bluuebunny/crossref_metadata_2025 huggingface dataset:
The architecture and transformation of governance systems: Power, knowledge, and conflict
Authors: Burns Tom R. , Stöhr Christian
Published: December 2019

This article aims at contributing to governance conceptualization and its application to case study analyses. Two of the challenges which the theoretical and empirical work in the present article address concern a specification of universal dimensions of governance systems and an identification of selected mechanisms of governance formation and transformation – specifying a few key drivers that explain how governance systems are established, maintained or changed through power, knowledge, and contestation/conflict processes. These tools are applied to empirical cases of governance structures as well as cases of governance transformation.
Managing recruitment and selection in the digital age: e-HRM and resumes
Authors: Furtmueller Elfi , Wilderom Celeste , Tate Mary
Published: December 2019

Recruiters, in the business of screening job applicants, are increasingly dependent on information systems especially digital resume databases. However, the current literature does not provide a consensus on the requirements for resume content for digital recruiting. This research contributes to the understanding of the different requirements of recruiters for offline and online resumes. We offer an analysis of the relevant literature; interviews with recruiters; and content analysis of the resume fields of 40 e-Recruiting sites. Based on this we identified a number of challenges in categorizing digital resume data and digital matching between resumes and job advertisements. We identify areas for further research on the maintenance and extension of online resume databases and derive recommendations for digital resume design.
Sustainable Development requires diverse Sound Cultures
Authors: Hiwaki Kensei
Published: December 2019

A viable human future may necessitate Sustainable Development that, in turn, requires soundness of diverse society-specific cultures (‘Cultures’) across the world. It is not farfetched to think that Sustainable Development relies on a constantly generated entelechy of all humanity—the most intrinsic energy source of human societies—that may naturally require a perpetual enrichment of diverse Cultures. Such enrichment may, no doubt, conduce to generating reasonably sound cultures (‘Sound Cultures’) across the world to help maintain perpetually a long-term, future-oriented sound communal value system that consists of human integrity, solidarity, continuity and mutuality. Above all, such enrichment may conduce to a dynamic communal harmony that perpetually integrates and equilibrates material-and-spiritual values, individual-and-communal values, traditional-and-progressive values and own-and-other's values. Such diverse Sound Cultures across the world may generate relational mutuality that pays due respects to all peoples and societies in the world. Also, Sound Cultures enhance human entelechy for personal vitality, organizational invigoration and viable socioeconomic development, as well as morality, cooperation and amicable relationship. Given the on-going devastation of diverse Cultures and natural environment (‘Nature’), which robs a viable human future, it is most important for us to start immediately enriching vigorously, perpetually and collaboratively the diverse Cultures across the world—a paradigm shift for Sustainable Development.
Comprehending transformational critical thinking
Authors: Karras Sotirios
Published: December 2019

Looking at the societal functions that cause radical societal change as the products of us – our society's producers and users– entails investigating systems functioning within the nature of our human nature. This article shows the interchange of these systems, the lack of balance among them and their seemingly random overlaps that form in us, all different kinds of persons. A comprehensive framework for these systems allows addressing the fact that scholars too are subjected to them, while we discover and present our research findings. The attestation that we engage in the world making things in our own image, according to the systems functioning in us, while getting to know our way around, shows that our society too is structured in our own image. The article contributes the discovery of a largely overlooked new agent in the systems functioning in us. And it discloses another new, also overlooked societal agent, which we also produce in our image. With its two contributions, the article shows how the new agent in us can become a solution to our transformation and the new societal agent a solution to societal change.
Technology changes at work and employee reactions: The role of leader behavior
Authors: Lilly Juliana D. , Durr David W.
Published: December 2019

New technology is implemented frequently in the workplace, placing new demands on employees that may cause stress and anxiety in the process. In addition, many people now engage in virtual work with few human interactions and an increased possibility of frustration with new, complicated technology. Employee attitudes toward new technology are important because attitudes influence behavior. Thus, manager behavior that impacts employee attitudes toward new technology may, in turn, influence employee work behaviors that are necessary for efficiency and productivity. Cognitive dissonance theory [7] is used in the present study to examine the link between manager behavior, employee attitude toward new technology, employee attitude toward virtual work, and organizational citizenship behavior (OCB). Results show that relationship-oriented leader behavior is positively related to attitude toward new technology and the OCB dimensions of civic virtue and loyalty, but task-oriented leader behavior is not. Attitude toward new technology is positively related to attitude toward virtual work, civic virtue and loyalty. These findings suggest that manager behavior does influence employee attitudes toward new technology and toward virtual work. As a result, managers may want to consider their leadership style when introducing new technology in the workplace.
Energy simulation of embedded XScale systems with XEEMU
Authors: Herczeg Zoltán , Schmidt Daniel , Kiss Ákos , Wehn Norbert , Gyimóthy Tibor
Published: December 2019

