Hypercubes, Peak Patterns and Universal Positive Epistasis

Genes and their interactions with one another crucially affect reproductive success, commonly referred to as fitness. Biallelic models have been used in the past as a mathematical framework to model and explain these interactions. One approach is to represent L biallelic loci as hypercubic graphs, known as L-cubes. On these $L$-cubes, vertices model genotypes and the edges connect the vertices that differ by a single locus value. Assigning fitness values to genotypes gives edges a direction towards higher fitness. Local optimal genotypes, called peaks, then have a higher fitness than all their direct neighbors. Recently, researchers have introduced the notion of peak patterns, referring to the set of peaks that are unique up to relabeling of vertices. However, a complete characterization of all possible peak patterns has not yet been performed for L => 4. This work concerns itself with an analysis for L=4 regarding peak patterns and all possible instances of sign and reciprocal sign epistasis, substantiating the importance of peak patterns. Additionally a lower bound proportional to $2^{2^{L-1}}$ is provided for the set containing all possible peak patterns for a given L. Informed by this, all peak patterns up to L=6 are computed and joined with a variant of Fishers Geometric Model having a one dimensional phenotype. Moreover peak patterns are used to calculate the maximal number of peaks for the staircase triangulation up to L=8

Application of biomarker compounds as tracers for sources and fates of natural and anthropogenic organic matter in the environment

Determination of the source and fate of natural (higher plant lipids, marine lipids, etc.) and anthropogenically (e.g., petroleum, coal emissions) derived hydrocarbons and oxygenated compounds in the environment was accomplished using gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS) to characterize or identify molecular biomarkers to be utilized as tracers. The distributions and abundances of biomarkers such as straight chain homologous series (e.g., n-alkanes, n-alkanoic acids, n-alkan-2-ones, n-alkanols, etc.) and cyclic terpenoid compounds (e.g., sesquiterpenoids, diterpenoids, steroids, triterpenoids) were identified in epicuticular waxes from conifers of western North America (natural emissions). These biomarkers and their thermal alteration derivatives were also identified in smoke emissions from known vegetation sources (e.g., conifers, deciduous trees and grasses) and were then applied as tracers in soils, soils that contained wildfire residues and soil/river mud washout after wildfire burning. Where possible, the reaction pathways of transformation from the parent precursor compounds to intermediate and final alteration products were determined from GC-MS data. In addition, molecular tracer analysis was applied to air, water and sediment samples collected from a lacustrine setting (Crater Lake, OR) in order to determine the identities, levels and fates of anthropogenic (i.e., petroleum hydrocarbon contamination from boating and related activities) hydrocarbons in a pristine organic matter sink. This work demonstrated that biomarker tracer analysis is a useful tool for developing environmental management and pollution mitigation strategies

Occurrence and Sources of Triterpenoid Methyl Ethers and Acetates in Sediments of the Cross-River System, Southeast Nigeria

Pentacyclic triterpenol methyl ethers (PTMEs), germanicol methyl ether (miliacin), 3-methoxyfern-9(11)-ene (arundoin), β-amyrin methyl ether (iso-sawamilletin), and 3-methoxytaraxer-14-ene (sawamilletin or crusgallin) were characterized in surface sediments of the Cross-River system using gas chromatography-mass spectrometry (GC-MS). Triterpenol esters (mainly α- and β-amyrinyl acetates and hexanoates, and lupeyl acetate and hexanoate) were also found. These distinct compounds are useful for assessing diagenesis that can occur during river transport of organic detritus. Poaceae, mainly Gramineae and Elaeis guineensis higher plant species, are proposed as primary sources for the PTMEs and esters in the sediments. PTMEs are biomarkers of specific higher plant subspecies, while the triterpenol esters are indicators of early diagenetic alteration of higher plant detritus

Creación de un modelo predictivo de cesárea, resultado perinatal y análisis económico de la inducción de parto

