ARTICLE | doi:10.20944/preprints202004.0480.v1
Subject: Biology, Other Keywords: causal statement; causal interaction; directed molecular interaction; minimum information; standardization, systems biology
Online: 27 April 2020 (05:07:57 CEST)
A large variety of molecular interactions occurs between biomolecular components in cells. When one or a cascade of molecular interactions results in a regulatory effect, by one component onto a downstream component, a so-called ‘causal interaction’ takes place. Causal interactions constitute the building blocks in our understanding of larger regulatory networks in cells. These causal interactions and the biological processes they enable (e.g., gene regulation) need to be described with a careful appreciation of molecular interactions that occur between entities. A proper description of this information enables archiving, sharing, and reuse by humans and for computational science. Various representations of causal relationships between biological components are currently used in a variety of resources. Here, we propose a checklist that accommodates current representations, and call it the Minimum Information about a Molecular Interaction CAusal STatement (MI2CAST). This checklist defines both the required core information, as well as a comprehensive set of other contextual details valuable to the end user and relevant for reusing and reproducing causal molecular interaction information. The MI2CAST checklist can be used as reporting guidelines when annotating and curating causal statements, while assuring uniformity and interoperability of the data across resources.
ARTICLE | doi:10.20944/preprints202002.0066.v3
Subject: Keywords: information theory; causal inference; causal tensors; transfer entropy; partial information decomposition; left monotonicity; identity property; unobserved common cause
Online: 27 February 2020 (10:55:05 CET)
We propose a partial information decomposition based on the newly introduced framework of causal tensors, i.e., multilinear stochastic maps that transform source data into destination data. The innovation that causal tensors introduce is that the framework allows for an exact expression of an indirect association in terms of the constituting, direct associations. This is not possible when expressing associations only in measures like mutual information or transfer entropy. Instead of a priori expressing associations in terms of mutual information or transfer entropy, the a posteriori expression of associations in these terms results in an intuitive definition of a nonnegative and left monotonic redundancy, which also meets the identity property. Our proposed redundancy satisfies the three axioms introduced by Williams and Beer. Symmetry and self-redundancy axioms follow directly from our definition. The data processing inequality ensures that the monotonicity axiom is satisfied. Because causal tensors can describe both mutual information as transfer entropy, the partial information decomposition applies to both measures. Results show that the decomposition closely resembles the decomposition of other another approach that expresses associations in terms of mutual information a posteriori. A negative synergistic term could indicate that there is an unobserved common cause.
REVIEW | doi:10.20944/preprints202101.0035.v1
Subject: Life Sciences, Biochemistry Keywords: GWAS; genetics; Mendelian Randomization; causal inference
Online: 4 January 2021 (12:36:41 CET)
With the rapidly increasing availability of large genetic data sets in recent years, Mendelian Randomization (MR) has quickly gained popularity as a novel secondary analysis method. Leveraging genetic variants as instrumental variables, MR can be used to estimate the causal effects of one phenotype on another even when experimental research is not feasible, and therefore has the potential to be highly informative. It is dependent on strong assumptions however, often producing strongly biased results if these are not met. It is therefore imperative that these assumptions are well-understood by researchers aiming to use MR, in order to evaluate their validity in the context of their analyses and data. The aim of this perspective is therefore to further elucidate these assumptions and the role they play in MR, as well as how different kinds of data can be used to further support them.
ARTICLE | doi:10.20944/preprints202206.0069.v1
Subject: Social Sciences, Other Keywords: Industry 4.0; SME; agent-based simulation; causal loop
Online: 6 June 2022 (08:37:39 CEST)
ASEAN SME has a role as the regional socioeconomic stabilizer. This particular role is inseparable from endogenous multi-sector collaboration. Although, Indonesian SMEs were struggled in adopting Industry 4.0 correspond to digital infrastructure and digital literacy problems. This study evaluates Indonesian SME collaboration dynamics with government and technology startup (TS). The integration of agent-based model and causal loop simulation were employed to assess the TS collaboration impact on SME Industry 4.0 adoption and SME competition with larger competitors. The simulation results imply the SME collaboration with TS can lead to early adoption of Industry 4.0 which balances the business competition environment. The model also shows rising the government aid exponentially can help the SME to late adoption of Industry 4.0 which unable to sustain the SME in business competition. Thus, the developed integrative simulation model is a state-action planning model with each state result bounded to the previous state result that determined by initial input parameters. Conclusively, the model can be used as a resiliency planner for SME Industry 4.0 adoption.
