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Renal fibrosis, a detrimental feature of irreversible kidney damage, remains a sinister consequence of long-term calcineurin inhibitor (CNI) immunosuppressive therapy. Our study not only incorporates renal fibroblasts into the growing list of cell types negatively impacted by CNIs but also identifies renal fibroblast-to-myofibroblast transition as a process mediated via a TGF-β-dependent mechanism. This insight will direct future studies investigating the feasibility of inhibiting TGF-β signaling to maintain CNI-mediated immunosuppression while ultimately preserving kidney health.

Objectives This study was aimed to describe the interviewer-assessed measures present in the 2015/2016 Round of National Social Life, Health, and Aging Project (NSHAP), outline strengths of interviewer-assessed measures, and explore how interviewer assessments in the domains of home environment and personal characteristics are associated with older adult health. Method Data come from the 2015/2016 Round of the NSHAP. Results We provide descriptive results from the interviewer assessments of personal attributes, indoor home environment, and outdoor residential context. We present an illustrative analysis of reports of falls, a health outcome that might be predicted by characteristics assessed by the interviewer, and we suggest directions for further research. Discussion Interviewer assessments collected in NSHAP are useful as proxy measures and can be used in combination with respondent’s reports and ecological measures to generate insights into healthy aging.

Objectives Our primary objective was to examine the distribution of 3-m usual walk, five repeated chair stands, and three static balance stance performances among age and gender subgroups of adults at least 65 years in two national data sets. We secondarily determined whether demographic–function associations varied across data sets, birth cohorts, or models incorporating data from those “unable to do” tasks. Methods Two nationally representative data sets were used to generate survey weight-adjusted performance distributions: the 2015–2016 National Social Life Health and Aging Project and the 2016 National Health and Aging Trends Study. We then regressed walk and chair stand performance on age, gender, and race/ethnicity, examining differences across data sets, birth cohorts (1920–1947, 1948–1965), and before/after incorporating the “unable to do” performers. Results Findings confirmed the gradual decline in function with age and allowed estimation of “relative” performance within age/gender subgroups. Data set distribution differences were noted, possibly due to recruitment, eligibility, and protocol variations. Demographic associations were similar across data sets but generally weaker among the 1948–1965 cohort and in models including the sizable “unable to do” group. Discussion We present the largest, most current Short Physical Performance Battery reference data in U.S. adults aged 65 or older. Findings support standardization of administration protocols in research and clinical care and differentiating absolute from relative performance.

Objectives In this article, we present the theoretical framework that guided the development of the National Social Life, Health, and Aging Project (NSHAP) including the measures of social health. We discuss the literature that links social measures to other outcomes, and we discuss in detail how researchers might construct common measures of social health, including those that reflect social relationships, sexuality, social networks, social resources, and social participation. Methods The NSHAP includes multiple detailed measures of social health, collected in the rounds of data collection carried out in 2005, 2010, and 2015, allowing for study of changes over time and as people age among a nationally representative sample of the community-dwelling population of older adults in the United States. Results We define indicators of social health, describe measures of each in the 2015 round of NSHAP, and show the distribution of the measures by gender and age. We present scales of dimensions of social health that have been developed elsewhere and describe their properties. Discussion We briefly discuss the distribution of these measures by age and gender in the 2015 round of NSHAP. Simple analyses of these categorized measures reveal differences by age and gender that deserve closer attention in future investigations using the NSHAP data.

Nitrogen pollution of surface water systems is becoming a global problem, especially within river networks that receive run-off from agricultural land. Methods such as riparian buffering and the co...

Hearing impairment impacts fluidity of communication and social interactions and thus may contribute to loneliness. We investigated the cross-sectional association between hearing impairment and loneliness in community-dwelling older U.S. adults using data from the National Social Life, Health, and Aging Project ( N = 3,196). Individuals reporting fair/poor hearing had 50% (95% confidence interval [CI] = [1.09–2.05]) higher odds of any loneliness compared with those reporting excellent hearing after adjusting for comorbidity index, functional and cognitive ability, self-reported health, and demographic characteristics. Test for trend suggests a dose–response relationship over levels of hearing impairment. Hearing impairment is highly prevalent and may be an important target for consideration in interventions to reduce loneliness. Further investigation of whether treatment of hearing impairment alleviates loneliness and its disabling effects is also needed.

