scholarly journals A Computational Solution to Bolster Epigenetic Clock Reliability for Clinical Trials and Longitudinal Tracking

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 5-5
Author(s):  
Albert Higgins-Chen ◽  
Kyra Thrush ◽  
Tina Hu-Seliger ◽  
Yunzhang Wang ◽  
Sara Hagg ◽  
...  
Keyword(s):  
Clinical Trials ◽  
High Reliability ◽  
Principal Component ◽  
Epigenetic Clock ◽  
Age Related ◽  
Longitudinal Tracking ◽  
Short And Long Term ◽  
Epigenetic Biomarker ◽  
Computational Solution

Abstract Epigenetic clocks are widely used aging biomarkers, but they are calculated from methylation data for individual CpGs that can be surprisingly unreliable. We report that technical noise causes six major epigenetic clocks to deviate by 3 to 9 years between replicates. We present a novel computational solution: we perform principal component analysis followed by biological age prediction using principal components, extracting shared age-related changes across CpGs while ignoring noise from individual CpGs. Our novel principal-component versions of six clocks show agreement between most technical replicates within 1 year, and increased stability in short- and long-term longitudinal studies. This requires only one additional step compared to traditional clocks, does not require prior knowledge of CpG reliabilities, and can improve the reliability of any existing or future epigenetic biomarker. The extremely high reliability of principal component epigenetic clocks makes them particularly useful for personalized medicine and clinical trials evaluating novel aging interventions.

scholarly journals A computational solution for bolstering reliability of epigenetic clocks: Implications for clinical trials and longitudinal tracking

2021 ◽  
Author(s):  
Albert T. Higgins-Chen ◽  
Kyra L. Thrush ◽  
Yunzhang Wang ◽  
Pei-Lun Kuo ◽  
Meng Wang ◽  
...  
Keyword(s):  
Clinical Trials ◽  
High Reliability ◽  
Random Noise ◽  
Principal Component ◽  
Methylation Data ◽  
Technical Noise ◽  
Longitudinal Tracking ◽  
Level Data ◽  
Epigenetic Biomarker ◽  
Age Prediction

Epigenetic clocks are widely used aging biomarkers calculated from DNA methylation data. Unfortunately, measurements for individual CpGs can be surprisingly unreliable due to technical noise, and this may limit the utility of epigenetic clocks. We report that noise produces deviations up to 3 to 9 years between technical replicates for six major epigenetic clocks. The elimination of low-reliability CpGs does not ameliorate this issue. Here, we present a novel computational multi-step solution to address this noise, involving performing principal component analysis on the CpG-level data followed by biological age prediction using principal components as input. This method extracts shared systematic variation in DNAm while minimizing random noise from individual CpGs. Our novel principal-component versions of six clocks show agreement between most technical replicates within 0 to 1.5 years, equivalent or improved prediction of outcomes, and more stable trajectories in longitudinal studies and cell culture. This method entails only one additional step compared to traditional clocks, does not require prior knowledge of CpG reliabilities, and can improve the reliability of any existing or future epigenetic biomarker. The high reliability of principal component-based epigenetic clocks will make them particularly useful for applications in personalized medicine and clinical trials evaluating novel aging interventions.

scholarly journals Recent advances in understanding and treating vasculitis

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 1436 ◽  
Author(s):  
Matthew J. Koster ◽  
Kenneth J. Warrington
Keyword(s):  
Monoclonal Antibody ◽  
Clinical Trials ◽  
Long Term Effects ◽  
Dose Frequency ◽  
Treatment Regimens ◽  
Recent Advances ◽  
Short And Long Term ◽  
Anti Cd20 ◽  
Long Term Adverse Effects

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAVs) are near universally fatal conditions if untreated. Although effective therapeutic options are available for these diseases, treatment regimens are associated with both short- and long-term adverse effects. The recent identification of effective B-cell-targeted therapy with an anti-CD20 monoclonal antibody has transformed the treatment landscape of AAV. Questions, nevertheless, remain regarding the appropriate timing, dose, frequency, duration, and long-term effects of treatment. The aim of this article is to provide an overview of the current information, recent advances, ongoing clinical trials, and future treatment possibilities in AAV.

