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Group sequential designs for pragmatic clinical trials with early outcomes : methods and guidance for planning and implementation
Get PDFBackground: Group sequential designs are one of the most widely used methodologies for adaptive design in randomized clinical trials. In settings where early outcomes are available, they offer large gains in efficiency compared to a fixed design. However, such designs are underused and used predominantly in therapeutic areas where there is expertise and experience in implementation. One barrier to their greater use is the requirement to undertake simulation studies at the planning stage that require considerable knowledge, coding experience and additional costs. Based on some modest assumptions about the likely patterns of recruitment and the covariance structure of the outcomes, some simple analytic expressions are presented that negate the need to undertake simulations. Methods: A model for longitudinal outcomes with an assumed approximate multivariate normal distribution and three contrasting simple recruitment models are described, based on fixed, increasing and decreasing rates. For assumed uniform and exponential correlation models, analytic expressions for the variance of the treatment effect and the effects of the early outcomes on reducing this variance at the primary outcome time-point are presented. Expressions for the minimum and maximum values show how the correlations and timing of the early outcomes affect design efficiency. Results: Simulations showed how patterns of information accrual varied between correlation and recruitment models, and consequentially to some general guidance for planning a trial. Using a previously reported group sequential trial as an exemplar, it is shown how the analytic expressions given here could have been used as a quick and flexible planning tool, avoiding the need for extensive simulation studies based on individual participant data. Conclusions: The analytic expressions described can be routinely used at the planning stage of a putative trial, based on some modest assumptions about the likely number of outcomes and when they might occur and the expected recruitment patterns. Numerical simulations showed that these models behaved sensibly and allowed a range of design options to be explored in a way that would have been difficult and time-consuming if the previously described method of simulating individual trial participant data had been used
Co-producing an online patient public community research hub : a qualitative study exploring the perspectives of national institute for health research (NIHR) research champions in England
Get PDFBackground: Patient and Public Involvement and Engagement (PPIE) should be embedded as part of researchers’ everyday practice. However, this can be challenging. Creating a digital presence for PPIE as part of Higher Education Institutes’ (HEIs) infrastructure may be one way of supporting this. This can support how information is made available to patients and members of the public, but relatively little is known about how HEIs can best do this. Our aim was to develop a university website for patients and members of the public to learn about ways to get actively involved in research and be able to access the results of health and social care research. Methods: This project involved working as partners with five National Institute for Health and Care Research (NIHR) Research Champions. NIHR Research Champions are volunteers who raise awareness and share experiences about health and social care research. Content of a prototype Patient Public Community Research Hub website was co-produced with the Research Champions, and then 15 NIHR Research Champions from across England were asked for their views about the website. Findings: The information collected told us that the Patient Public Community Research Hub was viewed as being beneficial for increasing visibility of PPIE opportunities and sharing the findings of studies though needs further work: to make the information more user-friendly; to improve the methods for directing people to the site and to create new ways of connecting with people. It provides a foundation for further co-development and evaluation. A set of recommendations has been developed that may be of benefit to other HEIs and organisations who are committed to working with patients and members of the public
Enhancement in the production of phenolic compounds from Fagonia indica callus cultures via Fusarium oxysporum triggered elicitation
No full textFagonia indica Burm.f. (1768) is a medicinally important plant showing diverse pharmaceutical benefits. It is renowned for its ability to biosynthesize several anticancer and anti-inflammatory metabolites. For the eco-friendly and sustainable synthesis of phytochemicals and plant biomass, a biotechnological technique, “elicitation,” is a highly effective method in various in vitro cultures. The present study includes using various concentrations of Fusarium oxysporum Schlecht. as an elicitor in callus cultures of Fagonia indica. The main goal was to achieve enhancement in biomass production and secondary metabolism. The findings demonstrated that maximum biomass production (FW: 167.42 ± 3.99 g per 100 mL; DW: 12.53 ± 1.04 g per 100 mL) was observed at 50 mg L−1 of Fusarium oxysporum as compared to the control. Secondary metabolites showed immense production (phenolic content (9.68 ± 0.23 µg