Epigenetic-based age acceleration in a representative sample of older Americans: Associations with aging-related morbidity and mortality.

Biomarkers developed from DNA methylation (DNAm) data are of growing interest as predictors of health outcomes and mortality in older populations. However, it is unknown how epigenetic aging fits within the context of known socioeconomic and behavioral associations with aging-related health outcomes in a large, population-based, and diverse sample. This study uses data from a representative, panel study of US older adults to examine the relationship between DNAm-based age acceleration measures in the prediction of cross-sectional and longitudinal health outcomes and mortality. We examine whether recent improvements to these scores, using principal component (PC)-based measures designed to remove some of the technical noise and unreliability in measurement, improve the predictive capability of these measures. We also examine how well DNAm-based measures perform against well-known predictors of health outcomes such as demographics, SES, and health behaviors. In our sample, age acceleration calculated using "second and third generation clocks," PhenoAge, GrimAge, and DunedinPACE, is consistently a significant predictor of health outcomes including cross-sectional cognitive dysfunction, functional limitations and chronic conditions assessed 2 y after DNAm measurement, and 4-y mortality. PC-based epigenetic age acceleration measures do not significantly change the relationship of DNAm-based age acceleration measures to health outcomes or mortality compared to earlier versions of these measures. While the usefulness of DNAm-based age acceleration as a predictor of later life health outcomes is quite clear, other factors such as demographics, SES, mental health, and health behaviors remain equally, if not more robust, predictors of later life outcomes.

Factor structure of the Harmonized Cognitive Assessment Protocol neuropsychological battery in the Health and Retirement Study.

OBJECTIVE: The Harmonized Cognitive Assessment Protocol (HCAP) describes an assessment battery and a family of population-representative studies measuring neuropsychological performance. We describe the factorial structure of the HCAP battery in the US Health and Retirement Study (HRS). METHOD: The HCAP battery was compiled from existing measures by a cross-disciplinary and international panel of researchers. The HCAP battery was used in the 2016 wave of the HRS. We used factor analysis methods to assess and refine a theoretically driven single and multiple domain factor structure for tests included in the HCAP battery among 3,347 participants with evaluable performance data. RESULTS: For the eight domains of cognitive functioning identified (orientation, memory [immediate, delayed, and recognition], set shifting, attention/speed, language/fluency, and visuospatial), all single factor models fit reasonably well, although four of these domains had either 2 or 3 indicators where fit must be perfect and is not informative. Multidimensional models suggested the eight-domain model was overly complex. A five-domain model (orientation, memory delayed and recognition, executive functioning, language/fluency, visuospatial) was identified as a reasonable model for summarizing performance in this sample (standardized root mean square residual = 0.05, root mean square error of approximation = 0.05, confirmatory fit index = 0.94). CONCLUSIONS: The HCAP battery conforms adequately to a multidimensional structure of neuropsychological performance. The derived measurement models can be used to operationalize notions of neurocognitive impairment, and as a starting point for prioritizing pre-statistical harmonization and evaluating configural invariance in cross-national research.

Dried blood spot based biomarkers in the Health and Retirement Study: 2006 to 2016.

INTRODUCTION: The Health and Retirement Study (HRS) has collected biomarker data over multiple waves. Such data can help improve our understanding of health changes in individuals and the causal pathways related to health. There are, however, technical challenges to using the HRS dried blood spots (DBS) biomarker data due to changes over time in assay protocols, platforms, and laboratories. We provide technical and summary information on biological indicators collected as part of the HRS from 2006 to 2016 that should be helpful to users of the data. METHODS: We describe the opportunities and challenges provided by the HRS DBS data as well as insights provided by the data. The HRS collected DBS from its nationally representative sample of respondents 51 years of age or older from 2006 to 2016. DBS-based biomarkers were collected from half the sample in 2006, 2010, and 2014, and from the other half of the sample in 2008, 2012, and 2016. These DBS specimens were used to assay total and HDL cholesterol, glycosylated hemoglobin, C-reactive protein, and cystatin C from 2006 to 2016, and Interleukin 6 was added in 2014/2016. Samples included approximately 6000 individuals at each wave, and completion rates ranged from 81% to 90%. HRS transformed DBS values into venous blood equivalents to make them more comparable to those of the whole blood-based assays collected in most other studies and to facilitate longitudinal analysis. RESULTS: Distribution of changes over time by age shows that total cholesterol levels decreased for each age, while HbA1c levels increased. Cystatin C shows a clear age gradient, but a number of other markers do not. Non-Hispanic Black persons and Hispanic respondents have a higher incidence of risk levels of each biomarker except for CRP among non-Hispanic Black older persons. CONCLUSION: These public-use DBS data provide analysis opportunities that can be used to improve our understanding of health change with age in both populations and among individuals.

