bluuebunny/crossref_metadata_2025 huggingface dataset:
Flexible manufacturing systems require flexible people*
Authors: Graham Margaret B.W. , Rosenthal Stephen R.
Published: December 2019

This article draws on findings from a recent study of the procurement of Flexible Machining Systems (FMS). Based on intensive fieldwork in eight companies, and corroborating data from numerous other sites, the paper emphasizes the interaction between FMS technology and the people who plan and operate it. It argues that even in highly traditional manufacturing environments FMS mandates progressive initiatives in the use of people. The study finds that specific needs for human flexibility occur in several critical areas: (1) the composition and organization of the project management teams; (2) the relationships between the in-house team and the vendor team; and, (3) the selection, compensation and organization of the FMS workforce. Indicators of flexibility in human systems include such factors as broad skill mixes, previous experience with start-ups, cross-training, cross-functional cooperation, job rotation, team-building, and provision for continuing experimentation and adaptation. The article presents particular examples to show that those projects that have stressed the needs for flexibility in these areas early have been satisfied with the results; while those that have paid no attention to these matters during the procurement and planning phases have often found it necessary to change their approaches during implementation and start-up.
Economic technical and managerial influences on the adoption of flexible manufacturing systems: A decision process model*
Authors: Parkinson Stephen T. , Avlonitis George J.
Published: December 2019

This paper examines the relative influence of economic technical and managerial factors on an organisation's decision to adopt or reject a flexible manufacturing system. Based on interviews within 31 British and West German companies the authors develop a process model of the adoption decision which provides an organising framework for their discussion. Their findings support the view developed by Gerwin and Leung that the rate of adoption of such a significant innovation depends as much upon the appropriate organisational infrastructure, the key people involved and the role of manufacturing in the overall corporate planning process, as it does upon the economic and technical case for FMS.
The relationship of organizational subcultures to DSS user satisfaction
Authors: Kendall Kenneth E. , Buffington James R. , Kendall Julie E.
Published: December 2019

First and foremost, decision support systems must be accepted by their users if the systems are to be used. Recently, user satisfaction with DSS has been studied in several different ways. This paper explores the relationship between organizational subcultures and users of DSS, in order to discover how subcultures can be useful in explaining user satisfaction with decision support systems. Active DSS users from three functional areas of a large midwestern financial institution participated in the study. The existence of organizational subcultures was determined through multiple methods and questionnaires were used to determine user satisfaction for the same population of DSS users. The three subcultures were more successful than demographic variables in explaining variation. Implications of this study include utilizing information about subcultures to design decision support systems acceptable to the various subcultures.
Habitual domain analysis and effective goal setting for better performance*
Authors: Yu P.L. , Chien I.S.
Published: December 2019

Utilizing the concepts of behavior mechanisms and habitual domains, we offer a classification of decision problems and a general principle of effective goal setting as to select control variables (the set of measurable goals, their achievement levels and supportive systems) which can create favorable working conditions and relative high levels of charges and confidence on the performers so that they can allocate as much attention time as possible to perform the desired job-related operations in a most efficient and effective way. We give a detailed discussion on the applications of this principle over various classes of problems.
Matching support systems: Information systems for supporting matching processes*
Authors: Yuan Yufei , Kochen Manfred
Published: December 2019

Guidelines and principles for the design of information systems to support general matching processes are presented. These are based on a new model of matching processes and an analysis of key decision issues. Thus, a fruitful new avenue of inquiry into assignment problems that do not assume perfect information by match participants is opened.
Bat'a-system of management: Managerial excellence found
Authors: Zeleny Milan
Published: December 2019

We provide a short outline of Bat'a-system management principles as a contribution to the ongoing search for world-class management systems and managerial excellence in general. It appears that Bat'a-system, being both European and American in its origins and being based on labor and knowledge integration (rather than division and specialization), represents a candidate management system of uncommon appeal. More, Bat'a-system is not based on theory but rooted in practical experience of unprecedented performance, quality and business success. The Bat'a-system experience leads directly to modern theory of process-oriented quality management, based on high-technology support and decision-making autonomy of employees.
What is integrated process management?
Authors: Zeleny Milan
Published: December 2019

New trans-national management principles, arising from the teachings of Deming, Juran, Tribus, Ishikawa and others, are now synthesized into management system approach identified as Integrated Process Management (IPM). Its major characteristic is customer integration in the production process.
Job stress and the VDT clerical worker
Authors: Gardner Ella P. , Ruth Stephen R. , Render Barry
Published: December 2019

The objective of this research was to compare the results of a recent study of the effects of VDT use on worker well-being with two other broad-based studies done previously in different areas of the United States. The populations sampled represent the millions of clerical and administrative workers whose jobs are being automated. The 140 clerical and administrative workers in the current study represent a sample of U.S. Navy civilian employees in the Washington, DC area. Our results found that: (1) there are a variety of health complaints associated with increased hours of VDT use; (2) more VDT users experience job boredom than non-users; (3) frequent users experience more work pressure and more control by management than occasional users. The authors confirm that VDT operators, especially those who use VDTs more than four hours a day, experience more stress than non-users.
Changing the Corporate Culture – A Roadmap for the Change Agent
Authors: Tribus Myron
Published: December 2019