ARTICLE | doi:10.20944/preprints202112.0018.v1
Subject: Medicine & Pharmacology, Oncology & Oncogenics Keywords: metastatic breast cancer; metastasis; causal learning; machine learning
Online: 1 December 2021 (13:40:33 CET)
Background: Risk of metastatic recurrence of breast cancer after initial diagnosis and treatment depends on the presence of a number of risk factors. Although most univariate risk factors have been identified using classical methods, machine-learning methods are also being conducted to tease out non-obvious contributors to a patient’s individual risk of developing late distant metastasis. Bayesian-network algorithms may predict not only risk factors but also interactions among these risks, which consequently lead to metastatic breast cancer. We proposed to apply a previously developed machine-learning method to predict risk factors of 5-, 10- and 15-year metastasis. Methods: We applied a previously validated algorithm named the Markov Blanket and Interactive risk factor Learner (MBIL) on the electronic health record (EHR)-based Lynn Sage database (LSDB) from the Lynn Sage Comprehensive Breast Cancer at Northwestern Memorial Hospital. This algorithm provided an output of both single and interactive risk factors of 5-, 10-, and 15-year metastasis from LSDB. We individually examined and interpreted the clinical relevance of these interactions based on years to metastasis and the reliance on interactivity between risk factors. Results: We found that with lower alpha values (low interactivity score), the prevalence of variables with an independent influence on long term metastasis was higher (i.e., HER2, TNEG). As the value of alpha increased to 480, stronger interactions were needed to define clusters of factors that increased the risk of metastasis (i.e., ER, smoking, race, alcohol usage). Conclusion: MBIL identified single and interacting risk factors of metastatic breast cancer, many of which were supported by clinical evidence. These results strongly recommend the development of further large data studies with different databases to validate the degree to which some of these variables impact metastatic breast cancer in the long term.
ARTICLE | doi:10.20944/preprints201803.0127.v1
Subject: Behavioral Sciences, Social Psychology Keywords: causal relationship model; disposing of used batteries; households
Online: 16 March 2018 (05:07:24 CET)
This research aimed to develop a causal relationship model of the behavior of a Thai rural community in disposing of used batteries. The variables studied were 1) the household latent variable (three observable variables); 2) the social latent variable (six observable variables); 3) the intention latent variable (three observable variable); and 4) the behavior latent variable (three observable variables). Six hundred households were surveyed using a questionnaire. The questionnaire developed was validated by seven experts and its reliability was established by testing it with a sample group. Results showed that the modified model do present a good overall level of fit. The House and social positively and directly influenced intention. Intention positively and directly influenced behavior. The theoretical and practical implications relating specifically to intention to the behavior in disposing of used dry batteries by households are emphasized. The modified model indicated eighty-nine percent of the variance in the behavior in disposing of used dry batteries by households was explained by the intention factors. The most direct effect on behavior was the intention factors with 0.89 of effect size. The factors with indirect effects on behavior were household and social factors with an effect size of 0.52 and 0.35.
Subject: Keywords: COVID-19; description; prediction; causal inference; extrapolation; simulation; projection
Online: 10 August 2020 (10:44:46 CEST)
The models used to estimate disease transmission, susceptibility and severity determine what epidemiology can (and cannot tell) us about COVID-19. These include: ‘model organisms’ chosen for their phylogenetic/aetiological similarities; multivariable statistical models to estimate the strength/direction of (potentially causal) relationships between variables (through ‘causal inference’), and the (past/future) value of unmeasured variables (through ‘classification/prediction’); and a range of modelling techniques to predict beyond the available data (through ‘extrapolation’), compare different hypothetical scenarios (through ‘simulation’), and estimate key features of dynamic processes (through ‘projection’). Each of these models: address different questions using different techniques; involve assumptions that require careful assessment; and are vulnerable to generic and specific biases that can undermine the validity and interpretation of their findings. It is therefore necessary that the models used: can actually address the questions posed; and have been competently applied. In this regard, it is important to stress that extrapolation, simulation and projection cannot offer accurate predictions of future events when the underlying mechanisms (and the contexts involved) are poorly understood and subject to change. Given the importance of understanding such mechanisms/contexts, and the limited opportunity for experimentation during outbreaks of novel diseases, the use of multivariable statistical models to estimate the strength/direction of potentially causal relationships between two variables (and the biases incurred through their misapplication/misinterpretation) warrant particular attention. Such models must be carefully designed to address: ‘selection-collider bias’, ‘unadjusted confounding bias’ and ‘inferential mediator adjustment bias’ – all of which can introduce effects capable of enhancing, masking or reversing the estimated (true) causal relationship between the two variables examined. Selection-collider bias occurs when these two variables independently cause a third (the ‘collider’), and when this collider determines/reflects the basis for selection in the analysis. It is likely to affect all incompletely representative samples, although its effects will be most pronounced wherever selection is constrained (e.g. analyses focusing on infected/hospitalised individuals). Unadjusted confounding bias disrupts the estimated (true) causal relationship between two variables when: these share one (or more) common cause(s); and when the effects of these causes have not been adjusted for in the analyses (e.g. whenever confounders are unknown/unmeasured). Inferentially similar biases can occur when: one (or more) variable(s) (or ‘mediators’) fall on the causal path between the two variables examined (i.e. when such mediators are caused by one of the variables and are causes of the other); and when these mediators are adjusted for in the analysis. Such adjustment is commonplace when: mediators are mistaken for confounders; prediction models are mistakenly repurposed for causal inference; or mediator adjustment is used to estimate direct and indirect causal relationships (in a mistaken attempt at ‘mediation analysis’). These three biases are central to ongoing and unresolved epistemological tensions within epidemiology. All have substantive implications for our understanding of COVID-19, and the future application of artificial intelligence to ‘data-driven’ modelling of similar phenomena. Nonetheless, competently applied and carefully interpreted, multivariable statistical models may yet provide sufficient insight into mechanisms and contexts to permit more accurate projections of future disease outbreaks.
