A proposal for a comprehensive grading of Parkinson's disease severity combining motor and non-motor assessments: meeting an unmet need.

Non-motor symptoms are present in Parkinson's disease (PD) and a key determinant of quality of life. The Non-motor Symptoms Scale (NMSS) is a validated scale that allows quantifying frequency and severity (burden) of NMS. We report a proposal for using NMSS scores to determine levels of NMS burden (NMSB) and to complete PD patient classification

Prostaglandin contribution to postexercise hyperemia is dependent on tissue oxygenation during rhythmic and isometric contractions

© 2020 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society. The role of prostaglandins (PGs) in exercise hyperemia is controversial. We tested their contributions in moderate intensity forearm exercise, whether their release is oxygen (O2)-dependent or affected by aging. A total of 12 young (21 ± 1 years) and 11 older (66 ± 2 years) recreationally active men performed rhythmic and isometric handgrip contractions at 60% maximum voluntary contraction for 3 min during air breathing after placebo, after cyclooxygenase (COX) inhibition with aspirin, while breathing 40% O2 and during their combination (aspirin + 40% O2). Forearm blood flow (FBF) was recorded with venous occlusion plethysmography (forearm vascular conductance (FVC): FBF/mean arterial pressure). Venous efflux of PGI2 and PGE2 were assessed by immunoassay. Postcontraction increases in FVC were similar for rhythmic and isometric contractions in young and older men, and accompanied by similar increases in efflux of PGI2 and PGE2. Aspirin attenuated the efflux of PGI2 by 75%–85%, PGE2 by 50%–70%, (p .05 young versus. older), and postcontraction increases in FVC by 22%–27% and 17%–21% in young and older men, respectively (p <.05 within group and young versus. older). In both age groups, 40% O2 and aspirin + 40% O2 caused similar inhibition of the increases in FVC and efflux of PGs as aspirin alone (p <.05 within group). These results indicate that PGs make substantial contributions to the postcontraction hyperemia of rhythmic and isometric contractions at moderate intensities in recreationally active young and older men. Given PGI2 is mainly released by endothelium and PGE2 by muscle fibers, we propose PG generation is dependent on the contraction-induced falls in O2 at these sites

Holographic detection of nanoparticles using acoustically actuated nanolenses

The optical detection of nanoparticles, including viruses and bacteria, underpins many of the biological, physical and engineering sciences. However, due to their low inherent scattering, detection of these particles remains challenging, requiring complex instrumentation involving extensive sample preparation methods, especially when sensing is performed in liquid media. Here we present an easy-to-use, high-throughput, label-free and cost-effective method for detecting nanoparticles in low volumes of liquids (25 nL) on a disposable chip, using an acoustically actuated lens-free holographic system. By creating an ultrasonic standing wave in the liquid sample, placed on a low-cost glass chip, we cause deformations in a thin liquid layer (850 nm) containing the target nanoparticles (≥140 nm), resulting in the creation of localized lens-like liquid menisci. We also show that the same acoustic waves, used to create the nanolenses, can mitigate against non-specific, adventitious nanoparticle binding, without the need for complex surface chemistries acting as blocking agents

Hierarchical Fuzzy Systems: Interpretability and Complexity

Hierarchical fuzzy systems (HFSs) have been regarded as a useful solution for overcoming the major issues in fuzzy logic systems (FLSs), i.e., rule explosion due to the increase in the number of input variables. In HFS, the standard FLS are reformed into a low-dimensional FLS subsystem network. Moreover, the rules in HFS usually have antecedents with fewer variables than the rules in standard FLS with equivalent functions, because the number of input variables in each subsystem is less. Consequently, HFSs manage to decrease rule explosion, which minimises complexity and improves model interpretability. Nevertheless, the issues related to the question of “Does the complexity reduction of HFSs that have multiple subsystems, layers and different topologies really improve their interpretability?” are not clear and persist. In this paper, a comparison focusing on interpretability and complexity is made between two HFS’ topologies: parallel and serial. A detailed measurement of the interpretability and complexity with different configurations for both topologies is provided. This comparative study aims to examine the correlation between interpretability and complexity in HFS

