The geriatric minimum data set for clinical trials (GMDS)

To overcome the weak evidence base coming from often poor and insufficient clinical research in older people, a minimum data set to achieve harmonisation is highly advisable. This will lead to uniform nomenclature and to the standardisation of the assessment tools. Our primary objective was to develop a Geriatric Minimum Data Set (GMDS) for clinical research.

The Utility of Fractional Exhaled Nitric Oxide Suppression in the Identification of Nonadherence in Difficult Asthma

Rationale: Nonadherence to inhaled corticosteroid therapy (ICS) is a major contributor to poor control in difficult asthma, yet it is challenging to ascertain. Objectives: Identify a test for nonadherence using fractional exhaled nitric oxide (FENO) suppression after directly observed inhaled corticosteroid (DOICS) treatment. Methods: Difficult asthma patients with an elevated FENO (>45 ppb) were recruited as adherent (ICS prescription filling >80%) or nonadherent (filling <50%). They received 7 days of DOICS (budesonide 1,600 µg) and a test for nonadherence based on changes in FENO was developed. Using this test, clinic patients were prospectively classified as adherent or nonadherent and this was then validated against prescription filling records, prednisolone assay, and concordance interview. Measurements and Main Results: After 7 days of DOICS nonadherent (n = 9) compared with adherent subjects (n = 13) had a greater reduction in FENO to 47 ± 21% versus 79 ± 26% of baseline measurement (P = 0.003), which was also evident after 5 days (P = 0.02) and a FENO test for nonadherence (area under the curve = 0.86; 95% confidence interval, 0.68-1.00) was defined. Prospective validation in 40 subjects found the test identified 13 as nonadherent; eight confirmed nonadherence during interview (three of whom had excellent prescription filling but did not take medication), five denied nonadherence, two had poor inhaler technique (unintentional nonadherence), and one also denied nonadherence to prednisolone despite nonadherent blood level. Twenty-seven participants were adherent on testing, which was confirmed in 21. Five admitted poor ICS adherence but of these, four were adherent with oral steroids and one with omalizumab. Conclusions: FENO suppression after DOICS provides an objective test to distinguish adherent from nonadherent patients with difficult asthma. Clinical trial registered with www.clinicaltrials.gov (NCT 01219036). Copyright © 2012 by the American Thoracic Society.

The role of regret minimisation in lifestyle choices affecting the risk of coronary heart disease

This paper introduces the discrete choice model-paradigm of Random Regret Minimisation (RRM) to the field of health economics. The RRM is a regret-based model that explores a driver of choice different from the traditional utility-based Random Utility Maximisation (RUM). The RRM approach is based on the idea that, when choosing, individuals aim to minimise their regret–regret being defined as what one experiences when a non-chosen alternative in a choice set performs better than a chosen one in relation to one or more attributes. Analysing data from a discrete choice experiment on diet, physical activity and risk of a fatal heart attack in the next ten years administered to a sample of the Northern Ireland population, we find that the combined use of RUM and RRM models offer additional information, providing useful behavioural insights for better informed policy appraisal.

Smart meter devices and the effect of feedback on residential electricity consumption: Evidence from a natural experiment in Northern Ireland

Using a unique set of data and exploiting a large-scale natural experiment, we estimate the effect of real-time usage information on residential electricity consumption in Northern Ireland. Starting in April 2002, the utility replaced prepayment meters with advanced meters that allow the consumer to track usage in real-time. We rely on this event, account for the endogeneity of price and payment plan with consumption through a plan selection correction term, and find that the provision of information is associated with a decline in electricity consumption of 11-17%. We find that the reduction is robust to different specifications, selection-bias correction methods and subsamples of the original data. The advanced metering program delivers reasonably cost-effective reductions in carbon dioxide emissions, even under the most conservative usage reduction scenarios.

