Magnetic Resonance Imaging to Detect Early Molecular and Cellular Changes in Alzheimer’s Disease

Recent pharmaceutical trials have demonstrated that slowing or reversing pathology in Alzheimer's disease is likely to be possible only in the earliest stages of disease, perhaps even before significant symptoms develop. Pathology in Alzheimer's disease accumulates for well over a decade before symptoms are detected giving a large potential window of opportunity for intervention. It is therefore important that imaging techniques detect subtle changes in brain tissue before significant macroscopic brain atrophy. Current diagnostic techniques often do not permit early diagnosis or are too expensive for routine clinical use. Magnetic Resonance Imaging (MRI) is the most versatile, affordable, and powerful imaging modality currently available, being able to deliver detailed analyses of anatomy, tissue volumes, and tissue state. In this mini-review, we consider how MRI might detect patients at risk of future dementia in the early stages of pathological change when symptoms are mild. We consider the contributions made by the various modalities of MRI (structural, diffusion, perfusion, relaxometry) in identifying not just atrophy (a late-stage AD symptom) but more subtle changes reflective of early dementia pathology. The sensitivity of MRI not just to gross anatomy but to the underlying “health” at the cellular (and even molecular) scales, makes it very well suited to this task

Identifying Priority and “Bright-Spot” Counties for Diabetes Preventive Care in Appalachia: An Exploratory Analysis

Introduction: Type 2 diabetes mellitus (T2DM) prevalence and mortality in Appalachian counties is substantially higher when compared to non-Appalachian counties, although there is significant variation within Appalachia. Purpose: The objectives of this research were to identify low-performing (priority) and high-performing (bright spot) counties with respect to improving T2DM preventive care. Methods: Using data from the Centers for Medicare and Medicaid (CMS), the Dartmouth Atlas of Health Care, and the Appalachia Regional Commission, conditional maps were created using county-level estimates for T2DM prevalence, mortality, and annual hemoglobin A1c (HbA1c) testing rates. Priority counties were identified using the following criteria: top 33rd percentile for T2DM mortality; top 33rd percentile for T2DM prevalence; bottom 50th percentile for A1c testing rates. Bright spot counties were identified as counties in the bottom 33rd percentile for T2DM mortality, the top 33rd percentile for T2DM prevalence; and the top 50th percentile for HbA1c testing rates. Results: Forty-one priority counties were identified (those with high T2DM mortality, high T2DM prevalence, and low HbA1c testing rates), which were located primarily in Central and North Central Appalachia; and 17 bright spot counties were identified (high T2DM prevalence, low T2DM mortality, and high HbA1c testing rates), which were scattered throughout Appalachia. Eight of the 17 bright spot counties were adjacent to priority counties. Implications: By employing conditional mapping to T2DM, multiple variables can be summarized into a single, easily interpretable map. This could be valuable for T2DM-prevention programs seeking to prioritize diagnostic and intervention resources for the management of T2DM in Appalachia

Evidence synthesis for constructing directed acyclic graphs (ESC-DAGs): a novel and systematic method for building directed acyclic graphs

Background: Directed acyclic graphs (DAGs) are popular tools for identifying appropriate adjustment strategies for epidemiological analysis. However, a lack of direction on how to build them is problematic. As a solution, we propose using a combination of evidence synthesis strategies and causal inference principles to integrate the DAG-building exercise within the review stages of research projects. We demonstrate this idea by introducing a novel protocol: ‘Evidence Synthesis for Constructing Directed Acyclic Graphs’ (ESC-DAGs)’.\ud Methods: ESC-DAGs operates on empirical studies identified by a literature search, ideally a novel systematic review or review of systematic reviews. It involves three key stages: (i) the conclusions of each study are ‘mapped’ into a DAG; (ii) the causal structures in these DAGs are systematically assessed using several causal inference principles and are corrected accordingly; (iii) the resulting DAGs are then synthesised into one or more ‘integrated DAGs’. This demonstration article didactically applies ESC-DAGs to the literature on parental influences on offspring alcohol use during adolescence. Conclusions: ESC-DAGs is a practical, systematic and transparent approach for developing DAGs from background knowledge. These DAGs can then direct primary data analysis and DAG-based sensitivity analysis. ESC-DAGs has a modular design to allow researchers who are experienced DAG users to both use and improve upon the approach. It is also accessible to researchers with limited experience of DAGs or evidence synthesis

