The far right vote in France:from consolidation to collapse?

The presidential and legislative elections of 2007 are widely seen to have marked the end of the far right as a major political force in France. How could this occur only five years after Le Pen’s qualification for the presidential run-off, and with his party seemingly in the ascendant? This article discusses recent fluctuations in far-right electoral performance in France. It focuses largely on the presidential elections of 2002 and 2007, re-examining the (supposed) upswell of far-right support in 2002 and its (supposed) subsidence in 2007. Both elections require nuanced interpretation. Both confounded poll predictions, which in 2007 failed to measure the effect of Sarkozy’s hard-right campaign and, crucially, the extent to which the border between “mainstream right” and “far right” had shifted since 2002. This allowed Sarkozy to drain part of Le Pen’s electorate, and raises questions over the longer-term impact of Le Pen and the FN on the political agenda in France.

Associations between glia, neurons and prion protein (PrPsc) deposits in variant Creutzfeldt-Jakob disease (vCJD)

Glia may be important in the pathology of variant Creutzfeldt-Jakob disease (vCJD) in several ways: (1) glial cells could be involved in the formation of prion protein (PrPsc) deposits, (2) PrPsc deposits could stimulate the production of astrocytes and microglia, (3) PrPsc deposits could damage adjacent glial cells, and (4) glial cells could remove PrPsc from the brain. To investigate the significance of glial cells in vCJD, the relationships between PrPsc deposits and their associated glia, together with neurons and blood vessels, was studied in six cases of vCJD. Multicentric PrPsc deposits were the largest and least frequent type of deposit observed and were more commonly associated with glial cells, neuronal perikarya, and blood vessels than the more common diffuse and florid PrPsc deposits. Diffuse PrPsc deposits were more frequently associated with glial cells and neurons than the florid deposits. The ratio of astrocytes to oligodendrocytes adjacent to PrPsc deposits was similar to normal brain but the ratio of astrocytes and oligodendrocytes to microglia was less than in normal brain. The intensity of immunolabelling of multicentric PrPsc deposits was positively correlated with the presence of associated vacuoles and negatively correlated with the frequency of microglia. The patterns of correlation between deposit morphology and associated glial cells and neurons were similar for the diffuse and florid type PrPsc deposits. Deposit size was most consistently correlated with the number of associated neurons and vacuoles. The data suggest in vCJD: (1) no evidence that glia were necessary for the formation of PrPsc deposits, (2) an increase in microglia which may be an attempt to remove PrPsc from the bain, and (3) PrPsc deposits could affect adjacent astrocytes and damage the blood brain barrier (BBB).

Glia and the pathology of variant Creutzfeldt-Jakob disease (vCJD)

Glia may be implicated in the pathology of variant Creutzfeldt-Jakob disease (vCJD) in several ways: (1) glial cells could be involved in the formation of prion protein (PrPsc) deposits, (2) PrPsc deposits could stimulate the production of astrocytes and microglia, (3) PrPsc deposits could damage adjacent glial cells, and (4) glial cells could remove aggregates of PrPsc from the brain. To clarify the significance of glial cells in vCJD, the relationship between PrPsc deposits and their associated glia, together with neurons and blood vessels, was studied in six cases of vCJD. Multicentric PrPsc deposits were the largest and least frequent type of deposit observed and were more commonly associated with glial cells, neuronal perikarya, and blood vessels than the more common diffuse and florid PrPsc deposits. Diffuse PrPsc deposits were more frequently associated with glial cells and neurons than the florid deposits. The ratio of astrocytes to oligodendrocytes adjacent to PrPsc deposits was similar to normal brain but the ratio of astrocytes or oligodendrocytes to microglia was less than in normal brain. The intensity of immunolabelling of multicentric PrPsc deposits was positively correlated with the presence of associated vacuoles and negatively correlated with the frequency of microglia. The patterns of correlation between deposit morphology and associated glial cells and neurons were similar for the diffuse and florid type PrPsc deposits. Deposit size was most consistently correlated with the number of associated neurons and vacuoles. The data suggest in vCJD: (1) there was no evidence that glia were necessary for the formation of PrPsc deposits, (2) there is an increase in microglia which may be an attempt to remove PrPsc from the bain, and (3) PrPsc deposits could affect adjacent astrocytes and damage the blood brain barrier (BBB). © 2013 by Nova Science Publishers, Inc. All rights reserved.

