots Book-lovers' Library and the novel: The impact of a circulating library market on twentieth-century fiction

In a Report for the Society of Bookmen in 1928, British publishers estimated that between a quarter to two thirds of all the books they published went to four circulating libraries: Boots, Smith’s, Mudie’s, and The Times bookclub. This essay examines the literary impact of one of the largest of these, Boots Book-lovers’ Library (1899-66), which by 1935 had around 400 libraries attached to their high-street pharmacies catering for the tastes of over one million subscribers a year. Compared to the wealth of studies examining the influence of the library market in the Victorian period, the significance of the subscription libraries as key distributors of fiction in the twentieth century is not well known. But private libraries expanded rapidly in the early twentieth century to cater for what Sidney Dark termed a ‘new reading public’, and records in publishers’ archives indicate that authors routinely adapted their unpublished manuscripts in order to meet the perceived demands of this library reader. This article examines the impact of the Boots Book-lovers’ Library market on authors’ practices of writing and revision, and on literary marketing and censorship. It focuses in particular on the author James Hanley (1897-1985), using unpublished correspondence in the Chatto & Windus archive at the University of Reading to demonstrate how the publisher’s sense of the tastes and expectations of the Boots library reader influenced the editorial process.

Maternally expressed gene1 is a novel maize endosperm transfer cell-specific gene with a maternal parent-of-origin pattern of expression

Growth of the maize (Zea mays) endosperm is tightly regulated by maternal zygotic and sporophytic genes, some of which are subject to a parent-of-origin effect. We report here a novel gene, maternally expressed gene1 (meg1), which shows a maternal parent-of-origin expression pattern during early stages of endosperm development but biallelic expression at later stages. Interestingly, a stable reporter fusion containing the meg1 promoter exhibits a similar pattern of expression. meg1 is exclusively expressed in the basal transfer region of the endosperm. Further, we show that the putatively processed MEG1 protein is glycosylated and subsequently localized to the labyrinthine ingrowths of the transfer cell walls. Hence, the discovery of a parent-of-origin gene expressed solely in the basal transfer region opens the door to epigenetic mechanisms operating in the endosperm to regulate certain aspects of nutrient trafficking from the maternal tissue into the developing seed.

Archive fever: the publishers' archive and the history of the novel

In recent years, archives have been increasingly important to literary scholarship. Drawing upon Derrida’s description of ‘archive fever’ as an always elusive search for origins, this chapter considers the theoretical and methodological issues of reading in the publishers’ archive, questioning what this brings to our histories of the novel. Through examples drawn from the archives of two British publishers – the Hogarth Press (1917-46) and Chatto & Windus (established 1873) – focussing on Virginia Woolf’s Flush (1933) and James Hanley’s The Furys (1935), the chapter assesses the implications of bringing book history to bear on literary history.

Validation of the NANA (Novel Assessment of Nutrition and Ageing) touch screen system for use at home by older adults

Prospective measurement of nutrition, cognition, and physical activity in later life would facilitate early detection of detrimental change and early intervention but is hard to achieve in community settings. Technology can simplify the task and facilitate daily data collection. The Novel Assessment of Nutrition and Ageing (NANA) toolkit was developed to provide a holistic picture of an individual's function including diet, cognition and activity levels. This study aimed to validate the NANA toolkit for data collection in the community. Forty participants aged 65 years and over trialled the NANA toolkit in their homes for three 7-day periods at four-week intervals. Data collected using the NANA toolkit were compared with standard measures of diet (four-day food diary), cognitive ability (processing speed) and physical activity (self-report). Bland–Altman analysis of dietary intake (energy, carbohydrates, protein fat) found a good relationship with the food diary and cognitive processing speed and physical activity (hours) were significantly correlated with their standard counterparts. The NANA toolkit enables daily reporting of data that would otherwise be collected sporadically while reducing demands on participants; older adults can complete the daily reporting at home without a researcher being present; and it enables prospective investigation of several domains at once

Discovery of novel GPVI receptor antagonists by structure-based repurposing.

Inappropriate platelet aggregation creates a cardiovascular risk that is largely managed with thienopyridines and aspirin. Although effective, these drugs carry risks of increased bleeding and drug 'resistance', underpinning a drive for new antiplatelet agents. To discover such drugs, one strategy is to identify a suitable druggable target and then find small molecules that modulate it. A good and unexploited target is the platelet collagen receptor, GPVI, which promotes thrombus formation. To identify inhibitors of GPVI that are safe and bioavailable, we docked a FDA-approved drug library into the GPVI collagen-binding site in silico. We now report that losartan and cinanserin inhibit GPVI-mediated platelet activation in a selective, competitive and dose-dependent manner. This mechanism of action likely underpins the cardioprotective effects of losartan that could not be ascribed to its antihypertensive effects. We have, therefore, identified small molecule inhibitors of GPVI-mediated platelet activation, and also demonstrated the utility of structure-based repurposing.

Synthesis and evaluation of a novel hydrophilic 6,6′-bis(1,2,4-triazin-3-yl)-2,2′-bipyridine ligand for separating actinide(III) from lanthanide(III)

We report the synthesis and evaluation of a novel hydrophilic 6,6′-bis(1,2,4-triazin-3-yl)-2,2′-bipyridine (BTBP) ligand containing carboxylate groups as a selective aqueous complexing agent for the minor actinides over lanthanides. The novel ligand is able to complex and separate Am(III) from Eu(III) in alkaline solutions selectively.