Intra-individual Variation Research Articles

The Prevalence of Polyketide Synthase-Positive E. coli in Cystic Fibrosis.

Cystic fibrosis (CF) patients experience higher risks of colorectal cancer but the pathogenesis is unclear. In the general population, polyketide synthase-positive (pks+) E. coli is implicated in intestinal carcinogenesis via the production of colibactin; however, the relevance in CF is unknown. In this study, we investigate pks+E. coli prevalence in CF and potential associations between pks+E. coli, gastrointestinal inflammation, and microbiome dynamics with fecal calprotectin and 16SrRNA gene taxonomic data. Cross-sectional analysis demonstrated no difference in pks+E. coli carriage between CF patients and healthy controls, 21/55 (38%) vs. 26/55 (47%), p = 0.32. Pks+E. coli was not associated with significant differences in mean (SD) calprotectin concentration (124 (154) vs. 158 (268) mg/kg; p = 0.60), microbial richness (159 (76.5) vs. 147 (70.4); p = 0.50) or Shannon diversity index (2.78 (0.77) vs. 2.65 (0.74); p = 0.50) in CF. Additionally, there was no association with exocrine pancreatic status (p = 0.2) or overall antibiotic use (p = 0.6). Longitudinally, CF subjects demonstrated intra-individual variation in pks+E. coli presence but no significant difference in overall prevalence. Future investigation into the effects of repeat exposure on risk profile and analysis of older CF cohorts is necessary to identify if associations with colorectal cancer exist.

Analysis of the features of planning bioequivalence studies with adaptive design for drug products analogous to endogenous compounds ademetionine

Introduction. Adaptive design in clinical bioequivalence studies offers a more flexible approach, allowing for modifications to protocols during the trial based on accumulated data. This is particularly relevant for drugs that are analogs of endogenous compounds, such as ademetionine, due to the presence of endogenous concentrations, potential physiological fluctuations, and homeostatic mechanisms. Given that ademetionine is included in the clinical guidelines by the Ministry of Health of the Russian Federation for treating various liver diseases, there is significant interest in developing generic formulations, which necessitates careful planning of clinical studies.Aim. The aim of this work is to analyze approved protocols for bioequivalence studies with adaptive designs for a drug product that is an analog of the endogenous compound ademetionine, specifically enteric-coated tablets.Materials and methods. A search was conducted in the database of approved clinical trials by the State Register of Medicines of the Ministry of Health of the Russian Federation using keywords "adaptive design" and "bioequivalence" for the period from 2023 to 2024.Results and discussion. The article analyzes nine bioequivalence protocols with adaptive designs related to Potvin C's methodology for drugs analogous to the endogenous compound ademetionine in enteric-coated tablet form. The primary endpoints were pharmacokinetic parameters Cmax and AUC0–t. Ademetionine was studied as the evaluated analyte. In 77.8 % of the protocols, there was a planned assessment of the endogenous background of ademetionine followed by adjustments to pharmacokinetic parameters. Sample size calculations were not performed in these protocols due to the lack of reported values for the coefficient of intra-individual variation (CVintra) for Cmax and AUC0–t of ademetionine in literature.Conclusion. The analysis results indicate that a well-planned bioequivalence study with an adaptive design (until CVintra values for ademetionine are published in specialized literature) is rational for developing generic formulations of ademetionine, with an assessment of the endogenous background. Considering the modified dosage form, it is necessary to conduct bioequivalence studies with administration both fasting and after meals.

Machine Learning and digital Imaging for Spatiotemporal Monitoring of Stress Dynamics in the clonal plant Carpobrotus edulis: Uncovering a Functional Mosaic.

