Lattice Kinetic Monte Carlo Simulations of Platelet Aggregation and Deposition

Platelet aggregation is an essential process in forming a stable clot to prevent blood loss. The response of platelets to a complex signal of pro-clotting agonists determines the stability and size of the resulting clot. An underdeveloped clot represents a bleeding risk, while an overdeveloped clot can cause vessel occlusion, which can lead to heart attack or stroke. A multiscale model was developed to study the integration of platelet signaling within the complex phenomena driven by flow. The model is built upon a lattice kinetic Monte Carlo algorithm (LKMC) to track platelet motion and binding. First, a new method for including flow-driven particle motion in LKMC was derived from a timescale analysis of particle motion. Simple methods for simulating flow-driven motion were found to exhibit concentration dependent velocities violating the assumptions in the model. The nature of the error was analyzed mathematically and resolved by considering the chain length distribution on the lattice. The accuracy of the method was found to scale linearly with the lattice spacing. Second, the LKMC method was extended to study particle aggregation in complex flows. The LKMC results for simple flows were compared directly to a continuum population balance equation (PBE) approach. A contact time model was introduced to capture nonideal collisions in the LKMC model and a connection to the continuum collision efficiency was derived. The particle size distribution for a baffled geometry with regions of standing vortices and squeezing flows was determined using the LKMC method for varying baffle heights. Finally, the LKMC method was incorporated within a multiscale model to simulate platelet aggregation including platelet signaling (neural network model), blood flow (lattice Boltzmann method), and the release of soluble platelet agonists (finite element method). The neural network model for platelet signaling was trained on patient-specific, experimental measurements of intracellular calcium enabling patient-specific predictions of platelet function in flow. The model accurately predicted the order of potency for three antiplatelet therapies, donor-specific aggregate size, and donor-specific response to antiplatelet therapy as compared to microfluidic experiments of platelet aggregation

Computational fluid dynamics modeling for HPV fermentation bioreactors

The fermentation processes for the manufacture of HPV (GARDASIL AND GARDASIL 9) are currently conducted at multiple manufacturing scales. The goal of the bioreactor modeling project for HPV is to generate data and models to support robust manufacturing and process understanding initiatives across the multiple scales. Additionally, this knowledge can be utilized to aid in future process transfers. The modeling work is performed utilizing computer models (Computational Fluid Dynamics via Fluent) and historical data to predict metabolic behavior based on bioreactor configurations and processing conditions

John Lachs, Stoic Pragmatism

The point of view endorsed in John Lachs’s Stoic Pragmatism is easy to state, yet profound in its application. If pragmatists can be accused of sometimes under-appreciating the irremediable, and stoics of sometimes being fatalist in a manner that shuts out real possibilities, the two orientations may need each other. His perspective combines a pragmatic commitment to amelioratory achievement and a stoic recognition of unbridgeable limits. As the book conveys, the marriage of stoicism and prag..

Computational fluid dynamics modeling for fermentation risk reduction during technology transfer and risk understanding

Computational Fluid Dynamics modeling and in-depth scaling calculations have been utilized in partnership to generate data to support equipment design and facility fit during commercialization of a fermentation and primary recovery process for a vaccine candidate across multiple technical transfers. This analysis utilizing representative computer models for tank configurations, supplemented with traditional computational scaling approaches (ungassed P/V, gassed P/V, kLa, etc.), ensures full knowledge of a tank’s mixing and oxygen transfer capabilities allowing process understanding and robust manufacturing across technology transfer to multiple sites. Implementation of this approach across process steps as well as manufacturing sites allows increased knowledge prior to use in a process and/or prior to construction of a new vessel, therefore contributing to successful process transfer with reduced risks upon scale-up/scale-down and new facility introductions

Experimental Evaluation of Inlet Distortion on an Ejector Powered Hybrid Wing Body at Take-off and Landing Conditions

As part of the NASA Environmentally Responsible Aircraft project, an ultra high bypass ratio engine integration on a hybrid wing body demonstration was planned. The goal was to include engine and airframe integration concepts that reduced fuel consumption by at least 50% while still reducing noise 42 db cumulative on the ground. Since the engines would be mounted on the upper surface of the aft body of the aircraft, the inlets may be susceptible to vortex ingestion from the wing leading edge at high angles of attack and sideslip, and separated wing/body flow. Consequently, experimental and computational studies were conducted to collect flow surveys useful for characterizing engine operability. The wind tunnel tests were conducted at two NASA facilities, the 14- by 22-foot at NASA Langley and the 40- by 80-foot at NASA Ames Research Center. The test results included in this paper show that the distortion and pressure recovery levels were acceptable for engine operability. The CFD studies conducted to compare to experimental data showed excellent agreement for the angle of attacks examined, although failed to match the low speed experimental data at high sideslip angles

