Biomedical subjects

S Demissie

Publications and source records attributed to S Demissie.

At least 19 recordsLinked to original sources

PubMed2002

Association between the PPARA L162V polymorphism and plasma lipid levels: the Framingham Offspring Study.

Peroxisome proliferator activated receptor (PPAR) alpha is a member of the nuclear receptor superfamily that regulates key proteins involved in fatty acid oxidation, extracellular lipid metabolism, hemostasis, and inflammation. A L162V polymorphism at the PPARA locus has been associated with alterations in lipid and apolipoprotein concentrations. We studied the association among lipids, lipoproteins, and apolipoproteins and the presence of the L162V polymorphism in 2373 participants (1128 men and 1244 women) in the Framingham Offspring Study. The frequency of the less common allele (V162) was 0.069. The V162 allele was associated with increased serum concentrations of total and LDL cholesterol in men (P=0.0012 and P=0.0004, respectively) and apolipoprotein B in men (P=0.009) and women (P=0.03 after adjustment for age, body mass index, smoking, and use of beta-blockers, diuretics or estrogens). Apolipoprotein (apo) C-III concentrations were higher in carriers of the V162 allele. The association of the L162V polymorphism on LDL cholesterol concentration was greatest in those who also carried the E2 allele at the APOE locus and the G allele at the APOC3 3238C>G polymorphism. This suggests that alterations in triglyceride-rich lipoprotein metabolism may be involved in the generation of the increase in LDL cholesterol observed with the L162V PPARA polymorphism.

Amino Acid Substitution↗

PubMed2002

Genome scan for quantity of hand osteoarthritis: the Framingham Study.

OBJECTIVE: To search for markers linked to quantity of radiographic hand osteoarthritis (OA) in the Framingham Heart Study. METHODS: The sample included 684 original cohort members and 793 offspring in 296 pedigrees. Radiographic OA features evaluated included the Kellgren/Lawrence (K/L) score, osteophytes, and joint space narrowing (0-3 scale). Four quantitative phenotypes were computed from these measurements: sum of K/L scores across hand joints, sum of osteophyte scores, sum of joint space narrowing scores, and proportion of affected joints. Prior to linkage analysis, these phenotypes were adjusted for age using a linear regression analysis from which standardized residuals were computed. The regression analysis was performed separately for each sex and each generation. The variance component model (SOLAR) was then applied to the normalized scores of the residuals. RESULTS: The average age was 62 years for the original cohort and 54 years for the offspring. Fifty percent of the original cohort and 30% of their offspring had at least 1 affected joint (K/L score >or=2). Heritability ranged from 28% (proportion of joints affected with OA) to 34% (sum of K/L scores). Eight chromosomal regions indicated suggestive linkage (multipoint logarithm of odds [LOD] score >1.5) for at least 1 phenotype; LOD scores were highest for joint space narrowing, with a multipoint LOD score = 2.96 on chromosome 1p at D1S1665. Chromosomes 7, 9, 13, and 19 indicated consistent LOD score elevation for multiple OA phenotypes. CONCLUSION: There are several chromosomes that may harbor OA susceptibility genes. Further investigation of these regions using larger studies and finer maps will be important to confirm linkage.

Adult↗

PubMed2002

The internal validity of a dietary pattern analysis. The Framingham Nutrition Studies.

STUDY OBJECTIVES: To examine the internal validity of a dietary pattern analysis and its ability to discriminate clusters of people with similar dietary patterns using independently assessed nutrient intakes and heart disease risk factors. DESIGN AND PARTICIPANTS: Population based study characterising dietary patterns using cluster analysis applied to data from the semiquantitative Framingham food frequency questionnaire collected from 1942 women ages 18-76 years, between 1984-88. SETTING: Framingham, Massachusetts. MAIN RESULTS: Of 1942 women included in the cluster analysis, 1828 (94%) were assigned to one of the five dietary pattern clusters: Heart Healthy, Light Eating, Wine and Moderate Eating, High Fat, and Empty Calorie. Dietary patterns differed substantially in terms of individual nutrient intakes, overall dietary risk, heart disease risk factors, and predicted heart disease risk. Women in the Heart Healthy cluster had the most nutrient dense eating pattern, the lowest level of dietary risk, more favourable risk factor levels, and the lowest probability of developing heart disease. Those in the Empty Calorie cluster had a less nutritious dietary pattern, the greatest level of dietary risk, a heavier burden of heart disease risk factors, and a relatively higher probability of developing heart disease. Cluster reproducibility using discriminant analysis showed that 80% of the sample was correctly classified. The cluster technique was highly sensitive and specific (75% to 100%). CONCLUSIONS: These findings support the internal validity of a dietary pattern analysis for characterising dietary exposures in epidemiological research. The authors encourage other researchers to explore this technique when investigating relations between nutrition, health, and disease.

