Patient and public involvement in randomised clinical trials:a mixed-methods study of a clinical trials unit to identify good practice, barriers and facilitators

Abstract Background While patient and public involvement (PPI) in clinical trials is beneficial and mandated by some funders, formal guidance on how to implement PPI is limited and challenges have been reported. We aimed to investigate how PPI is approached within a UK Clinical Trials Unit (CTU)’s portfolio of randomised controlled trials, perceived barriers to/facilitators of its successful implementation, and perspectives on the CTU’s role in PPI. Methods A mixed-methods study design, involving (1) an online survey of 26 trial managers (TMs) and (2) Interviews with Trial Management Group members and public contributors from 8 case-study trials. Quantitative survey data were summarised using descriptive statistics and interview transcripts analysed thematically. Two public contributors advised throughout and are co-authors. Results (1) 21 TMs completed the survey; (2) 19 in-depth interviews were conducted with public contributors (n=8), TMs (n=5), chief investigators (n=3), PPI coordinators (n=2) and a researcher. 15/21 TMs surveyed reported that a public contributor was on the trial team, and 5 used another PPI method. 12/21 TMs reported that public contributors were paid (range £10–50/h). 5 TMs reported that training was provided for public contributors and few staff members had received any formal PPI training. The most commonly reported tasks undertaken by public contributors were the review of participant-facing materials/study documents and advising on recruitment/retention strategies. Public contributors wanted and valued feedback on changes made due to their input, but it was not always provided. Barriers to successful PPI included recruitment challenges, group dynamics, maintaining professional boundaries, negative attitudes to PPI amongst some researchers, a lack of continuity of trial staff, and the academic environment. Successful PPI required early and explicit planning, sharing of power and ownership of the trial with public contributors, building and maintaining relationships, and joint understanding and clarity about expectations/roles. CTUs have an important role to play in supporting recruitment, signposting and coordinating PPI. Conclusions While highly valuable, PPI in trials is currently variable. PPI representatives are recruited informally, may not be provided with any training and are paid inconsistently across trials. Study findings can help optimise PPI in trials and ensure researchers and public contributors are adequately supported

Measurement of ocular surface protection under natural blink conditions

abstract: Purpose: To evaluate a new method of measuring ocular exposure in the context of a natural blink pattern through analysis of the variables tear film breakup time (TFBUT), interblink interval (IBI), and tear film breakup area (BUA). Methods: The traditional methodology (Forced-Stare [FS]) measures TFBUT and IBI separately. TFBUT is measured under forced-stare conditions by an examiner using a stopwatch, while IBI is measured as the subject watches television. The new methodology (video capture manual analysis [VCMA]) involves retrospective analysis of video data of fluorescein-stained eyes taken through a slit lamp while the subject watches television, and provides TFBUT and BUA for each IBI during the 1-minute video under natural blink conditions. The FS and VCMA methods were directly compared in the same set of dry-eye subjects. The VCMA method was evaluated for the ability to discriminate between dry-eye subjects and normal subjects. The VCMA method was further evaluated in the dry eye subjects for the ability to detect a treatment effect before, and 10 minutes after, bilateral instillation of an artificial tear solution. Results: Ten normal subjects and 17 dry-eye subjects were studied. In the dry-eye subjects, the two methods differed with respect to mean TFBUTs (5.82 seconds, FS; 3.98 seconds, VCMA; P = 0.002). The FS variables alone (TFBUT, IBI) were not able to successfully distinguish between the dry-eye and normal subjects, whereas the additional VCMA variables, both derived and observed (BUA, BUA/IBI, breakup rate), were able to successfully distinguish between the dry-eye and normal subjects in a statistically significant fashion. TFBUT (P = 0.034) and BUA/IBI (P = 0.001) were able to distinguish the treatment effect of artificial tears in dry-eye subjects. Conclusion: The VCMA methodology provides a clinically relevant analysis of tear film stability measured in the context of a natural blink pattern.The final version of this article, as published in Clinical Ophthalmology, can be viewed online at: https://www.dovepress.com/measurement-of-ocular-surface-protection-under-natural-blink-condition-peer-reviewed-article-OPT

