What is the new medicines use review ‘patient survey’ attempting to capture in the context of existing patient satisfaction with pharmacy questionnaires and a new conceptual framework?

The community pharmacy service medicines use review (MUR) was introduced in 2005 ‘to improve patient knowledge, concordance and use of medicines’ through a private patient–pharmacist consultation. The MUR presents a fundamental change in community pharmacy service provision. While traditionally pharmacists are dispensers of medicines and providers of medicines advice, and patients as recipients, the MUR considers pharmacists providing consultation-type activities and patients as active participants. The MUR facilitates a two-way discussion about medicines use. Traditional patient–pharmacist behaviours transform into a new set of behaviours involving the booking of appointments, consultation processes and form completion, and the physical environment of the patient–pharmacist interaction moves from the traditional setting of the dispensary and medicines counter to a private consultation room. Thus, the new service challenges traditional identities and behaviours of the patient and the pharmacist as well as the environment in which the interaction takes place. In 2008, the UK government concluded there is at present too much emphasis on the quantity of MURs rather than on their quality.[1] A number of plans to remedy the perceived imbalance included a suggestion to reward ‘health outcomes’ achieved, with calls for a more focussed and scientific approach to the evaluation of pharmacy services using outcomes research. Specifically, the UK government set out the main principal research areas for the evaluation of pharmacy services to include ‘patient and public perceptions and satisfaction’as well as ‘impact on care and outcomes’. A limited number of ‘patient satisfaction with pharmacy services’ type questionnaires are available, of varying quality, measuring dimensions relating to pharmacists’ technical competence, behavioural impressions and general satisfaction. For example, an often cited paper by Larson[2] uses two factors to measure satisfaction, namely ‘friendly explanation’ and ‘managing therapy’; the factors are highly interrelated and the questions somewhat awkwardly phrased, but more importantly, we believe the questionnaire excludes some specific domains unique to the MUR. By conducting patient interviews with recent MUR recipients, we have been working to identify relevant concepts and develop a conceptual framework to inform item development for a Patient Reported Outcome Measure questionnaire bespoke to the MUR. We note with interest the recent launch of a multidisciplinary audit template by the Royal Pharmaceutical Society of Great Britain (RPSGB) in an attempt to review the effectiveness of MURs and improve their quality.[3] This template includes an MUR ‘patient survey’. We will discuss this ‘patient survey’ in light of our work and existing patient satisfaction with pharmacy questionnaires, outlining a new conceptual framework as a basis for measuring patient satisfaction with the MUR. Ethical approval for the study was obtained from the NHS Surrey Research Ethics Committee on 2 June 2008. References 1. Department of Health (2008). Pharmacy in England: Building on Strengths – Delivering the Future. London: HMSO. www. official-documents.gov.uk/document/cm73/7341/7341.pdf (accessed 29 September 2009). 2. Larson LN et al. Patient satisfaction with pharmaceutical care: update of a validated instrument. JAmPharmAssoc 2002; 42: 44–50. 3. Royal Pharmaceutical Society of Great Britain (2009). Pharmacy Medicines Use Review – Patient Audit. London: RPSGB. http:// qi4pd.org.uk/index.php/Medicines-Use-Review-Patient-Audit. html (accessed 29 September 2009).

Detection of somaclonal variation during cocoa somatic embryogenesis characterised using cleaved amplified polymorphic sequence and the new freeware Artbio

The scarcity and stochastic nature of genetic mutations presents a significant challenge for scientists seeking to characterise de novo mutation frequency at specific loci. Such mutations can be particularly numerous during regeneration of plants from in vitro culture and can undermine the value of germplasm conservation efforts. We used cleaved amplified polymorphic sequence (CAPS) analysis to characterise new mutations amongst a clonal population of cocoa plants regenerated via a somatic embryogenesis protocol used previously for cocoa cryopreservation. Efficacy of the CAPS system for mutation detection was greatly improved after an ‘a priori’ in silico screen of reference target sequences for actual and potential restriction enzyme recognition sites using a new freely available software called Artbio. Artbio surveys known sequences for existing restriction enzyme recognition sites but also identifies all single nucleotide polymorphism (SNP) deviations from such motifs. Using this software, we performed an in silico screen of seven loci for restriction sites and their potential mutant SNP variants that were possible from 21 restriction enzymes. The four most informative locus-enzyme combinations were then used to survey the regenerant populations for de novo mutants. We characterised the pattern of point mutations and, using the outputs of Artbio, calculated the ratio of base substitution in 114 somatic embryo-derived cocoa regenerants originating from two explant genotypes. We found 49 polymorphisms, comprising 26.3% of the samples screened, with an inferred rate of 2.8 × 10−3 substitutions/screened base. This elevated rate is of a similar order of magnitude to previous reports of de novo microsatellite length mutations arising in the crop and suggests caution should be exercised when applying somatic embryogenesis for the conservation of plant germplasm.

