Variation in gaze following across the life span: A process-level perspective.

Following eye gaze is fundamental for many social-cognitive abilities, for example, when judging what another agent can or cannot know. While the emergence of gaze following has been thoroughly studied on a group level, we know little about (a) the developmental trajectory beyond infancy and (b) the sources of individual differences. In Study 1, we examined gaze following across the lifespan (N = 478 3- to 19-year-olds from Leipzig, Germany; and N = 240 20- to 80-year-old international, remotely tested adults). We found a steep performance improvement during preschool years, in which children became more precise in locating the attentional focus of an agent. Precision levels then stayed comparably stable throughout adulthood with a minor decline toward old age. In Study 2, we formalized the process of gaze following in a computational cognitive model that allowed us to conceptualize individual differences in a psychologically meaningful way (N = 60 3- to 5-year-olds, 50 adults). According to our model, participants estimate pupil angles with varying levels of precision based on observing the pupil location within the agent's eyes. In Study 3, we empirically tested how gaze following relates to vector following in non-social settings and perspective-taking abilities (N = 102 4- to 5-year-olds). We found that gaze following is associated with both of these abilities but less so with other Theory of Mind tasks. This work illustrates how the combination of reliable measurement instruments and formal theoretical models allows us to explore the in(ter)dependence of core social-cognitive processes in greater detail. RESEARCH HIGHLIGHTS: Gaze following develops beyond infancy. The highest precision levels in localizing attentional foci are reached in young adulthood with a slight decrease towards old age. We present a computational model that describes gaze following as a process of estimating pupil angles and the corresponding gaze vectors. The model explains individual differences and recovers signature patterns in the data. To estimate the relation between gaze- and vector following, we designed a non-social vector following task. We found substantial correlations between gaze following and vector following, as well as Level 2 perspective-taking. Other Theory of Mind tasks did not correlate.

Activity concentration of indoor radon and its short-lived progeny (218Po, 214Pb, and 214Po) and their effect on atmospheric ionization rate in Sana'a, Yemen.

Exposure to ionizing radiation inside houses, especially radionuclides of radon and its progeny, poses serious health risks that can be exacerbated when inhaled as a result of interaction with human lung tissue. Also, air ionization is mainly due to these radionuclides. Therefore, accurate measurements of radon activity concentrations and its short-lived progeny are required to assess dose and environmental pollution and estimate ionization rates in indoor environments. For this purpose, we employed a previously tested and approved reliable method, following the three-count procedure. This method is based on airborne radon progeny sampling on polycarbonate membrane filters and alpha counting using a passive α-dosimetry technique with CR-39 detectors. The method also relies on a PC-based software we developed for solving mathematical equations and calculating all the necessary physical quantities. In this study, the concentrations of radon and individual short-lived radon progeny were measured in 20 houses in Sana'a, Yemen. Measurement conditions and meteorological variables were considered. The average activity concentrations of 222Rn, Equilibrium-Equivalent Concentration (EEC), 218Po, 214Pb, and 214Po were 73.1 ± 6.0, 29.2 ± 2.4, 44.4 ± 3.6, 30.5 ± 2.5, and 23.2 ± 1.9 Bq.m-3, respectively. The calculated average unattached fractions f1(218Po), f2(214Pb), and fp were found to be 0.24, 0.04, and 0.07 % respectively. The annual average values of ion-pair production rate caused by 222Rn and their progeny and air ion concentration, were 27.25 ions.cm-3s-1 and 1829 ions.cm-3 respectively. The annual effective dose was estimated to be 1.93 ± 0.16 mSv.y-1, well lower than the recommended 10 mSv.y-1.

Adult telomere length is positively correlated with survival and lifetime reproductive success in a wild passerine.

