The heart of the scientific enterprise is a rational effort to understand the causes behind the phenomena we observe. In large-scale complex dynamical systems such as the Earth system, real ...experiments are rarely feasible. However, a rapidly increasing amount of observational and simulated data opens up the use of novel data-driven causal methods beyond the commonly adopted correlation techniques. Here, we give an overview of causal inference frameworks and identify promising generic application cases common in Earth system sciences and beyond. We discuss challenges and initiate the benchmark platform causeme.net to close the gap between method users and developers.
Background Chronic stress increases chronic disease risk and may underlie the association between exposure to adverse socioeconomic conditions and adverse health outcomes. The relationship between ...exposure to such conditions and chronic stress is complex due to feedback loops between stressor exposure and psychological processes, encompassing different temporal (acute stress response to repeated exposure over the life course) and spatial (biological/psychological/social) scales. We examined the mechanisms underlying the relationship between exposure to adverse socioeconomic conditions and chronic stress from a complexity science perspective, focusing on amplifying feedback loops across different scales. Methods We developed a causal loop diagram (CLD) to interpret available evidence from this perspective. The CLD was drafted by an interdisciplinary group of researchers. Evidence from literature was used to confirm/contest the variables and causal links included in the conceptual framework and refine their conceptualisation. Our findings were evaluated by eight independent researchers. Results Adverse socioeconomic conditions imply an accumulation of stressors and increase the likelihood of exposure to uncontrollable childhood and life course stressors. Repetition of such stressors may activate mechanisms that can affect coping resources and coping strategies and stimulate appraisal of subsequent stressors as uncontrollable. We identified five feedback loops describing these mechanisms: (1) progressive deterioration of access to coping resources because of repeated insolvability of stressors; (2) perception of stressors as uncontrollable due to learned helplessness; (3) tax on cognitive bandwidth caused by stress; (4) stimulation of problem avoidance to provide relief from the stress response and free up cognitive bandwidth; and (5) susceptibility to appraising stimuli as stressors against a background of stress. Conclusions Taking a complexity science perspective reveals that exposure to adverse socioeconomic conditions implies recurrent stressor exposure which impacts chronic stress via amplifying feedback loops that together could be conceptualised as one vicious cycle. This means that in order for individual-level psychological interventions to be effective, the context of exposure to adverse socioeconomic conditions also needs to be addressed. Keywords: Socioeconomic status, Causal loop diagram, Chronic stress, Feedback loops
Various complex systems, such as the climate, ecosystems, and physical and mental health can show large shifts in response to small changes in their environment. These 'tipping points' are ...notoriously hard to predict based on trends. However, in the past 20 years several indicators pointing to a loss of resilience have been developed. These indicators use fluctuations in time series to detect critical slowing down preceding a tipping point. Most of the existing indicators are based on models of one-dimensional systems. However, complex systems generally consist of multiple interacting entities. Moreover, because of technological developments and wearables, multivariate time series are becoming increasingly available in different fields of science. In order to apply the framework of resilience indicators to multivariate time series, various extensions have been proposed. Not all multivariate indicators have been tested for the same types of systems and therefore a systematic comparison between the methods is lacking. Here, we evaluate the performance of the different multivariate indicators of resilience loss in different scenarios. We show that there is not one method outperforming the others. Instead, which method is best to use depends on the type of scenario the system is subject to. We propose a set of guidelines to help future users choose which multivariate indicator of resilience is best to use for their particular system.
The past decades of research have seen an increase in statistical tools to explore the complex dynamics of mental health from patient data, yet the application of these tools in clinical practice ...remains uncommon. This is surprising, given that clinical reasoning, e.g., case conceptualizations, largely coincides with the dynamical system approach. We argue that the gap between statistical tools and clinical practice can partly be explained by the fact that current estimation techniques disregard theoretical and practical considerations relevant to psychotherapy. To address this issue, we propose that case conceptualizations should be formalized. We illustrate this approach by introducing a computational model of functional analysis, a framework commonly used by practitioners to formulate case conceptualizations and design patient-tailored treatment.
