Systematic identification of small molecule adjuvants

Introduction: Adjuvants potentiate immune responses, reducing the amount and dosing frequency of antigen required for inducing protective immunity. Adjuvants are of special importance when considering subunit, epitope-based or more unusual vaccine formulations lacking significant innate immunogenicity. While numerous adjuvants are known, only a few are licensed for human use; principally alum, and squalene-based oil-in-water adjuvants. Alum, the most commonly used, is suboptimal. There are many varieties of adjuvant: proteins, oligonucleotides, drug-like small molecules and liposome-based delivery systems with intrinsic adjuvant activity being perhaps the most prominent. Areas covered: This article focuses on small molecules acting as adjuvants, with the author reviewing their current status while highlighting their potential for systematic discovery and rational optimisation. Known small molecule adjuvants (SMAs) can be synthetically complex natural products, small oligonucleotides or drug-like synthetic molecules. The author provides examples of each class, discussing adjuvant mechanisms relevant to SMAs, and exploring the high-throughput discovery of SMAs. Expert opinion: SMAs, particularly synthetic drug-like adjuvants, are amenable to the plethora of drug-discovery techniques able to optimise the properties of biologically active small molecules. These range from laborious synthetic modifications to modern, rational, effort-efficient computational approaches, such as QSAR and structure-based drug design. In principal, any property or characteristic can thus be designed in or out of compounds, allowing us to tailor SMAs to specific biological functions, such as targeting specific cells or pathways, in turn affording the power to tailor SMAs to better address different diseases.

State-of-the-art in lean design engineering:a literature review on white collar lean

Lean is usually associated with the ‘operations’ of a manufacturing enterprise; however, there is a growing awareness that these principles may be transferred readily to other functions and sectors. The application to knowledge-based activities such as engineering design is of particular relevance to UK plc. Hence, the purpose of this study has been to establish the state-of-the-art, in terms of the adoption of Lean in new product development, by carrying out a systematic review of the literature. The authors' findings confirm the view that Lean can be applied beneficially away from the factory; that an understanding and definition of value is key to success; that a set-based (or Toyota methodology) approach to design is favoured together with the strong leadership of a chief engineer; and that the successful implementation requires organization-wide changes to systems, practices, and behaviour. On this basis it is felt that this review paper provides a useful platform for further research in this topic.

Reducing the risk of sexually transmitted infections in genitourinary medicine clinic patients:A systematic review and meta-analysis of behavioural interventions

Objectives: Are behavioural interventions effective in reducing the rate of sexually transmitted infections (STIs) among genitourinary medicine (GUM) clinic patients? Design: Systematic review and meta-analysis of published articles. Data sources: Medline, CINAHL, Embase, PsychINFO, Applied Social Sciences Index and Abstracts, Cochrane Library Controlled Clinical Trials Register, National Research Register (1966 to January 2004). Review methods: Randomised controlled trials of behavioural interventions in sexual health clinic patients were included if they reported change to STI rates or self reported sexual behaviour. Trial quality was assessed using the Jadad score and results pooled using random effects meta-analyses where outcomes were consistent across studies. Results: 14 trials were included; 12 based in the United States. Experimental interventions were heterogeneous and most control interventions were more structured than typical UK care. Eight trials reported data on laboratory confirmed infections, of which four observed a greater reduction in their intervention groups (in two cases this result was statistically significant, p<0.05). Seven trials reported consistent condom use, of which six observed a greater increase among their intervention subjects. Results for other measures of sexual behaviour were inconsistent. Success in reducing STIs was related to trial quality, use of social cognition models, and formative research in the target population. However, effectiveness was not related to intervention format or length. Conclusions: While results were heterogeneous, several trials observed reductions in STI rates. The most effective interventions were developed through extensive formative research. These findings should encourage further research in the United Kingdom where new approaches to preventing STIs are urgently required.