Development and trialling of a behavioural intervention for patients with atrial fibrillation initiating oral anticoagulation:the 'treat' study

Purpose: Atrial fibrillation (AF) is the most common heart arrhythmia and is associated with an increased risk of stroke. Stroke risk is commonly treated with oral anticoagulation (OAC) with a narrow therapeutic range (INR 2.0 to 3.0); which is poorly controlled in practice. Barriers to adherence include poor knowledge, and inaccurate perceptions surrounding illness and medications. Trial registration: ISRCTN93952605. Systematic review: Seven trials of educational, self-monitoring and decision aid interventions were included in a systematic review. Pooled analysis suggested education OR, 95% CI 7.89 (5.54-10.24) and self monitoring OR (95% CI) 5.47(2.55-8.39) significantly improve TTR; whereas decision aids are no more effective in reducing decision conflict than usual care, OR (95% CI) -0.10 (-0.17 to -0.02). Intervention development: The intervention was theoretically-driven (utilising the common sense and beliefs about medication models) and developed with expert patient feedback. Described using behavioural change techniques, the one-off group session included an educational booklet, ‘expert-patient’ focussed DVD, and worksheet. Methods: Ninety seven warfarin-naïve AF patients were randomised to receive the intervention (n=43), or usual care (n=54). The primary endpoint was time within therapeutic range (TTR), secondary endpoints included knowledge, quality of life (AF-QoL-18), beliefs about medication (BMQ), illness perceptions (IPQ-B), and anxiety and depression (HADS). Results: Intervention group had significantly higher TTR than usual care (78.5% vs. 66.7%; p=0.01). Knowledge changed significantly across time (F (3, 47) = 6.4; p<0.01), but not between groups (F (1, 47) = 3.3; p = 0.07). At six months knowledge predicted TTR (r=0.245; p=0.04). Illness concern negatively correlated with TTR (r= - 0.199; p=0.05). General Harm scores at one month predicted TTR (F (1, 72) = 4.08; p=0.048). There were significant differences in emotional representations (F (3, 49) = 3.3 (3, 49); p= 0.03), anxiety (F (3, 46) = 25.2; p<0.01) and depression (F (3, 46) = 37.7; p<0.01) across time. Conclusion: A theory-driven educational intervention can improve TTR in AF patients and potentially reduce the risk of adverse clinical outcomes. Improving education provision for AF patients is essential to ensure efficacious treatment.

Coexistence of macro- and micro-vascular abnormalities in newly diagnosed normal tension glaucoma patients

Purpose: To investigate the coexistence of ocular microvascular and systemic macrovascular abnormalities in early stage, newly diagnosed and previously untreated normal tension glaucoma patients (NTG). Methods: Retinal vascular reactivity to flickering light was assessed in 19 NTG and 28 age-matched controls by means of dynamic retinal vessel analysis (IMEDOS GmbH, Jena, Germany). Using a newly developed computational model, the entire dynamic vascular response profile to flicker light was imaged and used for analysis. In addition, assessments of carotid intima-media thickness (IMT) and pulse wave analysis (PWA) were conducted on all participants, along with blood pressure (BP) measurements and blood analyses for lipid metabolism markers. Results: Patients with NTG demonstrated an increased right and left carotid IMT (p = 0.015, p = 0.045) and an elevated PWA augmentation index (p = 0.017) in comparison with healthy controls, along with an enhanced retinal arterial constriction response (p = 0.028), a steeper retinal arterial constriction slope (p = 0.031) and a reduced retinal venous dilation response (p = 0.026) following flicker light stimulation. Conclusions: Early stage, newly diagnosed, NTG patients showed signs of subclinical vascular abnormalities at both macro- and micro-vascular levels, highlighting the need to consider multi-level circulation-related pathologies in the development and progression of this type of glaucoma.

