Validation of an arterial constitutive model accounting for collagen content and crosslinking

During the progression of pulmonary hypertension (PH), proximal pulmonary arteries (PAs) increase in both thickness and stiffness. Collagen, a component of the extracellular matrix, is mainly responsible for these changes via increased collagen fiber amount (or content) and crosslinking. We sought to differentiate the effects of collagen content and cross-linking on mouse PA mechanical changes using a constitutive model with parameters derived from experiments in which collagen content and cross-linking were decoupled during hypoxic pulmonary hypertension (HPH). We employed an eight-chain orthotropic element model to characterize collagen’s mechanical behavior and an isotropic neo-Hookean form to represent elastin. Our results showed a strong correlation between the material parameter related to collagen content and measured collagen content (R2 = 0.82, P < 0.0001) and a moderate correlation between the material parameter related to collagen crosslinking and measured crosslinking (R2 = 0.24, P = 0.06). There was no significant change in either the material parameter related to elastin or the measured elastin content from histology. The model-predicted pressure at which collagen begins to engage was ∼25 mmHg, which is consistent with experimental observations. We conclude that this model may allow us to predict changes in the arterial extracellular matrix from measured mechanical behavior in PH patients, which may provide insight into prognoses and the effects of therapy

Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks for 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017

Background The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 comparative risk assessment (CRA) is a comprehensive approach to risk factor quantification that offers a useful tool for synthesising evidence on risks and risk–outcome associations. With each annual GBD study, we update the GBD CRA to incorporate improved methods, new risks and risk–outcome pairs, and new data on risk exposure levels and risk–outcome associations. Methods We used the CRA framework developed for previous iterations of GBD to estimate levels and trends in exposure, attributable deaths, and attributable disability-adjusted life-years (DALYs), by age group, sex, year, and location for 84 behavioural, environmental and occupational, and metabolic risks or groups of risks from 1990 to 2017. This study included 476 risk–outcome pairs that met the GBD study criteria for convincing or probable evidence of causation. We extracted relative risk and exposure estimates from 46 749 randomised controlled trials, cohort studies, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. Using the counterfactual scenario of theoretical minimum risk exposure level (TMREL), we estimated the portion of deaths and DALYs that could be attributed to a given risk. We explored the relationship between development and risk exposure by modelling the relationship between the Socio-demographic Index (SDI) and risk-weighted exposure prevalence and estimated expected levels of exposure and risk-attributable burden by SDI. Finally, we explored temporal changes in risk-attributable DALYs by decomposing those changes into six main component drivers of change as follows: (1) population growth; (2) changes in population age structures; (3) changes in exposure to environmental and occupational risks; (4) changes in exposure to behavioural risks; (5) changes in exposure to metabolic risks; and (6) changes due to all other factors, approximated as the risk-deleted death and DALY rates, where the risk-deleted rate is the rate that would be observed had we reduced the exposure levels to the TMREL for all risk factors included in GBD 2017. Findings In 2017, 34·1 million (95% uncertainty interval [UI] 33·3–35·0) deaths and 1·21 billion (1·14–1·28) DALYs were attributable to GBD risk factors. Globally, 61·0% (59·6–62·4) of deaths and 48·3% (46·3–50·2) of DALYs were attributed to the GBD 2017 risk factors. When ranked by risk-attributable DALYs, high systolic blood pressure (SBP) was the leading risk factor, accounting for 10·4 million (9·39–11·5) deaths and 218 million (198–237) DALYs, followed by smoking (7·10 million [6·83–7·37] deaths and 182 million [173–193] DALYs), high fasting plasma glucose (6·53 million [5·23–8·23] deaths and 171 million [144–201] DALYs), high body-mass index (BMI; 4·72 million [2·99–6·70] deaths and 148 million [98·6–202] DALYs), and short gestation for birthweight (1·43 million [1·36–1·51] deaths and 139 million [131–147] DALYs). In total, risk-attributable DALYs declined by 4·9% (3·3–6·5) between 2007 and 2017. In the absence of demographic changes (ie, population growth and ageing), changes in risk exposure and risk-deleted DALYs would have led to a 23·5% decline in DALYs during that period. Conversely, in the absence of changes in risk exposure and risk-deleted DALYs, demographic changes would have led to an 18·6% increase in DALYs during that period. The ratios of observed risk exposure levels to exposure levels expected based on SDI (O/E ratios) increased globally for unsafe drinking water and household air pollution between 1990 and 2017. This result suggests that development is occurring more rapidly than are changes in the underlying risk structure in a population. Conversely, nearly universal declines in O/E ratios for smoking and alcohol use indicate that, for a given SDI, exposure to these risks is declining. In 2017, the leading Level 4 risk factor for age-standardised DALY rates was high SBP in four super-regions: central Europe, eastern Europe, and central Asia; north Africa and Middle East; south Asia; and southeast Asia, east Asia, and Oceania. The leading risk factor in the high-income super-region was smoking, in Latin America and Caribbean was high BMI, and in sub-Saharan Africa was unsafe sex. O/E ratios for unsafe sex in sub-Saharan Africa were notably high, and those for alcohol use in north Africa and the Middle East were notably low. Interpretation By quantifying levels and trends in exposures to risk factors and the resulting disease burden, this assessment offers insight into where past policy and programme efforts might have been successful and highlights current priorities for public health action. Decreases in behavioural, environmental, and occupational risks have largely offset the effects of population growth and ageing, in relation to trends in absolute burden. Conversely, the combination of increasing metabolic risks and population ageing will probably continue to drive the increasing trends in non-communicable diseases at the global level, which presents both a public health challenge and opportunity. We see considerable spatiotemporal heterogeneity in levels of risk exposure and risk-attributable burden. Although levels of development underlie some of this heterogeneity, O/E ratios show risks for which countries are overperforming or underperforming relative to their level of development. As such, these ratios provide a benchmarking tool to help to focus local decision making. Our findings reinforce the importance of both risk exposure monitoring and epidemiological research to assess causal connections between risks and health outcomes, and they highlight the usefulness of the GBD study in synthesising data to draw comprehensive and robust conclusions that help to inform good policy and strategic health planning

