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.

A novel method for assessing risks to pollinators from plant protection products using honeybees as a model species

Pollination is one of the most important ecosystem services in agroecosystems and supports food production. Pollinators are potentially at risk being exposed to pesticides and the main route of exposure is direct contact, in some cases ingestion, of contaminated materials such as pollen, nectar, flowers and foliage. To date there are no suitable methods for predicting pesticide exposure for pollinators, therefore official procedures to assess pesticide risk are based on a Hazard Quotient. Here we develop a procedure to assess exposure and risk for pollinators based on the foraging behaviour of honeybees (Apis mellifera) and using this species as indicator representative of pollinating insects. The method was applied in 13 European field sites with different climatic, landscape and land use characteristics. The level of risk during the crop growing season was evaluated as a function of the active ingredients used and application regime. Risk levels were primarily determined by the agronomic practices employed (i.e. crop type, pest control method, pesticide use), and there was a clear temporal partitioning of risks through time. Generally the risk was higher in sites cultivated with permanent crops, such as vineyard and olive, than in annual crops, such as cereals and oil seed rape. The greatest level of risk is generally found at the beginning of the growing season for annual crops and later in June–July for permanent crops.

Novel margin management to enhance Auchenorrhyncha biodiversity in intensive grasslands

Agricultural intensification, including changes in cutting, grazing and fertilizer regimes, has led to declines in UK and NW European grassland biodiversity. We aimed to develop field margin management practices that would support invertebrate diversity and abundance on intensively managed grassland farms, focusing on planthoppers and leafhoppers (Auchenorrhyncha). Replicated across four farms in south-west England, we manipulated conventional management practices (inorganic fertilizer, cutting frequency and height, and aftermath grazing) to create seven treatments along a gradient of decreasing management intensity and increasing sward architectural complexity. Auchenorrhyncha were sampled annually between 2003 and 2005. Auchenorrhyncha abundance and species richness was highest in the most extensively managed treatments. Abundance was lowest with frequent cutting, while species richness was lowest where cattle grazing occurred. Unexpectedly, application of inorganic fertilizer had no effect on Auchenorrhyncha abundance or species richness. Management options that enhance invertebrate diversity, while allowing the remainder of the field to be managed conventionally, represent a potentially important conservation tool for many lowland improved grasslands. Extensification of conventional management in field margin areas of such grasslands are likely to benefit this numerically dominant component of grassland invertebrate fauna. These management practices have the potential to be incorporated into existing UK and European agri-environment schemes.

In vitro fermentation and prebiotic potential of novel low molecular weight polysaccharides derived from agar and alginate seaweeds

Fermentation properties and prebiotic potential of novel low molecular weight polysaccharides (LMWPs) derived from agar and alginate bearing seaweeds was investigated. Ten LMWPs were supplemented to pH, temperature controlled anaerobic batch cultures inoculated with human feces from three donors, in triplicate. Microbiota changes were monitored using Fluorescent in-situ hybridization and short chain fatty acids, the fermentation end products were analysed using gas chromatography. Of the ten LMWPs tested, Gelidium seaweed CC2253 of molecular weight 64.64 KDa showed a significant increase in bifidobacterial populations from log(10) 8.06 at 0 h to log(10) 8.55 at 24 h (p = 0.018). For total bacterial populations, alginate powder CC2238 produced a significant increase from log(10) 9.01 at 0 h to log(10) 9.58 at 24 h (p = 0.032). No changes were observed in the other bacterial groups tested viz. Bacteroides, Lactobacilli/Enterococci, Eubacterium rectale/Clostridium coccoides and Clostridium histolyticum. The polysaccharides also showed significant increases in total SCFA production, particularly acetic and propionic acids, indicating that they were readily fermented. In conclusion, some LMWPs derived from agar and alginate bearing seaweeds were fermented by gut bacteria and exhibited potential to be used a novel source of prebiotics.

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.

