Gold Standard Measure Research Articles

Home-based video assessment of children's autism-related behaviours: Psychometric analysis and linkages with parental responsiveness and context.

Assessment of autism-related behaviours (ARBs) in children has generally been limited to direct observations in clinical settings or informant-based reports. The widespread availability of video-streaming devices has made home observations of children's ARBs feasible. This approach could enable assessment of the generalization and durability of interventions and may be able to overcome methodological limitations of predominant current assessment approaches (response biases, limited sensitivity to treatment). Forty-four autistic children and their families participated in a repeated-measures study with a correlational design. Approximately 10 hr of unprompted behaviour at home were videorecorded over the course of a week (2 hr per day) for each participant. Gold standard measures of ARBs were also administered (ADOS-2 and ADI-R). Two home-based observational measures of ARBs utilizing streaming video were developed and evaluated: the ARCHER and the CHEERS. Trained independent evaluators made ratings on the ARCHER, CHEERS and an observational measure of parental responsiveness. Correlations with the ADOS-2 and ADI-R were .47 and .34 for ARCHER scores and .51 and .48 for CHEERS scores, respectively. In linear mixed models, more responsive parenting was associated with fewer ARBs on a daily basis. Children spent their afternoons engaged in many typical activities including electronics, homework and games with family members, and ARBs were more prominent in some of these contexts (e.g., electronics) than others (e.g., family games). Home-based observational assessment of ARBs may be useful for clinical and descriptive research.

Higher-order evidence.

Higher-order evidence is evidence about evidence. Epidemiologic examples of higher-order evidence include the settings where the study data constitute first-order evidence and estimates of misclassification comprise the second-order evidence (e.g., sensitivity, specificity) of a binary exposure or outcome collected in the main study. While sampling variability in higher-order evidence is typically acknowledged, higher-order evidence is often assumed to be free of measurement error (e.g., gold standard measures). Here we provide two examples, each with multiple scenarios where second-order evidence is imperfectly measured, and this measurement error can either amplify or attenuate standard corrections to first-order evidence. We propose a way to account for such imperfections that requires third-order evidence. Further illustrations and exploration of how higher-order evidence impacts results of epidemiologic studies is warranted.

Quantification of creatinine in whole blood by a paper-based device using an RGB sensor.

Creatinine, an important biomarker for renal functions, is often conventionally estimated using the gold standard Jaffe reaction from blood, which involves the usage of a spectrophotometric measurement, thus restricting its utilization scope in point-of-care settings. Here, we report the development of a method for the single-step quantification of creatinine from whole blood using a paper-based microfluidic device. Our platform uses Whatman filter paper integrated with an LF1 membrane. The on-chip separation of blood plasma is achieved through the LF1 membrane, while the Whatman component of the device contains the embedded reagents for the Jaffe reaction. The combination of two different grades of paper enables a single-step quantification of creatinine as the separated blood plasma traverses to the reaction zone through capillary imbibition. Colorimetric readouts were quantified using an RGB sensor instead of a smartphone, which is highly platform dependent and incurs a relatively higher cost compared to the other components in typical point-of care (POC) devices. Our sensor was integrated within a 3D box, thereby making the detection virtually instrument free and perfectly suited for POC settings. The limit of detection (LOD) of our device was 0.219 mg dL-1, which falls within the lower range of physiological values. The coefficient of determination (R2) for the linearity and median accuracy were 0.978 and 94.047%, respectively. The relative standard deviation (RSD) for precision measurements remained below 5% for the developed protocol. Furthermore, we validated the performance of our device with 35 clinical samples in laboratory settings against the gold standard measurements. Our Bland-Altman plot as well as t-test and chi-square test results clearly confirmed the validity of our device within a 95% confidence interval.

A mutual information measure of phase-amplitude coupling using gamma generalized linear models.

