The association between sidewalk length and walking for different purposes in established neighborhoods

ABSTRACT: BACKGROUND: Walking in neighborhood environments is undertaken for different purposes including for transportation and leisure. We examined whether sidewalk availability was associated with participation in, and minutes of neighborhood-based walking for transportation (NWT) and recreation (NWR) after controlling for neighborhood self-selection. METHOD: Baseline survey data from respondents (n=1813) who participated in the RESIDential Environment (RESIDE) project (Perth, Western Australia) were used. Respondents were recruited based on their plans to move to another neighborhood in the following year. Usual weekly neighborhood-based walking, residential preferences, walking attitudes, and demographics were measured. Characteristics of the respondent's baseline neighborhood were measured including transportation-related walkability and sidewalk length. A Heckman two-stage modeling approach (multivariate Probit regression for walking participation, followed by a sample selection-bias corrected OLS regression for walking minutes) estimated the relative contribution of sidewalk length to NWT and NWR. RESULTS: After adjustment, neighborhood sidewalk length and walkability were positively associated with a 2.97 and 2.16 percentage point increase in the probability of NWT participation, respectively. For each 10km increase in sidewalk length, NWT increased by 5.38 min/wk and overall neighborhood-based walking increased by 5.26 min/wk. Neighborhood walkability was not associated with NWT or NWR minutes. Moreover, sidewalk length was not associated with NWR minutes. CONCLUSION: Sidewalk availability in established neighborhoods may be differentially associated with walking for different purposes. Our findings suggest that large investments in sidewalk construction alone would yield small increases in walking.     

Rapid tolerance and locomotor sensitization in ethanol-naïve adolescent rhesus macaques

Background: Acute and chronic tolerance, as well as locomotor sensitization, have been linked to ethanol intake. This study examined the change in response between 2 acutely administered doses of ethanol in adolescent rhesus macaques, with the objective of investigating rapid tolerance and locomotor sensitization to the behavioral effects of ethanol, and whether these phenomena are related to voluntary ethanol consumption in nonhuman primates. Methods: Rhesus macaques (n = 109, 42 males, 67 females) were administered 2 sequential intravenous doses of ethanol (2.2 g/kg for males, 2.0 g/kg for females) separated by a period of 5 to 30 days. Following each injection, subjects underwent a 30‐minute behavior assessment. Behavioral data were summarized using factor analysis, and compared between the 2 doses using repeated measures ANOVA. The relationship between behavioral response measures and the number of days between doses was analyzed using regression analyses. Following the second ethanol dose, subjects were given free access to an aspartame‐sweetened 8.4% ethanol solution for 1 hour a day for 4 weeks. Percent change in behavioral response measures from dose 1 to dose 2 was analyzed for associations with ethanol consumption using multiple regression analyses. Results: Factor analysis yielded 3 factors: ataxia, stimulation, and jumping. From dose 1 to dose 2 there was a significant decrease in ataxia and a significant increase in stimulation. Peak blood ethanol concentration did not differ between doses. There were no significant associations between the number of days between doses and the magnitude of change in response for any of the behavioral measures. Percent change in stimulation from dose 1 to dose 2 was positively associated with subsequent oral ethanol consumption only in females tested in a social setting. Conclusions: Adolescent rhesus macaques develop rapid tolerance to the motor‐impairing effects of alcohol, while at the same time developing locomotor sensitization. These changes in response are not necessarily short lived, and may persist for some time following the first ethanol dose. Clear and consistent associations between rapid tolerance and locomotor sensitization and ethanol intake levels have yet to be demonstrated, however.     

STAT3 is required for IL-21-induced secretion of IgE from human naive B cells

The production of immunoglobulin E (IgE) is tightly regulated. This is evidenced by the fact that it comprises less than 0.0001% of serum Ig, and aberrant production causes atopic conditions, including allergy, rhinitis, and anaphylaxis. Interleukin-4 (IL-4) is a well-characterized inducer of IgE by human and murine B cells, whereas interferon-gamma can antagonize this effect. IL-21 has also been recognized for its ability to suppress IL-4-induced IgE production by murine B cells. Here, we identified IL-21 as an inducer of IgE production by CD40L-stimulated human naive B cells. Furthermore, there was a striking synergy between IL-4 and IL-21 on inducing IgE secretion by CD40L-stimulated human B cells, such that the levels detected under these conditions exceeded those induced by IL-4 or IL-21 alone by more than 10-fold. IL-21 induced activation of STAT3 and analysis of B cells from patients with loss-of-function STAT3 mutations revealed that the ability of IL-21 to induce IgE secretion, and augment that driven by IL-4, was STAT3-dependent. These findings highlight a fundamental difference between the regulation of IgE production by human and murine B cells and have implications for the dysregulated production of IgE in conditions characterized by extremely high levels of serum IgE.