Publications by authors named "Andrew W Brown"

76 Publications

Improving open and rigorous science: ten key future research opportunities related to rigor, reproducibility, and transparency in scientific research.

F1000Res 2020 14;9:1235. Epub 2020 Oct 14.

Indiana University School of Public Health, Bloomington, IN, 47403, USA.

As part of a coordinated effort to expand research activity around rigor, reproducibility, and transparency (RRT) across scientific disciplines, a team of investigators at the Indiana University School of Public Health-Bloomington hosted a workshop in October 2019 with international leaders to discuss key opportunities for RRT research. The workshop aimed to identify research priorities and opportunities related to RRT. Over two-days, workshop attendees gave presentations and participated in three working groups: (1) Improving Education & Training in RRT, (2) Reducing Statistical Errors and Increasing Analytic Transparency, and (3) Looking Outward: Increasing Truthfulness and Accuracy of Research Communications. Following small-group discussions, the working groups presented their findings, and participants discussed the research opportunities identified. The investigators compiled a list of research priorities, which were circulated to all participants for feedback. Participants identified the following priority research questions: (1) Can RRT-focused statistics and mathematical modeling courses improve statistics practice?; (2) Can specialized training in scientific writing improve transparency?; (3) Does modality (e.g. face to face, online) affect the efficacy RRT-related education?; (4) How can automated programs help identify errors more efficiently?; (5) What is the prevalence and impact of errors in scientific publications (e.g., analytic inconsistencies, statistical errors, and other objective errors)?; (6) Do error prevention workflows reduce errors?; (7) How do we encourage post-publication error correction?; (8) How does 'spin' in research communication affect stakeholder understanding and use of research evidence?; (9) Do tools to aid writing research reports increase comprehensiveness and clarity of research reports?; and (10) Is it possible to inculcate scientific values and norms related to truthful, rigorous, accurate, and comprehensive scientific reporting? Participants identified important and relatively unexplored questions related to improving RRT. This list may be useful to the scientific community and investigators seeking to advance meta-science (i.e. research on research).
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http://dx.doi.org/10.12688/f1000research.26594.1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7898357PMC
October 2020

Persistent confusion in nutrition and obesity research about the validity of classic nonparametric tests in the presence of heteroscedasticity: evidence of the problem and valid alternatives.

Am J Clin Nutr 2021 03;113(3):517-524

Department of Epidemiology and Biostatistics, Indiana University School of Public Health-Bloomington, Bloomington, IN, USA.

The use of classic nonparametric tests (cNPTs), such as the Kruskal-Wallis and Mann-Whitney U tests, in the presence of unequal variance for between-group comparisons of means and medians may lead to marked increases in the rate of falsely rejecting null hypotheses and decreases in statistical power. Yet, this practice remains prevalent in the scientific literature, including nutrition and obesity literature. Some nutrition and obesity studies use a cNPT in the presence of unequal variance (i.e., heteroscedasticity), sometimes because of the mistaken rationale that the test corrects for heteroscedasticity. Herein, we discuss misconceptions of using cNPTs in the presence of heteroscedasticity. We then discuss assumptions, purposes, and limitations of 3 common tests used to test for mean differences between multiple groups, including 2 parametric tests: Fisher's ANOVA and Welch's ANOVA; and 1 cNPT: the Kruskal-Wallis test. To document the impact of heteroscedasticity on the validity of these tests under conditions similar to those used in nutrition and obesity research, we conducted simple simulations and assessed type I error rates (i.e., false positives, defined as incorrectly rejecting the null hypothesis). We demonstrate that type I error rates for Fisher's ANOVA, which does not account for heteroscedasticity, and Kruskal-Wallis, which tests for differences in distributions rather than means, deviated from the expected significance level. Greater deviation from the expected type I error rate was observed as the heterogeneity increased, especially in the presence of an imbalanced sample size. We provide brief tutorial guidance for authors, editors, and reviewers to identify appropriate statistical tests when test assumptions are violated, with a particular focus on cNPTs.
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http://dx.doi.org/10.1093/ajcn/nqaa357DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7948897PMC
March 2021

Contrary to the Conclusions Stated in the Paper, Only Dry Fat-Free Mass Was Different between Groups upon Reanalysis. Comment on: "Intermittent Energy Restriction Attenuates the Loss of Fat-Free Mass in Resistance Trained Individuals. A Randomized Controlled Trial".

J Funct Morphol Kinesiol 2020 Nov 20;5(4). Epub 2020 Nov 20.

Faculty of Science, School of Human Sciences, The University of Western Australia, Crawley, WA 6009, Australia.