Creating a culture for critical and situated technology use through effective learning design

The purpose of this concise paper is to propose, with evidence gathered through a systematic evaluation of an academic development programme in the UK, that training in the use of new and emerging learning technologies should be holistically embedded in every learning and training opportunity in learning, teaching and assessment in higher education, and not only as stand-alone modules or one-off opportunities. The future of learning in higher education cannot afford to allow Universities to disregard that digital literacy is an expected professional skill for their entire staff.

Effectiveness and uptake of screening programmes for coronary heart disease and diabetes:a realist review of design components used in interventions

Objective - To evaluate behavioural components and strategies associated with increased uptake and effectiveness of screening for coronary heart disease and diabetes with an implementation science focus. Design - Realist review. Data sources - PubMed, Web of Knowledge, Cochrane Database of Systematic Reviews, Cochrane Controlled Trials Register and reference chaining. Searches limited to English language studies published since 1990. Eligibility criteria - Eligible studies evaluated interventions designed to increase the uptake of cardiovascular disease (CVD) and diabetes screening and examined behavioural and/or strategic designs. Studies were excluded if they evaluated changes in risk factors or cost-effectiveness only. Results - In 12 eligible studies, several different intervention designs and evidence-based strategies were evaluated. Salient themes were effects of feedback on behaviour change or benefits of health dialogues over simple feedback. Studies provide mixed evidence about the benefits of these intervention constituents, which are suggested to be situation and design specific, broadly supporting their use, but highlighting concerns about the fidelity of intervention delivery, raising implementation science issues. Three studies examined the effects of informed choice or loss versus gain frame invitations, finding no effect on screening uptake but highlighting opportunistic screening as being more successful for recruiting higher CVD and diabetes risk patients than an invitation letter, with no differences in outcomes once recruited. Two studies examined differences between attenders and non-attenders, finding higher risk factors among non-attenders and higher diagnosed CVD and diabetes among those who later dropped out of longitudinal studies. Conclusions - If the risk and prevalence of these diseases are to be reduced, interventions must take into account what we know about effective health behaviour change mechanisms, monitor delivery by trained professionals and examine the possibility of tailoring programmes according to contexts such as risk level to reach those most in need. Further research is needed to determine the best strategies for lifelong approaches to screening.

The servitization of manufacturing:a systematic literature review of interdependent trends

Purpose: The servitization of manufacturing is a diverse and complex field of research interest. The purpose of this paper is to provide an integrative and organising lens for viewing the various contributions to knowledge production from those research communities addressing servitization. To achieve this, the paper aims to set out to address two principal questions, namely where are the knowledge stocks and flows amongst the research communities? And what are generic research concerns being addressed by these communities? Design/methodology/approach: Using an evidenced-based approach, the authors have performed a systematic review of the research literature associated with the servitization of manufacturing. This investigation incorporates a descriptive and thematic analysis of 148 academic and scholarly papers from 103 different lead authors in 68 international peer-reviewed journals. Findings: The work proposes support for the existence of distinct researcher communities, namely services marketing, service management, operations management, product-service systems and service science management and engineering, which are contributing to knowledge production in the servitization of manufacturing. Knowledge stocks within all communities associated with research in the servitization of manufacturing have dramatically increased since the mid-1990s. The trends clearly reveal that the operations community is in receipt of the majority of citations relating to the servitization of manufacturing. In terms of knowledge flows, it is apparent that the more mature communities are drawing on more locally produced knowledge stocks, whereas the emergent communities are drawing on a knowledge base more evenly distributed across all the communities. The results are indicative of varying degrees of interdependency amongst the communities. The generic research concerns being addressed within the communities are associated with the concepts of product-service differentiation, competitive strategy, customer value, customer relationships and product-service configuration. Originality/value: This research has further developed and articulated the identities of distinct researcher communities actively contributing to knowledge production in the servitization of manufacturing, and to what extent they are pursuing common research agendas. This study provides an improved descriptive and thematic awareness of the resulting body of knowledge, allowing the field of servitization to progress in a more informed and multidisciplinary fashion. © Emerald Group Publishing Limited.

