Variation of clinical outcomes used in glaucoma randomised controlled trials:a systematic review

Purpose: In randomised clinical trials (RCTs) the selection of appropriate outcomes is crucial to the assessment of whether one intervention is better than another. The purpose of this review is to identify different clinical outcomes reported in glaucoma trials.

Methods We conducted a systematic review of glaucoma RCTs. A sample or selection of glaucoma trials were included bounded by a time frame (between 2006 and March 2012). Only studies in English language were considered. All clinical measured and reported outcomes were included. The possible variations of clinical outcomes were defined prior to data analysis. Information on reported clinical outcomes was tabulated and analysed using descriptive statistics. Other data recorded included type of intervention and glaucoma, duration of the study, defined primary outcomes, and outcomes used for sample size calculation, if nominated.

Results The search strategy identified 4323 potentially relevant abstracts. There were 315 publications retrieved, of which 233 RCTs were included. A total of 967 clinical measures were reported. There were large variations in the definitions used to describe different outcomes and their measures. Intraocular pressure was the most commonly reported outcome (used in 201 RCTs, 86%) with a total of 422 measures (44%). Safety outcomes were commonly reported in 145 RCTs (62%) whereas visual field outcomes were used in 38 RCTs (16%).

Conclusions There is a large variation in the reporting of clinical outcomes in glaucoma RCTs. This lack of standardisation may impair the ability to evaluate the evidence of glaucoma interventions.

On the maximum energy of shock-accelerated cosmic rays at ultra-relativistic shocks

The maximum energy to which cosmic rays can be accelerated at weakly magnetised ultra-relativistic shocks is investigated. We demonstrate that for such shocks, in which the scattering of energetic particles is mediated exclusively by ion skin-depth scale structures, as might be expected for a Weibel-mediated shock, there is an intrinsic limit on the maximum energy to which particles can be accelerated. This maximum energy is determined from the requirement that particles must be isotropized in the downstream plasma frame before the mean field transports them far downstream, and falls considerably short of what is required to produce ultra-high-energy cosmic rays. To circumvent this limit, a highly disorganized field is required on larger scales. The growth of cosmic ray-induced instabilities on wavelengths much longer than the ion-plasma skin depth, both upstream and downstream of the shock, is considered. While these instabilities may play an important role in magnetic field amplification at relativistic shocks, on scales comparable to the gyroradius of the most energetic particles, the calculated growth rates have insufficient time to modify the scattering. Since strong modification is a necessary condition for particles in the downstream region to re-cross the shock, in the absence of an alternative scattering mechanism, these results imply that acceleration to higher energies is ruled out. If weakly magnetized ultra-relativistic shocks are disfavoured as high-energy particle accelerators in general, the search for potential sources of ultra-high-energy cosmic rays can be narrowed.

AcT-2: A Novel Myotropic and Antimicrobial Type 2 Tryptophyllin from the Skin Secretion of the Central American Red-Eyed Leaf Frog, Agalychnis callidryas

Tryptophyllins are a diverse family of amphibian peptides originally found in extracts of phyllomedusine frog skin by chemical means. Their biological activities remain obscure. Here we describe the isolation and preliminary pharmacological characterization of a novel type 2 tryptophyllin, named AcT-2, from the skin secretion of the red-eyed leaf frog, Agalychnis callidryas. The peptide was initially identified during smooth muscle pharmacological screening of skin secretion HPLC fractions and the unique primary structure—GMRPPWF-NH2—was established by both Edman degradation and electrospray MS/MS fragmentation sequencing. A. cDNA encoding the biosynthetic precursor of AcT-2 was successfully cloned from a skin secretion-derived cDNA library by means of RACE PCR and this contained an open-reading frame consisting of 62 amino acid residues with a single AcT-2 encoding sequence located towards the C-terminus. A synthetic replicate of AcT-2 was found to relax arterial smooth muscle (EC50 = 5.1 nM) and to contract rat urinary bladder smooth muscle (EC50 = 9.3 μM). The peptide could also inhibit the growth of the microorganisms, Staphylococcus aureus, (MIC = 256 mg/L) Escherichia coli (MIC = 512 mg/L), and Candida albicans (128 mg/L). AcT-2 is thus the first amphibian skin tryptophyllin found to possess both myotropic and antimicrobial activities.