A novel, non-canonical mechanism of regulation of MST3 (mammalian Sterile20-related kinase 3)

The canonical pathway of regulation of the germinal centre kinase (GCK) III subgroup member, mammalian Sterile20-related kinase 3 (MST3), involves a caspase-mediated cleavage between N-terminal catalytic and C-terminal regulatory domains with possible concurrent autophosphorylation of the activation loop MST3(Thr178-), induction of Ser-/Thr-protein kinase activity and nuclear localisation. We identified an alternative ‘non-canonical’ pathway of MST3 activation (regulated primarily through dephosphorylation) which may also be applicable to other GCKIII (and GCKVI) subgroup members. In the basal state, inactive MST3 co-immunoprecipitated with the Golgi protein, GOLGA2/gm130. Activation of MST3 by calyculin A (a protein Ser-/Thr- phosphatase 1/2A inhibitor) stimulated (auto)phosphorylation of MST3(Thr178-) in the catalytic domain with essentially simultaneous cis-autophosphorylation of MST3(Thr328-) in the regulatory domain, an event also requiring the MST3(341-376) sequence which acts as a putative docking domain. MST3(Thr178-) phosphorylation increased MST3 kinase activity but this activity was independent of MST3(Thr328-) phosphorylation. Interestingly, MST3(Thr328-) lies immediately C-terminal to a STRAD pseudokinase-like site recently identified as being involved in binding of GCKIII/GCKVI members to MO25 scaffolding proteins. MST3(Thr178- /Thr328-) phosphorylation was concurrent with dissociation of MST3 from GOLGA2/gm130 and association of MST3 with MO25, and MST3(Thr328-) phosphorylation was necessary for formation of the activated MST3-MO25 holocomplex.

Blood pressure lowering effects of beetroot juice and novel beetroot enriched bread products in normotensive male subjects

A number of vegetables have a high nitrate content which after ingestion can be reduced to 36 nitrite by oral bacteria, and further to vasoprotective nitric oxide endogenously. Two separate 37 randomly controlled, single blind, cross-over, postprandial studies were performed in 38 normotensive volunteers. Ambulatory blood pressure was measured over a 24 h period 39 following consumption of either four doses of beetroot juice (BJ) 0 g, 100 g, 250 g and 500 g 40 (n = 18) or three bread products, control bread (0 g beetroot), red beetroot and white beetroot 41 enriched breads (n =14). Total urinary nitrate/nitrite (NOx) was measured at baseline, 2, 4 42 and 24 h post ingestion. BJ consumption significantly, and in a near dose dependent manner, 43 lowered systolic (P <0.01) and diastolic BP (P <0.001) over a period of 24 h, compared to 44 water control. Furthermore, bread products enriched with 100 g red or white beetroot lowered 45 systolic and diastolic BP over a period of 24 h (red beetroot enriched bread, P <0.05), with no 46 statistical differences between varieties. Total urinary NOx significantly increased following 47 consumption of 100 g (P<0.01), 250 g (P <0.001) and 500 g BJ (P <0.001) and after red 48 beetroot bread (P <0.05), but did not reach significance for white beetroot bread compared to 49 the no beetroot condition. These studies demonstrated significant hypotensive effects of a low 50 dose (100 g) of beetroot which was unaffected by processing, or the presence of betacyanins. 51 This data strengthens the evidence for cardioprotective BP lowering effects of dietary nitrate-52 rich vegetables.

A novel human-machine interface using subdermal magnetic implants

This paper explores a novel tactile human-machine interface based on the controlled stimulation of mechanoreceptors by a subdermal magnetic implant manipulated through an external electromagnet. The selection of a suitable implant magnet and implant site is discussed and an external interface for manipulating the implant is described. The paper also reports on the basic properties of such an interface, including magnetic field strength sensitivity and frequency sensitivity obtained through experimentation on two participants. Finally, the paper presents two practical application scenarios for the interface.

A novel bogie design made of glass fibre reinforced plastic

This paper presents a completely new design of a bogie-frame made of glass fibre reinforced composites and its performance under various loading conditions predicted by finite element analysis. The bogie consists of two frames, with one placed on top of the other, and two axle ties connecting the axles. Each frame consists of two side arms and a transom between. The top frame is thinner and more compliant and has a higher curvature compared with the bottom frame. Variable vertical stiffness can be achieved before and after the contact between the two frames at the central section of the bogie to cope with different load levels. Finite element analysis played a very important role in the design of this structure. Stiffness and stress levels of the full scale bogie presented in this paper under various loading conditions have been predicted by using Marc provided by MSC Software. In order to verify the finite element analysis (FEA) models, a fifth scale prototype of the bogie has been made and tested under quasi-static loading conditions. Results of testing on the fifth scale bogie have been used to fine tune details like contact and friction in the fifth scale FEA models. These conditions were then applied to the full scale models. Finite element analysis results show that the stress levels in all directions are low compared with material strengths.

