A novel application of capnography during controlled human exposure to air pollution

BACKGROUND: The objective was to determine the repeatability and stability of capnography interfaced with human exposure facility. METHODS: Capnographic wave signals were obtained from five healthy volunteers exposed to particle-free, filtered air during two consecutive 5 min intervals, 10 min apart, within the open and then the sealed and operational human exposure facility (HEF). Using a customized setup comprised of the Oridion Microcap(® )portable capnograph, DA converter and AD card, the signal was acquired and saved as an ASCII file for subsequent processing. The minute ventilation (VE), respiratory rate (RR) and expiratory tidal volume (V(TE)) were recorded before and after capnographic recording and then averaged. Each capnographic tracing was analyzed for acceptable waves. From each recorded interval, 8 to 19 acceptable waves were selected and measured. The following wave parameters were obtained: total length and length of phase II and III, slope of phase II and III, area under the curve and area under phase III. In addition, we recorded signal measures including the mean, standard deviation, mode, minimum, maximum – which equals end-tidal CO(2 )(EtCO(2)), zero-corrected maximum and true RMS. RESULTS: Statistical analysis using a paired t-test for means showed no statistically significant changes of any wave parameters and wave signal measures, corrected for RR and V(TE), comparing the measures when the HEF was open vs. sealed and operational. The coefficients of variation of the zero-corrected and uncorrected EtCO(2), phase II absolute difference, signal mean, standard deviation and RMS were less than 10% despite a sub-atmospheric barometric pressure, and slightly higher temperature and relative humidity within the HEF when operational. CONCLUSION: We showed that a customized setup for the acquisition and processing of the capnographic wave signal, interfaced with HEF was stable and repeatable. Thus, we expect that analysis of capnographic waves in controlled human air pollution exposure studies is a feasible tool for characterization of cardio-pulmonary effects of such exposures

Does respiratory health contribute to the effects of long-term air pollution exposure on cardiovascular mortality?

BACKGROUND: There is growing epidemiological evidence that short-term and long-term exposure to high levels of air pollution may increase cardiovascular morbidity and mortality. In addition, epidemiological studies have shown an association between air pollution exposure and respiratory health. To what extent the association between cardiovascular mortality and air pollution is driven by the impact of air pollution on respiratory health is unknown. The aim of this study was to investigate whether respiratory health at baseline contributes to the effects of long-term exposure to high levels of air pollution on cardiovascular mortality in a cohort of elderly women. METHOD: We analyzed data from 4750 women, aged 55 at the baseline investigation in the years 1985–1994. 2593 of these women had their lung function tested by spirometry. Respiratory diseases and symptoms were asked by questionnaire. Ambient air pollution exposure was assessed by the concentrations of NO(2 )and total suspended particles at fixed monitoring sites and by the distance of residency to a major road. A mortality follow-up of these women was conducted between 2001 and 2003. For the statistical analysis, Cox' regression was used. RESULTS: Women with impaired lung function or pre-existing respiratory diseases had a higher risk of dying from cardiovascular causes. The impact of impaired lung function declined over time. The risk ratio (RR) of women with forced expiratory volume in one second (FEV(1)) of less than 80% predicted to die from cardiovascular causes was RR = 3.79 (95%CI: 1.64–8.74) at 5 years survival time and RR = 1.35 (95%CI: 0.66–2.77) at 12 years. The association between air pollution levels and cardiovascular death rate was strong and statistically significant. However, this association did only change marginally when including indicators of respiratory health into the regression analysis. Furthermore, no interaction between air pollution and respiratory health on cardiovascular mortality indicating a higher risk of those with impaired respiratory health could be detected. CONCLUSION: Respiratory health is a predictor for cardiovascular mortality. In women followed about 15 years after the baseline investigation at age 55 years long-term air pollution exposure and impaired respiratory health were independently associated with increased cardiovascular mortality

Information Transfer in Gonadotropin-releasing Hormone (GnRH) Signaling: extracellular signal-regulated kinase (ERK)-mediated feedback loops control hormone sensing

