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Brain research has progressed with anesthetized animal experiments for a long time. Recent progress in research techniques allows us to measure neuronal activity in awake animals combined with behavioral tasks. The trends became more prominent in the last decade. This new research style triggers the paradigm shift in the research of brain science, and new insights into brain function have been revealed. It is reasonable to consider that awake animal experiments are more ideal for understanding naturalistic brain function than anesthetized ones. However, the anesthetized animal experiment still has advantages in some experiments. To take advantage of the anesthetized animal experiments, it is important to understand the mechanism of anesthesia and carefully handle the obtained data. In this minireview, we will shortly summarize the molecular mechanism of anesthesia in animal experiments, a recent understanding of the neuronal activities in a sensory system in the anesthetized animal brain, and consider the advantages and disadvantages of the anesthetized and awake animal experiments. This discussion will help us to use both research conditions in the proper manner., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Nagayama, Hasegawa-Ishii and Kikuta.)

Background: Working with research animals can be both rewarding and challenging. The rewarding part of the work is associated with understanding the necessity for animal research to improve the health of humans and animals and the knowledge that one can provide care and compassion for the animals. Challenges with animal research include witnessing stress/pain in animals necessitated by scientific requirements, end of study euthanasia, and societal stigmatization about animal research. These challenges could be compounded with more general workplace stresses, in turn, impacting job retention and satisfaction. However, these factors have yet to be formally evaluated. Therefore, the purpose of this survey was to comprehensively evaluate professional quality of life's correlation with key workplace metrics., Methods: Six institutions were recruited to participate in a longitudinal intervention trial on compassion fatigue resiliency. This manuscript reports key baseline metrics from this survey. A cross-sectional mixed methods survey was developed to evaluate professional quality of life, job satisfaction, retention, and factors influencing compassion fatigue resiliency. Quantitative data were analyzed via general linear models and qualitative data were analyzed by theme., Results: Baseline data was collected from 198 participants. Personnel who reported higher compassion satisfaction also reported higher retention and job satisfaction. Conversely, personnel who reported higher burnout also reported lower job satisfaction. In response to open-ended questions, participants said their compassion fatigue was impacted by institutional culture (70% of participants), animal research (58%), general mental health (41%), and specific compassion fatigue support (24%)., Conclusions: In conclusion, these results show that professional quality of life is related to important operational metrics of job satisfaction and retention. Furthermore, compassion fatigue is impacted by factors beyond working with research animals, including institutional culture and general mental health support. Overall, this project provides rationale and insight for institutional support of compassion fatigue resiliency., Competing Interests: All authors are employed by the institution noted in their affiliation except for Lauren Young who was a student during data collection and initial writing and then transitioned to a full-time role with the 3Rs Collaborative during manuscript revision. All authors are also members of the 3Rs Collaborative’s Compassion Fatigue Initiative. Elizabeth Nunamaker and Sally Thompson-Iritani also sat on the board of directors and leadership team of the 3Rs Collaborative during publication. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Young et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

When performing animal experimentation in Pediatric Urology studies, it is important to be aware of physiological differences between species and to understand when relevant disease models are available. Diseased animal models may be more relevant in many cases, rather than performing studies in healthy and normally developed animals. For example, they may be more appropriate for the study of congenital malformations, to investigate the secondary effects of prenatal urinary obstruction, to study the effect of prenatal exposure to endogenous or exogenous factors which may lead to disease, or in testing bioengineered structures. In this short educational article, we aim to describe some disease models that have been used to simulate human pathologies and how, if properly designed, these studies can lead to important new knowledge for human translation. In addition, we also highlight the importance of formulating a research question(s) before deciding on the animal experimental model and species to choose., (Copyright © 2023. Published by Elsevier Ltd.)

Why and when is animal experimentation relevant? The answer to this question depends on the research question. In this short educational article we aim to raise awareness of the importance of formulating a very specific research question before choosing an animal species. An awareness of anatomical and physiological differences vis-a-vis similarities between species, will increase the potential for obtaining data that is relevant for translation to human conditions., Competing Interests: Conflict of interest None., (Copyright © 2023. Published by Elsevier Ltd.)

