Alkali Extraction of Arsenic from Groundwater Treatment Sludge: An Essential Initial Step for Arsenic Recovery.

Arsenic (As)-bearing Fe(III) precipitate groundwater treatment sludge has traditionally been viewed by the water sector as a disposal issue rather than a resource opportunity, partly due to assumptions of the low value of As. However, As has now been classified as a Critical Raw Material (CRM) in many regions, providing new incentives to recover As and other useful components of the sludge, such as phosphate (P) and the reactive hydrous ferric oxide (HFO) sorbent. Here, we investigate alkali extraction to separate As from a variety of field and synthetic As-bearing HFO sludges, which is a critical first step to enable sludge upcycling. We found that As extraction was most effective using NaOH, with the As extraction efficiency increasing up to >99% with increasing NaOH concentrations (0.01, 0.1, and 1 M). Extraction with Na2CO3 and Ca(OH)2 was ineffective (<5%). Extraction time (hour, day, week) played a secondary role in As release but tended to be important at lower NaOH concentrations. Little difference in As extraction efficiency was observed for several key variables, including sludge aging time (50 days) and cosorbed oxyanions (e.g., Si, P). However, the presence of ∼10 mass% calcite decreased As release from field and synthetic sludges considerably (<70% As extracted). Concomitant with As release, alkali extraction promoted crystallization of poorly ordered HFO and decreased particle specific surface area, with structural modifications increasing with NaOH concentration and extraction time. Taken together, these results provide essential information to inform and optimize the design of resource recovery methods for As-bearing treatment sludge.

Comparing cadmium uptake kinetics, xylem translocation, chemical forms, and subcellular distribution of two tobacco (Nicotiana tabacum L.) cultivars.

Tobacco (Nicotiana tabacum L.) is a potential phytoremediator that can reduce soil cadmium (Cd) contamination. Pot and hydroponic experiments were conducted to investigate the difference in absorption kinetics, translocation patterns, accumulation capacity, and extraction amounts between two leading tobacco cultivars in China. We studied the chemical forms and subcellular distribution of Cd in the plants to understand the diversity of the detoxification mechanism of the cultivars. The concentration-dependent kinetics of Cd accumulation in leaves, stems, roots, and xylem sap for cultivars Zhongyan 100 (ZY100) and K326, fitted well with the Michaelis-Menten equation. K326 exhibited high biomass, Cd tolerance, Cd translocation, and phytoextraction abilities. The acetic acid, sodium chloride, and water-extractable fractions accounted for > 90% of Cd in all ZY100 tissues but only in K326 roots and stems. Moreover, the acetic acid and NaCl fractions were the predominant storage forms, while the water fraction was the transport form. The ethanol fraction also contributed significantly to Cd storage in K326 leaves. As the Cd treatment increased, more NaCl and water fractions were found in K326 leaves, while only NaCl fractions increased in ZY100 leaves. For subcellular distribution, > 93% Cd proportions were primarily stored in both cultivars' soluble or cell wall fraction. The proportion of Cd in the cell wall fraction of ZY100 roots was less than that of K326, while that proportion in the soluble fraction in ZY100 leaves was higher than in K326 leaves. These findings demonstrate that Cd accumulation patterns, detoxification, and storage strategies differ between the cultivars, providing a deeper understanding of Cd tolerance and accumulation mechanism in tobacco plants. It also guides the screening of germplasm resources or gene modification to improve the Cd phytoextraction efficiency of tobacco.

Temporal patterns of multi-morbidity in 570157 ischemic heart disease patients: a nationwide cohort study.