The computation model used in the study of GnRH signalling which was used to generate the data appearing in this paper is in ORE at http://hdl.handle.net/10871/27844Cell signaling pathways are noisy communication channels, and statistical measures derived from information theory can be used to quantify the information they transfer. Here we use single cell signaling measures to calculate mutual information as a measure of information transfer via gonadotropin-releasing hormone (GnRH) receptors (GnRHR) to extracellular signal-regulated kinase (ERK) or nuclear factor of activated T-cells (NFAT). This revealed mutual information values <1 bit, implying that individual GnRH-responsive cells cannot unambiguously differentiate even two equally probable input concentrations. Addressing possible mechanisms for mitigation of information loss, we focused on the ERK pathway and developed a stochastic activation model incorporating negative feedback and constitutive activity. Model simulations revealed interplay between fast (min) and slow (min-h) negative feedback loops with maximal information transfer at intermediate feedback levels. Consistent with this, experiments revealed that reducing negative feedback (by expressing catalytically inactive ERK2) and increasing negative feedback (by Egr1-driven expression of dual-specificity phosphatase 5 (DUSP5)) both reduced information transfer from GnRHR to ERK. It was also reduced by blocking protein synthesis (to prevent GnRH from increasing DUSP expression) but did not differ for different GnRHRs that do or do not undergo rapid homologous desensitization. Thus, the first statistical measures of information transfer via these receptors reveals that individual cells are unreliable sensors of GnRH concentration and that this reliability is maximal at intermediate levels of ERK-mediated negative feedback but is not influenced by receptor desensitization.This work was supported by a Biochemical and Biophysical Science Research Council award (BBSRC BB/J014699/1; to C. A. M. and K. T.-A.)

Particulate matter air pollution and national and county life expectancy loss in the USA: a spatiotemporal analysis

Background Exposure to fine particulate matter pollution (PM2.5) is hazardous to health. Our aim was to directly estimate the health and longevity impacts of current PM2.5 concentrations, and the benefits of reductions from 1999 to 2015, nationally and at county level, for the entire contemporary population of the contiguous United States. Methods and findings We used vital registration and population data with information on sex, age, cause of death and county of residence. We used four Bayesian spatio-temporal models, with different adjustments for other determinants of mortality, to directly estimate mortality and life expectancy loss due to current PM2.5 pollution, and the benefits of reductions since 1999, nationally and by county. The covariates included in the adjusted models were per capita income; percentage of population whose family income is below the poverty threshold, who are of Black or African American race, who have graduated from high-school, who live in urban areas, and who are unemployed; cumulative smoking; and mean temperature and relative humidity. In the main model, which adjusted for these covariates and for unobserved county characteristics through the use of county random intercepts, PM2.5 pollution in excess of the lowest observed concentration (2.8 µg/m3) was responsible for an estimated 15,612 deaths (95% credible interval 13,248-17,945) in females and in 14,757 deaths (12,617-16,919) for males. These deaths would lower national life expectancy by an estimated 0.15 years (0.13-0.17) for women and 0.13 years (0.11-0.15) for men. The life expectancy loss due to PM2.5 was largest around Los Angeles and in some southern states, such as Arkansas, Oklahoma or Alabama. At any PM2.5 concentration, life expectancy loss was, on average, larger in counties with lower income than in wealthier counties. Reductions in PM2.5 since 1999 have lowered mortality in all but 14 counties where PM2.5 increased slightly. The main limitation of our study, similar to other observational studies, is that it is not guaranteed for the observed associations to be causal. We did not have annual county-level data on other important determinants of mortality, such as healthcare access and quality and diet, but these factors were adjusted for with use of county random intercepts. Conclusions According to our estimates, recent reductions in particulate matter pollution in the USA have resulted in public health benefits. Nonetheless, we estimate that current concentrations are associated with mortality impacts and loss of life expectancy, with larger impacts in counties with lower income and higher poverty rate

Leg disorders in broiler chickens : prevalence, risk factors and prevention

Broiler (meat) chickens have been subjected to intense genetic selection. In the past 50 years, broiler growth rates have increased by over 300% (from 25 g per day to 100 g per day). There is growing societal concern that many broiler chickens have impaired locomotion or are even unable to walk. Here we present the results of a comprehensive survey of commercial flocks which quantifies the risk factors for poor locomotion in broiler chickens.We assessed the walking ability of 51,000 birds, representing 4.8 million birds within 176 flocks.We also obtained information on approximately 150 different management factors associated with each flock. At a mean age of 40 days, over 27.6% of birds in our study showed poor locomotion and 3.3% were almost unable to walk. The high prevalence of poor locomotion occurred despite culling policies designed to remove severely lame birds from flocks. We show that the primary risk factors associated with impaired locomotion and poor leg health are those specifically associated with rate of growth. Factors significantly associated with high gait score included the age of the bird (older birds), visit (second visit to same flock), bird genotype, not feeding whole wheat, a shorter dark period during the day, higher stocking density at the time of assessment, no use of antibiotic, and the use of intact feed pellets. The welfare implications are profound. Worldwide approximately 261010 broilers are reared within similar husbandry systems.We identify a range of management factors that could be altered to reduce leg health problems, but implementation of these changes would be likely to reduce growth rate and production. A debate on the sustainability of current practice in the production of this important food source is required

