Chronic Health Conditions as a Risk Factor for Falls among the Community-Dwelling US Older Adults: A Zero-Inflated Regression Modeling Approach

Falls are an important health concern among older adults due to age-related changes in the body. Having a medical history of chronic health condition may pose even higher risk of falling. Only few studies have assessed a number of chronic health conditions as risk factor for falls over a large nationally representative sample of US older adults. In this study, Behavioral Risk Factor Surveillance System (BRFSS) 2014 participants aged 65 years and older (n = 159,336) were evaluated. It was found that 29.7% (n = 44,550) of the sample experienced at least one fall and 16.3% (n = 20,444) experienced more than one fall in the past 12 months. According to the study findings, having a medical history of stroke, CKD, arthritis, depression, and diabetes independently predict the risk of first-time falling as well as the risk of recurrent falling in older adult population while controlling for other factors. On the other hand, having a medical history of the heart attack, angina, asthma, and COPD did not predict the risk of first-time falling, but did predict the risk of recurrent falling after experiencing the first fall in this population

Generalized Algebraic Algorithm for Scene-based Nonuniformity Correction

ABSTRACT This paper presents an overview of three recently developed scene-based nonuniformity correction techniques, namely, the algebraic scene-based algorithm (ASBA), the extended radiometrically accurate scene-based algorithm (RASBA) and the generalized algebraic scene-based algorithm (GASBA). The ASBA uses pairs of image frames that exhibit one-dimension sub-pixel motion to algebraically extract estimates of bias nonuniformity. The RASBA incorporates arbitrary sub-and super-pixel two-dimensional motion in conjunction with limited perimeter-only absolute calibration to obtain radiometrically accurate estimates of the bias nonuniformity. The RASBA provides the advantage of being able to maintain radiometry in the interior photodetectors without interrupting their operation. The GASBA is a generalized non-radiometric form of the algorithm that uses image pairs with arbitrary two-dimensional motion and encompasses both the ASBA and RASBA algorithms. This generalization is accomplished by initially guaranteeing bias uniformity in the perimeter detectors. This uniformity can be achieved by first applying the ASBA estimates. The generalized algorithm is then able to automatically maintain perimeter uniformity without the need for re-application of the ASBA. Thus, the GASBA is able to operate completely in a non-radiometric mode, alleviating the need for the perimeter calibration system if desired. The generalized algorithm is applied to real infrared imagery obtained from both cooled and uncooled infrared cameras. A hardware implementation of the proposed algorithm will also be discussed along with several ongoing commercial applications of the technology

Effect of Canopy Location on Yield Components and Fruit Composition in Pinot noir Grapevines Trained to the Scott Henry Trellis System

Pinot noir vines, trained to the Scott Henry trellising system were separated into four different quadrants: Bottom canopy, trained toward the ground; Top canopy, trained upwards; East orientation, receiving the morning sunlight; and West orientation, receiving afternoon sunlight. Yield components and fruit composition were measured for each canopy, orientation, and then for each quadrant. The bottom canopy had higher yield, cluster weight, titratable acidity, and total sugar per vine, than did the top canopy. Must soluble solids were not significantly different between the two canopies. The top canopy had a significantly higher pH. The East side of the vine, the side that receives direct morning sunlight, had a higher yield, cluster weight, and total sugar per vine than did the West side of the vine. The West side of the vine, the side that receives direct afternoon sunlight, had higher titratable acidity than did the East side of the vine. Must soluble solids were not significantly different between the two sides of the vine. The bottom-east quadrant had a significantly higher yield, and total sugar per vine, than did the other three quadrants

Development of Viticultural Practices to Improve Winegrape Performance : Experiment II: Effect of Canopy Location on Yield Components and Fruit Composition in Pinot noir Grapevines Trained to the Scott Henry Trellis System

For this trial, established Pinot noir vines, located on the valley floor of the Umpqua Valley in Oregon were used. In 1996 and 1997 sixteen vines trained to the Scott Henry trellising system were separated into four different quadrants, determined by shoot orientation: Bottom canopy, shoots trained toward the ground; top canopy, shoots trained upwards; east orientation, shoots receiving the morning sunlight; and west orientation, shoots receiving afternoon sunlight. Yield components and fruit composition were measured for each quadrant. In 1996, wines were produced from fruit harvested by quadrant and subjected to sensory analysis. In 1996 the bottom canopy had higher yield, cluster weight, and titratable acidity than did the top canopy. In 1997 the top canopy had a higher yield than did the bottom canopy. In 1996 the east oriented canopy had a higher yield, cluster weight, and skin anthocyanins than did the west oriented canopy. Must soluble solids were not significantly different between vine canopy or orientation in 1996. In 1997 the west oriented canopy had higher brix, pH, and lower titratable acidity than the east oriented canopy. The bottom-east quadrant had a significantly higher yield than did the other three quadrants in 1996. There were no significant differences seen in quadrant yields in 1997. Significant differences were seen in wine attributes between the quadrants

Cholesterol Sulfotransferase SULT2B1b Modulates Sensitivity to Death Receptor Ligand TNFα in Castration-Resistant Prostate Cancer