Campbell and colleagues recently published a randomised controlled trial investigating the effects of diets involving intermittent energy restriction versus continuous energy restriction on changes in body composition and resting metabolic rate (RMR) in resistance-trained adults[...].
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http://dx.doi.org/10.3390/jfmk5040085DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7739336PMC
November 2020

Double-counting of effect sizes and inappropriate exclusion of studies in "The influence of vitamin D supplementation on IGF-1 levels in humans: A systematic review and meta-analysis".

Ageing Res Rev 2021 03 15;66:101236. Epub 2020 Dec 15.

Department of Epidemiology and Biostatistics, Indiana University School of Public Health-Bloomington, Bloomington, Indiana, USA.

We read with interest the review by Kord-Varkaneh et al. which examined the effects of vitamin D supplementation on IGF-1 levels in humans. We believe that the article suffers from severe methodological faults and subsequently the conclusions are likely to be biased. Thus, the authors should address the mentioned limitations and update the analyses to provide robust and trustful estimates. We are concerned that without correction, the analyses may lead to erroneous findings and conclusions.
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http://dx.doi.org/10.1016/j.arr.2020.101236DOI Listing
March 2021

Overstated Claims of Efficacy and Safety. Comment On: "Optimal Nutritional Status for a Well-Functioning Immune System Is an Important Factor to Protect Against Viral Infections". 2020, , 1181.

Nutrients 2020 09 3;12(9). Epub 2020 Sep 3.

Department of Applied Health Science, Indiana University School of Public Health-Bloomington, Bloomington, IN 47405, USA.

Calder et al [...].
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http://dx.doi.org/10.3390/nu12092690DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7551966PMC
September 2020

The influence of hypoxia and energy depletion on the response of endothelial cells to the vascular disrupting agent combretastatin A-4-phosphate.

Sci Rep 2020 06 18;10(1):9926. Epub 2020 Jun 18.

Tumour Microcirculation Group, Department of Oncology and Metabolism, University of Sheffield, School of Medicine, Beech Hill Road, Sheffield, S10 2RX, United Kingdom.

Combretastatin A-4 phosphate (CA4P) is a microtubule-disrupting tumour-selective vascular disrupting agent (VDA). CA4P activates the actin-regulating RhoA-GTPase/ ROCK pathway, which is required for full vascular disruption. While hypoxia renders tumours resistant to many conventional therapies, little is known about its influence on VDA activity. Here, we found that active RhoA and ROCK effector phospho-myosin light chain (pMLC) were downregulated in endothelial cells by severe hypoxia. CA4P failed to activate RhoA/ROCK/pMLC but its activity was restored upon reoxygenation. Hypoxia also inhibited CA4P-mediated actinomyosin contractility, VE-cadherin junction disruption and permeability rise. Glucose withdrawal downregulated pMLC, and coupled with hypoxia, reduced pMLC faster and more profoundly than hypoxia alone. Concurrent inhibition of glycolysis (2-deoxy-D-glucose, 2DG) and mitochondrial respiration (rotenone) caused profound actin filament loss, blocked RhoA/ROCK signalling and rendered microtubules  CA4P-resistant. Withdrawal of the metabolism inhibitors restored the cytoskeleton and CA4P activity. The AMP-activated kinase AMPK was investigated as a potential mediator of pMLC downregulation. Pharmacological AMPK activators that generate AMP, unlike allosteric activators, downregulated pMLC but only when combined with 2DG and/or rotenone. Altogether, our results suggest that Rho/ROCK and actinomyosin contractility are regulated by AMP/ATP levels independently of AMPK, and point to hypoxia/energy depletion as potential modifiers of CA4P response.
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http://dx.doi.org/10.1038/s41598-020-66568-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7303175PMC
June 2020

Exceptional Reported Effects and Data Anomalies Merit Explanation from "A randomized controlled trial of coordination exercise on cognitive function in obese adolescents" by.

Psychol Sport Exerc 2020 Jan 20;46. Epub 2019 Oct 20.

Department of Epidemiology and Biostatistics, Indiana University School of Public Health-Bloomington, Bloomington, IN, USA.

We read the recent article in Psychology of Sport and Exercise by Liu et al. ("A randomized controlled trial of coordination exercise on cognitive function in obese adolescents") with great interest. Our interest in the article stemmed from the extraordinary differences in obesity-related outcomes reported in response to a rope-jumping intervention. We requested the raw data from the authors to confirm the results and, after the journal editors reinforced our request, the authors graciously provided us with their data. We share our evaluation of the original data herein, which includes concerns that weight and BMI loss by the intervention appears extraordinary in both magnitude and aspects of the distributions. We request that the authors address our findings by providing explanations of the extraordinary data or correcting any errors that may have occurred in the original report, as appropriate.
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http://dx.doi.org/10.1016/j.psychsport.2019.101604DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7189777PMC
January 2020

Murine genetic models of obesity: type I error rates and the power of commonly used analyses as assessed by plasmode-based simulation.

