Causal Consequence Research Articles

Inferring the genetic relationship between brain imaging-derived phenotypes and risk of complex diseases by Mendelian randomization and genome-wide colocalization

Observational studies consistently disclose brain imaging-derived phenotypes (IDPs) as critical markers for early diagnosis of both brain disorders and cardiovascular diseases. However, it remains unclear about the shared genetic landscape between brain IDPs and the risk of brain disorders and cardiovascular diseases, restricting the applications of potential diagnostic techniques through brain IDPs. Here, we reported genetic correlations and putative causal relationships between 921 brain IDPs, 20 brain disorders and six cardiovascular diseases by leveraging their large-scale genome-wide association study (GWAS) summary statistics. Applications of Mendelian randomization (MR) identified significant putative causal effects of multiple region-specific brain IDPs in relation to the increased risks for amyotrophic lateral sclerosis (ALS), major depressive disorder (MDD), autism spectrum disorder (ASD) and schizophrenia (SCZ). We also found brain IDPs specifically from temporal lobe as a putatively causal consequence of hypertension. The genome-wide colocalization analysis identified three genomic regions in which MDD, ASD and SCZ colocalized with the brain IDPs, and two novel SNPs to be associated with ASD, SCZ, and multiple brain IDPs. Furthermore, we identified a list of candidate genes involved in the shared genetics underlying pairs of brain IDPs and MDD, ASD, SCZ, ALS and hypertension. Our results provide novel insights into the genetic relationships between brain disorders and cardiovascular diseases and brain IDP, which may server as clues for using brain IDPs to predict risks of diseases.

Current challenges in agricultural supply chains: an empirical assessment based on expert perspectives

The food industry is an essential sector of any country, and it should ensure the continuous supply of food to consumers. Currently, more and more companies are turning to international trade to meet the demands of their markets and at the same time ensure the profitability of their own business. This market transformation has resulted in food supply chains evolving from simple regional supply to a complex network supply that is highly vulnerable and unstable, due to the inhomogeneity of supply chain actors, especially in times of crisis. This vulnerability is related to numerous challenges and associated consequences. This study examines the impact of the current crises on the food supply chain, as well as the strategies adopted by supply chain actors to ensure the stability and sustainability of their businesses. For this purpose, a qualitative analysis was undertaken, based on 17 expert interviews with representatives of the entire supply chain, ranging from seed producers to retailers and including agricultural cooperatives, consulting companies, food networks. The results revealed that the combined effects of the Ukraine-Russia conflict, the COVID-19 pandemic, and customer behavior have had a significant impact on the food supply chain, such as a pronounced shortage of raw materials, supply shortages, price volatility and increased energy costs. The causal consequence of this is unrestrained market volatility which ultimately results in planning uncertainties for the companies involved; at the same time, supply chain actors are responding by implementing strategies to address these challenges. Strategies include the discovery of new markets and target groups, renewable energy sources and the consolidation of strategic suppliers, as well as the relocation of operations from abroad to the domestic market. The results of the study explain recent experience and serve as a starting point for further research that can help better understand and predict future crises.

Foundational Grounding and Creaturely Freedom

Abstract According to classical theism, the universe depends on God in a way that goes beyond mere (efficient) causation. I have previously argued that this ‘deep dependence’ of the universe on God is best understood as a type of grounding. In a recent paper in this journal, Aaron Segal argues that this doctrine of deep dependence causes problems for creaturely free will: if our choices are grounded in facts about God, and we have no control over these facts, then we do not control our choices and are therefore not free. This amounts to a grounding analogue of the Consequence Argument for the incompatibility of free will and determinism. If successful, it would have application beyond classical theism: similar concerns would apply to any view that takes our choices to be grounded in a deeper reality which is beyond our control. However, I show that the argument is not successful. Segal’s Grounding Consequence Argument is so closely analogous to the Causal Consequence Argument that any response to the one provides a response to the other. As a result, if you don’t think that prior causes (whether deterministic or indeterministic) undermine free will, you shouldn’t think that prior grounds undermine free will.