BACKGROUND/OBJECTIVES Prognostic indices rarely include cognition. We determined if a comprehensive cognitive screen or brief individual items were associated with improved mortality predictions of a widely used prognostic index. DESIGN, SETTING, AND PARTICIPANTS The National Social Life Health and Aging Project Wave 2, a nationally representative, cross-sectional, in-home survey conducted in 2010 to 2011 on 3,199 community-dwelling adults aged 60 to 99 years. MEASUREMENTS Cognition was measured using a Survey-Adapted Montreal Cognitive Assessment (MoCA-SA) grouped into three screened categories: screen normal (≥24 points), screen positive for mild cognitive impairment (18-23 points), and screen positive for dementia (

A large number of older adults have physical and/or cognitive challenges and require help to manage everyday activities. Many older adults receive care from a spouse. Over the long term, this has adverse consequences for caregiver health and well-being. Less is known about the outcomes associated with the early transition to becoming a spousal caregiver. Nor is it clear how mild-cognitive decline worsens caregiver outcomes. The present study uses dyadic data from 588 couples in the National Social Life, Health, and Aging Project to compare mental and social well-being in marital partners who became a spousal caregiver versus those who remained noncaregivers or became caregivers for someone other than a spouse between 2010 and 2015. Cognitive ability was assessed using a validated version of the Montreal Cognitive Assessment. Moderated Actor-Partner Independence Models revealed that becoming a caregiver was associated with an increase in perceived stress in both men and women, and an increase in anxiety among men. Partners' cognitive limitations moderated, in a dose-dependent fashion, the association between becoming a caregiver and changes in well-being. Specifically, becoming a caregiver was associated with increased support from friends for wives at lower levels of husband's cognitive ability, and with increased anxiety for husbands at lower levels of wife's cognitive ability. Associations were independent of demographic characteristics and physical limitations. We discuss the value of using population-based samples to study the transition to caregiving and implications for interventions during the early transition to a caregiving role for even modestly cognitively impaired partners. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

SummaryThe budding yeast, Saccharomyces cerevisiae, has emerged as a model system for studying the aging processes in eukaryotic cells. However, the full complement of tools available in this organism has not been fully applied, in part because of limitations in throughput that restrict the ability to carry out detailed analyses. Recent advances in microfluidics have provided direct longitudinal observation of entire yeast lifespans, but have not yet achieved the normal scale of operation possible in this model system. Here we present a microfluidic platform, called the Yeast Lifespan Machine, where we combine improvements in microfluidics, image acquisition, and image analysis tools to increase robustness and throughput of lifespan measurements in aging yeast cells. We demonstrate the platform’s ability to measure the lifespan of large populations of cells and distinguish long- and short-lived mutants, all with minimal involvement of the experimenter. We also show that environmental pH is capable of significantly modulating lifespan depending on the growth media, highlighting how microfluidic technologies reveal determinants of lifespan that are otherwise difficult to ascertain.

BACKGROUND: Functional gastroduodenal disorders include functional dyspepsia, chronic nausea and vomiting syndromes, and gastroparesis. These disorders are common, but their overlapping symptomatology poses challenges to diagnosis, research, and therapy. This study aimed to introduce and validate a standardized patient symptom-logging system and App to aid in the accurate reporting of gastroduodenal symptoms for clinical and research applications. METHODS: The system was implemented in an iOS App including pictographic symptom illustrations, and two validation studies were conducted. To assess convergent and concurrent validity, a diverse cohort with chronic gastroduodenal symptoms undertook App-based symptom logging for 4 h after a test meal. Individual and total post-prandial symptom scores were averaged and correlated against two previously validated instruments: PAGI-SYM (for convergent validity) and PAGI-QOL (for concurrent validity). To assess face and content validity, semi-structured qualitative interviews were conducted with patients. KEY RESULTS: App-based symptom reporting demonstrated robust convergent validity with PAGI-SYM measures of nausea (rS =0.68), early satiation (rS =0.55), bloating (rS =0.48), heartburn (rS =0.47), upper gut pain (rS =0.40), and excessive fullness (rS =0.40); all p

