scholarly journals Germline mutation rates in young adults predict longevity and reproductive lifespan

2019 ◽  
Author(s):  
Richard M. Cawthon ◽  
Huong D. Meeks ◽  
Thomas A. Sasani ◽  
Ken R. Smith ◽  
Richard A. Kerber ◽  
...  
Keyword(s):  
Young Adults ◽  
Germline Mutation ◽  
Linear Regression Analysis ◽  
Mutation Accumulation ◽  
Mutation Rates ◽  
Medical Institute ◽  
Accumulation Rates ◽  
Population Database ◽  
University Of Utah ◽  
The University

SUMMARYBACKGROUNDAnalysis of sequenced genomes from large three-generation families allows de novo mutations identified in Generation II individuals to be attributed to each of their parents’ germlines in Generation I. Because germline mutations increase with age, we hypothesized that they directly limit the duration of childbearing in women, and if correlated with mutation accumulation in somatic tissues, also reflect systemic aging in both sexes. Here we test whether the germline mutation rates of Generation I individuals when they were young adults predict their remaining survival, as well as the women’s reproductive lifespans.METHODSGermline autosomal mutation counts in 122 Generation I individuals (61 women, 61 men) from 41 three-generation Utah CEPH families were converted to germline mutation rates by normalizing each subject’s number of mutations to the callable portion of their genome. Age at death, cause of death, all-site cancer incidence, and reproductive histories were provided by the Utah Population Database, Cancer Registry, and Utah Genetic Reference Project. Fertility analyses were restricted to the 53 women whose age at last birth (ALB) was at least 30 years, the approximate age when the decline in female fertility begins. Cox proportional hazard regression models were used to test the association of age-adjusted mutation rates (AAMRs) with aging-related outcomes. Linear regression analysis was used to estimate the age when adult germline mutation accumulation rates are established.FINDINGSQuartiles of increasing AAMRs were associated with increasing all-cause mortality rates in both sexes combined (test for trend, p=0.009); subjects in the top quartile of AAMRs experienced more than twice the mortality of bottom quartile subjects (hazard ratio [HR], 2.07; 95% confidence interval [CI], 1.21-3.56; p=0.008; median survival difference = 4.7 years). Women with higher AAMRs had significantly fewer live births and a younger ALB. The analyses also indicate that adult germline mutation accumulation rates are established in adolescence, and that later menarche in women may delay mutation accumulation.INTERPRETATIONParental-age-adjusted germline mutation rates in healthy young adults may provide a measure of both reproductive and systemic aging. Puberty may induce the establishment of adult mutation accumulation rates, just when DNA repair genes’ expression levels are known to begin their lifelong decline.FUNDINGNIH R01AG038797 and R21AG054962 (to R.M.C.); University of Utah Program in Personalized Health (to H.D.M.); NIH T32GM007464 (to T.A.S.); NIH R01AG022095 (to K.R.S.); NIH R01HG006693, R01HG009141, and R01GM124355 (to A.R.Q.); NIH GM118335 and GM059290 (to L.B.J.); NIH P30CA2014 (to the Utah Population Database, a.k.a. the UPDB); National Center for Research Resources Public Health Services grant M01RR00064 (to the Huntsman General Clinical Research Center, University of Utah); National Center for Advancing Translational Sciences NIH grant UL1TR002538 (to the University of Utah’s Center for Clinical and Translational Science); Howard Hughes Medical Institute funding (to Ray White); gifts from the W.M. Keck Foundation (to Stephen M. Prescott and M.F.L.) and from the George S. and Delores Doré Eccles Foundation (to the University of Utah) that supported the Utah Genetic Reference Project (UGRP). Sequencing of the CEPH samples was funded by the Utah Genome Project, the George S. and Dolores Doré Eccles Foundation, and the H.A. and Edna Benning Foundation. We thank the Pedigree and Population Resource of the Huntsman Cancer Institute, University of Utah (funded in part by the Huntsman Cancer Foundation) for its role in the ongoing collection, maintenance and support of the UPDB.