Role and Relevance of Neurocognitive Assessment in Clinical Trials of Patients With CNS Tumors

2006 ◽  
Vol 24 (8) ◽  
pp. 1305-1309 ◽  
Author(s):  
Christina A. Meyers ◽  
Paul D. Brown
Keyword(s):  
Clinical Trials ◽  
Cns Tumors ◽  
Tumor Control ◽  
End Points ◽  
Treatment Regimens ◽  
Neurocognitive Assessment ◽  
Short And Long Term ◽  
Effect Of Treatment ◽  
Cognitive Problems

The inclusion of neurocognitive end points in clinical trials of patients with CNS tumors is increasing. Neurocognitive end points are used to understand what cognitive problems exist before treatment to establish a baseline by which the effect of treatment is judged, and to determine whether different treatment regimens improve neurocognitive function due to better tumor control, slow expected neurocognitive deterioration due to the tumor, or have more or less short- and long-term neurotoxicity. However, the use of neurocognitive end points in clinical trials for patients with CNS tumors is in its infancy, so that long-term outcomes are difficult to predict and the ability to determine the effects of different agents and treatment approaches is scant. Including this aspect of patient evaluation in addition to survival and time to tumor progression will yield better risk-versus-benefit assessments as well as provide a basis for improving interventions.

scholarly journals Evaluation of Adolescents’ and Young Adults’ Attitudes Toward Participation in Cancer Clinical Trials

2020 ◽  
Vol 16 (3) ◽  
pp. e280-e289
Author(s):  
Jeremy Lewin ◽  
Jennifer A. H. Bell ◽  
Kate Wang ◽  
Victoria Forcina ◽  
Seline Tam ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Young Adults ◽  
Logistic Regression ◽  
Adolescents And Young Adults ◽  
Cancer Clinical Trials ◽  
Patient Centered ◽  
Logistic Regression Models ◽  
Age Related ◽  
Tumor Types

PURPOSE: Participation in cancer clinical trials (CCTs) for adolescents and young adults (AYAs) remains the lowest of any patient group with cancer. Little is known about the personal barriers to AYA accrual. The aim of this study was to explore AYA attitudes that influence CCT participation. METHODS: A mixed-methods approach was used. AYAs and non-AYAs (≥ 40 years) completed the Cancer Treatment subscale of the Attitudes Toward Cancer Trials Scales and 9 supplementary questions formed from interview analysis. Differences between AYA and non-AYA cohorts were analyzed using the Mann-Whitney U test, and logistic regression models were constructed to evaluate the effect of demographics on perceptions of CCTs. RESULTS: Surveys were distributed to 61 AYAs (median age, 29 years; range, 17-39 years) and 74 non-AYAs (median age, 55 years; range, 40-88 years). Compared with non-AYAs, AYAs perceived CCTs to be unsafe/more difficult (Personal Barrier/Safety domain; P = .01). There were no differences based on age in other domains. AYAs were also more concerned with CCT interference in their long-term goals ( P = .04). Multivariable ordered logistic regression identified increased personal barriers in the Personal Barrier/Safety domain for AYAs ( P = .01), in patients with English as a second language (ESL; P < .01), and in patients previously not offered a clinical trial ( P = .03). Long-term goals were identified as a barrier in particular tumor types ( P = .01) and in patients with ESL ( P < .01), with a trend identified in AYAs ( P = .12). CONCLUSION: Age-related differences in attitudes toward CCTs suggest that tailored approaches to CCT accrual are warranted. Patient-centered delivery of information regarding CCTs, particularly in patients with ESL and who are trial naïve, may improve accrual.