The Sufferings of the Biblical Job as an Icon of Postmodernity: The ‘loneliness’ of God and the human being in a consumerist paradise

This article explores ways in which the attitudes of the biblical Job may enrich postmodernist philosophy by addressing some of its inherent problems. The discussion focuses in particular on the biblical Book of Job that can serve as an example of confronting suffering as a dramatic implication of human life that denies the sense of happiness. In an attempt to suppress this fear, the postmodern human contests, in various ways, the truth of their ontic frailty and the fragility of their constructed “happiness”. The questions that the biblical Job posed to God with a distinct air of resentment and regret seem at first sight to be meaningless as they are thrown into the void of a terrifying Universe. The critique offered here comes out of a Christian philosophical and theological base which posits that belief in the sacrum, transcendence, God and the hope of eternal life are key elements in a meaning system that fosters mental health and human happiness. In the postmodern system of meaning, individuals may no longer question the existence of God for the sake of human freedom, nor seek evidence of God’s non-existence, but simply live as if God does not exist. From a Christian perspective, it appears that non-belief in a transcendent spiritual dimension can inline people in postmodern society to feel that they live in an atmosphere of existential anxiety. Similarly, a Christian critique would consider that it is the postmodernist view of fluidity in all aspects of human life that leads to uncertainty and suffering, a causal consequence that people may not advert to. In this way, confronted with many postmodern phenomena, they may unknowingly live in a world of illusion. The Christian critique would also see it is as necessary and important to address constructively the challenges raised by cultural postmodernity. For this reason, the article will reflect on the realism of human suffering, the forgetting and rejection of God, as well as transcendence.

Design and Validation of Performance Evaluation Model of National Accreditation Schemes in Hospitals: A Mixed-Method Study

Background: Performance evaluation of accreditation schemes can improve the quality of hospital accreditation significantly. An effective accreditation system is one that performs the accreditation process properly and achieves acceptable results. Objective: This study aimed to design and validate the performance evaluation model of national accreditation schemes in hospitals. Materials and Methods: This study was performed in a mixed method. The performance evaluation dimensions of the national accreditation models for hospitals were identified, classified, and modeled using the qualitative research method. The quantitative aspect of the obtained model was tested using structural equation modeling. Results: All identified variables were classified into six dimensions including causal conditions, strategic conditions, axial phenomenon, context conditions, intermediary/interventional conditions, and consequence. The results of the quantitative part suggested that the proposed model had a good fit and its validity and reliability were confirmed. Conclusions: The results of the present study revealed that the performance evaluation model of national accreditation schemes in hospitals had a good fit and might be used as an effective model in accreditation organizations as a roadmap to better evaluate accreditation schemes, such as those used in hospitals.

Punch-Drunk or Drunken Boxing? The Etiology of Alcohol-Related Physical Violence through Adolescence and Young Adulthood

Background Alcohol-related physical violence (ARPV) can be a causal consequence of alcohol consumption, but only for specific individuals (e.g., those predisposed to violence). Studies have not accounted for the shared etiology explaining comorbidity between alcohol use and violent behavior as a potential third-variable explanation of ARPV. The current study examined genetically-informed associations between ARPV, heavy alcohol use (HAU) and overall physical violence (OPV) in adolescence and young adulthood, by testing two proposed theories of ARPV processes (HAU causes ARPV, causal relationships depend upon OPV) and how overarching shared covariance may account for these associations. Methods Using the twin and sibling subsample from the National Longitudinal Study of Adolescent to Adult Health (Add Health), a series of biometric models tested hypotheses individually in adolescence and young adulthood. This included estimating bivariate Cholesky and direction-of-causality models, and trivariate Cholesky, independent pathway, and common pathway models. Results HAU had a causal effect on ARPV in adolescence and young adulthood. This effect was not moderated by OPV at either developmental stage. A shared etiology or common latent factor did not explain associations between ARPV, OPV, and HAU, even though ARPV strongly covaried independently with HAU and with OPV. Finally, OPV also had a causal effect on ARPV in adolescence, and in young adulthood for adolescent-onset drinkers. Conclusions Causal theories of ARPV still hold when accounting for shared genetic and environmental variance. Further research on the exact role of violence (predispositions, environmental contexts) is required, as both phenotypes substantially (and separately) explain influences driving ARPV. Supplemental data for this article is available online at https://doi.org/10.1080/10826084.2021.1887244.