Energy efficiency is key in embedded system design. Understanding the complex issue of software power consumption in early design phases is of extreme importance to make the right design decisions. Here, not only the CPU but also the external memory plays a very important role. Power simulators offer flexibility and allow a detailed view on the sources of power consumption. However, many simulators lack accuracy and focus only on the CPU core without considering the memory subsystem. In this paper, we present XEEMU, a fast, cycle-accurate simulator, which aims at accurately simulating the power consumption of an XScale-based system including its memory subsystem. It has been validated using measurements on real hardware and shows a high accuracy for runtime, instantaneous power, and total energy consumption estimation. The average error is as low as 3.0% and 1.6% for runtime and CPU energy consumption estimation, respectively.
Automatic generation of safe handlers for multi-task systems
Authors: Rutten Eric , Marchand Hervé
Published: December 2019

We are interested in the programming of real-time embedded control systems, such as in robotic, automotive or avionic systems. They are designed with multiple tasks, each with multiple modes. It is complex to design task handlers that control the switching of activities in order to insure safety properties of the global system. We propose a model of tasks in terms of transition systems, designed especially with the purpose of applying existing discrete controller synthesis techniques. This provides us with a systematic methodology, for the automatic generation of safe task handlers, with the support of synchronous languages and associated tools.
Performance considerations of embedded computations in distributed databases
Authors: Hasegawa Masaki , Bhalla Subhash , Yang Laurence T.
Published: December 2019

In many applications using database systems, the conventional method of transaction processing can not be used. This is on account of lack of integration and existence of centralized solutions. Such situations exist within heterogeneous systems, mobile database transactions and time-critical applications requiring admission on priority for a select group of transactions. For example, in conventional methods, the deadlock detection is based on use of delay to cause and watch deadlocks. It generates many difficulties, such as, (a) high overheads of periodic checking (b) Non-deterministic nature of the delays, and (c) difficulties to scale-up the centralized solutions. The existing proposal lacks in local processing for distributed transactions. The proposed technique uses normal message communication among peers. The proposal leads to enhanced role for resource sites. The proposal introduces asynchronous operations in transaction processing. As a result the detection processes do not wait for occurrences of time-outs delays. In most cases the technique eliminates the possibility of occurrence of waiting delays.
Discussion of an instrumented screw pile load test and connected pile group load settlement behavior
Authors: Van Impe P.O. , Van Impe W.F. , Seminck L.
Published: December 2019

The aim of the paper is to discuss a fully instrumented screw pile load test up to failure, in difficult heterogeneous soil conditions along the shaft. The pre-stressing of the pile during its installation process has been brought to attention as an important item to assisting in explaining the differences in pile capacity and load settlement curve on the one hand, and the data as registered from the pile shaft instrumentation. In the second part of the paper, starting info on the registered load settlement data of the foundation slabs of each of the three, closely positioned, oil tanks of 48 m diameter and 19 m of height are shared and briefly analyzed.
Instability of unsaturated soils: A review of theoretical methods
Authors: Buscarnera Giuseppe , Mihalache Constance
Published: December 2019

The paper reviews a series geomechanical approaches for interpreting instabilities in unsaturated geomaterials, a class of solids involved in numerous geo-engineering problems, such as hazard forecasting, infrastructure management, underground disposal of by-products and energy technologies. The review details the connection between second-order work input, loss of controllability and material failure. Hydro-mechanical problems are addressed, focusing on a specific class of environmental perturbations that can cause sharp changes in both mechanical and hydrologic variables. A procedure to define the second-order work input to an unsaturated soil volume is discussed first. It is pointed out that this energy measure motivates the incremental form of the constitutive laws for stability analyses. It is then discussed how to link the theory of hydro-mechanical controllability with constitutive approaches for unsaturated soils, which are typically based on the framework of strain-hardening plasticity with extended hardening. In doing so, the crucial role of the properties that govern the interactions between soil skeleton and fluid-retention processes is emphasized. The implications of these findings are commented with reference to a specific application: the forecasting of landslide triggering in natural slopes. It is shown that the use of suitable stability indices allows one to differentiate between frictional slips and volumetric collapses turning into flows. These results suggest that geomechanical theories calibrated for site-specific properties can support the quantitative assessment of landslide susceptibility, as well as a number of other engineering applications involving the instability of unsaturated porous media.
Effects of residual stresses on shaft friction of bored cast in situ piles in sand
Authors: Mascarucci Ylenia , Mandolini Alessandro , Miliziano Salvatore
Published: December 2019

The existence of residual stresses locked-in prefabricated displacement piles is a well-known problem and has been addressed by a number of researchers in the last decades. This is not the case with cast in situ piles: as a consequence of concrete curing, pile-soil interaction starts soon after concrete casting, causing stress changes in terms of both normal and shear stresses. Such circumstance has been confirmed by few experimental evidences, reported in the paper, in saturated or dry soil conditions. In order to evaluate the influence of residual stresses on the subsequent pile response to axial loading, a broad parametric study has been carried out by means of numerical modelling. Particular focus is given to the effects induced on the shaft friction of floating bored piles embedded in wet and dry sandy soils. The results have been interpreted with the aim of highlighting errors commonly made if a stress-free pile is assumed when interpreting a specific load test results on instrumented piles and/or arranging general design methods.
Widespread Heterogeneous Neuronal Loss Across the Cerebral Cortex in Huntington's Disease
Authors: Nana Alissa L. , Kim Eric H. , Thu Doris C.V. , Oorschot Dorothy E. , Tippett Lynette J. , Hogg Virginia M. , Synek Beth J. , Roxburgh Richard , Waldvogel Henry J. , Faull Richard L.M.
Published: December 2019