BACKGROUND: Patients diagnosed with ischemic heart disease (IHD) are becoming increasingly multi-morbid, and studies designed to analyze the full spectrum are few. METHODS: Disease trajectories, defined as time-ordered series of diagnoses, were used to study the temporality of multi-morbidity. The main data source was The Danish National Patient Register (NPR) comprising 7,179,538 individuals in the period 1994-2018. Patients with a diagnosis code for IHD were included. Relative risks were used to quantify the strength of the association between diagnostic co-occurrences comprised of two diagnoses that were overrepresented in the same patients. Multiple linear regression models were then fitted to test for temporal associations among the diagnostic co-occurrences, termed length two disease trajectories. Length two disease trajectories were then used as basis for constructing disease trajectories of three diagnoses. RESULTS: In a cohort of 570,157 IHD disease patients, we identified 1447 length two disease trajectories and 4729 significant length three disease trajectories. These included 459 distinct diagnoses. Disease trajectories were dominated by chronic diseases and not by common, acute diseases such as pneumonia. The temporal association of atrial fibrillation (AF) and IHD differed in different IHD subpopulations. We found an association between osteoarthritis (OA) and heart failure (HF) among patients diagnosed with OA, IHD, and then HF only. CONCLUSIONS: The sequence of diagnoses is important in characterization of multi-morbidity in IHD patients as the disease trajectories. The study provides evidence that the timing of AF in IHD marks distinct IHD subpopulations; and secondly that the association between osteoarthritis and heart failure is dependent on IHD.

Population projections of an endangered cactus suggest little impact of climate change.

Population projections coupled with downscaled climate projections are a powerful tool that allows predicting future population dynamics of vulnerable plants in the face of a changing climate. Traditional approaches used to predict the vulnerability of plants to climate change (e.g. species distribution models) fail to mechanistically describe the basis of a population's dynamics and thus cannot be expected to correctly predict its temporal trends. In this study, we used a 23-year demographic dataset of the acuña cactus, an endangered species, to predict its population dynamics to the end of the century. We used integral projection models to describe its vital rates and population dynamics in relation to plant volume and key climatic variables. We used the resulting climate-driven IPM along with climatic projections to predict the population growth rates from 1991 to 2099. We found the average population growth rate of this population between 1991 and 2013 to be 0.70 (95% CI 0.61-0.79). This result confirms that the population of acuña cactus has been declining and that this decline is due to demographic structure and climate conditions. However, the projection model also predicts that, up to 2080, the population will remain relatively stable mainly due to the survival of its existing adult individuals. Notwithstanding, the long-term viability of the populations can only be achieved through the recruitment of new individuals.

Evaluation of pH-Dependent Metal Speciation Artifacts in Whole-Cell Bioreporter Analysis.

Whole-cell bacterial biosensors (bioreporters) are commonly applied for determination of metal toxicity and bioavailability in environmental samples. This is accomplished using a standard procedure whereby the sample is mixed with bioreporter cells suspended in a buffered medium at a fixed pH (set-point pH assay). This experimental approach can alter the sample pH. We therefore hypothesized that metal speciation artifacts compromising our ability to use bioreporters for determination of the "true" metal bioavailability in environmental samples may be introduced. Using the copper-specific bioreporter DF57-Cu15 as a model, we compared the conventional set-point pH assay to a flexible pH assay allowing for bioavailability determination at in situ sample pH. Our results demonstrate that pH-dependent metal speciation bias may occur when using the conventional set-point pH assay, and we recommend performing bioreporter measurements and calibrations at in situ sample pH. Although we only studied copper bioavailability, our results also have implications for bioreporter determination of other analytes displaying pH-dependent speciation such as other metals and some organics. We call for additional bioreporter studies of chemical speciation artifacts as this represents a problem hitherto overlooked in bioreporter literature. We thus conclude that there may be considerable scope for optimization of existing bioreporter assays for assessment of environmental pollutant bioavailability.

Long-term changes in abundances of Sonoran Desert lizards reveal complex responses to climatic variation.