Explaining variation in individual fitness is a key goal in evolutionary biology. Recently, telomeres, repeating DNA sequences capping chromosome ends, have gained attention as a biomarker for body state, physiological costs, and senescence. Existing research has provided mixed evidence for whether telomere length correlates with fitness, including survival and reproductive output. Moreover, few studies have examined how the rate of change in telomere length correlates with fitness in wild populations. Here, we intensively monitored an insular population of house sparrows, and collected longitudinal telomere and life history data (16 years, 1225 individuals). We tested whether telomere length and its rate of change predict fitness measures, namely survival, lifespan and annual and lifetime reproductive effort and success. Telomere length positively predicted short-term survival, independent of age, but did not predict lifespan, suggesting either a diminishing telomere length-survival correlation with age or other extrinsic factors of mortality. The positive association of telomere length with survival translated into reproductive benefits, as birds with longer telomeres produced more genetic recruits, hatchlings and reared more fledglings over their lifetime. In contrast, there was no association between telomere dynamics and annual reproductive output, suggesting telomere dynamics might not reflect the costs of reproduction in this population, potentially masked by variation in individual quality. The rate of change of telomere length did not correlate with neither lifespan nor lifetime reproductive success. Our results provide further evidence that telomere length correlates with fitness, and contribute to our understanding of the selection on, and evolution of, telomere dynamics.

Simulation of FES on the forearm with muscle-specific activation resolution.

Introduction: Functional electrical stimulation (FES) is an established method of supporting neurological rehabilitation. However, particularly on the forearm, it still cannot elicit selective muscle activations that form the basis of complex hand movements. Current research approaches in the context of selective muscle activation often attempt to enable targeted stimulation by increasing the number of electrodes and combining them in electrode arrays. In order to determine the best stimulation positions and settings, manual or semi-automated algorithms are used. This approach is limited due to experimental limitations. The supportive use of simulation studies is well-established, but existing simulation models are not suitable for analyses of selective muscle activation due to missing or arbitrarily arranged innervation zones. Methods: This study introduces a new modeling method to design a person-specific digital twin that enables the prediction of muscle activations during FES on the forearm. The designed individual model consists of three parts: an anatomically based 3D volume conductor, a muscle-specific nerve fiber arrangement in various regions of interest (ROIs), and a standard nerve model. All processes were embedded in scripts or macros to enable automated changes to the model and the simulation setup. Results: The experimental evaluation of simulated strength-duration diagrams showed good coincidence. The relative differences of the simulated amplitudes to the mean amplitude of the four experiments were in the same range as the inter-experimental differences, with mean values between 0.005 and 0.045. Based on these results, muscle-specific activation thresholds were determined and integrated into the simulation process. With this modification, simulated force-intensity curves showed good agreement with additionally measured curves. Discussion: The results show that the model is suitable for simulating realistic muscle-specific activations. Since complex hand movements are physiologically composed of individual, selective muscle activations, it can be assumed that the model is also suitable for simulating these movements. Therefore, this study presents a new and very promising approach for developing new applications and products in the context of the rehabilitation of sensorimotor disorders.

High-speed train drivers' human error under fatigue and stress: the role of situation awareness and individual differences.

Fatigue and stress are critical variables that impair railway train drivers' safety performance, and individual differences may influence these effects. This study investigates how fatigue and stress affect high-speed train drivers' human error and the role of individual differences. We hypothesised that situation awareness (SA) mediates the effects of fatigue and stress on human error, and individual differences (age and work experience) moderate these effects. We surveyed 1,391 male drivers from eight Chinese railway bureaus and used PROCESS Macro for data analysis. The results revealed that fatigue and stress increased human error, directly and indirectly through SA. Age and work experience moderated the effect of fatigue and stress on SA, respectively. Older drivers had better SA under high fatigue, while more experienced drivers had better SA under high stress. These findings can inform more tailored safety management strategies to lower human error and enhance the safety of high-speed train operations.

A cross-sectional survey of 1,391 high-speed train drivers in China indicated that fatigue and stress amplify human error by impairing situation awareness (SA). Age and work experience were observed to moderate the impact of fatigue and stress on SA, respectively. These insights guide the advancement of safety management strategies.

Use of acoustic signals in Cape fur seal mother-pup reunions: individual signature, signal propagation and pup home range.

