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Biomedical Engineering Online Dec 2023This systematic review and meta-analysis were conducted to objectively evaluate the evidence of machine learning (ML) in the patient diagnosis of Intracranial Hemorrhage... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This systematic review and meta-analysis were conducted to objectively evaluate the evidence of machine learning (ML) in the patient diagnosis of Intracranial Hemorrhage (ICH) on computed tomography (CT) scans.
METHODS
Until May 2023, systematic searches were conducted in ISI Web of Science, PubMed, Scopus, Cochrane Library, IEEE Xplore Digital Library, CINAHL, Science Direct, PROSPERO, and EMBASE for studies that evaluated the diagnostic precision of ML model-assisted ICH detection. Patients with and without ICH as the target condition who were receiving CT-Scan were eligible for the research, which used ML algorithms based on radiologists' reports as the gold reference standard. For meta-analysis, pooled sensitivities, specificities, and a summary receiver operating characteristics curve (SROC) were used.
RESULTS
At last, after screening the title, abstract, and full paper, twenty-six retrospective and three prospective, and two retrospective/prospective studies were included. The overall (Diagnostic Test Accuracy) DTA of retrospective studies with a pooled sensitivity was 0.917 (95% CI 0.88-0.943, I = 99%). The pooled specificity was 0.945 (95% CI 0.918-0.964, I = 100%). The pooled diagnostic odds ratio (DOR) was 219.47 (95% CI 104.78-459.66, I = 100%). These results were significant for the specificity of the different network architecture models (p-value = 0.0289). However, the results for sensitivity (p-value = 0.6417) and DOR (p-value = 0.2187) were not significant. The ResNet algorithm has higher pooled specificity than other algorithms with 0.935 (95% CI 0.854-0.973, I = 93%).
CONCLUSION
This meta-analysis on DTA of ML algorithms for detecting ICH by assessing non-contrast CT-Scans shows the ML has an acceptable performance in diagnosing ICH. Using ResNet in ICH detection remains promising prediction was improved via training in an Architecture Learning Network (ALN).
Topics: Humans; Prospective Studies; Sensitivity and Specificity; Retrospective Studies; Algorithms; Machine Learning; Diagnostic Tests, Routine
PubMed: 38049809
DOI: 10.1186/s12938-023-01172-1 -
BioMed Research International 2023Schistosomiasis is causing high morbidity and significant mortality in endemic areas. Kato-Katz stool examination and urine filtration techniques are the conventional... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Schistosomiasis is causing high morbidity and significant mortality in endemic areas. Kato-Katz stool examination and urine filtration techniques are the conventional methods for the detection of intestinal and urinary schistosomiasis. The most appropriate diagnostic tools for the detection of schistosomiasis especially in low-prevalence settings should be used. Therefore, this study is aimed at investigating the diagnostic accuracy of and diagnostic tools in sub-Saharan Africa.
METHODS
Electronic databases such as PubMed, PubMed Central/Medline, HINARI, Scopus, EMBASE, Science Direct, Google Scholar, and Cochrane Library were reviewed. The pooled estimates and heterogeneity were determined using Midas in Stata 14.0. The diagnostic accuracy of index tests was compared using the hierarchical summary of the receiver operating characteristic (HSROC) curve in Stata 14.0.
RESULTS
Twenty-four studies consisting of 12,370 individuals were tested to evaluate the accuracy of antigen, antibody, and molecular test methods for the detection of and . The pooled estimate of sensitivity and specificity of CCA was 88% (95% CI: 83-92) and 72 (95% CI: 62-80), respectively, when it is compared with parasitological stool examination for detection. On the other hand, ELISA showed a pooled estimate of sensitivity and specificity of 95% (95% CI: 93-96) and 35% (95% CI: 21-52), respectively, for the examination of using stool examination as a reference test. With regard to , the pooled estimate of sensitivity and specificity of polymerase chain reaction was 97% (95% CI: 78-100) and 94% (95% CI: 74-99), respectively. Moreover, the sensitivity and specificity of urine CCA vary between 41-80% and 55-91%, respectively, compared to urine microscopy.
