scholarly journals PathoClock and PhysioClock in mice recapitulate human multimorbidity and heterogeneous aging

2021 ◽  
Vol 3 (4) ◽  
pp. 107-126
Author(s):  
Shabnam Salimi ◽  
◽  
Christina Pettan-Brewer ◽  
Warren Ladiges
Keyword(s):  
Regression Models ◽  
Intervention Studies ◽  
Prediction Models ◽  
Health Concern ◽  
Chronological Age ◽  
Mouse Strains ◽  
Public Health Concern ◽  
Aging Intervention ◽  
Body Organ ◽  
Similarities And Differences

Background: Multimorbidity is a public health concern and an essential component of aging and healthspan but understudied because investigative tools are lacking that can be translatable to capture similarities and differences of the aging process across species and variability between individuals and individual organs. Methods: To help address this need, body organ disease number (BODN) borrowed from human studies was applied to C57BL/6 (B6) and CB6F1 mouse strains at 8, 16, 24, and 32 months of age, as a measure of systems morbidity based on pathology lesions to develop a mouse PathoClock resembling clinically-based Body Clock in humans, using Bayesian inference. A mouse PhysioClock was also developed based on measures of physiological domains including cardiovascular, neuromuscular, and cognitive function in the same two mouse strains so that alignment with BODN was predictable. Results: Between- and within-age variabilities in PathoClock and PhysioClock, as well as between-strain variabilities. Both PathoClock and PhysioClock correlated with chronological age more strongly in CB6F1 than C57BL/6. Prediction models were then developed, designated as PathoAge and PhysioAge, using regression models of pathology and physiology measures on chronological age. PathoAge better predicted chronological age than PhysioAge as the predicted chronological and observed chronological age for PhysioAge were complex rather than linear. Conclusion: PathoClock and PhathoAge can be used to capture biological changes that predict BODN, a metric developed in humans, and compare multimorbidity across species. These mouse clocks are potential translational tools that could be used in aging intervention studies. Keywords: Multimorbidity, aging, pathology, physiology, pathoClock, physioClock, pathoAge, physioAge

scholarly journals PathoClock and PhysioClock in mice recapitulate human multimorbidity and heterogeneous aging

2021 ◽  
Author(s):  
Shabnam Salimi ◽  
Christina Pettan-Brewer ◽  
Warren Ladiges
Keyword(s):  
Regression Models ◽  
Intervention Studies ◽  
Prediction Models ◽  
Health Concern ◽  
Chronological Age ◽  
Mouse Strains ◽  
Public Health Concern ◽  
Aging Intervention ◽  
Body Organ ◽  
Similarities And Differences

Multimorbidity is a public health concern and an essential component of aging and healthspan but understudied because investigative tools are lacking that can be translatable to capture similarities and differences of the aging process across species and variability between individuals and individual organs. To help address this need, body organ disease number (BODN) borrowed from human studies was applied to C57BL/6 (B6) and CB6F1 mouse strains at 8, 16, 24, and 32 months of age, as a measure of systems morbidity based on pathology lesions to develop a mouse PathoClock resembling clinically-based Body Clock in humans, using Bayesian inference. A mouse PhysioClock was also developed based on measures of physiological domains including cardiovascular, neuromuscular, and cognitive function in the same two mouse strains so that alignment with BODN was predictable. The results revealed between- and within-age variabilities in PathoClock and PhysioClock, as well as between-strain variabilities. Both PathoClock and PhysioClock correlated with chronological age more strongly in CB6F1 than C57BL/6. Prediction models were then developed, designated as PathoAge and PhysioAge, using regression models of pathology and physiology measures on chronological age. PathoAge better predicted chronological age than PhysioAge as the predicted chronological and observed chronological age for PhysioAge were complex rather than linear. In conclusion, PathoClock and PhathoAge can be used to capture biological changes that predict BODN, a metric developed in humans, and compare multimorbidity across species. These mouse clocks are potential translational tools that could be used in aging intervention studies.

scholarly journals Correlation Constraints for Regression Models: Controlling Bias in Brain Age Prediction

