Causal Basis Research Articles

Changes in memory and cognition during the SARS-CoV-2 human challenge study

Patient-reported outcomes and cross-sectional evidence show an association between COVID-19 and persistent cognitive problems. The causal basis, longevity and domain specificity of this association is unclear due to population variability in baseline cognitive abilities, vulnerabilities, virus variants, vaccination status and treatment. Thirty-four young, healthy, seronegative volunteers were inoculated with Wildtype SARS-CoV-2 under prospectively controlled conditions. Volunteers completed daily physiological measurements and computerised cognitive tasks during quarantine and follow-up at 30, 90, 180, 270, and 360 days. Linear modelling examined differences between 'infected' and 'inoculated but uninfected' individuals. The main cognitive endpoint was the baseline corrected global cognitive composite score across the battery of tasks administered to the volunteers. Exploratory cognitive endpoints included baseline corrected scores from individual tasks. The study was registered on ClinicalTrials.gov with the identifier NCT04865237 and took place between March 2021 and July2022. Eighteen volunteers developed infection by qPCR criteria of sustained viral load, one without symptoms and the remainder with mild illness. Infected volunteers showed statistically lower baseline-corrected global composite cognitive scores than uninfected volunteers, both acutely and during follow up (mean difference over all time points=-0.8631, 95% CI=-1.3613,-0.3766) with significant main effect of group in repeated measures ANOVA (F (1,34)=7.58, p=0.009). Sensitivity analysis replicated this cross-group difference after controlling for community upper respiratory tract infection, task-learning, remdesivir treatment, baseline reference and model structure. Memory and executive function tasks showed the largest between-group differences. No volunteers reported persistent subjective cognitive symptoms. These results support larger cross sectional findings indicating that mild Wildtype SARS-CoV-2 infection can be followed by small changes in cognition and memory that persist for at least a year. The mechanistic basis and clinical implications of these small changes remain unclear. This study was funded through the UK Vaccine Taskforce of the Department for Business, Energy and Industrial Strategy (BEIS) of Her Majesty's Government. WT was funded by the EPSRC through the CDT for Neurotechnology Imperial College London.

Gender at the causal basis of the new libertarian right

Gender at the causal basis of the new libertarian right

Perspective: Observational Studies Involving Low-Soy Intake Populations Have Limited Ability for Providing Insight into the Health Effects of Soybean Isoflavones

Isoflavones are naturally occurring plant compounds found in uniquely high amounts in soybeans and foods made from this legume. These soybean constituents have been proposed to exert several health benefits and as such they have been the subject of an enormous amount of research. This research includes randomized controlled trials (RCTs) and epidemiologic investigations. Although statistically significant associations between isoflavone intake and a wide range of health outcomes have been identified in cohorts involving low-isoflavone intake populations, we suggest that these associations are unlikely to have a causal basis because exposure is too low for isoflavones to exert physiologic effects. In cohorts involving predominantly non-Asian, non-vegetarian populations, the highest isoflavone intake category is typically ≤3 mg/d, an amount of isoflavones provided by ∼30 mL (2 tablespoons) of soymilk made from whole soybeans. In comparison, mean isoflavone intake in the upper intake categories in observational studies involving high-isoflavone intake populations is typically ≥50 mg/d. In RCTs, intervention doses of isoflavones typically range between 40 and 100 mg/d. Health professionals advising patients and clients about soy food and isoflavone intake need to be aware of the limitations of epidemiologic research involving low-isoflavone intake populations. Intake recommendations are best based on the results of RCTs using clinically relevant doses of isoflavones and epidemiologic studies involving populations for whom soy foods are a habitual part of the diet.

Аргументативное развертывание текста парламентских выступлений на микроуровне (на материале французского языка)

The research aims to identify functional types of semantic dependence within a fragment of the text of parliamentary speeches – the argumentative component. The paper examines the notion of an argumentative component and identifies its main elements. To establish an intentionally determined semantic dependence within this text segment, the notion of an argumentative move (AM) is introduced, which is understood as a functional unit of the addresser’s general communicative strategy and which is aimed at realizing a specific communicative intention. The relations of the functional-semantic connection, updating its argumentative moves, as well as the linguistic means that represent them are described. The scientific novelty of the work lies in the fact that based on the material of the French language, it typologizes the relations of semantic dependence at the micro level of the argumentative construction of the text of parliamentary speeches, taking into account the functional-communicative aspect. As a result of the research, the intentionally determined semantic relations typical for the corpus of texts under study were determined: proper causation (AM ‘causal basis’), nonproper causation (AM ‘argument’), consequence (AM ‘conclusion’), concession (AM ‘insufficient basis’), disjunctiveness (AM ‘expanded alternative’ and AM ‘alternative motivation’), their linguistic markers were identified and systematized.

