OBJECTIVES:Epidemiologic models used to model cognitive aging and decline often rely on a linear random slopes model, although clinicians rely on accelerated cognitive decline for diagnosis. This study examined the extent to which accelerated versus linearized models of cognitive decline are biased by study design and analytic choices. METHODS:Data on participants of the Health and Retirement Study (1998-2019) who completed cognitive monitoring and lacked cognitive functional limitations or a history of stroke at baseline were included. Episodic memory was measured as the outcome at each time-point. Experiments manipulated sample size, gaps between observations, and waves/participants, and the degree of censoring due to factors in the model, and the degree of cognitive functional limitations. The outcome was the degree of bias in rates of cognitive decline estimated by different models when compared with the full sample. RESULTS:This study used data from 30,740 Health and Retirement Study participants followed 194,818 times and for 335,025.73 person-years of cognitive assessment. While linear models were often biased by relatively small changes in sample design, attrition, and analytic choices, quadratic models and nested nonlinear models provided results that were less biased. Nested nonlinear models were less biased than linear models across 4/5 experimental conditions and were less biased than quadratic models in 3/5 experimental conditions. DISCUSSION:Linearized models of cognitive decline yielded high levels of bias that were sensitive to variations in study design and analytic choices. Results support shifting toward methods modeling accelerated decline in studies of cognitive aging and decline.

Introduction: Osteoarthritis (OA) is one of the leading causes of chronic disability in older adults, often causing significant impairment of mobility. OA symptoms have been linked to mental functioning, including depression, anxiety, and negative affect. Method: To examine whether anger and anxiety mediate the relationship between social support and mobility among older adults with knee osteoarthritis, data from the Everyday Quality of Life in Older Blacks and Whites with Osteoarthritis (EQUAL) study (N = 336) were analyzed using Hayes’ PROCESS model in SPSS to test the direct effect of social support on mobility as well as mediation by anxiety and anger. Results: While univariate models for both anxiety and anger were significant, only anxiety mediated the relationship between social support and mobility. Conclusion: Although limited by their cross-sectional nature, the findings suggest that at least part of the association of social support with mobility may be explained by the role of support in alleviating anxiety.

High arsenic (As) exposure (≥ 100 µg/l) is associated with cardiovascular (CVD) outcomes, however, the CVD risk from low-to-moderate As exposure (< 100 µg/l) has been less explored. There is a paucity of systematic reviews that comprehensively evaluate both urine and water As exposure metrics in assessing As-related CVD outcomes within the general population. To fill this gap, this review sought to update and consolidate data regarding the correlation between low-to-moderate As exposure and specific CVD outcomes, including stroke, ischemic heart disease (IHD), acute myocardial infarction (AMI), and heart failure (HF). A search for peer-reviewed articles indexed in PubMed, Embase, CINAHL, the Global Medicos Index, and Web of Science and unpublished dissertations in Prospero until October 31, 2024, was performed. Nineteen studies were included. Relative risks were pooled by contrasting the highest v/s lowest exposure groups across studies. Positive associations were observed between urine As and stroke incidence, and water As with IHD incidence. Associations between water As and IHD and AMI mortality were suggestive and became stronger after excluding ecological studies. Sex-stratified analyses suggested an increased risk for all groups with strongest indication of an increased risk of AMI mortality in men. Increased risk was suggested for HF but only two studies assessed this outcome. These findings underscore potential risk for CVD outcomes in relation to low-to-moderate As exposure, and highlight the necessity for additional rigorous, well-structured studies to more clearly delineate the possible effects of low-to-moderate As exposure on different CVD outcomes.