GEO Label:user and producer perspectives on a label for geospatial data

One of the aims of the Science and Technology Committee (STC) of the Group on Earth Observations (GEO) was to establish a GEO Label- a label to certify geospatial datasets and their quality. As proposed, the GEO Label will be used as a value indicator for geospatial data and datasets accessible through the Global Earth Observation System of Systems (GEOSS). It is suggested that the development of such a label will significantly improve user recognition of the quality of geospatial datasets and that its use will help promote trust in datasets that carry the established GEO Label. Furthermore, the GEO Label is seen as an incentive to data providers. At the moment GEOSS contains a large amount of data and is constantly growing. Taking this into account, a GEO Label could assist in searching by providing users with visual cues of dataset quality and possibly relevance; a GEO Label could effectively stand as a decision support mechanism for dataset selection. Currently our project - GeoViQua, - together with EGIDA and ID-03 is undertaking research to define and evaluate the concept of a GEO Label. The development and evaluation process will be carried out in three phases. In phase I we have conducted an online survey (GEO Label Questionnaire) to identify the initial user and producer views on a GEO Label or its potential role. In phase II we will conduct a further study presenting some GEO Label examples that will be based on Phase I. We will elicit feedback on these examples under controlled conditions. In phase III we will create physical prototypes which will be used in a human subject study. The most successful prototypes will then be put forward as potential GEO Label options. At the moment we are in phase I, where we developed an online questionnaire to collect the initial GEO Label requirements and to identify the role that a GEO Label should serve from the user and producer standpoint. The GEO Label Questionnaire consists of generic questions to identify whether users and producers believe a GEO Label is relevant to geospatial data; whether they want a single "one-for-all" label or separate labels that will serve a particular role; the function that would be most relevant for a GEO Label to carry; and the functionality that users and producers would like to see from common rating and review systems they use. To distribute the questionnaire, relevant user and expert groups were contacted at meetings or by email. At this stage we successfully collected over 80 valid responses from geospatial data users and producers. This communication will provide a comprehensive analysis of the survey results, indicating to what extent the users surveyed in Phase I value a GEO Label, and suggesting in what directions a GEO Label may develop. Potential GEO Label examples based on the results of the survey will be presented for use in Phase II.

Joint tenancies and English commorientes:a question of survivorship or severance?

The aim of this article is to provide a critical appraisal of the English law in relation to the doctrine of commorientes with particular reference to its implications in respect of property held on a joint tenancy. The article suggests a measure of reform which would produce a fairer dsitribution of joint property in circusmtances where all joint tenants have died in a common disaster and it cannot be ascertained which joint tenant died first.

Evaluating the use of IT by the third party logistics in South East Asia to achieve competitive advantage and its future trend

As the number of using 3PL providers are increasing rapidly in recent years, 3PL providers play a major role in the logistics industry. Due to customers demands are raising and changing, it has facilitated 3PL providers to invest IT systems that could meet customer requirements and create competitive advantage. The use of IT systems could assist 3PL providers to achieve supply chain visibility and enhance supply chain collaboration with business partners. In this paper, it is mainly focus on the Europe and Far East 3PL providers in terms of current and future IT systems, IT motivators and barriers, as well as the future supply chain demands that address by IT systems. The common IT system that implemented in both regions is information technology, which is mainly used to collaborate and share information with supply chain partners. Some of the common motivations and barriers were existed and 3PL providers need to be understood. Given the future demands of IT implementation and supply chain collaboration, IT systems such as RFID and integration systems would be strongly focus in the future. The suggestion about the advanced integration system such as business process management (BPM) could be the next key IT systems in the future logistics industry. © 2012 AICIT.

Focus group method and methodology:current practice and recent debate

This paper considers the contemporary use of focus groups as a method of data collection within qualitative research settings. The authors draw upon their own experiences of using focus groups in educational and 'community' user-group environments in order to provide an overview of recent issues and debates surrounding the deployment of focus group methods and to pick out specific areas of contention in relation to both their epistemological and practical implications. Accordingly, the paper reflects on some of the realities of 'doing' focus groups whilst, at the same time, highlighting common problems and dilemmas which beginning researchers might encounter in their application. In turn, the paper raises a number of related issues around which there appears to have been a lack of academic discussion to date.

Extra compensation for inventive employees:is our system equitable, unbiased and motivating?