Is the Mind a Magic Trick? Illusionism about Consciousness in the “Consciousness-Only” Theory of Vasubandhu and Sthiramati

Illusionists about consciousness boldly argue that phenomenal consciousness does not fundamentally exist—it only seems to exist. For them, the impression of having a private inner life of conscious qualia is nothing more than a cognitive error, a conjuring trick put on by a purely physical brain. Some phenomenal realists have accused illusionism of being a byproduct of modern Western scientism and overzealous naturalism. However, Jay Garfield has endorsed illusionism by explicitly drawing support from the classical Yogācāra Buddhist philosopher Vasubandhu. In this paper, I assess the degree to which Garfield’s illusionist interpretation accurately captures the views of Vasubandhu and his commentator Sthiramati in their extant Sanskrit works. As it turns out, Vasubandhu and Sthiramati converge with contemporary illusionists in taking an unconscious causal basis of cognitive/linguistic processes to be responsible for generating the illusion of representational states with apparently phenomenal contents. Within their constitutive understanding of the mind as the “imagination of what is non-existent” (abhūtaparikalpa), I raise possible candidates for what might seem to be real instances of phenomenality—mental appearances (pratibhāsa), affective sensory experience (vedanā), and “intrinsic luminosity” (prakṛtiprabhāsvara)—and consider possible responses on behalf of an illusionist interpreter. I conclude that Vasubandhu and Sthiramati really do appear to be strong illusionists about phenomenal consciousness, particularly if phenomenal states are assumed to be essentially representational.

Plant evolution: Streptophyte multicellularity, ecology, and the acclimatisation of plants to life on land

Land plants are celebrated as one of the three great instances of complex multicellularity, but new phylogenomic and phenotypic analyses are revealing deep evolutionary roots of multicellularity among algal relatives, prompting questions about the causal basis of this major evolutionary transition.

Revisiting the definition of dyslexia.

The International Dyslexia Association definition of dyslexia was updated 20years ago and has been referenced frequently in research and practice. In this paper, researchers from the Florida Center for Reading Research consider the components of the definition and make recommendations for revisions. These include recognizing the persistence of word-reading, decoding, and spelling difficulties, acknowledging the multifactorial causal basis of dyslexia, clarifying exclusionary factors, and denoting comorbidity with other developmental disorders. It is also suggested that the academic and psychosocial consequences of dyslexia be highlighted to reinforce a preventive service delivery model. Lastly, the inclusion of dyslexia within a specific learning disability category is supported.

EPIGENETIC AGE ACCELERATION AND IMMUNE CELL COUNT: A TWIN STUDY

Abstract Accelerated aging, as measured by epigenetic clocks, is associated with declines in immune system functioning. Investigating the causal basis of this association may provide mechanistic insight into the link between DNA methylation, on which epigenetic clocks are based, and age-related changes in immune cell composition. Using preliminary data from the Louisville Twin Study, this study examined the genetic and environmental sources of covariation between immune cell count (neutrophils, lymphocytes) and GrimAge Acceleration. GrimAge is a composite biomarker derived from 7 DNA methylation-based surrogates associated with mortality and smoking pack years. GrimAge Acceleration is the residual of GrimAge regressed onto chronological age. Participants consisted of 43 monozygotic twin pairs and 30 (18 same-sex) dizygotic twin pairs with a mean age of 54.5 years (sd = 5.27). Phenotypic analyses revealed that GrimAge Acceleration was significantly associated with neutrophil and lymphocyte count (r = 0.45 and -0.49, respectively). To examine the sources of covariation between these variables, biometric regression models were used to decompose the covariance between GrimAge Acceleration and neutrophils (and lymphocytes) into genetic and environmental components. Bivariate analyses revealed moderate, marginally significant genetic correlations between GrimAge Acceleration and immune cell count (rg = 0.32 and -0.38 for neutrophils and lymphocytes, respectively) and large, significant nonshared environmental correlations (re = .58 and -.54 for neutrophils and lymphocytes, respectively). Common genetic factors accounted for 39% of the phenotypic correlation in neutrophils and 43% in lymphocytes, whereas common nonshared environmental factors accounted for 61% and 57% of the correlation in these cell types, respectively.