Huntington's disease is an autosomal dominant neurodegenerative disease characterized by neuronal degeneration in the basal ganglia and cerebral cortex, and a variable symptom profile. Although progressive striatal degeneration is known to occur and is related to symptom profile, little is known about the cellular basis of symptom heterogeneity across the entire cerebral cortex. To investigate this, we have undertaken a double blind study using unbiased stereological cell counting techniques to determine the pattern of cell loss in six representative cortical regions from the frontal, parietal, temporal, and occipital lobes in the brains of 14 Huntington's disease cases and 15 controls. The results clearly demonstrate a widespread loss of total neurons and pyramidal cells across all cortical regions studied, except for the primary visual cortex. Importantly, the results show that cell loss is remarkably variable both within and between Huntington's disease cases. The results also show that neuronal loss in the primary sensory and secondary visual cortices relate to Huntington's disease motor symptom profiles, and neuronal loss across the associational cortices in the frontal, parietal and temporal lobes is related to both Huntington's disease motor and to mood symptom profiles. This finding considerably extends a previous study (Thu et al., Brain, 2010; 133:1094–1110) which showed that neuronal loss in the primary motor cortex was related specifically to the motor symptom profiles while neuronal loss in the anterior cingulate cortex was related specifically to mood symptom profiles. The extent of cortical cell loss in the current study was generally related to the striatal neuropathological grade, but not to CAG repeat length on the HTT gene. Overall our findings show that Huntington's disease is characterized by a heterogeneous pattern of neuronal cell loss across the entire cerebrum which varies with symptom profile.
Kinase Signalling in Huntington's Disease
Authors: Bowles Kathryn R. , Jones Lesley
Published: December 2019

Alterations in numerous signal transduction pathways and aberrant activity of specific kinases have been identified in multiple cell and mouse models of Huntington's disease (HD), as well as in human HD brain. The balance and integration of a network of kinase signalling pathways is paramount for the regulation of a wide range of cellular and physiological processes, such as proliferation, differentiation, inflammation, neuronal plasticity and apoptosis. Unbalanced activity within these pathways provides a potential mechanism for many of the pathological phenotypes associated with HD, such as transcriptional dysregulation, inflammation and ultimately neurodegeneration. The characterisation of aberrant kinase signalling regulation in HD has been inconsistent and may be a result of failure to consider integration between multiple signalling pathways, as well as alterations that may occur over time with both age and disease progression. Collating the information about the effect of mHTT on signalling pathways demonstrates that it has wide ranging effects on multiple pro- and anti-apoptotic kinases, resulting in the dysregulation of numerous complex interactions within a dynamic network.
The Co-Occurrence of Alzheimer's Disease and Huntington's Disease: A Neuropathological Study of 15 Elderly Huntington's Disease Subjects
Authors: Davis Marie Y. , Keene C. Dirk , Jayadev Suman , Bird Thomas
Published: December 2019

Background: Dementia is a common feature in both Huntington's disease (HD) and Alzheimer's disease (AD), as well as in the general elderly population. Few studies have examined elderly HD patients with dementia for neuropathologic evidence of both HD and AD. Objective: We present neuropathological findings in a retrospective case series of 15 elderly HD patients (ages 60–91 years), 11 of whom had prominent clinical dementia. Methods: Post-mortem brain tissue was examined and stained for evidence of both HD and AD including Vonsattel grading and Htt-repeat expansion, Bielskowsky, tau, β amyloid, and TDP43 immunostaining. Results: Mean age at death was 76.8 years, mean disease duration was 18.6 years, and mean CAG repeat expansion was 42. Evidence of AD in addition to HD pathology was present in 9 of 11 (82%) patients with prominent dementia, suggesting that AD may be more commonly co-occurring with HD than previously appreciated. Two patients had only HD as the basis of dementia and four patients did not have prominent dementia. One patient with marked parkinsonian features was not L-dopa responsive and had no substantia nigra Lewy bodies at autopsy. Conclusions: Our study suggests that AD may frequently contribute to cognitive decline in elderly HD patients which complicates the assessment and management of such individuals. Further study is needed to determine if there is a higher incidence of AD in persons with HD compared to the general population. In addition, our series includes one HD patient whose clinical features masqueraded as Parkinson's disease but was not responsive to levodopa therapy.
Coexistence of Amyotrophic Lateral Sclerosis and Myasthenia Gravis
Authors: Yamashita Satoshi , Fujimoto Akiko , Mori Yukiko , Hirahara Tomoo , Mori Akira , Hirano Teruyuki , Maeda Yasushi , Uchino Makoto , Ando Yukio
Published: December 2019

