Evaluating cutpoints for the MHI-5 and MCS using the GHQ-12: a comparison of five different methods

Background The Mental Health Inventory (MHI-5) and the Mental Health Component Summary score (MCS) derived from the Short Form 36 (SF-36) instrument are well validated and reliable scales. A drawback of their construction is that neither has a clinically validated cutpoint to define a case of common mental disorder (CMD). This paper aims to produce cutpoints for the MHI-5 and MCS by comparison with the General Health Questionnaire (GHQ-12). Methods Data were analysed from wave 9 of the British Household Panel Survey (2000), providing a sample size of 14,669 individuals. Receiver Operating Characteristic (ROC) curves were used to compare the scales and define cutpoints for the MHI-5 and MCS, using the following optimisation criteria: the Youden Index, the point closest to (0,1) on the ROC curve, minimising the misclassification rate, the minimax method, and prevalence matching. Results For the MHI-5, the Youden Index and the (0,1) methods both gave a cutpoint of 76, minimising the misclassification rate gave a cutpoint of 60 and the minimax method and prevalence matching gave a cutpoint of 68. For the MCS, the Youden Index and the (0,1) methods gave cutpoints of 51.7 and 52.1 respectively, minimising the error rate gave a cutpoint of 44.8 and both the minimax method and prevalence matching gave a cutpoint of 48.9. The correlation between the MHI-5 and the MCS was 0.88. Conclusion The Youden Index and (0,1) methods are most suitable for determining a cutpoint for the MHI-5, since they are least dependent on population prevalence. The choice of method is dependent on the intended application. The MHI-5 performs remarkably well against the longer MCS

Impacts of increasing anthropogenic soluble iron and nitrogen deposition on ocean biogeochemistry

Author Posting. © American Geophysical Union, 2009. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Global Biogeochemical Cycles 23 (2009): GB3016, doi:10.1029/2008GB003440.We present results from transient sensitivity studies with the Biogeochemical Elemental Cycling (BEC) ocean model to increasing anthropogenic atmospheric inorganic nitrogen (N) and soluble iron (Fe) deposition over the industrial era. Elevated N deposition results from fossil fuel combustion and agriculture, and elevated soluble Fe deposition results from increased atmospheric processing in the presence of anthropogenic pollutants and soluble Fe from combustion sources. Simulations with increasing Fe and increasing Fe and N inputs raised simulated marine nitrogen fixation, with the majority of the increase in the subtropical North and South Pacific, and raised primary production and export in the high-nutrient low-chlorophyll (HNLC) regions. Increasing N inputs alone elevated small phytoplankton and diatom production, resulting in increased phosphorus (P) and Fe limitation for diazotrophs, hence reducing nitrogen fixation (∼6%). Globally, the simulated primary production, sinking particulate organic carbon (POC) export. and atmospheric CO2 uptake were highest under combined increase in Fe and N inputs compared to preindustrial control. Our results suggest that increasing combustion iron sources and aerosol Fe solubility along with atmospheric anthropogenic nitrogen deposition are perturbing marine biogeochemical cycling and could partially explain the observed trend toward increased P limitation at station ALOHA in the subtropical North Pacific. Excess inorganic nitrogen ([NO3 −] + [NH4 +] − 16[PO4 3−]) distributions may offer useful insights for understanding changing ocean circulation and biogeochemistry.This work was supported by funding from NSF grant OCE-0452972 to J. K. Moore and C. S. Zender. Computations were supported by the Earth System Modeling Facility at UCI (NSFATMO321380) and by the Climate Simulation Laboratory at National Center for Atmospheric Research. The National Center for Atmospheric Research is sponsored by the U.S. National Science Foundation. N.M. would like to acknowledge the assistance of NSF– Carbon and Water (ATM-0628472), and N.M., S.D., and C.L. would like to acknowledge the assistance of NASA-IDS (NNX07AL80G)

Evaluation in artificial intelligence: From task-oriented to ability-oriented measurement

The final publication is available at Springer via http://dx.doi.org/ 10.1007/s10462-016-9505-7.The evaluation of artificial intelligence systems and components is crucial for the progress of the discipline. In this paper we describe and critically assess the different ways AI systems are evaluated, and the role of components and techniques in these systems. We first focus on the traditional task-oriented evaluation approach. We identify three kinds of evaluation: human discrimination, problem benchmarks and peer confrontation. We describe some of the limitations of the many evaluation schemes and competitions in these three categories, and follow the progression of some of these tests. We then focus on a less customary (and challenging) ability-oriented evaluation approach, where a system is characterised by its (cognitive) abilities, rather than by the tasks it is designed to solve. We discuss several possibilities: the adaptation of cognitive tests used for humans and animals, the development of tests derived from algorithmic information theory or more integrated approaches under the perspective of universal psychometrics. We analyse some evaluation tests from AI that are better positioned for an ability-oriented evaluation and discuss how their problems and limitations can possibly be addressed