Psychiatric nosological historiography - Part I: until the raising and fall of the psychodynamic theory

Introduction: The history of psychiatry encompasses the evolving concepts about the relationship between body and mind and also of the definition of normality, which depend on the knowledge and customs of different times and places. For a better understanding of this journey, this study privileged the presentation of the influential figures on the construction of psychiatric nosology and classifications mainly unfolded on a descriptive or causal basis, from psychics or somatics driving, since the western renaissance. Because of the length of this historical path, this study is divided into two parts. This paper, the first in a two-part series, is a preamble to the development of the new nosography and psychopharmacology of the 21st century, merit of the second paper in this series. Method: Narrative review based on secondary sources. Results: Part One includes a review of prior studies concluding that the psychiatric nosography construction has many stations and it passes through the 18th century more structured morbid classifications based on taxonomies of the natural sciences. Psychiatric classifications navigate the course between different psychiatric theories, often marked by inherent prejudices, alongside advances achieved in neuroscience and its intricate connections with the physiology of emotions, cognition and behaviors, shedding light on their deviations or disorders. This evolution goes in parallel with that of the macro and microanatomy, physiology, chemistry, pharmacology, genetics, internal medicine, mainly neurology, apace with evaluation techniques that also reach the Blood-oxygen-level-dependent imaging (BOLD) fMRI (functional magnetic resonance imaging) that indirectly study the action of neurotransmitters and neuronal signalling. The biologic approach stands in contrast to the psychodynamic theory, particularly dominant until roughly the mid-20th century. Conclusion: The study of psychiatric nosohistoriography helps to understand the conceptual evolution of mental illnesses and the most recent importance of psychopharmacology for this.

Psychiatric nosological historiography - Part II: psychopharmacology and somatogenic perspectives

Introduction: The history of psychiatry encompasses the evolving concepts about the relationship between body and mind and also of the definiton of normality, which depend on the knowledge and customs of different times and places. For a better understanding of this journey, this study privileged the presentation of the main influential figures on the construction of psychiatric nosology and classifications mainly unfolded on a descriptive or causal basis, from psychics or somatics driving, since the Western Renaissance. This article, the second in a two-part series, mainly discusses the importance of psychopharmacology for a better understanding of mental disorders and their classifications. Part one is a preamble to the historical development of the new nosography and psychopharmacology. Method: Narrative review based on secondary sources. Results: The current article illustrates how the understanding of the pathophysiological mechanisms underlying mental illness improves, mainly employing the psychopharmacology that may lead to the reclassification of certain mental disorders. This natural reductionism view of the sciences must be in cooperation with an integrative understanding of the human being, as is customary in the humanities. Conclusion: The study of psychiatric nosohistoriography helps to understand the conceptual evolution of mental illnesses and the most recent importance of psychopharmacology for this.

Comparative biology and non-traditional approaches for basic aging research for facilitating translational studies.

As humans, we aspire to healthy aging and ideally reaching our maximal lifespan. That, however, requires optimizing resilience to stressors and minimizing exposure to factors that accelerate aging. Understanding the complexities of aging processes involves characterizing the causal bases of physical, physiological, and cognitive deficits that accumulate over time, eventually culminating in reduced functionality and decreased resistance to disease and environmental stressors. Both the progression of age-related conditions and onset of diseases are affected by environmental stressors; however, the basis for increased susceptibility remains poorly understood. Furthermore, the actions of some environmental stressors, such as endocrine disruptors, can alter both developmental and aging processes, contributing to lifelong issues with inflammatory and neurodegenerative conditions. This manuscript focuses on the comparative biology and evolution of aging and longevity. The status of an array of animal models and potential for specific geroscience translational applications is addressed by asking these questions. What animal models are currently available for aging and translational geroscience? What are the key roadblocks and barriers for studies of healthy aging, and how might specific animal models be useful? Are research tools available? Which vertebrate animal models can specifically address targeted questions in human aging processes? Can information be synthesized for a range of vertebrate species to identify suitable animal models for addressing specific research questions in geroscience, especially relative to basic physiological function, timing and trajectory of disease progression, effects of environmental stressors, and potential for regenerative medicine?

