Ethical considerations for the age of non-governmental space exploration.

Mounting ambitions and capabilities for public and private, non-government sector crewed space exploration bring with them an increasingly diverse set of space travelers, raising new and nontrivial ethical, legal, and medical policy and practice concerns which are still relatively underexplored. In this piece, we lay out several pressing issues related to ethical considerations for selecting space travelers and conducting human subject research on them, especially in the context of non-governmental and commercial/private space operations.

Association of post-COVID phenotypic manifestations with new-onset psychiatric disease.

Acute COVID-19 infection can be followed by diverse clinical manifestations referred to as Post Acute Sequelae of SARS-CoV2 Infection (PASC). Studies have shown an increased risk of being diagnosed with new-onset psychiatric disease following a diagnosis of acute COVID-19. However, it was unclear whether non-psychiatric PASC-associated manifestations (PASC-AMs) are associated with an increased risk of new-onset psychiatric disease following COVID-19. A retrospective electronic health record (EHR) cohort study of 2,391,006 individuals with acute COVID-19 was performed to evaluate whether non-psychiatric PASC-AMs are associated with new-onset psychiatric disease. Data were obtained from the National COVID Cohort Collaborative (N3C), which has EHR data from 76 clinical organizations. EHR codes were mapped to 151 non-psychiatric PASC-AMs recorded 28-120 days following SARS-CoV-2 diagnosis and before diagnosis of new-onset psychiatric disease. Association of newly diagnosed psychiatric disease with age, sex, race, pre-existing comorbidities, and PASC-AMs in seven categories was assessed by logistic regression. There were significant associations between a diagnosis of any psychiatric disease and five categories of PASC-AMs with odds ratios highest for neurological, cardiovascular, and constitutional PASC-AMs with odds ratios of 1.31, 1.29, and 1.23 respectively. Secondary analysis revealed that the proportions of 50 individual clinical features significantly differed between patients diagnosed with different psychiatric diseases. Our study provides evidence for association between non-psychiatric PASC-AMs and the incidence of newly diagnosed psychiatric disease. Significant associations were found for features related to multiple organ systems. This information could prove useful in understanding risk stratification for new-onset psychiatric disease following COVID-19. Prospective studies are needed to corroborate these findings.

A comprehensive SARS-CoV-2 and COVID-19 review, Part 2: host extracellular to systemic effects of SARS-CoV-2 infection.

COVID-19, the disease caused by SARS-CoV-2, has caused significant morbidity and mortality worldwide. The betacoronavirus continues to evolve with global health implications as we race to learn more to curb its transmission, evolution, and sequelae. The focus of this review, the second of a three-part series, is on the biological effects of the SARS-CoV-2 virus on post-acute disease in the context of tissue and organ adaptations and damage. We highlight the current knowledge and describe how virological, animal, and clinical studies have shed light on the mechanisms driving the varied clinical diagnoses and observations of COVID-19 patients. Moreover, we describe how investigations into SARS-CoV-2 effects have informed the understanding of viral pathogenesis and provide innovative pathways for future research on the mechanisms of viral diseases.

Communication consistency, completeness, and complexity of digital ideography in trustworthy mobile extended reality.

Communication barriers long-associated with ideographs, including combinatorial grapholinguistic complexity, computational encoding-decoding complexity, and technological rendering and deployment, become trivialized through advancements in interoperable smart mobile digital devices. Such technologies impart unprecedented extended-reality user hazards only mitigated by unprecedented colloquial and bureaucratic societal norms. Digital age norms thus influence natural ideographic language origins and evolution in ways novel to human history.

Ownership psychology as a "cognitive cell" adaptation: A minimalist model of microbial goods theory.

Microbes perfect social interactions with intuitive logics and goal-directed reciprocity. These multilevel, cognition-resembling adaptations in Dictyostelid cellular molds enable individual-to-group viability through public/private bacterial farming and dynamic marketspaces. Like humans and animals, Dictyostelid livestock-ownership depends on environmental sensing, cooperation, and competition. Moreover, social-norm policing of cosmopolitan colonies coordinates farmer decisions, phenotypes, and ownership identities with bacteria herding, privatization, and consumption.

Microbial biomanufacturing for space-exploration-what to take and when to make.

