RESUMEN
BACKGROUND: Sensitive measures to predict neuromotor outcomes from data collected early in infancy are lacking. Measures derived from the recordings of infant movement using wearable sensors may be a useful new technique. METHODS: We collected full-day leg movement of 41 infants in rural Guatemala across 3 visits between birth and 6 months of age using wearable sensors. Average leg movement rate and fuzzy entropy, a measure to describe the complexity of signals, of the leg movements' peak acceleration time series and the time series itself were derived. We tested the three measures for the predictability of infants' developmental outcome, Bayley Scales of Infant and Toddler Development III motor, language, or cognitive composite score assessed at 12 months of age. We performed quantile regressions with clustered standard errors, accounting for the multiple visits for each infant. RESULTS: Fuzzy entropy was associated with the motor composite score at the 0.5 quantiles; this association was not found for the other two measures. Also, no leg movement characteristic was associated with language or cognitive composite scores. CONCLUSION: We propose that the entropy of leg movement associated peak accelerations calculated from the wearable sensor data collected for a full-day can be considered as one predictor for infants' motor developmental outcome assessed with Bayley Scales of Infant and Toddler Development III at 12 months of age.
RESUMEN
Lack of physical activity (PA) at a young age can result in health issues. Thus, monitoring PA is important. Wearable accelerometers are the preferred tool to monitor PA in children. Validated thresholds are used to classify activity intensity levels, e.g., sedentary, light, and moderate-to-vigorous, in ambulatory children. No previous work has developed accelerometer thresholds for infancy (pre-ambulatory children). Therefore, this work aims to develop accelerometer thresholds for PA intensity levels in pre-ambulatory infants. Infants (n = 10) were placed in a supine position and allowed free movement. Their movements were synchronously captured using video cameras and accelerometers worn on each ankle. The video data were labeled by activity intensity level (sedentary, light, and moderate-to-vigorous) in two-second epochs using observational rating (gold standard). Accelerometer thresholds were developed for acceleration and jerk using two optimization approaches. Four sets of thresholds were developed for dual (two ankles) and for single-worn (one ankle) accelerometers. Of these, for a typical use case, we recommend using acceleration-based thresholds of 1.00 m/s to distinguish sedentary and light activity and 2.60 m/s to distinguish light and moderate-to-vigorous activity. Acceleration and jerk are both suitable for measuring PA.
Asunto(s)
Acelerometría , Ejercicio Físico , Humanos , Acelerometría/instrumentación , Acelerometría/métodos , Lactante , Ejercicio Físico/fisiología , Masculino , Femenino , Dispositivos Electrónicos VestiblesRESUMEN
The neural processes underpinning cognition and language development in infancy are of great interest. We investigated EEG power and coherence in infancy, as a reflection of underlying cortical function of single brain region and cross-region connectivity, and their relations to cognition and early precursors of speech and language development. EEG recordings were longitudinally collected from 21 infants with typical development between approximately 1 and 7 months. We investigated relative band power at 3-6Hz and 6-9Hz and EEG coherence of these frequency ranges at 25 electrode pairs that cover key brain regions. A correlation analysis was performed to assess the relationship between EEG measurements across frequency bands and brain regions and raw Bayley cognitive and language developmental scores. In the first months of life, relative band power is not correlated with cognitive and language scales. However, 3-6Hz coherence is negatively correlated with receptive language scores between frontoparietal regions, and 6-9Hz coherence is negatively correlated with expressive language scores between frontoparietal regions. The results from this preliminary study contribute to the existing literature on the relationship between electrophysiological development, cognition, and early speech precursors in this age group. Future work should create norm references of early development in these domains that can be compared with infants at risk for neurodevelopmental disabilities.
