The association of trauma with self-reported flares and disease activity in systemic lupus erythematosus (SLE).

OBJECTIVES: Trauma has been linked to incident SLE, but its relationship with SLE disease activity is unknown. This analysis examines associations between trauma exposures and patient-reported SLE disease activity and flares. METHODS: Data were from the California Lupus Epidemiology Study (CLUES). Flares were self-reported as any flare and, of those, flares accompanied by medical care (hospitalization or physician contact). The Systemic Lupus Activity Questionnaire (SLAQ) assessed disease activity. The Brief Trauma Questionnaire (BTQ) assessed all historical trauma exposures. The Adverse Childhood Experiences (ACEs) questionnaire was available for a subset. Multivariable regression analyses (n = 252) examined whether trauma exposure was associated with flares or SLAQ controlling for age, sex, poverty, race/ethnicity, comorbidities, perceived stress, disease duration and self-reported disease damage. RESULTS: Excluding exposure to serious illness, 63.4% reported ≥1 trauma exposure. Any traumatic event, excluding illness, doubled the odds of a flare [OR 2.27 (95% CI 1.24, 4.17)] and was associated with significantly higher SLAQ scores [ß 2.31 (0.86, 3.76)]. Adjusted odds of any flare and flare with medical care were significantly elevated for those with both BTQ and ACE exposures [5.91 (2.21, 15.82) and 4.69 (1.56, 14.07), respectively]. SLAQ scores were also higher for those with both exposures [ß 5.22 (3.00, 7.44)]. CONCLUSION: In this cohort, those with a history of trauma reported more flares and greater disease activity. Identifying mechanisms of associations between trauma and disease activity and flares, as well as interventions to mitigate the effects of trauma exposures is critical, given the high rates of trauma exposures.

Caregiving and Self-Esteem in Mid and Later Life: Is There Variation by Age, Parental Status, and Gender?

Caregiving may prove either beneficial or harmful for caregiver well-being, depending on the circumstances surrounding care provision. Using data from the two most recent waves of the National Survey of Midlife Development in the United States (MIDUS, 2004-2014; N = 1,100), we examine whether providing care for an adult at both time points (i.e., 8-10 years apart) is associated with changes to self-esteem over the ten-year period, in comparison with providing care at only one time point, or not at all. We also examine moderation by caregivers' age, parental status, and gender. Findings indicated (1) caregiving at both waves was associated with decreases in self-esteem among younger and midlife adults, but this effect weakened and even reversed with age; and (2) caregiving at both waves was associated with increased self-esteem among participants without children, but not among those with children. We discuss implications for identifying caregivers at greatest risk of diminished well-being.

Understanding pulse oximetry in hematology patients: Hemoglobinopathies, racial differences, and beyond.

Pulse oximetry (SpO2 ) is a widely used, non-invasive method of estimating arterial oxygen saturation. Measurement of SpO2 relies on comparing the relative absorption of light in the red and infrared regions with the expected absorption pattern of oxygenated and deoxygenation adult hemoglobin. As this screening tool has entered common clinical use, test limitations have emerged, including concern about the risk of overestimation of oxygen saturation by pulse oximetry in a disproportionate number of people with dark skin pigment, leading to potential for underdiagnosis of true hypoxemia. In addition, a range of challenges may arise in patients with increased levels of methemoglobin - whether acquired or inherited - carboxyhemoglobin, or in patients with a subset of inherited variant hemoglobins. It is important for Hematologists, and indeed all clinicians who rely on pulse oximetry, to understand the principles and limitations of this ubiquitous test.

A day in the life of caregivers to older adults with and without dementia: Comparisons of care time and emotional health.

INTRODUCTION: How care-related time and emotional health over the day differ for those assisting older adults with and without dementia is unclear. METHODS: Using 2134 time diaries from the National Study of Caregiving, we compared emotional health and care time for caregivers of older adults with and without dementia. RESULTS: Caregivers to older adults with dementia experienced worse (higher scores) on a composite measure of negative emotional health (4.2 vs 3.3; P < .05) and provided more physical/medical care (33.7 vs 16.2 minutes; P < .05) and less transportation assistance (12.6 vs 24.8 minutes; P < .05) than other caregivers. In models, providing physical/medical care was associated with worse emotional health (ß = 0.15; P < .01) and socializing with the care recipient was associated with worse emotional health when the recipient had dementia (ß = 0.28; P < .01). DISCUSSION: Findings highlight the opportunity for targeted interventions to address the emotional consequences of different types of care time in the context of dementia.