A novel study of the polymerisation process involved in the formation of the network component of polymer-stabilised liquid crystals within electro-optic cells using high performance liquid chromatography

Polymer-stabilised liquid crystals are systems in which a small amount of monomer is dissolved within a liquid crystalline host, and then polymerised in situ to produce a network. The progress of the polymerisation, performed within electro-optic cells, was studied by establishing an analytical method novel to these systems. Samples were prepared by photopolymerisation of the monomer under well-defined reaction conditions; subsequent immersion in acetone caused the host and any unreacted monomer to dissolve. High performance liquid chromatography was used to separate and detect the various solutes in the resulting solutions, enabling the amount of unreacted monomer for a given set of conditions to be quantified. Longer irradiations cause a decrease in the proportion of unreacted monomer since more network is formed, while a more uniform LC director alignment (achieved by decreasing the sample thickness) or a higher level of order (achieved by decreasing the polymerisation temperature) promotes faster reactions.

A novel X-ray rheometer for in situ studies of polymer melts and solutions during shear flow

A novel X-ray rheometer based on a parallel plate geometry is described. This system allows time-resolved X-ray scattering intensity data to be obtained from polymeric samples subjected to shear flow. The range of quantitative structural parameters, such as molecular orientation and inter chain correlations, which can be obtained from the data is highlighted. Examples of the utility of X-ray scattering in examining optically opaque samples and the extraction of 〈P2〉 and 〈P4〉 orientation parameters are given using anisotropic hydroxypropylcellulose solutions as the sample.

A detailed single chain model for molten poly(tetrafluoroethylene) from a novel structure refinement technique on neutron scattering data

We present a new methodology that couples neutron diffraction experiments over a wide Q range with single chain modelling in order to explore, in a quantitative manner, the intrachain organization of non-crystalline polymers. The technique is based on the assignment of parameters describing the chemical, geometric and conformational characteristics of the polymeric chain, and on the variation of these parameters to minimize the difference between the predicted and experimental diffraction patterns. The method is successfully applied to the study of molten poly(tetrafluoroethylene) at two different temperatures, and provides unambiguous information on the configuration of the chain and its degree of flexibility. From analysis of the experimental data a model is derived with CC and CF bond lengths of 1.58 and 1.36 Å, respectively, a backbone valence angle of 110° and a torsional angle distribution which is characterized by four isometric states, namely a split trans state at ± 18°, giving rise to a helical chain conformation, and two gauche states at ± 112°. The probability of trans conformers is 0.86 at T = 350°C, which decreases slightly to 0.84 at T = 400°C. Correspondingly, the chain segments are characterized by long all-trans sequences with random changes in sign, rather anisotropic in nature, which give rise to a rather stiff chain. We compare the results of this quantitative analysis of the experimental scattering data with the theoretical predictions of both force fields and molecular orbital conformation energy calculations.

Approaches to the synthesis of novel photoactive side chain liquid crystalline polymers containing analogues of the cinnamate ester group

A series of chain liquid crystalline copolymers of 4-cyanophenyl 4′-(6-methacryloyloxyhexyloxy)benzoate and 2-methacryloyloxyethyl β-(1-naphthyl)-propenoate were prepared by free radical polymerization. The corresponding polyacrylates could not be prepared in the same way and an alternative method was used for their preparation involving the synthesis of copolymers of the mesogenic monomer and 2-hydroxyethyl acrylate followed by treatment of the resulting polymers with β-(1-naphthyl)propenoyl chloride. The materials are of interest as photoactive liquid crystalline polymers. The effect of introducing a bulky nonmesogenic group into a liquid crystalline copolymer generally lowers the clearing temperature and raises Tg but also gives rise to contrasting phase behaviour in these two series of polymers. Polymethacrylates which show mesomorphism have sharp transitions and continue to exhibit a highly ordered smectic phase over the bulk of their liquid crystal range. Polyacrylates, on the other hand, exhibit a weakening and broadening-out of their thermal transitions consistent with a lowering of order. These results emphasize the effect of the polymer backbone on phase behaviour.