Fight or flight: will nurses and ambulance personnel go to work in disaster situations?

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A Weibull-count approach for handling under- and overdispersed longitudinal/clustered data structures

© 2018 SAGE Publications. A Weibull-model-based approach is examined to handle under- and overdispersed discrete data in a hierarchical framework. This methodology was first introduced by Nakagawa and Osaki (1975, IEEE Transactions on Reliability, 24, 300–301), and later examined for under- and overdispersion by Klakattawi et al. (2018, Entropy, 20, 142) in the univariate case. Extensions to hierarchical approaches with under- and overdispersion were left unnoted, even though they can be obtained in a simple manner. This is of particular interest when analysing clustered/longitudinal data structures, where the underlying correlation structure is often more complex compared to cross-sectional studies. In this article, a random-effects extension of the Weibull-count model is proposed and applied to two motivating case studies, originating from the clinical and sociological research fields. A goodness-of-fit evaluation of the model is provided through a comparison of some well-known count models, that is, the negative binomial, Conway–Maxwell–Poisson and double Poisson models. Empirical results show that the proposed extension flexibly fits the data, more specifically, for heavy-tailed, zero-inflated, overdispersed and correlated count data. Discrete left-skewed time-to-event data structures are also flexibly modelled using the approach, with the ability to derive direct interpretations on the median scale, provided the complementary log–log link is used. Finally, a large simulated set of data is created to examine other characteristics such as computational ease and orthogonality properties of the model, with the conclusion that the approach behaves best for highly overdispersed cases.status: publishe

Choice of Mouse Strain Influences the Outcome in a Mouse Model of Chemical-Induced Asthma

Background: The development of occupational asthma is the result of interactions between environmental factors and individual susceptibility. We assessed how our model of chemical-induced asthma is influenced by using different mouse strains. Methodology/Principal Findings: On days 1 and 8, male mice of 7 different strains (BALB/c, BP/2, A/J, C57Bl/6, DBA/2, CBA and AKR) were dermally treated with toluene-2,4-diisocyanate (TDI) (0.3%) or vehicle (acetone/olive oil, AOO, 2:3) on each ear (20 ml). On day 15, they received an oropharyngeal instillation of TDI (0.01%) or AOO (1:4). Airway reactivity to methacholine, total and differential cell counts in bronchoalveolar lavage (BAL) and total serum IgE and IgG2a levels were measured. Lymphocyte subpopulations in auricular lymph nodes and in vitro release of cytokines by ConA stimulated lymphocytes were assessed. In TDI-sensitized and challenged mice, airway hyper-reactivity was only observed in BALB/c, BP/ 2, A/J and AKR mice; airway inflammation was most pronounced in BALB/c mice; numbers of T-helper (CD4 +), T-activated (CD4 + CD25 +), T-cytotoxic (CD8 +) and B- lymphocytes (CD19 +) were increased in the auricular lymph nodes of BALB/c, BP/2, A/J and CBA mice; elevated concentrations of IL-4, IL-10, IL-13 and IFN-c were detected in supernatant of lymphocytes from BALB/c, BP/2, A/J, C57Bl/6 and CBA mice cultured with concanavaline A, along with an increase in total serum IgE. Conclusion: The used mouse strain has considerable and variable impacts on different aspects of the asthma phenotype

Cytokine production by co-cultures exposed to monodisperse amorphous silica nanoparticles: the role of size and surface area.

The aim of this study was to test the influence of nanoparticle size and surface area (SA) on cytokine secretion by co-cultures of pulmonary epithelial cells (A549), macrophages (differentiated THP-1 cells) and endothelium cells (EA.hy926) in a two-compartment system. We used monodisperse amorphous silica nanoparticles (2, 16, 60 and 104 nm) at concentrations of 5 μg/cm² cell culture SA or 10 cm² particle SA/cm². A549 and THP-1 cells were exposed to nanoparticles for 24h, in the presence of EA.hy926 cells cultured in an insert introduced above the bi-culture after 12h. Supernatants from both compartments were recovered and TNF-α, IL-6, IL-8 and MIP-1α were measured. Significant secretion of all cytokines was observed for the 2 nm particles at both concentrations and in both compartments. Larger particles of 60 nm induced significant cytokine secretion at the dose of 10 cm² particle SA/cm². The use of multiple cellular types showed that cytokine secretion in single cell cultures is amplified or mitigated in co-cultures. The release of pro-inflammatory mediators by endothelial cells not directly exposed to nanoparticles indicates a possible endothelium activation after inhalation of silica particles. This work shows the role of size and SA in cellular response to amorphous nanosilica

Radar graphs of the different mouse strains.