A thermodynamic basis for teleological causality.

We show how distinct terminally disposed self-organizing processes can be linked together so that they collectively suppress each other's self-undermining tendency despite also potentiating it to occur in a restricted way. In this way, each process produces the supportive and limiting boundary conditions for the other. The production of boundary conditions requires dynamical processes that decrease local entropy and increase local constraints. Only the far-from-equilibrium dissipative dynamics of self-organized processes produce these effects. When two such complementary self-organizing processes are linked by a shared substrate-the waste product of one that is the necessary ingredient for the other-the co-dependent structure that results develops toward a self-sustaining target state that avoids the termination of the whole, and any of its component processes. The result is a perfectly naturalized model of teleological causation that both escapes the threat of backward influences and does not reduce teleology to selection, chemistry or chance. This article is part of the theme issue 'Thermodynamics 2.0: Bridging the natural and social sciences (Part 1)'.

Natralization without associationist reduction: a brief rebuttal to Yoshimi

AbstractYoshimi has attempted to defuse my argument concerning the identification of network abstraction with empiricist abstraction - thus entailing psychologism - by claiming that the argument does not generalize from the example of simple feed-forward networks. I show that such details of networks are logically irrelevant to the nature of the abstractive process they employ. This is ultimately because deep artificial neural networks (ANNs) and dynamical systems theory applied to the mind (DST) are both associationisms - that is, empiricist theories that derive the principles of thought from the causal history of the organism/system. On this basis, I put forward a new aspect of the old argument by noting that ANNs & DST are the causal bases of the phenomena of passive synthesis, whereas the language of thought hypothesis (LOT) and the symbolic computational theory of mind (CTM) are the causal bases of the phenomena of active synthesis. If the phenomena of active synthesis are not distinct in kind from and are thus reducible to those of passive synthesis, psychologism results. Yoshimi’s program, insofar as it denies this fundamental phenomenological distinction, is revealed to be the true anti-pluralist program, by essentially denying the causal efficacy of the mechanistic foundations of active synthesis by referring phenomenology exclusively to associationism for its causal foundation.

Causal inference and large‐scale expert validation shed light on the drivers of SDM accuracy and variance

AbstractAimTo develop a causal understanding of the drivers of Species distribution model (SDM) performance.LocationUnited Kingdom (UK).MethodsWe measured the accuracy and variance of SDMs fitted for 518 species of invertebrate and plant in the UK. Our measure of variance reflects variation among replicate model fits, and taxon experts assessed model accuracy. Using directed acyclic graphs, we developed a causal model depicting plausible effects of explanatory variables (e.g. species' prevalence, sample size) on SDM accuracy and variance and quantified those effects using a multilevel piecewise path model.ResultsAccording to our model, sample size and niche completeness (proportion of a species' niche covered by sampling) directly affect SDM accuracy and variance. Prevalence and range completeness have indirect effects mediated by sample size. Challenging conventional wisdom, we found that the effect of prevalence on SDM accuracy is positive. This reflects the facts that sample size has a positive effect on accuracy and larger sample sizes are possible for widespread species. It is possible, however, that the omission of an unobserved confounder biased this effect. Previous studies, which reported negative correlations between prevalence and SDM accuracy, conditioned on sample size.Main conclusionsOur model explicates the causal basis of previously reported correlations between SDM performance and species/data characteristics. It also suggests that niche completeness has similarly large effects on SDM accuracy and variance as sample size. Analysts should consider niche completeness, or proxies thereof, in addition to sample size when deciding whether modelling is worthwhile.