Subject: Medicine & Pharmacology, Other Keywords: directed acyclic graph; DAG; causal inference; bias; inferential statistics; reproducibility
Online: 8 October 2022 (02:57:44 CEST)
The origins of directed acyclic graphs (DAGs) date back to the emergence of ‘graph theory’ in the early 1700s (Biggs et al. 1986). DAGs are conceptual or literal, diagrammatic representations of causal paths between variables which are constructed – as their name suggests – on the basis of two over-riding principles: first, that all causal paths are ‘directed’ (i.e. for each pair of variables, only one can represent the cause, while the other must be its consequence); and second, that no direct cyclical paths, or indirect cyclical pathways (comprising sequences of consecutive paths) are allowed, such that no consequence can be considered its own direct or indirect cause (hence ‘acyclic’; Law et al., 2012). As such DAGs reflect the knowledge, presumptions, assumptions and/or speculation of the analyst(s) concerned regarding the causal relationships between each of the variables included therein. Current convention dictates that variables are represented as nodes/vertices, and that any causal paths between variables are represented as directed arcs/edges/lines, often in the form of arrows (see Figure 1). Although each arc indicates the presence and direction of a known/presumed/assumed/speculative causal relationship between the two variables concerned, drawing an arc does not require the sign, magnitude, precision or shape of the relationship to be known or declared (Tennant et al., 2021). In this respect, DAGs provide a simple, uncomplicated, accessible and entirely nonparametric approach for postulating causal relationships amongst any variables of interest even when these are uncertain, unknown or entirely speculative (Ellison, 2020). Nonetheless, as a result of the parametric constraints imposed by the presence/absence of possible arcs within any given DAG, these also reflect and support a number of more sophisticated statistical applications which make it possible to use DAGs to inform the design of multivariable statistical models that reflect the causal structure(s) involved – albeit without the need to know or understand the mathematical technicalities on which these are based (Lewis and Kuerbis, 2016). These features make DAGs attractive cognitive, educational and analytical tools for strengthening the epistemological, theoretical and empirical basis of causal inference, and there has been a recent proliferation in the use of DAGs across a range of applied scientific disciplines (e.g. Knight and Winship, 2013), and an associated upsurge in analytical methods training (e.g. Elwert, 2011; Gilthorpe, 2017; Hernán 2018; Roy, 2021; Hünermund, 2021). This Chapter reflects on a decade of delivering medical statistics training to undergraduate medical students at the University of Leeds between 2012-2021 in which the third year research, evaluation and special studies module (‘RESS3’) has used DAGs to support the development of applied statistical skills relevant to the extended student-selected research and evaluation projects (ESREP) students undertake in their fourth and final years (Ellison, 2021; Ellison et al., 2014a,b). Based on successive iterations of the structure and content of the RESS3 module, together with notes made during formal and informal planning and review meetings with module leads, lecturers, tutors and students, we draw on the claims and criticisms made of DAGs in the epidemiological literature to identify a number of explicit strengths (and associated, often implicit. weaknesses) that are central to their use in prediction and causal inference modelling. While using DAGs requires (and benefits from) a clear understanding of their non-parametric nature and parametric implications, the weaknesses of DAGs seem likely to reflect both: the challenges inherent in the modelling of data generating processes when these are imperfectly understood; and troublesome cognitive and heuristic tendencies common to all analytical tools – in which the tool facilitates the task in hand by reducing the necessity (and benefits of) exploring uncertainties and identifying assumptions. These, more epistemological considerations appear particularly challenging for medical undergraduates to grasp (Ellison, 2021), but also appear poorly understood by many established analysts and clinical epidemiologists (Ellison, 2020).
ARTICLE | doi:10.20944/preprints202206.0418.v1
Subject: Behavioral Sciences, Other Keywords: transformational leadership; workplace engagement; education; meta-analysis; endogeneity; causal studies
Online: 30 June 2022 (07:43:16 CEST)
One of the major areas of research in a business setting has been the effect of the transformational leadership style on workplace engagement. Much debate has taken place on the definitions of both constructs but in recent years, general agreement appears to have been reached on the Multi-Factor Leadership Questionnaire (MLQ) (Avolio and Bass, 2004) as the measure of transformational leadership, and on workplace engagement measured by the Utrecht Work Engagement Scale (UWES) (Schaufeli et al, 2006). However, in the education setting, there is much less agreement on the definition of transformational leadership. Furthermore, there is less of a focus on workplace engagement than in the business field even though available evidence suggests that workplace engagement worldwide is in crisis. This study sought to address both the lack of agreement on the transformational leadership definition and the lack of focus on workplace engagement in educational research by means of a meta-analysis. The meta-analysis resulted in a significant pooled effect size although due recognition is given to the endogeneity problem in causal studies. The endogeneity issue together with the results of the meta-analysis are discussed with a view to furthering educational leadership research.
