Generalized Multivariate Extreme Value Models for Explicit Route Choice Sets

This paper analyses a class of route choice models with closed-form probability expressions, namely, Generalized Multivariate Extreme Value (GMEV) models. A large group of these models emerge from different utility formulas that combine systematic utility and random error terms. Twelve models are captured in a single discrete choice framework. The additive utility formula leads to the known logit family, being multinomial, path-size, paired combinatorial and link-nested. For the multiplicative formulation only the multinomial and path-size weibit models have been identified; this study also identifies the paired combinatorial and link-nested variations, and generalizes the path-size variant. Furthermore, a new traveller's decision rule based on the multiplicative utility formula with a reference route is presented. Here the traveller chooses exclusively based on the differences between routes. This leads to four new GMEV models. We assess the models qualitatively based on a generic structure of route utility with random foreseen travel times, for which we empirically identify that the variance of utility should be different from thus far assumed for multinomial probit and logit-kernel models. The expected travellers' behaviour and model-behaviour under simple network changes are analysed. Furthermore, all models are estimated and validated on an illustrative network example with long distance and short distance origin-destination pairs. The new multiplicative models based on differences outperform the additive models in both tests

Complete genome sequence of the Clostridium difficile laboratory strain 630Δerm reveals differences from strain 630, including translocation of the mobile element CTn5

Molecular Technology and Informatics for Personalised Medicine and Healt

Climate change, gender and aquatic food systems: call for action to address gender and social inequalities matters in the nexus

The uneven distribution of the adverse impacts of climate change on aquatic food systems is not only being felt between countries, but also within them. Particularly hard-hit are people who already experience intersecting power inequalities due to gender, socioeconomic class, age, location, ethnicity, ability, religion and caste. Among poor and marginalized groups, women are especially vulnerable to climate change due to their over-dependence on natural resources. They have limited coping and adaptive capacity owing to their multiple, competing responsibilities, further exacerbated by power inequalities. Therefore, research on the resilience of aquatic food systems to climate change must take gender and intersectional dimensions into account. Quantitative and qualitative research must transcend the household level and gender-binary (men-women) focus to explore adaptation strategies of actors in small-scale fisheries and aquaculture chains. In addition, to address entrenched power inequalities at formal, informal, local and systemic levels, it is imperative that there be more collaboration across research, interventions and policies on climate adaptation and mitigation, and on aquatic food systems. A collaborative agenda premised on the diversity inherent in small-scale fisheries and aquaculture has the potential to build resilient, equitable, efficient and effective aquatic food systems

Climate change, gender and aquatic food systems: call for action to address gender and social inequalities matters in the nexus

The uneven distribution of the adverse impacts of climate change on aquatic food systems is not only being felt between countries, but also within them. Particularly hard-hit are people who already experience intersecting power inequalities due to gender, socioeconomic class, age, location, ethnicity, ability, religion and caste. Among poor and marginalized groups, women are especially vulnerable to climate change due to their over-dependence on natural resources. They have limited coping and adaptive capacity owing to their multiple, competing responsibilities, further exacerbated by power inequalities. Therefore, research on the resilience of aquatic food systems to climate change must take gender and intersectional dimensions into account. Quantitative and qualitative research must transcend the household level and gender-binary (men-women) focus to explore adaptation strategies of actors in small-scale fisheries and aquaculture chains. In addition, to address entrenched power inequalities at formal, informal, local and systemic levels, it is imperative that there be more collaboration across research, interventions and policies on climate adaptation and mitigation, and on aquatic food systems. A collaborative agenda premised on the diversity inherent in small-scale fisheries and aquaculture has the potential to build resilient, equitable, efficient and effective aquatic food systems

Nanopore Sequencing Enables Comprehensive Transposable Element Epigenomic Profiling

Transposable elements (TEs) drive genome evolution and are a notable source of pathogenesis, including cancer. While CpG methylation regulates TE activity, the locus-specific methylation landscape of mobile human TEs has to date proven largely inaccessible. Here, we apply new computational tools and long-read nanopore sequencing to directly infer CpG methylation of novel and extant TE insertions in hippocampus, heart, and liver, as well as paired tumor and non-tumor liver. As opposed to an indiscriminate stochastic process, we find pronounced demethylation of young long interspersed element 1 (LINE-1) retrotransposons in cancer, often distinct to the adjacent genome and other TEs. SINE-VNTR-Alu\ua0(SVA) retrotransposons, including their internal tandem repeat-associated CpG island, are near-universally methylated. We encounter allele-specific TE methylation and demethylation of aberrantly expressed young LINE-1s in normal tissues. Finally, we recover the complete sequences of tumor-specific LINE-1 insertions and their retrotransposition hallmarks, demonstrating how long-read sequencing can simultaneously survey the epigenome and detect somatic TE mobilization

Effects of Various Doses of Selenite on Stinging Nettle (Urtica dioica L.)