CONCLUSION
The effort of schistosomiasis elimination requires accurate case identification especially in low-intensity infections. This study showed that CCA had the highest sensitivity and moderate specificity for the diagnosis of . Similarly, the sensitivity of ELISA was excellent, but its specificity was low. The diagnostic accuracy of PCR for the detection of was excellent compared to urine microscopic examination.
Topics: Humans; Animals; Microscopy; Schistosoma mansoni; Urinalysis; Africa South of the Sahara; Diagnostic Tests, Routine
PubMed: 37621699
DOI: 10.1155/2023/3769931 -
Preventive Medicine Reports Aug 2022Although diagnostic procedures are crucial for secondary prevention and patient disease control, they often trigger fear and anxiety. These reactions highlight the need... (Review)
Review
Although diagnostic procedures are crucial for secondary prevention and patient disease control, they often trigger fear and anxiety. These reactions highlight the need to adopt effective interventions to improve patients' experience and satisfaction. Recently, educational videos have been employed in preparing diagnostic procedures; however, there is no integrated understanding of their effects. This systematic review and -analysis aimed to assess the effectiveness of educational videos on patients' anxiety and satisfaction regarding preparation for diagnostic procedures. Three scientific databases (PubMed; Web of Science, Scopus), were used in this systematic review. Studies about educational videos as a form of preparation for patients undergoing diagnostic procedures published between 2000 and 2021 were included. A -analysis was also conducted. Sixteen studies met the inclusion criteria for systematic review, and seven were included in the -analysis. Nine studies of the total sample were about vascular procedures and seven studies about other medical image procedures. Of the fourteen studies that evaluated the use of educational videos on patients' anxiety, nine proved to reduce it significantly. Of the thirteen studies that evaluated satisfaction, seven showed a significant increase in the experimental group. Studies included in the -analysis show that educational video patient groups had lower anxiety levels than the control groups after the procedure. Although future studies are required, the results suggest that educational videos effectively prepare patients for diagnostic procedures, improving care quality.
PubMed: 35855928
DOI: 10.1016/j.pmedr.2022.101895 -
Medicina Oral, Patologia Oral Y Cirugia... Sep 2019Despite decades of research, our knowledge of several important aspects of periodontal pathogenesis remains incomplete. Epigenetics allows to perform dynamic analysis of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Despite decades of research, our knowledge of several important aspects of periodontal pathogenesis remains incomplete. Epigenetics allows to perform dynamic analysis of different variations in gene expression, providing this great advantage to the static measurement provided by genetic markers. The aim of this systematic review is to analyze the possible relationships between different epigenetic mechanisms and periodontal diseases, and to assess their potential use as biomarkers of periodontitis.
MATERIAL AND METHODS
A systematic search was conducted in six databases using MeSH and non-MeSH terms. The review fulfilled PRISMA criteria (Preferred Reporting Items for Systematic reviews and Meta-analysis).
RESULTS
36 studies met the inclusion criteria. Due to the heterogeneity of the articles, it was not possible to conduct quantitative analysis. Regarding qualitative synthesis, however, it was found that epigenetic mechanisms may be used as biological markers of periodontal disease, as their dynamism and molecular stability makes them a valuable diagnostic tool.
CONCLUSIONS
Epigenetic markers alter gene expression, producing either silencing or over-expression of molecular transcription that respond to the demands of the cellular surroundings. Gingival crevicular fluid collection is a non-invasive and simple procedure, which makes it an ideal diagnostic medium for detection of both oral and systemic issues. Although further research is needed, this seems to be a promising field of research in the years to come.
Topics: Epigenesis, Genetic; Gingival Crevicular Fluid; Humans; Periodontal Diseases; Periodontics; Periodontitis
PubMed: 31433392
DOI: 10.4317/medoral.23008 -
Health Technology Assessment... Oct 2022Coeliac disease is an autoimmune disorder triggered by ingesting gluten. It affects approximately 1% of the UK population, but only one in three people is thought to...
BACKGROUND
Coeliac disease is an autoimmune disorder triggered by ingesting gluten. It affects approximately 1% of the UK population, but only one in three people is thought to have a diagnosis. Untreated coeliac disease may lead to malnutrition, anaemia, osteoporosis and lymphoma.
OBJECTIVES
The objectives were to define at-risk groups and determine the cost-effectiveness of active case-finding strategies in primary care.
