Effects of memory on the shapes of simple outbreak trees

Genomic tools, including phylogenetic trees derived from sequence data, are increasingly used to understand outbreaks of infectious diseases. One challenge is to link phylogenetic trees to patterns of transmission. Particularly in bacteria that cause chronic infections, this inference is affected by variable infectious periods and infectivity over time. It is known that non-exponential infectious periods can have substantial effects on pathogens’ transmission dynamics. Here we ask how this non-Markovian nature of an outbreak process affects the branching trees describing that process, with particular focus on tree shapes. We simulate Crump-Mode-Jagers branching processes and compare different patterns of infectivity over time. We find that memory (non-Markovian-ness) in the process can have a pronounced effect on the shapes of the outbreak’s branching pattern. However, memory also has a pronounced effect on the sizes of the trees, even when the duration of the simulation is fixed. When the sizes of the trees are constrained to a constant value, memory in our processes has little direct effect on tree shapes, but can bias inference of the birth rate from trees. We compare simulated branching trees to phylogenetic trees from an outbreak of tuberculosis in Canada, and discuss the relevance of memory to this dataset

A metric on phylogenetic tree shapes

The shapes of evolutionary trees are influenced by the nature of the evolutionary process but comparisons of trees from different processes are hindered by the challenge of completely describing tree shape. We present a full characterization of the shapes of rooted branching trees in a form that lends itself to natural tree comparisons. We use this characterization to define a metric, in the sense of a true distance function, on tree shapes. The metric distinguishes trees from random models known to produce different tree shapes. It separates trees derived from tropical versus USA influenza A sequences, which reflect the differing epidemiology of tropical and seasonal flu. We describe several metrics based on the same core characterization, and illustrate how to extend the metric to incorporate trees’ branch lengths or other features such as overall imbalance. Our approach allows us to construct addition and multiplication on trees, and to create a convex metric on tree shapes which formally allows computation of average tree shapes

Magnitude and sources of bias in the detection of mixed strain M. tuberculosis infection.

AbstractHigh resolution tests for genetic variation reveal that individuals may simultaneously host more than one distinct strain of Mycobacterium tuberculosis. Previous studies find that this phenomenon, which we will refer to as “mixed infection”, may affect the outcomes of treatment for infected individuals and may influence the impact of population-level interventions against tuberculosis. In areas where the incidence of TB is high, mixed infections have been found in nearly 20% of patients; these studies may underestimate the actual prevalence of mixed infection given that tests may not be sufficiently sensitive for detecting minority strains. Specific reasons for failing to detect mixed infections would include low initial numbers of minority strain cells in sputum, stochastic growth in culture and the physical division of initial samples into parts (typically only one of which is genotyped). In this paper, we develop a mathematical framework that models the study designs aimed to detect mixed infections. Using both a deterministic and a stochastic approach, we obtain posterior estimates of the prevalence of mixed infection. We find that the posterior estimate of the prevalence of mixed infection may be substantially higher than the fraction of cases in which it is detected. We characterize this bias in terms of the sensitivity of the genotyping method and the relative growth rates and initial population sizes of the different strains collected in sputum

Additive energy forward curves in a Heath-Jarrow-Morton framework

One of the peculiarities of power and gas markets is the delivery mechanism of forward contracts. The seller of a futures contract commits to deliver, say, power, over a certain period, while the classical forward is a financial agreement settled on a maturity date. Our purpose is to design a Heath-Jarrow-Morton framework for an additive, mean-reverting, multicommodity market consisting of forward contracts of any delivery period. The main assumption is that forward prices can be represented as affine functions of a universal source of randomness. This allows us to completely characterize the models which prevent arbitrage opportunities: this boils down to finding a density between a risk-neutral measure $\mathbb{Q}$, such that the prices of traded assets like forward contracts are true $\mathbb{Q}$-martingales, and the real world probability measure $\mathbb{P}$, under which forward prices are mean-reverting. The Girsanov kernel for such a transformation turns out to be stochastic and unbounded in the diffusion part, while in the jump part the Girsanov kernel must be deterministic and bounded: thus, in this respect, we prove two results on the martingale property of stochastic exponentials. The first allows to validate measure changes made of two components: an Esscher-type density and a Girsanov transform with stochastic and unbounded kernel. The second uses a different approach and works for the case of continuous density. We apply this framework to two models: a generalized Lucia-Schwartz model and a cross-commodity cointegrated market.Comment: 28 page

