Intra-individual Correlation Research Articles

Discordance between mean glucose and time in range in relation to HbA1c in individuals with type 1 diabetes: results from the GOLD and SILVER trials

Aims/hypothesisPrevious studies have shown that individuals with similar mean glucose levels (MG) or percentage of time in range (TIR) may have different HbA1c values. The aim of this study was to further elucidate how MG and TIR are associated with HbA1c.MethodsData from the randomised clinical GOLD trial (n=144) and the follow-up SILVER trial (n=98) of adults with type 1 diabetes followed for 2.5 years were analysed. A total of 596 paired HbA1c/continuous glucose monitoring measurements were included. Linear mixed-effects models were used to account for intra-individual correlations in repeated-measures data.ResultsIn the GOLD trial, the mean age of the participants (± SD) was 44±13 years, 63 (44%) were female, and the mean HbA1c (± SD) was 72±9.8 mmol/mol (8.7±0.9%). When correlating MG with HbA1c, MG explained 63% of the variation in HbA1c (r=0.79, p<0.001). The variation in HbA1c explained by MG increased to 88% (r=0.94, p value for improvement of fit <0.001) when accounting for person-to-person variation in the MG–HbA1c relationship. Time below range (TBR; <3.9 mmol/l), time above range (TAR) level 2 (>13.9 mmol/l) and glycaemic variability had little or no effect on the association. For a given MG and TIR, the HbA1c of 10% of individuals deviated by >8 mmol/mol (0.8%) from their estimated HbA1c based on the overall association between MG and TIR with HbA1c. TBR and TAR level 2 significantly influenced the association between TIR and HbA1c. At a given TIR, each 1% increase in TBR was related to a 0.6 mmol/mol lower HbA1c (95% CI 0.4, 0.9; p<0.001), and each 2% increase in TAR level 2 was related to a 0.4 mmol/mol higher HbA1c (95% CI 0.1, 0.6; p=0.003). However, neither TIR, TBR nor TAR level 2 were significantly associated with HbA1c when accounting for MG.Conclusions/interpretationInter-individual variations exist between MG and HbA1c, as well as between TIR and HbA1c, with clinically important deviations in relatively large groups of individuals with type 1 diabetes. These results may provide important information to both healthcare providers and individuals with diabetes in terms of prognosis and when making diabetes management decisions.Graphical

Virtual non-iodine photon-counting CT-angiography for aortic valve calcification scoring.

Photon-counting detector (PCD)-CT allows for reconstruction of virtual non-iodine (VNI) images from contrast-enhanced datasets. This study assesses the diagnostic performance of aortic valve calcification scoring (AVCS) derived from VNI datasets generated with a 1st generation clinical dual-source PCD-CT. AVCS was evaluated in 123 patients (statistical analysis only comprising patients with aortic valve calcifications [n = 56; 63.2 ± 11.6years]), who underwent contrast enhanced electrocardiogram-gated (either prospective or retrospective or both) cardiac CT on a clinical PCD system. Patient data was reconstructed at 70keV employing a VNI reconstruction algorithm. True non-contrast (TNC) scans at 70keV without quantum iterative reconstruction served as reference in all individuals. Subgroup analysis was performed in 17 patients who received both, prospectively and retrospectively gated contrast enhanced scans (n = 8 with aortic valve calcifications). VNI images with prospective/retrospective gating had an overall sensitivity of 69.2%/56.0%, specificity of 100%/100%, accuracy of 85.4%/81.0%, positive predictive value of 100%/100%, and a negative predictive value of 78.2%/75.0%. VNI images with retrospective gating achieved similar results. For both gating approaches, AVCSVNI showed high correlation (r = 0.983, P < 0.001 for prospective; r = 0.986, P < 0.001 for retrospective) with AVCSTNC. Subgroup analyses demonstrated excellent intra-individual correlation between different acquisition modes (r = 0.986, P < 0.001). Thus, VNI images derived from cardiac PCD-CT allow for excellent diagnostic performance in the assessment of AVCS, suggesting potential for the omission of true non-contrast scans in the clinical workup of patients with aortic calcifications.