An overview of domestic energy models and a new approach with agent based modelling

Government targets for CO2 reductions are being progressively tightened, the Climate Change Act set the UK target as an 80% reduction by 2050 on 1990 figures. The residential sector accounts for about 30% of emissions. This paper discusses current modelling techniques in the residential sector: principally top-down and bottom-up. Top-down models work on a macro-economic basis and can be used to consider large scale economic changes; bottom-up models are detail rich to model technological changes. Bottom-up models demonstrate what is technically possible. However, there are differences between the technical potential and what is likely given the limited economic rationality of the typical householder. This paper recommends research to better understand individuals’ behaviour. Such research needs to include actual choices, stated preferences and opinion research to allow a detailed understanding of the individual end user. This increased understanding can then be used in an agent based model (ABM). In an ABM, agents are used to model real world actors and can be given a rule set intended to emulate the actions and behaviours of real people. This can help in understanding how new technologies diffuse. In this way a degree of micro-economic realism can be added to domestic carbon modelling. Such a model should then be of use for both forward projections of CO2 and to analyse the cost effectiveness of various policy measures.

Neuroprotective effects of phenolic antioxidant tBHQ associate with inhibition of FoxO3a nuclear translocation and activity

The Forkhead transcription factor, FoxO3a induces genomic death responses in neurones following translocation from the cytosol to the nucleus. Nuclear translocation of FoxO3a is triggered by trophic factor withdrawal, oxidative stress and the stimulation of extrasynaptic NMDA receptors. Receptor activation of phosphatidylinositol 3-kinase (PI3K) – Akt signalling pathways retains FoxO3a in the cytoplasm thereby inhibiting the transcriptional activation of death promoting genes. We hypothesised that phenolic antioxidants such as tert-Butylhydroquinone (tBHQ), which is known to stimulate PI3K-Akt signalling, would inhibit FoxO3a translocation and activity. Treatment of cultured cortical neurones with NMDA increased the nuclear localisation of FoxO3a, reduced the phosphorylation of FoxO3a, increased caspase activity and upregulated Fas ligand expression. In contrast the phenolic antioxidant tBHQ caused retention of FoxO3a in the cytosol coincident with enhanced PI3K- dependent phosphorylation of FoxO3a. tBHQ-induced nuclear exclusion of FoxO3a was associated with reduced FoxO-mediated transcriptional activity. Exposure of neurones to tBHQ inhibited NMDA-induced nuclear translocation of FoxO3a prevented NMDA-induced upregulation of FoxO-mediated transcriptional activity, blocked caspase activation and protected neurones from NMDA-induced excitotoxic death. Collectively, these data suggest that phenolic antioxidants such as tBHQ oppose stress-induced activation of FoxO3a and therefore have potential neuroprotective utility in neurodegeneration.

NATO, Britain, France and the FRG: Nuclear Strategies and Forces for Europe, 1949-2000

This is vol. I of my two-volume study of the nuclear strategies/strategy preferences of NATO collectively, and individually of Britain, France, and West Germany in the Cold War. It shows that NATO strategy was a fragile compromise, and that these three countries, all within range of Soviet medium/intermediate range nuclear missiles and thus with less geostrategic difference than in previous military threat contexts, had wildly divergent strategies/preferences which cannot be explained merely by geography. It raises the question of what made them so different, addressed in Volume II "Nuclear Mentalities" (q.v.)

Housing densities and consumer choice

From 2001, the construction of flats and high-density developments increased in England and the building of houses declined. Does this indicate a change in taste or is it a result of government planning policies? In this paper, an analysis is made of the long-term effects of the policy of constraint which has existed for the past 50 years but the increase in density is identified as occurring primarily after new, revised, planning guidance was issued in England in 2000 which discouraged low-density development. To substantiate this, it is pointed out that the change which occurred in England did not occur in Scotland where guidance was not changed to encourage high-density residential development. The conclusion that the change is the result of planning policies and not of a change in taste is confirmed by surveys of the occupants of new high-rise developments in Leeds. The new flat-dwellers were predominantly young and childless and expressed the intention, in the near future, when they could, of moving out of the city centre and into houses. From recent changes in guidance by the new coalition government, it is expected that the construction of flats in England will fall back to earlier levels over the next few years.

