Computational evidence for an early, amplified systemic inflammation program in polytrauma patients with severe extremity injuries

Extremity and soft tissue injuries contribute significantly to inflammation and adverse in-hospital outcomes for trauma survivors; accordingly, we examined the complex association between clinical outcomes inflammatory responses in this setting using in silico tools. Two stringently propensity-matched, moderately/severely injured (Injury Severity Score > 16) patient sub-cohorts of ~30 patients each were derived retrospectively from a cohort of 472 blunt trauma survivors and segregated based on their degree of extremity injury severity (above or below 3 on the Abbreviated Injury Scale). Serial blood samples were analyzed for 31 plasma inflammatory mediators. In addition to standard statistical analyses, Dynamic Network Analysis (DyNA) and Principal Component Analysis (PCA) were used to model systemic inflammation following trauma. Patients in the severe extremity injury sub-cohort experienced longer intensive care unit length of stay (LOS), total LOS, and days on a mechanical ventilator, with higher Marshall Multiple Organ Dysfunction (MOD) Scores over the first 7 days post-injury as compared to the mild/moderate extremity injury sub-cohort. The higher severity cohort had statistically significant elevated lactate, base deficit, and creatine phosphokinase on first blood draw, along with significant changes in multiple circulating inflammatory mediators. DyNA pointed to a sustained role for type 17 immunity in both sub-cohorts, along with IFN-γ in the severe extremity injury group. DyNA network complexity increased over 7 days post-injury in the severe injury group, while generally decreasing over this same time period in the mild/moderate injury group. PCA suggested a more robust activation of multiple pathways in the severe extremity injury group as compared to the mild/moderate injury group. These studies thus point to the possibility of self-sustaining inflammation following severe extremity injury vs. resolving inflammation following less severe extremity injury

The Ontology of Intentional Agency in Light of Neurobiological Determinism: Philosophy Meets Folk Psychology

The moot point of the Western philosophical rhetoric about free will consists in examining whether the claim of authorship to intentional, deliberative actions fits into or is undermined by a one-way causal framework of determinism. Philosophers who think that reconciliation between the two is possible are known as metaphysical compatibilists. However, there are philosophers populating the other end of the spectrum, known as the metaphysical libertarians, who maintain that claim to intentional agency cannot be sustained unless it is assumed that indeterministic causal processes pervade the action-implementation apparatus employed by the agent. The metaphysical libertarians differ among themselves on the question of whether the indeterministic causal relation exists between the series of intentional states and processes, both conscious and unconscious, and the action, making claim for what has come to be known as the event-causal view, or between the agent and the action, arguing that a sort of agent causation is at work. In this paper, I have tried to propose that certain features of both event-causal and agent-causal libertarian views need to be combined in order to provide a more defendable compatibilist account accommodating deliberative actions with deterministic causation. The ‘‘agent-executed-eventcausal libertarianism’’, the account of agency I have tried to develop here, integrates certain plausible features of the two competing accounts of libertarianism turning them into a consistent whole. I hope to show in the process that the integration of these two variants of libertarianism does not challenge what some accounts of metaphysical compatibilism propose—that there exists a broader deterministic relation between the web of mental and extra-mental components constituting the agent’s dispositional system—the agent’s beliefs, desires, short-term and long-term goals based on them, the acquired social, cultural and religious beliefs, the general and immediate and situational environment in which the agent is placed, etc. on the one hand and the decisions she makes over her lifetime on the basis of these factors. While in the ‘‘Introduction’’ the philosophically assumed anomaly between deterministic causation and the intentional act of deciding has been briefly surveyed, the second section is devoted to the task of bridging the gap between compatibilism and libertarianism. The next section of the paper turns to an analysis of folk-psychological concepts and intuitions about the effects of neurochemical processes and prior mental events on the freedom of making choices. How philosophical insights can be beneficially informed by taking into consideration folk-psychological intuitions has also been discussed, thus setting up the background for such analysis. It has been suggested in the end that support for the proposed theory of intentional agency can be found in the folk-psychological intuitions, when they are taken in the right perspective

The articulation of enkinaesthetic entanglement

In this article I present an argument for the necessary co-articulation of meaning within our felt enkinaesthetic engagement with our world. The argument will be developed through a series of stages, the first of which will be an elaboration of the notion of articulation of and through the body. This will be followed by an examination of enkinaesthetic experiential entanglement and the role it plays in rendering our world meaningful and our actions values-realising. At this stage I will begin to extend Husserl’s notion of intentional transgression to the enkinaesthetic sphere of lived experience, and in support of this claim I will examine the theoretical and practical work of osteopathic manual listening [Gens & Roche 2014] and the ‘felt sense’ in focusing [Gendlin] which makes possible a shift from a somatic articulation to a semantic, and potentially conceptual, one. Throughout, my position will be compatible with Merleau-Ponty’s claim that “Whenever I try to understand myself, the whole fabric of the perceptible world comes too, and with it comes the others who are caught in it.” [Merleau-Ponty 1964a, p.15]

