Random Coefficient Regression Analysis Research Articles

Promotive Voice, Leader-member Exchange, and Creativity Endorsement: The Role of Supervisor-Attributed Motives

Employee voice is perceived as an approach with both significant advantages and disadvantages. The current study aims to analyse the behaviours of supervisors when endorsing the ideas of employees who raise promotive voices and consider the employees positively for the development of quality relationships. Specifically, 970 employees were recruited from various small and medium enterprises (SMEs), including manufacturing and electronics companies, in Pakistan for the current study participation. Data collection was conducted in two stages through two sources (supervisors and subordinates) before examining the collected data on the Mplus software for random coefficient regression analyses. Subordinates’ promotive voice was significantly and positively correlated to the Leader-Member-Exchange (LMX) quality and creative idea endorsement when supervisors interpreted the voice as driven more by performance enhancement motives instead of impression management motives. The findings suggested that performance enhancement motives and impression management motives would produce contrasting material consequences for subordinates. The present study limitations and future research directions were also discussed.

Is there a combined effect of depression and cognitive reserve on cognitive function? Findings from a population-based study

Objective To analyse the combined effect of depression and cognitive reserve (CR) on cognition over a three-year follow-up period; and to explore this relationship specifically in individuals aged 65+ years. Design Data from the ‘Edad con Salud’ project were analysed (n = 1,144; 50+ years). Main Outcome Measures The Composite International Diagnostic Interview was used to evaluate depression. CR was assessed with the Cognitive Reserve Questionnaire. Episodic memory was assessed with the word list memory and recall. Verbal fluency was measured through the animal naming task. Random coefficient regression analyses were performed. Results Depression was associated with lower scores in episodic memory, whereas increased levels of CR were related with higher scores across all the cognitive tests. Among older-aged individuals, cognition decreased at lower levels of CR regardless of depression, while participants with depression exhibited decreased values in both measures of memory at higher levels of CR. Conclusion Depression and CR were related with cognitive performance. Among older individuals, those with low levels of CR may constitute a vulnerable group with poor cognitive prognosis, whilst a harmful effect of depression on memory performance was observed among individuals with greater CR. Further evidence needs to be gathered to understand these associations.

1172-P: Impact of Telemedicine Clinics in the Management of Type 1 Diabetes

Background: Our institution began telemedicine clinics at rural hospitals in 2013, with standard office visits delivered synchronously via video conferencing. This project aims to assess the impact of telemedicine clinics in T1D care at our institution. Methods: IRB approval was obtained to access records of people with T1D with three or more telemedicine visits from Nov 2013 to Oct 2019. To assess change in A1c, we used a random coefficient regression model and estimated the effect of time on A1c, controlling for gender and age at start of treatment. Data were collected on change in treatment and prior provider (PCP, outside/academic endocrinologist). Results: The 139 patients evaluated (average age 45 y (range 16-94), 58% F) had an average of 8 A1c values (2-23) over an average duration of 32 mos (4-69). The scatterplot and fitted regression line show a temporal A1c decline. Similarly, random coefficient regression analysis provided overwhelming evidence for an A1c decline (P< 0.001). Each year in telemedicine care was associated with a decline of 0.13 in A1c (95% CI: -0.20, -0.06). Age and gender were not associated with A1c. A1c decline was noted irrespective of prior provider or treatment change (ie, starting CGM/pump therapy). Conclusions: Our data supports the concept that T1D can be effectively managed via telemedicine. Declines in A1c were seen in all groups, irrespective of age, prior provider and additions of diabetes technology. Disclosure L.A. Eiland: None. M. Siahpush: None. P. Akkireddy: None. L. Kuechenmeister: None.

Health Insurance and Poverty in Trajectories of Out-of-Pocket Expenditure among Low-Income Middle-Aged Adults.

To assess the effects of longitudinal patterns of health insurance and poverty on out-of-pocket expenditures among low-income late middle-aged adults. Six waves (2002-2012) of the Health and Retirement Study, in combination with RAND Center for the Study of Aging data, were used. A random coefficient regression analysis was conducted in a multilevel growth curve framework to estimate the impact of health insurance and poverty on out-of-pocket expenditures. At baseline, individuals with private insurance or unstable coverage were more likely to have out-of-pocket expenditures and financial burdens than public insurance holders. Over time, the poor who had no insurance, unstable coverage, or insurance type change had higher out-of-pocket expenditures; private coverage holders had higher odds of financial burden. Unstable insurance coverage had a discernible effect on the long-term, out-of-pocket expenditures among low-income adults. Findings have an important policy implication to protect poor late middle-aged population; as this population enters old age, the high financial burden it faces may exacerbate persistent socioeconomic health disparity among older people with unstable insurance coverage.

