Low probability states, data statistics, and entropy estimation

A fundamental problem in analysis of complex systems is getting a reliable estimate of entropy of their probability distributions over the state space. This is difficult because unsampled states can contribute substantially to the entropy, while they do not contribute to the Maximum Likelihood estimator of entropy, which replaces probabilities by the observed frequencies. Bayesian estimators overcome this obstacle by introducing a model of the low-probability tail of the probability distribution. Which statistical features of the observed data determine the model of the tail, and hence the output of such estimators, remains unclear. Here we show that well-known entropy estimators for probability distributions on discrete state spaces model the structure of the low probability tail based largely on few statistics of the data: the sample size, the Maximum Likelihood estimate, the number of coincidences among the samples, the dispersion of the coincidences. We derive approximate analytical entropy estimators for undersampled distributions based on these statistics, and we use the results to propose an intuitive understanding of how the Bayesian entropy estimators work

A framework for studying behavioral evolution by reconstructing ancestral repertoires

Although extensive behavioral changes often exist between closely related animal species, our understanding of the genetic basis underlying the evolution of behavior has remained limited. Here, we propose a new framework to study behavioral evolution by computational estimation of ancestral behavioral repertoires. We measured the behaviors of individuals from six species of fruit flies using unsupervised techniques and identified suites of stereotyped movements exhibited by each species. We then fit a Generalized Linear Mixed Model to estimate the suites of behaviors exhibited by ancestral species, as well as the intra- and inter-species behavioral covariances. We found that much of intraspecific behavioral variation is explained by differences between individuals in the status of their behavioral hidden states, what might be called their "mood." Lastly, we propose a method to identify groups of behaviors that appear to have evolved together, illustrating how sets of behaviors, rather than individual behaviors, likely evolved. Our approach provides a new framework for identifying co-evolving behaviors and may provide new opportunities to study the genetic basis of behavioral evolution

Effect of Organic Nutrition in the Nursery Growth and Nutrimental Content of Native Avocados of Ometepec, Guerrero, Mexico

In Mexico, there are several types of wild and criollo avocados that constitute a genetic heritage of this species; these avocados currently grow in an unordered manner on farmer's lands and in backyards, and they need to be studied as they are being lost because of agricultural activities and edaphoclimatic and phytosanitary factors. On the other hand, in orchards and avocado nurseries, high amounts of chemical fertilizers and pesticides are used affecting the physicochemical and microbiological properties of the soil, modifying the flora and fauna and polluting aquifers and springs that cause health problems among consumers. Therefore, it is very important to have a more friendly agriculture with the nature. The aim of this work was to evaluate under nursery conditions, the effect of organic fertilizers on 12 genotypes (rootstocks) of native avocados of Ometepec, Guerrero, Mexico, under an experimental design of random blocks, with four treatments: T1: sheep manure,T2: Bovine manure, T3: mycorrhizae and T4 (control: water) in four replicates. The variables were: plant height (PH), stem diameter (SD), number of leaves: young (NYL) and mature (NML) per plant; and the content of NO3-, K+, Ca2+ and Na+ ions obtained by petiole extraction, and the chlorophyll content measured with SPAD, in young (CYL) and mature (CML) leaves. Additionally, an analysis of variance and Tukey mean tests (P ≤ 0.01 and 0.05) and LSD (P ≤ 0.05) were done. It was found that sheep manure was superior to other treatments in PH (76.7 cm), SD (7.2 mm), NYL (6.5 leaves/plant), NML (18.4 leaves/plant), CML (40.2 SPAD) and Ca2+(1495ppm). In conclusion, the sheep manure was better than the bovine, mycorrhiza and control (water) as it affected positively the behavior of rootstocks in plant height, stem diameter and number of young and mature leaves. In addition, organic nutrition showed no significant response in the chlorophyll content of young and mature leaves. Young leaves only reached 50% of the chlorophyll content compared to mature leaves

Chronic Exposure to Arsenic and Markers of Cardiometabolic Risk: A Cross-Sectional Study in Chihuahua, Mexico

