Missing data are ubiquitous in medical research. Although there is increasing guidance on how to handle missing data, practice is changing slowly and misapprehensions abound, particularly in ...observational research. Importantly, the lack of transparency around methodological decisions is threatening the validity and reproducibility of modern research. We present a practical framework for handling and reporting the analysis of incomplete data in observational studies, which we illustrate using a case study from the Avon Longitudinal Study of Parents and Children. The framework consists of three steps: 1) Develop an analysis plan specifying the analysis model and how missing data are going to be addressed. An important consideration is whether a complete records’ analysis is likely to be valid, whether multiple imputation or an alternative approach is likely to offer benefits and whether a sensitivity analysis regarding the missingness mechanism is required; 2) Examine the data, checking the methods outlined in the analysis plan are appropriate, and conduct the preplanned analysis; and 3) Report the results, including a description of the missing data, details on how the missing data were addressed, and the results from all analyses, interpreted in light of the missing data and the clinical relevance. This framework seeks to support researchers in thinking systematically about missing data and transparently reporting the potential effect on the study results, therefore increasing the confidence in and reproducibility of research findings.
•Missing data are ubiquitous in medical research.•Guidance is available, but missing data are still often not handled appropriately.•We present a framework for handling and reporting analyses of incomplete data.•This framework encourages researchers to think systematically about missing data.•Adoption of this framework will increase the reproducibility of research findings.•This article provides a much needed framework for handling and reporting the analysis of incomplete data in observational studies.•The framework puts a strong emphasis on preplanning the statistical analysis and encourages transparency when reporting the results of a study.•Adoption of this framework will increase the confidence in and reproducibility of research findings.
Recent changes in the seasonal timing (phenology) of familiar biological events have been one of the most conspicuous signs of climate change. However, the lack of a standardized approach to ...analysing change has hampered assessment of consistency in such changes among different taxa and trophic levels and across freshwater, terrestrial and marine environments. We present a standardized assessment of 25 532 rates of phenological change for 726 UK terrestrial, freshwater and marine taxa. The majority of spring and summer events have advanced, and more rapidly than previously documented. Such consistency is indicative of shared large scale drivers. Furthermore, average rates of change have accelerated in a way that is consistent with observed warming trends. Less coherent patterns in some groups of organisms point to the agency of more local scale processes and multiple drivers. For the first time we show a broad scale signal of differential phenological change among trophic levels; across environments advances in timing were slowest for secondary consumers, thus heightening the potential risk of temporal mismatch in key trophic interactions. If current patterns and rates of phenological change are indicative of future trends, future climate warming may exacerbate trophic mismatching, further disrupting the functioning, persistence and resilience of many ecosystems and having a major impact on ecosystem services.
The two tandem bromodomains of the BET (bromodomain and extraterminal domain) proteins enable chromatin binding to facilitate transcription. Drugs that inhibit both bromodomains equally have shown ...efficacy in certain malignant and inflammatory conditions. To explore the individual functional contributions of the first (BD1) and second (BD2) bromodomains in biology and therapy, we developed selective BD1 and BD2 inhibitors. We found that steady-state gene expression primarily requires BD1, whereas the rapid increase of gene expression induced by inflammatory stimuli requires both BD1 and BD2 of all BET proteins. BD1 inhibitors phenocopied the effects of pan-BET inhibitors in cancer models, whereas BD2 inhibitors were predominantly effective in models of inflammatory and autoimmune disease. These insights into the differential requirement of BD1 and BD2 for the maintenance and induction of gene expression may guide future BET-targeted therapies.
Summary
Trait‐based approaches are increasingly being used to test mechanisms underlying species assemblages and biotic interactions across a wide range of organisms including terrestrial arthropods ...and to investigate consequences for ecosystem processes. Such an approach relies on the standardized measurement of functional traits that can be applied across taxa and regions. Currently, however, unified methods of trait measurements are lacking for terrestrial arthropods and related macroinvertebrates (terrestrial invertebrates hereafter).
Here, we present a comprehensive review and detailed protocol for a set of 29 traits known to be sensitive to global stressors and to affect ecosystem processes and services. We give recommendations how to measure these traits under standardized conditions across various terrestrial invertebrate taxonomic groups.