Intraindividual Correlation and Comparison of Maximal Aerobic Capacity and Maximum Power in Hand-Crank and Bicycle Spiroergometry.

Spiroergometry is important for modern performance diagnostics, and reference values have been evaluated for bicycle and treadmill ergometers. The aim of this study is to assess the comparability of bicycle and hand-crank spiroergometry and its associated parameters, as hand-crank spiroergometry can be used during rehabilitation in patients with definitive or temporally impairment of the lower extremity. Thirty-seven healthy volunteers completed 2 exhausting performance diagnostics on hand-crank and bicycle spiroergometry. Participants' anthropometric characteristics, maximum power, multiple exertion criteria, maximum aerobic capacity, and maximum heart rate were detected, and ventilatoryand metabolic thresholds were determined. The maximum power, maximum heart rate, maximum aerobic capacity, and ventilatory thresholds were significant higher on the bicycle ergometer (P < .001). The metabolic thresholds occurred on higher lactate values on the hand-crank ergometer. Equations for calculating maximum aerobic capacity from the maximum power measured in either hand-crank or bicycle ergometer could be found through regression analysis. Although there are problems in interpreting results of different ergometries due to severe physiology differences, the equations can be used for patients who are temporally unable to complete the established ergometry due to a deficit in the lower extremity. This could improve training recommendations for patients and para-athletes in particular.

Statistical modeling of diffusive CO2 emissions before the creation of the SINOP hydroelectric reservoir, Brazil.

Several discussions have arisen about energy from hydroelectric plants being considered clean energy and its reservoirs have been investigated due to the large emission of greenhouse gases (GHG), such as carbon dioxide, methane, and nitrous oxide. The present work shows a statistical study of the diffusive CO2 emissions before the formation of the reservoir of the hydroelectric power plant (HPP) of SINOP, Brazil. The association between emissions collected at the surface (water-air) and at the bottom of the reservoir (sediment-water) was investigated during four data collection campaigns, carried out from November 2017 to September 2018. This study aims to compare the effect of reservoir depth on the diffusive flow of CO2 at 34 collection points. The variable depth analyzed was defined from points collected on the surface and bottom of the reservoir. The objective is to detect whether different periods of time and whether the depth of the reservoir have a direct impact on the behavior of diffusive CO2 emissions. As the measurements of the observational unit are repeatedly observed, there is a multilevel structure, individuals are independent of each other, but there is an intra-individual correlation. Considering this data configuration, an estimation of generalized equations (GEE) was performed, which is a technique that estimates the intra-individual correlation matrix and thus produces estimates for the parameters of the generalized regression models (Generalized Regression Models - GLM) that are not biased. The study showed that the average diffusive CO2 emissions are higher on the reservoir surface. The study also found that, on average, there are more emissions during the rainy season in the region than during the dry season.

Non-Invasive Quantitative Approximation of Intracranial Pressure in Pediatric Idiopathic Intracranial Hypertension Based on Point-of-Care Ultrasound of the Optic Nerve Sheath Diameter.

To investigate whether ultrasound-based optic nerve sheath diameter (US-ONSD) is a reliable measure to follow up children with idiopathic intracranial hypertension (IIH). In addition, to analyze the inter- and intra-individual relationships between US-ONSD and intracranial pressure (ICP), and to investigate whether an individualized mathematical regression equation obtained from two paired US-ONSD/ICP values can be used to approximate ICP from US-ONSD values. 159 US examinations and 53 invasive ICP measures via lumbar puncture (LP) were performed in 28 children with IIH. US-ONSD was measured using a 12 Mhz linear transducer and compared to ICP values. In 15 children, a minimum of 2 paired US-ONSD/ICP determinations were performed, and repeated-measures correlation (rmcorr) and intra-individual correlations were analyzed. The cohort correlation between US-ONSD and ICP was moderate (r = 0.504, p < 0.01). Rmcorr (r = 0.91, p < 0.01) and intra-individual correlations (r = 0.956-1) of US-ONSD and ICP were excellent. A mathematical regression equation can be calculated from two paired US-ONSD/ICP values and applied to the individual patient to approximate ICP from US-ONSD. Related to excellent intra-individual correlations between US-ONSD and ICP, an individualized regression formula, created from two pairs of US-ONSD/ICP values, may be used to directly approximate ICP based on US-ONSD values. Hence, US-ONSD may become a non-invasive and reliable measure to control treatment efficacy in pediatric IIH.