Rapid, large-scale monitoring is critical to understanding spatiotemporal plant stress dynamics, but current physiological stress markers are costly, destructive, and time-consuming. This study aimed to evaluate the potential of machine learning to non-destructively predict leaf betalains-yellow to reddish pigments unique to Caryophyllales species-for the first time, and to explore betalains' intra-individual variation on a clonal species and its role to respond to stressful periods. We characterized the betalainic profile of an invasive clonal plant for the first time, Carpobrotus edulis (L.) NE Br. (the cape fig), via HPLC. We measured multiple stress markers over a year, including betalain content using our optimized method, where the species is spreading. Additionally, 3,735 digital images at the leaf level were taken. Machine learning regression algorithms were trained to predict betalain accumulation from digital images, outperforming classic spectroradiometer measurements. Betalain content increased sharply in non-reproductive ramets during extreme abiotic conditions in summer and during senescence in reproductive ramets. The stress markers revealed a strong intra-individual functional mosaic, underscoring the importance of spatiotemporal dimensions in stress tolerance. We developed a scalable, non-destructive tool for betalain research that integrates digital imaging with machine learning. This approach opens new possibilities for understanding spatiotemporal stress responses, particularly in clonal plant systems, using artificial intelligence.

Assessing the predictive value of peak alpha frequency for the sensitivity to pain.

Pain perception varies considerably between and within individuals. How the brain determines these variations has yet to be fully understood. The peak frequency of alpha oscillations has recently been shown to predict an individual's sensitivity to longer-lasting experimental and clinical pain. Peak alpha frequency (PAF) is, thus, discussed as a potential biomarker and novel target for neuromodulatory treatments of pain. Here, we scrutinized the generalizability of the relation between PAF and pain. We applied brief painful laser stimuli to 159 healthy participants and related interindividual and intraindividual variations of pain perception to PAF measured with electroencephalography. Comprehensive multiverse analyses replicated across 2 sessions did not provide consistent evidence for a predictive role of PAF for brief experimental pain. This indicates that the relationship between PAF and pain does not generalize to all types of pain and calls for a systematic exploration of the relationship between PAF, pain perception, and other neuropsychiatric symptoms. Such explorations help to understand the prospects and limits of biomarkers and might guide future research on biomarkers of pain and neuropsychiatric disorders.

Predicting Postprandial Glycemic Responses With Limited Data in Type 1 and Type 2 Diabetes.

A core challenge in managing diabetes is predicting glycemic responses to meals. Prior work identified significant interindividual variation in responses and developed personalized forecasts. However, intraindividual variation is still not well understood, and the most accurate approaches require invasive microbiome data. We aimed to investigate (1) whether postprandial glycemic responses (PPGRs) can be predicted with limited data and (2) sources of intraindividual variation. We used data collected from 397 people with Type 1 Diabetes (T1DEXI) and 100 people with Type 2 Diabetes (ShanghaiT2DM) who wore continuous glucose monitors (CGMs) and logged meals. Using dietary, demographic, and temporal features, we predicted 2 hours PPGR, and peak 2 hours postprandial glucose rise (Glumax). We evaluated the contribution of food features (eg, macronutrients, food category) and use of personal training data and investigated intraindividual variability in responses. We achieved comparable accuracy to prior work for PPGR (T1DEXI R = 0.61, ShanghaiT2DM R = 0.72) and Glumax (T1DEXI R = 0.64, ShanghaiT2DM R = 0.73), without using invasive data like microbiome. Including food category features led to higher accuracy than macronutrients alone. Analysis of glycemic responses to duplicate meals identified time of day (PPGR: T1DEXI P < .05 for lunch, ShanghaiT2DM P < .001 for lunch and dinner) and menstrual cycle (Glumax: P < .05 for perimenstrual) as sources of variability. We demonstrate that in individuals with T1D and T2D, glycemic responses to meals can be predicted without personalized training data or invasive physiological data.