Understanding recreational targets and ecological consequences: increased northern pike stocking reflected in top avian predator diet

Fish stocking is commonly used to enhance recreational fisheries; however, the side effects of stocking at the ecosystem scale have rarely been tested. Avian predators, because of their high position in food webs, can serve as indicators of environmental change, including prey-species abundance. The scope of this study was to understand whether recent changes in northern pike (Esox lucius) stocking on a national scale could cascade through food webs and significantly shape the diet of a predator––the white-tailed eagle (Haliaeetus albicilla). The stocking of pike in state-owned waters in Lithuania has increased two- to threefold since 2005. A significant increase in the proportion of pike in the breeding-season diet of the white-tailed eagle has also been observed. We explain the increase in pike in the predator’s diet as being a causal consequence of pike stocking. We encourage consideration of the entire food web when launching/terminating recreational fish stocking programmes.

A phenome-wide association and Mendelian Randomisation study of polygenic risk for depression in UK Biobank

Depression is a leading cause of worldwide disability but there remains considerable uncertainty regarding its neural and behavioural associations. Here, using non-overlapping Psychiatric Genomics Consortium (PGC) datasets as a reference, we estimate polygenic risk scores for depression (depression-PRS) in a discovery (N = 10,674) and replication (N = 11,214) imaging sample from UK Biobank. We report 77 traits that are significantly associated with depression-PRS, in both discovery and replication analyses. Mendelian Randomisation analysis supports a potential causal effect of liability to depression on brain white matter microstructure (β: 0.125 to 0.868, pFDR < 0.043). Several behavioural traits are also associated with depression-PRS (β: 0.014 to 0.180, pFDR: 0.049 to 1.28 × 10−14) and we find a significant and positive interaction between depression-PRS and adverse environmental exposures on mental health outcomes. This study reveals replicable associations between depression-PRS and white matter microstructure. Our results indicate that white matter microstructure differences may be a causal consequence of liability to depression.

Role of questions in inquiry-based instruction: towards a design taxonomy for question-asking and implications for design

Many theories and models describe the various cognitive processes individuals engage in as they solve ill-structured problems. While diverse in perspectives, these theories and models uniformly agree that essential aspects of complex problem solving include iteration and inquiry. This paper further argues that an important yet overlooked component of knowledge construction during problem-solving is the ability to ask meaningful questions. What is needed, but not adequately articulated and validated, is a theoretical taxonomy of question-asking to better understand and guide a learner’s reasoning process. Based on the expert–novice literature, we proffer the following question taxonomy: shallow/simple (verification, disjunctive, concept completion), testing (example, feature specification, quantification, definition, comparison), and deep/complex questions (interpretation, causal antecedent, causal consequence, goal orientation, instrumental/procedural, enablement, expectation, and judgmental). We, therefore, build on existing theories/models of problem-solving, failure, and reflection and their implications towards a taxonomy of question-asking. Given this taxonomy, researchers and designers can better understand learners’ level of understanding and problem-solving trajectories.

Convergent Evidence for Predispositional Effects of Brain Gray Matter Volume on Alcohol Consumption

BackgroundAlcohol use has been reliably associated with smaller subcortical and cortical regional gray matter volumes (GMVs). Whether these associations reflect shared predisposing risk factors or causal consequences of alcohol use remains poorly understood. MethodsData came from 3 neuroimaging samples (N = 2423), spanning childhood or adolescence to middle age, with prospective or family-based data. First, we identified replicable GMV correlates of alcohol use. Next, we used family-based and longitudinal data to test whether these associations may plausibly reflect a predispositional liability for alcohol use or a causal consequence of alcohol use. Finally, we used heritability, gene-set enrichment, and transcriptome-wide association study approaches to evaluate whether genome-wide association study–defined genomic risk for alcohol consumption is enriched for genes that are preferentially expressed in regions that were identified in our neuroimaging analyses. ResultsSmaller right dorsolateral prefrontal cortex (DLPFC) (i.e., middle and superior frontal gyri) and insula GMVs were associated with increased alcohol use across samples. Family-based and prospective longitudinal data suggest that these associations are genetically conferred and that DLPFC GMV prospectively predicts future use and initiation. Genomic risk for alcohol use was enriched in gene sets that were preferentially expressed in the DLPFC and was associated with replicable differential gene expression in the DLPFC. ConclusionsThese data suggest that smaller DLPFC and insula GMV plausibly represent genetically conferred predispositional risk factors for, as opposed to consequences of, alcohol use. DLPFC and insula GMV represent promising biomarkers for alcohol-consumption liability and related psychiatric and behavioral phenotypes.

