13 resultados para Spatial pattern and association

em DigitalCommons@The Texas Medical Center


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Background: Children's active commuting to school, i.e. walking or cycling to school, was associated with greater moderate-to-vigorous physical activity, although studies among ethnic minorities are sparse. Objectives: Among a low-income, ethnic minority sample of fourth grade students from eight public schools, we examined (1) correlates of active commuting to school and (2) the relationship between active commuting to school and moderate-to-vigorous physical activity. Methods: We conducted a cross-sectional analysis of baseline measurements from a sample of participants (n=149) aged 9-12 years from a walk to school intervention study in Houston, Texas. The primary outcome was the weekly rate of active commuting to school. Daily moderate-to-vigorous physical activity, measured by accelerometers, was a secondary outcome. Child self-efficacy (alpha=0.75), parent self-efficacy (alpha=0.88), and parent outcome expectations (alpha=0.78) were independent variables. Participant characteristics (age, gender, race/ethnicity, distance from home to school, acculturation, and BMI percentile) were independent sociodemographic variables. We used mixed-model regression analyses to account for clustering by school and a stepwise procedure with backward elimination of non-significant interactions and covariates to identify significant moderators and predictors. School-level observations of student pedestrians were assessed and compared using chi-square tests of independence. Results: Among our sample, which was 61.7% Latino, the overall rate of active commuting to school was 43%. In the mixed model for active commuting to school, parent self-efficacy (std. beta = 0.18, p=0.018) and age (std. beta = 0.18, p=0.018) were positively related. Latino students had lower rates of active commuting to school than non-Latinos ( 16.5%, p=0.040). Distance from home to school was inversely related to active commuting to school (std. beta = 0.29, p<0.001). In the mixed model for moderate-to-vigorous physical activity, active commuting to school was positively associated (std. beta = 0.31, p <0.001). Among the Latino subsample, child acculturation was negatively associated with active commuting to school (std. beta = -0.23, p=0.01). With regard to school-level pedestrian safety observations, 37% of students stopped at the curb and 2.6% looked left-right-left before crossing the street. Conclusion: Although still below national goals, the rate of active commuting was relatively high, while the rate of some pedestrian safety behaviors was low among this low-income, ethnic minority population. Programs and policies to encourage safe active commuting to school are warranted and should consider the influence of parents, acculturation, and ethnicity.

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Orofacial clefts (OFC; MIM 119530) are among the most common major birth defects. Here, we carried out mutation screening of the PVR and PVRL2 genes, which are both located at an OFC linkage region at 19q13 (OFC3) and are closely related to PVRL1, which has been associated with both syndromic and non-syndromic cleft lip and palate (nsCLP). We screened a total of 73 nsCLP patients and 105 non-cleft controls from the USA for variants in PVR and PVRL2, including all exons and encompassing all isoforms. We identified four variants in PVR and five in PVRL2. One non-synonymous PVR variant, A67T, was more frequent among nsCLP patients than among normal controls, but this difference did not achieve statistical significance.

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The authors test single nucleotide polymorphisms (SNPs) in coding sequences of 12 candidate genes involved in glucose metabolism and obesity for associations with spina bifida. Genotyping was performed on 507 children with spina bifida and their parents plus anonymous control DNAs from Hispanic and Caucasian individuals. The transmission disequilibrium test was performed to test for genetic associations between transmission of alleles and spina bifida in the offspring (P < .05). A statistically significant association between Lys481 of HK1 (G allele), Arg109Lys of LEPR (G allele), and Pro196 of GLUT1 (A allele) was found ( P = .019, .039, and .040, respectively). Three SNPs on 3 genes involved with glucose metabolism and obesity may be associated with increased susceptibility to spina bifida.