Asunto(s)
Electroencefalografía , Habla , Lactante , Humanos , Electroencefalografía/métodos , Desarrollo del Lenguaje , Cognición/fisiología , EncéfaloRESUMEN
BACKGROUND: Tools to accurately assess infants' neurodevelopmental status very early in their lives are limited. Wearable sensors may provide a novel approach for very early assessment of infant neurodevelopmental status. This may be especially relevant in rural and low-resource global settings. METHODS: We conducted a longitudinal observational study and used wearable sensors to repeatedly measure the kinematic leg movement characteristics of 41 infants in rural Guatemala three times across full days between birth and 6 months of age. In addition, we collected sociodemographic data, growth data, and caregiver estimates of swaddling behaviors. We used visual analysis and multivariable linear mixed models to evaluate the associations between two leg movement kinematic variables (awake movement rate, peak acceleration per movement) and infant age, swaddling behaviors, growth, and other covariates. RESULTS: Multivariable mixed models of sensor data showed age-dependent increases in leg movement rates (2.16 [95% CI 0.80,3.52] movements/awake hour/day of life) and movement acceleration (5.04e-3 m/s2 [95% CI 3.79e-3, 6.27e-3]/day of life). Swaddling time as well as growth status, poverty status and multiple other clinical and sociodemographic variables had no impact on either movement variable. CONCLUSIONS: Collecting wearable sensor data on young infants in a rural low-resource setting is feasible and can be used to monitor age-dependent changes in movement kinematics. Future work will evaluate associations between these kinematic variables from sensors and formal developmental measures, such as the Bayley Scales of Infant and Toddler Development.
Asunto(s)
Aceleración , Pierna , Lactante , Humanos , Proyectos Piloto , Fenómenos Biomecánicos , GuatemalaRESUMEN
BACKGROUND: Infants with prematurity, low birthweight, and medical comorbidities are at high risk for developmental delays and neurodevelopmental disabilities and require close monitoring. Due to the COVID-19 pandemic, high-risk infant follow-up (HRIF) programs have adapted to perform developmental assessments via telehealth. OBJECTIVES: Describe the referral rates to initiate, continue, or increase/add early intervention (EI) therapies based on in-person use of the Bayley Scales of Infant and Toddler Development, 4th Edition (BSID-IV) or telehealth use of the Developmental Assessment in Young Children, 2nd Edition (DAYC-2). METHODS: A retrospective chart review was conducted on 203 patients seen in the HRIF program at an academic medical center in Southern California. Patients were divided into in-person (BSID-IV) and telehealth (DAYC-2) assessment groups. Statistical analyses were performed to describe demographic characteristics, medical information, and referral rates for EI therapies by the types of visits. RESULTS: The in-person and telehealth groups demonstrated similar demographic and clinical characteristics and comparable referral rates for initiating EI therapies. Telehealth patients already receiving therapies were recommended to increase/add EI therapies at a higher rate compared to in-person patients. CONCLUSIONS: The BSID-IV is widely used to assess for developmental delays in the high-risk infant population, but in-person administration of this tool poses limitations on its accessibility. Telehealth administration of an alternative tool, such as the DAYC-2, can lead to similar EI referral rates as in-person administration of the BSID-IV. Increased use of telehealth developmental assessments can promote timely detection of developmental delays and minimize gaps in healthcare access.
Asunto(s)
Discapacidades del Desarrollo , Telemedicina , Recién Nacido , Lactante , Niño , Humanos , Preescolar , Discapacidades del Desarrollo/diagnóstico , Discapacidades del Desarrollo/epidemiología , Discapacidades del Desarrollo/terapia , Estudios Retrospectivos , Pandemias , Derivación y Consulta , Desarrollo InfantilRESUMEN
PURPOSE: The purpose of this study was to determine the agreement between Gross Motor Ability Estimator-2 (GMAE-2) and Gross Motor Ability Estimator-3 (GMAE-3) calculations of Gross Motor Function Measure-66 (GMFM-66) scores in infants and young children with cerebral palsy. METHODS: Data from 53 children 5 to 53 months of age were analyzed. Agreement between GMFM-66 scores using the GMAE-2 and the GMAE-3 was calculated using Bland-Altman plots and interclass correlation coefficients (ICCs). Eleven participants who had at least 1 GMFM-66 score of less than 25 using either method were identified for further analysis. RESULTS: The average difference between GMFM-66 scores was 0.27 for all participants and 0.63 for the subset of lower-scoring participants. Good agreement was found for GMFM-66 scores for all participants (ICC = 0.998) and for subset of lower-scoring participants (ICC = 0.879). CONCLUSIONS: High levels of agreement exist between the GMAE-2 and the GMAE-3, which suggests that scores are comparable using either algorithm.