The Cape fur seal (Arctocephalus pusillus pusillus) is one of the most colonial mammals, with colonies of up to hundreds of thousands of individuals during the breeding season. During the lactation period, mothers and pups are regularly separated as females undertake multi-day foraging trips at sea. Mothers and pups use a mutual vocal recognition system to reunite after separation. Such communication is highly constrained by both high background noise and risk of individual confusion owing to the density of seals. This study aimed to experimentally assess the acoustic features relevant for mother-pup vocal identification and the propagation properties of their calls. Playback experiments revealed that mother and pup individual vocal signatures rely on both temporal and frequency parameters: amplitude and frequency modulations, timbre and fundamental frequency (f0). This is more parameters than in any colonial species studied so far. The combinational use of acoustic features reinforces the concept that both environmental and social constraints may have acted as selective pressures on the individual vocal recognition systems. Theoretical propagation distances of mother and pup vocalisations were estimated to be below the range of distances at which mother-pup reunions can occur. This suggests that Cape fur seals may have strong abilities to extract vocal signals from the background noise, as previously demonstrated in the highly colonial king penguin. Investigating the transmission of information throughout the propagation of the signal as well as the ability of the receiving individual to decipher vocal signatures is crucial to understanding vocal recognition systems in the wild.

Applications of MRI in Schizophrenia: Current Progress in Establishing Clinical Utility.

Schizophrenia is a severe mental illness that significantly impacts the lives of affected individuals and with increasing mortality rates. Early detection and intervention are crucial for improving outcomes but the lack of validated biomarkers poses great challenges in such efforts. The use of magnetic resonance imaging (MRI) in schizophrenia enables the investigation of the disorder's etiological and neuropathological substrates in vivo. After decades of research, promising findings of MRI have been shown to aid in screening high-risk individuals and predicting illness onset, and predicting symptoms and treatment outcomes of schizophrenia. The integration of machine learning and deep learning techniques makes it possible to develop intelligent diagnostic and prognostic tools with extracted or selected imaging features. In this review, we aimed to provide an overview of current progress and prospects in establishing clinical utility of MRI in schizophrenia. We first provided an overview of MRI findings of brain abnormalities that might underpin the symptoms or treatment response process in schizophrenia patients. Then, we summarized the ongoing efforts in the computer-aided utility of MRI in schizophrenia and discussed the gap between MRI research findings and real-world applications. Finally, promising pathways to promote clinical translation were provided. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 3.

Certainty in holistic thinking and responses to contradiction: Dialectical proverbs, counter-attitudinal change and ambivalence.

The present research examined whether consideration of individuals' certainty in their holism can enhance the ability of this individual difference to predict how they respond to contradiction-relevant outcomes. Across four studies, participants first completed a standardized measure of holistic-analytic thinking. Then, they rated how certain they were in their responses to the holism scale or were experimentally induced to feel high or low certainty. Next, participants were exposed to dialectical proverbs (Study 1a and 1b), to a counter-attitudinal change induction (Study 2), or to a paradigm of attitudinal ambivalence (Study 3). Results revealed that participants with higher certainty in their holistic thinking exhibited higher preference for dialectical proverbs (Study 1a and 1b), changed their attitude less following a counter-attitudinal task (Study 2) and showed weaker correspondence between objective and subjective ambivalence (Study 3). Beyond examining new domains and discovering novel findings, the present work was designed to be the first to show moderation of previously identified effects in the domain of holistic thinking and responses to contradiction.

The effect of practice environments and psychological empowerment perceptions of nurses on their care behaviours: A cross-sectional study.

AIM: The aim of this study was to examine the effect of professional and individual characteristics, practice environments and psychological empowerment perceptions of nurses on their care behaviours. DESIGN: The study used a cross-sectional research design following the STROBE guidelines. METHODS: The sample of this descriptive and correlational study consisted of 584 nurses working in a university hospital in Turkey. The data were collected between January and June 2023 using the Nursing Information Form, the Practice Environment Scale of the Nursing Work Index (PES-NWI), the Psychological Empowerment Scale (PES), and the Caring Behaviours Scale-30, and analysed using descriptive statistics, Spearman's correlation and multiple linear regression. RESULTS: It was determined that PES-NWI, PES and Caring Behaviours Scale (CBI-30) scores of nurses were higher than the average. The study revealed that certain professional and individual characteristics of nurses, practice environments and psychological empowerment perceptions had an effect on their care behaviours. CONCLUSION: The results of the study showed that nurses' PES-NWI, PES and CBI-30 scores were higher than the average, and that certain professional and individual characteristics of nurses, practice environments and psychological empowerment perceptions had an effect on care behaviours. Nursing service managers, in particular, are required to understand the importance of this relationship and create appropriate working conditions which are integrated with psychological empowerment to improve caring behaviours of nurses.

