Light and flow regimes regulate the metabolism of rivers.

Mean annual temperature and mean annual precipitation drive much of the variation in productivity across Earth's terrestrial ecosystems but do not explain variation in gross primary productivity (GPP) or ecosystem respiration (ER) in flowing waters. We document substantial variation in the magnitude and seasonality of GPP and ER across 222 US rivers. In contrast to their terrestrial counterparts, most river ecosystems respire far more carbon than they fix and have less pronounced and consistent seasonality in their metabolic rates. We find that variation in annual solar energy inputs and stability of flows are the primary drivers of GPP and ER across rivers. A classification schema based on these drivers advances river science and informs management.

The influence of loss to follow-up in autism screening research: Taking stock and moving forward.

BACKGROUND: How best to improve the early detection of autism spectrum disorder (ASD) is the subject of significant controversy. Some argue that universal ASD screeners are highly accurate, whereas others argue that evidence for this claim is insufficient. Relatedly, there is no clear consensus as to the optimal role of screening for making referral decisions for evaluation and treatment. Published screening research can meaningfully inform these questions-but only through careful consideration of children who do not complete diagnostic follow-up. METHODS: We developed two simulation models that re-analyze the results of a large-scale validation study of the M-CHAT-R/F by Robins et al. (2014, Pediatrics, 133, 37). Model #1 re-analyzes screener accuracy across six scenarios, each reflecting different assumptions regarding loss to follow-up. Model #2 builds on this by closely examining differential attrition at each point of the multi-step detection process. RESULTS: Estimates of sensitivity ranged from 40% to 94% across scenarios, demonstrating that estimates of accuracy depend on assumptions regarding the diagnostic status of children who were lost to follow-up. Across a range of plausible assumptions, data also suggest that children with undiagnosed ASD may be more likely to complete follow-up than children without ASD, highlighting the role of clinicians and caregivers in the detection process. CONCLUSIONS: Using simulation modeling as a quantitative method to examine potential bias in screening studies, analyses suggest that ASD screening tools may be less accurate than is often reported. Models also demonstrate the critical importance of every step in a detection process-including steps that determine whether children should complete an additional evaluation. We conclude that parent and clinician decision-making regarding follow-up may contribute more to detection than is widely assumed.

Employing user-centered design to develop a remote technology kit for studying young children's social communication skills.

OBJECTIVE: The COVID-19 pandemic required behavioral researchers to rapidly pivot to the implementation of remote study protocols to facilitate data collection. Remote implementation required robust and flexible research protocols including reliable audio/visual technology that met all the quality, security, and privacy hallmarks of lab-based equipment, while also being portable and usable by nontechnical staff and participants. The project's primary purpose was to develop a technology kit that could be deployed for data collection in homes with young children. The secondary objective was to determine the feasibility of the kit for use longitudinally across four disparate sites. METHOD: User-centered design principles were employed in the development and implementation of a technology kit deployed across urban, suburban, and rural participant locations in four states. Preliminary feasibility and usability data were gathered to determine the reliability of the kit across three timepoints. RESULTS: In study 1, a technology kit was constructed addressing all project needs including the provision of the internet to connect remotely with participants. Staff training protocols and participant-facing materials were developed to accompany deployment procedures. In study 2, data gathered in technology logs demonstrated successful capturing of video footage in 96% of opportunities with most technology challenges mitigated. Subsequent behavioral coding indicated 100% of captured assessment footage has been successfully coded to date. Moreover, participants needed less support for technology setup at their later timepoints, and staff rated the kit as highly usable. CONCLUSION: This study offers a model for future development of technology use in remote community- and home-based pediatric research.

Parental prenatal representations of the child are related to 18-month-old children's social-emotional competence.

Parental representations of the child are linked to positive developmental outcomes in children, but the impact of prenatal representations on early social-emotional development, particularly from fathers, is less understood. This study explores how fathers' and mothers' prenatal representations within two-parent families are associated with early social-emotional development. Prenatal representations of fathers (n = 88) and mothers (n = 92) were assessed between 28 and 32 weeks of gestation using the Working Model of the Child Interview, categorizing them as balanced or nonbalanced. The children's (n = 97; 49.5% girls) social-emotional and behavioral problems and competencies were measured at 18 months using the Brief Infant-Toddler Social and Emotional Assessment. Balanced prenatal representations of both parents were related to higher social-emotional competence in toddlers. However, prenatal representations were not related to social-emotional and behavioral problems. The results highlight the benefits of balanced prenatal representations in promoting early social-emotional competence in children.