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Obesity and related chronic diseases represent a tremendous public health burden among Mexican Americans, a young and rapidly-expanding population. This study investigated the impact of variation within eight candidate obesity genes, which include leptin (LEP), leptin receptor (LEPR), neuropeptide Y (NPY), NPYY1 receptor (NPYY1), glucagon-like peptide-1 (GLP-1), GLP-1 receptor (GLP1R), beta-3 adrenergic receptor (3AR), and uncoupling protein (UCP1), on variation in human obesity status and/or quantitative traits related to obesity in Mexican Americans from Starr County, Texas. The Trp64Arg polymorphism within 3AR was typed in 820 random individuals and 240 pedigrees (N = 2,044). The Arg allele frequency was significantly greater in obese versus non-obese individuals (0.20 versus 0. 15, respectively). In addition, within the random sample, the Arg allele was associated with significantly greater body weight (p = 0.031) and body mass index (BMI, p = 0.008) than the Trp allele. In the family sample, the Trp64Arg locus was also linked to percent fat (p = 0.045) but not to body weight or BMI. No linkage between obesity, diabetes, hypertension, or gallbladder disease and the Trp64Arg mutation was observed in families using affected sib pair linkage analysis or the transmission disequilibrium test. Microsatellite markers proximate to the remaining seven genes were typed in 302 individuals from 59 families. Sib pair linkage analysis provided evidence for linkage between obesity and NPY within affected sibling pairs (p = 0.042; n = 170 pairs). NPY was also linked to weight (p = 0.020), abdominal circumference (p = 0.031), hip circumference (p = 0.012), DBP (p 0.005), and a composite measure of body mass/fat (p 0.048) in all sibling pairs (n = 545 pairs). Additionally, LEP was linked to waist/hip ratio (p 0.009), total cholesterol (p 0.030), and HDL cholesterol (p 0.026), and LEPR was linked to fasting blood glucose (p 0.018) and DBP (p 0.003). Subsequent to the linkage analyses, the NPY gene was sequenced and eight variant sites identified. Two variant sites (-880I/D and 69I/D) were typed in a random sample of 914 individuals. The 880I/D variant was significantly associated with waist/hip ratio (p = 0.035) in the entire sample (N = 914) and with BMI (p = 0. 031), abdominal circumference (p = 0.044), and waist/hip ratio (p = 0.041) in a non-obese subsample (BW < 30 kg/m2, n = 594). The 69I/D variant was a rare mutation observed in only one pedigree and was not associated with obesity or body size/mass within this pedigree. Results of this study indicate that variation at or near 3AR, LEP, LEPR, and NPY may exert effects which increase obesity susceptibility and influence obesity-related measures in this population. ^

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Cardiovascular disease (CVD) is highly preventable, yet it is a leading cause of death among women in Texas. The primary goals of this research were to examine past and current trends of CVD, as well as identify whether there is an association between the insurance coverage and mortality from CVD among women aged 6065 in Texas between 2000 and 2011. ^ The systematic review of the research is based on the guidelines and recommendations set by the Centre for Reviews and Dissemination for conducting reviews in health care. Over 47 citations of peer-reviewed articles from Ovid MEDLINE and PubMed databases and five websites were identified, of which 7 studies met inclusion criteria for the first systematic review to examine the trends of CVD in Texas. Ten citations of peer-reviewed articles from Ovid MEDLINE and PubMed databases and five web sites were reviewed for the second systematic review (to study the association between insurance coverage and cardiovascular health among Texas women 6064 years of age), of which 3 studies met inclusion criteria and were included in the research. The results of the study highlighted key gaps in the existing literature and important areas for the further research, as well as determined directions for future public health CVD prevention programs in Texas. ^ Based on the conducted research, the major determinants of premature mortality among women attributed to cardiovascular disease are based on individual level characteristics, more specifically sex, age, race/ethnicity, and education. The results indicate that African American and non-Hispanic white women are more likely to have higher CVD mortality rates than Hispanic women due to higher prevalence of cardiac risk factors. The data also shows higher levels of mortality from CVD in the southeastern United States, with Texas ranking as the third state with the highest prevalence of CVD among women. According to the Texas Department of State Health Services, there are approximately 56,000 deaths caused by CVD annually in Texas, which represents about one death every ten minutes. Coronary artery disease and stroke were the causes of 31.2 percent of all female deaths in Texas in 2009, meaning that approximately 68 women die from any form of cardiac disease in Texas each day. ^ The data of the reviewed studies indicate that women' lack of health insurance was significantly associated with a higher prevalence of cardiovascular disease. The uninsured women were more likely to be unaware of their risk factors and more likely to have undiagnosed diabetesa co-morbidity factor of CVD. One of the studies also reports strong correlation between state rates of uninsured and lower rates of preventive care. Given these strong correlations, those who were chronically uninsured were at a higher risk of mortality than the insured, due to prolonged periods of time without basic access to preventive and medical care. ^ Suggested recommendations to decrease CVD mortality rates in Texas are consistent with the existing literature and include state policy development that addresses elimination of health disparities, consideration of potential benefits of universal health coverage by the legislative policymakers, and maintenance of solid partnerships between public health agencies and hospitals to educate on, diagnose, and treat CVD among the female population in Texas. ^