Polymer depletion interaction between two parallel repulsive walls

The depletion interaction between two parallel repulsive walls confining a dilute solution of long and flexible polymer chains is studied by field-theoretic methods. Special attention is paid to self-avoidance between chain monomers relevant for polymers in a good solvent. Our direct approach avoids the mapping of the actual polymer chains on effective hard or soft spheres. We compare our results with recent Monte Carlo simulations [A. Milchev and K. Binder, Eur. Phys. J. B 3, 477 (1998)] and with experimental results for the depletion interaction between a spherical colloidal particle and a planar wall in a dilute solution of nonionic polymers [D. Rudhardt, C. Bechinger, and P. Leiderer, Phys. Rev. Lett. 81, 1330 (1998)].Comment: 17 pages, 3 figures. Final version as publishe

Quantum Theory and Time Asymmetry

The relation between quantum measurement and thermodynamically irreversible processes is investigated. The reduction of the state vector is fundamentally asymmetric in time and shows an observer-relatedness which may explain the double interpretation of the state vector as a representation of physical states as well as of information about them. The concept of relevance being used in all statistical theories of irreversible thermodynamics is shown to be based on the same observer-relatedness. Quantum theories of irreversible processes implicitly use an objectivized process of state vector reduction. The conditions for the reduction are discussed, and I speculate that the final (subjective) observer system might even be carried by a spacetime point.Comment: Latex version of a paper published in 1979 (with minor revisions), 18 page

Circulation first – the time has come to question the sequencing of care in the ABCs of trauma; an American Association for the Surgery of Trauma multicenter trial

Background The traditional sequence of trauma care: Airway, Breathing, Circulation (ABC) has been practiced for many years. It became the standard of care despite the lack of scientific evidence. We hypothesized that patients in hypovolemic shock would have comparable outcomes with initiation of bleeding treatment (transfusion) prior to intubation (CAB), compared to those patients treated with the traditional ABC sequence. Methods This study was sponsored by the American Association for the Surgery of Trauma multicenter trials committee. We performed a retrospective analysis of all patients that presented to trauma centers with presumptive hypovolemic shock indicated by pre-hospital or emergency department hypotension and need for intubation from January 1, 2014 to July 1, 2016. Data collected included demographics, timing of intubation, vital signs before and after intubation, timing of the blood transfusion initiation related to intubation, and outcomes. Results From 440 patients that met inclusion criteria, 245 (55.7%) received intravenous blood product resuscitation first (CAB), and 195 (44.3%) were intubated before any resuscitation was started (ABC). There was no difference in ISS, mechanism, or comorbidities. Those intubated prior to receiving transfusion had a lower GCS than those with transfusion initiation prior to intubation (ABC: 4, CAB:9, p = 0.005). Although mortality was high in both groups, there was no statistically significant difference (CAB 47% and ABC 50%). In multivariate analysis, initial SBP and initial GCS were the only independent predictors of death. Conclusion The current study highlights that many trauma centers are already initiating circulation first prior to intubation when treating hypovolemic shock (CAB), even in patients with a low GCS. This practice was not associated with an increased mortality. Further prospective investigation is warranted. Trial registration IRB approval number: HM20006627. Retrospective trial not registered

Encouraging versatile thinking in algebra using the computer

In this article we formulate and analyse some of the obstacles to understanding the notion of a variable, and the use and meaning of algebraic notation, and report empirical evidence to support the hypothesis that an approach using the computer will be more successful in overcoming these obstacles. The computer approach is formulated within a wider framework ofversatile thinking in which global, holistic processing complements local, sequential processing. This is done through a combination of programming in BASIC, physical activities which simulate computer storage and manipulation of variables, and specific software which evaluates expressions in standard mathematical notation. The software is designed to enable the user to explore examples and non-examples of a concept, in this case equivalent and non-equivalent expressions. We call such a piece of software ageneric organizer because if offers examples and non-examples which may be seen not just in specific terms, but as typical, or generic, examples of the algebraic processes, assisting the pupil in the difficult task of abstracting the more general concept which they represent. Empirical evidence from several related studies shows that such an approach significantly improves the understanding of higher order concepts in algebra, and that any initial loss in manipulative facility through lack of practice is more than made up at a later stage

Seasonal changes in patterns of gene expression in avian song control brain regions.

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Photoperiod and hormonal cues drive dramatic seasonal changes in structure and function of the avian song control system. Little is known, however, about the patterns of gene expression associated with seasonal changes. Here we address this issue by altering the hormonal and photoperiodic conditions in seasonally-breeding Gambel's white-crowned sparrows and extracting RNA from the telencephalic song control nuclei HVC and RA across multiple time points that capture different stages of growth and regression. We chose HVC and RA because while both nuclei change in volume across seasons, the cellular mechanisms underlying these changes differ. We thus hypothesized that different genes would be expressed between HVC and RA. We tested this by using the extracted RNA to perform a cDNA microarray hybridization developed by the SoNG initiative. We then validated these results using qRT-PCR. We found that 363 genes varied by more than 1.5 fold (>log(2) 0.585) in expression in HVC and/or RA. Supporting our hypothesis, only 59 of these 363 genes were found to vary in both nuclei, while 132 gene expression changes were HVC specific and 172 were RA specific. We then assigned many of these genes to functional categories relevant to the different mechanisms underlying seasonal change in HVC and RA, including neurogenesis, apoptosis, cell growth, dendrite arborization and axonal growth, angiogenesis, endocrinology, growth factors, and electrophysiology. This revealed categorical differences in the kinds of genes regulated in HVC and RA. These results show that different molecular programs underlie seasonal changes in HVC and RA, and that gene expression is time specific across different reproductive conditions. Our results provide insights into the complex molecular pathways that underlie adult neural plasticity