A variational approach to learning curves

We combine the replica approach from statistical physics with a variational approach to analyze learning curves analytically. We apply the method to Gaussian process regression. As a main result we derive approximative relations between empirical error measures, the generalization error and the posterior variance.

A review of barriers to kerbside recycling household waste in the UK

The aim of this work is to use systematic review methodology to answer the question “What are the current barriers to kerbside recycling of household waste in the UK?” A systematic search of electronic databases and journals was undertaken to identify academic published work. A critical scoping review of research published between 2000 – 2008 profiles theory and research design. The systematic review identified twelve relevant papers, of which seven contain original data. To define the current barriers the explanations of barriers were systematically aggregated into four main categories: household / individual behaviour; services / local situation; attitudes / motivation; information and knowledge. The purpose of the work is to inform future marketing campaigns which will assist the UK to reach the statutory targets of waste diversion. The synthesis will be useful to environmental professionals working in waste authorities and researchers and students. The framework offers an opportunity to develop better marketing and communications strategies to help more people recycle more things more often and will inform future recycling policy development.

Diversity and the perceived barriers to participation in volunteer activity by older people

The first chapter introduces the subject from a psychological and sociological perspective emphasising the basic human activity of helping those in need. Governmental prominence for policies that assist this activity is briefly discussed with special mention of the programmes that encourage volunteering. Programmes particularly directed at older people, such as the Age Concern ‘Debate of the Age’ are considered briefly. An extensive review of the extant literature is the subject of the second chapter. The pervious research is explored to discover the formulae used to define a volunteer. A definition relative to this research is created. Volunteering issues aggravated by the demographic situation of older people are explored. Empirical volunteer survey research by mutual organisations is explored to ascertain the extent and nature of the already recorded volunteer population. The penultimate section of this chapter investigates the nature of old age and the strategies that older people adopt to enjoy the benefits and contain the problems. The issue of diversity arises from consideration of the literature suggesting that, although it is an essential voluntary sector strength, it is also a further barrier to recruitment. A model diversity is proposed. Chapter three reviews the theoretical processes, procedures and technologies used to collect and analyse the data required to discover the answer to the research problem. Analysis of the questionnaire survey data received is the subject of chapter four. The discovery of the agency uniqueness of volunteer profiles is the principle finding of this part of the research. The fifth chapter is the qualitative analysis of the oral and written statements received. A content analysis of the scripts and texts provided rich data covering motivational factors. Motivational factors were the same for volunteers in the same organisation, but differed between organisations. Finally, the analysed data is collated and discussed progressively toward a theory of diversity. The individuality of each branch of each agency is progressively described culminating in the creation of a model that infers that diversity is a barrier that aggravates all other barriers. The personal realisations of the researcher are described.

Biological barriers to the nasal delivery of peptide drugs

The nasal absorption of larger peptide and protein drugs is generally low. The importance of the mucus layer and enzymic degradation in reducing absorption were investigated. Reversed-phase high-performance liquid chromatographic (HPLC) methods were developed to assay a variety of compounds. Pig gastric mucus (PGM) was selected to investigate the importance of the mucus layer. A method of treating and storing PGM was developed and evaluated which was representative of the gel in vivo. The nature of the mucus barrier was evaluated in vitro with three-compartment diffusion cells and a series of compounds with differing physicochemical properties. Mucus retarded the diffusion of all the compounds with molecular weight and charge exerting a marked effect. Binding to mucus was investigated by a centrifugation method. All of the compounds tested were found to bind to mucus with the exception of the negatively charged molecule benzoic acid. The small peptides did not demonstrate greater binding to mucus than any of the other compounds evaluated. The effect of some absorption enhancers upon the rate of diffusion of tryptophan through mucus was determined in vi tro. At the concentrations employed the enhancers EDTA, N-acetylcysteine and taurodeoxycholic acid exerted no effect, whilst taurocholic acid and cholic acid, were found to slightly reduce the rate of diffusion. The intracellular and luminal proteolytic activity of the nose was investigated in the sheep animal model with a nasal mucosal homogenate and a nasal wash preparation respectively and a series of chemically similar peptides. Hydrolysis was also investigated with the proteolytic enzymes carboxypeptidase A, cytosolic leucine aminopeptidase and microsomal leucine aminopeptidase. Sheep nasal mucosa possesses significant peptide hydrolase activity capable of degrading all the substrates tested. Considerable variation in susceptibility was observed. Degradation occurred excl us i ve ly at the pept ide bond between the aromatic amino ac id and glycine, indicating some specificity for aromatic amino acids. Hydrolysis profiles indicated the presence of both aminopeptidase and carboxypeptidase enzymes. The specific activity of the microsomal fraction was found to be greater than the cytosolic fraction. Hydrolysis in the nasal wash indicated the presence of either luminal or loosely-bound proteases, which can degrade peptide substrates. The same specificity for aromatic amino acids was observed and aminopeptidase activity demonstrated. The specific activity of the nasal wash was smaller than that of the homogenate.

