Modest Correlation Research Articles

Inflammatory Markers and Fatigue in Individuals With Moderate to Severe Chronic Obstructive Pulmonary Disease.

Fatigue, a prevalent complex symptom among patients with chronic obstructive pulmonary disease (COPD), is considered an important clinical indicator of disease severity. However, the underlying mechanisms of COPD-related fatigue are not fully understood. This analysis explored the relationships between peripheral inflammatory markers and COPD-related fatigue in people with moderate to severe COPD. This is a secondary analysis of a longitudinal observational study of individuals with COPD examining the biological causes and functional consequences of depression. The data used in this study were collected at baseline. Systemic inflammation markers included C-reactive protein (CRP) and three pro-inflammatory cytokines consisting of interleukin-6 (IL-6), IL-8, and tumor necrosis factor-α. COPD-related fatigue was self-reported using the Chronic Respiratory Questionnaire. Covariates included age; gender; smoking status; disease severity; symptoms of depression, anxiety, and pain; and social support. Multivariable linear regression analyses were conducted. The sample included 300 adults living with COPD; 80% were male, and the average age was 67.6 years. Modest correlations were found between two systemic inflammatory markers (CRP and IL-8) and COPD-related fatigue. CRP was the only inflammatory marker significantly associated with fatigue symptoms after adjusting for covariates in multivariable analyses. Depression, pain, and education level were also significant predictors of COPD-related fatigue. The findings suggest that altered immune response based on CRP may contribute to COPD-related fatigue. Management of depression and pain may work as an effective treatment strategy for COPD-related fatigue. Further longitudinal studies with a broader range of inflammatory markers and multidimensional measures of fatigue symptoms are warranted.

The diagnostic accuracy of preoperative perfusion index as a predictor of postspinal anesthesia hypotension in parturients undergoing cesarean delivery: A prospective non-blinded observational study.

Spinal anesthesia is the technique of choice for elective cesarean section with a prominent side effect of postspinal anesthesia hypotension (PSH). This needs an early prediction to avoid feto-maternal complication. This study aimed to assess the diagnostic accuracy of perfusion index (PI) and inferior vena cava collapsibility index (IVCCI) in the prediction of PSH. Thirty parturients of American Society of Anesthesiologists Physical Status (ASA-PS) 1 and two undergoing cesarean delivery participated in the study. IVCCI, PI, baseline systolic blood pressure (SBP), diastolic blood pressure (DBP), mean blood pressure (MBP), and heart rate (HR) were noted in the preoperative period. The fall of MBP by 20% from baseline or below 65 mm Hg was considered PSH. After spinal anesthesia, SBP, DBP, MBP, and HR were noted again for diagnosing PSH. It did not show any statistical difference when comparing the PI between the PSH and non-PSH groups in both the PSH definition groups. IVCCI was significantly higher when PSH was considered MBP <65 mm Hg (P = 0.01). However, IVCCI was found to be statistically insignificant if PSH was considered a 20% reduction in baseline MBP. The correlation matrix between IVCCI and PI showed Pearson's r-value of 0.525, indicating a substantial relationship between the two (P = 0.003). Multivariate logistic regression analysis had shown that neither IVCCI nor PI was a good predictor of PSH in parturients for both definition groups for PSH. Although there is a modest correlation between PI and IVCCI, both cannot be used to predict postspinal hypotension in parturients undergoing elective lower-segment cesarean section (LSCS).

Solar radio bursts impact on the International GNSS Service Network during Solar Cycle 24

Solar radio bursts (SRB) are a known source of noise for Global Navigation Satellite Systems (GNSS) such as GPS or Galileo. They can degrade the carrier-to-noise ratio of satellite signals, thereby diminishing system performance and, in severe cases, causing total service outages. Although a small amount of particularly intense events have already been studied in detail, the commonness and intensity of SRBs that could potentially impair GNSS performance remain uncertain. This study broadens the scope beyond merely extreme SRBs, studying the impact of SRBs on GNSS throughout Solar Cycle 24. Solar 1.4 GHz observations from the Radio Solar Telescope Network are used to find the 20 most intense SRBs at that frequency. The impact of each SRB is then evaluated in terms of GNSS signal strength decrease, reduction in the number of available satellites, and precision degradation. The results show that at the GPS L1 frequency only one event presented extended service degradation, while at the L2 frequency, minimum operational requirements were not met by at least one station during seven of the SRBs. Only a modest correlation between performance degradation and SRB intensity is found. In particular, it is reported how some mild SRBs affected satellite signals while others almost ten times more intense went unnoticed. The fundamental role that the SRB circular polarization plays in these discrepancies is shown with new 1.4 GHz circular polarization observations from the SMOS satellite. The different responses of GNSS receivers to SRBs depending on the receiver manufacturer are also explored.

Similar Tuning of Distortion-Product Otoacoustic Emission Ratio Functions and Cochlear Vibrations in Mice.