Robustness of apparent diffusion coefficient–based lymph node classification for diagnosis of prostate cancer metastasis

ObjectivesThe aim of this proof-of-principle study combining data analysis and computer simulation was to evaluate the robustness of apparent diffusion coefficient (ADC) values for lymph node classification in prostate cancer under conditions comparable to clinical practice.Materials and methodsTo assess differences in ADC and inter-rater variability, ADC values of 359 lymph nodes in 101 patients undergoing simultaneous prostate-specific membrane antigen (PSMA)-PET/MRI were retrospectively measured by two blinded readers and compared in a node-by-node analysis with respect to lymph node status. In addition, a phantom and 13 patients with 86 lymph nodes were prospectively measured on two different MRI scanners to analyze inter-scanner agreement. To estimate the diagnostic quality of the ADC in real-world application, a computer simulation was used to emulate the blurring caused by scanner and reader variability. To account for intra-individual correlation, the statistical analyses and simulations were based on linear mixed models.ResultsThe mean ADC of lymph nodes showing PSMA signals in PET was markedly lower (0.77 × 10−3 mm2/s) compared to inconspicuous nodes (1.46 × 10−3 mm2/s, p < 0.001). High inter-reader agreement was observed for ADC measurements (ICC 0.93, 95%CI [0.92, 0.95]). Good inter-scanner agreement was observed in the phantom study and confirmed in vivo (ICC 0.89, 95%CI [0.84, 0.93]). With a median AUC of 0.95 (95%CI [0.92, 0.97]), the simulation study confirmed the diagnostic potential of ADC for lymph node classification in prostate cancer.ConclusionOur model-based simulation approach implicates a high potential of ADC for lymph node classification in prostate cancer, even when inter-rater and inter-scanner variability are considered.Clinical relevance statementThe ADC value shows a high diagnostic potential for lymph node classification in prostate cancer. The robustness to scanner and reader variability implicates that this easy to measure and widely available method could be readily integrated into clinical routine.Key Points• The diagnostic value of the apparent diffusion coefficient (ADC) for lymph node classification in prostate cancer is unclear in the light of inter-rater and inter-scanner variability.• Metastatic and inconspicuous lymph nodes differ significantly in ADC, resulting in a high diagnostic potential that is robust to inter-scanner and inter-rater variability.• ADC has a high potential for lymph node classification in prostate cancer that is maintained under conditions comparable to clinical practice.Graphical abstract

Effect of cosmetic hair treatment and natural hair colour on hair testosterone concentrations.

Testosterone analysis in hair allows for retrospective evaluation of endogenous testosterone concentrations, but studies devoted to investigating confounders in hair testosterone analysis have hitherto been scarce. The current study examined the stability of testosterone concentrations between two hair samples collected three months apart and investigated two potential confounding factors: natural hair colour and cosmetic hair treatments. Testosterone was analysed with an in-house radioimmunoassay with a limit of detection adequate for the purpose. The testosterone concentrations from the two samplings, at baseline and three months later, had an intra-individual correlation of moderate strength (rho = 0.378, p<0.001, n = 146). Hair treatment, such as colouring or bleaching, seemed to increase testosterone concentrations (p = 0.051, n = 191, and in a paired analysis in a subset of the cohort p = 0.005, n = 24), while no effect of natural colour in untreated hair (p = 0.133) could be detected. The current results suggest that cosmetic hair treatments need to be considered in hair testosterone analyses and demonstrate the utility of a radioimmunoassay to reliably measure testosterone concentrations in small hair samples in women.

Conceptual overlap among texts impedes comprehension monitoring.