Cross frequency coupling (CFC) between electrophysiological signals in the brain is a long-studied phenomenon and its abnormalities have been observed in conditions such as Parkinson's disease and epilepsy. More recently, CFC has been observed in stomach-brain electrophysiologic studies and thus becomes an enticing possible target for diseases involving aberrations of the gut-brain axis. However, current methods of detecting coupling, specifically phase-amplitude coupling (PAC), do not attempt to capture the phase and amplitude statistical relationships. In this paper, we first demonstrate a method of modeling these joint statistics with a flexible parametric approach, where we model the conditional distribution of amplitude given phase using a gamma distributed generalized linear model (GLM) with a Fourier basis of regressors. We perform model selection with minimum description length (MDL) principle, demonstrate a method for assessing goodness-of-fit (GOF), and showcase the efficacy of this approach in multiple electroencephalography (EEG) datasets. Secondly, we showcase how we can utilize the mutual information, which operates on the joint distribution, as a canonical measure of coupling, as it is non-zero and non-negative if and only if the phase and amplitude are not statistically independent. In addition, we build off of previous work by Martinez-Cancino et al., and Voytek et al., and show that the information density, evaluated using our method along the given sample path, is a promising measure of time-resolved PAC. Using synthetically generated gut-brain coupled signals, we demonstrate that our method outperforms the existing gold-standard methods for detectable low-levels of phase-amplitude coupling through receiver operating characteristic (ROC) curve analysis. To validate our method, we test on invasive EEG recordings by generating comodulograms, and compare our method to the gold standard PAC measure, Modulation Index, demonstrating comparable performance in exploratory analysis. Furthermore, to showcase its use in joint gut-brain electrophysiology data, we generate topoplots of simultaneous high-density EEG and electrgastrography recordings and reproduce seminal work by Richter et al. that demonstrated the existence of gut-brain PAC. Using simulated data, we validate our method for different types of time-varying coupling and then demonstrate its performance to track time-varying PAC in sleep spindle EEG and mismatch negativity (MMN) datasets. Our new measure of PAC using Gamma GLMs and mutual information demonstrates a promising new way to compute PAC values using the full joint distribution on amplitude and phase. Our measure outperforms the most common existing measures of PAC, and show promising results in identifying time varying PAC in electrophysiological datasets. In addition, we provide for using our method with multiple comparisons and show that our measure potentially has more statistical power in electrophysiologic recordings using simultaneous gut-brain datasets.

A Qualitative Study of Rehabilitation Professionals' Practices to Define the Presence of Arm Morbidity After Breast Cancer Surgery

Background: Rehabilitation professionals (RPs) play a major role in identifying, managing, and treating upper-body issues in individuals following breast cancer surgery. Varying definitions of postoperative arm morbidity in the literature have hampered development of standardized surveillance programs for people undergoing breast cancer surgery within clinical care. Our objective was to explore RPs' practices in defining the presence of arm morbidity after breast cancer surgery. Methods: This qualitative study used semistructured focus group interviews with 29 RPs from 5 health authorities in British Columbia, Canada. Transcripts were analyzed using content analysis. Results: Two categories captured RPs' overarching lack of consensus in defining the presence of postoperative arm morbidity: (1) Complex concerns, complex considerations; and (2) Many ways of measuring arm morbidity. Varying perspectives exist as to which upper-body issues and functional criteria constitute arm morbidity, as well as which characteristics to consider in identifying who is at risk of developing arm morbidity. In tandem, there is currently no gold standard outcome measure or standardized assessment to identify arm morbidity. Conclusion: Because of the complex interaction between different breast cancer treatments and various environmental and personal factors, there is currently a lack of consensus among RPs about how to define and assess arm morbidity. Our findings demonstrate the presence of arm morbidity is challenging to characterize, given its multifaceted presentation, inconsistent approaches to risk stratification across clinical settings and geographical regions the RPs worked, and numerous ways of measuring arm morbidity.

Monash-Alfred protocol for assessment of atypical parkinsonian syndromes (MAP-APS)

IntroductionAtypical parkinsonian syndromes (APS) are rare neurodegenerative syndromes for which parkinsonism is one significant feature. APS includes progressive supranuclear palsy (PSP), multiple system atrophy (MSA) and corticobasal syndrome (CBS). The...

Comparison of three methods for nucleus pulposus volume measurement in rabbit lumbar spines: a preclinical model for measurement of the effectiveness of prophylactic intervertebral disk fenestration in dogs.