A high-content imaging assay for the quantification of the Burkholderia pseudomallei induced multinucleated giant cell (MNGC) phenotype in murine macrophages

BACKGROUND: Burkholderia pseudomallei (Bp), a Gram-negative, motile, facultative intracellular bacterium is the causative agent of melioidosis in humans and animals. The Bp genome encodes a repertoire of virulence factors, including the cluster 3 type III secretion system (T3SS-3), the cluster 1 type VI secretion system (T6SS-1), and the intracellular motility protein BimA, that enable the pathogen to invade both phagocytic and non-phagocytic cells. A unique hallmark of Bp infection both in vitro and in vivo is its ability to induce cell-to-cell fusion of macrophages to form multinucleated giant cells (MNGCs), which to date are semi-quantitatively reported following visual inspection. RESULTS: In this study we report the development of an automated high-content image acquisition and analysis assay to quantitate the Bp induced MNGC phenotype. Validation of the assay was performed using T6SS-1 (∆hcp1) and T3SS-3 (∆bsaZ) mutants of Bp that have been previously reported to exhibit defects in their ability to induce MNGCs. Finally, screening of a focused small molecule library identified several Histone Deacetylase (HDAC) inhibitors that inhibited Bp-induced MNGC formation of macrophages. CONCLUSIONS: We have successfully developed an automated HCI assay to quantitate MNGCs induced by Bp in macrophages. This assay was then used to characterize the phenotype of the Bp mutants for their ability to induce MNGC formation and identify small molecules that interfere with this process. Successful application of chemical genetics and functional reverse genetics siRNA approaches in the MNGC assay will help gain a better understanding of the molecular targets and cellular mechanisms responsible for the MNGC phenotype induced by Bp, by other bacteria such as Mycobacterium tuberculosis, or by exogenously added cytokines

The covering factor of high redshift damped Lyman-α\alpha systems

We have used the Very Long Baseline Array to image 18 quasars with foreground damped Lyman-$\alpha$ systems (DLAs) at 327, 610 or 1420 MHz, to measure the covering factor $f$ of each DLA at or near its redshifted HI 21cm line frequency. Including six systems from the literature, we find that none of 24 DLAs at $0.09 < z < 3.45$ has an exceptionally low covering factor, with $f \sim 0.45 - 1$ for the 14 DLAs at $z > 1.5$, $f \sim 0.41 - 1$ for the 10 systems at $z < 1$, and consistent covering factor distributions in the two sub-samples. The observed paucity of detections of HI 21cm absorption in high-$z$ DLAs thus cannot be explained by low covering factors and is instead likely to arise due to a larger fraction of warm HI in these absorbers.Comment: 6 pages, 20 figures; MNRAS (Letters), in pres

27th Annual Midwest/Midsouth Estate Planning Institute

Materials from the 27th Annual Midwest/Midsouth Estate Planning Institute held by UK/CLE in July 2000

Quantum chaos in a deformable billiard: Applications to quantum dots

We perform a detailed numerical study of energy-level and wavefunction statistics of a deformable quantum billiard focusing on properties relevant to semiconductor quantum dots. We consider the family of Robnik billiards generated by simple conformal maps of the unit disk; the shape of this family of billiards may be varied continuously at fixed area by tuning the parameters of the map. The classical dynamics of these billiards is well-understood and this allows us to study the quantum properties of subfamilies which span the transition from integrability to chaos as well as families at approximately constant degree of chaoticity (Kolmogorov entropy). In the regime of hard chaos we find that the statistical properties of interest are well-described by random-matrix theory and completely insensitive to the particular shape of the dot. However in the nearly-integrable regime non-universal behavior is found. Specifically, the level-width distribution is well-described by the predicted $\chi^2$ distribution both in the presence and absence of magnetic flux when the system is fully chaotic; however it departs substantially from this behavior in the mixed regime. The chaotic behavior corroborates the previously predicted behavior of the peak-height distribution for deformed quantum dots. We also investigate the energy-level correlation functions which are found to agree well with the behavior calculated for quasi-zero-dimensional disordered systems.Comment: 25 pages (revtex 3.0). 16 figures are available by mail or fax upon request at [email protected]

