Specific and shared cognitive predictors of drawing and block building in typically developing children.

Introduction: Spatial construction is a complex ability involving attention, global/local visual processing, mental representation, visuo-motor coordination and, to varying extent, working memory and executive functions, and verbal abilities. In developmental neuropsychology, little attention has been paid to comprehend whether and to what extent the above cognitive processes are involved in two main spatial construction tasks, that is drawing and block building. Method: We used path analysis to test shared and specific effects of verbal and spatial working memory, spatial attention, inhibition, verbal abilities (vocabulary and naming), figure disembedding, mental rotation, and visual-motor coordination, as well as of demographics (sex, age and socio-economic status), on two classical drawing (Rey-Osterrieth Complex Figure; ROCF) and block building (Block design; BD) tasks in a sample of 195 typically developing children (age range: 7-11 years). Results: Figure disembedding and visuo-motor coordination were the only shared predictors of both spatial construction tasks. Moreover, ROCF score was directly related with spatial attention and inhibition, while BD score was directly related with sex, vocabulary, mental rotation and backward spatial working memory. Discussion: These findings distinguish between abilities involved in spatial construction regardless of the type of task and those specifically related to ROCF or Block Design, thus providing clues relevant to neuropsychological assessment and intervention in children with spatial construction disorders.

Autistic traits linked to anxiety and dichotomous thinking: sensory sensitivity and intolerance of uncertainty as mediators in non-clinical population.

A recent theoretical cognitive model posits that three cognitive constructs-intolerance of uncertainty, lack of predictive processing, and dichotomous thinking-may interact with anxiety in autistic individuals. However, the interrelationships among these constructs remain unclear. We investigated this relationship in a non-clinical population using five questionnaires (Autism Spectrum Quotient, Glasgow Sensory Questionnaire, Short Intolerance of Uncertainty Scale, Penn State Worry Questionnaire, and Dichotomous Thinking Inventory) and conducted a path analysis. Data were collected from 405 adults (aged 20-22 years) in Experiment 1 and 628 (aged 20-49 years) in Experiment 2. In both experiments, autistic traits were significantly associated with both anxiety and dichotomous thinking, mediated by intolerance of uncertainty. Autistic traits were linked to intolerance of uncertainty, mediated by atypical sensory processing. Furthermore, autistic traits were directly associated with anxiety. No direct association was observed between anxiety and dichotomous thinking. Our results confirm the validity of Stark's cognitive model in a non-clinical population. These findings provide new insights into anxiety and dichotomous thinking and shed light on the cognitive styles of autistic individuals.

Adverse childhood experiences and profiles of healthy orthorexia versus orthorexia nervosa: towards an explanatory model of orthorexia as a multidimensional eating style.

BACKGROUND: Orthorexia is a complex phenomenon comprising distinct dimensions, including orthorexia nervosa (ON) and healthy orthorexia (HO). However, little is known about the factors influencing these dimensions, their disparities, and the psychological factors underlying orthorexia behaviours. OBJECTIVES: This study aims to explore ON versus HO dimensions and the predictive role of adverse childhood experiences (ACEs) in a nationally representative sample of Polish individuals. In addition, we aim to investigate the mediating roles of alexithymia, embodiment, and experiential avoidance levels in this association. METHODS: A representative sample of Polish adults (n = 3557) participated in this study. Dimensions of orthorexia (HO, ON) were assessed using the Teruel Orthorexia Scale, while ACEs were evaluated using the Adverse Childhood Experiences Questionnaire. Levels of alexithymia were measured using the Toronto Alexithymia Scale, experiential avoidance through the Acceptance and Action Questionnaire, and embodiment intensity via the Experience of Embodiment Scale. RESULTS: Cluster analysis identified two distinctive orthorexia profiles in the whole sample, i.e., HO (n = 469) and ON (n = 1217), alongside three intermediate HO/ON profiles (n = 1871). The number of ACEs predicted ON tendencies as opposed to HO behaviours in participants. The mediating role of alexithymia, experiential avoidance, and embodiment in the association between ACEs and ON was also observed. CONCLUSIONS: Our study suggests that orthorexia is a multidimensional eating style shaped by socio-cultural factors. Adverse childhood experiences may be related to ON behaviours by mediating psychological factors such as experiential avoidance, alexithymia, and embodiment. Effective education and collaborative support are necessary for addressing ON tendencies.

Explaining maternal antenatal attachment by psychological, clinical and sociodemographic factors: a path analysis study.