Understanding how climatic variation affects animal populations and communities is essential for addressing threats posed by climate change, especially in systems where impacts are projected to be high. We evaluated abundance dynamics of five common species of diurnal lizards over 25 years in a Sonoran Desert transition zone where precipitation decreased and temperature increased across time, and assessed hypotheses for the influence of climatic flux on spatiotemporal variation in abundances. We repeatedly surveyed lizards in spring and summer of each year at up to 32 sites, and used hierarchical mixture models to estimate detection probabilities, abundances, and population growth rates. Among terrestrial species, abundances of a short-lived, winter-spring breeder increased markedly by an estimated 237%-285% across time, while two larger spring-summer breeders with higher thermal preferences declined by up to 64%. Abundances of two arboreal species that occupy shaded and thus sheltered microhabitats fluctuated but did not decline systematically. Abundances of all species increased with precipitation at short lag times (1-1.5 years) likely due to enhanced food availability, but often declined after periods of high precipitation at longer lag times (2-4 years) likely due to predation and other biotic pressures. Although rising maximum daily temperatures (Tmax ) are expected to drive global declines of lizards, associations with Tmax were variable and weak for most species. Instead, abundances of all species declined with rising daily minimum temperatures, suggesting degradation of cool refugia imposed widespread metabolic or other costs. Our results suggest climate warming and drying are having major impacts on lizard communities by driving declines in species with traits that augment exposure to abiotic extremes and by modifying species interactions. The complexity of patterns we report indicates that evaluating and responding to the influence of climate change on biodiversity must consider a broad array of ecological processes.

Comparison of Metals and Tetracycline as Selective Agents for Development of Tetracycline Resistant Bacterial Communities in Agricultural Soil.

Environmental selection of antibiotic resistance may be caused by either antibiotic residues or coselecting agents. Using a strictly controlled experimental design, we compared the ability of metals (Cu or Zn) and tetracycline to (co)select for tetracycline resistance in bacterial communities. Soil microcosms were established by amending agricultural soil with known levels of Cu, Zn, or tetracycline known to represent commonly used metals and antibiotics for pig farming. Soil bacterial growth dynamics and bacterial community-level tetracycline resistance were determined using the [3H]leucine incorporation technique, whereas soil Cu, Zn, and tetracycline exposure were quantified by a panel of whole-cell bacterial bioreporters. Tetracycline resistance increased significantly in soils containing environmentally relevant levels of Cu (≥365 mg kg-1) and Zn (≥264 mg kg-1) but not in soil spiked with unrealistically high levels of tetracycline (up to 100 mg kg-1). These observations were consistent with bioreporter data showing that metals remained bioavailable, whereas tetracycline was only transiently bioavailable. Community-level tetracycline resistance was correlated to the initial toxicant-induced inhibition of bacterial growth. In conclusion, our study demonstrates that toxic metals in some cases may exert a stronger selection pressure for environmental selection of resistance to an antibiotic than the specific antibiotic itself.

Heavy Metal Leaching as Affected by Long-Time Organic Waste Fertilizer Application.

The recycling of urban waste products as fertilizers in agriculture may introduce contaminants such as heavy metals into soil that may leach and contaminate groundwater. In the present study, we investigated the leaching of heavy metals from intact soil cores collected in the long-term agricultural field trial CRUCIAL. At the time of sampling, the equivalent of >100 yr of urban waste fertilizers following Danish legislation had been applied. The leaching of Cu was significantly increased in the treatments receiving organic waste products compared with the unfertilized control but remained below the permissible level following Danish drinking water guidelines. The leaching of Cu was controlled primarily by the topsoil Cu content and by the leaching of dissolved organic carbon (DOC) but at the same time significantly correlated with leaching of colloids in soils that had not received fertilizer or had received an organic fertilizer with a low concentration of Cu. The leaching of Zn, Cd, and Co was not significantly increased in urban waste-fertilized treatments. The leaching of Mo was elevated in accelerated waste treatments (both agricultural and urban), and the leaching of Mo was linked to the leaching of DOC. Since leaching of Cr and Pb was strongly linked to the level of colloid leaching, leaching of these metals was reduced in the urban waste treatments. Overall, the results presented should not raise concern regarding the agricultural use of urban waste products in agriculture as long as the relevant guidelines are followed.

Online Radiology Reporting with Peer Review as a Learning and Feedback Tool in Radiology; Implementation, Validity, and Student Impressions.

