A bayesian way to correct for measurement error in drug risk estimates from EHR data.

Introduction Data from electronic medical records is now readily available and records information needed in pharmacoepidemiological studies not usually found in administrative data such as risk factors and biometrics. Yet, EMR data leads to measurement error due to primary non-adherence. Bayesian bias correction could provide corrected estimates from administrative data. Objectives and Approach We present a method for correcting risk estimates from EMR data using linked data. In our example, we estimate the risk of cardiovascular events from oral-hypoglycemics in patients with type-2 diabetes in Boston, Quebec, and the UK between 2009 and 2012. Using linked EMR and administrative data in Quebec, we compute a positive and negative predicting value of prescription on dispensation for each class of oral-hypoglycemics. The cardiovascular risk is then analysed using a bayesian Weibull survival model adjusted for potential confounders. A similar model is then computed that accounts for exposure measurement error using the PPV and NPV. Results The Quebec and Boston cohorts have similar sizes with 1197 and 2346 patients, but the UK was bigger at 41370 patients. In Quebec's data, there were important differences in PPV and NPV by class of oral-hypoglycemics with PPVs for Biguanides at 0.81, Sulphonylureas at 0.65, and others at 0.50. The pattern for NPV differed with the same classes having respectively values of 0.56, 0.97, and 0.99. Estimates from the naïve model are typical of similar analysis but compared to their correction, they were generally overprecise and biased towards the null. The adjusted estimated were adequately representing the increased uncertainty with hazard ratios for Sulphonylureas going from 1.72 (1.22, 2.41) to 3.19 (1.36, 5.93), and from 1.09 (0.86, 1.39) to 1.05 (0.45, 2.16) for no drugs Conclusion/Implications Bayesian adjustment for measurement error allowed us to use linked data to regenerate uncertainty and to correct the bias in our risk estimates. Our approach was impacted by the observed low predictive value of prescribing, by reduced transportability of our PPV and NPV estimates, and other sources of bias

Effect of historical changes in land use and climate on the water budget of an urbanizing watershed

Author Posting. © American Geophysical Union, 2006. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Water Resources Research 42 (2006): W03426, doi:10.1029/2005WR004131.We assessed the effects of historical (1931-1998) changes in both land-use and climate on the water budget of a rapidly urbanizing watershed, Ipswich River basin (IRB), in northeastern Massachusetts. Water diversions and extremely low flow during summer are major issues in the IRB. Our study centers on a detailed analysis of diversions and a combined empirical/modeling treatment of evapotranspiration (ET) response to changes in climate and land-use. A detailed accounting of diversions showed that net diversions increased due to increases in water withdrawals (primarily ground water pumping) and export of sewage. Net diversions constitute a major component of runoff (20% of streamflow). Using a combination of empirical analysis and physically based modeling we related an increase in precipitation (2.7 mm/yr) and changes in other climate variables to an increase in ET (1.7 mm/yr). Simulations with a physically based water-balance model showed that the increase in ET could be attributed entirely to a change in climate, while the effect of land-use change was negligible. The land-use change effect was different from ET and runoff trends commonly associated with urbanization. We generalized these and other findings to predict future streamflow using climate change scenarios. Our study could serve as a framework for studying suburban watersheds, being the first study of a suburban watershed that addresses long-term effects of changes in both land-use and climate, and accounts for diversions and other unique aspects of suburban hydrology.This research was partially supported by NSF grants (DEB-9726862, OCE-9726921 and OCE-0423565)

Deciphering mollusc shell production: the roles of genetic mechanisms through to ecology, aquaculture and biomimetics