Compare 3 methods of nucleus pulposus (NP) volume measurement using the rabbit lumbar spines as a preclinical model to determine the effectiveness of prophylactic intervertebral disk fenestration in dogs. Twelve 9-month-old, skeletally mature female entire New Zealand White rabbits weighing between 3.5 to 4.5 kg. NP volume measurements of dissected rabbit lumber spines between L1 and L6 were made and compared using gross measurements, reconstructed MRI images, and water volumetry based on Archimedes' principle. Water volumetry was used as the true gold standard volume measurement in this study. The true volume (mean ± SD) of the nucleus pulposus NP as measured by water volumetry increased caudally from L1/L2 (16.26 ± 3.32 mm3) to L5/L6 (22.73 ± 6.09 mm3). Volume estimates made by MRI were significantly higher than those made using water volumetry at all sites (L1/L2 [P = .044], L2/L3 [P = .012], L3/L4 [P = .015], L4/L5 [P < .001], and L5/L6 [P < .001]). Gross measurements also significantly overestimated volume when compared to water volumetry at all sites; L1/L2 (P = .021), L2/L3 (P = .025), L3/L4 (P = .001), L4/L5 (P < .001), and L5/L6 (P < .001). MRI and gross volume estimates were significantly different at L4/L5 (P = .035) and L5/L6 (P = .030). The findings of this preclinical model might be relevant to veterinary surgeons who perform prophylactic fenestration for which there is no reliable method to determine the amount of NP to be removed. Preclinical ex vivo and in vivo fenestration studies with pre- and postoperative NP volume assessment are required.

The Percentage of Patients Experiencing Financial Strain Depends on the Screening Measure: Evidence From a Cross-Sectional Survey of Adult Members of an Integrated Healthcare Delivery System.

Financial strain has important consequences for patients, providers, and health care systems. However, there is currently no gold standard measure to screen for financial strain. This study compared the performance of 3 single-item screeners using a composite measure of financial strain as a "gold standard." We conducted a secondary analysis of unweighted data from a 2021 survey of Kaiser Permanente Northern California health plan members comparing the percentages of adults who experienced financial strain based on 3 general single-item screeners, a screener specific to medical and dental health care use, and a composite financial strain measure. The study sample was comprised of 2734 non-Medicaid insured adults who answered all financial strain questions. Kappa statistics evaluating agreement of the 3 general screeners with the composite measure were calculated for the sample overall, by age group, and within age group, by 4 levels of income and 4 racial/ethnic subgroups. Among 947 adults aged 35 to 65, 30.7% had just enough money or not enough money to make ends meet, 23.3% had a somewhat hard or hard time paying for basics, 18.8% had trouble paying for ≥1 type of expense, 20.5% had delayed/used less medical/dental care, and 41.5% had experienced financial strain based on the composite measure. Among 1787 adults aged 66 to 85, the percentages who screened positive on these measures were 22.7%, 19.4%, 12.9%, 19.8%, and 34.4%, respectively. Across the sample, by income categories and racial/ethnic groups, the making ends meet screener identified higher percentages of adults experiencing financial strain and performed better when compared with the composite measure than the hard to pay for the very basics and trouble paying for expenses screeners. Overall, substantial decreases in the percentages of adults who screened positive on the financial strain measures were seen as level of income increased. Within income categories, middle-aged adults were more likely than older adults to have experienced financial strain based on the composite and general single-item screeners. As social risk screening becomes part of the standard of care, it will be important to assess how well different brief screeners for financial strain perform with diverse patient populations.

Aortic stenosis assessment from the 3-chamber cine: Ratio of balanced steady-state-free-precession (bSSFP) blood signal between the aorta and left ventricle predicts severity

