Traffic-Related Air Pollution and All-Cause Mortality during Tuberculosis Treatment in California.

BackgroundAmbient air pollution and tuberculosis (TB) have an impact on public health worldwide, yet associations between the two remain uncertain.ObjectiveWe determined the impact of residential traffic on mortality during treatment of active TB.MethodsFrom 2000-2012, we enrolled 32,875 patients in California with active TB and followed them throughout treatment. We obtained patient data from the California Tuberculosis Registry and calculated traffic volumes and traffic densities in 100- to 400-m radius buffers around residential addresses. We used Cox models to determine mortality hazard ratios, controlling for demographic, socioeconomic, and clinical potential confounders. We categorized traffic exposures as quintiles and determined trends using Wald tests.ResultsParticipants contributed 22,576 person-years at risk. There were 2,305 deaths during treatment for a crude mortality rate of 1,021 deaths per 10,000 person-years. Traffic volumes and traffic densities in all buffers around patient residences were associated with increased mortality during TB treatment, although the findings were not statistically significant in all buffers. As the buffer size decreased, fifth-quintile mortality hazards increased, and trends across quintiles of traffic exposure became more statistically significant. Increasing quintiles of nearest-road traffic volumes in the 100-m buffer were associated with 3%, 14%, 19%, and 28% increased risk of death during TB treatment [first quintile, referent; second quintile hazard ratio (HR)=1.03 [95% confidence interval (CI): 0.86, 1.25]; third quintile HR=1.14 (95% CI: 0.95, 1.37); fourth quintile HR=1.19 (95% CI: 0.99, 1.43); fifth quintile HR=1.28 (95% CI: 1.07, 1.53), respectively; p-trend=0.002].ConclusionsResidential proximity to road traffic volumes and traffic density were associated with increased all-cause mortality in patients undergoing treatment for active tuberculosis even after adjusting for multiple demographic, socioeconomic, and clinical factors, suggesting that TB patients are susceptible to the adverse health effects of traffic-related air pollution. https://doi.org/10.1289/EHP1699

Interpersonal and affective dimensions of psychopathic traits in adolescents : development and validation of a self-report instrument

We report the development and psychometric evaluations of a self-report instrument designed to screen for psychopathic traits among mainstream community adolescents. Tests of item functioning were initially conducted with 26 adolescents. In a second study the new instrument was administered to 150 high school adolescents, 73 of who had school records of suspension for antisocial behavior. Exploratory factor analysis yielded a 4-factor structure (Impulsivity α = .73, Self-Centredness α = .70, Callous-Unemotional α = .69, and Manipulativeness α = .83). In a third study involving 328 high school adolescents, 130 with records of suspension for antisocial behaviour, competing measurement models were evaluated using confirmatory factor analysis. The superiority of a first-order model represented by four correlated factors that was invariant across gender and age was confirmed. The findings provide researchers and clinicians with a psychometrically strong, self-report instrument and a greater understanding of psychopathic traits in mainstream adolescents

The Epidemiology of Lead Toxicity in Adults: Measuring Dose and Consideration of Other Methodologic Issues

We review several issues of broad relevance to the interpretation of epidemiologic evidence concerning the toxicity of lead in adults, particularly regarding cognitive function and the cardiovascular system, which are the subjects of two systematic reviews that are also part of this mini-monograph. Chief among the recent developments in methodologic advances has been the refinement of concepts and methods for measuring individual lead dose in terms of appreciating distinctions between recent versus cumulative doses and the use of biological markers to measure these parameters in epidemiologic studies of chronic disease. Attention is focused particularly on bone lead levels measured by K-shell X-ray fluorescence as a relatively new biological marker of cumulative dose that has been used in many recent epidemiologic studies to generate insights into lead’s impact on cognition and risk of hypertension, as well as the alternative method of estimating cumulative dose using available repeated measures of blood lead to calculate an individual’s cumulative blood lead index. We review the relevance and interpretation of these lead biomarkers in the context of the toxico-kinetics of lead. In addition, we also discuss methodologic challenges that arise in studies of occupationally and environmentally exposed subjects and those concerning race/ethnicity and socioeconomic status and other important covariates

Laser Cooling of Optically Trapped Molecules

Calcium monofluoride (CaF) molecules are loaded into an optical dipole trap (ODT) and subsequently laser cooled within the trap. Starting with magneto-optical trapping, we sub-Doppler cool CaF and then load $150(30)$ CaF molecules into an ODT. Enhanced loading by a factor of five is obtained when sub-Doppler cooling light and trapping light are on simultaneously. For trapped molecules, we directly observe efficient sub-Doppler cooling to a temperature of $60(5)$ $\mu\text{K}$. The trapped molecular density of $8(2)\times10^7$ cm$^{-3}$ is an order of magnitude greater than in the initial sub-Doppler cooled sample. The trap lifetime of 750(40) ms is dominated by background gas collisions.Comment: 5 pages, 5 figure

