What do patients want to know? An empirical approach to explanation generation and validation

This article describes an empirical, user-centred approach to explanation design. It reports three studies that investigate what patients want to know when they have been prescribed medication. The question is asked in the context of the development of a drug prescription system called OPADE. The system is aimed primarily at improving the prescribing behaviour of physicians, but will also produce written explanations for indirect users such as patients. In the first study, a large number of people were presented with a scenario about a visit to the doctor, and were asked to list the questions that they would like to ask the doctor about the prescription. On the basis of the results of the study, a categorization of question types was developed in terms of how frequently particular questions were asked. In the second and third studies a number of different explanations were generated in accordance with this categorization, and a new sample of people were presented with another scenario and were asked to rate the explanations on a number of dimensions. The results showed significant differences between the different explanations. People preferred explanations that included items corresponding to frequently asked questions in study 1. For an explanation to be considered useful, it had to include information about side effects, what the medication does, and any lifestyle changes involved. The implications of the results of the three studies are discussed in terms of the development of OPADE's explanation facility.

Systemic gut microbial modulation of bile acid metabolism in host tissue compartments

We elucidate the detailed effects of gut microbial depletion on the bile acid sub-metabolome of multiple body compartments (liver, kidney, heart, and blood plasma) in rats. We use a targeted ultraperformance liquid chromatography with time of flight mass-spectrometry assay to characterize the differential primary and secondary bile acid profiles in each tissue and show a major increase in the proportion of taurine-conjugated bile acids in germ-free (GF) and antibiotic (streptomycin/penicillin)-treated rats.Although conjugated bile acids dominate the hepatic profile (97.0 ± 1.5%) of conventional animals, unconjugated bile acids comprise the largest proportion of the total measured bile acid profile in kidney (60.0±10.4%) andheart (53.0 ± 18.5%) tissues. In contrast, in the GF animal, taurine-conjugated bile acids (especially taurocholic acid and tauro-β-muricholic acid) dominated the bile acid profiles (liver: 96.0 ± 14.5%; kidney: 96 ± 1%; heart: 93 ± 1%; plasma: 93.0 ± 2.3%), with unconjugated and glycine-conjugated species representing a small proportion of the profile. Higher free taurine levels were found in GF livers compared with the conventional liver (5.1-fold; P < 0.001). Bile acid diversity was also lower in GF and antibiotic-treated tissues compared with conventional animals. Because bile acids perform important signaling functions, it is clear that these chemical communication networks are strongly influencedbymicrobial activitiesormodulation, as evidenced by farnesoid X receptor-regulated pathway transcripts. The presence of specific microbial bile acid co-metabolite patterns in peripheral tissues (including heart and kidney) implies a broader signaling role for these compounds and emphasizes the extent of symbiotic microbial influences in mammalian homeostasis.

Systemic and persistent effect of neem (Azadirachta indica) formulations against root-knot nematodes, Meloidogyne javanica and their storage life

Neem leaves, neem cake (a by-product left after the extraction of oil from neem seed) and a commercially refined product aza (azadirachtin) extracted from seed were evaluated. Aqueous extracts of crude neem formulations used as a seedling dip treatment significantly reduced the number of females and egg masses in roots whereas the refined one did not. A split-root technique was used to demonstrate the translocation of active compounds within a plant and their subsequent effect on the development of nematodes. When applied to the root portion all formulations significantly reduced the number of egg masses and eggs per egg mass. Whereas on the untreated root portion, neem cake at 3% w/w and aza at 0.1% w/w significantly reduced the number of egg masses as compared with neem leaves at 3% w/w, aza at 0.05% and control. All the neern formulations significantly reduced the number of eggs per egg mass on' the untreated root portion. The effect of neem leaves and cake on the development of root-knot nematodes was tested at 2, 4, 6, 8, and 16 weeks after their application to soil. Even after 16 weeks all the treatments significantly reduced the galling index and number of egg masses but their effectiveness declined over time. After storing neem leaves, cake and aza for 8 months under ambient conditions the efficacy of neem leaves and aza, against root-knot nematodes, remained stable whereas that of cake declined. (c) 2006 Elsevier Ltd. All rights reserved.