BackgroundCardiovascular magnetic resonance (CMR) imaging is an important tool for evaluating the severity of aortic stenosis (AS), co-existing aortic disease, and concurrent myocardial abnormalities. Acquiring this additional information requires protocol adaptations and additional scanner time, but is not necessary for the majority of patients who do not have AS. We observed that the relative signal intensity of blood in the ascending aorta on a balanced steady state free precession (bSSFP) 3-chamber cine was often reduced in those with significant aortic stenosis. We investigated whether this effect could be quantified and used to predict AS severity in comparison to existing gold-standard measurements. MethodsMulti-centre, multi-vendor retrospective analysis of patients with AS undergoing CMR and transthoracic echocardiography (TTE). Blood signal intensity was measured in a ∼1 cm2 region of interest (ROI) in the aorta and left ventricle (LV) in the 3-chamber bSSFP cine. Because signal intensity varied across patients and scanner vendors, a ratio of the mean signal intensity in the aorta ROI to the LV ROI (Ao:LV) was used. This ratio was compared using Pearson correlations against TTE parameters of AS severity: aortic valve peak velocity, mean pressure gradient and the dimensionless index. The study also assessed whether field strength (1.5 T vs. 3 T) and patient characteristics (presence of bicuspid aortic valves (BAV), dilated aortic root and low flow states) altered this signal relationship. Results314 patients (median age 69 [IQR 57–77], 64% male) who had undergone both CMR and TTE were studied; 84 had severe AS, 78 had moderate AS, 66 had mild AS and 86 without AS were studied as a comparator group. The median time between CMR and TTE was 12 weeks (IQR 4–26). The Ao:LV ratio at 1.5 T strongly correlated with peak velocity (r = −0.796, p = 0.001), peak gradient (r = −0.772, p = 0.001) and dimensionless index (r = 0.743, p = 0.001). An Ao:LV ratio of < 0.86 was 84% sensitive and 82% specific for detecting AS of any severity and a ratio of 0.58 was 83% sensitive and 92% specific for severe AS. The ability of Ao:LV ratio to predict AS severity remained for patients with bicuspid aortic valves, dilated aortic root or low indexed stroke volume. The relationship between Ao:LV ratio and AS severity was weaker at 3 T. ConclusionsThe Ao:LV ratio, derived from bSSFP 3-chamber cine images, shows a good correlation with existing measures of AS severity. It demonstrates utility at 1.5 T and offers an easily calculable metric that can be used at the time of scanning or automated to identify on an adaptive basis which patients benefit from dedicated imaging to assess which patients should have additional sequences to assess AS.

Exploratory study evaluating the relationships between perinatal adversity, oxidative stress, and infant neurodevelopment across the first year of life.

Early childhood adversity increases risk for negative lifelong impacts on health and wellbeing. Identifying the risk factors and the associated biological adaptations early in life is critical to develop scalable early screening tools and interventions. Currently, there are limited, reliable early childhood adversity measures that can be deployed prospectively, at scale, to assess risk in pediatric settings. The goal of this two-site longitudinal study was to determine if the gold standard measure of oxidative stress, F2-Isoprostanes, is potentially a reliable measure of a physiological response to adversity of the infant and mother. The study evaluated the independent relationships between F2-Isoprostanes, perinatal adversity and infant neurocognitive development. The study included mother-infant dyads born >36 weeks' gestation. Maternal demographic information and mental health assessments were utilized to generate a perinatal cumulative risk score. Infants' development was assessed at 6 and 12 months and both mothers and infants were assayed for F2-isoprostane levels in blood and urine, respectively. Statistical analysis revealed that cumulative risk scores correlated with higher maternal (p = 0.01) and infant (p = 0.05) F2-isoprostane levels at 6 months. Infant F2-isoprostane measures at 2 months were negatively associated with Mullen Scales of Early Learning Composite scores at 12 months (p = 0.04). Lastly, higher cumulative risk scores predicted higher average maternal F2-isoprostane levels across the 1-year study time period (p = 0.04). The relationship between perinatal cumulative risk scores and higher maternal and infant F2-isoprostanes at 6 months may reflect an oxidative stress status that informs a sensitive period in which a biomarker can be utilized prospectively to reveal the physiological impact of early adversity.

Bridging the Gap from Molecular Surveillance to Programmatic Decisions for Malaria Control and Elimination.

An increasing number of molecular and genomic assays are available to study malaria parasite populations. However, so far they have played a marginal role in informing policy and programmatic decision-making. Currently, molecular data are mainly used for monitoring drug efficacy against Plasmodium falciparum; assessing molecular markers of drug and insecticide resistance; and assessing P. falciparum histidine-rich protein 2 and 3 genes (Pfhrp2/3) deletion. We argue that additional use cases for molecular routine surveillance could be implemented in the near future, especially in transmission settings approaching elimination. These would include using quantitative polymerase chain reaction to monitor the prevalence of sub-patent infections in asymptomatic carriers, monitoring parasite genetic diversity as transmission intensity is changing, using genomic data to determine the origin of imported infections and characterize transmission chains in settings with very low malaria transmission, and using serology to monitor recent and past exposures in low-transmission settings. Molecular surveillance could inform control programs on adapting novel strategies, such as reactive case detection or focal mass drug administration, and help evaluate the impact of interventions currently in place. To better integrate molecular and genomic data into control program decision-making, engagement of national malaria control experts is crucial. Local laboratory capacity needs to be strengthened, shortening the time from sample collection to data availability. Here, we discuss opportunities and challenges of the use of molecular and genomic data for supporting malaria control and elimination efforts, as well as the avenues to link molecular and genomic data with gold standard epidemiological measurements through mathematical modeling.

