Overcoming challenges to data quality in the ASPREE clinical trial

© 2019 The Author(s). Background: Large-scale studies risk generating inaccurate and missing data due to the complexity of data collection. Technology has the potential to improve data quality by providing operational support to data collectors. However, this potential is under-explored in community-based trials. The Aspirin in reducing events in the elderly (ASPREE) trial developed a data suite that was specifically designed to support data collectors: the ASPREE Web Accessible Relational Database (AWARD). This paper describes AWARD and the impact of system design on data quality. Methods: AWARD's operational requirements, conceptual design, key challenges and design solutions for data quality are presented. Impact of design features is assessed through comparison of baseline data collected prior to implementation of key functionality (n = 1000) with data collected post implementation (n = 18,114). Overall data quality is assessed according to data category. Results: At baseline, implementation of user-driven functionality reduced staff error (from 0.3% to 0.01%), out-of-range data entry (from 0.14% to 0.04%) and protocol deviations (from 0.4% to 0.08%). In the longitudinal data set, which contained more than 39 million data values collected within AWARD, 96.6% of data values were entered within specified query range or found to be accurate upon querying. The remaining data were missing (3.4%). Participant non-attendance at scheduled study activity was the most common cause of missing data. Costs associated with cleaning data in ASPREE were lower than expected compared with reports from other trials. Conclusions: Clinical trials undertake complex operational activity in order to collect data, but technology rarely provides sufficient support. We find the AWARD suite provides proof of principle that designing technology to support data collectors can mitigate known causes of poor data quality and produce higher-quality data. Health information technology (IT) products that support the conduct of scheduled activity in addition to traditional data entry will enhance community-based clinical trials. A standardised framework for reporting data quality would aid comparisons across clinical trials

A Review of the fossil record of turtles of the clade Baenidae

The fossil record of the turtle clade Baenidae ranges from the Early Cretaceous (Aptian—Albian) to the Eocene. The group is present throughout North America during the Early Cretaceous, but is restricted to the western portions of the continents in the Late Cretaceous and Paleogene. No credible remains of the clade have been reported outside of North America to date. Baenids were warmadapted freshwater aquatic turtles that supported high levels of diversity at times through niche partitioning, particularly by adapting to a broad range of dietary preferences ranging from omnivorous to molluscivorous. Current phylogenies place Baenidae near the split of crown-group Testudines. Within Baenidae three more inclusive, named clades are recognized: Baenodda, Palatobaeninae and Eubaeninae. A taxonomic review of the group concludes that of 49 named taxa, 30 are nomina valida, 12 are nomina invalida and 7 are nomina dubia

A deep dive into the ecology of Gamay (Botany Bay, Australia): current knowledge and future priorities for this highly modified coastal waterway

Context: Gamay is a coastal waterway of immense social, cultural and ecological value. Since European settlement, it has become a hub for industrialisation and human modification. There is growing desire for ecosystem-level management of urban waterways, but such efforts are often challenged by a lack of integrated knowledge. Aim and methods: We systematically reviewed published literature and traditional ecological knowledge (TEK), and consulted scientists to produce a review of Gamay that synthesises published knowledge of Gamay’s aquatic ecosystem to identify knowledge gaps and future research opportunities. Key results: We found 577 published resources on Gamay, of which over 70% focused on ecology. Intertidal rocky shores were the most studied habitat, focusing on invertebrate communities. Few studies considered multiple habitats or taxa. Studies investigating cumulative human impacts, long-term trends and habitat connectivity are lacking, and the broader ecological role of artificial substrate as habitat in Gamay is poorly understood. TEK of Gamay remains a significant knowledge gap. Habitat restoration has shown promising results and could provide opportunities to improve affected habitats in the future. Conclusion and implications: This review highlights the extensive amount of knowledge that exists for Gamay, but also identifies key gaps that need to be filled for effective management