Lifetime occupational skill and later-life cognitive function among older adults in the United States, Mexico, India, and South Africa.

INTRODUCTION: We conducted a cross-national comparison of the association between main lifetime occupational skills and later-life cognitive function across four economically and socially distinct countries. METHODS: Data were from population-based studies of aging and their Harmonized Cognitive Assessment Protocols (HCAPs) in the US, South Africa, India, and Mexico (N = 10,037; Age range: 50 to 105 years; 2016 to 2020). Main lifetime occupational skill was classified according to the International Standard Classification of Occupations. Weighted, adjusted regression models estimated pooled and country-specific associations between main lifetime occupational skill and later-life general cognitive function in men and women. RESULTS: We observed positive gradients between occupational skill and later-life cognitive function for men and women in the US and Mexico, a positive gradient for women but not men in India, and no association for men or women in South Africa. DISCUSSION: Main lifetime occupations may be a source of later-life cognitive reserve, with cross-national heterogeneity in this association. HIGHLIGHTS: No studies have examined cross-national differences in the association of occupational skill with cognition. We used data from Harmonized Cognitive Assessment Protocols in the US, Mexico, India, and South Africa. The association of occupational skill with cognitive function varies by country and gender.

Positive Effects of Religion and Social Ties on the Health of Former NFL Athletes.

This study explores the relationship between religious service attendance, social ties, and health among former NFL players, a population with relatively high levels of religious attendance who endure physically demanding occupations. Research shows that frequent religious service attenders tend to have better health, partly because of social connections formed through religious involvement. We analyzed a sample of 1029 former NFL players. Consistent with previous research, bivariate and multivariate OLS regression models show that frequent religious attenders have statistically significantly better self-rated health. However, this relationship is moderated by social ties. Respondents who scored lower on the social ties index exhibited a stronger significant relationship between frequent religious attendance and health; those scoring higher on the social ties index exhibited no relationship between frequent attendance and health. Future research should examine how benefits of religious attendance vary depending upon strength of social relationships.

Thermodynamics of a Two-Step Electroweak Phase Transition.

New field content beyond that of the standard model of particle physics can alter the thermal history of electroweak symmetry breaking in the early Universe. In particular, the symmetry breaking may have occurred through a sequence of successive phase transitions. We study the thermodynamics of such a scenario in a real triplet extension of the standard model, using nonperturbative lattice simulations. Two-step electroweak phase transition is found to occur in a narrow region of allowed parameter space with the second transition always being first order. The first transition into the phase of nonvanishing triplet vacuum expectation value is first order in a non-negligible portion of the two-step parameter space. A comparison with two-loop perturbative calculation is provided and significant discrepancies with the nonperturbative results are identified.

Burnout, Work Satisfaction, and Well-being Among Non-consultant Psychiatrists in Ireland.

OBJECTIVE: The aim of this study was to explore the areas of psychological well-being, satisfaction at work, and burnout among non-consultant psychiatrists in Ireland, and to assess for potential contributory factors. METHODS: The College of Psychiatrists of Ireland distributed the survey online to 100 non-consultant psychiatry doctors working in Ireland. The survey contained questions relating to demographic and work-related variables, the Abbreviated-Maslach Burnout Inventory (a-MBI), Basic Needs Satisfaction at Work (BNSW) scale, and WHO-5 Well-being Index. Descriptive statistics were used by the authors to summarize the data and univariate associations were explored between baseline data and subscales. RESULTS: Sixty-nine percent of our sample completed the survey. Thirty-six percent of the sample met the criteria for burnout, with lack of supervision the only variable significantly associated with this. Lack of regular supervision was associated with lower scores across all work satisfaction domains of the BNSW scale. The WHO-5 Well-being Index identified that 30% of respondents scored low in personal well-being, indicating that this proportion screened positive for depression, based on international diagnostic criteria. Lack of regular supervision was found to be significantly associated with low psychological well-being. CONCLUSION: This study indicates that lack of supervision is significantly associated with burnout, lower satisfaction at work, and poorer psychological well-being. Close evaluation of these areas is important to identify vulnerable individuals and areas of training which can be improved upon, which may lead to relevant measures being implemented for the benefit of psychiatrists, patients, and the wider society.

