Learning why things change: The Difference-Based Causality Learner

In this paper, we present the Difference-Based Causality Learner (DBCL), an algorithm for learning a class of discrete-time dynamic models that represents all causation across time by means of difference equations driving change in a system. We motivate this representation with real-world mechanical systems and prove DBCL's correctness for learning structure from time series data, an endeavour that is complicated by the existence of latent derivatives that have to be detected. We also prove that, under common assumptions for causal discovery, DBCL will identify the presence or absence of feedback loops, making the model more useful for predicting the effects of manipulating variables when the system is in equilibrium. We argue analytically and show empirically the advantages of DBCL over vector autoregression (VAR) and Granger causality models as well as modified forms of Bayesian and constraintbased structure discovery algorithms. Finally, we show that our algorithm can discover causal directions of alpha rhythms in human brains from EEG data

African Land Ecology: Opportunities and Constraints for Agricultural Development

Current agriculture in Sub-Sahara Africa is undeveloped and the Green Revolution has left the continent largely untouched. Poor performance is often related to a number of socio-economic factors. In this paper we argue that there are also some specifities of natural resources, namely local homogeneity and spatial diversity of the pre-dominant Basement Complex soils, that imply that simple fertilizer strategies may not produce the yield increases obtained elsewhere. Keywords: Sub-Sahara Africa, Agro-Ecology, Land use, Land resources, Basement Complex, Green Revolution, Micronutrients, Fertilizer Policy

Building a super-resolution fluorescence cryomicroscope

Correlated super-resolution fluorescence microscopy and cryo-electron microscopy enables imaging with both high labeling specificity and high resolution. Naturally, combining two sophisticated imaging techniques within one workflow also introduces new requirements on hardware, such as the need for a super-resolution fluorescence capable microscope that can be used to image cryogenic samples. In this chapter, we describe the design and use of the “cryoscope”; a microscope designed for single-molecule localization microscopy (SMLM) of cryoEM samples that fits right into established cryoEM workflows. We demonstrate the results that can be achieved with our microscope by imaging fluorescently labeled vimentin, an intermediate filament, within U2OS cells grown on EM grids, and we provide detailed 3d models that encompass the entire design of the microscope

Dairy products and kidney function decline after myocardial infarction:A prospective analysis in the Alpha Omega Cohort

Background &amp; aims: Population-based studies have shown both beneficial and neutral associations between dairy consumption and kidney function outcomes. We investigated the association between dairy products and kidney function decline in drug-treated post-myocardial infarction (MI) patients. Methods: We analysed data of 2169 post–MI patients (aged 60–80 years, 81% male) of the Alpha Omega Cohort. Dietary data were collected at baseline (2002–2006) using a validated 203-item food frequency questionnaire. The 2021 Chronic Kidney Disease Epidemiology (CKD-EPI) equation was used to estimate 40-months change in creatinine-cystatin C based glomerular filtration rate (eGFRcr-cysC, mL/min per 1.73 m2). Beta coefficients and 95% confidence intervals (CIs) for dairy products in relation to annual eGFRcr-cysC change were obtained from multivariable linear regression, adjusted for age, sex, energy intake, and other lifestyle and dietary factors. Results: Baseline energy-adjusted median intakes were 64 g/day for total milk, 20 g/day for hard cheeses, 18 g/day for plain yogurt, and 70 g/day for dairy desserts. Mean ± SD eGFRcr-cysC was 84 ± 20 (13% with CKD), and annual eGFRcr-cysC change was −1.71 ± 3.85. In multivariable models, high vs. low intakes of total milk, cheese, and dairy desserts were not associated with annual eGFRcr-cysC change (βtotal milk: −0.21 [−0.60; 0.19], βcheese: −0.08 [−0.52; 0.36], βdairy desserts: −0.24 [−0.72; 0.24]). High vs. low intake of yogurt was adversely associated with annual eGFRcr-cysC change (βtotal yogurt: −0.50 [−0.91;-0.09]), but subsequent spline analyses showed no clear dose–response association. Conclusions: Intakes of milk, cheese or dairy desserts were not associated with a delayed kidney function decline after MI. The observed adverse association for yogurt should be interpreted with caution. Our findings require confirmation in other cohorts of coronary heart disease patients.</p

