scholarly journals Operationalizing Healthspan as an Outcome for Clinical Trials in Geroscience

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 347-348
Author(s):  
Jamie Justice
Keyword(s):  
Clinical Trials ◽  
Functional Decline ◽  
Operational Definition ◽  
Biological Aging ◽  
Deficit Accumulation ◽  
Composite Measures ◽  
Biomarkers Of Aging ◽  
Clinically Meaningful Outcomes ◽  
Definition Of ◽  
Multiple Chronic Diseases

Abstract Efforts targeting biological aging pathways are advancing interventions which could extend healthy lifespan. Design of clinical trials to test such interventions necessitates an operational definition of healthspan, such as slowed accumulation or progression of multiple chronic diseases, functional decline, and disability. In this talk we explore these composite measures of healthspan proposed as outcomes for clinical trials in aging. This will be examined in example cases including multimorbidity and deficit accumulation frailty indices in an 8-Year intensive lifestyle intervention trial, and an update on multimordbity, functional, and biomarker endpoints in the trial Targeting Aging with MEtformin (TAME). Through these examples we will explore issues related to effect sizes and statistical challenges related to composite endpoints. Finally, we will discuss the role existing and emerging biomarkers of aging in clinical trials in geroscience and summarize evidence linking biomarkers to clinically meaningful outcomes.

scholarly journals Aging Biomarkers for Clinical Trials and Drug Discovery

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 4-5
Author(s):  
Margarita Meer ◽  
Raghav Sehgal ◽  
Morgan Levine
Keyword(s):  
Clinical Trials ◽  
Initial Step ◽  
Biological Aging ◽  
Working Definition ◽  
Biomarkers Of Aging ◽  
Epigenetic Aging ◽  
Aging Mechanisms ◽  
Definition Of

Abstract Developing targeted therapies first requires a working definition of the condition of interest. Unfortunately for aging, this very initial step poses a challenge since chronological age is often not indicative of biological age nor modifiable. This symposium will demonstrate the enormous progress being made towards developing more reliable and valid measures for quantifying biological aging. First, Dr. Albert T. Higgins Chen will show how inaccuracy caused by noise at individual CpG sites can lead to high technical variability in the most widely applied biomarkers of aging—epigenetic clocks. He will further discuss how this can be overcome through novel statistical techniques. Second, Dr. Benoit Lehallier, will discuss plasma proteomic clocks and share insights into their potential roles in Alzheimer's disease and utilization in clinical trials. Third, quantifying the multifactorial aging process can be facilitated by projects incorporating multimodal biomarker data. Pei-Lun Kuo from the Baltimore Longitudinal Study of Aging will present an analysis of longitudinal trajectories of more than 30 phenotypes, which when combined into a single summarized score yield important insights. Fourth, our ability to uncover aging mechanisms and perform drug screens, requires valid and reliable measures that can be applied in vitro. Christopher Minteer who developed in cellulo epigenetic markers will demonstarte how epigenetic aging changes that can be induced in culture shed light on aging in vivo. Finally, a summarizing discussion will be held by Dr. Nir Barzilai, an expert in the field, who is leading the Targeting Aging with Metformin (TAME) clinical trial.

scholarly journals BIOMARKER STRATEGIES FOR GEROSCIENCE-GUIDED CLINICAL TRIALS

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S745-S746
Author(s):  
Jamie N Justice ◽  
George A Kuchel ◽  
Nir Barzilai ◽  
Stephen Kritchevsky
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Biological Aging ◽  
Expert Committee ◽  
Biomarkers Of Aging ◽  
Age Related ◽  
Trial Outcomes ◽  
Biology Of Aging ◽  
Potential Use ◽  
Selection Of

Abstract Significant progress in the biology of aging and animal models supports the geroscience hypothesis: by targeting biological aging the onset of age-related diseases can be delayed. Geroscience investigators will test this hypothesis in a multicenter clinical trial, to determine if interventions on biological aging processes can prevent accumulation of multiple age-related diseases and aging phenotypes in older adults. Prodigious activity is underway to develop markers of biological aging, but currently there is no aging biomarker consensus to support geroscience-guided clinical trial outcomes. We convened an expert committee to establish a framework for selection of blood-based biomarkers, emphasizing: feasibility/reliability; aging relevance; ability to predict clinical trial outcomes; and responsiveness to intervention. We applied this framework and identified a short-list of blood-based biomarkers with potential use in multicenter trials on aging. We review progress on efforts to test these candidate biomarkers of aging and development of biomarkers strategy for geroscience-guided clinical trials.

