Free radicals and redox signalling in T-cells during chronic inflammation and ageing

During chronic inflammation and ageing, the increase in oxidative stress in both intracellular and extracellular compartments is likely to influence local cell functions. Redox changes alter the T-cell proteome in a quantitative and qualitative manner, and post-translational modifications to surface and cytoplasmic proteins by increased reactive species can influence T-cell function. Previously, we have shown that RA (rheumatoid arthritis) T-cells exhibit reduced ROS (reactive oxygen species) production in response to extracellular stimulation compared with age-matched controls, and basal ROS levels [measured as DCF (2',7'-dichlorofluorescein) fluorescence] are lower in RA T-cells. In contrast, exposing T-cells in vitro to different extracellular redox environments modulates intracellular signalling and enhances cytokine secretion. Together, these data suggest that a complex relationship exists between intra- and extra-cellular redox compartments which contribute to the T-cell phenotype.

Evaluation of the Heart of Birmingham teaching Primary Care Trust (HoBtPCT): My Choice Weight Management Programme:report commissioned by Heart of Birmingham teaching Primary Care Trust

This report details an evaluation of the My Choice Weight Management Programme undertaken by a research team from the School of Pharmacy at Aston University. The My Choice Weight Management Programme is delivered through community pharmacies and general practitioners (GPs) contracted to provide services by the Heart of Birmingham teaching Primary Care Trust. It is designed to support individuals who are ‘ready to change’ by enabling the individual to work with a trained healthcare worker (for example, a healthcare assistant, practice nurse or pharmacy assistant) to develop a care plan designed to enable the individual to lose 5-10% of their current weight. The Programme aims to reduce adult obesity levels; improve access to overweight and obesity management services in primary care; improve diet and nutrition; promote healthy weight and increased levels of physical activity in overweight or obese patients; and support patients to make lifestyle changes to enable them to lose weight. The Programme is available for obese patients over 18 years old who have a Body Mass Index (BMI) greater than 30 kg/m2 (greater than 25 kg/m2 in Asian patients) or greater than 28 kg/m2 (greater than 23.5 kg/m2 in Asian patients) in patients with co-morbidities (diabetes, high blood pressure, cardiovascular disease). Each participant attends weekly consultations over a twelve session period (the final iteration of these weekly sessions is referred to as ‘session twelve’ in this report). They are then offered up to three follow up appointments for up to six months at two monthly intervals (the final of these follow ups, taking place at approximately nine months post recruitment, is referred to as ‘session fifteen’ in this report). A review of the literature highlights the dearth of published research on the effectiveness of primary care- or community-based weight management interventions. This report may help to address this knowledge deficit. A total of 451 individuals were recruited on to the My Choice Weight Management Programme. More participants were recruited at GP surgeries (n=268) than at community pharmacies (n=183). In total, 204 participants (GP n=102; pharmacy n=102) attended session twelve and 82 participants (GP n=22; pharmacy 60) attended session fifteen. The unique demographic characteristics of My Choice Weight Management Programme participants – participants were recruited from areas with high levels of socioeconomic deprivation and over four-fifths of participants were from Black and Minority Ethnic groups; populations which are traditionally underserved by healthcare interventions – make the achievements of the Programme particularly notable. The mean weight loss at session 12 was 3.8 kg (equivalent to a reduction of 4.0% of initial weight) among GP surgery participants and 2.4 kg (2.8%) among pharmacy participants. At session 15 mean weight loss was 2.3 kg (2.2%) among GP surgery participants and 3.4 kg (4.0%) among pharmacy participants. The My Choice Weight Management Programme improved the general health status of participants between recruitment and session twelve as measured by the validated SF-12 questionnaire. While cost data is presented in this report, it is unclear which provider type delivered the Programme more cost-effectively. Attendance rates on the Programme were consistently better among pharmacy participants than among GP participants. The opinions of programme participants (both those who attended regularly and those who failed to attend as expected) and programme providers were explored via semi-structured interviews and, in the case of the participants, a selfcompletion postal questionnaire. These data suggest that the Programme was almost uniformly popular with both the deliverers of the Programme and participants on the Programme with 83% of questionnaire respondents indicating that they would be happy to recommend the Programme to other people looking to lose weight. Our recommendations, based on the evidence provided in this report, include: a. Any consideration of an extension to the study also giving comparable consideration to an extension of the Programme evaluation. The feasibility of assigning participants to a pharmacy provider or a GP provider via a central allocation system should also be examined. This would address imbalances in participant recruitment levels between provider type and allow for more accurate comparison of the effectiveness in the delivery of the Programme between GP surgeries and community pharmacies by increasing the homogeneity of participants at each type of site and increasing the number of Programme participants overall. b. Widespread dissemination of the findings from this review of the My Choice Weight Management Project should be undertaken through a variety of channels. c. Consideration of the inclusion of the following key aspects of the My Choice Weight Management Project in any extension to the Programme: i. The provision of training to staff in GP surgeries and community pharmacies responsible for delivery of the Programme prior to patient recruitment. ii. Maintaining the level of healthcare staff input to the Programme. iii. The regular schedule of appointments with Programme participants. iv. The provision of an increased variety of printed material. d. A simplification of the data collection method used by the Programme commissioners at the individual Programme delivery sites.