with some of the tools and ideas that appear within the paper. Finally, we enumerate a series of lessons learnt and generic guidelines to be used when an AI evaluation scheme is under consideration.I thank the organisers of the AEPIA Summer School On Artificial Intelligence, held in September 2014, for giving me the opportunity to give a lecture on 'AI Evaluation'. This paper was born out of and evolved through that lecture. The information about many benchmarks and competitions discussed in this paper have been contrasted with information from and discussions with many people: M. Bedia, A. Cangelosi, C. Dimitrakakis, I. GarcIa-Varea, Katja Hofmann, W. Langdon, E. Messina, S. Mueller, M. Siebers and C. Soares. Figure 4 is courtesy of F. Martinez-Plumed. Finally, I thank the anonymous reviewers, whose comments have helped to significantly improve the balance and coverage of the paper. This work has been partially supported by the EU (FEDER) and the Spanish MINECO under Grants TIN 2013-45732-C4-1-P, TIN 2015-69175-C4-1-R and by Generalitat Valenciana PROMETEOII2015/013.José Hernández-Orallo (2016). Evaluation in artificial intelligence: From task-oriented to ability-oriented measurement. Artificial Intelligence Review. 1-51. https://doi.org/10.1007/s10462-016-9505-7S151Abel D, Agarwal A, Diaz F, Krishnamurthy A, Schapire RE (2016) Exploratory gradient boosting for reinforcement learning in complex domains. arXiv preprint arXiv:1603.04119Adams S, Arel I, Bach J, Coop R, Furlan R, Goertzel B, Hall JS, Samsonovich A, Scheutz M, Schlesinger M, Shapiro SC, Sowa J (2012) Mapping the landscape of human-level artificial general intelligence. AI Mag 33(1):25–42Adams SS, Banavar G, Campbell M (2016) I-athlon: towards a multi-dimensional Turing test. AI Mag 37(1):78–84Alcalá J, Fernández A, Luengo J, Derrac J, García S, Sánchez L, Herrera F (2010) Keel data-mining software tool: data set repository, integration of algorithms and experimental analysis framework. J Mult Valued Logic Soft Comput 17:255–287Alexander JRM, Smales S (1997) Intelligence, learning and long-term memory. Personal Individ Differ 23(5):815–825Alpcan T, Everitt T, Hutter M (2014) Can we measure the difficulty of an optimization problem? In: IEEE information theory workshop (ITW)Alur R, Bodik R, Juniwal G, Martin MMK, Raghothaman M, Seshia SA, Singh R, Solar-Lezama A, Torlak E, Udupa A (2013) Syntax-guided synthesis. In: Formal methods in computer-aided design (FMCAD), 2013, IEEE, pp 1–17Alvarado N, Adams SS, Burbeck S, Latta C (2002) Beyond the Turing test: performance metrics for evaluating a computer simulation of the human mind. In: Proceedings of the 2nd international conference on development and learning, IEEE, pp 147–152Amigoni F, Bastianelli E, Berghofer J, Bonarini A, Fontana G, Hochgeschwender N, Iocchi L, Kraetzschmar G, Lima P, Matteucci M, Miraldo P, Nardi D, Schiaffonati V (2015) Competitions for benchmarking: task and functionality scoring complete performance assessment. IEEE Robot Autom Mag 22(3):53–61Anderson J, Lebiere C (2003) The Newell test for a theory of cognition. Behav Brain Sci 26(5):587–601Anderson J, Baltes J, Cheng CT (2011) Robotics competitions as benchmarks for AI research. Knowl Eng Rev 26(01):11–17Arel I, Rose DC, Karnowski TP (2010) Deep machine learning—a new frontier in artificial intelligence research. IEEE Comput Intell Mag 5(4):13–18Asada M, Hosoda K, Kuniyoshi Y, Ishiguro H, Inui T, Yoshikawa Y, Ogino M, Yoshida C (2009) Cognitive developmental robotics: a survey. IEEE Trans Auton Ment Dev 1(1):12–34Aziz H, Brill M, Fischer F, Harrenstein P, Lang J, Seedig HG (2015) Possible and necessary winners of partial tournaments. J Artif Intell Res 54:493–534Bache K, Lichman M (2013) UCI machine learning repository. http://archive.ics.uci.edu/mlBagnall AJ, Zatuchna ZV (2005) On the classification of maze problems. In: Bull L, Kovacs T (eds) Foundations of learning classifier system. Studies in fuzziness and soft computing, vol. 183, Springer, pp 305–316. http://rd.springer.com/chapter/10.1007/11319122_12Baldwin D, Yadav SB (1995) The process of research investigations in artificial intelligence - a unified view. IEEE Trans Syst Man Cybern 25(5):852–861Bellemare MG, Naddaf Y, Veness J, Bowling M (2013) The arcade learning environment: an evaluation platform for general agents. J Artif Intell Res 47:253–279Besold TR (2014) A note on chances and limitations of psychometric ai. In: KI 2014: advances in artificial intelligence. Springer, pp 49–54Biever C (2011) Ultimate IQ: one test to rule them all. New Sci 211(2829, 10 September 2011):42–45Borg M, Johansen SS, Thomsen DL, Kraus M (2012) Practical implementation of a graphics Turing test. In: Advances in visual computing. Springer, pp 305–313Boring EG (1923) Intelligence as the tests test it. New Repub 35–37Bostrom N (2014) Superintelligence: paths, dangers, strategies. Oxford University Press, OxfordBrazdil P, Carrier CG, Soares C, Vilalta R (2008) Metalearning: applications to data mining. Springer, New YorkBringsjord S (2011) Psychometric artificial intelligence. J Exp Theor Artif Intell 23(3):271–277Bringsjord S, Schimanski B (2003) What is artificial intelligence? Psychometric AI as an answer. In: International joint conference on artificial intelligence, pp 887–893Brundage M (2016) Modeling progress in ai. AAAI 2016 Workshop on AI, Ethics, and SocietyBuchanan BG (1988) Artificial intelligence as an experimental science. Springer, New YorkBuhrmester M, Kwang T, Gosling SD (2011) Amazon’s mechanical turk a new source of inexpensive, yet high-quality, data? Perspect Psychol Sci 6(1):3–5Bursztein E, Aigrain