Most molluscs possess shells, constructed from a vast array of microstructures and architectures. The fully formed shell is composed of calcite or aragonite. These CaCO3 crystals form complex biocomposites with proteins, which although typically less than 5% of total shell mass, play significant roles in determining shell microstructure. Despite much research effort, large knowledge gaps remain in how molluscs construct and maintain their shells, and how they produce such a great diversity of forms. Here we synthesize results on how shell shape, microstructure, composition and organic content vary among, and within, species in response to numerous biotic and abiotic factors. At the local level, temperature, food supply and predation cues significantly affect shell morphology, whilst salinity has a much stronger influence across latitudes. Moreover, we emphasize how advances in genomic technologies [e.g. restriction site-associated DNA sequencing (RAD-Seq) and epigenetics] allow detailed examinations of whether morphological changes result from phenotypic plasticity or genetic adaptation, or a combination of these. RAD-Seq has already identified single nucleotide polymorphisms associated with temperature and aquaculture practices, whilst epigenetic processes have been shown significantly to modify shell construction to local conditions in, for example, Antarctica and New Zealand. We also synthesize results on the costs of shell construction and explore how these affect energetic trade-offs in animal metabolism. The cellular costs are still debated, with CaCO3 precipitation estimates ranging from 1-2 J/mg to 17-55 J/mg depending on experimental and environmental conditions. However, organic components are more expensive (~29 J/mg) and recent data indicate transmembrane calcium ion transporters can involve considerable costs. This review emphasizes the role that molecular analyses have played in demonstrating multiple evolutionary origins of biomineralization genes. Although these are characterized by lineage-specific proteins and unique combinations of co-opted genes, a small set of protein domains have been identified as a conserved biomineralization tool box. We further highlight the use of sequence data sets in providing candidate genes for in situ localization and protein function studies. The former has elucidated gene expression modularity in mantle tissue, improving understanding of the diversity of shell morphology synthesis. RNA interference (RNAi) and clustered regularly interspersed short palindromic repeats - CRISPR-associated protein 9 (CRISPR-Cas9) experiments have provided proof of concept for use in the functional investigation of mollusc gene sequences, showing for example that Pif (aragonite-binding) protein plays a significant role in structured nacre crystal growth and that the Lsdia1 gene sets shell chirality in Lymnaea stagnalis. Much research has focused on the impacts of ocean acidification on molluscs. Initial studies were predominantly pessimistic for future molluscan biodiversity. However, more sophisticated experiments incorporating selective breeding and multiple generations are identifying subtle effects and that variability within mollusc genomes has potential for adaption to future conditions. Furthermore, we highlight recent historical studies based on museum collections that demonstrate a greater resilience of molluscs to climate change compared with experimental data. The future of mollusc research lies not solely with ecological investigations into biodiversity, and this review synthesizes knowledge across disciplines to understand biomineralization. It spans research ranging from evolution and development, through predictions of biodiversity prospects and future-proofing of aquaculture to identifying new biomimetic opportunities and societal benefits from recycling shell products.FCT: UID/Multi/04326/2019; European Marine Biological Research Infrastructure Cluster-EMBRIC (EU H2020 research and innovation program) 654008; European Union Seventh Framework Programme [FP7] ITN project 'CACHE: Calcium in a Changing Environment' under REA 60505; NERC Natural Environment Research Council NE/J500173/1info:eu-repo/semantics/publishedVersio

Double trouble at high density::Cross-level test of ressource-related adaptive plasticity and crowding-related fitness.

Population size is often regulated by negative feedback between population density and individual fitness. At high population densities, animals run into double trouble: they might concurrently suffer from overexploitation of resources and also from negative interference among individuals regardless of resource availability, referred to as crowding. Animals are able to adapt to resource shortages by exhibiting a repertoire of life history and physiological plasticities. In addition to resource-related plasticity, crowding might lead to reduced fitness, with consequences for individual life history. We explored how different mechanisms behind resource-related plasticity and crowding-related fitness act independently or together, using the water flea Daphnia magna as a case study. For testing hypotheses related to mechanisms of plasticity and crowding stress across different biological levels, we used an individual-based population model that is based on dynamic energy budget theory. Each of the hypotheses, represented by a sub-model, is based on specific assumptions on how the uptake and allocation of energy are altered under conditions of resource shortage or crowding. For cross-level testing of different hypotheses, we explored how well the sub-models fit individual level data and also how well they predict population dynamics under different conditions of resource availability. Only operating resource-related and crowding-related hypotheses together enabled accurate model predictions of D. magna population dynamics and size structure. Whereas this study showed that various mechanisms might play a role in the negative feedback between population density and individual life history, it also indicated that different density levels might instigate the onset of the different mechanisms. This study provides an example of how the integration of dynamic energy budget theory and individual-based modelling can facilitate the exploration of mechanisms behind the regulation of population size. Such understanding is important for assessment, management and the conservation of populations and thereby biodiversity in ecosystems

