In vivo "real-time" monitoring of glucose in the brain with an amperometric enzyme-based biosensor based on gold coated tungsten (W-Au) microelectrodes

Biosensors based on Pt or Pt/Ir based needle-type microelectrodes have been successfully employed for continuous in vivo real-time brain biomonitoring of biomarkers such as glutamate and glucose. However, when implanted, these biosensors often bend, thereby damaging its surface and degrading its bioanalytical properties. In addition, downscaling of Pt and Pt/Ir needle-type biosensors, to improve the spatial resolution and decrease tissue damage, is technically challenging. In that sense, we investigated whether the use of a material with low malleability, tungsten (W), coated with a highly conductive material, gold (Au) could be as an alternative for conventional needle-type based biosensors. Therefore, we developed implantable needle-type (50 tim 0) gold coated tungsten (W-Au) amperometric microbiosensors. First, we evaluated electrochemically, the ability of W-Au microelectrodes (50 tim 0) to continuously monitor changes in H2O2. After, we functionalized, using a layer-by-layer assembly, the surface of W-Au microelectrodes. First with permselective membrane(s) (Nafion and Nafion-PPD) and after with an enzymatic hydrogel, containing an enzyme selective for glucose (glucose oxidase). Both the enzyme loading and the applied potential were optimized and the performance of functionalized W-Au microelectrodes and fully assembled biosensors was evaluated electrochemically. Additionally, the surface of bare and functionalized microelectrodes was also characterized by imaging techniques (scanning electron microscopy). In vivo experiments revealed that, W-Au based glucose biosensors, were able to accurately monitor, in real-time, changes in brain glucose in response to relevant pharmacological challenges. (C) 2018 Elsevier B.V. All rights reserved

U.S. IOOS coastal and ocean modeling testbed: Evaluation of tide, wave, and hurricane surge response sensitivities to mesh resolution and friction in the Gulf of Mexico: IOOS TESTBED-RESOLUTION AND FRICTION

This paper investigates model response sensitivities to mesh resolution, topographical details, bottom friction formulations, the interaction of wind waves and circulation, and nonlinear advection on tidal and hurricane surge and wave processes at the basin, shelf, wetland, and coastal channel scales within the Gulf of Mexico. Tides in the Gulf of Mexico are modestly energetic processes, whereas hurricane surge and waves are highly energetic. The unstructured-mesh, coupled wind-wave and circulation modeling system, SWAN+ ADCIRC, is implemented to generate modeled tidal harmonic constituents and hurricane waves and surge for a Hurricane Ike (2008) hindcast. In the open ocean, mesh resolution requirements are less stringent in achieving accurate tidal signals or matching hurricane surge and wave responses; however, coarser resolution or the absence of intertidal zones decreases accuracy along protected nearshore and inland coastal areas due to improper conveyance and/or lateral attenuation. Bottom friction formulations are shown to have little impact on tidal signal accuracy, but hurricane surge is much more sensitive, especially in shelf waters, where development of a strong shore-parallel current is essential to the development of Ike's geostrophic setup. The spatial and temporal contributions of wave radiation stress gradients and nonlinear advection were charted for Ike. Nonlinear advection improves model performance by capturing an additional 10―20 cm of geostrophic setup and increasing resonant cross-shelf waves by 30―40 cm. Wave radiation stress gradients improve performance at coastal stations by adding an extra 20―40 cm to water levels

Hindcast and validation of Hurricane Ike (2008) waves, forerunner, and storm surge: HINDCAST AND VALIDATION OF HURRICANE IKE

[1] Hurricane Ike (2008) made landfall near Galveston, Texas, as a moderate intensity storm. Its large wind field in conjunction with the Louisiana‐Texas coastline's broad shelf and large scale concave geometry generated waves and surge that impacted over 1000 km of coastline. Ike's complex and varied wave and surge response physics included: the capture of surge by the protruding Mississippi River Delta; the strong influence of wave radiation stress gradients on the Delta adjacent to the shelf break; the development of strong wind driven shore‐parallel currents and the associated geostrophic setup; the forced early rise of water in coastal bays and lakes facilitating inland surge penetration; the propagation of a free wave along the southern Texas shelf; shore‐normal peak wind‐driven surge; and resonant and reflected long waves across a wide continental shelf. Preexisting and rapidly deployed instrumentation provided the most comprehensive hurricane response data of any previous hurricane. More than 94 wave parameter time histories, 523 water level time histories, and 206 high water marks were collected throughout the Gulf in deep water, along the nearshore, and up to 65 km inland. Ike's highly varied physics were simulated using SWAN + ADCIRC, a tightly coupled wave and circulation model, on SL18TX33, a new unstructured mesh of the Gulf of Mexico, Caribbean Sea, and western Atlantic Ocean with high resolution of the Gulf's coastal floodplain from Alabama to the Texas‐Mexico border. A comprehensive validation was made of the model's ability to capture the varied physics in the system

Hurricane Gustav (2008) Waves and Storm Surge: Hindcast, Synoptic Analysis, and Validation in Southern Louisiana