Objective This study explores the relationship between World Trade Center (WTC) response activities (WRAs) and cognitive impairment (CI) and uses a moderated-mediation model to examine the role of wearing a surgical/nuisance dust mask. Methods This study includes 3285 WTC responders. Responders were placed into eight WRA groups based on self-report structured responses and free-text descriptions of activities at the WTC. The presence/absence of surgical/nuisance dust mask usage was self-reported. The outcome was CI as determined using a Montreal Cognitive Assessment score < 23. Robust Poisson regression was used to examine the main effect, and counterfactual moderated-mediation analysis was used to determine the role of mask usage. Results The risk of CI was higher across most WRAs when compared to supervision. Mask usage was reported by 63 % of responders and varied across WRAs and was associated with a reduced risk of CI (adjusted risk ratio [aRR]=0.77, p = 0.008) after controlling for WRAs. Moderation effects indicated that responders are more likely to wear masks when encountering more dangerous exposures, even within the same WRA group. Responders in the WRA-enclosed group had a lower risk of CI through a moderated intermediary effect of mask usage (aRR=0.92, p = 0.05). Conclusion Surgical/nuisance dust mask usage provided mild protection against air pollution exposures during WTC response activities when compared to not wearing a mask. Results suggest that response workers at disaster sites might benefit from wearing surgical/nuisance dust masks when respirators are unavailable even when the air seems safe.

INTRODUCTION:Limited observational windows lead to conflicting results in studies examining educational differences in Alzheimer's disease and related dementias (ADRD) risk, due to observational window bias relative to onset of accelerated cognitive decline. This study tested a novel model to address observational window bias and tested for the presence and sources of disparities in accelerated cognitive declines due to ADRD. METHODS:The sample examined 167,314 cognitive assessments from 32,441 Health and Retirement Study participants. We implemented a parametric non-linear nested longitudinal regression and reported multivariable-adjusted nodal incidence ratios (aNIR). RESULTS:University degrees were associated with lower incidence (aNIR = 0.253, 95% confidence interval [CI] = [0.221 to 0.289], p < 0.001), while black participants had a higher incidence (aNIR = 1.995, [1.858 to 2.141], p < 0.001) of accelerated cognitive decline, adjusting for demographic, sociobehavioral, and medical risk factors. Sex-stratified analyses identified diminished educational returns for women and increased incidence among minoritized women. DISCUSSION:Addressing observational window bias reveals large social inequalities in the onset of accelerated cognitive declines indicative of ADRD. HIGHLIGHTS:This study identifies observational window bias as a source of conflicting results among previous studies of educational achievement in Alzheimer's disease and related dementias (ADRD) disparities. The study locates preclinical accelerated cognitive decline, which is indicative of ADRD while occurring 10+ years prior to symptom onset, as a site to study ADRD disparities that mitigates observational window bias. A novel method, nested non-linear regression, is developed to test for differences in the onset of accelerated cognitive decline. Educational and racial/ethnic disparities are demonstrated in the onset of accelerated cognitive decline, as are their intersecting differences with sex/gender.

Abstract Objectives To better understand bidirectional longitudinal relationships between social networks and cognitive decline. Method: We examined nine waves of data from the National Health and Aging Trends Study (2011-2019). Our primary outcome was global cognition, consisting of a summation of scores on episodic memory, orientation, and executive function tests. Social network measures included measures of social participation, number and type of social ties, attributes of network alter, and neighborhood markers of social cohesion and disorder. We applied linear mixed models to study associations between time-invariant measures of social cohesion and disorder with cognitive decline over time. We employed dual-outcomes mixed models to examine the bidirectional linkages between time-varying measures of social network structures and cognitive decline. Result: Eligible participants (N = 7,325) were included at baseline and followed for an average of 4.86±3.22 years/waves. Having more friend-ties and a higher percentage of college graduates within a social network at baseline were associated with slower declines in global cognition and episodic memory. Additionally, higher global cognition at baseline was associated with smaller reductions in social network size. Less disorientation at baseline was associated with a slower decline in social participation. Social cohesion and environmental disorder were not associated with cognitive decline. Conclusion Social networks may improve cognitive health but are also vulnerable to declining orientation. Results suggest that bidirectional longitudinal relationships link social network structure with cognitive decline and inform our understanding of the framework of associations between diverse aspects of social resources and cognitive decline in a longitudinal setting.