2021 ◽  
Vol 12 ◽  
Author(s):  
Matthias S. Treder ◽  
Jonathan P. Shock ◽  
Dan J. Stein ◽  
Stéfan du Plessis ◽  
Soraya Seedat ◽  
...  
Keyword(s):  
Regression Models ◽  
Optimization Problem ◽  
Prediction Models ◽  
Chronological Age ◽  
Training Procedure ◽  
Constrained Optimization Problem ◽  
The Difference ◽  
Model Training ◽  
Brain Age ◽  
Age Prediction

In neuroimaging, the difference between chronological age and predicted brain age, also known as brain age delta, has been proposed as a pathology marker linked to a range of phenotypes. Brain age delta is estimated using regression, which involves a frequently observed bias due to a negative correlation between chronological age and brain age delta. In brain age prediction models, this correlation can manifest as an overprediction of the age of young brains and an underprediction for elderly ones. We show that this bias can be controlled for by adding correlation constraints to the model training procedure. We develop an analytical solution to this constrained optimization problem for Linear, Ridge, and Kernel Ridge regression. The solution is optimal in the least-squares sense i.e., there is no other model that satisfies the correlation constraints and has a better fit. Analyses on the PAC2019 competition data demonstrate that this approach produces optimal unbiased predictive models with a number of advantages over existing approaches. Finally, we introduce regression toolboxes for Python and MATLAB that implement our algorithm.

scholarly journals Association of FTO rs9939609 with Obesity in the Kuwaiti Population: A Public Health Concern?

2018 ◽  
Vol 27 (2) ◽  
pp. 145-151 ◽  
Author(s):  
Ahmad Al-Serri ◽  
Suzanne A. Al-Bustan ◽  
Maisa Kamkar ◽  
Daisy  Thomas ◽  
Osama Alsmadi ◽  
...  
Keyword(s):  
Genetic Variants ◽  
Regression Models ◽  
Health Concern ◽  
Public Health Concern ◽  
Fto Gene ◽  
Kuwait University ◽  
Logistic Regression Models ◽  
The Common ◽  
Fto Rs9939609 ◽  
Kuwaiti Population

Objective: To investigate the effect of the common fat mass and obesity-associated (FTO) gene polymorphism rs9939609 on body mass index (BMI) in one of the most obese populations worldwide. Subjects and Methods: Genotypic data for FTO rs9939609 were available for 1,034 unrelated Kuwaiti adults obtained from Kuwait’s Dasman Diabetes Institute and Kuwait University. The association between the FTO polymorphism with BMI as continuous and categorical (normal BMI [< 25] vs. overweight/obese [> 25]) variables was analyzed using both linear and logistic regression models, respectively, with the assumption of both dominant and additive genetic models performed using the SNPassoc package from R statistics. Results: The A allele was associated with increased BMI (β = 1.21; 95% CI = 0.16–2.26; p = 0.023). In concordance, the categorical BMI (normal vs. overweight/obese) also showed a significant association between the A allele and overweight/obesity (OR = 1.47; 95% CI = 1.01–2.12; p = 0.041). However, no association between the FTO variant was observed with cardiometabolic traits. Conclusion: We observed an association between the common FTO rs9939609 polymorphism and increased BMI (overweight/obesity) in Kuwaiti adults, which is consistent with previous research in other populations. Our findings encourage further investigation of genetic variants to elucidate the mechanisms involved in the development of obesity in such an obesogenic population.

scholarly journals Tuberculosis in HIV-Associated Cryptococcal Meningitis is Associated with an Increased Risk of Death

2020 ◽  
Vol 9 (3) ◽  
pp. 781
Author(s):  
Morris K. Rutakingirwa ◽  
Fiona V. Cresswell ◽  
Richard Kwizera ◽  
Kenneth Ssebambulidde ◽  
Enock Kagimu ◽  
...  
Keyword(s):  
Cryptococcal Meningitis ◽  
Regression Models ◽  
Proportional Hazards ◽  
Health Concern ◽  
Hiv Disease ◽  
Public Health Concern ◽  
Risk Of Death ◽  
Proportional Hazards Regression ◽  
Increased Risk ◽  
Advanced Hiv Disease