Aircraft Regional-Scale Flux Measurements over Complex Landscapes of Mangroves, Desert, and Marine Ecosystems of Magdalena Bay, Mexico

Natural ecosystems are rarely structurally simple or functionally homogeneous. This is true for the complex coastal region of Magdalena Bay, Baja California Sur, Mexico, where the spatial variability in ecosystem fluxes from the Pacific coastal ocean, eutrophic lagoon, mangroves, and desert were studied. The Sky Arrow 650TCN environmental research aircraft proved to be an effective tool in characterizing land–atmosphere fluxes of energy, CO2, and water vapor across a heterogeneous landscape at the scale of 1 km. The aircraft was capable of discriminating fluxes from all ecosystem types, as well as between nearshore and coastal areas a few kilometers distant. Aircraft-derived average midday CO2 fluxes from the desert showed a slight uptake of −1.32 μmol CO2 m−2 s−1, the coastal ocean also showed an uptake of −3.48 μmol CO2 m−2 s−1, and the lagoon mangroves showed the highest uptake of −8.11 μmol CO2 m−2 s−1. Additional simultaneous measurements of the normalized difference vegetation index (NDVI) allowed simple linear modeling of CO2 flux as a function of NDVI for the mangroves of the Magdalena Bay region. Aircraft approaches can, therefore, be instrumental in determining regional CO2 fluxes and can be pivotal in calculating and verifying ecosystem carbon sequestration regionally when coupled with satellite-derived products and ecosystem models

COSORE: A community database for continuous soil respiration and other soil‐atmosphere greenhouse gas flux data

Globally, soils store two to three times as much carbon as currently resides in the atmosphere, and it is critical to understand how soil greenhouse gas (GHG) emissions and uptake will respond to ongoing climate change. In particular, the soil‐to‐atmosphere CO2 flux, commonly though imprecisely termed soil respiration (RS), is one of the largest carbon fluxes in the Earth system. An increasing number of high‐frequency RS measurements (typically, from an automated system with hourly sampling) have been made over the last two decades; an increasing number of methane measurements are being made with such systems as well. Such high frequency data are an invaluable resource for understanding GHG fluxes, but lack a central database or repository. Here we describe the lightweight, open‐source COSORE (COntinuous SOil REspiration) database and software, that focuses on automated, continuous and long‐term GHG flux datasets, and is intended to serve as a community resource for earth sciences, climate change syntheses and model evaluation. Contributed datasets are mapped to a single, consistent standard, with metadata on contributors, geographic location, measurement conditions and ancillary data. The design emphasizes the importance of reproducibility, scientific transparency and open access to data. While being oriented towards continuously measured RS, the database design accommodates other soil‐atmosphere measurements (e.g. ecosystem respiration, chamber‐measured net ecosystem exchange, methane fluxes) as well as experimental treatments (heterotrophic only, etc.). We give brief examples of the types of analyses possible using this new community resource and describe its accompanying R software package

The FLUXNET2015 dataset and the ONEFlux processing pipeline for eddy covariance data

The FLUXNET2015 dataset provides ecosystem-scale data on CO2, water, and energy exchange between the biosphere and the atmosphere, and other meteorological and biological measurements, from 212 sites around the globe (over 1500 site-years, up to and including year 2014). These sites, independently managed and operated, voluntarily contributed their data to create global datasets. Data were quality controlled and processed using uniform methods, to improve consistency and intercomparability across sites. The dataset is already being used in a number of applications, including ecophysiology studies, remote sensing studies, and development of ecosystem and Earth system models. FLUXNET2015 includes derived-data products, such as gap-filled time series, ecosystem respiration and photosynthetic uptake estimates, estimation of uncertainties, and metadata about the measurements, presented for the first time in this paper. In addition, 206 of these sites are for the first time distributed under a Creative Commons (CC-BY 4.0) license. This paper details this enhanced dataset and the processing methods, now made available as open-source codes, making the dataset more accessible, transparent, and reproducible.Peer reviewe