Is it all tough talking at the top? A post-structuralist analysis of the construction of gendered speaker identities of British business leaders within interview narratives

This paper uses a feminist post-structuralist approach to examine the gendered identities of a sample of British business leaders in Britain. While recent national surveys offer many material reasons why women are acutely under-represented as business leaders, the role of language is rarely addressed. This paper explores the ways in which ten senior women and men construct their sense of leadership identities through the medium of interview narratives. Drawing upon two poststructuralist models of analysis (Derrida’s 1987 theory of deconstruction and Bakhtin’s 1927/1981 concept of double-voiced discourse), the paper shows how both females and males are able to shift pragmatically between interwoven corporate discourses, which demand competing cultural allegiances from one moment to the next, allegiances constantly tested by the rapid change and uncertainty that characterise global business. While male leaders experience a relative freedom of movement between different cultural discourses, female leaders are circumscribed by negative and reductive representations of female speech and behaviour. In sum, senior women are required constantly to observe, review, police and repair their use of leadership language, which potentially undermines their confidence and authority as leaders.

Dynamic ocular thermography

The ability to measure ocular surface temperature (OST) with thermal imaging offers potential insight into ocular physiology that has been acknowledged in the literature. The TH7102MX thermo-camera (NEC San-ei, Japan) continuously records dynamic information about OST without sacrificing spatial resolution. Using purpose-designed image analysis software, it was possible to select and quantify the principal components of absolute temperature values and the magnitude plus rate of temperature change that followed blinking. The techniques was examined for repeatability, reproducibility and the effects of extrinsic factors: a suitable experimental protocol was thus developed. The precise source of the measured thermal radiation has previously been subject toe dispute: in this thesis, the results of a study examining the relationships between physical parameters of the anterior eye and OST, confirmed a principal role for the tear film in OST. The dynamic changes in OST were studied in a large group of young subjects: quantifying the post-blink changes in temperature with time also established a role for tear flow dynamics in OST. Using dynamic thermography, the effects of hydrogel contact lens wear on OST were investigated: a model eye for in vivo work, and both neophyte and adapted contact lens wearers for in vivo studies. Significantly greater OST was observed in contact lens wearers, particularly with silicone hydrogel lenses compared to etafilcon A, and tended to be greatest when lenses had been worn continuously. This finding is important to understanding the ocular response to contact lens wear. In a group of normal subjects, dynamic thermography appeared to measure the ocular response to the application of artificial tear drops: this may prove to be a significant research and clinical tool.

Beyond securitisation : Western Mediterranean international relations from a security perspective 1989-2002

Following the end of the Cold War and the ensuing changes to the international landscape, thinking about security has tended to become more discursive and interpretative in nature. What counts as security has increasingly derived from security discourses (that is, 'securitisation') and uncertainty about the multi-faceted future facing various countries and regions. Within this post-Cold War discourse, the Western Mediterranean has emerged as a region fraught with latent and manifest threats in the economic, political, societal and military sectors. Improved access to EU markets for Maghrebi exports; the security of energy supplies to the EU from Algeria and Libya; lack of democracy and the advance of political Islam; the flow of northward migration and worries about law and order in France, Italy and Spain; the growth in military expenditure and weapons proliferation in the Maghreb; all have been central to the securitisation agenda. However, this agenda has often lacked credibility especially when inter-linkages have purportedly been established between economic underdevelopment and political instability, between the advance of political Islam and the threat to energy supplies, or between immigration and the threat to national identity. Such inter-sectoral linkages distract from the credibility of those 'securitisation instances' which correspond to reality; the former linkages have often been exploited by extremist politicians in south-west European countries as well as by regimes in the Maghreb to advance their respective interests. Thus, securitisation may defeat its main purpose; it may generate responses out of keeping with the aims proclaimed at the outset, aims centred on the countering of real threats and the ensuring of greater stability.