An Active Externalism about Personality

People display recognizably characteristic behavioral patterns across time and situations, with a given degree of regularity. These patterns may justify the attribution of personality traits. It is arguably the commonsense view that the proper explanation of these behavioral regularities is given by intrinsic properties of the agent’s psychology. In this paper, I argue for an externalistic view of the causal basis of personality-characteristic behaviors. According to the externalistic view, the relevant behavioral regularities are better understood as the result of a systematic interaction between features internal to the agent and environmental-situational factors. Moreover, if the premise is granted that people are typically able to exercise a certain degree of control over the environmental-situational conditions they find themselves in, the resulting picture is of active sort of externalism, as people may at times engage in selection and manipulation of environmental-situational conditions as a way of managing their own behavioral tendencies.

The Emerging Prevalence of Obesity within Families in Europe and its Associations with Family Socio-Demographic Characteristics and Lifestyle Factors; A Cross-Sectional Analysis of Baseline Data from the Feel4Diabetes Study.

The Feel4Diabetes study is a type 2 diabetes prevention program that recruited 12,193 children [age: 8.20 (±1.01) years] and their parents from six European countries. The current work used pre-intervention data collected from 9576 children-parents pairs, to develop a novel family obesity variable and to examine its associations with family sociodemographic and lifestyle characteristics. Family obesity, defined as the presence of obesity in at least two family members, had a prevalence of 6.6%. Countries under austerity measures (Greece and Spain) displayed higher prevalence (7.6%), compared to low-income (Bulgaria and Hungary: 7%) and high-income countries (Belgium and Finland: 4.5%). Family obesity odds were significantly lower when mothers (OR: 0.42 [95% CI: 0.32, 0.55]) or fathers (0.72 [95% CI: 0.57, 0.92]) had higher education, mothers were fully (0.67 [95% CI: 0.56, 0.81]) or partially employed (0.60 [95% CI: 0.45, 0.81]), families consumed breakfast more often (0.94 [95% CI: 0.91 0.96]), more portions of vegetables (0.90 [95% CI: 0.86, 0.95]), fruits (0.96 [95% CI: 0.92, 0.99]) and wholegrain cereals (0.72 [95% CI: 0.62, 0.83]), and for more physically active families (0.96 [95% CI: 0.93, 0.98]). Family obesity odds increased when mothers were older (1.50 [95% CI: 1.18, 1.91]), with the consumption of savoury snacks (1.11 [95% CI: 1.05, 1.17]), and increased screen time (1.05 [95% CI: 1.01, 1.09]). Clinicians should familiarise themselves with the risk factors for family obesity and choose interventions that target the whole family. Future research should explore the causal basis of the reported associations to facilitate devising tailored family-based interventions for obesity prevention.

Causal knowledge graph construction and evaluation for clinical decision support of diabetic nephropathy

BackgroundMany important clinical decisions require causal knowledge (CK) to take action. Although many causal knowledge bases for medicine have been constructed, a comprehensive evaluation based on real-world data and methods for handling potential knowledge noise are still lacking. ObjectiveThe objectives of our study are threefold: (1) propose a framework for the construction of a large-scale and high-quality causal knowledge graph (CKG); (2) design the methods for knowledge noise reduction to improve the quality of the CKG; (3) evaluate the knowledge completeness and accuracy of the CKG using real-world data. Material and methodsWe extracted causal triples from three knowledge sources (SemMedDB, UpToDate and Churchill's Pocketbook of Differential Diagnosis) based on rule methods and language models, performed ontological encoding, and then designed semantic modeling between electronic health record (EHR) data and the CKG to complete knowledge instantiation. We proposed two graph pruning strategies (co-occurrence ratio and causality ratio) to reduce the potential noise introduced by SemMedDB. Finally, the evaluation was carried out by taking the diagnostic decision support (DDS) of diabetic nephropathy (DN) as a real-world case. The data originated from a Chinese hospital EHR system from October 2010 to October 2020. The knowledge completeness and accuracy of the CKG were evaluated based on three state-of-the-art embedding methods (R-GCN, MHGRN and MedPath), the annotated clinical text and the expert review, respectively. ResultsThis graph included 153,289 concepts and 1,719,968 causal triples. A total of 1427 inpatient data were used for evaluation. Better results were achieved by combining three knowledge sources than using only SemMedDB (three models: area under the receiver operating characteristic curve (AUC): p < 0.01, F1: p < 0.01), and the graph covered 93.9 % of the causal relations between diseases and diagnostic evidence recorded in clinical text. Causal relations played a vital role in all relations related to disease progression for DDS of DN (three models: AUC: p > 0.05, F1: p > 0.05), and after pruning, the knowledge accuracy of the CKG was significantly improved (three models: AUC: p < 0.01, F1: p < 0.01; expert review: average accuracy: + 5.5 %). ConclusionsThe results demonstrated that our proposed CKG could completely and accurately capture the abstract CK under the concrete EHR data, and the pruning strategies could improve the knowledge accuracy of our CKG. The CKG has the potential to be applied to the DDS of diseases.