For decades, research on metacomprehension has demonstrated that many learners struggle to accurately discriminate their comprehension of texts. However, while reviews of experimental studies on relative metacomprehension accuracy have found average intra-individual correlations between predictions and performance of around .27 for adult readers, in some contexts even lower near-zero accuracy levels have been reported. One possible explanation for those strikingly low levels of accuracy is the high conceptual overlap between topics of the texts. To test this hypothesis, in the present work participants were randomly assigned to read one of two text sets that differed in their degree of conceptual overlap. Participants judged their understanding and completed an inference test for each topic. Across two studies, mean relative accuracy was found to match typical baseline levels for the low-overlap text sets and was significantly lower for the high-overlap text sets. Results suggest text similarity is an important factor impacting comprehension monitoring accuracy that may have contributed to the variable and sometimes inconsistent results reported in the metacomprehension literature.

Ethanol Kinetics in the Human Brain Determined by Magnetic Resonance Spectroscopy.

In many parts of the world, ethanol is a widely consumed substance that displays its effect in the brain, the target organ for desired, but also negative impact. In a previous study, the ethanol concentrations were analyzed in different regions of the brain by magnetic resonance spectroscopy (MRS). In this study, the same method is used to demonstrate the kinetics of the ethanol concentration in the human brain after oral ethanol uptake. A drinking study was performed with 10 healthy participants. After the uptake of ethanol in a calculated amount leading to a plasma ethanol concentration of 0.92 g/L (19.95 mM corresponding to a blood ethanol concentration of 0.7 g/kg), brain ethanol concentrations were continuously measured by means of MRS on a 3 Tesla human magnetic resonance imaging (MRI) system. For the data acquisition a single-voxel sLASER sequence was used, with the volume of interest located in the occipital cortex. Intermittently, blood samples were taken and plasma was analyzed for ethanol using headspace gas chromatography with flame ionization detection (HS-GC-FID). The obtained MRS brain ethanol curves showed distinct inter-individual differences; however, a good intra-individual correlation of plasma and brain ethanol concentrations was observed. The results suggest a rapid equilibration between blood and brain. The ethanol concentrations measured in the brain were substantially lower than the measured plasma ethanol results, suggesting an MRS visibility of about 63% for ethanol in brain tissue. The maximum individual ethanol concentrations in the brain (normalized to water content) ranged between 7.1 and 14.1 mM across the cohort, while the highest measured plasma concentrations were in the range between 0.35 g/L (9.41 mM) and 0.95 g/L (20.52 mM).

Stable eye versus mouth preference in a live speech-processing task

Looking at the mouth region is thought to be a useful strategy for speech-perception tasks. The tendency to look at the eyes versus the mouth of another person during speech processing has thus far mainly been studied using screen-based paradigms. In this study, we estimated the eye-mouth-index (EMI) of 38 adult participants in a live setting. Participants were seated across the table from an experimenter, who read sentences out loud for the participant to remember in both a familiar (English) and unfamiliar (Finnish) language. No statistically significant difference in the EMI between the familiar and the unfamiliar languages was observed. Total relative looking time at the mouth also did not predict the number of correctly identified sentences. Instead, we found that the EMI was higher during an instruction phase than during the speech-processing task. Moreover, we observed high intra-individual correlations in the EMI across the languages and different phases of the experiment. We conclude that there are stable individual differences in looking at the eyes versus the mouth of another person. Furthermore, this behavior appears to be flexible and dependent on the requirements of the situation (speech processing or not).

Comparison of clean catch and bag urine using LC–MS/MS proteomics in infants

BackgroundUrinary proteomics identifies the totality of urinary proteins and can therefore help in getting an early and precise diagnosis of various pathological processes in the kidneys. In infants, non-invasive urine collection is most commonly accomplished with a urine bag or clean catch. The influence of those two collection methods on urinary proteomics was assessed in this study.MethodsThirty-two urine samples were collected in infants using urine bag and clean catch within 24 h. Nine boys and seven girls with a mean age of 4.3 ± 2.9 months were included (5 × post-pyelonephritis, 10 × non-kidney disease, 1 × chronic kidney disease (CKD)). Liquid chromatography-mass spectrometry (LC–MS/MS) was performed in data-independent acquisition (DIA) mode. Protein identification and quantification were achieved using Spectronaut.ResultsA total of 1454 urinary proteins were detected. Albumin and α-1-microglobulin were detected the most. The 18 top-abundant proteins accounted for 50% of total abundance. The number of proteins was slightly, but insignificantly higher in clean catch (957 ± 245) than in bag urine (876 ± 255). The median intensity was 1.2 × higher in the clean catch. Overall, differential detection of proteins was 29% between the collection methods; however, it diminished to 3% in the 96 top-abundant proteins. Pearson’s correlation coefficient was 0.81 ± 0.11, demonstrating a high intraindividual correlation. A principal component analysis and a heat map showed clustering according to diagnoses and patients rather than to the collection method.ConclusionUrinary proteomics shows a high correlation with minor variation in low-abundant proteins between the two urine collection methods. The biological characteristics overrule this variation.Graphical abstractA higher resolution version of the Graphical abstract is available as Supplementary information.