Adolescent↗

PubMed2001

Effects of race and hypertension on flow-mediated and nitroglycerin-mediated dilation of the brachial artery.

Black Americans have increased morbidity and mortality rates from cardiovascular disease, greater prevalence of hypertension, and altered responses to vasodilator medications compared with those of white Americans. Hypertension and black race have been linked to impaired vascular function in the microcirculation. To examine these effects and their interaction in the conduit vasculature, we examined vasomotor responses of the brachial artery by using high-resolution vascular ultrasound in 228 subjects (48% hypertensive, 54% black). Subjects had no history of diabetes mellitus and were matched for age and gender. Flow-mediated dilation (8.5+/-5.3% versus 11.7+/-6.3%, P<0.001) and nitroglycerin-mediated vasodilation (14.9+/-6.0 versus 18.5+/-7.8, P=0.003) were both impaired in hypertensive compared with normotensive individuals. Multivariate analysis identified higher systolic blood pressure (P=0.003) and larger baseline vessel (P<0.001) size as independent predictors of lower flow-mediated dilation. Race did not significantly influence flow-mediated dilation. In contrast, blacks had a greater vasodilator response to nitroglycerin compared with whites (17.7+/-7.5% versus 15.0+/-6.2%, respectively; P=0.02). By multivariate analysis, black race (P=0.004), smaller vessel size (P=0.001), lower serum glucose (P=0.02), lower systolic blood pressure (P=0.02), and lower serum total cholesterol (P=0.04) were independent predictors of higher nitroglycerin-mediated dilation. Thus, hypertension is associated with impaired NO-mediated vasodilation in the conduit brachial artery. Overall, race did not influence flow-mediated dilation, but black race was associated with an enhanced response to sublingual nitroglycerin. This later observation provides further evidence of racial differences in the responses to medical therapy that may be relevant to the treatment of patients with cardiovascular disease.

Adult↗

PubMed2001

Adjuvant tamoxifen: predictors of use, side effects, and discontinuation in older women.

PURPOSE: To identify predictors of adjuvant tamoxifen use, side effects, and discontinuation in older women. PATIENTS AND METHODS: We followed a cohort of 303 women > or = 55 years of age diagnosed with stage I or stage II breast cancer for nearly 3 years. Data were collected from women's surgical records and from computer-assisted telephone interviews at 5, 21, and 33 months after primary tumor therapy. RESULTS: Two hundred ninety-two (96%) of 303 patients in the study provided information about tamoxifen use. Tamoxifen use was reported by 189 patients (65%); 26 (15%) discontinued use during the follow-up period. Patients who were 65 to 74 years of age (relative to those 55 to 64 years of age), had stage II disease, were estrogen receptor-positive, saw a greater number of breast cancer physicians, and had better perceptions of their abilities to discuss treatment options with physicians had greater odds of tamoxifen use. Those who had better physical function, had received standard primary tumor therapy, and had obtained helpful breast cancer information from books or magazines had lesser odds of tamoxifen use. Patients > or = 75 years of age (relative to those 55 to 64 years of age) and patients with better emotional health had significantly lesser odds of reporting side effects. Patients who were estrogen receptor-positive were less likely to stop taking tamoxifen; patients who experienced side effects were more likely to stop taking tamoxifen. CONCLUSION: Deviations from a prescribed course of adjuvant tamoxifen occur relatively frequently. The clinical consequences of this deviation need to be identified.

Aged↗

PubMed2001

Family-based association tests for qualitative and quantitative traits using single-nucleotide polymorphism and microsatellite data.