Light enables vision and exerts widespread effects on physiology and behavior, including regulating circadian rhythms, sleep, hormone synthesis, affective state, and cognitive processes. Appropriate lighting in animal facilities may support welfare and ensure that animals enter experiments in an appropriate physiological and behavioral state. Furthermore, proper consideration of light during experimentation is important both when it is explicitly employed as an independent variable and as a general feature of the environment. This Consensus View discusses metrics to use for the quantification of light appropriate for nonhuman mammals and their application to improve animal welfare and the quality of animal research. It provides methods for measuring these metrics, practical guidance for their implementation in husbandry and experimentation, and quantitative guidance on appropriate light exposure for laboratory mammals. The guidance provided has the potential to improve data quality and contribute to reduction and refinement, helping to ensure more ethical animal use., Competing Interests: RJL has received research grant funding from Philips Lighting/Signify and honoraria from Samsung Electronics. GCB has received research grant funding from the Nova Institute, Toshiba Materials Science, Seoul Semiconductor, BIOS, Robern, and PhotoPharmics Inc. He has a current patent (USPTO 7678140 B2) that is licensed by Litebook Company Ltd. He is a paid member of the PhotoPharmics Scientific Advisory Board; has been a paid consultant by Lutron, Inc. and McCullough Hill LLC; and has received honoraria from the Institute for Functional Medicine. BNG has received funding from Tecniplast to travel and present at a symposium. RAH has received research grant funding from Philips Lighting/Signify and is a scientific advisor for the Good Light Group and Chrono@Work. JST is a co-founder and SAB member of Synchronicity Pharma. SNP has received consulting fees from NASA Ames and Sleep Standards., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

The laboratory mouse is a key player in preclinical oncology research. However, emphasis of techniques reporting at the expense of critical animal-related detail compromises research integrity, animal welfare, and, ultimately, the translation potential of mouse-based oncology models. To evaluate current reporting practices, we performed a cross-sectional survey of 400 preclinical oncology studies using mouse solid-tumour models. Articles published in 2020 were selected from 20 journals that specifically endorsed the ARRIVE (Animal Research: Reporting of In Vivo Experiments) preclinical reporting guidelines. We assessed reporting compliance for 22 items in five domains: ethical oversight assurance, animal signalment, husbandry, welfare, and euthanasia. Data were analysed using hierarchical generalised random-intercept models, clustered on journal. Overall, reporting of animal-related items was poor. Median compliance over all categories was 23%. There was little or no association between extent of reporting compliance and journal or journal impact factor. Age, sex, and source were reported most frequently, but verifiable strain information was reported for <10% of studies. Animal husbandry, housing environment, and welfare items were reported by <5% of studies. Fewer than one in four studies reported analgesia use, humane endpoints, or an identifiable method of euthanasia. Of concern was the poor documentation of ethical oversight information. Fewer than one in four provided verifiable approval information, and almost one in ten reported no information, or information that was demonstrably false. Mice are the "invisible actors" in preclinical oncology research. In spite of widespread endorsement of reporting guidelines, adherence to reporting guidelines on the part of authors is poor and journals fail to enforce guideline reporting standards. In particular, the inadequate reporting of key animal-related items severely restricts the utility and translation potential of mouse models, and results in research waste. Both investigators and journals have the ethical responsibility to ensure animals are not wasted in uninformative research., Competing Interests: The authors have declared that no competing interests exist.