Variability of the high-velocity outflow in the quasar PDS 456

We present a comparison of two Suzaku X-ray observations of the nearby (z = 0.184), luminous (L ∼ 10 erg s) type I quasar, PDS 456. A new 125 ks Suzaku observation in 2011 caught the quasar during a period of low X-ray flux and with a hard X-ray spectrum, in contrast with a previous 190 ks Suzaku observation in 2007 when the quasar appeared brighter and had a steep (Γ > 2) X-ray spectrum. The 2011 X-ray spectrum contains a pronounced trough near 9 keV in the quasar rest frame, which can be modeled with blueshifted iron K-shell absorption, most likely from the He- and H-like transitions of iron. The absorption trough is observed at a similar rest-frame energy as in the earlier 2007 observation, which appears to confirm the existence of a persistent high-velocity wind in PDS 456, at an outflow velocity of 0.25-0.30c. The spectral variability between 2007 and 2011 can be accounted for by variations in a partial covering absorber, increasing in covering fraction from the brighter 2007 observation to the hard and faint 2011 observation. Overall, the low-flux 2011 observation can be explained if PDS 456 is observed at relatively low inclination angles through a Compton-thick wind, originating from the accretion disk, which significantly attenuates the X-ray flux from the quasar. © 2014. The American Astronomical Society. All rights reserved.

Ornithokinin (avian bradykinin) from the skin of the Chinese bamboo odorous frog, Odorrana versabilis

One of the most widespread and abundant families of pharmacologically active peptides in amphibian defensive skin secretions is the bradykinins and related peptides. Despite retaining certain primary structural attributes that assign them to this peptide family, bradykinins and related peptides are unique among amphibian skin peptides in that they exhibit a wide range of primary structural variations, post-translational modifications and/or N-terminal or C-terminal extensions. Initially it was believed that their high degree of primary structural heterogeneity was reflective of random gene mutations within species, but latterly, there is an increasing body of evidence that the spectrum of structural modifications found within this peptide family is reflective of the vertebrate predator spectrum of individual species. Here we report the discovery of ornithokinin (avian bradykinin – Thr6, Leu8-bradykinin) in the skin secretion of the Chinese bamboo odorous frog, Odorrana versabilis. Molecular cloning of its biosynthetic precursor-encoding cDNA from a skin secretion-derived cDNA library revealed a deduced open-reading frame of 86 amino acid residues, encoding a single copy of ornithokinin towards its C-terminus. The domain architecture of this ornithokinin precursor protein was consistent with that of a typical amphibian skin peptide and quite different to that of the ornithokininogen from chicken plasma. Ornithokinin was reported to induce hypotension in the chicken and to contract the chicken oviduct but to have no obvious effect on the rat uterus. However, in this study, synthetic ornithokinin was found to contract the rat ileum (EC50 = 539 nM) and to increase contraction frequency in the rat uterus (EC50 = 1.87 μM).

Molecular Cloning of a Novel Tryptophyllin Peptide from the Skin of the Orange-Legged Monkey Frog, Phyllomedusa hypochondrialis