Asunto(s)
Parálisis Cerebral , Destreza Motora , Niño , Lactante , Humanos , Preescolar , Parálisis Cerebral/rehabilitación , Evaluación de la Discapacidad , AlgoritmosRESUMEN
Joint attention (JA) is the purposeful coordination of an individual's focus of attention with that of another and begins to develop within the first year of life. Delayed, or atypically developing, JA is an early behavioral sign of many developmental disabilities and so assessing JA in infancy can improve our understanding of trajectories of typical and atypical development. This scoping review identified the most common methods for assessing JA in the first year of life. Methods of JA were divided into qualitative and quantitative categories. Out of an identified 13,898 articles, 106 were selected after a robust search of four databases. Frequent methods used were eye tracking, electroencephalography (EEG), behavioral coding and the Early Social Communication Scale (ECSC). These methods were used to assess JA in typically and atypically developing infants in the first year of life. This study provides a comprehensive review of the past and current state of measurement of JA in the literature, the strengths and limitations of the measures used, and the next steps to consider for researchers interested in investigating JA to strengthen this field going forwards.
RESUMEN
PURPOSE: This case report describes daily leg movement quantity and kinematic characteristics of a child with spinal muscular atrophy (SMA) with 2 copies of SMN2, who was symptomatic at the time of treatment with disease-modifying therapies. KEY POINTS: Compared with infants with typical development, this child had differing values for leg movement quantity, duration, average acceleration, and peak acceleration measured across full days in the natural environment by wearable sensors. In addition, movement quantity and clinician-rated outcomes increased with age. CONCLUSIONS: Wearable sensors recorded movement quantity and kinematic characteristics in a treated infant with SMA (2 copies SMN2). These movement parameters were consistently different compared anecdotally with published data from infants with typical development, demonstrating their potential to add unique and complementary information to the assessment of motor function in SMA. RECOMMENDATIONS: Larger longitudinal studies are needed to determine the utility of wearable sensors as an assessment tool and an early predictor of motor outcomes in children with SMA.
Asunto(s)
Pierna , Atrofia Muscular Espinal , Lactante , Humanos , Niño , Fenómenos Biomecánicos , Ambiente , Movimiento , Proteína 2 para la Supervivencia de la Neurona MotoraRESUMEN
In ambulatory care, monitoring process performance measures (PPMs) is essential to meet regulatory requirements, establish targets for care, seek reimbursement, and evaluate patient care responsibilities. We implemented a comprehensive program, "Engage to Sustain," for licensed practical nurses (LPNs) and certified medical assistants (CMAs) to practice at the top of their licensure/certification. Screening rates for 4 key PPMs (depression screening, fall risk screening, and tobacco use screening and counseling) markedly increased following this intervention across 18 ambulatory departments with more than 2 million patient visits. These results suggest that shifting responsibilities for patient screening from physicians and advanced practitioners to LPNs and CMAs may improve screening rates.
Asunto(s)
Técnicos Medios en Salud , Atención Ambulatoria , Humanos , Certificación , Evaluación de Procesos, Atención de SaludRESUMEN
BACKGROUND: Maternal stress has negative consequences on infant behavioral development, and COVID-19 presented uniquely stressful situations to mothers of infants born during the pandemic. We hypothesized that mothers with higher levels of perceived stress during the pandemic would report higher levels of infant regulatory problems including crying and interrupted sleep patterns. METHODS: As part 6 sites of a longitudinal study, mothers of infants born during the pandemic completed the Perceived Stress Scale, the Brief Infant Sleep Questionnaire, and an Infant Crying survey at 6 (n = 433) and 12 (n = 344) months of infant age. RESULTS: Maternal perceived stress, which remained consistent at 6 and 12 months of infant age, was significantly positively correlated with time taken to settle infants. Although maternal perceived stress was not correlated with uninterrupted sleep length, time taken to put the infant to sleep was correlated. Perceived stress was also correlated with the amount of infant crying and fussiness reported at 6 months. CONCLUSIONS: Mothers who reported higher levels of perceived stress during the pandemic reported higher levels of regulatory problems, specifically at 6 months. Examining how varying levels of maternal stress and infant behaviors relate to overall infant developmental status over time is an important next step. IMPACT: Women giving birth during the COVID-19 pandemic who reported higher levels of stress on the Perceived Stress Scale also reported higher levels of infant fussiness and crying at 6 months old, and more disruptive sleep patterns in their infants at 6 months and 12 months old. Sleeping problems and excessive crying in infancy are two regulatory problems that are known risk factors for emotional and behavioral issues in later childhood. This paper is one of the first studies highlighting the associations between maternal stress and infant behaviors during the COVID-19 pandemic.