The mechanisms by which amyotrophic lateral sclerosis (ALS) causes motor neuron degeneration remain unknown. We present the case of a 77-year-old Japanese female with clinically probable ALS, who developed ALS symptoms 41 years after onset of myasthenia gravis (MG). We concluded that neither the relapse of MG nor the adverse effects of anti-cholinesterase medication aggravated her symptoms. Although MG and ALS are extremely rare, we reviewed several case reports describing their coexistence. We suggest that clinicians should consider the possibility of ALS occurring with MG. Further investigations will improve our understanding of the pathogenic relationship between ALS and MG.
The Relationship between Abnormalities of Saccadic and Manual Response Times in Parkinson's Disease
Authors: Antoniades Chrystalina A. , Xu Zheyu , Carpenter R.H.S. , Barker Roger A.
Published: December 2019

Background: Clinicians normally use subjective rating scales to estimate the impairment of patients with Parkinson's disease (PD). More objective and quantitative methods of assessment would greatly aid our understanding of the disease. One promising approach is to measure reaction time: the large amount of data recorded in a short period provides precise, reproducible evaluation of the underlying neural decision processes. Manual evoked reaction times and repetitive tapping speed are often used, but differences of experimental design and analysis tend to obscure their interpretation. Saccadic latency, in many ways a simpler and more standardised task, is also normally affected in PD, but its relation to the kind of movement impairment that affects patients' quality of life is less obvious. Objestive: The aim of this study was to evaluate these tasks in detail and also see whether their use in combination could provide a better measure than each in isolation. Methods: We compared three reaction time tasks: saccadometry, and evoked and spontaneous tapping, using protocols as similar as possible, correlating the measurements within a group of PD patients and of age-matched controls. Results: Surprisingly, manual and saccadic performance is uncorrelated in the normal population; but both are similarly affected by PD. The differences between groups are strengthened when the three measures are combined. Conclusions: Saccadic latency can be regarded as an appropriate surrogate for more general kinds of motor impairment. The combination of saccadic and manual parameters enhances their potential use in quantifying disease status and evaluating treatments.
Neuronal Expression of Familial Parkinson's Disease A53T α-Synuclein Causes Early Motor Impairment, Reduced Anxiety and Potential Sleep Disturbances in Mice
Authors: Rothman Sarah M. , Griffioen Kathleen J. , Vranis Neil , Ladenheim Bruce , Cong Wei-na , Cadet Jean-Lud , Haran Jamie , Martin Bronwen , Mattson Mark P.
Published: December 2019

Background: Mutations in the human α-synuclein gene lead to early-onset Parkinson's disease (PD); however, phenotypes of α-synuclein mutant mice vary depending upon the promoter driving transgene expression. Objective: The goal of this study was to characterize behavior and neurochemical alterations in mice expressing mutant (A53T) human α-synuclein, controlled by a neuron-specific Thy-1 promoter. Our data provide important additional phenotypic and biochemical characterization of a previously generated model of PD. Methods: A53T (SNCA) and wild type (WT) littermate mice were evaluated for motor function (rotarod and stride length) and anxiety (elevated plus maze and open field) every 2 weeks. At 24 weeks mice were evaluated in a Comprehensive Lab Animal Monitoring System (CLAMS). A separate cohort of mice were euthanized at 12, 24 and 36 weeks for immunoblot analysis of α-synuclein, dopamine transporter (DAT) and tyrosine hydroxylase (TH) in the striatum, and hypothalamic serotonin and metabolites were measured. Results: SNCA mice display significant motor deficits at 14–18 weeks of age compared to WT mice, which progress over time. CLAMS analysis revealed an increase in activity during the dark phase and a reduction in overall estimated sleep time for SNCA mice compared to WT consistent with clinical reports of sleep abnormalities in PD. A transient change in the levels of DAT appeared at 12 weeks in the striatum and serotonin levels were also altered in the hypothalamus at this time point. Conclusions: This PD model displays consistent and clinically relevant motor and sleep phenotypes. Anxiety phenotypes are consistent with other α-synuclein based PD models yet incongruous with typical clinical symptoms. Early increases in serotonin levels potentially explain reductions in anxiety behaviors and sleep.
Inhaled Apomorphine in Patients with ‘on-off’ Fluctuations: A Randomized, Double-blind, Placebo-controlled, Clinic and Home Based, Parallel-group Study
Authors: Grosset Katherine A. , Malek Naveed , Morgan Frazer , Grosset Donald G.
Published: December 2019