Exploring the Predictors of AI Chatbot Usage Intensity Among Students: Within- and Between-Person Relationships Using the Technology Acceptance Model

The current research investigated the factors associated with the intensity of AI chatbot usage among university students, applying the Technology Acceptance Model (TAM) and its extended version, TAM3. A daily diary study over five days was conducted among univserity students, distinguishing between inter-individual (between-person) and intra-individual (within-person) variations. Multilevel structural equation modeling (SEM) was used to analyze the data. In Study 1 (N = 72), results indicated that AI chatbot anxiety was associated with perceived ease of use (PEOU) and perceived usefulness (PU), which serially mediated the link with AI chatbot usage intensity. Study 2 (N = 153), supported these findings and further explored the roles of facilitating conditions and subjective norm as additional predictors of PEOU and PU. Results from both studies demonstrated that, at the between-person level, students with higher average levels of PEOU and PU reported more intensive AI chatbot usage. In Study 1, the relationship between PEOU and usage intensity was mediated through PU at the within-person level, while the mediation model was not supported in Study 2. Post-hoc comparisons highlighted much higher variability in PEOU and PU in Study 1 compared to Study 2. The results have practical implications for enhancing AI chatbot adoption in educational settings. Emphasizing user-friendly interfaces, reducing AI-related anxiety, providing robust technical support, and leveraging peer influence may enhance the usage intensity of AI chatbots. This study underscores the necessity of considering both stable individual differences and dynamic daily influences to better understand AI chatbot usage patterns among students.

Asymmetry During Landing Impacts Following Jumps With Aerial Rotation in Collegiate Men's Basketball Players.

Harry, JR, Park, S, Stewart, M, Hite, M, Simms, A, Larsen, M, and Bishop, C. Asymmetry during landing impacts following jumps with aerial rotation in collegiate men's basketball players. J Strength Cond Res 39(3): 352-359, 2025-This project explored whether (a) landing performances and (b) impact force asymmetries were different during countermovement jump (CMJ) landings with leftward versus rightward aerial rotation in 19 collegiate men's basketball players. Replicated single-subject analyses were performed to identify differences that were both statistically significant and important for each individual. Countermovement jump landing performance and loading, attenuation, and control phase durations were compared, while interlimb vertical ground reaction forces (GRF) were compared during each phase of CMJ landings with leftward and rightward rotations, respectively, using the model statistic and coefficient of variation techniques. The model statistic provided random chance probability ( α = 0.05). The coefficient of variation provided whether differences exceeded the largest amount of variation from each limb or rotation direction. The bilateral asymmetry index (BAI; difference between dominant and nondominant limbs divided by the sum of the 2 limbs) was also calculated. Statistically significant (model statistic results) and important (coefficient of variation results) differences in landing performance were detected between rotation conditions in 4 subjects. Most subjects did not display significant and important asymmetries for the changes of vertical GRF during any phase of CMJ landings with leftward or rightward rotations. Large amounts of intra-individual variation seem to be an influential factor for these results, as basketball players seem to have unrefined landing strategies that could require targeted training. Because the BAI values reached as high as ± 531% without coinciding with significant and important asymmetry, researchers and practitioners may need to reevaluate the way in which asymmetry indices are interpreted.

The influence of training load and schedule on youth athletes' sleep.

Sleep is important for youth athletes, supporting sport-related recovery and performance, as well as growth and development. Sleep may be influenced by training factors; therefore, this study aimed to characterise youth athletes' sleep, and examine associations between training load, schedule and frequency, and sleep. Twenty-six youth basketballers (age: 14.22 ± 0.74 years, 13 male, 13 female) from a high-performance sporting school were monitored for a period of 8 weeks. Sleep measures (via actigraphy and sleep diaries) were collected alongside training diaries (recording time, duration and perceived exertion). Youth athletes who finished training after 20:30 hours had significantly less total sleep time than when training finished before 20:30 hours. Higher daily total training duration was associated with decreased total sleep time. There is a potential contradiction with findings related to the number of sessions per day, as participants who completed two training sessions in a day had more sleep than those who completed one session per day; but this was not observed for athletes with three sessions per day. Participants had large intra-individual variations (mean intra-individual standard deviation) in bedtime (1.06 hr) and sleep time (0.84 hr). In conclusion: (1) late night training sessions appear to reduce total sleep time and should be avoided in youth athletes; (2) total daily training duration had a greater negative effect on sleep than session frequency; and (3) participants' large intra-individual variation in bedtime may reduce sleep quality and efficiency.

Semiparametric Confidence Sets for Arbitrary Effect Sizes in Longitudinal Neuroimaging.