BackgroundExposure to arsenic (As) concentrations in drinking water > 150 μg/L has been associated with risk of diabetes and cardiovascular disease, but little is known about the effects of lower exposures.ObjectiveThis study aimed to examine whether moderate As exposure, or indicators of individual As metabolism at these levels of exposure, are associated with cardiometabolic risk.MethodsWe analyzed cross-sectional associations between arsenic exposure and multiple markers of cardiometabolic risk using drinking-water As measurements and urinary As species data obtained from 1,160 adults in Chihuahua, Mexico, who were recruited in 2008–2013. Fasting blood glucose and lipid levels, the results of an oral glucose tolerance test, and blood pressure were used to characterize cardiometabolic risk. Multivariable logistic, multinomial, and linear regression were used to assess associations between cardiometabolic outcomes and water As or the sum of inorganic and methylated As species in urine.ResultsAfter multivariable adjustment, concentrations in the second quartile of water As (25.5 to < 47.9 μg/L) and concentrations of total speciated urinary As (< 55.8 μg/L) below the median were significantly associated with elevated triglycerides, high total cholesterol, and diabetes. However, moderate water and urinary As levels were also positively associated with HDL cholesterol. Associations between arsenic exposure and both dysglycemia and triglyceridemia were higher among individuals with higher proportions of dimethylarsenic in urine.ConclusionsModerate exposure to As may increase cardiometabolic risk, particularly in individuals with high proportions of urinary dimethylarsenic. In this cohort, As exposure was associated with several markers of increased cardiometabolic risk (diabetes, triglyceridemia, and cholesterolemia), but exposure was also associated with higher rather than lower HDL cholesterol.CitationMendez MA, González-Horta C, Sánchez-Ramírez B, Ballinas-Casarrubias L, Hernández Cerón R, Viniegra Morales D, Baeza Terrazas FA, Ishida MC, Gutiérrez-Torres DS, Saunders RJ, Drobná Z, Fry RC, Buse JB, Loomis D, García-Vargas GG, Del Razo LM, Stýblo M. 2016. Chronic exposure to arsenic and markers of cardiometabolic risk: a cross-sectional study in Chihuahua, Mexico. Environ Health Perspect 124:104–111; http://dx.doi.org/10.1289/ehp.140874

Adipose-derived mesenchymal stromal cells for the treatment of patients with severe SARS-CoV-2 pneumonia requiring mechanical ventilation. A proof of concept study

Background: Identification of effective treatments in severe cases of COVID-19 requiring mechanical ventilation represents an unmet medical need. Our aim was to determine whether the administration of adipose-tissue derived mesenchymal stromal cells (AT-MSC) is safe and potentially useful in these patients. Methods: Thirteen COVID-19 adult patients under invasive mechanical ventilation who had received previous antiviral and/or anti-inflammatory treatments (including steroids, lopinavir/ritonavir, hydroxychloroquine and/or tocilizumab, among others) were treated with allogeneic AT-MSC. Ten patients received two doses, with the second dose administered a median of 3 days (interquartile range-IQR- 1 day) after the first one. Two patients received a single dose and another patient received 3 doses. Median number of cells per dose was 0.98 × 106 (IQR 0.50 × 106) AT-MSC/kg of recipient's body weight. Potential adverse effects related to cell infusion and clinical outcome were assessed. Additional parameters analyzed included changes in imaging, analytical and inflammatory parameters. Findings: First dose of AT-MSC was administered at a median of 7 days (IQR 12 days) after mechanical ventilation. No adverse events were related to cell therapy. With a median follow-up of 16 days (IQR 9 days) after the first dose, clinical improvement was observed in nine patients (70%). Seven patients were extubated and discharged from ICU while four patients remained intubated (two with an improvement in their ventilatory and radiological parameters and two in stable condition). Two patients died (one due to massive gastrointestinal bleeding unrelated to MSC therapy). Treatment with AT-MSC was followed by a decrease in inflammatory parameters (reduction in C-reactive protein, IL-6, ferritin, LDH and d-dimer) as well as an increase in lymphocytes, particularly in those patients with clinical improvement. Interpretation: Treatment with intravenous administration of AT-MSC in 13 severe COVID-19 pneumonia under mechanical ventilation in a small case series did not induce significant adverse events and was followed by clinical and biological improvement in most subjects. Funding: None.We would like to acknowledge the Instituto de Salud Carlos III (ISCIII) through the project “RD16/0011: Red de Terapia Celular”, from the sub-program RETICS, integrated in the “Plan Estatal de I+D+I 2013-2016” and co-financed by the European Regional Development Fund “A way to make Europe”, groups RD16/0011/0001, -/0002, -/005, -/0013, -/0015, -/0029), the Centro en Red de Medicina Regenerativa y Terapia Celular de Castilla y León, Spain and AvanCell-CM (Red de Investigación de Terapia Celular de la Comunidad de Madrid, Spain), for supporting some personnel and networking activities