Communicating radiological reports to peers has pedagogical value. Students may be uneasy with the process due to a lack of communication and peer review skills or to their failure to see value in the process. We describe a communication exercise with peer review in an undergraduate veterinary radiology course. The computer code used to manage the course and deliver images online is reported, and we provide links to the executable files. We tested to see if undergraduate peer review of radiological reports has validity and describe student impressions of the learning process. Peer review scores for student-generated radiological reports were compared to scores obtained in the summative multiple choice (MCQ) examination for the course. Student satisfaction was measured using a bespoke questionnaire. There was a weak positive correlation (Pearson correlation coefficient = 0.32, p < 0.01) between peer review scores students received and the student scores obtained in the MCQ examination. The difference in peer review scores received by students grouped according to their level of course performance (high vs. low) was statistically significant (p < 0.05). No correlation was found between peer review scores awarded by the students and the scores they obtained in the MCQ examination (Pearson correlation coefficient = 0.17, p = 0.14). In conclusion, we have created a realistic radiology imaging exercise with readily available software. The peer review scores are valid in that to a limited degree they reflect student future performance in an examination. Students valued the process of learning to communicate radiological findings but do not fully appreciated the value of peer review.

Method for assessment of stormwater treatment facilities - Synthetic road runoff addition including micro-pollutants and tracer.

Stormwater treatment facilities (STFs) are becoming increasingly widespread but knowledge on their performance is limited. This is due to difficulties in obtaining representative samples during storm events and documenting removal of the broad range of contaminants found in stormwater runoff. This paper presents a method to evaluate STFs by addition of synthetic runoff with representative concentrations of contaminant species, including the use of tracer for correction of removal rates for losses not caused by the STF. A list of organic and inorganic contaminant species, including trace elements representative of runoff from roads is suggested, as well as relevant concentration ranges. The method was used for adding contaminants to three different STFs including a curbstone extension with filter soil, a dual porosity filter, and six different permeable pavements. Evaluation of the method showed that it is possible to add a well-defined mixture of contaminants despite different field conditions by having a flexibly system, mixing different stock-solutions on site, and use bromide tracer for correction of outlet concentrations. Bromide recovery ranged from only 12% in one of the permeable pavements to 97% in the dual porosity filter, stressing the importance of including a conservative tracer for correction of contaminant retention values. The method is considered useful in future treatment performance testing of STFs. The observed performance of the STFs is presented in coming papers.

Unraveling the Complex Behavior of AgNPs Driving NP-Cell Interactions and Toxicity to Algal Cells.

While the importance of nanoparticle (NP) characterization under relevant test conditions is widely recognized in nanotoxicology, few studies monitor NPs behavior in the presence of exposed organisms. Here we studied the behavior of nine types of silver nanoparticles (AgNPs) during the 48 h algal toxicity test. In particular, we investigated NP aggregation and dissolution by time-resolved inductively coupled plasma mass spectrometry and ultrafiltration and performed mass balance measurements to study the distribution of Ag in the test system. We also determined the amount of extra- and intracellular Ag by chemically etching AgNPs on the surface of algal cells and used dark field microscopy for their imaging. We observed that positively charged branched polyethilenimine (bPEI)-coated AgNPs tend to aggregate in the presence of algae and interact with test vessels and algal cells, while citrate-coated AgNPs have a tendency to dissolve. On the other hand, with large variation of half-maximum effective concentration (EC50) across tested NPs (5.4 to 300 ngAg mL-1), Ag internalized by the algal cells at EC50 was similar (0.8 to 3.6 ngAg mL-1) for all AgNP types. These data show that while sorption to the vessels, dissolution, and aggregation impact on the distribution of AgNPs in the test system and on interactions with algal cells, AgNP toxicity is strongly correlated with the NP-cell surface interaction and internalization of Ag.

Ultrastructure and mitochondrial numbers in pre- and postpubertal pig oocytes.