As renewed interest in human space-exploration intensifies, a coherent and modernized strategy for mission design and planning has become increasingly crucial. Biotechnology has emerged as a promising approach to increase resilience, flexibility, and efficiency of missions, by virtue of its ability to effectively utilize in situ resources and reclaim resources from waste streams. Here we outline four primary mission-classes on Moon and Mars that drive a staged and accretive biomanufacturing strategy. Each class requires a unique approach to integrate biomanufacturing into the existing mission-architecture and so faces unique challenges in technology development. These challenges stem directly from the resources available in a given mission-class-the degree to which feedstocks are derived from cargo and in situ resources-and the degree to which loop-closure is necessary. As mission duration and distance from Earth increase, the benefits of specialized, sustainable biomanufacturing processes also increase. Consequentially, we define specific design-scenarios and quantify the usefulness of in-space biomanufacturing, to guide techno-economics of space-missions. Especially materials emerged as a potentially pivotal target for biomanufacturing with large impact on up-mass cost. Subsequently, we outline the processes needed for development, testing, and deployment of requisite technologies. As space-related technology development often does, these advancements are likely to have profound implications for the creation of a resilient circular bioeconomy on Earth.

Neural Field Continuum Limits and the Structure-Function Partitioning of Cognitive-Emotional Brain Networks.

In The cognitive-emotional brain, Pessoa overlooks continuum effects on nonlinear brain network connectivity by eschewing neural field theories and physiologically derived constructs representative of neuronal plasticity. The absence of this content, which is so very important for understanding the dynamic structure-function embedding and partitioning of brains, diminishes the rich competitive and cooperative nature of neural networks and trivializes Pessoa's arguments, and similar arguments by other authors, on the phylogenetic and operational significance of an optimally integrated brain filled with variable-strength neural connections. Riemannian neuromanifolds, containing limit-imposing metaplastic Hebbian- and antiHebbian-type control variables, simulate scalable network behavior that is difficult to capture from the simpler graph-theoretic analysis preferred by Pessoa and other neuroscientists. Field theories suggest the partitioning and performance benefits of embedded cognitive-emotional networks that optimally evolve between exotic classical and quantum computational phases, where matrix singularities and condensations produce degenerate structure-function homogeneities unrealistic of healthy brains. Some network partitioning, as opposed to unconstrained embeddedness, is thus required for effective execution of cognitive-emotional network functions and, in our new era of neuroscience, should be considered a critical aspect of proper brain organization and operation.

Post-COVID Phenotypic Manifestations are Associated with New-Onset Psychiatric Disease: Findings from the NIH N3C and RECOVER Studies.

Acute COVID-19 infection can be followed by diverse clinical manifestations referred to as Post Acute Sequelae of SARS-CoV2 Infection (PASC). Studies have shown an increased risk of being diagnosed with new-onset psychiatric disease following a diagnosis of acute COVID-19. However, it was unclear whether non-psychiatric PASC-associated manifestations (PASC-AMs) are associated with an increased risk of new-onset psychiatric disease following COVID-19. A retrospective EHR cohort study of 1,603,767 individuals with acute COVID-19 was performed to evaluate whether non-psychiatric PASC-AMs are associated with new-onset psychiatric disease. Data were obtained from the National COVID Cohort Collaborative (N3C), which has EHR data from 65 clinical organizations. EHR codes were mapped to 151 non-psychiatric PASC-AMs recorded 28-120 days following SARS-CoV-2 diagnosis and before diagnosis of new-onset psychiatric disease. Association of newly diagnosed psychiatric disease with age, sex, race, pre-existing comorbidities, and PASC-AMs in seven categories was assessed by logistic regression. There was a significant association between six categories and newly diagnosed anxiety, mood, and psychotic disorders, with odds ratios highest for cardiovascular (1.35, 1.27-1.42) PASC-AMs. Secondary analysis revealed that the proportions of 95 individual clinical features significantly differed between patients diagnosed with different psychiatric disorders. Our study provides evidence for association between non-psychiatric PASC-AMs and the incidence of newly diagnosed psychiatric disease. Significant associations were found for features related to multiple organ systems. This information could prove useful in understanding risk stratification for new-onset psychiatric disease following COVID-19. Prospective studies are needed to corroborate these findings. Funding: NCATS U24 TR002306.

Smart Device-Driven Corticolimbic Plasticity in Cognitive-Emotional Restructuring of Space-Related Neuropsychiatric Disease and Injury.

Escalating government and commercial efforts to plan and deploy viable manned near-to-deep solar system exploration and habitation over the coming decades now drives next-generation space medicine innovations. The application of cutting-edge precision medicine, such as brain stimulation techniques, provides powerful clinical and field/flight situation methods to selectively control vagal tone and neuroendocrine-modulated corticolimbic plasticity, which is affected by prolonged cosmic radiation exposure, social isolation or crowding, and weightlessness in constricted operational non-terran locales. Earth-based clinical research demonstrates that brain stimulation approaches may be combined with novel psychotherapeutic integrated memory structure rationales for the corrective reconsolidation of arousing or emotional experiences, autobiographical memories, semantic schema, and other cognitive structures to enhance neuropsychiatric patient outcomes. Such smart cotherapies or countermeasures, which exploit natural, pharmaceutical, and minimally invasive neuroprosthesis-driven nervous system activity, may optimize the cognitive-emotional restructuring of astronauts suffering from space-related neuropsychiatric disease and injury, including mood, affect, and anxiety symptoms of any potential severity and pathophysiology. An appreciation of improved neuropsychiatric healthcare through the merging of new or rediscovered smart theragnostic medical technologies, capable of rendering personalized neuroplasticity training and managed psychotherapeutic treatment protocols, will reveal deeper insights into the illness states experienced by astronauts. Future work in this area should emphasize the ethical role of telemedicine and/or digital clinicians to advance the (semi)autonomous, technology-assisted medical prophylaxis, diagnosis, treatment, monitoring, and compliance of astronauts for elevated health, safety, and performance in remote extreme space and extraterrestrial environments.