There is a presumption that invention is good. It provides us with innovative goods, services and ways of doing things leading to greater employment, wealth and health. This article looks at the two recent UK cases regarding statutory extra compensation that may be awarded to employee inventors under the Patents Act 1977. Most universities worldwide and many companies have individual inventor reward schemes. Researchers now work in teams made up of both industry and academic researchers who are often based in different countries where different legal regimes apply. Is leaving the decision to award employees extra financial compensation up to individual companies unfair, unequal and de-motivating? Is having differing legislative systems in different European countries counter productive and a barrier to economic growth? There must be a balance between the inventor and the innovator. Do we have it right and if not what should it be? Legislation: Patents Act 1977 s.39 , s.40 , s.41 Cases: Kelly v GE Healthcare Ltd [2009] EWHC 181 (Pat); [2009] R.P.C. 12 (Ch D (Patents Ct)) Shanks v Unilever Plc [2010] EWCA Civ 1283; [2011] R.P.C. 12 (CA (Civ Div))

Leader‐Member Exchange (LMX) and performance:a meta‐analytic review

This paper reports a meta-analysis that examines the relationship between leader-member exchange (LMX) relationship quality and a multidimensional model of work performance (task, citizenship, and counterproductive performance). The results show a positive relationship between LMX and task performance (146 samples, ρ = .30) as well as citizenship performance (97 samples, ρ = .34), and negatively with counterproductive performance (19 samples, ρ = -.24). Of note, there was a positive relationship between LMX and objective task performance (20 samples, ρ = .24). Trust, motivation, empowerment, and job satisfaction mediated the relationship between LMX and task and citizenship performance with trust in the leader having the largest effect. There was no difference due to LMX measurement instrument (e.g., LMX7, LMX-MDM). Overall, the relationship between LMX and performance was weaker when (a) measures were obtained from a different source or method and (b) LMX was measured by the follower than the leader (with common source- and method-biased effects stronger for leader-rated LMX quality). Finally, there was evidence for LMX leading to task performance but not for reverse or reciprocal directions of effects.