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Adult monkeys (Macaca mulatta) with lesions of the hippocampal formation, perirhinal cortex, areas TH/TF, as well as controls were tested on tasks of object, spatial and contextual recognition memory. ^ Using a visual paired-comparison (VPC) task, all experimental groups showed a lack of object recognition relative to controls, although this impairment emerged at 10 sec with perirhinal lesions, 30 sec with areas TH/TF lesions and 60 sec with hippocampal lesions. In contrast, only perirhinal lesions impaired performance on delayed nonmatching-to-sample (DNMS), another task of object recognition memory. All groups were tested on DNMS with distraction (dDNMS) to examine whether the use of active cognitive strategies during the delay period could enable good performance on DNMS in spite of impaired recognition memory (revealed by the VPC task). Distractors affected performance of animals with perirhinal lesions at the 10-sec delay (the only delay in which their DNMS performance was above chance). They did not affect performance of animals with areas TH/TF lesions. Hippocampectomized animals were impaired at the 600-sec delay (the only delay at which prevention of active strategies would likely affect their behavior). ^ While lesions of areas TH/TF impaired spatial location memory and object-in-place memory, hippocampal lesions impaired only object-in-place memory. The pattern of results for perirhinal cortex lesions on the different task conditions indicated that this cortical area is not critical for spatial memory. ^ Finally, all three lesions impaired contextual recognition memory processes. The pattern of impairment appeared to result from the formation of only a global representation of the object and background, and suggests that all three areas are recruited for associating information across sources. ^ These results support the view that (1) the perirhinal cortex maintains storage of information about object and the context in which it is learned for a brief period of time, (2) areas TH/TF maintain information about spatial location and form associations between objects and their spatial relationship (a process that likely requires additional time) and (3) the hippocampal formation mediates associations between objects, their spatial relationship and the general context in which these associations are formed (an integrative function that requires additional time). ^

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A population based ecological study was conducted to identify areas with a high number of TB and HIV new diagnoses in Harris County, Texas from 2009 through 2010 by applying Geographic Information Systems to determine whether distinguished spatial patterns exist at the census tract level through the use of exploratory mapping. As of 2010, Texas has the fourth highest occurrence of new diagnoses of HIV/AIDS and TB.[31] The Texas Department of State Health Services (DSHS) has identified HIV infected persons as a high risk population for TB in Harris County.[29] In order to explore this relationship further, GIS was utilized to identify spatial trends. ^ The specific aims were to map TB and HIV new diagnoses rates and spatially identify hotspots and high value clusters at the census tract level. The potential association between HIV and TB was analyzed using spatial autocorrelation and linear regression analysis. The spatial statistics used were ArcGIS 9.3 Hotspot Analysis and Cluster and Outlier Analysis. Spatial autocorrelation was determined through Global Moran's I and linear regression analysis. ^ Hotspots and clusters of TB and HIV are located within the same spatial areas of Harris County. The areas with high value clusters and hotspots for each infection are located within the central downtown area of the city of Houston. There is an additional hotspot area of TB located directly north of I-10 and a hotspot area of HIV northeast of Interstate 610. ^ The Moran's I Index of 0.17 (Z score = 3.6 standard deviations, p-value = 0.01) suggests that TB is statistically clustered with a less than 1% chance that this pattern is due to random chance. However, there were a high number of features with no neighbors which may invalidate the statistical properties of the test. Linear regression analysis indicated that HIV new diagnoses rates (=0.006, SE=0.147, p=0.970) and census tracts (=0.000, SE=0.000, p=0.866) were not significant predictors of TB new diagnoses rates. ^ Mapping products indicate that census tracts with overlapping hotspots and high value clusters of TB and HIV should be a targeted focus for prevention efforts, most particularly within central Harris County. While the statistical association was not confirmed, evidence suggests that there is a relationship between HIV and TB within this two year period.^