Association Between Variants in Arsenic (+3 Oxidation State) Methyltranserase ( AS3MT ) and Urinary Metabolites of Inorganic Arsenic: Role of Exposure Level

Variants in AS3MT, the gene encoding arsenic (+3 oxidation state) methyltranserase, have been shown to influence patterns of inorganic arsenic (iAs) metabolism. Several studies have suggested that capacity to metabolize iAs may vary depending on levels of iAs exposure. However, it is not known whether the influence of variants in AS3MT on iAs metabolism also vary by level of exposure. We investigated, in a population of Mexican adults exposed to drinking water As, whether associations between 7 candidate variants in AS3MT and urinary iAs metabolites were consistent with prior studies, and whether these associations varied depending on the level of exposure. Overall, associations between urinary iAs metabolites and AS3MT variants were consistent with the literature. Referent genotypes, defined as the genotype previously associated with a higher percentage of urinary dimethylated As (DMAs%), were associated with significant increases in the DMAs% and ratio of DMAs to monomethylated As (MAs), and significant reductions in MAs% and iAs%. For 3 variants, associations between genotypes and iAs metabolism were significantly stronger among subjects exposed to water As >50 versus ≤50 ppb (water As X genotype interaction P < .05). In contrast, for 1 variant (rs17881215), associations were significantly stronger at exposures ≤50 ppb. Results suggest that iAs exposure may influence the extent to which several AS3MT variants affect iAs metabolism. The variants most strongly associated with iAs metabolism—and perhaps with susceptibility to iAs-associated disease—may vary in settings with exposure level

Associations between Arsenic Species in Exfoliated Urothelial Cells and Prevalence of Diabetes among Residents of Chihuahua, Mexico

Background: A growing number of studies link chronic exposure to inorganic arsenic (iAs) with the risk of diabetes. Many of these studies assessed iAs exposure by measuring arsenic (As) species in urine. However, this approach has been criticized because of uncertainties associated with renal function and urine dilution in diabetic individuals

Metabolomic Characteristics of Arsenic-Associated Diabetes in a Prospective Cohort in Chihuahua, Mexico

Chronic exposure to inorganic arsenic (iAs) has been linked to an increased risk of diabetes, yet the specific disease phenotype and underlying mechanisms are poorly understood. In the present study we set out to identify iAs exposure-associated metabolites with altered abundance in nondiabetic and diabetic individuals in an effort to understand the relationship between exposure, metabolomic response, and disease status. A nested study design was used to profile metabolomic shifts in urine and plasma collected from 90 diabetic and 86 nondiabetic individuals matched for varying iAs concentrations in drinking water, body mass index, age, and sex. Diabetes diagnosis was based on measures of fasting plasma glucose and 2-h blood glucose. Multivariable models were used to identify metabolites with altered abundance associated with iAs exposure among diabetic and nondiabetic individuals. A total of 132 metabolites were identified to shift in urine or plasma in response to iAs exposure characterized by the sum of iAs metabolites in urine (U-tAs). Although many metabolites were altered in both diabetic and nondiabetic 35 subjects, diabetic individuals displayed a unique response to iAs exposure with 59 altered metabolites including those that play a role in tricarboxylic acid cycle and amino acid metabolism. Taken together, these data highlight the broad impact of iAs exposure on the human metabolome, and demonstrate some specificity of the metabolomic response between diabetic and nondiabetic individuals. These data may provide novel insights into the mechanisms and phenotype of diabetes associated with iAs exposure