When elicited by two stimulus tones (at frequencies f1 and f2, f2 > f1), the amplitudes of specific distortion-product otoacoustic emission (DPOAE) components exhibit a characteristic bandpass shape as the ratio between f2 and f1 is varied. This bandpass shape has been attributed to various mechanisms including intracochlear resonance, suppression, and wave interference, and has been proposed to be related to cochlear frequency tuning. While human studies suggest modest correlations between psychophysical tuning and the tuning of DPOAE amplitude vs. f2/f1 ratio functions, a relationship between the latter and the tuning of cochlear mechanical responses has yet to be established. This was addressed here through direct comparisons of DPOAEs and cochlear vibrations in wild-type CBA/CaJ mice. DPOAEs were elicited using a fixed-f2, swept-f1 paradigm, and optical coherence tomography was used to measure displacements from cochlear locations with characteristic frequencies near f2. The tuning sharpness of 2f1-f2 DPOAE ratio functions was found to be remarkably similar to that of basilar membrane and/or tectorial membrane responses to single tones, with the tuning sharpness of all responses increasing similarly with decreasing stimulus level. This relationship was observed for f2 frequencies ranging from ~8 to 22 kHz. Intracochlear distortion products did not exhibit a bandpass shape as the f2/f1 ratio was varied, indicating that interference between distortion products traveling to the stapes may be responsible for the tuning of the DPOAE ratio function. While these findings suggest that DPOAE ratio functions could be used to noninvasively infer cochlear tuning, it remains to be determined whether this relationship holds in other species and for lower frequency regions.

Testing the validity of the smartphone pervasiveness scale for adolescents with self-reported objective smartphone use data.

An ongoing and heated scientific debate pertains to the conceptualization and quantification of adolescents' problematic smartphone use (PSU). To address the limitations of existing surveys, the smartphone pervasiveness scale for adolescents (SPS-A) has been designed to measure the subjective frequency of smartphone usage during significant moments within daily routines. Given the weak correlations in prior literature between self-reported PSU metrics and objective use data, this study investigates the relationships between diverse self-reported objective metrics of smartphone engagement-that is duration, frequency, and count of notifications-and the SPS-A scale, employing a cohort of Swiss adolescents (N = 1396; Mage = 15.8, SDage = 0.81; 59% female). The findings reveal a substantial correlation between the total objectively measured duration of smartphone engagement and the SPS-A scale (r = .41 for iOS users and r = .42 for Android users). Moreover, a similar trend emerges as users are categorized by their level of objective use, with each category displaying a linear augmentation in smartphone pervasiveness levels. Instead, modest correlations emerge when considering the quantity of device unlocks and notifications. Noteworthy, no gender disparities emerged. These results add to our knowledge about the usefulness of the concept and measurement of smartphone pervasiveness: not only the SPS-A is a valid alternative to scales on "smartphone addiction" to capture non-pathological PSU, but it is also a better predictor of smartphone objective duration of use than self-reported measures. The correlation found between self-reported pervasiveness and actual use is discussed in light of the debate about the relevance of screen time in the study of PSU.

Species dependent correlation analysis and regression models of body weight on linear body measures in indigenous sheep and goats of Zimbabwe

&lt;p&gt;Measurements of live weight in goats and sheep are an important source of information for a range of scientific fields and applications in animal husbandry activities. The study was conducted to investigate the relationship between body weight and body measurements and to predict live body weight from body measurements in indigenous Matabele goats and indigenous Sabi sheep at Matopos Research Station in Zimbabwe. For this purpose, data on body weight (BWT) and linear body measurements (LBM) such as heart girth (HG), body length (BL), wither height (WTH), and rump height (RH) were collected from randomly selected females of each species at the age of 4 years. The corresponding means, standard deviations (SD), and coefficients of variation (CV) were determined for body weight and linear body measurements. Bivariate correlations between bodyweight and linear body measure characteristics were also determined. Simple and multiple regression were used to develop a model to predict BWT using linear body measures. Indigenous Matabele goat females’ CV ranged from 15.77% to 22.68%, while indigenous Sabi sheep females’ CV ranged from 19.16% to 19.37%. The CV was calculated by dividing the mean by the standard deviation. At 4 years of age, the mean BWT of the indigenous Sabi sheep and female Matabele goat were 35.96 ± 0.83 kg and 27.90 ± 0.66 kg, respectively. In indigenous Matabele goat females, the average linear body measures were HW (74.20 ± 0.53 cm), WTH (48.55 ± 0.53 cm), BL (47.53 ± 0.61 cm), and RH (57.50 ± 0.88 cm). The mean values for native Sabi sheep were 63.33 ± 0.70 cm, WTH (52.00 ± 0.80 cm), BL (51.26 ± 0.78 cm), and HW (85.56 ± 1.04 cm). The results showed a strong and positive correlation between BWT and linear body measures in female indigenous Matabele goats. The phenotypic correlation values were HG (&lt;em&gt;r&lt;/em&gt; = 0.79), BL (r = 0.70), WTH (&lt;em&gt;r&lt;/em&gt; = 0.68), and RH (&lt;em&gt;r&lt;/em&gt; = 0.56), in decreasing order. In indigenous Sabi sheep, the phenotypic correlation for BWT and linear body measurement was high and positive for HG (&lt;em&gt;r&lt;/em&gt; = 0.73), and positive and moderate to low with WTH (&lt;em&gt;r&lt;/em&gt; = 0.41), BL (&lt;em&gt;r =&lt;/em&gt; 0.32), and RH (&lt;em&gt;r&lt;/em&gt; = 0.36). Again, the results also indicated that HG had a high and positive phenotypic correlation with BL (&lt;em&gt;r&lt;/em&gt; = 0.53), while modest correlation was observed with HG and WTH (&lt;em&gt;r&lt;/em&gt; = 0.41) and HG and RH (0.32). The optimal regression models for easily measuring body weight using HHG are BWT = −46.711 + 1.006 HG (&lt;em&gt;R&lt;/em&gt;&lt;sup&gt;2&lt;/sup&gt; = 60%) and BWT = −15.209 + 0.586 HG (&lt;em&gt;R&lt;/em&gt;&lt;sup&gt;2&lt;/sup&gt; = 53%) for indigenous Matabele goats and indigenous Sabi sheep, respectively. It is recommended that smallholder farmers use HG measurements to estimate body weight in both indigenous Sabi sheep and indigenous Matabele goat females at the age of 4 years.&lt;/p&gt;