scholarly journals Assessing the Impact of Relationship Length in the SMEs and Bank Association

2017 ◽  
Vol 9 (5) ◽  
pp. 17 ◽  
Author(s):  
Mark Ojeme
Keyword(s):  
Regression Analysis ◽  
Principal Component ◽  
Building Blocks ◽  
Relationship Building ◽  
Internal Reliability ◽  
Relationship Length ◽  
Relationship Context ◽  
Short And Long Term ◽  
The Impact

Despite the importance of satisfaction, loyalty and relationship length in the literature, there is very little evidence of studies within the Nigerian Business to Business (B2B) Relationship terrain. This paper seeks to investigate the effect of relationship length on SMEs association with their banks in Nigeria. Measurement Items were adapted from various scale sets presented in existing studies were combined to investigate the B2B relationship context. Data were collected from 221 SMEs via a self-administered questionnaire completed either by the SME owner or senior manager with responsibility for relationship with their bank, providing 199 usable records. Principal Component Exploratory Analysis (PCA) was used to determine the underlying data structure, with subsequent deployment of Cronbach’s alpha as a post-hoc assessment of the internal reliability of the retained factors. Subsequently, regression analysis was employed to determine the impact of satisfaction on loyalty in a short and long term relationship contexts. The analysis presented suggests that the SMEs’ had evidence of been satisfied with their bank, however, the regression analysis for both short and long term relationship length were both significant in impacting their loyalty towards their bank. The originality of this paper lies in the investigation of a B2B relationship involving SMEs and banks within a relationship context that hitherto was unknown and the validation of relevant relationship building blocks. 

scholarly journals SCHIZOPHRENIA EPIGENETIC AGING PATTERNS REFLECT ALTERED MORTALITY AND CANCER RISKS

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S893-S893
Author(s):  
Albert T Higgins-Chen ◽  
Christiaan Vinkers ◽  
Marco P Boks ◽  
Morgan E Levine
Keyword(s):  
Accelerated Aging ◽  
Principal Component ◽  
Epidemiological Studies ◽  
Mitotic Rate ◽  
Biological Aging ◽  
Data Sets ◽  
Epigenetic Clock ◽  
Medication Effects ◽  
Age Related ◽  
Associated Proteins

Abstract Schizophrenia (SZ) is associated with large increases in all-cause mortality, high smoking rates, and elevated levels of age-associated proteins—suggesting individuals with SZ may experience accelerated rates of biological aging. Yet surprisingly, multiple previous studies found no association between SZ and biological age using Horvath’s epigenetic clock, a well-recognized and validated biomarker of aging based on DNA methylation (DNAm) levels. However, numerous epigenetic clocks have been developed to date, many of which are better indicators of differential lifespan and healthspan than the original Horvath clock. Thus, we hypothesize that these epigenetic clocks may be better proxies for the presumed accelerated aging rate in SZ. Here we investigate 14 epigenetic clocks using three publicly available DNAm datasets from whole blood, comparing SZ to non-psychiatric controls (NPC). In all data sets, we find SZ age acceleration in three clocks previously shown to be most predictive of age-related morbidity and mortality risk. In contrast, two clocks developed to capture mitotic rate are decelerated in SZ, consistent with low cancer rates despite smoking observed in epidemiological studies of SZ. We use these clocks to investigate the determinants of altered aging in SZ, such as smoking, alcohol, BMI, age-associated proteins, blood cell composition, and psychotropic medications. Principal component analysis suggests mortality clock acceleration, mitotic clock deceleration, and medication effects are independent phenomena in SZ. Our study demonstrates the importance of studying the various epigenetic clocks in tandem and highlights their potential utility for understanding how mental illness influences long-term outcomes including cancer and early mortality.