Association between Estimated Pulse Wave Velocity and Incident Nonalcoholic Fatty Liver Disease in Korean Adults

Introduction: Nonalcoholic fatty liver disease (NAFLD) is associated with vascular dysfunction, one of the signs of which is arterial stiffness. Carotid-femoral pulse wave velocity (PWV), which is considered the gold standard measure of arterial stiffness, can be estimated using two commonly assessed clinical variables: age and blood pressure. This study aimed to evaluate the association between estimated PWV (ePWV) and the prevalence and incidence of NAFLD among Korean adults. Methods: This study used data from the Ansan-Ansung cohort study, a subset of the Korean Genome and Epidemiology Study, and included 8,336 adult participants with and without NAFLD at baseline. The participants were subdivided into three tertile groups according to ePWV. Results: At baseline, the prevalence of NAFLD was 10.5, 27.5, and 35.0% in the first (lowest), second, and third (highest) tertiles of ePWV, respectively. During the 18-year follow-up period, 2,467 (42.9%) incident cases of NAFLD were identified among 5,755 participants who did not have NAFLD at baseline. After adjustment for clinically relevant variables, participants in the second (adjusted hazard ratio [HR], 1.25; 95% confidence interval [CI], 1.12–1.40) and third (adjusted HR, 1.42; 95% CI, 1.24–1.64) tertiles of ePWV had a significantly higher risk of incident NAFLD than those in the first tertile. Conclusion: Higher ePWV is independently associated with an elevated risk of NAFLD in the general population.

Cognitive function in older adults with hearing loss; outcomes for treated versus untreated groups at 3‐year follow‐up.

AbstractBackgroundHearing loss has been identified as the largest potentially modifiable risk factor for dementia and affects 50% adults aged 50‐64 years, and 70% aged 70 years and older. The quality of evidence the effect of hearing aid use on cognition in older adults is currently poor due to methodological limitations. Few studies have objectively studied these outcomes beyond 6‐12 months. This prospective longitudinal observational cohort study investigated the effects of hearing aid use on cognitive performance in older adults over 3 years.Method183 first‐time hearing aid users aged 60 years and older with mild to severe hearing loss were assessed using gold standard measures before hearing aid fitting, with subsets of this group re‐assessed after 18 and 36 months as they reached these timepoints. Outcomes for the treatment group were compared with those of participants of a large longitudinal cohort study of community‐living older adults (AIBL) using the same measures. Objective assessment measures included cognitive function, hearing loss, hearing aid use, genetic phenotyping, and speech perception. Subjective measures included hearing disability, mood, quality of life, social isolation, and loneliness.ResultThe treatment group showed good hearing aid compliance, significant improvement in speech perception (quiet and noise) and decreased self‐reported listening disability despite further significant hearing loss over the 3‐year follow‐up. There was significant improvement in cognitive performance from baseline for the treatment group versus the comparative group for working memory, attention, psychomotor function, and visual learning. Comparatively, AIBL participants showed statistically significant decline across all cognitive functions.ConclusionOlder adults with untreated hearing loss are expected to decline cognitively at 2‐5 times the rate of adults without hearing loss. Comparatively, cognitive performance in treated participants in this study instead improved after 3 years of hearing aid use, while the comparative group declined. These results suggest that treatment of hearing loss with hearing aids may delay cognitive decline.

Dimensional interaction is driven by feature integration: A binding theory of garner interference.