Vorticity, Kinetic Energy, and Suppressed Gravitational-Wave Production in Strong First-Order Phase Transitions.

We have performed the first three-dimensional simulations of strong first-order thermal phase transitions in the early universe. For deflagrations, we find that the rotational component of the fluid velocity increases as the transition strength is increased. For detonations, however, the rotational velocity component remains constant and small. We also find that the efficiency with which kinetic energy is transferred to the fluid falls below theoretical expectations as we increase the transition strength. The probable origin of the kinetic energy deficit is the formation of reheated droplets of the metastable phase during the collision, slowing the bubble walls. The rate of increase in the gravitational wave energy density for deflagrations in strong transitions is suppressed compared to that predicted in earlier work. This is largely accounted for by the reduction in kinetic energy. Current modeling therefore substantially overestimates the gravitational wave signal for strong transitions with deflagrations, in the most extreme case by a factor of 10^{3}. Detonations are less affected.

The Health and Retirement Study Harmonized Cognitive Assessment Protocol Project: Study Design and Methods.

INTRODUCTION: The Harmonized Cognitive Assessment Protocol (HCAP) Project is a substudy within the Health and Retirement Study (HRS), an ongoing nationally representative panel study of about 20,000 adults aged 51 or older in the United States. The HCAP is part of an international research collaboration funded by the National Institute on Aging to better measure and identify cognitive impairment and dementia in representative population-based samples of older adults, in the context of ongoing longitudinal studies of aging in high-, middle-, and low-income countries around the world. METHODS: The HCAP cognitive test battery was designed to measure a range of key cognitive domains affected by cognitive aging (including attention, memory, executive function, language, and visuospatial function) and to allow harmonization and comparisons to other studies in the United States and around the world. The HCAP included a pair of in-person interviews, one with the target HRS respondent (a randomly selected HRS sample member, aged 65+) that lasted approximately 1 h and one with an informant nominated by the respondent that lasted approximately 20 min. The final HRS HCAP sample included 3,496 study subjects, representing a 79% response rate among those invited to participate. CONCLUSION: Linking detailed HCAP cognitive assessments to the wealth of available longitudinal HRS data on cognition, health, biomarkers, genetics, health care utilization, informal care, and economic resources and behavior will provide unique and expanded opportunities to study cognitive impairment and dementia in a nationally representative US population-based sample. The fielding of similar HCAP projects in multiple countries around the world will provide additional opportunities to study international differences in the prevalence, incidence, and outcomes of dementia globally with comparable data. Like all HRS data, HCAP data are publicly available at no cost to researchers.

Recent trends in wealth inequality among older Americans in two surveys.

We document changes in wealth inequality across American households with a member aged 55 or older, comparing data in the Health and Retirement Study (HRS) with that in the Survey of Consumer Finances (SCF) between 1998 and 2016. We examine net wealth including housing, financial and nonfinancial assets and debt, without the cash value of insurances, DB pensions or Social Security wealth. We find very similar distributions of net wealth in the two surveys between the 25th and 90th percentiles, but substantially higher wealth in the SCF at the top of the distribution. Both surveys show an increase in wealth inequality between 1998 and 2016, first mostly due to increased wealth at the top, and, after 2012, due to an increase in the share of households with very little wealth as well. Both surveys agree that wealth inequality by education and race, already substantial in 1998, increased further by 2016.

Fibroblasts Promote Inflammation and Pain via IL-1α Induction of the Monocyte Chemoattractant Chemokine (C-C Motif) Ligand 2.