En la tesis titulada "Creación de un modelo predictivo de cesárea, resultado perinatal y análisis económico de la inducción de parto" se ha realizado un análisis de diferentes elementos relacionados con la inducción como compendio de publicaciones.En el primer artículo se valora la reproducibilidad de dos técnicas diagnósticas para la valoración de las condiciones cervicales de la gestante al ingreso para inducción: la medición cervical mediante ecografía y el cálculo de Test de Bishop en las manos inexpertas de residentes de Ginecología de primer año.En el segundo artículo se realiza un análisis económico del coste de la inducción atendiendo a los costes directos. Se tiene en cuenta, no solo el tipo de parto sino todo el proceso de inducción, lo que permite poner en evidencia el coste real del procedimiento.En el tercer artículo se evalúa un grupo de pacientes cuya gestación se ha visto afectada por la alteración del crecimiento fetal, que precisan inducción de parto. En estos fetos se valoran parámetros como RCP cerebral para evaluar su grado de bienestar. En el artículo se evidencia que la unión de RCP junto con las condiciones cervicales maternas son los mejores predictores del tipo de parto tras inducción.En el cuarto y último artículo, se analiza al grupo de pacientes a las que con más frecuencia se realiza una inducción de parto, las gestaciones cronológicamente prolongadas, de forma que se estudia tanto los tipos de parto como el coste de los mismos en este grupo de pacientes.<br /

Terpenoid Compositions of Resins from Callitris Species (Cupressaceae)

The environmental fate of conifer resins and their natural product compounds as mixtures is of importance for source, alteration, and transport studies. The compound compositions of resins of the common Callitris species (Cupressaceae) based on gas chromatography-mass spectrometry have not been reported. Results show that diterpenoids were the most abundant components and callitrisic acid was present in the resin extracts of all Callitris species analyzed. Significant amounts of 4-epi-pimaric and sandaracopimaric acids, with lesser communic, ozic, and lambertianic acids, were also in the mixtures. Phenolic diterpenoids, for example, ferruginol, hinokiol, were found in trace quantities in some samples. Thus, callitrisic acid and 4-epi-pimaric acid are the characteristic diterpenoids of Callitris species that are amenable to molecular biomarker analyses in geological or environmental applications

An examination of nervous system revealed unexpected immunoreactivity of both secretory apparatus and excretory canals in plerocercoids of two broad tapeworms (Cestoda: Diphyllobothriidea)

Dibothriocephalus ditremus and Dibothriocephalus latus are diphyllobothriidean tapeworms autochthonous to Europe. Their larval stages (plerocercoids) may seriously alter health of their intermediate fish hosts (D. ditremus) or cause intestinal diphyllobothriosis of the final human host (D. latus). Despite numerous data on the internal structure of broad tapeworms, many aspects of the morphology and physiology related to host–parasite co-existence remain unclear for these 2 species. The main objective of this work was to elucidate functional morphology of the frontal part (scolex) of plerocercoids, which is crucial for their establishment in fish tissues and for an early attachment in final hosts. The whole-mount specimens were labelled with different antibodies and examined by confocal microscope to capture their complex 3-dimensional microanatomy. Both species exhibited similar general pattern of immunofluorescent signal, although some differences were observed. In the nervous system, FMRF amide-like immunoreactivity (IR) occurred in the bi-lobed brain, 2 main nerve cords and surrounding nerve plexuses. Differences between the species were found in the structure of the brain commissures and the size of the sensilla. Synapsin IR examined in D. ditremus occurred mainly around FMRF amide-like IR brain lobes and main cords. The unexpected finding was an occurrence of FMRF amide-like IR in terminal reservoirs of secretory gland ducts and excretory canals, which has not been observed previously in any tapeworm species. This may indicate that secretory/excretory products, which play a key role in host–parasite relationships, are likely to contain FMRF amide-related peptide/s

Impact of suspected preterm labor during pregnancy on cardiometabolic profile and neurodevelopment during childhood: a prospective cohort study protocol

Introduction: Suspected preterm labor (SPL), defined as the presence of regular and painful uterine contractions and cervical shortening, represents a prenatal insult with potential long-term consequences. However, despite recent evidence demonstrating suboptimal neurodevelopment at 2 years in this population, it remains underestimated as a significant risk factor for neurodevelopmental disorders or other chronic diseases. The aim of this study is to assess the impact of suspected preterm labor during pregnancy on cardiometabolic profile and neurodevelopment during childhood (6–8 years). Methods and analysis: Prospective cohort study including children whose mothers suffered suspected preterm labour during pregnancy and paired controls. Neurodevelopmental, cardiovascular, and metabolic assessments will be performed at 6–8 years of age. A trained psychologist will carry out the neurodevelopment assessment including intelligence, visual perception, and behavioral assessment. Body composition and physical fitness assessment will be performed by one trained pediatrician and nurse. Finally, cardiovascular evaluation, including echocardiography and blood pressure, will be performed by two pediatric cardiologists. Data regarding perinatal and postnatal characteristics, diet, lifestyle, and weekly screen time of the child will be obtained from medical history and direct interviews with families. Primary outcome measures will include body mass index and adiposity, percentage of fat mass and total and regional lean mass, bone mineral content and density, cardiorespiratory resistance, isometric muscle strength, dynamic lower body strength, systolic and diastolic blood pressure, left ventricle (LV) systolic and diastolic function, general intelligence index, visuospatial working memory span, oculomotor control test, index of emotional, and behavioral problems