The majority of neuroimaging inference focuses on hypothesis testing rather than effect estimation. With concerns about replicability, there is growing interest in reporting standardized effect sizes from neuroimaging group-level analyses. Confidence sets are a recently developed approach to perform inference for effect sizes in neuroimaging but are restricted to univariate effect sizes and cross-sectional data. Thus, existing methods exclude increasingly common multigroup or nonlinear longitudinal associations of biological brain measurements with inter- and intra-individual variations in diagnosis, development, or symptoms. We broadly generalize the confidence set approach by developing a method for arbitrary effect sizes in longitudinal studies. Our method involves robust estimation of the effect size image and spatial and temporal covariance function based on generalized estimating equations. We obtain more efficient effect size estimates by concurrently estimating the exchangeable working covariance and using a nonparametric bootstrap to determine the joint distribution of effect size across voxels used to construct confidence sets. These confidence sets identify regions of the image where the lower or upper simultaneous confidence interval is above or below a given threshold with high probability. We evaluate the coverage and simultaneous confidence interval width of the proposed procedures using realistic simulations and perform longitudinal analyses of aging and diagnostic differences of cortical thickness in Alzheimer's disease and diagnostic differences of resting-state hippocampal activity in psychosis. This comprehensive approach along with the visualization functions integrated into the pbj R package offers a robust tool for analyzing repeated neuroimaging measurements.

Skin microbiomes of frogs vary among individuals and body regions, revealing differences that reflect known patterns of chytrid infection.

The amphibian skin microbiome is an important line of defense against pathogens including the deadly chytrid fungus, Batrachochytrium dendrobatidis ( Bd ). Intra-species variation in disease susceptibility and intra-individual variation in infection distribution across the skin, therefore, may relate to differences in skin microbiomes. However, characterization of microbiome variation within and among amphibian individuals is needed. We utilized 16S rRNA gene amplicon sequencing to compare microbiomes of ten body regions from nine captive R. sierrae individuals and their tank environments. While frogs harbored distinct microbial communities compared to their tank environments, tank identity was associated with more variation in frog microbiomes than individual frog identity. Within individuals, we detected differences between microbiomes of body regions where Bd infection would be expected compared to regions that infrequently experience infection. Notably, the bacterial families Burkholderiaceae (phylum Proteobacteria) and Rubritaleaceae (phylum Verrucomicrobia) were dominant on frog skin, and the relative abundances of undescribed members of these families were important to describing differences among and within individuals. Two undescribed Burkholderiaceae taxa were found to be putatively Bd -inhibitory, and both showed higher relative abundance on body regions where Bd infection is often localized. These findings highlight the importance of considering intrapopulation and intraindividual heterogeneities, which could provide insights relevant to predicting localized interactions with pathogens.

Drivers of individual differences in the sleep behaviour of fallow deer neonates.

Inter-individual differences are necessary for selection to act, while plasticity (intra-individual variation) may buffer against selection. Sleep is a critical self-maintenance behaviour but, unlike most behaviours, the causes and consequences of its inter- and intra-individual variation in wild animals is poorly understood, particularly in neonates where sleep plays a key role in development. We have shown previously that free-ranging neonate fallow deer (Dama dama) differ in sleep during the first few weeks of life. Here, we test whether individual variability in sleep is organised systematically across the population, and whether these individual differences are associated with chronic stress measured using hair cortisol, or the timing of birth. Four dimensions of sleep behaviour (total sleep time, sleep fragmentation, sleep quality, and sleep distribution over 24-h) were quantified using state-of-the-art triaxial accelerometers. We then used a multivariate mixed-effects model in a Bayesian framework to evaluate covariation between multiple dimensions of sleep behaviour, and quantify the relative importance of chronic stress and the timing of birth, while accounting for the confounding effects of environmental conditions and age. We found that the timing of birth and chronic stress were not associated with changes in sleep between individuals. While both total sleep time and the number of bouts per day declined with age, their rate of development covaried, but no other sleep dimensions covaried. Our results represent an in-depth analysis of natural variation in sleep, and show that individual differences in four aspects of sleep architecture in free-living fallow deer fawns are strong but independent of one another and unrelated to chronic stress or the timing of birth. We suggest that covariation between sleep dimensions might emerge later in life and effects of cortisol and birth timing might be very short and transient.