These comments are directed to ‘change agents’, those hardy souls who dare to tell other people that what they have been doing is no longer satisfactory and they must begin to do something else. Being a change agent is, at best, a hazardous occupation. You will not be thanked by those whose positions are reduced by the change (there are always some in that category) and you will not be supported by those who will benefit from the change because until it is accomplished, they will not understand and when it is all over they will not understand what you did. If they like the result they will forget you did it. The best time to make a change in overall culture is at a time of deep distress. That is why technological change comes so rapidly during time of war. There are always a few hardy discontents around who are willing to change when times are good but they are a minority. The majority, as the advertisements used to say, would ‘rather fight than switch’. But change is inevitable and oftentimes an enterprise is faced with the necessity to change and to change drastically. If you are the agent of change be grateful for hard times. As the changes begin to occur you will appreciate why so many change agents before you have come to regard good times as the enemy. If the good times come before your work has been completed, your efforts may be for naught. T'is a sad fact; change agents often welcome the voice of doom! They go around prophesying disaster if you do not do what they say. The fact that they are correct is irrelevant; they are the bearers of bad tidings and as such are not welcomed.
Managing in a Robotic Age
Authors: Shenkar Oded
Published: December 2019

A decade after robots have been introduced to the work place in substantial numbers, knowledge regarding their impact on the human resource system remains limited. This paper assesses the impact of industrial robots on organizations and their employees, and addresses some of the implications for managerial roles in the modern factory.
Disorder and Contradiction: An Empirical Perspective on Self-Organization
Authors: Watts D.L.
Published: December 2019

Self-organization is frequently used more for purposes of prescription in the management field than to support analytical insights. Terms have changed such as organizational learning in place of organizational change; but it remains questionable whether our empirical understanding of this phenomenon has been altered. In the following discussion, cognitive, structural, and political barriers will be examined in terms of behaviors which appear to inhibit organizational learning. It will be argued that these ‘sources of deception’ are in fact, built into the design of organizations. We do observe however, organizations which revise their strategies and reorient policies. Illustrations from a case study of the U.S. Peace Corps of the 1960's, will provide the basis for examining internal redundancies and competitive behavior and their potential to support conditions of self-organization.
The Stable Long-term Employment System and the Postwar Economy of Japan
Authors: Hiwaki Kensei
Published: December 2019

In the present article, the stable long-term employment system (SLES) is placed in a scope of perspective which is much broader than that of the usual arena of microeconomics. This article, together with the previous one, constitutes a new theoretical exposition and re-interpretation of the postwar Japanese economy, as well as of the employment system itself. To begin with, it provides a rudimentary argument for a microeconomic foundation of macroeconomics in the Japanese context, by relating the microeconomic effects of SLES on “communal saving” and investments to major macroeconomic variables and by stressing the SLES-induced coordination of aggregate savings and investments. Also, it provides an analytical framework for the SLES-induced acceleration of growth in investments, exports and gross national product. Further, it explores a possible explanation of the “Japan Paradox,” viz., the economy's dynamic transfiguration from “capital poor” to “capital rich” within a few decades after the devastations of World War II. Still further, the article tries to relate SLES with the aggressive marketing, cross-shareholding, labor market discrimination, “producer sovereignty,” and some other socio-economic distortions. Finally, it suggests a pragmatic first step toward moderation particularly of the prevailing labor-market discrimination, for the sake of more amicable economic relations with the trading partners, as well as for greater welfare of the very nation.
A Management System Based on Consent
Authors: van Vlissingen Rogier Fentener
Published: December 2019

Sociocracy, an empowering management methodology from the Netherlands finding application world-wide. Self-organization and conflict resolution are hallmarks. Consent defined as the absence of reasoned objection; need to give reasoning initiates problem solving. Four simple rules govern organizational details, creating mechanism for regular self-organization, including cloning, expansion, contraction, etc. Strong vertical linkage provides powerful transition mechanism from command and control to information-based management. Incentive compensation and no absentee ownership are key elements of the method.
Designing Humanized Systems for Multiple Criteria Decision Making
Authors: Angehrn Albert A.
Published: December 2019

Triple C is a new visual interactive system which supports the exploration of multicriteria decisions. The novelty of this sytem consists in an overall utilization of Visual Interaction for supporting all the information processing activities related to the task of incrementally defining and analyzing a multicriteria decision situation. This paper reports on how a visual interactive approach can be successfully applied to the design of systems matching the original objectives of Decision Support. Human judgement and creativity are neither substituted with a formal model nor restricted by an inflexible, prescriptive tool. On the contrary, the DSS aims at facilitating and stimulating a learning process in which decision-makers are enabled to incrementally (1) model and refine their views of a specific decision situation, (2) understand the impact of different problem components, (3) question and/or justify their individual choices and preferences, and finally (4) communicate them easily – a crucial factor in group decisions.
A systematic framework for performance appraisal and compensation strategy
Authors: Chen Hai Ming , Fu Peng Chuan
Published: December 2019