Non-orthogonal version of the arbitrary polygonal C-grid and a new diamond grid

Quasi-uniform grids of the sphere have become popular recently since they avoid parallel scaling bottle- necks associated with the poles of latitude–longitude grids. However quasi-uniform grids of the sphere are often non- orthogonal. A version of the C-grid for arbitrary non- orthogonal grids is presented which gives some of the mimetic properties of the orthogonal C-grid. Exact energy conservation is sacrificed for improved accuracy and the re- sulting scheme numerically conserves energy and potential enstrophy well. The non-orthogonal nature means that the scheme can be used on a cubed sphere. The advantage of the cubed sphere is that it does not admit the computa- tional modes of the hexagonal or triangular C-grids. On var- ious shallow-water test cases, the non-orthogonal scheme on a cubed sphere has accuracy less than or equal to the orthog- onal scheme on an orthogonal hexagonal icosahedron. A new diamond grid is presented consisting of quasi- uniform quadrilaterals which is more nearly orthogonal than the equal-angle cubed sphere but with otherwise similar properties. It performs better than the cubed sphere in ev- ery way and should be used instead in codes which allow a flexible grid structure.

Generic relationships and dating of lineages in Winteraceae based on nuclear (ITS) and plastid (rpS16 and psbA-trnH) sequence data

Phylogenetic analyses of representative species from the five genera of Winteraceae (Drimys, Pseudowintera, Takhtajania, Tasmannia, and Zygogynum s.l.) were performed using ITS nuclear sequences and a combined data-set of ITS + psbA-trnH + rpS16 sequences (sampling of 30 and 15 species, respectively). Indel informativity using simple gap coding or gaps as a fifth character was examined in both data-sets. Parsimony and Bayesian analyses support the monophyly of Drimys, Tasmannia, and Zygogynum s.l., but do not support the monophyly of Belliolum, Zygogynum s.s., and Bubbia. Within Drimys, the combined data-set recovers two subclades. Divergence time estimates suggest that the splitting between Drimys and its sister clade (Pseudowintera + Zygogynum s.l.) occurred around the end of the Cretaceous; in contrast, the divergence between the two subclades within Drimys is more recent (15.5-18.5 MY) and coincides in time with the Andean uplift. Estimates suggest that the earliest divergences within Winteraceae could have predated the first events of Gondwana fragmentation. (C) 2009 Elsevier Inc. All rights reserved.

Effect of power densities and irradiation times on the degree of conversion and temperature increase of a microhybrid dental composite resin

The different parameters used for the photoactivation process provide changes in the degree of conversion (DC%) and temperature rise (TR) of the composite resins. Thus, the purpose of this study was to evaluate the DC (%) and TR of the microhybrid composite resin photoactivated by a new generation LED. For the KBr pellet technique, the composite resin was placed into a metallic mould (1-mm thickness and 4-mm diameter) and photoactivated as follows: continuous LED LCU with different power density values (50-1000 mW/cm(2)). The measurements for the DC (%) were made in a FTIR Spectrometer Bomen (model MB-102, Quebec-Canada). The spectroscopy (FTIR) spectra for both uncured and cured samples were analyzed using an accessory for the diffuse reflectance. The measurements were recorded in the absorbance operating under the following conditions: 32 scans, 4-cm(-1) resolution, and a 300 to 4000-cm(-1) wavelength. The percentage of unreacted carbon-carbon double bonds (% C=C) was determined from the ratio of the absorbance intensities of aliphatic C=C (peak at 1638 cm(-1)) against an internal standard before and after the curing of the specimen: aromatic C-C (peak at 1608 cm-1). For the TR, the samples were made in a metallic mould (2-mm thickness and 4-mm diameter) and photoactivated during 5, 10, and 20 s. The thermocouple was attached to the multimeter to allow the temperature readings. The DC (%) and TR were calculated by the standard technique and submitted to ANOVA and Tukey`s test (p < 0.05). The degree of conversion values varied from 35.0 (+/- 1.3) to 45.0 (+/- 2.4) for 5 s, 45.0 (+/- 1.3) to 55.0 (+/- 2.4) for 10 s, and 47.0 (+/- 1.3) to 52.0 (+/- 2.4) for 20 s. For the TR, the values ranged from 0.3 (+/- 0.01) to 5.4 (+/- 0.11)degrees C for 5 s, from 0.5 (+/- 0.02) to 9.3 (+/- 0.28)degrees C for 10 s, and from 1.0 (+/- 0.06) to 15.0 (+/- 0.95)degrees C for 20 s. The power densities and irradiation times showed a significant effect on the degree of conversion and temperature rise.