Impact of survival on health care charges during melanoma treatment.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e20043-e20043
Author(s):  
Diana I. Brixner ◽  
Brandon Kyle Bellows ◽  
Arati Dahal ◽  
David D. Stenehjem
Keyword(s):  
Index Date ◽  
Linear Models ◽  
Stage Iv ◽  
Disease Stage ◽  
Population Database ◽  
University Of Utah ◽  
Survival Status ◽  
Probability Of Survival ◽  
Stage Iv Disease ◽  
The University

e20043 Background: Treatment charges increase during the last year of life in patients with melanoma, but it remains unknown if charges differ between patients who die during treatment and survivors. The objective of this study was to examine annualized mean charges by melanoma survival status. Methods: The University of Utah Enterprise Data Warehouse was used to analyze patients ≥18 years with a diagnosis of melanoma identified by ICD-9 code (first diagnosis defined as index date) treated at the Huntsman Cancer institute (HCI) from 2002-2010. The HCI tumor registry was used to determine stage at diagnosis and other cancer diagnoses. Cause and date of death was captured from the Utah Population Database. Cancer-related (CR) and non-CR charges were assessed by ICD-9 codes from index date until death or end of the follow-up period, were weighted by the inverse probability of survival, and annualized. Generalized linear models (GLM) with gamma distribution and log link function were used to examine charges by survival status, adjusting for baseline characteristics including demographics, disease stage, and comorbidities. Results: A total of 1205 patients were included, of which 218 (18%) died. Compared to alive patients, deceased patients were older (60 vs. 56), more female (40% vs. 28%), more were diagnosed with stage IV disease (19% vs. 3%), and less with stage I disease (26% vs. 66%) (all p≤0.001). Mean unadjusted annualized charges were not significantly different between the two groups for CR charges (deceased $15,109 vs. alive $14,519; p=0.89), but non-CR charges were higher for deceased patients ($77,390 vs. $18,719; p<0.001). GLM results indicated deceased patients, relative to survivors, had 59% higher annualized CR charges (p<0.001) overall, with higher CR charges at stages I and II (86% and 76%, respectively; both p<0.001), and lower CR charges at stage IV (-127%; p<0.001). Death was associated with 154% higher annualized non-CR charges (p<0.001) at stages I, II, III, and IV (210%, 167%, 119%, and 73%, respectively; all p<0.05). Conclusions: When adjusting for confounders, deceased melanoma patients had higher charges overall compared to melanoma survivors. The exception was for decreased CR charges in stage IV, most likely related to earlier death.

scholarly journals Germline mutation rates in young adults predict longevity and reproductive lifespan

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Richard M. Cawthon ◽  
Huong D. Meeks ◽  
Thomas A. Sasani ◽  
Ken R. Smith ◽  
Richard A. Kerber ◽  
...  
Keyword(s):  
Young Adults ◽  
Germline Mutation ◽  
Mutation Rates

scholarly journals Germline mutation rates and the long-term phenotypic effects of mutation accumulation in wild-type laboratory mice and mutator mice

2015 ◽  
Vol 25 (8) ◽  
pp. 1125-1134 ◽  
Author(s):  
Arikuni Uchimura ◽  
Mayumi Higuchi ◽  
Yohei Minakuchi ◽  
Mizuki Ohno ◽  
Atsushi Toyoda ◽  
...  
Keyword(s):  
Germline Mutation ◽  
Mutation Accumulation ◽  
Mutation Rates ◽  
Laboratory Mice ◽  
Wild Type

Faktor – Faktor Yang Mempengaruhi Minat Berwirausaha Mahasiswa Program Studi Manajemen Fakultas Ekonomi Universitas Flores

Analisis ◽  
2020 ◽  
Vol 19 (1) ◽  
pp. 76-84
Author(s):  
Nasarius Aban ◽  
Gabriel Tanusi
Keyword(s):  
Emotional Intelligence ◽  
Regression Analysis ◽  
Family Environment ◽  
Linear Regression Analysis ◽  
Simple Random Sampling ◽  
Coefficient Of Determination ◽  
Test Results ◽  
Study Program ◽  
Management Study ◽  
The University

This study aims to determine the effect of emotional intelligence, independent attitude and family environment on the interest in entrepreneurship at the University of Flores Management Faculty of Economics. This research is an associative research. The population in this study were students of the Management Study Program of the Faculty of Economics of the University of Flores in the class of 2015-2016 who had passed the entrepreneurship courses of 170 people. Samples taken in this study were 105 respondents, with sampling techniques using simple random sampling. Data collection using questionnaires and interviews, while data analysis was performed using multiple linear regression analysis. The results of multiple regression analysis are Y = 1.060 + 0.594X1 + 0.114X2 + 0.421X3 + e. The coefficient of determination R2 for the variables X1, X2, X3 is 0.675, which means that entrepreneurial interest can be influenced by emotional intelligence, independent attitude and family environment by 67.50% and the remaining 32.50% is influenced by other factors including factors of education, skills, motivation and others. F test results show the value of Fcount> Ftable (28.442> 2.69) with a significant level of 0.000 <0.05 meaning that there is a positive and significant influence between emotional intelligence, independent attitude and family environment together on the entrepreneurial interest of the Faculty of Management Study Program Students The economy. Partial test results (t) show 1) Emotional intelligence factors have a positive and significant effect on entrepreneurial interest 2) Family environment factors have a positive and significant effect on entrepreneurial interest 3) Independent attitude factor has no positive and significant effect on entrepreneurial interest.