For nearly half a century now, Garner interference has been serving as the gold standard measure of dimensional interaction and selective attention. But the mechanisms that generate Garner interference are still not well understood. The current study proposes a novel theory that ascribes the interference (and dimensional interaction in general) to episodic feature integration processes at the micro (trial-to-trial) level. The novel account builds on earlier well-established notions of "feature integration" and "object files," and is augmented by formal derivations. The sequential binding account predicts that the magnitude of Garner interference is related to the strength of feature integration along consecutive trials. Three experiments were set to test this novel binding theory. Experiment 1 and Experiment 2 tested performance with integral dimensions (chroma and value, and width and height of rectangles); whereas Experiment 3 examined performance with a pair of separable dimensions (circle's size and angle of a diameter). In addition, the time lag ensuing between consecutive trials was manipulated. The results strongly supported the predictions of the sequential binding account: (a) with integral dimensions, substantial amounts of Garner interference were correlated with large partial repetition costs (e.g., consensual markers of feature integration), but this pattern was not observed with separable dimensions, and (b) the magnitude of both Garner interference and partial repetition costs diminished as a function of the ensuing time lag between consecutive trials, pointing to a common time-dependent memory mechanism. These results adduce strong support in the predictions of the feature binding theory of Garner interference, giving currency to the idea that dimensional interaction is driven by feature integration. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

The association of hearing loss with frailty among community-dwelling older adults: findings from the National Health and Aging Trends Study

BackgroundThe identification of modifiable risk factors is crucial for the prevention and/or reversal of frailty, which is associated with significant morbidity and mortality. Hearing loss affects two-thirds of older adults in the United States (U.S.) and is associated with physical and cognitive decline which may increase frailty risk. We investigated the association of hearing loss and hearing aid use with frailty and pre-frailty in a nationally representative sample of older adults in the U.S.MethodsCross-sectional analysis of the National Health and Aging Trends Study (2021 round). The better-hearing ear pure-tone average (BPTA) at speech-frequencies (0.5–4 kHz) was modeled continuously (per 10 dB) and categorically (no ≤ 25 dB, mild 26–40 dB, moderate or greater > 40 dB hearing loss). Hearing aid use was self-reported. The physical frailty phenotype (frail, pre-frail, robust) was determined based on Fried criteria: unintentional weight loss, exhaustion, low physical activity, weakness, slow walking speed. We used multinomial multivariable regression adjusted for sociodemographic and health characteristics (odds ratios [95% Confidence Intervals]).ResultsAmong 2,361 participants (mean age = 81 years, 56% female, 19% Black), 860 (36%) had mild and 864 (37%) had moderate or greater hearing loss. Worse hearing was associated with greater odds of being frail versus robust (OR = 1.20 [1.05–1.38] per 10 dB difference). Categorically, moderate or greater hearing loss was associated with greater odds of being frail (OR = 1.84 [1.01–3.08]) and pre-frail (OR = 1.46 [1.01–2.10]) versus robust. Among 1,724 participants with hearing loss, compared to hearing aid users (N = 522), nonusers had greater odds of being frail (OR = 2.54 [1.54–4.18]) and pre-frail (OR = 1.51 [1.05–2.17]) versus robust, and frail versus pre-frail (OR = 1.68 [1.04–2.72]).ConclusionsIn a nationally representative sample of older adults in the U.S., using gold-standard hearing measures and a validated frailty phenotype, hearing loss and lack of hearing aid use was cross-sectionally associated with frailty and pre-frailty. Future longitudinal studies are needed to establish if hearing loss is a risk factor for frailty, which may have significant clinical importance.

AimSeg: A machine-learning-aided tool for axon, inner tongue and myelin segmentation.

Electron microscopy (EM) images of axons and their ensheathing myelin from both the central and peripheral nervous system are used for assessing myelin formation, degeneration (demyelination) and regeneration (remyelination). The g-ratio is the gold standard measure of assessing myelin thickness and quality, and traditionally is determined from measurements made manually from EM images-a time-consuming endeavour with limited reproducibility. These measurements have also historically neglected the innermost uncompacted myelin sheath, known as the inner tongue. Nonetheless, the inner tongue has been shown to be important for myelin growth and some studies have reported that certain conditions can elicit its enlargement. Ignoring this fact may bias the standard g-ratio analysis, whereas quantifying the uncompacted myelin has the potential to provide novel insights in the myelin field. In this regard, we have developed AimSeg, a bioimage analysis tool for axon, inner tongue and myelin segmentation. Aided by machine learning classifiers trained on transmission EM (TEM) images of tissue undergoing remyelination, AimSeg can be used either as an automated workflow or as a user-assisted segmentation tool. Validation results on TEM data from both healthy and remyelinating samples show good performance in segmenting all three fibre components, with the assisted segmentation showing the potential for further improvement with minimal user intervention. This results in a considerable reduction in time for analysis compared with manual annotation. AimSeg could also be used to build larger, high quality ground truth datasets to train novel deep learning models. Implemented in Fiji, AimSeg can use machine learning classifiers trained in ilastik. This, combined with a user-friendly interface and the ability to quantify uncompacted myelin, makes AimSeg a unique tool to assess myelin growth.