Int J Obes (Lond) 2020 06 25;44(6):1440-1449. Epub 2020 Feb 25.

Department of Epidemiology and Biostatistics, Indiana University School of Public Health-Bloomington, Bloomington, IN, USA.

Background/objectives: Genetic contributors to obesity are frequently studied in murine models. However, the sample sizes of these studies are often small, and the data may violate assumptions of common statistical tests, such as normality of distributions. We examined whether, in these cases, type I error rates and power are affected by the choice of statistical test.

Subjects/methods: We conducted "plasmode"-based simulation using empirical data on body mass (weight) from murine genetic models of obesity. For the type I error simulation, the weight distributions were adjusted to ensure no difference in means between control and mutant groups. For the power simulation, the distributions of the mutant groups were shifted to ensure specific effect sizes. Three to twenty mice were resampled from the empirical distributions to create a plasmode. We then computed type I error rates and power for five common tests on the plasmodes: Student's t test, Welch's t test, Wilcoxon rank sum test (aka, Mann-Whitney U test), permutation test, and bootstrap test.

Results: We observed type I error inflation for all tests, except the bootstrap test, with small samples (≤5). Type I error inflation decreased as sample size increased (≥8) but remained. The Wilcoxon test should be avoided because of heterogeneity of distributions. For power, a departure from the reference was observed with small samples for all tests. Compared with the other tests, the bootstrap test had less power with small samples.

Conclusions: Overall, the bootstrap test is recommended for small samples to avoid type I error inflation, but this benefit comes at the cost of lower power. When sample size is large enough, Welch's t test is recommended because of high power with minimal type I error inflation.
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http://dx.doi.org/10.1038/s41366-020-0554-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7261642PMC
June 2020

Science dialogue mapping of knowledge and knowledge gaps related to the effects of dairy intake on human cardiovascular health and disease.

Crit Rev Food Sci Nutr 2021 19;61(2):179-195. Epub 2020 Feb 19.

Department of Epidemiology and Biostatistics, Indiana University School of Public Health-Bloomington, Bloomington, Indiana, USA.

Dairy has been described as everything from a superfood to a poison; yet, arguments, assumptions, and data justifying these labels are not always clear. We used an issue-based information system, "dialogue mapping™," to summarize scientific points of a live panel discussion on the putative effects of dairy on cardiovascular diseases (CVD) from a day-long session among experts in nutrition and CVD. Dialogue mapping captures relations among ideas to explicitly, logically, and visually connect issues/questions, ideas, pro/con arguments, and agreements, even if discussed at different times. Experts discussed two propositions: for CVD risk, consumption of full-fat dairy products 1) should be minimized, in part because of their saturated fat content, or 2) need not be minimized, despite their saturated fat content. The panel discussed the dairy-CVD relation through blood lipids, diabetes, obesity, energy balance, blood pressure, dairy bioactives, biobehavioral components, and other putative causal pathways. Associations and effects reported in the literature have varied by fat content of dairy elements considered, study design, intake methods, and biomarker versus disease outcomes. Two conceptual topics emerged from the discussion: 1) individual variability: whether recommendations should be targeted only to those at high CVD risk; 2) quality of evidence: whether data on dairy-CVD relations are strong enough for reliable conclusions-positive, negative, or null. Future procedural improvements for science dialog mapping include using singular rather than competing propositions for discussion.
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http://dx.doi.org/10.1080/10408398.2020.1722941DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7434715PMC
December 2020

Data anomalies and apparent reporting errors in 'Randomized controlled trial testing weight loss and abdominal obesity outcomes of moxibustion'.

Biomed Eng Online 2020 Feb 18;19(1):11. Epub 2020 Feb 18.

Department of Epidemiology and Biostatistics, Indiana University School of Public Health-Bloomington, 1025 E 7th St, Bloomington, IN, 47405, USA.

Randomized Controlled Trials (RCTs) are the best method to determine causal effects for treatments if they are well done and well reported. Good evidence about proposed treatments for obesity is needed, and Hsieh et al. (Biomed Eng Online 17:149, 2018) are to be commended for putting moxibustion to the test. However, careful evaluation of the paper reveals inconsistencies and apparent reporting errors, which raise doubts about conclusions from the study.
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http://dx.doi.org/10.1186/s12938-020-0753-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7029490PMC
February 2020

Toward fulfilling the aspirational goal of science as self-correcting: A call for editorial courage and diligence for error correction.

