Pharmaceutical strategies towards optimising polypharmacy in older people

This paper focuses on the issue of polypharmacy in older people and potential pharmaceutical strategies to optimize the use of multiple medicines. Although polypharmacy has long been viewed negatively, increasing emphasis is being placed on the difference between appropriate and inappropriate polypharmacy. This is largely being driven by the increasing prevalence of multimorbidity and the use of evidence-based guidelines. In this paper, we outline a number of key considerations that are pertinent to optimizing polypharmacy, notably prescribing appropriate polypharmacy, pharmaceutical formulations, the involvement of older people in clinical trials and patient adherence.

Optimising power take-off of an oscillating wave surge converter using high fidelity numerical simulations

Oscillating wave surge converters are a promising technology to harvest ocean wave energy in the near shore region. Although research has been going on for many years, the characteristics of the wave action on the structure and especially the phase relation between the driving force and wave quantities like velocity or surface elevation have not been investigated in detail. The main reason for this is the lack of suitable methods. Experimental investigations using tank tests do not give direct access to overall hydrodynamic loads, only damping torque of a power take off system can be measured directly. Non-linear computational fluid dynamics methods have only recently been applied in the research of this type of devices. This paper presents a new metric named wave torque, which is the total hydrodynamic torque minus the still water pitch stiffness at any given angle of rotation. Changes in characteristics of that metric over a wave cycle and for different power take off settings are investigated using computational fluid dynamics methods. Firstly, it is shown that linearised methods cannot predict optimum damping in typical operating states of OWSCs. We then present phase relationships between main kinetic parameters for different damping levels. Although the flap seems to operate close to resonance, as predicted by linear theory, no obvious condition defining optimum damping is found.

Coupled Temperature-Displacement Modelling of Injection Stretch Blow Moulding of PET bottles using Buckley Model

This study presents a fully coupled temperature–displacement finite element modelling of the injection stretch-blow moulding (ISBM) process of polyethylene terephthalate (PET) bottles using ABAQUS with a view to optimising the process conditions. A physically-based material model (Buckley model) was used to predict the mechanical behaviour of PET at temperatures slightly above its glass transition temperature. A model incorporating heat transfer between the stretch rod, the preform and the mould was built using axisymmetric solid elements. Extensive finite element analyses were carried out to predict the deformation, the distribution and history of strain and temperature during ISBM of a 20 g–330 ml bottle, which was made in an in situ test on a Sidel SB06 machine. Comparisons of numerical results with the measurements demonstrate that the model can satisfactorily model the sidewall thickness and material distributions. It is also shown that significant non-linear differentials exist in temperature and strain in both bottle thickness and length directions during the process. This justifies the employment of a volume approach to accurately predict the final mechanical properties of the bottles governed by the orientation and crystallinity which are highly temperature and strain dependent.

The contribution of qualitative research in designing a complex intervention for secondary prevention of coronary heart disease in two different healthcare systems

Background: Developing complex interventions for testing in randomised controlled trials is of increasing importance in healthcare planning. There is a need for careful design of interventions for secondary prevention of coronary heart disease (CHD). It has been suggested that integrating qualitative research in the development of a complex intervention may contribute to optimising its design but there is limited evidence of this in practice. This study aims to examine the contribution of qualitative research in developing a complex intervention to improve the provision and uptake of secondary prevention of CHD within primary care in two different healthcare systems.

Methods: In four general practices, one rural and one urban, in Northern Ireland and the Republic of Ireland, patients with CHD were purposively selected. Four focus groups with patients (N = 23) and four with staff (N = 29) informed the development of the intervention by exploring how it could be tailored and integrated with current secondary prevention activities for CHD in the two healthcare settings. Following an exploratory trial the acceptability and feasibility of the intervention were discussed in four focus groups (17 patients) and 10 interviews (staff). The data were analysed using thematic analysis.

Results: Integrating qualitative research into the development of the intervention provided depth of information about the varying impact, between the two healthcare systems, of different funding and administrative arrangements, on their provision of secondary prevention and identified similar barriers of time constraints, training needs and poor patient motivation. The findings also highlighted the importance to patients of stress management, the need for which had been underestimated by the researchers. The qualitative evaluation provided depth of detail not found in evaluation questionnaires. It highlighted how the intervention needed to be more practical by minimising administration, integrating role plays into behaviour change training, providing more practical information about stress management and removing self-monitoring of lifestyle change.

Conclusion: Qualitative research is integral to developing the design detail of a complex intervention and tailoring its components to address individuals' needs in different healthcare systems. The findings highlight how qualitative research may be a valuable component of the preparation for complex interventions and their evaluation.