We outline the general approach of formalizing idiographic theories, drawing on the example of a functional analysis for a patient suffering from panic disorder. We specified the system using a series of differential equations and simulated different scenarios; first, we simulated data without intervening in the system to examine the effects of avoidant coping on the development of panic symptomatic. Second, we formalized two interventions commonly used in cognitive behavioral therapy (CBT; exposure and cognitive reappraisal) and subsequently simulated their effects on the system.
The first simulation showed that the specified system could recover several aspects of the phenomenon (panic disorder), however, also showed some incongruency with the nature of panic attacks (e.g., rapid decreases were not observed). The second simulation study illustrated differential effects of CBT interventions for this patient. All tested interventions could decrease panic levels in the system.
Formalizing idiographic theories is promising in bridging the gap between complexity science and clinical practice and can help foster more rigorous scientific practices in psychotherapy, through enhancing theory development. More precise case conceptualizations could potentially improve intervention planning and treatment outcomes. We discuss applications in psychotherapy and future directions, amongst others barriers for systematic theory evaluation and extending the framework to incorporate interactions between individual systems, relevant for modeling social learning processes. With this report, we hope to stimulate future efforts in formalizing clinical frameworks.
Neutrophils are one of the key players in the human innate immune system (HIIS). In the event of an insult where the body is exposed to inflammation triggering moieties (ITMs), neutrophils are ...mobilized towards the site of insult and antagonize the inflammation. If the inflammation is cleared, neutrophils go into a programmed death called apoptosis. However, if the insult is intense or persistent, neutrophils take on a violent death pathway called necrosis, which involves the rupture of their cytoplasmic content into the surrounding tissue that causes local tissue damage, thus further aggravating inflammation. This seemingly paradoxical phenomenon fuels the inflammatory process by triggering the recruitment of additional neutrophils to the site of inflammation, aimed to contribute to the complete neutralization of severe inflammation. This delicate balance between the cost and benefit of the neutrophils' choice of death pathway has been optimized during the evolution of the innate immune system. The goal of our work is to understand how the tradeoff between the cost and benefit of the different death pathways of neutrophils, in response to various levels of insults, has been optimized over evolutionary time by using the concepts of evolutionary game theory.
We show that by using evolutionary game theory, we are able to formulate a game that predicts the percentage of necrosis and apoptosis when exposed to various levels of insults.
By adopting an evolutionary perspective, we identify the driving mechanisms leading to the delicate balance between apoptosis and necrosis in neutrophils' cell death in response to different insults. Using our simple model, we verify that indeed, the global cost of remaining ITMs is the driving mechanism that reproduces the percentage of necrosis and apoptosis observed in data and neutrophils need sufficient information of the overall inflammation to be able to pick a death pathway that presumably increases the survival of the organism.
Abstract Symmetry detection, the task of discovering the underlying symmetries of a given dataset, has been gaining popularity in the machine learning community, particularly in science and ...engineering applications. Most previous works focus on detecting ‘canonical’ symmetries such as translation, scaling, and rotation, and cast the task as a modeling problem involving complex inductive biases and architecture design of neural networks. We challenge these assumptions and propose that instead of constructing biases, we can learn to detect symmetries from raw data without prior knowledge. The approach presented in this paper provides a flexible way to scale up the detection procedure to non-canonical symmetries, and has the potential to detect both known and unknown symmetries alike. Concretely, we focus on predicting the generators of Lie point symmetries of partial differential equations, more specifically, evolutionary equations for ease of data generation. Our results demonstrate that well-established neural network architectures are capable of recognizing symmetry generators, even in unseen dynamical systems. These findings have the potential to make non-canonical symmetries more accessible to applications, including model selection, sparse identification, and data interpretability.