Cholesterol sulfotransferase, SULT2B1b, has been demonstrated to modulate both androgen receptor activity and cell growth properties. However, the mechanism(s) by which SULT2B1b alters these properties within prostate cancer cells has not been described. Furthermore, specific advantages of SULT2B1b expression in prostate cancer cells is not understood. In these studies, single-cell mRNA sequencing (scRNA-seq) was conducted to compare the transcriptomes of SULT2B1b knockdown (KD) versus Control KD LNCaP cells. Over 2,000 differentially expressed (DE) genes were identified along with alterations in numerous canonical pathways, including the death receptor signaling pathway. The studies herein demonstrate that SULT2B1b KD increases tumor necrosis factor alpha (TNF) expression in prostate cancer cells and results in NF-κB activation in a TNF-dependent manner. More importantly, SULT2B1b KD significantly enhances TNF-mediated apoptosis in both TNF-sensitive LNCaP cells and TNF-resistant C4–2 cells. Overexpression of SULT2B1b in LNCaP cells also decreases sensitivity to TNF-mediated cell death, suggesting that SULT2B1b modulates pathways dictating the TNF sensitivity capacity of prostate cancer cells. Probing human prostate cancer patient datasets further support this work by providing evidence that SULT2B1b expression is inversely correlated with TNF-related genes, including TNF, CD40LG, FADD, and NFKB1. Together, these data provide evidence that SULT2B1b expression in prostate cancer cells enhances resistance to TNF and may provide a growth advantage. In addition, targeting SULT2B1b may induce an enhanced therapeutic response to TNF treatment in advanced prostate cancer

Intrinsic and extrinsic epigenetic age acceleration are associated with hypertensive target organ damage in older African Americans

Abstract Background Epigenetic age acceleration, a measure of biological aging based on DNA methylation, is associated with cardiovascular mortality. However, little is known about its relationship with hypertensive target organ damage to the heart, kidneys, brain, and peripheral arteries. Methods We investigated associations between intrinsic (IEAA) or extrinsic (EEAA) epigenetic age acceleration, blood pressure, and six types of organ damage in a primarily hypertensive cohort of 1390 African Americans from the Genetic Epidemiology Network of Arteriopathy (GENOA) study. DNA methylation from peripheral blood leukocytes was collected at baseline (1996–2000), and measures of target organ damage were assessed in a follow-up visit (2000–2004). Linear regression with generalized estimating equations was used to test for associations between epigenetic age acceleration and target organ damage, as well as effect modification of epigenetic age by blood pressure or sex. Sequential Oligogenic Linkage Analysis Routines (SOLAR) was used to test for evidence of shared genetic and/or environmental effects between epigenetic age acceleration and organ damage pairs that were significantly associated. Results After adjustment for sex, chronological age, and time between methylation and organ damage measures, higher IEAA was associated with higher urine albumin to creatinine ratio (UACR, p = 0.004), relative wall thickness (RWT, p = 0.022), and left ventricular mass index (LVMI, p = 0.007), and with lower ankle-brachial index (ABI, p = 0.014). EEAA was associated with higher LVMI (p = 0.005). Target organ damage associations for all but IEAA with LVMI remained significant after further adjustment for blood pressure and antihypertensive use (p < 0.05). Further adjustment for diabetes attenuated the IEAA associations with UACR and RWT, and adjustment for smoking attenuated the IEAA association with ABI. No effect modification by age or sex was observed. Conclusions Measures of epigenetic age acceleration may help to better characterize the functional mechanisms underlying organ damage from cellular aging and/or hypertension. These measures may act as subclinical biomarkers for damage to the kidney, heart, and peripheral vasculature; however more research is needed to determine whether these relationships remain independent of lifestyle factors and comorbidities.https://deepblue.lib.umich.edu/bitstream/2027.42/152221/1/12920_2019_Article_585.pd

Factors Influencing Cost-Related Nonadherence to Medication in Older Adults: A Conceptually Based Approach

Although multiple noncost factors likely influence a patient's propensity to forego treatment in the face of cost pressures, little is known about how patients' sociodemographic characteristics, physical and behavioral health comorbidities, and prescription regimens influence cost-related nonadherence (CRN) to medications. We sought to determine both financial and nonfinancial factors associated with CRN in a nationally representative sample of older adults.We used a conceptual model developed by Piette and colleagues that describes financial and nonfinancial factors that could increase someone's risk of CRN, including income, comorbidities, and medication regimen complexity. We used data from the 2004 wave of the Health and Retirement Study and the 2005 HRS Prescription Drug Study to examine the influence of factors within each of these domains on measures of CRN (including not filling, stopping, or skipping doses) in a nationally representative sample of Americans age 65+ in 2005.Of the 3071 respondents who met study criteria, 20% reported some form of CRN in 2005. As in prior studies, indicators of financial stress such as higher out-of-pocket payments for medications and lower net worth were significantly associated with CRN in multivariable analyses. Controlling for these economic pressures, relatively younger respondents (ages 65–74) and depressive symptoms were consistent independent risk factors for CRN.Noncost factors influenced patients' propensity to forego treatment even in the context of cost concerns. Future research encompassing clinician and health system factors should identify additional determinants of CRN beyond patients' cost pressures.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/78680/1/j.1524-4733.2009.00679.x.pd