Systematical strategic fit benefits organization's performance and makes the organization systemic. Researches of performance appraisal strategy and compensation strategy are extensive, but most of them only focused on the single subject without the synergy of them. An extensive literature review is provided in this research to build up a systematic theoretical framework for performance appraisal and compensation strategy. Four propositions of the criteria and methods of performance appraisal and compensation strategy are inferred in this systematic framework. Furthermore, four situations of 2×2 combinations with the criteria and methods above are discussed for the new systematic performance appraisal and compensation strategy. Through this framework, an organization can appropriately focus on employees' representation or individual to evaluate and motive employees with rational or humanistic way.
Exploring the benefits of measuring intellectual capital. The Aimag case study
Authors: Chiucchi M. Serena
Published: December 2019

In recent years many studies on intellectual capital measurement and reporting systems (ICMRSs) have been carried out. In this paper, a longitudinal case study, of a multi-utility Italian company, Aimag S.p.A., is illustrated. The case shows that ICMRS cannot be simply considered an accounting phenomenon but one that promotes managerial and cultural changes within a company.
Ideals without ideology
Authors: Singer Alan E.
Published: December 2019

The limitations of market based systems yield a basis for comparing HSM and CSR, whilst placing them relative to other variants of capitalism. In order to meet the full set of criteria for social responsiveness and ethicality, all the “variants” would have to be augmented in such as way that humane ideals are more effectively promoted. More generally, ethical enterprises operating within any systems of capitalism should not only refrain from exploiting market limitations, they should attempt to proactively compensate for all of them. This is nothing other than a rational and moral prescription for the strategic behaviour of productive entities. It is not an ideology.
Transferring management knowledge into China: A conceptual model and case study
Authors: Zhu Zhichang
Published: December 2019

The over-half-a-century collective experience of transferring management knowledge from the West into China is analysed based on a pragmatic conception of knowledge and a contingency model of transfer. Findings suggest that cross-border transmission will be more effective if actors (1) carefully investigate the transferabilities of ideals, tools and practice in management innovations, and (2) consciously pursue theoretically informed copying, adapting and mutual learning strategies. This allows a proposition that a culturally and institutionally sensitive perspective that nurtures international communities of knowing is crucial for globally informed indigenous management.
Disruptive Internet-service innovation diffusion
Authors: Georgantzas Nicholas C. , Katsamakas Evangelos
Published: December 2019

A disruptive innovation strategy (DIS) entails innovation that makes customers embrace new value propositions shifting the basis of competition. Prevalent in fast-changing Internet and IT markets, DIS challenges incumbent firms and has the potential to transform industry structure. This article contributes toward rigorous DIS theory building with a system dynamics (SD) simulation model of disruptive innovation diffusion. The model shows disruptive innovation diffusion as a replicable process that can enable business growth for disruptive innovators. It builds on diffusion processes in marketing and epidemiology to show customer switching in the market segments that disruptive innovators exploit. Multiple computed scenarios examine the dynamic performance effects of disrupters' attack on high-end market segments and incumbent retaliation. Data from firm d, an entrant Internet-services provider, enable model calibration and examination of the strategic concerns of a real start-up firm, providing multiple insights into disruptive Internet-service innovation management.
Foundations of intelligent knowledge management
Authors: Zhang Lingling , Li Jun , Shi Yong , Liu Xiaohui
Published: December 2019

Knowledge or hidden patterns discovered by data mining from large databases has great novelty, which is often unavailable from experts' experience. Its unique irreplaceability and complementarity has brought new opportunities for decision-making and it has become important means of expanding knowledge bases to derive business intelligence in the information era. The challenging problem, however, is whether the results of data mining can be really regarded as “knowledge”. To address this issue, the theory of knowledge management should be applied. Unfortunately, there appears little work in the cross-field between data mining and knowledge management. In data mining, researchers focus on how to explore algorithms to extract patterns that are non-trivial, implicit, previously unknown and potentially useful, but overlook the knowledge components of these patterns. In knowledge management, most scholars investigate methodologies or frameworks of using existing knowledge (either implicit or explicit ones) support business decisions while the detailed technical process of uncovering knowledge from databases is ignored. This paper aims to bridge the gap between these two fields by trying to establish foundations of intelligent knowledge management using large data bases. It enables to generate “special” knowledge, called intelligent knowledge base on the hidden patterns created by data mining. Furthermore, this paper systematically analyzes the process of intelligent knowledge management – a new proposition from original data, rough knowledge, intelligent knowledge, and actionable knowledge as well as the four transformations (4T) of these items. This study not only promotes more significant research beyond data mining, but also enhances the quantitative analysis of knowledge management on hidden patterns from data mining.
HRM capabilities as a determinant and enabler of productivity for manufacturing SMEs
Authors: Fabi Bruno , Lacoursière Richard , Raymond Louis , St-Pierre Josée
Published: December 2019

