Dynamic Bayesian belief network to model the development of walking and cycling schemes

This paper aims to describe a model which represents the formulation of decision-making processes (over a number of years) affecting the step-changes of walking and cycling (WaC) schemes. These processes can be seen as being driven by a number of causal factors, many of which are associated with the attitudes of a variety of factors, in terms of both determining whether any scheme will be implemented and, if it is implemented, the extent to which it is used. The outputs of the model are pathways as to how the future might unfold (in terms of a number of future time steps) with respect to specific pedestrian and cyclist schemes. The transitions of the decision making processes are formulated using a qualitative simulation method, which describes the step-changes of the WaC scheme development. In this article a Bayesian belief network (BBN) theory is extended to model the influence between and within factors in the dynamic decision making process

Neuronal birthdate reveals topography in a vestibular brainstem circuit for gaze stabilization

Across the nervous system, neurons with similar attributes are topographically organized. This topography reflects developmental pressures. Oddly, vestibular (balance) nuclei are thought to be disorganized. By measuring activity in birthdated neurons, we revealed a functional map within the central vestibular projection nucleus that stabilizes gaze in the larval zebrafish. We first discovered that both somatic position and stimulus selectivity follow projection neuron birthdate. Next, with electron microscopy and loss-of-function assays, we found that patterns of peripheral innervation to projection neurons were similarly organized by birthdate. Finally, birthdate revealed spatial patterns of axonal arborization and synapse formation to projection neuron outputs. Collectively, we find that development reveals previously hidden organization to the input, processing, and output layers of a highly conserved vertebrate sensorimotor circuit. The spatial and temporal attributes we uncover constrain the developmental mechanisms that may specify the fate, function, and organization of vestibulo-ocular reflex neurons. More broadly, our data suggest that, like invertebrates, temporal mechanisms may assemble vertebrate sensorimotor architecture

Prospective validation of a checklist to predict short-term death in older patients after emergency department admission in Australia and Ireland

Abstract Background Emergency departments (EDs) are pressured environment where patients with supportive and palliative care needs may not be identified. We aimed to test the predictive ability of the CriSTAL (Criteria for Screening and Triaging to Appropriate aLternative care) checklist to flag patients at risk of death within 3 months who may benefit from timely end-of-life discussions. Methods Prospective cohorts of >65-year-old patients admitted for at least one night via EDs in five Australian hospitals and one Irish hospital. Purpose-trained nurses and medical students screened for frailty using two instruments concurrently and completed the other risk factors on the CriSTAL tool at admission. Postdischarge telephone follow-up was used to determine survival status. Logistic regression and bootstrapping techniques were used to test the predictive accuracy of CriSTAL for death within 90 days of admission as primary outcome. Predictability of in-hospital death was the secondary outcome. Results A total of 1,182 patients, with median age 76 to 80 years (IRE-AUS), were included. The deceased had significantly higher mean CriSTAL with Australian mean of 8.1 (95% confidence interval [CI] = 7.7–8.6) versus 5.7 (95% CI = 5.1–6.2) and Irish mean of 7.7 (95% CI = 6.9–8.5) versus 5.7 (95% CI = 5.1–6.2). The model with Fried frailty score was optimal for the derivation (Australian) cohort but prediction with the Clinical Frailty Scale (CFS) was also good (areas under the receiver-operating characteristic [AUROC] = 0.825 and 0.81, respectively). Values for the validation (Irish) cohort were AUROC = 0.70 with Fried and 0.77 using CFS. A minimum of five of 29 variables were sufficient for accurate prediction, and a cut point of 7+ or 6+ depending on the cohort was strongly indicative of risk of death. The most significant independent predictor of short-term death in both cohorts was frailty, carrying a twofold risk of death. CriSTAL's accuracy for in-hospital death prediction was also good (AUROC = 0.795 and 0.81 in Australia and Ireland, respectively), with high specificity and negative predictive values. Conclusions The modified CriSTAL tool (with CFS instead of Fried's frailty instrument) had good discriminant power to improve certainty of short-term mortality prediction in both health systems. The predictive ability of models is anticipated to help clinicians gain confidence in initiating earlier end-of-life discussions. The practicalities of embedding screening for risk of death in routine practice warrant further investigation

Severe Little Ice Age drought in the midcontinental United States during the Mississippian abandonment of Cahokia

Drought has long been suspected as playing an important role in the abandonment of pre-Columbian Native American settlements across the midcontinental United States between 1350 and 1450 CE. However, high-resolution paleoclimatic reconstructions reflecting local effective moisture (the ratio of precipitation to evaporation) that are located in proximity to Mississippi period (1050–1450 CE) population centers are lacking. Here, we present a 1600-year-long decadally resolved oxygen isotope (δ18O) record from Horseshoe Lake (Collinsville, IL), an evaporatively influenced oxbow lake that is centrally located within the largest and mostly densely populated series of Mississippian settlements known as Greater Cahokia. A shift to higher δ18O in the Horseshoe Lake sediment record from 1200 to 1400 CE indicates that strongly evaporative conditions (i.e., low effective moisture) were persistent during the leadup to Cahokia’s abandonment. These results support the hypothesis that climate, and drought specifically, strongly impacted agriculturally based pre-Columbian Native American cultures in the midcontinental US and highlights the susceptibility of this region, presently a global food production center, to hydroclimate extremes

