Systematic techniques for assisting recruitment to trials (START): study protocol for embedded, randomized controlled trials

BACKGROUND: Randomized controlled trials play a central role in evidence-based practice, but recruitment of participants, and retention of them once in the trial, is challenging. Moreover, there is a dearth of evidence that research teams can use to inform the development of their recruitment and retention strategies. As with other healthcare initiatives, the fairest test of the effectiveness of a recruitment strategy is a trial comparing alternatives, which for recruitment would mean embedding a recruitment trial within an ongoing host trial. Systematic reviews indicate that such studies are rare. Embedded trials are largely delivered in an ad hoc way, with interventions almost always developed in isolation and tested in the context of a single host trial, limiting their ability to contribute to a body of evidence with regard to a single recruitment intervention and to researchers working in different contexts. METHODS/DESIGN: The Systematic Techniques for Assisting Recruitment to Trials (START) program is funded by the United Kingdom Medical Research Council (MRC) Methodology Research Programme to support the routine adoption of embedded trials to test standardized recruitment interventions across ongoing host trials. To achieve this aim, the program involves three interrelated work packages: (1) methodology - to develop guidelines for the design, analysis and reporting of embedded recruitment studies; (2) interventions - to develop effective and useful recruitment interventions; and (3) implementation - to recruit host trials and test interventions through embedded studies. DISCUSSION: Successful completion of the START program will provide a model for a platform for the wider trials community to use to evaluate recruitment interventions or, potentially, other types of intervention linked to trial conduct. It will also increase the evidence base for two types of recruitment intervention. TRIAL REGISTRATION: The START protocol covers the methodology for embedded trials. Each embedded trial is registered separately or as a substudy of the host trial

Associations with photoreceptor thickness measures in the UK Biobank.

Spectral-domain OCT (SD-OCT) provides high resolution images enabling identification of individual retinal layers. We included 32,923 participants aged 40-69 years old from UK Biobank. Questionnaires, physical examination, and eye examination including SD-OCT imaging were performed. SD OCT measured photoreceptor layer thickness includes photoreceptor layer thickness: inner nuclear layer-retinal pigment epithelium (INL-RPE) and the specific sublayers of the photoreceptor: inner nuclear layer-external limiting membrane (INL-ELM); external limiting membrane-inner segment outer segment (ELM-ISOS); and inner segment outer segment-retinal pigment epithelium (ISOS-RPE). In multivariate regression models, the total average INL-RPE was observed to be thinner in older aged, females, Black ethnicity, smokers, participants with higher systolic blood pressure, more negative refractive error, lower IOPcc and lower corneal hysteresis. The overall INL-ELM, ELM-ISOS and ISOS-RPE thickness was significantly associated with sex and race. Total average of INL-ELM thickness was additionally associated with age and refractive error, while ELM-ISOS was additionally associated with age, smoking status, SBP and refractive error; and ISOS-RPE was additionally associated with smoking status, IOPcc and corneal hysteresis. Hence, we found novel associations of ethnicity, smoking, systolic blood pressure, refraction, IOPcc and corneal hysteresis with photoreceptor thickness

Using oxygen isotopes to quantitatively assess residual CO2 saturation during the CO2CRC Otway Stage 2B Extension residual saturation test

Residual CO2 trapping is a key mechanism of secure CO2 storage, an essential component of the Carbon Capture and Storage technology. Estimating the amount of CO2 that will be residually trapped in a saline aquifer formation remains a significant challenge. Here, we present the first oxygen isotope ratio (δ18O) measurements from a single-well experiment, the CO2CRC Otway 2B Extension, used to estimate levels of residual trapping of CO2. Following the initiation of the drive to residual saturation in the reservoir, reservoir water δ18O decreased, as predicted from the baseline isotope ratios of water and CO2, over a time span of only a few days. The isotope shift in the near-wellbore reservoir water is the result of isotope equilibrium exchange between residual CO2 and water. For the region further away from the well, the isotopic shift in the reservoir water can also be explained by isotopic exchange with mobile CO2 from ahead of the region driven to residual, or continuous isotopic exchange between water and residual CO2 during its back-production, complicating the interpretation of the change in reservoir water δ18O in terms of residual saturation. A small isotopic distinction of the baseline water and CO2 δ18O, together with issues encountered during the field experiment procedure, further prevents the estimation of residual CO2 saturation levels from oxygen isotope changes without significant uncertainty. The similarity of oxygen isotope-based near-wellbore saturation levels and independent estimates based on pulsed neutron logging indicates the potential of using oxygen isotope as an effective inherent tracer for determining residual saturation on a field scale within a few days

The provenance of the Devonian Old Red Sandstone of the Dingle Peninsula, SW Ireland; the earliest record of Laurentian and peri-Gondwanan sediment mixing in Ireland