The role of social networks in maintaining cognitive health is unclear, in part because few longitudinal studies have explored bidirectional associations between changes in social network structures and cognition. Secondary analyses of data collected during nine waves of the National Health and Aging Trends Study (NHATS; 2011-2019) were conducted. Global cognition was the main outcome, but domain-specific analyses examined episodic memory, orientation, and executive function. Linear mixed models were used to investigate longitudinal effects of neighborhood social cohesion and physical environment on cognitive decline. Dual-outcomes models were used to examine bidirectional associations between social network structures and cognitive decline. Covariates included socioeconomic status, physical measurements, mental health, and lifestyle indicators. Eligible participants (N = 7,325) were recruited at baseline and followed for an average of 4.86±3.22 years. Bivariate correlations indicated that slopes of changes in social networks or participation and cognitive decline were positively correlated. Having more friend ties and a higher percentage of college graduates at baseline were associated with slower declines in global cognition and episodic memory, whereas higher global cognition at baseline was associated with smaller changes in social network size. Less disorientation at baseline was associated with a slower decline in social participation. Findings indicate bidirectional longitudinal relationships between social network structure and cognitive decline. Social networks may improve cognitive health but are also vulnerable to cognitive decline related to disorientation.

A 75-year-old woman with coronary artery disease presented to the emergency department with chest wall pain after a motor vehicle collision. She was a restrained driver in a rear-end collision without airbag deployment. She had normal vital signs and an unremarkable cardiopulmonary physical examination. An ECG showed new lateral ST elevations with reciprocal inferior ST depressions (Figure 1). Point-of-care cardiac ultrasound demonstrated a newly reduced ejection fraction and acute anterolateral regional wall motion abnormalities compared with a normal echocardiogram 2 months previously (Figure 2; Video E1). The initial troponin level was 3.40 ng/mL. The patient received aspirin and heparin, and urgent cardiac catheterization demonstrated no progression of existing coronary artery disease.Figure 2Point-of-care transthoracic cardiac ultrasound demonstrated a reduced ejection fraction and anterolateral regional wall motion abnormalities.View Large Image Figure ViewerDownload Hi-res image Download (PPT) Blunt cardiac injury. She was admitted for telemetry, and within 2 days, her troponin concentration and echocardiographic abnormalities normalized. This represents a spectrum of pathology that occurs in 20% of blunt thoracic trauma—chiefly motor vehicle collisions—and can vary from chest pain to arrhythmia to free wall rupture.1Schultz J.M. Trunkey D.D. Blunt cardiac injury.Crit Care Clin. 2004; 20: 57-70Abstract Full Text Full Text PDF PubMed Scopus (85) Google Scholar The Eastern Association for the Surgery of Trauma guidelines provide a level 1 recommendation that all patients with suspected blunt cardiac injury receive a screening ECG.2Clancy K. Velopulos C. Bilaniuk J.W. et al.Screening for blunt cardiac injury: an Eastern Association for the Surgery of Trauma practice management guideline.J Trauma Acute Care Surg. 2012; 73: S301-S306Crossref PubMed Scopus (119) Google Scholar In stable patients with a normal troponin level, an ECG without ischemic or conduction abnormalities effectively rules out blunt cardiac injury.2Clancy K. Velopulos C. Bilaniuk J.W. et al.Screening for blunt cardiac injury: an Eastern Association for the Surgery of Trauma practice management guideline.J Trauma Acute Care Surg. 2012; 73: S301-S306Crossref PubMed Scopus (119) Google Scholar Echocardiography is an effective adjunctive tool to diagnose complications, including aortic pathology, tamponade, valvular injury, and free wall rupture.3Garcia-Fernandez M. Lopez-Perez J. Perez-Castellano N. et al.Role of transesophageal echocardiography in the assessment of patients with blunt chest trauma: correlation of echocardiographic findings with the electrocardiogram and creatine kinase monoclonal antibody measurements.Am Heart J. 1998; 135: 476-481Crossref PubMed Scopus (65) Google Scholar eyJraWQiOiI4ZjUxYWNhY2IzYjhiNjNlNzFlYmIzYWFmYTU5NmZmYyIsImFsZyI6IlJTMjU2In0.eyJzdWIiOiIzNTAwMWVhZDI2MmM3NWM3NmY1MTBhM2Q5NTJmODkxNiIsImtpZCI6IjhmNTFhY2FjYjNiOGI2M2U3MWViYjNhYWZhNTk2ZmZjIiwiZXhwIjoxNjg5MDMyMjY3fQ.TN9QR9UFR3QOEKopxq0umZ-dbwSFTC5z11LKMNIIYAElEXrhlf0y5r1Urioq0rBw8Z8Qg23_k-6FJozuEnOYd0Ae1Lm4rfa-aTUB0Hl0i6q9s_lZ8ezHgyyvC5MX7LoRIaBivGxWieppy9Rf3jYn8_U63kA3qMEczBh-UirWSwiTTxRi_r6b9bTmcYth5OV4PY359dIMDCPVbSDW3GW_SEMbrlXId4o8JpCWTqxdIuc9EyCMnWnpXZ09Vcfa-YO1KweDHEBibudTo00kf10Br2TdPPU3r3srLGgBAdrRJB8tR4cvON2_Ppj_XGOlPw_cdeXX4Q07EXerdJkNOXpZJQ Download .mp4 (3.04 MB) Help with .mp4 files Video E1Point-of-care transthoracic cardiac ultrasound demonstrated a reduced ejection fraction and anterolateral regional wall motion abnormalities.