Educational Attainment Differences in Attitudes toward Provisions of IADL Care for Older Adults in the U.S.

Educational attainment is increasingly associated with family inequality in the U.S., but there is little understanding about whether and how education stratifies attitudes toward eldercare. Using the General Social Survey 2012 Eldercare Module, I test the association between educational attainment and attitudes toward eldercare provisions of Instrumental Activities of Daily Living (IADL) including different combinations of help and payment for help. IADLs are the most common care received by older adults and needs are projected to grow, so understanding attitudes toward this type of care is timely and relevant. Results show that adults with a bachelor's degree or graduate/professional degree, compared to adults with less than a high school degree, are more likely to support complete family IADL eldercare, where families provide the care and any payment necessary for care, compared to complete outside IADL eldercare, where outside institutions provide both care and payment. Educational attainment is an important axis of stratification in the U.S. and may explain potentially bifurcated policy solutions desired among different groups.

Family embeddedness and older adult mortality in the United States.

Do different operationalizations of family structure offer different understandings of the links between family structure and older adult mortality? Using the American Health and Retirement Study (N = 29,665), we examine mortality risks by three measures of family structure: whether respondents have different family statuses (e.g. married vs. unmarried), volume of family members available (e.g. having one vs. two living immediate family members), and family embeddedness (e.g. having neither spouse nor child vs. having spouse but no child). We focus on three kin types: partner/spouse, children, and siblings. We find that differences in empirical estimates across measures of family structure are not dramatic, but that family embeddedness can show some additional heterogeneity in mortality patterns over family status variables or the volume of ties. This paper tests different ways of operationalizing family structure to study mortality outcomes and advances our understanding of how family functions as a key social determinant of health.

Intergenerational Relationships, Family Caregiving Policy, and COVID-19 in the United States.

Families and intergenerational relationships are important sources of risk for COVID-19 infection, especially for older adults who are at high risk of complications from the disease. If one family member is exposed to the virus they could serve as a source of transmission or, if they fall ill, the resources they provide to others could be severed. These risks may be especially heightened for family members who work outside the home and provide care, or for those family members who care for multiple generations. Policies have the potential to help families bear the burden of these decisions. This essay argues that policies that address health, employment, and other social issues have implications for families, and that policies aimed at families and caregivers can affect the health, employment, and the general well-being of the nation.

Beyond Household Walls: The Spatial Structure of American Extended Kinship Networks.

How far do Americans live from their close and extended kin? The answer is likely to structure the types of social, instrumental, and financial support that they are able to provide to one another. Based on the Panel Study of Income Dynamics, kin pairs vary widely in odds of household co-residence, co-residence in the same administrative units, and inter-tract distances if they do not live in the same census tract. Multivariate regression tests show that family structure, educational attainment, and age are closely associated with kin proximity. Fixed effects models demonstrate that fam ily formation shapes spatial relations between kin.

Mothers' Time and Relationship with Their Adolescent Children: The Intersecting Influence of Family Structure and Maternal Labor Force Participation.

We investigate whether the anticipated risks of increasing maternal work hours for mother-adolescent relationships differ across family structures: Do intensive mothering norms exacerbate these risks particularly for mothers in two-parent biological families or does their partners' greater involvement significantly mitigate these risks? We predict mothers' accessible time, engaged time, and the quality of their relationship with their adolescent children using the National Study of Adolescent to Adult Health. Although the association between mothers' labor force participation and mothers' accessible time is significantly weaker in stepfather families relative to two-parent biological families, family structure does not moderate the associations between mothers' labor force participation and mother's engaged time or the quality of her relationship with her adolescent. We conclude that mothers face strong normative pressure to privilege their relationship with their child even in the face of long work hours and weaker family support.

Single-parent households and mortality among children and youth.

Although many studies have examined associations between family structure and child outcomes, few have considered how the increase in single-parent households since the 1960s may have affected child mortality rates. We examined state-level changes in the percentage of children living with single parents between 1968 and 2010 and state-level trends in mortality among children and youth (age 19 or younger) in the United States. Regression models with state and year fixed effects revealed that increases in single parenthood were associated with small increments in accidental deaths and homicides.