J, Moscicki A, Mitchell JC (2014) The end is nigh: generic solving of text-based captchas. In: Proceedings of the 8th USENIX conference on Offensive Technologies, USENIX Association, p 3Campbell M, Hoane AJ, Hsu F (2002) Deep Blue. Artif Intell 134(1–2):57–83Cangelosi A, Schlesinger M, Smith LB (2015) Developmental robotics: from babies to robots. MIT Press, CambridgeCaputo B, Müller H, Martinez-Gomez J, Villegas M, Acar B, Patricia N, Marvasti N, Üsküdarlı S, Paredes R, Cazorla M et al (2014) Imageclef 2014: overview and analysis of the results. In: Information access evaluation. Multilinguality, multimodality, and interaction, Springer, pp 192–211Carlson A, Betteridge J, Kisiel B, Settles B, Hruschka ER Jr, Mitchell TM (2010) Toward an architecture for never-ending language learning. In: AAAI, vol 5, p 3Carroll JB (1993) Human cognitive abilities: a survey of factor-analytic studies. Cambridge University Press, CambridgeCaruana R (1997) Multitask learning. Mach Learn 28(1):41–75Chaitin GJ (1982) Gödel’s theorem and information. Int J Theor Phys 21(12):941–954Chandrasekaran B (1990) What kind of information processing is intelligence? In: The foundation of artificial intelligence—a sourcebook. Cambridge University Press, pp 14–46Chater N (1999) The search for simplicity: a fundamental cognitive principle? Q J Exp Psychol Sect A 52(2):273–302Chater N, Vitányi P (2003) Simplicity: a unifying principle in cognitive science? Trends Cogn Sci 7(1):19–22Chu Z, Gianvecchio S, Wang H, Jajodia S (2010) Who is tweeting on twitter: human, bot, or cyborg? In: Proceedings of the 26th annual computer security applications conference, ACM, pp 21–30Cochran WG (2007) Sampling techniques. Wiley, New YorkCohen PR, Howe AE (1988) How evaluation guides AI research: the message still counts more than the medium. AI Mag 9(4):35Cohen Y (2013) Testing and cognitive enhancement. Technical repor, National Institute for Testing and Evaluation, Jerusalem, IsraelConrad JG, Zeleznikow J (2013) The significance of evaluation in AI and law: a case study re-examining ICAIL proceedings. In: Proceedings of the 14th international conference on artificial intelligence and law, ACM, pp 186–191Conrad JG, Zeleznikow J (2015) The role of evaluation in ai and law. In: Proceedings of the 15th international conference on artificial intelligence and law, pp 181–186Deary IJ, Der G, Ford G (2001) Reaction times and intelligence differences: a population-based cohort study. Intelligence 29(5):389–399Decker KS, Durfee EH, Lesser VR (1989) Evaluating research in cooperative distributed problem solving. Distrib Artif Intell 2:487–519Demšar J (2006) Statistical comparisons of classifiers over multiple data sets. J Mach Learn Res 7:1–30Detterman DK (2011) A challenge to Watson. Intelligence 39(2–3):77–78Dimitrakakis C (2016) Personal communicationDimitrakakis C, Li G, Tziortziotis N (2014) The reinforcement learning competition 2014. AI Mag 35(3):61–65Dowe DL (2013) Introduction to Ray Solomonoff 85th memorial conference. In: Dowe DL (ed) Algorithmic probability and friends. Bayesian prediction and artificial intelligence, lecture notes in computer science, vol 7070. Springer, Berlin, pp 1–36Dowe DL, Hajek AR (1997) A computational extension to the Turing Test. In: Proceedings of the 4th conference of the Australasian cognitive science society, University of Newcastle, NSW, AustraliaDowe DL, Hajek AR (1998) A non-behavioural, computational extension to the Turing test. In: International conference on computational intelligence and multimedia applications (ICCIMA’98), Gippsland, Australia, pp 101–106Dowe DL, Hernández-Orallo J (2012) IQ tests are not for machines, yet. Intelligence 40(2):77–81Dowe DL, Hernández-Orallo J (2014) How universal can an intelligence test be? Adapt Behav 22(1):51–69Drummond C (2009) Replicability is not reproducibility: nor is it good science. In: Proceedings of the evaluation methods for machine learning workshop at the 26th ICML, Montreal, CanadaDrummond C, Japkowicz N (2010) Warning: statistical benchmarking is addictive. Kicking the habit in machine learning. J Exp Theor Artif Intell 22(1):67–80Duan Y, Chen X, Houthooft R, Schulman J, Abbeel P (2016) Benchmarking deep reinforcement learning for continuous control. arXiv preprint arXiv:1604.06778Eden AH, Moor JH, Soraker JH, Steinhart E (2013) Singularity hypotheses: a scientific and philosophical assessment. Springer, New YorkEdmondson W (2012) The intelligence in ETI—what can we know? Acta Astronaut 78:37–42Elo AE (1978) The rating of chessplayers, past and present, vol 3. Batsford, LondonEmbretson SE, Reise SP (2000) Item response theory for psychologists. L. Erlbaum, HillsdaleEvans JM, Messina ER (2001) Performance metrics for intelligent systems. NIST Special Publication SP, pp 101–104Everitt T, Lattimore T, Hutter M (2014) Free lunch for optimisation under the universal distribution. In: 2014 IEEE Congress on evolutionary computation (CEC), IEEE, pp 167–174Falkenauer E (1998) On method overfitting. J Heuristics 4(3):281–287Feldman J (2003) Simplicity and complexity in human concept learning. Gen Psychol 38(1):9–15Ferrando PJ (2009) Difficulty, discrimination, and information indices in the linear factor analysis model for continuous item responses. Appl Psychol Meas 33(1):9–24Ferrando PJ (2012) Assessing the discriminating power of item and test scores in the linear factor-analysis model. Psicológica 33:111–139Ferri C, Hernández-Orallo J, Modroiu R (2009) An experimental comparison of performance measures for classification. Pattern Recogn Lett 30(1):27–38Ferrucci D, Brown E, Chu-Carroll J, Fan J, Gondek