Publications

IMPORTANCE

Smoke-free laws are associated with a lower prevalence of smoking.

OBJECTIVE

To quantify the effect of 100% smoke-free laws on the smoking behavior of adolescents and young adults in a longitudinal analysis.

DESIGN, SETTING, AND PARTICIPANTS

Pooled logistic regression and zero-inflated negative binomial regression analysis of participants in the National Longitudinal Survey of Youth 1997 (data from 1997 to 2007), with complete data on initiation of smoking (n = 4098) and number of days respondents reported smoking in the past 30 days (n = 3913).

EXPOSURES

Laws for 100% smoke-free workplaces, laws for 100% smoke-free bars, and state cigarette taxes.

MAIN OUTCOMES AND MEASURES

Smoking initiation (first report of smoking cigarette), current (for 30 days) smoking, and number of days respondents reported smoking in the past 30 days among current smokers.

RESULTS

Laws for 100% smoke-free workplaces, but not bars, were associated with significantly lower odds of initiating smoking (odds ratio, 0.66 [95% CI, 0.44-0.99]). Laws for 100% smoke-free bars were associated with lower odds of being a current smoker (odds ratio, 0.80 [95% CI, 0.71-0.90]) and fewer days of smoking (incidence rate ratio, 0.85 [95% CI, 0.80-0.90]) among current smokers. Taxes were associated with a lower percentage of new smokers but not current smokers among adolescents and young adults. The effect of smoke-free workplace laws on smoking initiation is equivalent to a $1.57 (in 2007 dollars) tax increase. Smoke-free bar laws are associated with lower rates of current smoking, as well as a decrease in the number of days reported smoking among current smokers.

CONCLUSIONS AND RELEVANCE

Smoke-free laws are an important tobacco control tool. They not only protect bystanders from secondhand smoke but also contribute to less smoking among adolescents and young adults.

BACKGROUND

Prognosis associated with metastatic renal cell carcinoma (mRCC) can vary widely.

METHODS

This study used pretreatment nephrectomy specimens from a randomized phase III trial. Expression levels of candidate genes were determined from archival tumors using the OpenArray® platform for TaqMan® RT-qPCR. The dataset was randomly divided at 2:1 ratio into training (n = 221) and testing (n = 103) sets to develop a multigene prognostic signature.

FINDINGS

Gene expressions were measured in 324 patients. In the training set, multiple models testing 424 candidate genes identified a prognostic signature containing 8 genes plus MSKCC clinical risk factors. In the testing set, the time dependent (td) AUC for a prognostic model containing the 8 genes with and without MSKCC risk factors were 0.72 and 0.69, respectively. The tdAUC for the clinical risk factors alone was 0.61. Additional primary mRCCs from patients with mRCC (n = 12) were sampled in multiple sites and standard deviations of gene expressions within a tumor were used as a measure of heterogeneity. All 8 genes in the final prognostic model met our criteria for minimal heterogeneity.

CONCLUSIONS

A molecular prognostic signature based on 8 genes was developed and is ready for external validation in this patient population and other related settings such as nonmetastatic RCC.

To examine the T cell receptor structure in the absence of B cells, the TCR β CDR3 was sequenced from DNA of 15 X-linked agammaglobulinemia (XLA) subjects and 18 male controls, using the Illumina HiSeq platform and the ImmunoSEQ analyzer. V gene usage and the V-J combinations, derived from both productive and non-productive sequences, were significantly different between XLA samples and controls. Although the CDR3 length was similar for XLA and control samples, the CDR3 region of the XLA T cell receptor contained significantly fewer deletions and insertions in V, D, and J gene segments, differences intrinsic to the V(D)J recombination process and not due to peripheral T cell selection. XLA CDR3s demonstrated fewer charged amino acid residues, more sharing of CDR3 sequences, and almost completely lacked a population of highly modified Vβ gene segments found in control DNA, suggesting both a skewed and contracted T cell repertoire in XLA.

BACKGROUND

Human immunodeficiency virus (HIV) infection and associated immune activation predict the risk of cardiovascular disease in resource-rich areas. Less is known about these relationships in sub-Saharan Africa.

METHODS

Beginning in 2005, we enrolled subjects in southwestern Uganda into a cohort at the time of antiretroviral therapy (ART) initiation. Multiple immune activation measures were assessed before and 6 months after ART initiation. Beginning in 2013, participants aged >40 years underwent metabolic profiling, including measurement of hemoglobin A1c and lipid levels and carotid ultrasonography. We fit regression models to identify traditional and HIV-specific correlates of common carotid intima media thickness (CCIMT).

RESULTS

A total of 105 participants completed carotid ultrasonography, with a median completion time of 7 years following ART initiation. Age, low-density lipoprotein cholesterol level, and pre-ART HIV load were correlated with CCIMT. No association was found between CCIMT and any pre-ART biomarkers of immune activation. However, in multivariable models adjusted for cardiovascular disease risk factors, lower absolute levels of soluble CD14 and interleukin 6 and greater declines in the CD14 level and kynurenine-tryptophan ratio after 6 months of ART predicted a lower CCIMT years later (P < .01).

CONCLUSIONS

Persistent immune activation despite ART-mediated viral suppression predicts the future atherosclerotic burden among HIV-infected Ugandans. Future work should focus on clinical correlates of these relationships, to elucidate the long-term health priorities for HIV-infected people in the region.