Longitudinal Relationship Among Physical Fitness, Walking-Related Physical Activity, and Fatigue in Children With Cerebral Palsy.

A vicious circle of decreased physical fitness, early fatigue, and low physical activity levels (PAL) is thought to affect children with cerebral palsy (CP). However, the relationship of changes in physical fitness to changes in PAL and fatigue is unclear. The objective of this study was to investigate the associations among changes in physical fitness, walking-related PAL, and fatigue in children with CP. This study was a secondary analysis of a randomized controlled trial with measurements at baseline, 6 months (after the intervention period), and 12 months. Twenty-four children with bilateral spastic CP and 22 with unilateral spastic CP, aged 7 to 13 years, all walking, participated in this study. Physical fitness was measured by aerobic capacity, anaerobic threshold, anaerobic capacity, and isometric and functional muscle strength. Walking-related PAL was measured using an ankle-worn activity monitor for 1 week. Fatigue was determined with the Pediatric Quality of Life (PedsQL) Multidimensional Fatigue Scale. Longitudinal associations were analyzed by random coefficient regression analysis. In children with bilateral CP, all fitness parameters showed a positive, significant association with walking-related PAL, whereas no associations between physical fitness and walking-related PAL were seen in children with unilateral CP. No clinically relevant association between physical fitness and fatigue was found. Although random coefficient regression analysis can be used to investigate longitudinal associations between parameters, a causal relationship cannot be determined. The actual direction of the association between physical fitness and walking-related PAL, therefore, remains inconclusive. Children with bilateral spastic CP might benefit from improved physical fitness to increase their PAL or vice versa, although this is not the case in children with unilateral CP. There appears to be no relationship between physical fitness and self-reported fatigue in children with CP. Interventions aimed at improving PAL may be differently targeted in children with either bilateral or unilateral CP.

Dynamics of Organizational Identification, Psychological Contract Breach and Prestige During Early Socialization

Though it is well accepted that employees have multiple identities which change over time, little is known about how organizational identification changes and the factors that cause these changes. The study reported in this paper examined the dynamic relationships of organizational identification with psychological contract breach, and perceived organizational prestige during the period of early socialization of newcomers in an organization. This longitudinal research used data from 1346 newcomers in an Indian IT services organization over their early-socialization journey consisting of organizational orientation, technical training and initial project work. Using random coefficient modelling and regression analyses the study shows that change in psychological contract breach is significantly related to change in organizational identification and change in perceived organizational prestige is significantly related to change in organizational identification. The study also shows that psychological contract breach change and perceived organizational prestige change impact organizational identification changes independently. These findings provide new insights to researchers on the lesser known dynamics of organizational identification, psychological contract breach and perceived organizational prestige, while informing practitioners about improving identification through higher focus on fulfilling psychological contracts, and maintaining the perceived prestige of the organization.

Trajectories in functional recovery for patients receiving inpatient rehabilitation for unilateral hip or knee replacement

The purpose of this study was to explore trajectories of recovery in patients with lower extremity joint replacements receiving post-acute rehabilitation. A retrospective cohort design was used to examine data from the Uniform Data System for Medical Rehabilitation (UDSMR®) for 7434 patients with total knee replacement (TKR) and 4765 patients with total hip replacement (THR) who received rehabilitation from 2008 to 2010. Functional Independence Measure (FIM)™ instrument ratings were obtained at admission, discharge, and 80–180 days after discharge. Random coefficient regression analyses using linear mixed models were used to estimate mean ratings for items within the four motor subscales (self-care, sphincter control, transfers, and locomotion) and the cognitive domain of the FIM instrument. Mean improvements at discharge for motor items ranged from 1.16 (95% confidence interval [CI]: 1.14, 1.19) to 2.69 (95% CI: 2.66, 2.71) points for sphincter control and locomotion, respectively. At follow-up mean motor improvements ranged from 2.17 (95% CI: 2.15, 2.20) to 4.06 (95% CI: 4.03, 4.06) points for sphincter control and locomotion, respectively. FIM cognition yielded smaller improvements: discharge=0.47 (95% CI: 0.46, 0.48); follow-up=0.83 (95% CI: 0.81, 0.84). Persons who were younger, female, non-Hispanic white, unmarried, with fewer comorbid conditions, and who received a TKR demonstrated slightly higher functional motor ratings. Overall, patients with unilateral knee or hip replacement experienced substantial improvement in motor functioning both during and up to six months following inpatient rehabilitation.