Validation of pressure - derived microvascular resistance reserve (MRR) by Doppler wire measurement - the impact of correction for the error of hydrostatic pressure

Abstract Background The pressure-bounded coronary flow reserve (CFRpb) defines the possible CFR interval (between CFRpbmin and CFRpbmax) using intracoronary pressure data. However, its correlation to the Doppler wire measurement was reported to be poor, partly due to the non-inclusion of the hydrostatic pressure error in the calculations. Microvascular resistance reserve (MRR), a specific index of coronary microcirculation, can be calculated from CFR and intracoronary pressure data (Pa: aortic pressure, Pd: distal pressure) by the following equation: MRR= CFR; × (Pa, rest)/(pd, hyper). Purpose We aimed to design a prediction model of MRR using intracoronary pressure data and to validate the results against the gold-standard Doppler wire measurement. Methods In our study, hydrostatic pressure between the tip of the catheter and the sensor of the pressure wire was calculated by height difference measurement from a lateral angiographic view. After hydrostatic pressure error correction, the pressure-bounded MRR interval (between MRRpbmin and MRRpbmax) was determined by the aforementioned equation. In the training population, 23 actual MRRp-3D were defined within the pressure-bounded interval by hemodynamic calculations using the measured intracoronary pressure data and the angiography-based 3D anatomical features. These results were analyzed by regression analyses to find relations between the MRRpb and the actual MRRp-3D. Results Using the established linear relation (MRRpredicted=1.04+0.51×MRRpbmax), our prediction was tested in the population of 21 patients undergoing the gold standard Doppler wire measurements, and a significant correlation was found (r=0.54, p=0.01). If the area stenosis was included in the prediction model, the correlation had even improved (r=0.63, p=0.004). In parallel, the Bland-Altman analysis showed reduced mean differences between the predicted MRR and the MRR values determined during the Doppler wire measurement from 0.04 (±1.96SD: 0.88, –0.8) to –0.01 (±1.96SD: 0.77, –0.79). The latter prediction utilized the quadratic relation between the area stenosis in % (AS) and the ratio of the (MRRmax−MRRp-3D)/(MRRmax−MRRmin) (ratio=0.0047+0.0067×AS+0.000039×AS2). Conclusions The MRR can be predicted reliably by our simple model to assess microvascular function. After the correction for hydrostatic pressure error, the pressure data during routine FFR measurement (especially with the inclusion of area stenosis) provides a simultaneous physiological assessment of the macro- and microvasculature.Flow chart of the calculations

Correlation between non-invasive measurements and intracardiac pressures using machine learning techniques

Abstract Background Solutions targeting early recognition of congestion in heart failure (HF) patients have the potential to prevent readmissions and can thus significantly reduce the burden on HF care. A gold standard measure of congestion is the invasively measured pulmonary capillary wedge pressure (PCWP). However, the invasive nature and accessibility of this measurement limits its clinical use. Non-invasive approximation of the PCWP using biosensing wearables could be a promising replacement for HF monitoring. Purpose The primary aim of this retrospective study was to create a model that estimates the PCWP based on non-invasive measurements of vital signs using both traditional statistics and machine learning (ML) techniques. Methods The study cohort consisted of right-sided heart catheterizations between 23/6/2017 and 19/8/2022. The following models were used: linear regression or classification, k-nearest neighbors, random forest, gradient boosting and multilayer perceptron. The outcome measure for the regression models was the continuous PCWP as measured during the catheterization. The two outcome classes for the classification models were low (&amp;lt;12 mmHg) and high (≥12 mmHg) PCWP. Non-invasive mean arterial blood pressure (MAP), saturation, heart rate, weight and temperature measured at most 72 hours before or after the catheterization were collected as the features for the models. Additionally, ECG-signals acquired during the catheterization were used to calculate the heart rate variability (HRV). The data was split in a validation (20%) and training (80%) data set. The models were built based on the training set and then applied on the validation set to determine the coefficient of determination (R2) for the regression models and the AUC of the ROC for the classification models. Results A total of 859 catheterizations were included of which 31.2% had HF as primary diagnosis. Average age of the cohort was 59 ± 14 years and 52.2% were male. In the HF group, the features with the highest correlation with the PCWP were the HRV and gender (Table 1). All the used regression techniques resulted in low R2 values of up to 0.10 and the classification techniques in AUC of the ROC values of up to 0.61 (Table 2). Conclusion In the current study, PCWP could not be approximated with non-invasive measurements using traditional statistics and ML techniques. These findings support the notion that traditional measures for monitoring HF are poorly correlated with hemodynamic parameters. Perhaps repeated measurements over time could overcome the shortcomings of a single vital signs measurement for congestion evaluation. Future prospective research is needed to evaluate the potential of wearable devices measuring trends over a longer period and their potential in predicting hemodynamics.