Association between intrarenal venous flow from Doppler ultrasonography and acute kidney injury in patients with sepsis in critical care: a prospective, exploratory observational study

BackgroundIntrarenal venous flow (IRVF) patterns assessed using Doppler renal ultrasonography are real-time bedside visualizations of renal vein hemodynamics. Although this technique has the potential to detect renal congestion during sepsis resuscitation, there have been few studies on this method. We aimed to examine the relationship between IRVF patterns, clinical parameters, and outcomes in critically ill adult patients with sepsis. We hypothesized that discontinuous IRVF was associated with elevated central venous pressure (CVP) and subsequent acute kidney injury (AKI) or death.MethodsWe conducted a prospective observational study in two tertiary-care hospitals, enrolling adult patients with sepsis who stayed in the intensive care unit for at least 24 h, had central venous catheters placed, and received invasive mechanical ventilation. Renal ultrasonography was performed at a single time point at the bedside after sepsis resuscitation, and IRVF patterns (discontinuous vs. continuous) were confirmed by a blinded assessor. The primary outcome was CVP obtained at the time of renal ultrasonography. We also repeatedly assessed a composite of Kidney Disease Improving Global Outcomes of Stage 3 AKI or death over the course of a week as a secondary outcome. The association of IRVF patterns with CVP was examined using Student's t-test (primary analysis) and that with composite outcomes was assessed using a generalized estimating equation analysis, to account for intra-individual correlations. A sample size of 32 was set in order to detect a 5-mmHg difference in CVP between IRVF patterns.ResultsOf the 38 patients who met the eligibility criteria, 22 (57.9%) showed discontinuous IRVF patterns that suggested blunted renal venous flow. IRVF patterns were not associated with CVP (discontinuous flow group: mean 9.24 cm H2O [standard deviation: 3.19], continuous flow group: 10.65 cm H2O [standard deviation: 2.53], p = 0.154). By contrast, the composite outcome incidence was significantly higher in the discontinuous IRVF pattern group (odds ratio: 9.67; 95% confidence interval: 2.13–44.03, p = 0.003).ConclusionsIRVF patterns were not associated with CVP but were associated with subsequent AKI in critically ill adult patients with sepsis. IRVF may be useful for capturing renal congestion at the bedside that is related to clinical patient outcomes.Graphical abstract

Evaluation of sternocleidomastoid muscle cutaneous silent period in patients with cervical dystonia

Purpose: The aim of this study to examine the in changes inhibitory interneurons of the brainstem, which are likely to be involved in pathophysiology of cervical dystonia, using the cutaneous silent period(SP) method which is an inhibitor reflex.&#x0D; Materials and Methods: SP latency and interval values were obtained from bilateral sternocleidomastoid (SCM) muscles of individuals in 20 patients with cervical dystonia and 25 healthy volunteers using superficial electrodes. SP parameters obtained were compared within and between groups. Furthermore, intra-individual correlation analysis was performed for SP parameters from bilateral SCMs of the individuals in both groups.&#x0D; Results: The mean age of the patients participating in the study was 49.3 ± 14.7, and the control group was 48.0 ± 13.7. There was no statistically significant difference between the two groups in terms of age and gender. No significant difference was found in the comparison of SP parameters both within and between groups. There was a strong intra-individual correlation between SP latencies of bilateral SCMs of both patient and control groups. It was determined that the strongly positive intra-individual correlation between SP intervals also continued in the control group, whereas at patient group disappeared.&#x0D; Conclusion: The loss of correlation between bilateral SCM SP durations in the dystonia group indicates that the abnormality in interneuron connections, which is thought to be present in dystonia, may actually be a loss of order. This “disorganization” may explain the discrepancies in the results of cutaneous SP studies in dystonia patients.