AD51B in Familial Breast Cancer

Common variation on 14q24.1, close to RAD51B, has been associated with breast cancer: rs999737 and rs2588809 with the risk of female breast cancer and rs1314913 with the risk of male breast cancer. The aim of this study was to investigate the role of RAD51B variants in breast cancer predisposition, particularly in the context of familial breast cancer in Finland. We sequenced the coding region of RAD51B in 168 Finnish breast cancer patients from the Helsinki region for identification of possible recurrent founder mutations. In addition, we studied the known rs999737, rs2588809, and rs1314913 SNPs and RAD51B haplotypes in 44,791 breast cancer cases and 43,583 controls from 40 studies participating in the Breast Cancer Association Consortium (BCAC) that were genotyped on a custom chip (iCOGS). We identified one putatively pathogenic missense mutation c.541C>T among the Finnish cancer patients and subsequently genotyped the mutation in additional breast cancer cases (n = 5259) and population controls (n = 3586) from Finland and Belarus. No significant association with breast cancer risk was seen in the meta-analysis of the Finnish datasets or in the large BCAC dataset. The association with previously identified risk variants rs999737, rs2588809, and rs1314913 was replicated among all breast cancer cases and also among familial cases in the BCAC dataset. The most significant association was observed for the haplotype carrying the risk-alleles of all the three SNPs both among all cases (odds ratio (OR): 1.15, 95% confidence interval (CI): 1.11–1.19, P = 8.88 x 10−16) and among familial cases (OR: 1.24, 95% CI: 1.16–1.32, P = 6.19 x 10−11), compared to the haplotype with the respective protective alleles. Our results suggest that loss-of-function mutations in RAD51B are rare, but common variation at the RAD51B region is significantly associated with familial breast cancer risk

Velocity-space sensitivity of the time-of-flight neutron spectrometer at JET

The velocity-space sensitivities of fast-ion diagnostics are often described by so-called weight functions. Recently, we formulated weight functions showing the velocity-space sensitivity of the often dominant beam-target part of neutron energy spectra. These weight functions for neutron emission spectrometry (NES) are independent of the particular NES diagnostic. Here we apply these NES weight functions to the time-of-flight spectrometer TOFOR at JET. By taking the instrumental response function of TOFOR into account, we calculate time-of-flight NES weight functions that enable us to directly determine the velocity-space sensitivity of a given part of a measured time-of-flight spectrum from TOFOR

Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2015: A systematic analysis for the Global Burden of Disease Study 2015

Background: The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context. Methods: We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defined criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors—the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specific DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI). Findings: Between 1990 and 2015, global exposure to unsafe sanitation, household air pollution, childhood underweight, childhood stunting, and smoking each decreased by more than 25%. Global exposure for several occupational risks, high body-mass index (BMI), and drug use increased by more than 25% over the same period. All risks jointly evaluated in 2015 accounted for 57·8% (95% CI 56·6–58·8) of global deaths and 41·2% (39·8–42·8) of DALYs. In 2015, the ten largest contributors to global DALYs among Level 3 risks were high systolic blood pressure (211·8 million [192·7 million to 231·1 million] global DALYs), smoking (148·6 million [134·2 million to 163·1 million]), high fasting plasma glucose (143·1 million [125·1 million to 163·5 million]), high BMI (120·1 million [83·8 million to 158·4 million]), childhood undernutrition (113·3 million [103·9 million to 123·4 million]), ambient particulate matter (103·1 million [90·8 million to 115·1 million]), high total cholesterol (88·7 million [74·6 million to 105·7 million]), household air pollution (85·6 million [66·7 million to 106·1 million]), alcohol use (85·0 million [77·2 million to 93·0 million]), and diets high in sodium (83·0 million [49·3 million to 127·5 million]). From 1990 to 2015, attributable DALYs declined for micronutrient deficiencies, childhood undernutrition, unsafe sanitation and water, and household air pollution; reductions in risk-deleted DALY rates rather than reductions in exposure drove these declines. Rising exposure contributed to notable increases in attributable DALYs from high BMI, high fasting plasma glucose, occupational carcinogens, and drug use. Environmental risks and childhood undernutrition declined steadily with SDI; low physical activity, high BMI, and high fasting plasma glucose increased with SDI. In 119 countries, metabolic risks, such as high BMI and fasting plasma glucose, contributed the most attributable DALYs in 2015. Regionally, smoking still ranked among the leading five risk factors for attributable DALYs in 109 countries; childhood underweight and unsafe sex remained primary drivers of early death and disability in much of sub-Saharan Africa. Interpretation: Declines in some key environmental risks have contributed to declines in critical infectious diseases. Some risks appear to be invariant to SDI. Increasing risks, including high BMI, high fasting plasma glucose, drug use, and some occupational exposures, contribute to rising burden from some conditions, but also provide opportunities for intervention. Some highly preventable risks, such as smoking, remain major causes of attributable DALYs, even as exposure is declining. Public policy makers need to pay attention to the risks that are increasingly major contributors to global burden. Funding: Bill & Melinda Gates Foundation