Left-behind children (LBC) in China, of which there are 40 million, are a significant concern due to reported mental health issues including depression. Recent research has shown the negative correlation between resilience and the poor mental health outcomes of LBC, but the underlying mechanisms of this resilience have remained unclear. This study utilized the Risk and Resilience framework and conceptualized that resilience is an outcome of the absence of depressive symptoms when protective factors mitigate the negative impact of risk factors. This study examined whether protective factors were correlated with a reduction in the association between risk factors and LBC's depressive symptoms, thereby contributing to LBC's resilience. Participants were recruited from first and second-year middle school students in Henan province, aged 11-15 years (N = 841). Researchers delivered the questionnaires to the classrooms. Logistic regression analyses were conducted to examine the association between hope and depressive symptoms as well as to examine the moderating role of hope on the correlations between risk factors and depressive symptoms. The same analyses were stratified by gender. Hope was negatively correlated with LBC's depressive symptoms. For males, there was a significant interaction between hope and stressful life events, but the interaction was not significant for females. The results suggest that LBC boys' resilience can improve if hope mitigates the negative impact of stressful life events on LBC's depressive symptoms.

Elder Orphans, socially/physically isolated older adults without caregiving support, are of interest in an aging population. Lack of caregivers for Elder Orphans may influence relocation to residential care facilities, including skilled nursing or assisted living facilities, compared to aging in place. Using the National Health and Aging Trends Study (NHATS), Competing Risk Survival Analyses were performed to determine if Elder Orphans or those At Risk for becoming elder orphans had increased risk for residential care relocation over nine NHATS waves (2011-2019). Elder Orphans had significantly higher risk for moving to residential care facilities in unadjusted (SHR = 1.780; p = 0.001) and adjusted (SHR = 1.571; p = 0.043) models. Those At Risk for becoming an elder orphan had significantly decreased risk for residential care residence in unadjusted (SHR = 0.517; p < 0.001) and adjusted (SHR = 0.726; p = 0.037) models. As aging in place becomes prioritized in the US healthcare system, understanding caregiving needs of older adults is vital to their health outcomes.

As the population of elder orphans grows, little research has investigated the health outcomes of these socially and physically isolated older adults without caregiving support. Umbrella and scoping reviews were performed for studies examining health outcomes of older adults experiencing elements of elder orphanhood. Studies published 2010- June 2021 and indexed on PubMed, Web of Science, CINAHL, Medline, or SocINDEX were eligible. Results of included studies were examined both by individual category and overall to determine overlapping outcomes.Umbrella review returned 1686 studies, with 14 meeting criteria for social isolation (n = 10) and physical isolation (n = 4). The scoping review of studies examining unmet caregiving need returned 3741 results: five met inclusion criteria. Included studies reviewed differing health outcomes in older adults, with a focus on dementia, frailty, and healthcare utilization. Further studies are needed that appraise targeted policies and interventions to improve health outcomes of elder orphans.