Developmental links between well-being, self-concept and prosocial behaviour in early primary school.

Well-being is a key aspect of children's education, yet measurement issues have limited studies in early primary school. The current 12-month longitudinal study assesses the temporal stability of child- and parent-reported school well-being and examines developmental links with academic self-concept and parent-rated prosocial behaviour. We tracked a sample of 206 children across the transition from the first (T1) to the second (T2) year of primary school (T1 child Mage = 5.3, SD = .46, 54.3% girls) and gathered ratings of well-being, prosocial behaviour and academic self-concept at both timepoints. We used cross-lagged analyses to investigate developmental links between these three constructs. Parent and child reports of children's well-being showed similar temporal stability and converged over time, such that informants' reports showed a modest but significant correlation at T2. Girls reported greater well-being than boys at both timepoints and received higher parental ratings of well-being than boys at T2. For both girls and boys, associations between the constructs were asymmetric: early well-being predicted later self-concept and prosocial behaviour, but the reciprocal associations were not significant. These findings support the validity of young children's self-reported well-being, highlight the early onset of gender differences in school well-being and demonstrate that early well-being heralds later prosocial behaviour and positive academic self-concepts.

Albedo on a glacial foreland at ground level and landscape scale driven by vegetation-substrate patterns

Recent anthropogenic climate change has caused both glacial retreat and increased vegetative growth on Arctic and subarctic tundra landscapes resulting in changing albedo and energy budgets. Glacial forelands are topographically and ecologically heterogeneous landscapes comprising ice-contact and outwash deposits subject to primary succession. The most recent moraines on the foreland of the Skaftafellsjökull in southern Iceland are mostly unvegetated, but vegetation cover increases with the age in a general sense. Vegetated outwash channel terraces occur between the moraines, and a broad vegetated outwash plain occurs distal to the oldest moraine. Variations in albedo were measured at ground level to determine the specific role of vegetation types and varying substrates. Albedo and coverage by major plant groups were measured along transects established on moraines ranging in age from 20 to 130 years and the terrace of one outwash channel and three locations on the outwash plain. Total vegetation cover and coverage by mosses increases on the glacial moraines largely as a function of time but is subject to strong aspect effects. Total vegetation cover and moss cover are highest on outwash deposits, possibly due to a sheltered aspect and greater uniformity of the outwash surface. Measured albedo exhibits a modest positive correlation with total vegetation cover and a modest negative correlation with rock and soil exposure. The strongest positive correlation was found between albedo and moss cover. The differences in brightness between moraines and outwash deposits are evident visually at the landscape scale on satellite photographs and quantifiable by image-processing software.

Exploring NDVI change patterns across the Tibetan Plateau at the hillslope scale using geomorphons

ABSTRACTWithin the Tibetan Plateau (TP), grassland degradation is of great concern, and there is a need to better understand the spatial variability and landscape patterns in grassland degradation across the TP. This study explores potential patterns in grassland degradation, estimated using Landsat-derived normalized difference vegetation index (NDVI) growing season change products generated by a prior study. Shuttle Radar Topography Mission (SRTM) digital terrain model (DTM)-derived geomorphons, topographic slope and the topographic position index (TPI) were used to explore grassland degradation and assess whether changes in growing season NDVI are associated with specific grasslands or landforms. An increase in NDVI within the TP was observed especially during the 1990 to 2018 and 2000 to 2018 time periods. Higher growing season median NDVI change values were found for the Southeast Tibet Shrublands and Meadows (SETSM) and TP Alpine Shrublands and Meadows (TPASM) grasslands in comparison to the other grassland types analysed, suggesting a more pronounced greening trend in the eastern portion of the plateau in comparison to the western portion. Small differences in NDVI change were observed for different geomorphon-based landforms, while topographic slope and TPI showed only modest correlations with NDVI change for all time periods and grassland types. More localized patterns of grassland degradation were masked by the widespread greening trends. Further analysis of only pixels that experienced a decreasing NDVI magnitude of less than or equal to −0.1 also generally suggested more change in the SETSM and TPASM. While this study generally supports the use of geomorphons as an analysis and aggregating unit for studying change patterns at the hillslope scale, more research is required to fully grasp the dynamics of landscape change at the hillslope scale in the TP.