Emotional intelligence buffers the effect of physiological arousal on dishonesty

We studied the emotional processes that allow people to balance two competing desires: benefitting from dishonesty and keeping a positive self-image. We recorded physiological arousal (skin conductance and heart rate) during a computer card game in which participants could cheat and fail to report a certain card when presented on the screen to avoid losing their money. We found that higher skin conductance corresponded to lower cheating rates. Importantly, emotional intelligence regulated this effect; participants with high emotional intelligence were less affected by their physiological reactions than those with low emotional intelligence. As a result, they were more likely to profit from dishonesty. However, no interaction emerged between heart rate and emotional intelligence. We suggest that the ability to manage and control emotions can allow people to overcome the tension between doing right or wrong and license them to bend the rules

Ras Conformational Switching: Simulating Nucleotide-Dependent Conformational Transitions with Accelerated Molecular Dynamics

Ras mediates signaling pathways controlling cell proliferation and development by cycling between GTP- and GDP-bound active and inactive conformational states. Understanding the complete reaction path of this conformational change and its intermediary structures is critical to understanding Ras signaling. We characterize nucleotide-dependent conformational transition using multiple-barrier-crossing accelerated molecular dynamics (aMD) simulations. These transitions, achieved for the first time for wild-type Ras, are impossible to observe with classical molecular dynamics (cMD) simulations due to the large energetic barrier between end states. Mapping the reaction path onto a conformer plot describing the distribution of the crystallographic structures enabled identification of highly populated intermediate structures. These structures have unique switch orientations (residues 25–40 and 57–75) intermediate between GTP and GDP states, or distinct loop3 (46–49), loop7 (105–110), and α5 C-terminus (159–166) conformations distal from the nucleotide-binding site. In addition, these barrier-crossing trajectories predict novel nucleotide-dependent correlated motions, including correlations of α2 (residues 66–74) with α3-loop7 (93–110), loop2 (26–37) with loop10 (145–151), and loop3 (46–49) with α5 (152–167). The interconversion between newly identified Ras conformations revealed by this study advances our mechanistic understanding of Ras function. In addition, the pattern of correlated motions provides new evidence for a dynamic linkage between the nucleotide-binding site and the membrane interacting C-terminus critical for the signaling function of Ras. Furthermore, normal mode analysis indicates that the dominant collective motion that occurs during nucleotide-dependent conformational exchange, and captured in aMD (but absent in cMD) simulations, is a low-frequency motion intrinsic to the structure

Fungal iron availability during deep seated candidiasis is defined by a complex interplay involving systemic and local events

Peer reviewedPublisher PD

Serotype-specific mortality from invasive Streptococcus pneumoniae disease revisited

BACKGROUND: Invasive infection with Streptococcus pneumoniae (pneumococci) causes significant morbidity and mortality. Case series and experimental data have shown that the capsular serotype is involved in the pathogenesis and a determinant of disease outcome. METHODS: Retrospective review of 464 cases of invasive disease among adults diagnosed between 1990 and 2001. Multivariate Cox proportional hazard analysis. RESULTS: After adjustment for other markers of disease severity, we found that infection with serotype 3 was associated with an increased relative risk (RR) of death of 2.54 (95% confidence interval (CI): 1.22–5.27), whereas infection with serotype 1 was associated with a decreased risk of death (RR 0.23 (95% CI, 0.06–0.97)). Additionally, older age, relative leucopenia and relative hypothermia were independent predictors of mortality. CONCLUSION: Our study shows that capsular serotypes independently influenced the outcome from invasive pneumococcal disease. The limitations of the current polysaccharide pneumococcal vaccine warrant the development of alternative vaccines. We suggest that the virulence of pneumococcal serotypes should be considered in the design of novel vaccines

Plasmodium falciparum: Differential Selection of Drug Resistance Alleles in Contiguous Urban and Peri-Urban Areas of Brazzaville, Republic of Congo

The African continent is currently experiencing rapid population growth, with rising urbanization increasing the percentage of the population living in large towns and cities. We studied the impact of the degree of urbanization on the population genetics of Plasmodium falciparum in urban and peri-urban areas in and around the city of Brazzaville, Republic of Congo. This field setting, which incorporates local health centers situated in areas of varying urbanization, is of interest as it allows the characterization of malaria parasites from areas where the human, parasite, and mosquito populations are shared, but where differences in the degree of urbanization (leading to dramatic differences in transmission intensity) cause the pattern of malaria transmission to differ greatly. We have investigated how these differences in transmission intensity affect parasite genetic diversity, including the amount of genetic polymorphism in each area, the degree of linkage disequilibrium within the populations, and the prevalence and frequency of drug resistance markers. To determine parasite population structure, heterozygosity and linkage disequilibrium, we typed eight microsatellite markers and performed haplotype analysis of the msp1 gene by PCR. Mutations known to be associated with resistance to the antimalarial drugs chloroquine and pyrimethamine were determined by sequencing the relevant portions of the crt and dhfr genes, respectively. We found that parasite genetic diversity was comparable between the two sites, with high levels of polymorphism being maintained in both areas despite dramatic differences in transmission intensity. Crucially, we found that the frequencies of genetic markers of drug resistance against pyrimethamine and chloroquine differed significantly between the sites, indicative of differing selection pressures in the two areas