Using the Genetic Analysis Workshop 12 simulated data, we contrasted results for association tests in nuclear families and extended pedigrees using single-nucleotide polymorphism (SNP) data, and we compared results for different trait definitions, for outbred and isolate populations, and for SNP and microsatellite data. SNPs in major genes 1 and 6 were analyzed using transmission disequilibrium testing (TDT) [Spielman et al., Am J Hum Genet 52:506-16, 1993], sibship disequilibrium testing (SDT) [Horvath and Laird, Am J Hum Genet 63:1886-97, 1998], family-based association testing (FBAT) [Horvath et al., Eur J Hum Genet 9:301-6, 2001], and a chi-square analysis of founders. TDT and SDT were applied in a sample of independent nuclear families, while FBAT was applied in extended pedigrees. SNPs and microsatellites were analyzed with dichotomous and quantitative trait definitions using FBAT in the isolate and outbred populations. The results of the TDT, SDT, and FBAT analyses are comparable using SNP data to identify the disease gene. However, these tests of association were not helpful in discriminating between functional and non-functional SNPs in disequilibrium. SNP data were able to identify association with affection status in a gene that influences the liability directly (MG6), but did not perform as well when assessing association with affection status in a gene that influences the outcome only through a quantitative trait (MG1). Association with MG1 was observed using the SNP data when the outcome was defined quantitatively. Microsatellite data were relatively unsuccessful in identifying association with the markers in the region of a major gene. The magnitude of the associations between SNPs and the dichotomous or quantitative trait definitions were similar in the outbred and isolated populations.

Adult↗

PubMed2001

Influence of marker heterozygosity and genetic heterogeneity on fine mapping.

The purpose of the current study was to utilize the Genetic Analysis Workshop 12 simulated data to evaluate fine-mapping strategies for quantitative traits. We approached the analysis as if it was a follow-up to a genome scan that had identified two regions of interest and used the provided 1-cM density microsatellite typing data to mimic fine mapping of these regions. As these investigators knew the true locations of the putative genes under study, we explored the effects of the informativeness of microsatellite markers (marker heterozygosity) and the effects of genetic heterogeneity across families for ten replicates of the data. These results shed a cautionary light on the reliability of fine-mapping efforts on refining mapping locations as the position and the strength of the lod score can be markedly affected by the sampling of the population, the amount of variation accounted for by the gene, and the informativeness of the marker. Our studies did not reveal a large effect of unlinked families on the shape of the lod score peak.

Chromosome Mapping↗

PubMed2001

Validation of a dietary pattern approach for evaluating nutritional risk: the Framingham Nutrition Studies.

OBJECTIVE: To validate the use of cluster analysis for characterizing population dietary patterns. DESIGN: Cluster analysis was applied to a food frequency questionnaire to define dietary patterns. Independent estimates of nutrient intake were derived from 3-day food records. Heart disease risk factors were assessed using standardized protocols in a clinic setting. SETTING: Adult women (n = 1,828) participating in the Framingham Offspring-Spouse study. STATISTICAL ANALYSES: Age-adjusted mean nutrient intakes were determined for each cluster. Analysis of covariance was used to evaluate pairwise differences in intake across clusters. Compliance with published recommendations was determined for selected heart disease risk factors. Differences in age-adjusted compliance across clusters were evaluated using logistic regression. RESULTS: Cluster analysis identified 5 distinct dietary patterns characterized by unique food behaviors and significantly different nutrient intake profiles. Patterns rich in fruits, vegetables, grains, low-fat dairy, and lean protein foods resulted in higher nutrient density. Patterns rich in fatty foods, added fats, desserts, and sweets were less nutrient-dense. Women who consumed an Empty Calorie pattern were less likely to achieve compliance with clinical risk factor guidelines in contrast to most other groups of women. CONCLUSIONS: Cluster analysis is a valid tool for evaluating nutrition risk by considering overall patterns and food behaviors. This is important because dietary patterns appear to be linked with other health-related behaviors that confer risk for chronic disease. Therefore, insight into dietary behaviors of distinct clusters within a population can help to design intervention strategies for prevention and management of chronic health conditions including obesity and cardiovascular disease.

Aged↗

PubMed2001

Association of the Sst-I polymorphism at the APOC3 gene locus with variations in lipid levels, lipoprotein subclass profiles and coronary heart disease risk: the Framingham offspring study.