Plant-based dietary patterns and the risk of dementia:a population-based study

Background: Plant-based dietary patterns are increasingly popular in western countries and are supported by many governments and health organisations for their potential beneficial role in the prevention of chronic diseases. Yet, the potential role of plant-based dietary patterns in the development of dementia remains unclear. Objective: To evaluate the association between plant-based dietary patterns and the risk of dementia. Methods: Dietary intake was measured at baseline in 9,543 dementia-free participants (mean age 64 years, birth years 1897–1960, 58% women) of the prospective population-based Rotterdam Study, using food frequency questionnaires. Based on these questionnaires, we calculated an overall plant-based dietary index (PDI), healthy PDI (hPDI) and unhealthy PDI (uPDI), with higher scores reflecting higher consumption of (any, healthy and unhealthy, respectively) plant-based foods and lower consumption of animal-based foods. We analysed the association of the PDIs with incident dementia using Cox proportional hazard models. Results: During a mean follow-up of 14.5 years, 1,472 participants developed dementia. Overall, the PDIs were not associated with the risk of dementia (hazard ratio [95% confidence interval] per 10-point increase: 0.99 [0.91–1.08] for PDI, 0.93 [0.86–1.01] for hPDI, 1.02 [0.94–1.10] for uPDI). However, among men and APOE ε4 carriers, a higher hPDI was linearly associated with a lower risk of dementia (0.86 [0.75–0.99] and 0.83 [0.73–0.95], respectively), while this association was U-shaped among APOE ε4 non-carriers (P value for non-linearity = 0.01). Conclusions:We found no strong evidence for an overall association between plant-based eating and the risk of dementia. Our findings in stratified analyses warranted further investigation.</p

Diet quality in relation to kidney function and its potential interaction with genetic risk of kidney disease among Dutch post-myocardial infarction patients

Purpose: We examined the relation between diet quality, its components and kidney function decline in post-myocardial infarction (MI) patients, and we explored differences by genetic risk of chronic kidney disease (CKD). Methods: We analysed 2169 patients from the Alpha Omega Cohort (aged 60–80 years, 81% male). Dietary intake was assessed at baseline (2002–2006) using a validated food-frequency questionnaire and diet quality was defined using the Dutch Healthy Diet Cardiovascular Disease (DHD-CVD) index. We calculated 40-months change in estimated glomerular filtration rate (eGFR, mL/min per 1.73m2). We constructed a weighted genetic risk score (GRS) for CKD using 88 single nucleotide polymorphisms previously linked to CKD. Betas with 95%-confidence intervals (CIs) were obtained using multivariable linear regression models for the association between DHD-CVD index and its components and eGFR change, by GRS. Results: The average DHD-CVD index was 79 (SD 15) points and annual eGFR decline was 1.71 (SD 3.86) mL/min per 1.73 m2. The DHD-CVD index was not associated with annual eGFR change (per 1-SD increment in adherence score: -0.09 [95% CI -0.26,0.08]). Results for adherence to guidelines for red meat showed less annual eGFR decline (per 1-SD: 0.21 [0.04,0.38]), whereas more annual eGFR decline was found for legumes and dairy (per 1-SD: -0.20legumes [-0.37,-0.04] and − 0.18dairy [-0.34,-0.01]). Generally similar results were obtained in strata of GRS. Conclusion: The DHD-CVD index for overall adherence to Dutch dietary guidelines for CVD patients was not associated with kidney function decline after MI, irrespective of genetic CKD risk. The preferred dietary pattern for CKD prevention in CVD patients warrants further research.</p

Dietary nitrate intake in relation to the risk of dementia and imaging markers of vascular brain health:a population-based study

Background: Nitric oxide is a free radical that can be produced from dietary nitrate and positively affects cardiovascular health. With cardiovascular health playing an important role in the etiology of dementia, we hypothesized a link between dietary nitrate intake and the risk of dementia. Objectives: This study aimed to find the association of total, vegetable, and nonvegetable dietary nitrate intake with the risk of dementia and imaging markers of vascular brain health, such as total brain volume, global cerebral perfusion, white matter hyperintensity volume, microbleeds, and lacunar infarcts. Methods: Between 1990 and 2009, dietary intake was assessed using food-frequency questionnaires in 9543 dementia-free participants (mean age, 64 y; 58% female) from the prospective population-based Rotterdam Study. Participants were followed up for incidence dementia until January 2020. We used Cox models to determine the association between dietary nitrate intake and incident dementia. Using linear mixed models and logistic regression models, we assessed the association of dietary nitrate intake with changes in imaging markers across 3 consecutive examination rounds (mean interval between images 4.6 y). Results: Participants median dietary nitrate consumption was 85 mg/d (interquartile range, 55 mg/d), derived on average for 81% from vegetable sources. During a mean follow-up of 14.5 y, 1472 participants developed dementia. A higher intake of total and vegetable dietary nitrate was associated with a lower risk of dementia per 50-mg/d increase [hazard ratio (HR): 0.92; 95% confidence interval (CI): 0.87, 0.98; and HR: 0.92; 95% CI: 0.86, 0.97, respectively] but not with changes in neuroimaging markers. No association between nonvegetable dietary nitrate intake and the risk of dementia (HR: 1.15; 95% CI: 0.64, 2.07) or changes in neuroimaging markers were observed. Conclusions: A higher dietary nitrate intake from vegetable sources was associated with a lower risk of dementia. We found no evidence that this association was driven by vascular brain health.</p