Asunto(s)
COVID-19 , Pandemias , Lactante , Humanos , Femenino , Embarazo , Niño , Estudios Longitudinales , Conducta del Lactante/psicología , Madres/psicología , Llanto/psicología , Estrés Psicológico/etiologíaRESUMEN
The COVID-19 pandemic has had a significant impact on mental health. Identifying risk factors and susceptible subgroups will guide efforts to address mental health concerns during the pandemic and long-term management and monitoring after the pandemic. We aimed to examine associations of insecurity (concerns about food, health insurance, and/or money), social support, and change in family relationships with poor mental health and to explore disparities in these associations. An online survey was collected from 3952 US adults between May and August 2020. Symptoms of anxiety, depression, stress, and trauma-related disorders were assessed by the Generalized Anxiety Disorder 7-item scale, the Patient Health Questionnaire-9, the Perceived Stress Scale-4, and the Primary Care Post-Traumatic Stress Disorder Screen, respectively. Social support was measured by the Oslo Social Support Scale. Logistic regression was used and stratified analyses by age, race/ethnicity, and sex were performed. We found a higher prevalence of poor mental health among those who were younger, female, with lower socioeconomic status, and racial/ethnic minorities. Participants who were worried about money, health insurance, or food had higher odds of symptoms of anxiety (OR = 3.74, 95% CI: 3.06-4.56), depression (OR = 3.20, 95% CI: 2.67-3.84), stress (OR = 3.08, 95% CI: 2.67-3.57), and trauma-related disorders (OR = 2.93, 95% CI: 2.42-3.55) compared to those who were not. Compared to poor social support, moderate and strong social support was associated with lower odds of all four symptoms. Participants who had changes in relationships with parents, children, or significant others had worse mental health. Our findings identified groups at higher risk for poor mental health, which offers insights for implementing targeted interventions.
Asunto(s)
COVID-19 , Salud Mental , Niño , Adulto , Femenino , Humanos , Pandemias , COVID-19/epidemiología , Relaciones Familiares , Apoyo Social , Ansiedad/epidemiología , Depresión/epidemiologíaRESUMEN
OBJECTIVES: The CF Foundation sponsored competitive awards for Mental Health Coordinators (MHCs) from 2016 to 2018 to implement the international guidelines for mental health screening and treatment in US CF centers. Longitudinal surveys evaluated success in implementing these guidelines using the Consolidated Framework for Implementation Research (CFIR). METHODS: MHCs completed annual surveys assessing implementation from preparation/basic implementation (e.g., using recommended screeners) to full implementation/sustainability (e.g., providing evidence-based treatments). Points were assigned to questions through consensus, with higher scores assigned to more complex tasks. Linear regression and mixed effects models were used to: (1) examine differences in centers and MHC characteristics, (2) identify predictors of success, (3) model the longitudinal trajectory of implementation scores. RESULTS: A total of 122 MHCs (88.4% responded): Cohort 1, N = 80; Cohort 2, N = 30; and Cohort 3, N = 12. No differences in center characteristics were found. Significant improvements in implementation were observed across centers over time. Years of experience on a CF team was the only significant predictor of success; those with 1-5 years or longer reported the highest implementation scores. Change over time was predicted by >5 years of experience. CONCLUSIONS: Implementation of the mental health guidelines was highly successful over time. Funding for MHCs with dedicated time was critical. Longitudinal modeling indicated that CF centers with diverse characteristics could implement them, supported by evidence from the CF Patient Registry showing nearly universal uptake of mental health screening in the United States. Years of experience predicted better implementation, suggesting that education and training of MHCs and retention of experienced providers are critical to success.