Objectives Elder mistreatment has negative consequences for older adults’ health and well-being. As such, scholars aim to understand its causes, the contexts in which it occurs, how to prevent victimization, and how to design interventions for mistreated older adults. This paper provides a detailed overview of the 2015–2016 National Social Life, Health, and Aging Project (NSHAP) Round 3 Elder Mistreatment Module (EMM) to encourage further research on the topic. Method This paper reviews previous elder mistreatment scholarship, describes the EMM, provides descriptive analyses of elder mistreatment among community-dwelling older adults, and discusses promising approaches and limitations to future research with these data. Results The EMM includes 10 stem questions to measure elder mistreatment behaviors experienced since age 60 and 2 follow-up questions about perceived severity and the identity of the perpetrator. The stem questions can be analyzed individually or combined into a scale, and researchers can account for severity as a robustness check. Analysts can also group the measures into specific types of elder mistreatment. A major strength of the EMM is its ability to identify perpetrators in victims’ core social networks. Discussion The NSHAP Round 3 EMM provides scholars an opportunity to study older Americans’ mistreatment experiences, particularly as they relate to their physical and mental health, their social networks and personal relationships, and their broader social contexts.

Objectives In this article, we seek to provide assistance to those who might want to use data from the National Social Life, Health, and Aging Project (NSHAP) Rounds 1–3 to compare those born in different cohorts. We outline 2 theoretical models that underlie the design of NSHAP—the life course model and the birth cohorts model—and review examples of social and political changes that may have differentially affected cohorts of older adults. Then we present 2 ways that NSHAP data might be used to compare cohorts, show examples of analyses of cohort differences in measures in NSHAP, and discuss features of the data that might affect their use for this purpose. Methods Round 3 of the NSHAP added a group of respondents born between 1948 and 1965, the Baby Boom. Together with data from an earlier cohort, interviewed in Rounds 1–3, these data allow analysis of birth cohorts of older adults in the United States. We show examples of some approaches. Results Our age-matched cohort differences approach included all observations where the respondent was aged 57–67 at the time of interview in different time periods (3,816 observations overall; 2,316 for the Silent Generation cohort and 1,500 for the Baby Boom cohort). Our second approach, age, period, and cohort effects, models the effects of age and birth year using restricted cubic splines, with one model excluding the linear effect of birth year, and the other excluding the linear effect of period. We present examples of analyses using each of these methods. Discussion We describe features of the NSHAP data of which researchers should be aware when conducting cohort analyses with these data.

Free-living nitrogen-fixing bacteria can improve growth yields of some non-leguminous plants and, if enhanced through bioengineering approaches, have the potential to address major nutrient imbalances in global crop production by supplementing inorganic nitrogen fertilisers. However, nitrogen fixation is a highly resource-costly adaptation and is de-repressed only in environments in which sources of reduced nitrogen are scarce. Here we investigate nitrogen fixation (nif) gene expression and nitrogen starvation response signaling in the model diazotroph Klebsiella oxytoca (Ko) M5a1 during ammonium depletion and the transition to growth on atmospheric N2. Exploratory RNA-sequencing revealed that over 50% of genes were differentially expressed under diazotrophic conditions, among which the nif genes are among the most highly expressed and highly upregulated. Isotopically labelled QconCAT standards were designed for multiplexed, absolute quantification of Nif and nitrogen-stress proteins via multiple reaction monitoring mass spectrometry (MRM-MS). Time-resolved Nif protein concentrations were indicative of bifurcation in the accumulation rates of nitrogenase subunits (NifHDK) and accessory proteins. We estimate that the nitrogenase may account for more than 40% of cell protein during diazotrophic growth and occupy approximately half the active ribosome complement. The concentrations of free amino acids in nitrogen-starved cells were insufficient to support the observed rates of Nif protein expression. Total Nif protein accumulation was reduced 10-fold when the NifK protein was truncated and nitrogenase catalysis lost (nifK1–1203), implying that reinvestment of de novo fixed nitrogen is essential for further nif expression and a complete diazotrophy transition. Several amino acids accumulated in non-fixing ΔnifLA and nifK1–1203 mutants, while the rest remained highly stable despite prolonged N starvation. Monitoring post-translational uridylylation of the PII-type signaling proteins GlnB and GlnK revealed distinct nitrogen regulatory roles in Ko M5a1. GlnK uridylylation was persistent throughout the diazotrophy transition while a ΔglnK mutant exhibited significantly reduced Nif expression and nitrogen fixation activity. Altogether, these findings highlight quantitatively the scale of resource allocation required to enable the nitrogen fixation adaptation to take place once underlying signaling processes are fulfilled. Our work also provides an omics-level framework with which to model nitrogen fixation in free-living diazotrophs and inform rational engineering strategies.