Research on the relationship between causal factors and consequences of incidents occurred in tank farm using ordinal logistic regression

The analysis of incidents occurred is beneficial for the prevention of incidents in the future and the improvement of system design and management capability. This paper presents statistical analysis of the incidents related to tank farms of China from 1960 to 2018. Apart from major accidents which attract national or international media attention, a large number of near misses and ordinary incidents were also collected in order to more fully present and analyze problems in the design and management of tank farms. This study concentrates on exploring the relationship between causal factors and different levels of consequences. The causal factors were considered to cover five major categories which were equipment failure, environmental factors, human factors, organization/management factors and other factors specifically and subdivided into fifteen subcategories, and the consequences were divided into four levels according to financial losses and casualties. The cross-tabulation analysis of causal factors and consequence levels was performed to reveal the contribution of different factors to specific consequences and present each factor which tends to be classified what the level of consequence. Further analyses aim to determine whether there were significant correlations between the cause factor and the specific level of consequences based on the ordinal logistic regression. The results show that different causal factors tend to trigger consequences of various degrees of severity, and several organization/management factors have the significant effect on the consequences of higher level.

Cesarean Section as a Predictor for Autism: a Case-Control Study in Valencia (Spain)

Growing interest has been shown in recent decades in the role of perinatal factors in relation to autistic spectrum disorders (ASD). Several studies have identified that cesarean sections (CS) could be a risk factor for ASD. The objective was to evaluate the relationship between CS and ASD in childhood as an early indicator for ASD diagnosis. This is a hospital-based nested case-control study in a retrospective cohort of births during 1996–2011. Cases were defined as children diagnosed with ASD at the Neuropediatric Unit of the La Fe Hospital in the last 10 years and controls as children without ASD. After pairing controls with cases for children’s date of birth at a 4:1 ratio, 251 mother-child pairs (53 cases, 198 controls) were studied, for whom information about perinatal risk factors, such as mode of delivery (vaginal vs. CS), and potential confounders was collected. Of the children identified, the control group was made up of 100 boys and 98 girls while the case group included 47 boys and 6 girls. A multivariable conditional logistic regression model was built (matched by children’s date of birth) to assess any potential association in relation with ASD diagnosis, where birth by CS presented a cOR = 3.37 (95% CI 1.57–7.25) of ASD. The adjusted model (for maternal age, child’s sex, gravidity, and gestation weeks) suggested a relation between CS and ASD (aOR = 3.36, 95% CI 1.44–7.85). The results suggest that the probability of ASD after a birth by CS is over three times that observed after unassisted vaginal delivery. Large prospective studies are needed to understand if this relationship is a causal pathway or consequence of ASD. The results suggest that using birth by CS as a predictor for ASD by pediatric health professionals in their patient follow-ups may be an appropriate tool that could improve early ASD detection.

The abundance, distribution, and physical nature of highly ionized oxygen O vi, O vii, and O viii in IllustrisTNG

We explore the abundance, spatial distribution, and physical properties of the OVI, OVII, and OVIII ions of oxygen in circumgalactic and intergalactic media (the CGM, IGM, and WHIM). We use the TNG100 and TNG300 large volume cosmological magneto-hydrodynamical simulations. Modeling the ionization states of simulated oxygen, we find good agreement with observations of the low-redshift OVI column density distribution function (CDDF), and present its evolution for all three ions from z=0 to z=4. Producing mock quasar absorption line spectral surveys, we show that the IllustrisTNG simulations are fully consistent with constraints on the OVI content of the CGM from COS-Halos and other low redshift observations, producing columns as high as observed. We measure the total amount of mass and average column densities of each ion using hundreds of thousands of simulated galaxies spanning 10^11 < Mhalo/Msun < 10^15 corresponding to 10^9 < M*/Msun < 10^12 in stellar mass. Stacked radial profiles of OVI are computed in 3D number density and 2D projected column, decomposing into the 1-halo and 2-halo terms. Relating halo OVI to properties of the central galaxy, we find a correlation between the (g-r) color of a galaxy and the total amount of OVI in its CGM. In comparison to the COS-Halos finding, this leads to a dichotomy of columns around star-forming versus passive galaxies at fixed stellar (or halo) mass. We demonstrate that this correlation is a direct result of blackhole feedback associated with quenching and represents a causal consequence of galactic-scale baryonic feedback impacting the physical state of the circumgalactic medium.