Fibroblasts persist within fibrotic scar tissue and exhibit considerable phenotypic and functional plasticity. Herein, we hypothesized that scar-associated fibroblasts may be a source of stress-induced inflammatory exacerbations and pain. To test this idea, we used a human model of surgery-induced fibrosis, total knee arthroplasty (TKA). Using a combination of tissue protein expression profiling and bioinformatics, we discovered that many months after TKA, the fibrotic joint exists in a state of unresolved chronic inflammation. Moreover, the infrapatellar fat pad, a soft tissue that becomes highly fibrotic in the post-TKA joint, expresses multiple inflammatory mediators, including the monocyte chemoattractant, chemokine (C-C motif) ligand (CCL) 2, and the innate immune trigger, IL-1α. Fibroblasts isolated from the post-TKA fibrotic infrapatellar fat pad express the IL-1 receptor and on exposure to IL-1α polarize to a highly inflammatory state that enables them to stimulate the recruitment of monocytes. Blockade of fibroblast CCL2 or its transcriptional regulator NF-κB prevented IL-1α-induced monocyte recruitment. Clinical investigations discovered that levels of patient-reported pain in the post-TKA joint correlated with concentrations of CCL2 in the joint tissue, such that the chemokine is effectively a pain biomarker in the TKA patient. We propose that an IL-1α-NF-κB-CCL2 signaling pathway, operating within scar-associated fibroblasts, may be therapeutically manipulated for alleviating inflammation and pain in fibrotic joints and other tissues.

Lifespan adversity and later adulthood telomere length in the nationally representative US Health and Retirement Study.

Stress over the lifespan is thought to promote accelerated aging and early disease. Telomere length is a marker of cell aging that appears to be one mediator of this relationship. Telomere length is associated with early adversity and with chronic stressors in adulthood in many studies. Although cumulative lifespan adversity should have bigger impacts than single events, it is also possible that adversity in childhood has larger effects on later life health than adult stressors, as suggested by models of biological embedding in early life. No studies have examined the individual vs. cumulative effects of childhood and adulthood adversities on adult telomere length. Here, we examined the relationship between cumulative childhood and adulthood adversity, adding up a range of severe financial, traumatic, and social exposures, as well as comparing them to each other, in relation to salivary telomere length. We examined 4,598 men and women from the US Health and Retirement Study. Single adversities tended to have nonsignificant relations with telomere length. In adjusted models, lifetime cumulative adversity predicted 6% greater odds of shorter telomere length. This result was mainly due to childhood adversity. In adjusted models for cumulative childhood adversity, the occurrence of each additional childhood event predicted 11% increased odds of having short telomeres. This result appeared mainly because of social/traumatic exposures rather than financial exposures. This study suggests that the shadow of childhood adversity may reach far into later adulthood in part through cellular aging.

Correction to: The WOMAC score can be reliably used to classify patient satisfaction after total knee arthroplasty.

Unfortunately, Fig. 1 in the original article contained incorrect information. Hereby, the correct figure is published and we apologise for the inconvenience.

An Overview and Predictors of Achieving the Postoperative Ceiling Effect of the WOMAC Score Following Total Knee Arthroplasty.

BACKGROUND: To describe the ceiling effect for the components of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score and identify preoperative independent predictors for patients who achieve maximal scores (ceiling effect) after total knee arthroplasty (TKA). METHODS: A retrospective cohort of 2589 patients undergoing a primary TKA were identified from an established arthroplasty database. Patient demographics, WOMAC and Short Form 12 (SF-12) scores were collected preoperatively and 1 year postoperatively. Logistic regression analysis was used to identify independent preoperative predictors of patients achieving ceiling scores. RESULTS: The ceiling effect was 26.8% (n = 695) for the pain score, 6.4% (n = 165) for the function score, and 21.2% (n = 548) for the stiffness score. Lower body mass index (P = .001), absence of gastric ulceration (P = .04), absence of anemia (P = .02), absence of depression (P = .004), and absence of back pain (P < .001) and better preoperative WOMAC pain and SF-12 physical (P = .01) and mental (P < .001) scores were associated with a ceiling WOMAC pain score. Male gender (P = .03), lower body mass index (P = .040), absence of gastric ulceration (P = .004), and absence of back pain (P < .001) and better preoperative SF-12 physical (P = .02) scores were associated with a ceiling WOMAC function score. Male gender (P = .001), absence of back pain (P < .001), and better preoperative WOMAC stiffness score (P = .005) and SF-12 mental (P = .001) scores were associated with a ceiling WOMAC stiffness score. CONCLUSION: The WOMAC pain and stiffness components demonstrated a high ceiling effect but in contrast the functional score had a low ceiling effect. The absence of back pain was a common predictive factor for all 3 components and had the greatest impact upon the likelihood of achieving a ceiling score.