DESIGN
(1) Systematic review of the accuracy of potential diagnostic indicators for coeliac disease. (2) Routine data analysis to develop prediction models for identification of people who may benefit from testing for coeliac disease. (3) Systematic review of the accuracy of diagnostic tests for coeliac disease. (4) Systematic review of the accuracy of genetic tests for coeliac disease (literature search conducted in April 2021). (5) Online survey to identify diagnostic thresholds for testing, starting treatment and referral for biopsy. (6) Economic modelling to identify the cost-effectiveness of different active case-finding strategies, informed by the findings from previous objectives.
DATA SOURCES
For the first systematic review, the following databases were searched from 1997 to April 2021: MEDLINE (National Library of Medicine, Bethesda, MD, USA), Embase (Elsevier, Amsterdam, the Netherlands), Cochrane Library, Web of Science™ (Clarivate™, Philadelphia, PA, USA), the World Health Organization International Clinical Trials Registry Platform ( WHO ICTRP ) and the National Institutes of Health Clinical Trials database. For the second systematic review, the following databases were searched from January 1990 to August 2020: MEDLINE, Embase, Cochrane Library, Web of Science, Kleijnen Systematic Reviews ( KSR ) Evidence, WHO ICTRP and the National Institutes of Health Clinical Trials database. For prediction model development, Clinical Practice Research Datalink GOLD, Clinical Practice Research Datalink Aurum and a subcohort of the Avon Longitudinal Study of Parents and Children were used; for estimates for the economic models, Clinical Practice Research Datalink Aurum was used.
REVIEW METHODS
For review 1, cohort and case-control studies reporting on a diagnostic indicator in a population with and a population without coeliac disease were eligible. For review 2, diagnostic cohort studies including patients presenting with coeliac disease symptoms who were tested with serological tests for coeliac disease and underwent a duodenal biopsy as reference standard were eligible. In both reviews, risk of bias was assessed using the quality assessment of diagnostic accuracy studies 2 tool. Bivariate random-effects meta-analyses were fitted, in which binomial likelihoods for the numbers of true positives and true negatives were assumed.
RESULTS
People with dermatitis herpetiformis, a family history of coeliac disease, migraine, anaemia, type 1 diabetes, osteoporosis or chronic liver disease are 1.5-2 times more likely than the general population to have coeliac disease; individual gastrointestinal symptoms were not useful for identifying coeliac disease. For children, women and men, prediction models included 24, 24 and 21 indicators of coeliac disease, respectively. The models showed good discrimination between patients with and patients without coeliac disease, but performed less well when externally validated. Serological tests were found to have good diagnostic accuracy for coeliac disease. Immunoglobulin A tissue transglutaminase had the highest sensitivity and endomysial antibody the highest specificity. There was little improvement when tests were used in combination. Survey respondents ( = 472) wanted to be 66% certain of the diagnosis from a blood test before starting a gluten-free diet if symptomatic, and 90% certain if asymptomatic. Cost-effectiveness analyses found that, among adults, and using serological testing alone, immunoglobulin A tissue transglutaminase was most cost-effective at a 1% pre-test probability (equivalent to population screening). Strategies using immunoglobulin A endomysial antibody plus human leucocyte antigen or human leucocyte antigen plus immunoglobulin A tissue transglutaminase with any pre-test probability had similar cost-effectiveness results, which were also similar to the cost-effectiveness results of immunoglobulin A tissue transglutaminase at a 1% pre-test probability. The most practical alternative for implementation within the NHS is likely to be a combination of human leucocyte antigen and immunoglobulin A tissue transglutaminase testing among those with a pre-test probability above 1.5%. Among children, the most cost-effective strategy was a 10% pre-test probability with human leucocyte antigen plus immunoglobulin A tissue transglutaminase, but there was uncertainty around the most cost-effective pre-test probability. There was substantial uncertainty in economic model results, which means that there would be great value in conducting further research.
LIMITATIONS
The interpretation of meta-analyses was limited by the substantial heterogeneity between the included studies, and most included studies were judged to be at high risk of bias. The main limitations of the prediction models were that we were restricted to diagnostic indicators that were recorded by general practitioners and that, because coeliac disease is underdiagnosed, it is also under-reported in health-care data. The cost-effectiveness model is a simplification of coeliac disease and modelled an average cohort rather than individuals. Evidence was weak on the probability of routine coeliac disease diagnosis, the accuracy of serological and genetic tests and the utility of a gluten-free diet.