Decentralization Effects in Ecological Fiscal Transfers: A Bayesian Structural Time Series Analysis for Portugal

Portugal has a unitary system in which the central government transfers funds to lower government levels for their public functions. In 2007, Portugal introduced Ecological Fiscal Transfers (EFT), where municipalities receive transfers for hosting protected areas (PA). We study whether introducing EFT in Portugal incentivized municipalities to designate PA and has led to a decentralization of conservation decisions. We employ a Bayesian structural time series approach to estimate the effect of introducing EFT in comparison to a simulated counterfactual time series. Quantitative results show a significant increase in the ratio of municipal and national PA designations following Portugal’s EFT introduction—which we infer to be a causal consequence. The analysis furthermore places emphasis on the importance of relevant municipal conservation competencies for the functioning of the instrument. Results have important implications for conservation policy-making in terms of allocating budgets and competencies in multi-level governments.

Population Fluctuation and the Adoption of Food Production in Prehistoric Korea: Using Radiocarbon Dates as a Proxy for Population Change

AbstractPopulation growth has been evoked both as a causal factor and consequence of the transition to agriculture. The use of radiocarbon (14C) dates as proxies for population allows for reevaluations of population as a variable in the transition to agriculture. In Korea, numerous rescue excavations during recent decades have offered a wealth of14C data for this application. A summed probability distribution (SPD) of14C dates is investigated to reconstruct population trends preceding and following adoptions of food production in prehistoric Korea. Important cultivars were introduced to Korea in two episodes: millets during the Chulmun Period (ca. 6000–1500 BCE) and rice during the Mumun Period (ca. 1500–300 BCE). The SPD suggests that while millet production had little impact on Chulmun populations, a prominent surge in population appears to have followed the introduction of rice. The case in prehistoric Korea demonstrates that the adoption of food production does not lead inevitably towards sustained population growth. Furthermore, the data suggest that the transition towards intensive agriculture need not occur under conditions of population pressure resulting from population growth. Rather, intensive rice farming in prehistoric Korea began during a period of population stagnation.

A Multiply Qualified Conditional Analysis of Disposition Ascription: Mapping the Conceptual Topography of Ceteris Paribus

Given that an analysis of disposition ascription cannot be made in terms of a simple subjunctive conditional, we present a multiply qualified conditional analysis that places disposition ascription within an implicit fundamental causal conceptual typography within which a disposition ascription is embedded, framed, and understood. By placing the multiply qualified analysis within an implicit causal matrix involving a focal cause, pathway of influence, mechanism of action (via the intrinsic property responsible for the disposition), contributing/partial cause, mediator (i.e., transmitting agent), extrinsic moderator, (protective factor, inhibitory factor), intrinsic moderator, and manifestation (causal consequence), we show how this analysis evades counterexamples and arguments raised against the simple conditional analysis. We then indicate how the causal conceptual landscape provides a roadmap for unpacking and explicating parameters of the ceteris paribus qualifier to acquit the analysis of charges of being vacuous or irredeemably vague.

Integrating and extending ecological river assessment: Concept and test with two restoration projects