Buckling optimization of variable stiffness helicoidal composite laminates based on semi-analytical method

Variable stiffness laminates and helicoidal composites have gained significant attention in recent years. This paper introduces a novel structure called variable stiffness helicoidal composite laminates, which combines these two materials. The fibers in each layer are arranged in curved paths, and all the layers are stacked in a helicoidal pattern. To ensure uniform thickness throughout the laminate, an equidistant placement method is proposed for designing the curvilinear fibers. By establishing the energy equation and fitting the displacements with Legendre polynomials, a semi-analytical method is proposed to determine the critical buckling load. An integrated design framework is developed to obtain the optimal design. The optimized models show more than 10% enhancement in the critical buckling load compared to the quasi-isotropic laminate under uniaxial compression and in-plane shear

Ammonia Oxidizers in a Pilot-Scale Multilayer Rapid Infiltration System for Domestic Wastewater Treatment

<div><p>A pilot-scale multilayer rapid infiltration system (MRIS) for domestic wastewater treatment was established and efficient removal of ammonia and chemical oxygen demand (COD) was achieved in this study. The microbial community composition and abundance of ammonia oxidizers were investigated. Efficient biofilms of ammonia oxidizers in the stationary phase (packing material) was formed successfully in the MRIS without special inoculation. DGGE and phylogenetic analyses revealed that proteobacteria dominated in the MRIS. Relative abundance of ammonia-oxidizing archaea (AOA) and ammonia-oxidizing bacteria (AOB) showed contrary tendency. In the flowing phase (water effluent), AOA diversity was significantly correlated with the concentration of dissolve oxygen (DO), NO₃-N and NH₃-N. AOB abundance was significantly correlated with the concentration of DO and chemical oxygen demand (COD). NH₃-N and COD were identified as the key factors to shape AOB community structure, while no variable significantly correlated with that of AOA. AOA might play an important role in the MRIS. This study could reveal key environmental factors affecting the community composition and abundance of ammonia oxidizers in the MRIS.</p></div