GENDER AND THE MBA: Differences in Career Trajectories, Institutional Support, and Outcomes.

This study asks how men's and women's careers diverge following MBA graduation from an elite university, using qualitative interview data from 74 respondents. We discover men and women follow three career pathways post-graduation: lockstep (stable employment), transitory (3 or more employers), and exit (left workforce). While similar proportions of men and women followed the lockstep pathways and launched accelerated careers, sizable gender differences emerged on the transitory pathway; men's careers soared as women's faltered on this path-the modal category for both. On the transitory path, men fared much better than women when moving to new organizations, suggesting that gender may become more salient when people have a shorter work history with a company. Our findings suggest that clear building blocks to promotions reduce gender bias and ambiguity in the promotion process, but multiple external moves hamper women, putting them at a clear disadvantage to men whose forward progress is less likely to be stalled by such moves.

Linking Oxidative Stress and Magnitude of Compensatory Responses with Life-Stage Specific Differences in Sensitivity of White Sturgeon (Acipenser transmontanus) to Copper or Cadmium.

Sensitivity of white sturgeon (Acipenser transmontanus) to copper (Cu) or cadmium (Cd) has been shown to significantly differ as a function of life-stage. This study investigated oxidative stress, metal homeostasis, and associated compensatory responses as potential mechanisms of this sensitivity pattern in three early life-stages. Sturgeon were most sensitive to Cu at 15 days post hatch (dph), which was accompanied by a significant increase in lipid peroxidation (LPO). Genes involved with amelioration of oxidative stress were significantly less inducible at this stage than in older, less sensitive fry. At 48 dph, acute lethality of sturgeon exposed to Cd was greatest and body LPO was significantly induced by 3.5-fold at 5 µg Cd/L. Moreover, there was a small but significant increase in antioxidative responses. At 139 dph, sturgeon were most tolerant to Cu and Cd and accumulation of these metals was least. Also, expression of metallothionein (MT) and apoptotic genes were greatest while expression of metal transporters was reduced and concentration of LPO was not different from controls. Our results suggest that life-stage specific sensitivity of white sturgeon to metals is complex, encompassing differences in the ability to mount compensatory responses important for metal homeostasis and combating oxidative stress and concomitant damages.

Is hepatic oxidative stress a main driver of dietary selenium toxicity in white sturgeon (Acipenser transmontanus)?

Most species of sturgeon have experienced significant population declines and poor recruitment over the past decades, leading many, including white sturgeon (Acipenser transmontanus), to be listed as endangered. Reasons for these declines are not yet fully understood but benthic lifestyle, longevity, and delayed sexual maturation likely render sturgeon particularly susceptible to factors such as habitat alteration and contaminant exposures. One contaminant of particular concern to white sturgeon is selenium (Se), especially in its more bioavailable form selenomethionine (SeMet), as it is known to efficiently bioaccumulate in prey items of this species. Studies have shown white sturgeon to be among the most sensitive species of fish to dietary SeMet as well as other pollutants such as metals, dioxin-like chemicals and endocrine disrupters. One of the primary hypothesized mechanisms of toxicity of SeMet in fish is oxidative stress; however, little is know about the specific mode by which SeMet affects the health of white sturgeon. Therefore, the aim of this study was to characterize oxidative stress and associated antioxidant responses as a molecular event of toxicity, and to link it with the pathological effects observed previously. Specifically, three-year-old white sturgeon were exposed for 72 days via their diet to 1.4, 5.6, 22.4 or 104.4µg Se per g feed (dm). Doses were chosen to range over a necessary Se intake level, current environmentally relevant intakes and an intake representing predicted increases of Se release. Lipid hydroperoxides, which are end products of lipid oxidation, were quantified as a marker of oxidative stress. Changes in gene expression of glutathione peroxidase (GPx), superoxide dismutase, catalase, glutathione S-transferase, apoptosis inducing factor and caspase 3 were quantified as markers of the response to oxidative stress. Concentrations of lipid hydroperoxides were highly variable within dose groups and no dose response was observed. GPx expression was significantly increased in the low dose group indicating an induced antioxidant response. Expression of other genes were not significantly induced or suppressed. Overall, there was very little evidence of oxidative stress, and therefore, in contrast to previous reports on other species of teleost fishes, oxidative stress is not believed to be a main driver of toxicity in white sturgeon exposed to SeMet.