Asunto(s)
Fibrosis Quística , Humanos , Estados Unidos , Fibrosis Quística/diagnóstico , Fibrosis Quística/terapia , Fibrosis Quística/psicología , Salud Mental , Tamizaje Masivo , Encuestas y Cuestionarios , Estudios LongitudinalesRESUMEN
Background: Physical disability in individuals with cerebral palsy (CP) creates lifelong mobility challenges and healthcare costs. Despite this, very little is known about how infants at high risk for CP learn to move and acquire early locomotor skills, which set the foundation for lifelong mobility. The objective of this project is to characterize the evolution of locomotor learning over the first 18 months of life in infants at high risk for CP. To characterize how locomotor skill is learned, we will use robotic and sensor technology to provide intervention and longitudinally study infant movement across three stages of the development of human motor control: early spontaneous movement, prone locomotion (crawling), and upright locomotion (walking). Study design: This longitudinal observational/intervention cohort study (ClinicalTrials.gov Identifier: NCT04561232) will enroll sixty participants who are at risk for CP due to a brain injury by one month post-term age. Study participation will be completed by 18 months of age. Early spontaneous leg movements will be measured monthly from 1 to 4 months of age using inertial sensors worn on the ankles for two full days each month. Infants who remain at high risk for CP at 4 months of age, as determined from clinical assessments of motor function and movement quality, will continue through two locomotor training phases. Prone locomotor training will be delivered from 5 to 9 months of age using a robotic crawl training device that responds to infant behavior in real-time. Upright locomotor training will be delivered from 9 to 18 months of age using a dynamic weight support system to allow participants to practice skills beyond their current level of function. Repeated assessments of locomotor skill, training characteristics (such as movement error, variability, movement time and postural control), and variables that may mediate locomotor learning will be collected every two months during prone training and every three months during upright training. Discussion: This study will develop predictive models of locomotor skill acquisition over time. We hypothesize that experiencing and correcting movement errors is critical to skill acquisition in infants at risk for CP and that locomotor learning is mediated by neurobehavioral factors outside of training.Project Number 1R01HD098364-01A1.ClinicalTrials.gov Identifier: NCT04561232.
RESUMEN
Traditional methods do not capture the multidimensional domains and dynamic nature of infant behavioral patterns. We aim to compare full-day, in-home leg movement data between infants with typical development (TD) and infants at risk of developmental disabilities (AR) using barcoding and nonlinear analysis. Eleven infants with TD (2-10 months) and nine infants AR (adjusted age: 2-14 months) wore a sensor on each ankle for 7 days. We calculated the standard deviation for linear variability and sample entropy (SampEn) of leg acceleration and angular velocity for nonlinear variability. Movements were also categorized into 16 barcoding states, and we calculated the SampEn and proportions of the barcoding. All variables were compared between the two groups using independent-samples t-test or Mann-Whitney U test. The AR group had larger linear variability compared to the TD group. SampEn was lower in the AR group compared to TD group for both acceleration and angular velocity. Two barcoding states' proportions were significantly different between the two groups. The results showed that nonlinear analysis and barcoding could be used to identify the difference of dynamic multidimensional movement patterns between infants AR and infants with TD. This information may help early diagnosis of developmental disabilities in the future.
Asunto(s)
Discapacidades del Desarrollo , Pierna , Niño , Humanos , Lactante , Estudios Transversales , Discapacidades del Desarrollo/diagnóstico , Movimiento , AceleraciónRESUMEN
Quantity and quality of motor exploration are proposed to be fundamental for infant motor development. However, it is still not clear what types of motor exploration contribute to learning. To determine whether changes in quantity of leg movement and/or variability of leg acceleration are related to performance in a contingency learning task, twenty 6-8-month-old infants with typical development participated in a contingency learning task. During this task, a robot provided reinforcement when the infant's right leg peak acceleration was above an individualized threshold. The correlation coefficient between the infant's performance and the change in quantity of right leg movement, linear variability, and nonlinear variability of right leg movement acceleration from baseline were calculated. Simple linear regression and multiple linear regression were calculated to explain the contribution of each variable to the performance individually and collectively. We found significant correlation between the performance and the change in quantity of right leg movement (r = 0.86, p < 0.001), linear variability (r = 0.71, p < 0.001), and nonlinear variability (r = 0.62, p = 0.004) of right leg movement acceleration, respectively. However, multiple linear regression showed that only quantity and linear variability of leg movements were significant predicting factors for the performance ratio (p < 0.001, adjusted R2 = 0.94). These results indicated that the quantity of exploration and variable exploratory strategies could be critical for the motor learning process during infancy.