Mother-Infant Interaction and Maternal Postnatal Psychological Distress Associate with Child's Social-Emotional Development During Early Childhood: A FinnBrain Birth Cohort Study.

We studied the effects of mother-infant interaction and maternal pre- and postnatal psychological distress on children's social-emotional problems and competences, as well as whether interaction quality moderates the association between distress and children's outcomes. Maternal pre- and postnatal psychological distress were measured using the SCL and EPDS questionnaires, whereas mother-infant interaction was measured when the child was 8 months old using the EA Scales. Children's social-emotional development was measured using the BITSEA questionnaire at 2 years old and using the SDQ questionnaire at 4 years old, where higher maternal structuring was associated with fewer social-emotional problems in children and higher maternal sensitivity was associated with greater social-emotional competence in children at 2 years old. Further, higher postnatal distress was found associated with greater social-emotional problems at 2 years old, though neither these effects nor moderating effects at 4 years old were observed after multiple-comparison corrections. Our findings support direct associations of both mother-infant interaction and maternal postnatal psychological distress with children's social-emotional development during toddlerhood.

Child social-emotional and behavioral problems and competencies contribute to changes in developmental functioning during Early Intervention.

This study examined how social-emotional and behavioral (SEB) problems and competencies contribute to changes in developmental functioning among children enrolled in Part C Early Intervention (EI), a U.S. program supporting young children with developmental delays and disabilities. The sample included 1,055 children enrolled in EI from 2011-2019 (mean age at EI entry = 17 months; 64% male; 72% marginalized racial and ethnic backgrounds). Standardized developmental assessments, drawn from administrative records, characterized developmental functioning at EI entry and exit and parents reported SEB functioning. Hierarchical regression analyses revealed that SEB problems and competencies interacted in predicting change in developmental functioning from EI entry to exit. Monitoring, identifying, and addressing SEB problems and competencies may optimize developmental outcomes for young children with developmental delays and disabilities.

Educational inequality in multimorbidity: causality and causal pathways. A mendelian randomisation study in UK Biobank.

BACKGROUND: Multimorbidity, typically defined as having two or more long-term health conditions, is associated with reduced wellbeing and life expectancy. Understanding the determinants of multimorbidity, including whether they are causal, may help with the design and prioritisation of prevention interventions. This study seeks to assess the causality of education, BMI, smoking and alcohol as determinants of multimorbidity, and the degree to which BMI, smoking and alcohol mediate differences in multimorbidity by level of education. METHODS: Participants were 181,214 females and 155,677 males, mean ages 56.7 and 57.1 years respectively, from UK Biobank. We used a Mendelian randomization design; an approach that uses genetic variants as instrumental variables to interrogate causality. RESULTS: The prevalence of multimorbidity was 55.1%. Mendelian randomization suggests that lower education, higher BMI and higher levels of smoking causally increase the risk of multimorbidity. For example, one standard deviation (equivalent to 5.1 years) increase in genetically-predicted years of education decreases the risk of multimorbidity by 9.0% (95% CI: 6.5 to 11.4%). A 5 kg/m2 increase in genetically-predicted BMI increases the risk of multimorbidity by 9.2% (95% CI: 8.1 to 10.3%) and a one SD higher lifetime smoking index increases the risk of multimorbidity by 6.8% (95% CI: 3.3 to 10.4%). Evidence for a causal effect of genetically-predicted alcohol consumption on multimorbidity was less strong; an increase of 5 units of alcohol per week increases the risk of multimorbidity by 1.3% (95% CI: 0.2 to 2.5%). The proportions of the association between education and multimorbidity explained by BMI and smoking are 20.4% and 17.6% respectively. Collectively, BMI and smoking account for 31.8% of the educational inequality in multimorbidity. CONCLUSIONS: Education, BMI, smoking and alcohol consumption are intervenable causal risk factors for multimorbidity. Furthermore, BMI and lifetime smoking make a considerable contribution to the generation of educational inequalities in multimorbidity. Public health interventions that improve population-wide levels of these risk factors are likely to reduce multimorbidity and inequalities in its occurrence.