Folate Receptor Beta Designates Immunosuppressive Tumor-Associated Myeloid Cells That Can Be Reprogrammed with Folate-Targeted Drugs

Although immunotherapies of tumors have demonstrated promise for altering the progression of malignancies, immunotherapies have been limited by an immunosuppressive tumor microenvironment (TME) that prevents infiltrating immune cells from performing their anticancer functions. Prominent among immunosuppressive cells are myeloid-derived suppressor cells (MDSC) and tumor-associated macrophages (TAM) that inhibit T cells via release of immunosuppressive cytokines and engagement of checkpoint receptors. Here, we explore the properties of MDSCs and TAMs from freshly isolated mouse and human tumors and find that an immunosuppressive subset of these cells can be distinguished from the nonimmunosuppressive population by its upregulation of folate receptor beta (FRβ) within the TME and its restriction to the TME. This FRβ+ subpopulation could be selectively targeted with folate-linked drugs. Delivery of a folate-targeted TLR7 agonist to these cells (i) reduced their immunosuppressive function, (ii) increased CD8+ T-cell infiltration, (iii) enhanced M1/M2 macrophage ratios, (iv) inhibited tumor growth, (v) blocked tumor metastasis, and (vi) improved overall survival without demonstrable toxicity. These data reveal a broadly applicable strategy across tumor types for reprogramming MDSCs and TAMs into antitumorigenic immune cells using a drug that would otherwise be too toxic to administer systemically. The data also establish FRβ as the first marker that distinguishes immunosuppressive from nonimmunosuppressive subsets of MDSCs and TAMs. Because all solid tumors accumulate MDSCs and TAMs, a general strategy to both identify and reprogram these cells should be broadly applied in the characterization and treatment of multiple tumors

Association of Mitochondrial DNA Copy Number With Brain MRI Markers and Cognitive Function: A Meta-Analysis of Community-Based Cohorts

BACKGROUND AND OBJECTIVES: Previous studies suggest that lower mitochondrial DNA (mtDNA) copy number (CN) is associated with neurodegenerative diseases. However, whether mtDNA CN in whole blood is related to endophenotypes of Alzheimer disease (AD) and AD-related dementia (AD/ADRD) needs further investigation. We assessed the association of mtDNA CN with cognitive function and MRI measures in community-based samples of middle-aged to older adults. METHODS: We included dementia-free participants from 9 diverse community-based cohorts with whole-genome sequencing in the Trans-Omics for Precision Medicine (TOPMed) program. Circulating mtDNA CN was estimated as twice the ratio of the average coverage of mtDNA to nuclear DNA. Brain MRI markers included total brain, hippocampal, and white matter hyperintensity volumes. General cognitive function was derived from distinct cognitive domains. We performed cohort-specific association analyses of mtDNA CN with AD/ADRD endophenotypes assessed within ±5 years (i.e., cross-sectional analyses) or 5-20 years after blood draw (i.e., prospective analyses) adjusting for potential confounders. We further explored associations stratified by sex and age (≥60 years). Fixed-effects or sample size-weighted meta-analyses were performed to combine results. Finally, we performed mendelian randomization (MR) analyses to assess causality. RESULTS: We included up to 19,152 participants (mean age 59 years, 57% women). Higher mtDNA CN was cross-sectionally associated with better general cognitive function (β = 0.04; 95% CI 0.02-0.06) independent of age, sex, batch effects, race/ethnicity, time between blood draw and cognitive evaluation, cohort-specific variables, and education. Additional adjustment for blood cell counts or cardiometabolic traits led to slightly attenuated results. We observed similar significant associations with cognition in prospective analyses, although of reduced magnitude. We found no significant associations between mtDNA CN and brain MRI measures in meta-analyses. MR analyses did not reveal a causal relation between mtDNA CN in blood and cognition. DISCUSSION: Higher mtDNA CN in blood is associated with better current and future general cognitive function in large and diverse communities across the United States. Although MR analyses did not support a causal role, additional research is needed to assess causality. Circulating mtDNA CN could serve nevertheless as a biomarker of current and future cognitive function in the community

Measurement of the helicity asymmetry E for the γ→ p→ → pπ reaction in the resonance region: The CLAS Collaboration

The double-spin-polarization observable E for γ→ p→ → pπ has been measured with the CEBAF Large Acceptance Spectrometer (CLAS) at photon beam energies Eγ from 0.367 to 2.173GeV (corresponding to center-of-mass energies from 1.240 to 2.200GeV) for pion center-of-mass angles, cosθπ0c.m. , between - 0.86 and 0.82. These new CLAS measurements cover a broader energy range and have smaller uncertainties compared to previous CBELSA data and provide an important independent check on systematics. These measurements are compared to predictions as well as new global fits from The George Washington University, Mainz, and Bonn-Gatchina groups. Their inclusion in multipole analyses will allow us to refine our understanding of the single-pion production contribution to the Gerasimov-Drell-Hearn sum rule and improve the determination of resonance properties, which will be presented in a future publication