Probabilistic program analysis for parallelizing compilers

Parallelizing compilers have difficulty analysing and optimising complex code. To address this, some analysis may be delayed until run-time, and techniques such as speculative execution used. Furthermore, to enhance performance, a feedback loop may be setup between the compile time and run-time analysis systems, as in iterative compilation. To extend this, it is proposed that the run-time analysis collects information about the values of variables not already determined, and estimates a probability measure for the sampled values. These measures may be used to guide optimisations in further analyses of the program. To address the problem of variables with measures as values, this paper also presents an outline of a novel combination of previous probabilistic denotational semantics models, applied to a simple imperative language.

A computational model for the cooling phase of injection moulding

This paper discusses the approaches and techniques used to build a realistic numerical model to analyse the cooling phase of the injection moulding process. The procedures employed to select an appropriate mesh and the boundary and initial conditions for the problem are discussed and justified. The final model is validated using direct comparisons with experimental results generated in an earlier study. The model is shown to be a useful tool for further studies aimed at optimising the cooling phase of the injection moulding process. Using the numerical model provides additional information relating to changes in conditions throughout the process, which otherwise could not be deduced or assessed experimentally. These results, and other benefits related to the use of the model, are also discussed in the paper. © 2007 Elsevier B.V. All rights reserved.

Pharmaceutical care of patients with gestational diabetes mellitus

Rationale, aims and objective To investigate whether the introduction of a programme of optimising drug treatment, intensive education and self-monitoring of patients diagnosed with gestational diabetes mellitus (GDM) at an early stage (

Molecular subtyping of breast cancer: Opportunities for new therapeutic approaches

Evidence is accumulating that breast cancer is not one disease but many separate diseases. DNA microarray-based gene expression profiling has demonstrated subtypes with distinct phenotypic features and clinical responses. Prominent among the new subtypes is 'basal-like' breast cancer, one of the 'intrinsic' subtypes defined by negativity for the estrogen, progesterone, and HER2/neu receptors and positivity for cytokeratins-5/6. Focusing on basal-like breast cancer, we discuss how molecular technologies provide new chemotherapy targets, optimising treatment whilst sparing patients from un-necessary toxicity. Clinical trials are needed that incorporate long-term follow-up of patients with well-characterised tumour markers. Whilst the absence of an obvious dominant oncogene driving basallike breast cancer and the lack of specific therapeutic agents are serious stumbling blocks, this review will highlight several promising therapeutic candidates currently under evaluation. Thus, new molecular technologies should provide a fundamental foundation for better understanding breast and other cancers which may be exploited to save lives.

Auditory sensory deficits in developmental dyslexia: A longitudinal ERP study

The core difficulty in developmental dyslexia across languages is a "phonological deficit", a specific difficulty with the neural representation of the sound structure of words. Recent data across languages suggest that this phonological deficit arises in part from inefficient auditory processing of the rate of change of the amplitude envelope at syllable onset (inefficient sensory processing of rise time). Rise time is a complex percept that also involves changes in duration and perceived intensity. Understanding the neural mechanisms that give rise to the phonological deficit in dyslexia is important for optimising educational interventions. In a three-deviant passive 'oddball' paradigm and a corresponding blocked 'deviant-alone' control condition we recorded ERPs to tones varying in rise time, duration and intensity in children with dyslexia and typically developing children longitudinally. We report here results from test Phases 1 and 2, when participants were aged 8-10. years. We found an MMN to duration, but not to rise time nor intensity deviants, at both time points for both groups. For rise time, duration and intensity we found group effects in both the Oddball and Blocked conditions. There was a slower fronto-central P1 response in the dyslexic group compared to controls. The amplitude of the P1 fronto-centrally to tones with slower rise times and lower intensity was smaller compared to tones with sharper rise times and higher intensity in the Oddball condition, for children with dyslexia only. The latency of this ERP component for all three stimuli was shorter on the right compared to the left hemisphere, only for the dyslexic group in the Blocked condition. Furthermore, we found decreased N1c amplitude to tones with slower rise times compared to tones with sharper rise times for children with dyslexia, only in the Oddball condition. Several other effects of stimulus type, age and laterality were also observed. Our data suggest that neuronal responses underlying some aspects of auditory sensory processing may be impaired in dyslexia. © 2011 Elsevier Inc.

Assessment of groundwater quality recovery strategies using nitrate transport modelling. Application to the Saône alluvial formations (Tournus, Saône-et-Loire)