BACKGROUND: Antenatal attachment is a fundamental concept relative to human transition to parenthood and may be influenced by several factors. The aim of this study is to find the best model to explain maternal antenatal attachment based on the interaction among sociodemographic, clinical, and psychological variables. METHODS: Pregnant women (N = 407) were interviewed during the second trimester of pregnancy while waiting for medical consultations. A sociodemographic, obstetric, and psychometric protocol was used. STATISTICAL ANALYSES: path analysis. INDEPENDENT VARIABLES: psychopathological symptomatology, depression, anxiety, stress, occupational stress, attitudes about pregnancy and motherhood, coping styles, marital satisfaction, sociodemographic, and clinical variables. DEPENDENT VARIABLES: maternal antenatal attachment in its several dimensions; quality of attachment (QA), intensity of preoccupation (IP), and global attachment (GA). RESULTS: Depression, anxiety, attitudes, and marital satisfaction explained 37% of maternal antenatal QA. Age, depression, anxiety, attitudes, and marital satisfaction explained 26% of maternal antenatal IP. Age, depression, anxiety, attitudes, and marital satisfaction explained 34% of the statistical variance of maternal antenatal GA. CONCLUSIONS: Factors like emotional states (depression and anxiety), attitudes towards pregnancy and motherhood, marital satisfaction, and a sociodemographic variable (age) contribute significantly for the explanation of maternal antenatal attachment.

Like mama always said: family socio-economic status, maternal attitudes and leader role occupancy in adulthood.

Leadership research has always recognised the importance of childhood factors for the occupation of formal or informal leader positions later in life. Still, empirical research in the field has mainly been based on retrospective accounts from selective and small samples. Such research has also concentrated on individual traits and experiences, less on characteristics of the family. Our aim is to fill this void by prospectively examining the role of the family of origin on educational attainment and holding a managerial position in adulthood. Analyses were based on the Stockholm Multigenerational Study, including register and survey data, regarding 3,088 males born between 1950 and 1976 and their mothers' attitudes to education and child-rearing in the late 1960s. Our results showed a significant effect of family socio-economic status (SES) on managerial role occupancy in late adulthood. This effect was mainly mediated through educational level. However, a noteworthy share of the total effect of family SES was channelled through maternal attitudes towards education. Positive attitudes towards education in the home environment accounted for an equally large share of the total indirect effect of family SES as the offspring's cognitive capacity did. Authoritarian attitudes to child-rearing among mothers were also found to have a negative impact on cognitive capacity and educational level - two well-known antecedents to leader emergence. Parental attitudes may boost or modify structural characteristics and individual traits associated with holding formal leader roles such as a managerial position - but also showed an independent effect several decades later.

Individual quality and environmental factors interact to shape reproduction and survival in a resident bird of prey.

Investigating among-individual differences in reproductive success and survival is essential for understanding eco-evolutionary processes. We used 5 years of demographic data from 556 breeding barn owls (Tyto alba) to estimate associations between intrinsic and extrinsic covariates on survival and reproduction throughout the annual cycle. As males and females have distinct roles in reproduction, environmental conditions and individual quality may be differentially linked to their fitness at different time points. Males breeding early and inhabiting prey-rich areas experienced higher reproductive success but faced greater reproductive costs. Indeed, the number of offspring a male cared for was negatively associated with his body condition and survival. However, our results indicate that these influences can be mitigated in males experiencing favourable post-breeding environmental conditions. For female owls, early breeding and high food availability during the breeding period were linked with increased reproductive success. Prey availability during incubation and higher reproductive output were associated with higher survival into the next breeding period in females. Unlike males, females did not exhibit obvious trade-offs between reproductive success and survival. Our research demonstrates trade-offs between fecundity and survival, and that females paired with males able to provide sufficient food experience higher survival and reproduction.

The effect of concept mapping in nursing education on critical thinking motivation: A path analysis.

