Use of a novel pedal-operated compressor is non-inferior to the use of a standard hand-compressed bag-valve mask.

BACKGROUND: The standard bag-valve mask (BVM) used universally requires that a single healthcare practitioner affix the mask to the face with 1 hand while compressing a self-inflating bag with the second hand. Studies have demonstrated that creating a 2-handed seal (with 2 healthcare practitioners) is superior. Our study aims to assess the efficacy of a novel single-practitioner BVM device that uses a foot pedal as the bag compressor, allowing both hands to be available for the seal to facilitate delivery of appropriate tidal volumes during single-practitioner resuscitation. METHODS: This was a prospective, randomized, cross-over study. Participants with various BVM ventilation experience performed 2 minutes of metronome-guided BVM ventilation using a standard BVM and the pedal-operated compressor on a high-fidelity simulation mannequin. Analysis examining differences in mean tidal volume delivered was conducted using a regression model that adjusted for covariates. A secondary analysis using a series of Wilcoxon tests was conducted to compare differences in the additional out-of-range sensed breaths metrics to compare differences by prior BVM ventilation experience. RESULTS: A total of 58 subjects participated. The pedal-operated compressor unadjusted mean tidal volume delivered was 446.5 mL (95% confidence interval [CI], 425.9-467.1) compared with 340.6 mL (95% CI, 312.2-369.0) by standard BVM (mean change, 105.9 mL [95% CI, 71.2-140.6]; P < .001). When modeling a generalized estimation equation regression model, standard BVM ventilation provided a mean difference of 105.9 mL less than pedal-operated compressor ventilation after adjusting for covariates (P = 0.01). For the secondary outcome, the pedal-operated compressor did have a significantly lower median number of out-of-range breaths (median, 3; interquartile range [IQR], 1-11.5) compared with the standard device (median, 13.5; IQR, 6-19; P < 0.001). CONCLUSIONS: Use of a novel pedal-operated compressor may allow a single healthcare practitioner, regardless of prior experience, to deliver consistent, appropriate tidal volumes with more ease compared with the standard BVM during manual respiratory resuscitation.

Motility-limited aggregation of mammary epithelial cells into fractal-like clusters.

Migratory cells transition between dispersed individuals and multicellular collectives during development, wound healing, and cancer. These transitions are associated with coordinated behaviors as well as arrested motility at high cell densities, but remain poorly understood at lower cell densities. Here, we show that dispersed mammary epithelial cells organize into arrested, fractal-like clusters at low density in reduced epidermal growth factor (EGF). These clusters exhibit a branched architecture with a fractal dimension of [Formula: see text], reminiscent of diffusion-limited aggregation of nonliving colloidal particles. First, cells display diminished motility in reduced EGF, which permits irreversible adhesion upon cell-cell contact. Subsequently, leader cells emerge that guide collectively migrating strands and connect clusters into space-filling networks. Thus, this living system exhibits gelation-like arrest at low cell densities, analogous to the glass-like arrest of epithelial monolayers at high cell densities. We quantitatively capture these behaviors with a jamming-like phase diagram based on local cell density and EGF. These individual to collective transitions represent an intriguing link between living and nonliving systems, with potential relevance for epithelial morphogenesis into branched architectures.

Morphological single cell profiling of the epithelial-mesenchymal transition.

Single cells respond heterogeneously to biochemical treatments, which can complicate the analysis of in vitro and in vivo experiments. In particular, stressful perturbations may induce the epithelial-mesenchymal transition (EMT), a transformation through which compact, sensitive cells adopt an elongated, resistant phenotype. However, classical biochemical measurements based on population averages over large numbers cannot resolve single cell heterogeneity and plasticity. Here, we use high content imaging of single cell morphology to classify distinct phenotypic subpopulations after EMT. We first characterize a well-defined EMT induction through the master regulator Snail in mammary epithelial cells over 72 h. We find that EMT is associated with increased vimentin area as well as elongation of the nucleus and cytoplasm. These morphological features were integrated into a Gaussian mixture model that classified epithelial and mesenchymal phenotypes with >92% accuracy. We then applied this analysis to heterogeneous populations generated from less controlled EMT-inducing stimuli, including growth factors (TGF-ß1), cell density, and chemotherapeutics (Taxol). Our quantitative, single cell approach has the potential to screen large heterogeneous cell populations for many types of phenotypic variability, and may thus provide a predictive assay for the preclinical assessment of targeted therapeutics.