Association of long-term exposure to ambient air pollution with retinal neurodegeneration: the prospective Alienor study

Chronic exposure to air pollution may have adverse effects on neurodegenerative diseases. Glaucoma, the second leading cause of blindness worldwide, is a neurodegenerative disease of the optic nerve, characterized by progressive thinning of the retinal nerve fiber layer (RNFL). We investigated the relationship of air pollution exposure with longitudinal changes of RNFL thickness in the Alienor study, a population-based cohort of residents of Bordeaux, France, aged 75 years or more. Peripapillary RNFL thickness was measured using optical coherence tomography imaging every 2 years from 2009 to 2020. Measurements were acquired and reviewed by specially trained technicians to control quality. Air pollution exposure (particulate matter ≤2.5 μm (PM2.5), black carbon (BC), nitrogen dioxide (NO2)) was estimated at the participants’ geocoded residential address using land-use regression models. For each pollutant, the 10-year average of past exposure at first RNFL thickness measurement was estimated. Associations of air pollution exposure with RNFL thickness longitudinal changes were assessed using linear mixed models adjusted for potential confounders, allowing for intra-eye and intra-individual correlation (repeated measurements).The study included 683 participants with at least one RNFL thickness measurement (62% female, mean age 82 years). The average RNFL was 90 μm (SD:14.4) at baseline. Exposure to higher levels of PM2.5 and BC in the previous 10 years was significantly associated with a faster RNFL thinning during the 11-year follow-up (−0.28 μm/year (95% confidence interval (CI) [-0.44;-0.13]) and −0.26 μm/year (95% CI [-0.40;-0.12]) per interquartile range increment; p < 0.001 for both). The size of the effect was similar to one year of age in the fitted model (−0.36 μm/year). No statistically significant associations were found with NO2 in the main models.This study evidenced a strong association of chronic exposure to fine particulate matter with retinal neurodegeneration, at air pollution levels below the current recommended thresholds in Europe.

Risk of serious hypoglycemia in patients with atrial fibrillation and diabetes concurrently taking antidiabetic drugs and oral anticoagulants: A nationwide cohort study.

Evidence regarding the risks of serious hypoglycemia for patients with atrial fibrillation (AF) and diabetes mellitus (DM) taking antidiabetic medications with concurrent non-vitamin K antagonist oral anticoagulants (NOACs) versus warfarin is limited. This study aimed to investigate this knowledge gap. This retrospective cohort study used nationwide data from Taiwan's National Health Insurance Research Database and included a total of 56,774 adult patients treated with antidiabetic medications and oral anticoagulants between January 1, 2012 and December 31, 2020. The incidence rate ratios (IRRs) of serious hypoglycemia were estimated for patients taking antidiabetic drugs with NOACs versus warfarin. Poisson regression models with generalized estimating equations accounting for intra-individual correlation across follow-up periods were used. Stabilized inverse probability of treatment weighting was used to create treatment groups with balanced characteristics for comparisons. Compared to concurrent use of antidiabetic drugs with warfarin, those with NOACs showed a significantly lower risk of serious hypoglycemia (IRR = 0.73, 95% CI: 0.63-0.85, p<0.001). In the analyses of each NOAC, patients taking dabigatran (IRR = 0.76, 95% CI: 0.63-0.91, p = 0.002), rivaroxaban (IRR = 0.72, 95% CI: 0.61-0.86, p<0.001), and apixaban (IRR = 0.71, 95% CI: 0.57-0.89, p = 0.003) showed a significantly lower risk of serious hypoglycemia than those taking warfarin. In patients with AF and DM taking antidiabetic drugs, concurrent use of NOACs was associated with a lower risk of serious hypoglycemia than concurrent use of warfarin.