Field evaluation of systemic inducing resistance chemicals at different growth stages for the control of apple (Venturia inaequalis) and pear (Venturia pirina) scab

Two field trials were conducted using established apple (Malus cv. Golden Delicious) and pear (Pyrus communis 'Williams' Bon Chretien') to assess the efficacy of three commercially available systemic inducing resistance (SIR) products, Messenger (a.i. Harpin protein), Phoenix (a.i. Potassium phosphite) and Rigel (a.i. Salicylic acid derivative) applied at four different growth stages of tree development (bud break, green cluster, 90% petal fall, early fruitlet) against the foliar pathogens Venturia inaequalis and Venturia pirina which cause apple and pear scab respectively. A conventional synthetic fungicide (penconazole) used within the UK for apple and pear scab control was included for comparison. Little efficacy as scab protectants was demonstrated when each SIR product and penconazole was applied at only two growth stages (bud break, green cluster). However when the above compounds were applied at three or more growth stages efficacy as scab protectants was confirmed. The synthetic fungicide penconazole provided greatest protection against apple and pear scab in both the 2006 and 2007 field trials. There was little difference in the magnitude of scab protection conferred by each SIR agent. Results suggest application of at least three sprays during bud break to early fruitlet formation with an appropriate SIR agent may provide a useful addition to existing methods of apple and pear scab management under field conditions. (C) 2009 Published by Elsevier Ltd.

Evidence for unusual spatial location coding in Williams syndrome: an explanation for the local bias in visuo-spatial construction tasks?

Individuals with Williams syndrome (WS) display poor visuo-spatial cognition relative to verbal abilities. Furthermore, whilst perceptual abilities are delayed, visuo-spatial construction abilities are comparatively even weaker, and are characterised by a local bias. We investigated whether his differentiation in visuo-spatial abilities can be explained by a deficit in coding spatial location in WS. This can be measured by assessing participants' understanding of the spatial relations between objects within a visual scene. Coordinate and categorical spatial relations were investigated independently in four participant groups: 21 individuals with WS; 21 typically developing (TD) children matched for non-verbal ability; 20 typically developing controls of a lower non-verbal ability; and 21 adults. A third task measured understanding of visual colour relations. Results indicated first, that the comprehension of categorical and coordinate spatial relations is equally poor in WS. Second, that the comprehension of visual relations is also at an equivalent level to spatial relational understanding in this population. These results can explain the difference in performance on visuo-spatial perception and construction tasks in WS. In addition, both the WS and control groups displayed response biases in the spatial tasks. However, the direction of bias differed across the groups. This finding is explored in relation to current theories of spatial location coding. (c) 2005 Elsevier Inc. All rights reserved.

Persistent, symptomless, systemic, and seed-borne infection of lettuce by Botrytis cinerea

Experiments are presented which show that Botrytis cinerea, the cause of gray mould disease, is often present in symptomless lettuce plants as a systemic, endophytic, infection which may arise from seed. The fungus was isolated on selective media from surface sterilized sections of roots, stem pieces and leaf discs from symptomless plants grown in a conventional glasshouse and in a spore-free air-flow provided by an isolation propagator. The presence of B. cinerea was confirmed by immuno-labelling the tissues with the Botrytis-specific monoclonal antibody BC-12.CA4. As plants grew, infection spread from the roots to stems and leaves. Surface sterilization of seeds reduced the number of infected symptomless plants. Artificial infection of seedlings with dry conidia increased the rate of infection in some experiments. Selected isolates were genetically finger-printed using microsatellite loci. This confirmed systemic spread of the inoculating isolates but showed that other isolates were also present and that single plants hosted multiple isolates. This shows that B. cinerea commonly grows in lettuce plants as an endophyte, as has already been shown for Primula. If true for other hosts, the endophytic phase may be as important a component of the species population as the aggressive necrotrophic phase.

Carnauba wax nanoparticles enhance strong systemic and mucosal cellular and humoral immune responses to HIV-gp140 antigen

Induction of humoral responses to HIV at mucosal compartments without inflammation is important for vaccine design. We developed charged wax nanoparticles that efficiently adsorb protein antigens and are internalized by DC in the absence of inflammation. HIV-gp140-adsorbed nanoparticles induced stronger in vitro T-cell proliferation responses than antigen alone. Such responses were greatly enhanced when antigen was co-adsorbed with TLR ligands. Immunogenicity studies in mice showed that intradermal vaccination with HIV-gp140 antigen-adsorbed nanoparticles induced high levels of specific IgG. Importantly, intranasal immunization with HIV-gp140-adsorbed nanoparticles greatly enhanced serum and vaginal IgG and IgA responses. Our results show that HIV-gp140-carrying wax nanoparticles can induce strong cellular/humoral immune responses without inflammation and may be of potential use as effective mucosal adjuvants for HIV vaccine candidates.