Pathophysiology and Treatment of Non-motor Dysfunction in Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis is a progressive and fatal neurodegenerative disease typically presenting with bulbar or limb weakness. There is increasing evidence that amyotrophic lateral sclerosis is a multisystem disease with early and frequent impacts on cognition, behaviour, sleep, pain and fatigue. Dysfunction of normal physiological and metabolic processes also appears common. Evidence from pre-symptomatic studies and large epidemiological cohorts examining risk factors for the future development of amyotrophic lateral sclerosis have reported a high prevalence of changes in behaviour and mental health before the emergence of motor weakness. This suggests that changes beyond the motor system are underway at an early stage with dysfunction across brain networks regulating a variety of cognitive, behavioural and other homeostatic processes. The full impact of non-motor dysfunction continues to be established but there is now sufficient evidence that the presence of non-motor symptoms impacts overall survival in amyotrophic lateral sclerosis, and with up to 80% reporting non-motor symptoms, there is an urgent need to develop more robust therapeutic approaches. This review provides a contemporary overview of the pathobiology of non-motor dysfunction, offering readers a practical approach with regard to assessment and management. We review the current evidence for pharmacological and non-pharmacological treatment of non-motor dysfunction in amyotrophic lateral sclerosis and highlight the need to further integrate non-motor dysfunction as an important outcome measure for future clinical trial design

Resource-aware Video Multicasting via Access Gateways in Wireless Mesh Networks

Abstract—This paper studies video multicasting in large scale areas using wireless mesh networks. The focus is on the use of Internet access gateways that allow a choice of alternative routes to avoid potentially lengthy multi-hop wireless paths with low capacity. A set of heuristic-based algorithms are described that together aim to maximize network capacity: the two-tier integrated architecture algorithm, the weighted gateway uploading algorithm, the link-controlled routing tree algorithm, and the alternative channel assignment algorithm. These algorithms use different approaches to arrange multicast group members into a clustered and two-tier integrated architecture in which network protocols can make use of multiple gateways to improve system throughput. Simulation results are used to determine the performance of the different approaches. I

Resource-aware Video Multicasting via Access Gateways in Wireless Mesh Networks

This paper studies video multicasting in large scale areas using wireless mesh networks. The focus is on the use of Internet access gateways that allow a choice of alternative routes to avoid potentially lengthy multi-hop wireless paths with low capacity. A set of heuristic-based algorithms are described that together aim to maximize network capacity: the two-tier integrated architecture algorithm, the weighted gateway uploading algorithm, the link-controlled routing tree algorithm, and the alternative channel assignment algorithm. These algorithms use different approaches to arrange multicast group members into a clustered and two-tier integrated architecture in which network protocols can make use of multiple gateways to improve system throughput. Simulation results are used to determine the performance of the different approaches

Regulation of the dystrophin-associated glycoprotein complex composition by the metabolic properties of muscle fibres

The dystrophin-glycoprotein complex (DGC) links the muscle cytoskeleton to the extracellular matrix and is responsible for force transduction and protects the muscle fibres from contraction induced damage. Mutations in components of the DGC are responsible for muscular dystrophies and congenital myopathies. Expression of DGC components have been shown to be altered in many myopathies. In contrast we have very little evidence of whether adaptive changes in muscle impact on DGC expression. In this study we investigated connection between muscle fibre phenotype and the DGC. Our study reveals that the levels of DGC proteins at the sarcolemma differ in highly glycolytic muscle compared to wild-type and that these changes can be normalised by the super-imposition of an oxidative metabolic programme. Importantly we show that the metabolic properties of the muscle do not impact on the total amount of DGC components at the protein level. Our work shows that the metabolic property of a muscle fibre is a key factor in regulating the expression of DGC proteins at the sarcolemma

Arsenic hyperaccumulation by different fern species

Pteris vittata was the first identified arsenic (As) hyperaccumulator. Our aim was to test whether As hyperaccumulation occurs in other fern species, and whether P. vittata collected from both contaminated and uncontaminated environments accumulates As similarly. Three accessions of P. vittata, two cultivars of Pteris cretica, Pteris longifoliaandPteris umbrosa were grown with 0-500 mg As kg(-1) added to the substrate. A second experiment compared As uptake by five common ferns obtained from commercial suppliers. The results show that, in addition to P. vittata, P. cretica, P. longifolia and P. umbrosa also hyperaccumulate As to a similar extent. There was little difference between different Pteris species, or between different accessions of P. vittata. By contrast, Asplenium nidus , Davallia canarensis, Polypodium aureum, Polystichum tsus-simense do not hyperaccumulate As. This study identified three new species of As hyperaccumulators in the Pteris genus and suggests that As hyperaccumulation is a constitutive property in P. vittata

CRK9 contributes to regulation of mitosis and cytokinesis in the procyclic form of Trypanosoma brucei