CONCLUSIONS
Population screening with immunoglobulin A tissue transglutaminase (1% pre-test probability) and of immunoglobulin A endomysial antibody followed by human leucocyte antigen testing or human leucocyte antigen testing followed by immunoglobulin A tissue transglutaminase with any pre-test probability appear to have similar cost-effectiveness results. As decisions to implement population screening cannot be made based on our economic analysis alone, and given the practical challenges of identifying patients with higher pre-test probabilities, we recommend that human leucocyte antigen combined with immunoglobulin A tissue transglutaminase testing should be considered for adults with at least a 1.5% pre-test probability of coeliac disease, equivalent to having at least one predictor. A more targeted strategy of 10% pre-test probability is recommended for children (e.g. children with anaemia).
FUTURE WORK
Future work should consider whether or not population-based screening for coeliac disease could meet the UK National Screening Committee criteria and whether or not it necessitates a long-term randomised controlled trial of screening strategies. Large prospective cohort studies in which all participants receive accurate tests for coeliac disease are needed.
STUDY REGISTRATION
This study is registered as PROSPERO CRD42019115506 and CRD42020170766.
FUNDING
This project was funded by the National Institute for Health and Care Research ( NIHR ) Health Technology Assessment programme and will be published in full in ; Vol. 26, No. 44. See the NIHR Journals Library website for further project information.
Topics: United States; Adult; Child; Male; Humans; Female; Celiac Disease; Longitudinal Studies; Prospective Studies; Skin Neoplasms; Immunoglobulin A; Osteoporosis; Randomized Controlled Trials as Topic
PubMed: 36321689
DOI: 10.3310/ZUCE8371 -
Ultrasound in Medicine & Biology Mar 2022The aim of this scoping review was to investigate ultrasound imaging (USI) acquisition procedures and guidelines used to assess the first metatarsophalangeal joint... (Review)
Review
The aim of this scoping review was to investigate ultrasound imaging (USI) acquisition procedures and guidelines used to assess the first metatarsophalangeal joint (MTPJ). MEDLINE, CINAHL, AMED and SPORTDiscus were systematically searched in May 2021. Studies were included if they used grey-scale USI or power Doppler and reported a USI procedure to assess the first MTPJ. Screening and data extraction were performed by two independent assessors. The scoping review was reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses extension for scoping reviews (PRISMA-ScR). A total of 403 citations were identified for screening, with 36 articles included in the final analysis. There was wide variation in USI acquisition procedures used to evaluate the first MTPJ. Inconsistencies in reporting may be attributable to the number of elements the USI acquisition procedure encompasses, which include the model of the USI device, the type of transducer, USI modalities and settings, patient position, transducer orientation, surfaces scanned and the scanning technique used. The review found inconsistencies against international guidelines and limited implementation of consensus-based recommendations to guide image acquisition. Current guidelines require further refinement of anatomical reference points to establish a standardised USI acquisition procedure, subsequently improving interpretability and reproducibility between USI studies that evaluate the first MTPJ.
Topics: Consensus; Humans; Metatarsophalangeal Joint; Reproducibility of Results; Ultrasonography
PubMed: 34969521
DOI: 10.1016/j.ultrasmedbio.2021.11.009 -
The Lancet. Microbe Apr 2024Accurate diagnosis is pivotal for implementing strategies for surveillance, control, and elimination of schistosomiasis. Despite their low sensitivity in low-endemicity... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Accurate diagnosis is pivotal for implementing strategies for surveillance, control, and elimination of schistosomiasis. Despite their low sensitivity in low-endemicity areas, microscopy-based urine filtration and the Kato-Katz technique are considered as reference diagnostic tests for Schistosoma haematobium and Schistosoma mansoni infections, respectively. We aimed to collate all available evidence on the accuracy of other proposed diagnostic techniques.