Sustained Institutional Effects of an Evidence-based HIV Prevention Intervention

Limited data are available as to what happens in institutions involved in behavioral intervention trials after the trial has ended. Specifically, do the trainers continue to administer the behavioral intervention that had been the focus of the trial? To address this question, we examined data in grade six schools before a year-long behavioral intervention had been delivered in some schools (and a year-long control condition in others) and data obtained again 6 and 7years later in the same two sets of schools. Data were derived from the baseline surveys of two interventions: (1) national implementation of the evidence-based Focus on Youth in the Caribbean (FOYC) intervention in 2011; and (2) the randomized, controlled trial of the FOYC intervention in 2004/2005. Cross-sectional, longitudinal comparisons and random coefficient regression analysis were conducted to evaluate long-term intervention effects. Results indicate that grade six students in 2011 from schools in which the FOYC intervention had been implemented in 2004/2005 had a higher level of HIV/AIDS knowledge, increased reproductive health skills, increased self-efficacy regarding their ability to prevent HIV infection, and greater intention to use protection if they were to have sex compared to their counterparts from schools where no such training took place. We concluded that new cohorts of students benefited from the extensive training and/or experience in teaching the FOYC curriculum received by teachers, guidance counselors and administrators in schools which had delivered the FOYC intervention as part of a randomized trial several years earlier. The findings suggest that teachers who previously were trained to deliver the FOYC intervention may continue to teach at least some portions of the curriculum to subsequent classes of students attending these schools.

The impact of depression on abstinence self-efficacy and substance use outcomes among emerging adults in residential treatment.

A large proportion of emerging adults treated for substance use disorder (SUD) present with symptoms of negative affect and major depressive disorder (MDD). However, little is known regarding how these comorbidities influence important mechanisms of treatment response, such as increases in abstinence self-efficacy (ASE). This study tested the degree to which MDD and/or depressive symptoms interacted with during-treatment changes in ASE and examined these variables' relation to outcome at 3 months' posttreatment. Participants (N = 302; 74% male) completed measures at intake, midtreatment, end-of-treatment, and at 3-month follow-up. ASE was measured with the Alcohol and Drug Use Self-Efficacy (ADUSE) scale; depressive symptoms were assessed with the Brief Symptom Inventory 18 (BSI 18) Depression scale; and current MDD diagnoses were deduced from the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV). Random coefficient regression analyses focused on during-treatment changes in ASE, with BSI 18 scores and MDD diagnosis included as moderators. At intake, individuals with MDD or high levels of depressive symptoms had significantly lower ASE, particularly in negative affect situations. No evidence for moderation was found: ASE significantly increased during treatment regardless of MDD status. There was a main effect of BSI 18 Depression scores: those with lower BSI 18 scores had lower ASE scores at each time point. MDD and BSI 18 Depression did not predict 3-month outcome, but similar to previous findings ASE did predict abstinence status at 3 months. Treatment-seeking emerging adults with MDD merit particular clinical attention because of their lower reported self-efficacy throughout treatment.