Acceptance of animal research by the public depends on several characteristics of the specific experimental study. In particular, acceptance decreases as potential animal pain or distress increases. Our objective in this study was to quantify the magnitude of pain/distress that university undergraduate students and faculty would find to be justifiable in animal research, and to see how that justifiability varied according to the purpose of the research, or the species to which the animal belonged. We also evaluate how demographic characteristics of respondents may be associated with their opinions about justifiability. To accomplish this goal, we developed and administered a survey to students and faculty at the University of Wisconsin-Madison. Our survey employed Likert-style questions that asked them to designate the level of animal pain or distress that they felt was justifiable for each of the following six purposes-animal disease, human disease, basic research, human medicine, chemical testing, or cosmetic testing. These questions were asked about five different species of animals including monkeys, dogs/cats, pig/sheep, rats/mice, or small fish. We used the data to establish a purpose-specific pain/distress scale, a species-specific pain/distress scale, and a composite pain/distress scale that, for each respondent, averaged the extent of justifiable pain/distress across all purposes and species. For purpose, students were more likely to choose higher levels of pain for animal disease research, followed by human disease, basic research, human medicine, chemical testing, and cosmetic testing. Faculty were more likely to choose the same level of pain for the first four purposes, followed by lower levels of pain for chemical and cosmetic testing. For species, students were more likely to choose higher levels of pain for small fish and rats/mice (tied), pigs/sheep and monkeys (tied), than for dogs/cats. For faculty, order from least to most justifiable pain/distress was small fish, rats/mice, pigs/sheep, then dogs/cats and monkeys (the latter two tied). Interestingly, exploratory factor analysis of the pain/distress scales indicated that when it comes to justifying higher levels of pain and distress, respondents identified two distinct categories of purposes, chemical and cosmetic testing, for which respondents were less likely to justify higher levels of pain or distress as compared to other purposes; and two distinct categories of species, small fish and rats/mice, for which respondents were more likely to justify higher levels of pain/distress than other species. We found that the spread of acceptance of animal research was much smaller when survey questions included pain/distress compared to when only purpose or species were part of the question. Demographically, women, vegetarians/vegans, and respondents with no experience in animal research justified less animal pain/distress than their counterparts. Not surprisingly, a lower level of support for animal research in general was correlated with lower justifiability of pain/distress. Based on these findings, we discuss the role of animal pain/distress in regulatory considerations underlying decisions about whether to approve specific animal uses, and suggest ways to strengthen the ethical review and public acceptance of animal research., Competing Interests: The authors have declared that no competing interests exist.

Improving the reproducibility of biomedical research is a major challenge. Transparent and accurate reporting is vital to this process; it allows readers to assess the reliability of the findings and repeat or build upon the work of other researchers. The ARRIVE guidelines (Animal Research: Reporting In Vivo Experiments) were developed in 2010 to help authors and journals identify the minimum information necessary to report in publications describing in vivo experiments. Despite widespread endorsement by the scientific community, the impact of ARRIVE on the transparency of reporting in animal research publications has been limited. We have revised the ARRIVE guidelines to update them and facilitate their use in practice. The revised guidelines are published alongside this paper. This explanation and elaboration document was developed as part of the revision. It provides further information about each of the 21 items in ARRIVE 2.0, including the rationale and supporting evidence for their inclusion in the guidelines, elaboration of details to report, and examples of good reporting from the published literature. This document also covers advice and best practice in the design and conduct of animal studies to support researchers in improving standards from the start of the experimental design process through to publication., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: AA is the editor in chief of the British Journal of Pharmacology. WJB, ICC, and ME are authors of the original ARRIVE guidelines. WJB serves on the Independent Statistical Standing Committee of the funder CHDI foundation. AC is a Senior Editor for PLOS ONE. AC, CJM, MM, and ESS were involved in the IICARus trial. ME, MM, and ESS have received funding from NC3Rs. ME sits on the MRC ERPIC panel. STH is chair of the NC3Rs board; trusteeship of the BLF, Kennedy Trust, DSRU, and CRUK; member of Governing Board, Nuffield Council of Bioethics, member Science Panel for Health (EU H2020); founder and NEB Director Synairgen; consultant Novartis, Teva, and AZ; and chair MRC/GSK EMINENT Collaboration. VH, KL, EJP, and NPdS are NC3Rs staff; role includes promoting the ARRIVE guidelines. SEL and UD are on the advisory board of the UK Reproducibility Network. CJM has shareholdings in Hindawi, is on the publishing board of the Royal Society, and on the EU Open Science policy platform. UD, MM, NPdS, CJM, ESS, TS, and HW are members of EQIPD. MM is a member of the Animals in Science Committee and on the steering group of the UK Reproducibility Network. NPdS and TS are associate editors of BMJ Open Science. OHP is vice president of Academia Europaea, editor in chief of Function, senior executive editor of the Journal of Physiology, and member of the Board of the European Commission’s SAPEA (Science Advice for Policy by European Academies). FR is an NC3Rs board member and has shareholdings in GSK. FR and NAK have shareholdings in AstraZeneca. PR is a member of the University of Florida Institutional Animal Care and Use Committee and editorial board member of Shock. ESS is editor in chief of BMJ Open Science. SDS’s role is to provide expertise and does not represent the opinion of the NIH. TS has shareholdings in Johnson & Johnson. SA, MTA, MB, PG, DWH, and KR declared no conflict of interest.

