Phylogeographic analysis of North American populations of the parasitic herbaceous plant Monotropa hypopitys reveals a complex history of range expansion from multiple late glacial refugia

Aim We carried out a phylogeographic study across the range of the herbaceous plant species Monotropa hypopitys L. in North America to determine whether its current disjunct distribution is due to recolonization from separate eastern and western refugia after the Last Glacial Maximum (LGM). Location North America: Pacific Northwest and north-eastern USA/south-eastern Canada. Methods Palaeodistribution modelling was carried out to determine suitable climatic regions for M. hypopitys at the LGM. We analysed between 155 and 176 individuals from 39 locations spanning the species' entire range in North America. Sequence data were obtained for the chloroplast rps2 gene (n=168) and for the nuclear ITS region (n=158). Individuals were also genotyped for eight microsatellite loci (n=176). Interpolation of diversity values was used to visualize the range-wide distribution of genetic diversity for each of the three marker classes. Minimum spanning networks were constructed showing the relationships between the rps2 and ITS haplotypes, and the geographical distributions of these haplotypes were plotted. The numbers of genetic clusters based on the microsatellite data were estimated using Bayesian clustering approaches. Results The palaeodistribution modelling indicated suitable climate envelopes for M. hypopitys at the LGM in both the Pacific Northwest and south-eastern USA. High levels of genetic diversity and endemic haplotypes were found in Oregon, the Alexander Archipelago, Wisconsin, and in the south-eastern part of the species' distribution range. Main conclusions Our results suggest a complex recolonization history for M. hypopitys in North America, involving persistence in separate eastern and western refugia. A generally high degree of congruence between the different marker classes analysed indicated the presence of multiple refugia, with at least two refugia in each area. In the west, putative refugia were identified in Oregon and the Alexander Archipelago, whereas eastern refugia may have been located in the southern part of the species' current distribution, as well as in the 'Driftless Area'. These findings are in contrast to a previous study on the related species Orthilia secunda, which has a similar disjunct distribution to M. hypopitys, but which appears to have recolonized solely from western refugia. © 2011 Blackwell Publishing Ltd.

Methods for measuring proteasome activity: Current limitations and future developments

The proteasome has been validated as a therapeutic target, with proteasome inhibitors showing particular efficacy in the treatment of Multiple Myeloma. A wide range of methods have been developed to profile proteasome activity. These include the current method of choice fluorogenic peptide substrates, as well as bioluminescent imaging, immunological methods, and more recently, site-specific fluorescent probes. The aim of this review is to evaluate the currently available methods for profiling proteasome activity and their suitability for use in translational studies. Ongoing development of techniques for profiling proteasome activity will facilitate future research into proteasome-related pathologies, thus accelerating the development of more specific drug regimes. (C) 2010 Elsevier Ltd. All rights reserved.

Towards accurate estimation of the proportion of true null hypotheses in multiple testing

Background

Biomedical researchers are now often faced with situations where it is necessary to test a large number of hypotheses simultaneously, eg, in comparative gene expression studies using high-throughput microarray technology. To properly control false positive errors the FDR (false discovery rate) approach has become widely used in multiple testing. The accurate estimation of FDR requires the proportion of true null hypotheses being accurately estimated. To date many methods for estimating this quantity have been proposed. Typically when a new method is introduced, some simulations are carried out to show the improved accuracy of the new method. However, the simulations are often very limited to covering only a few points in the parameter space.

Results

Here I have carried out extensive in silico experiments to compare some commonly used methods for estimating the proportion of true null hypotheses. The coverage of these simulations is unprecedented thorough over the parameter space compared to typical simulation studies in the literature. Thus this work enables us to draw conclusions globally as to the performance of these different methods. It was found that a very simple method gives the most accurate estimation in a dominantly large area of the parameter space. Given its simplicity and its overall superior accuracy I recommend its use as the first choice for estimating the proportion of true null hypotheses in multiple testing.

The use of process simulation methods in support of organisational learning in availability contracting

Traditional business models in the aerospace industry are based on a conventional supplier to customer relationship based on the design, manufacture and subsequent delivery of the physical product. Service provision, from the manufacturer's perspective, is typically limited to the supply of procedural documentation and the provision of spare parts to the end user as the product passes through the latter stages of its intended lifecycle. Challenging economic and political conditions have resulted in end users re-structuring their core business activities, particularly in the defence sector. This has resulted in the need for original equipment manufacturers (OEMs) to integrate and manage support service activities in partnership with the customer to deliver platform availability. This improves the probability of commercial sustainability for the OEM through shared operational risks while reducing the cost of platform ownership for the customer. The need for OEMs to evolve their design, manufacture and supply strategies by focusing on customer requirements has revealed a need for reconstruction of traditional internal behaviours and design methodologies. Application of organisational learning is now a well recognised principle for innovative companies to achieve long term growth and sustained technical development, and hence, greater market command. It focuses on the process by which the organisation's knowledge and value base changes, leading to improved problem solving ability and capacity for action. From the perspective of availability contracting, knowledge and the processes by which it is generated, used and retained, become primary assets within the learning organisation. This paper will introduce the application of digital methods to asset management by demonstrating how the process of learning can benefit from a digital approach, how product and process design can be integrated within a virtual framework and finally how the approach can be applied in a service context.