BACKGROUND: Social isolation and loneliness are critical to the health of older adults, but they have not been well-described at the end of life. OBJECTIVES: To determine the prevalence and correlates of social isolation and loneliness among older adults in the last years of life. DESIGN: Nationally-representative, cross-sectional survey. SETTING: Health and Retirement Study, 2006–2016 data. PARTICIPANTS: Adults age >50 interviewed once in the last four years of life (n=3,613). MEASUREMENTS: We defined social isolation using a 15-item scale measuring household contacts, social network interaction, and community engagement, and frequent loneliness using the 3-item UCLA Loneliness Scale. We used multivariable logistic regression to determine their adjusted prevalence by time prior-to-death and by subgroups of interest. RESULTS: Approximately 19% experienced social isolation, 18% loneliness, and 5% both in the last four years of life (correlation=0.11). The adjusted prevalence of social isolation was higher for individuals nearer to death (4 years: 18% vs 0–3 months: 27%, p=0.05) and there was no significant change in loneliness (4 years: 19% vs 0–3 months: 23%, p=0.13). Risk factors for both isolation and loneliness included (p

Background and Objectives Elder mistreatment victims at risk of poor physical and psychological health may benefit from increased social support. This article identifies mistreatment victims among community-dwelling older Americans and maps their social networks to guide the design of social support interventions. Research Design and Methods Using nationally representative survey data from Wave 3 (2015–2016) of the National Social Life, Health, and Aging Project (N = 2,334) and descriptive, latent class, and regression analyses, we estimate the prevalence of mistreatment since age 60, identify the alleged perpetrators’ relationships to the victims, and examine victims’ social networks. Results Self-reported lifetime prevalence of elder mistreatment is as high as 21%, depending on the mistreatment behavior measured. Latent class analysis reveals two mistreatment classes: 12% of older adults experienced multiple types of mistreatment (polyvictimization), and 6% experienced primarily financial mistreatment. Although alleged perpetrators are unlikely to appear in older adults’ core social networks, the most commonly reported perpetrators are children and relatives. Regression analyses show that experiencing mistreatment since age 60 is associated with having less current social support, more social strain, and fewer kin in the core social network. Older adults reporting polyvictimization also have less-dense core networks. Discussion and Implications Increasing family support should be done cautiously because children and relatives are frequently named as mistreatment perpetrators. Increasing communication across polyvictimization victims’ network members may support their well-being. Providing outside assistance with financial management could benefit financial mistreatment victims.

ObjectiveWe describe each childhood background measure available in the National Social Life, Health, and Aging Project (NSHAP), report preliminary population estimates for each measure by age and gender, and validate the childhood measures by showing that the associations between the NSHAP childhood measures and later-life health outcomes are consistent with previous studies on this topic.MethodChildhood background measures included family life happiness, family structure, parental educational attainment, perceived financial situation, experience of violence, witness of violence, childhood health, and place of birth. We measured self-rated health, depressive symptoms, and social support to assess later-life physical, mental, and social health. Logistic and linear regression models were used for the binary and continuous outcome variables, respectively.ResultsOlder age groups were more likely than those in younger age groups to report a poor financial situation in childhood, lower parental education, and intact family structure and were less likely to have experienced or witnessed a violent event as a child. Growing up in a happy and well-educated family was associated with better physical, mental, and social health in older ages.DiscussionNSHAP childhood data included a variety of measures assessing the family social environment during childhood, providing a valuable resource for the study of early-life determinants of health and well-being over the life course.

Objectives This article examines the association between cognitive impairment, including mild cognitive impairment (MCI) and early dementia (ED), and sexual activity in a large, longitudinal sample of community-dwelling older adults. We focus here on sexual activity, which includes both sexual activity with a partner and masturbation. Methods We analyzed 3,777 older individuals and members of 955 intimate dyads using the National Social Life, Health, and Aging Project (2010 and 2015). We used ordered probit regression, cross-lagged panels models, and probit regression. Results We find that older adults with cognitive limitations, either MCI or ED, are about as likely to be sexually active with a partner as those with normal cognitive function. This is the case both in the cross-section and longitudinally. Both men and women with ED are less likely to have masturbated, however. Among married and cohabiting couples, we find no association between cognitive impairment in either the husband, the wife, or in both partners and their joint sexual activity. Women whose measured cognitive function is lower than their husbands are less likely to report any masturbation. Discussion Sex with a partner, a fundamentally social activity, seems to be conserved in the face of cognitive limitation but masturbation, a solitary activity, does not. We argue that the intimate dyad plays an important role in conserving partnered sexual activity. Results can inform strategies to maintain the sexual well-being of older adults with cognitive impairment and their partners as part of overall strategies to improve quality of life.