Time-sensitive testing pressures and COVID-19 outcomes: are socioeconomic inequalities over the first year of the pandemic explained by selection bias?

BACKGROUND: There are many ways in which selection bias might impact COVID-19 research. Here we focus on selection for receiving a polymerase-chain-reaction (PCR) SARS-CoV-2 test and how known changes to selection pressures over time may bias research into COVID-19 infection. METHODS: Using UK Biobank (N = 420,231; 55% female; mean age = 66.8 [SD = 8·11]) we estimate the association between socio-economic position (SEP) and (i) being tested for SARS-CoV-2 infection versus not being tested (ii) testing positive for SARS-CoV-2 infection versus testing negative and (iii) testing negative for SARS-CoV-2 infection versus not being tested. We construct four distinct time-periods between March 2020 and March 2021, representing distinct periods of testing pressures and lockdown restrictions and specify both time-stratified and combined models for each outcome. We explore potential selection bias by examining associations with positive and negative control exposures. RESULTS: The association between more disadvantaged SEP and receiving a SARS-CoV-2 test attenuated over time. Compared to individuals with a degree, individuals whose highest educational qualification was a GCSE or equivalent had an OR of 1·27 (95% CI: 1·18 to 1·37) in March-May 2020 and 1·13 (95% CI: 1.·10 to 1·16) in January-March 2021. The magnitude of the association between educational attainment and testing positive for SARS-CoV-2 infection increased over the same period. For the equivalent comparison, the OR for testing positive increased from 1·25 (95% CI: 1·04 to 1·47), to 1·69 (95% CI: 1·55 to 1·83). We found little evidence of an association between control exposures, and any considered outcome. CONCLUSIONS: The association between SEP and SARS-CoV-2 testing changed over time, highlighting the potential of time-specific selection pressures to bias analyses of COVID-19. Positive and negative control analyses suggest that changes in the association between SEP and SARS-CoV-2 infection over time likely reflect true increases in socioeconomic inequalities.

Separating the direct effects of traits on atherosclerotic cardiovascular disease from those mediated by type 2 diabetes.

AIMS/HYPOTHESIS: Type 2 diabetes and atherosclerotic CVD share many risk factors. This study aimed to systematically assess a broad range of continuous traits to separate their direct effects on coronary and peripheral artery disease from those mediated by type 2 diabetes. METHODS: Our main analysis was a two-step Mendelian randomisation for mediation to quantify the extent to which the associations observed between continuous traits and liability to atherosclerotic CVD were mediated by liability to type 2 diabetes. To support this analysis, we performed several univariate Mendelian randomisation analyses to examine the associations between our continuous traits, liability to type 2 diabetes and liability to atherosclerotic CVD. RESULTS: Eight traits were eligible for the two-step Mendelian randomisation with liability to coronary artery disease as the outcome and we found similar direct and total effects in most cases. Exceptions included fasting insulin and hip circumference where the proportion mediated by liability to type 2 diabetes was estimated as 56% and 52%, respectively. Six traits were eligible for the analysis with liability to peripheral artery disease as the outcome. Again, we found limited evidence to support mediation by liability to type 2 diabetes for all traits apart from fasting insulin (proportion mediated: 70%). CONCLUSIONS/INTERPRETATION: Most traits were found to affect liability to atherosclerotic CVD independently of their relationship with liability to type 2 diabetes. These traits are therefore important for understanding atherosclerotic CVD risk regardless of an individual's liability to type 2 diabetes.

Applying Mendelian randomization to appraise causality in relationships between nutrition and cancer.

