Relative Convex Hull Determination from Convex Hulls in the Plane

A new algorithm for the determination of the relative convex hull in the plane of a simple polygon A with respect to another simple polygon B which contains A, is proposed. The relative convex hull is also known as geodesic convex hull, and the problem of its determination in the plane is equivalent to find the shortest curve among all Jordan curves lying in the difference set of B and A and encircling A. Algorithms solving this problem known from Computational Geometry are based on the triangulation or similar decomposition of that difference set. The algorithm presented here does not use such decomposition, but it supposes that A and B are given as ordered sequences of vertices. The algorithm is based on convex hull calculations of A and B and of smaller polygons and polylines, it produces the output list of vertices of the relative convex hull from the sequence of vertices of the convex hull of A.Comment: 15 pages, 4 figures, Conference paper published. We corrected two typing errors in Definition 2: $I_S$ has to be defined based on $O_S$, and $I_E$ has to be defined based on $O_E$ (not just using $O$). These errors appeared in the text of the original conference paper, which also contained the pseudocode of an algorithm where $I_S$ and $I_E$ appeared as correctly define

Childbirth and consequent atopic disease: emerging evidence on epigenetic effects based on the hygiene and EPIIC hypotheses

Background: In most high and middle income countries across the world, at least 1:4 women give birth by cesarean section. Rates of labour induction and augmentation are rising steeply; and in some countries up to 50 % of laboring women and newborns are given antibiotics. Governments and international agencies are increasingly concerned about the clinical, economic and psychosocial effects of these interventions. Discussion: There is emerging evidence that certain intrapartum and early neonatal interventions might affect the neonatal immune response in the longer term, and perhaps trans-generationally. Two theories lead the debate in this area. Those aligned with the hygiene (or ‘Old Friends’) hypothesis have examined the effect of gut microbiome colonization secondary to mode of birth and intrapartum/neonatal pharmacological interventions on immune response and epigenetic phenomena. Those working with the EPIIC (Epigenetic Impact of Childbirth) hypothesis are concerned with the effects of eustress and dys-stress on the epigenome, secondary to mode of birth and labour interventions. Summary: This paper examines the current and emerging findings relating to childbirth and atopic/autoimmune disease from the perspective of both theories, and proposes an alliance of research effort. This is likely to accelerate the discovery of important findings arising from both approaches, and to maximize the timely understanding of the longer-term consequences of childbirth practices

Transforming matters: sustaining gold lifeways in artisanal and small-scale mining

Growth strategies in mining regions promote gold extraction basedonindustrial mining, associating Artisanal and Small-scale Gold Mining (ASGM) with persistent informality. Against this background, we consider how to approach transformations to sustainability in ASGM. Acknowledging how problematic this topic is for sustainability debates,given howASGM is associated with a host of environmental and social problems,we argue that a justice lens demands we confront such challenges within the global politics of sustainability. This leads us to review advances inthe study of ASGM, linked to debates on extractivism, resource materialities, and informality. We use the notion of gold lifeways to capture how the matter of mining shapes different worlds of extraction. We argue that consideration of the potential for transformations to sustainability needs to be grounded within the realities of ASGM. This necessitates giving value to miners’ knowledge(s), perspectives and interests, while recognising the plurality of mining futures. Nevertheless, we conclude that between the immediacy of precarious work and the structural barriers to change in ASGM, the challenges for transformation cannot be underestimated.NWOGlobal Challenges (FSW

Identification of dynamic glucocorticoid-induced methylation changes at the FKBP5 locus.