Study protocol for a randomised controlled trial: treatment of early intrauterine growth restriction with low molecular weight heparin (TRACIP)

Introduction: The incidence of intrauterine growth restriction (IUGR) is estimated at about 3% of pregnancies, and it is associated with 30% of all perinatal mortality and severe morbidity with adverse neurodevelopmental and cardiovascular health consequences in adult life. Early onset IUGR represents 20%-30% of all cases and is highly associated with severe placental insufficiency. The existing evidence suggests that low molecular weight heparin (LMWH) has effects beyond its antithrombotic action, improving placental microvessel structure and function of pregnant women with vascular obstetric complications by normalising proangiogenic and antiapoptotic protein levels, cytokines and inflammatory factors. The objective of our study is to demonstrate the effectiveness of LMWH in prolonging gestation in pregnancies with early-onset IUGR. Methods and analysis: This is a multicentre, triple-blind, parallel-arm randomised clinical trial. Singleton pregnancies qualifying for early (20-32 weeks at diagnosis) placental IUGR (according to Delphi criteria) will be randomised to subcutaneous treatment with bemiparin 3500 IU/0.2 mL/day or placebo from inclusion at diagnosis to the time of delivery. Analyses will be based on originally assigned groups (intention-to-treat). The primary objective will be analysed by comparing gestational age and prolongation of pregnancy (days) in each group with Student's t-tests for independent samples and by comparing Kaplan-Maier survival curves (from inclusion to delivery, log-rank test). A linear regression model for gestational age at birth will consider the following covariates: gestational age at inclusion (continuous) and pre-eclampsia (binary). Ethics and dissemination: The study will be conducted in accordance with the principles of Good Clinical Practice. This study was approved by the Clinical Research Ethics Committee (CEIC) of Sant Joan de Déu Hospital, on 13 July 2017. The trial is registered in the public registry www.clinicaltrial.gov. according to Science Law 14/2011, and the results will be published in an open access journal

First-Trimester Sequential Screening for Preeclampsia Using Angiogenic Factors : Study Protocol for a Prospective, Multicenter, Real Clinical Setting Study

The incidence of preeclampsia (PE) is about 2-8%, making it one of the leading causes of perinatal morbidity and maternal mortality in the world. Early prophylactic low dose administration (150 mg) of acetylsalicylic acid is associated with a significant reduction in the incidence of early-onset PE, intrauterine growth restriction (IUGR), and neonatal mean stay in the intensive care unit (ICU). Universal implementation of a first-trimester screening system including angiogenic and antiangiogenic markers [the Placental Growth Factor (PlGF) and/or soluble fms-like Tyrosine Kinase-1 (sFlt-1)] has shown a prediction rate of 90% for early-onset PE but entails a high financial cost. The aim of this study is to determine the predictive and preventive capacity of a universal PE first-trimester two-step sequential screening model, determining the PlGF only in patients previously classified as intermediate risk by means of a multivariate model based on resources already used in the standard pregnancy control, in a real clinical setting. We hypothesize that this screening model will achieve similar diagnostic performance as the universal determination of PlGF but at a lower economic cost. This is a prospective, multicentric, cohort study in a real-world clinical setting. Every singleton pregnancy will be recruited at the routine first pregnancy visit. In a first step, the first-trimester risk of PE will be calculated using a multivariate Gaussian distribution model, based on medical history, mean blood pressure, Pregnancy-Associated Plasma Protein A (PAPP-A), and Uterine Artery Doppler Pulsatility Index (UTPI). Patients will be classified into three risk groups for PE: (1) risk ≥ 1/50, high-risk with no further testing (blinded PlGF); (2) risk between 1/51 and 1/500, medium-risk requiring further testing; and (3) risk ≤ 1/501, low-risk with no further testing. In a second step, the PlGF will only be determined in those patients classified as intermediate risk after this first step, and then reclassified into high- or low-risk groups. Prophylactic administration of aspirin (150 mg/day) will be prescribed only in high risk patients. As a secondary objective, sFlt-1 values will be blindly determined in patients with high and intermediate risk to assess its potential performance in the screening for PE. The study will be conducted in accordance with the principles of Good Clinical Practice. This study is approved by the Aragon Research Ethics Committee (CEICA) on 3 July 2020 (15/2020). , identifier: NCT04767438