Abstract 14675: The Role of Biomechanics in Diagnosis and Evaluation of Coronary Artery Disease

While there is a strong need to assess the safety and efficacy of novel therapies prior to evaluation in human patients, the ability to accurately model the complexities of coronary disease in-vitro and/or animal models is somewhat limited. Animal models, even those with genetic predispositions toward coronary disease do not exhibit high grade stenoses, similar to those that require treatment in human patients. At the same time, most in-vitro models and simulations of fluid-structure interactions cannot simultaneously capture the complex geometries, hemodynamics, and biomechanical response of human coronary disease. Here, we introduce a robust workflow to replicate an in-vitro platform incorporating compliant, realistic diseased coronary arteries in a flow loop under physiological conditions. Through ex-vivo imaging of cadaveric specimens, coupled with co-registered measurements of coronary biomechanics, we developed protocols that allow for fabrication and testing of highly realistic 3D printed models. The anatomical and biomechanical features of the coronary arteries, including local variations associated with the observed disease burdens were extracted and 3D printed, in high spatial resolution, using commercially available printers, making this methodology conveniently reproducible. Subsequently, the models were incorporated in a testing platform made of flow loops and valve resistance to mimic circulation and microvascular resistance respectively. Under physiological boundary conditions, we successfully collected measurements along the length of the vessels that exhibit a range of biomechanical characteristics from low to high values of modulus and assessed the impact of biomechanics on gold standard diagnostic and prognostic measures such as Fractional Flow Reserve. We demonstrated that incorporating the effects of local biomechanics significantly improves the predicted hemodynamics metrics with respect to ex-vivo coronaries.

Getting to grips with Resilience: Towards large-scale phenotyping of this complex trait

The capacity of animals to cope with environmental perturbations, hereafter called resilience, is an increasingly important trait. Resilience at the level of the animal is an emergent property of multiple underlying mechanisms (physiological, immunological, behavioral). This means that there is no direct measure of resilience, no easy key traits. It is a latent variable that may be inferred from multivariate measures. Further, the flexibility that resilience provides is evidenced in the rate of response to, and rate of recovery from, the environmental perturbation. Thus, it requires time-series measurements. The increasing availability of on-farm precision livestock technologies, that are capable of providing time-series measures of performance and of various physiological and health biomarkers, offer the opportunity to move toward large-scale phenotyping of resilience. There have been numerous studies putting forward methods to quantify resilience. These methods can be classified as being data-driven or concept driven. However, new candidate resilience proxies need to be validated. This is tricky to do as there is no direct measure of resilience, no easy gold standard measure. Per definition, good resilience will benefit the animal. Thus, the accumulated consequences of resilience can be used to evaluate resilience proxies. All other things being equal, it is expected that good resilience will be associated with a longer functional longevity (longevity adjusted for production level), with more reproductive cycles, and with fewer disease events. Recent examples of this approach of evaluating resilience proxies against the accumulated consequences of resilience are discussed. They show clearly that operational resilience proxies that are heritable and have been validated against the consequences of good resilience can be derived from on-farm time-series data. With the aim of deriving more nuanced phenotypes, there are an increasing number of studies that have taken up the challenge of attempting to statistically combine the information coming from multiple time-series measures. These studies show how multivariate time-series statistics can be used to derive more nuanced resilience phenotypes that capture some of the underlying mechanisms of resilience. In conclusion, the recent studies reviewed here have shown that operational and heritable resilience proxies exist, that they can form the basis for selection for resilience, and that more nuanced phenotypes are attainable which will allow selection for resilience to be tailored according to prevailing environmental challenge types.