The Multi-Causal Basis of Developmental Potential Construction

In this article we analyse the issue of what accounts for developmental potential, i.e., the possible phenotypes a developing organism can manifest during ontogeny. We shall argue in favour of two theses. First, although the developing organism is the unit of development, the complete causal basis for its potential to develop does neither lie entirely in itself as a whole nor in any specific part of itself (such as its genome). Thus, the extra-organismal environment must be counted as one of the three necessary, partial and complementary causal bases for development potential. Secondly, we shall defend a constructivist view of the developmental process. If the genome, the developing organism and the extra-organismal environment are to be counted as proper elements of the causal basis for an organism’s developmental potential, the latter is not a given. Rather, it is the result of an interaction-based construction, a process sometimes generating genuine developmental novelty. We will thus argue for an interactionist multi-causal basis view of developmental potential construction. We contend that our view provides a biologically tenable and metaphysically coherent account of developmental dynamics.

Investigation of genetic variants and causal biomarkers associated with brain aging

Delta age is a biomarker of brain aging that captures differences between the chronological age and the predicted biological brain age. Using multimodal data of brain MRI, genomics, and blood-based biomarkers and metabolomics in UK Biobank, this study investigates an explainable and causal basis of high delta age. A visual saliency map of brain regions showed that lower volumes in the fornix and the lower part of the thalamus are key predictors of high delta age. Genome-wide association analysis of the delta age using the SNP array data identified associated variants in gene regions such as KLF3-AS1 and STX1. GWAS was also performed on the volumes in the fornix and the lower part of the thalamus, showing a high genetic correlation with delta age, indicating that they share a genetic basis. Mendelian randomization (MR) for all metabolomic biomarkers and blood-related phenotypes showed that immune-related phenotypes have a causal impact on increasing delta age. Our analysis revealed regions in the brain that are susceptible to the aging process and provided evidence of the causal and genetic connections between immune responses and brain aging.

Contextuality and context-sensitivity in probabilistic models of cognition

The context-sensitivity of cognition has been demonstrated across a wide range of cognitive functions such as perception, memory, judgement and decision making. A related term, ‘contextuality’, has appeared from the field of quantum cognition, with mounting empirical evidence demonstrating that cognitive phenomena are sometimes contextual. Contextuality is a subtle notion that influences how we must view the properties of the cognitive phenomenon being studied. This article addresses the questions: What does it mean for a cognitive phenomenon to be contextual? What are the implications of contextuality for probabilistic models of cognition? How does contextuality differ from context-sensitivity? Starting from George Boole’s “conditions of possible experience”, we argue that a probabilistic model of a cognitive phenomenon is necessarily subject to an assumption of realism. By this we mean that the phenomenon being studied is assumed to have cognitive properties with a definite value independent of observation. In contrast, quantum cognition holds that a cognitive property maybe indeterminate, i.e., its properties do not have well established values prior to observation. We argue that indeterminacy is sufficient for incompatibility between cognitive properties. In turn, incompatibility is necessary for their contextuality. The significance of this argument for cognitive psychology is the following:if a cognitive phenomenon is found to be contextual, then there is reason to believe it may be indeterminate. We illustrate by means of two crowdsourced experiments how context-sensitivity and contextuality of cognitive properties in the form of facial trait judgements can be characterized from empirical data. Finally, we conceptually and formally contrast contextuality with context-sensitivity. We propose that both involve a form of context dependence, with causality being the differentiating factor: the context dependence in context-sensitivity has a causal basis, whereas the context dependence in contextuality is acausal. The resulting implications for probabilistic models of cognition are discussed.