ARTICLE | doi:10.20944/preprints202111.0524.v1
Subject: Life Sciences, Biochemistry Keywords: Self-reference; cognition; consciousness; computation; causal structure; integrated information theory
Online: 29 November 2021 (11:51:43 CET)
Ordinary computing machines prohibit self-reference because it leads to logical inconsistencies and undecidability. In contrast, the human mind can understand self-referential statements without necessitating physically impossible brain states. Why can the brain make sense of self-reference? Here, we address this question by defining the Strange Loop Model, which features causal feedback between two brain modules, and circumvents the paradoxes of self-reference and negation by unfolding the inconsistency in time. We also argue that the metastable dynamics of the brain inhibit and terminate unhalting inferences. Finally, we show that the representation of logical inconsistencies in the Strange Loop Model leads to causal incongruence between brain subsystems in Integrated Information Theory.
ARTICLE | doi:10.20944/preprints202007.0622.v1
Subject: Life Sciences, Other Keywords: causal statement; metadata; curation guidelines; curation web interface; VSM; MI2CAST
Online: 25 July 2020 (18:24:10 CEST)
Molecular causal interactions are defined as regulatory connections between biological components. They are commonly retrieved from biological experiments, and can be used for connecting biological molecules into regulatory computational models that represent biological systems. However, including a molecular causal interaction into a model requires assessing its relevance to that model, based on detailed knowledge about the biomolecules, interaction type, and biological context. In order to standardize the representation of this knowledge in ‘causal statements’, we recently developed the MI2CAST guidelines. Here we introduce causalBuilder: an intuitive web-based curation interface for the annotation of molecular causal interactions that comply with the MI2CAST standard. The causalBuilder prototype essentially embeds the MI2CAST curation guidelines in its interface, and makes its rules easy to follow by a curator. In addition, causalBuilder serves as an original application of the VSM general-purpose curation technology, and provides both curators and tool developers with an interface that can be fully configured to allow focusing on selected MI2CAST concepts to annotate. After information is entered, the causalBuilder prototype produces genuine causal statements that can be exported in different formats.
REVIEW | doi:10.20944/preprints202007.0123.v1
Subject: Life Sciences, Other Keywords: causal interactions; databases; interoperability; biological pathway; logical modeling; computational biology
Online: 7 July 2020 (09:50:40 CEST)
Causal molecular interactions represent key building blocks used in computational modeling, where they facilitate the assembly of regulatory networks. These regulatory networks can then be used to predict biological and cellular behavior by system perturbations and in silico simulations. Today, broad sets of these interactions are being made available in a variety of biological knowledge resources. Moreover, different visions, based on distinct biological interests, have led to the development of multiple ways to describe and annotate causal molecular interactions. Therefore, data users can find it challenging to efficiently explore resources of causal interaction and to be aware of recorded contextual information that ensures valid use of the data. This manuscript presents a review of public resources collecting causal interactions and the different views they convey, together with a thorough description of the export formats established to store and retrieve these interactions. Our goal is to raise awareness amongst the targeted audience, i.e., logical modelers, but also any scientist interested in molecular causal interactions, about existing data resources and how to get familiar with them.
ARTICLE | doi:10.20944/preprints202301.0317.v1
Subject: Medicine & Pharmacology, Pediatrics Keywords: vitamin D; pediatric type 2 diabetes; Mendelian randomization; GWAS; causal inference
Online: 18 January 2023 (03:40:38 CET)
Observational studies have linked vitamin D insufficiency to pediatric type 2 diabetes (T2D) , but evidence from vitamin D supplementation trials is sparse. Given the rising prevalence of pediatric T2D in all ethnicities, determining a protective role of vitamin D has significant public health importance. We tested whether serum 25-hydroxyvitamin D (25OHD) levels are causally linked to youth-onset T2D risk using Mendelian randomization (MR). We selected 54 single nucleotide polymorphisms (SNPs) associated with 25OHD in a European genome-wide association study (GWAS) on 443,734 individuals and obtained their effects on pediatric T2D from the multi-ethnic PRODIGY GWAS (3,006 cases/6,061 controls). We applied inverse variance weighted (IVW) MR, and a series of MR methods to control for pleiotropy. We undertook sensitivity analyses in ethnic sub-cohorts of PRODIGY, and using SNPs in core vitamin D genes or ancestry-informed 25OHD SNPs. Multivariable MR accounted for mediating effects of body mass index. We found that a standard deviation increase in 25OHD in the logarithmic scale did not affect youth-onset T2D risk (IVW MR odds ratio (OR) = 1.04, 95% CI=0.96-1.13, P=0.35) in the multi-ethnic analysis, and sensitivity, ancestry-specific and multivariable MR analyses showed consistent results. Our study had limited power to detect small/moderate effects of 25OHD (OR of pediatric T2D < 1.39 to 2.1). In conclusion, 25OHD levels are unlikely to have large effects on risk of youth-onset T2D across different ethnicities.