Background: In later stages of Parkinson's disease, treatment of ‘off’ periods with subcutaneous apomorphine is helpful but requires injection; inhaled apomorphine would be potentially more convenient. Objectives: To identify optimal efficacy, safety and tolerability for inhaled apomorphine in reversing Parkinson's disease ‘off’ periods. Methods: A randomized, double-blind, 2:1 active:placebo, parallel-group, ascending dose titration study was conducted at 16 centres in 3 countries. Inhaled apomorphine was administered under observation, at escalating fine particle doses of 1.5, 2.5, 3.5 and 4.5 mg. This was followed by at-home patient self-treatment for 2 to 4 weeks, assessed from ‘on-off’ diaries. Results: In 55 patients, mean age 65.6 years (range 47–79), mean disease duration 12 years (range 5–22), the mean improvement in the unified PD rating scale part 3 (UPDRS 3) was significantly greater for apomorphine (mean dose 2.3 mg) at 19.5 (standard deviation 13.6) than for placebo at 9.9 (9.6), least squares mean difference 8.4 (95% confidence interval 1.2 to 15.5, p = 0.023). During at-home testing, mean ‘off’ time per day was reduced by 139.8 minutes (standard deviation 149.6) for apomorphine versus 68.0 (108.6) minutes for placebo, least squares mean difference not significant at 100.5 minutes (95% confidence interval −12.0 to 212.9, p = 0.078). The onset of action was faster for apomorphine (mean 8.1 SD 6.2 minutes) than placebo (mean 13.1 SD 6.6 minutes) (p < 0.0001). Reversal of ‘off’ episodes was significantly more likely for episodes treated with apomorphine than those treated with placebo: apomorphine 64.6% SD 32.3 of episodes versus placebo 11.1% SD 15.3 (p < 0.0001). During at-home treatment, 36% of apomorphine and 20% of placebo patients experienced adverse events. Conclusions: Inhaled apomorphine in the dose range 1.5 to 4.5 mg, significantly improved UPDRS 3 scores in the clinic, and aborted a greater proportion of ‘off’ periods at-home, compared to placebo. However, daily ‘off’ time was not significantly reduced by the use of inhaled apomorphine.
Personality Affects Aspects of Health-Related Quality of Life in Parkinson's Disease via Psychological Coping Strategies
Authors: Whitworth Stephanie R. , Loftus Andrea M. , Skinner Timothy C. , Gasson Natalie , Barker Roger A. , Bucks Romola S. , Thomas Meghan G.
Published: December 2019

BACKGROUND: Personality traits influence health-related quality of life (HRQoL) in Parkinson's disease (PD). Further, an individual's personality traits can influence the strategies they use to cope with a particular stressful situation. However, in PD, the interplay between personality traits, choice of coping strategy, and their subsequent effect on HRQoL remains unclear. OBJECTIVE: The objective of this study was to examine whether personality (neuroticism and extraversion) indirectly affects HRQoL through the use of specific psychological coping strategies. METHODS: One hundred and forty-six patients with PD completed questionnaires on personality (Big Five Aspects Scale; BFAS), coping (Ways of Coping Questionnaire; WCQ), and mood-specific (Depression, Anxiety and Stress Scale; DASS-21) and disease-specific HRQoL (Parkinson's Disease Questionnaire; PDQ-39). RESULTS: After controlling for gender, age at diagnosis, and age at testing, the emotion-focused coping strategy of escape-avoidance was significantly correlated with neuroticism and certain aspects of HRQoL (cognitive impairment and social support). This suggests that neurotic personality traits may negatively impact on some aspects of HRQoL due to an increased use of escape-avoidance coping strategies. By contrast, planned problem-solving and escape-avoidance coping strategies were both significantly linked to extraversion and interpersonal and mood-related domains of HRQoL. This suggests that extraversion may positively impact on some aspects of HRQoL due to patients adopting greater planned, problem-solving coping strategies, and using fewer escape-avoidance coping mechanisms. CONCLUSIONS: Psychological interventions aimed at targeting maladaptive coping strategies, such as the use of escape-avoidance coping, may be effective in minimising the negative impact of neuroticism on HRQoL in PD.
Prevalence of Parkinson Disease Among the Navajo: A Preliminary Examination
Authors: Gordon Paul H. , Zhao Hongwei , Bartley Denise , Sims LT James G. , Begay Mae-Gilene , Pirio Richardson Sarah , Lewis Johnnye , Rowland Andrew S.
Published: December 2019

Background: The prevalence of Parkinson disease (PD) varies by geographic location and ethnicity, but has never been studied among the Navajo. Methods: Period prevalence was calculated using the number of people diagnosed with PD in the Shiprock Service Unit Indian Health Service database during 1995–1999, 2000–2004, and 2005–2009 as the numerator, and the number seen for any reason as the denominator. Age-standardized rates were calculated using the 2000 US population. Results: During 2005–2009, 126 people were seen with PD (crude prevalence = 203.7/100,000 population). The age-adjusted rate was 335.9 (95% C. I. 277.8–394.0) overall, 438.5 (95% C.I. 336.5–540.5) in men and 259.7 (95% C.I. 192.8–326.7; p = 0.004) in women. The adjusted rate increased with age: 788.8 (95% C.I. 652.0–925.7) for age 40 and above to 1964.9 (95% C.I. 1613.7–2316.1) for age 60 and above. Adjusted rates were 246.6 (95% C.I. 187.2–306.0) in 1995–1999 and 284.7 (95% C.I. 227.0–342.4) in 2000–2004. Conclusion: Parkinson disease appears common among the Navajo. Estimates increased with age and time, and were higher in men. In-person interviews are needed to confirm these estimates, and to determine incidence, quality of care, and risk factors for PD among the Navajo.
Airway Somatosensory Deficits and Dysphagia in Parkinson's Disease
Authors: Hammer Michael J. , Murphy Caitlin A. , Abrams Trisha M.
Published: December 2019