While the number of river restoration projects is increasing, studies on their success or failure relative to expectations are still rare. Only a few decision support methodologies and integrative methods for evaluating the ecological status of rivers are used in river restoration projects, thereby limiting informed management decisions in restoration planning as well as success control. Moreover, studies quantifying river restoration effects are often based on the assessment of a single organism group, and the effects on terrestrial communities are often neglected. In addition, potential effects of water quality or hydrological degradation are often not considered for the evaluation of restoration projects.We used multi-attribute value theory to re-formulate an existing river assessment protocol and extend it to a more comprehensive, integrated ecological assessment program. We considered habitat conditions, water quality regarding nutrients, micropollutants and heavy metals, and five instream and terrestrial organism groups (fish, benthic invertebrates, aquatic vegetation, ground beetles and riparian vegetation). The physical, chemical and biological states of the rivers were assessed separately and combined to value the overall ecological state.The assessment procedure was then applied to restored and unrestored sites at two Swiss rivers to test its feasibility in quantifying the effect of river restoration. Uncertainty in observations was taken into account and propagated through the assessment framework to evaluate the significance of differences between the ecological states of restored and unrestored reaches. In the restored sites, we measured a higher width variability of the river, as well as a higher width of the riparian zone and a higher richness of organism groups. According to the ecological assessment, the river morphology and the biological states were significantly better at the restored sites, with the largest differences detected for ground beetles and fish communities, followed by benthic invertebrates and riparian vegetation. The state of the aquatic vegetation was slightly lower at the restored sites. According to our assessment, the presence of invasive plant species counteracted the potential ecological gain. Water quality could be a causal factor contributing to the absence of larger improvements.Overall, we found significantly better biological and physical states, and integrated ecological states at the restored sites. Even in the absence of comprehensive before-after data, based on the similarity of the reaches before restoration and mechanistic biological knowledge, this can be safely interpreted as a causal consequence of restoration. An integrative perspective across aquatic and riparian organism groups was important to assess the biological effects, because organism groups responded differently to restoration. In addition, the potential deteriorating effect of water quality demonstrates the importance of integrated planning for the reduction of morphological, water quality and hydrological degradation.

Teacher and Student Questions: A Case Study in Malaysian Secondary School Problem-Based Learning

Problem-based learning (PBL) promotes high order questioning and stimulates student thinking, thus playing an important role in preparing students to face real-world challenges. Yet, PBL is an uncommon instructional strategy in Malaysian secondary school science classrooms. Occurrence of questioning in the traditional spoon-feeding classroom is low. Thus, the PBL model adapted from Barrows has been introduced. This article investigates whether PBL is able to promote high order questioning and thinking in the Malaysian science classroom. A PBL class with 1 teacher and 17 students divided into 4 groups was observed, video-and audio-recorded, and the verbatim were analysed. Questions are categorized into high order, low order, eliciting ideas, and evaluating ideas questions. Findings show that the percentage of student questions is 67.9% while for teacher questions is 32.1%. The amount of student questions per hour is relatively high at 8.2 questions per student. Nearly half of the classroom questions are low order questions (47.9%), such as clarification, verification, concept completion, disjunctive, definition, example, quantification, and feature specification questions. High order questions consist of 16.3%, which include causal antecedent, causal consequence, goal orientation, comparison, enablement, and reflective questions. Eliciting ideas questions raised by the teacher cover 8.8% while evaluating ideas questions by students cover 27.1%. This study shows that the PBL environment promotes active learning, student thinking, and questioning in the Malaysian science classroom. However, student and teacher questions should be enhanced to be at higher order level. Several suggestions to extend low order questions into high order questions are discussed in this paper.

Determining Growth Saturation Point for Sustainable Development

As economic growth may reach a point where further socio-economic development is not sustainable due to continual environmental degradation having negative development impact, the paper proposes a methodology for determining global central tendency for the saturation point of economic growth in its impact on sustainable development. The theoretical framework adopts a modified classical growth model, where economic growth is considered a means towards development, just as capital stock constitutes a means towards economic growth. In such a model, the impact of economic growth on sustainable development exhibits diminishing “marginal social productivity”, until development reaches a stationary state, where the impact of growth reaches its climax and any further growth will bring a decline on the level of development. Economic growth is measured by per capita income while selected development indicators measure development. The factors responsible for the diminishing “marginal social productivity” of economic growth are population growth and depreciation rates of capital stock and physical environment. For empirical investigation, econometric studies explored the dependence of various development indicators on per capita income (US$ PPP) for 99 countries, with a-priori expectation that the development indicators will progress with economic growth at a decreasing rate and reach saturation point. The results revealed that the saturation point or ultimate level of sustainable development is attained at per capita income of $36,400 500 (PPP), a level exceeded by 13 percent of the countries. Results also showed that environmental degradation is both a causal factor and consequence of contemporary growth.

A New Definition of Aging?

A New Definition of Aging?