REVIEW | doi:10.20944/preprints202102.0179.v1
Subject: Medicine & Pharmacology, Allergology Keywords: evidence-based practice; clinical reasoning; causal model; intervention theory; Concept Mapping
Online: 8 February 2021 (10:35:52 CET)
Significant efforts in the past decades to teach evidence-based practice (EBP) implementation has emphasized increasing knowledge of EBP and developing interventions to support adoption to practice. These efforts have resulted in only limited sustained improvements in the daily use of evidence-based interventions in clinical practice in most health professions. Many new interven-tions with limited evidence of effectiveness are readily adopted each year - indicating openness to change is not the problem. The selection of an intervention is the outcome of an elaborate and complex cognitive process which is shaped by how they represent the problem in their mind and is mostly invisible processes to others. Therefore, the complex thinking process which support appropriate adoption of interventions should be taught more explicitly. Making the process visible to clinicians increases the acquisition of the skills required to judiciously select one in-tervention over others. The purpose of this paper is to provide a review of the selection process and the critical analysis that is required to appropriately decide to trial or not trial new intervention strategies with patients.
ARTICLE | doi:10.20944/preprints202003.0178.v3
Subject: Physical Sciences, Other Keywords: consciousness; meta-causation; pre-reflective self-consciousness; physicalism; causal productivity; dynamism; laws of nature; laws of physics; temporal non-locality
Online: 27 August 2020 (08:27:28 CEST)
How, if at all, consciousness can be part of the physical universe remains a baffling problem. This article outlines a new, developing philosophical theory of how it could do so, and offers a preliminary mathematical formulation of a physical grounding for key aspects of the theory. Because the philosophical side has radical elements, so does the physical-theory side. The philosophical side is radical, first, in proposing that the productivity or dynamism in the universe that many believe to be responsible for its systematic regularities is actually itself a physical constituent of the universe, along with more familiar entities. Indeed, it proposes that instances of dynamism can themselves take part in physical interactions with other entities, this interaction then being “meta-dynamism” (a type of meta-causation). Secondly, the theory is radical, and unique, in arguing that consciousness is necessarily partly constituted of meta-dynamic auto-sensitivity, in other words it must react via meta-dynamism to its own dynamism, and also in conjecturing that some specific form of this sensitivity is sufficient for and indeed constitutive of consciousness. The article proposes a way for physical laws to be modified to accommodate meta-dynamism, via the radical step of including elements that explicitly refer to dynamism itself. Additionally, laws become, explicitly, temporally non-local in referring directly to quantity values holding at times prior to a given instant of application of the law. The approach therefore implicitly brings in considerations about what information determines states. Because of the temporal non-locality, and also because of the deep connections between dynamism and time-flow, the approach also implicitly connects to the topic of entropy insofar as this is related to time.
ARTICLE | doi:10.20944/preprints201912.0227.v1
Subject: Keywords: information; process; process algebra; causal tapestry; process tapestry; transience; contextuality; emergence
Online: 17 December 2019 (10:07:58 CET)
The Process Algebra model has been shown to provide an alternative mathematical framework for non-relativistic quantum mechanics (NRQM). It reproduces the wave functions of non-relativistic quantum mechanics to a high degree of accuracy. It posits a fundamental level of finite, discrete events upon which the usual entities of NRQM supervene. It has been suggested that the Process Algebra model provides a true completion of NRQM, free of divergences and paradoxes, with causally local information propagation, contextuality and realism. Arguments in support of these claims have been mathematical. Missing has been an ontology of this fundamental level from which the formalism naturally emerges. In this paper it is argued that information and information flow provides this ontology. Higher level constructs such as energy, momentum, mass, spacetime, are all emergent from this fundamental level.
ARTICLE | doi:10.20944/preprints202210.0403.v1
Subject: Life Sciences, Genetics Keywords: causal effects; irritable bowel syndrome; Mendelian randomization; calcium; vitamin D; parathy-roid hormone
Online: 26 October 2022 (07:56:35 CEST)
Several observational studies have indicated the potential associations between calcium, vitamin D(Vit-D) and irritable bowel syndrome (IBS). However, the causal relationship deduced from these studies is subjected to residual confounding factors and reverse causation. Therefore, we aim to explore the bidirectional causal effects between serum calcium, Vit-D, PTH and IBS at the genetic level by a two-sample Mendelian randomization (MR) analysis. Sensitivity analyses were performed to evaluate the robustness. The estimates were presented as odds ratio (OR) with their 95% confidence intervals (CIs). The results of the inverse-variance-weighted method did not re-veal any causal relationship shared between genetically predisposed calcium (OR = 0.92, 95% CI: 0.80-1.06, P = 0.25) and Vit-D (OR = 0.99, 95% CI: 0.83-1.19, P = 0.94) level and the risk of IBS. The bidirectional analysis demonstrated that genetic predisposition to IBS was associated with a de-creased level of PTH (beta: -0.19, 95%CI: -0.34 to -0.04, P = 0.01). In conclusion, the present study indicates no causal relationship between the serum calcium and Vit-D concentrations and the risk of IBS. The potential mechanisms by which IBS affects serum PTH need to be further investigated.