Quantum decision corrections for the neuroeconomics of irrational movement control and goal attainment.

Quantum decision theory corrects categorical and propositional logic pathologies common to classic statistical goal-oriented reasoning, such as rational neuroeconomics-based optimal foraging. Within this ecosalient framework, motivation, perception, learning, deliberation, brain computation, and conjunctive risk-order errors may be understood for subjective utility judgments underlying either rational or irrational canonical decisions-actions used to choose, procure, and consume rewarding nutrition with variable fitness.

Digital life, a theory of minds, and mapping human and machine cultural universals.

Emerging cybertechnologies, such as social digibots, bend epistemological conventions of life and culture already complicated by human and animal relationships. Virtually-augmented niches of machines and organic life promise new free-energy-governed selection of intelligent digital life. These provocative eco-evolutionary contexts demand a theory of (natural and artificial) minds to characterize and validate the immersive social phenomena universally-shaping cultural affordances.

Unpredictable homeodynamic and ambient constraints on irrational decision making of aneural and neural foragers.

Foraging for nutritional sustenance represents common significant learned/heritable survival strategies evolved for phylum-diverse cellular life on Earth. Unicellular aneural to multicellular neural foragers display conserved rational or irrational decision making depending on outcome predictions for noise-susceptible real/illusory homeodynamic and ambient dietary cues. Such context-dependent heuristic-guided foraging enables optimal, suboptimal, or fallacious decisions that drive organismal adaptation, health, longevity, and life history.

Neurotropic enteroviruses co-opt "fair-weather-friend" commensal gut microbiota to drive host infection and central nervous system disturbances.

Some neurotropic enteroviruses hijack Trojan horse/raft commensal gut bacteria to render devastating biomimicking cryptic attacks on human/animal hosts. Such virus-microbe interactions manipulate hosts' gut-brain axes with accompanying infection-cycle-optimizing central nervous system (CNS) disturbances, including severe neurodevelopmental, neuromotor, and neuropsychiatric conditions. Co-opted bacteria thus indirectly influence host health, development, behavior, and mind as possible "fair-weather-friend" symbionts, switching from commensal to context-dependent pathogen-like strategies benefiting gut-bacteria fitness.

Natural chunk-and-pass language processing: Just another joint source-channel coding model?

A recent theoretical treatment by Christiansen and Chater attempts to address fundamental challenges significant to language processing and evolution with one major operational constraint called the "Now-or-Never" bottleneck. The authors' "Chunk-and-Pass" processing putatively mitigates the severe multilevel Now-or-Never bottleneck via fast linguistic coding and compression, hierarchical language representation and pattern duality, and incrementally learned item-based predictions useful for grammaticalization over wide spacetime scales. Despite being a promising explanation of language processes, structure, and development, the Chunk-and-Pass model manages the Now-or-Never constraint with seeming reliance on optimal joint source-channel coding, a set of computational attributes for natural and artificial speech based on Shannon's noisy channel theorems. Restating the Now-or-Never bottleneck with information-theoretic source-channel capacity limitations stresses tradeoffs inherent in the authors' model involving multilevel lossy code-transmission rate and security. Such attributes render evolvable associative networks capable of Chunk-and-Pass speech acquisition, recognition, generation, and adaptation, suggesting Chunk-and-Pass processing represents a special case of joint source-channel coding.

Possible origins of consciousness in simple control over "involuntary" neuroimmunological action.

The origin(s) and purpose(s) of consciousness continue to be fervently debated by neuroscientists. A recent unconventional hypothesis put forth by Morsella et al. suggests the primary function of consciousness is the integration, selection, and execution of advantageous lower-level voluntary skeletal muscle behavior on surrounding external environments. However, at main issue is whether more precise, adaptable voluntary skeletal motor action, and therefore the corresponding workings of consciousness, first emerged and evolved in animals to exert control over external environments or internal ones regulated by less flexible autonomic function. Using the example of voluntary immunomodulation, one can identify the strengths and weaknesses of either rationale. For instance, highly trained meditative techniques for immunomodulation more-or-less conform to Morsella et al.'s assumptions on higher-level indirect conscious control of autonomic function. Whereas, untrained skeletal motor resolution of infection-related approach-avoidance conflicts support conclusions contrary to those of Morsella et al. In such cases, primitive voluntary changes in host respiration rate and volume may selectively facilitate/inhibit acute autonomic psychophysiological stress responses to pathogen insult. This and other types of scenarios predictably give evolutionary and ecological rise to self-awareness of (visceral) internal states as well as to voluntary regulation of internal state action conflicts.