Children's Attention-Deficit/Hyperactivity Disorder Symptoms Predict Lower Diet Quality but Not Vice Versa:Results from Bidirectional Analyses in a Population-Based Cohort

BACKGROUND: As an adjuvant for medication, dietary changes focused on specific nutrients have been proposed to prevent or reduce attention-deficit/hyperactivity disorder (ADHD) symptoms. However, whether an overall healthy dietary pattern is associated with ADHD symptom severity during childhood remains unclear. Furthermore, it is not clear what the direction of this association is. OBJECTIVES: We aimed to examine the association between dietary patterns and ADHD symptoms in school-aged children. In addition, we aimed to identify the temporal direction of this association-that is, whether dietary patterns predict ADHD symptoms or vice versa. METHODS: We analyzed data from 3680 children participating in the Generation R Study, a prospective cohort in Rotterdam, Netherlands. ADHD symptoms were assessed with parent-report questionnaires at ages 6 and 10 y using the Child Behavior Checklist. Dietary intake was assessed at the age of 8 y with a validated food-frequency questionnaire. We computed a diet quality score reflecting adherence to dietary guidelines. We examined bidirectional associations of diet quality with ADHD symptom scores using multivariable linear regression analysis and cross-lagged modeling. RESULTS: Linear regressions showed that more ADHD symptoms at age 6 y were associated with a lower diet quality score at age 8 y (SD score = -0.08; 95% CI: -0.11, -0.05) but that diet quality at age 8 y was not associated with ADHD symptoms at age 10 y. Cross-lagged models confirmed a unidirectional relation from ADHD symptoms to diet quality but not vice versa. Associations did not differ by overweight status or between boys and girls. CONCLUSION: Our study suggests that children with more ADHD symptoms may be at higher risk of an unhealthy diet but that overall diet quality does not affect ADHD risk

The healthy beverage index is not associated with insulin resistance, prediabetes and type 2 diabetes risk in the Rotterdam Study

Purpose:Whether beverage quality affects changes in glycaemic traits and type 2 diabetes (T2D) risk is unknown. We examined associations of a previously developed Healthy Beverage Index (HBI) with insulin resistance, and risk of prediabetes and T2D. Methods: We included 6769 participants (59% female, 62.0 ± 7.8 years) from the Rotterdam Study cohort free of diabetes at baseline. Diet was assessed using food-frequency questionnaires at baseline. The HBI included 10 components (energy from beverages, meeting fluid requirements, water, coffee and tea, low-fat milk, diet drinks, juices, alcohol, full-fat milk, and sugar-sweetened beverages), with a total score ranging from 0 to 100. A higher score represents a healthier beverage pattern. Data on study outcomes were available from 1993 to 2015. Multivariable linear mixed models and Cox proportional-hazards regression models were used to examine associations of the HBI (per 10 points increment) with two measurements of HOMA-IR (a proxy for insulin resistance), and risk of prediabetes and T2D. Results: During follow-up, we documented 1139 prediabetes and 784 T2D cases. Mean ± SD of the HBI was 66.8 ± 14.4. Higher HBI score was not associated with HOMA-IR (β: 0.003; 95% CI − 0.007, 0.014), or with risk of prediabetes (HR: 1.01; 95% CI 0.97, 1.06), or T2D (HR: 1.01; 95% CI 0.96, 1.07). Conclusion: Our findings suggest no major role for overall beverage intake quality assessed with the HBI in insulin resistance, prediabetes and T2D incidence. The HBI may not be an adequate tool to assess beverage intake quality in our population.</p