Tuberculosis (TB) and cryptococcal meningitis are leading causes of morbidity and mortality in advanced HIV disease. Data are limited on TB co-infection among individuals with cryptococcal meningitis. We performed a retrospective analysis of HIV-infected participants with cryptococcal meningitis from 2010–2017. Baseline demographics were compared between three groups: ‘prevalent TB’ if TB treated >14 days prior to cryptococcal meningitis diagnosis, ‘concurrent TB’ if TB treated ± 14 days from diagnosis, or ‘No TB at baseline’. We used time-updated proportional-hazards regression models to assess TB diagnosis as a risk for death. Of 870 participants with cryptococcal meningitis, 50 (6%) had prevalent TB, 67 (8%) had concurrent TB, and 753 (86%) had no baseline TB. Among participants without baseline TB, 67 (9%) were diagnosed with incident TB (after >14 days), with a median time to TB incidence of 41 days (IQR, 22–69). The 18-week mortality was 50% (25/50) in prevalent TB, 46% (31/67) in concurrent TB, and 45% (341/753) in the no TB group (p = 0.81). However, TB co-infection was associated with an increased hazard of death (HR = 1.75; 95% CI, 1.33–2.32; p < 0.001) in a time-updated model. TB is commonly diagnosed in cryptococcal meningitis, and the increased mortality associated with co-infection is a public health concern.

An Overview of Dementias

2012 ◽  
Vol 21 (3) ◽  
pp. 75-84
Author(s):  
Venkata Vijaya K. Dalai ◽  
Jason E. Childress ◽  
Paul E Schulz
Keyword(s):  
Clinical Presentation ◽  
Treatment Options ◽  
Current Treatment ◽  
Great Variability ◽  
Health Concern ◽  
Public Health Concern ◽  
Life Threatening ◽  
The Common ◽  
Neurodegenerative Dementias ◽  
Made In

Dementia is a major public health concern that afflicts an estimated 24.3 million people worldwide. Great strides are being made in order to better diagnose, prevent, and treat these disorders. Dementia is associated with multiple complications, some of which can be life-threatening, such as dysphagia. There is great variability between dementias in terms of when dysphagia and other swallowing disorders occur. In order to prepare the reader for the other articles in this publication discussing swallowing issues in depth, the authors of this article will provide a brief overview of the prevalence, risk factors, pathogenesis, clinical presentation, diagnosis, current treatment options, and implications for eating for the common forms of neurodegenerative dementias.

Reframing Fatness: Critiquing ‘Obesity’

2018 ◽  
Author(s):  
Bethan Evans ◽  
Charlotte Cooper
Keyword(s):  
Public Health ◽  
Weight Loss ◽  
Michel Foucault ◽  
Overweight And Obesity ◽  
Health Concern ◽  
Public Health Concern ◽  
Policy Language ◽  
Religious Imagery ◽  
Fat Bodies

Over the last twenty years or so, fatness, pathologised as overweight and obesity, has been a core public health concern around which has grown a lucrative international weight loss industry. Referred to as a ‘time bomb’ and ‘the terror within’, analogies of ‘war’ circulate around obesity, framing fatness as enemy.2 Religious imagery and cultural and moral ideologies inform medical, popular and policy language with the ‘sins’ of ‘gluttony’ and ‘sloth’, evoked to frame fat people as immoral at worst and unknowledgeable victims at best, and understandings of fatness intersect with gender, class, age, sexuality, disability and race to make some fat bodies more problematically fat than others. As Evans and Colls argue, drawing on Michel Foucault, a combination of medical and moral knowledges produces the powerful ‘obesity truths’ through which fatness is framed as universally abject and pathological. Dominant and medicalised discourses of fatness (as obesity) leave little room for alternative understandings.

European Surveillance of Antimicrobial Consumption: the ESAC programme

2004 ◽  
Vol 8 (32) ◽  
Author(s):  
Keyword(s):  
Public Health ◽  
Antimicrobial Resistance ◽  
Health Concern ◽  
Antimicrobial Consumption ◽  
Public Health Concern ◽  
Major Public Health Concern

Resistance to antimicrobials has become a major public health concern, and it has been shown that there is a relationship, albeit complex, between antimicrobial resistance and consumption

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