In this article we assume that the entrepreneurial capability of SME owner-managers is reflected in the choices they make to coordinate their action in terms of human resource management (HRM), research and development (R&D), and advanced manufacturing technologies (AMT). However, to what extent do managerial choices made in these areas affect the performance of SMEs? And to what extent do the interactions of HRM capabilities with R&D and AMT capabilities also affect the performance of these enterprises? In order to answer these questions, an empirical study was conducted among 182 Canadian SMEs. Emanating from a perspective based on human systems and contingency theory, the results of this study indicate that the development of HRM capabilities allow SMEs not only to improve their productivity but also to significantly amplify the effect of R&D and AMT capabilities on this same productivity.
Blinds, fuzziness and habitual domain tools in decision making with changeable spaces
Authors: Yu Po-Lung , Chen Yen-Chu
Published: December 2019

In most challenging decision problems, relevant parameters are changing. Decision blinds, decision traps, and fuzziness, would unavoidably occur in the process of dealing with this kind of problems. To make effective decisions, it is important to be aware of the existence and changing nature of the potential parameters. In this article we first discuss a main cause of fuzziness and unknowns in decision making, and then introduce the relevant parameters including those in human behavioral systems and in decision processes. The concepts of habitual domains, decision blinds and decision traps are explored. The tools of habitual domains are proposed to enable decision makers to more effectively expand and enrich their visions and perceptions on the problems as to reduce decision blinds and fuzziness, and avoid decision traps. Consequentially, effective solutions for decision making in changeable spaces can be located.
Product development: An integrative tool and activity research framework
Authors: de Waal Gerrit Anton , Knott Paul
Published: December 2019

The paper addresses research issues in new product development (NPD) activity, practices and tools, in particular the need to integrate the set of tools practitioners use with the praxis of how they use these tools in day-to-day activity. It draws on the strategy-as-practice literature to derive a model that integrates the concepts of NPD practices, practitioners and praxis. It then draws on a systematic review and synthesis of existing NPD literature to develop a generic multi-stage, 12-perspective organizing framework for NPD activity, and provides examples from the literature of twelve corresponding classes of NPD tools. The literature currently lacks such a framework and hence uses individually defined schemes, resulting in a fragmented and incomplete picture. We have designed our generic framework so that it can both integrate existing findings and stimulate research that overcomes this fragmentation. We use the framework and our model of NPD practitioners, practices and project execution to articulate a comprehensive set of research challenges in NPD tool adoption and use. Our 12-perspective framework could also provide a basis for practitioners to develop or redesign NPD processes for specific situations and purposes.
Privacy concerns and expectation of control
Authors: Chen Jeng-Jung Victor , Huang Albert H. , Muzzerall Aaron
Published: December 2019

This study collected empirical data from over 200 Web users and investigated the relationships between three constructs related to privacy of Web users' data: user privacy concern about personal data collection, user expectation of control over collected personal data, and user self-regulation. A structural model showed that significant relationships existed among the three constructs. The results suggest that businesses would be wise to address the need that users feel for increased privacy, and that personal characteristics such as self-regulation may be used to tailor the level of user control over personal data.
Skeletal Muscle Atrophy in R6/2 Mice – Altered Circulating Skeletal Muscle Markers and Gene Expression Profile Changes
Authors: Magnusson-Lind Anna , Davidsson Marcus , Silajdžić Edina , Hansen Christian , McCourt Andrew C. , Tabrizi Sarah J. , Björkqvist Maria
Published: December 2019

Background: In addition to classical neurological symptoms, Huntington's disease (HD) is complicated by peripheral pathology, including progressive skeletal muscle wasting, and common skeletal muscle gene expression changes have been shown in HD mice and human HD. Objective: To highlight possible mechanisms underlying muscle wasting in HD, we examined gene expression in pathways governing skeletal muscle contractility, skeletal myogenesis, skeletal muscle wasting, apoptosis and the NFκB signaling pathway in two HD mouse models (the transgenic R6/2 and full-length knock-in Q175). In addition, we assessed circulating markers that increase in response to skeletal muscle injury, skeletal Troponin I (sTnI), fatty acid binding protein 3 (FABP3), and Myosin light chain 3 (Myl3). Methods: We measured gene expression in muscle tissue as well as in cultured primary myocytes using qPCR. Concentrations of cytokines and muscle proteins were obtained using multiplex ELISA. Results: Circulating markers of muscle injury (sTnI, FABP3, and Myl3) were significantly increased in mouse serum. In skeletal muscle, we observed reduced gene expression of components involved in muscle contractility, with pronounced downregulation of Acta1, Myh2 and Tnni2, among others. Alongside, we found increased expression of caspases (3 and 8) and key elements of the NFκB signaling pathway, p65/RelA, Tradd, and TRAF5. We also found similar gene expression alterations in cultured primary myocytes from R6/2 mice stimulated with TNF-α. Conclusions: Our results indicate that activation of apoptotic and NFκB pathways occur alongside down-regulation of key compartments of the muscle contractility unit in skeletal muscle of HD mice, and muscle atrophy could possibly be a source of circulating disease progression markers.
Optimising Mobility Outcome Measures in Huntington's Disease
Authors: Busse Monica , Quinn Lori , Khalil Hanan , McEwan Kirsten ,   the Outcome Measures Subgroup of the European Huntington's Disease Network
Published: December 2019

