Authors: Kong, Lan | Ali, Maher | Deogun, Jitender S.
Article Type: Research Article
Abstract: In this paper, we investigate the problem of Preplanned Recovery with Redundant Multicast Trees (PRRMT) in optical networks. The redundant trees ensure the source node remains connected to all destination nodes for a multicast session request under single edge or node failures. Our objective is to minimize the total number of links used for both trees. We show that PRRMT can be formulated as an integer linear program (ILP), and also develop a heuristic algorithm. The ILP approach and heuristic algorithm are experimentally evaluated on 14-node NSFNET, 21-node Italian network, and a randomly generated 40-node mesh network. From experimental results, …we conclude that: (1) ILP approach leads to optimal solutions for NSFNET and Italian network but does not converge for many instances of arbitrary topologies, (2) Our heuristic algorithm yields optimal or near optimal results in very short time, and (3) The edge-disjoint trees can protect the transmission for an edge failure or a node failure. Show more
Keywords: Protection, Preplanned Recovery, Multicast Tress, VDM optical networks
Citation: Journal of High Speed Networks, vol. 15, no. 4, pp. 379-398, 2006
Authors: Chen, Mingbin | Chen, Zhenyu | Kong, Lan | Zeng, Yong
Article Type: Research Article
Abstract: The design and functional complexity of medical devices have increased during the past 50 years. As device functionality is becoming complex, safety, reliability, and comfort are becoming increasingly critical in the medical devices design. Case studies show that the majority of failures of medical devices come from the ignorance of important design requirements in the design stage. Based on the environment-based design model, this paper studies the sources of medical devices design requirements and proposes a systematic approach to guiding the gathering and collection of these requirements.
Keywords: medical devices, design requirements, human factors
Citation: Journal of Integrated Design & Process Science, vol. 9, no. 4, pp. 61-70, 2005
Authors: Lewis, Mechelle M. | Albertson, Richard M. | Du, Guangwei | Kong, Lan | Foy, Andrew | Huang, Xuemei
Article Type: Research Article
Abstract: Background: Recent randomized clinical trials using hydrophobic statins reported no influence on Parkinson’s disease (PD) clinical progression. Hydrophobicity is a key determinant for blood-brain barrier penetrance. Objective: Investigate a potential effect of statins on PD progression. Methods: Statin use was determined at baseline and subtyped according to hydrophobicity in 125 PD patients participating in the PD Biomarker Program (PDBP, 2012–2015) at our site. Clinical (N = 125) and susceptibility MRI (N = 86) data were obtained at baseline and 18-months. Movement Disorders Society-Unified PD Rating Scales were used to track progression of non-motor (MDS-UPDRS-I) and motor (MDS-UPDRS-II) symptoms, and rater-based scores (MDS-UPDRS-III) …of patients in the “on” drug state. R2* values were used to capture pathological progression in the substantia nigra. Associations between statin use, its subtypes, and PD progression were evaluated with linear mixed effect regressions. Results: Compared to statin non-users, overall statin or lipophilic statin use did not significantly influence PD clinical or imaging progression. Hydrophilic statin users, however, demonstrated faster clinical progression of non-motor symptoms [MDS-UPDRS-I (β= 4.8, p = 0.010)] and nigral R2* (β= 3.7, p = 0.043). A similar trend was found for MDS-UPDRS-II (β= 3.9, p = 0.10), but an opposite trend was observed for rater-based MDS-UPDRS-III (β= –7.3, p = 0.10). Compared to lipophilic statin users, hydrophilic statin users also showed significantly faster clinical progression of non-motor symptoms [MDS-UPDRS-I (β= 5.0, p = 0.020)], but R2* did not reach statistical significance (β= 2.5, p = 0.24). Conclusion: This study suggests that hydrophilic, but not lipophilic, statins may be associated with faster PD progression. Future studies may have clinical and scientific implications. Show more
Keywords: Parkinson’s disease, lipophilic statins, hydrophilic statins, MDS-UPDRS scores, susceptibility imaging, MRI, substantia nigra, R2*
DOI: 10.3233/JPD-212819
Citation: Journal of Parkinson's Disease, vol. 12, no. 3, pp. 821-830, 2022
Authors: He, Lu | Lee, Eun-Young | Sterling, Nicholas W. | Kong, Lan | Lewis, Mechelle M. | Du, Guangwei | Eslinger, Paul J. | Huang, Xuemei
Article Type: Research Article
