Addressing potentially inappropriate prescribing in older patients: development and pilot study of an intervention in primary care (the OPTI-SCRIPT study)

Background: Potentially inappropriate prescribing (PIP) in older people is common in primary care and can result in increased morbidity, adverse drug events, hospitalizations and mortality. The prevalence of PIP in Ireland is estimated at 36% with an associated expenditure of over [euro sign]45 million in 2007. The aim of this paper is to describe the application of the Medical Research Council (MRC) framework to the development of an intervention to decrease PIP in Irish primary care.

Methods: The MRC framework for the design and evaluation of complex interventions guided the development of the study intervention. In the development stage, literature was reviewed and combined with information obtained from experts in the field using a consensus based methodology and patient cases to define the main components of the intervention. In the pilot stage, five GPs tested the proposed intervention. Qualitative interviews were conducted with the GPs to inform the development and implementation of the intervention for the main randomised controlled trial.

Results: The literature review identified PIP criteria for inclusion in the study and two initial intervention components - academic detailing and medicines review supported by therapeutic treatment algorithms. Through patient case studies and a focus group with a group of 8 GPs, these components were refined and a third component of the intervention identified - patient information leaflets. The intervention was tested in a pilot study. In total, eight medicine reviews were conducted across five GP practices. These reviews addressed ten instances of PIP, nine of which were addressed in the form of either a dose reduction or a discontinuation of a targeted medication. Qualitative interviews highlighted that GPs were receptive to the intervention but patient preference and time needed both to prepare for and conduct the medicines review, emerged as potential barriers. Findings from the pilot study allowed further refinement to produce the finalised intervention of academic detailing with a pharmacist, medicines review with web-based therapeutic treatment algorithms and tailored patient information leaflets.

Conclusions: The MRC framework was used in the development of the OPTI-SCRIPT intervention to decrease the level of PIP in primary care in Ireland. Its application ensured that the intervention was developed using the best available evidence, was acceptable to GPs and feasible to deliver in the clinical setting. The effectiveness of this intervention is currently being tested in a pragmatic cluster randomised controlled trial.

Trial registration: Current controlled trials ISRCTN41694007.© 2013 Clyne et al.; licensee BioMed Central Ltd.

An evaluation of strain softening of glacial tills as a result of pore pressure dynamics.

Deep-seated progressive failures of cuttings in heavily overconsolidated clays have been observed in the field and are well documented, especially for London Clays (Potts, Kovacevic, & Vaughan, 1997; Smethurst, Powrie, & Clarke, 2006; Take, 2003), however, the process of softening and the development of a rupture surface in other clays, including the clay fraction of glacial tills, is still to be established. Recent decades have witnessed extreme weather conditions in Northern Ireland with dry summers and wet winters. The dynamics of this pore pressure variation can trigger strength reduction and progressive plastic straining, both of which will lead to slope failure. The aim of this research is to evaluate the effect of pore pressure variations on the deformation and long-term stability of large cuttings in glacial tills in Northern Ireland. This paper outlines the overall research program and presents initial laboratory findings (Carse, 2013).

Do Changes in Current Flow as a Result of Arrays of Tidal Turbines Have an Effect on Benthic Communities?

Arrays of tidal energy converters have the potential to provide clean renewable energy for future generations. Benthic communities may, however, be affected by changes in current speeds resulting from arrays of tidal converters located in areas characterised by strong currents. Current speed, together with bottom type and depth, strongly influence benthic community distributions; however the interaction of these factors in controlling benthic dynamics in high energy environments is poorly understood. The Strangford Lough Narrows, the location of SeaGen, the world’s first single full-scale, grid-compliant tidal energy extractor, is characterised by spatially heterogenous high current flows. A hydrodynamic model was used to select a range of benthic community study sites that had median flow velocities between 1.5–2.4 m/s in a depth range of 25–30 m. 25 sites were sampled for macrobenthic community structure using drop down video survey to test the sensitivity of the distribution of benthic communities to changes in the flow field. A diverse range of species were recorded which were consistent with those for high current flow environments and corresponding to very tide-swept faunal communities in the EUNIS classification. However, over the velocity range investigated, no changes in benthic communities were observed. This suggested that the high physical disturbance associated with the high current flows in the Strangford Narrows reflected the opportunistic nature of the benthic species present with individuals being continuously and randomly affected by turbulent forces and physical damage. It is concluded that during operation, the removal of energy by marine tidal energy arrays in the far-field is unlikely to have a significant effect on benthic communities in high flow environments. The results are of major significance to developers and regulators in the tidal energy industry when considering the environmental impacts for site licences.