Editorial overview:new protein production tools for structural biology

Full text: The idea of producing proteins from recombinant DNA hatched almost half a century ago. In his PhD thesis, Peter Lobban foresaw the prospect of inserting foreign DNA (from any source, including mammalian cells) into the genome of a λ phage in order to detect and recover protein products from Escherichia coli [ 1 and 2]. Only a few years later, in 1977, Herbert Boyer and his colleagues succeeded in the first ever expression of a peptide-coding gene in E. coli — they produced recombinant somatostatin [ 3] followed shortly after by human insulin. The field has advanced enormously since those early days and today recombinant proteins have become indispensable in advancing research and development in all fields of the life sciences. Structural biology, in particular, has benefitted tremendously from recombinant protein biotechnology, and an overwhelming proportion of the entries in the Protein Data Bank (PDB) are based on heterologously expressed proteins. Nonetheless, synthesizing, purifying and stabilizing recombinant proteins can still be thoroughly challenging. For example, the soluble proteome is organized to a large part into multicomponent complexes (in humans often comprising ten or more subunits), posing critical challenges for recombinant production. A third of all proteins in cells are located in the membrane, and pose special challenges that require a more bespoke approach. Recent advances may now mean that even these most recalcitrant of proteins could become tenable structural biology targets on a more routine basis. In this special issue, we examine progress in key areas that suggests this is indeed the case. Our first contribution examines the importance of understanding quality control in the host cell during recombinant protein production, and pays particular attention to the synthesis of recombinant membrane proteins. A major challenge faced by any host cell factory is the balance it must strike between its own requirements for growth and the fact that its cellular machinery has essentially been hijacked by an expression construct. In this context, Bill and von der Haar examine emerging insights into the role of the dependent pathways of translation and protein folding in defining high-yielding recombinant membrane protein production experiments for the common prokaryotic and eukaryotic expression hosts. Rather than acting as isolated entities, many membrane proteins form complexes to carry out their functions. To understand their biological mechanisms, it is essential to study the molecular structure of the intact membrane protein assemblies. Recombinant production of membrane protein complexes is still a formidable, at times insurmountable, challenge. In these cases, extraction from natural sources is the only option to prepare samples for structural and functional studies. Zorman and co-workers, in our second contribution, provide an overview of recent advances in the production of multi-subunit membrane protein complexes and highlight recent achievements in membrane protein structural research brought about by state-of-the-art near-atomic resolution cryo-electron microscopy techniques. E. coli has been the dominant host cell for recombinant protein production. Nonetheless, eukaryotic expression systems, including yeasts, insect cells and mammalian cells, are increasingly gaining prominence in the field. The yeast species Pichia pastoris, is a well-established recombinant expression system for a number of applications, including the production of a range of different membrane proteins. Byrne reviews high-resolution structures that have been determined using this methylotroph as an expression host. Although it is not yet clear why P. pastoris is suited to producing such a wide range of membrane proteins, its ease of use and the availability of diverse tools that can be readily implemented in standard bioscience laboratories mean that it is likely to become an increasingly popular option in structural biology pipelines. The contribution by Columbus concludes the membrane protein section of this volume. In her overview of post-expression strategies, Columbus surveys the four most common biochemical approaches for the structural investigation of membrane proteins. Limited proteolysis has successfully aided structure determination of membrane proteins in many cases. Deglycosylation of membrane proteins following production and purification analysis has also facilitated membrane protein structure analysis. Moreover, chemical modifications, such as lysine methylation and cysteine alkylation, have proven their worth to facilitate crystallization of membrane proteins, as well as NMR investigations of membrane protein conformational sampling. Together these approaches have greatly facilitated the structure determination of more than 40 membrane proteins to date. It may be an advantage to produce a target protein in mammalian cells, especially if authentic post-translational modifications such as glycosylation are required for proper activity. Chinese Hamster Ovary (CHO) cells and Human Embryonic Kidney (HEK) 293 cell lines have emerged as excellent hosts for heterologous production. The generation of stable cell-lines is often an aspiration for synthesizing proteins expressed in mammalian cells, in particular if high volumetric yields are to be achieved. In his report, Buessow surveys recent structures of proteins produced using stable mammalian cells and summarizes both well-established and novel approaches to facilitate stable cell-line generation for structural biology applications. The ambition of many biologists is to observe a protein's structure in the native environment of the cell itself. Until recently, this seemed to be more of a dream than a reality. Advances in nuclear magnetic resonance (NMR) spectroscopy techniques, however, have now made possible the observation of mechanistic events at the molecular level of protein structure. Smith and colleagues, in an exciting contribution, review emerging ‘in-cell NMR’ techniques that demonstrate the potential to monitor biological activities by NMR in real time in native physiological environments. A current drawback of NMR as a structure determination tool derives from size limitations of the molecule under investigation and the structures of large proteins and their complexes are therefore typically intractable by NMR. A solution to this challenge is the use of selective isotope labeling of the target protein, which results in a marked reduction of the complexity of NMR spectra and allows dynamic processes even in very large proteins and even ribosomes to be investigated. Kerfah and co-workers introduce methyl-specific isotopic labeling as a molecular tool-box, and review its applications to the solution NMR analysis of large proteins. Tyagi and Lemke next examine single-molecule FRET and crosslinking following the co-translational incorporation of non-canonical amino acids (ncAAs); the goal here is to move beyond static snap-shots of proteins and their complexes and to observe them as dynamic entities. The encoding of ncAAs through codon-suppression technology allows biomolecules to be investigated with diverse structural biology methods. In their article, Tyagi and Lemke discuss these approaches and speculate on the design of improved host organisms for ‘integrative structural biology research’. Our volume concludes with two contributions that resolve particular bottlenecks in the protein structure determination pipeline. The contribution by Crepin and co-workers introduces the concept of polyproteins in contemporary structural biology. Polyproteins are widespread in nature. They represent long polypeptide chains in which individual smaller proteins with different biological function are covalently linked together. Highly specific proteases then tailor the polyprotein into its constituent proteins. Many viruses use polyproteins as a means of organizing their proteome. The concept of polyproteins has now been exploited successfully to produce hitherto inaccessible recombinant protein complexes. For instance, by means of a self-processing synthetic polyprotein, the influenza polymerase, a high-value drug target that had remained elusive for decades, has been produced, and its high-resolution structure determined. In the contribution by Desmyter and co-workers, a further, often imposing, bottleneck in high-resolution protein structure determination is addressed: The requirement to form stable three-dimensional crystal lattices that diffract incident X-ray radiation to high resolution. Nanobodies have proven to be uniquely useful as crystallization chaperones, to coax challenging targets into suitable crystal lattices. Desmyter and co-workers review the generation of nanobodies by immunization, and highlight the application of this powerful technology to the crystallography of important protein specimens including G protein-coupled receptors (GPCRs). Recombinant protein production has come a long way since Peter Lobban's hypothesis in the late 1960s, with recombinant proteins now a dominant force in structural biology. The contributions in this volume showcase an impressive array of inventive approaches that are being developed and implemented, ever increasing the scope of recombinant technology to facilitate the determination of elusive protein structures. Powerful new methods from synthetic biology are further accelerating progress. Structure determination is now reaching into the living cell with the ultimate goal of observing functional molecular architectures in action in their native physiological environment. We anticipate that even the most challenging protein assemblies will be tackled by recombinant technology in the near future.