Hurricane Gustav (2008) made landfall in southern Louisiana on 1 September 2008 with its eye never closer than 75 km to New Orleans, but its waves and storm surge threatened to flood the city. Easterly tropical-storm-strength winds impacted the region east of the Mississippi River for 12-15 h, allowing for early surge to develop up to 3.5 m there and enter the river and the city's navigation canals. During landfall, winds shifted from easterly to southerly, resulting in late surge development and propagation over more than 70 km of marshes on the river's west bank, over more than 40 km of Caernarvon marsh on the east bank, and into Lake Pontchartrain to the north. Wind waves with estimated significant heights of 15 m developed in the deep Gulf of Mexico but were reduced in size once they reached the continental shelf. The barrier islands further dissipated the waves, and locally generated seas existed behind these effective breaking zones. The hardening and innovative deployment of gauges since Hurricane Katrina (2005) resulted in a wealth of measured data for Gustav. A total of 39 wind wave time histories, 362 water level time histories, and 82 high water marks were available to describe the event. Computational models-including a structured-mesh deepwater wave model (WAM) and a nearshore steady-state wave (STWAVE) model, as well as an unstructured-mesh "simulating waves nearshore'' (SWAN) wave model and an advanced circulation (ADCIRC) model-resolve the region with unprecedented levels of detail, with an unstructured mesh spacing of 100-200 m in the wave-breaking zones and 20-50 m in the small-scale channels. Data-assimilated winds were applied using NOAA's Hurricane Research Division Wind Analysis System (H*Wind) and Interactive Objective Kinematic Analysis (IOKA) procedures. Wave and surge computations from these models are validated comprehensively at the measurement locations ranging from the deep Gulf of Mexico and along the coast to the rivers and floodplains of southern Louisiana and are described and quantified within the context of the evolution of the storm

Assessing professionals' adoption readiness for eMental health:Development and validation of the eMental health adoption readiness scale

BACKGROUND: The last few decades have witnessed significant advances in the development of digital tools and applications for mental health care. Despite growing evidence for their effectiveness, acceptance and use of these tools in clinical practice remain low. Hence, a validated and easy-to-use instrument for assessing professionals’ readiness to adopt eMental health (EMH) is necessary to gain further insights into the process of EMH adoption and facilitate future research on this topic. OBJECTIVE: The aim of this study is to develop and validate an instrument for assessing mental health care professionals’ readiness to adopt EMH. METHODS: Item generation was guided by literature and inputs from mental health care professionals and experts in survey development. Exploratory factor analyses were conducted on an initial set of 29 items completed by a sample of mental health care professionals (N=432); thereafter, the scale was reduced to 15 items in an iterative process. The factor structure thus obtained was subsequently tested using a confirmatory factor analysis with a second sample of mental health care professionals (N=363). The internal consistency, convergent validity, and predictive validity of the eMental Health Adoption Readiness (eMHAR) Scale were assessed. RESULTS: Exploratory factor analysis resulted in a 3-factor solution with 15 items. The factors were analyzed and labeled as perceived benefits and applicability of EMH, EMH proactive innovation, and EMH self-efficacy. These factors were confirmed through a confirmatory factor analysis. The total scale and subscales showed a good internal consistency (Cronbach α=.73-.88) along with acceptable convergent and predictive relationships with related constructs. CONCLUSIONS: The constructed eMHAR Scale showed a conceptually interpretable 3-factor structure having satisfactory characteristics and relationships with relevant concepts. Its ease of use allows for quick acquisition of data that can contribute to understanding and facilitating the process of adoption of EMH by clinical professionals

On the Use of Multiple Probe Insertions at the Same Site for Repeated Intracerebral Microdialysis Experiments in the Nigrostriatal Dopamine System of Rats

The effects of implantation of a dialysis probe into the striatum of awake rats on indices of dopamine (DA) and serotonin neurotransmission were assessed, first over 24 h following initial insertion of a probe, and then again following reinsertion of a probe at the same site 1 week later. It was found that the basal concentration of DA in dialysate stabilized within 20–40 min after probe implantation, although DA showed a modest decline 24 h later. There was, however, no significant difference in basal DA between two test sessions separated by 1 week. On the other hand, the basal concentrations of the DA metabolites, 3,4-dihydroxyphenylacetic acid and homovanillic acid, progressively increased for 2–3 h after probe implantation and decreased markedly by 24 h later. Furthermore, in contrast to DA, the DA metabolites decreased even further after the second probe insertion. Amphetamine-stimulated DA release was also greatly attenuated following the second probe insertion, relative to the first probe insertion. Two probe insertions had only modest effects on the concentration of 5-hydroxyindoleacetic acid in dialysate, relative to the DA metabolites. It is suggested the effects of two probe insertions on DA metabolism and amphetamine-stimulated DA release described here are indicative of probe-induced damage to the nigrostriatal DA system. If this is the case, multiple probe insertions may not provide a feasible strategy for within-subjects design dialysis experiments over extended periods of time, at least in the DA system of small animals. It is suggested further that a stable basal concentration of DA in dialysate may be an especially poor indicator of the integrity of the dopaminergic input to the striatum.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65235/1/j.1471-4159.1992.tb10044.x.pd

Functional analysis identifies damaging CHEK2 missense variants associated with increased cancer risk.