In this chapter, we review current and foundational research on sexuality in older adulthood. We briefly review neuroendocrine perspectives, sexual script theory, and interdisciplinary biopsychosocial frameworks, as a prelude to summarizing current work on sexual interest, attitudes towards sex, sex as a dyadic phenomenon, health and well-being outcomes, and sexual satisfaction. At each stage, we draw out lessons that the field should use to frame new investigations. We close with recommendations for future research directions, particularly around researching a greater range of gender and sexual identities, employing new modes of data collection, and recognizing the importance of international and intercultural comparisons. We find that the field has grown empirically, and in theoretical sophistication over the past several decades. However, new social and demographic changes require researchers to press forward into new topics, and with greater methodological sophistication.

/////////////~~~ ~~~~~~~~~~ The United States is a religious nation. The vast majority of Americans, when asked, profess a belief in God and affi rm that religion is at least "fairly impor- tant" in their lives (Myers 2000, 285); about three-fi fths of the population reports membership in a religious organization and 45 percent state that they attend religious services at least monthly (Sherkat and Ellison 1999). Almost all established religions encourage marriage and parenthood, and provide both guidance and support in these key tasks of adulthood. So it is no surprise that married adults and parents of school-age children are more likely to belong to and participate in religious organizations than are those who are not married. Indeed, a good deal of religious practice and religious observance takes place within the family or jointly with family members. Parents may take their chil- dren to church, say grace at meals, or prayers at bedtime. Spouses may attend services together or pray together at home (Schmidt 2005). In this study we use the National Survey of Families and Households (NSFH) to explore the social and demographic characteristics associated with religious intermarriage, homogamy, and conversion. 1 We examine changes across marriage cohorts in the chances of in-marriage, intermarriage and con- version, and explore changes over time in the impact of religious denomina- tion on marital homogamy.

The modern history of North Atlantic sea surface temperature shows variability coinciding with changes in air temperature and rainfall over the Northern Hemisphere. There is a debate about this variability and, in particular, whether it is internal to the ocean‐atmosphere system or is forced by external factors (natural and anthropogenic). Here we present a temperature record, obtained using the Sr/Ca ratio measured in a skeleton of a sclerosponge, that shows agreement with the instrumental record over the past 150 years as well as multidecadal temperature variability over the last 600 years. Comparison with climate simulations of the last millennium shows that large cooling events recorded, in the sclerosponge, are consistent with natural (primarily volcanic activity) and anthropogenic forcings. There are, however, multidecadal periods not connected to current estimates of external forcing over the last millennium allowing for alternative explanations, such as internally driven changes in ocean and atmospheric circulation.

Objectives This report introduces National Social Life, Health, and Aging Project (NSHAP) data users to 2 new measures—one that assesses older adults’ resilience, defined as personal attributes that indicate an adaptive reserve that can be drawn on during adversity, and a second that expands on existing measures of social support received from others to also assess social support given to close others. Method Data from 4,604 NSHAP respondents born 1920–1965 were used to conduct psychometric analyses and validation of our measures of resilience and social support-giving. Results Scale reliabilities were acceptable for the 4-item resilience scale, and the 2-item scales for family support-giving and friend support-giving. The 2 spousal support-giving items did not cohere well as a single scale. The resilience scale exhibited significant correlations with criterion validation variables, even after adjusting for correlated personality traits. The support-giving scales, and the spousal support-giving items, also exhibited significant correlations with criteria, and with the resilience scale, even after adjusting for social support receipt. Scale means exhibited demographic differences. Discussion The resilience and social support-giving measures have acceptable psychometric characteristics (with the exception of spousal support-giving), convergent validity, and predictive utility net of related variables. NSHAP data users are offered several suggestions (key points) in the use of these measures in future research.