Salting-out assisted liquid-liquid extraction for UPLC-MS/MS determination of bile acids and kynurenine-, indole- and serotonin-pathway metabolites of tryptophan in human serum of healthy probands.

Salting-out assisted liquid-liquid extraction for UPLC-MS/MS determination of bile acids and kynurenine-, indole- and serotonin-pathway metabolites of tryptophan in human serum of healthy probands.

Heterogeneity of Locked-Pasture Snow Conditions Modulate Habitat and Movement Choices of a Facultative Migrant.

Habitat selection and movement are key mechanisms by which animals can respond to and potentially cope with highly variable environmental conditions. Optimal responses likely vary, however, depending on the severity and scope of conditions. We tested this hypothesis using a facultative migrant species, the Great Gray Owl (Strix nebulosa), which exhibits high inter- and intra-individual variation in the timing, direction, and distance of winter movements. Specifically, we evaluated whether episodic, spatiotemporally variable "locked-pasture" snow conditions, which restrict access to subnivean food, prompted shifts in habitat selection or long-distance movements by owls. We quantified the movement of 42 owls using global positioning system (GPS) data within the Greater Yellowstone Ecosystem, USA, during 2017-2022. We used a novel ecological application of SnowModel, a snow evolution modeling system, to estimate fine-scale, physical snow properties likely to influence access to prey. Variables included snow depth, snow crusts produced by wind, and ice crusts produced by melt-freeze and rain-on-snow events. Owls avoided heterogeneously distributed wind crusts via local shifts in habitat selection. More homogenous ice crusts elicited long-distance movements away from affected home ranges. Finally, owls employed both proximate shifts in habitat selection and long-distance movements to avoid deeper snow. Ultimately, owls exhibited behavioral flexibility in response to limiting snow conditions that can vary in terms of severity, spatial extent, and duration. Such behavioral responses determine species distribution, with implications for population and community dynamics in spatiotemporally variable systems. Understanding the effects of, and responses to, environmental controls is increasingly important given the scope of on-going global change.

Hourly Variations in Glymphatic Function Based on MRI Scan Times in Cognitively Normal Individuals.

Hourly Variations in Glymphatic Function Based on MRI Scan Times in Cognitively Normal Individuals.

Toward a Psychology of Individuals: The Ergodicity Information Index and a Bottom-up Approach for Finding Generalizations

In the last half of the twentieth century, psychology and neuroscience have experienced a renewed interest in intraindividual variation. To date, there are few quantitative methods to evaluate whether a population (between-person) structure is likely to hold for individual people, often referred to as ergodicity. We introduce a new network information theoretic metric, the ergodicity information index (EII), that quantifies the amount of information lost by representing all individuals with a between-person structure. A Monte Carlo simulation demonstrated that EII can effectively delineate between ergodic and nonergodic systems. A bootstrap test is derived to statistically determine whether the empirical data is likely generated from an ergodic process. When a process is identified as nonergodic, then it’s possible that a mixture of groups exist. To evaluate whether groups exist, we develop an information theoretic clustering method to detect groups. Finally, two empirical examples are presented using intensive longitudinal data from personality and neuroscience domains. Both datasets were found to be nonergodic, and meaningful groupings were identified in each dataset. Subsequent analysis showed that some of these groups are ergodic, meaning that the individuals can be represented with a single population structure without significant loss of information. Notably, in the neuroscience data, we could correctly identify two clusters of individuals (young vs. older adults) measured by a pattern separation task that were related to hippocampal connectivity to the default mode network.

Flower Position and Clonal Integration Drive Intra-Individual Floral Trait Variation in Water-Hyacinth (Eichhornia crassipes, Pontederiaceae).