Objectives This research examined main and moderating effects of global depressive symptoms upon in-the-moment associations of pain and affect among individuals with knee osteoarthritis (OA). Effects of depression on short-term change in pain and affect were also examined. Method Older adults with physician-confirmed OA (N = 325) completed a baseline interview tapping global depressive symptoms, followed by an experience sampling protocol that captured momentary pain and affect 4 times daily for 7 days. Multilevel models controlling demographics and health conditions examined main and moderating effects of depression on momentary associations of pain with positive affect (PA) and negative affect (NA). Similar methods addressed short-term change in pain and affect. Auxiliary analyses explored broad associations of depressive symptoms with person-level averages and variability in pain and affect. Results Global depression predicted current pain, PA, and NA, as well as change in pain and affect over a 3- to 8-h period. Furthermore, both in the moment and over short periods, the association of pain and NA was stronger among persons higher in depressive symptoms. No moderating effect for the PA-pain association was found. Depressive symptoms were also associated with variability in pain and affect, particularly NA. Discussion Results confirm previous work on the relation of chronic pain with both global depressive symptoms and short-term affect. This research further demonstrates a unique moderating role of depression on the association of momentary pain with NA and suggests that the causal path may be stronger from pain to affect than vice versa.

This study examines the relative contributions of giving versus receiving support to longevity in a sample of older married adults. Baseline indicators of giving and receiving support were used to predict mortality status over a 5-year period in the Changing Lives of Older Couples sample. Results from logistic regression analyses indicated that mortality was significantly reduced for individuals who reported providing instrumental support to friends, relatives, and neighbors, and individuals who reported providing emotional support to their spouse. Receiving support had no effect on mortality once giving support was taken into consideration. This pattern of findings was obtained after controlling for demographic, personality, health, mental health, and marital-relationship variables. These results have implications for understanding how social contact influences health and longevity.

Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease characterized by flares ranging from mild to life-threatening. Severe flares and complications can require hospitalizations, which account for most of the direct costs of SLE care. This study investigates two machine learning approaches in predicting SLE hospitalizations using longitudinal data from 925 patients enrolled in a multicenter electronic health record (EHR)-based lupus cohort. Our first Differential approach accounts for the time dependencies in sequential data by introducing additional lagged variables between consecutive time steps. We next evaluate the performance of LSTM, a state-of-the-art deep learning model designed for time series. Our experimental results demonstrate that both methods can effectively predict lupus hospitalizations, but each has its strengths and limitations. Specifically, the Differential approach can be integrated into any non-temporal machine learning algorithms and is preferred for tasks with short observation periods. On the contrary, the LSTM model is desirable for studies utilizing long observation intervals attributing to its capability in capturing long-term dependencies embedded in the longitudinal data. Furthermore, the Differential approach has more options in handling class imbalance in the underlying data and delivers stable performance across different prognostic horizons. LSTM, on the other hand, demands more class-balanced training data and outperforms the Differential approach when there are sufficient positive samples facilitating model training. Capitalizing on our experimental results, we further study the optimal length of patient monitoring periods for different prediction horizons.

To further a just energy transition, jobs lost at retiring coal plants could be replaced by jobs at wind and solar plants. No research quantifies the feasibility and costs of such an undertaking across the United States. Complicating such an undertaking are workers' place-based preferences that could prevent them from moving long distances, e.g. to high renewable resource regions. We formulate a bottom-up optimization model to quantify the technical feasibility and costs of replacing coal plant jobs with local versus distant jobs in the renewables sector. For the contiguous United States, we find replacing coal generation and employment with local wind and solar investments is feasible. Siting renewables local to instead of distant from retiring coal plants increases replacement costs by 5%-33% across sub-national regions and by $83 billion, or 24%, across the United States. These costs are modest relative to overall energy transition costs.