Asynchronous Bilateral Total Knee Arthroplasty: Predictors of the Functional Outcome and Patient Satisfaction for the Second Knee Replacement.

BACKGROUND: The primary aim of this study is to identify independent preoperative predictors of outcome and patient satisfaction for the second total knee arthroplasty (TKA). METHODS: A retrospective cohort of 454 patients undergoing an asynchronous (6 weeks or more apart) bilateral primary TKA were identified from an arthroplasty database. Patient demographics, comorbidities, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and Short Form-12 scores were collected preoperatively and 1 year postoperatively. Overall patient satisfaction was assessed at 1 year. RESULTS: The 1 year WOMAC pain score (P = .01), and improvement in WOMAC pain (P < .001) and functional (P = .002) scores were significantly lower for the second TKA. Worse preoperative WOMAC pain, function, and stiffness scores were demonstrated to be independent predictors of improvement in the WOMAC pain, function, and stiffness scores, respectively, for both the first and second TKA. The overall rate of satisfaction with the first TKA was 94.0% and 94.7% for the second TKA (P = .67). The rate of satisfaction for the second TKA was 77.8% for patients that were dissatisfied with their first TKA, which was an independent predictor of dissatisfaction (P = .02). CONCLUSION: Improvement in pain and function is less with the second TKA, but the satisfaction rate remains similar. There are common independent predictors for change in the WOMAC score for the first and second TKA; however, the predictors of satisfaction were different with no common factors. Patients that were dissatisfied with their first TKA were more likely to be dissatisfied with their second TKA. LEVEL OF EVIDENCE II: Prognostic retrospective cohort study.

Nonperturbative Analysis of the Electroweak Phase Transition in the Two Higgs Doublet Model.

We perform a nonperturbative study of the electroweak phase transition (EWPT) in the two Higgs doublet model (2HDM) by deriving a dimensionally reduced high-temperature effective theory for the model, and matching to known results for the phase diagram of the effective theory. We find regions of the parameter space where the theory exhibits a first-order phase transition. In particular, our findings are consistent with previous perturbative results suggesting that the primary signature of a first-order EWPT in the 2HDM is m_{A_{0}}>m_{H_{0}}+m_{Z}.

Gravitational waves from a first-order electroweak phase transition: a brief review.

We review the production of gravitational waves by an electroweak first-order phase transition. The resulting signal is a good candidate for detection at next-generation gravitational wave detectors, such as LISA. Detection of such a source of gravitational waves could yield information about physics beyond the Standard Model that is complementary to that accessible to current and near-future collider experiments. We summarize efforts to simulate and model the phase transition and the resulting production of gravitational waves.This article is part of the Theo Murphy meeting issue 'Higgs cosmology'.

What is the Minimum Clinically Important Difference for the WOMAC Index After TKA?