Walking and Running Economy

The purpose of this study was to test the hypothesis that V˙O2peak is positively correlated with the regression coefficients of the curve-linear relationship between V˙O2 and speed during a protocol consisting of submaximal walking and running. Nineteen healthy men (mean ± SD: age = 26.4 ± 6.4 yr, height = 179.9 ± 7.2 cm, weight = 77.7 ± 8.7 kg, % fat = 16.3 ± 7.3) and 21 healthy women (age = 25.6 ± 4.9 yr, height = 167.2 ± 5.4 cm, weight = 61.6 ± 7.7 kg, % fat = 24.0 ± 6.8) underwent an incremental treadmill test to determine VO2peak and on two separate days performed an exercise protocol consisting of treadmill walking on a level grade at 2.0 mph (54 m·min−¹), 3.0 mph (80 m·min−¹), and 4.0 mph (107 m·min−¹) and running at 6.0 mph (161 m·min−¹). Subjects exercised for 5 min at each velocity, with 3 min of rest in between each exercise bout. Pulmonary ventilation (VE) and gas exchange were measured breath-by-breath each minute. The average of VO2 values obtained during the last 2 min of exercise for both exercise sessions was used in polynomial random coefficient regression analysis. In the polynomial random coefficient regression analysis for walking speeds only, both linear (r = 0.31, P = 0.053) and quadratic (r = 0.35, P = 0.029) coefficients were modestly correlated with VO2peak. Steady-state VO2 during walking at 3.0 and 4.0 mph and running at 6.0 mph was also modestly correlated with VO2peak (r = 0.30-0.48). The results confirm our hypothesis and suggest that, as walking speed increases, the increase in VO2 is positively correlated with the VO2peak. Our findings are consistent with the notion that cardiorespiratory fitness and exercise economy are inversely related.

Trends in Pulmonary Function and Prevalence of Asthma in Hexamethylene Diisocyanate Workers During a 19-Year Period

To identify if 1,6-hexamethylene diisocyanate (HDI) workers demonstrated an increased prevalence of occupational asthma or accelerated decline in pulmonary function. Employees from two plants manufacturing or producing 1,6-HDI monomer and/or HDI polyisocyanates were matched to a control population by age, gender, race, and smoking status. A random coefficient regression analysis compared the decline in pulmonary function test values over time. Retrospective medical review was used to identify potential cases of occupationally induced asthma. No significantly accelerated annual decline in force expiratory volume after 1 second in the HDI exposure group compared to the matched control group was observed. No cases of adult onset asthma, beyond those present at time of hire, and no cases of occupational asthma were identified. This study provides support for the current American Conference of Governmental Industrial Hygienists threshold limit value time-weighted average of 5 ppb.

Longitudinal changes in drug use severity and physical health-related quality of life among untreated stimulant users

The primary objective of this study was to investigate whether drug use severity is associated with physical health-related quality of life (HRQL) over time. Data are from a longitudinal, multi-state, natural history community study of users of cocaine and/or methamphetamine who were interviewed at 6-month intervals over 2 years with a 79% follow-up participation rate. Physical HRQL was assessed with the physical component summary (PCS) of the SF-8™ Health Survey and drug, alcohol, and psychiatric severity were all assessed with the Addiction Severity Index (ASI). Random coefficient regression analyses were conducted to test for longitudinal associations between the independent variables and SF-8 PCS scores. Reductions in drug use severity over time were accompanied by only minor improvements in SF-8 PCS scores, underscoring the potential long-term harm of illicit drug use on physical health. Greater psychiatric severity was strongly associated with lower SF-8 PCS scores, suggesting that clinical attention to mental health issues could potentially lead to improvements in perceived physical health as well as among stimulant users.

The influence of parents and peers on adolescent indoor tanning behavior: Findings from a multi-city sample

Indoor tanning is common among adolescents. Our purpose was to examine the influence of parents and peers on adolescent indoor tanning. Telephone interviews were conducted with 5274 teen-parent pairs in the 100 largest US cities. Random coefficient regression analyses were conducted to examine the relationship between parental and peer factors and adolescent indoor tanning. Teens' report of whether their parents allow them to tan indoors was the strongest predictor (adjusted odds ratio [aOR]: 5.6), whereas parents' modeling (aOR: 1.2), attitudes (aOR: 1.1), and concern about teen tanning (aOR: 1.9) were significantly but less strongly associated. Teens thinking most of their peers like to be tan (aOR: 1.7) and perceived percentage of peers who tan indoors (aOR: 1.0) also were significantly associated. The cross-sectional design was a limitation of this study. Interventions targeting adolescent indoor tanning should address both family- and peer-related factors.