Tryptophyllins are a group of small (4–14 amino acids), heterogenous peptides, mostly from the skins of hylid frogs from the genera, Phyllomedusa and Litoria. To date, more than forty TPHs have been discovered in species from these two genera. Here, we describe the identification of a novel tryptophyllin type 3 peptide, PhT-3, from the extracts of skin of the orange-legged monkey frog, Phyllomedusa hypochondrialis, and molecular cloning of its precursor-encoding cDNA from a cDNA library constructed from the same skin sample. Full primary structural characterization was achieved using a combination of direct Edman degradation, mass spectrometry and deduction from cloned skin-derived cDNA. The open-reading frame of the precursor cDNA was found to consist of 63 amino acid residues. The mature peptide arising from this precursor contains a post-translationally modified N-terminal pyroglutamate (pGlu) residue, formed from acid-mediated cyclization of an N-terminal Gln (Q) residue, and with the structure: pGlu-Asp-Lys-Pro-Phe-Trp-Pro-Pro-Pro-Ile-Tyr-Pro-Met. Pharmacological assessment of a synthetic replicate of this peptide on phenylephrine preconstricted rat tail artery segments, revealed a reduction in relaxation induced by bradykinin. PhT-3 was also found to mediate antiproliferative effects on human prostate cancer cell lines.

Dissidents with an innovation cause? Non-institutionalized actors ’ online social knowledge sharing, solution-finding tensions and technology management innovation

Purpose
– Traditionally, most studies focus on institutionalized management-driven actors to understand technology management innovation. The purpose of this paper is to argue that there is a need for research to study the nature and role of dissident non-institutionalized actors’ (i.e. outsourced web designers and rapid application software developers). The authors propose that through online social knowledge sharing, non-institutionalized actors’ solution-finding tensions enable technology management innovation.

Design/methodology/approach
– A synthesis of the literature and an analysis of the data (21 interviews) provided insights in three areas of solution-finding tensions enabling management innovation. The authors frame the analysis on the peripherally deviant work and the nature of the ways that dissident non-institutionalized actors deviate from their clients (understood as the firm) original contracted objectives.

Findings
– The findings provide insights into the productive role of solution-finding tensions in enabling opportunities for management service innovation. Furthermore, deviant practices that leverage non-institutionalized actors’ online social knowledge to fulfill customers’ requirements are not interpreted negatively, but as a positive willingness to proactively explore alternative paths.

Research limitations/implications
– The findings demonstrate the importance of dissident non-institutionalized actors in technology management innovation. However, this work is based on a single country (USA) and additional research is needed to validate and generalize the findings in other cultural and institutional settings.

Originality/value
– This paper provides new insights into the perceptions of dissident non-institutionalized actors in the practice of IT managerial decision making. The work departs from, but also extends, the previous literature, demonstrating that peripherally deviant work in solution-finding practice creates tensions, enabling management innovation between IT providers and users.

An accelerated method of developing DBT projects using CDIO partner institutions as parallel processors

The cycle of the academic year impacts on efforts to refine and improve major group design-build-test (DBT) projects since the time to run and evaluate projects is generally a full calendar year. By definition these major projects have a high degree of complexity since they act as the vehicle for the application of a range of technical knowledge and skills. There is also often an extensive list of desired learning outcomes which extends to include professional skills and attributes such as communication and team working. It is contended that student project definition and operation, like any other designed product, requires a number of iterations to achieve optimisation. The problem however is that if this cycle takes four or more years then by the time a project’s operational structure is fine tuned it is quite possible that the project theme is no longer relevant. The majority of the students will also inevitably experience a sub-optimal project experience over the 5 year development period. It would be much better if the ratio were flipped so that in 1 year an optimised project definition could be achieved which had sufficient longevity that it could run in the same efficient manner for 4 further years. An increased number of parallel investigators would also enable more varied and adventurous project concepts to be examined than a single institution could undertake alone in the same time frame.
This work-in-progress paper describes a parallel processing methodology for the accelerated definition of new student DBT project concepts. This methodology has been devised and implemented by a number of CDIO partner institutions in the UK & Ireland region. An agreed project theme was operated in parallel in one academic year with the objective of replacing a multi-year iterative cycle. Additionally the close collaboration and peer learning derived from the interaction between the coordinating academics facilitated the development of faculty teaching skills in line with CDIO standard 10.

