The ongoing dissection of the genetic architecture of autistic spectrum disorder

The development of robust, non-hypothesis based case/control studies has led to a large push forward towards identifying common genetic variants that contribute to complex traits. However, despite many attempts, the search for common disease-predisposing variants in childhood developmental disorders has largely failed. Recently, a role for rare causal variants and de novo mutations is emerging in the genetic architecture of some of these disorders, particularly those that incur a large degree of selection against the phenotype. In this paper, we examine these data and use classic genetic epidemiological approaches to gain insights into the genetic architecture of ASD. Future studies using next generation sequencing should elucidate the precise role de novo mutations play in disorders traditionally thought to have resulted from polygenic or common disease, common variants inheritance

Phase transitions and magnetic domain coexistence in Nd0.5Sr0.5MnO3 thin films

We present a study of the physical properties of perovskite oxide Nd0.5Sr0.5MnO3 (NSMO) thin films grown on (110)-oriented SrTiO3 substrates. In bulk form, NSMO displays coupled magnetic and electronic transitions from paramagnetic/insulator to ferromagnetic (FM)/metal and then to antiferromagnetic (AFM)/charge-ordered insulator with decreasing temperature. In thin films, the AFM ordering only occurs when the films exist in an anisotropic strain state such as those obtained on (110)-oriented cubic substrates. In this work, resonant X-ray reflectivity, soft X-ray photoemission electron microscopy (X-PEEM), and magnetometry measurements showed that the NSMO film displays both vertical and lateral magnetic phase separation. Specifically, the film consists of three layers with different density and magnetic properties. The FM and AFM properties of the main NSMO layer were probed as a function of temperature using soft X-ray magnetic spectroscopy, and the coexistence of lateral FM and AFM domains was demonstrated at 110 K using X-PEEM

Functional neuroimaging of post-mortem tissue: lithium-pilocarpine seized rats express reduced brain mass and proportional reductions of left ventral cerebral theta spectral power

AbstractStructural imaging tools can be used to identify neuropathology in post-mortem tissue whereas functional imaging tools including quantitative electroencephalography (QEEG) are thought to be restricted for use in living subjects. We are not aware of any study which has used electrophysiological methods decades after death to infer pathology. We therefore attempted to discriminate between chemically preserved brains which had incurred electrical seizures and those that did not using functional imaging. Our data indicate that modified QEEG technology involving needle electrodes embedded within chemically fixed neural tissue can be used to discriminate pathology. Forty (n = 40) rat brains preserved in ethanol-formalin-acetic acid (EFA) were probed by needle electrodes inserted into the dorsal and ventral components of the left and right cerebral hemispheres. Raw microvolt potentials were converted to spectral power densities within classical electroencephalographic frequency bands (1.5 Hz to 40 Hz). Brain mass differences were shown to scale with left hemispheric ventral theta-band spectral power densities in lithium-pilocarpine seized rats. This relationship was not observed in non-seized rats. A conspicuous absence of pathological indicators within dorsal regions as inferred by microvolt fluctuations was expected given the known localization of post-ictal damage in lithium-pilocarpine seized rats. Together, the data demonstrate that post-mortem neuroimaging is both possible and potentially useful as a means to identify neuropathology without structural imaging techniques or dissection

Developing conceptual hydrogeological model for Potsdam sandstones in southwestern Quebec, Canada

A hydrogeological study was conducted in Potsdam sandstones on the international border between Canada (Quebec) and the USA (New York). Two sandstone formations, arkose and conglomerate (base) and well-cemented quartz arenite (upper), underlie the study area and form the major regional aquifer unit. Glacial till, littoral sand and gravel, and marine silt and clay discontinuously overlie the aquifer. In both sandstone formations, sub-horizontal bedding planes are ubiquitous and display significant hydraulic conductivities that are orders of magnitude more permeable than the intact rock matrix. Aquifer tests demonstrate that the two formations have similar bulk hydrologic properties, with average hydraulic conductivities ranging from 2×10−5 to 4×10−5 m/s. However, due to their different lithologic and structural characteristics, these two sandstones impose rather different controls on groundwater flow patterns in the study area. Flow is sustained through two types of fracture networks: sub-horizontal, laterally extensive fractures in the basal sandstone, where hydraulic connectivity is very good horizontally but very poor vertically and each of the water-bearing bedding planes can be considered as a separate planar two-dimensional aquifer unit; and the more fractured and vertically jointed system found in the upper sandstone that promotes a more dispersed, three-dimensional movement of groundwater. Une étude hydrogéologique a été entreprise dans les grès de Potsdam, sur la frontière entre le Canada (Québec) et les Etats-Unis (New York). Sous le secteur d’étude, deux formations gréseuses, les arkoses et conglomérats (base) et les arénites quartzeuses cimentées (sommet), forment une unité aquifère majeure à l’échelle régionale. Les moraines glaciaires, les sables et graviers littoraux, et les argiles et silts marins recouvrent l’aquifère de manière discontinue. Dans les deux formations gréseuses, les litages sub-horizontaux sont omniprésents, et présentent des conductivités hydrauliques significatives, supérieures de plusieurs ordres de grandeur à celles de la matrice rocheuse intacte. Les pompages d’essai démontrent que les deux formations ont des propriétés hydrologiques apparentes comparables, avec notamment des conductivités hydrauliques comprises entre 2×10−5 et 4× 10−5 m/s. Cependant, du fait de leurs lithologies et de leurs caractéristiques structurales contrastées, ces deux formations gréseuses imposent des contrôles différents sur les écoulements souterrains dans le secteur d’étude. L’écoulement est soutenu par deux types de réseaux de fractures : des fractures latéralement extensives subhorizontales dans les grès de base, où la connectivité hydraulique est très bonne horizontalement mais médiocre verticalement, et où chacun des plans aquifères peut être considéré comme une unité aquifère isolée plane bidimensionnelle, et un système fissuré verticalement et plus fracturé situé dans les grès supérieurs, qui favorise des écoulements souterrains tridimensionnels et plus dispers