Apolipoprotein (apo) CIII participates in the regulation of the metabolism of triglyceride-rich lipoproteins and it is a major component of chylomicrons and VLDL. The APOC3 gene is on chromosome 11q23 and is highly polymorphic. The less common allele (S2) of the SstI polymorphism on the 3' untranslated region of the APOC3 gene has been previously associated with increased triglycerides, total cholesterol (TC), and apoCIII levels and cardiovascular risk on several, but not all, studies. The aim of this study was to examine the association of this polymorphism with plasma lipid levels, lipoprotein subfractions and coronary heart disease (CHD) risk in a population-based study: The Framingham Offspring Study. The frequency of the S2 allele was 0.086, consistent with previous reports in Caucasian populations. In men, the S2 allele was associated with lower concentrations of high-density lipoprotein cholesterol (HDL-C; P<0.04) and HDL2-C (P<0.02) and a significant increase in apoCIII non-HDL (P<0.05). TG levels were higher in men carriers of the S2 allele, but this association did not reach statistical significance (P=0.30). Conversely, in women, the S2 allele was associated with increased TC (P<0.03), low-density lipoprotein cholesterol (LDL-C; P<0.03), and ApoB levels (P<0.04). Lipoproteins subfractions were also examined using nuclear magnetic resonance (NMR) spectroscopy. S2 male carriers had significantly lower concentrations of large LDL and a significant reduction in LDL particle size (P<0.04). In women, there was a significant increase in intermediate LDL particles (P<0.05) with no significant effect on lipoprotein diameters. We also examined the associations between the S2 allele and biochemical markers of glucose metabolism. In men, the S2 allele was associated with elevated fasting insulin concentrations (P<0.04), whereas no significant associations were observed in women. Despite the described associations with lipid and glucose metabolism related risk factors, we did not find any significant increase in CHD risk associated with the S2 allele in this population.

Alleles↗

PubMed2001

Cultural identification and alcohol use among "Black" adolescents.

This study examined the relationship between cultural identification and alcohol use among Black adolescents--77 African-American and 185 Haitian Black adolescents. The Orthogonal Cultural Identification Scale assessed cultural identification. A logistic regression analysis was used to evaluate the association between cultural identification association between cultural identification, friendships, and alcohol use. Results indicate no relationship between cultural identification and alcohol use. Drinking during the past six months was significantly associated with having close friends who drink. Although the direction of friend influence is unclear. Differences were observed in the context of drinking between the two groups and, importantly, youths in both groups reported drinking alone and to relax/because of stress. Sociocultural factors, context and the basis of drinking need to be addressed in programs for youth.

Adolescent↗

PubMed2001

Reliability of information collected by proxy in family studies of Alzheimer's disease.

The study evaluated the reliability of data obtained from proxy informants. The index subjects in this study were 81 nondemented participants in the Multi-Institutional Research in Alzheimer Genetic Epidemiology (MIRAGE) study. These index subjects and 159 proxy informants, identified by the index subjects, participated in the study. The kappa statistic with multiple raters per subject (for dichotomous variables) and the intraclass correlation coefficient (for continuous variables) were used to measure reliability. Among proxy respondents who provided answers, there was excellent agreement between proxy responses and the responses of the index subjects (0.7 < or = kappa < or =0.9), with the exception of questions about head injury (kappa = 0.4). A large proportion (>90%) of the proxy informants in this study were able to provide information on most items. Higher nonresponse rates (as high as 30%) were observed for medication history and women's health questions. This study supports the reliability of proxy responses for most categories of questions that are elicited in typical epidemiological studies, including the MIRAGE study.

Aged↗

PubMed2000

Effects of early inhaled beclomethasone therapy on tracheal aspirate inflammatory mediators IL-8 and IL-1ra in ventilated preterm infants at risk for bronchopulmonary dysplasia.