Differential immune responses of C57BL/6 mice to infection by Salmonella enterica serovar Typhimurium strain SL1344, CVCC541 and CMCC50115

With a broad range of hosts, Salmonella enterica serovar Typhimurium (S. Typhimurium) is the major cause of gastroenteritis in human beings and systemic disease in susceptible mice strains. However, different S. Typhimurium strains differ in regard to virulence and host adaptation. Here, C57BL/6 mice were infected, respectively, with different S. Typhimurium strains SL1344 (calf), CVCC541 (chicken) and CMCC50115 (mutton) to determine their virulence and host immune responses. It was found that mice were less susceptible to infection by S. Typhimurium CVCC541 and CMCC50115 strains, with lower lethality and decreased bacterial burden in liver and spleen. Besides, S. Typhimurium strains CVCC541 and CMCC50115 enhanced host innate immune responses by increased frequencies of macrophages and neutrophils 3 days after infection. But SL1344 strain evaded immune response by inducing apoptosis of macrophages. Moreover, CVCC541 could elicit adaptive immune responses of host 11 days after infection upon examination of the proliferation and activation of CD4+ T cells. In addition, 125 and 138 unique mutant coding genes, respectively, in S. Typhimurium strains CVCC541 and CMCC50115 and 78 shared mutant coding genes were annotated by genomic alignment to SL1344 genome and the signal pathways involving these genes were further analyzed. The acquired results indicate that different original S. Typhimurium strains show differential virulence and may induce diverse immune responses in the same host infected

Short-term effects of air pollution on daily mortality and years of life lost in Nanjing, China

The deteriorating air quality in Chinese cities is attracting growing public concern. We conducted analyses to quantify the associations between daily changes in ambient air pollution and mortality in Nanjing, China. Daily mortality, air pollution, and meteorological data from 1 January 2009 to 31 December 2013 were collected. Over-dispersed Poisson regression models were used to evaluate the risk of daily non-accidental mortality and years of life lost (YLL) from exposure to respirable particulate matter (PM10) and gaseous pollutants (NO2, SO2). Stratified analysis was conducted to indentify the modifying effect of individual-level factors on the association between air pollutants and mortality. We found that interquartile range (IQR) increases in the two-day average of PM10, NO2 and SO2 were significantly associated with 1.6% [95% confidence interval (CI):0.7%-2.6%], 2.9% (95% CI: 1.7%-4.2%) and 2.4% (95% CI: 1.2%-3.6%) higher rates of non-accidental mortality; and related to YLL increases of 20.5 (95% CI: 6.3-34.8), 34.9 (95% CI: 16.9-52.9) and 30.3 (95% CI: 12.2-48.4) years, respectively; Associations between air pollution and mortality were more pronounced in the warm season than in the cool season. We conclude that the risks of mortality and YLL were elevated corresponding to an increase in current ambient concentrations of the air pollutants, and season may modify the effects of outdoor air pollution in Nanjing

The copy numbers of AOB and AOA <i>amo</i>A genes from the flowing (A) and the stationary phase (B).

<p>All data are the means of values obtained from three parallel experiments ± SD (<i>t</i>-test, <i>p</i><0.01) using the ΔΔCT method. A1–5: the Inlet, Sampling port 1–3, and the Outlet, correspondingly; P1–8: Packing 1–8, correspondingly.</p

Triplot of RDA for AOB in the flowing phase.

<p>The first and the second axes explained 76.8% and 6.8% of the total variation respectively. The length of each arrow is correlated with the degree of relationship between the response variables. The arrows point in the direction of the maximum change for the associated variable. Open symbols represent samples from the flowing phase.</p

Phylogenetic analysis of 16S rRNA genes.

<p>Phylogenetic tree was constructed using the Neighbor-Joining method by MEGA v4.0.2 software. The numbers at the nodes are bootstrap values (<i>n</i> = 1000) and the Random seed value is 64,238.</p