[The relationship between intraocular pressure and age-related variations in ocular rigidity]. / Vzaimosvyaz' vnutriglaznogo davleniya s involyutsionnymi kolebaniyami rigidnosti glaza.

PURPOSE: This study aimed to identify the correlation between age-related fluctuations in the average values of rigidity of the fibrous tunic of the eye (FTE) and corresponding ranges of true intraocular pressure (IOP) in healthy eyes and eyes with open-angle glaucoma (OAG); using the identified ranges of FTE rigidity, to establish the appropriate IOP zones for healthy and glaucomatous eyes, taking into account the aging periods as classified by the World Health Organization (WHO). MATERIAL AND METHODS: Ocular-Response Analyzer tonometry was used according to the Koshits-Svetlova dynamic diagnostic method to examine 674 patients with healthy eyes and 518 patients with glaucomatous eyes, aged 18 to 90 years, classified according to the WHO aging periods, and a theoretical analysis was conducted to estimate clinical values of FTE rigidity, the current level of true IOP, and the calculated individual IOP level in a patient's eye during youth. RESULTS: The following IOP level zones were identified for patients with healthy and glaucomatous eyes: low IOP zone (≤13 mm Hg); medium IOP zone (14-20 mm Hg); elevated IOP zone (21-26 mm Hg); high IOP zone (27-32 mm Hg); subcompensated IOP zone (33-39 mm Hg); and decompensated IOP zone (≥40 mm Hg). CONCLUSION: The fundamental physiological criterion "rigidity" does not depend on central corneal thickness and consistently reflects the current level of true IOP. In all examined patients, both with healthy and glaucomatous eyes, healthy and glaucoma eyes with the same level of current rigidity had the same level of IOP. The ability to assign a given healthy or glaucomatous eye to a specific individual IOP zone is particularly important for the polyclinic system.

Temporal and individual variation in the feeding habits of Asiatic black bears (Ursus thibetanus).

Foraging plays a vital role in the survival of wildlife, and shifts in food availability can impact species fitness and survival. Ursids are known to consume a wide variety of foods and are known to be opportunistic omnivores. Consequently, seasonal shifts in diet, which correspond to temporal and spatial shifts in the availability of food resources, have long captivated researchers studying the foraging behavior of Ursidae. Nevertheless, comprehensive dietary studies encompassing both the population and individual levels remain scarce. In this study, we investigated the dietary patterns of Asiatic black bears (Ursus thibetanus) at both the population and individual levels, using data collected through GPS collars and field surveys of individual bear scat samples in Nagano Prefecture, Japan, from 2016 to 2020. From early April to late June, bears mainly foraged on green vegetation. During this period, male and large-bodied female bears showed a strong preference for green vegetation. Small-bodied female bears also ate mostly green vegetation but tended to consume more fruit than other bears towards the end of this period. From June to October, bears' diets included a substantial amount of fruit, with notable peaks in fruit consumption in late June and early September. During the summer months, female bears often incorporated social insects into their diet compared to the population-level trend. In mid-September, the consumption of seeds from the Fagaceae family surged, becoming the primary dietary component during this period. This trend was consistently observed across the population. These findings underscore the importance conducting in-depth dietary analyses that take into account individual characteristics such as sex, age, and body weight.

Self-reported sensibility to bodily signals predicts individual differences in autobiographical memory: an exploratory study.