Associations of variants In the hexokinase 1 and interleukin 18 receptor regions with oxyhemoglobin saturation during sleep

Sleep disordered breathing (SDB)-related overnight hypoxemia is associated with cardiometabolic disease and other comorbidities. Understanding the genetic bases for variations in nocturnal hypoxemia may help understand mechanisms influencing oxygenation and SDB-related mortality. We conducted genome-wide association tests across 10 cohorts and 4 populations to identify genetic variants associated with three correlated measures of overnight oxyhemoglobin saturation: average and minimum oxyhemoglobin saturation during sleep and the percent of sleep with oxyhemoglobin saturation under 90%. The discovery sample consisted of 8,326 individuals. Variants with p −6 were analyzed in a replication group of 14,410 individuals. We identified 3 significantly associated regions, including 2 regions in multi-ethnic analyses (2q12, 10q22). SNPs in the 2q12 region associated with minimum SpO2 (rs78136548 p = 2.70 × 10−10). SNPs at 10q22 were associated with all three traits including average SpO2 (rs72805692 p = 4.58 × 10−8). SNPs in both regions were associated in over 20,000 individuals and are supported by prior associations or functional evidence. Four additional significant regions were detected in secondary sex-stratified and combined discovery and replication analyses, including a region overlapping Reelin, a known marker of respiratory complex neurons.These are the first genome-wide significant findings reported for oxyhemoglobin saturation during sleep, a phenotype of high clinical interest. Our replicated associations with HK1 and IL18R1 suggest that variants in inflammatory pathways, such as the biologically-plausible NLRP3 inflammasome, may contribute to nocturnal hypoxemia

The ENCODE Project at UC Santa Cruz

The goal of the Encyclopedia Of DNA Elements (ENCODE) Project is to identify all functional elements in the human genome. The pilot phase is for comparison of existing methods and for the development of new methods to rigorously analyze a defined 1% of the human genome sequence. Experimental datasets are focused on the origin of replication, DNase I hypersensitivity, chromatin immunoprecipitation, promoter function, gene structure, pseudogenes, non-protein-coding RNAs, transcribed RNAs, multiple sequence alignment and evolutionarily constrained elements. The ENCODE project at UCSC website () is the primary portal for the sequence-based data produced as part of the ENCODE project. In the pilot phase of the project, over 30 labs provided experimental results for a total of 56 browser tracks supported by 385 database tables. The site provides researchers with a number of tools that allow them to visualize and analyze the data as well as download data for local analyses. This paper describes the portal to the data, highlights the data that has been made available, and presents the tools that have been developed within the ENCODE project. Access to the data and types of interactive analysis that are possible are illustrated through supplemental examples

Regionally consistent Western North America paleomagnetic directions from 15 to 35 ka: Assessing chronology and uncertainty with paleosecular variation (PSV) stratigraphy

New Paleomagnetic Secular Variation (PSV) data from Fish Lake, Utah, USA, along with previously published regional records, allow us to build an independently dated Western North America PSV stack (WNAM17) from about 35 to 15 ka that quantifies dating and paleomagnetic uncertainties. In February 2014, we recovered a composite 11-m-long sediment record from Fish Lake, Utah that retrieved glacially influenced and post-glacial sediments. Computed tomography (CT) scans and magnetic susceptibility were used to build a precise depth scale, while radiocarbon dating of terrestrial macrofossils and tephrostratigraphy provide tight age-control. Glacially influenced sediments have well-defined characteristic remanent magnetizations with all maximum angular deviation values < 5 degrees, resolving a record of Late Pleistocene PSV. Comparison to the PSV records at Bear Lake, Utah/Idaho, USA and Bessette Creak, British Columbia, Canada, which also contain terrestrial material radiocarbon age-control points, allow us to develop the WNAM17 PSV stack which considers both dating and magnetic acquisition uncertainties. We utilize a regional PSV chronostratigraphic modeling approach to assign chronology and uncertainty to the PSV signal and to evaluate the fidelity of age-control points at the site level that are difficult to objectively evaluate otherwise. The greatest strength of our age-depth model is that by approaching chronostratigraphy from a regional perspective, assuming a common geomagnetic signal, we can address sources of geologic uncertainty that would be difficult to quantify using only one site. We illustrate the potential stratigraphic opportunities using the WNAM17 PSV template through assessing the timing of paleoenvironmental and paleomagnetic events in Western North America, including the timing of glaciations in the Fish Lake and Bear Lake catchments and the stratigraphic context for the Late Pleistocene geomagnetic excursion recorded at Mono Lake. (C) 2018 Elsevier Ltd. All rights reserved