<p>Abstract</p> <p>Background</p> <p>The <it>Trypanosoma brucei </it>cell cycle is regulated by combinations of cyclin/CRKs (cdc2 related kinases). Recently, two additional cyclins (CYC10, CYC11) and six new CRK (CRK7-12) homologues were identified in the <it>T. brucei </it>genome database <abbrgrp><abbr bid="B1">1</abbr><abbr bid="B2">2</abbr></abbrgrp>.</p> <p>Results</p> <p>Individual RNAi knockdowns of these new proteins in the procyclic form of <it>T. brucei </it>showed no apparent phenotype except for the CRK9 depletion, which enriched the cells in G2/M phase. But a similar CRK9 knockdown in the bloodstream form caused no apparent phenotype. CRK9 lacks the typical PSTAIRE motif for cyclin binding and the phenylalanine "gatekeeper" but binds to cyclin B2 <it>in vitro </it>and localizes to the nucleus in both forms of <it>T. brucei</it>. CRK9-depleted procyclic-form generated no detectable anucleate cells, suggesting an inhibition of cytokinesis by CRK9 depletion as well. The knockdown enriched cells with one nucleus, one kinetoplast and two closely associated basal bodies with an average distance of 1.08 mm in between, which was shorter than the control value of 1.36 μm, and the cells became morphologically deformed and rounded with time.</p> <p>Conclusion</p> <p>CRK9 may play a role in mediating the segregation between the two kinetoplast/basal body pairs prior to cytokinetic initiation. Since such a segregation over a relatively significant distance is essential for cytokinetic initiation only in the procyclic but may not be in the bloodstream form, CRK9 could be specifically involved in regulating cytokinetic initiation in the procyclic form of <it>T. brucei</it>.</p

The Reform of Employee Compensation in China’s Industrial Enterprises

Although employee compensation reform in Chinese industrial sector has been discussed in the literature, the real changes in compensation system and pay practices have received insufficient attention and warrant further examination. This paper briefly reviews the pre- and post-reform compensation system, and reports the results of a survey of pay practices in the four major types of industrial enterprises in China. The research findings indicate that the type of enterprise ownership has little influence on general compensation practices, adoption of profit-sharing plans, and subsidy and allowance packages. In general, pay is linked more to individual performance and has become an important incentive to Chinese employees. However, differences are found across the enterprise types with regard to performance-related pay. Current pay practices are positively correlated to overall effectiveness of the enterprise

Prospective study of clinician-entered research data in the Emergency Department using an Internet-based system after the HIPAA Privacy Rule

BACKGROUND: Design and test the reliability of a web-based system for multicenter, real-time collection of data in the emergency department (ED), under waiver of authorization, in compliance with HIPAA. METHODS: This was a phase I, two-hospital study of patients undergoing evaluation for possible pulmonary embolism. Data were collected by on-duty clinicians on an HTML data collection form (prospective e-form), populated using either a personal digital assistant (PDA) or personal computer (PC). Data forms were uploaded to a central, offsite server using secure socket protocol transfer. Each form was assigned a unique identifier, and all PHI data were encrypted, but were password-accessible by authorized research personnel to complete a follow-up e-form. RESULTS: From April 15, 2003-April 15 2004, 1022 prospective e-forms and 605 follow-up e-forms were uploaded. Complexities of PDA use compelled clinicians to use PCs in the ED for data entry for most forms. No data were lost and server log query revealed no unauthorized entry. Prospectively obtained PHI data, encrypted upon server upload, were successfully decrypted using password-protected access to allow follow-up without difficulty in 605 cases. Non-PHI data from prospective and follow-up forms were available to the study investigators via standard file transfer protocol. CONCLUSIONS: Data can be accurately collected from on-duty clinicians in the ED using real-time, PC-Internet data entry in compliance with the Privacy Rule. Deidentification-reidentification of PHI was successfully accomplished by a password-protected encryption-deencryption mechanism to permit follow-up by approved research personnel

Analysing trajectories of a longitudinal exposure: A causal perspective on common methods in lifecourse research

Longitudinal data is commonly analysed to inform prevention policies for diseases that may develop throughout life. Commonly methods interpret the longitudinal data as a series of discrete measurements or as continuous patterns. Some of the latter methods condition on the outcome, aiming to capture ‘average’ patterns within outcome groups, while others capture individual-level pattern features before relating these to the outcome. Conditioning on the outcome may prevent meaningful interpretation. Repeated measurements of a longitudinal exposure (weight) and later outcome (glycated haemoglobin levels) were simulated to match three scenarios: one with no causal relationship between growth rate and glycated haemoglobin; two with a positive causal effect of growth rate on glycated haemoglobin. Two methods that condition on the outcome and one that did not were applied to the data in 1000 simulations. The interpretation of the two-step method matched the simulation in all causal scenarios, but that of the methods conditioning on the outcome did not. Methods that condition on the outcome do not accurately represent a causal relationship between a longitudinal pattern and outcome. Researchers considering longitudinal data should carefully determine if they wish to analyse longitudinal data as a series of discrete time points or by extracting pattern features