Fitness reduction and potential extinction of wild populations of Atlantic salmon, Salmo salar, as a result of interactions with escaped farm salmon.

The high level of escapes from Atlantic salmon farms, up to two million fishes per year in the North Atlantic, has raised concern about the potential impact on wild populations. We report on a twogeneration experiment examining the estimated lifetime successes, relative to wild natives, of farm, F1 and F2 hybrids and BC1 backcrosses to wild and farm salmon. Offspring of farm and hybrids (i.e. all F1 , F2 and BC1 groups) showed reduced survival compared with wild salmon but grew faster as juveniles and displaced wild parr, which as a group were significantly smaller. Where suitable habitat for these emigrant parr is absent, this competition would result in reduced wild smolt production. In the experimental conditions, where emigrants survived downstream, the relative estimated lifetime success ranged from 2% (farm) to 89% (BC1 wild) of that of wild salmon, indicating additive genetic variation for survival . Wild salmon primarily returned to fresh water after one sea winter (1SW) but farm and hybrids produced proportionately more 2SW salmon. However, lower overall survival means that this would result in reduced recruitment despite increased 2SW fecundity. We thus demonstrate that interaction of farm with wild salmon results in lowered fitness, with repeated escapes causing cumulative fitness depression and potentially an extinction vortex in vulnerable populations.

Depressed mood and dietary fish intake: Direct relationship or indirect relationship as a result of diet and lifestyle?

Previous studies have suggested an association between depressed mood and the dietary intake of fish. In all cases, however, dietary fish intake has been considered at the exclusion of all other aspects of the diet. This analysis investigates associations between depressed mood and dietary fish intake, while also concurrently investigating intake of a number of other dietary components. The analysis is conducted on data from 10,602 men from Northern Ireland and France screened for inclusion into the PRIME cohort study. Depressed mood was assessed using a self-report questionnaire based on the Welsh Pure Depression sub-scale of the Minnesota Multiphasic Personality Inventory, diet was assessed using a Food Frequency Questionnaire, and limited demographics were also measured. Using regression, depressed mood is initially inversely associated with dietary fish intake. On inclusion of all other dietary variables, the strength of this relationship reduces but remains, and significant associations with a number of other foods are also found. On additional inclusion of all demographic variables, the strength of the above relationships again reduces, and associations with various measures of socio-economic status and education are also significant. These findings suggest that depressed mood is associated with fish intake both directly, and indirectly as part of a diet that is associated with depression and as part of a lifestyle that is associated with depression. Additional support for these conclusions is also provided in the pattern of associations between depressed mood and diet in the two countries. The relative contributions of fish intake to depressed mood both directly and indirectly are yet to be determined. However, while diet is not measured and until lifestyle can be adequately measured, the potential roles of diet and lifestyle in the association between depressed mood and dietary fish intake should not be ignored.

High levels of genetic structuring as a result of population fragmentation in the tropical tree species Caesalpinia echinata Lam.

We have investigated levels of genetic diversity within and among seven remnant populations of Caesalpinia echinata Lam., an endangered species found as fragmented populations in three major areas around the coastal regions of Brazil. Using amplified fragment length polymorphism (AFLP) genetic markers, we detected levels of within-population genetic diversity ranging from 0.092 to 0.163, with the lowest values generally being found in the smallest populations. Estimates of between-population genetic differentiation were strongly correlated with geographical distance ( r = 0.884, p <0.001), which, along with a neighbour-joining phylogenetic analysis, strongly suggested high levels of genetic isolation by distance. Over half (62%) of the total genetic diversity was partitioned between populations, further highlighting the genetic distinctness of individual populations. Taken together, these results suggest that fragmentation has led to an increase in population differentiation between fragments of C. echinata. These formations will be of great value in the development of conservation plans for species exhibiting high levels of genetic differentiation due to fragmentation, such as indication of conservation unit size, which populations should be chosen as priority in conservation plans and which samples should be introduced in areas with a low number of individuals of brazilwood.