Background: Many of the performance-based mobility measures that are currently used in Huntington's disease (HD) were developed for assessment in other neurological conditions such as stroke. Objective: We aimed to assess the individual item-response of commonly used performance-based mobility measures, with a view to optimizing the scales for specific application in Huntington's Disease (HD). Method: Data from a larger multicentre, observational study were used. Seventy-five people with HD (11 pre-manifest & 64 manifest) were assessed on the Six-Minute Walk Test, 10-Meter Walk Test, Timed “Up & Go” Test (TUG), Berg Balance Scale (BBS), Physical Performance Test (PPT), Four Square Step Test, and Tinetti Mobility Test (TMT). The Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, Functional Assessment Scale and Total Functional Capacity scores were recorded, alongside cognitive measures. Standard regression analysis was used to assess predictive validity. Individual item responses were investigated using a sequence of approaches to allow for gradual removal of items and the subsequent creation of shortened versions. Psychometric properties (reliability and discriminant ability) of the shortened scales were assessed. Results: TUG (β 0.46, CI 0.20-3.47), BBS (β −0.35, CI −2.10-0.14), and TMT (β −0.45, CI −3.14-0.64) were good disease-specific mobility measures. PPT was the best measure of functional performance (β 0.42, CI 0.00-0.43 for TFC & β 0.57 CI 0.15-0.81 for FAS). Shortened versions of BBS and TMT were developed based on item analysis. The resultant BBS and TMT shortened scales were reliable for use in manifest HD. ROC analysis showed that shortened scales were able to discriminate between manifest and pre-manifest disease states. Discussion: Our data suggests that the PPT is appropriate as a general measure of function in individuals with HD, and we have identified shortened versions of the BBS and TMT that measure the unique gait and balance impairments in HD. These scales, alongside the TUG, may therefore be important measures to consider in future clinical trials.
Unawareness of Deficits in Huntington's Disease
Authors: Sitek Emilia J. , Thompson Jennifer C. , Craufurd David , Snowden Julie S.
Published: December 2019

People with Huntington's disease (HD) may show reduced awareness of physical and mental changes in themselves. This article reviews the evidence for loss of awareness (anosognosia) in an attempt to elucidate its characteristics and possible underlying mechanisms. It is shown that defective awareness occurs across domains. People with HD may under-report the presence or severity of involuntary movements, under-estimate cognitive impairment and deny behavioural change. Nevertheless, awareness is not all or none. Moreover, it may be affected differentially for different symptom domains and emerge at different stages of disease, raising the possibility of distinct contributory mechanisms. Findings of an inverse relationship between insight and severity of disease suggest that cognitive impairment, in particular executive dysfunction, may be an important contributory factor. Evidence has accrued to support this argument. However, cognitive impairment cannot fully account for patients' lack of awareness of involuntary movements. Findings that patients accurately report consequences but not the experience of involuntary movements, and better acknowledge their presence when watching videotapes of themselves suggests that physiological factors play an important role. The putative role of denial as a coping mechanism is discussed. Recognition by clinicians of deficient self-awareness is crucial because of its implications for diagnosis and optimal clinical management of HD.
Postural/Gait and Cognitive Function as Predictors of Driving Performance in Parkinson's Disease
Authors: Crizzle Alexander M. , Classen Sherrilene , Lanford Desiree N. , Malaty Irene A. , Okun Michael S. , Wang Yanning , Wagle Shukla Aparna , Rodriguez Ramon L. , McFarland Nikolaus R.
Published: December 2019

Background: The primary influence of motor symptoms on driving performance remains unclear due to the inconsistent use of various motor rating scales used in prior studies. Objective: This study aimed to determine which of three measures utilized in PD, the Unified Parkinson's Disease Rating Scale (UPDRS) motor section; the Modified Hoehn and Yahr; and the Rapid Paced Walk Test would best predict pass/fail outcomes on a road test in a sample of PD drivers. Methods: All participants (N = 55; 79% men) completed a road test. Receiver Operating Characteristics were then contrasted for all subjects based on assessments from all three disease severity indices. MMSE scores were then modelled with significant disease severity measures (if any) to determine if the predictive accuracy could be improved. Results: The Rapid Paced Walk Test and the Modified Hoehn & Yahr both predicted pass/fail outcomes on the road test (Area under the curve of 0.73 and 0.82, respectively). UPDRS motor scores, however, did not predict safe driving. When optimal cut-off points on the Modified Hoehn & Yahr (≥2.5) and Rapid Paced Walk Test (>6.22 seconds) were modelled with MMSE scores indicative of mild cognitive impairment (<27), the model accurately classified 92% and 100% as failing the road test, respectively. Conclusion: Although the Rapid Paced Walk Test had a slight advantage in differentiating between pass/fail outcomes compared to the Modified Hoehn & Yahr, both tests alone cannot be used in isolation to predict driving safety. Predictive accuracy can be improved using both select cut-off points on the Modified Hoehn & Yahr and Rapid Paced Walk test with MMSE scores in PD drivers. Though these findings are useful, an on-road test is still the gold standard, and screening should always be followed by formal testing.
Found in transcription: Accurate Parkinson's disease classification in peripheral blood
Authors: Karlsson Magdalena Kauczynska , Sharma Praveen , Aasly Jan , Toft Mathias , Skogar Örjan , Sæbø Solve , Lönneborg Anders
Published: December 2019