Which is the Only Game in Town? Minority Rights Issues in Estonia and Slovakia During and after EU Accession:Perspectives on European Politics and Society

Post-communist transition went hand in hand with the European integration process. Much of the literature on EU accession focuses on the rational decision to implement a set of European norms into domestic legislation pre-accession. It is often concluded that once EU membership is achieved, states succumb their rationality and act on the basis of internalised norms. The paper claims that the past literature overlooks the wider framework within which policy-makers operate before and after the accession, namely domestic sovereignty over policy-making and implementation. Tracing the policy dynamics in the area of minority rights in Estonia and Slovakia, we demonstrate that the European integration ushered greater domestic control over policy implementation on minority issues in two states exposed to a heavy dose of conditionality. As we observe, both states have consolidated their state- and nation-building policies referencing EU conditionality in the course of accession and later EU membership to assert centrality of domestic objectives for policy-making and implementation.

Levels and patterns of population genetic diversity in the red seaweed Chondrus crispus (Florideophyceae): a direct comparison of single nucleotide polymorphisms and microsatellites

Single nucleotide polymorphisms (SNPs) are predicted to supersede microsatellites as the marker of choice for population genetic studies in the near future. To date, however, very few studies have directly compared both marker systems in natural populations, particularly in non-model organisms. In the present study, we compared the utility of SNPs and microsatellites for population genetic analysis of the red seaweed Chondrus crispus (Florideophyceae). Six SNP loci yielded very different patterns of intrapopulation genetic diversity compared to those obtained using seven moderately (mean 5.2 alleles) polymorphic microsatellite loci, although Bayesian clustering analysis gave largely congruent results between the two marker classes. A weak but significant pattern of isolation-by-distance was observed across scales from a few hundred metres to approximately 200?km using the combined SNP and microsatellite data set of 13 loci. Over larger scales, however, there was little correlation between genetic divergence and geographical distance. Our findings suggest that even a moderate number of SNPs is sufficient to determine patterns of genetic diversity across natural populations, and also highlight the fact that patterns of genetic variation in seaweeds arise through a complex interplay of short- and long-term natural processes, as well as anthropogenic influence.

Production and evaluation of the utility of novel phage display-derived peptide ligands to Salmonella spp. for magnetic separation

Aims: The objectives of this study were to produce Salmonella-specific peptide ligands by phage display biopanning and evaluate their use for magnetic separation (MS).
Methods and Results: Four phage display biopanning rounds were performed and the peptides expressed by the two most Salmonella-specific (on the basis of phage binding ELISA results) phage clones, MSal020401 and MSal020417, were chemically synthesized and coupled to MyOne™ tosylactivated Dynabeads®. Peptide capture capability for whole Salmonella cells from non-enriched broth cultures was quantified by MS + plate counts and MS + Greenlight™ detection, and compared to capture capability of anti-Salmonella (antibody-coated) Dynabeads®. MS + Greenlight™ gave a more comprehensive picture of capture capability than MS + plate counts and showed that Peptide MSal020417-coated beads exhibited at least similar, if not better, capture capability to anti-Salmonella Dynabeads® (mean capture values of 36.0 ± 18.2 % and 31.2 ± 20.1 %, respectively, over Salmonella spp. concentration range 3 x 101 - 3 x 106 cfu ml-1) with minimal cross-reactivity (= 1.9 %) to three other foodborne bacteria.
Conclusions: One of the phage display-derived peptide ligands was demonstrated by MS + Greenlight™ to be a viable antibody-alternative for MS of Salmonella spp.
Significance and Impact of Study: This study demonstrates an antibody-free approach to Salmonella detection and opens substantial possibilities for more rapid tests for this bacterium.

Ensuring the statistical soundness of competitive gene set approaches: gene filtering and genome-scale coverage are essential

In this article, we focus on the analysis of competitive gene set methods for detecting the statistical significance of pathways from gene expression data. Our main result is to demonstrate that some of the most frequently used gene set methods, GSEA, GSEArot and GAGE, are severely influenced by the filtering of the data in a way that such an analysis is no longer reconcilable with the principles of statistical inference, rendering the obtained results in the worst case inexpressive. A possible consequence of this is that these methods can increase their power by the addition of unrelated data and noise. Our results are obtained within a bootstrapping framework that allows a rigorous assessment of the robustness of results and enables power estimates. Our results indicate that when using competitive gene set methods, it is imperative to apply a stringent gene filtering criterion. However, even when genes are filtered appropriately, for gene expression data from chips that do not provide a genome-scale coverage of the expression values of all mRNAs, this is not enough for GSEA, GSEArot and GAGE to ensure the statistical soundness of the applied procedure. For this reason, for biomedical and clinical studies, we strongly advice not to use GSEA, GSEArot and GAGE for such data sets.