The influence of location, source, and emission type in estimates of the human health benefits of reducing a ton of air pollution

The benefit per ton ($/ton) of reducing PM2.5 varies by the location of the emission reduction, the type of source emitting the precursor, and the specific precursor controlled. This paper examines how each of these factors influences the magnitude of the$/ton estimate. We employ a reduced-form air quality model to predict changes in ambient PM2.5 resulting from an array of emission control scenarios affecting 12 different combinations of sources emitting carbonaceous particles, NOx, SOx, NH3, and volatile organic compounds. We perform this modeling for each of nine urban areas and one nationwide area. Upon modeling the air quality change, we then divide the total monetized health benefits by the PM2.5 precursor emission reductions to generate $/ton metrics. The resulting$/ton estimates exhibit the greatest variability across certain precursors and sources such as area source SOx, point source SOx, and mobile source NH3. Certain $/ton estimates, including mobile source NOx, exhibit significant variability across urban areas. Reductions in carbonaceous particles generate the largest$/ton across all locations

Effects of Particulate Air Pollution on Cardiovascular Health: A Population Health Risk Assessment

Particulate matter (PM) air pollution is increasingly recognized as an important and modifiable risk factor for adverse health outcomes including cardiovascular disease (CVD). However, there are still gaps regarding large population risk assessment. Results from the nationwide Behavioral Risk Factor Surveillance System (BRFSS) were used along with air quality monitoring measurements to implement a systematic evaluation of PM-related CVD risks at the national and regional scales. CVD status and individual-level risk factors were collected from more than 500,000 BRFSS respondents across 2,231 contiguous U.S. counties for 2007 and 2009. Chronic exposures to PM pollutants were estimated with spatial modeling from measurement data. CVD outcomes attributable to PM pollutants were assessed by mixed-effects logistic regression and latent class regression (LCR), with adjustment for multicausality. There were positive associations between CVD and PM after accounting for competing risk factors: the multivariable-adjusted odds for the multiplicity of CVD outcomes increased by 1.32 (95% confidence interval: 1.23–1.43) and 1.15 (1.07–1.22) times per 10 µg/m3 increase in PM2.5 and PM10 respectively in the LCR analyses. After controlling for spatial confounding, there were moderate estimated effects of PM exposure on multiple cardiovascular manifestations. These results suggest that chronic exposures to ambient particulates are important environmental risk factors for cardiovascular morbidity

Biodistribution of gold nanoparticles in mouse lung following intratracheal instillation

<p>Abstract</p> <p>Background</p> <p>The fate of gold nanoparticles, 2, 40 and 100 nm, administered intratracheally to adult female mice was examined. The nanoparticles were traced by autometallography (AMG) at both ultrastructural and light microscopic levels. Also, the gold content was quantified by inductively coupled plasma mass spectrometry (ICP-MS) and neutron activation analysis (NAA). The liver is the major site of deposition of circulating gold nanoparticles. Therefore the degree of translocation was determined by the hepatic deposition of gold. Mice were instilled with 5 intratracheal doses of gold nanoparticles distributed over a period of 3 weeks and were killed 24 h after the last dose. One group of mice were given a single intratracheal dose and were killed after 1 h.</p> <p>Results</p> <p>The instilled nanoparticles were found in lung macrophages already 1 h after a single instillation. In mice instilled treated repeatedly during 3 weeks, the load was substantial. Ultrastructurally, AMG silver enhanced gold nanoparticles were found in lysosome-/endosome-like organelles of the macrophages and analysis with AMG, ICP-MS and NAA of the liver revealed an almost total lack of translocation of nanoparticles. In mice given repeated instillations of 2 nm gold nanoparticles, 1.4‰ (by ICP-MS) to 1.9‰ (by NAA) of the instilled gold was detected in the liver. With the 40 nm gold, no gold was detected in the liver (detection level 2 ng, 0.1‰) except for one mouse in which 3‰ of the instilled gold was found in the liver. No gold was detected in any liver of mice instilled with 100 nm gold (detection level 2 ng, 0.1‰) except in a single animal with 0.39‰ of the dose in the liver.</p> <p>Conclusion</p> <p>We found that that: (1) inert gold nanoparticles, administered intratracheally are phagocytosed by lung macrophages; (2) only a tiny fraction of the gold particles is translocated into systemic circulation. (3) The translocation rate was greatest with the 2 nm gold particles.</p