Background: Individuals with Parkinson's disease (PD) often experience substantial impairment of swallow control, and are typically unaware of the presence or severity of their impairments suggesting that these individuals may also experience airway sensory deficits. However, the degree to which impaired swallow function in PD may relate to airway sensory deficits has yet to be formally tested. Objective: The purpose of this study was to examine whether airway sensory function is associated with swallow impairment in PD. Methods: Eighteen PD participants and 18 healthy controls participated in this study and underwent endoscopic assessment of airway somatosensory function, endoscopic assessment of swallow function, and clinical ratings of swallow and disease severity. Results: PD participants exhibited abnormal airway somatosensory function and greater swallow impairment compared with healthy controls. Swallow and sensory deficits in PD were correlated with disease severity. Moreover, PD participants reported similar self-rated swallow function as healthy controls, and swallow deficits were correlated with sensory function suggesting an association between impaired sensory function and poor self-awareness of swallow deficits in PD. Conclusions: These results suggest that control of swallow is influenced by airway somatosensory function, that swallow-related deficits in PD are related to abnormal somatosensation, and that swallow and airway sensory function may degrade as a function of disease severity. Therefore, the basal ganglia and related neural networks may play an important role to integrate airway sensory input for swallow-related motor control. Furthermore, the airway deficits observed in PD suggest a disintegration of swallow-related sensory and motor control.
Saffron Pre-Treatment Offers Neuroprotection to Nigral and Retinal Dopaminergic Cells of MPTP-Treated mice
Authors: Purushothuman Sivaraman , Nandasena Charith , Peoples Cassandra L. , El Massri Nabil , Johnstone Daniel M. , Mitrofanis John , Stone Jonathan
Published: December 2019

Background: There is growing evidence that the spice saffron, which contains powerful anti-oxidants, offers protection against neurodegenerative disorders, including age-related macular degeneration and Alzheimer's disease. Objective: We examined whether saffron pre-treatment protects dopaminergic cells of the substantia nigra pars compacta (SNc) and retina in an acute MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) mouse model of Parkinson's disease. Methods: BALB/c mice received MPTP or saline injections over a 30 hour period, followed by six days survival. For five days prior to injections, the drinking water of the saffron groups was supplemented with saffron (0.01% w/v), while non-saffron groups received normal tap water. After the survival period was complete, brains were processed for tyrosine hydroxylase (TH) immunochemistry and the number of TH+ cells was analysed using the optical fractionator method. Results: In both the SNc and retina, non-conditioned MPTP-injected mice had a reduced number of TH+ cells (30–35%) compared to the saline-injected controls. Saffron pre-conditioning mitigated the reduction, with pre-conditioned MPTP-injected mice having SNc and retinal TH+ cell numbers close to control levels, significantly (25–35%) higher than in non-conditioned MPTP-injected mice. Conclusions: Our results indicated that saffron pre-treatment of mice saved many dopaminergic cells of the SNc and retina from parkinsonian (MPTP) insult.
Aerodynamic Assessment of Phonatory Onset in Parkinson's Disease: Evidence of Decreased Scaling of Laryngeal and Respiratory Control
Authors: Hammer Michael J.
Published: December 2019

Background: Phonatory onset is important for speech and voice and may be substantially impaired in people with Parkinson's Disease (PD). However, the physiologic contributions of laryngeal and respiratory control to phonatory onset in PD are not well understood. Acoustic measurement of phonatory onset in neurological disease has been limited due to the confounding effects of dysarthria and the limited yield of physiologic detail. Objective: The purpose of this study was to test whether air flow measures would be useful to characterize respiratory and laryngeal contributions to phonatory onset, whether acoustic and air flow measures of phonatory onset were aberrant in PD, and whether deficits were significantly associated with voice severity. Methods: Twenty-one PD participants were tested and compared with 25 healthy controls. Testing included acoustic and air flow measures of phonatory onset during syllable production ([pa]) and measures of voice severity. Results: Air flow assessment was possible for all participants; acoustic assessment was only possible for 86% of PD participants. Air flow and acoustic measures revealed shorter phonatory onset times for PD participants than controls. Air flow measures also revealed that PD participants expelled less lung air volume per syllable. Aberrant timing of phonatory onset and reduced lung air volume were associated with increased voice severity. Conclusions: These findings suggest that air flow measures may be useful to assess the laryngeal and respiratory contributions to phonatory onset. These results also suggest that both respiratory and laryngeal control deficits may contribute to phonatory errors in PD, and that phonatory onset deficits are associated with voice severity.
Movement Activation and Inhibition in Parkinson's Disease: A Functional Imaging Study
Authors: Disbrow Elizabeth A. , Sigvardt Karen A. , Franz Elizabeth A. , Turner Robert S. , Russo Kim A. , Hinkley Leighton B. , Herron Timothy J. , Ventura Maria I. , Zhang Lin , Malhado-Chang Norika
Published: December 2019