ARTICLE | doi:10.20944/preprints202111.0459.v1
Subject: Physical Sciences, Particle & Field Physics Keywords: Unification; extra dimensions; causal sets; proper time; Standard Model; dark sector; quantum gravity
Online: 24 November 2021 (13:11:05 CET)
Unification based upon the generalisation of proper time is proposed as a comprehensive framework to account for the fundamental structure of matter, in a manner contrasting with the more familiar approach based on extra dimensions of space. The elementary properties of matter to be incorporated include the Standard Model of particle physics together with a source for the dark sector and a coherent formalism for quantum gravity. We elaborate upon the manner in which all such material phenomena and empirical properties as distributed in an extended 4-dimensional spacetime can be encompassed within, and derived from, the continuous flow of time alone via a generalised arithmetic form for infinitesimal intervals of proper time. This approach will also be compared and contrasted with the basic structure of causal set theory as a means of demonstrating how it is possible to construct a full physical theory essentially from elements of time alone, as explicitly developed from the most elementary level. The conception of time as utilised and elucidated in this theory, with emphasis upon the causal continuum properties and as the basis for unification, will be clarified.
ARTICLE | doi:10.20944/preprints202006.0144.v1
Subject: Life Sciences, Other Keywords: Corynebacterium pseudotuberculosis; RNA-Seq; co-expression networks; influence genes; stress condition; causal genes
Online: 12 June 2020 (08:46:02 CEST)
Corynebacterium pseudotuberculosis is a Gram-positive bacterium that causes caseous lymphadenitis, a disease that predominantly affects sheep, goat, cattle, buffalo, and horses, but has also been recognized in other animals. This bacterium generates a severe economic impact on countries producing meat. Gene expression studies using RNA-seq is one of the most commonly used techniques to perform transcriptional experiments. Computational analysis on such data through reverse-engineering algorithms leads to a better understanding of the genome-wide complexity of gene interactomes, enabling the identification of genes having the most significant functions inferred by the activated stress response pathways. In this study, we identified the influential or causal genes from four RNA-seq data-sets from different stress conditions (high iron, low iron, acid, osmosis, and PH) in C. pseudotuberculosis, using a consensus-based network inference algorithm called miRsig and identified the causal genes in the network using the miRinfluence tool, which is based on the influence diffusion model. We found that over 50\% of the genes identified as influential have some essential cellular functions in the genomes. In the strains analyzed, most of the causal genes have crucial roles or participate in processes associated with response to extracellular stresses, pathogenicity, membrane components, and essential genes. This research brings new insight into the understanding of virulence and infection by C. pseudotuberculosis.
ARTICLE | doi:10.20944/preprints202001.0002.v1
Subject: Earth Sciences, Environmental Sciences Keywords: sensor robot; causal inference; robot communication; safety lighting; mobile application; ad-hoc network
Online: 1 January 2020 (15:07:58 CET)
The object of this research is designing of new robot-to-robot communication system working in the middle of highway/roads to support mobile safety for approaching vehicles. The result of research project directs to a group of safety robot devices which induce a vehicle on a bypass route, as a vehicle guidance method using the same, and a vehicle safety guidance system. According to an embodiment of the present invention, a safety device includes a detector configured to detect a vehicle approaching the safety device, and an image projector configured to project an image onto a road surface approaching the vehicle when the detector recognizes an approach of the vehicle. It can include. According to the present invention, when it is necessary to guide the vehicle to the bypass route, the driver of the vehicle can grasp the detour route in time and move the vehicle to the next lane.
Subject: Physical Sciences, Particle & Field Physics Keywords: spacetime models; causal models; nonlinear dynamics; relativity theory; quantum field theory; quantum loops
Online: 21 May 2019 (11:24:32 CEST)
Quantum loops are processes that constitute quantum objects. In the causal model of quantum loops and quantum objects presented here, the nonlinear processes involve the elementary units of spacetime and the associated elementary units of quantum fields. As such, quantum loop processes are the sources of gravitational fields (i.e., spacetime curvature) and of the quantum objects wave function. The model may be viewed as a derivative of loop quantum gravity, spin networks and causal dynamical triangulation, although significant deviations to these theories exist. The causal model of quantum loops is based on a causal model of spacetime dynamics where space(-time) consists of interconnected space points, each of which is connected to a small number of neighboring space points. The curvature of spacetime is expressed by the density of these space points and by the arrangement of the connections between them. The quantum loop emerges in a nonlinear collective behavioral process from a collection of space points that carry energy and quantum field attributes.
ARTICLE | doi:10.20944/preprints202302.0350.v1
Subject: Medicine & Pharmacology, General Medical Research Keywords: COVID-19; vaccination; all-cause mortality; excess mortality; causal inferences; ecological fallacy; individualistic fallacy
Online: 21 February 2023 (03:49:52 CET)
We primarily study a possible link between 2021 COVID-19 vaccination uptake in Europe and monthly 2022 excess all-cause mortality, i.e., mortality higher than before the pandemic. Analyses of 31 countries weighted by population size show that all-cause mortality during the first nine months of 2022 increased more the higher the 2021 vaccination uptake; a one percentage point increase in 2021 vaccination uptake was associated with a monthly mortality increase in 2022 by 0.105 percent (95% CI, 0.075-0.134). When controlling for alternative explanations, the association remained robust, and we discuss the result emphasizing causality as well as potential ecological fallacy. Also, the study shows that 2021 all-cause mortality was lower the higher the vaccination uptake, but this association became non-significant when controlling for alternative explanations.