BackgroundEpigenetic mechanisms may play a major role in the biological embedding of early-life stress (ELS). One proposed mechanism is that glucocorticoid (GC) release following ELS exposure induces long-lasting alterations in DNA methylation (DNAm) of important regulatory genes of the stress response. Here, we investigate the dynamics of GC-dependent methylation changes in key regulatory regions of the FKBP5 locus in which ELS-associated DNAm changes have been reported.ResultsWe repeatedly measured DNAm in human peripheral blood samples from 2 independent cohorts exposed to the GC agonist dexamethasone (DEX) using a targeted bisulfite sequencing approach, complemented by data from Illumina 450K arrays. We detected differentially methylated CpGs in enhancers co-localizing with GC receptor binding sites after acute DEX treatment (1h, 3h, 6h), which returned to baseline levels within 23h. These changes withstood correction for immune cell count differences. While we observed main effects of sex, age, body mass index, smoking, and depression symptoms on FKBP5 methylation levels, only the functional FKBP5 SNP (rs1360780) moderated the dynamic changes following DEX. This genotype effect was observed in both cohorts and included sites previously shown to be associated with ELS.ConclusionOur study highlights that DNAm levels within regulatory regions of the FKBP5 locus show dynamic changes following a GC challenge and suggest that factors influencing the dynamics of this regulation may contribute to the previously reported alterations in DNAm associated with current and past ELS exposure

A Role of Oxytocin Receptor Gene Brain Tissue Expression Quantitative Trait Locus rs237895 in the Intergenerational Transmission of the Effects of Maternal Childhood Maltreatment

ObjectiveWomen exposed to childhood maltreatment (CM) are more likely to exhibit insensitive parenting, which may have consequences for their offspring's development. Variation in the oxytocin-receptor gene (OXTR) moderates risk of CM-associated long-term sequelae associated with mother-child attachment, although functionality of previously investigated single nucleotide polymorphisms (SNPs) remained elusive. Here, we investigated the role of OXTR rs237895, a brain tissue expression quantitative trait locus (eQTL), as a moderator of the relationship between CM and maternal behavior (MB) and the association between MB and offspring attachment security.MethodOf 110 women with information on rs237895 genotype (T-allele = 64, CC = 46), 107 had information on CM (CTQ) and 99 on standardized observer-based ratings of MB at 6 months postpartum (responsivity and detachment), which were used in principal component analysis to obtain a latent factor representing MB. Offspring (n = 86) attachment was evaluated at 12 months of age. Analyses predicting MB were adjusted for socioeconomic status, age, postpartum depression, and genotype-based ethnicity. Analyses predicting child attachment were adjusted for infant sex, socioeconomic status, and postpartum depression.Resultsrs237895 significantly moderated the relationship between CM and MB (F1;66 = 7.99, p < .01), indicating that CM was associated with maternal insensitivity only in high-OXTR-expressing T-allele carriers but not in low-OXTR-expressing CC homozygotes. Moreover, maternal insensitivity predicted offspring insecure attachment (B = -0.551; p < .05).ConclusionWomen with a high OXTR expressing genotype are more susceptible to CM-related impairments in MB that, in turn, predict attachment security in their children, supporting the role of the OT system in the intergenerational transmission of risk associated with maternal CM

Dynamic DNA methylation changes in the maternal oxytocin gene locus (OXT) during pregnancy predict postpartum maternal intrusiveness

Maternal behavior (MB) is observable across mammals and represents an important feature of environmental variation during early postnatal development. Oxytocin (OT) plays a crucial role in MB. Even prior to childbirth, pregnancy induces epigenetic and other downstream changes in the maternal OT-system, likely mediated by the actions of steroid hormones. However, little is known about the nature and consequences of epigenetic modifications in the maternal OT-encoding gene (OXT) during pregnancy. Our study aims to investigate temporal dynamics of OXT promoter DNA methylation (DNAm) throughout pregnancy in predicting MB in humans. In 107 mother-child dyads, maternal OXT DNAm was serially analyzed in whole blood in early, mid and late pregnancy. MB was coded based on standardized mother-child interactions at six months postpartum. After controlling for cellular heterogeneity, race/ethnicity, age, and socioeconomic status, OXT-promoter DNAm exhibited a dynamic profile during pregnancy (b = 0.026, t=-3.37, p < .001), with decreases in DNAm from early to mid-pregnancy and no further change until late pregnancy. Moreover, dynamic DNAm trajectories of the OXT-promoter region predicted MB (intrusiveness) at six months postpartum (b = 0.006, t = 2.0, p < 0.05), with 6% higher OXT DNAm in late pregnancy in intrusive compared to non-intrusive mothers. We here demonstrate that OXT promoter DNAm changes significantly throughout gestation in peripheral blood and that these changes are associated with variability in MB, providing a novel potential biomarker predicting postnatal MB