Background: Parkinson's disease (PD), traditionally considered a movement disorder, has been shown to affect executive function such as the ability to adapt behavior in response to new environmental situations. Objective: to identify the impact of PD on neural substrates subserving two specific components of normal movement which we refer to as activation (initiating an un-cued response) and inhibition (suppressing a cued response). Methods: We used fMRI to measure pre-movement processes associated with activating an un-cued response and inhibiting a cued response plan in 13 PD (ON anti-parkinsonian medications) and 13 control subjects. Subjects were shown a visual arrow cue followed by a matched or mismatched response target that instructed them to respond with a right, left, or bilateral button press. In mismatched trials, an un-cued (new) response was initiated, or the previously cued response was suppressed. Results: We were able to isolate pre-movement responses in dorsolateral prefrontal cortex, specifically in the right hemisphere. During the activation of an un-cued movement, PD subjects showed decreased activity in the putamen and increased cortical activity in bilateral DLPFC, SMA, subcentral gyrus and inferior frontal operculum. During inhibition of a previously cued movement, the PD group showed increased activation in SMA, S1/M1, premotor and superior parietal areas. Conclusion: Right DLPFC plays a role in pre-movement processes, and DLPFC activity is abnormal in PD. Decreased specificity of responses was observed in multiple ROI's. The basal ganglia are involved in circuits that coordinate activation and inhibition involved in action selection as well as execution.
Unaltered lactate and glucose transporter levels in the MPTP mouse model of Parkinson's disease
Authors: Puchades Maja , Sogn Carl Johan , Maehlen Jan , Bergersen Linda H. , Gundersen Vidar
Published: December 2019

Background: Metabolic impairment contributes to development of Parkinson's disease (PD). Mitochondrial dysfunction is involved in degeneration of nigral dopamine neurons. Also, in PD there are alterations in glucose metabolism in nigro-striatal pathways, and increased cerebral lactate levels have been found. Objectives: We raise the question of whether changes in the amount transporters of energy substrates are involved in the pathogenesis of PD. Methods: We have used confocal immunofluorescence and immunogold postembedding electron microscopic techniques to study whether there are altered levels of the transporters for monocarboxylates (MCT1 and MCT2) and glucose (GLUT1) in the MPTP mouse model of PD. Results: We found that MCT1 and GLUT1 were densely located in blood vessel endothelium, while MCT2 was present in perivascular astrocytic end feet processes in the substantia nigra and the striatum of control mice. We found that the localisation and densities of MCTs and GLUT1 were unaltered in the PD model. Discussion: This is the first study reporting on the distribution of metabolic transporters in PD. Our results suggest that, although there are metabolic impairments in PD, the levels of MCT1, MCT2 and GLUT1 is not changed following dopaminergic neurodegeneration. This is in contrast to findings in other neurodegenerative disease, such as mesial temporal lobe epilepsy, where there are large alterations in MCT levels.
Iron Deficiency in Parkinsonism: Region-Specific Iron Dysregulation in Parkinson's Disease and Multiple System Atrophy
Authors: Visanji Naomi P. , Collingwood Joanna F. , Finnegan Mary E. , Tandon Anurag , House Emily , Hazrati Lili-Naz
Published: December 2019

Alpha synuclein pathology is widespread and found in diverse cell types in multiple system atrophy (MSA) as compared to Parkinson's disease (PD). The reason for this differential distribution is unknown. Regional differences in the distribution of iron are associated with neurodegenerative diseases, and here we characterize the relationship between iron homeostasis proteins and regional concentration, distribution and form of iron in MSA and PD. In PD substantia nigra, tissue iron and expression of the iron export protein ferroportin increased, while the iron storage protein ferritin expression was unchanged. In the basis pontis of MSA cases, increased total iron concentration coupled with a disproportionate increase in ferritin in dysmorphic microglia and a reduction in ferroportin expression. This is supported by isothermal remanent magnetisation evidence consistent with elevated concentrations of ferritin-bound iron in MSA basis pontis. Conventional opinion holds that excess iron is involved in neurodegeneration. Our data support that this may be the case in PD. While region-specific changes in iron are evident in both PD and MSA, the mechanisms of iron dysregulation appear quite distinct, with a failure to export iron from the MSA basis pontis coupling with significant intracellular accumulation of ferritin iron. This pattern also occurs, to a lesser extent, in the MSA putamen. Despite the excess tissue iron, the manner of iron dysregulation in MSA is reminiscent of changes in anemia of chronic disease, and our preliminary data, coupled with the widespread pathology and involvement of multiple cell types, may evidence a deficit in bioavailabile iron.
Relationship Between Cognitive Dysfunction and Behavioural Symptoms in Nigerian Patients with Parkinson's Disease No dementia
Authors: Ojagbemi Akin
Published: December 2019