Understanding functional illiteracy from a policy, adult education, and cognition point of view: Towards a joint referent framework

2019 ◽  
Vol 30 (2) ◽  
pp. 109-122
Author(s):  
Aleksandar Bulajić ◽  
Miomir Despotović ◽  
Thomas Lachmann
Keyword(s):  
Adult Education ◽  
Operational Definition ◽  
Literacy Skills ◽  
Point Of View ◽  
Industrialized Countries ◽  
Functional Illiteracy ◽  
Scale Levels ◽  
Components Of Reading ◽  
The One ◽  
Definition Of

Abstract. The article discusses the emergence of a functional literacy construct and the rediscovery of illiteracy in industrialized countries during the second half of the 20th century. It offers a short explanation of how the construct evolved over time. In addition, it explores how functional (il)literacy is conceived differently by research discourses of cognitive and neural studies, on the one hand, and by prescriptive and normative international policy documents and adult education, on the other hand. Furthermore, it analyses how literacy skills surveys such as the Level One Study (leo.) or the PIAAC may help to bridge the gap between cognitive and more practical and educational approaches to literacy, the goal being to place the functional illiteracy (FI) construct within its existing scale levels. It also sheds more light on the way in which FI can be perceived in terms of different cognitive processes and underlying components of reading. By building on the previous work of other authors and previous definitions, the article brings together different views of FI and offers a perspective for a needed operational definition of the concept, which would be an appropriate reference point for future educational, political, and scientific utilization.

“The Unconscious” in Current Psychology

2010 ◽  
Vol 15 (3) ◽  
pp. 193-201 ◽  
Author(s):  
Elisabeth Norman
Keyword(s):  
Cognitive Psychology ◽  
Verbal Report ◽  
Psychological Research ◽  
Operational Definition ◽  
The Unconscious ◽  
Apparent Lack ◽  
Unconscious Processing ◽  
Unconscious Processes ◽  
Intermediate States ◽  
Definition Of

A series of vignette examples taken from psychological research on motivation, emotion, decision making, and attitudes illustrates how the influence of unconscious processes is often measured in a range of different behaviors. However, the selected studies share an apparent lack of explicit operational definition of what is meant by consciousness, and there seems to be substantial disagreement about the properties of conscious versus unconscious processing: Consciousness is sometimes equated with attention, sometimes with verbal report ability, and sometimes operationalized in terms of behavioral dissociations between different performance measures. Moreover, the examples all seem to share a dichotomous view of conscious and unconscious processes as being qualitatively different. It is suggested that cognitive research on consciousness can help resolve the apparent disagreement about how to define and measure unconscious processing, as is illustrated by a selection of operational definitions and empirical findings from modern cognitive psychology. These empirical findings also point to the existence of intermediate states of conscious awareness, not easily classifiable as either purely conscious or purely unconscious. Recent hypotheses from cognitive psychology, supplemented with models from social, developmental, and clinical psychology, are then presented all of which are compatible with the view of consciousness as a graded rather than an all-or-none phenomenon. Such a view of consciousness would open up for explorations of intermediate states of awareness in addition to more purely conscious or purely unconscious states and thereby increase our understanding of the seemingly “unconscious” aspects of mental life.