METHODS
In this systematic review and meta-analysis, we searched PubMed, Embase, the Cochrane Library, and LILACS for studies published from database inception to Dec 31, 2022, investigating the sensitivity and specificity of diagnostic tests for S haematobium and S mansoni infections against Kato-Katz thick smears or urine microscopy (reference tests) involving adults (aged ≥18 years), school-aged children (aged 7 to 18 years), or preschool-aged children (aged 1 month to 7 years). We extracted raw data on true positives, true negatives, false positives, and false negatives for the diagnostic tests and data on the number of participants, study authors, publication year, journal, study design, participants' age and sex, prevalence of Schistosoma infection, and treatment status. To account for imperfect reference tests, we used a hierarchical Bayesian latent class meta-analysis to model test accuracy.
FINDINGS
Overall, we included 121 studies, assessing 28 different diagnostic techniques. Most studies (103 [85%] of 121) were done in Africa, 14 (12%) in South America, one (1%) in Asia, and one (1%) in an unknown country. Compared with the reference test, Kato-Katz thick smears, circulating cathodic antigen urine cassette assay version 1 (CCA1, 36 test comparisons) had excellent sensitivity (95% [95% credible interval 88-99]) and reasonable specificity (74% [63-83]) for S mansoni. ELISA-based tests had a performance comparable to circulating cathodic antigen, but there were few available test comparisons. For S haematobium, proteinuria (42 test comparisons, sensitivity 73% [62-82]; specificity 94% [89-98]) and haematuria (75 test comparisons, sensitivity 85% [80-90]; specificity 96% [92-99]) reagent strips showed high specificity, with haematuria reagent strips having better sensitivity. Despite limited data, nucleic acid amplification tests (NAATs; eg, PCR or loop-mediated isothermal amplification [LAMP]) showed promising results with sensitivity estimates above 90%. We found an unclear risk of bias of about 70% in the use of the reference or index tests and of 50% in patient selection. All analyses showed substantial heterogeneity (I>80%).
INTERPRETATION
Although NAATs and immunological diagnostics show promise, the limited information available precludes drawing definitive conclusions. Additional research on diagnostic accuracy and cost-effectiveness is needed before the replacement of conventional tests can be considered.
FUNDING
WHO and Luxembourg Institute of Health.
Topics: Child; Child, Preschool; Adult; Animals; Humans; Adolescent; Schistosoma mansoni; Schistosoma haematobium; Hematuria; Reagent Strips; Microscopy; Bayes Theorem; Feces; Antigens, Helminth; Urinalysis; Schistosomiasis haematobia; Diagnostic Tests, Routine
PubMed: 38467130
DOI: 10.1016/S2666-5247(23)00377-4 -
Acta Dermato-venereologica Oct 2021Trichotillomania is formally classified as a mental health disorder, but it is commonly diagnosed by dermatologists. The aim of this systematic review is to assess the...
Trichotillomania is formally classified as a mental health disorder, but it is commonly diagnosed by dermatologists. The aim of this systematic review is to assess the diagnostic value of trichoscopy in diagnosing trichotillomania. The analysis identified the 7 most specific trichoscopic features in trichotillomania. These features had the following prevalence and specificity: trichoptilosis (57.5%; 73/127 and 97.5%, respectively), v-sign (50.4%; 63/125 and 99%), hook hairs (43.1%; 28/65 and 100%), flame hairs (37.1%; 52/140 and 96.5%), coiled hairs (36.8%; 46/125 and 99.6%), tulip hairs (36.4%; 28/77 and 89.6%), and hair powder (35.6%; 42/118 and 97.9%). The 2 most common, but least specific, features were broken hairs and black dots. In conclusion, trichoscopy is a reliable new diagnostic method for hair loss caused by hair pulling. Trichoscopy should be included as a standard procedure in the differential diagnosis of trichotillomania in clinical practice.
Topics: Alopecia; Dermoscopy; Diagnosis, Differential; Hair; Humans; Trichotillomania
PubMed: 34184065
DOI: 10.2340/00015555-3859 -
Ultrasound in Obstetrics & Gynecology :... Jan 2015To estimate procedure-related risks of miscarriage following amniocentesis and chorionic villus sampling (CVS) based on a systematic review of the literature and a... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
To estimate procedure-related risks of miscarriage following amniocentesis and chorionic villus sampling (CVS) based on a systematic review of the literature and a meta-analysis.