Clinical surrogates of dysautonomia predict lethal outcome in COVID-19 on intensive care unit

BackgroundUnpredictable vegetative deteriorations made the treatment of patients with acute COVID-19 on intensive care unit particularly challenging during the first waves of the pandemic. Clinical correlates of dysautonomia and their impact on the disease course in critically ill COVID-19 patients are unknown.MethodsWe retrospectively analyzed data collected during a single-center observational study (March 2020–November 2021) which was performed at the University Medical Center Hamburg-Eppendorf, a large tertiary medical center in Germany. All patients admitted to ICU due to acute COVID-19 disease during the study period were included (n = 361). Heart rate variability (HRV) and blood pressure variability (BPV) per day were used as clinical surrogates of dysautonomia and compared between survivors and non-survivors at different time points after admission. Intraindividual correlation of vital signs with laboratory parameters were calculated and corrected for age, sex and disease severity.ResultsPatients who deceased in ICU had a longer stay (median days ± IQR, survivors 11.0 ± 27.3, non-survivors 14.1 ± 18.7, P = 0.85), in contrast time spent under invasive ventilation was not significantly different (median hours ± IQR, survivors 322 ± 782, non-survivors 286 ± 434, P = 0.29). Reduced HRV and BPV predicted lethal outcome in patients staying on ICU longer than 10 days after adjustment for age, sex, and disease severity. Accordingly, HRV was significantly less correlated with inflammatory markers (e.g. CRP and Procalcitonin) and blood carbon dioxide in non-survivors in comparison to survivors indicating uncoupling between autonomic function and inflammation in non-survivors.ConclusionsOur study suggests autonomic dysfunction as a contributor to mortality in critically ill COVID-19 patients during the first waves of the pandemic. Serving as a surrogate for disease progression, these findings could contribute to the clinical management of COVID-19 patients admitted to the ICU. Furthermore, the suggested measure of dysautonomia and correlation with other laboratory parameters is non-invasive, simple, and cost-effective and should be evaluated as an additional outcome parameter in septic patients treated in the ICU in the future.

Living in a City Where Automated Taxis are Operating and Using Them: Does This Affect Consumers’ Preferences?

In this paper we study the impact of having used an automated taxi (AT) or simply living in a city where ATs are operating on users’ preferences for and attitudes toward ATs. This paper aims then to contribute to the research on ATs and on the impact of experiencing innovations. Data were collected in three major cities in China where ATs were in operation (AT cities), and other major cities where only normal taxis (NTs) were operating (NT cities). A stated choice (SC) experiment was built that included level-of-services attributes, specific AT in-vehicle features, levels of AT adoption and customers’ reviews. In addition, a set of attitudinal statements was included to measure injunctive norms, hedonic motivation and trust. Hybrid choice models were estimated accounting for intra-individual correlation. Results show that living in a city where AT are operating does not affect the willingness to pay for travel and waiting time, which is an expected result. But those living in AT cities compared with those living in NT cities are willing to pay just half the amount to have the in-vehicle feature “change destination during the trip” and around three times as much for good reviews about ATs for trips less than 30 min. Interestingly, trust has a positive and significant impact on the choice of AT only for those living in NT cities, while hedonic motivation is significant only for those living in AT cities. Finally, we did not find differences between those who had used an AT and those who had never used it.

Temperament traits and glucocorticoid metabolites in tropical screech owl (Megascops choliba)

Animals constantly respond to stimuli from their surroundings, showing individual behavioral and endocrine differences upon perceived challenging and/or threatening stimuli. The temperament of 13 captive tropical screech owls (Megascops choliba) was defined by performing three challenge tests (novel space, taxidermist predator and trapping) to identify inter-individual differences and their possible relationship with the production of glucocorticoid metabolites (GCM). Feces samples of each bird were taken pre-and-post predator challenge to quantify GCM concentration by means of enzymatic immunoassay (EIA). The intensity of 13 adjectives selected to describe the owls' temperament was determined by three judges during behavioral testing. Only 3 adjectives (passive, vulnerable, and attentive) that showed strong inter-test and intra-individual correlation coefficients were considered. These adjectives were later grouped in a single dimension named “shyness”, enabling establishment of individual scores. The temperament of the owls showed correlation to post-predator challenge GCM levels (ρ = 0.79; p < 0.001). However, no significant differences were found in GCM levels before and after predator challenge. Our results both confirm that nocturnal behavior raptorial birds show positive relation between shy temper and adrenal response, and offer the non-invasive herein implemented methods for establishment of new hypotheses that will assess welfare of species kept under human care.