Background: A blood-based test for the early detection of Parkinson's disease (PD) would be an important diagnostic tool and useful for patient selection when developing novel drugs or treatments for the disease. Objective: Here, we aimed to identify potential biomarkers associated with PD. Methods: We applied gene expression profiling to the study of peripheral blood from 75 healthy control subjects and 79 PD patients at different stages of the disease. Healthy control subjects were matched for age and gender with PD subjects, and the diagnosis of patients was based on clinical evaluation by specialists in movement disorders. RNA was extracted from the blood samples and the gene expressions were measured using the Illumina HumanHT-12 v4.0 Expression BeadChip. Results: Our results support previous studies that gene expression in blood may be instrumental in the search for molecular biomarkers for PD. Single cross-validation results show that PD can be correctly classified from healthy controls with an agreement of 88% to clinical diagnosis. De novo PD patients are classified with a sensitivity of 87%, which is close to what was achieved for the patients having a confirmed PD diagnosis with disease duration <5 and >5 years (93% and 88%). A double cross-validation procedure showed that using a selected set of around 650 informative genes, similar results are achieved. Functional analysis of the selected genes showed genes significantly associated to mitochondrial dysfunction, protein ubiquitination, gene expression and cell death. Conclusions: PD affects gene expression in blood, suggesting the potential for the development of a blood-based gene expression test.
A Systematic Review of Impulse Control Disorders in Parkinson's Disease
Authors: Callesen Mette Buhl , Scheel-Krüger Jørgen , Kringelbach Morten L. , Møller Arne
Published: December 2019

Throughout the past decade it has been recognized that dopaminergic medication administered to remedy motor symptoms in Parkinson's disease is associated with an enhanced risk for impulse control disorders and related compulsive behaviors such as hobbyism, punding, and the dopamine dysregulation syndrome. These complications are relatively frequent, affecting 6–15.5% of patients, and they most often appear, or worsen, after initiation of dopaminergic therapy or dosage increase. Recently, impulse control disorders have also been associated with subthalamic nucleus deep brain stimulation. Here we present a systematic overview of literature published between 2000 and January 2013 reporting impulse control disorders in Parkinson's disease. We consider prevalence rates and discuss the functional neuroanatomy, the impact of dopamine-serotonin interactions, and the cognitive symptomatology associated with impulse control disorders in Parkinson's disease. Finally, perspectives for future research and management of impulse control disorders in Parkinson's disease are discussed.
Objective Motion Sensor Assessment Highly Correlated with Scores of Global Levodopa-Induced Dyskinesia in Parkinson's Disease
Authors: Mera Thomas O. , Burack Michelle A. , Giuffrida Joseph P.
Published: December 2019

Background: Chronic use of medication for treating Parkinson's disease (PD) can give rise to peak-dose dyskinesia. Adjustments in medication often sacrifice control of motor symptoms, and thus balancing this trade-off poses a significant challenge for disease management. Objective: To determine whether a wrist-worn motion sensor unit could be used to ascertain global dyskinesia severity over a levodopa dose cycle and to develop a severity scoring algorithm highly correlated with clinician ratings. Methods: Fifteen individuals with PD were instrumented with a wrist-worn motion sensor unit, and data were collected with arms in resting and extended positions once every hour for three hours after taking a levodopa dose. Two neurologists blinded to treatment status viewed subject videos and rated global and upper extremity dyskinesia severity based on the modified Abnormal Involuntary Movement Scale (mAIMS). Linear regression models were developed using kinematic features extracted from motion sensor data and extremity, global, or combined (average of extremity and global) mAIMS scores. Results: Dyskinesia occurring during a levodopa dose cycle was successfully measured using a wrist-worn sensor. The logarithm of the power spectrum area between 0.3–3 Hz and the combined clinician scores resulted in the best model performance, with a correlation coefficient between clinician and model scores of 0.81 and root mean square error of 0.55, both averaged across the arms resting and extended postures. Conclusions: One sensor unit worn on either hand can effectively predict global dyskinesia severity during the arms resting or extended positions.
Improving Detection of Psychiatric Disturbances in Parkinson's Disease: The Role of Informants
Authors: Hirsch Elaina S. , Adler Geri , Amspoker Amber B. , Williams James R. , Marsh Laura
Published: December 2019