Une étude générique du metteur en scène au théâtre:son émergence et son rôle moderne et contemporain

The theatre director (metteur en scene in French) is a relatively new figure in theatre practice. It was not until the I820s that the term 'mise en scene' gained currency. The term 'director' was not in general use until the I880s. The emergence and the role of the director has been considered from a variety of perspectives, either through the history of theatre (Allevy, Jomaron, Sarrazac, Viala, Biet and Triau); the history of directing (Chinoy and Cole, Boll, Veinstein, Roubine); semiotic approaches to directing (Whitmore, Miller, Pavis); the semiotics of performance (De Marinis); generic approaches to the mise en scene (Thomasseau, Banu); post-dramatic approaches to theatre (Lehmann); approaches to performance process and the specifics of rehearsal methodology (Bradby and Williams, Giannachi and Luckhurst, Picon-Vallin, Styan). What the scholarly literature has not done so far is to map the parameters necessarily involved in the directing process, and to incorporate an analysis of the emergence of the theatre director during the modem period and consider its impact on contemporary performance practice. Directing relates primarily to the making of the performance guided by a director, a single figure charged with the authority to make binding artistic decisions. Each director may have her/his own personal approaches to the process of preparation prior to a show. This is exemplified, for example, by the variety of terms now used to describe the role and function of directing, from producer, to facilitator or outside eye. However, it is essential at the outset to make two observations, each of which contributes to a justification for a generic analysis (as opposed to a genetic approach). Firstly, a director does not work alone, and cooperation with others is involved at all stages of the process. Secondly, beyond individual variation, the role of the director remains twofold. The first is to guide the actors (meneur de jeu, directeur d'acteurs, coach); the second is to make a visual representation in the performance space (set designer, stage designer, costume designer, lighting designer, scenographe). The increasing place of scenography has brought contemporary theatre directors such as Wilson, Castellucci, Fabre to produce performances where the performance space becomes a semiotic dimension that displaces the primacy of the text. The play is not, therefore, the sole artistic vehicle for directing. This definition of directing obviously calls for a definition of what the making of the performance might be. The thesis defines the making of the performance as the activity of bringing a social event, by at least one performer, providing visual and/or textual meaning in a performance space. This definition enables us to evaluate four consistent parameters throughout theatre history: first, the social aspect associated to the performance event; second, the devising process which may be based on visual and/or textual elements; third, the presence of at least one performer in the show; fourth, the performance space (which is not simply related to the theatre stage). Although the thesis focuses primarily on theatre practice, such definition blurs the boundaries between theatre and other collaborative artistic disciplines (cinema, opera, music and dance). These parameters illustrate the possibility to undertake a generic analysis of directing, and resonate with the historical, political and artistic dimensions considered. Such a generic perspective on the role of the director addresses three significant questions: an historical question: how/why has the director emerged?; a sociopolitical question: how/why was the director a catalyst for the politicisation of theatre, and subsequently contributed to the rise of State-funded theatre policy?; and an artistic one: how/why the director has changed theatre practice and theory in the twentieth-century? Directing for the theatre as an artistic activity is a historically situated phenomenon. It would seem only natural from a contemporary perspective to associate the activity of directing to the function of the director. This is relativised, however, by the question of how the performance was produced before the modern period. The thesis demonstrates that the rise of the director is a progressive and historical phenomenon (Dort) rather than a mere invention (Viala, Sarrazac). A chronological analysis of the making of the performance throughout theatre history is the most useful way to open the study. In order to understand the emergence of the director, the research methodology assesses the interconnection of the four parameters above throughout four main periods of theatre history: the beginning of the Renaissance (meneur de jeu), the classical age (actor-manager and stage designer-manager), the modern period (director) and the contemporary period (director-facilitator, performer). This allows us properly to appraise the progressive emergence of the director, as well as to make an analysis of her/his modern and contemporary role. The first chapter argues that the physical separation between the performance space and its audience, which appeared in the early fifteenth-century, has been a crucial feature in the scenographic, aesthetic, political and social organisation of the performance. At the end of the Middle Ages, French farces which raised socio-political issues (see Bakhtin) made a clear division on a single outdoor stage (treteau) between the actors and the spectators, while religious plays (drame fiturgique, mystere) were mostly performed on various outdoor and opened multispaces. As long as the performance was liturgical or religious, and therefore confined within an acceptable framework, it was allowed. At the time, the French ecclesiastical and civil authorities tried, on several occasions, to prohibit staged performances. As a result, practitioners developed non-official indoor spaces, the Theatre de fa Trinite (1398) being the first French indoor theatre recognized by scholars. This self-exclusion from the open public space involved breaking the accepted rules by practitioners (e.g. Les Confreres de fa Passion), in terms of themes but also through individual input into a secular performance rather than the repetition of commonly known religious canvases. These