Impact of high pressure homogenization on physical properties, extraction yield and biopolymer structure of soybean okara

The effect of high pressure homogenization (HPH) on soy okara was studied. To this purpose, okara dispersions (10 g/100 g) were subjected to 1 pass at 50, 100 and 150 MPa and to 5 passes at 150 MPa. Samples were analyzed for stability, particle size, microstructure, and viscosity. Results highlighted that the increase of HPH intensity was associated with the structural disruption of okara particles, leading to physically stable homogenates having increasing viscosity. This was mainly attributed to an increase in okara solubility, due to fibre and protein release. The latter resulted almost complete, reaching values up to 90% of the protein originally entrapped in okara matrix. Absorbance at 280 nm, SH groups and dimension of proteins revealed that HPH treatments favoured the extraction of the main protein fractions even if, at the higher intensity level, extracted proteins probably underwent conformational changes and reassembling phenomena

Risk of Preeclampsia and Adverse Pregnancy Outcomes after Heterologous Egg Donation: Hypothesizing a Role for Kidney Function and Comorbidity

Background and objectives: Preeclampsia (PE) is a risk factor for kidney diseases; egg-donation (ED) increasingly used for overcoming fertility reduction, is a risk factor for PE. CKD is also a risk factor for PE. However, kidney function is not routinely assessed in ED pregnancies. Objective of the study is seeking to assess the importance of kidney function and maternal comorbidity in ED pregnancies. Design, setting, participants and measurements. Design: retrospective observational study from clinical charts. Setting: Sant'Anna Hospital, Turin, Italy (over 7000 deliveries per year). Selection: cases: 296 singleton pregnancies from ED (gestation > 24 weeks), who delivered January 2008-February 2019. Controls were selected from the TOrino Cagliari Observational Study (1407 low-risk singleton pregnancies 2009-2016). Measurements: Standard descriptive analysis. Logistic multiple regression analysis tested: PE; pregnancy-induced hypertension; preterm delivery; small for gestational age; explicatory variables: age; BMI; parity; comorbidity (kidney diseases; immunologic diseases; thyroid diseases; other). Delivery over time was analyzed according to Kaplan Meier; ROC (Relative Operating Characteristic) curves were tested for PE and pre-term delivery, employing serum creatinine and e-GFR as continuous variables. The analysis was performed with SPSS v.14.0 and MedCalc v.18. Results: In keeping with ED indications, maternal age was high (44 years). Comorbidity was common: at least one potential comorbid factor was found in about 40% of the cases (kidney disease: 3.7%, immunologic 6.4%, thyroid disease 18.9%, other-including hypertension, previous neoplasia and all other relevant diseases-10.8%). No difference in age, parity and BMI is observed in ED women with and without comorbidity. Patients with baseline renal disease or "other" comorbidity had a higher risk of developing PE or preterm delivery after ED. PE was recorded in 23% vs. 9%, OR: 2.513 (CI 1.066-5.923; p = 0.039); preterm delivery: 30.2% vs. 14%, OR 2.565 (CI: 1.198-5.488; p = 0.044). Limiting the analysis to 124 cases (41.9%) with available serum creatinine measurement, higher serum creatinine (dichotomised at the median: 0.67 mg/dL) was correlated with risk of PE (multivariate OR 17.277 (CI: 5.125-58.238)) and preterm delivery (multivariate OR 2.545 (CI: 1.100-5.892). Conclusions: Within the limits of a retrospective analysis, this study suggests that the risk of PE after ED is modulated by comorbidity. While the cause effect relationship is difficult to ascertain, the relationship between serum creatinine and outcomes suggests that more attention is needed to baseline kidney function and comorbidity

Associations between the LEP -2548G/A Promoter and Baseline Weight and between LEPR Gln223Arg and Lys656Asn Variants and Change in BMI z Scores in Arab Children and Adolescents Treated with Risperidone