BACKGROUND: The WOMAC score is a validated outcome measure for use in patients undergoing TKA. Defining meaningful changes in the WOMAC score is important for sample-size calculations in clinical research and for interpreting published studies. However, inconsistencies among published studies regarding key definitions for changes in the WOMAC score after TKA potentially could result in incorrectly powered studies and the misinterpretation of clinical research results. QUESTIONS/PURPOSES: (1) To identify the minimum clinically important difference (MCID) for the total WOMAC score and its components 1 year after TKA using an anchor-based methodology. (2) To define the minimum important change (MIC) and the minimum detectable change with 95% confidence (MDC95) for the total WOMAC score and its components 1 year after TKA. METHODS: Between 2003 and 2013, 3641 patients underwent primary TKA at one center. Of those, 460 patients (13%) were excluded from this retrospective study for prespecified reasons (mainly secondary OA and bilateral surgery), and 592 patients (16%) were either lost to followup or could not be included because of incomplete questionnaires. WOMAC scores were recorded preoperatively and at 1 year postoperatively. Patient demographics and preoperative Short Form-12 and WOMAC scores were no different for the 16% of patients who were lost to followup or failed to complete 1-year questionnaires and the study cohort (n = 2589). At 1 year, patients were asked "How much did the knee replacement surgery improve the quality of your life?" Their responses were recorded as: a great improvement, moderate improvement, little improvement, no improvement at all, or the quality of my life is worse. The MCID was defined as the difference in the mean change in the WOMAC score between patients with no improvement compared with those with little improvement according to the anchor question. The MIC was defined as the change in the WOMAC score relative to the baseline score for patients who reported a little improvement in their quality of life. The MDC is the smallest change for an individual who is likely to be beyond the measurement error of the scoring tool and represents true change rather than variability in the scoring measure; we report it with 95% confidence bounds defining real change rather than variability in the scoring measure (MDC95). We calculated this with distribution-based methods for the whole cohort. Patients recording a little improvement (n = 211) and no improvement (n = 115) were used as anchor responses to calculate the MCID (using regression analysis to adjust for potential confounding variables such as age, gender, BMI and preoperative Short Form-12 or WOMAC scores) and the MIC (using receiver operative characteristics curves). RESULTS: After adjusting for confounding variables such as age, gender, BMI as well as preoperative Short Form-12 and WOMAC scores, the MCID was 11 for pain, 9 for function, 8 for stiffness and 10 for the total WOMAC score. The MIC was 21 for pain, 16 for function, 13 for stiffness and 17 for the total WOMAC score. The MDC95 was 23 for pain, 11 for function, 27 for stiffness and 12 for the total WOMAC score. CONCLUSIONS: The MCID and MIC for the WOMAC score represent the smallest meaningful effect sizes when comparing the outcome of two groups (difference in mean change between the groups) or when assessing a cohort (a change in score for the group) after TKA, respectively, helping the reader to distinguish between a clinically important effect size and a mere statistical difference. We determined that the error in measurement (based on the MDC95) for the function component and total WOMAC scores were less than the MIC, which suggests changes beyond the MIC are clinically real and not due to uncertainty in the score. These parameters are essential to interpret TKA outcomes research and to ensure clinical research studies are amply powered to detect meaningful differences. Future studies using the WOMAC score to assess TKA outcomes should report not only the statistical significance (a p value) but also the clinical importance using the reported MCID and MIC values. LEVEL OF EVIDENCE: Level III, diagnostic study.

The WOMAC score can be reliably used to classify patient satisfaction after total knee arthroplasty.

PURPOSE: The primary aim of this study was to define a classification in the WOMAC score after total knee arthroplasty (TKA) according to patient satisfaction. The secondary aims were to describe patient demographics for each level of satisfaction. METHODS: A retrospective cohort consisting of 2589 patients undergoing a primary TKA were identified from an established arthroplasty database. Patient demographics, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and short form (SF) 12 scores were collected pre-operatively and 1 year post-operatively. In addition, patient satisfaction was assessed at 1 year with four responses: very satisfied, satisfied, dissatisfied or very dissatisfied. Receiver operating characteristic (ROC) curves were used to identify values in the components and total WOMAC scores that were predictive of each level of satisfaction, which were used to define the categories of excellent, good, fair and poor. RESULTS: At 1 year, there were 1740 (67.5%) very satisfied, 572 (22.2%) satisfied, 190 (7.4%) dissatisfied and 76 (2.9%) very dissatisfied patients. ROC curve analysis identified excellent, good, fair and poor categories for the pain (> 78, 59-78, 44-58, < 44), function (> 72, 54-72, 41-53, < 41), stiffness (> 69, 56-69, 43-55, < 43) and total (> 75, 56-75, 43-55, < 43) WOMAC scores, respectively. Patients with lung disease, diabetes, gastric ulcer, kidney disease, liver disease, depression, back pain, with worse pre-operative functional scores (WOMAC and SF-12) and those with less of an improvement in the scores, had a significantly lower level of satisfaction. CONCLUSION: This study has defined a post-operative classification of excellent, good, fair and poor for the components and total WOMAC scores after TKA. The predictors of level of satisfaction should be recognised in clinical practice and patients at risk of a lower level of satisfaction should be made aware in the pre-operative consent process. LEVEL OF EVIDENCE: III.