Improving the Management and Monitoring of the Clinical Experiences of Nurse Practitioner Learners

The transition of the degree requirements for nurse practitioners from a master’s degree (MS) to a doctor of nursing practice (DNP) degree will deliver a workforce of advanced practice nurses with the knowledge and skills necessary to meet the complex health care needs of patients and populations. The Institute of Medicine (2010) has forecasted an impending shortage of nurses by 2020, and one of the major challenges facing educational programs is lack of training sites. The shortage of quality clinical sites and experiences for students in primary care is a national challenge as well as a local challenge (AACN, 2014). While creating different clinical opportunities is an important element in the DNP program, another challenge faced by faculty is the ability to assess the students’ clinical learning experiences throughout the program. Historically, programs have maintained manual paper processes for clinical time tracking, logs, preceptor evaluations, and clinical instructor evaluations that limit the ability of the faculty to review individual student experiences. This method of tracking is not easily accessible to faculty or clinical preceptors, making it difficult to review progress and evaluate throughout the clinical experiences. In order for faculty to better assess the quality of the clinical experiences and to improve the process of communication with clinical preceptors, the University of Vermont (UVM) graduate nurse practitioner program implemented a centralized clinical tracking system that students utilize to document their experiences, preceptors utilize to complete evaluations, and faculty use to get a real-time understanding of student’s experiences throughout the semester and the program. The purpose of this project was to improve faculty insight to DNP students’ clinical experiences. Through a pilot implementation with the first cohort of DNP students in their initial clinical course (GRNS 408), the project was developed to provide the graduate program with tools to streamline the student’s tracking of clinical experiences, improve the preceptor evaluation of the student process, create reports to evaluate the students’ clinical experiences, and facilitate communication among the student, faculty, and clinical preceptors. The approach used to identify the impact of the intervention on the insights of the clinical faculty and how it relates to the clinical experiences of the DNP learners was a frequent retrospective data review process. Additionally, to control the rate of change of the intervention and ensure that the outcomes were linked to the intervention, we used a rapid cycle improvement process. The outcomes measured following implementation included review of the reports in the program throughout the semester, and the feedback from the users at the end of semester survey. The pilot phase of the project that changed the logging and evaluation of UVM DNP learners from a manual to an automated process was successful. With limited training for learners, preceptors and faculty, the project was able to provide easy tools for learners to log clinical experiences and for preceptors to evaluate students. With access to the data in real-time, the clinical faculty were able to get a snapshot of the clinical experiences every few weeks, and use that information to create meaningful discussions during clinical seminar time, and objectively evaluate the learner at specific points in time through the semester as well as an objective final faculty evaluation

Amyotrophic lateral sclerosis: new genes, new models, and new mechanisms

Research aimed at understanding amyotrophic lateral sclerosis (ALS) has seen exceptional growth in the past few years. New genes, new models, and new mechanisms have not only improved our understanding, but also contributed to the increasing complexity of ALS pathogenesis. The focus of this piece is to highlight some of the more notable developments in the field and to encourage a re-appreciation for the superoxide dismutase 1 (SOD1) mouse models

The development of 3-D, in vitro, endothelial culture models for the study of coronary artery disease

The response of the vascular endothelium to wall shear stress plays a central role in the development and progression of atherosclerosis. Current studies have investigated endothelial response using idealized in vitro flow chambers. Such cell culture models are unable to accurately replicate the complex in vivo wall shear stress patterns arising from anatomical geometries. To better understand this implication, we have created both simplified/tubular and anatomically realistic in vitro endothelial flow models of the human right coronary artery. A post-mortem vascular cast of the human left ventricular outflow tract was used to create geometrically accurate silicone elastomer models. Straight, tubular models were created using a custom made mold. Following the culture of human abdominal aortic endothelial cells within the inner lumen, cells were exposed to steady flow (Re = 233) for varying time periods. The resulting cell morphology was analyzed in terms of shape index and angle of orientation relative to the flow direction. In both models a progressive elongation and alignment of the endothelium in the flow direction was observed following 8, 12, and 24 hours. This change, however, was significantly less pronounced in the anatomical model (as observed from morphological variations indicative of localized flow features). Differences were also observed between the inner and outer walls at the disease-prone proximal region. Since morphological adaptation is a visual indication of endothelial shear stress activation, the use of anatomical models in endothelial genetic and biochemical studies may offer better insight into the disease process