The aim of this study was to investigate the effects of selenium (Se) on the growth, accumulation and possible mechanisms of Se transport in certain parts (roots, leaves, stamp and apex) of nettle (Urtica dioica L.) plants. Se was supplemented by one-shot and two repeated doses to the soil (2.0 and 4.0 mg Se per kg of substrate). Selenium content in roots increased linearly with dose and was significantly higher compared to other plant parts of interest. However, growth of the above-ground parts of plant as well as roots was slightly inhibited with increasing selenium concentration in comparison to the untreated plants. The content of phytochelatin2, a low molecular mass peptide containing a sulfhydryl group, correlated well with the Se content. This suggests a possible stimulation of synthesis of this plant peptide by Se

D-cycloserine augmentation of exposure-based cognitive behavior therapy for anxiety, obsessive-compulsive, and posttraumatic stress disorders: a systematic review and meta-analysis of individual participant data

Importance: Whether and under which conditions D-cycloserine (DCS) augments the effects of exposure-based cognitive behavior therapy for anxiety, obsessive-compulsive, and posttraumatic stress disorders is unclear. Objective: To clarify whether DCS is superior to placebo in augmenting the effects of cognitive behavior therapy for anxiety, obsessive-compulsive, and posttraumatic stress disorders and to evaluate whether antidepressants interact with DCS and the effect of potential moderating variables. Data Sources: PubMed, EMBASE, and PsycINFO were searched from inception to February 10, 2016. Reference lists of previous reviews and meta-analyses and reports of randomized clinical trials were also checked. Study Selection: Studies were eligible for inclusion if they were (1) double-blind randomized clinical trials of DCS as an augmentation strategy for exposure-based cognitive behavior therapy and (2) conducted in humans diagnosed as having specific phobia, social anxiety disorder, panic disorder with or without agoraphobia, obsessive-compulsive disorder, or posttraumatic stress disorder. Data Extraction and Synthesis: Raw data were obtained from the authors and quality controlled. Data were ranked to ensure a consistent metric across studies (score range, 0-100). We used a 3-level multilevel model nesting repeated measures of outcomes within participants, who were nested within studies. Results: Individual participant data were obtained for 21 of 22 eligible trials, representing 1047 of 1073 eligible participants. When controlling for antidepressant use, participants receiving DCS showed greater improvement from pretreatment to posttreatment (mean difference, -3.62; 95% CI, -0.81 to -6.43; P = .01; d = -0.25) but not from pretreatment to midtreatment (mean difference, -1.66; 95% CI, -4.92 to 1.60; P = .32; d = -0.14) or from pretreatment to follow-up (mean difference, -2.98, 95% CI, -5.99 to 0.03; P = .05; d = -0.19). Additional analyses showed that participants assigned to DCS were associated with lower symptom severity than those assigned to placebo at posttreatment and at follow-up. Antidepressants did not moderate the effects of DCS. None of the prespecified patient-level or study-level moderators was associated with outcomes. Conclusions and Relevance: D-cycloserine is associated with a small augmentation effect on exposure-based therapy. This effect is not moderated by the concurrent use of antidepressants. Further research is needed to identify patient and/or therapy characteristics associated with DCS response.2018-05-0

A Population Model of Time-Dependent Changes in Serum Creatinine in (Near)term Neonates with Hypoxic-Ischemic Encephalopathy During and After Therapeutic Hypothermia

The objective was to apply a population model to describe the time course and variability of serum creatinine (sCr) in (near)term neonates with moderate to severe encephalopathy during and after therapeutic hypothermia (TH). The data consisted of sCr observations up to 10 days of postnatal age in neonates who underwent TH during the first 3 days after birth. Available covariates were birth weight (BWT), gestational age (GA), survival, and acute kidney injury (AKI). A previously published population model of sCr kinetics in neonates served as the base model. This model predicted not only sCr but also the glomerular filtration rate normalized by its value at birth (GFR/GFR0). The model was used to compare the TH neonates with a reference full term non-asphyxiated population of neonates. The estimates of the model parameters had good precision and showed high between subject variability. AKI influenced most of the estimated parameters denoting a strong impact on sCr kinetics and GFR. BWT and GA were not significant covariates. TH transiently increased sCr in TH neonates over the first days compared to the reference group. Asphyxia impacted not only GFR, but also the sCr synthesis rate. We also observed that AKI neonates exhibit a delayed onset of postnatal GFR increase and have a higher sCr synthesis rate compared to no-AKI patients. Our findings show that the use of sCr as marker of renal function in asphyxiated neonates treated with TH to guide dose selection for renally cleared drugs is challenging, while we captured the postnatal sCr patterns in this specific population. Graphical Abstract: [Figure not available: see fulltext.].</p

Navigation and Exploration in 3D-Game Automated Play Testing

To enable automated software testing, the ability to automatically navigate to a state of interest and to explore all, or at least sufficient number of, instances of such a state is fundamental. When testing a computer game the problem has an extra dimension, namely the virtual world where the game is played on. This world often plays a dominant role in constraining which logical states are reachable, and how to reach them. So, any automated testing algorithm for computer games will inevitably need a layer that deals with navigation on a virtual world. Unlike e.g. navigating through the GUI of a typical web-based application, navigating over a virtual world is much more challenging. This paper discusses how concepts from geometry and graph-based path finding can be applied in the context of game testing to solve the problem of automated navigation and exploration. As a proof of concept, the paper also briefly discusses the implementation of the proposed approach