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Wilms tumor (WT) is a childhood tumor of the kidney and a productive model for understanding the role of genetic alteration and interactions in tumorigenesis. The Wilms tumor gene 1 (WT1) is a transcriptional factor and one of the few genes known to have genetic alterations in WT and has been shown be inactivated in 20% of WTs. However, the mechanisms of how WT1 mutations lead to Wilms tumorigenesis and its influence on downstream genes are unknown. Since it has been established that WT1 is a transcriptional regulator, it has been hypothesized that the loss of WT1 leads to the dysregulation of downstream genes, in turn result in the formation of WTs. To identify the dysregulated downstream genes following WT1 mutations, an Affymetrix GeneChip Human Genome Array was previously conducted to assess the differentially expressed genes in the WT1-wildtype human and WT1-mutant human WTs. Approximately 700 genes were identified as being significantly dysregulated. These genes were further prioritized based on their statistical significance, fold change, chromosomal region, spatial pattern of gene expression and known or putative cellular functions. Mesenchyme homeobox 2 (MEOX2) was one of the most significantly upregulated genes in WT1-mutant WT. MEOX2 is known to play a role in cell proliferation, apoptosis, and differentiation. In addition to its biological roles, it is expressed during early kidney development in the condensed mesenchyme similar to WT1. Furthermore, the use of the Match web-based tool from the BIOBASE Biological Data base identified a significant predicted WT1 binding site within the first intron of MEOX2. The similarity in spatial gene expression in the developing kidney and the significant predicted WT1 binding site found in the first intron of MEOX2 lead to the development of my hypothesis that MEOX2 is upregulated via a WT1-dependent manner. Here as a part of my masters work, I have validated the Affymetrix GeneChip Human Genome Array data using an independent set of Wilms tumors. MEOX2 remained upregulated in the mutant WT1 Wilms tumor by 41-fold. Wt1 and Meox2 gene expression were assessed in murine newborn kidney; both Wt1 and Meox2 were expressed in the condensed, undifferentiated metanephric mesenchyme. I have shown that the in vivo ablation of Wt1 during embryonic development at embryonic day (E) 13.5 resulted in the slight increase of Meox2 gene expression by two fold. In order to functionally demonstrate the effect of the loss of Wt1 on Meox2 gene expression in undifferentiated metanephric mesenchyme, I have generated a kidney mesenchymal cell line to genetically ablate Wt1 in vitro by adenoviral infection. The ablation of Wt1 in the kidney mesenchymal cell line resulted in the upregulation of Meox2 by 61-fold. Moreover, the upregulation of Meox2 resulted in the significant induction of p21 and Itgb5. In addition to the dysregulation of these genes the ablation of Wt1 in the kidney mesenchymal cells resulted in decrease in cell growth and loss of cellular adherence. However, it is uncertain whether the upregulation of Meox2 caused this particular cellular phenotype. Overall, I have demonstrated that the upregulation of Meox2 is Wt1-dependent during early kidney development.

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Morphogenesis is the process by which the 3-dimensional structure of the developing embryo takes shape. We are studying xlcaax-1, a gene whose product can be used as a molecular marker for several morphogenetic events. We report here the cellular and subcellular localization of the xlcaax-1 protein during development of Xenopus laevis. Whole mount immunocytochemistry and immunoperoxidase staining of tissue sections showed that during development the xlcaax-1 protein accumulation was coincident with the differentiation of the epidermis, pronephros and mesonephros. In the pronephros and mesonephros the xlcaax-1 protein was localized to the basolateral membrane of differentiated tubule epithelial cells. Thus, the xlcaax-1 protein served as a marker for tubule formation and polarization during Xenopus kidney development. Xlcaax-1 may also be used as a marker for the functional differentiation of the epidermis and the epidermally derived portions of the lens and some cranial nerves. The xlcaax-1 protein was most abundant in kidney and immunogold EM analysis showed that the xlcaax-1 protein was highly enriched in the basal infoldings of the basolateral membrane of the epithelial cells in adult kidney distal tubules. The xlcaax-1 protein was also localized in other ion transporting epithelia. The localization pattern and preliminary functional assays of xlcaax-1 suggest that the protein may function in association with an ion transport channel or pump.^ Cell migration and cell-cell interactions play important roles in numerous processes during morphogenesis. One of these is the formation of the pronephric (wolffian) duct (PD), which connects the pronephros to the cloaca. It is currently accepted that in most amphibians the pronephric duct is formed by active migration of the pronephric duct rudiment (PDR) cells along a pre-determined pathway. However, there is evidence that in Xenopus, the PD may be formed entirely by in situ segregation of cells out of the lateral mesoderm. In this study, we showed, using PDR ablation and X. laevis - X. borealis chimeras, that PD elongation in Xenopus required both active cell migration and an induced recruitment of cells from the posterior lateral plate mesoderm. We also showed that PDR cell migration was limited to only a few stages during development and that this temporal control is due, at least in part, to changes in the competence of the PD pathway to support cell migration. In addition, our data suggested that an alkaline phosphatase (APase) adhesion gradient may be involved in determining this competence. ^