D, Kalyanpur AA, Lally A, Murdock J, Nyberg E, Prager J et al (2010) Building Watson: an overview of the DeepQA project. AI Mag 31(3):59–79Fogel DB (1991) The evolution of intelligent decision making in gaming. Cybern Syst 22(2):223–236Gaschnig J, Klahr P, Pople H, Shortliffe E, Terry A (1983) Evaluation of expert systems: issues and case studies. Build Exp Syst 1:241–278Geissman JR, Schultz RD (1988) Verification & validation. AI Exp 3(2):26–33Genesereth M, Love N, Pell B (2005) General game playing: overview of the AAAI competition. AI Mag 26(2):62Gerónimo D, López AM (2014) Datasets and benchmarking. In: Vision-based pedestrian protection systems for intelligent vehicles. Springer, pp 87–93Goertzel B, Pennachin C (eds) (2007) Artificial general intelligence. Springer, New YorkGoertzel B, Arel I, Scheutz M (2009) Toward a roadmap for human-level artificial general intelligence: embedding HLAI systems in broad, approachable, physical or virtual contexts. Artif Gen Intell Roadmap InitiatGoldreich O, Vadhan S (2007) Special issue on worst-case versus average-case complexity editors’ foreword. Comput complex 16(4):325–330Gordon BB (2007) Report on panel discussion on (re-)establishing or increasing collaborative links between artificial intelligence and intelligent systems. In: Messina ER, Madhavan R (eds) Proceedings of the 2007 workshop on performance metrics for intelligent systems, pp 302–303Gulwani S, Hernández-Orallo J, Kitzelmann E, Muggleton SH, Schmid U, Zorn B (2015) Inductive programming meets the real world. Commun ACM 58(11):90–99Hand DJ (2004) Measurement theory and practice. A Hodder Arnold Publication, LondonHernández-Orallo J (2000a) Beyond the Turing test. J Logic Lang Inf 9(4):447–466Hernández-Orallo J (2000b) On the computational measurement of intelligence factors. In: Meystel A (ed) Performance metrics for intelligent systems workshop. National Institute of Standards and Technology, Gaithersburg, pp 1–8Hernández-Orallo J (2000c) Thesis: computational measures of information gain and reinforcement in inference processes. AI Commun 13(1):49–50Hernández-Orallo J (2010) A (hopefully) non-biased universal environment class for measuring intelligence of biological and artificial systems. In: Artificial general intelligence, 3rd International Conference. Atlantis Press, Extended report at http://users.dsic.upv.es/proy/anynt/unbiased.pdf , pp 182–183Hernández-Orallo J (2014) On environment difficulty and discriminating power. Auton Agents Multi-Agent Syst. 29(3):402–454. doi: 10.1007/s10458-014-9257-1Hernández-Orallo J, Dowe DL (2010) Measuring universal intelligence: towards an anytime intelligence test. Artif Intell 174(18):1508–1539Hernández-Orallo J, Dowe DL (2013) On potential cognitive abilities in the machine kingdom. Minds Mach 23:179–210Hernández-Orallo J, Minaya-Collado N (1998) A formal definition of intelligence based on an intensional variant of Kolmogorov complexity. In: Proceedings of international symposium of engineering of intelligent systems (EIS’98), ICSC Press, pp 146–163Hernández-Orallo J, Dowe DL, España-Cubillo S, Hernández-Lloreda MV, Insa-Cabrera J (2011) On more realistic environment distributions for defining, evaluating and developing intelligence. In: Schmidhuber J, Thórisson K, Looks M (eds) Artificial general intelligence, LNAI, vol 6830. Springer, New York, pp 82–91Hernández-Orallo J, Flach P, Ferri C (2012a) A unified view of performance metrics: translating threshold choice into expected classification loss. J Mach Learn Res 13(1):2813–2869Hernández-Orallo J, Insa-Cabrera J, Dowe DL, Hibbard B (2012b) Turing Tests with Turing machines. In: Voronkov A (ed) Turing-100, EPiC Series, vol 10, pp 140–156Hernández-Orallo J, Dowe DL, Hernández-Lloreda MV (2014) Universal psychometrics: measuring cognitive abilities in the machine kingdom. Cogn Syst Res 27:50–74Hernández-Orallo J, Martínez-Plumed F, Schmid U, Siebers M, Dowe DL (2016) Computer models solving intelligence test problems: progress and implications. Artif Intell 230:74–107Herrmann E, Call J, Hernández-Lloreda MV, Hare B, Tomasello M (2007) Humans have evolved specialized skills of social cognition: the cultural intelligence hypothesis. Science 317(5843):1360–1366Hibbard B (2009) Bias and no free lunch in formal measures of intelligence. J Artif Gen Intell 1(1):54–61Hingston P (2010) A new design for a Turing Test for bots. In: 2010 IEEE symposium on computational intelligence and games (CIG), IEEE, pp 345–350Hingston P (2012) Believable bots: can computers play like people?. Springer, New YorkHo TK, Basu M (2002) Complexity measures of supervised classification problems. IEEE Trans Pattern Anal Mach Intell 24(3):289–300Hutter M (2007) Universal algorithmic intelligence: a mathematical top $$\rightarrow$$ → down approach. In: Goertzel B, Pennachin C (eds) Artificial general intelligence, cognitive technologies. Springer, Berlin, pp 227–290Igel C, Toussaint M (2005) A no-free-lunch theorem for non-uniform distributions of target functions. J Math Model Algorithms 3(4):313–322Insa-Cabrera J (2016) Towards a universal test of social intelligence. Ph.D. thesis, Departament de Sistemes Informátics i Computació, UPVInsa-Cabrera J, Dowe DL, España-Cubillo S, Hernández-Lloreda MV, Hernández-Orallo J (2011a) Comparing humans and ai agents. In: Schmidhuber J, Thórisson K, Looks M (eds) Artificial general intelligence, LNAI, vol 6830. Springer, New York, pp 122–132Insa-Cabrera J, Dowe DL, Hernández-Orallo J (2011) Evaluating a reinforcement learning algorithm with a general intelligence test. In: Lozano JA, Gamez JM (eds) Current topics in artificial