BACKGROUND: The integration of concept mapping into nursing education represents a pivotal strategy aimed at enhancing critical thinking skills, which is a necessity in navigating the complexities of healthcare. This educational tool's role in stimulating students' analytical abilities and motivation towards critical thinking has become increasingly relevant in preparing nursing professionals for the dynamic challenges of their field. OBJECTIVES: The aim of this study is to examine how the implementation of concept mapping affects critical thinking motivation among nursing students, investigate the relationship between them, and support its use as an innovative educational strategy in the field of nursing. DESIGN: This study was conducted using a descriptive and exploratory design. METHODS: This research was carried out between May and June 2023, involving 435 nursing students. For data collection within an online classroom framework, the study applied a trio of tools: the Student Descriptive Information Form, the Scale for the Effectiveness of Concept Maps in Nursing Education, and the Critical Thinking Motivation Scale. The analysis of the compiled data was undertaken utilizing SPSS version 25.0 and JAMOVI software, with statistical significance set at a p-value of <0.05. RESULTS: Engagement in social/scientific activities, library usage, and book reading habits were positively correlated with higher scores on both the Critical Thinking Motivation Scale and the Scale for the Effectiveness of Concept Maps in Nursing Education. Notably, concept mapping significantly enhanced critical thinking motivation among the participating students, as evidenced by the path analysis (ß = 0.758, R = 0.563, p < 0.001). CONCLUSION: The findings underscore the significant role of concept mapping in elevating critical thinking motivation among nursing students, suggesting its strategic inclusion in nursing curricula to meet the evolving demands of healthcare education in the twenty-first century.

Effects of brackish water irrigation with different exogenous salt concentrations on the growth and rhizosphere salinity of Lycium barbarum.

To investigate the effects of different typical exogenous salt concentrations on total soil salinity and the growth of Lycium barbarum under brackish water irrigation, and to determine the salinity threshold of irrigated brackish water that is conducive to the normal growth of Lycium barbarum while mitigating soil salinity accumulation. Four typical exogenous salts (NaCl, CaCl2, NaHCO3, Na2SO4) were selected and set at four concentrations (0.1, 0.5, 2.0, 4.0 g L-1) to conduct a field crossover experiments in the downstream region of the Hetao Irrigation District. The results showed that in the same fertility period, the growth rates of new branches, ground diameter, and crown width first increased and then decreased with rising concentrations of NaCl, CaCl2, and Na2SO4, but showed an inverse relationship with NaHCO3 concentrations. Furthermore, increasing salt concentrations linearly reduced the yield of dry fruits from Lycium barbarum and led to a notable accumulation of total soil salts. Utilizing an experimental research approach, a comprehensive analysis of involving multiple growth indices, stable yield, and soil salinity control of Lycium barbarum revealed that optimal growth occurs at salt concentrations of 0.1-0.5 g L-1 for different water quality areas within the irrigation area; using the method of path analysis identified the total soil salt and crown width as the primary direct and indirect factors influencing the yield of Lycium barbarum. The results of this study provide scientific basis and significant theoretical support for the safe and rational utilization of brackish water and cultivation of Lycium barbarum in typical regions with varying saline water qualities of Hetao irrigation area.

A new input-output-based framework for measuring the active and passive water use.

•Construct a dual-perspective framework for measuring water use.•Define the water use fluctuating due to macroeconomic condition changes.•Introduce a new indicator to measure the rate of passive water use.•Estimate the key water use channels from a passive perspective through SPA.•Discuss the supply chain's intermediate sector's role for the water use.

Leading by Example: Identity Leadership and Mental Health in Men's Sheds Members.

The impact of leadership on members' mental health outcomes in community-based mutual-aid organizations such as Men's Shed is unknown. We analyzed (a) whether identity leadership is associated with Shed members' mental health, and (b) whether these links are mediated by psychological safety, social network quality, and social identity. Path analysis on data collected from 162 Australian Men's Shed members revealed statistically significant associations between identity leadership and each mechanism, and our model accounted for significant variance in mental health outcomes (14%-24%, ps < .001). Only social network quality and psychological safety were associated with unique variance in mental health outcomes. All indirect effects via social network quality and psychological safety were significant. These findings suggest the proposed mechanisms explain the relationship between identity leadership mental health outcomes in mutual-aid organizations such as Men's Sheds.

The association of food insecurity with non-alcoholic fatty liver disease (NAFLD) in a sample of Iranian adults: a path analysis of a cross-sectional survey.