A computational framework to emulate the human perspective in flow cytometric data analysis

Background: In recent years, intense research efforts have focused on developing methods for automated flow cytometric data analysis. However, while designing such applications, little or no attention has been paid to the human perspective that is absolutely central to the manual gating process of identifying and characterizing cell populations. In particular, the assumption of many common techniques that cell populations could be modeled reliably with pre-specified distributions may not hold true in real-life samples, which can have populations of arbitrary shapes and considerable inter-sample variation. &lt;p/&gt;Results: To address this, we developed a new framework flowScape for emulating certain key aspects of the human perspective in analyzing flow data, which we implemented in multiple steps. First, flowScape begins with creating a mathematically rigorous map of the high-dimensional flow data landscape based on dense and sparse regions defined by relative concentrations of events around modes. In the second step, these modal clusters are connected with a global hierarchical structure. This representation allows flowScape to perform ridgeline analysis for both traversing the landscape and isolating cell populations at different levels of resolution. Finally, we extended manual gating with a new capacity for constructing templates that can identify target populations in terms of their relative parameters, as opposed to the more commonly used absolute or physical parameters. This allows flowScape to apply such templates in batch mode for detecting the corresponding populations in a flexible, sample-specific manner. We also demonstrated different applications of our framework to flow data analysis and show its superiority over other analytical methods. &lt;p/&gt;Conclusions: The human perspective, built on top of intuition and experience, is a very important component of flow cytometric data analysis. By emulating some of its approaches and extending these with automation and rigor, flowScape provides a flexible and robust framework for computational cytomics

Computational Image Analysis of Guided Acoustic Waves Enables Rheological Assessment of Sub-nanoliter Volumes

We present a method for the computational image analysis of high frequency guided sound waves based upon the measurement of optical interference fringes, produced at the air interface of a thin film of liquid. These acoustic actuations induce an affine deformation of the liquid, creating a lensing effect that can be readily observed using a simple imaging system. We exploit this effect to measure and analyze the spatiotemporal behavior of the thin liquid film as the acoustic wave interacts with it. We also show that, by investigating the dynamics of the relaxation processes of these deformations when actuation ceases, we are able to determine the liquid’s viscosity using just a lens-free imaging system and a simple disposable biochip. Contrary to all other acoustic-based techniques in rheology, our measurements do not require monitoring of the wave parameters to obtain quantitative values for fluid viscosities, for sample volumes as low as 200 pL. We envisage that the proposed methods could enable high throughput, chip-based, reagent-free rheological studies within very small samples

A regularity class for the roots of nonnegative functions

We investigate the regularity of the positive roots of a non-negative function of one-variable. A modified H\"older space $\mathcal{F}^\beta$ is introduced such that if $f\in \mathcal{F}^\beta$ then $f^\alpha \in C^{\alpha \beta}$. This provides sufficient conditions to overcome the usual limitation in the square root case ($\alpha = 1/2$) for H\"older functions that $f^{1/2}$ need be no more than $C^1$ in general. We also derive bounds on the wavelet coefficients of $f^\alpha$, which provide a finer understanding of its local regularity.Comment: 12 page

Defining the molecular role of gp91phox in the immune manifestation of acute allergic asthma using a preclinical murine model