CONCEPT PAPER | doi:10.20944/preprints202105.0767.v1
Subject: Biology, Animal Sciences & Zoology Keywords: evidential integration; causal explanation; early animal evolution; phylogenetics; macroevolution; evolutionary scenario; cross-disciplinary research
Online: 31 May 2021 (12:25:44 CEST)
Molecular methods have revolutionised virtually every area of biology, and metazoan phylogenetics is no exception: molecular phylogenies, molecular clocks, comparative phylogenomics, and developmental genetics have collectively transformed our understanding of the evolutionary history of animals. Moreover, the diversity of methods and models within molecular phylogenetics has resulted in significant disagreement among molecular phylogenies as well as between these and traditional phylogenies. Here, I argue that tackling this multifaceted problem lies in integrating evidence to infer the best evolutionary scenario. I begin with an overview of recent developments in early metazoan phylogenetics, followed by a discussion of key conceptual issues in phylogenetics revolving around phylogenetic evidence and theory. I then argue that integration of different kinds of evidence is necessary for arriving at the best evolutionary scenario rather than the best-fitting cladogram. Finally, I discuss the prospects of this view in stimulating interdisciplinary cross-talk in early metazoan research and beyond.
ARTICLE | doi:10.20944/preprints201608.0143.v1
Subject: Engineering, Civil Engineering Keywords: participatory modelling; causal loop diagram development; structural analysis; systems modelling; construction innovation; Russian Federation
Online: 15 August 2016 (08:56:30 CEST)
This research integrates systemic and participatory techniques to model the Russian Federation construction innovation system. Understanding this complex construction innovation system, and determining the best levers for enhancing it, requires the dynamic modelling of a number of factors such as flows of resources and activities, policies, uncertainty and time. To build the foundations for such a dynamic model, the employed study method utilised an integrated stakeholder-based participatory approach coupled with structural analysis (MICMAC - Matrice d'Impacts Croisés Multiplication Appliquée à un Classement Cross-Impact Matrix). This method identified the key factors of the Russian Federation construction innovation system, their causal relationship (i.e. influence/dependence map) and ultimately a causal loop diagram. The generated model reveals pathways to improving construction innovation in the Russian Federation, and underpins the future development of an operationalised systems dynamic model.
ARTICLE | doi:10.20944/preprints202007.0480.v1
Subject: Engineering, General Engineering Keywords: unsustainabiliy; complex systems; holism; systemic approach; creative emergence; causal emergence; downward causation; macroscale; microscale; synergy
Online: 21 July 2020 (11:43:40 CEST)
The nature of the sustainability crisis is characterized by high levels of complexity, thus it is not amenable to be approached from the linearity or reductionist paradigm. Emergence is a multilevel phenomenon that is characterized by qualitative novelty and is recognized as an important attribute of complex systems produced by self-organized processes, unveiled from a holistic stance. This conceptual-analytical article explores the emergence phenomenon and questions whether it can be a way of enhancing the solution process to meet the sustainability challenges. Emergent properties or behaviors emerge only when the system parts interact in a wider whole. Moreover, a systemic approach is proposed as an intermediary component in the process of emergence of creative and wise solutions to the wicked problems of unsustainability. This requires observation and entails analyzing open systems as a whole and recognizing the impact of traversing macro- and micro- scales on causal and creative emergence. The study also emphasizes synergies between emergence and creativity aimed at sustainability. Sustainable development requires leapfrogging past conventional practices, in an accelerated way, and the emergence phenomenon at play between systems levels, coupled with purposefully structured creative processes, holds the potential for catalyzing sustainable development efforts.
ARTICLE | doi:10.20944/preprints202001.0106.v1
Subject: Keywords: information theory; transfer entropy; time-delayed mutual information; data processing inequality; time series; causal tensor
Online: 11 January 2020 (11:24:45 CET)
We propose a novel tensor-based formalism for inferring causal structures from time series. An information theoretical analysis of transfer entropy (TE), shows that TE results from transmission of information over a set of communication channels. Tensors are the mathematical equivalents of these multi-channel causal channels. A multi-channel causal channel is a generalization of a discrete memoryless channel (DMC). We consider a DMC as a single-channel causal channel. Investigation of a system comprising three variables shows that in our formalism, bivariate analysis suffices to differentiate between direct and indirect relations. For this to be true, we have to combine the output of multi-channel causal channels with the output of single-channel causal channels. We can understand this result when we consider the role of noise. Subsequent transmission of information over noisy channels can never result in less noisy transmission overall. This implies that a Data Processing Inequality (DPI) exists for transfer entropy.
ARTICLE | doi:10.20944/preprints201911.0271.v1
Subject: Life Sciences, Genetics Keywords: breast cancer risk; GWAS; candidate causal variant; chromatin conformation capture; reporter gene activity; enhancer; promoter
Online: 24 November 2019 (05:12:07 CET)
Genome-wide association studies have revealed a locus at 8p12 that is associated with breast cancer risk. Fine-mapping of this locus identified 16 candidate causal variants (CCVs). However, as these variants are intergenic, their function is unclear. To map chromatin looping from this risk locus to a previously identified candidate target gene, DUSP4, we performed chromatin conformation capture analyses in normal and tumoral breast cell lines. We identified putative regulatory elements, containing CCVs, that loop to the DUSP4 promoter region. Using reporter gene assays, we found that the risk allele of CCV rs7461885 reduced the activity of a DUSP4 enhancer element, consistent with the function of DUSP4 as a tumor suppressor gene. Furthermore, the risk allele of CCV rs12155535, located in another DUSP4 enhancer element, was negatively correlated with looping of this element to the DUSP4 promoter region, suggesting that this allele would be associated with reduced expression. These findings provide the first evidence that CCV risk alleles downregulate DUSP4 expression, suggesting that this gene is a regulatory target of the 8p12 breast cancer risk locus.