developments heralded the authorised theatres that began to emerge from the mid-sixteenth century, which in some cases were subsidised in their construction. The construction of authorised indoor theatres associated with the development of printing led to a considerable increase in the production of dramatic texts for the stage. Profoundly affecting the reception of the dramatic text by the audience, the distance between the stage and the auditorium accompanied the changing relationship between practitioners and spectators. This distance gave rise to a major development of the role of the actor and of the stage designer. The second chapter looks at the significance of both the actor and set designer in the devising process of the performance from the sixteenth-century to the end of the nineteenth-century. The actor underwent an important shift in function in this period from the delivery of an unwritten text that is learned in the medieval oral tradition to a structured improvisation produced by the commedia dell 'arte. In this new form of theatre, a chef de troupe or an experienced actor shaped the story, but the text existed only through the improvisation of the actors. The preparation of those performances was, moreover, centred on acting technique and the individual skills of the actor. From this point, there is clear evidence that acting began to be the subject of a number of studies in the mid-sixteenth-century, and more significantly in the seventeenth-century, in Italy and France. This is revealed through the implementation of a system of notes written by the playwright to the actors (stage directions) in a range of plays (Gerard de Vivier, Comedie de la Fidelite Nuptiale, 1577). The thesis also focuses on Leoni de' Sommi (Quatro dialoghi, 1556 or 1565) who wrote about actors' techniques and introduced the meneur de jeu in Italy. The actor-manager (meneur de jeu), a professional actor, who scholars have compared to the director (see Strihan), trained the actors. Nothing, however, indicates that the actor-manager was directing the visual representation of the text in the performance space. From the end of the sixteenth-century, the dramatic text began to dominate the process of the performance and led to an expansion of acting techniques, such as the declamation. Stage designers carne from outside the theatre tradition and played a decisive role in the staging of religious celebrations (e.g. Actes des Apotres, 1536). In the sixteenth-century, both the proscenium arch and the borders, incorporated in the architecture of the new indoor theatres (theatre a l'italienne), contributed to create all kinds of illusions on the stage, principally the revival of perspective. This chapter shows ongoing audience demands for more elaborate visual effects on the stage. This led, throughout the classical age, and even more so during the eighteenth-century, to grant the stage design practitioner a major role in the making of the performance (see Ciceri). The second chapter demonstrates that the guidance of the actors and the scenographic conception, which are the artistic components of the role of the director, appear to have developed independently from one another until the nineteenth-century. The third chapter investigates the emergence of the director per se. The causes for this have been considered by a number of scholars, who have mainly identified two: the influence of Naturalism (illustrated by the Meiningen Company, Antoine, and Stanislavski) and the invention of electric lighting. The influence of the Naturalist movement on the emergence of the modem director in the late nineteenth-century is often considered as a radical factor in the history of theatre practice. Naturalism undoubtedly contributed to changes in staging, costume and lighting design, and to a more rigorous commitment to the harmonisation and visualisation of the overall production of the play. Although the art of theatre was dependent on the dramatic text, scholars (Osborne) demonstrate that the Naturalist directors did not strictly follow the playwright's indications written in the play in the late nineteenth-century. On the other hand, the main characteristic of directing in Naturalism at that time depended on a comprehensive understanding of the scenography, which had to respond to the requirements of verisimilitude. Electric lighting contributed to this by allowing for the construction of a visual narrative on stage. However, it was a master technician, rather than an emergent director, who was responsible for key operational decisions over how to use this emerging technology in venues such as the new Bayreuth theatre in 1876. Electric lighting reflects a normal technological evolution and cannot be considered as one of the main causes of the emergence of the director. Two further causes of the emergence of the director, not considered in previous studies, are the invention of cinema and the Symbolist movement (Lugne-Poe, Meyerhold). Cinema had an important technological influence on the practitioners of the Naturalist movement. In order to achieve a photographic truth on the stage (tableau, image), Naturalist directors strove to decorate the stage with the detailed elements that would be expected to be found if the situation were happening in reality. Film production had an influence on the work of actors (Walter). The filmmaker took over a primary role in the making of the film, as the source of the script, the filming process and the editing of the film. This role influenced the conception that theatre directors had of their own work. It is this concept of the director which influenced the development of the theatre director. As for the Symbolist movement, the director's approach was to dematerialise the text of the playwright, trying to expose the spirit, movement, colour and rhythm of the text. Therefore, the Symbolists disengaged themselves from the material aspect of the production, and contributed to give greater artistic autonomy to the role of the director. Although the emergence of the director finds its roots amongst the Naturalist practitioners (through a rigorous attempt to provide a strict visual interpretation of the text on stage), the Symbolist director heralded the modem perspective of the making of performance. The emergence of the director significantly changed theatre practice and theory. For instance, the