Background: Under-recognition of psychiatric disturbances in patients with Parkinson's disease (PD) contributes to greater overall morbidity. Little is known about the value of collateral psychiatric history, obtained using standardized assessments with informants, for increasing recognition of PD-related psychiatric illness. Objective: To examine the extent to which informants provide critical information that enabled psychiatrists to establish psychiatric diagnoses in patients with PD. Methods: Individuals with PD (n = 223) and an informant were interviewed separately regarding the PD patient's psychiatric history and current status. A six-psychiatrist panel rated the extent to which informant data was required to establish the final consensus best-estimate current psychiatric diagnoses. Informants rated as “Crucial” or “Significantly Informative” comprised a “Critical Informant” (CI) subgroup; remaining informants were classified as the “Non-Critical Informant” (NCI) subgroup. Results: Of the informants, 71 (31.4%) were “critical” for determining a psychiatric diagnosis. Without a CI, 81.3% of those with impulse control disorders and 43.8% of those with anxiety disorders would not have been diagnosed. Male PD patients and those with less severe motor deficits were also more likely to require a CI. Conclusions: Informants aid in the identification of psychiatric diagnoses, especially impulse control and anxiety disorders. This has implications for clinical practice and conduction of clinical trials.
Measurement of LRRK2 and Ser910/935 Phosphorylated LRRK2 in Peripheral Blood Mononuclear Cells from Idiopathic Parkinson's Disease Patients
Authors: Dzamko Nicolas , Chua Germaine , Ranola Madelaine , Rowe Dominic B. , Halliday Glenda M.
Published: December 2019

A significant number of autosomal dominantly inherited Parkinson's disease (PD) cases are due to mutations in the leucine-rich repeat kinase 2 (LRRK2) gene. In cells, these pathogenic mutations have a number of differing effects on LRRK2 enzymatic activity and protein stability. In particular, five of the six described pathogenic LRRK2 mutations ablate the constitutive phosphorylation of LRRK2 on Ser910 and Ser935, two residues required for binding of LRRK2 to 14-3-3 proteins. This suggests a potential pathogenic role for these residues. However, LRRK2 kinase inhibitors, which have shown early promise as neuroprotective agents, also ablate the phosphorylation of Ser910 and Ser935. Additionally, LRRK2 is phosphorylated on Ser910 and Ser935 following activation of the inflammatory toll-like receptor pathway and inflammatory cytokines are often increased in PD patients. Whether LRRK2 protein or phosphorylation is altered in idiopathic PD is unknown. We therefore measured LRRK2 protein and its phosporylation in peripheral blood mononuclear cells (PBMCs) from 33 idiopathic Parkinson's disease patients and 27 age-matched controls. We found no significant difference in total LRRK2 protein levels in PBMCs from PD patients compared to controls. Furthermore, total LRRK2 protein expression was not effected by age, disease duration, disease severity or levodopa medication. The amount of phosphorylation on LRRK2 at both Ser910 and Ser935 correlated highly with total LRRK2 levels and was also unchanged in PD patients. Therefore, changes in LRRK2 Ser910/Ser935 phosphorylation in PBMCs are unlikely to contribute to idiopathic Parkinson's disease or be of utility as a disease biomarker. However, the invariance of Ser910 and Ser935 phosphorylation in PD PBMC's suggests that these residues could be used as pharmacodynamic biomarkers for the effectiveness of LRRK2 kinase inhibitors in patients.
The Role of Basal Ganglia in Language Production: Evidence from Parkinson's Disease
Authors: Macoir Joël , Fossard Marion , Mérette Chantal , Langlois Mélanie , Chantal Sophie , Auclair-Ouellet Noémie
Published: December 2019

According to the dominant view in the literature, basal ganglia do not play a direct role in language but are involved in cognitive control required by linguistic and non-linguistic processing. In Parkinson's disease, basal ganglia impairment leads to motor symptoms and language deficits; those affecting the production of verbs have been frequently explored. According to a controversial theory, basal ganglia play a specific role in the conjugation of regular verbs as compared to irregular verbs. We report the results of 15 patients with Parkinson's disease in experimental conjugation tasks. They performed below healthy controls but their performance did not differ for regular and irregular verbs. These results confirm that basal ganglia are involved in language processing but do not play a specific role in verb production.
Pacific Northwest Udall Center of Excellence Clinical Consortium: Study Design and Baseline Cohort Characteristics
Authors: Cholerton Brenna A. , Zabetian Cyrus P. , Quinn Joseph F. , Chung Kathryn A. , Peterson Amie , Espay Alberto J. , Revilla Fredy J. , Devoto Johnna , Watson G. Stennis , Hu Shu-Ching , Edwards Karen L. , Montine Thomas J. , Leverenz James B.
Published: December 2019