Masks as methodology and the phenomenological turn: issues of interpretation

The purposes of this chapter are to argue for (i) the heuristic value of the concept of mask and masking in research which has its basis in psychodynamic theory but relating it to socio-cultural theory as means to understanding self-experience (ii) the value of creating and performing masks as one valuable methodological ‘embodied’ form in social and educational research that represent individuals’ richly textured self-other constructions and allow for the interrogation of any simplistic dichotomies associated with notions of ‘inside’ ‘outside’ categories (iii) exploring possibilities and dilemmas of interpretation within this frame

The student experience in Objective Structured Clinical Examinations (OSCEs): phenomenological analysis

Background and purpose
The dominant psychometric discourse of OSCEs may lead to unexpected problems, such as a checklist-based student performance1 which under emphasises the clinical relationship with student and standardised patient (SP). Such encounters can be dehumanising for SPs2 and have implications for what students learn about relational skills through the assessment process. In this study we explore medical students’ experiences of undertaking OSCEs using a phenomenological frame.
Methodology
Interpretative phenomenological analysis is a form of qualitative methodology which has strong resonance with existentialism and focuses on the lived experience without significant reference to external political or discursive
forces.
Six 4th year undergraduate medical students from Queen’s University Belfast were recruited in December 2013. Maximum variation sampling was used. Students were interviewed by a researcher in the week prior to the
OSCE and then again in the week following the OSCE in Jan 2014. Interviews were minimally structured in order to be open to respondents, rather than adhering to a fixed topic guide, but focussed on participants’ experiences, thoughts and feelings about taking part in OSCEs. Interviews were audio-recorded and
transcribed. Students were also asked to complete a short diary entry in the days prior to the OSCEs and another immediately following. Diary entries were written, emailed or audio-recorded at student’s preference.
Results
Transcripts are currently being analysed by interpretative phenomenological analysis. Preliminary analysis has demonstrated the significance of students’ relationships within the OSCE triad (student, SP and examiner); the effect of the immediate examination environment; realism versus roleplay; students’ perceptions of the purpose of assessment; and coping mechanisms.
Full results will be available by the time of the conference.
Conclusion and Discussion
Understanding the student experience in OSCEs is a crucial step in understanding the complex construction of relationships within the OSCE triad. The focus in OSCEs is typically on standardisation and reliability, but in exploring social interactions we may refocus attention on their inherent potential for learning and effects on both students and patients.
References
1. Hodges B. Medical education and the maintenance of incompetence. Med Teach 2006;28(8):690-6
2. Johnston JL, Lundy G, McCullough M, Gormley GJ. The view from over there: reframing the OSCE through the experience of standardised patient
raters. Med Educ 2013;47(9):899-909

Macroprudential Ideas and Contested Social Purpose: A Response to Terrence Casey

In response to Terrence Casey's argument that the emergence of macroprudential regulation since the financial crash can and should save neoliberalism we raise five objections. 1). The Debt-Driven Growth Hypothesis (DDG) and the Financial Instability Hypothesis (FIH), as Casey terms them, are just as likely to be complementary as they are oppositional and they are by no means incompatible. 2) Casey's empirics are too thin and static, drawn from the 1980s and 1990s, while Anglo Liberal Financialised Capitalism (ALFC) is a complex adaptive system that has continued to evolve throughout the 2000s. 3) Casey overlooks the dynamic relationship between potentially excessive financialisation and the performance of the wider economy, which is becoming a growing concern for many policy makers using the macroprudential frame. 4) Macroprudential as a series of ideas about the economy are often incompatible with neoliberal premises and their ontological foundations. 5) Many of the policy makers who have acted as the biggest champions of macroprudential regulation have also been highly critical of ALFC and view the macroprudential turn as making a contribution to a much needed deeper financial reformation that would over time transform some of the constituent economic and social relations of the existing political economy. We conclude that what we call the social purpose of macroprudential regulation (the question of whether it is intended to patch up or transform the existing system) is contested, and that macroprudential regulation has much potential beyond saving ‘neoliberalism’.