Examination of plasma YKL‐40 as a clinical biomarker for Alzheimer’s disease

AbstractBackgroundBlood biomarkers represent a potential non‐invasive and cost‐effective strategy for the clinical detection and monitoring of neurodegenerative conditions including Alzheimer’s disease (AD). YKL‐40 is a secreted glycoprotein associated with inflammatory processes, and elevated cerebrospinal fluid levels have been observed in AD and other neurodegenerative conditions. Fewer studies have examined plasma YKL‐40. We examined relationships between plasma YKL‐40 and clinical indices of AD in a large cross‐sectional sample from a clinical cohort registry.MethodThe sample included 569 participants from the Boston University Alzheimer’s Disease Research Center, including participants with normal cognition (NC; n = 235), mild cognitive impairment due to suspected AD (MCI; n = 181), and AD dementia (n = 153). Blood plasma samples were analyzed using standard ELISA methods; values were log transformed and standardized into z‐scores. Cross‐sectional analyses investigated the relationships between YKL‐40 and clinical indices of functioning including diagnostic status, dementia severity (on the Clinical Dementia Rating scale [CDR]), and neuropsychological test performance. Age, sex, education, race, and APOE ε4 carrier status were included as covariates in all analyses.ResultNo significant differences in plasma YKL‐40 were observed between participants with NC, MCI, and AD dementia after accounting for covariates. The comparison between MCI and dementia was marginally significant (p = .07), with an adjusted mean difference of Z = 0.19. For participants with dementia (CDR scores 1‐3), non‐significant trends were observed for relationships between plasma YKL‐40 values and dementia severity, including for Sum of Boxes (Pearson partial correlation: r = .14, p = .10) and Total Score (ordinal logistic regression: OR = 1.38; 95% CI: [0.98,1.93]), p = .06. Modest but significant correlations were observed between YKL‐40 and performance on 4/12 neuropsychological tests including Animal Fluency (r = ‐.10), Vegetable Fluency (r = ‐.09), and Neuropsychological Assessment Battery List Learning Trials 1‐3 (r = ‐.10) and Short Delay (r = ‐.12).ConclusionPlasma YKL‐40 biomarker levels were modestly related to neuropsychological assessments of language and memory but not significantly related to cognitive diagnosis of AD or dementia severity. This biomarker may reflect underlying inflammatory processes in the context of AD. However, the use of plasma YKL‐40 to assess the presence and severity of AD in a larger cross‐sectional sample size, and using a multiple biomarker approach, warrant further study.

Developing a DNAm Surrogate to Predict Cognitive Functioning among Older Adults

AbstractBackgroundBlood‐based epigenetic measures are being developed and used to predict aging‐related health outcomes. Specifically, researchers have developed “epigenetic clocks” based on predictions of chronological age and age‐related health declines by DNA methylation. However, these markers are meant to predict aging per se and are not disease specific. Recently, scholars have developed “DNAm surrogates” to predict specific outcomes. This methodological technique has yet to be applied to cognitive functioning despite its potential to improve prediction of cognitive health in later life and provide insight into the role of biological aging.MethodThis study developed a novel DNAm surrogate measure for cognitive functioning (DNAmCogScore) based on an elastic net approach linking using 833,865 CpG sites predicting the Telephone Interview Cognitive Status score (TICS) available in the Health and Retirement Study (HRS), a nationally representative sample of older adults in the United States. Additionally, we evaluate the association of this DNAm surrogate and other neuropathology biomarkers. We used used ridge regression to create DNAmCogScore with 50% of the sample for training and 50% for testing (N = 2009 for each subsample). The Irish Longitudinal Study of Aging (TILDA) will be used for validation (results forthcoming).ResultWe find a positive association and modest predictive value between DNAmCogScore and TICS (see Figure 1, r = .4). Table 1 shows the strong associations with the DNAmCogScore and demographic characteristics. Overall, we find a strong positive coefficient between DNAmCogScore with attenuation after controlling for demographic characteristics, from 1.12 in Model 1 to .20 in Model 3, but remaining statistically significant throughout. Table 3 shows modest negative correlations between DNAmCogScore and NfL, pTau181, and GFAP (ranging from ‐.24 to ‐.36) and no correlation with AB42:40.ConclusionThis study is among the first to create a DNA methylation surrogate measure of cognitive functioning. Our measure is associated with cognitive functioning, even after adjusting for key demographic characteristics. And it has the expected association with other more neuropathology biomarkers. Overall, it suggests that changes in DNA methylation may be a molecular‐level mechanisms by which biological aging impacts cognitive health, and this measure may provide useful prediction of cognitive impairment before the onset of symptoms.