Asunto(s)
Pierna , Movimiento , Humanos , Lactante , Aprendizaje , Desarrollo InfantilRESUMEN
This article is intended for use among all cystic fibrosis care team members. It covers common mental health concerns and their unique presentations in persons with cystic fibrosis (pwCF) in areas such as depression, anxiety, trauma, behavioral disorders emerging in childhood, sleep, problematic eating patterns, and the impact of substance use. Furthermore, the authors address ways to manage these mental health symptoms through risk assessment, psychological interventions, and/or psychotropic medications. Quick reference tables are provided for evidence-based psychological interventions and medications often used for mental health conditions in pwCF.
Asunto(s)
Fibrosis Quística , Trastornos Mentales , Humanos , Fibrosis Quística/psicología , Trastornos Mentales/epidemiología , Trastornos Mentales/terapiaRESUMEN
Individuals with cystic fibrosis (CF) are at high risk for depression and anxiety, with negative consequences for health and quality of life. Cystic Fibrosis Foundation/European Cystic Fibrosis Society guidelines recommend routine screening, treatment, and preventative efforts. Cognitive-behavioral therapy (CBT) has a large evidence-base for depression/anxiety prevention and treatment. However, traditional CBT protocols require adaptation to address the emotional challenges of coping with CF, stressors related to disease management, and barriers to access to care. The goal of this study was to partner with the CF community to develop an innovative CBT-based intervention for the prevention and treatment of depression and anxiety tailored to CF-specific needs. In-depth feedback was collected via audio-recorded telephone interviews with 16 adults with CF from 3 U.S. CF centers, with purposive sampling across gender, age, ethnicity, and disease severity. A semi-structured interview guide elicited discussion of patient experiences of coping with CF, and perspectives on the acceptability of the content, structure, and delivery model of the proposed intervention. Qualitative analysis utilized a content analytic approach. Participants ranged from 21 to 53 years (M = 35); eight were female; three were Hispanic. Patient-reported most recent FEV1, a measure of lung function based on forced expiratory volume in in one second, ranged from 25 to 113% predicted (M = 72). One participant was post-double lung transplant. Qualitative interviews were analyzed thematically revealing core themes related to the experience of coping with CF. The most frequently cited CF-related stressors were Treatment Burden, Illness Uncertainty, and Financial/Insurance Stress. Participants talked about the interaction of physical symptoms and emotional distress in their daily lives, a topic not typically discussed in routine CF care. Resilience was also a major theme with participants describing strategies they use to cope with CF and hospitalizations. Description of patients' experiences was incorporated into the program's intervention manual and patient workbook. Participants also provided direct feedback on the proposed program. Feedback was largely positive regarding program content and structure, suggesting the acceptability of a CF-specific CBT-based intervention for adults with CF. Features to increase accessibility of care including telehealth, inpatient delivery, and team-based care were perceived as advantageous, and participants emphasized the value of a CF-specific mental health intervention. Qualitative findings directly informed the development of CF-CBT, a cognitive-behavioral skills-based program to promote emotional well-being for adults with CF.
RESUMEN
Our primary objective was to document COVID-19 induced changes to perinatal care across the USA and examine the implication of these changes for maternal mental health. We performed an observational cross-sectional study with convenience sampling using direct patient reports from 1918 postpartum and 3868 pregnant individuals collected between April 2020 and December 2020 from 10 states across the USA. We leverage a subgroup of these participants who gave birth prior to March 2020 to estimate the pre-pandemic prevalence of specific birthing practices as a comparison. Our primary analyses describe the prevalence and timing of perinatal care changes, compare perinatal care changes depending on when and where individuals gave birth, and assess the linkage between perinatal care alterations and maternal anxiety and depressive symptoms. Seventy-eight percent of pregnant participants and 63% of postpartum participants reported at least one change to their perinatal care between March and August 2020. However, the prevalence and nature of specific perinatal care changes occurred unevenly over time and across geographic locations. The separation of infants and mothers immediately after birth and the cancelation of prenatal visits were associated with worsened depression and anxiety symptoms in mothers after controlling for sociodemographic factors, mental health history, number of pregnancy complications, and general stress about the COVID-19 pandemic. Our analyses reveal widespread changes to perinatal care across the US that fluctuated depending on where and when individuals gave birth. Disruptions to perinatal care may also exacerbate mental health concerns, so focused treatments that can mitigate the negative psychiatric sequelae of interrupted care are warranted.