Dietary factors are assumed to play an important role in cancer risk, apparent in consensus recommendations for cancer prevention that promote nutritional changes. However, the evidence in this field has been generated predominantly through observational studies, which may result in biased effect estimates because of confounding, exposure misclassification, and reverse causality. With major geographical differences and rapid changes in cancer incidence over time, it is crucial to establish which of the observational associations reflect causality and to identify novel risk factors as these may be modified to prevent the onset of cancer and reduce its progression. Mendelian randomization (MR) uses the special properties of germline genetic variation to strengthen causal inference regarding potentially modifiable exposures and disease risk. MR can be implemented through instrumental variable (IV) analysis and, when robustly performed, is generally less prone to confounding, reverse causation and measurement error than conventional observational methods and has different sources of bias (discussed in detail below). It is increasingly used to facilitate causal inference in epidemiology and provides an opportunity to explore the effects of nutritional exposures on cancer incidence and progression in a cost-effective and timely manner. Here, we introduce the concept of MR and discuss its current application in understanding the impact of nutritional factors (e.g., any measure of diet and nutritional intake, circulating biomarkers, patterns, preference or behaviour) on cancer aetiology and, thus, opportunities for MR to contribute to the development of nutritional recommendations and policies for cancer prevention. We provide applied examples of MR studies examining the role of nutritional factors in cancer to illustrate how this method can be used to help prioritise or deprioritise the evaluation of specific nutritional factors as intervention targets in randomised controlled trials. We describe possible biases when using MR, and methodological developments aimed at investigating and potentially overcoming these biases when present. Lastly, we consider the use of MR in identifying causally relevant nutritional risk factors for various cancers in different regions across the world, given notable geographical differences in some cancers. We also discuss how MR results could be translated into further research and policy. We conclude that findings from MR studies, which corroborate those from other well-conducted studies with different and orthogonal biases, are poised to substantially improve our understanding of nutritional influences on cancer. For such corroboration, there is a requirement for an interdisciplinary and collaborative approach to investigate risk factors for cancer incidence and progression.

The impact of education inequality on rheumatoid arthritis risk is mediated by smoking and body mass index: Mendelian randomization study.

OBJECTIVE: To estimate the causal relationship between educational attainment-as a proxy for socioeconomic inequality-and risk of RA, and quantify the roles of smoking and BMI as potential mediators. METHODS: Using the largest genome-wide association studies (GWAS), we performed a two-sample Mendelian randomization (MR) study of genetically predicted educational attainment (instrumented using 1265 variants from 766 345 individuals) and RA (14 361 cases, 43 923 controls). We used two-step MR to quantify the proportion of education's effect on RA mediated by smoking exposure (as a composite index capturing duration, heaviness and cessation, using 124 variants from 462 690 individuals) and BMI (517 variants, 681 275 individuals), and multivariable MR to estimate proportion mediated by both factors combined. RESULTS: Each s.d. increase in educational attainment (4.2 years of schooling) was protective of RA (odds ratio 0.37; 95% CI: 0.31, 0.44). Higher educational attainment was also protective for smoking exposure (ß = -0.25 s.d.; 95% CI: -0.26, -0.23) and BMI [ß = -0.27 s.d. (∼1.3 kg/m2); 95% CI: -0.31, -0.24]. Smoking mediated 24% (95% CI: 13%, 35%) and BMI 17% (95% CI: 11%, 23%) of the total effect of education on RA. Combined, the two risk factors explained 47% (95% CI: 11%, 82%) of the total effect. CONCLUSION: Higher educational attainment has a protective effect on RA risk. Interventions to reduce smoking and excess adiposity at a population level may reduce this risk, but a large proportion of education's effect on RA remains unexplained. Further research into other risk factors that act as potentially modifiable mediators are required.

Risk factors mediating the effect of body mass index and waist-to-hip ratio on cardiovascular outcomes: Mendelian randomization analysis.

BACKGROUND: Higher body mass index (BMI) and waist-to-hip ratio (WHR) increase the risk of cardiovascular disease, but the extent to which this is mediated by blood pressure, diabetes, lipid traits, and smoking is not fully understood. METHODS: Using consortia and UK Biobank genetic association summary data from 140,595 to 898,130 participants predominantly of European ancestry, Mendelian randomization mediation analysis was performed to investigate the degree to which systolic blood pressure (SBP), diabetes, lipid traits, and smoking mediated an effect of BMI and WHR on the risk of coronary artery disease (CAD), peripheral artery disease (PAD) and stroke. RESULTS: The odds ratio of CAD per 1-standard deviation increase in genetically predicted BMI was 1.49 (95% CI 1.39 to 1.60). This attenuated to 1.34 (95% CI 1.24 to 1.45) after adjusting for genetically predicted SBP (proportion mediated 27%, 95% CI 3% to 50%), to 1.27 (95% CI 1.17 to 1.37) after adjusting for genetically predicted diabetes (41% mediated, 95% CI 18% to 63%), to 1.47 (95% CI 1.36 to 1.59) after adjusting for genetically predicted lipids (3% mediated, 95% -23% to 29%), and to 1.46 (95% CI 1.34 to 1.58) after adjusting for genetically predicted smoking (6% mediated, 95% CI -20% to 32%). Adjusting for all the mediators together, the estimate attenuated to 1.14 (95% CI 1.04 to 1.26; 66% mediated, 95% CI 42% to 91%). A similar pattern was observed when considering genetically predicted WHR as the exposure, and PAD or stroke as the outcome. CONCLUSIONS: Measures to reduce obesity will lower the risk of cardiovascular disease primarily by impacting downstream metabolic risk factors, particularly diabetes and hypertension. Reduction of obesity prevalence alongside control and management of its mediators is likely to be most effective for minimizing the burden of obesity.