mg−1); flavonoid content (2.814808 ± 0.11 µg mg−1)) in callus cultures treated with 10 mg L−1 of Fusarium oxysporum as compared with control. Moreover, the cultures possessed the highest antioxidant capacity, as determined by 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS•+) radical cation based assay and α, α-diphenyl-β-picrylhydrazyl (DPPH) free radical scavenging assay, ((821.51 ± 3.20 µmol TEAC per mg DW of ABTS inhibition) (91% ± 1.45 of DPPH inhibition)) at 10 mg L−1 concentration of Fusarium oxysporum, and the maximum ferric ion reducing activity (219.29 ± 2.36 µmol TEAC per mg DW) was noticed at 1.0 mg L−1 concentration of F. oxysporum. Fagonia indica cultures also indicated the highest percent inhibition against cyclooxygenases (COX-1: 51.93% ± 1.74 and COX-2: 40.57% ± 1.99), lipoxygenase (15-LOX: 65.72% ± 1.44), and phospholipase A2 (sPLA2: 49.29% ± 1.75), when treated with different concentrations of F. oxysporum. HPLC analyses showed a significant accumulation of pharmacologically active components in the treated samples, with kaempferol (1245.56 mg g−1) and myricetin (1139.63 mg g−1) as the most accumulated compounds in the cultures with 10.0 mg L−1 concentration of Fusarium in contrast to the control. These findings revealed that in callus cultures of F. indica, F. oxysporum could boost biomass accumulation and secondary metabolite production
Talk shows and ‘tanorexia’ : motherhood and ‘sunbed addiction’ on British television in the 1990s
No full textThe rise in melanoma skin cancer rates from the 1950s in mostly fair-skinned populations, such as Britain, triggered a global panic on skin cancer in the 1990s. Some countries tightened restrictions on sunbeds to lower these rates, eventually leading to outright bans. However, the British government, medical experts and the media could not deter sunbed operators and instead focused on discouraging sunbed users. Soon, the media, endorsed by psychologists, confirmed a widespread ‘condition’ across Britain, termed as either ‘sunbed addiction’ or ‘tanorexia’. This ‘disorder’ became a hot topic on new women-centred talk shows in mid-1990s Britain. As this talk show genre originated in America, it encouraged an ‘American style’ of public confession culture. Although ‘American’ openness did not resonate with the expectation of the British ‘stiff upper lip’, audience members aggressively contributed when topics touched on motherhood. This reflected the unanimous consensus that mothers should be ‘selfless’ and act in the best interest of their children. As such, topics on motherhood became a double-edged sword; the mothers, as talk show guests, received intense public support and scrutiny. By focusing on ‘tanorexia’, this chapter, therefore, demonstrates how new television genres linked to third-wave feminism continued a long-standing tradition of pathologising women’s pleasure – especially if it deterred from maternal responsibilities. By historicising and contextualising talk shows, this chapter also offers novel approaches for health historians to build on, including how to evaluate the rhetorical and emotional reactions of its subjects and audience members
Multi-disciplinary perspectives on citizen science – synthesizing five “paradigms” of citizen involvement
Get PDFResearch on Open Innovation in Science (OIS) investigates how open and collaborative practices influence the scientific and societal impact of research. Since 2019, the OIS Research Conference has brought together scholars and practitioners from diverse backgrounds to discuss OIS research and case examples. In this meeting report, we describe four session formats that have allowed our multi-disciplinary community to have productive discussions around opportunities and challenges related to citizen involvement in research. However, these sessions also highlighted the need for a better understanding of the underlying rationales of citizen involvement in an increasingly diverse project landscape. Building on the discussions at the 2023 and prior editions of the conference, we outline a conceptual framework of five crowd paradigms and present an associated tool that help understand how citizen involvement in particular projects can help advance science. We illustrate this tool using cases presented at the 2023 conference and discuss how it can facilitate discussions at future conferences as well as guide future research and practice in citizen science
Sulfur dioxide in the mid-infrared transmission spectrum of WASP-39b
No full textThe recent inference of sulfur dioxide (SO2) in the atmosphere of the hot (approximately 1,100 K), Saturn-mass exoplanet WASP-39b from near-infrared JWST observations1–3 suggests that photochemistry is a key process in high-temperature exoplanet atmospheres4. This is because of the low (<1 ppb) abundance of SO2 under thermochemical equilibrium compared with that produced from the photochemistry of H2O and H2S (1–10 ppm)4–9. However, the SO2 inference was made from a single, small molecular feature in the transmission spectrum of WASP-39b at 4.05 μm and, therefore, the detection of other SO2 absorption bands at different wavelengths is needed to better constrain the SO2 abundance. Here we report the detection of SO2 spectral features at 7.7 and 8.5 μm in the 5–12-μm transmission spectrum of WASP-39b measured by the JWST Mid-Infrared Instrument (MIRI) Low Resolution Spectrometer (LRS)10. Our observations suggest an abundance of SO2 of 0.5–25 ppm (1σ range), consistent with previous findings4. As well as SO2, we find broad water-vapour absorption features, as well as an unexplained decrease in the transit depth at wavelengths longer than 10 μm. Fitting the spectrum with a grid of atmospheric forward models, we derive an atmospheric heavy-element content (metallicity) for WASP-39b of approximately 7.1–8.0 times solar and demonstrate that photochemistry shapes the spectra of WASP-39b across a broad wavelength range