Abstract
Network analysis is gaining momentum as an accepted practice to identify which factors in causal loop diagrams (CLDs)—mental models that graphically represent causal relationships between a ...system’s factors—are most likely to shift system-level behaviour, known as leverage points. This application of network analysis, employed to quantitatively identify leverage points without having to use computational modelling approaches that translate CLDs into sets of mathematical equations, has however not been duly reflected upon. We evaluate whether using commonly applied network analysis metrics to identify leverage points is justified, focusing on betweenness- and closeness centrality. First, we assess whether the metrics identify the same leverage points based on CLDs that represent the same system but differ in inferred causal structure—finding that they provide unreliable results. Second, we consider conflicts between assumptions underlying the metrics and CLDs. We recognise six conflicts suggesting that the metrics are not equipped to take key information captured in CLDs into account. In conclusion, using betweenness- and closeness centrality to identify leverage points based on CLDs is at best premature and at worst incorrect—possibly causing erroneous identification of leverage points. This is problematic as, in current practice, the results can inform policy recommendations. Other quantitative or qualitative approaches that better correspond with the system dynamics perspective must be explored.
In financial markets, participants locally optimize their profit which can result in a globally unstable state leading to a catastrophic change. The largest crash in the past decades is the ...bankruptcy of Lehman Brothers which was followed by a trust-based crisis between banks due to high-risk trading in complex products. We introduce information dissipation length (IDL) as a leading indicator of global instability of dynamical systems based on the transmission of Shannon information, and apply it to the time series of USD and EUR interest rate swaps (IRS). We find in both markets that the IDL steadily increases toward the bankruptcy, then peaks at the time of bankruptcy, and decreases afterwards. Previously introduced indicators such as 'critical slowing down' do not provide a clear leading indicator. Our results suggest that the IDL may be used as an early-warning signal for critical transitions even in the absence of a predictive model.
Quantifying synergy among stochastic variables is an important open problem in information theory. Information synergy occurs when multiple sources together predict an outcome variable better than ...the sum of single-source predictions. It is an essential phenomenon in biology such as in neuronal networks and cellular regulatory processes, where different information flows integrate to produce a single response, but also in social cooperation processes as well as in statistical inference tasks in machine learning. Here we propose a metric of synergistic entropy and synergistic information from first principles. The proposed measure relies on so-called synergistic random variables (SRVs) which are constructed to have zero mutual information about individual source variables but non-zero mutual information about the complete set of source variables. We prove several basic and desired properties of our measure, including bounds and additivity properties. In addition, we prove several important consequences of our measure, including the fact that different types of synergistic information may co-exist between the same sets of variables. A numerical implementation is provided, which we use to demonstrate that synergy is associated with resilience to noise. Our measure may be a marked step forward in the study of multivariate information theory and its numerous applications.
It is still unclear under which conditions temporary combined antiretroviral therapy (cART) results in a prolonged remission after interruption. Clinical trials have contradicting reposts about the ...effect of cART during primary HIV infection on the disease progression. Here we propose that the apparent contradiction is due the presence of a window of opportunity for cART treatment observed in the in silico studies. We study non-linear correlations in the HIV dynamics over time using information theory. This approach requires a large dataset of CD4+ T lymphocytes and viral load concentrations over time. Since it is unfeasible to collect the required amount of data in clinical trials we use C-ImmSim, a clinically validated in silico model of the HIV infection, to simulate the HIV infection and temporary cART in 500 virtual patients for a period of 6 years post infection in time steps of 8 hours. We validate the results of our model with two published clinical trials of temporary cART in acute infection and analyse the impact of cART on the immune response. Our quantitative analysis predicts a "window of opportunity" of about ten months after the acute phase during which a temporary cART has significantly longer-lasting beneficial effects on the immune system as compared to treatment during the chronic phase. This window may help to explain the controversial outcomes of clinical trials that differ by the starting time and duration of the short-term course cART and provides a critical insight to develop appropriate protocols for future clinical trials.
PDF