Automated nonlinear system modelling with multiple neural networks

This article discusses the identification of nonlinear dynamic systems using multi-layer perceptrons (MLPs). It focuses on both structure uncertainty and parameter uncertainty, which have been widely explored in the literature of nonlinear system identification. The main contribution is that an integrated analytic framework is proposed for automated neural network structure selection, parameter identification and hysteresis network switching with guaranteed neural identification performance. First, an automated network structure selection procedure is proposed within a fixed time interval for a given network construction criterion. Then, the network parameter updating algorithm is proposed with guaranteed bounded identification error. To cope with structure uncertainty, a hysteresis strategy is proposed to enable neural identifier switching with guaranteed network performance along the switching process. Both theoretic analysis and a simulation example show the efficacy of the proposed method.

The Evolution of European Identity: Using biographical methods to study the development of European identity

Based upon the original application to the European Commission, this article gives insights into the thinking of the Euroidentities team at the point that the project began. The question: “Is the European ‘identity project’ failing?” is posed in the sense that the political and economic attainments of the European Union have not been translated into a sense of identity with or commitment to Europe from the populaces that have benefited from them. The urgency of European ‘identity work’ is asserted with a number of levels for the construction of European identity being hypothesized. Euroidentities is intended to break conceptual ground by bringing together on an equal footing two apparently antagonistic views of identity -- the collective and institutional and the individual and biographical – to give a more anchored and nuanced view of identity formation and transformation than either can provide on its own. Rather than following the dominant approaches to research on European identity that have been macro-theoretical and ‘top-down’, retrospective in-depth qualitative biographical interviews are planned since they provide the ideal means of gaining insight into the formation of a European identity or multiple identities from the ‘bottom up’ perspective of non-elite groups. The reliability of analysis will be buttressed by the use of contrastive comparison between cases, culminating in contrastive comparison across the national project teams between cases drawn from different ‘sensitized groups’ that provide the fieldwork structure of the project. The paper concludes with a summary of some of the more significant findings.

Interlaboratory comparison of real-time polymerase chain reaction methods to detect Coxiella burnetii, the causative agent of Q fever

The bacterium Coxiella burnetii, which has a wide host range, causes Q fever. Infection with C burnetii can cause abortions, stillbirth, and the delivery of weak offspring in ruminants. Coxiella burnetii infection is zoonotic, and in human beings it can cause chronic, potentially fatal disease. Real-time polymerase chain reaction (PCR) is increasingly being used to detect the organism and to aid in diagnosis both in human and animal cases. Many different real-time PCR methods, which target different genes, have been described. To assess the comparability of the C. burnetii real-time PCR assays in use in different European laboratories, a panel of nucleic acid extracts was dispatched to 7 separate testing centers. The testing centers included laboratories from both human and animal health agencies. Each laboratory tested the samples using their in-house real-time PCR methods. The results of this comparison show that the most common target gene for real-time PCR assays is the IS1111 repeat element that is present in multiple copies in the C. burnetii genome. Many laboratories also use additional real-time PCR tests that target single-copy genes. The results of the current study demonstrate that the assays in use in the different laboratories are comparable, with general agreement of results for the panel of samples.

Absorbing new knowledge in small and medium-sized enterprises: A multiple case analysis of Six Sigma

The primary aim of this article is to critically analyse the development of Six Sigma theory and practice within small and medium-sized enterprises (SMEs) using a multiple case study approach. The article also explores the subsequent development of Lean Six Sigma as a means of addressing the perceived limitations of the efficacy of Six Sigma in this context. The overarching theoretical framework is that of absorptive capacity, where Six Sigma is conceptualized as new knowledge to be absorbed by smaller firms. The findings from a multiple case study involving repeat interviews and focus groups informed the development of an analytical model demonstrating the dynamic underlying routines for the absorptive capacity process and the development of a number of summative propositions relating the characteristics of SMEs to Six Sigma and Lean Six Sigma implementation.