intelligence. CAEPIA 2011, LNAI series 7023. Springer, New YorkInsa-Cabrera J, Benacloch-Ayuso JL, Hernández-Orallo J (2012) On measuring social intelligence: experiments on competition and cooperation. In: Bach J, Goertzel B, Iklé M (eds) AGI, lecture notes in computer science, vol 7716. Springer, New York, pp 126–135Jacoff A, Messina E, Weiss BA, Tadokoro S, Nakagawa Y (2003) Test arenas and performance metrics for urban search and rescue robots. In: Proceedings of 2003 IEEE/RSJ international conference on intelligent robots and systems, 2003 (IROS 2003), IEEE, vol 4, pp 3396–3403Japkowicz N, Shah M (2011) Evaluating learning algorithms. Cambridge University Press, CambridgeJiang J (2008) A literature survey on domain adaptation of statistical classifiers. http://sifaka.cs.uiuc.edu/jiang4/domain_adaptation/surveyJohnson M, Hofmann K, Hutton T, Bignell D (2016) The Malmo platform for artificial intelligence experimentation. In: International joint conference on artificial intelligence (IJCAI)Keith TZ, Reynolds MR (2010) Cattell–Horn–Carroll abilities and cognitive tests: what we’ve learned from 20 years of research. Psychol Schools 47(7):635–650Ketter W, Symeonidis A (2012) Competitive benchmarking: lessons learned from the trading agent competition. AI Mag 33(2):103Khreich W, Granger E, Miri A, Sabourin R (2012) A survey of techniques for incremental learning of HMM parameters. Inf Sci 197:105–130Kim JH (2004) Soccer robotics, vol 11. Springer, New YorkKitano H, Asada M, Kuniyoshi Y, Noda I, Osawa E (1997) Robocup: the robot world cup initiative. In: Proceedings of the first international conference on autonomous agents, ACM, pp 340–347Kleiner K (2011) Who are you calling bird-brained? An attempt is being made to devise a universal intelligence test. Economist 398(8723, 5 March 2011):82Knuth DE (1973) Sorting and searching, volume 3 of the art of computer programming. Addison-Wesley, ReadingKoza JR (2010) Human-competitive results produced by genetic programming. Genet Program Evolvable Mach 11(3–4):251–284Krueger J, Osherson D (1980) On the psychology of structural simplicity. In: Jusczyk PW, Klein RM (eds) The nature of thought: essays in honor of D. O. Hebb. Psychology Press, London, pp 187–205Langford J (2005) Clever methods of overfitting. Machine Learning (Theory). http://hunch.netLangley P (1987) Research papers in machine learning. Mach Learn 2(3):195–198Langley P (2011) The changing science of machine learning. Mach Learn 82(3):275–279Langley P (2012) The cognitive systems paradigm. Adv Cogn Syst 1:3–13Lattimore T, Hutter M (2013) No free lunch versus Occam’s razor in supervised learning. Algorithmic Probability and Friends. Springer, Bayesian Prediction and Artificial Intelligence, pp 223–235Leeuwenberg ELJ, Van Der Helm PA (2012) Structural information theory: the simplicity of visual form. Cambridge University Press, CambridgeLegg S, Hutter M (2007a) Tests of machine intelligence. In: Lungarella M, Iida F, Bongard J, Pfeifer R (eds) 50 Years of Artificial Intelligence, Lecture Notes in Computer Science, vol 4850, Springer Berlin Heidelberg, pp 232–242. doi: 10.1007/978-3-540-77296-5_22Legg S, Hutter M (2007b) Universal intelligence: a definition of machine intelligence. Minds Mach 17(4):391–444Legg S, Veness J (2013) An approximation of the universal intelligence measure. Algorithmic Probability and Friends. Springer, Bayesian Prediction and Artificial Intelligence, pp 236–249Levesque HJ (2014) On our best behaviour. Artif Intell 212:27–35Levesque HJ, Davis E, Morgenstern L (2012) The winog

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

Proceedings of the 8th Annual Conference on the Science of Dissemination and Implementation

A1 Introduction to the 8(th) Annual Conference on the Science of Dissemination and Implementation: Optimizing Personal and Population Health David Chambers, Lisa Simpson D1 Discussion forum: Population health D&I research Felicia Hill-Briggs D2 Discussion forum: Global health D&I research Gila Neta, Cynthia Vinson D3 Discussion forum: Precision medicine and D&I research David Chambers S1 Predictors of community therapists’ use of therapy techniques in a large public mental health system Rinad Beidas, Steven Marcus, Gregory Aarons, Kimberly Hoagwood, Sonja Schoenwald, Arthur Evans, Matthew Hurford, Ronnie Rubin, Trevor Hadley, Frances Barg, Lucia Walsh, Danielle Adams, David Mandell S2 Implementing brief cognitive behavioral therapy (CBT) in primary care: Clinicians' experiences from the field Lindsey Martin, Joseph Mignogna, Juliette Mott, Natalie Hundt, Michael Kauth, Mark Kunik, Aanand Naik, Jeffrey Cully S3 Clinician competence: Natural variation, factors affecting, and effect on patient outcomes Alan McGuire, Dominique White, Tom Bartholomew, John McGrew, Lauren Luther, Angie Rollins, Michelle Salyers S4 Exploring the multifaceted nature of sustainability in community-based prevention: A mixed-method approach Brittany Cooper, Angie Funaiole S5 Theory informed behavioral health integration in primary care: Mixed methods evaluation of the implementation of routine depression and alcohol screening and assessment Julie Richards, Amy Lee, Gwen Lapham, Ryan Caldeiro, Paula Lozano, Tory Gildred, Carol Achtmeyer, Evette Ludman, Megan Addis, Larry Marx, Katharine Bradley S6 Enhancing the evidence for specialty mental health probation through a hybrid efficacy and implementation study Tonya VanDeinse, Amy Blank Wilson, Burgin Stacey, Byron Powell, Alicia Bunger, Gary Cuddeback S7 Personalizing evidence-based child mental health care within a fiscally mandated policy reform Miya Barnett, Nicole