Testate amoebae (thecamoebians) as water quality indicators in lakes: development of a modern distributional dataset from the Greater Toronto Area

Thecamoebians were examined from 123 surface sediment samples collected from 45 lakes in the Greater Toronto Area (GTA) and the surrounding region to i) elucidate the controls on faunal distribution in modern lake environments; and ii) to consider the utility of thecamoebians in quantitative studies of water quality change. This area was chosen because it includes a high density of lakes that are threatened by urban development and where water quality has deteriorated locally as a result of contaminant inputs, particularly nutrients. Canonical Correspondence analysis (CCA) and a series of partial CCAs were used to examine species-environment relationships. Twenty-four environmental variables were considered, including water properties (e.g. pH, DO, conductivity), substrate characteristics, nutrient loading, and environmentally available metals. The thecamoebian assemblages showed a strong association with Olsen's Phosphorus, reflecting the eutrophic status of many of the lakes, and locally to elevated conductivity measurements, which appear to reflect road salt inputs associated with winter de-icing operations. A transfer function was developed for Olsen P using this training set based on weighted averaging with inverse deshrinking (WA Inv). The model was applied to infer past changes in Phosphorus enrichment in core samples from several lakes, including eutrophic Haynes Lake within the GTA. Thecamoebian-inferred changes in sedimentary Phosphorus from a 210Pb dated core from Haynes Lake are related to i) widespread introduction of chemical fertilizers to agricultural land in the post WWII era; ii) a steep decline in Phosphorous with a change in agricultural practices in the late 1970s; and iii) the construction of a golf course in close proximity to the lake in the early 1990s. This preliminary study confirms that thecamoebians have considerable potential as indicators of eutrophication in lakes and can provide an estimate of baseline conditions.

Developing the specifications of an open angle glaucoma screening intervention in the United Kingdom: a Delphi approach.

Abstract
BACKGROUND:
Glaucoma is a leading cause of blindness. Early detection is advocated but there is insufficient evidence from randomized controlled trials (RCTs) to inform health policy on population screening. Primarily, there is no agreed screening intervention. For a screening programme, agreement is required on the screening tests to be used, either individually or in combination, the person to deliver the test and the location where testing should take place. This study aimed to use ophthalmologists (who were experienced glaucoma subspecialists), optometrists, ophthalmic nurses and patients to develop a reduced set of potential screening tests and testing arrangements that could then be explored in depth in a further study of their feasibility for evaluation in a glaucoma screening RCT.
METHODS:
A two-round Delphi survey involving 38 participants was conducted. Materials were developed from a prior evidence synthesis. For round one, after some initial priming questions in four domains, specialists were asked to nominate three screening interventions, the intervention being a combination of the four domains; target population, (age and higher risk groups), site, screening test and test operator (provider). More than 250 screening interventions were identified. For round two, responses were condensed into 72 interventions and each was rated by participants on a 0-10 scale in terms of feasibility.
RESULTS:
Using a cut-off of a median rating of feasibility of =5.5 as evidence of agreement of intervention feasibility, six interventions were identified from round 2. These were initiating screening at age 50, with a combination of two or three screening tests (varying combinations of tonometry/measures of visual function/optic nerve damage) organized in a community setting with an ophthalmic trained technical assistant delivering the tests. An alternative intervention was a 'glaucoma risk score' ascertained by questionnaire. The advisory panel recommended that further exploration of the feasibility of screening higher risk populations and detailed specification of the screening tests was required.
CONCLUSIONS:
With systematic use of expert opinions, a shortlist of potential screening interventions was identified. Views of users, service providers and cost-effectiveness modeling are now required to identify a feasible intervention to evaluate in a future glaucoma screening trial.