An Analysis of the Demand for Reporting on Internal Control

2000 ◽  
Vol 14 (3) ◽  
pp. 325-341 ◽  
Author(s):  
Heather M. Hermanson
Keyword(s):  
Decision Making ◽  
Financial Reporting ◽  
Internal Control ◽  
Operational Definition ◽  
Financial Statement ◽  
Individual Investors ◽  
Internal Auditors ◽  
Additional Information ◽  
User Groups ◽  
Definition Of

The purpose of this study is to analyze the demand for reporting on internal control. Nine financial statement user groups were identified and surveyed to determine whether they agree that: (1) management reports on internal control (MRIC) are useful, (2) MRICs influence decisions, and (3) financial reporting is improved by adding MRICs. In addition, the paper examined whether responses varied based on: (1) the definition of internal control used (manipulated as broad, operational definition vs. narrow, financial-reporting definition) and (2) user group. The results indicate that financial statement users agree that internal controls are important. Respondents agreed that voluntary MRICs improved controls and provided additional information for decision making. Respondents also agreed that mandatory MRICs improved controls, but did not agree about their value for decision making. Using a broad definition of controls, respondents strongly agreed that MRICs improved controls and provided a better indicator of a company's long-term viability. Executive respondents were less likely to agree about the value of MRICs than individual investors and internal auditors.

Shape Dynamics and the Linking Theory

2018 ◽  
Author(s):  
Flavio Mercati
Keyword(s):  
Phase Space ◽  
Degrees Of Freedom ◽  
Line Element ◽  
Hamiltonian Formulation ◽  
Operational Definition ◽  
Extended Phase Space ◽  
Extended Phase ◽  
Problem Of Time ◽  
Definition Of ◽  
Matter Fields

This chapter explains in detail the current Hamiltonian formulation of SD, and the concept of Linking Theory of which (GR) and SD are two complementary gauge-fixings. The physical degrees of freedom of SD are identified, the simple way in which it solves the problem of time and the problem of observables in quantum gravity are explained, and the solution to the problem of constructing a spacetime slab from a solution of SD (and the related definition of physical rods and clocks) is described. Furthermore, the canonical way of coupling matter to SD is introduced, together with the operational definition of four-dimensional line element as an effective background for matter fields. The chapter concludes with two ‘structural’ results obtained in the attempt of finding a construction principle for SD: the concept of ‘symmetry doubling’, related to the BRST formulation of the theory, and the idea of ‘conformogeometrodynamics regained’, that is, to derive the theory as the unique one in the extended phase space of GR that realizes the symmetry doubling idea.

scholarly journals Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Daniel L. McCartney ◽  
Josine L. Min ◽  
Rebecca C. Richmond ◽  
Ake T. Lu ◽  
Maria K. Sobczyk ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Genome Wide Association Study ◽  
Association Studies ◽  
Genome Wide Association ◽  
Biological Aging ◽  
Genome Wide Association Studies ◽  
Genetic Loci ◽  
Biomarkers Of Aging ◽  
Genome Wide ◽  
Shared Genetic

Abstract Background Biological aging estimators derived from DNA methylation data are heritable and correlate with morbidity and mortality. Consequently, identification of genetic and environmental contributors to the variation in these measures in populations has become a major goal in the field. Results Leveraging DNA methylation and SNP data from more than 40,000 individuals, we identify 137 genome-wide significant loci, of which 113 are novel, from genome-wide association study (GWAS) meta-analyses of four epigenetic clocks and epigenetic surrogate markers for granulocyte proportions and plasminogen activator inhibitor 1 levels, respectively. We find evidence for shared genetic loci associated with the Horvath clock and expression of transcripts encoding genes linked to lipid metabolism and immune function. Notably, these loci are independent of those reported to regulate DNA methylation levels at constituent clock CpGs. A polygenic score for GrimAge acceleration showed strong associations with adiposity-related traits, educational attainment, parental longevity, and C-reactive protein levels. Conclusion This study illuminates the genetic architecture underlying epigenetic aging and its shared genetic contributions with lifestyle factors and longevity.

scholarly journals The scale of effect depends on operational definition of forest cover—evidence from terrestrial mammals of the Brazilian savanna

2021 ◽  
Author(s):  
Christophe Amiot ◽  
Cyntia Cavalcante Santos ◽  
Damien Arvor ◽  
Beatriz Bellón ◽  
Hervé Fritz ◽  
...  
Keyword(s):  
Forest Cover ◽  
Operational Definition ◽  
Brazilian Savanna ◽  
Terrestrial Mammals ◽  
Scale Of Effect ◽  
Definition Of
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