Predicting and characterizing new molecular species at a high-level theoretical approach: HSeCl, HClSe, and SeCl

New molecular species HSeCl, HClSe, and SeCl were investigated at a high level of theory, CCSD(T), with a series of correlation consistent basis sets with extrapolation to the CBS limit. Account has been taken for valence-only and core-valence correlation effects, and of anharmonic effects on the vibrational frequencies. HSeCl is 43.25 kcal mol (1) more stable than HClSe. A barrier (Delta G(#)) of 47.20 kcal mol (1) separates these species. Internuclear distances are generally overestimated by 0.008 angstrom in the valence-only correlation calculations. Inclusion of anharmonicity leads to much improved vibrational frequencies. For SeCl, we estimate Delta H(f) (0 K) = 23.96 and Delta H(f) (298.15 K) = 24.64 kcal mol (1); for HSeCl, we had 4.20 and 4.97 kcal mol (1), respectively. (C) 2010 Elsevier B.V. All rights reserved.

Natural chromens and chromene derivatives as potential anti-trypanosomal agents

The aim of the study was to investigate the anti-trypanocidal activities of natural chromene and chromene derivatives. Five chromenes were isolated from Piper gaudichaudianum and P. aduncum, and a further seven derivatives were prepared using standard reduction, methylation and acetylation procedures. These compounds were assayed in vitro against epimastigote forms of Trypanosoma cruzi, the causative agent of Chagas disease. The results showed that the most of the compounds, especially those possessing electron-donating groups as substituents on the aromatic ring, showed potent trypanocidal activity. The most active compound, [(2S)-methyl-2-methyl-8-(3 ``-methylbut-2 ``-enyl)-2-(4`-methylpent-3`-enyl)-2H-chromene-6-carboxylate], was almost four times more potent than benznidazole (the positive control) and showed an IC50 of 2.82 mu M. The results reveal that chromenes exhibit significant anti-trypanocidal activities and indicate that this class of natural product should be considered further in the development of new and more potent drugs for use in the treatment of Chagas disease.

Effects of plant densities and management of purple nutsedge on sugarcane yield and effect of growth stages and main way of herbicides contact and absorption on the control of tubers

Field experiments carried out with Cyperus rotundus L. at low (58-246), medium (318773), and high (675-1198 shoots/m(2)) densities showed sugarcane yield reductions of 13.5, 29.3, and 45.2%, respectively in relation to the control. In the second field experiment, the integration of a mechanic method with two sequences of plowing and disking operations in the dry season, and complementary applications of trifloxysulfuron-sodium + ametrine and sulfentrazone (rainy season) was studied. Average of the chain connected to original shoot showed 92, 95, and 65% of reduction with trifloxysulfuron-sodium + ametrine and surfactant, at the application stages early, preflowering, and full flowering, respectively.

Expanded description of Lamproglena monodi (Copepoda: Lernaeidae), parasitizing native and introduced fishes in Brazil

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Nonlocal description of the nuclear interaction

Extensive systematizations of theoretical and experimental nuclear densities and of optical potential strengths extracted from heavy-ion elastic scattering data analyses at low and intermediate energies are presented. The energy-dependence of the nuclear potential is accounted for within a model based on the nonlocal nature of the interaction. The systematics indicates that the heavy-ion nuclear potential can be described in a simple global way through a double-folding shape, which basically depends only on the density of nucleons of the partners in the collision. The possibility of extracting information about the nucleon-nucleon interaction from the heavy-ion potential is investigated.

The nucleon structure function and the quark effective potential

By considering a statistical model for the quark content of the nucleon, where the quark levels are generated by a Dirac equation with a harmonic scalar-plus-vector potential, we note that a good fit for the ratio between the structure functions of the neutron and proton, F-2(n)/F-2(p), can be obtained if different strengths are used for the effective confining potentials of the up and down quarks.