Recent theoretical perspectives have advanced that autobiographical memory processes are supported by interoception, the perception of internal bodily sensations. Yet, this relationship remains largely underexplored. The present study addressed this critical gap in the literature by systematically investigating the association between self-reported Interoceptive Sensibility and various individual differences measures of autobiographical memory. In Study 1, using a correlational approach in a large sample of participants (N = 247), we identified significant correlations between standardised measures of interoception and the general experience of autobiographical memory and the frequency of involuntary mental time travel. These associations remained significant even after controlling for potential confounding factors in terms of age, gender, and trait affectivity, underscoring their robustness. Study 2 replicated and extended the associations identified in Study 1 in another large participant sample (N = 257), further validating them by accounting for the potential confounding effect of well-being. Our findings demonstrate that individuals' ability to perceive and understand bodily signals robustly relates to how they experience autobiographical memories. By adopting an exploratory approach based on individual differences, our results provide novel and concrete insights into the association between interoception and autobiographical memory, providing a strong foundation for future investigations into the causal mechanisms connecting these two constructs.

Structure-Based Analysis of Cefaclor Pharmacokinetic Diversity According to Human Peptide Transporter-1 Genetic Polymorphism.

Cefaclor is a substrate of human-peptide-transporter-1 (PEPT1), and the impact of inter-individual pharmacokinetic variation due to genetic polymorphisms of solute-carrier-family-15-member-1 (SLC15A1) has been a topic of great debate. The main objective of this study was to analyze and interpret cefaclor pharmacokinetic variations according to genetic polymorphisms in SLC15A1 exons 5 and 16. The previous cefaclor bioequivalence results were integrated with additional SLC15A1 exons 5 and 16 genotyping results. An analysis of the structure-based functional impact of SLC15A1 exons 5 and 16 genetic polymorphisms was recently performed using a PEPT1 molecular modeling approach. In cefaclor pharmacokinetic analysis results according to SLC15A1 exons 5 and 16 genetic polymorphisms, no significant differences were identified between genotype groups. Furthermore, in the population pharmacokinetic modeling, genetic polymorphisms in SLC15A1 exons 5 and 16 were not established as effective covariates. PEPT1 molecular modeling results also confirmed that SLC15A1 exons 5 and 16 genetic polymorphisms did not have a significant effect on substrate interaction with cefaclor and did not have a major effect in terms of structural stability. This was determined by comprehensively considering the insignificant change in energy values related to cefaclor docking due to point mutations in SLC15A1 exons 5 and 16, the structural change in conformations confirmed to be less than 0.05 Å, and the relative stabilization of molecular dynamic simulation energy values. As a result, molecular structure-based analysis recently suggested that SLC15A1 exons 5 and 16 genetic polymorphisms of PEPT1 were limited to being the main focus in interpreting the pharmacokinetic diversity of cefaclor.

A Head-to-Head Comparison of the First-Line Treatments for Locally Advanced or Metastatic Urothelial Cancer: Is There Still a Role for Chemotherapy?

BACKGROUND: Patients with locally advanced/metastatic urothelial cancer have been conventionally treated with platinum-based chemotherapy. Recently, numerous new treatments have been proposed to improve overall survival (OS) and reduce adverse effects, but no direct head-to-head comparisons among these agents are available. METHODS: The treatments evaluated in our analyses included (a) monotherapy with immune checkpoint inhibitors (ICI); (b) combinations of an ICI with chemotherapy; and (c) combinations of an ICI with other drugs. Using OS as the endpoint, a series of indirect comparisons were performed to rank the most effective regimens against both chemotherapy and each other. Our analysis was based on the application of an artificial intelligence software program (IPDfromKM method) that reconstructs individual patient data from the information reported in the graphs of Kaplan-Meier curves. RESULTS: A total of five studies published in six articles were included. In our main analysis, nivolumab plus chemotherapy showed better OS compared to chemotherapy (HR = 0.70, 95% CI: 0.59-0.82), while durvalumab plus tremelimumab showed no OS benefit (HR = 0.95, 95% CI 0.82-1.11). More interestingly, enfortumab vedotin plus pembrolizumab significantly prolonged OS compared to both chemotherapy alone (HR = 0.53, 95% CI 0.45-0.63) and nivolumab plus chemotherapy (HR = 0.76, 95% CI 0.60-0.97). DISCUSSION AND CONCLUSION: Among new treatments for locally advanced and metastatic urothelial cancer, enfortumab vedotin plus pembrolizumab showed the best efficacy in terms of OS. Our results support the use of this combination as a first-line treatment in this setting.

