Local cell metrics: a novel method for analysis of cell-cell interactions

<p>Abstract</p> <p>Background</p> <p>The regulation of many cell functions is inherently linked to cell-cell contact interactions. However, effects of contact interactions among adherent cells can be difficult to detect with global summary statistics due to the localized nature and noise inherent to cell-cell interactions. The lack of informatics approaches specific for detecting cell-cell interactions is a limitation in the analysis of large sets of cell image data, including traditional and combinatorial or high-throughput studies. Here we introduce a novel histogram-based data analysis strategy, termed local cell metrics (LCMs), which addresses this shortcoming.</p> <p>Results</p> <p>The new LCM method is demonstrated via a study of contact inhibition of proliferation of MC3T3-E1 osteoblasts. We describe how LCMs can be used to quantify the local environment of cells and how LCMs are decomposed mathematically into metrics specific to each cell type in a culture, e.g., differently-labelled cells in fluorescence imaging. Using this approach, a quantitative, probabilistic description of the contact inhibition effects in MC3T3-E1 cultures has been achieved. We also show how LCMs are related to the naïve Bayes model. Namely, LCMs are Bayes class-conditional probability functions, suggesting their use for data mining and classification.</p> <p>Conclusion</p> <p>LCMs are successful in robust detection of cell contact inhibition in situations where conventional global statistics fail to do so. The noise due to the random features of cell behavior was suppressed significantly as a result of the focus on local distances, providing sensitive detection of cell-cell contact effects. The methodology can be extended to any quantifiable feature that can be obtained from imaging of cell cultures or tissue samples, including optical, fluorescent, and confocal microscopy. This approach may prove useful in interpreting culture and histological data in fields where cell-cell interactions play a critical role in determining cell fate, e.g., cancer, developmental biology, and tissue regeneration.</p

Tricomponent composites with cellulose nanocrystals and chitin nanofibers - Exploring potential synergy through component interactions

Bio-based materials are being investigated increasingly as alternatives for synthetic materials in a variety of application areas, including composite materials. Among the options for bio-based materials, cellulose and chitin are abundant and increasingly available in different forms, including nanofibers. Due to their anticipated mechanical properties and anisotropic structure, nanofibers of cellulose and chitin lend themselves naturally for use as reinforcing fillers in polymer matrix composites, and the use of each in composites has been studied. However, composites containing both nanofillers has been explored to a lesser extent, and this composite design may provide benefits beyond those seen when the nanofibers are used separately. Therefore, the objective of this work is to examine how nanoscale forms of cellulose and chitin may be used separately and together in composite constructs. Specifically, we are preparing and characterizing composites composed of cellulose nanocrystals (CNCs) and/or chitin nanofibers (ChNFs) in a poly(vinyl alcohol) (PVA) matrix to understand more fully how component interactions affect the structure-property relationships in these materials and how these interactions may be used to produce synergistic improvements. For the specific CNCs and ChNFs used in this work, the nanofillers have opposite surface charge, with CNCs having a negative surface charge and ChNFs having a positive surface charge. Additionally, the components have an ability to interact through hydrogen bonding. These different types of interactions are anticipated to play a role in the structural development in the composites through the processing steps. To probe the effect of these interactions further, we have studied consolidated films as well as hydrogels. The results of these studies indicate that composites containing certain CNC/ChNF ratios possess better mechanical properties than composites containing only one type of nanofiber. Additionally, composites containing CNC/ChNF ratios where surface charges are more evenly balanced experience increased aggregation, presumably due to charge-driven association between the fillers. Mechanical property trends in consolidated films and hydrogels were qualitatively similar, suggesting a general behavior resulting from the component interactions. References 1. C.W. Irvin, C.C. Satam, J.C. Meredith, and M.L. Shofner, “Mechanical reinforcement and thermal properties of PVA tricomponent nanocomposites with chitin nanofibers and cellulose nanocrystals”, Composites Part A: Applied Science and Manufacturing, 116, 147-157 (2019)

Cloud condensation nuclei activity of six pollenkitts and the influence of their surface activity