Impact of Varying Levels of Protein Intake on Protein Status Indicators after Gastric Bypass in Patients with Multiple Complications Requiring Nutritional Support

<6% of patients who undergo Roux-en-Y gastric bypass (RYGBP) for morbid obesity require nutritional support after surgery. Protein and caloric needs have been estimated as 14-21 kcal, 1.2 g protein/kg/current body weight/day in uncomplicated morbidly obese patients. This study assesses the effect of varying protein-calorie intake in complicated patients after RYGBP on two markers of protein status: thyroxine-binding prealbumin (TBPA) and serum albumin. This 25-month retrospective study consisted of 22 patients with postoperative complications. Serum albumin, TBPA, medical nutrition care-plans, laboratory data and history were reviewed. These post-RYGBP patients who had BMI>35 and no multi-system organ failure or fistulas, had complications after surgery requiring nutrition support services (NSS). Serum albumin and TBPA were matched to fed levels of protein using random coefficient regression analysis. Mean incremental increases of 2.34 mg/dl (TBPA, P=0.0113) and 0.11 g/dl (serum albumin, P=0.0272) were found with each 0.5 g protein intake increase/kg ideal body weight/day (kg/IBW/day). Patients required NSS for 23+/-21 (mean+/-SD) days, with 15+/-19 days fed at goal rate. Initial serum albumin was 2.3+/-0.5, with a final measure of 2.7+/-0.5 g/dl. Goal protein and calorie intake were 2.1 g and 17 kcal/kg IBW/day versus actual intake of 1.6 g and 13 kcal/kg IBW/day. Morbidly obese patients requiring NSS following RYGBP risk iatrogenic protein malnutrition. There was a positive linear relationship between protein status and protein intake that warrants further study of higher protein feeding in complicated post-RYGBP patients.

Factors influencing quality of life in breast cancer survivors.

Longitudinal data from 195 breast cancer survivors were used to identify factors affecting the level and rate of change in quality of life after completion of treatment. Women were interviewed up to four times at approximately yearly intervals using Kaplan and Bush's Quality of Well Being instrument (QWB). Random coefficient regression analysis was used to model QWB as a function of time since diagnosis and personal characteristics. QWB scores decreased over time and the rate of decline increased with age (p = 0.032). This was similar to declines in women with benign breast biopsies, but overall QWB levels were lower in women with breast cancer. Having a spouse tended to slow the rate of decline in breast cancer survivors (p = 0.004). The presence of comorbidity was associated with significantly lower QWB levels (p = 0.037) but did not affect the rate of change over time. Education, family history of breast cancer, cancer stage and treatment modalities were not significantly related to QWB levels or rates of change. Breast cancer survivors experience a reduction in quality of life that persists for years after treatment and is similar in magnitude to that associated with other health problems.

Short-term estradiol supplementation augments growth hormone (GH) secretory responsiveness to dose-varying GH-releasing peptide infusions in healthy postmenopausal women.