As members of a university community that sponsors animal research, we developed a survey to improve our knowledge about factors underlying the perceived justifiability of animal research among faculty and undergraduate students. To accomplish this objective, we gathered quantitative data about their general views on animal use by humans, their specific views about the use of different species to address different categories of scientific questions, and their confidence in the translatability of animal research to humans. Students and faculty did not differ in their reported levels of concern for the human use of animals, but women reported significantly higher levels of concern than men. Among students, experience with animal research was positively correlated with less concern with animal use, and having practiced vegetarianism or veganism was associated with more concern. Gender, experience with animal research, and dietary preferences were similarly correlated with the extent of justifiability of animal use across all research purposes and species. Faculty responses resembled those for students, with the exception that justifiability varied significantly based on academic discipline: biological sciences faculty were least concerned about human use of animals and most supportive of animal research regardless of purpose or species. For both students and faculty, justifiability varied depending on research purpose or animal species. Research purposes, ranked in order of justifiability from high to low, was animal disease, human disease, basic research, human medicine, animal production, chemical testing, and cosmetics. Justifiability by purpose was slightly lower for students than for faculty. Species justifiability for students, from high to low, was small fish, rats or mice, pigs or sheep, monkeys, and dogs or cats. Faculty order was the same except that monkeys and dogs or cats were reversed in order. Finally, confidence in the translatability of animal research to our understanding of human biology and medicine was not different between students and faculty or between genders, but among faculty it was highest in biological sciences followed by physical sciences, social sciences, and then arts and humanities. Those with experience in animal research displayed the most confidence, and vegetarians/vegans displayed the least. These findings demonstrate that, although the range of views in any subcategory is large, views about animal research justifiability can vary significantly among respondent subpopulations in predictable ways. In particular, research purpose and choice of animal species are important variables for many people. This supports the claim that ensuring purpose and species are robustly integrated into research proposal reviews and approvals should be considered to be a best practice. We suggest that strengthening this integration beyond what is described in current regulations would better meet the justifiability criteria expressed by members of our campus community., Competing Interests: The authors have declared that no competing interests exist.

A common feature of preclinical animal experiments is repeated measurement of the outcome, e.g., body weight measured in mice pups weekly for 20 weeks. Separate time point analysis or repeated measures analysis approaches can be used to analyze such data. Each approach requires assumptions about the underlying data and violations of these assumptions have implications for estimation of precision, and type I and type II error rates. Given the ethical responsibilities to maximize valid results obtained from animals used in research, our objective was to evaluate approaches to reporting repeated measures design used by investigators and to assess how assumptions about variation in the outcome over time impact type I and II error rates and precision of estimates. We assessed the reporting of repeated measures designs of 58 studies in preclinical animal experiments. We used simulation modelling to evaluate three approaches to statistical analysis of repeated measurement data. In particular, we assessed the impact of (a) repeated measure analysis assuming that the outcome had non-constant variation at all time points (heterogeneous variance) (b) repeated measure analysis assuming constant variation in the outcome (homogeneous variance), (c) separate ANOVA at individual time point in repeated measures designs. The evaluation of the three model fitting was based on comparing the p-values distributions, the type I and type II error rates and by implication, the shrinkage or inflation of standard error estimates from 1000 simulated dataset. Of 58 studies with repeated measures design, three provided a rationale for repeated measurement and 23 studies reported using a repeated-measures analysis approach. Of the 35 studies that did not use repeated-measures analysis, fourteen studies used only two time points to calculate weight change which potentially means collected data was not fully utilized. Other studies reported only select time points (n = 12) raising the issue of selective reporting. Simulation studies showed that an incorrect assumption about the variance structure resulted in modified error rates and precision estimates. The reporting of the validity of assumptions for repeated measurement data is very poor. The homogeneous variation assumption, which is often invalid for body weight measurements, should be confirmed prior to conducting the repeated-measures analysis using homogeneous covariance structure and adjusting the analysis using corrections or model specifications if this is not met., Competing Interests: The authors have declared that no competing interests exist.

Competing Interests: LAR is a current paid employee at Public Library of Science.