ARTICLE | doi:10.20944/preprints201804.0379.v2
Subject: Physical Sciences, Particle & Field Physics Keywords: spacetime models; discrete spacetime; relativity theory; causal models; quantum field theory; spin networks; quantum loops
Online: 12 June 2018 (12:43:15 CEST)
Based on a local causal model of the dynamics of curved discrete spacetime, a causal model of quantum field theory in curved discrete spacetime is described. On the elementary level, space(-time) is assumed to consists of interconnected space points. Each space point is connected to a small discrete set of neighboring space points. Density distribution of the space points and the lengths of the space point connections depend on the distance from the gravitational sources. This leads to curved spacetime in accordance with general relativity. Dynamics of spacetime (i.e., the emergence of space and the propagation of space changes) dynamically assigns "in-connections" and "out-connections" to the affected space points. Emergence and propagation of quantum fields (including particles) are mapped to the emergence and propagation of space changes by utilizing identical paths of in/out-connections. Compatibility with standard quantum field theory (QFT) requests the adjustment of the QFT techniques (e.g., Feynman diagrams, Feynman rules, creation/annihilation operators), which typically apply to three in/out connections, to n > 3 in/out connections. In addition, QFT computation in position space has to be adapted to a curved discrete space-time.
ARTICLE | doi:10.20944/preprints201805.0100.v1
Subject: Physical Sciences, Particle & Field Physics Keywords: quantum field theory; local causal models; general relativity theory; spacetime models; discrete spacetime; computer simulations
Online: 7 May 2018 (05:45:19 CEST)
Based on a local causal model of the dynamics of curved discrete spacetime, a causal model of quantum field theory in curved discrete spacetime is described. At the elementary level, space(-time) is assumed to consists of interconnected space points. Each space point is connected to a small discrete set of neighbor space points. Density distribution of the space points and the lengths of the space point connections depend on the distance from the gravitational sources. This leads to curved spacetime in accordance with general relativity. Dynamics of spacetime (i.e., the emergence of space and the propagation of space changes) dynamically assigns "in-connections" and "out-connections" to the affected space points. Emergence and propagation of quantum fields (including particles) are mapped to the emergence and propagation of space changes by utilizing identical paths of in/out-connections. Compatibility with standard quantum field theory (QFT) requests the adjustment of the QFT techniques (e.g., Feynman diagrams, Feynman rules, creation/annihilation operators), which typically apply to three in/out connections, to n > 3 in/out connections. In addition, QFT computation in position space has to be adapted to a curved discrete space-time.
Subject: Medicine & Pharmacology, General Medical Research Keywords: bed bugs; Cimex spp.; Hong Kong; sleep disturbance; health impact; public health; causal agent; infectious agent; vector
Online: 6 October 2021 (09:09:17 CEST)
Bedbug (Cimex spp.) are a nuisance public-health pest that is on the rise globally, particularly in crowded cities such as Hong Kong. To investigate the health impacts of bedbug infestations among bedbug victims, online surveys were distributed in Hong Kong between June 2019 to July 2020. Data on sociodemographics, self-rated health, average hours of sleep per day, and details of bedbug infestation were collected. Bivariate and multivariable analysis were performed using logistic regression. The survey identified 422 bedbug victims; among them, 223 (52.9%) experienced ≥5 bites in the past month, most bites occurred on the arms (n=202, 47.8%) and legs (n=215, 51%), and the most common reaction to bites were itchiness (n=322, 76.3%), redness, and swelling of the skin (n=246, 58.1%), and difficulties sleeping or restlessness (n=125, 29.6%). Bites usually occurred during sleep (n=230, 54.5%). For impact on daily life in the past month, most bedbug victims reported moderate to severe impact on mental and emotional health (n=223, 52.8%) and sleeping quality (n=239, 56.6%). Lower self-rated health (aOR<1) was independently associated with impact to physical appearance (p=0.008), spending money on medication or doctor consultation (p=0.04), number of bites in the past month (p=0.023), and irregular time of bites (p=0.003). Lower average hours of sleep per day (aOR<1) was independently associated with impact on mental and emotional health (p=0.016). This study brings attention to the neglected issue of bedbug infestation by considering bedbugs as an infectious agent instead of a vector and providing empirical evidence describing its health impacts.
Subject: Behavioral Sciences, Clinical Psychology Keywords: involuntary memories; causal logic and semiotical logic; unconscious; mathematical model of the mind-matter relation; idiotope; category; discrete cofibration
Online: 14 February 2020 (11:44:16 CET)
Using classical clinical observations, we first outline an elementary conceptual model for the Mind Representation System, then move to a more elaborate mathematical model that refers to discrete cofibration with enriched fibers.