Aerosol absorption using in situ filter-based photometers and ground-based sun photometry in the Po Valley urban atmosphere

Abstract. Light-absorbing aerosols (LAAs) are short-lived climate forcers with a significant impact on Earth's radiative balance. LAAs include dust aerosols, black carbon (BC) and organic light-absorbing carbonaceous aerosol (collectively termed brown carbon, BrC), which have also been proven to be highly toxic. In this study, aerosol absorption at five wavelengths (ranging from ultraviolet to infrared) was monitored continuously using filter-based photometers during two winter seasons in 2020 and 2021 in the city of Modena (southern central Po Valley, northern Italy), at two regulatory air quality monitoring sites, along with other pollutants (coarse particulate matter, PM10; fine particulate matter, PM2.5; O3; NO; NO2; and C6H6) and the vehicular traffic rate. The aerosol optical depth (AOD) and other column aerosol optical properties were concurrently monitored at four wavelengths by an AErosol RObotic NETwork (AERONET) sun photometer under urban background conditions within Modena. In situ absorption levels were apportioned to both sources (fossil fuel and biomass burning) and species (BC and BrC), while columnar absorption was apportioned to BC, BrC and mineral dust. The combined analysis of the atmospheric aerosol and gas measurements and of the meteorological conditions (in situ and from the ERA5 reanalysis) identified the location of potential urban sources of BC and BrC, most likely related to traffic and biomass burning. In situ data show different diurnal/weekly patterns for BrC from biomass burning and BC from traffic, with minor differences between the background and the urban traffic conditions. AERONET version 3 absorption aerosol optical depth (AAOD) retrievals at four wavelengths allowed the estimation of the absorptive direct radiative effect due to LAAs over the same period under the reasonable assumption that the AOD signal is concentrated within the mixing layer. AERONET retrievals showed a modest correlation of columnar absorption with planetary boundary layer (PBL)-scaled in situ observations, although the correlation improved significantly during a desert dust transport event that affected both in situ aerosol and columnar absorption, particularly in the blue spectrum range. A low correlation occurred between the contribution of BrC to aerosol absorption for the in situ and the columnar observations, with the BrC contribution being generally larger for in situ observations. Finally, evidence of a highly layered atmosphere during the study period, featuring significant spatial mixing and modest vertical mixing, was shown by ERA5-based atmospheric temperature profiles and by the large correlation of concurrent AERONET AOD retrievals in Modena and in Ispra (on the northwestern side of the Po Valley, ca. 225 km from Modena).

The Interpretation of Standard Cardiopulmonary Exercise Test Indices of Cardiac Function in Chronic Kidney Disease

Background and Aims: As there is growing interest in the application of cardiopulmonary exercise test (CPX) in chronic kidney disease (CKD), it is important to understand the utility of conventional exercise test parameters in quantifying the cardiopulmonary fitness of patients with CKD. Merely extrapolating information from heart failure (HF) patients would not suffice. In the present study, we evaluated the utility of CPX parameters such as the peak O2-pulse and the estimated stroke volume (SV) in assessing the peak SV by comparing with the actual measured values. Furthermore, we compared the anaerobic threshold (AT), peak circulatory power, and ventilatory power with that of the measured values of the peak cardiac power (CPOpeak) in representing the cardiac functional reserve in CKD. We also performed such analyses in patients with HF for comparison. Method: A cross sectional study of 70 asymptomatic male CKD patients [CKD stages 2–5 (pre-dialysis)] without primary cardiac disease or diabetes mellitus and 25 HF patients. A specialized CPX with a CO2 rebreathing technique was utilized to measure the peak cardiac output and peak cardiac power output. The peak O2 consumption (VO2peak) and AT were also measured during the test. Parameters such as the O2-pulse, stroke volume, arteriovenous difference in O2 concentration [C(a-v)O2], peak circulatory power, and peak ventilatory power were all calculated. Pearson’s correlation, univariate, and multivariate analyses were applied. Results: Whereas there was a strong correlation between the peak O2-pulse and measured peak SV in HF, the correlation was less robust in CKD. Similarly, the correlation between the estimated SV and the measured SV was less robust in CKD compared to HF. The AT only showed a modest correlation with the CPOpeak in HF and only a weak correlation in CKD. A stronger correlation was demonstrated between the peak circulatory power and CPOpeak, and the ventilatory power and CPOpeak. In HF, the central cardiac factor was the predominant determinant of the standard CPX-derived surrogate indices of cardiac performance. By contrast, in CKD both central and peripheral factors played an equally important role, making such indices less reliable markers of cardiac performance per se in CKD. Conclusion: The results highlight that the standard CPX-derived surrogate markers of cardiac performance may be less reliable in CKD, and that further prospective studies comparing such surrogate markers with directly measured cardiac hemodynamics are required before adopting such markers into clinical practice or research in CKD.