Varieties of Economic Crisis, Varieties of Ideational Change: How and Why Macroeconomic Policy and Financial Regulation Differ

One of the principal tasks facing post-crash academic political economy is to analyse patterns of ideational change and the conditions that produce such change. What has been missing from the existing literature on ideational change at times of crises however, is a sense of how processes of persuasive struggle, and how the success of those ‘norm entrepreneurs’ arguing for ideational change is shaped by two contextual variables: the most immediate material symptoms and problems that a crisis displays (the variety of crisis); and the institutional character of the policy subsystem that agents have to operate within to affect change. Introducing these two variables into our accounts of persuasive struggle and ideational change enables us to deepen our understanding of the dynamics of ideational change at times of crisis. The article identifies that a quite rapid and radical intellectual change has been evident in the field of financial regulation in the form of an embrace of a macroprudential frame. In contrast in the field of macroeconomic policy - both monetary and fiscal policy, many pre-crash beliefs remain prominent, there is evidence of ideational stickiness and inertia, and despite some policy experimentation, overarching policy frameworks and their rationales have not been overhauled. The article applies Peter Hall’s framework of three orders of policy changes to help illuminate and explain the variation in patterns of change in the fields of financial regulation and macroeconomic policy since the financial crash of 2008. The different patterns of ideational change in macroeconomic policy and financial regulation in the post-crash period can be explained by timing and variety of crisis; sequencing of policy change; and institutional political differences between micro policy sub systems and macro policy systems.

Seismic Assessment of a Steel Braced Plan Mass Symmetric/Asymmetric Building Structure

This paper presents a seismic response investigation into a code designed concentrically braced frame structure that is subjected to but not designed for in-plan mass eccentricity. The structure has an accidental uneven distribution of mass in plan resulting in an increased torsional component of vibration. The level of inelasticity that key structural elements in plan mass asymmetric structures are subjected to is important when analysing their ability to sustain uneven seismic demands. In-plan mass asymmetry of moment resisting frame and shear wall type structures have received significant investigation, however, the plan asymmetric response of braced frame type structures is less well understood. A three-dimensional non-linear time history analysis (NLTHA) model is created to capture the torsional response of the plan mass asymmetric structure to quantify the additional ductility demand, interstorey drifts and floor rotations. Results show that the plan mass asymmetric structure performs well in terms of ductility demand, but poorly in terms of interstorey drifts and floor rotations when compared to the plan mass symmetric structure. New linear relationships are developed between the normalised ductility demand and normalised slenderness of the bracing on the sides of the plan mass symmetric/asymmetric structures that the mass is distributed towards and away from.

Direction-contingent duration compression is primarily retinotopic

Previous research has shown that prior adaptation to a spatially circumscribed, oscillating grating results in the duration of a subsequent stimulus briefly presented within the adapted region being underestimated. There is an on-going debate about where in the motion processing pathway the adaptation underlying this distortion of sub-second duration perception occurs. One position is that the LGN and, perhaps, early cortical processing areas are likely sites for the adaptation; an alternative suggestion is that visual area MT+ contains the neural mechanisms for sub-second timing; and a third position proposes that the effect is driven by adaptation at multiple levels of the motion processing pathway. A related issue is in what frame of reference – retinotopic or spatiotopic – does adaptation induced duration distortion occur. We addressed these questions by having participants adapt to a unidirectional random dot kinematogram (RDK), and then measuring perceived duration of a 600 ms test RDK positioned in either the same retinotopic or the same spatiotopic location as the adaptor. We found that, when it did occur, duration distortion of the test stimulus was direction contingent; that is it occurred when the adaptor and test stimuli drifted in the same direction, but not when they drifted in opposite directions. Furthermore the duration compression was evident primarily under retinotopic viewing conditions, with little evidence of duration distortion under spatiotopic viewing conditions. Our results support previous research implicating cortical mechanisms in the duration encoding of sub-second visual events, and reveal that these mechanisms encode duration within a retinotopic frame of reference.