Deuterium in the Galactic Centre as a result of recent infall of low-metallicity gas

The Galactic Centre is the most active and heavily processed region of the Milky Way, so it can be used as a stringent test for the abundance of deuterium (a sensitive indicator of conditions in the first 1,000 seconds in the life of the Universe). As deuterium is destroyed in stellar interiors, chemical evolution models 1 predict that its Galactic Centre abundance relative to hydrogen is D/H = 5 x 10(-12), unless there is a continuous source of deuterium from relatively primordial (low-metallicity) gas. Here we report the detection of deuterium (in the molecule DCN) in a molecular cloud only 10 parsecs from the Galactic Centre. Our data, when combined with a model of molecular abundances, indicate that D/H = (1.7 +/- 0.3) x 10(-6), five orders of magnitude larger than the predictions of evolutionary models with no continuous source of deuterium. The most probable explanation is recent infall of relatively unprocessed metal-poor gas into the Galactic Centre (at the rate inferred by Wakker(2)). Our measured D/H is nine times less than the local interstellar value, and the lowest D/H observed in the Galaxy. We conclude that the observed Galactic Centre deuterium is cosmological, with an abundance reduced by stellar processing and mixing, and that there is no significant Galactic source of deuterium.

A Review of an Initiative to Introduce a Short Ethics Component into a Non-Ethics Course at a U.K. University

This paper discusses the introduction of a short ethics component into a first-year undergraduate accounting information systems course at a UK university. The influence of this ethics component on students’ ethical perceptions – where ethical perceptions are represented by the extent to which students’ conclusions regarding unethical actions coincide with those of experts in the field – is then assessed using computer-based scenarios to represent seven categories of ethical norms. The ethical perceptions in each of the scenarios are then statistically compared between two groups of students, namely those who have studied the ethics component and those who have not. Results indicate no significant difference in ethical perceptions between the two groups across all of the ethical norms. Possible explanations for this result are discussed and implications for future ethics teaching are considered.

Universality and self-similarity of an energy-constrained sandpile model with random neighbors

We study an energy-constrained sandpile model with random neighbors. The critical behavior of the model is in the same universality class as the mean-field self-organized criticality sandpile. The critical energy E-c depends on the number of neighbors n for each site, but the various exponents are independent of n. A self-similar structure with n-1 major peaks is developed for the energy distribution p(E) when the system approaches its stationary state. The avalanche dynamics contributes to the major peaks appearing at E-Pk = 2k/(2n - 1) with k = 1,2,...,n-1, while the fine self-similar structure is a natural result of the way the system is disturbed. [S1063-651X(99)10307-6].

Effect of plasticizer viscosity on the sensitivity of an [RU(bpy)(3)(2+)(Ph4B-)(2)]-based optical oxygen sensor

The quenching of the electronically-excited, lumophoric state of [Ru(bpy)(3)(2+)(Ph4B-)(2)] by oxygen is studied in a wide variety of neat plasticizers. The Stern-Volmer constant, K-SV, is found to be inversely dependent upon the viscosity of the quenching medium, although the natural lifetime of the electronically excited state of [RU(bPY)(3)(2+)(Ph4B-)(2)] is largely independent of medium. The least viscous of the plasticizers tested, triethyl phosphate, did not, however, produce highly sensitive optical oxygen sensors when used to plasticize [RU(bPY)(3)(2+)(Ph4B-)(2)]-containing cellulose acetate butyrate (CAB) and poly(methyl methacrylate) (PMMA) films, Instead, the compatibility of the polymer-plasticizer combination, as measured by the difference in the values of the solubility parameter of the two, appears to be a major factor in determining the overall oxygen sensitivity of the thin plastic films. For highly compatible polymer-plasticizer combinations, the plasticizer with the lowest viscosity produces films of the highest oxygen sensitivity. This situation arises because in the film the quenching process is partly diffusion-controlled and, as a result, the quenching rate constant is inversely proportional to the effective viscosity of the reaction medium.

Identification and Validation of an Anthracycline/Cyclophosphamide–Based Chemotherapy Response Assay in Breast Cancer

Background: There is no method routinely used to predict response to anthracycline and cyclophosphamide–based chemotherapy in the clinic; therefore patients often receive treatment for breast cancer with no benefit. Loss of the Fanconi anemia/BRCA (FA/BRCA) DNA damage response (DDR) pathway occurs in approximately 25% of breast cancer patients through several mechanisms and results in sensitization to DNA-damaging agents. The aim of this study was to develop an assay to detect DDR-deficient tumors associated with loss of the FA/BRCA pathway, for the purpose of treatment selection.