Comparison between self‐ and informant‐rated versions of the Mild behavioral impairment checklist in patients with mild cognitive impairment

AbstractBackgroundMild behavioral impairment (MBI) describes de novo emergent and persistent neuropsychiatric symptoms in older individuals. MBI is common in individuals with mild cognitive impairment (MCI), but self‐endorsed symptoms may not align with reports from informants. In this study, we explore the consistency between self‐ and informant‐rated versions of the Mild behavioral impairment checklist (MBI‐C), which is used to assess MBI.MethodWe included 68 individuals with MCI (MMSE 26.59±2.55) who underwent neurological, extensive neuropsychological examination and brain MRI within the Czech Brain Aging Study and had no history of prior psychiatric disorder. Both participants and their close informants completed The Czech version of the MBI‐C (MBI‐C self and MBI‐C informant, respectively). The consistency and differences between the MBI‐C self and informant total and domain scores (i.e. motivation, affect, impulse dyscontrol, social inappropriateness and psychotic symptoms), and the presence of MBI based on a cut‐off of ≥7, were examined using Wilcoxon signed‐rank test, the binomial test and Spearman´s rank correlation. Further, we explored the association between the informant‐self score difference with the MMSE as a measure of global cognition.ResultThere was no difference between MBI‐C self and informant total score (both median ratings were 5.0). Among the domain scores, we observed a difference between self and informant ratings in the impulse dyscontrol (Z = ‐2.97, p = 0.003), but not in any other score. Disagreements on the presence of MBI were observed in 19 participants (28%), but both patients and informants were equally likely to disagree on the MBI presence vs. absence. We observed weak to modest correlations between MBI‐C self and informant total and domain scores (rS = 0.34‐0.53, ps&lt;0.01). The informant‐self score difference in MBI‐C impulse dyscontrol was negatively associated with the MMSE (rS = ‐0.39, p = 0.001).ConclusionPatients with MCI and their informants were not consistent regarding the presence of MBI, but among those who disagreed, neither informants nor patients were more likely to report MBI. The informants reported more severe impulse dyscontrol symptoms compared to the patients with MCI themselves and this difference was negatively associated with lower MMSE. The observed inconsistencies provide implications for clinical and research settings.

Association of p16, a Biomarker of Cellular Senescence, with Receipt of Therapy for Plasma Cell Disorders

Introduction Multiple myeloma (MM) and immunoglobulin light chain (AL) amyloidosis are clonal plasma cell disorders (PCDs) of aging, with median ages at diagnosis of 69 and 76 years, respectively. The care of adults with these disorders is often challenging due to the higher prevalence of vulnerabilities with advancing age. We examined patterns of senescence biomarkers and associations with therapy receipt among adults treated for plasma cell disorders. Methods Adults undergoing treatment for PCDs were recruited to a longitudinal observational study (NCT03717844) from 2018 to 2020. Study participants provided blood samples and completed study assessments at pre-specified intervals. Cellular senescence was quantified by measuring mRNA expression of p16 in peripheral blood T lymphocytes. Expression of p16 is reported as log2 arbitrary units. A linear regression formula previously derived from p16 expression in 633 subjects was utilized to translate p16 expression levels into an age equivalent. These values were used to calculate the p16AgeGap, a difference between an individual's p16 expression and their chronological age. Subjects with p16 levels below the age-appropriate population mean have a negative p16AgeGap, and those with p16 above the population mean have a positive p16AgeGap. Exposures included both treatment receipt and duration of therapy. Treatment was assessed via categorical classification of treatment intensity, and treatment duration was quantified from diagnosis to time of p16 blood draw. Descriptive statistics were calculated for baseline demographic and disease characteristic variables. The p16 and p16AgeGap variables were summarized in terms of means and 95% confidence intervals (CI). The significance of associations between p16/p16AgeGap and categorical variables was assessed via Kruskal-Wallis or Wilcoxon rank-sum tests. Associations between continuous variables were assessed via calculation of Pearson correlation coefficients. Results The cohort consisted of 109 individuals (88 with multiple myeloma and 21 with other plasma cell disorders). Mean age was 68 years (range 39-91). The sample was predominantly male (56.9%) and White (70.6%). Samples for p16 were drawn prior to any treatment in 20 subjects. The remainder had received prior therapy and 36 had relapsed/refractory disease. There was a significant association between the treatment receipt and p16 as well as between the treatment receipt and p16AgeGap (Figure 1). We observed a significant modest positive correlation between the duration of treatment and p16 (correlation coefficient 0.27, p=0.007) and p16AgeGap (0.22, p=0.03). Among those who had undergone transplant, we observed higher mean p16 (mean 12.84 [95% CI 12.46-13.23] vs 11.81 [11.51-12.11] for non-recipients, p=0.0001) and p16AgeGap (mean 50.6 [39.6-61.6] vs 16.9 [8.4-25.4], p &amp;lt;0.0001). There was a significant association between receipt of bortezomib-containing regimens with both p16 levels p16AgeGap, with higher mean p16 &amp; mean p16AgeGap for those who did not receive bortezomib. For the subset of patients with transplant date before the p16 collection date (N=38), there was no significant association between time since transplant and either p16 level or p16AgeGap. Conclusion This study elucidates the relationship between markers of cellular senescence, specifically p16 levels and the p16AgeGap, and the impact of treatment receipt and duration in a cohort of patients undergoing treatment for plasma cell disorders. There was a clear significant association between the receipt of treatment and both markers of senescence, along with a modest positive correlation between the duration of treatment and these markers. Further analyses involving this cohort will evaluate the relationship between these biomarkers and patient-centered endpoints, including disease-related symptoms and functional outcomes.