Data on baseline (antipsychotic-naïve) age, weight, and height and change in these over three subsequent follow up time points up to 313.6 days (CI 303.5-323.7), were collected from 181 risperidone-treated children and adolescents (mean age 12.58 years, SD 4.99, range 2.17-17.7) attending a pediatric neurology clinic in Saudi Arabia. Owing to differences in genotypic distributions in subsamples, results are reported from the white Arabs (N=144). Age and gender-normed BMI-standardised z scores (BMI z) were calculated (lmsgrowth program). Linear regression was performed for baseline weight and BMI z, while change in BMI z was assessed using random effects ordered logistic regression. The following SNPs were analyzed: rs7799039 in the LEP promoter, rs1805094 (previously rs8179183), rs1137100 and rs1137101 in the LEPR, and rs1414334 in HTR2C. We found a nominally significant association between rs7799309 and baseline weight, adjusting for height, age, gender and diagnosis (A/G, P=0.035, β=-3.62, compared to G/G). rs1137101 (G/G, P=0.018, OR=4.13 compared to A/A) and rs1805094 C-allele carriers (P=0.019, OR=0.51) showed nominally significant associations with change in BMI z categories. Our data support and replicate previous relevant associations for these variants including with weight gain on risperidone, whilst being the first to report such associations in those of Arab ethnicity

Il database e l'atlante corologico della flora del Sulcis (Sardegna sud-occidentale)

The database and the chorological atlas of the flora of Sulcis (south-western Sardinia) – We present the Database and the chorological atlas of the flora of Sulcis (south-western Sardinia). In the creation of the DbFlora Database application, a system was adopted that enables access both geographically and alphanumerically. The alphanumeric section features the usual browsing and database management functions. It is based on the widely-used Microsoft Access DBMS engine and its main characteristic are the individual records (index cards) created for each floral specimen. Each card features a main template screen where the taxon’s identifying data is summarised and five sub-sections relating to linguistic, biological, ecological and chorological data, as well as the rarity of the specimen. Every sub-section features a series of fields, which enable the interaction with the cartographic reticules and the other georeferenced data. The Geographic Information System was utilised both to georeference the area of study and to create the chorological atlas. The basic cartographic grid was created according to the international UTM reference system and that one adopted in Central Europe for floristic cartography. In the first case, a square grid with 1 kmq cells was built, whilst in the second case, the grid is rectangular with cells of 6’ in latitude by 10’ in longitude. The two systems interact because of connecting software, which enables the instantaneous processing of the distribution maps for each species or, vice versa, to find all the taxa present in a specific section of the reticule. Thanks to the database and the atlas and through the Geographic Information Systems, it has been possible to make the research on flora compatible with all the other existing data for the area

Telomere length: role of the effect of stress on psychiatric disorders vulnerability and on its transgenerational transmission

Telomeres are repeated sequences of DNA-protein complexes located at the ends of chromosomes and are involved in preventing chromosome fusion and maintaining genome stability. Telomere shortening is a physiological process that occurs in each cell division and is considered a marker of cellular aging. Indeed insufficient telomere length has been observed after exposure to stress (Tyrka et al., 2010), and associated with an increased risk for age-related chronic diseases (Haycock et al., 2014). Preliminary data have reported that individuals exposed to childhood trauma have, in adult age, shorter telomeres. Telomere may be shortened also from excessive attrition due to decreased telomerase activity. Indeed, telomerase can counteract by adding TTAGGG repeats to the chromosome ends. In this project I have measured in a cellular model of stress, fibroblast cell cultures exposed to deprivation of nutriments and oxygen, telomere length. Moreover, I have performed similar analyses in the brain of animals exposed to a paradigm of prenatal stress. Moreover as shorter telomere length has been found in newborns whose mothers were exposed to stress during pregnancy (Entringer et al., 2013) my further interest is to assess telomere length in individuals at high risk to develop psychiatric disease but that haven\u2019t yet experienced it. Therefore I\u2018m now assessing whether alterations in telomere length observed in the brain of an animal model of early life stress can be observed also in the blood of individuals assessed for exposure to childhood trauma. From these combined data obtained from cellular, animal and human studies, I will identify the role of telomere in the inheritance of the vulnerability risk to develop stress related psychopathologies