Idiosyncratic fixation patterns generalize across dynamic and static facial expression recognition.

Facial expression recognition (FER) is crucial for understanding the emotional state of others during human social interactions. It has been assumed that humans share universal visual sampling strategies to achieve this task. However, recent studies in face identification have revealed striking idiosyncratic fixation patterns, questioning the universality of face processing. More importantly, very little is known about whether such idiosyncrasies extend to the biological relevant recognition of static and dynamic facial expressions of emotion (FEEs). To clarify this issue, we tracked observers' eye movements categorizing static and ecologically valid dynamic faces displaying the six basic FEEs, all normalized for time presentation (1 s), contrast and global luminance across exposure time. We then used robust data-driven analyses combining statistical fixation maps with hidden Markov Models to explore eye-movements across FEEs and stimulus modalities. Our data revealed three spatially and temporally distinct equally occurring face scanning strategies during FER. Crucially, such visual sampling strategies were mostly comparably effective in FER and highly consistent across FEEs and modalities. Our findings show that spatiotemporal idiosyncratic gaze strategies also occur for the biologically relevant recognition of FEEs, further questioning the universality of FER and, more generally, face processing.

Customized voluntary waiting period before first insemination in primiparous dairy cows. Effect on milk production, fertility and health.

Customized voluntary waiting period (VWP) before first insemination was tested in 18 commercial dairy herds in Sweden, to assess milk production, fertility and health in primiparous cows expected to be suited for extended VWP. Cow selection for extended VWP was based on 3 criteria in early lactation: 1) the 10% of cows with highest genomic persistency index, 2) cows with a difficult calving or disease during the first month of lactation, and 3) cows with higher yield during d 4-33 after calving than the herd average for primiparous cows. Cows meeting at least one of these criteria were randomly assigned to either the ExtExt treatment (extended VWP of at least 175 d, n = 174; calving interval (CInt) = 16.3 mo) or the ExtConv treatment (conventional VWP of maximum 100 d n = 173; CInt = 12.4 mo). Cows not meeting any of the criteria were assigned to the ConvConv treatment (conventional VWP, n = 183; CInt = 12.0 mo). There were no differences in milk yield per day in the CInt between treatments, although 305-d and whole-lactation (WL) milk yields were higher for ExtExt cows (10,371 and 13,803 kg) than ExtConv cows (9,812 and 10,257 kg). Milk yield at the last test milking before dry-off was lower in ExtExt compared with ExtConv cows (24.9 vs 28.3), however the results showed no difference in dry period length between the treatments. Regarding reproductive performance, the ExtExt cows had higher first service conception rate (FSCR; 60% vs. 45%) and lower number of inseminations per conception (NINS; 1.67 vs. 2.19), compared with the ExtConv cows. As expected, ConvConv cows had the lowest milk yield in 305-d, in WL, and per day in the CInt, however, FSCR and NINS did not differ between ConvConv cows and cows in the other 2 VWP treatments. Disease incidence was higher for cows in the ExtConv compared with the ConvConv treatment, but there was no difference between ExtExt and the 2 other VWP treatments. Further, no difference in proportion of cows with good udder health or culling rate was detected between any of the treatments, though due to low prevalence the study lacked power to draw major conclusions on these results. Thus prolonging VWP for suitable primiparous cows can produce benefits such as improved fertility in the form of higher FSCR and lower NINS, as well as lower dry-off yield, without compromising milk yield or prolonging dry period length.

Monitoring of surgical staff x-ray exposure in the operating room with DosiBadge.