Cardiac PET Myocardial Blood Flow Quantification Assessment of Early Cardiac Allograft Vasculopathy

BackgroundPositron emission tomography (PET) has demonstrated utility for diagnostic and prognostic assessment of cardiac allograft vasculopathy (CAV) but has not been evaluated in the first year after transplant. ObjectivesThe authors sought to evaluate CAV at 1 year by PET myocardial blood flow (MBF) quantification. MethodsAdults at 2 institutions enrolled between January 2018 and March 2021 underwent prospective 3-month (baseline) and 12-month (follow-up) post-transplant PET, endomyocardial biopsy, and intravascular ultrasound examination. Epicardial CAV was assessed by intravascular ultrasound percent intimal volume (PIV) and microvascular CAV by endomyocardial biopsy. ResultsA total of 136 PET studies from 74 patients were analyzed. At 12 months, median PIV increased 5.6% (95% CI: 3.6%-7.1%) with no change in microvascular CAV incidence (baseline: 31% vs follow-up: 38%; P = 0.406) and persistent microvascular disease in 13% of patients. Median capillary density increased 30 capillaries/mm2 (95% CI: −6 to 79 capillaries/mm2). PET myocardial flow reserve (2.5 ± 0.7 vs 2.9 ± 0.8; P = 0.001) and stress MBF (2.7 ± 0.6 vs 2.9 ± 0.6; P = 0.008) increased, and coronary vascular resistance (CVR) (49 ± 13 vs 47 ± 11; P = 0.214) was unchanged. At 12 months, PET and PIV had modest correlation (stress MBF: r = −0.35; CVR: r = 0.33), with lower stress MBF and higher CVR across increasing PIV tertiles (all P < 0.05). Receiver-operating characteristic curves for CAV defined by upper-tertile PIV showed areas under the curve of 0.74 for stress MBF and 0.73 for CVR. ConclusionsThe 1-year post-transplant PET MBF is associated with epicardial CAV, supporting potential use for early noninvasive CAV assessment. (Early Post Transplant Cardiac Allograft Vasculopahty [ECAV]; NCT03217786)

Preference for Harmony: A Preference for Structural Simplicity, Familiarity, or Both?

The preference for harmony (PfH) has been posited to represent an individual difference in the preference for stimuli that are relatively simple, regular, and/or harmonious. We tested whether variations in PfH may also reflect the extent to which individuals prefer stimuli that are more familiar, irrespective of their structural features. To this end, we examined the association between PfH and two behavioral measures of the preference for familiarity, one based on individual differences in the strength of the mere-exposure effect and the other based on preferences for musical chords that appear more versus less frequently within Western musical corpora. Our results showed modest but reliable positive correlations between PfH and both measures. These findings qualify the original interpretation of PfH by suggesting that it at least partially reflects a predilection for stimuli that are more familiar, not just structurally simpler, more regular, and/or more harmonious.

The optimal QTc selection in patients of acute myocardial infarction with poor perioperative prognosis

BackgroundThe predictive utility of QTc values, calculated through various correction formulas for the incidence of postoperative major adverse cardiovascular and cerebrovascular events (MACCE) in patients experiencing acute myocardial infarction (AMI), warrants further exploration. This study endeavors to ascertain the predictive accuracy of disparate QTc values for MACCE occurrences in patients with perioperative AMI.MethodsA retrospective cohort of three hundred fourteen AMI patients, comprising 81 instances of in-hospital MACCE and 233 controls, was assembled, with comprehensive collection of baseline demographic and clinical data. QTc values were derived employing the correction formulas of Bazett, Fridericia, Hodges, Ashman, Framingham, Schlamowitz, Dmitrienko, Rautaharju, and Sarma. Analytical methods encompassed comparative statistics, Spearman correlation analysis, binary logistic regression models, receiver operating characteristic (ROC) curves, and decision curve analysis (DCA).ResultsQTc values were significantly elevated in the MACCE cohort compared to controls (P < 0.05). Spearman’s correlation analysis between heart rate and QTc revealed a modest positive correlation for the Sarma formula (QTcBaz) (ρ = 0.46, P < 0.001). Within the multifactorial binary logistic regression, each QTc variant emerged as an independent risk factor for MACCE, with the Sarma formula-derived QTc (QTcSar) presenting the highest hazard ratio (OR = 1.025). ROC curve analysis identified QTcSar with a threshold of 446 ms as yielding the superior predictive capacity (AUC = 0.734), demonstrating a sensitivity of 60.5% and a specificity of 82.8%. DCA indicated positive net benefits for QTcSar at high-risk thresholds ranging from 0 to 0.66 and 0.71–0.96, with QTcBaz, prevalent in clinical settings, showing positive net benefits at thresholds extending to 0-0.99.ConclusionFor perioperative AMI patients, QTcSar proves more advantageous in monitoring QTc intervals compared to alternative QT correction formulas, offering enhanced predictive prowess for subsequent MACCE incidents.

