MULTIPLE MODEL EVALUATION ABSENT THE GOLD STANDARD VIA MODEL COMBINATION

We describe a method for evaluating an ensemble of predictive models given a sample of observations comprising the model predictions and the outcome event measured with error. Our formulation allows us to simultaneously estimate measurement error parameters, true outcome — aka the gold standard — and a relative weighting of the predictive scores. We describe conditions necessary to estimate the gold standard and for these estimates to be calibrated and detail how our approach is related to, but distinct from, standard model combination techniques. We apply our approach to data from a study to evaluate a collection of BRCA1/BRCA2 gene mutation prediction scores. In this example, genotype is measured with error by one or more genetic assays. We estimate true genotype for each individual in the dataset, operating characteristics of the commonly used genotyping procedures and a relative weighting of the scores. Finally, we compare the scores against the gold standard genotype and find that Mendelian scores are, on average, the more refined and better calibrated of those considered and that the comparison is sensitive to measurement error in the gold standard

The invisible maze task (IMT): Interactive exploration of sparse virtual environments to investigate action-driven formation of spatial representations

© Springer Nature Switzerland AG 2018. The neuroscientific study of human navigation has been constrained by the prerequisite of traditional brain imaging studies that require participants to remain stationary. Such imaging approaches neglect a central component that characterizes navigation - the multisensory experience of self-movement. Navigation by active movement through space combines multisensory perception with internally generated self-motion cues. We investigated the spatial microgenesis during free ambulatory exploration of interactive sparse virtual environments using motion capture synchronized to high resolution electroencephalographic (EEG) data as well AS psychometric and self-report measures. In such environments, map-like allocentric representations must be constructed out of transient, egocentric first-person perspective 3-D spatial information. Considering individual differences of spatial learning ability, we studied if changes in exploration behavior coincide with spatial learning of an environment. To this end, we analyzed the quality of sketch maps (a description of spatial learning) that were produced after repeated learning trials for differently complex maze environments. We observed significant changes in active exploration behavior from the first to the last exploration of a maze: a decrease in time spent in the maze predicted an increase in subsequent sketch map quality. Furthermore, individual differences in spatial abilities as well as differences in the level of experienced immersion had an impact on the quality of spatial learning. Our results demonstrate converging evidence of observable behavioral changes associated with spatial learning in a framework that allows the study of cortical dynamics of navigation

Protocol for a 20-year follow-up after a randomized controlled trial of a Mediterranean diet in pregnancy:maternal and offspring risk factors for cardiovascular disease

Background: An inadequate maternal diet during pregnancy can impair offspring health and may increase the risk of cardiovascular disease later in life. The purpose of the proposed study is to assess the risk factors associated with cardiovascular disease in both mothers and their offspring 20 years following their participation in a Mediterranean diet intervention trial during pregnancy.Methods: The “Cardiovascular Risk Reduction Diet In Pregnancy” (CARRDIP) study was a randomized controlled trial performed between 1999 and 2001. The participants were randomized to adhere to either a Mediterranean diet or their regular diet during pregnancy. An extensive amount of data such as diet information, ultrasound measurements, anthropometry, and biomarkers from these mothers during pregnancy and their offspring in the neonatal period were collected. The mother–offspring pairs (n = 269) from the CARRDIP study will be invited to participate in a clinical examination and blood sample collection. This follow-up study, conducted 20 years after the original CARRDIP study, will investigate cardiovascular risk factors in mothers and offspring. The primary outcome will be the blood pressure of the offspring. In addition, the study will explore various aspects of cardiovascular health, including metabolic and inflammatory status, clinical history, and body composition of the participants.Discussion: Previous studies investigating the effects of nutrition during pregnancy on maternal and offspring health have been either observational studies, animal studies, or randomized controlled trials with a follow-up period of less than 5 years. This project aims to study the long-term effects of dietary intervention during pregnancy on maternal and offspring cardiovascular risk markers.Clinical Trial Registration: Clinicaltrials.gov, identifier (NCT05030922)

Capsular profiling of the Cronobacter genus and the association of specific Cronobacter sakazakii and C. malonaticus capsule types with neonatal meningitis and necrotizing enterocolitis

Background: Cronobacter sakazakii and C. malonaticus can cause serious diseases especially in infants where they are associated with rare but fatal neonatal infections such as meningitis and necrotising enterocolitis. Methods: This study used 104 whole genome sequenced strains, covering all seven species in the genus, to analyse capsule associated clusters of genes involved in the biosynthesis of the O-antigen, colanic acid, bacterial cellulose, enterobacterial common antigen (ECA), and a previously uncharacterised K-antigen. Results: Phylogeny of the gnd and galF genes flanking the O-antigen region enabled the defining of 38 subgroups which are potential serotypes. Two variants of the colanic acid synthesis gene cluster (CA1 and CA2) were found which differed with the absence of galE in CA2. Cellulose (bcs genes) were present in all species, but were absent in C. sakazakii sequence type (ST) 13 and clonal complex (CC) 100 strains. The ECA locus was found in all strains. The K-antigen capsular polysaccharide Region 1 (kpsEDCS) and Region 3 (kpsMT) genes were found in all Cronobacter strains. The highly variable Region 2 genes were assigned to 2 homology groups (K1 and K2). C. sakazakii and C. malonaticus isolates with capsular type [K2:CA2:Cell+] were associated with neonatal meningitis and necrotizing enterocolitis. Other capsular types were less associated with clinical infections. Conclusion: This study proposes a new capsular typing scheme which identifies a possible important virulence trait associated with severe neonatal infections. The various capsular polysaccharide structures warrant further investigation as they could be relevant to macrophage survival, desiccation resistance, environmental survival, and biofilm formation in the hospital environment, including neonatal enteral feeding tubes