Effects of pesticide exposure on oxidative stress and DNA methylation urinary biomarkers in Czech adults and children from the CELSPAC-SPECIMEn cohort

Current-use pesticide (CUP) exposure occurs mainly through diet and environmental application in both agricultural and urban settings. While pesticide exposure has been associated with many adverse health outcomes, the intermediary molecular mechanisms are still not completely elucidated. Among others, their roles in epigenetics (DNA methylation) and DNA damage due to oxidative stress are presumed. Scientific evidence on urinary biomarkers of such body response in general population is limited, especially in children.A total of 440 urine samples (n = 110 parent-child pairs) were collected during the winter and summer seasons in order to describe levels of overall DNA methylation (5-mC, 5-mdC, 5-hmdC, 7-mG, 3-mA) and oxidative stress (8-OHdG) biomarkers and investigate their possible associations with metabolites of pyrethroids (3-PBA, t/c-DCCA), chlorpyrifos (TCPY), and tebuconazole (TEB-OH). Linear mixed-effects models accounting for intraindividual and intrahousehold correlations were utilized. We applied false discovery rate procedure to account for multiplicity and adjusted for potential confounding variables.Higher urinary levels of most biological response biomarkers were measured in winter samples. In adjusted repeated measures models, interquartile range (IQR) increases in pyrethroid metabolites were associated with higher oxidative stress. t/c-DCCA and TCPY were associated with higher urinary levels of cytosine methylation biomarkers (5-mC and/or 5-mdC). The most robust association was observed for tebuconazole metabolite with 3-mA (−15.1% change per IQR increase, 95% CI = −23.6, −5.69) suggesting a role of this pesticide in reduced demethylation processes through possible DNA glycosylase inhibition.Our results indicate an urgent need to extend the range of analyzed environmental chemicals such as azole pesticides (e.g. prothioconazole) in human biomonitoring studies. This is the first study to report urinary DNA methylation biomarkers in children and associations between CUP metabolites and a comprehensive set of biomarkers including methylated and oxidized DNA alterations. Observed associations warrant further large-scale research of these biomarkers and environmental pollutants including CUPs.

Reliability of the Polygraphic Home Sleep Test for OSA Determined by the Severity and Pattern Changes of Two Consecutive Examinations

Diagnosis and effective treatment of obstructive sleep apnea syndrome (OSA) in adults is an important health priority. Home respiratory polygraphy is a cost-effective alternative to polysomnography in OSA. The aim of this study was to investigate the variability of two consecutive home respiratory polygraphic examinations by comparing the severity characteristics and pattern (supine dominant, continuous, etc.) variability. We examined 100 patients with clinically suspected OSA on two consecutive nights by home respiratory polygraphy. The correlation of time in bed (TIB), apnea-hypopnea index (AHI), oxygen desaturation index (ODI), and T90 of the two examinations were compared by the Pearson test. The severity ranks and nocturnal apnea patterns of the two periods were compared using Spearman and Wilcoxon tests. Pearson’s correlations represented a strong correlation of the AHI, ODI, and T90, but only moderate for TIB. The severity-specific correlation was the highest for AHI in the severe group. Out of 100 pairs of polygraphic examinations, 25 cases showed change in the severity ranking (decreased in 11, increased in 14); 15 cases showed a change in the polygraphic pattern (supine, non-supine, etc.), with severity change in 6 cases. Therapy change based on the second examination was initiated in 6 cases. Our results revealed a good intra-individual correlation between the severity grades of the two nights, with the highest value in the severe cases. In some cases, the nightly variation in the polygraphic pattern may explain the change in the severity. From a therapeutic point of view, the low number of severity changes between moderate and severe groups revealed good reliability.