Speckle tracking echocardiography allows for the detection of subclinical myocardial dysfunction resulting from perfusion abnormalities confirmed by SPECT-based CFR measurement

Abstract Background Speckle tracking echocardiography (STE) is helpful for the detection of subclinical systolic function abnormalities. Coronary flow reserve (CFR) measured by dynamic 99mTc-MIBI SPECT-CZT gamma camera allows the diagnosis of myocardial perfusion defects in patients with suspected coronary artery disease (CAD). Purpose The aim of our study is to assess the diagnostic value of STE and SPECT-based CFR in patients with suspected coronary artery disease (CAD). Methods 85 patients (pts) (37.6% females, mean age 65.4 ± 8.5 years) with suspected CAD underwent 2D and 3D STE, as well as myocardial perfusion study with novel solid-state CZT nuclear camera (dipyridamole stress protocol). We calculated global longitudinal left ventricular strain (GLS), as well as LS of individual coronary artery territories (LAD LS, Cx LS and RCA LS). Total CFR and CFR in three coronary territories were also measured. The presence of CAD (coronary artery stenosis &amp;gt; 70%) was assessed by coronary angiography. Results Significant CAD was confirmed in 50 patients. Mean total CFR (1.71 ± 0.61 vs 2.1 ± 0.52, p = 0.002), as well as CFR in LAD territories (1.54 ± 0.68 vs 1.91 ± 0.56, p = 0.02), RCA territories (1.58 ± 0.82 vs 1.95 ± 0.68, p = 0.048) and Cx territories (1.58 ± 0.78 vs 2.08 ±0.76, p = 0.01) were lower in pts with CAD. In the ROC curve analysis of total CFR for the diagnosis of CAD the AUC was found to be 0.7 (p = 0.001). Mean absolute 2D GLS in pts with total CFR &amp;lt; 2.0 was significantly lower than in pts with CFR &amp;gt;= 2.0 (-14.5 ± 4.3 vs -16.9 ± 3.4, p = 0.005). Similar differences were observed in all three coronary territories (p ≤ 0.05). The same results were not observed in case of 3D GLS . Modest but significant correlations were detected between total CFR and 2D GLS values (r = -0.38; p &amp;lt; 0.001), LAD CFR and 2D LAD LS (r = -0.33; p = 0.002), LCx CFR and 2 D LCx LS (r = -0.39; p &amp;lt; 0.001), total CFR and EF (r = 0.36; p &amp;lt; 0.001). GLS at rest had good diagnostic value for detecting total CFR &amp;lt; 2 (AUC= 0.7; p = 0.004). The criterion with the highest diagnostic accuracy was GLS &amp;gt; (- 18.5) – its sensitivity was 84%, specificity 42%, positive predictive value 0.7, negative predictive value 0.7 and overall accuracy 66%. Conclusions CFR assessed by SPECT provides acceptable diagnostic accuracy for the detection of significant CAD. STE allows for identification of patients with subclinical dysfunction resulting from perfusion abnormalities confirmed by SPECT-based CFR measurement.

Abstract 18244: A Multi-Ancestry GWAS of Calcific Aortic Stenosis Among 2.7 Million Individuals

Introduction: Calcific aortic stenosis (CAS) is a common, progressive fibrocalcific pathology of the aortic valve without medical therapy. The genetics of CAS remain only partially understood. Methods: We performed a genome wide association study (GWAS) of CAS among 2,799,598 individuals from the International Aortic Valve Genetics Consortium (IAVGC), comprising 28 cohorts. CAS was identified using a common ICD/CPT based phenotype. GWAS were meta-analyzed using inverse variance weighting with adjustment by linkage-disequilibrium score regression (LDSR) intercept. Unique genome-wide significant (GWS) loci and causal genes were annotated by nearest gene and eQTL colocalization. Genetic correlations were performed against atherosclerotic, adiposity, and lipid traits using LDSR with publicly available GWAS (CARDIoGRAMplusC4D for coronary artery disease [CAD], Million Veteran Program for peripheral artery disease [PAD], MEGASTROKE for ischemic stroke [IS], GIANT for body mass index [BMI], and GLGC for lipids). Results: There were 85,329 individuals with CAS (79,397 White, 3,126 Black, 1,403 Hispanic, and 1,403 East Asian) among 2,799,598 individuals. Meta-analysis of GWAS resulted in 224 unique GWS genomic regions, of which 205 were novel. The majority of the GWS genomic regions (134) did not overlap with prior risk loci for CAD, PAD, IS, BMI, or lipids. Genetic correlation demonstrated modest but significant correlations between CAS and CAD ( r =0.26, p=3.3x10 -18 ), PAD ( r =0.41, p=1.4x10 -30 ), IS ( r =0.18,p=2.8x10 -7 ), BMI ( r =0.22,p=8.6x10 -30 ), and lipids (LDL-C r =0.17,p=3.6x10 -10 ;triglycerides r =0.10,p=1.9x10 -5 ; HDL-C r =-0.07,p=8.0x10 -4 ). Conclusions: This largest to-date multi-ancestry GWAS of CAS identified 205 novel genomic regions. We demonstrate that CAS is genetically distinct from cardiometabolic traits, with only modest genetic correlations and with a majority of CAS risk loci having no overlap with cardiometabolic GWAS risk loci.