Background: The substantial proportion of individuals with Parkinson's disease (PD) who have or are expected to develop concomitant cognitive impairment emphasizes the need for large, well-characterized participant cohorts to serve as a basis for research into the causes, manifestations, and potential treatments of cognitive decline in those with PD. Objective: To establish a multi-site clinical core that cognitively and clinically characterizes patients with PD by obtaining quality longitudinal clinical, neuropsychological, and validated biomarker data. Methods: Six hundred nineteen participants with idiopathic PD (68.0 ± 9.1 years, 7.1 ± 6.2 years since diagnosis, 70% males) were enrolled in the Pacific Northwest Udall Center (PANUC), one of the Morris K. Udall Centers of Excellence for Parkinson's Research, Clinical Consortium and underwent comprehensive clinical and neuropsychological assessment. Participants were diagnosed with no cognitive impairment (PD-NCI), mild cognitive impairment (PD-MCI), or dementia (PDD) at a diagnostic consensus conference. Results: A substantial proportion of the overall sample was diagnosed with cognitive impairment at baseline: 22% with PDD and 59% with PD-MCI. A higher rate of cognitive impairment was observed in men than women (87% vs. 68%, p < 0.0001), despite a higher level of education. Most patients older than 50 years at the time of diagnosis and with disease duration greater than 10 years were cognitively impaired or demented. Conclusions: The PANUC Clinical Consortium is a clinically and cognitively well-characterized cohort of patients with PD. Baseline cohort characteristics demonstrate a high rate of cognitive impairment in the sample, as well as potential sex differences with regard to cognitive diagnosis. The PANUC Clinical Consortium, with its access to biomarker, genetic, and autopsy data, provides an excellent foundation for detailed research related to cognitive impairment in PD.
Increased Expression of ABCA8 in Multiple System Atrophy Brain is Associated with Changes in Pathogenic Proteins
Authors: Bleasel Jonathan M. , Hsiao Jen-Hsiang T. , Halliday Glenda M. , Kim Woojin Scott
Published: December 2019

Background: Multiple system atrophy (MSA) is a fatal neurodegenerative disease of unknown aetiology characterised by the accumulation of insoluble α-synuclein (α-syn) aggregates in the cytoplasm of myelin-producing oligodendrocytes. Dysfunction of the lipid-rich myelin membrane may precede α-syn pathology in MSA pathogenesis. ATP-binding cassette transporter A8 (ABCA8) is a little-studied lipid transporter, which has recently been found to be highly expressed in oligodendrocyte-rich white matter regions of the human brain. ABCA8 expression promotes sphingomyelin production in oligodendrocytes in vitro, suggesting a role in myelin formation and maintenance. Objective: We hypothesise that aberrant ABCA8 expression in oligodendrocytes plays a role in the early pathogenesis of MSA by impacting myelin stability and regulation of α-syn and p25α. Methods: We measured the expression of ABCA8, α-syn and p25α in MSA brains in disease-affected grey matter (GM, putamen and cerebellum), disease-affected white matter (WM, under the motor cortex) and an unaffected brain region (visual cortex). We transfected human oligodendrocytes with ABCA8 and assessed its impact on α-syn and p25α expression. Results: ABCA8 expression was significantly increased in the disease-affected GM and WM with no significant change in the unaffected brain region. α-syn and p25α expression were significantly increased in the disease-affected WM and GM respectively. Overexpression of ABCA8 in oligodendrocytes caused significant increases in both α-syn and p25α expression. Conclusions: These data suggest a direct relationship between the levels of ABCA8 and the ectopic expression of α-syn and increased expression of p25α. As these data reflect results found in MSA, we hypothesise that increased ABCA8 may precipitate MSA pathology.
Reduced Striatal Dopamine Synthesis Capacity is Associated with Symptoms of Depression in Patients with de novo Unmedicated Parkinson's Disease
Authors: Joutsa Juho , Rinne Juha O. , Eskola Olli , Kaasinen Valtteri
Published: December 2019

Previous studies have suggested that impaired striatal dopamine function might be independently related to depression in patients with Parkinson's disease (PD), but the results are not uniform. In this study, we investigated de novo unmedicated and medicated PD patients with more advanced disease using 18F-fluorodopa-PET. In unmedicated de novo patients, but not in medicated patients, higher depression scores were associated with lower striatal 18F-fluorodopa uptake. These results indicate that impaired striatal dopaminergic function in PD is related to depressive symptoms and that these effects can be observed in de novo patients without the confounding effects of advanced neurodegeneration and medications.
New Perspectives in Nuclear Neurology for the Evaluation of Parkinson's Disease
Authors: Benadiba Marcel , Luurtsema Gert , Tumas Vitor , Buchpigel Carlos Alberto , Busatto Geraldo F.
Published: December 2019

The pathophysiology of Parkinson's disease (PD) has not yet been completely elucidated. However, during the past few years, significant progress has been made in understanding the intra- and extracellular mechanisms by which proteins such as alpha-synuclein and neuroinflammatory molecules may display impaired function and/or expression in PD. Recent developments in imaging techniques based on positron emission tomography (PET) and single photon emission computed tomography (SPECT) now allow the non-invasive tracking of such molecular targets of known relevance to PD in vivo. This article summarizes recent PET and SPECT studies of new radiopharmaceuticals and discusses their potential role and perspectives for use in the fields of newdrug development and early diagnosis for PD, as well to aid in differential diagnosis and monitoring of the progression of PD.