Guidelines and considerations for conducting experiments using tissue microarrays

Tissue microarrays (TMAs) represent a powerful method for undertaking large-scale tissue-based biomarker studies. While TMAs offer several advantages, there are a number of issues specific to their use which need to be considered when employing this method. Given the investment in TMA-based research, guidance on design and execution of experiments will be of benefit and should help researchers new to TMA-based studies to avoid known pitfalls. Furthermore, a consensus on quality standards for TMA-based experiments should improve the robustness and reproducibility of studies, thereby increasing the likelihood of identifying clinically useful biomarkers. In order to address these issues, the National Cancer Research Institute Biomarker and Imaging Clinical Studies Group organized a 1-day TMA workshop held in Nottingham in May 2012. The document herein summarizes the conclusions from the workshop. It includes guidance and considerations on all aspects of TMA-based research, including the pre-analytical stages of experimental design, the analytical stages of data acquisition, and the postanalytical stages of data analysis. A checklist is presented which can be used both for planning a TMA experiment and interpreting the results of such an experiment. For studies of cancer biomarkers, this checklist could be used as a supplement to the REMARK guidelines.

Sparkling wine choice from supermarket shelves: the impact of certification of origin and production practices

We report the results of a study based on revealed and stated preference data on choice of Prosecco wines in retail stores close to the origin of production in Northern Italy. Emphasis is placed on ability to reconcile the utility structure of stated preference data with that underlying revealed preference data. We extend the analysis to cover nonattendance of key attributes, such as price and certification of origin, while controlling for the large range of brand effects.

Rethinking the Sacred and Secular Divide. Accounting and Accountability Practices in the Diocese of Ferrara (1431-1457)

Purpose – Informed by the work of Laughlin and Booth, the paper analyses the role of accounting and accountability practices within the 15th century Roman Catholic Church, more specifically within the Diocese of Ferrara (northern Italy), in order to determine the presence of a sacred-secular dichotomy. Pope Eugenius IV had embarked upon a comprehensive reform of the Church to counter the spreading moral corruption within the clergy and the subsequent disaffection with the Church by many believers. The reforms were notable not only for the Pope’s determination to restore the moral authority and power of the Church but for the essential contributions of ‘profane’ financial and accounting practices to the success of the reforms.
Design/methodology/approach – Original 15th century Latin documents and account books of the Diocese of Ferrara are used to highlight the link between the new sacred values imposed by Pope Eugenius IV’s reforms and accounting and accountability practices.
Findings – The documents reveal that secular accounting and accountability practices were not regarded as necessarily antithetical to religious values, as would be expected by Laughlin and Booth. Instead, they were seen to assume a role which was complementary to the Church’s religious mission. Indeed, they were essential to its sacred mission during a period in which the Pope sought to arrest the moral decay of the clergy and reinstate the Church’s authority. Research implications/limitations – The paper shows that the sacred-secular dichotomy cannot be considered as a priori valid in space and time. There is also scope for examining other Italian dioceses where there was little evidence of Pope Eugenius’ reforms.
Originality/value – The paper presents a critique of the sacred-secular divide paradigm by considering an under-researched period and a non Anglo-Saxon context.

Medical consensus, guidelines, and position papers: A policy for the ECFS

The terms consensus, guideline and position paper are sometimes employed as if they were interchangeable, but the purpose of such documents and the robustness of advice vary as the evidence base does not have the same depth in each. The Board of the European Cystic Fibrosis Society deemed it to be helpful to provide a short commentary on the definition of these terms, on their interconnections and on how ECFS considers them in documents endorsed by the society.

The implausibility of ‘usual care’ in an open system: sedation and weaning practices in Paediatric Intensive Care Units (PICUs) in the United Kingdom (UK).

Background
The power of the randomised controlled trial depends upon its capacity to operate in a closed system whereby the intervention is the only causal force acting upon the experimental group and absent in the control group, permitting a valid assessment of intervention efficacy. Conversely, clinical arenas are open systems where factors relating to context, resources, interpretation and actions of individuals will affect implementation and effectiveness of interventions. Consequently, the comparator (usual care) can be difficult to define and variable in multi-centre trials. Hence outcomes cannot be understood without considering usual care and factors that may affect implementation and impact on the intervention.

Methods
Using a fieldwork approach, we describe PICU context, ‘usual’ practice in sedation and weaning from mechanical ventilation, and factors affecting implementation prior to designing a trial involving a sedation and ventilation weaning intervention. We collected data from 23 UK PICUs between June and November 2014 using observation, individual and multi-disciplinary group interviews with staff.

