Objective-A pilot study of the density of dendritic spines on pyramidal neurons in layer III of human temporal and frontal cerebral neocortex in schizophrenia. Methods-Postmortem material from a group of eight prospectively diagnosed schizophrenic patients, five archive schizophrenic patients, 11 nonschizophrenic controls, and one patient with schizophrenia-like psychosis, thought to be due to substance misuse, was impregnated with a rapid Golgi method. Spines were counted on the dendrites of pyramidal neurons in temporal and frontal association areas, of which the soma was in layer III (which take part in corticocortical connectivity) and which met strict criteria for impregnation quality. Altogether 25 blocks were studied in the schizophrenic group and 21 in the controls. If more than one block was examined from a single area, the counts for that area were averaged. All measurements were made blind: diagnoses were only disclosed by a third party after measurements were completed. Possible confounding aVects of coexisiting Alzheimer's disease were taken into account, as were the eVects of age at death and postmortem interval. Results-There was a significant (p<0.001) reduction in the numerical density of spines in schizophrenia (276/mm in control temporal cortex and 112/mm in schizophrenic patients, and 299 and 101 respectively in the frontal cortex). An analysis of variance, taking out eVects of age at death and postmortem interval, which might have explained the low spine density for some of the schizophrenic patients, did not aVect the significance of the results. Conclusion-The results support the concept of there being a defect in the fine structure of dendrites of pyramidal neurons, involving loss of spines, in schizophrenia and may help to explain the loss of cortical volume without loss of neurons in this condition, although the eVect of neuroleptic drugs cannot be ruled out. (J Neurol Neurosurg Psychiatry 1998;65:446-453)

Rationale: Air pollution is a known asthma trigger and has been associated with short-term asthma symptoms, airway inflammation, decreased lung function, and reduced response to asthma rescue medications. Objectives: To assess a causal relationship between air pollution and childhood asthma using data that address temporality by estimating air pollution exposures before the development of asthma and to establish the generalizability of the association by studying diverse racial/ethnic populations in different geographic regions. Methods: This study included Latino (n ¼ 3,343) and African American (n ¼ 977) participants with and without asthma from five urban regions in the mainland United States and Puerto Rico. Residential history and data from local ambient air monitoring stations were used to estimate average annual exposure to five air pollutants: ozone, nitrogen dioxide (NO 2 ), sulfur dioxide, particulate matter not greater than 10 mm in diameter, and particulate matter not greater than 2.5 mm in diameter. Within each region, we performed logistic regression to determine the relationship between early-life exposure to air pollutants and subsequent asthma diagnosis. Arandom-effectsmodelwasusedtocombinetheregionspecific effects and generate summary odds ratios for each pollutant. Measurements and Main Results: After adjustment for confounders, a 5-ppb increase in average NO 2 during the first year of life was associated with an odds ratio of 1.17 for physician-diagnosed asthma (95% confidence interval, 1.04-1.31). Conclusions: Early-life NO 2 exposure is associated with childhood asthma in Latinos and African Americans. These results add to a growing body of evidence that traffic-related pollutants may be causally related to childhood asthma.

Ground level ozone concentrations ([O 3 ]) typically show a direct linear relationship with surface air temperature. Three decades of California measurements provide evidence of a statistically significant change in the ozone-temperature slope (Δm O3-T ) under extremely high temperatures (>312 K). This Δm O3-T leads to a plateau or decrease in [O 3 ], reflecting the diminished role of nitrogen oxide sequestration by peroxyacetyl nitrates and reduced biogenic isoprene emissions at high temperatures. Despite inclusion of these processes in global and regional chemistry-climate models, a statistically significant change in Δm O3-T has not been noted in prior studies. Future climate projections suggest a more frequent and spatially widespread occurrence of this Δm O3-T response, confounding predictions of extreme ozone events based on the historically observed linear relationship. (4-10), and several studies have attempted to isolate the drivers of this relationship, as summarized in ref. 11. Early studies investigating the ozone-temperature relationship noted the impact of peroxyacetyl nitrate (PAN) decomposition on ozone formation (4, 12). The PAN sink for NO x and odd hydrogen (HO x ) decreases exponentially as temperatures increase, implying a saturation of ozone formation from PAN decomposition as temperatures increase above ∼310 K. Sillman and Samson (10) found that m O3-T is a function of multiple chemical processes, including the reaction rate of PAN, emissions of biogenic volatile organic compounds (VOC), photolysis rates, and water vapor concentrations. Therefore whereas absolute temperature is a strong predictor of the effects of incremental temperature change on ozone (2), chemical kinetics and temperature-dependent emission rates further complicate this relationship. For example, prior studies have noted that m O3-T varies between regions with different NO x ∕VOC ratios (13), and can decrease following significant NO x emissions reductions (6). The m O3-T relationship has been called a climate change "penalty," signifying that emissions reductions will need to be more stringent to counteract the effects of warming temperatures (6,14). However, the stationarity of this ozone-temperature relationship has yet to be evaluated using observations over a broad range of temperatures.High concentrations of tropospheric ozone ([O 3 ]) are an indicator of poor air quality, and adversely affect the health of humans and ecosystems (15,16). A suite of chemical and meteorological factors contributes to the formation of ozone. Photochemically driven reactions of VOC in the presence of nitrogen oxides (NO x ) can form ozone at the surface (17), whereas stagnant meteorological conditions promote and maintain ozone events.Changes in the frequency of certain meteorological features such as fewer midlatitude cyclones (18,19) or shallower boundary layer depths (20) (Fig. S1). Daily maximum surface air temperature (T max ) data are obtained from a statistically interpolated gridded product of ground-based National Oceanic a...

