Consciousness as Recursive, Spatiotemporal Self-Location

At the phenomenal level, consciousness arises in a consistently coherent fashion as a singular, unified field of recursive self-awareness (subjectivity) with explicitly orientational characteristics—that of a subject located both spatially and temporally in an egocentrically-extended domain. Understanding these twin elements of consciousness begins with the recognition that ultimately (and most primitively), cognitive systems serve the biological self-regulatory regime in which they subsist. The psychological structures supporting self-located subjectivity involve an evolutionary elaboration of the two basic elements necessary for extending self-regulation into behavioral interaction with the environment: an orientative reference frame which consistently structures ongoing interaction in terms of controllable spatiotemporal parameters, and processing architecture that relates behavior to homeostatic needs via feedback. Over time, constant evolutionary pressures for energy efficiency have encouraged the emergence of anticipative feedforward processing mechanisms, and the elaboration, at the apex of the sensorimotor processing hierarchy, of self-activating, highly attenuated recursively-feedforward circuitry processing the basic orientational schema independent of external action output. As the primary reference frame of active waking cognition, this recursive self-locational schema processing generates a zone of subjective self-awareness in terms of which it feels like something to be oneself here and now. This is consciousness-as-subjectivity

Through The Ages

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Theories of Consciousness as Reflexivity

Consciousness is best understood in context, as one element of an interactive waking state in which the greater part of cognitive processing takes place in a nonconscious fashion. But if conscious and nonconscious processing are combined in the waking state, what distinguishes the former form the latter, what is consciousness, and what is its purpose? The answer to the second question depends crucially on our conclusion regarding the first. What is the property in virtue of which a state is conscious rather than nonconscious? In the following, it will be argued that of the answers most frequently proposed—intentionality, subjectivity, accessibility, reflexivity—only the final characteristic, reflexive, autonoetic awareness, is unique to the conscious state. Reflexivity can best be explained not as the product of a self-representational data structure, but as the expression of a recursive processing regime, in which cognition registers the properties of the processing state to a greater extent than properties of the content represented. And the principal characteristic of a reflexive processing state is cognitive reflexivity or autonoetic awarenes

Multi-compartment profiling of cacterial and host metabolites identifies intestinal dysbiosis and its functional consequences in the critically ill child

Adverse physiology and antibiotic exposure devastate the intestinal microbiome in critical illness. Time and cost implications limit the immediate clinical potential of microbial sequencing to identify or treat intestinal dysbiosis. Here, we examined whether metabolic profiling is a feasible method of monitoring intestinal dysbiosis in critically ill children. Prospective multicenter cohort study. Three U.K.-based PICUs. Mechanically ventilated critically ill (n = 60) and age-matched healthy children (n = 55). Collection of urine and fecal samples in children admitted to the PICU. A single fecal and urine sample was collected in healthy controls. Untargeted and targeted metabolic profiling using 1H-nuclear magnetic resonance spectroscopy and liquid chromatography-mass spectrometry or urine and fecal samples. This was integrated with analysis of fecal bacterial 16S ribosomal RNA profiles and clinical disease severity indicators. We observed separation of global urinary and fecal metabolic profiles in critically ill compared with healthy children. Urinary excretion of mammalian-microbial co-metabolites hippurate, 4-cresol sulphate, and formate were reduced in critical illness compared with healthy children. Reduced fecal excretion of short-chain fatty acids (including butyrate, propionate, and acetate) were observed in the patient cohort, demonstrating that these metabolites also distinguished between critical illness and health. Dysregulation of intestinal bile metabolism was evidenced by increased primary and reduced secondary fecal bile acid excretion. Fecal butyrate correlated with days free of intensive care at 30 days (r = 0.38; p = 0.03), while urinary formate correlated inversely with vasopressor requirement (r = -0.2; p = 0.037). Disruption to the functional activity of the intestinal microbiome may result in worsening organ failure in the critically ill child. Profiling of bacterial metabolites in fecal and urine samples may support identification and treatment of intestinal dysbiosis in critical illness.This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