rehearsal period became a clear work in progress, a platform for both developing practitioners' techniques and staging the show. This chapter explores and contrasts several practitioners' methods based on the two aspects proposed for the definition of the director (guidance of the actors and materialisation of a visual space). The fourth chapter argues that the role of the director became stronger, more prominent, and more hierarchical, through a more political and didactic approach to theatre as exemplified by the cases of France and Germany at the end of the nineteenth-century and through the First World War. This didactic perspective to theatre defines the notion of political theatre. Political theatre is often approached by the literature (Esslin, Willett) through a Marxist interpretation of the great German directors' productions (Reinhardt, Piscator, Brecht). These directors certainly had a great influence on many directors after the Second World War, such as Jean Vilar, Judith Molina, Jean-Louis Barrault, Roger Planchon, Augusto Boal, and others. This chapter demonstrates, moreover, that the director was confirmed through both ontological and educational approaches to the process of making the performance, and consequently became a central and paternal figure in the organisational and structural processes practiced within her/his theatre company. In this way, the stance taken by the director influenced the State authorities in establishing theatrical policy. This is an entirely novel scholarly contribution to the study of the director. The German and French States were not indifferent to the development of political theatre. A network of public theatres was thus developed in the inter-war period, and more significantly after the Second World War. The fifth chapter shows how State theatre policies establish its sources in the development of political theatre, and more specifically in the German theatre trade union movement (Volksbiihne) and the great directors at the end of the nineteenth-century. French political theatre was more influenced by playwrights and actors (Romain Rolland, Louise Michel, Louis Lumet, Emile Berny). French theatre policy was based primarily on theatre directors who decentralised their activities in France during both the inter-war period and the German occupation. After the Second World War, the government established, through directors, a strong network of public theatres. Directors became both the artistic director and the executive director of those institutionalised theatres. The institution was, however, seriously shaken by the social and political upheaval of 1968. It is the link between the State and the institution in which established directors were entangled that was challenged by the young emerging directors who rejected institutionalised responsibility in favour of the autonomy of the artist in the 1960s. This process is elucidated in chapter five. The final chapter defines the contemporary role of the director in contrasting thework of a number of significant young theatre practitioners in the 1960s such as Peter Brook, Ariane Mnouchkine, The Living Theater, Jerzy Grotowski, Augusto Boal, Eugenio Barba, all of whom decided early on to detach their companies from any form of public funding. This chapter also demonstrates how they promoted new forms of performance such as the performance of the self. First, these practitioners explored new performance spaces outside the traditional theatre building. Producing performances in a non-dedicated theatre place (warehouse, street, etc.) was a more frequent practice in the 1960s than before. However, the recent development of cybertheatre questions both the separation of the audience and the practitioners and the place of the director's role since the 1990s. Secondly, the role of the director has been multifaceted since the 1960s. On the one hand, those directors, despite all their different working methods, explored western and non-western acting techniques based on both personal input and collective creation. They challenged theatrical conventions of both the character and the process of making the performance. On the other hand, recent observations and studies distinguish the two main functions of the director, the acting coach and the scenographe, both having found new developments in cinema, television, and in various others events. Thirdly, the contemporary director challenges the performance of the text. In this sense, Antonin Artaud was a visionary. His theatre illustrates the need for the consideration of the totality of the text, as well as that of theatrical production. By contrasting the theories of Artaud, based on a non-dramatic form of theatre, with one of his plays (Le Jet de Sang), this chapter demonstrates how Artaud examined the process of making the performance as a performance. Live art and autobiographical performance, both taken as directing the se(f, reinforce this suggestion. Finally, since the 1990s, autobiographical performance or the performance of the self is a growing practical and theoretical perspective in both performance studies and psychology-related studies. This relates to the premise that each individual is making a representation (through memory, interpretation, etc.) of her/his own life (performativity). This last section explores the links between the place of the director in contemporary theatre and performers in autobiographical practices. The role of the traditional actor is challenged through non-identification of the character in the play, while performers (such as Chris Burden, Ron Athey, Orlan, Franko B, Sterlac) have, likewise, explored their own story/life as a performance. The thesis demonstrates the validity of the four parameters (performer, performance space, devising process, social event) defining a generic approach to the director. A generic perspective on the role of the director would encompass: a historical dimension relative to the reasons for and stages of the 'emergence' of the director; a socio-political analysis concerning the relationship between the director, her/his institutionalisation, and the political realm; and the relationship between performance theory, practice and the contemporary role of the director. Such a generic approach is a new departure in theatre research and might resonate in the study of other collaborative artistic practices.