The Lower Old Red Sandstone in southern Ireland is hosted in the Early Devonian Dingle Basin, which lies immediately south of the Iapetus Suture on the Dingle Peninsula, County Kerry. The basin developed as a post-Caledonian pullapart structure prior to Acadian deformation, which in turn was followed by end-Carboniferous Variscan deformation. Detrital zircon U–Th–Pb geochronology is complemented by mica Ar–Ar and apatite U–Pb geochronology to gain a comprehensive understanding of the provenance of the Lower Devonian Lower Old Red Sandstone of the Dingle Basin and assess contributions of major tectonic components (e.g. Laurentia, Ganderia). Sedimentary rocks in the Lower Old Red Sandstone have similar detrital zircon age distributions, which are dominated by c. 1.2 Ga zircons as well as late Neoproterozoic grains. This indicates a dominant contribution of detritus of Laurentian affinity as well as contributions from westerly and southerly derived Ganderian detritus. Caledonian uplift of the area north of the Iapetus Suture would have facilitated a large contribution of (peri-)Laurentian material. The Upper Old Red Sandstone on the Dingle Peninsula has a distinctly different detrital zircon character including few late Neoproterozoic zircons and abundant zircons of c. 1.05 Ga age, indicating sediment derivation only from Laurentia and no recycling from the Lower Old Red Sandstone

Investigation of associations between retinal microvascular parameters and albuminuria in UK Biobank: a cross-sectional case-control study.

BACKGROUND: Associations between microvascular variation and chronic kidney disease (CKD) have been reported previously. Non-invasive retinal fundus imaging enables evaluation of the microvascular network and may offer insight to systemic risk associated with CKD. METHODS: Retinal microvascular parameters (fractal dimension [FD] - a measure of the complexity of the vascular network, tortuosity, and retinal arteriolar and venular calibre) were quantified from macula-centred fundus images using the Vessel Assessment and Measurement Platform for Images of the REtina (VAMPIRE) version 3.1 (VAMPIRE group, Universities of Dundee and Edinburgh, Scotland) and assessed for associations with renal damage in a case-control study nested within the multi-centre UK Biobank cohort study. Participants were designated cases or controls based on urinary albumin to creatinine ratio (ACR) thresholds. Participants with ACR ≥ 3 mg/mmol (ACR stages A2-A3) were characterised as cases, and those with an ACR < 3 mg/mmol (ACR stage A1) were categorised as controls. Participants were matched on age, sex and ethnic background. RESULTS: Lower FD (less extensive microvascular branching) was associated with a small increase in odds of albuminuria independent of blood pressure, diabetes and other potential confounding variables (odds ratio [OR] 1.18, 95% confidence interval [CI] 1.03-1.34 for arterioles and OR 1.24, CI 1.05-1.47 for venules). Measures of tortuosity or retinal arteriolar and venular calibre were not significantly associated with ACR. CONCLUSIONS: This study supports previously reported associations between retinal microvascular FD and other metabolic disturbances affecting the systemic vasculature. The association between retinal microvascular FD and albuminuria, independent of diabetes and blood pressure, may represent a useful indicator of systemic vascular damage associated with albuminuria

The Relationship Between Ambient Atmospheric Fine Particulate Matter (PM2.5) and Glaucoma in a Large Community Cohort.

Purpose: Glaucoma is more common in urban populations than in others. Ninety percent of the world's population are exposed to air pollution above World Health Organization (WHO) recommended limits. Few studies have examined the association between air pollution and glaucoma. Methods: Questionnaire data, ophthalmic measures, and ambient residential area air quality data for 111,370 UK Biobank participants were analyzed. Particulate matter with an aerodynamic diameter < 2.5 μm (PM2.5) was selected as the air quality exposure of interest. Eye measures included self-reported glaucoma, intraocular pressure (IOP), and average thickness of macular ganglion cell-inner plexiform layer (GCIPL) across nine Early Treatment Diabetic Retinopathy Study (ETDRS) retinal subfields as obtained from spectral-domain optical coherence tomography. We examined the associations of PM2.5 concentration with self-reported glaucoma, IOP, and GCIPL. Results: Participants resident in areas with higher PM2.5 concentration were more likely to report a diagnosis of glaucoma (odds ratio = 1.06, 95% confidence interval [CI] = 1.01-1.12, per interquartile range [IQR] increase P = 0.02). Higher PM2.5 concentration was also associated with thinner GCIPL (β = -0.56 μm, 95% CI = -0.63 to -0.49, per IQR increase, P = 1.2 × 10-53). A dose-response relationship was observed between higher levels of PM2.5 and thinner GCIPL (P < 0.001). There was no clinically relevant relationship between PM2.5 concentration and IOP. Conclusions: Greater exposure to PM2.5 is associated with both self-reported glaucoma and adverse structural characteristics of the disease. The absence of an association between PM2.5 and IOP suggests the relationship may occur through a non-pressure-dependent mechanism, possibly neurotoxic and/or vascular effects