We tested the hypothesis that inhaled beclomethasone therapy for prevention of bronchopulmonary dysplasia (BPD) reduces pulmonary inflammation. As part of a randomized, placebo-controlled trial, interleukin-8 (IL-8) and interleukin-1 receptor antagonist (IL-1ra) concentrations in tracheal aspirates were measured as markers of pulmonary inflammation. On study days 1 (baseline), 8, 15, and day 28 of age, samples were obtained from enrolled infants (birth weights <1,251 g, gestational age <33 week, 3 to 14 days of age) who remained ventilated and had not received systemic glucocorticoid therapy. Cytokine levels (pg/microg of free secretory component of immunoglobulin A) were compared between groups. We determined whether baseline cytokine levels modified treatment effect regarding subsequent need for systemic glucocorticoid therapy or occurrence of BPD (age 28 days). Tracheal aspirates were obtained from 161 infants (77 receiving beclomethasone, 84 receiving placebo). Median IL-8 levels were lower in beclomethasone versus placebo infants on study days 8 (82.9 vs. 209.2, P < 0.01) and 15 (37.4 vs. 77.4, P < 0.03) after controlling for antenatal glucocorticoid therapy and maternal race. Median IL-1ra levels were lower in beclomethasone versus placebo infants only on study day 8 (86.5 vs. 153.3, P < 0.01). Fewer beclomethasone infants with baseline IL-8 levels in the interquartile range required systemic glucocorticoid therapy (beclomethasone 30.6% vs. placebo 65.8%, P < 0.01) or developed BPD (beclomethasone 42.4% vs. placebo 69.4%, P < 0.03). We conclude that early-inhaled beclomethasone therapy was associated with a reduction in pulmonary inflammation after 1 week of therapy. Beclomethasone-treated infants with moderately elevated baseline IL-8 levels received less subsequent systemic glucocorticoid therapy and had a lower incidence of BPD than nontreated infants.

Administration, Inhalation↗

PubMed2000

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Journal Article↗

PubMed2000

What can we do to improve physical function in older persons with type 2 diabetes?

BACKGROUND: Older persons with type 2 diabetes are at higher risk for functional impairment than are their age-matched counterparts without-diabetes. We therefore sought to identify factors associated with impaired physical function in older persons with type 2 diabetes by using a cross-sectional study design. METHODS: We studied 1238 persons with type 2 diabetes who were 55 years of age or older and enrolled in the Type II Diabetes Patient Outcomes Research Team (PORT) project. Subjects were primary care patients at a large staff model health maintenance organization who had completed a mailed survey that collected information about demographics (age, race, marital status, income, education, gender, and body mass index [BMI]), health behaviors (exercise, smoking, and alcohol), care and control of diabetes (therapy, self-reported glucose control, home glucose monitoring, and disease duration), mood (Center for Epidemiologic Studies--Depression Scale [CES-D]), comorbidity, and the Short-Form-36 health survey (SF-36). We evaluated the bivariate relationships between the PFI- 10, a 10-item measure of physical function from the SF-36, and candidate independent variables from the domains described previously. Variables that were significant at an a level of .10 were entered into a multiple linear regression model. RESULTS: There were eight independent predictors of impaired physical function (all p < .05, R2 = .40). Factors associated with impaired function in order of their relative importance were as follows: a higher comorbidity score, older age, obesity, lack of regular exercise, CES-D score higher than 20, taking insulin, lower formal education, and abstinence from alcohol. CONCLUSIONS: Increased comorbidity and older age are associated with poorer function, as is the severity of diabetes and less formal education. Exercise, lower BMI, and better mood are associated with better function. Therefore, promoting regular exercise and weight loss, in addition to treating depression, are likely to preserve or even improve the functional status of older persons with type 2 diabetes. Moderate alcohol use may be beneficial as well. The extent to which these relationships persist in prospective studies or clinical trials remains to be evaluated.

Activities of Daily Living↗

PubMed2000

The North Carolina Black Churches United for Better Health Project: intervention and process evaluation.

The North Carolina Black Churches United for Better Health project was a 4-year intervention trial that successfully increased fruit and vegetable (F&V) consumption among rural African American adults, for cancer and chronic disease prevention. The multicomponent intervention was based on an ecological model of change. A process evaluation that included participant surveys, church reports, and qualitative interviews was conducted to assess exposure to, and relative impact of, interventions. Participants were 1,198 members of 24 intervention churches who responded to the 2-year follow-up survey. In addition, reports and interviews were obtained from 23 and 22 churches, respectively. Serving more F&V at church functions was the most frequently reported activity and had the highest perceived impact, followed by the personalized tailored bulletins, pastor sermons, and printed materials. Women, older individuals, and members of smaller churches reported higher impact of certain activities. Exposure to interventions was associated with greater F&V intake. A major limitation was reliance on church volunteers to collect process data.

Adult↗

PubMed1999

Early inhaled glucocorticoid therapy to prevent bronchopulmonary dysplasia.