New career models in UK professional service firms:from up-or-out to up-and-going-nowhere?

In this paper, we empirically examine how professional service firms are adapting their promotion and career models to new market and institutional pressures, without losing the benefits of the traditional up-or-out tournament. Based on an in-depth qualitative study of 10 large UK based law firms we find that most of these firms do not have a formal up-or-out policy but that the up-or-out rule operates in practice. We also find that most firms have introduced alternative roles and a novel career policy that offers a holistic learning and development deal to associates without any expectation that unsuccessful candidates for promotion to partner should quit the firm. While this policy and the new roles formally contradict the principle of up-or-out by creating permanent non-partner positions, in practice they coexist. We conclude that the motivational power of the up-or-out tournament remains intact, notwithstanding the changes to the internal labour market structure of these professional service firms.

Pharmacy (ISSN 2226-4787):a journal of pharmacy education and practice

A journal of pharmacy education and practice is an international scientific open access journal on pharmacy education and practice, and is published by MDPI online quarterly. The practice of pharmacy is changing at an unprecedented rate as the profession moves from a focus upon preparation and supply of medicines to a clinical patient-facing role. While an understanding of the science related to medicines remains core to pharmacy education, the changes in practice are driving changes to the traditional methods of pharmacy education. This is reflected at an international level by major changes in the educational standards set by statutory regulators and by policy statements from bodies such as the World Health Organisation. These changes reflect an increasing trend to look at educational policy at a supra-national level, typified by the “Pharmine Project” led by the Association of European Faculties of Pharmacy.

When moving information online diminishes change:advisory services to SMEs

Improving the performance of private sector small and medium sized enterprises (SMEs) in a cost effective manner is a major concern for government. Governments have saved costs by moving information online rather than through more expensive face-to-face exchanges between advisers and clients. Building on previous work that distinguished between types of advice, this article evaluates whether these changes to delivery mechanisms affect the type of advice received. Using a multinomial logit model of 1334 cases of business advice to small firms collected in England, the study found that advice to improve capabilities was taken by smaller firms who were less likely to have limited liability or undertake business planning. SMEs sought word-of-mouth referrals before taking internal, capability-enhancing advice. This is also the case when that advice was part of a wider package of assistance involving both internal and external aspects. Only when firms took advice that used extant capabilities did they rely on the Internet. Therefore, when the Internet is privileged over face-to-face advice the changes made by each recipient of advice are likely to diminish causing less impact from advice within the economy. It implies that fewer firms will adopt the sorts of management practices that would improve their productivity. © 2014 Taylor & Francis.

Hypnotic induction is followed by state-like changes in the organization of EEG functional connectivity in the theta and beta frequency bands in high-hypnotically susceptible individuals