A World of Research Subjects: Informed Consent and Benefit Sharing*

2010 ◽  
Vol 9 (4) ◽  
pp. 208-213
Author(s):  
George J. Annas ◽  
Michael A. Grodin
Keyword(s):  
At Risk ◽  
Clinical Trials ◽  
Informed Consent ◽  
Medical Research ◽  
Benefit Sharing ◽  
Research Subjects ◽  
Short And Long Term ◽  
Ethical Norms ◽  
Term Benefit

The most important question for any research project is whether the research should be done at all. Only after this is answered do issues of how and where to do the research become relevant. When doing research in another country, however, the whether and where questions become intertwined. This is because the recent globalization of clinical trials is itself suspect. What is the motivation for the sudden upsurge in clinical trials in other countries? Who benefits from the globalization of research, and who is put at risk? Some advantages have been suggested, including reduced regulation, less oversight, decreased costs, and more rapid results, but none of these alone (or together) is sufficient to justify the expansion of medical research to an underserved, disenfranchised, and exploitable population. The only justification is that the proposed research addresses a question that can only be answered by this unique population and the results must bring short- and long-term benefit. The research remains suspect until ethical norms are met. The subjects must never be worse off from participating in the trials than if they had never participated.

Working Memory Training From an Individual Differences Perspective

2019 ◽  
pp. 14-39
Author(s):  
Erika Borella ◽  
Barbara Carretti ◽  
Cesare Cornoldi ◽  
Rossana De Beni
Keyword(s):  
Older Adults ◽  
Working Memory ◽  
Task Demands ◽  
Memory Training ◽  
Training Procedure ◽  
Adaptive Procedure ◽  
Age Related ◽  
Short And Long Term ◽  
Underlying Processes

This chapter presents and discusses a verbal WM training developed for older adults. The model of working memory (WM) proposed by Cornoldi and Vecchi, which is based on an analysis of individual and age-related differences, is used as a framework for discussing the efficacy of the WM training procedure proposed and developed for older adults. The model (a) assumes that different WM tasks (and underlying processes) may be located along two continua that describe the type of content to be processed and the degree of active control required by the task and (b) considers metacognitive/motivational aspects, which also have a role in determining WM performance. The WM training procedure presented here takes into account not only the capacity to use WM resources and attentional control by adopting an adaptive procedure, but also the importance of including variations in the training task demands to produce a challenging and engaging task that sustains motivation and favor the training’s short- and long-term efficacy, at least in older adults. These aspects seem crucial in explaining the results obtained with this verbal WM training program in aging.

Efektivitas Dan Keamanan Vaksin Covid-19 : Studi Refrensi

2021 ◽  
Vol 9 (2) ◽  
pp. 61-107
Author(s):  
Setiyo Adi Nugroho ◽  
Indra Nur Hidayat
Keyword(s):  
Clinical Trials ◽  
Side Effects ◽  
Public Confidence ◽  
Study Approach ◽  
A Value ◽  
Study Results ◽  
Approach Method ◽  
Short And Long Term ◽  
Protective Effectiveness

Various strategies and development of the Covid-19 vaccine have been carried out for the control of the Covid-19 pandemic. Various vaccines have undergone clinical trials with promising results in various countries. The effectiveness and safety and short- and long-term side effects of vaccines are a major concern in clinical trials in these strategies and developments. Purpose: The purpose of this study is to find out the effectiveness and safety of the Covid-19 vaccine so that it can inform and increase public confidence in the Covid-19 vaccine through a reference study approach. Method: The research method we use here is a reference study using electronic databases through journals from international and national. Google Scholar, science direx, elsiver, Pubmed are used as the main Journal database for this reference study. Results: From the results of reference studies found that all vaccines in clinical trials have promising effectiveness and safety. The Pfizer-BiONTech vaccine is a vaccine that has a good level of effectiveness and safety with a value of 94.6% and does not cause serious side effects. Double-dose vaccination further improves the immune response in younger and older adults. Conclusion: The Covid-19 vaccine in clinical trials all demonstrates promising immunogenicity with varying levels of protective effectiveness and an acceptable safety profile.

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