Methods: DNA microarray data from 21 FA patients and 11 control subjects were analyzed to identify genetic processes associated with a deficiency in DDR. Unsupervised hierarchical clustering was then performed using 60 BRCA1/2 mutant and 47 sporadic tumor samples, and a molecular subgroup was identified that was defined by the molecular processes represented within FA patients. A 44-gene microarray-based assay (the DDR deficiency assay) was developed to prospectively identify this subgroup from formalin-fixed, paraffin-embedded samples. All statistical tests were two-sided.

Results: In a publicly available independent cohort of 203 patients, the assay predicted complete pathologic response vs residual disease after neoadjuvant DNA-damaging chemotherapy (5-fluorouracil, anthracycline, and cyclophosphamide) with an odds ratio of 3.96 (95% confidence interval [Cl] =1.67 to 9.41; P = .002). In a new independent cohort of 191 breast cancer patients treated with adjuvant 5-fluorouracil, epirubicin, and cyclophosphamide, a positive assay result predicted 5-year relapse-free survival with a hazard ratio of 0.37 (95% Cl = 0.15 to 0.88; P = .03) compared with the assay negative population.

Conclusions: A formalin-fixed, paraffin-embedded tissue-based assay has been developed and independently validated as a predictor of response and prognosis after anthracycline/cyclophosphamide–based chemotherapy in the neoadjuvant and adjuvant settings. These findings warrant further validation in a prospective clinical study.

Validation of an ultra high performance liquid chromatography-tandem mass spectrometry method for detection and quantitation of 19 endocrine disruptors in milk

An endocrine disruptor (ED) is an exogenous compound that interferes with the body's endocrine system. Exposure to EDs may result in adverse health effects such as infertility and cancer. EDs are composed of a vast group of chemicals including compounds of natural origin such as phytoestrogens or mycotoxins and a wide range of man-made chemicals such as pesticides. Synthetic compounds may find their way into the food chain where a number of them can biomagnify. Additionally, processing activities and food contact materials may add further to the already existing pool of food contaminants. Thus, our diet is considered to be one of the main exposure routes to EDs. Some precautionary legislation has already been introduced to control production and/or application of some persistent organic pollutants with ED characteristics. However, newly emerging EDs with bioaccumulative properties have recently been reported to appear at lower tiers of the food chain but have not been monitored at the grander scale. Milk and dairy products are a major component of our diet, thus it is important to monitor them for EDs. However, most methods developed to date are devoted to one group of compounds at a time. The UHPLC-MS/MS method described here has been validated according to EC decision 2002/657/EC and allows simultaneous extraction, detection, quantitation and confirmation of 19 EDs in milk. The method calibration range is between 0.50 and 20.0 μg kg with coefficients of determination above 0.99 for all analytes. Precision varied from 4.7% to 23.4% in repeatability and reproducibility studies. Established CCα and CCβ values (0.11-0.67 μg kg) facilitate fast, reliable, quantitative and confirmatory analysis of sub μg kg levels of a range of EDs in milk.

Nanoscale reinforced orthopaedic bone cement with graphene oxide - a possible solution to aseptic loosening of cemented hip implants? Preliminary results of an ongoing study

Hip replacement surgery is amongst the most common orthopaedic operations performed in the UK. Aseptic loosening is responsible for 40% of hip revision procedures. Aseptic loosening is a result of cement mantle fatigue. The aim of the current study is to analyse the effect of nanoscale Graphene Oxide (GO) on the mechanical properties of orthopaedic bone cement. Study Design A experimental thermal and mechanical analysis was conducted in a laboratory set up conforming to international standards for bone cement testing according to ISO 5583. Testing was performed on control cement samples of Colacryl bone cement, and additional samples reinforced with variable wt% of Graphene Oxide containing composites – 0.1%, 0.25%, 0.5% and 1.0% GO loading. Pilot Data Porosity demonstrated a linear relationship with increasing wt% loading compared to control (p<0.001). Thermal characterisation demonstrated maximal temperature during polymerization, and generated exotherm were inversely proportional to w%t loading (p<0.05) Fatigue strength performed on the control and 0.1 and 0.25%wt loadings of GO demonstrate increased average cycles to failure compared to control specimens. A right shift of the Weibull curve was demonstrated for both wt% available currently. Logistic regression analysis for failure demonstrated significant increases in number of cycles to failure for both specimens compared to a control (p<0.001). Forward Plan Early results convey positive benefits at low wt% loadings of GO containing bone cement. Study completion and further analysis is required in order to elude to the optimum w%t of GO which conveys the greatest mechanical advantage.