Quality of life instruments in studies of menorrhagia: a systematic review

BACKGROUND: The use of quality of life (QoL) instruments in menorrhagia research is increasing but there is concern that not enough emphasis is placed on patient-focus in these measurements, i.e. on issues which are of importance to patients and reflect their experiences and concerns (clinical face validity). The objective was to assess the quality of QoL instruments in studies of menorrhagia. STUDY DESIGN: A systematic review of published research. Papers were identified through MEDLINE (1966-April 2000), EMBASE (1980-April 2000), Science Citation Index (1981-April 2000), Social Science Citation Index (1981-April 2000), CINAHL (1982-1999) and PsychLIT (1966-1999), and by manual searching of bibliographies of known primary and review articles. Studies were selected if they assessed women with menorrhagia for life quality, either developing QoL instruments or applying them as an outcome measure. Selected studies were assessed for quality of their QoL instruments, using a 17 items checklist including 10 items for clinical face validity (issues of relevance to patients' expectations and concerns) and 7 items for measurement properties (such as reliability, responsiveness, etc.). RESULTS: A total of 19 articles, 8 on instrument development and 11 on application, were included in the review. The generic Short Form 36 Health Survey Questionnaire (SF36) was used in 12/19 (63%) studies. Only two studies developed new specific QoL instruments for menorrhagia but they complied with 7/17 (41%) and 10/17 (59%) of the quality criteria. Quality assessment showed that only 7/19 (37%) studies complied with more than half the criteria for face validity whereas 17/19 (90%) studies complied with more than half of the criteria for measurement properties (P = 0.0001). CONCLUSION: Among existing QoL instruments, there is good compliance with the quality criteria for measurement properties but not with those for clinical face validity. There is a need to develop methodologically sound disease specific QoL instruments in menorrhagia focussing both on face validity and measurement properties.

Medication errors in mental healthcare:a systematic review

Methods: It has been estimated that medication error harms 1-2% of patients admitted to general hospitals. There has been no previous systematic review of the incidence, cause or type of medication error in mental healthcare services. Methods: A systematic literature search for studies that examined the incidence or cause of medication error in one or more stage(s) of the medication-management process in the setting of a community or hospital-based mental healthcare service was undertaken. The results in the context of the design of the study and the denominator used were examined. Results: All studies examined medication management processes, as opposed to outcomes. The reported rate of error was highest in studies that retrospectively examined drug charts, intermediate in those that relied on reporting by pharmacists to identify error and lowest in those that relied on organisational incident reporting systems. Only a few of the errors identified by the studies caused actual harm, mostly because they were detected and remedial action was taken before the patient received the drug. The focus of the research was on inpatients and prescriptions dispensed by mental health pharmacists. Conclusion: Research about medication error in mental healthcare is limited. In particular, very little is known about the incidence of error in non-hospital settings or about the harm caused by it. Evidence is available from other sources that a substantial number of adverse drug events are caused by psychotropic drugs. Some of these are preventable and might probably, therefore, be due to medication error. On the basis of this and features of the organisation of mental healthcare that might predispose to medication error, priorities for future research are suggested.

Systematic review investigating the reporting of comorbidities and medication in randomized controlled trials of people with dementia

Objectives: dementia is a debilitating condition characterised by global loss of cognitive and intellectual functioning, which reduces social and occupational performance. This population frequently presents with medical co-morbidities such as hypertension, cardiovascular disease and diabetes. The CONSORT statement outlines recommended guidance on reporting of participant characteristics in clinical trials. It is, however, unclear how much these are adhered to in trials assessing people with dementia. This paper assesses the reporting of medical co-morbidities and prescribed medications for people with dementia within randomised controlled trial (RCT) reports. Design: a systematic review of the published literature from the databases AMED, CINAHL, MEDLINE, EMBASE and the Cochrane Clinical Trial Registry from 1 January 1997 to 9 January 2014 was undertaken in order to identify RCTs detailing baseline medical co-morbidities and prescribed medications . Eligible studies were appraised using the Critical Appraisal Skills Programme (CASP) RCT appraisal tool, and descriptive statistical analyses were calculated to determine point prevalence. Results: nine trials, including 1474 people with dementia, were identified presenting medical co-morbidity data. These indicated neurological disorders ( prevalence 91%), vascular disorders (prevalence 91%), cardiac disorders ( prevalence 74%) and ischaemic cerebrovascular disease ( prevalence 53%) were most frequently seen. Conclusions: published RCTs poorly report medical co-morbidities and medications for people with dementia. Future trials should include the report of these items to allow interpretation of whether the results are generalisable to frailer older populations.