The scientific community is increasingly concerned with the proportion of published "discoveries" that are not replicated in subsequent studies. The field of rodent behavioral phenotyping was one of the first to raise this concern, and to relate it to other methodological issues: the complex interaction between genotype and environment; the definitions of behavioral constructs; and the use of laboratory mice and rats as model species for investigating human health and disease mechanisms. In January 2015, researchers from various disciplines gathered at Tel Aviv University to discuss these issues. The general consensus was that the issue is prevalent and of concern, and should be addressed at the statistical, methodological and policy levels, but is not so severe as to call into question the validity and the usefulness of model organisms as a whole. Well-organized community efforts, coupled with improved data and metadata sharing, have a key role in identifying specific problems and promoting effective solutions. Replicability is closely related to validity, may affect generalizability and translation of findings, and has important ethical implications., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The occupational health and safety program is an integral component of a comprehensive animal care and use program. It is important to mitigate the risk of exposures of animal care and research personnel to allergens and physical, chemical, radiologic, and biologic hazards during the conduct of various tasks. This need is especially true in infectious disease and biocontainment research. One aspect of the program is the provision of personal protective equipment (PPE). Commercially available PPE should be carefully evaluated based on their material composition and performance according to manufacturer data. To help institutions and end users by providing them guidance on choosing appropriate PPE, we here discuss the regulatory framework, device standards, and materials engineering for various PPE, including gloves, shoe covers, head caps, gowns, aprons, masks, hearing and eye protection devices, and respirators. Ultimately, the choice of appropriate PPE is based on the risk assessment, which should include consideration for personnel comfort, correct device fitting, and the containment level for the hazard used.

Translation of disease-modifying therapies in neurodegenerative disease has been disappointing. Parkinson's disease (PD) was used to compare patterns of preclinical study design for symptomatic and potentially disease-modifying interventions. We examined the relationship of model, intervention type and timing, outcomes and outcome measures in 543 animal and human studies (1973-2015) across a contemporary cohort of animal and human interventional studies (n = 445), animal studies for approved interventions (n = 28), animal and human studies for those that failed to translate (n = 70). Detailed study design data were collected for 216 studies in non-human primate (NHP) and rodent toxin-induced models. Species-specific patterns of study design prevailed regardless of whether interventions were symptomatic or potentially disease-modifying. In humans and NHPs, interventions were typically given to both sexes well after the PD phenotype was established, and clinical outcome measures were collected at single (symptomatic) or multiple (disease-modifying) time-points. In rodents, interventions often preceded induction of the model, acute toxic protocols were common, usually given to young males, clinical outcome measures were used less commonly, and outcomes were less commonly assessed at multiple time points. These patterns were more prevalent in mice than rats. In contrast, study design factors such as randomization and blinding did not differ appreciably across symptomatic and disease-modifying intervention categories. The translational gap for potentially disease-modifying interventions in PD in part results from study designs, particularly in mice, that fail to model the progressive nature and relatively late intervention characteristic of PD, or that anchor mechanistic and neuropathologic data to longitudinal clinical outcomes. Even if measures to improve reproducibility are broadly adopted, perpetuation of these norms will continue to impede effective translation., Competing Interests: The authors have declared that no competing interests exist.

The United States federal animal welfare regulations and the Public Health Service Policy on Humane Care and Use of Laboratory Animals require that institutional animal care and use committees (IACUCs) conduct continuing reviews of all animal research activities. However, little is known about the lapse rate of IACUC continuing reviews, and how frequently investigators continue research activities during the lapse. It is also not clear what factors may contribute to an institution's lapse in IACUC continuing reviews. As part of the quality assurance program, the Department of Veterans Affairs (VA) has collected performance metric data for animal care and use programs since 2011. We analyzed IACUC continuing review performance data at 74-75 VA research facilities from 2011 through 2015. The IACUC continuing review lapse rates improved from 5.6% in 2011 to 2.7% in 2015. The rate of investigators continuing research activities during the lapse also decreased from 47.2% in 2012 to 7.4% in 2015. The type of IACUCs used and the size of animal research programs appeared to have no effect in facility's rates of lapse in IACUC continuing reviews. While approximately 80% of facilities reported no lapse in IACUC continuing reviews, approximately 14% of facilities had lapse rates of >10% each year. Some facilities appeared to be repeat offenders. Four facilities had IACUC lapse rates of >10% in at least 3 out of 5 years, suggesting a system problem in these facilities requiring remedial actions to improve their IACUC continuing review processes., Competing Interests: The authors have declared that no completing interest exist.