Prepubertal pig oocytes are associated with lower developmental competence. The aim of this experiment was to conduct an exhaustive survey of oocyte ultrastructure and to use a design-unbiased stereological approach to quantify the numerical density and total number of mitochondria in oocytes with different diameters from pre- and postpubertal pigs. The ultrastructure of smaller prepubertal immature oocytes indicated active cells in close contact with cumulus cells. The postpubertal oocytes were more quiescent cell types. The small prepubertal oocytes had a lower total mitochondrial number, but no differences were observed in mitochondrial densities between groups. Mature postpubertal oocytes adhered to the following characteristics: presence of metaphase II, lack of contact between cumulus cells and oocyte, absence of rough endoplasmic reticulum and Golgi complexes, peripheral location of cortical granules and central localisation of mitochondria, vesicles and lipid droplets. Prepubertal oocytes displayed more variation. The ultrastructure of large pre- and postpubertal oocytes was compatible with higher developmental competence, whereas that of smaller prepubertal oocytes could explain their reduced capacity. The higher number of mitochondria in large pre- and postpubertal oocytes could have an influence on oocyte competence, by increasing the pool of mitochondria available for early embryonic development.

Aluminum Oxide-Coated Sand for Improved Treatment of Urban Stormwater.

Infiltration facilities for urban stormwater runoff, such as biofilters, rain gardens, and curb extensions, typically contain an engineered soil mixture for effective drainage and retention of pollutants. The treatment efficiency of such soils is generally considered high for many pollutants. However, recent studies have revealed that in situ mobilization of soil organic matter may cause leaching of a range of pollutants and therefore diminish the long-term performance of engineered soils. The purpose of this study was to develop and test sand coated with aluminum (Al) oxides for improving the retention of organic matter and a range of common pollutants in engineered soils. Two alternative Al-coating methods were successfully developed in the laboratory. The Al coating of the sand increased the specific surface area from 0.3 to 1.1 m g to 0.87 to 2.2 m g depending on sand fraction. One method was upscaled to produce 100 kg coated sand. The stability of the coatings was studied in batch experiments. Dry shaking showed a high resistance of the coating against mechanical stress. Increasing the ionic strength by the addition of NaCl seemed to improve the stability of the coatings. Varying pH showed that acidic conditions could compromise the Al coating stability. Overall, one coating method showed slightly better results in terms of higher surface area and stability. The Al coating significantly improved the retention capacity of the sand toward dissolved organic carbon. The results document that it is possible to coat sand effectively with Al oxides and consequently to improve the retention capacity and lifetime of engineered soils for urban stormwater management.

Diffusive Gradients in Thin Films as a Reference Method for Assessing Soil Phosphorus by Visual and Near-Infrared Spectroscopy.

Phosphorus (P) deficiency is a severe challenge in many agricultural areas around the globe, while at the same time, aquatic environments are threatened by leaching and runoff of excess P in other areas. Accurate, cheap, and rapid assessment of crop P needs and risk of P loss is therefore necessary to optimize the use of P fertilizer worldwide. The purpose of this study was to develop a method to predict soil P concentrations by visual and near-infrared spectroscopy using reference P concentrations determined by diffusive gradients in thin films (DGT); Olsen P results were included for comparison. The study was conducted on paddy soils from six main rice-producing ( L.) provinces in southern China. Using DGT P as a reference resulted in a better visual and near-infrared calibration to predict soil P concentrations, as compared with using Olsen P.

Land management of bracken needs to account for bracken carcinogens--a case study from Britain.

Bracken ferns are some of the most widespread ferns in the World causing immense problems for land managers, foresters and rangers. Bracken is suspected of causing cancer in Humans due to its content of the carcinogen ptaquiloside. Ingestion of bracken, or food and drinking water contaminated with ptaquiloside may be the cause. The aim of this study was to monitor the content of ptaquiloside in 20 bracken stands from Britain to obtain a better understanding of the ptaquiloside dynamics and to evaluate the environmental implications of using different cutting regimes in bracken management. The ptaquiloside content in fronds ranged between 50 and 5790 µg/g corresponding to a ptaquiloside load in the standing biomass of up to 590 mg/m(2) in mature fronds. Ptaquiloside was also found in the underground rhizome system (11-657 µg/g) and in decaying litter (0.1-5.8 µg/g). The amount of ptaquiloside present in bracken stands at any given time is difficult to predict and did not show any correlations with edaphic growth factors. The content of ptaquiloside turned out to be higher in fronds emerging after cutting compared to uncut fronds. Environmental risk assessment and bracken management must therefore be based on actual and site specific determinations of the ptaquiloside content. Care must be taken to avoid leaching from cut ferns to aquifers and other recipients and appropriate precautionary measures must be taken to protect staff from exposure to bracken dust.