Ultra-low temperature (ULT) storage of microbial biomass is routinely practiced in biological laboratories. However, there is very little insight regarding the effects of biomass storage at ULT and the structure of the cell envelope, on cell viability. Eventually, these aspects influence bacterial cell lysis which is one of the critical steps for biomolecular extraction, especially protein extraction. Therefore, we studied the effects of ULT-storage (-80°C) on three different bacterial platforms: Escherichia coli, Bacillus subtilis and the cyanobacterium Synechocystis sp. PCC 6803. By using a propidium iodide assay and a modified MTT assay we determined the impact of ULT storage on cellular viability. Subsequently, the protein extraction efficiency was determined by analyzing the amount of protein released following the storage. The results successfully established that longer the ULT-storage time lower is the cell viability and larger is the protein extraction efficiency. Interestingly, E. coli and B. subtilis exhibited significant reduction in cell viability over Synechocystis 6803. This indicates that the cell membrane structure and composition may play a major role on cell viability in ULT storage. Interestingly, E. coli exhibited concomitant increase in cell lysis efficiency resulting in a 4.5-fold increase (from 109 μg/ml of protein on day 0 to 464 μg/ml of protein on day 2) in the extracted protein titer following ULT storage. Furthermore, our investigations confirmed that the protein function, tested through the extraction of fluorescent proteins from cells stored at ULT, remained unaltered. These results established the plausibility of using ULT storage to improve protein extraction efficiency. Towards this, the impact of shorter ULT storage time was investigated to make the strategy more time efficient to be adopted into protocols. Interestingly, E. coli transformants expressing mCherry yielded 2.7-fold increase (93 μg/mL to 254 μg/mL) after 10 mins, while 4-fold increase (380 μg/mL) after 120 mins of ULT storage in the extracted soluble protein. We thereby substantiate that: (1) the storage time of bacterial cells in -80°C affect cell viability and can alter protein extraction efficiency; and (2) exercising a simple ULT-storage prior to bacterial cell lysis can improve the desired protein yield without impacting its function.

Background: The COVID-19 pandemic led to a significant reduction in the provision of screening, case identification and hospital referrals to cancer patients. To our knowledge, no study has yet correlated quantitatively the consequences of these limitations for cancer patient management. This study evaluates the implications of such reductions for patients newly diagnosed with metastatic colorectal cancer (mCRC) in both the pre- and post-lockdown periods. Methods: We examined 80 newly identified mCRC patients from 18 different clinical centers. These cases come from the screening procedure of a clinical trial which is using circulating DNA (cirDNA) analysis to determine their RAS and BRAF status. Results: The tumor burden as evaluated by the median total plasma cirDNA concentration showed a statistically higher level in patients diagnosed post-lockdown compared to those diagnosed pre-lockdown (119.2 versus 17.3 ng/mL; p<0.0001). In order to link tumor burden to survival, we compared the survival of these mCRC patients with previous studies in which cirDNA was examined in the same way (median survival, 16.2 months; median follow up, 48.7 months, N=135). Given the poor survival rate of mCRC patients with high cirDNA levels (14.7 vs 20.0 and 8.8 vs 19.3 months median survival when dichotomizing the cohort by the median cirDNA concentration 24.4 and 100 ng/mL, respectively), our study points to the potential deleterious consequences of the COVID-19 pandemic. Conclusions: Recognizing that our exploratory study offers a snapshot of an evolving situation, our observations nonetheless clearly highlight the need to determine actions which would minimize delays in diagnosis during the ongoing and future waves of COVID-19.

acetate is a classical uncoupling agent, permeating the membrane at comparable rates in the dissociated and undissociated forms. The lactate concentration ratio changes markedly after an initial period of sustained glycolysis. This change is most readily explained as resulting from a lactate transport system that responds to an indicator of glycolytic activity. The data further indicate that lactate permeates the membrane in both dissociated and undissociated forms. Both acids, then, are capable of catalytically dissipating the proton-motive force.