Heterozygous carriers of germline loss-of-function variants in the tumor suppressor gene checkpoint kinase 2 (CHEK2) are at an increased risk for developing breast and other cancers. While truncating variants in CHEK2 are known to be pathogenic, the interpretation of missense variants of uncertain significance (VUS) is challenging. Consequently, many VUS remain unclassified both functionally and clinically. Here we describe a mouse embryonic stem (mES) cell-based system to quantitatively determine the functional impact of 50 missense VUS in human CHEK2. By assessing the activity of human CHK2 to phosphorylate one of its main targets, Kap1, in Chek2 knockout mES cells, 31 missense VUS in CHEK2 impaired protein function to a similar extent as truncating variants, and 9 CHEK2 missense VUS resulted in intermediate functional defects. Mechanistically, most VUS impaired CHK2 kinase function by causing protein instability or by impairing activation through (auto)phosphorylation. Quantitative results showed that the degree of CHK2 kinase dysfunction correlates with an increased risk for breast cancer. Both damaging CHEK2 variants as a group (OR 2,23; 95% CI 1,62-3,07; pG/p.D162G, was also identified, which co-segregated with familial prostate cancer. Altogether, these functional assays efficiently and reliably identified VUS in CHEK2 that associate with cancer

U.S. IOOS coastal and ocean modeling testbed : inter-model evaluation of tides, waves, and hurricane surge in the Gulf of Mexico

© The Author(s), 2013. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Journal of Geophysical Research: Oceans 118 (2013): 5129–5172, doi:10.1002/jgrc.20376.A Gulf of Mexico performance evaluation and comparison of coastal circulation and wave models was executed through harmonic analyses of tidal simulations, hindcasts of Hurricane Ike (2008) and Rita (2005), and a benchmarking study. Three unstructured coastal circulation models (ADCIRC, FVCOM, and SELFE) validated with similar skill on a new common Gulf scale mesh (ULLR) with identical frictional parameterization and forcing for the tidal validation and hurricane hindcasts. Coupled circulation and wave models, SWAN+ADCIRC and WWMII+SELFE, along with FVCOM loosely coupled with SWAN, also validated with similar skill. NOAA's official operational forecast storm surge model (SLOSH) was implemented on local and Gulf scale meshes with the same wind stress and pressure forcing used by the unstructured models for hindcasts of Ike and Rita. SLOSH's local meshes failed to capture regional processes such as Ike's forerunner and the results from the Gulf scale mesh further suggest shortcomings may be due to a combination of poor mesh resolution, missing internal physics such as tides and nonlinear advection, and SLOSH's internal frictional parameterization. In addition, these models were benchmarked to assess and compare execution speed and scalability for a prototypical operational simulation. It was apparent that a higher number of computational cores are needed for the unstructured models to meet similar operational implementation requirements to SLOSH, and that some of them could benefit from improved parallelization and faster execution speed.This project was supported by NOAA via the U.S. IOOS Office (award: NA10NOS0120063 and NA11NOS0120141

A theory of moving form perception: Synergy between masking, perceptual grouping, and motion computation in retinotopic and non-retinotopic representations

Because object and self-motion are ubiquitous in natural viewing conditions, understanding how the human visual system achieves a relatively clear perception for moving objects is a fundamental problem in visual perception. Several studies have shown that the visible persistence of a briefly presented stationary stimulus is approximately 120 ms under normal viewing conditions. Based on this duration of visible persistence, we would expect moving objects to appear highly blurred. However, in human vision, objects in motion typically appear relatively sharp and clear. We suggest that clarity of form in dynamic viewing is achieved by a synergy between masking, perceptual grouping, and motion computation across retinotopic and non-retinotopic representations. We also argue that dissociations observed in masking are essential to create and maintain this synergy

Affective Man-Machine Interface: Unveiling human emotions through biosignals

As is known for centuries, humans exhibit an electrical profile. This profile is altered through various psychological and physiological processes, which can be measured through biosignals; e.g., electromyography (EMG) and electrodermal activity (EDA). These biosignals can reveal our emotions and, as such, can serve as an advanced man-machine interface (MMI) for empathic consumer products. However, such a MMI requires the correct classification of biosignals to emotion classes. This chapter starts with an introduction on biosignals for emotion detection. Next, a state-of-the-art review is presented on automatic emotion classification. Moreover, guidelines are presented for affective MMI. Subsequently, a research is presented that explores the use of EDA and three facial EMG signals to determine neutral, positive, negative, and mixed emotions, using recordings of 21 people. A range of techniques is tested, which resulted in a generic framework for automated emotion classification with up to 61.31% correct classification of the four emotion classes, without the need of personal profiles. Among various other directives for future research, the results emphasize the need for parallel processing of multiple biosignals