Introduction There has been little work on the relationship between sarcopenia, a progressive skeletal muscle disorder, and age-related neurodegenerative diseases such as Parkinson's disease (PD). Objectives We aimed to determine: 1) the feasibility of characterizing skeletal muscle across a range of cognitive function in PD; 2) if muscle mitochondrial respiratory chain (MRC) function and content are preserved in older adults with PD. Methods Sarcopenia was defined using handgrip strength, chair rise and bioimpedance analysis. MRC function was assessed using phosphorous magnetic resonance spectroscopy (MRS) by estimating τ1/2 PCr (s) (phosphocreatine half-time recovery) in the calf muscles following a bout of aerobic exercise. Biopsy of the vastus lateralis muscle was performed, and MRC content assessed by fluorescent immunohistochemistry for porin and components of MRC Complexes I and IV. Results Nine participants (78% male; mean age 79.9; PD duration 3.3 years) were recruited. Four had cognitive impairment. Six participants had probable sarcopenia. Eight participants completed MRS and had mean (SD) τ1/2 PCr of 37.8 (7.6) seconds, suggesting preserved mitochondrial function. Muscle biopsies were obtained in all and the procedure was well tolerated. Porin Z-score, a proxy for mitochondrial mass, was lower than expected compared to controls (0–89% of fibres with low porin). There was a small amount of Complex I (0.16–4.59%) and Complex IV (0–3.79%) deficiency. Conclusions Detailed phenotyping, muscle biopsy and imaging was feasible and acceptable across a spectrum of cognitive function in PD. Sarcopenia was relatively common and may be associated with lower mitochondrial mass and low levels of MRC deficiency.

Global imbalances of the nitrogen cycle are increasingly recognized as a major challenge to human development, and are exacerbated by the use of synthetic inorganic fertilizers. Biotechnology alternatives to inorganic fertilizers include biofertilisation from nitrogen fixing bacteria (diazotrophs), expressing nitrogenase and auxiliary genes (nif genes). In order to directly quantify all twenty Nif proteins through multiple reaction monitoring (MRM) MS, we established a high throughput pipeline to generate a set of Klebsiella oxytoca Nif protein QconCATs as quantotypic standards. A stringent validation of the pipeline and QconCATs application with regards to isotopic labelling efficiency (100%), limits of detection and quantification, analyte to internal standard concentration boundaries was used for optimisation. Using three QconCATs for the measurement of 20 likely low, middle and high Nif protein abundances enabled detection of all Nif proteins, 19 of which could be accurately quantified and their variation over time monitored. Stoichiometries between Klebsiella oxytoca Nif proteins and changes between early and late transition into diazotrophy suggest i) a temporal regulation of nif gene cluster expression that may be linked to nitrogenase expression and maturation; ii) vast disparities in Nif protein abundances and iii) high dependency on the nifLA master regulator pair for nif gene expression.

Background Frailty is associated with lower mean activity; however, hourly activity is highly variable among older individuals. We aimed to relate frailty to hourly activity variance beyond frailty’s association with mean activity. Method Using the 2010–2011 National Social Life, Health and Aging Project wrist accelerometry data (n = 647), we employed a mixed-effects location scale model to simultaneously determine whether an adapted phenotypic frailty scale (0–4) was associated with the log10-mean hourly counts per minute (cpm) and between-and within-subject hourly activity variability, adjusting for demographics, health characteristics, season, day-of-week, and time-of-day. We tested the significance of a Frailty × Time-of-day interaction and whether adjusting for sleep time altered relationships. Results Each additional frailty point was associated with a 7.6% (10–0.0343, β = −0.0343; 95% CI: −0.05, −0.02) lower mean hourly cpm in the morning, mid-day, and late afternoon but not evening. Each frailty point was also associated with a 24.5% (e0.219, β = 0.219; 95% CI: 0.09, 0.34) greater between-subject hourly activity variance across the day; a 7% (e0.07, β = 0.07; 95% CI: 0.01¸ 0.13), 6% (e0.06, β = 0.06; 95% CI: 0, 0.12), and 10% (e0.091, β = 0.091; 95% CI: 0.03, 0.15) greater within-subject hourly activity variance in the morning, mid-day, and late afternoon, respectively; and a 6% (e−0.06, β = −0.06; 95% CI: −0.12, −0.003) lower within-subject hourly activity variance in the evening. Adjusting for sleep time did not alter results. Conclusions Frail adults have more variable hourly activity levels than robust adults, a potential novel marker of vulnerability. These findings suggest a need for more precise activity assessment in older adults.