Estrogen is a prominent stimulus to GH secretion throughout the human life span, albeit via neuroendocrine mechanisms that are incompletely defined. Here, we test the hypothesis that estradiol replacement in postmenopausal women enhances the responsiveness of the hypothalamo-pituitary unit to the GH-releasing effect of GH-releasing peptide-2 (GHRP-2). GHRP-2 is a potent and selective synthetic hexapeptide capable of activating an endogenous GHRP receptor/effector pathway, for which a (3)Ser-octanoylated 28-amino acid ligand was cloned recently. To examine this postulate, we studied 10 healthy estrogen-withdrawn postmenopausal women, who were given oral placebo or estrogen supplementation [1 mg micronized 17 beta-estradiol (E(2)) twice daily for 7-15 days] in a patient-blinded, prospective, randomized, and within-subject cross-over design. The GH-releasing actions of five semilogarithmically increasing doses of GHRP-2 (absolute range, 0.03-3 microg/kg by bolus iv infusion) vs. saline were evaluated by frequent blood sampling on separate days in the morning while fasting. Serum GH concentrations were determined in blood sampled every 10 min using an ultrasensitive chemiluminescence assay and analyzed by multiparameter deconvolution to calculate the summed mass of GH secreted during the 2-h interval after bolus GHRP-2 infusion. Logarithmically transformed secretory responses were compared across the different dosages of infused GHRP-2 by two-way repeated measures ANOVA. Estradiol replacement increased the global mean (+/-SEM) serum E(2) concentration from 15 +/- 0.8 to 470 +/- 17 pg/mL (55 +/- 2.9 to 1725 +/- 62 pmol/L; P = 0.004) and lowered insulin-like growth factor I levels by approximately 27% (P = 0.087). Administration of E(2) elevated the geometric mean basal (saline-infused) GH secretory burst mass by 2.1-fold (95% confidence interval, 1.4- to 3.1-fold) compared with placebo ingestion (geometric mean ratios; P < 0.001). E(2) exposure enhanced the efficacy of the highest GHRP-2 dose tested (3 microg/kg) by 2.1-fold (1.3- to 3.3-fold; P = 0.010). Compared with the effect of placebo and saline, E(2) combined with the highest dose of GHRP-2 stimulated GH secretory burst mass by a total of 31-fold (24- to 41-fold; P < 0.001). Random coefficient regression analysis of the relationship between the logarithm of GHRP-2 dose and GH secretory burst mass revealed that E(2) significantly augmented the amount of GH secreted per unit GHRP-2 dose (E(2), 16.6 +/- 1.8 slope units; placebo, 10.1 +/- 1.4 slope units; P = 0.03). Although the global mean endogenous GH half-life did not differ between the E(2) and placebo sessions (E(2), 18 +/- 0.6 min; placebo, 17 +/- 0.5 min), GH half-life varied directly with dose of GHRP-2 (and, hence, the mean serum GH concentration) in both the E(2) and placebo sessions (test of zero slope hypothesis, P = 0.0018). The deconvolved GH secretory burst peaked within 8-13 min of the bolus iv injection of GHRP-2, and this latency was not altered by E(2). Based on a mixed effects analysis of covariance model, GHRP-2 dose and E(2), but not the plasma insulin-like growth factor I concentration, determined the magnitude of the GH secretory response (P < 0.001). We conclude that short-term oral E(2) repletion in postmenopausal women selectively augments GH secretory pulse mass, enhances the steepness of the GHRP-2 dose-GH secretory response relationship (greater sensitivity), and heightens the maximal GH secretory response to the highest dose of GHRP-2 tested (greater efficacy). These data point to a facilitative interaction between E(2) and the GHRP receptor/effector pathway in driving the mass of GH secreted per burst.

The acute-phase response varies with time and predicts serum albumin levels in hemodialysis patients

Cross sectional studies have established that the serum albumin level is dependent on serum levels of acute-phase proteins (APPs) or cytokine levels in hemodialysis patients. While the acute-phase response is generally associated with acute inflammatory events, a cross sectional analysis relating laboratory values to outcomes assumes these values to be unchanging. The longitudinal relationship among laboratory measurements and how they vary over time in a population of patients are unknown. Patients who were enrolled in the HEMO Study were recruited into an ancillary longitudinal study to establish the predictive effect of temporal variation in the levels of APPs and of temporal variation in normalized protein catabolic rate (nPCR) on the serum albumin concentration. nPCR was measured monthly using a double-pool method. The positive APPs-C-reactive protein (CRP), alpha1 acid glycoprotein (alpha1-AG), and ceruloplasmin-and the negative APP-transferrin (Trf)-were measured in serum obtained before each dialysis session for six weeks and then monthly in 37 hemodialysis patients. A random coefficient regression analysis was used to assess the association of serum albumin with other measured parameters at each time point, as well as fixed patient characteristics. The within-subject coefficients of variation of albumin (median, range of 25th to 75th percentiles; median, 0.0614; range, 0.0485 to 0.0690) were significantly less than that of APPs (CRP, median, 0.878; range, 0.595 to 1.314, P < 0. 05; and alpha1 AG, median, 0.173; range, 0.116 to 0.247, P < 0.05). The levels of APPs and albumin varied considerably over time. The primary predictor of current albumin was the current CRP level (P = 0.0014). nPCR also was a significant predictor for albumin levels (P = 0.0440) after controlling for the effect of APPs, suggesting an effect of nPCR on serum albumin concentration irrespective of the acute-phase response. Age and the presence of an arteriovenous graft were significant predictors that were associated with reduced albumin. The acute-phase response is intermittent and is not a continuous feature in individual dialysis patients. Levels of APPs are the most powerful predictors for the levels of albumin concentration in hemodialysis in a longitudinal setting. Since variations in albumin are small, measurement of variations in APPs may provide greater insight into the dynamics of clinically relevant processes.