Eur J Clin Invest 2020 02 18;50(2):e13190. Epub 2020 Jan 18.

Department of Epidemiology and Biostatistics, Indiana University School of Public Health-Bloomington, Bloomington, IN, USA.

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http://dx.doi.org/10.1111/eci.13190DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7422661PMC
February 2020

Does exclusion of extreme reporters of energy intake (the "Goldberg cutoffs") reliably reduce or eliminate bias in nutrition studies? Analysis with illustrative associations of energy intake with health outcomes.

Am J Clin Nutr 2019 11;110(5):1231-1239

Department of Epidemiology and Biostatistics, Indiana University School of Public Health-Bloomington, Bloomington, IN, USA.

Background: The Goldberg cutoffs are used to decrease bias in self-reported estimates of energy intake (EISR). Whether the cutoffs reduce and eliminate bias when used in regressions of health outcomes has not been assessed.

Objective: We examined whether applying the Goldberg cutoffs to data used in nutrition studies could reliably reduce or eliminate bias.

Methods: We used data from the Comprehensive Assessment of Long-Term Effects of Reducing Intake of Energy (CALERIE), the Interactive Diet and Activity Tracking in American Association of Retired Persons (IDATA) study, and the National Diet and Nutrition Survey (NDNS). Each data set included EISR, energy intake estimated from doubly labeled water (EIDLW) as a reference method, and health outcomes including baseline anthropometric, biomarker, and behavioral measures and fitness test results. We conducted 3 linear regression analyses using EISR, a plausible EISR based on the Goldberg cutoffs (EIG), and EIDLW as an explanatory variable for each analysis. Regression coefficients were denoted ${\hat{\beta }_{\rm SR}}$, ${\hat{\beta }_{\rm G}}$, and ${\hat{\beta }_{\rm DLW}}$, respectively. Using the jackknife method, bias from ${\hat{\beta }_{\rm SR}}$ compared with ${\hat{\beta }_{\rm DLW}}$ and remaining bias from ${\hat{\beta }_{\rm G}}$ compared with ${\hat{\beta }_{\rm DLW}}$ were estimated. Analyses were repeated using Pearson correlation coefficients.

Results: The analyses from CALERIE, IDATA, and NDNS included 218, 349, and 317 individuals, respectively. Using EIG significantly decreased the bias only for a subset of those variables with significant bias: weight (56.1%; 95% CI: 28.5%, 83.7%) and waist circumference (WC) (59.8%; 95% CI: 33.2%, 86.5%) with CALERIE, weight (20.8%; 95% CI: -6.4%, 48.1%) and WC (17.3%; 95% CI: -20.8%, 55.4%) with IDATA, and WC (-9.5%; 95% CI: -72.2%, 53.1%) with NDNS. Furthermore, bias significantly remained even after excluding implausible data for various outcomes. Results obtained with Pearson correlation coefficient analyses were qualitatively consistent.

Conclusions: Some associations between EIG and outcomes remained biased compared with associations between EIDLW and outcomes. Use of the Goldberg cutoffs was not a reliable method for eliminating bias.
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http://dx.doi.org/10.1093/ajcn/nqz198DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6821551PMC
November 2019

Dropout rates of in-person psychosocial substance use disorder treatments: a systematic review and meta-analysis.

Addiction 2020 02 6;115(2):201-217. Epub 2019 Nov 6.

Department of Health Behavior, University of Alabama at Birmingham School of Public Health, Birmingham, AL, USA.

Background And Aims: Relapse rates for psychosocial substance use disorder (SUD) treatments are high, and dropout is a robust predictor of relapse. This study aimed to estimate average dropout rates of in-person psychosocial SUD treatments and to assess predictors of dropout.

Design: A comprehensive meta-analysis of dropout rates of studies of in-person psychosocial SUD treatment. Studies included randomized controlled trials (RCTs) and cohort studies.

Setting: Studies conducted anywhere in the world that examined SUD treatment and were published from 1965 to 2016, inclusive.

Participants/cases: One hundred and fifty-one studies, 338 study arms and 299 dropout rates including 26 243 participants.

Measurements: Databases were searched for studies of SUD treatment that included an in-person psychosocial component. Meta-analyses and meta-regressions were conducted to estimate dropout rates and identify predictors of dropout, including participant characteristics, facilitator characteristics and treatment characteristics. Pooled estimates were calculated with random-effects analyses accounting for the hierarchical structure of study arms nested within studies.