OBJECTIVES: The present study aims to examine the hypothetical model of the relationship between food insecurity and Non-alcoholic fatty liver disease (NAFLD) in a sample of Iranian adults. METHODS: In this cross-sectional study, 275 subjects (18-70 years old) who met the inclusion criteria were recruited. Fatty liver was diagnosed by abdominal ultrasonography, and eligible patients underwent liver fibro scan assessment to determine fibrosis and steatosis. Food insecurity was assessed using the validated six-item Short Questionnaire of Household Food Security Scale (SQHFSS). Data were analyzed using SPSS 24.0 and IBM SPSS Amos 24.0. RESULTS: Among 275 subjects (44.37 ± 11.67 years old, 51.6% male) included in the analysis, 23.6% were food insecure. Food insecurity, general and abdominal obesity were associated with an increased risk of NAFLD, even after multiple adjustments (OR: 2.95, 95% CI: 1.02, 8.57; OR: 3.27, 95% CI: 1.50, 7.11; and OR: 3.81, 95% CI: 1.55, 9.32, respectively). According to the primary hypothesis, food insecurity and NAFLD were fitted into a model (χ2/df = 1.36, GFI = 0.982, AGFI = 0.952, CFI = 0.954, IFI = 0.959, SRMR = 0.040, RMSEA = 0.037); accordingly, food insecurity and obesity (general and abdominal) directly affected NAFLD (ß = 0.12, P = 0.03; ß = 0.13, P = 0.02; ß = 0.31, P < 0.001, respectively). CONCLUSION: Food insecurity was a predictor of, and directly associated with, NAFLD. Social determinants should be considered in the pathogenesis of NAFLD, although the possible underlying biological mechanisms in this association are yet to be determined.

Mindful eating and orthorexia nervosa: How do they interact?

The present study explored the associations between orthorexia nervosa, social media addiction, emotion regulation difficulties, perfectionism and BMI with four facets of mindful eating, using path analysis to assess these relationships. A sample of 551 students (127 males, 424 females, mean age = 22.6 years) completed an online self-report questionnaire evaluating these constructs. Analyses revealed that mindful eating contributed to emotion dysregulation and orthorexia nervosa and was related to social media addiction. Significant indirect paths were identified from mindful eating, social media addiction and adaptive perfectionism through emotion dysregulation to maladaptive perfectionism. While no direct paths were observed between mindful eating and perfectionism, a direct path was found between adaptive perfectionism and orthorexia nervosa. These findings suggest a more nuanced understanding of eating behaviours is required. Individuals susceptible to eating disorders should approach mindful eating with caution and seek support from healthcare providers to ensure it is used in a way that supports overall wellbeing. Future research should aim to replicate and further clarify these associations to reveal the long-term effects of mindful eating.

Investigating the correlation between health-promoting lifestyle and health hardiness with quality of life.

INTRODUCTION: Quality of life (QOL) is a key concept in the field of health and future human life depends on understanding the factors affecting the QOL. This study aimed to investigate the relationship between health hardiness and health-promoting lifestyle with QOL among residents of Bastak city. METHODS: The present cross-sectional study was conducted on the adult population above the age of 18 years living in Bastak city in Hormozgan province. A total number of 400 subjects were selected using a convenient sampling method. An online questionnaire was used to collect the data, which consisted of four sections: demographic information, health hardiness questionnaire, health-promoting lifestyle questionnaire and world health organization quality of life questionnaire (WHOQOL-BREF). Data were analyzed using statistical tests including Pearson correlation analysis, path analysis and structural equation modeling (SEM) with SPSS 24 and AMOS 21 statistical software. RESULTS: A total of 400 subjects with the mean age of 34.81 ± 8.94 years participated in this study. There were significant positive relationships between health hardiness (r = .499, p = .000), health value (r = .491, p = .000), internal health locus of control (r = .468, p = .000), external health locus of control (r = .19, p = .000), perceived health competence (r = .415, p = .000), health responsibility (r = .473, p = .000), physical activity (r = .356, p = .000), nutrition (r = .392, p = .000), interpersonal relations (r = .458, p = .000), spiritual growth (r = .619, p = .000), stress management (r = .514, p = .000) and health promoting life-style (r = .593, p = .000) With QOL. CONCLUSION: According to our findings, health-promoting lifestyle has a positive relationship with QOL. Therefore, the policy makers and executive managers of the health sector can improve people's QOL by designing and implementing educational interventions that are focused on improvement the level of individual's physical activity, spiritual growth, interpersonal interactions, stress management, nutrition and individual responsibility.

Influence of Laser-Based Powder Bed Fusion of Metals Process Parameters on the Formation of Defects in Al-Zn-Mg-Cu Alloy Using Path Analysis.