Results
Pain and sedation practices were broadly similar in terms of drug usage and assessment tools. Sedation protocols linking assessment to appropriate titration of sedatives and sedation holds were rarely used (9 % and 4 % of PICUs respectively). Ventilator weaning was primarily a medical-led process with 39 % of PICUs engaging senior nurses in the process: weaning protocols were rarely used (9 % of PICUs). Weaning methods were variably based on clinician preference. No formal criteria or use of spontaneous breathing trials were used to test weaning readiness. Seventeen PICUs (74 %) had prior engagement in multi-centre trials, but limited research nurse availability. Barriers to previous trial implementation were intervention complexity, lack of belief in the evidence and inadequate training. Facilitating factors were senior staff buy-in and dedicated research nurse provision.

Conclusions
We examined and identified contextual and organisational factors that may impact on the implementation of our intervention. We found usual practice relating to sedation, analgesia and ventilator weaning broadly similar, yet distinctively different from our proposed intervention, providing assurance in our ability to evaluate intervention effects. The data will enable us to develop an implementation plan; considering these factors we can more fully understand their impact on study outcomes.

Mixed Messages: American Correspondences in Visual and Verbal Practices

Mixed Messages presents and interrogates ten distinct moments from the arts of nineteenth, twentieth and twenty-first century America where visual and verbal forms blend and clash. Charting correspondences concerned with the expression and meaning of human experience, this volume moves beyond standard interdisciplinary theoretical approaches to consider the written and visual artwork in embodied, cognitive, and contextual terms.

Offering a genuinely interdisciplinary contribution to the intersecting fields of art history, avant-garde studies, word-image relations, and literary studies, Mixed Messages takes in architecture, notebooks, poetry, painting, conceptual art, contemporary art, comic books, photographs and installations, ending with a speculative conclusion on the role of the body in the experience of digital mixed media. Each of the ten case studies explores the juxtaposition of visual and verbal forms in a manner that moves away from treating verbal and visual symbols as operating in binary or oppositional systems, and towards a consideration of mixed media, multi-media and intermedia work as brought together in acts of creation, exhibition, reading, viewing, and immersion. The collection advances research into embodiment theory, affect, pragmatist aesthetics, as well as into the continuing legacy of romanticism and of dada, conceptual art and surrealism in an American context.

Sound Art and Spatial Practices: Situating Sound Installation Art Since 1958

This dissertation examines the emergence and development of sound installation art, an under-recognized tradition that has developed between music, architecture, and media art practices since the late 1950s. Unlike many musical works, which are concerned with organizing sounds in time, sound installations organize sounds in space; they thus necessitate new theoretical and analytical models that take into consideration the spatial situated-ness of sound. Existing discourses on “spatial sound” privilege technical descriptions of sound localization. By contrast, this dissertation examines the ways in which concepts of space are socially, culturally, and politically construed, and how spatially-organized sound works reflect and resist these different constructions. Using an interdisciplinary methodology of critical spatial analysis and critical studies in music, this dissertation explores such topics as: conceptions of acoustic space in postwar Western art music, architecture, and media theory; the development of sound installation art in relation to philosophies of everyday life and social space; the historical links between musical performance, conceptual art, and sound sculpture; the body as a site for sound installations; and sonicspatial strategies that confront politics of race and gender. Through these different investigations, this dissertation proposes an “ontopological” model for considering sound: a critical model of analysis and reception that privileges an understanding of sound in relation to ontologies of space and place.

On being a good nurse: reflections on the past and preparing for the future

On being a good nurse: reflections on the past and preparing for the future. The objectives of this paper include reflecting on the attributes of the ‘good’ nurse in the past, outlining thematically the essential attributes (virtues) required by the ‘good’ nurse today and presenting an original four- point framework for ethics in practice. While there is no doubt that nurses in the past were highly professional, the culture within which they practiced tended to stifle the emergence of autonomy, assertiveness, advocacy and accountability. An original table of contemporary attributes, which is congruent with a neo Aristotelian virtue ethical approach, is arranged in themes of Intellectual and Practical Attributes, Dispositional Attributes and Moral Attributes. A framework for professional practice, the ‘Four As’ is then extrapolated from these themes. These four key professional attributes, autonomy, advocacy, accountability and assertiveness, along with the virtues listed in the themes, exemplify the ‘good’ nurse and are identified as the linchpins of modern professional ethics and good conduct.

Discovery and Evidence in Transnational Antitrust Cases: Current Framework and the Way Forward

This paper identifies and analyses the means of accessing and collecting foreign-based evidence in transnational antitrust cases. It makes an original contribution to the existing scholarship by critically addressing the available mechanisms of judicial cooperation, the possibility of reliance on domestic discovery in transnational context, as well as the existing instruments allowing for cooperation between antitrust agencies. It identifies the shortcomings of the current regulatory framework and points out to the existing good practices in those jurisdictions which provide their antitrust agencies with more leeway in sharing confidential information with foreign counterparts.