MIX STAR-AUTONOMOUS QUANTALES AND THE CONTINUOUS WEAK ORDER

International audienceThe set of permutations on a finite set can be given a lattice structure (known as the weak Bruhat order). The lattice structure is generalized to the set of words on a fixed alphabet Σ = { x, y, z,. .. }, where each letter has a fixed number of occurrences (these lattices are known as multinomial lattices and, in dimension 2, as lattices of lattice paths). By interpreting the letters x, y, z,. .. as axes, these words can be interpreted as discrete increasing paths on a grid of a d-dimensional cube, where d = card(Σ). We show in this paper how to extend this order to images of continuous monotone paths from the unit interval to a d-dimensional cube. The key tool used to realize this construction is the quantale L ∨ (I) of join-continuous functions from the unit interval to itself; the construction relies on a few algebraic properties of this quantale: it is-autonomous and it satisfies the mix rule. We begin developing a structural theory of these lattices by characterizing join-irreducible elements, and by proving these lattices are generated from their join-irreducible elements under infinite joins

Randomized phase III trial in elderly patients comparing LV5FU2 with or without irinotecan for first-line treatment of metastatic colorectal cancer (FFCD 2001–02)

International audienceBACKGROUND:Metastatic colorectal cancer (mCRC) frequently occurs in elderly patients. However, data from a geriatric tailored randomized trial about tolerance to and the efficacy of doublet chemotherapy (CT) with irinotecan in the elderly are lacking. The benefit of first-line CT intensification remains an issue in elderly patients.PATIENTS AND METHODS:Elderly patients (75+) with previously untreated mCRC were randomly assigned in a 2 × 2 factorial design (four arms) to receive 5-FU (5-fluorouracil)-based CT, either alone (FU: LV5FU2 or simplified LV5FU2) or in combination with irinotecan [IRI: LV5FU2-irinotecan or simplified LV5FU2-irinotecan (FOLFIRI)]. The CLASSIC arm was defined as LV5FU2 or LV5FU2-irinotecan and the SIMPLIFIED arm as simplified LV5FU2 or FOLFIRI. The primary end point was progression-free survival (PFS). Secondary end points were overall survival (OS), safety and objective response rate (ORR).RESULTS:From June 2003 to May 2010, 71 patients were randomly assigned to LV5FU2, 71 to simplified LV5FU2, 70 to LV5FU2-irinotecan and 70 to FOLFIRI. The median age was 80 years (range 75-92 years). No significant difference was observed for the median PFS: FU 5.2 months versus IRI 7.3 months, hazard ratio (HR) = 0.84 (0.66-1.07), P = 0.15 and CLASSIC 6.5 months versus SIMPLIFIED 6.0 months, HR = 0.85 (0.67-1.09), P = 0.19. The ORR was superior in IRI (P = 0.0003): FU 21.1% versus IRI 41.7% and in CLASSIC (P = 0.04): CLASSIC 37.1% versus SIMPLIFIED 25.6%. Median OS was 14.2 months in FU versus 13.3 months in IRI, HR = 0.96 (0.75-1.24) and 15.2 months in CLASSIC versus 11.4 months in SIMPLIFIED, HR = 0.71 (0.55-0.92). More patients presented grade 3-4 toxicities in IRI (52.2% versus 76.3%).CONCLUSION:In this elderly population, adding irinotecan to an infusional 5-FU-based CT did not significantly increase either PFS or OS. Classic LV5FU2 was associated with an improved OS compared with simplified LV5FU2.CLINICALTRIALSGOV:NCT00303771