High-strength aluminium alloys are prone to porosity and cracking during laser-based powder bed fusion of metals (PBF-LB/M) due to the complex solidification behaviour, thus limiting the preparation of high-quality aluminium alloys. In order to effectively reduce the defect formation, this study investigated the influence mechanism of different process parameters on the formation of porosity and cracks in Al-Zn-Mg-Cu alloys in the PBF-LB/M process by combining experimental and numerical simulation. The degree of influence of the process parameters on the temperature field and the temperature field on the defect formation was also quantified using path analysis. The results show that modulation of the process parameters can effectively reduce the formation of cracks and pores, although it is difficult to eliminate them. The melt pool temperature has a significant effect on the formation of porosity, and the temperature gradient has a significant effect on the formation of cracks. The degree of influence of laser power on the melt pool temperature and temperature gradient was greater than that of scanning speed, with values of 0.980 and 0.989, respectively. Therefore, the priority of modulating the laser power is higher than that of scanning speed in order to reduce the formation of defects more effectively.

Path analysis of influencing factors for anxiety and depression among first-trimester pregnant women.

Background: Prenatal anxiety and depression exert a significant influence on the physiological and psychological health outcomes of both expectant mothers and their infants. The aim of this study was to explore the intrinsic relationships between maternal anxiety, depression in early pregnancy, and their influencing factors. The findings of this study provide scientific basis for developing targeted preventive interventions. Methods: The study involved 887 expectant mothers in the early stages of pregnancy residing in Changsha City from March to August 2022. The sociodemographic characteristics, health and lifestyle factors, and pregnancy-related factors of participants were collected. The Edinburgh Postnatal Depression Scale and the Self-Rating Anxiety Scale were used to assess depression and anxiety, respectively. Chi-square tests and multivariate logistic regression models using SPSS 26.0 were used to assess factors impacting early pregnancy anxiety and depression. Amos 23.0 was used to construct a path model to determine the potential pathways of the influencing factors. Results: In early pregnancy, the prevalence of depression and anxiety were 17.4% and 15.8%, respectively. Path analysis showed that early pregnancy anxiety and illness during pregnancy had a direct effect on early pregnancy depression. Anxiety had the greatest overall impact on early pregnancy depression. Education, maternal comorbidities, symptoms of pregnancy, electronic device usage time, work stress, active smoking in the 6 months before pregnancy, and sleep quality were found to solely exert indirect effects on early pregnancy depression. Sleep quality had the greatest overall impact on early pregnancy anxiety. Active smoking in the 6 months before pregnancy, sleep quality, and work stress only had a direct impact on early pregnancy anxiety. Additionally, electronic device usage duration and monthly per capita household income exclusively indirectly impacted symptoms of early pregnancy anxiety. Conclusion: The study highlights the importance of targeted interventions in early screening. Avoiding excessive use of electronic devices and active smoking in the 6 months before pregnancy, alleviating work stress and symptoms of pregnancy, increasing education levels and monthly per capita household income, improving sleep quality, and actively preventing illnesses during pregnancy and maternal comorbidities might reduce anxiety and depression in early pregnancy.

From negative feelings to impairments: A longitudinal study on the development of climate change anxiety.

People may experience anxiety and related distress when they come in contact with climate change (i.e., climate change anxiety). Climate change anxiety can be conceptualized as either emotional-based response (the experience of anxiety-related emotions) or impairment-based response (the experience of impairment in daily functioning). To date, it remains uncertain how these distinct manifestations of climate change anxiety are related. Conceptually, the experience of climate change anxiety may transform from an adaptive and healthy emotional response to an impairment in daily functioning. We conducted two two-wave longitudinal studies to examine the possible bidirectional relationships between three manifestations of climate change anxiety. We recruited 942 adults (mean age = 43.1) and 683 parents (mean age = 46.2) in Studies 1 and 2, respectively. We found that Time 1 emotion-based response was positively linked to Time 2 cognitive-emotional impairment, while Time 1 cognitive-emotional impairment was positively related to Time 2 functional impairment. In Study 2, we also found a bidirectional positive relationship between generalized anxiety and emotion-based climate change anxiety over time. Overall, our findings provide initial support to the temporal relationships between different manifestations of climate change anxiety, corroborating that climate change anxiety may develop from emotional responses to impairment in functioning.

Factors influencing recommendation intentions for autonomous vehicles: A path analysis in a pilot study.