Background: There is presently no information on the behavioural symptoms that are related to cognitive dysfunction in African patients with Parkinson's disease. Objectives: This study highlights the behavioral symptoms that are related to global cognitive dysfunction without dementia, as well as the caregivers' distress they create in a population of Nigerians with idiopathic Parkinson's disease. Methods: Fifty patients with idiopathic Parkinson's disease, confirmed using the United Kingdom Parkinson's Disease Society (UKPDS) Brain Bank Clinical Diagnostic Criteria, were cross-sectionally assessed for cognitive functions using the modified Mini-mental State Examination (MMSE), motor symptoms using the Unified Parkinson's disease Rating Scale (UPDRS), as well as neuropsychiatric symptoms and caregivers' distress using the Neuropsychiatric Inventory (NPI). Additional information obtained from all the participants and their caregivers included demographic data, personal history, psychiatric history, medical history and family history. The behavioural, caregivers' distress and motor correlates of cognitive dysfunction were explored. Results: In all, 24.0% of the patients had cognitive dysfunction according to the local norm of the MMSE. Hallucinations (Chi2 = 5.556, p = 0.018) and agitation (Chi2 = 5.556, p = 0.018) were related to cognitive dysfunctions. There was more behaviour related caregivers' distress in those with cognitive dysfunction than those without (Chi2 = 2.208, p = 0.032). The MMSE scores correlated inversely with the score for rigidity (r = −0.506, p = 0.0002), bradykinesia (r = −0.592, p < 0.0001), and the UPDRS total score (r = −0.503, p = 0.0002). Conclusion: The psychotic symptoms of hallucinations and agitations differentiated Parkinson's disease patients with cognitive dysfunction from those with normal cognition. Generally, the presence of behavioural symptom led to more distress in the caregivers of patients with cognitive dysfunction.
Corticomotor Excitability in Parkinson's Disease During Observation, Imagery and Imitation of Action: Effects of Rehabilitation Using Wii Fit and Comparison to Healthy Controls
Authors: Esculier Jean-Francois , Vaudrin Joanie , Tremblay Louis E.
Published: December 2019

Background: Parkinson's disease (PD) is responsible for a progressive motor impairment. Wii Fit game represents an innovative treatment modality using external visual cueing, which can be used to help patients with PD in executing motor tasks and improving function. Objectives: The objectives of this study were (1) to compare lower limb corticomotor activation in subjects with and without PD during action observation (OBS), motor imagery (IMAG), and imitation (IMIT), and (2) to evaluate the effects of a 6-week training program using Wii Fit on corticomotor excitability during these 3 conditions. Methods: Using transcranial magnetic stimulation, we assessed motor evoked potentials (MEPs) in Quadriceps Femoris (QF) and Soleus (SOL) muscles in 8 subjects with moderate PD (PD group) and 8 healthy subjects (HS group) before and after 6 weeks of training using Wii Fit during OBS, IMAG and IMIT of a mini-squat action. Results: At baseline, PD showed significantly less MEPs in QF during OBS, IMAG and IMIT compared with HS. In SOL, MEPs were reduced in PD only during IMIT. Following training, PD increased QF MEPs during OBS, which was opposite to the decrease in QF MEPs noted in HS. During IMAG, increased MEPs were found only in PD for SOL. During IMIT, both groups significantly reduced MEPs in both QF and SOL. Conclusion: Subjects with PD may have improved their dual-task ability considering changes observed during OBS and IMIT. Visual cueing training using Wii Fit may provide an interesting rehabilitation method for PD.
Limelight on Alpha-Synuclein: Pathological and Mechanistic Implications in Neurodegeneration
Authors: Wales Pauline , Pinho Raquel , Lázaro Diana F. , Outeiro Tiago F.
Published: December 2019

The pathogenesis of many neurodegenerative disorders arises in association with the misfolding and accumulation of a wide variety of proteins. Much emphasis has been placed on understanding the nature of these protein accumulations, including their composition, the process by which they are formed and the physiological impact they impose at cellular and, ultimately, organismal levels. Alpha-synuclein (ASYN) is the major component of protein inclusions known as Lewy bodies and Lewy neurites, which are the typical pathological hallmarks in disorders referred to as synucleinopathies. In addition, mutations or multiplications in the gene encoding for ASYN have also been shown to cause familial cases of PD, the most common synucleinopathy. Although the precise function of ASYN remains unclear, it appears to be involved in a vast array of cellular processes. Here, we review, in depth, a spectrum of cellular and molecular mechanisms that have been implicated in synucleinopathies. Importantly, detailed understanding of the biology/pathobiology of ASYN may enable the development of novel avenues for diagnosis and/or therapeutic intervention in synucleinopathies.
Inhibition, Executive Function, and Freezing of Gait
Authors: Cohen Rajal G. , Klein Krystal A. , Nomura Mariko , Fleming Michael , Mancini Martina , Giladi Nir , Nutt John G. , Horak Fay B.
Published: December 2019

Background: Studies suggest that freezing of gait (FoG) in people with Parkinson's disease (PD) is associated with declines in executive function (EF). However, EF is multi-faceted, including three dissociable components: inhibiting prepotent responses, switching between task sets, and updating working memory. Objective: This study investigated which aspect of EF is most strongly associated with FoG in PD. Method: Three groups were studied: adults with PD (with and without FoG) and age-matched, healthy adults. All participants completed a battery of cognitive tasks previously shown to discriminate among the three EF components. Participants also completed a turning-in-place task that was scored for FoG by neurologists blind to subjects' self-reported FoG. Results: Compared to both other groups, participants with FoG showed significant performance deficits in tasks associated with inhibitory control, even after accounting for differences in disease severity, but no significant deficits in task-switching or updating working memory. Surprisingly, the strongest effect was an intermittent tendency of participants with FoG to hesitate, and thus miss the response window, on go trials in the Go-Nogo task. The FoG group also made slower responses in the conflict condition of the Stroop task. Physician-rated FoG scores were correlated both with failures to respond on go trials and with failures to inhibit responses on nogo trials in the Go-Nogo task. Conclusion: These results suggest that FoG is associated with a specific inability to appropriately engage and release inhibition, rather than with a general executive deficit.