Phenotypic heterogeneity in clonal bacterial batch cultures is an important adaptive strategy to changing environments, including in diazotrophs with the unique capacity to convert di-nitrogen into bio-available ammonium. In diazotrophicKlebsiella oxytocawe simultaneously measured mRNA levels of key regulatory (glnK-amtB, nifLA) and structural (nifHDK) operons required for establishing nitrogen fixation, using dual molecule, single cell RNA-FISH. Through stochastic transcription models and mutual information analysis we revealed likely molecular origins for heterogeneity in nitrogenase expression. In wildtype and regulatory variant strains we inferred contributions from intrinsic and extrinsic noise, finding thatnifHDKtranscription is inherently bursty, but that noise propagation through signalling is also significant. The regulatory geneglnKhad the highest discernible effect onnifHDKvariance, while noise from factors outside of the regulatory pathway were negligible. Results provide evidence that heterogeneity is a fundamental property of this regulatory system, indicating potential constraints for engineering homogeneous nitrogenase expression.

BACKGROUND The Montreal Cognitive Assessment (MoCA) has not been administered to a representative national sample, precluding comparison of patient scores to the general population and for risk factor identification. METHODS A validated survey-based adaptation of the MoCA (MoCA-SA) was administered to a probability sample of home-dwelling US adults aged 62 to 90, using the National Social Life, Health, and Aging Project (n=3129), yielding estimates of prevalence in the United States. The association between MoCA-SA scores and sociodemographic and health-related risk factors were determined. RESULTS MoCA-SA scores decreased with age, and there were substantial differences among sex, education, and race/ethnicity groups. Poor physical health, functional status, and depression were also associated with lower cognitive performance; current health behaviors were not. Using the recommended MoCA cut-point score for Mild Cognitive Impairment (MoCA score

Background Older adults receive important health benefits from more robust social capital. Yet, the mechanisms behind these associations are not fully understood. Some evidence suggests that higher levels of social capital ultimately affect health through alterations in physical activity (PA), but most of this research has relied on self-reported levels of PA. The aim of this study was to determine whether components of social capital, including social network size and composition as well as the frequency of participation in various social and community activities, were associated with accelerometry-measured PA levels in a nationally representative sample of community-dwelling older adults (≥ 62 years). Methods We conducted a cross-sectional analysis using data from the wrist accelerometry sub-study (n = 738) within Wave 2 of the National Social, Health, and Aging Project (NSHAP), a population-based longitudinal study that collects extensive survey data on the physical, cognitive, and social health of older adults. Participants’ physical activity was measured with a wrist accelerometer worn for 72 consecutive hours. We related seven, self-reported social relationship variables (network size, network proportion friends, and frequencies of socializing with friends and family, visiting with neighbors, attending organized group meetings, attending religious services, and volunteering) to accelerometer-measured PA (mean counts-per-minute) using multivariate linear regression analysis, while adjusting for potential confounders. Results Larger social networks (p = 0.042), higher network proportion friends (p = 0.013), more frequent visiting with neighbors (p = 0.009), and more frequent attendance at organized group meetings (p = 0.035) were associated with higher PA levels after controlling for demographic and health covariates. Volunteering was significant prior to adjusting for covariates. No significant associations were found between frequencies of socializing with friends and relatives or attendance at religious services and PA. Conclusions This study suggests social capital is significantly related to objectively measured PA levels among older adults, and that friendships as well as social participation in groups and with neighbors may be particularly pertinent to PA. These findings expand our understanding of and offer a potential mechanism linking social relationships and overall health among older adults. They also have implications for how we might motivate older adults to be more physically active. Electronic supplementary material The online version of this article (10.1186/s12889-018-5664-6) contains supplementary material, which is available to authorized users.

Although the Sr/Ca ratio in the skeletons of sclerosponges appears to be robustly correlated with water temperature, the measurement of Sr/Ca ratios from several specimens by different workers yields unexpectedly large (up to 5 °C) increases in temperature over the past 150 years. This is considerably greater than spatially and temporally averaged observational temperature increases. One possible culprit for the larger than anticipated temperature changes in these samples arises from the calibration between temperature and Sr/Ca ratios of the skeleton that was derived from specimens grown in a relatively narrow range of high temperatures (26 to 30 °C). In order to improve the calibration, we acquired a number of samples of sclerosponges collected at lower average water temperatures (different localities and deeper water depths), and combined measurements of the Sr/Ca ratios from bulk samples representing the last ~15 years of growth with the previous calibration dataset. Analyses of these samples have produced a revised relationship between temperature and Sr/Ca ratios in the skeletons of sclerosponges. Application of this new calibration equation to published sclerosponge data reduces the magnitude of the increase in temperature reconstructed from Sr/Ca ratios to values in better agreement with spatially and temporally gridded observational ocean temperature data sets. However, the acceleration of warming indicated by nearly all Caribbean sclerosponge records over the last several decades remains unchanged by this revised calibration.