Single-parent households and children's educational achievement: A state-level analysis.

Although many studies have examined associations between family structure and children's educational achievement at the individual level, few studies have considered how the increase in single-parent households may have affected children's educational achievement at the population level. We examined changes in the percentage of children living with single parents between 1990 and 2011 and state mathematics and reading scores on the National Assessment of Educational Progress. Regression models with state and year fixed effects revealed that changes in the percentage of children living with single parents were not associated with test scores. Increases in maternal education, however, were associated with improvements in children's test scores during this period. These results do not support the notion that increases in single parenthood have had serious consequences for U.S. children's school achievement.

Ultrasensitive Response Explains the Benefit of Combination Chemotherapy Despite Drug Antagonism.

Most aggressive lymphomas are treated with combination chemotherapy, commonly as multiple cycles of concurrent drug administration. Concurrent administration is in theory optimal when combination therapies have synergistic (more than additive) drug interactions. We investigated pharmacodynamic interactions in the standard 4-drug "CHOP" regimen in peripheral T-cell lymphoma (PTCL) cell lines and found that CHOP consistently exhibits antagonism and not synergy. We tested whether staggered treatment schedules could improve tumor cell kill by avoiding antagonism, using in vitro models of concurrent or staggered treatments. Surprisingly, we observed that tumor cell kill is maximized by concurrent drug administration despite antagonistic drug-drug interactions. We propose that an ultrasensitive dose response, as described in radiology by the linear-quadratic (LQ) model, can reconcile these seemingly contradictory experimental observations. The LQ model describes the relationship between cell survival and dose, and in radiology has identified scenarios favoring hypofractionated radiotherapy-the administration of fewer large doses rather than multiple smaller doses. Specifically, hypofractionated treatment can be favored when cells require an accumulation of DNA damage, rather than a "single hit," to die. By adapting the LQ model to combination chemotherapy and accounting for tumor heterogeneity, we find that tumor cell kill is maximized by concurrent administration of multiple drugs, even when chemotherapies have antagonistic interactions. Thus, our study identifies a new mechanism by which combination chemotherapy can be clinically beneficial that is not contingent on positive drug-drug interactions.

A Care Paradox: The Relationship Between Older Adults' Caregiving Arrangements and Institutionalization and Mortality.

We investigate how the type of caregiving arrangement is associated with older Americans' outcomes. We use the Health and Retirement Study (2004-2018) and discrete-time event history analysis to assess the odds of institutionalization or death over a 14-year period among older adults with limitations in Activities of Daily Living (ADLs; e.g., bathing). We consider caregiving arrangements as conventional (i.e., spouse or adult child), unconventional (e.g., extended family, employee, friend), or self-directed (i.e., no caregiver). We find a "care paradox" in that self-directing one's own care was associated with a lower risk of institutionalization or death compared with having conventional care (spouse/adult caregiver) and unconventional care (employee). Relative to conventional care, having an employee caregiver was associated with increased risk of institutionalization. Findings are still observed when controlling for level of impairment and various health-related factors. More research is needed to understand older adults who self-direct their own care.

Effects of the glyphosate-based herbicide roundup on C. elegans and S. cerevisiae mortality, reproduction, and transcription fidelity.

Glyphosate-based weed killers such as Roundup have been implicated in detrimental effects on single- and multicellular eukaryotic model organism health and longevity. However, the mode(s) of action for these effects are currently unknown. In this study, we investigate the impact of exposure to Roundup on two model organisms: Saccharomyces cerevisiae and Caenorhabditis elegans and test the hypothesis that exposure to Roundup decreases transcription fidelity. Population growth assays and motility assays were performed in order to determine the phenotypic effects of Roundup exposure. We also used Rolling-Circle Amplification RNA sequencing to quantify the impact of exposure to Roundup on transcription fidelity in these two model organisms. Our results show that exposure to the glyphosate-based herbicide Roundup increases mortality, reduces reproduction, and increases transcription error rates in C. elegans and S. cerevisiae. We suggest that these effects may be due in part to the involvement of inflammation and oxidative stress, conditions which may also contribute to increases in transcription error rates.