Photon collisions with atoms and ions within an intermediate-energy R-matrix framework

Recent experimental advances in light technology necessitate the availability of sophisticated theoretical models which can incorporate an accurate treatment of double-electron continua. We describe here a new intermediate-energy R-matrix approach to photoionisation and photo-double-ionisation and illustrate its feasibilty by application to photoionisation and photo-double-ionisation of He, and photodetachment and photo-double-detachment of H^-. Results are shown to be in excellent agreement with previous theoretical and experimental studies. This work is a key step in the development of a multipurpose R-matrix code for multiple-electron ejection. © 2012 American Physical Society

Understanding and Supporting Young Children’s Transitions into State Care: Schlossberg’s Transition Framework and Child-Centred Practice

There is a growing body of research regarding children and young people in state care that is organised around the concept of transition. Focusing mainly on young people leaving care, the research highlights their experiences of multiple transitions that can contribute to poor long-term outcomes in terms of emotional and psychological well-being, educational attainment and employment prospects. The smaller body of research that focuses on young children shows that their journeys before and when in state care are also marked by multiple and fragmented transitions. Despite the growing knowledge base, there are two areas that remain under-developed—research that draws attention to the lived experiences of young children regarding their transitions into state care; and the development of conceptual frameworks that centralise young children's perspectives to support the development of practice. This article begins to address these gaps by applying Schlossberg's transition framework to a case study of a young child regarding their transition into state care. The article highlights, through the child's perspectives, the multiple impacts of the transition and considers the implications for the development of better child-centred practice.

"They come with multiple morbidities":a qualitative assessment of pharmacist prescribing

This paper presents qualitative findings from a larger sequential mixed methods study which sought to provide an in-depth understanding of pharmacist prescribing from the perspective of pharmacist prescribers, medical colleagues and key stakeholders in Northern Ireland. Transcriptions were analyzed using thematic analysis as the interviews progressed and emergent themes were identified and coded (along with supporting quotes) independently and by consensus of the research team. Three major themes emerged in relation to pharmacist prescribing: the effect on patient care; challenges facing pharmacist prescribers and the importance of the interprofessional team (where two or more different professions with varied, yet complementary experience work together with a common purpose). Pharmacist prescribing may have the potential to reduce the medication burden for patients (as reported by pharmacists) as pharmacists tend to provide a more comprehensive medication review than doctors; the additional time for consultations made this possible. Further research is required on how interprofessional team working can be maximized in the context of pharmacist prescribing, particularly in relation to the management of multi-morbidity.

Development and application of a multiple linear regression model to consider the impact of weekly waste container capacity on the yield from kerbside recycling programmes

The paper describes the development and application of a multiple linear regression model to identify how the key elements of waste and recycling infrastructure, namely container capacity and frequency of collection affect the yield from municipal kerbside recycling programmes. The overall aim of the research was to gain an understanding of the factors affecting the yield from municipal kerbside recycling programmes in Scotland. The study isolates the principal kerbside collection service offered by 32 councils across Scotland, eliminating those recycling programmes associated with flatted properties or multi occupancies. The results of a regression analysis model has identified three principal factors which explain 80% of the variability in the average yield of the principal dry recyclate services: weekly residual waste capacity, number of materials collected and the weekly recycling capacity. The use of the model has been evaluated and recommendations made on ongoing methodological development and the use of the results in informing the design of kerbside recycling programmes. The authors hope that the research can provide insights for the ongoing development of methods to optimise the design and operation of kerbside recycling programmes.

Digital Methods for Process Development in Manufacturing and Their Relevance to Value Driven Design

This paper examines the applicability of a digital manufacturing framework to the implementation of a Value Driven Design (VDD) approach for the development of a stiffened composite panel. It presents a means by which environmental considerations can be integrated with conventional product and process design drivers within a customized, digital environment. A composite forming process is used as an exemplar for the work which creates a collaborative environment for the integration of more traditional design drivers with parameters related to manufacturability as well as more sustainable processes and products. The environmental stakeholder is introduced to the VDD process through a customized product/process/resource (PPR) environment where application specific power consumption and material waste data has been measured and characterised in the process design interface. This allows the manufacturing planner to consider power consumption as a concurrent design driver and the inclusion of energy as a parameter in a VDD approach to the development of efficiently manufactured, sustainable transport systems.

Distinguished algebraic semantics for t-norm based fuzzy logics:Methods and algebraic equivalencies

This paper is a contribution to Mathematical fuzzy logic, in particular to the algebraic study of t-norm based fuzzy logics. In the general framework of propositional core and ?-core fuzzy logics we consider three properties of completeness with respect to any semantics of linearly ordered algebras. Useful algebraic characterizations of these completeness properties are obtained and their relations are studied. Moreover, we concentrate on five kinds of distinguished semantics for these logics-namely the class of algebras defined over the real unit interval, the rational unit interval, the hyperreals (all ultrapowers of the real unit interval), the strict hyperreals (only ultrapowers giving a proper extension of the real unit interval) and finite chains, respectively-and we survey the known completeness methods and results for prominent logics. We also obtain new interesting relations between the real, rational and (strict) hyperreal semantics, and good characterizations for the completeness with respect to the semantics of finite chains. Finally, all completeness properties and distinguished semantics are also considered for the first-order versions of the logics where a number of new results are proved. © 2009 Elsevier B.V. All rights reserved.