Background Childhood asthma prevalence and morbidity varies among Latinos in the United States, with Puerto Ricans having the highest and Mexicans the lowest. Objective To determine whether genetic ancestry is associated with the odds of asthma among Latinos, and secondarily whether genetic ancestry is associated with lung function among Latino children. Methods We analyzed 5,493 Latinos with and without asthma from three independent studies. For each participant we estimated the proportion of African, European, and Native American ancestry using genome-wide data. We tested whether genetic ancestry was associated with the presence of asthma and lung function among subjects with and without asthma. Odds ratios (OR) and effect sizes were assessed for every 20% increase in each ancestry. Results Native American ancestry was associated with lower odds of asthma (OR=0.72, 95% confidence interval [CI]: 0.66–0.78, p=8.0×10−15), while African ancestry was associated with higher odds of asthma (OR=1.40, 95%CI: 1.14–1.72, p=0.001). These associations were robust to adjustment for covariates related to early life exposures, air pollution and socioeconomic status. Among children with asthma, African ancestry was associated with lower lung function, including both pre- and post-bronchodilator measures of forced expiratory volume in the first second (−77±19 ml, p=5.8×10−5 and −83±19 ml, p=1.1×10−5, respectively) and forced vital capacity (−100±21 ml, p=2.7×10−6 and −107±22 ml, p=1.0×10−6, respectively). Conclusion Differences in the proportions of genetic ancestry can partially explain disparities in asthma susceptibility and lung function among Latinos.

Rationale: Obesity is associated with increased asthma morbidity, lower drug responsiveness to inhaled corticosteroids, and worse asthma control. However, most prior investigations on obesity and asthma control have not focused on pediatric populations, considered environmental exposures, or included minority children. Objectives: To examine the association between body mass index categories and asthma control among boys and girls; and whether these associations are modified by age and race/ethnicity. Methods: Children and adolescents ages 8-19 years (n ¼ 2,174) with asthma were recruited from the Genes-environments and Admixture in Latino Americans (GALA II) Study and the Study of African Americans, Asthma, Genes, and Environments (SAGE II). Ordinal logistic regression was used to estimate odds ratios (OR) and their confidence intervals (95% CI) for worse asthma control. Measurements and Main Results: In adjusted analyses, boys who were obese had a 33% greater chance of having worse asthma control than their normal-weight counterparts (OR, 1.33; 95% CI, 1.04-1.71). However, for girls this association varied with race and ethnicity (P interaction ¼ 0.008). When compared with their normal-weight counterparts, obese African American girls (OR, 0.65; 95% CI, 0.41-1.05) were more likely to have better controlled asthma, whereas Mexican American girls had a 1.91 (95% CI, 1.12-3.28) greater odds of worse asthma control. Conclusions: Worse asthma control is uniformly associated with increased body mass index in boys. Among girls, the direction of this association varied with race/ethnicity. Keywords: obesity; asthma control; race and ethnicity; age; sex Obesity and asthma are among the most challenging health conditions affecting children and adolescents in the United States. Among this segment of the population, obesity (1) and asthma (2) prevalence vary by sex. For example, obesity is more common among boys (18.6%) than among girls (15%) aged 2-19 years old (1). This is also true for asthma with boys (10.5%) being more likely to have asthma than girls (8.2%) (2). Given these sex differences, obesity and asthma should be examined among boys and girls separately.Further variations on obesity and asthma are observed across age and race/ethnicity (1, 2). It is estimated that 32.6% of US children ages 6-11 years and 33.6% of adolescents ages 12-19 are overweight or obese (1). The prevalence of obesity is significantly higher among Mexican (23.9%) and African American (23.7%) children compared with non-Hispanic whites (16.1%) (1). Moreover, there are sex-specific differences in Obesity and asthma are common health conditions among US children. Obesity is associated with asthma control, although the mechanism is not well-understood. What This Study Adds to the FieldWorse asthma control is uniformly associated with increased body mass index in boys. Boys who were obese had increased odds of having worse asthma control than their normal-weight counterparts after adjusting for selected characteristics. For girls, this associat...