Il naturalismo culturale di Dewey

The essay focuses on John Dewey’s pragmatic naturalism in order to show that the relatively recent naturalizing trend in philosophy should be considered a historically and culturally situated restriction of other forms of naturalism. Dewey’s cultural naturalism is based on a strong continuity between nature and culture, assuming that human intelligent behaviour arises from already existing organic and environmental resources in an entirely contingent manner. This kind of naturalism does not involve physical reductionism: more complex interactions between organisms and their environment, such as human mental behaviour, are seen as innovative, in the sense that they produce forms of organization that, on the one hand, are not reducible to the simple association of pre-existing elements. On the other hand, innovative modes of interaction between human organisms and their naturally social environment have consequence on the natural world: they produce changes within it. The second part of the text presents Dewey’s non-substantive conception of the mind, which has its roots in the non-reversible consequences of the advent of highly communicative and linguistic interactions in the human world as well as in the possibility for human organism to reconsider analytically or reflectively their primarily holistic, qualitatively felt experiences.The essay focuses on John Dewey’s pragmatic naturalism in order to show that the relatively recent naturalizing trend in philosophy should be considered a historically and culturally situated restriction of other forms of naturalism. Dewey’s cultural naturalism is based on a strong continuity between nature and culture, assuming that human intelligent behaviour arises from already existing organic and environmental resources in an entirely contingent manner. This kind of naturalism does not involve physical reductionism: more complex interactions between organisms and their environment, such as human mental behaviour, are seen as innovative, in the sense that they produce forms of organization that, on the one hand, are not reducible to the simple association of pre-existing elements. On the other hand, innovative modes of interaction between human organisms and their naturally social environment have consequence on the natural world: they produce changes within it. The second part of the text presents Dewey’s non-substantive conception of the mind, which has its roots in the non-reversible consequences of the advent of highly communicative and linguistic interactions in the human world as well as in the possibility for human organism to reconsider analytically or reflectively their primarily holistic, qualitatively felt experiences

Circulating microRNAs in sera correlate with soluble biomarkers of immune activation but do not predict mortality in ART treated individuals with HIV-1 infection: A case control study

Introduction: The use of anti-retroviral therapy (ART) has dramatically reduced HIV-1 associated morbidity and mortality. However, HIV-1 infected individuals have increased rates of morbidity and mortality compared to the non-HIV-1 infected population and this appears to be related to end-organ diseases collectively referred to as Serious Non-AIDS Events (SNAEs). Circulating miRNAs are reported as promising biomarkers for a number of human disease conditions including those that constitute SNAEs. Our study sought to investigate the potential of selected miRNAs in predicting mortality in HIV-1 infected ART treated individuals. Materials and Methods: A set of miRNAs was chosen based on published associations with human disease conditions that constitute SNAEs. This case: control study compared 126 cases (individuals who died whilst on therapy), and 247 matched controls (individuals who remained alive). Cases and controls were ART treated participants of two pivotal HIV-1 trials. The relative abundance of each miRNA in serum was measured, by RTqPCR. Associations with mortality (all-cause, cardiovascular and malignancy) were assessed by logistic regression analysis. Correlations between miRNAs and CD4+ T cell count, hs-CRP, IL-6 and D-dimer were also assessed. Results: None of the selected miRNAs was associated with all-cause, cardiovascular or malignancy mortality. The levels of three miRNAs (miRs -21, -122 and -200a) correlated with IL-6 while miR-21 also correlated with D-dimer. Additionally, the abundance of miRs -31, -150 and -223, correlated with baseline CD4+ T cell count while the same three miRNAs plus miR- 145 correlated with nadir CD4+ T cell count. Discussion: No associations with mortality were found with any circulating miRNA studied. These results cast doubt onto the effectiveness of circulating miRNA as early predictors of mortality or the major underlying diseases that contribute to mortality in participants treated for HIV-1 infection

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