Copper use and accumulation in catfish culture in the Mekong Delta, Vietnam.

Aquaculture of Pangasius hypophthalmus (striped catfish) in Vietnam reached 1.1 million tonnes in 2011 and catfish fillets are exported worldwide. The intensive cultures of catfish mainly in earth ponds have made it necessary to apply CuSO4 and other chemicals to control external parasites and other pathogens. However, accumulation of Cu in aquaculture ponds may pose a hazard to growth of fish or to the aquatic environment. The aim of this study was to determine accumulation of Cu in sediment, water and fish in a catfish pond with a history of repeated treatment with CuSO4 in the Mekong Delta, Vietnam. Copper concentrations in pond sediment were in the interval 21.3-45.7 mg kg(-1) dw and did not exceed the Vietnamese values for soil to be used for agricultural production (70 mg kg(-1) dw.). During three samplings the total mean concentration of Cu in pond water (4 µg L(-1)) did not exceed the LC50-value (70 µg L(-1)) for catfish and the mean dissolved concentration of Cu (0.986 µg L(-1)) did not seem to constitute a risk for the stability of the aquatic ecosystem. No significant variation in Cu concentrations between sampling sites in the pond and depth of sediment profile were determined. The accumulation of Cu in catfish was highest in the liver compared to the skin, gills and muscle tissue. With the current practice of removing pond sludge three to four times during a production cycle little if any Cu seems to accumulate in catfish ponds despite repeated anti-parasite treatments with CuSO4. Further studies are needed to assess the eco-toxicity and impact on agricultural production when pond sediment is discharged into aquatic recipients and used as soil fertilizer.

Co-cropping vetiver grass and legume for the phytoremediation of an acid mine drainage (AMD) impacted soil.

Acid mine drainage (AMD) is a form of environmental pollution from mining activity that can negatively affect soil environments by acidification, salinisation, and metal(loid) contamination. The use of plants to remediate (phytoremediation) these impacted environments while generating plant-based value is a promising approach to more accessible and cost-benefiting restoration of post-mining, marginal lands. In this study, a 3-month growth-chamber pot experiment was conducted to investigate the influence of co-cropping two plant species, Chrysopogon zizanioides (vetiver grass) and the legume Medicago truncatula (barrel clover) with a wheat straw biochar amendment on the phytostabilisation of metal(loid)s Cr, Zn, and As and the phytoextraction of rare earth element (REE) in an AMD impacted soil from a gold mining region in South Africa. The results showed that co-cropping with vetiver significantly lowered the legume's Cr, Zn, and As root contents by 80%, 32% and 54%, respectively, and improved the plant's overall metal(loid) tolerance by increasing its translocation from root to shoot tissue. The biochar further inhibited root uptake of Cr and Zn, by 71% and 36%, and increased the legume biomass by 40%. Both plant species and cropping treatments exhibited low REE extraction capabilities by shoot tissue, which accounted for less than 0.2% of total soil REE contents. The study shows that co-cropping with vetiver and biochar amendment are effective tools for the phytoremediation of AMD impacted soil mainly by lowering plant uptake and improving plant metal(loid) tolerance. Likely mechanisms at play include the alteration of rhizosphere chemistry and species-specific physiological and molecular responses. These effects offer support for the phytostabilisation of AMD impacted soil with the generation of plant-based value through dual (and safe) cultivation (phytoprotection) rather than through REE recovery from plant biomass (phytoextraction). These techniques could allow for the simultaneous restoration of post-mining, mining-impacted and marginal lands with agricultural production.

The robot butler: How and why should we study predictive algorithms and artificial intelligence (AI) in healthcare?

