Additive Modulation of DNA-DNA Interactions by Interstitial Ions

Quantitative understanding of biomolecular electrostatics, particularly involving multivalent ions and highly charged surfaces, remains lacking. Ion-modulated interactions between nucleic acids provide a model system in which electrostatics plays a dominant role. Using ordered DNA arrays neutralized by spherical cobalt3+ hexammine and Mg2+ ions, we investigate how the interstitial ions modulate DNA-DNA interactions. Using methods of ion counting, osmotic stress, and x-ray diffraction, we systematically determine thermodynamic quantities, including ion chemical potentials, ion partition, DNA osmotic pressure and force, and DNA-DNA spacing. Analyses of the multidimensional data provide quantitative insights into their interdependencies. The key finding of this study is that DNA-DNA forces are observed to linearly depend on the partition of interstitial ions, suggesting the dominant role of ion-DNA coupling. Further implications are discussed in light of physical theories of electrostatic interactions and like-charge attraction

Personalization Paradox in Behavior Change Apps:Lessons from a Social Comparison-Based Personalized App for Physical Activity

Social comparison-based features are widely used in social computing apps. However, most existing apps are not grounded in social comparison theories and do not consider individual differences in social comparison preferences and reactions. This paper is among the first to automatically personalize social comparison targets. In the context of an m-health app for physical activity, we use artificial intelligence (AI) techniques of multi-armed bandits. Results from our user study (n=53) indicate that there is some evidence that motivation can be increased using the AI-based personalization of social comparison. The detected effects achieved small-to-moderate effect sizes, illustrating the real-world implications of the intervention for enhancing motivation and physical activity. In addition to design implications for social comparison features in social apps, this paper identified the personalization paradox, the conflict between user modeling and adaptation, as a key design challenge of personalized applications for behavior change. Additionally, we propose research directions to mitigate this Personalization Paradox

An open dataset of Plasmodium falciparum genome variation in 7,000 worldwide samples.

MalariaGEN is a data-sharing network that enables groups around the world to work together on the genomic epidemiology of malaria. Here we describe a new release of curated genome variation data on 7,000 Plasmodium falciparum samples from MalariaGEN partner studies in 28 malaria-endemic countries. High-quality genotype calls on 3 million single nucleotide polymorphisms (SNPs) and short indels were produced using a standardised analysis pipeline. Copy number variants associated with drug resistance and structural variants that cause failure of rapid diagnostic tests were also analysed.  Almost all samples showed genetic evidence of resistance to at least one antimalarial drug, and some samples from Southeast Asia carried markers of resistance to six commonly-used drugs. Genes expressed during the mosquito stage of the parasite life-cycle are prominent among loci that show strong geographic differentiation. By continuing to enlarge this open data resource we aim to facilitate research into the evolutionary processes affecting malaria control and to accelerate development of the surveillance toolkit required for malaria elimination

Pf7: an open dataset of Plasmodium falciparum genome variation in 20,000 worldwide samples

We describe the MalariaGEN Pf7 data resource, the seventh release of Plasmodium falciparum genome variation data from the MalariaGEN network.  It comprises over 20,000 samples from 82 partner studies in 33 countries, including several malaria endemic regions that were previously underrepresented.  For the first time we include dried blood spot samples that were sequenced after selective whole genome amplification, necessitating new methods to genotype copy number variations.  We identify a large number of newly emerging crt mutations in parts of Southeast Asia, and show examples of heterogeneities in patterns of drug resistance within Africa and within the Indian subcontinent.  We describe the profile of variations in the C-terminal of the csp gene and relate this to the sequence used in the RTS,S and R21 malaria vaccines.  Pf7 provides high-quality data on genotype calls for 6 million SNPs and short indels, analysis of large deletions that cause failure of rapid diagnostic tests, and systematic characterisation of six major drug resistance loci, all of which can be freely downloaded from the MalariaGEN website

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Correction to: Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

The original version of this article unfortunately contained a mistake

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Integration and Competition in Immune Cell Models

Cell motility plays an integral role in most biological processes. One principle of motility is the protrusions and retractions of cellular membranes called pseudopods. The physical force behind pseudopod formation is actin polymerization. As the physical driver, actin polymerization integrates the cells’ upstream biochemical signaling cascades and turns the signals into action as the combined output and readout of the state of the cell. Actin polymerization not only occurs within pseudopods but propagates throughout a cell in waves that can be understood and modeled as excitable media.This dissertation focuses on actin wave dynamics in the context of directed cell mi- gration using both experimental and numerical techniques. The directional guidance of cell migration is essential in physiological processes including embryonic development, cancer metastasis, and wound healing. In this thesis, I analyze how immune-like cells are guided by external stimuli that are common in wound environments: electric fields, chemical gradients, and surface texture. A focus of this work is on the emergent excitable wave behavior of actin, and the pseudopods they generate, in simplified, in vitro environments. Actin waves have been previously shown to respond to and be guided by the topography of an underlying substrate. Additionally, static quantifications of actin filaments during or after electric field stimulation have shown that filaments become asymmetrically distributed within the cytoplasm. In neutrophils, the combination of cues leads to higher control of cell motility by guiding the internal actin waves. Using an optical flow algorithm, I quantify the actin waves on multiple length scales to ascertain the role of each guidance cue in affecting cell motion. I find that the waves preferentially polymerize near and travel along the nanoridges. Actin waves nucleate preferentially on the cathode side and reorient the cell’s axis of polarity (i.e., the position of the dominant pseudopod). The second example of competing guidance cues involves studying the collective motion of cells in response to cell-cell signal relay in competition with surface topography. I use Dictyostelium discoideum cells as a model system for this work, as they migrate collectively due to signal relay. The signal relay of these cells is similar to many immune cell species. Using a combination of image analysis tools and a coarse-grained stochastic model, I find that guidance by nanoridges overrides the chemical signal relay and forces cells to migrate individually, suppressing streaming behavior. I model both the secretion and propagation of chemical signals using an excitable systems framework. This work highlights that bidirectional signals can be effective at suppressing cell-cell attraction and streaming motion. The response of immune cells to external stimuli in the wound environment is not universal. Macrophages, one of the largest immune cells, are observed to migrate away from the wound upon wound-induced electric field generation. In the third example, I study actin dynamics of M0 (resting) macrophage cells to elucidate how these cells interact with external electric fields. This cell type exhibits oscillatory actin waves at rest. With electric field stimulation, the oscillatory actin waves start to generate protrusions. Often, the protrusions begin with actin-depleted regions, indicating that contractile ele- ments are involved in conjunction with overall cell volume conservation. This thesis highlights the different methods in which actin waves integrate external cues, specifically electric fields, into cell responses that are cell-type specific