We provide considerations and approaches that apply to almost all traits described, such as the selection of species and individuals needed for the measurements, the importance of intraspecific trait variability, how many populations or communities to sample and over which spatial scales.
The approaches outlined here provide a means to improve the reliability and predictive power of functional traits to explain community assembly, species diversity patterns and ecosystem processes and services within and across taxa and trophic levels, allowing comparison of studies and running meta‐analyses across regions and ecosystems.
This handbook is a crucial first step towards standardizing trait methodology across the most studied terrestrial invertebrate groups, and the protocols are aimed to balance general applicability and requirements for special cases or particular taxa. Therefore, we envision this handbook as a common platform to which researchers can further provide methodological input for additional special cases.
A lay summary is available for this article.
Lay Summary
Mosses are a highly diverse lineage of land plants, whose diversification, spanning at least 400 million years, remains phylogenetically ambiguous due to the lack of fossils, massive early ...extinctions, late radiations, limited morphological variation, and conflicting signal among previously used markers. Here, we present phylogenetic reconstructions based on complete organellar exomes and a comparable set of nuclear genes for this major lineage of land plants. Our analysis of 142 species representing 29 of the 30 moss orders reveals that relative average rates of non-synonymous substitutions in nuclear versus plastid genes are much higher in mosses than in seed plants, consistent with the emerging concept of evolutionary dynamism in mosses. Our results highlight the evolutionary significance of taxa with reduced morphologies, shed light on the relative tempo and mechanisms underlying major cladogenic events, and suggest hypotheses for the relationships and delineation of moss orders.
Global warming has advanced the timing of biological events, potentially leading to disruption across trophic levels. The potential importance of phenological change as a driver of population trends ...has been suggested. To fully understand the possible impacts, there is a need to quantify the scale of these changes spatially and according to habitat type. We studied the relationship between phenological trends, space and habitat type between 1965 and 2012 using an extensive UK dataset comprising 269 aphid, bird, butterfly and moth species. We modelled phenologies using generalized additive mixed models that included covariates for geographical (latitude, longitude, altitude), temporal (year, season) and habitat terms (woodland, scrub, grassland). Model selection showed that a baseline model with geographical and temporal components explained the variation in phenologies better than either a model in which space and time interacted or a habitat model without spatial terms. This baseline model showed strongly that phenologies shifted progressively earlier over time, that increasing altitude produced later phenologies and that a strong spatial component determined phenological timings, particularly latitude. The seasonal timing of a phenological event, in terms of whether it fell in the first or second half of the year, did not result in substantially different trends for butterflies. For moths, early season phenologies advanced more rapidly than those recorded later. Whilst temporal trends across all habitats resulted in earlier phenologies over time, agricultural habitats produced significantly later phenologies than most other habitats studied, probably because of nonclimatic drivers. A model with a significant habitat‐time interaction was the best‐fitting model for birds, moths and butterflies, emphasizing that the rates of phenological advance also differ among habitats for these groups. Our results suggest the presence of strong spatial gradients in mean seasonal timing and nonlinear trends towards earlier seasonal timing that varies in form and rate among habitat types.
The study charts the phenology of more than 250 UK birds and insects in the context of global warming, using information about habitat and local geography to explain variation in aphid, moth and butterfly migration and bird egg‐laying.
Although we have known anecdotally that insects have been declining in Great Britain for more than 100 years, insect declines have only been statistically estimated over the last 20 years. Estimation ...of the rate of those declines is still hotly debated, fuelled by a lack of standardised, systematically collected data.
More than 24 million individual moths and aphids collected from 112 light traps and 25 12.2 m suction‐traps, respectively, were analysed using mixed models. Our objective was to estimate the long‐term trends in both groups based on annual totals recorded every year between 1969 and 2016.
The models showed that two paradigms existed: Over 47 years, long‐term linear trends showed that moths had declined significantly by −31%, but short‐term trends indicated that there were periods of significant decline and recovery in most decades since the 1960s. Conversely, despite aphid annual totals fluctuating widely, this group was in a steady state over the long‐term, with a non‐significant decline of −7.6%. Sensitivity analysis revealed that moth trends were not driven by a group of abundant species, but the sign of the overall aphid trends may have been driven by three of the most abundant species.