Artificial intelligence (AI) and algorithms are heralded as significant solutions to the widening gap between the rising healthcare needs of ageing and multi-morbid populations and the scarcity of resources to provide such care. Objective: This article investigates how the PMHnet algorithm - an AI prognostication tool developed in Denmark to predict the one-year all-cause mortality risk for patients hospitalized with ischemic heart disease - was presented to cardiologists working in the hospital setting, and how they responded to this novel decision-support tool. Methods: Empirically, we draw upon ethnographic fieldwork in the Danish-led international research project, PM Heart, which since 2019 has developed the PMHnet algorithm and implemented the software into the electronic health record system in hospitals in Eastern Denmark (the Capital Region and Region Zealand). Results: Paying careful attention to the hopes and concerns of cardiologists who will have to embrace and adapt to algorithmic tools in their everyday work of diagnosing and treating patients, we identify three analytical themes meriting attention when AI is implemented in healthcare: 1) the re-negotiation of agency and autonomy in human-algorithm relations, 2) accountability in algorithmic prognostication and 3) the complex relationship between association and causation actualized by predictive algorithms. From these analytical themes, we elicit methodological questions to guide future ethnographic explorations of how AI and advanced algorithms are put to use in the healthcare system, with what implications, and for whom. Conclusion: We conclude that local, qualitative investigations of how algorithms are used, embraced and contested in everyday clinical practice are needed in order to understand their implications - good and bad, intended and unintended - for clinicians, patients and healthcare provision.

Multi-cancer risk stratification based on national health data: a retrospective modelling and validation study.

BACKGROUND: Health care is experiencing a drive towards digitisation, and many countries are implementing national health data resources. Although a range of cancer risk models exists, the utility on a population level for risk stratification across cancer types has not been fully explored. We aimed to close this gap by evaluating pan-cancer risk models built on electronic health records across the Danish population with validation in the UK Biobank. METHODS: In this retrospective modelling and validation study, data for model development and internal validation were derived from the following Danish health registries: the Central Person Registry, the Danish National Patient Registry, the death registry, the cancer registry, and full-text medical records from secondary care records in the capital region. The development data included adults aged 16-86 years without previous malignant cancers in the time period from Jan 1, 1995, to Dec 31, 2014. The internal validation period was from Jan 1, 2015, to April 10, 2018, and the data included all adults without a previous indication of cancer aged 16-75 years on Dec 31, 2014. The external validation cohort from the UK Biobank included all adults without a previous indication of cancer aged 50-75 years. We used time-dependent Bayesian Cox hazard models built on the combined medical history of Danish individuals. A set of 1392 covariates from available clinical disease trajectories, text-mined basic health factors, and family histories were used to train predictive models of 20 major cancer types. The models were validated on cancer incidence between 2015 and 2018 across Denmark and on individuals in the UK Biobank. The primary outcomes were discrimination and calibration performance. FINDINGS: From the Danish registries, we included 6 732 553 individuals covering 60 million hospital visits, 90 million diagnoses, and a total of 193 million life-years between Jan 1, 1978, and April 10, 2018. Danish registry data covering the period from Jan 1, 2015, to April 10, 2018, were used to internally validate risk models, containing a total of 4 248 491 individuals who remained at risk of a primary malignant cancer diagnosis and 67 401 cancer cases recorded. For the external validation, we evaluated the same time period in the UK Biobank covering 377 004 individuals with 11 486 cancer cases. The predictive performance of the models on Danish data showed good discrimination (concordance index 0·81 [SD 0·08], ranging from 0·66 [95% CI 0·65-0·67] for cervix uteri cancer to 0·91 [0·90-0·92] for liver cancer). Performance was similar on the UK Biobank in a direct transfer when controlling for shifts in the age distribution (concordance index 0·66 [SD 0·08], ranging from 0·55 [95% CI 0·44-0·66] for cervix uteri cancer to 0·78 [0·77-0·79] for lung cancer). Cancer risks were associated, in addition to heritable components, with a broad range of preceding diagnoses and health factors. The best overall performance was seen for cancers of the digestive system (oesophageal, stomach, colorectal, liver, and pancreatic) but also thyroid, kidney, and uterine cancers. INTERPRETATION: Data available in national electronic health databases can be used to approximate cancer risk factors and enable risk predictions in most cancer types. Model predictions generalise between the Danish and UK health-care systems. With the emergence of multi-cancer early detection tests, electronic health record-based risk models could supplement screening efforts. FUNDING: Novo Nordisk Foundation and the Danish Innovation Foundation.