Effect of medications with anti-cholinergic properties on cognitive function, delirium, physical function and mortality:a systematic review

Objectives: to determine the effect of drugs with anti-cholinergic properties on relevant health outcomes.Design: electronic published and unpublished literature/trial registries were systematically reviewed. Studies evaluating medications with anti-cholinergic activity on cognitive function, delirium, physical function or mortality were eligible.Results: forty-six studies including 60,944 participants were included. Seventy-seven percent of included studies evaluating cognitive function (n = 33) reported a significant decline in cognitive ability with increasing anti-cholinergic load (P < 0.05). Four of five included studies reported no association with delirium and increasing anti-cholinergic drug load (P > 0.05). Five of the eight included studies reported a decline in physical function in users of anti-cholinergics (P < 0.05). Three of nine studies evaluating mortality reported that the use of drugs with anti-cholinergic properties was associated with a trend towards increased mortality, but this was not statistically significant. The methodological quality of the evidence-base ranged from poor to very good.Conclusion: medicines with anti-cholinergic properties have a significant adverse effect on cognitive and physical function, but limited evidence exists for delirium or mortality outcomes. © The Author 2014. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved.

Using a systems approach in logistics design and planning

The international economic and business environment continues to develop at a rapid rate. Increasing interactions between economies, particularly between Europe and Asia, has raised many important issues regarding transport infrastructure, logistics and broader supply chain management. The potential exists to further stimulate trade provided that these issues are addressed in a logical and systematic manner. However, if this potential is to be realised in practice there is a need to re-evaluate current supply chain configurations. A mismatch currently exists between the technological capability and the supply chain or logistical reality. This mismatch has sharpened the focus on the need for robust approaches to supply chain re-engineering. Traditional approaches to business re-engineering have been based on manufacturing systems engineering and business process management. A recognition that all companies exist as part of bigger supply chains has fundamentally changed the focus of re-engineering. Inefficiencies anywhere in a supply chain result in the chain as a whole being unable to reach its true competitive potential. This reality, combined with the potentially radical impact on business and supply chain architectures of the technologies associated with electronic business, requires organisations to adopt innovative approaches to supply chain analysis and re-design. This paper introduces a systems approach to supply chain re-engineering which is aimed at addressing the challenges which the evolving business environment brings with it. The approach, which is based on work with a variety of both conventional and electronic supply chains, comprises underpinning principles, a methodology and guidelines on good working practice, as well as a suite of tools and techniques. The adoption of approaches such as that outlined in this paper helps to ensure that robust supply chains are designed and implemented in practice. This facilitates an integrated approach, with involvement of all key stakeholders throughout the design process.

Interoperability of Cross-Border European Egovernment Services: Some Design Issues

The authors analyse some of the research outcomes achieved during the implementation of the EC GUIDE research project “Creating an European Identity Management Architecture for eGovernment”, as well as their personal experience. The project goals and achievements are however considered in a broader context. The key role of Identity in the Information Society was emphasised, that the research and development in this field is in its initial phase. The scope of research related to Identity, including the one related to Identity Management and Interoperability of Identity Management Systems, is expected to be further extended. The authors analyse the abovementioned issues in the context established by the EC European Interoperability Framework (EIF) as a reference document on interoperability for the Interoperable Delivery of European eGovernment Services to Public Administrations, Business and Citizens (IDABC) Work Programme. This programme aims at supporting the pan-European delivery of electronic government services.