Heritable Disorders of Connective Tissue (HDCTs) are syndromes that disrupt connective tissue integrity. They include Osteogenesis Imperfecta (OI), Ehlers Danlos Syndrome (EDS), Marfan Syndrome (MFS), Loeys-Dietz Syndrome (LDS), Epidermolysis Bullosa (EB), Stickler Syndrome (STL), Wagner Syndrome, and Pseudoxanthoma Elasticum (PXE). Because many patients with HDCTs have ocular symptoms, commonly myopia, they will often present to the clinic seeking refractive surgery. Currently, corrective measures are limited, as the FDA contraindicates laser-assisted in-situ keratomileusis (LASIK) in EDS and discourages the procedure in OI and MFS due to a theoretically increased risk of post-LASIK ectasia, poor wound healing, poor refractive predictability, underlying keratoconus, and globe rupture. While these disorders present with a wide range of ocular manifestations that are associated with an increased risk of post-LASIK complications (e.g., thinned corneas, ocular fragility, keratoconus, glaucoma, ectopia lentis, retinal detachment, angioid streaks, and ocular surface disease), their occurrence and severity are highly variable among patients. Therefore, an HDCT diagnosis should not warrant an immediate disqualification for refractive surgery. Patients with minimal ocular manifestations can consider LASIK. In contrast, those with preoperative signs of corneal thinning and ocular fragility may find the combination of collagen cross-linking (CXL) with either photorefractive keratotomy (PRK), small incision lenticule extraction (SMILE) or a phakic intraocular lens (pIOL) implant to be more suitable options. However, evidence of refractive surgery performed on patients with HDCTs is limited, and surgeons must fully inform patients of the unknown risks and complications before proceeding. This paper serves as a guideline for future studies to evaluate refractive surgery outcomes in patients with HDCTs.

The plant pathogen Pseudomonas syringae pv. tomato DC3000 uses a type III secretion system (T3SS) to transfer effector proteins into the host. The expression of T3SS proteins is controlled by the HrpL σ factor. Transcription of hrpL is σ54-dependent and bacterial enhancer-binding proteins HrpR and HrpS coactivate the hrpL promoter. The HrpV protein imposes negative control upon HrpR and HrpS through direct interaction with HrpS. HrpG interacts with HrpV and relieves such negative control. The sequence alignments across Hrp group I-type plant pathogens revealed conserved HrpV and HrpG amino acids. To establish structure–function relationships in HrpV and HrpG, either truncated or alanine substitution mutants were constructed. Key functional residues in HrpV and HrpG are found within their C-terminal regions. In HrpG, L101 and L105 are indispensable for the ability of HrpG to directly interact with HrpV and suppress HrpV-dependent negative regulation of HrpR and HrpS. In HrpV, L108 and G110 are major determinants for interactions with HrpS and HrpG. We propose that mutually exclusive binding of HrpS and HrpG to the same binding site of HrpV governs a transition from negative control to activation of the HrpRS complex leading to HrpL expression and pathogenicity of P. syringae.

Background and objectives Although the role of place on health is not new, less is known about how place matters for cognition. By investigating both neighborhood and home as the sociospatial realms of older adults, we explore associations between health and place across multiple contexts. We also distinguish objective and subjective measures of place and disentangle their differential associations with cognition. Research design and methods We analyzed place effects on cognition from the National Social Life, Health, and Aging Project (N = 2,260) linked to neighborhood characteristics and crime data. We measured place in four ways: (a) objective indicators of neighborhood such as police-reported crime rates and interviewer-reported on presence of disordered conditions on the streets; (b) perceptions of neighborhood by respondents (perceived danger and social cohesion); (c) objective conditions of home (interviewer's report on presence of clutters, odor, and messiness); (4) perceived social support, strain, and threat by household members. The MoCA-SA was used to assess cognitive functioning. Results Subjective interpretations appeared to have more direct effects on cognition than did objective indicators of neighborhood or home. When examining these living environments together, we found the association between neighborhood and cognition is partially explained by characteristics of home environment, especially perceived social support. We found a buffering effect of social support on cognition for women, not for men. Discussion and implications Late life living environments are important contexts for aging. Aging-in-Place interventions should address subjective interpretations of place to reduce future risks of cognitive decline.