The Animal Research: Reporting of In Vivo Experiments (ARRIVE) guidelines were developed to address the lack of reproducibility in biomedical animal studies and improve the communication of research findings. While intended to guide the preparation of peer-reviewed manuscripts, the principles of transparent reporting are also fundamental for in vivo databases. Here, we describe the benefits and challenges of applying the guidelines for the International Mouse Phenotyping Consortium (IMPC), whose goal is to produce and phenotype 20,000 knockout mouse strains in a reproducible manner across ten research centres. In addition to ensuring the transparency and reproducibility of the IMPC, the solutions to the challenges of applying the ARRIVE guidelines in the context of IMPC will provide a resource to help guide similar initiatives in the future.

Gene expression profiling is a tool to gain mechanistic understanding of adverse effects in response to compound exposure. However, little is known about how the common handling procedures of experimental animals during a preclinical study alter baseline gene expression. We report gene expression changes in the livers of female Sprague-Dawley rats following common handling procedures. Baseline gene expression changes identified in this study provide insight on how these changes may affect interpretation of gene expression profiles following compound exposure. Rats were divided into three groups. One group was not subjected to handling procedures and served as controls for both handled groups. Animals in the other two groups were weighed, subjected to restraint in Broome restrainers, and administered water via oral gavage daily for 1 or 4 days with tail vein blood collections at 1, 2, 4, and 8 hours postdose on days 1 and 4. Significantly altered genes were identified in livers of animals following 1 or 4 days of handling when compared to the unhandled animals. Gene changes in animals handled for 4 days were similar to those handled for 1 day, suggesting a lack of habituation. The altered genes were primarily immune function related genes. These findings, along with a correlating increase in corticosterone levels suggest that common handling procedures may cause a minor immune system perturbance.

The article reviews the early history of FRAME from the perspective of its first "Scientific Administrator". The roles of Mrs Hegarty the founder, and other early contributors to FRAME's development are described. In addition, the article discusses FRAME's strategic approach to the subject and how Mrs Hegarty's background influenced the development of that approach., (2009 FRAME.)

Background: Few studies have examined the impact of novel indices of comorbidity, frailty, and disability on outcomes after transcatheter aortic valve replacement (TAVR).Objectives: This study analyzed patients from the Medtronic CoreValve U.S. Pivotal Trial program to develop a simple scoring system that incorporates standard and novel predictor variables.Methods: A multidisciplinary heart team used objective criteria, such as The Society of Thoracic Surgeons Predicted Risk of Mortality (STS PROM), and subjective criteria to assess patients' eligibility for TAVR. The analysis included 3,687 patients randomly divided (2:1) into a derivation cohort (n = 2,482) and a validation cohort (n = 1,205). The study evaluated predictors of all-cause death, which were used to calculate a risk score for each patient.Results: The overall mortality rate was 5.8% at 30 days and 22.8% at 1 year. Home oxygen use, assisted living, albumin levels <3.3 g/dl, and age >85 years predicted death at 30 days. Home oxygen use, albumin levels <3.3 g/dl, falls in the past 6 months, STS PROM score >7%, and severe (≥5) Charlson comorbidity score predicted death at 1 year. A simple scoring system created on the basis of these multivariable predictors effectively stratified risk at 30 days and 1 year into low-risk, moderate-risk, and high-risk subsets. This score showed a 3-fold difference in mortality rates for the low-risk and high-risk subsets at 30 days (3.6% and 10.9%, respectively) and 1 year (12.3% and 36.6%, respectively). The 1-year mortality model was more stable than the 30-day model (C-statistics: 0.79 vs. 0.75).Conclusions: A simple score dominated by novel predictors of outcome effectively stratified early and late mortality rates in extreme-risk and high-risk patients and may assist in selecting appropriate candidates for TAVR. (Safety and Efficacy Study of the Medtronic CoreValve System in the Treatment of Symptomatic Severe Aortic Stenosis in High Risk and Very High Risk Subjects Who Need Aortic Valve Replacement; NCT01240902). [ABSTRACT FROM AUTHOR]