Stadnick, Lauren Brookman-Frazee, Anna Lau S8 Leveraging an existing resource for technical assistance: Community-based supervisors in public mental health Shannon Dorsey, Michael Pullmann S9 SBIRT implementation for adolescents in urban federally qualified health centers: Implementation outcomes Shannon Mitchell, Robert Schwartz, Arethusa Kirk, Kristi Dusek, Marla Oros, Colleen Hosler, Jan Gryczynski, Carolina Barbosa, Laura Dunlap, David Lounsbury, Kevin O'Grady, Barry Brown S10 PANEL: Tailoring Implementation Strategies to Context - Expert recommendations for tailoring strategies to context Laura Damschroder, Thomas Waltz, Byron Powell S11 PANEL: Tailoring Implementation Strategies to Context - Extreme facilitation: Helping challenged healthcare settings implement complex programs Mona Ritchie S12 PANEL: Tailoring Implementation Strategies to Context - Using menu-based choice tasks to obtain expert recommendations for implementing three high-priority practices in the VA Thomas Waltz S13 PANEL: The Use of Technology to Improve Efficient Monitoring of Implementation of Evidence-based Programs - Siri, rate my therapist: Using technology to automate fidelity ratings of motivational interviewing David Atkins, Zac E. Imel, Bo Xiao, Doğan Can, Panayiotis Georgiou, Shrikanth Narayanan S14 PANEL: The Use of Technology to Improve Efficient Monitoring of Implementation of Evidence-based Programs - Identifying indicators of implementation quality for computer-based ratings Cady Berkel, Carlos Gallo, Irwin Sandler, C. Hendricks Brown, Sharlene Wolchik, Anne Marie Mauricio S15 PANEL: The Use of Technology to Improve Efficient Monitoring of Implementation of Evidence-based Programs - Improving implementation of behavioral interventions by monitoring emotion in spoken speech Carlos Gallo, C. Hendricks Brown, Sanjay Mehrotra S16 Scorecards and dashboards to assure data quality of health management information system (HMIS) using R Dharmendra Chandurkar, Siddhartha Bora, Arup Das, Anand Tripathi, Niranjan Saggurti, Anita Raj S17 A big data approach for discovering and implementing patient safety insights Eric Hughes, Brian Jacobs, Eric Kirkendall S18 Improving the efficacy of a depression registry for use in a collaborative care model Danielle Loeb, Katy Trinkley, Michael Yang, Andrew Sprowell, Donald Nease S19 Measurement feedback systems as a strategy to support implementation of measurement-based care in behavioral health Aaron Lyon, Cara Lewis, Meredith Boyd, Abigail Melvin, Semret Nicodimos, Freda Liu, Nathanial Jungbluth S20 PANEL: Implementation Science and Learning Health Systems: Intersections and Commonalities - Common loop assay: Methods of supporting learning collaboratives Allen Flynn S21 PANEL: Implementation Science and Learning Health Systems: Intersections and Commonalities - Innovating audit and feedback using message tailoring models for learning health systems Zach Landis-Lewis S22 PANEL: Implementation Science and Learning Health Systems: Intersections and Commonalities - Implementation science and learning health systems: Connecting the dots Anne Sales S23 Facilitation activities of Critical Access Hospitals during TeamSTEPPS implementation Jure Baloh, Marcia Ward, Xi Zhu S24 Organizational and social context of federally qualified health centers and variation in maternal depression outcomes Ian Bennett, Jurgen Unutzer, Johnny Mao, Enola Proctor, Mindy Vredevoogd, Ya-Fen Chan, Nathaniel Williams, Phillip Green S25 Decision support to enhance treatment of hospitalized smokers: A randomized trial Steven Bernstein, June-Marie Rosner, Michelle DeWitt, Jeanette Tetrault, James Dziura, Allen Hsiao, Scott Sussman, Patrick O’Connor, Benjamin Toll S26 PANEL: Developing Sustainable Strategies for the Implementation of Patient-Centered Care across Diverse US Healthcare Systems - A patient-centered approach to successful community transition after catastrophic injury Michael Jones, Julie Gassaway S27 PANEL: Developing Sustainable Strategies for the Implementation of Patient-Centered Care across Diverse US Healthcare Systems - Conducting PCOR to integrate mental health and cancer screening services in primary care Jonathan Tobin S28 PANEL: Developing Sustainable Strategies for the Implementation of Patient-Centered Care across Diverse US Healthcare Systems - A comparative effectiveness trial of optimal patient-centered care for US trauma care systems Douglas Zatzick S29 Preferences for in-person communication among patients in a multi-center randomized study of in-person versus telephone communication of genetic test results for cancer susceptibility Angela R Bradbury, Linda Patrick-Miller, Brian Egleston, Olufunmilayo I Olopade, Michael J Hall, Mary B Daly, Linda Fleisher, Generosa Grana, Pamela Ganschow, Dominique Fetzer, Amanda Brandt, Dana Farengo-Clark, Andrea Forman, Rikki S Gaber, Cassandra Gulden, Janice Horte, Jessica Long, Rachelle Lorenz Chambers, Terra Lucas, Shreshtha Madaan, Kristin Mattie, Danielle McKenna, Susan Montgomery, Sarah Nielsen, Jacquelyn Powers, Kim Rainey, Christina Rybak, Michelle Savage, Christina Seelaus, Jessica Stoll, Jill Stopfer, Shirley Yao and Susan Domchek S30 Working towards de-implementation: A mixed methods study in breast cancer surveillance care Erin Hahn, Corrine Munoz-Plaza, Jianjin Wang, Jazmine Garcia Delgadillo, Brian Mittman Michael Gould S31Integrating evidence-based practices for increasing cancer screenings in safety-net primary care systems: A multiple case study using the consolidated framework for implementation research Shuting (Lily) Liang, Michelle C. Kegler, Megan Cotter, Emily Phillips, April