The long and short of it : benchmarking viromics using Illumina, Nanopore and PacBio sequencing technologies
Get PDFViral metagenomics has fuelled a rapid change in our understanding of global viral diversity and ecology. Long-read sequencing and hybrid assembly approaches that combine long- and short-read technologies are now being widely implemented in bacterial genomics and metagenomics. However, the use of long-read sequencing to investigate viral communities is still in its infancy. While Nanopore and PacBio technologies have been applied to viral metagenomics, it is not known to what extent different technologies will impact the reconstruction of the viral community. Thus, we constructed a mock bacteriophage community of previously sequenced phage genomes and sequenced them using Illumina, Nanopore and PacBio sequencing technologies and tested a number of different assembly approaches. When using a single sequencing technology, Illumina assemblies were the best at recovering phage genomes. Nanopore- and PacBio-only assemblies performed poorly in comparison to Illumina in both genome recovery and error rates, which both varied with the assembler used. The best Nanopore assembly had errors that manifested as SNPs and INDELs at frequencies 41 and 157 % higher than found in Illumina only assemblies, respectively. While the best PacBio assemblies had SNPs at frequencies 12 and 78 % higher than found in Illumina-only assemblies, respectively. Despite high-read coverage, long-read-only assemblies recovered a maximum of one complete genome from any assembly, unless reads were down-sampled prior to assembly. Overall the best approach was assembly by a combination of Illumina and Nanopore reads, which reduced error rates to levels comparable with short-read-only assemblies. When using a single technology, Illumina only was the best approach. The differences in genome recovery and error rates between technology and assembler had downstream impacts on gene prediction, viral prediction, and subsequent estimates of diversity within a sample. These findings will provide a starting point for others in the choice of reads and assembly algorithms for the analysis of viromes
Elusive specific variance : a marginal effect on the accuracy of personality judgment
No full textIt has become popular to demonstrate that the specific variance can make a substantial contribution to accurate personality judgements. This study challenges the main assumption that transformation of manifest scores into residual scores is capable of separating the specific from the common variance. Based on two large samples (N = 11,086), in which participants and their well-acquainted observers completed either the NEO-PI-3 or the HEXACO-PI-R personality inventory, we demonstrated that the residual scores still contain a substantial amount of the common variance, which inflates correlations with criterion variables. An alternative method using multiple regression showed that different forms of residual scores have a modest incremental improvement of explained variance beyond the effects of the common variance contained in the manifest scores. On average, the specific variance improves the self-other agreement less than 4 % consequently having a marginal effect on accurate personality judgments
Most people’s life satisfaction matches their personality traits : true correlations in multi-trait, multi-rater, multi-sample data
Get PDFGendered conditions of higher education access : advancing a gender prism analytic through the case of Haryana, India
Get PDFThis article argues that a holistic, nuanced analytical framework for analysing gender and access to higher education (HE) would be of great benefit to the field, especially in an era where many country contexts are declaring that gender inequalities in HE access are solved due to the use of the gender parity index (GPI) as a measure of success. As such, this article proposes a framework to analyse gendered conditions of access to HE, referring to the various ways in which young people of different genders arrive in HE but with different gendered backgrounds behind them and different gendered expectations of their futures ahead of them, even when they were born into the same families and communities. Drawing on feminist sociological and poststructuralist thinking, the proposed framework promotes a refractive perspective to unpack the varied gendered influences that shape young people’s educational trajectories. The article illustrates the framework with the case of the north-Indian state of Haryana, based on an in-depth mixed-methods empirical study of gendered HE access in government colleges. The analysis reveals enduring gendered disparities that are otherwise masked by the use of GPI, including gendered differences in the perceived purpose of HE for young people, which results in differentiated prioritisation of e.g. quality of institution or subject choice. The article aims to provide future studies in this area with a framework that can be applied in and beyond the Indian context