Mendelian randomisation for mediation analysis: current methods and challenges for implementation.

Mediation analysis seeks to explain the pathway(s) through which an exposure affects an outcome. Traditional, non-instrumental variable methods for mediation analysis experience a number of methodological difficulties, including bias due to confounding between an exposure, mediator and outcome and measurement error. Mendelian randomisation (MR) can be used to improve causal inference for mediation analysis. We describe two approaches that can be used for estimating mediation analysis with MR: multivariable MR (MVMR) and two-step MR. We outline the approaches and provide code to demonstrate how they can be used in mediation analysis. We review issues that can affect analyses, including confounding, measurement error, weak instrument bias, interactions between exposures and mediators and analysis of multiple mediators. Description of the methods is supplemented by simulated and real data examples. Although MR relies on large sample sizes and strong assumptions, such as having strong instruments and no horizontally pleiotropic pathways, our simulations demonstrate that these methods are unaffected by confounders of the exposure or mediator and the outcome and non-differential measurement error of the exposure or mediator. Both MVMR and two-step MR can be implemented in both individual-level MR and summary data MR. MR mediation methods require different assumptions to be made, compared with non-instrumental variable mediation methods. Where these assumptions are more plausible, MR can be used to improve causal inference in mediation analysis.

Developmental Outcomes in Early-Identified Children Who Are Hard of Hearing at 2 to 3 Years of Age.

OBJECTIVES: This study examined the psychosocial, adaptive behavior, and language outcomes of young children who are hard of hearing (HH) without additional disabilities or neurocognitive impairments. Relations between early developmental outcomes and child and parent demographic variables, and parenting stress and self-efficacy were also explored. DESIGN: Participants were 39 children with early identified, permanent mild to severe hearing loss, between the ages of 2 and 3 years, and a comparison group of 47 children with normal hearing (NH). Developmental outcomes were measured using clinician-administered standardized tests and parent-completed behavior rating instruments specific to language, psychosocial functioning, and adaptive behavior. Mothers completed self-report measures that assess parenting stress and maternal self-efficacy. RESULTS: The children who are HH were similar to the children with NH in terms of their psychosocial functioning and adaptive behavior, with the exception of their socialization skills. As a group, the children who are HH performed significantly worse than their peers with NH on all measures of language ability. Among the children who are HH, maternal self-efficacy showed a strong positive correlation with adaptive behavior outcomes; however, it failed to contribute unique variance above that explained by language ability and gender. Maternal self-efficacy was also significantly correlated with better psychosocial outcomes, but only parenting stress proved to be a significant predictor of child behavioral problems once other variables considered were in the model. CONCLUSIONS: Early-identified young children who are HH can demonstrate age-appropriate development in multiple domains, including language, psychosocial, and adaptive behavior. However, mild to severe hearing loss places young children with no additional disabilities or neurocognitive impairments at risk for language delays. Although the children who are HH demonstrated no more emotional or behavioral problems than their same-age peers with NH, results suggest that language delays increase their vulnerability for delays in various aspects of social competence.

How well are DSM-5 diagnostic criteria for ASD represented in standardized diagnostic instruments?