Hermstad, Rentonia Morton, Derrick Beasley, Jeremy Martinez, Kara Riehman S32 Observations from implementing an mHealth intervention in an FQHC David Gustafson, Lisa Marsch, Louise Mares, Andrew Quanbeck, Fiona McTavish, Helene McDowell, Randall Brown, Chantelle Thomas, Joseph Glass, Joseph Isham, Dhavan Shah S33 A multicomponent intervention to improve primary care provider adherence to chronic opioid therapy guidelines and reduce opioid misuse: A cluster randomized controlled trial protocol Jane Liebschutz, Karen Lasser S34 Implementing collaborative care for substance use disorders in primary care: Preliminary findings from the summit study Katherine Watkins, Allison Ober, Sarah Hunter, Karen Lamp, Brett Ewing S35 Sustaining a task-shifting strategy for blood pressure control in Ghana: A stakeholder analysis Juliet Iwelunmor, Joyce Gyamfi, Sarah Blackstone, Nana Kofi Quakyi, Jacob Plange-Rhule, Gbenga Ogedegbe S36 Contextual adaptation of the consolidated framework for implementation research (CFIR) in a tobacco cessation study in Vietnam Pritika Kumar, Nancy Van Devanter, Nam Nguyen, Linh Nguyen, Trang Nguyen, Nguyet Phuong, Donna Shelley S37 Evidence check: A knowledge brokering approach to systematic reviews for policy Sian Rudge S38 Using Evidence Synthesis to Strengthen Complex Health Systems in Low- and Middle-Income Countries Etienne Langlois S39 Does it matter: timeliness or accuracy of results? The choice of rapid reviews or systematic reviews to inform decision-making Andrea Tricco S40 Evaluation of the veterans choice program using lean six sigma at a VA medical center to identify benefits and overcome obstacles Sherry Ball, Anne Lambert-Kerzner, Christine Sulc, Carol Simmons, Jeneen Shell-Boyd, Taryn Oestreich, Ashley O'Connor, Emily Neely, Marina McCreight, Amy Labebue, Doreen DiFiore, Diana Brostow, P. Michael Ho, David Aron S41 The influence of local context on multi-stakeholder alliance quality improvement activities: A multiple case study Jillian Harvey, Megan McHugh, Dennis Scanlon S42 Increasing physical activity in early care and education: Sustainability via active garden education (SAGE) Rebecca Lee, Erica Soltero, Nathan Parker, Lorna McNeill, Tracey Ledoux S43 Marking a decade of policy implementation: The successes and continuing challenges of a provincial school food and nutrition policy in Canada Jessie-Lee McIsaac, Kate MacLeod, Nicole Ata, Sherry Jarvis, Sara Kirk S44 Use of research evidence among state legislators who prioritize mental health and substance abuse issues Jonathan Purtle, Elizabeth Dodson, Ross Brownson S45 PANEL: Effectiveness-Implementation Hybrid Designs: Clarifications, Refinements, and Additional Guidance Based on a Systematic Review and Reports from the Field - Hybrid type 1 designs Brian Mittman, Geoffrey Curran S46 PANEL: Effectiveness-Implementation Hybrid Designs: Clarifications, Refinements, and Additional Guidance Based on a Systematic Review and Reports from the Field - Hybrid type 2 designs Geoffrey Curran S47 PANEL: Effectiveness-Implementation Hybrid Designs: Clarifications, Refinements, and Additional Guidance Based on a Systematic Review and Reports from the Field - Hybrid type 3 designs Jeffrey Pyne S48 Linking team level implementation leadership and implementation climate to individual level attitudes, behaviors, and implementation outcomes Gregory Aarons, Mark Ehrhart, Elisa Torres S49 Pinpointing the specific elements of local context that matter most to implementation outcomes: Findings from qualitative comparative analysis in the RE-inspire study of VA acute stroke care Edward Miech S50 The GO score: A new context-sensitive instrument to measure group organization level for providing and improving care Edward Miech S51 A research network approach for boosting implementation and improvement Kathleen Stevens, I.S.R.N. Steering Council S52 PANEL: Qualitative methods in D&I Research: Value, rigor and challenge - The value of qualitative methods in implementation research Alison Hamilton S53 PANEL: Qualitative methods in D&I Research: Value, rigor and challenge - Learning evaluation: The role of qualitative methods in dissemination and implementation research Deborah Cohen S54 PANEL: Qualitative methods in D&I Research: Value, rigor and challenge - Qualitative methods in D&I research Deborah Padgett S55 PANEL: Maps & models: The promise of network science for clinical D&I - Hospital network of sharing patients with acute and chronic diseases in California Alexandra Morshed S56 PANEL: Maps & models: The promise of network science for clinical D&I - The use of social network analysis to identify dissemination targets and enhance D&I research study recruitment for pre-exposure prophylaxis for HIV (PrEP) among men who have sex with men Rupa Patel S57 PANEL: Maps & models: The promise of network science for clinical D&I - Network and organizational factors related to the adoption of patient navigation services among rural breast cancer care providers Beth Prusaczyk S58 A theory of de-implementation based on the theory of healthcare professionals’ behavior and intention (THPBI) and the becker model of unlearning David C. Aron, Divya Gupta, Sherry Ball S59 Observation of registered dietitian nutritionist-patient encounters by dietetic interns highlights low awareness and implementation of evidence-based nutrition practice guidelines Rosa Hand, Jenica Abram, Taylor Wolfram S60 Program sustainability action planning: Building capacity for program sustainability using the program sustainability assessment tool Molly Hastings, Sarah Moreland-Russell S61 A review of D&I study designs