Stellar Diameters and Temperatures II. Main Sequence K & M Stars

We present interferometric diameter measurements of 21 K- and M- dwarfs made with the CHARA Array. This sample is enhanced by literature radii measurements to form a data set of 33 K-M dwarfs with diameters measured to better than 5%. For all 33 stars, we compute absolute luminosities, linear radii, and effective temperatures (Teff). We develop empirical relations for \simK0 to M4 main- sequence stars between the stellar Teff, radius, and luminosity to broad-band color indices and metallicity. These relations are valid for metallicities between [Fe/H] = -0.5 and +0.1 dex, and are accurate to ~2%, ~5%, and ~4% for Teff, radius, and luminosity, respectively. Our results show that it is necessary to use metallicity dependent transformations to convert colors into stellar Teffs, radii, and luminosities. We find no sensitivity to metallicity on relations between global stellar properties, e.g., Teff-radius and Teff-luminosity. Robust examinations of single star Teffs and radii compared to evolutionary model predictions on the luminosity-Teff and luminosity-radius planes reveals that models overestimate the Teffs of stars with Teff < 5000 K by ~3%, and underestimate the radii of stars with radii < 0.7 R\odot by ~5%. These conclusions additionally suggest that the models overestimate the effects that the stellar metallicity may have on the astrophysical properties of an object. By comparing the interferometrically measured radii for single stars to those of eclipsing binaries, we find that single and binary star radii are consistent. However, the literature Teffs for binary stars are systematically lower compared to Teffs of single stars by ~ 200 to 300 K. Lastly, we present a empirically determined HR diagram for a total of 74 nearby, main-sequence, A- to M-type stars, and define regions of habitability for the potential existence of sub-stellar mass companions in each system. [abridged]Comment: 73 pages, 12 Tables, 18 Figures. Accepted for publication in The Astrophysical Journa

Oralism: a sign of the times? The contest for deaf communication in education provision in late nineteenth-century Scotland

Disability history is a diverse field. In focussing upon children within deaf education in late nineteenth-century Scotland, this essay reflects some of that diversity. In 1880, the International Congress on the Education of the Deaf in Milan stipulated that speech should have ‘preference’ over signs in the education of deaf children. The mode of achieving this, however, effectively banned sign language. Endeavours to teach deaf children to articulate were not new, but this decision placed pressures on deaf institutions to favour the oral system of deaf communication over other methods. In Scotland efforts were made to adopt oralism, and yet educators were faced with the reality that this was not good educational practice for most pupils. This article will consider responses of Scottish educators of deaf children from the 1870s until the beginning of the twentieth century

A Threat Assessment and Security Analysis of the Three Sports Facilities of Indiana University-Purdue University, Indianapolis NCAA Softball Fields, Carroll Stadium, and the IU Natatorium

This research report provides a security assessment of the Softball Fields, Carroll Stadium, and the Natatorium Complex at Indiana University-Purdue University Indianapolis (IUPUI). The purpose of this report is to prevent and mitigate harm to visitors and these facilities which resulting from human-made or natural disasters. Research is guided by the hypothesis that these facilities- due to their respective importance, locations, and attendance patterns are in harm’s way; and that certain strategies of prevention, protection, and mitigation coupled with effective preparedness, response, and recovery can lessen risk, improve security and provide A THREAT ASSESSMENT AND SECURITY ANALYSIS 5 added resilience. Further, “harm’s way” is considered to be either a natural disaster or a human-made disaster, accident, active provocation, or act of terrorism. Methods of analysis include applied research; predominantly utilizing qualitative data with some quantitative investigation. Results of this assessment illustrate that these venues possess numerous vulnerabilities to both natural and human-made threats that if exposed, could result in serious consequences. The two most likely natural hazards identified include straight-line winds and tornadoes. Further, the most likely human threats to these facilities arise from a potential terrorist vehicle attack (TVA) and an active shooter. This project also identifies a specific need for additional planning to prevent an IED or VBIED attack on the Natatorium. Common themes from the attached three case studies reveal that given theses vulnerabilities, the following safety and security adjustments are recommended: Surveillance equipment Metal detectors Security bollards or other temporary barriers Evacuation routes and shelter in place plans Special event security procedures Weather related technology and protocols Staff training for emergency situation