Altered state theories of hypnosis posit that a qualitatively distinct state of mental processing, which emerges in those with high hypnotic susceptibility following a hypnotic induction, enables the generation of anomalous experiences in response to specific hypnotic suggestions. If so then such a state should be observable as a discrete pattern of changes to functional connectivity (shared information) between brain regions following a hypnotic induction in high but not low hypnotically susceptible participants. Twenty-eight channel EEG was recorded from 12 high susceptible (highs) and 11 low susceptible (lows) participants with their eyes closed prior to and following a standard hypnotic induction. The EEG was used to provide a measure of functional connectivity using both coherence (COH) and the imaginary component of coherence (iCOH), which is insensitive to the effects of volume conduction. COH and iCOH were calculated between all electrode pairs for the frequency bands: delta (0.1-3.9 Hz), theta (4-7.9 Hz) alpha (8-12.9 Hz), beta1 (13-19.9 Hz), beta2 (20-29.9 Hz) and gamma (30-45 Hz). The results showed that there was an increase in theta iCOH from the pre-hypnosis to hypnosis condition in highs but not lows with a large proportion of significant links being focused on a central-parietal hub. There was also a decrease in beta1 iCOH from the pre-hypnosis to hypnosis condition with a focus on a fronto-central and an occipital hub that was greater in high compared to low susceptibles. There were no significant differences for COH or for spectral band amplitude in any frequency band. The results are interpreted as indicating that the hypnotic induction elicited a qualitative change in the organization of specific control systems within the brain for high as compared to low susceptible participants. This change in the functional organization of neural networks is a plausible indicator of the much theorized "hypnotic-state". © 2014 Jamieson and Burgess.

When to use the Bonferroni correction

PURPOSE: The Bonferroni correction adjusts probability (p) values because of the increased risk of a type I error when making multiple statistical tests. The routine use of this test has been criticised as deleterious to sound statistical judgment, testing the wrong hypothesis, and reducing the chance of a type I error but at the expense of a type II error; yet it remains popular in ophthalmic research. The purpose of this article was to survey the use of the Bonferroni correction in research articles published in three optometric journals, viz. Ophthalmic & Physiological Optics, Optometry & Vision Science, and Clinical & Experimental Optometry, and to provide advice to authors contemplating multiple testing. RECENT FINDINGS: Some authors ignored the problem of multiple testing while others used the method uncritically with no rationale or discussion. A variety of methods of correcting p values were employed, the Bonferroni method being the single most popular. Bonferroni was used in a variety of circumstances, most commonly to correct the experiment-wise error rate when using multiple 't' tests or as a post-hoc procedure to correct the family-wise error rate following analysis of variance (anova). Some studies quoted adjusted p values incorrectly or gave an erroneous rationale. SUMMARY: Whether or not to use the Bonferroni correction depends on the circumstances of the study. It should not be used routinely and should be considered if: (1) a single test of the 'universal null hypothesis' (Ho ) that all tests are not significant is required, (2) it is imperative to avoid a type I error, and (3) a large number of tests are carried out without preplanned hypotheses.

Effects of short-term detraining on postprandial metabolism, endothelial function, and inflammation in endurance-trained men:dissociation between changes in triglyceride metabolism and endothelial function

Endurance-trained athletes experience a low level of postprandial lipaemia, but this rapidly increases with detraining. We sought to determine whether detraining-induced changes to postprandial metabolism influenced endothelial function and inflammation. Eight endurance-trained men each undertook two oral fat tolerance tests [blood taken fasted and for 6 h following a high-fat test meal (80 g fat, 80 g carbohydrate)]: one during a period of their normal training (trained) and one after 1 wk of no exercise (detrained). Endothelial function in the cutaneous microcirculation was assessed using laser Doppler imaging with iontophoresis in the fasted state and 4 h postprandially during each test. Fasting plasma triglyceride (TG) concentrations increased by 35% with detraining (P = 0.002), as did postprandial plasma (by 53%, P = 0.002), chylomicron (by 68%, P = 0.02) and very low-density lipoprotein (by 51%, P = 0.005) TG concentrations. Endothelial function decreased postprandially in both the trained (by 17%, P = 0.03) and detrained (by 22%, P = 0.03) conditions but did not differ significantly between the trained and detrained conditions in either the fasted or the postprandial states. These results suggest that, although fat ingestion induces endothelial dysfunction, interventions that alter postprandial TG metabolism will not necessarily concomitantly influence endothelial function.