Diagnosis and management of hyponatraemia: AGREEing the guidelines

Hyponatraemia is a common electrolyte disorder associated with significant complications and controversies regarding its optimal management. Clinical practice guidelines and consensus statements have attempted to provide clinicians with evidence-based diagnostic and treatment strategies for hyponatraemia. Recently published guidance documents differ in their methods employed to review the quality of available evidence. Nagler et al. used the Appraisal of Guideline for Research and Evaluation (AGREE II) instrument in a systematic review of guidelines and consensus statements for the diagnosis and management of hyponatraemia. Nagler and colleagues highlighted the variability in methodological rigour applied to guideline development and inconsistencies between publications in relation to management of hyponatraemia (including the recommended rate of correction of a low serum sodium concentration). These differences could cause confusion for practising physicians managing patients with hyponatraemia.

Architecture as Pedagogy: Alive and Kicking

This workshop draws on an emerging collaborative body of research by Lovett, Morrow and McClean that aims to understand architecture and its processes as a form of pedagogical practice: a civic pedagogy.

Architectural education can be valued not only as a process that delivers architecture-specific skills and knowledges, but also as a process that transforms people into critically active contributors to society. We are keen to examine how and where those skills are developed in architectural education and trace their existence and/or application within practice. We intend to examine whether some architectural and spatial practices are intrinsically pedagogical in their nature and how the level of involvement of clients, users and communities can mimic the project-based learning of architectural education – in particularly in the context of ‘live project learning’

1. This workshop begins with a brief discussion paper from Morrow that sets out the arguments behind why and how architecture can be understood as pedagogy. It will do so by presenting firstly the relationship between architectural practice and pedagogy, drawing out both contemporary and historical examples of architecture and architects acting pedagogically. It will also consider some other forms of creative practice that explicitly frame themselves pedagogically, and focus on participatory approaches in architectural practice that overlap with inclusive and live pedagogies, concluding with a draft and tentative abstracted pedagogical framework for architectural practice.

2. Lovett will examine practices of architectural operation that have a pedagogical approach, or which recognise within themselves an educational subtext/current. He is most interested in a 'liveness' beyond the 'Architectural Education' of university institutions. The presentation will question the scope for both spatial empowerment / agency and a greater understanding and awareness of the value of good design when operating as architects with participant-clients younger than 18, older than 25 or across varied parts of society. Positing that the learning might be greatest when there are no prescribed 'Learning Outcomes' and that such work might depend on risk-taking and playfulness, the presentation will be a curated showcase drawing on his own ongoing work.

Both brief presentations will inform the basis of the workshop’s discussion which hopes to draw on participants views and expereinces to enrich the research process. The intention is that the overall workshop will lead to a call for contributors and respondents to a forthcoming publication on ‘Architecture as Pedagogy’.

Regular medication reviews for children and young people with ADHD

The National Institute for Health and Care Excellence's (2008) guidelines for the diagnosis and management of attention deficit hyperactivity disorder (ADHD) recommend a full clinical and psychological assessment by an appropriately trained clinician; this should include a detailed developmental and psychiatric history. Stimulant medications, which are Schedule II controlled drugs, are the most commonly prescribed medicines in the UK and across the world for the management of ADHD. Children and young people with a diagnosis of ADHD receiving these stimulant medications are required to attend regular review appointments with a consultant child and adolescent psychiatrist or specialist nurse under shared care guidelines with general practices, and it has long been recognized that appropriately educated nurses can assist in the management of ADHD. Owing to the pharmacological action of the stimulant medication on neurotransmission, there is potential for misuse and dependence. A growing body of evidence suggests that adolescents with ADHD can become involved in drug diversion and that the topic should be explored during assessment. The level of misuse of prescribed stimulants is increasing, and adolescents and young people with ADHD may misuse to enhance cognitive function for academic purposes. The following scenario highlights some of the challenges and opportunities for independent nurse prescribers working in child and adolescent mental health services.

EuroClonality/BIOMED-2 guidelines for interpretation and reporting of Ig/TCR clonality testing in suspected lymphoproliferations.

PCR-based immunoglobulin (Ig)/T-cell receptor (TCR) clonality testing in suspected lymphoproliferations has largely been standardized and has consequently become technically feasible in a routine diagnostic setting. Standardization of the pre-analytical and post-analytical phases is now essential to prevent misinterpretation and incorrect conclusions derived from clonality data. As clonality testing is not a quantitative assay, but rather concerns recognition of molecular patterns, guidelines for reliable interpretation and reporting are mandatory. Here, the EuroClonality (BIOMED-2) consortium summarizes important pre- and post-analytical aspects of clonality testing, provides guidelines for interpretation of clonality testing results, and presents a uniform way to report the results of the Ig/TCR assays. Starting from an immunobiological concept, two levels to report Ig/TCR profiles are discerned: the technical description of individual (multiplex) PCR reactions and the overall molecular conclusion for B and T cells. Collectively, the EuroClonality (BIOMED-2) guidelines and consensus reporting system should help to improve the general performance level of clonality assessment and interpretation, which will directly impact on routine clinical management (standardized best-practice) in patients with suspected lymphoproliferations.