Findings: The average dropout rate across all studies and study arms was 30.4% [95% confidence interval (CI) = 27.2-33.8 and 95% prediction interval (PI) = 6.25-74.15], with substantial heterogeneity (I  = 93.7%, P < 0.0001). Studies including a higher percentage of African Americans and lower-income individuals were associated with higher dropout rates. At intake, more cigarettes/day and a greater percentage of heroin use days were associated with lower dropout rates, whereas heavier cocaine use was associated with higher dropout rates. Dropout rates were highest for studies targeting cocaine, methamphetamines and major stimulants (broadly defined) and lowest for studies targeting alcohol, tobacco and heroin, although there were few studies on methamphetamines, major stimulants and heroin. Programs characterized by more treatment sessions and greater average session length were associated with higher dropout rates. Facilitator characteristics were not significantly associated with dropout.

Conclusions: On average, approximately 30% of participants drop out of in-person psychosocial SUD treatment studies, but there is wide variability. Drop-out rates vary with the treated population, the substance being targeted, and the characteristics of the treatment.
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http://dx.doi.org/10.1111/add.14793DOI Listing
February 2020

Childhood obesity intervention studies: A narrative review and guide for investigators, authors, editors, reviewers, journalists, and readers to guard against exaggerated effectiveness claims.

Obes Rev 2019 11 19;20(11):1523-1541. Epub 2019 Aug 19.

Department of Epidemiology and Biostatistics, Indiana University School of Public Health-Bloomington, Bloomington, Indiana.

Being able to draw accurate conclusions from childhood obesity trials is important to make advances in reversing the obesity epidemic. However, obesity research sometimes is not conducted or reported to appropriate scientific standards. To constructively draw attention to this issue, we present 10 errors that are commonly committed, illustrate each error with examples from the childhood obesity literature, and follow with suggestions on how to avoid these errors. These errors are as follows: using self-reported outcomes and teaching to the test; foregoing control groups and risking regression to the mean creating differences over time; changing the goal posts; ignoring clustering in studies that randomize groups of children; following the forking paths, subsetting, p-hacking, and data dredging; basing conclusions on tests for significant differences from baseline; equating "no statistically significant difference" with "equally effective"; ignoring intervention study results in favor of observational analyses; using one-sided testing for statistical significance; and stating that effects are clinically significant even though they are not statistically significant. We hope that compiling these errors in one article will serve as the beginning of a checklist to support fidelity in conducting, analyzing, and reporting childhood obesity research.
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http://dx.doi.org/10.1111/obr.12923DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7436851PMC
November 2019

Spin in the abstract in "Impact of motivational interviewing on outcomes of an adolescent obesity treatment: Results from the MI Values randomized controlled pilot trial".

Clin Obes 2019 10 4;9(5):e12332. Epub 2019 Aug 4.

Department of Epidemiology and Biostatistics, School of Public Health-Bloomington, Indiana University, Bloomington, Indiana.

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http://dx.doi.org/10.1111/cob.12332DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6718333PMC
October 2019

Differences in Nominal Significance (DINS) Error leads to invalid conclusions: Letter regarding, "Diet enriched with fresh coconut decreases blood glucose levels and body weight in normal adults".

J Complement Integr Med 2019 06 12;16(2). Epub 2019 Jun 12.

Department of Epidemiology and Biostatistics, Indiana University School of Public Health-Bloomington, Bloomington, IN,United States of America.

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http://dx.doi.org/10.1515/jcim-2018-0037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6957306PMC
June 2019

Evaluation of Sydnone-Based Analogues of Combretastatin A-4 Phosphate (CA4P) as Vascular Disrupting Agents for Use in Cancer Therapy.

ChemMedChem 2018 12 8;13(24):2618-2626. Epub 2018 Nov 8.

Department of Oncology & Metabolism, The University of Sheffield, The Medical School, Beech Hill Road, Sheffield, S10 2RX, UK.

The combretastatins have attracted significant interest as small-molecule therapies for cancer due to their ability to function as vascular disrupting agents. We have successfully prepared a range of combretastatin analogues that are based on a novel sydnone heterocycle core, and their potential as tubulin binders has been assessed in vitro and in vivo. The most potent candidate was found to disrupt microtubules and affect cellular morphology at sub-micromolar levels. Moreover, it was found to bind reversibly to tubulin and significantly increase endothelial cell monolayer permeability, in a similar manner to combretastatin A4. Surprisingly, the compound did not exhibit efficacy in vivo, possibly due to rapid metabolism.
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http://dx.doi.org/10.1002/cmdc.201800567DOI Listing
December 2018