Positive psychosocial factors may protect against perceived stress in people with systemic lupus erythematosus with and without trauma history.

OBJECTIVE: Trauma history is associated with SLE onset and worse patient-reported outcomes; perceived stress is associated with greater SLE disease activity. Stress perceptions vary in response to life events and may be influenced by psychosocial factors. In an SLE cohort, we examined whether stressful events associated with perceived stress, whether psychosocial factors affected perceived stress, and whether these relationships varied by prior trauma exposure. METHODS: This is a cross-sectional analysis of data from the California Lupus Epidemiology Study, an adult SLE cohort. Multivariable linear regression analyses controlling for age, gender, educational attainment, income, SLE damage, comorbid conditions, glucocorticoids ≥7.5 mg/day and depression examined associations of recent stressful events (Life Events Inventory) and positive (resilience, self-efficacy, emotional support) and negative (social isolation) psychosocial factors with perceived stress. Analyses were stratified by lifetime trauma history (Brief Trauma Questionnaire (BTQ)) and by adverse childhood experiences (ACEs) in a subset. RESULTS: Among 242 individuals with SLE, a greater number of recent stressful events was associated with greater perceived stress (beta (95% CI)=0.20 (0.07 to 0.33), p=0.003). Positive psychosocial factor score representing resilience, self-efficacy and emotional support was associated with lower perceived stress when accounting for number of stressful events (-0.67 (-0.94 to -0.40), p<0.0001); social isolation was associated with higher stress (0.20 (0.14 to 0.25), p<0.0001). In analyses stratified by BTQ trauma and ACEs, associations of psychosocial factors and perceived stress were similar between groups. However, the number of recent stressful events was significantly associated with perceived stress only for people with BTQ trauma (0.17 (0.05 to 0.29), p=0.0077) and ACEs (0.37 (0.15 to 0.58), p=0.0011). CONCLUSION: Enhancing positive and lessening negative psychosocial factors may mitigate deleterious perceived stress, which may improve outcomes in SLE, even among individuals with a history of prior trauma who may be more vulnerable to recent stressful events.

The Changing Demography of Late-Life Family Caregiving: A Research Agenda to Understand Future Care Networks for an Aging U.S. Population.

Repeated claims that a dwindling supply of potential caregivers is creating a crisis in care for the U.S. aging population have not been well-grounded in empirical research. Concerns about the supply of family care do not adequately recognize factors that may modify the availability and willingness of family and friends to provide care to older persons in need of assistance or the increasing heterogeneity of the older population. In this paper, we set forth a framework that places family caregiving in the context of older adults' care needs, the alternatives available to them, and the outcomes of that care. We focus on care networks, rather than individuals, and discuss the demographic and social changes that may alter the formation of care networks in the future. Last, we identify research areas to prioritize in order to better support planning efforts to care for the aging U.S. population.

Cohabiting Adult Children's Transfers to Parents in the United States.

Objective: This brief report presents national estimates of transfers of time and money from cohabiting adult children (ages 18 to 65) to their parents (own and in-laws) to test whether cohabiting adults give differently from their counterparts. Background: Previous U.S. studies use data collected in the late 1980s and mid-1990s, when cohabitation was an emerging family form; they find mixed results. Rising rates of cohabitation and an aging population of parents who may rely on transfers from adult children necessitate updated estimates that can help develop the theory of institutionalization of cohabitation. Method: This study used the 2013 Panel Study of Income Dynamics (PSID) Rosters and Transfers Module, a sample of U.S. households (N=6,340), and logistic and negative binomial models to estimate the likelihood of giving any time or any money to parents by the respondent's union status, the amounts given, and parent type (own, in-laws). Results: Cohabitors were less likely to give time to their own parents than their never married counterparts, and gave fewer hours, but were more likely to give time and gave more hours than married adults. For financial transfers to own parents, cohabitors and married respondents gave similarly, but both were less likely to give any money than are single respondents. Cohabitators gave more hours to their in-laws than married respondents. Conclusion: Cohabitors behave somewhere in-between marital "greedy institution" norms and broader norms of solidarity with parents. More work should be done to understand how union status affects transfers to parents.