Brain-derived neurotrophic factor as an indicator of chemical neurotoxicity:an animal-free CNS cell culture model

Recent changes to the legislation on chemicals and cosmetics testing call for a change in the paradigm regarding the current 'whole animal' approach for identifying chemical hazards, including the assessment of potential neurotoxins. Accordingly, since 2004, we have worked on the development of the integrated co-culture of post-mitotic, human-derived neurons and astrocytes (NT2.N/A), for use as an in vitro functional central nervous system (CNS) model. We have used it successfully to investigate indicators of neurotoxicity. For this purpose, we used NT2.N/A cells to examine the effects of acute exposure to a range of test chemicals on the cellular release of brain-derived neurotrophic factor (BDNF). It was demonstrated that the release of this protective neurotrophin into the culture medium (above that of control levels) occurred consistently in response to sub-cytotoxic levels of known neurotoxic, but not non-neurotoxic, chemicals. These increases in BDNF release were quantifiable, statistically significant, and occurred at concentrations below those at which cell death was measureable, which potentially indicates specific neurotoxicity, as opposed to general cytotoxicity. The fact that the BDNF immunoassay is non-invasive, and that NT2.N/A cells retain their functionality for a period of months, may make this system useful for repeated-dose toxicity testing, which is of particular relevance to cosmetics testing without the use of laboratory animals. In addition, the production of NT2.N/A cells without the use of animal products, such as fetal bovine serum, is being explored, to produce a fully-humanised cellular model.

Monocyte subpopulation counts and TNF alpha associations with clinical outcome post ST elevation myocardial infarction

Background Monocytes are implicated in the initiation and progression of the atherosclerotic plaque contributing to its instability and rupture. Although peripheral monocytosis has been related to poor clinical outcome post ST elevation myocardial infarction (STEMI), only scarce information is available of mechanisms of this association. Tumour necrosis factor alpha (TNFα) is a key cytokine in the acute phase inflammatory response, and it is predominantly produced by inflammatory macrophages. Little is known about TNFα association with circulating monocyte subpopulations post STEMI. Method A total of 142 STEMI patients (mean age 62±13 years; 72% male) treated with percutaneous revascularization were recruited with blood samples obtained within first 24 hours from the onset and on day 10-14. Peripheral blood monocyte subpopulations were enumerated and characterized using flow cytometry after staining for CD14, CD16 and CCR2 and were defined as: CD14++CD16-CCR2+ (Mon1), CD14++CD16+CCR+ (Mon2) and CD14+CD16++CCR2- (Mon3) cells. Plasma levels of TNFα were measured by enzyme-linked immunosorbent assay (ELISA, Peprotec system, UK). Major adverse cardiac events (MACE), defined as recurrent STEMI, new diagnosis of heart failure and death were recorded at follow up, mean of 164±134 days. Results TNFα levels were significantly higher 24 hours post STEMI, compared to day 14 (paired t-test, p <0.001) with day 1 levels weakly correlated with total monocyte count as well as Mon1 (Spearman’s correlation, r=0.19, p=0.02 and r=0.22, p=0.01, respectively). There was no correlation between TNFα and Mon2 or Mon3 subpopulations. TNFα levels were significantly higher in patients with a recorded MACE (n=28, Mann-Whitney test, p<0.001) (figure 1).⇓

Clinical significance of medication reconciliation in children admitted to a UK pediatric hospital:observational study of neurosurgical patients

Background: In December 2007, the National Institute for Health and Clinical Excellence and the National Patient Safety Agency in the UK (NICE-NPSA) published guidance that recommends all adults admitted to hospital receive medication reconciliation, usually by pharmacy staff. A costing and report tool was provided indicating a resource requirement of d12.9 million for England per year. Pediatric patients are excluded from this guidance. Objective: To determine the clinical significance of medication reconciliation in children on admission to hospital. Methods: A prospective observational study included pediatric patients admitted to a neurosurgical ward at Birmingham Childrens Hospital, Birmingham, England, between September 2006 and March 2007. Medication reconciliation was conducted by a pharmacist after the admission of each of 100 consecutive eligible patients aged 4 months to 16 years. The clinical significance of prescribing disparities between pre-admission medications and initial admission medication orders was determined by an expert multidisciplinary panel and quantified using an analog scale. The main outcome measure was the clinical signficance of unintentional variations between hospital admission medication orders and physician-prescribed pre-admission medication for repeat (continuing) medications. Results: Initial admission medication orders for children differed from prescribed pre-admission medication in 39%of cases. Half of all resulting prescribing variations in this setting had the potential to cause moderate or severe discomfort or clinical deterioration. These results mirror findings for adults. Conclusions: The introduction of medication reconciliation in children on admission to hospital has the potential to reduce discomfort or clinical deterioration by reducing unintentional changes to repeat prescribed medication. Consequently, there is no justification for the omission of children from the NICENPSA guidance concerning medication reconciliation in hospitals, and costing tools should include pediatric patients. © 2010 Adis Data Information BV. All rights reserved.