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Divergence of anterior-posterior (AP) limb pattern and differences in vertebral column morphology are the two main examples of mammalian evolution. The Hox genes (homeobox containing gene) have been implicated in driving evolution of these structures. However, regarding Hox genes, how they contribute to the generation of mammalian morphological diversities, is still unclear. Implementing comparative gene expression and phenotypic rescue studies for different mammalian Hox genes could aid in unraveling this mystery. In the first part of this thesis, the expression pattern of Hoxd13 gene, a key Hox gene in the establishment of the limb AP pattern, was examined in developing limbs of bats and mice. Bat forelimbs exhibit a pronounced asymmetric AP pattern and offer a good model to study the molecular mechanisms that contribute to the variety of mammalian limbs. The data showed that the expression domain of bat Hoxd13 was shifted prior to the asymmetric limb plate expansion, whereas its domain in mice was much more symmetric. This finding reveals a correlation between the divergence of Hoxd13 expression and the AP patterning difference in limb development. The second part of this thesis details a phenotypic rescue approach by human HOXB1-9 transgenes in mice with Hoxb1-9 deletion, The mouse mutants displayed homeosis in cervical and anterior thoracic vertebrae. The human transgenes entirely rescued the mouse mutants, suggesting that these human HOX genes have similar functions to their mouse orthologues in anterior axial skeletal patterning. The anterior expressing human HOXB transgenes such as HOXB1-3 were expressed in the mouse embryonic trunk in a similar manner as their murine orthologues. However, the anterior boundary of human HOXB9 expression domain was more posterior than that of the mouse Hoxb9 by 2-3 somites. These data provide the molecular support for the hypothesis that Hox genes are responsible for maintaining similar anterior axial skeletal architectures cervical and anterior thoracic regions, but different architectures in lumbar and posterior thoracic regions between humans and mice. ^

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Genome-Wide Association Study analytical (GWAS) methods were applied in a large biracial sample of individuals to investigate variation across the genome for its association with a surrogate low-density lipoprotein (LDL) particle size phenotype, the ratio of LDL-cholesterol level over ApoB level. Genotyping was performed on the Affymetrix 6.0 GeneChip with approximately one million single nucleotide polymorphisms (SNPs). The ratio of LDL cholesterol to ApoB was calculated, and association tests used multivariable linear regression analysis with an additive genetic model after adjustment for the covariates sex, age and BMI. Association tests were performed separately in African Americans and Caucasians. There were 9,562 qualified individuals in the Caucasian group and 3,015 qualified individuals in the African American group. Overall, in Caucasians two statistically significant loci were identified as being associated with the ratio of LDL-cholesterol over ApoB: rs10488699 (p<5 x10-8, 11q23.3 near BUD13) and the SNP rs964184 (p<5 x10-8 11q23.3 near ZNF259). We also found rs12286037 ((p<4x10-7) (11q23.3) near APOA5/A4/C3/A1 with suggestive associate in the Caucasian sample. In exploratory analyses, a difference in the pattern of association between individuals taking and not taking LDL-cholesterol lowering medications was observed. Individuals who were not taking medications had smaller p-value than those taking medication. In the African-American group, there were no significant (p<5x10-8) or suggestive associations (p<4x10-7) with the ratio of LDL-cholesterol over ApoB after adjusting for age, BMI, and sex and comparing individuals with and without LDL-cholesterol lowering medication. Conclusions: There were significant and suggestive associations between SNP genotype and the ratio of LDL-cholesterol to ApoB in Caucasians, but these associations may be modified by medication treatment.^