'Regina v John Terry': The Discursive Construction of an Alleged Racist Event

This article explores the conformation in discourse of a verbal exchange and its subsequent mediatised and legal ramifications. The event concerns an allegedly racist insult directed by high profile English professional footballer John Terry towards another player, Anton Ferdinand, during a televised match in October 2011. The substance of Terry’s utterance, which included the noun phrase ‘fucking black cunt’, was found by a Chief Magistrate not to be a racist insult, although the fact that these actual words were framed within the utterance was not in dispute. The upshot of this ruling was that Terry was acquitted of a racially aggravated public order offence. A subsequent investigation by the regulatory commission of the English Football Association (FA) ruled, almost a year after the event, that Terry was guilty of racially abusing Ferdinand. Terry was banned for four matches and fined £220,000.

It is our contention that this event, played out in legal rulings, social media and print and broadcast media, constitutes a complex web of linguistic structures and strategies in discourse, and as such lends itself well to analysis with a broad range of tools from pragmatics, discourse analysis and cognitive linguistics. Amongst other things, such an analysis can help explain the seemingly anomalous - even contradictory - position adopted in the legal ruling with regard to the speech act status of ‘fucking black cunt’; namely, that the racist content of the utterance was not contested but that the speaker was found not to have issued a racist insult. Over its course, the article addresses this broader issue by making reference to the systemic-functional interpersonal function of language, particularly to the concepts of modality, polarity and modalisation. It also draws on models of verbal irony from linguistic pragmatics, notably from the theory of irony as echoic mention (c.f. Sperber and Wilson, 1981; Wilson and Sperber, 1992). Furthermore, the article makes use of the cognitive-linguistic framework, Text World Theory (c.f. Gavins, 2007; Werth, 1999) to examine the discourse positions occupied by key actors and adapts, from cognitive poetics, the theory of mind-modelling (c.f. Stockwell, 2009) to explore the conceptual means through which these actors discursively negotiate the event.

It is argued that the pragmatic and cognitive strategies that frame the entire incident go a long way towards mitigating the impact of so ostensibly stark an act of racial abuse. Moreover, it is suggested here that the reconciliation of Terry’s action was a result of the confluence of strategies of discourse with relations of power as embodied by the media, the law and perceptions of nationhood embraced by contemporary football culture. It is further proposed that the outcome of this episode, where the FA was put in the spotlight, and where both the conflict and its key antagonists were ‘intranational’, was strongly impelled by the institution of English football and its governing body both to reproduce and maintain social, cultural and ethnic cohesion and to avoid any sense that the event featured a discernable ‘out-group’.

Can less be more? Comparison of an 8-item placement quality measure with the 50-item Dundee Ready Educational Environment Measure (DREEM)

Clinical clerks learn more than they are taught and not all they learn can be measured. As a result, curriculum leaders evaluate clinical educational environments. The quantitative Dundee Ready Environment Measure (DREEM) is a de facto standard for that purpose. Its 50 items and 5 subscales were developed by consensus. Reasoning that an instrument would perform best if it were underpinned by a clearly conceptualized link between environment and learning as well as psychometric evidence, we developed the mixed methods Manchester Clinical Placement Index (MCPI), eliminated redundant items, and published validity evidence for its 8 item and 2 subscale structure. Here, we set out to compare MCPI with DREEM. 104 students on full-time clinical placements completed both measures three times during a single academic year. There was good agreement and at least as good discrimination between placements with the smaller MCPI. Total MCPI scores and the mean score of its 5-item learning environment subscale allowed ten raters to distinguish between the quality of educational environments. Twenty raters were needed for the 3-item MCPI training subscale and the DREEM scale and its subscales. MCPI compares favourably with DREEM in that one-sixth the number of items perform at least as well psychometrically, it provides formative free text data, and it is founded on the widely shared assumption that communities of practice make good learning environments.