BACKGROUND: The safety and efficacy of inhaled glucocorticoid therapy for asthma stimulated its use in infants to prevent bronchopulmonary dysplasia. We tested the hypothesis that early therapy with inhaled glucocorticoids would decrease the frequency of bronchopulmonary dysplasia in premature infants. METHODS: We conducted a randomized, multicenter trial of inhaled beclomethasone or placebo in 253 infants, 3 to 14 days old, born before 33 weeks of gestation and weighing 1250 g or less at birth, who required ventilation therapy. Beclomethasone was delivered in a decreasing dosage, from 40 to 5 microg per kilogram of body weight per day, for four weeks. The primary outcome measure was bronchopulmonary dysplasia at 28 days of age. Secondary outcomes included bronchopulmonary dysplasia at 36 weeks of postmenstrual age, the need for systemic glucocorticoid therapy, the need for bronchodilator therapy, the duration of respiratory support, and death. RESULTS: One hundred twenty-three infants received beclomethasone, and 130 received placebo. The frequency of bronchopulmonary dysplasia was similar in the two groups: 43 percent in the beclomethasone group and 45 percent in the placebo group at 28 days of age, and 18 percent in the beclomethasone group and 20 percent in the placebo group at 36 weeks of postmenstrual age. At 28 days of age, fewer infants in the beclomethasone group than in the placebo group were receiving systemic glucocorticoid therapy (relative risk, 0.6; 95 percent confidence interval, 0.4 to 1.0) and mechanical ventilation (relative risk, 0.8; 95 percent confidence interval, 0.6 to 1.0). CONCLUSIONS: Early beclomethasone therapy did not prevent bronchopulmonary dysplasia but was associated with lower rates of use of systemic glucocorticoid therapy and mechanical ventilation.

Administration, Inhalation↗

PubMed1999

Adrenal function in premature infants during inhaled beclomethasone therapy.

OBJECTIVE: We tested the hypothesis that inhaled beclomethasone therapy for prevention of bronchopulmonary dysplasia does not cause adrenal suppression. STUDY DESIGN: Infants receiving ventilatory support with birth weights </=1250 g and born at <33 weeks' gestation, age 3 to 14 days, were enrolled in a multicenter randomized trial to study the efficacy and safety of beclomethasone therapy versus placebo for prevention of bronchopulmonary dysplasia. Adrenal function was assessed on study day 21 (+/- 2 days) by determination of basal and stimulated plasma cortisol levels. Initially, cortisol response was assessed with insulin-induced hypoglycemia test (IIHT) (n = 63) until an interim analysis revealed insignificant cortisol response in both study groups. Thereafter, cosyntropin stimulation was used (n = 85). RESULTS: Beclomethasone therapy was associated with lower median basal cortisol levels (5 microg/dL beclomethasone, 6 microg/dL placebo, P =.04). IIHT revealed insignificant change in cortisol response within each group. Cortisol response to cosyntropin stimulation was similar for each group (17 microg/dL beclomethasone, 18 microg/dL placebo, P =.86). CONCLUSION: Beclomethasone therapy was associated with a small decrease in basal cortisol levels. There was no evidence of adrenal suppression in response to cosyntropin stimulation during beclomethasone therapy. Lack of cortisol response to hypoglycemia may reflect missed timing and/or decreased response of the premature infants' hypothalamic-pituitary-adrenal axis to hypoglycemia.

Administration, Inhalation↗

PubMed1999

Varying the message source in computer-tailored nutrition education.

The effect of message source on message recall and perceived credibility was examined in a randomized study comparing two different computer-tailored bulletins promoting fruit and vegetable consumption among rural African American church members. An expert oriented (EXP) bulletin was compared with a spiritual and pastor-oriented (SPIR) bulletin and a control group. Both bulletins had the same format and used an identical set of dietary and psychosocial variables for tailoring. At follow-up, the majority of both intervention groups recalled receiving the bulletin, however message trust was higher in the SPIR group (P < 0.05). The EXP group reported higher trust of health and nutrition information coming from scientific research (P < 0.01), and the SPIR group reported higher trust of information coming from the pastor (P < 0.05). Both bulletin groups increased fruit and vegetable consumption significantly compared to the control group; however, this difference could not be solely attributed to the tailored intervention which was part of a multi-component program.

Adolescent↗