To assess the efficiency of different agro-environmental strategies used to reduce groundwater pollution by nitrates, transport modelling in soils and groundwater has been carried out on two withdrawal areas in an alluvial plain. In a first time, the agro-environmental model AgriFlux allowed the simulation of water and nitrates fluxes flowing to groundwater. This model was calibrated for each agro-pedological unit of the studied territory. In a second time, the application of the hydrogeological model MODFLOW-MT3D allowed the simulation of nitrate transport in groundwater for the 1980-2004 period. This soil-groundwater coupled modelling has shown that soil nature is the first factor that conditions the vulnerability to nitrates. Thus, nitrate leaching occurs preferentially under sandy soils. Efficiency of different agro-environmental operations for groundwater quality recovery was quantified. The best results are obtained by combination of (1) grassland re-installation on sandy agricultural lots located in near well protection perimeter and (2) fertilization reduction on sandy agricultural lots located in the well alimentation area upstream the near protection perimeter. On other soils, the effect of grassland on groundwater quality improvement is more limited. Nevertheless, the control of nitrate fertilisation remains essential and is justified in both near and far well protection perimeters. Modelling thus allows optimising and priorizing agro-environmental actions in alluvial agricultural zones. [Comte J.-C., Banton O., Kockmann F., Villard A., Creuzot G. (2006), Assessment of groundwater quality recovery strategies using nitrate transport modelling. Application to the Saône alluvial formations (Tournus, Saône-et-Loire), Ingénieries Eau-Agriculture-Territoires, 45, 15-28]

The Paralax Infrastructure: Automatic Parallelization With a Helping Hand

Speeding up sequential programs on multicores is a challenging problem that is in urgent need of a solution. Automatic parallelization of irregular pointer-intensive codes, exempli?ed by the SPECint codes, is a very hard problem. This paper shows that, with a helping hand, such auto-parallelization is possible and fruitful. This paper makes the following contributions: (i) A compiler framework for extracting pipeline-like parallelism from outer program loops is presented. (ii) Using a light-weight programming model based on annotations, the programmer helps the compiler to ?nd thread-level parallelism. Each of the annotations speci?es only a small piece of semantic information that compiler analysis misses, e.g. stating that a variable is dead at a certain program point. The annotations are designed such that correctness is easily veri?ed. Furthermore, we present a tool for suggesting annotations to the programmer. (iii) The methodology is applied to autoparallelize several SPECint benchmarks. For the benchmark with most parallelism (hmmer), we obtain a scalable 7-fold speedup on an AMD quad-core dual processor. The annotations constitute a parallel programming model that relies extensively on a sequential program representation. Hereby, the complexity of debugging is not increased and it does not obscure the source code. These properties could prove valuable to increase the ef?ciency of parallel programming.

Automatic FPGA Synthesis of Memory Intensive C-based Kernels

Realising high performance image and signal processing
applications on modern FPGA presents a challenging implementation problem due to the large data frames streaming through these systems. Specifically, to meet the high bandwidth and data storage demands of these applications, complex hierarchical memory architectures must be manually specified
at the Register Transfer Level (RTL). Automated approaches which convert high-level operation descriptions, for instance in the form of C programs, to an FPGA architecture, are unable to automatically realise such architectures. This paper
presents a solution to this problem. It presents a compiler to automatically derive such memory architectures from a C program. By transforming the input C program to a unique dataflow modelling dialect, known as Valved Dataflow (VDF), a mapping and synthesis approach developed for this dialect can
be exploited to automatically create high performance image and video processing architectures. Memory intensive C kernels for Motion Estimation (CIF Frames at 30 fps), Matrix Multiplication (128x128 @ 500 iter/sec) and Sobel Edge Detection (720p @ 30 fps), which are unrealisable by current state-of-the-art C-based synthesis tools, are automatically derived from a C description of the algorithm.

Effect of increasing dietary folate on red-cell folate: Implications for prevention of neural tube defects

Background Recommendations by the UK Department of Health suggest that protection from neural tube defects (NTD) can be achieved through intakes of an extra 400 mu g daily of folate/folic acid as natural food, foods fortified with folic acid, or supplements. The assumption is that all three routes of intervention would have equal effects on folate status.

Methods We assessed the effectiveness of these suggested routes of intervention in optimising folate status. 62 women were recruited from the University staff and students to take part in a 3-month intervention study. Participants were randomly assigned to one of the following five groups: folic acid supplement (400 mu g/day; I); folic-acid-fortified foods (an additional 400 mu g/day; II); dietary folate (an additional 400 mu g/day; III); dietary advice (IV), and control (V). Responses to intervention were assessed as changes in red-cell folate between preintervention and postintervention values.

Findings 41 women completed the intervention study. Red-cell folate concentrations increased significantly over the 3 months in the groups taking folic acid supplements (group I) or food fortified with folic acid (group II) only (p<0.01 for both groups). By contrast, although aggressive intervention with dietary folate (group III) or dietary advice (group IV) significantly increased intake of food folate (p<0.001 and p<0.05, respectively), there was no significant change in folate status.

Interpretation We have shown that compared with supplements and fortified food, consumption of extra folate as natural food folate is relatively ineffective at increasing folate status. We believe that advice to women to consume folate-rich foods as a means to optimise folate status is misleading.

Automated design of DSP array processor chips

Details are presented of the DAC (DSP ASIC Compiler) silicon compiler framework. DAC allows a non-specialist to automatically design DSP ASICs and DSP ASIC cores directly form a high level specification. Typical designs take only several minutes and the resulting layouts are comparable in area and performance to handcrafted designs.