in published study protocols Rachel Tabak, Alex Ramsey, Ana Baumann, Emily Kryzer, Katherine Montgomery, Ericka Lewis, Margaret Padek, Byron Powell, Ross Brownson S62 PANEL: Geographic variation in the implementation of public health services: Economic, organizational, and network determinants - Model simulation techniques to estimate the cost of implementing foundational public health services Cezar Brian Mamaril, Glen Mays, Keith Branham, Lava Timsina S63 PANEL: Geographic variation in the implementation of public health services: Economic, organizational, and network determinants - Inter-organizational network effects on the implementation of public health services Glen Mays, Rachel Hogg S64 PANEL: Building capacity for implementation and dissemination of the communities that care prevention system at scale to promote evidence-based practices in behavioral health - Implementation fidelity, coalition functioning, and community prevention system transformation using communities that care Abigail Fagan, Valerie Shapiro, Eric Brown S65 PANEL: Building capacity for implementation and dissemination of the communities that care prevention system at scale to promote evidence-based practices in behavioral health - Expanding capacity for implementation of communities that care at scale using a web-based, video-assisted training system Kevin Haggerty, David Hawkins S66 PANEL: Building capacity for implementation and dissemination of the communities that care prevention system at scale to promote evidence-based practices in behavioral health - Effects of communities that care on reducing youth behavioral health problems Sabrina Oesterle, David Hawkins, Richard Catalano S68 When interventions end: the dynamics of intervention de-adoption and replacement Virginia McKay, M. Margaret Dolcini, Lee Hoffer S69 Results from next-d: can a disease specific health plan reduce incident diabetes development among a national sample of working-age adults with pre-diabetes? Tannaz Moin, Jinnan Li, O. Kenrik Duru, Susan Ettner, Norman Turk, Charles Chan, Abigail Keckhafer, Robert Luchs, Sam Ho, Carol Mangione S70 Implementing smoking cessation interventions in primary care settings (STOP): using the interactive systems framework Peter Selby, Laurie Zawertailo, Nadia Minian, Dolly Balliunas, Rosa Dragonetti, Sarwar Hussain, Julia Lecce S71 Testing the Getting To Outcomes implementation support intervention in prevention-oriented, community-based settings Matthew Chinman, Joie Acosta, Patricia Ebener, Patrick S Malone, Mary Slaughter S72 Examining the reach of a multi-component farmers’ market implementation approach among low-income consumers in an urban context Darcy Freedman, Susan Flocke, Eunlye Lee, Kristen Matlack, Erika Trapl, Punam Ohri-Vachaspati, Morgan Taggart, Elaine Borawski S73 Increasing implementation of evidence-based health promotion practices at large workplaces: The CEOs Challenge Amanda Parrish, Jeffrey Harris, Marlana Kohn, Kristen Hammerback, Becca McMillan, Peggy Hannon S74 A qualitative assessment of barriers to nutrition promotion and obesity prevention in childcare Taren Swindle, Geoffrey Curran, Leanne Whiteside-Mansell, Wendy Ward S75 Documenting institutionalization of a health communication intervention in African American churches Cheryl Holt, Sheri Lou Santos, Erin Tagai, Mary Ann Scheirer, Roxanne Carter, Janice Bowie, Muhiuddin Haider, Jimmie Slade, Min Qi Wang S76 Reduction in hospital utilization by underserved patients through use of a community-medical home Andrew Masica, Gerald Ogola, Candice Berryman, Kathleen Richter S77 Sustainability of evidence-based lay health advisor programs in African American communities: A mixed methods investigation of the National Witness Project Rachel Shelton, Lina Jandorf, Deborah Erwin S78 Predicting the long-term uninsured population and analyzing their gaps in physical access to healthcare in South Carolina Khoa Truong S79 Using an evidence-based parenting intervention in churches to prevent behavioral problems among Filipino youth: A randomized pilot study Joyce R. Javier, Dean Coffey, Sheree M. Schrager, Lawrence Palinkas, Jeanne Miranda S80 Sustainability of elementary school-based health centers in three health-disparate southern communities Veda Johnson, Valerie Hutcherson, Ruth Ellis S81 Childhood obesity prevention partnership in Louisville: creative opportunities to engage families in a multifaceted approach to obesity prevention Anna Kharmats, Sandra Marshall-King, Monica LaPradd, Fannie Fonseca-Becker S82 Improvements in cervical cancer prevention found after implementation of evidence-based Latina prevention care management program Deanna Kepka, Julia Bodson, Echo Warner, Brynn Fowler S83 The OneFlorida data trust: Achieving health equity through research & training capacity building Elizabeth Shenkman, William Hogan, Folakami Odedina, Jessica De Leon, Monica Hooper, Olveen Carrasquillo, Renee Reams, Myra Hurt, Steven Smith, Jose Szapocznik, David Nelson, Prabir Mandal S84 Disseminating and sustaining medical-legal partnerships: Shared value and social return on investment James Teufe

Machine learning for molecular and materials science

Here we summarize recent progress in machine learning for the chemical sciences. We outline machine-learning techniques that are suitable for addressing research questions in this domain, as well as future directions for the field. We envisage a future in which the design, synthesis, characterization and application of molecules and materials is accelerated by artificial intelligence.</p

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570