The humanness of artificial non-normative personalities.

Technoscientific ambitions for perfecting human-like machines, by advancing state-of-the-art neuromorphic architectures and cognitive computing, may end in ironic regret without pondering the humanness of fallible artificial non-normative personalities. Self-organizing artificial personalities individualize machine performance and identity through fuzzy conscientiousness, emotionality, extraversion/introversion, and other traits, rendering insights into technology-assisted human evolution, robot ethology/pedagogy, and best practices against unwanted autonomous machine behavior.

Insight and analysis problem solving in microbes to machines.

A key feature for obtaining solutions to difficult problems, insight is oftentimes vaguely regarded as a special discontinuous intellectual process and/or a cognitive restructuring of problem representation or goal approach. However, this nearly century-old state of art devised by the Gestalt tradition to explain the non-analytical or non-trial-and-error, goal-seeking aptitude of primate mentality tends to neglect problem-solving capabilities of lower animal phyla, Kingdoms other than Animalia, and advancing smart computational technologies built from biological, artificial, and composite media. Attempting to provide an inclusive, precise definition of insight, two major criteria of insight, discontinuous processing and problem restructuring, are here reframed using terminology and statistical mechanical properties of computational complexity classes. Discontinuous processing becomes abrupt state transitions in algorithmic/heuristic outcomes or in types of algorithms/heuristics executed by agents using classical and/or quantum computational models. And problem restructuring becomes combinatorial reorganization of resources, problem-type substitution, and/or exchange of computational models. With insight bounded by computational complexity, humans, ciliated protozoa, and complex technological networks, for example, show insight when restructuring time requirements, combinatorial complexity, and problem type to solve polynomial and nondeterministic polynomial decision problems. Similar effects are expected from other problem types, supporting the idea that insight might be an epiphenomenon of analytical problem solving and consequently a larger information processing framework. Thus, this computational complexity definition of insight improves the power, external and internal validity, and reliability of operational parameters with which to classify, investigate, and produce the phenomenon for computational agents ranging from microbes to man-made devices.

Evolution of affective and linguistic disambiguation under social eavesdropping pressures.

Contradicting new dual-pathway models of language evolution, cortico-striatal-thalamic circuitry disambiguate uncertainties in affective prosody and propositional linguistic content of language production and comprehension, predictably setting limits on useful complexity of articulate phonic and/or signed speech. Such limits likely evolved to ensure public information is discriminated by intended communicants and safeguarded against the ecological pressures of social eavesdropping within and across phylogenetic boundaries.

Basis for a neuronal version of Grover's quantum algorithm.

Grover's quantum (search) algorithm exploits principles of quantum information theory and computation to surpass the strong Church-Turing limit governing classical computers. The algorithm initializes a search field into superposed N (eigen)states to later execute nonclassical "subroutines" involving unitary phase shifts of measured states and to produce root-rate or quadratic gain in the algorithmic time (O(N (1/2))) needed to find some "target" solution m. Akin to this fast technological search algorithm, single eukaryotic cells, such as differentiated neurons, perform natural quadratic speed-up in the search for appropriate store-operated Ca(2+) response regulation of, among other processes, protein and lipid biosynthesis, cell energetics, stress responses, cell fate and death, synaptic plasticity, and immunoprotection. Such speed-up in cellular decision making results from spatiotemporal dynamics of networked intracellular Ca(2+)-induced Ca(2+) release and the search (or signaling) velocity of Ca(2+) wave propagation. As chemical processes, such as the duration of Ca(2+) mobilization, become rate-limiting over interstore distances, Ca(2+) waves quadratically decrease interstore-travel time from slow saltatory to fast continuous gradients proportional to the square-root of the classical Ca(2+) diffusion coefficient, D (1/2), matching the computing efficiency of Grover's quantum algorithm. In this Hypothesis and Theory article, I elaborate on these traits using a fire-diffuse-fire model of store-operated cytosolic Ca(2+) signaling valid for glutamatergic neurons. Salient model features corresponding to Grover's quantum algorithm are parameterized to meet requirements for the Oracle Hadamard transform and Grover's iteration. A neuronal version of Grover's quantum algorithm figures to benefit signal coincidence detection and integration, bidirectional synaptic plasticity, and other vital cell functions by rapidly selecting, ordering, and/or counting optional response regulation choices.