The impact of ageing on the barriers to drug delivery

Generally, we like to see ageing as a process that is happening to people older than ourselves. However the process of ageing impacts on a wide range of functions within the human body. Whilst many of the outcomes of ageing can now be delayed or reduced, age-related changes in cellular, molecular and physiological functionality of tissues and organs can also influence how drugs enter, distribute and are eliminated from the body. Therefore, the changing profile of barriers to drug delivery should be considered if we are to develop more age-appropriate medicines. Changes in the drug dissolution and absorption in older patients may require the formulation of oral delivery systems that offer enhanced retention at absorption sites to improve drug delivery. Alternatively, liquid and fast-melt dosage systems may address the need of patients who have difficulties in swallowing medication. Ageing-induced changes in the lung can also result in slower drug absorption, which is further compounded by disease factors, common in an ageing population, that reduce lung capacity. In terms of barriers to drug delivery to the eye, the main consideration is the tear film, which like other barriers to drug delivery, changes with normal ageing and can impact on the bioavailability of drugs delivery using eye drops and suspensions. In contrast, whilst the skin as a barrier changes with age, no significant difference in absorption of drugs from transdermal drug delivery is observed in different age groups. However, due to the age-related pharmacokinetic and pharmacodynamic changes, dose adaptation should still be considered for drug delivery across the skin. Overall it is clear that the increasing age demographic of most populations, presents new (or should that be older) barriers to effective drug delivery. © 2012 Elsevier B.V. All rights reserved.

Paediatric 'care closer to home':stake-holder views and barriers to implementation

In this study we explore the views of NHS stakeholders on providing paediatric ‘care closer to home’ (CCTH), in community-based outpatient clinics delivered by consultants. Design: Semi-structured interviews and thematic framework analysis. Setting: UK specialist children's hospital and surrounding primary care trusts. Participants: 37 NHS stakeholders including healthcare professionals, managers, commissioners and executive team members. Results: Participants acknowledged that outreach clinics would involve a change in traditional ways of working and that the physical setting of the clinic would influence aspects of professional practice. Different models of CCTH were discussed, as were alternatives for improving access to specialist care. Participants supported CCTH as a good principle for paediatric outpatient services; however the challenges of setting up and maintaining community clinics meant they questioned how far it could be achieved in practice. Conclusions: The place of service delivery is both an issue of physical location and professional identity. Policy initiatives which ignore assumptions about place, power and identity are likely to meet with limited success.

Advancing age and bleeding risk are the strongest barriers to anticoagulant prescription in atrial fibrillation

In clinical practice many patients with atrial fibrillation (AF) at high thromboembolic risk fail to receive adequate oral anticoagulation (OAC) [1]. The complex management of anticoagulant therapy [frequent international normalised ratio (INR) monitoring because of narrow therapeutic window, interaction with food and alcohol, concomitant medications and comorbities], the overestimation of bleeding risk and the underestimation of stroke risk, may partially explain physicians' reluctance to prescribe anticoagulation. In the current issue of Age and Ageing, Pugh and Mead [2] report a systematic review on physicians' attitudes concerning anticoagulant treatment among AF patients. Through surveys (questionnaire, clinical vignette and interview) on hypothetical case scenarios, they have identified the barriers to effective anticoagulant prescription, as follows: increasing age, bleeding risk or previous bleeding, fall risk, co-morbidities (e.g. chronic alcoholism or cognitive impairment) and lack of compliance. In particular, advanced age has been reported as the most striking reason for with-holding anticoagulation, while risk of falls and previous bleeding are also disproportionate barriers to warfarin prescription.

Firm growth and barriers to growth among small firms in India

Empirical work on micro and small firms focuses on developed countries, while existing work on developing countries is all too often based on small samples taken from ad hoc questionnaires. The census data we analyze here are fairly representative of small business structure in India. Consistent with findings from prior research on developed countries, size and age have a negative impact on firm growth in the majority of specifications. Enterprises managed by women have lower expected growth rates. Proprietary firms face lower growth on the whole, especially if they are young firms. Exporting has a positive effect on firm growth, especially for young firms and for female-owned firms. Although some small firms are able to convert know-how into commercial success, we find that many others are unable to translate it into superior growth.

Overcoming barriers to membrane protein structure determination

After decades of slow progress, the pace of research on membrane protein structures is beginning to quicken thanks to various improvements in technology, including protein engineering and microfocus X-ray diffraction. Here we review these developments and, where possible, highlight generic new approaches to solving membrane protein structures based on recent technological advances. Rational approaches to overcoming the bottlenecks in the field are urgently required as membrane proteins, which typically comprise ~30% of the proteomes of organisms, are dramatically under-represented in the structural database of the Protein Data Bank.