METHODS
A search of MEDLINE, EMBASE, CINHAL and The Cochrane Library (2000-2014) was performed to review relevant citations reporting procedure-related complications of amniocentesis and CVS. Only studies reporting data on more than 1000 procedures were included in this review to minimize the effect of bias from smaller studies. Heterogeneity between studies was estimated using Cochran's Q, the I(2) statistic and Egger bias. Meta-analysis of proportions was used to derive weighted pooled estimates for the risk of miscarriage before 24 weeks' gestation. Incidence-rate difference meta-analysis was used to estimate pooled procedure-related risks.
RESULTS
The weighted pooled risks of miscarriage following invasive procedures were estimated from analysis of controlled studies including 324 losses in 42 716 women who underwent amniocentesis and 207 losses in 8899 women who underwent CVS. The risk of miscarriage prior to 24 weeks in women who underwent amniocentesis and CVS was 0.81% (95% CI, 0.58-1.08%) and 2.18% (95% CI, 1.61-2.82%), respectively. The background rates of miscarriage in women from the control group that did not undergo any procedures were 0.67% (95% CI, 0.46-0.91%) for amniocentesis and 1.79% (95% CI, 0.61-3.58%) for CVS. The weighted pooled procedure-related risks of miscarriage for amniocentesis and CVS were 0.11% (95% CI, -0.04 to 0.26%) and 0.22% (95% CI, -0.71 to 1.16%), respectively.
CONCLUSION
The procedure-related risks of miscarriage following amniocentesis and CVS are much lower than are currently quoted.
Topics: Abortion, Spontaneous; Amniocentesis; Aneuploidy; Chorionic Villi Sampling; Decision Making; Female; Gestational Age; Humans; Odds Ratio; Patient Education as Topic; Pregnancy; Prenatal Diagnosis; Risk Factors
PubMed: 25042845
DOI: 10.1002/uog.14636 -
European Urology Oncology Apr 2021The 5-yr survival of early-stage renal cell carcinoma (RCC) is approximately 93%, but once metastasised, the 5-yr survival plummets to 12%, indicating that early RCC... (Review)
Review
CONTEXT
The 5-yr survival of early-stage renal cell carcinoma (RCC) is approximately 93%, but once metastasised, the 5-yr survival plummets to 12%, indicating that early RCC detection is crucial to improvement in survival. DNA methylation biomarkers have been suggested to be of potential diagnostic value; however, their current state of clinical translation is unclear and a comprehensive overview is lacking.
OBJECTIVE
To systematically review and summarise all literature regarding diagnostic DNA methylation biomarkers for RCC.
EVIDENCE ACQUISITION
We performed a systematic literature review of PubMed, EMBASE, Medline, and Google Scholar up to January 2019, according to the Preferred Reporting Items for Systematic Review and Meta-Analysis of Diagnostic Test Accuracy Studies (PRISMA-DTA) guidelines. Included studies were scored according to the Standards for Reporting of Diagnostic Accuracy Studies (STARD) criteria. Forest plots were generated to summarise diagnostic performance of all biomarkers. Level of evidence (LoE) and potential risk of bias were determined for all included studies.
EVIDENCE SYNTHESIS
After selection, 19 articles reporting on 44 diagnostic DNA methylation biomarkers and 11 multimarker panels were included; however, only 15 biomarkers were independently validated. STARD scores varied from 4 to 13 out of 23 points, with a median of 10 points. Large variation in subgroups, methods, and primer locations was observed. None of the reported biomarkers exceeded LoE III, and the majority of studies reported inadequately.
CONCLUSIONS
None of the reported biomarkers exceeded LoE III, indicating their limited clinical utility. Moreover, study reproducibility and further development of these RCC biomarkers are greatly hampered by inadequate reporting.
PATIENT SUMMARY
In this report, we reviewed whether specific biomarkers could be used to diagnose the most common form of kidney cancer. We conclude that due to limited evidence and reporting inconsistencies, none of these biomarkers can be used in clinical practice, and further development towards clinical use is hindered.
Topics: Biomarkers; Carcinoma, Renal Cell; DNA Methylation; Diagnostic Tests, Routine; Humans; Kidney Neoplasms; Reproducibility of Results
PubMed: 31402218
DOI: 10.1016/j.euo.2019.07.011