<p>The radar graphs give a visual overview of all results combined for the complete control group (0/0) (blue field) versus the complete TDI-treated group (1/1) (red field). Experimental groups are the same as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0012581#pone-0012581-g001" target="_blank">figure 1</a>. The lower limit of each axis is always 0. The upper limit of each axis is the maximum average for a specific parameter measured in one strain and is presented as 100%. AHR  =  area under the curve (AUC) of the airway hyper-reactivity (0–36 AUC of airway resistance) (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0012581#pone-0012581-g001" target="_blank">figure 1H</a>); BAL cells  =  total BAL cell count (0–18.2×10⁴ cells); Macro  =  total number of BAL macrophages (0–11.5×10⁴ cells) (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0012581#pone-0012581-g002" target="_blank">figure 2A and B</a>); Neutro  =  total number of BAL neutrophils (0–5.7×10⁴ cells) (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0012581#pone-0012581-g002" target="_blank">figure 2A and B</a>); Eosino  =  total number of BAL eosinophils (0–1.3×10⁴ cells) (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0012581#pone-0012581-g002" target="_blank">figure 2A and B</a>); IgE  =  total serum IgE (0–8000 ng/ml) (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0012581#pone-0012581-g004" target="_blank">figure 4</a>); IFN-γ, IL-10, IL-13 and IL-4  =  cytokines measured in supernatant of cultured auricular lymphocytes (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0012581#pone-0012581-t001" target="_blank">table 1</a>), IFN-γ (0–3400 pg/ml), IL-10 (0–116 pg/ml), IL-13 (0–530 pg/ml) and IL-4 (0–10.2 pg/ml); CD19⁺  =  CD19⁺ B-lymphocytes per auricular lymph node (0–2.1×10⁶ cells) (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0012581#pone-0012581-g003" target="_blank">figure 3D</a>); CD8⁺  =  CD3⁺CD8⁺ Tc-lymphocytes per auricular lymph node (0–0.6×10⁶ cells) (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0012581#pone-0012581-g003" target="_blank">figure 3C</a>); CD4⁺CD25⁺  =  CD3⁺CD4⁺CD25⁺ activated/Treg-lymphocytes per auricular lymph node (0–0.145×10⁶ cells) (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0012581#pone-0012581-g003" target="_blank">figure 3B</a>); CD4⁺  =  CD3⁺CD4⁺ Th-lymphocytes per auricular lymph node (0–1.8×10⁶ cells) (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0012581#pone-0012581-g003" target="_blank">figure 3A</a>). For specific significant differences between the 0/0 and the 1/1 group, check the specific graphs.</p

Lymphocyte subpopulations in the auricular lymph nodes of different mouse strains.

<p>Auricular lymph nodes were collected and FACS analyses were performed. A) CD3⁺CD4⁺ (Th-lymphocytes), B) CD3⁺CD4⁺CD25⁺ (activated/Treg-lymphocytes), C) CD3⁺CD8⁺ (Tc-lymphocytes) and D) CD19⁺ (B-lymphocytes) lymphocytes were characterized. Experimental groups are the same as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0012581#pone-0012581-g001" target="_blank">figure 1</a>. Data are presented as means ± S.D., n = 4−9, * p<0.05, ** p<0.01 and *** p<0.001 compared to the 0/0 group, # p<0.05, ## p<0.01 and ### p<0.001 compared to the 0/1 group.</p

Cytokines in supernatants of lymphocytes obtained from auricular lymph nodes.

<p>Auricular lymph node cells were cultured (42 h) with concanavaline A (2.5 µg/ml). Concentrations (pg/ml) of IL-2 (data not shown), IL-4, IL-10, IL-13, IL-17 (data not shown) and IFN-γ were measured, by Cytometric Bead Array, in the supernatant. Experimental groups are identical to those in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0012581#pone-0012581-g001" target="_blank">figure 1</a>. Data are presented as mean ± S.D., n = 4−11 values per group. * p<0.05, ** p<0.01 and *** p<0.001 compared to the 0/0 group and ^# p<0.05, ^## p<0.01 and ^### p<0.001 compared to the 0/1 group.</p