Over the past decade, the rapid development of artificial intelligence has propelled the transition of autonomous vehicles from laboratories to real-world applications. However, autonomous vehicles are a long way from fully integrating into most people's lives. Previous studies indicate that the word-of-mouth effect is often used by consumers to determine the quality of innovative technologies. Word-of-mouth recommendation can not only increase the income of enterprises by attracting new customers, but also greatly reduce the promotion and publicity expenses of enterprises. Through the word-of-mouth effect, the intention to recommend can contribute to the growth of the autonomous driving market. Therefore, current research explores the mechanisms among the perceived risk of privacy safety, perceived defect, perceived behavioral control, intention to use, and intention to recommend through path analysis. Our findings, based on 433 online questionnaires, indicate that the perceived risk of privacy safety, perceived defects, and perceived behavioral control influence the intention to recommend. Notably, perceived risk of privacy safety and perceived defect directly affects the intention to recommend and also correlates with perceived behavioral control. These findings provide some empirical evidence for the recommendation of autonomous vehicles and the expansion of consumer groups.

Exploring the relationship between early cognitive ability and age-60 sleep quality: The Newcastle Thousand Families Study birth cohort.

OBJECTIVES: Poor sleep quality has been linked to adverse health outcomes. It is important to understand factors contributing to sleep quality. Previous research has suggested increased cognition and education duration have a protective effect on sleep quality in old age. This study aimed to assess the hypothesis that age-11 intelligence quotient and highest achieved education level are associated with subjective sleep quality at age 60. METHODS: Participants are members of the Newcastle Thousand Families Study birth cohort, all born in 1947. Data included a calculated intelligence quotient score based on participant's 11-plus exam results, highest achieved education level, social class at ages 25 and 50 and global Pittsburgh Sleep Quality Index (PSQI) at age 60. Multivariable regression analysis was used to investigate effect sizes of variables on global PSQI, which formed the basis of a path analysis model. RESULTS: After excluding participants with incomplete data, and those who had been diagnosed with sleep apnea, 251 participants were included in the path analysis model. Education level was associated with global PSQI (R=-0.653; 95% CI -1.161, -0.145; P = .012) but age-11 intelligence quotient was not. While a similar association was seen for women in the stratified analysis, no such associations were seen for men. CONCLUSIONS: The results of this study show an inverse relationship between education level, but not childhood intelligence quotient, and sleep quality in later life, in women only. Future research is needed to examine the mechanism underlying this relationship.

Path analysis reveals combined winter climate and pollution effects on the survival of a marine top predator.

Marine ecosystems are experiencing growing pressure from multiple threats caused by human activities, with far-reaching consequences for marine food webs. Determining the effects of multiple stressors is complex, in part, as they can affect different aspects of biological organisation (behaviour, individual traits and demographic rates). Determining the combined effects of stressors, through different biological pathways, is key to predict the consequences for the viability of populations threatened by global change. Due to their position in the food chain, top predators such as seabirds are considered more sensitive to environmental changes. Climate change is affecting the prey resources available for seabirds, through bottom-up effects, while organic pollutants can bioaccumulate in food chains with the greatest impacts on top predators. However, knowledge of their combined effects on population dynamics is scarce. Using a path analysis, we quantify the effects of climate change and pollution on the survival of adult great black-backed gulls, both directly and through effects of individuals' body mass. Warmer ocean temperatures in gulls' winter foraging areas in the North Sea were correlated with higher survival, potentially explained by shifts in prey availability associated with global climate change. We also found support for indirect negative effects of organochlorines, highly toxic pollutants to seabirds, on survival, which acted, in part, through a negative effect on body mass. The results from this path analysis highlight how, even for such long-lived species where variance in survival tends to be limited, two stressors still have had a marked influence on adult survival and illustrate the potential of path models to improve predictions of population variability under multiple stressors.

Dynamic path analysis for exploring treatment effect mediation processes in clinical trials with time-to-event endpoints.

Why does a beneficial treatment effect on a longitudinal biomarker not translate into overall treatment benefit on survival, when the biomarker is in fact a prognostic factor of survival? In a recent exploratory data analysis in oncology, we were faced with this seemingly paradoxical result. To address this problem, we applied a theoretically principled methodology called dynamic path analysis, which allows us to perform mediation analysis with a longitudinal mediator and survival outcome. The aim of the analysis is to decompose the total treatment effect into a direct treatment effect and an indirect treatment effect mediated through a carefully constructed mediation path. The dynamic nature of the underlying methodology enables us to describe how these effects evolve over time, which can add to the mechanistic understanding of the underlying processes. In this paper, we present a detailed description of the dynamic path analysis framework and illustrate its application to survival mediation analysis using simulated and real data. The use case analysis provides clarity on the specific exploratory question of interest while the methodology generalizes to a wide range of applications in drug development where time-to-event is the primary clinical outcome of interest.