Five years after the publication of DSM-5 in 2013, three widely used diagnostic instruments have published algorithms designed to represent its (sub-)criteria for Autism Spectrum Disorder (ASD) in children and adolescents. This study aimed to: (1) establish the content validity of these three DSM-5-adapted algorithms, and (2) identify problems with the operationalization of DSM-5 diagnostic criteria in measurable and observable behaviors. Algorithm items of the Autism Diagnostic Observation Schedule-Second Edition (ADOS-2), Developmental, Dimensional and Diagnostic Interview (3di) and Diagnostic Interview for Social and Communication Disorders-11th edition (DISCO-11) were mapped onto DSM-5 sub-criteria. The development and decision-making rules integrated in their algorithms were then compared with DSM-5. Results demonstrated significant variability in the number and nature of sub-criteria covered by the ADOS-2, 3di and DISCO-11. In addition to differences in the development of algorithms and cut-off scores, instruments also differed in the extent to which they follow DSM-5 decision-making rules for diagnostic classification. We conclude that such differences in interpretation of DSM-5 criteria provide a challenge for symptom operationalization which will be most effectively overcome by consensus, testing and reformulation.

Introducing Typhoid Conjugate Vaccine in South Asia: Lessons From the Surveillance for Enteric Fever in Asia Project.

Enteric fever remains a public health concern in communities lacking sanitation infrastructure to separate sewage from drinking water. To bridge the gap until large-scale civil-engineering projects are implemented in high-burden countries, typhoid conjugate vaccine presents a promising disease-prevention technology. A new typhoid conjugate vaccine was prequalified by the World Health Organization in 2017 and is beginning to be introduced in countries around the world. To help inform vaccine introduction, the Surveillance for Enteric Fever in Asia Project (SEAP) conducts prospective enteric fever surveillance in Bangladesh, Nepal, and Pakistan. This supplement presents findings from Phase II of the study (2016-2019) on burden of disease, clinical presentation, the growing spread of drug-resistant strains, and policy and economic ramifications. These findings are delivered to support policymakers in their deliberations on strategies to introduce typhoid conjugate vaccine as a preventive tool against enteric fever.

Investigating the importance of individual mitochondrial genotype in susceptibility to drug-induced toxicity.

The mitochondrion is an essential organelle responsible for generating cellular energy. Additionally, mitochondria are a source of inter-individual variation as they contain their own genome. Evidence has revealed that mitochondrial DNA (mtDNA) variation can confer differences in mitochondrial function and importantly, these differences may be a factor underlying the idiosyncrasies associated with unpredictable drug-induced toxicities. Thus far, preclinical and clinical data are limited but have revealed evidence in support of an association between mitochondrial haplogroup and susceptibility to specific adverse drug reactions. In particular, clinical studies have reported associations between mitochondrial haplogroup and antiretroviral therapy, chemotherapy and antibiotic-induced toxicity, although study limitations and conflicting findings mean that the importance of mtDNA variation to toxicity remains unclear. Several studies have used transmitochondrial cybrid cells as personalised models with which to study the impact of mitochondrial genetic variation. Cybrids allow the effects of mtDNA to be assessed against a stable nuclear background and thus the in vitro elucidation of the fundamental mechanistic basis of such differences. Overall, the current evidence supports the tenet that mitochondrial genetics represent an exciting area within the field of personalised medicine and drug toxicity. However, further research effort is required to confirm its importance. In particular, efforts should focus upon translational research to connect preclinical and clinical data that can inform whether mitochondrial genetics can be useful to identify at risk individuals or inform risk assessment during drug development.

The Family Life Impairment Scale: Factor Structure and Clinical Utility with Young Children.

Although it is well-established that young children experience significant psychopathology, diagnostic decisions continue to be challenging, in part due to the way impairment is understood, defined, and measured. Most existing clinical tools assess impairment in an individualized manner, whereas for many young children, impairment is more accurately conceptualized as a family-oriented, multidimensional construct, impacting various parental and family activities. Two studies were completed using the Family Life Impairment Scale (FLIS), a multidimensional parent-report measure of family and associated impairment designed for young children. In Study 1, factor analysis was used in a large (n = 945) representative sample (23-48 months of age). FLIS associations with measures of parent and child well-being were explored to investigate convergent validity. Study 2 was completed in a sample (n = 174) of young children (18-33 months of age) diagnosed with autism spectrum disorders to explore factorial consistency in a clinical sample. Study 1 yielded evidence of a four-factor solution, including parent impairment (affecting parental well-being), family impairment (affecting family activities and routines), childcare impairment (affecting challenges with childcare), and positive growth (parental learning and growth associated with the child's problem). Evidence of convergent validity was also found, as factors were differentially associated with established measures of child symptoms and parent stress. Factor structure was supported in the clinical sample. Results support both the factorial structure and clinical utility of the FLIS for use across clinical and nonclinical populations of young children.