Systematic financial resources allocation processes:a model for critical resources mobilization and deployment for nigerian universities

Purpose – The purpose of this research is to study the perceived impact of some factors on the resources allocation processes of the Nigerian universities and to suggest a framework that will help practitioners and academics to understand and improve such processes. Design/methodology/approach – The study adopted the interpretive qualitative approach aimed at an ‘in-depth’ understanding of the resource allocation experiences of key university personnel and their perceived impact of the contextual factors affecting such processes. The analysis of individual narratives from each university established the conditions and factors impacting the resources allocation processes within each institution. Findings – The resources allocation process issues in the Nigerian universities may be categorised into people (core and peripheral units’ challenge, and politics and power); process (resources allocation processes); and resources (critical financial shortage and resources dependence response). The study also provides insight that resourcing efficiency in Nigerian universities appears strongly constrained by the rivalry among the resource managers. The efficient resources allocation process (ERAP) model is proposed to resolve the identified resourcing deficiencies. Research limitations/implications – The research is not focused to provide generalizable observations but ‘in-depth’ perceived factors and their impact on the resources allocation processes in Nigerian universities. The study is limited to the internal resources allocation issues within the universities and excludes the external funding factors. The resource managers’ responses to the identified factors may affect their internal resourcing efficiency. Further research using more empirical samples is required to obtain more widespread results and the implications for all universities. Originality/value – This study contributes a fresh literature framework to resources allocation processes focusing at ‘people’, ‘process’ and ‘resources’. Also a middle range theory triangulation is developed in relation to better understanding of resourcing process management. The study will be of interest to university managers and policy makers.

The design of contact lens based ocular drug delivery systems for single-day use:part (I) structural factors, surrogate ophthalmic dyes and passive diffusion studies

The poor retention and efficacy of instilled drops as a means of delivering drugs to the ophthalmic environment is well-recognised. The potential value of contact lenses as a means of ophthalmic drug delivery, and consequent improvement of pre-corneal retention is one obvious route to the development of a more effective ocular delivery system. Furthermore, the increasing availability and clinical use of daily disposable contact lenses provides the platform for the development of viable single-day use drug delivery devices based on existing materials and lenses. In order to provide a basis for the effective design of such devices, a systematic understanding of the factors affecting the interaction of individual drugs with the lens matrix is required. Because a large number of potential structural variables are involved, it is necessary to achieve some rationalisation of the parameters and physicochemical properties (such as molecular weight, charge, partition coefficients) that influence drug interactions. Ophthalmic dyes and structurally related compounds based on the same core structure were used to investigate these various factors and the way in which they can be used in concert to design effective release systems for structurally different drugs. Initial studies of passive diffusional release form a necessary precursor to the investigation of the features of the ocular environment that over-ride this simple behaviour. Commercially available contact lenses of differing structural classifications were used to study factors affecting the uptake of the surrogate actives and their release under 'passive' conditions. The interaction between active and lens material shows considerable and complex structure dependence, which is not simply related to equilibrium water content. The structure of the polymer matrix itself was found to have the dominant controlling influence on active uptake; hydrophobic interaction with the ophthalmic dye playing a major role. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Implementation of a machine tool performance measurement and diagnostic system and its impact on parts verification

Five axis machine tools are increasing and becoming more popular as customers demand more complex machined parts. In high value manufacturing, the importance of machine tools in producing high accuracy products is essential. High accuracy manufacturing requires producing parts in a repeatable manner and precision in compliance to the defined design specifications. The performance of the machine tools is often affected by geometrical errors due to a variety of causes including incorrect tool offsets, errors in the centres of rotation and thermal growth. As a consequence, it can be difficult to produce highly accurate parts consistently. It is, therefore, essential to ensure that machine tools are verified in terms of their geometric and positioning accuracy. When machine tools are verified in terms of their accuracy, the resulting numerical values of positional accuracy and process capability can be used to define design for verification rules and algorithms so that machined parts can be easily produced without scrap and little or no after process measurement. In this paper the benefits of machine tool verification are listed and a case study is used to demonstrate the implementation of robust machine tool performance measurement and diagnostics using a ballbar system.