The role of surfactants in governing water interactions of atmospheric aerosols has been a recurring topic in cloud microphysics for more than two decades. Studies of detailed surface thermodynamics are limited by the availability of aerosol samples for experimental analysis and incomplete validation of various proposed Kohler model frameworks for complex mixtures representative of atmospheric aerosol. Pollenkitt is a viscous material that coats grains of pollen and plays important roles in pollen dispersion and plant reproduction. Previous work suggests that it may also be an important contributor to pollen water uptake and cloud condensation nuclei (CCN) activity. The chemical composition of pollenkitt varies between species but has been found to comprise complex organic mixtures including oxygenated, lipid, and aliphatic functionalities. This mix of functionalities suggests that pollenkitt may display aqueous surface activity, which could significantly impact pollen interactions with atmospheric water. Here, we study the surface activity of pollenkitt from six different species and its influence on pollenkitt hygroscopicity. We measure cloud droplet activation and concentration-dependent surface tension of pollenkitt and its mixtures with ammonium sulfate salt. Experiments are compared to predictions from several thermodynamic models, taking aqueous surface tension reduction and surfactant surface partitioning into account in various ways. We find a clear reduction of surface tension by pollenkitt in aqueous solution and evidence for impact of both surface tension and surface partitioning mechanisms on cloud droplet activation potential and hygroscopicity of pollenkitt particles. In addition, we find indications of complex nonideal solution effects in a systematic and consistent dependency of pollenkitt hygroscopicity on particle size. The impact of pollenkitt surface activity on cloud microphysics is different from what is observed in previous work for simple atmospheric surfactants and more resembles recent observations for complex primary and secondary organic aerosol, adding new insight to our understanding of the multifaceted role of surfactants in governing aerosol-water interactions. We illustrate how the explicit characterization of pollenkitt contributions provides the basis for modeling water uptake and cloud formation of pollen and their fragments over a wide range of atmospheric conditions.Peer reviewe

Sources of unsafe primary care for older adults: a mixed-methods analysis of patient safety incident reports

Background: Older adults are frequent users of primary healthcare services, but are at increased risk of healthcare-related harm in this setting. Objectives: To describe the factors associated with actual or potential harm to patients aged 65 years and older, treated in primary care, to identify action to produce safer care. Design and Setting: A cross-sectional mixed-methods analysis of a national (England and Wales) database of patient safety incident reports from 2005 to 2013. Subjects: 1,591 primary care patient safety incident reports regarding patients aged 65 years and older. Methods: We developed a classification system for the analysis of patient safety incident reports to describe: the incident and preceding chain of incidents; other contributory factors; and patient harm outcome. We combined findings from exploratory descriptive and thematic analyses to identify key sources of unsafe care. Results: The main sources of unsafe care in our weighted sample were due to: medication-related incidents e.g. prescribing, dispensing and administering (n = 486, 31%; 15% serious patient harm); communication-related incidents e.g. incomplete or non-transfer of information across care boundaries (n = 390, 25%; 12% serious patient harm); and clinical decision-making incidents which led to the most serious patient harm outcomes (n = 203, 13%; 41% serious patient harm). Conclusion: Priority areas for further research to determine the burden and preventability of unsafe primary care for older adults, include: the timely electronic tools for prescribing, dispensing and administering medication in the community; electronic transfer of information between healthcare settings; and, better clinical decision-making support and guidance

Caregiver-Assisted Coping Skills Training for Lung Cancer: Results of a Randomized Clinical Trial

Lung cancer is one of the most common cancers in the U.S. and is associated with high levels of symptoms including pain, fatigue, shortness of breath, and psychological distress. Caregivers as well as patients are adversely affected. However, previous studies of coping skills training (CST) interventions have not been tested in patients with lung cancer nor systematically included caregivers

High-resolution in situ observations of electron precipitation-causing EMIC waves

Electromagnetic ion cyclotron (EMIC) waves are thought to be important drivers of energetic electron losses from the outer radiation belt through precipitation into the atmosphere. While the theoretical possibility of pitch angle scattering-driven losses from these waves has been recognized for more than four decades, there have been limited experimental precipitation observations to support this concept. We have combined satellite-based observations of the characteristics of EMIC waves, with satellite and ground-based observations of the EMIC-induced electron precipitation. In a detailed case study, supplemented by an additional four examples, we are able to constrain for the first time the location, size, and energy range of EMIC-induced electron precipitation inferred from coincident precipitation data and relate them to the EMIC wave frequency, wave power, and ion band of the wave as measured in situ by the Van Allen Probes. These observations will better constrain modeling into the importance of EMIC wave-particle interactions