Young Adults’ Perspectives of Childhood Food Allergies: Implications for School Nurses

2021 ◽  
pp. 105984052110190
Author(s):  
Abigail Anderson ◽  
Elizabeth M. Combs ◽  
Sheila Hurst ◽  
Cynthia F. Corbett
Keyword(s):  
Young Adults ◽  
South Carolina ◽  
School Nurses ◽  
Food Allergies ◽  
School Age Children ◽  
School Age ◽  
University Of South Carolina ◽  
Social Lives ◽  
Qualitative Descriptive ◽  
The University

The primary goal of this study was to examine young adults’ perspectives about the effects of their food allergies (FAs) on their social lives from school-age to young adulthood. Young adults aged 18–21 ( n = 10) at the University of South Carolina were interviewed. A qualitative descriptive method to find themes and commonalities from transcribed interviews was used for data analysis. Identified themes were (1) feeling different and being isolated, (2) strategies for managing feeling different and being isolated, (3) strategies for managing safety, and (4) acceptance of myself and by others. School-age children attributed the school lunch allergy table as contributing to social isolation. Additionally, participants described feeling different and concerns about safety. Strategies to mitigate those experiences were identified by participants. Implications for children with FAs, their parents, school nurses, and other education and health professionals who work with children are presented.

scholarly journals Nature of Deleterious Mutation Load in Drosophila

Genetics ◽  
1996 ◽  
Vol 144 (4) ◽  
pp. 1993-1999 ◽  
Author(s):  
Peter D Keightley
Keyword(s):  
Deleterious Mutation ◽  
Spontaneous Mutation ◽  
Mutation Accumulation ◽  
Mutation Rates ◽  
Mutation Load ◽  
Spontaneous Mutation Rate ◽  
A Minor ◽  
Chromosome I ◽  
Balancer Chromosomes ◽  
Balancer Chromosome

Much population genetics and evolution theory depends on knowledge of genomic mutation rates and distributions of mutation effects for fitness, but most information comes from a few mutation accumulation experiments in Drosophila in which replicated chromosomes are sheltered from natural selection by a balancer chromosome. I show here that data from these experiments imply the existence of a large class of minor viability mutations with approximately equivalent effects. However, analysis of the distribution of viabilities of chromosomes exposed to EMS mutagenesis reveals a qualitatively different distribution of effects lacking such a minor effects class. A possible explanation for this difference is that transposable element insertions, a common class of spontaneous mutation event in Drosophila, frequently generate minor viability effects. This explanation would imply that current estimates of deleterious mutation rates are not generally applicable in evolutionary models, as transposition rates vary widely. Alternatively, much of the apparent decline in viability under spontaneous mutation accumulation could have been nonmutational, perhaps due to selective improvement of balancer chromosomes. This explanation accords well with the data and implies a spontaneous mutation rate for viability two orders of magnitude lower than previously assumed, with most mutation load attributable to major effects.

Mechatronics education in the Department of Mechanical Engineering at the University of Utah

Mechatronics ◽  
2003 ◽  
Vol 13 (1) ◽  
pp. 1-11 ◽  
Author(s):  
Sanford Meek ◽  
Scott Field ◽  
Santosh Devasia
Keyword(s):  
Mechanical Engineering ◽  
University Of Utah ◽  
The University

Prediction of Wind Turbine Rotor Loads Using the Beddoes-Leishman Model for Dynamic Stall

1995 ◽  
Vol 117 (3) ◽  
pp. 200-204 ◽  
Author(s):  
K. Pierce ◽  
A. C. Hansen
Keyword(s):  
Wind Turbines ◽  
Aerodynamic Force ◽  
Unsteady Aerodynamics ◽  
Turbine Rotor ◽  
Dynamic Stall ◽  
University Of Utah ◽  
Horizontal Axis Wind Turbines ◽  
Wind Tunnel Data ◽  
The University ◽  
Wind Turbine Rotor

The Beddoes-Leishman model for unsteady aerodynamics and dynamic stall has recently been implemented in YawDyn, a rotor analysis code developed at the University of Utah for the study of yaw loads and motions of horizontal axis wind turbines. This paper presents results obtained from validation efforts for the Beddoes model. Comparisons of predicted aerodynamic force coefficients with wind tunnel data and data from the combined experiment rotor are presented. Also, yaw motion comparisons with the combined experiment rotor are presented. In general the comparisons with the measured data are good, indicating that the model is appropriate for the conditions encountered by wind turbines.

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