The limits of LoRaWAN in event-triggered wireless networked control systems

Wireless sensors and actuators offer benefits to large industrial control systems. The absence of wires for communication reduces the deployment cost, maintenance effort, and provides greater flexibility for sensor and actuator location and system architecture. These benefits come at a cost of a high probability of communication delay or message loss due to the unreliability of radio-based communication. This unreliability poses a challenge to contemporary control systems that are designed with the assumption of instantaneous and reliable communication. Wireless sensors and actuators create a paradigm shift in engineering energy-efficient control schemes coupled with robust communication schemes that can maintain system stability in the face of unreliable communication. This paper investigates the feasibility of using the low-power wide-area communication protocol LoRaWAN with an event-triggered control scheme through modelling in Matlab. We show that LoRaWAN is capable of meeting the maximum delay and message loss requirements of an event-triggered controller for certain classes of applications. We also expose the limitation in the use of LoRaWAN when message size or communication range requirements increase or the underlying physical system is exposed to significant external disturbances

ChIP on SNP-chip for genome-wide analysis of human histone H4 hyperacetylation

<p>Abstract</p> <p>Background</p> <p>SNP microarrays are designed to genotype Single Nucleotide Polymorphisms (SNPs). These microarrays report hybridization of DNA fragments and therefore can be used for the purpose of detecting genomic fragments.</p> <p>Results</p> <p>Here, we demonstrate that a SNP microarray can be effectively used in this way to perform chromatin immunoprecipitation (ChIP) on chip as an alternative to tiling microarrays. We illustrate this novel application by mapping whole genome histone H4 hyperacetylation in human myoblasts and myotubes. We detect clusters of hyperacetylated histone H4, often spanning across up to 300 kilobases of genomic sequence. Using complementary genome-wide analyses of gene expression by DNA microarray we demonstrate that these clusters of hyperacetylated histone H4 tend to be associated with expressed genes.</p> <p>Conclusion</p> <p>The use of a SNP array for a ChIP-on-chip application (ChIP on SNP-chip) will be of great value to laboratories whose interest is the determination of general rules regarding the relationship of specific chromatin modifications to transcriptional status throughout the genome and to examine the asymmetric modification of chromatin at heterozygous loci.</p

Wrinkle initiation and development in heated webs on drums

Wrinkles often occur in webs heated on drums and rollers. Anecdotal evidence from vacuum metalizers suggests that wrinkles are initiated by small grit particles or surface imperfections that lift the web off the drum. An elliptical patch of web centered on the dirt particle is lifted off the drum against the tension pressure acting to restore contact. A numerical "tent model", based on plate theory, has been formulated to predict the critical transverse direction (TD) stress at which the web spontaneously lifts off the grit, forming the wrinkle. The model iterates to find the tent shape for a given TD stress, and then uses an interval halving method to determine the critical TD stress. Results from the model will be presented. It turns out that a simpler, analytical "draped beam" model gives similar dependence on parameters but over-predicts the value.Once a wrinkle initiates, it may grow to a size where it is more visible, but has limited length and is restrained against further growth. Further increase in compression enables it to grow by relieving the TD compressive stress in both the lifted-off region and the neighboring web still in contact with the drum. It will also extend in the machine direction (MD). In vacuum coating, wrinkling causes a loss in thermal contact with the cooled drum, the web heats up, expands and the wrinkle grows catastrophically