Exploring types and functions of questions in police interviews

There is a proliferation of categorization schemes in the scientific literature that have mostly been developed from psychologists’ understanding of the nature of linguistic interactions. This has a led to problems in defining question types used by interviewers. Based on the principle that the overarching purpose of an interview is to elicit information and that questions can function both as actions in their own right and as vehicles for other actions, a Conversational Analysis approach was used to analyse a small number of police interviews. The analysis produced a different categorization of question types and, in particular, the conversational turns fell into two functional types: (i) Topic Initiation Questions and (ii) Topic Facilitation Questions. We argue that forensic interviewing requires a switch of focus from the ‘words’ used by interviewers in question types to the ‘function’ of conversational turns within interviews.

Definitions and factors associated with subthreshold depressive conditions:a systematic review

BACKGROUND: Subthreshold depressive disorders (minor and subthrehold depression) have been defined in a wide range of forms, varying on the number of symptoms and duration required. Disability associated with these conditions has also been reported. Our aim was to review the different definitions and to determine factors associated with these conditions in order to clarify the nosological implications of these disorders. METHODS: A Medline search was conducted of the published literature between January 2001 and September 2011. Bibliographies of the retrieved papers were also analysed. RESULTS: There is a wide heterogeneity in the definition and diagnostic criteria of minor and subthreshold depression. Minor depression was defined according to DSM-IV criteria. Regarding subthreshold depression, also called subclinical depression or subsyndromal symptomatic depression, between 2 and 5 depressive symptoms were required for the diagnosis, and a minimum duration of 2 weeks. Significant impairment associated with subthreshold depressive conditions, as well as comorbidity with other mental disorders, has been described. CONCLUSIONS: Depression as a disorder is better explained as a spectrum rather than as a collection of discrete categories. Minor and subthreshold depression are common conditions and patients falling below the diagnostic threshold experience significant difficulties in functioning and a negative impact on their quality of life. Current diagnostic systems need to reexamine the thresholds for depressive disorders and distinguish them from ordinary feelings of sadness.

Survey of General Optical Council disciplinary and fitness to practise hearings:2001-2011

The aim of this survey was to review 187 transcripts from the United Kingdom’s General Optical Council (GOC) Disciplinary and Fitness To Practise (FTP) Committee hearings from 2001 to 2011 in order to identify common themes and thereby help practitioners to avoid the more frequently occurring pitfalls that were recorded during this period. The study covered changes in GOC FTP regulations in 2005, which involved a change from a disciplinary to a fitness to practise process. The number of cases was very small compared to the total number of optometrist and dispensing optician registrants, which was 13709 in 2001-02 rising to 18582 in 2010-11. The main findings indicated that between 2001 and 2011 there was a three times greater likelihood that male registrants versus female registrants would be brought in front of a GOC Disciplinary or FTP Committee. In terms of erasures from the GOC registers between 2001 and 2011, male registrants were also more likely to be erased than females. The male: female split for erasures between 2001 and 2011 was five: one, increasing to seven: one when considering the situation post the 2005 GOC FTP rule change. Of the cases brought before the Disciplinary and FTP Committees between 2001 and 2011, it was noted that cases implicating theft and fraud were most frequent representing 27% of hearings examined (17% involving NHS fraud and 10% theft or fraud from an employer). The examination of transcripts revealed other hearings were more complex. These hearings often had a primary reason for the investigation that highlighted further secondary concerns that also required investigation.