Efficacy and Safety of Ixekizumab in the Treatment of Radiographic Axial Spondyloarthritis:Sixteen-Week Results From a Phase III Randomized, Double-Blind, Placebo-Controlled Trial in Patients With Prior Inadequate Response to or Intolerance of Tumor Necrosis Factor Inhibitors

Objective: To investigate the efficacy and safety of ixekizumab in patients with active radiographic axial spondyloarthritis (SpA) and prior inadequate response to or intolerance of 1 or 2 tumor necrosis factor inhibitors (TNFi). Methods: In this phase III randomized, double-blind, placebo-controlled trial, adult patients with an inadequate response to or intolerance of 1 or 2 TNFi and an established diagnosis of axial SpA (according to the Assessment of SpondyloArthritis international Society [ASAS] criteria for radiographic axial SpA, with radiographic sacroiliitis defined according to the modified New York criteria and ≥1 feature of SpA) were recruited and randomized 1:1:1 to receive placebo or 80-mg subcutaneous ixekizumab every 2 weeks (IXEQ2W) or 4 weeks (IXEQ4W), with an 80-mg or 160-mg starting dose. The primary end point was 40% improvement in disease activity according to the ASAS criteria (ASAS40) at week 16. Secondary outcomes and safety were also assessed. Results: A total of 316 patients were randomized to receive placebo (n = 104), IXEQ2W (n = 98), or IXEQ4W (n = 114). At week 16, significantly higher proportions of IXEQ2W patients (n = 30 [30.6%]; P = 0.003) or IXEQ4W patients (n = 29 [25.4%]; P = 0.017) had achieved an ASAS40 response versus the placebo group (n = 13 [12.5%]), with statistically significant differences reported as early as week 1 with ixekizumab treatment. Statistically significant improvements in disease activity, function, quality of life, and spinal magnetic resonance imaging–evident inflammation were observed after 16 weeks of ixekizumab treatment versus placebo. Treatment-emergent adverse events (AEs) with ixekizumab treatment were more frequent than with placebo. Serious AEs were similar across treatment arms. One death was reported (IXEQ2W group). Conclusion: Ixekizumab treatment for 16 weeks in patients with active radiographic axial SpA and previous inadequate response to or intolerance of 1 or 2 TNFi yields rapid and significant improvements in the signs and symptoms of radiographic axial SpA versus placebo

Reconstruction of primary vertices at the ATLAS experiment in Run 1 proton–proton collisions at the LHC

This paper presents the method and performance of primary vertex reconstruction in proton–proton collision data recorded by the ATLAS experiment during Run 1 of the LHC. The studies presented focus on data taken during 2012 at a centre-of-mass energy of √s=8 TeV. The performance has been measured as a function of the number of interactions per bunch crossing over a wide range, from one to seventy. The measurement of the position and size of the luminous region and its use as a constraint to improve the primary vertex resolution are discussed. A longitudinal vertex position resolution of about 30μm is achieved for events with high multiplicity of reconstructed tracks. The transverse position resolution is better than 20μm and is dominated by the precision on the size of the luminous region. An analytical model is proposed to describe the primary vertex reconstruction efficiency as a function of the number of interactions per bunch crossing and of the longitudinal size of the luminous region. Agreement between the data and the predictions of this model is better than 3% up to seventy interactions per bunch crossing

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

Three decades of climate mitigation: why haven't we bent the global emissions curve?

Despite three decades of political efforts and a wealth of research on the causes and catastrophic impacts of climate change, global carbon dioxide emissions have continued to rise and are 60% higher today than they were in 1990. Exploring this rise through nine thematic lenses—covering issues of climate governance, the fossil fuel industry, geopolitics, economics, mitigation modeling, energy systems, inequity, lifestyles, and social imaginaries—draws out multifaceted reasons for our collective failure to bend the global emissions curve. However, a common thread that emerges across the reviewed literature is the central role of power, manifest in many forms, from a dogmatic political-economic hegemony and influential vested interests to narrow techno-economic mindsets and ideologies of control. Synthesizing the various impediments to mitigation reveals how delivering on the commitments enshrined in the Paris Agreement now requires an urgent and unprecedented transformation away from today's carbon- and energy-intensive development paradigm