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Background. It is important to understand the association between diet and risk of pancreatic cancer in order to better understand the etiology of pancreatic cancer.^ Objectives. Describe the dietary patterns of cases of adenocarcinoma of the pancreas and non-cancer controls and evaluate the odds of having a healthy eating pattern among cases and non-cancer controls.^ Design and Methods. An ongoing hospital-based case-control study was conducted in Houston, Texas from 2000-2008 with 678 pancreatic adenocarcinoma cases and 724 controls. Participants completed a food frequency questionnaire and a risk factor questionnaire. Dietary patterns were derived by principal component analysis and associations between dietary patterns and pancreatic cancer risk were assessed using unconditional logistic regression.^ Results. Two dietary patterns were derived: fruit-vegetable and high fat-meat. There were no statistically significant associations between the fruit-vegetable pattern and pancreatic cancer. An inverse association was seen between the high fat-meat pattern and pancreatic cancer risk when comparing those in the upper intake quintile to those scoring in the lowest quintile after adjusting for demographic and risk factor variables (OR=0.67, p=0.03). In sex-stratified analysis adjusted for demographic and risk factor variables, females scoring in the upper intake quintile of the fruit-vegetable pattern had a 49% lower risk of pancreatic cancer compared to females scoring in the lowest quintile (OR=0.51, p=0.03). An inverse relationship was also seen for the high fat-meat pattern when comparing females in the upper intake quintile to females in the lowest quintile (OR=0.50, p=0.03). In males, neither dietary pattern was significantly associated with pancreatic cancer.^ Conclusions. The current findings for the fruit-vegetable pattern are similar to those of previous studies and support the hypothesis that there is an inverse association between a healthy diet (comprised of fruits, vegetables, and whole grains) and risk of having pancreatic cancer (in females only). However, the inverse relationship with the high fat-meat pattern and risk of pancreatic cancer is contrary to other results. Further research on dietary patters and pancreatic cancer risk may lead to better understanding of the etiologic cause of pancreatic cancer.^

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Epidemiologic studies of mental disorder have called attention to the need for identifying untreated cases and to the inadequacies of the instruments available for this purpose. Accurate case ascertainment devices are the basis of sound epidemiology. Without these, neither case classification nor analytic studies of risk factors is possible.^ The purpose of this research was to examine the reliability and validity of an instrument designed to measure depressive symptoms in community populations--the Center for Epidemiologic Studies Depression Scale (CES-D Scale). Two particular foci of the study were whether or not the scale had the same statistical structure across three ethnic groups and whether or not the magnitude and pattern of rates of symptoms for these groups were affected by one source of response error, that due to response tendencies. The effects of age and education on the pattern and magnitude of rates also were examined. In addition, the reliability and validity of the measures of response tendencies were assessed.^ The study population consisted of residents of Alameda County, California. A stratified sample of approximately 700 whites, blacks and Mexican-Americans was interviewed in the summer and fall of 1978.^ The results of the analysis indicated that the scale was reliable and measured a similar content domain across the three ethnic groups. The unadjusted sex- and ethnic-specific rates of depressive symptoms showed an ethnic pattern for both sexes: rates for whites were lowest, those for Mexican-Americans were highest, and those for blacks were intermediate. Measures of response tendencies--need for social approval, trait desirability, and acquiescence--affected the magnitude of the rates for most comparisons. Likewise, the pattern of rates changed somewhat from that originally observed. The one fairly consistent observation was that rates for Mexican-American women were higher than those for the other two female subgroups in most of the comparisons. These results must be considered in the context of the reliability and validity assessment of the measures of response tendencies which indicated the tenuousness of these measures.^ Age affected the ethnic pattern of rates for men in an inconsistent way; for women, Mexican-Americans continued to have higher rates than whites or blacks in all age categories. Education affected the magnitude of rates for women but not for men. For both men and women, Mexican-Americans had higher rates in all educational strata. Rates for women showed an inverse association with education while those for men did not. ^