Surgical procedures involving the use of x-rays in the operating room (OR) have increased in recent years, thereby increasing the exposure of OR staff to ionizing radiation. An individual dosimeter makes it possible to record the radiation exposure to which these personnel are exposed, but there is a lack of compliance in the wearing of these dosimeters for several practical reasons. This makes the dose results obtained unreliable. To try to improve the rate of dosimeter wearing in the OR, the Dosibadge project studied the association of the individual dosimeter with the hospital access badge, forming the Dosibadge. Through a study performed at the Tours University Hospital in eight different ORs for two consecutive periods of 3 months. The results show a significant increase in the systematic use of the dosimeter thanks to the Dosibadge, which improves the reliability of the doses obtained on the dosimeters and the monitoring of personnel. The increase is especially marked with clinicians. Following these results and the very positive feedback to this first single-centre study, we are then planning a second multicentre study to validate our proof of concept on different sites, with the three brands of individual dosimeters used in France i.e. dosimeters supplied by Dosilab; Landauer and IRSN.

Mapping Individual Differences in Intermodal Coupling in Neurodevelopment.

Within-individual coupling between measures of brain structure and function evolves in development and may underlie differential risk for neuropsychiatric disorders. Despite increasing interest in the development of structure-function relationships, rigorous methods to quantify and test individual differences in coupling remain nascent. In this article, we explore and address gaps in approaches for testing and spatially localizing individual differences in intermodal coupling. We propose a new method, called CIDeR, which is designed to simultaneously perform hypothesis testing in a way that limits false positive results and improve detection of true positive results. Through a comparison across different approaches to testing individual differences in intermodal coupling, we delineate subtle differences in the hypotheses they test, which may ultimately lead researchers to arrive at different results. Finally, we illustrate the utility of CIDeR in two applications to brain development using data from the Philadelphia Neurodevelopmental Cohort.

Development of in-silico drug cardiac toxicity evaluation system with consideration of inter-individual variability.

Safety pharmacology examines the potential for new drugs to have unusual, rare side effects such as torsade de pointes (TdP). Recently, as a part of the Comprehensive in vitro Proarrhythmia Assay (CiPA) project, techniques for predicting the development of drug-induced TdP through computer simulations have been proposed and verified. However, CiPA assessment generally does not consider the effect of cardiac cell inter-individual variability, especially related to metabolic status. The study aimed to explore whether rare proarrhythmic effects may be linked to the inter-individual variability of cardiac cells and whether incorporating this variability into computational models could alter the prediction of drugs' TdP risks. This study evaluated the contribution of two biological characteristics to the proarrhythmic effects. The first was spermine concentration, which varies with metabolic status; the second was L-type calcium permeability that could occur due to mutations. Twenty-eight drugs were examined throughout this study, and qNet was analyzed as an essential feature. Even though there were some discrepancies of TdP risk predictions from the baseline model, we found that considering the inter-individual variability might change the TdP risk of drugs. Several drugs in the high-risk drugs group were predicted to affect as intermediate and low-risk drugs in some individuals and vice versa. Also, most intermediate-risk drugs were expected to act as low-risk drugs. When compared, the effects of inter-individual variability of L-type calcium were more significant than spermine in altering the TdP risk of compounds. These results emphasize the importance of considering inter-individual variability to assess drugs.

Modelling individual differences in reading using an optimised MikeNet simulator: the impact of reading instruction.

Reading is vital for acquiring knowledge and studies have demonstrated that phonology-focused interventions generally yield greater improvements than meaning-focused interventions in English among children with reading disabilities. However, the effectiveness of reading instruction can vary among individuals. Among the various factors that impact reading skills like reading exposure and oral language skills, reading instruction is critical in facilitating children's development into skilled readers; it can significantly influence reading strategies, and contribute to individual differences in reading. To investigate this assumption, we developed a computational model of reading with an optimised MikeNet simulator. In keeping with educational practices, the model underwent training with three different instructional methods: phonology-focused training, meaning-focused training, and phonology-meaning balanced training. We used semantic reliance (SR), a measure of the relative reliance on print-to-sound and print-to-meaning mappings under the different training conditions in the model, as an indicator of individual differences in reading. The simulation results demonstrated a direct link between SR levels and the type of reading instruction. Additionally, the SR scores were able to predict model performance in reading-aloud tasks: higher SR scores were correlated with increased phonological errors and reduced phonological activation. These findings are consistent with data from both behavioral and neuroimaging studies and offer insights into the impact of instructional methods on reading behaviors, while revealing individual differences in reading and the importance of integrating OP and OS instruction approaches for beginning readers.