Corticosterone Potentiation of Cocaine-Induced Reinstatement of Conditioned Place Preference in Mice is Mediated by Blockade of the Organic Cation Transporter 3

The mechanisms by which stressful life events increase the risk of relapse in recovering cocaine addicts are not well understood. We previously reported that stress, via elevated corticosterone, potentiates cocaine-primed reinstatement of cocaine seeking following self-administration in rats and that this potentiation appears to involve corticosterone-induced blockade of dopamine clearance via the organic cation transporter 3 (OCT3). In the present study, we use a conditioned place preference/reinstatement paradigm in mice to directly test the hypothesis that corticosterone potentiates cocaine-primed reinstatement by blockade of OCT3. Consistent with our findings following self-administration in rats, pretreatment of male C57/BL6 mice with corticosterone (using a dose that reproduced stress-level plasma concentrations) potentiated cocaine-primed reinstatement of extinguished cocaine-induced conditioned place preference. Corticosterone failed to re-establish extinguished preference alone but produced a leftward shift in the dose–response curve for cocaine-primed reinstatement. A similar potentiating effect was observed upon pretreatment of mice with the non-glucocorticoid OCT3 blocker, normetanephrine. To determine the role of OCT3 blockade in these effects, we examined the abilities of corticosterone and normetanephrine to potentiate cocaine-primed reinstatement in OCT3-deficient and wild-type mice. Conditioned place preference, extinction and reinstatement of extinguished preference in response to low-dose cocaine administration did not differ between genotypes. However, corticosterone and normetanephrine failed to potentiate cocaine-primed reinstatement in OCT3-deficient mice. Together, these data provide the first direct evidence that the interaction of corticosterone with OCT3 mediates corticosterone effects on drug-seeking behavior and establish OCT3 function as an important determinant of susceptibility to cocaine use

The prevalence of common mental disorders and PTSD in the UK military: using data from a clinical interview-based study

<p>Abstract</p> <p>Background</p> <p>The mental health of the Armed Forces is an important issue of both academic and public interest. The aims of this study are to: a) assess the prevalence and risk factors for common mental disorders and post traumatic stress disorder (PTSD) symptoms, during the main fighting period of the Iraq War (TELIC 1) and later deployments to Iraq or elsewhere and enlistment status (regular or reserve), and b) compare the prevalence of depression, PTSD symptoms and suicidal ideation in regular and reserve UK Army personnel who deployed to Iraq with their US counterparts.</p> <p>Methods</p> <p>Participants were drawn from a large UK military health study using a standard two phase survey technique stratified by deployment status and engagement type. Participants undertook a structured telephone interview including the Patient Health Questionnaire (PHQ) and a short measure of PTSD (Primary Care PTSD, PC-PTSD). The response rate was 76% (821 participants).</p> <p>Results</p> <p>The weighted prevalence of common mental disorders and PTSD symptoms was 27.2% and 4.8%, respectively. The most common diagnoses were alcohol abuse (18.0%) and neurotic disorders (13.5%). There was no health effect of deploying for regular personnel, but an increased risk of PTSD for reservists who deployed to Iraq and other recent deployments compared to reservists who did not deploy. The prevalence of depression, PTSD symptoms and subjective poor health were similar between regular US and UK Iraq combatants.</p> <p>Conclusion</p> <p>The most common mental disorders in the UK military are alcohol abuse and neurotic disorders. The prevalence of PTSD symptoms remains low in the UK military, but reservists are at greater risk of psychiatric injury than regular personnel.</p

Synchronization to a bouncing ball with a realistic motion trajectory

Daily music experience involves synchronizing movements in time with a perceived periodic beat. It has been established for over a century that beat synchronization is less stable for the visual than for the auditory modality. This auditory advantage of beat synchronization gives rise to the hypotheses that the neural and evolutionary mechanisms underlying beat synchronization are modality-specific. Here, however, we found that synchronization to a periodically bouncing ball with a realistic motion trajectory was not less stable than synchronization to an auditory metronome. This finding challenges the auditory advantage of beat synchronization, and has important implications for the understanding of the biological substrates of beat synchronization

Open Science principles for accelerating trait-based science across the Tree of Life.

Synthesizing trait observations and knowledge across the Tree of Life remains a grand challenge for biodiversity science. Species traits are widely used in ecological and evolutionary science, and new data and methods have proliferated rapidly. Yet accessing and integrating disparate data sources remains a considerable challenge, slowing progress toward a global synthesis to integrate trait data across organisms. Trait science needs a vision for achieving global integration across all organisms. Here, we outline how the adoption of key Open Science principles-open data, open source and open methods-is transforming trait science, increasing transparency, democratizing access and accelerating global synthesis. To enhance widespread adoption of these principles, we introduce the Open Traits Network (OTN), a global, decentralized community welcoming all researchers and institutions pursuing the collaborative goal of standardizing and integrating trait data across organisms. We demonstrate how adherence to Open Science principles is key to the OTN community and outline five activities that can accelerate the synthesis of trait data across the Tree of Life, thereby facilitating rapid advances to address scientific inquiries and environmental issues. Lessons learned along the path to a global synthesis of trait data will provide a framework for addressing similarly complex data science and informatics challenges