<p>Abstract</p> <p>Objective</p> <p>The phenomena manifested during inflammation require interplay between circulating effector cells, local resident cells, soluble mediators and genetic host factors to establish, develop and maintain itself. Of the molecues involed in the initiation and perpetuation of acute allergic inflammation in asthma, the involvement of effector cells in redox reactions for producing O₂^-(superoxide anion) through the mediation of NADPH oxidase is a critical step. Prior data suggest that reactive oxygen species (ROS) produced by NADPH oxidase homologues in non-phagocytic cells play an important role in the regulation of signal transduction, while macrophages use a membrane-associated NADPH oxidase to generate an array of oxidizing intermediates which inactivate MMPs on or near them.</p> <p>Materials and Methods and Treatment</p> <p>To clarify the role of gp91phox subunit of NADPH oxidase in the development and progression of an acute allergic asthma phenotype, we induced allergen dependent inflammation in a gp91<it>^phox</it>-/- single knockout and a gp91phox-/-MMP-12-/- double knockout mouse models.</p> <p>Results</p> <p>In the knockout mice, both inflammation and airway hyperreactivity were more extensive than in wildtype mice post-OVA. Although OVA-specific IgE in plasma were comparable in wildtype and knockout mice, enhanced inflammatory cell recruitment from circulation and cytokine release in lung and BALf, accompanied by higher airway resistance as well as Penh in response to methacholine, indicate a regulatory role for NADPH oxidase in development of allergic asthma. While T cell mediated functions like Th2 cytokine secretion, and proliferation to OVA were upregulated synchronous with the overall robustness of the asthma phenotype, macrophage upregulation in functions such as proliferation, and mixed lymphocyte reaction indicate a regulatory role for gp91phox and an overall non-involvement or synergistic involvement of MMP12 in the response pathway (comparing data from gp91phox-/- and gp91phox-/-MMP-12-/- mice).</p

Game theory of mind

This paper introduces a model of ‘theory of mind’, namely, how we represent the intentions and goals of others to optimise our mutual interactions. We draw on ideas from optimum control and game theory to provide a ‘game theory of mind’. First, we consider the representations of goals in terms of value functions that are prescribed by utility or rewards. Critically, the joint value functions and ensuing behaviour are optimised recursively, under the assumption that I represent your value function, your representation of mine, your representation of my representation of yours, and so on ad infinitum. However, if we assume that the degree of recursion is bounded, then players need to estimate the opponent's degree of recursion (i.e., sophistication) to respond optimally. This induces a problem of inferring the opponent's sophistication, given behavioural exchanges. We show it is possible to deduce whether players make inferences about each other and quantify their sophistication on the basis of choices in sequential games. This rests on comparing generative models of choices with, and without, inference. Model comparison is demonstrated using simulated and real data from a ‘stag-hunt’. Finally, we note that exactly the same sophisticated behaviour can be achieved by optimising the utility function itself (through prosocial utility), producing unsophisticated but apparently altruistic agents. This may be relevant ethologically in hierarchal game theory and coevolution

Utilising Target Adjacency Information for Multi-target Prediction

In this paper, we explored how information on the cost of misprediction can be used to train supervised learners for multi-target prediction (MTP). In particular, our work uses depression, anxiety and stress severity level prediction as the case study. MTP describes proposals which results require the concurrent prediction of multiple targets. There is an increasing number of practical applications that involve MTP. They include global weather forecasting, social network users’ interaction and the thriving of different species in a single habitat. Recent work in MTP suggests the utilization of “side information” to improve prediction performance. Side information has been used in other areas, such as recommender systems, information retrieval and computer vision. Existing side information includes matrices, rules, feature representations, etc. In this work, we review very recent work on MTP with side information and propose the use of knowledge on the cost of incorrect prediction as side information. We apply this notion in predicting depression, anxiety and stress of 270,322 anonymous respondents to the DASS-21 psychometric scale in Malaysia. Predicting depression, anxiety and stress based on the DASS-21 fit an MTP problem. Often, a patient experiences anxiety as well as depression at the same time. This is not unusual since it has been discovered that both tend to co-exist at different degrees depending on a patient’s experience. By using existing machine learning algorithms to predict the severity levels of each category (i.e., depression, anxiety and stress), the result shows improved precision with the use of cost matrix as side information in MTP