The spatial extent of moth trends suggests that they are extremely heterogeneous. Uniquely, moth declines were different among several habitat types, with robust significant declines found in coastal, urban and woodland habitats, but notably not in agricultural, parkland and scrubland habitats. Conversely, aphid trends showed spatial synchrony extending to 338 km, albeit with local variation.
Graphical
Whilst the great majority of scientists agree that insects are in decline, there is much debate over the rate of decline, fuelled by a lack of standardised, systematically collected data.
The Rothamsted Insect Survey has the most comprehensive, standardised long‐term data on insects in the World. Here, we present an analysis of moth and aphid population linear and non‐linear trends.
We show, using 24 million individuals over 47 years, that moths have significantly declined by 31%, with differences between habitats. Aphids as a group were not in significant decline.
Differences in phenological responses to climate change among species can desynchronise ecological interactions and thereby threaten ecosystem function. To assess these threats, we must quantify the ...relative impact of climate change on species at different trophic levels. Here, we apply a Climate Sensitivity Profile approach to 10,003 terrestrial and aquatic phenological data sets, spatially matched to temperature and precipitation data, to quantify variation in climate sensitivity. The direction, magnitude and timing of climate sensitivity varied markedly among organisms within taxonomic and trophic groups. Despite this variability, we detected systematic variation in the direction and magnitude of phenological climate sensitivity. Secondary consumers showed consistently lower climate sensitivity than other groups. We used mid-century climate change projections to estimate that the timing of phenological events could change more for primary consumers than for species in other trophic levels (6.2 versus 2.5-2.9 days earlier on average), with substantial taxonomic variation (1.1-14.8 days earlier on average).
Background The choice between hemodiafiltration (HDF) or high-flux hemodialysis (HD) to treat end-stage kidney disease remains a matter of debate. The duration of recovery time after treatment has ...been associated with mortality, affects quality of life, and may therefore be important in informing patient choice. We aimed to establish whether recovery time is influenced by treatment with HDF or HD. Study Design Randomized patient-blinded crossover trial. Settings & Participants 100 patients with end-stage kidney disease were enrolled from 2 satellite dialysis units in Glasgow, United Kingdom. Intervention 8 weeks of HD followed by 8 weeks of online postdilution HDF or vice versa. Outcomes Posttreatment recovery time, symptomatic hypotension events, dialysis circuit clotting events, and biochemical parameters. Measurements Patient-reported recovery time in minutes, incidence of adverse events during treatments, hematology and biochemistry results, quality-of-life questionnaire. Results There was no overall difference in recovery time between treatments (medians for HDF vs HD of 47.5 IQR, 0-240 vs 30 IQR, 0-210 minutes, respectively; P = 0.9). During HDF treatment, there were significant increases in rates of symptomatic hypotension (8.0% in HDF vs 5.3% in HD; relative risk RR, 1.52; 95% CI, 1.2-1.9; P < 0.001) and intradialytic tendency to clotting (1.8% in HDF vs 0.7% in HD; RR, 2.7; 95% CI, 1.5-5.0; P = 0.002). Serum albumin level was significantly lower during HDF (3.2 vs 3.3 g/dL; P < 0.001). Health-related quality-of-life scores were equivalent. Limitations Single center; mean achieved HDF convection volume, 20.6 L. Conclusions Patients blinded to whether they were receiving HD or HDF in a randomized controlled crossover study reported similar posttreatment recovery times and health-related quality-of-life scores.
Advances in phenology (the annual timing of species' life-cycles) in response to climate change are generally viewed as bioindicators of climate change, but have not been considered as predictors of ...range expansions. Here, we show that phenology advances combine with the number of reproductive cycles per year (voltinism) to shape abundance and distribution trends in 130 species of British Lepidoptera, in response to ~0.5 °C spring-temperature warming between 1995 and 2014. Early adult emergence in warm years resulted in increased within- and between-year population growth for species with multiple reproductive cycles per year (n = 39 multivoltine species). By contrast, early emergence had neutral or negative consequences for species with a single annual reproductive cycle (n = 91 univoltine species), depending on habitat specialisation. We conclude that phenology advances facilitate polewards range expansions in species exhibiting plasticity for both phenology and voltinism, but may inhibit expansion by less flexible species.
PDF