Intra-individual variation in floral traits is linked to plant fitness, playing a central role in sexual selection. This variation can arise from architectural constraints, such as flower position on the inflorescence axis, and from environmental factors. In relation to the environmental influences on floral traits, the most common causes of variation are linked to the presence of pollinators, to plant resource acquisition strategies and to the availability of local resource pools. We investigated how clonal integration and resource depletion through defoliation affect floral trait stability in Eichhornia crassipes, testing whether clonal integration buffer floral traits against resource limitations. Using greenhouse experiments, we manipulated clonal structure and resource availability. We assessed the effects of floral position and clonal integration on floral traits through model selection. Our results showed that basal flowers generally had larger traits, more attractive to pollinators, and isolated or defoliated ramets exhibited significant reductions in floral traits, especially at distal flowers. Clonal integration stabilized floral traits across positions by mitigating the effects of resource variability. Clonal integration in E. crassipes enhances resilience to resource depletion, likely contributing to this species invasiveness. These findings highlight the significance of clonal and architectural integration in sustaining reproductive traits under environmental stress.

Three-dimensional analysis of lip and chin movements during mastication with artificial nasal obstruction.

Three-dimensional analysis of lip and chin movements during mastication with artificial nasal obstruction.

Community assembly of gut microbiomes in yolk sac fry of Atlantic salmon: host genetics, environmental microbiomes, and ecological processes.

In this study, we investigated the influence of host genetics and environmental microbiomes on the early gut microbiome of Atlantic salmon. We aimed at rearing the fish in either r- or K-selected environments, where the r-selected environment would be expected to be dominated by fast-growing opportunistic bacteria and thus represent more detrimental microbial environment than the K-selected water. Eggs from both wild and aquaculture strains of Atlantic salmon were hatched under germ-free conditions. One week after hatching, rearing flasks were inoculated with either r- or K-selected water communities. Three weeks after hatching, no effect of host strain on the gut microbiomes were observed. r-selection was found to take place in the rearing water of all flasks, including in the flasks added K-selected water. Still, the water microbiomes differed significantly between the flasks that had been added r- and K-selected water (Add-r and Add-K flasks, respectively). Lower alpha diversity and higher abundances of Pseudomonas were observed for the Add-K flasks, indicating a potential unfavorable microbial environment. Selection in the host structured the gut microbiomes, but an extensive interindividual variation was explained by stochastic processes in community assembly. The gut microbiomes also differed significantly between the Add-r and Add-K flasks. In Add-K flasks, they had higher similarities to the rearing water microbiomes, and the assembly of gut communities was less influenced by stochastic processes. The fish in Add-K flasks had lower growth rates than in Add-r flasks, probably as a result of negative host-microbe interactions. These findings highlight the importance of, but also the challenges related to, managing the microbial environment when cultivating fish.

Diet and landscape use at Faraoskop from C, N and Sr isotopes in multiple skeletal tissues

The isotopic composition of body tissues can provide information about diet and patterns of movement or migration during life. Here, we report δ13C, δ15N and 87Sr/86Sr analyses for a small sample of fauna and for the 12 humans buried at Faraoskop, and make inferences about how these people ranged across the landscape as they hunted and foraged. δ13C and δ15N values for collagen from cortical and cancellous bone and (for two individuals) desiccated muscle tissue are similar, reflecting consumption of isotopically similar, mostly terrestrial foods throughout life. Not all individuals had teeth preserved but for five we were able to measure 87Sr/86Sr in tooth enamel in an earlier- and a later-forming tooth. Where possible, teeth were analysed near the occlusal surface, half-way up the height of the crown and near the dentine/enamel junction, to assess variation during the period of crown formation. Only one of the five (UCT 394) showed significant intra-individual variation in 87Sr/86Sr, between 0.6 and 3.5 years of age. Two individuals yielded enamel 87Sr/86Sr like the geologically recent sediments of the coastal plain to the west of Faraoskop, while three individuals had values intermediate between the coastal plain and the more ancient shales and sandstones of the Table Mountain Group to the east. As young children, people buried at Faraoskop ranged over different areas of the local landscape, probably as part of different social groups.

Intra-Individual Variation in the Jump Smash for Elite Malaysian Male Badminton Players

Intra-Individual Variation in the Jump Smash for Elite Malaysian Male Badminton Players