Abstract: Background: The impact of motor- and non-motor symptoms on health-related quality of life (HRQOL) in Parkinson’s disease (PD) has received increasing attention. Objectives: To address this, the study explored a large cohort of patients enrolled in the PD Biomarker Program. Methods: The PD Questionnaire-39 (PDQ-39) measured HRQOL, whereas the Unified PD Rating Scale (UPDRS) assessed motor and non-motor symptoms. Determinants of HRQOL in PD patients were identified by stepwise linear regression analysis. The relationship between the PDQ-39 and UPDRS subscale scores then was explored through structural equation modeling. Results: The mean disease duration was 6.8 years and the mean PDQ-39 …summary index (PDQ-39SI) was 18.4. UPDRS-I (non-motor function) and UPDRS-II (motor questionnaire) scores demonstrated the strongest correlations with PDQ-39SI (r Ϡ 0.4, P < 0.05), whereas UPDRS-III (motor exam) and UPDRS-IV (motor complications) scores were correlated moderately with PDQ-39SI (0.3 < r < 0.4, P < 0.05). Multiple linear stepwise regression analyses showed that age (β= –0.13, P < 0.001), education (β= –0.07, P = 0.008), UPDRS-I (β= 0.32, P = 0.000), and UPDRS-II (β= 0.44, P < 0.001) significantly contributed to HRQOL, and cumulatively accounted for 69.1% of the PDQ-39SI variance. UPDRS-II score was the primary predictor of PDQ-39SI, accounting for 57.3% of the variance, whereas UPDRS-I score accounted for 7.5%. UPDRS-III and -IV and other factors measured did not survive stepwise regression. Structural equation modeling confirmed the association of UPDRS-II (β= 0.67, P < 0.001) and UPDRS-I (β= 0.35, P < 0.001) with the PDQ-39SI. Conclusion: Both motor and non-motor function scores impacted significantly HRQOL in PD. UPDRS-III, however, has limited contributions to HRQOL although it is used as a main outcome in many clinical trials. Show more
Keywords: Parkinson’s disease, quality of life, motor symptoms, non-motor symptoms, structural equation modeling, Unified Parkinson’s disease rating scales, structure, review
DOI: 10.3233/JPD-160851
Citation: Journal of Parkinson's Disease, vol. 6, no. 3, pp. 523-532, 2016
Authors: Lewis, Mechelle M. | Harkins, Elias | Lee, Eun-Young | Stetter, Christy | Snyder, Bethany | Corson, Tyler | Du, Guangwei | Kong, Lan | Huang, Xuemei
Article Type: Research Article
Abstract: Background/Objective: To synchronize data collection, the National Institute of Neurological Disorders and Stroke (NINDS) recommended Common Data Elements (CDEs) for use in Parkinson’s disease (PD) research. This study delineated the progression patterns of these CDEs in a cohort of PD patients. Methods: One hundred-twenty-five PD patients participated in the PD Biomarker Program (PDBP) at Penn State. CDEs, including MDS-Unified PD Rating Scale (UPDRS)-total, questionnaire-based non-motor (-I) and motor (-II), and rater-based motor (-III) subscales; Montreal Cognitive Assessment (MoCA); Hamilton Depression Rating Scale (HDRS); University of Pennsylvania Smell Identification Test (UPSIT); and PD Questionnaire (PDQ-39) were obtained at baseline and three …annual follow-ups. Annual change was delineated for PD or subgroups [early = PDE, disease duration (DD) <1 y; middle = PDM, DD = 1–5 y; and late = PDL, DD > 5 y] using mixed effects model analyses. Results: UPDRS-total, -II, and PDQ-39 scores increased significantly, and UPSIT decreased, whereas UPDRS-I, -III, MoCA, and HDRS did not change, over 36 months in the overall PD cohort. In the PDE subgroup, UPDRS-II increased and UPSIT decreased significantly, whereas MoCA and UPSIT decreased significantly in the PDM subgroup. In the PDL subgroup, UPDRS-II and PDQ-39 increased significantly. Other metrics within each individual subgroup did not change. Sensitivity analyses using subjects with complete data confirmed these findings. Conclusion: Among CDEs, UPDRS-total, -II, PDQ-39, and UPSIT all are sensitive metrics to track PD progression. Subgroup analyses revealed that these CDEs have distinct stage-dependent sensitivities, with UPSIT for DD < 5 y, PDQ-39 for DD > 5 y, UPDRS-II for early (DD < 1) or later stages (DD > 5). Show more
Keywords: Parkinson’s disease, common data elements, clinical progression, disease stage
DOI: 10.3233/JPD-201932
Citation: Journal of Parkinson's Disease, vol. 10, no. 3, pp. 1075-1085, 2020
Authors: Sterling, Nicholas W. | Cusumano, Joseph P. | Shaham, Noam | Piazza, Stephen J. | Liu, Guodong | Kong, Lan | Du, Guangwei | Lewis, Mechelle M. | Huang, Xuemei
Article Type: Research Article
Abstract: Background: Reduced arm swing amplitude, symmetry, and coordination during gait have been reported in Parkinson's disease (PD), but the relationship between dopaminergic depletion and these upper limb gait changes remains unclear. Objective: We aimed to investigate the effects of dopaminergic drugs on arm swing velocity, symmetry, and coordination in PD. Methods: Forearm angular velocity was recorded in 16 PD and 17 control subjects (Controls) during free walking trials. Angular velocity amplitude of each arm, arm swing asymmetry, and maximum cross-correlation were compared between control and PD groups, and between OFF- and ON-medication states among PD subjects. Results: Compared to Controls, …PD subjects in the OFF-medication state exhibited lower angular velocity amplitude of the slower- (p = 0.0018), but not faster- (p = 0.2801) swinging arm. In addition, PD subjects demonstrated increased arm swing asymmetry (p = 0.0046) and lower maximum cross-correlation (p = 0.0026). Following dopaminergic treatment, angular velocity amplitude increased in the slower- (p = 0.0182), but not faster- (p = 0.2312) swinging arm among PD subjects. Furthermore, arm swing asymmetry decreased (p = 0.0386), whereas maximum cross-correlation showed no change (p = 0.7436). Pre-drug angular velocity amplitude of the slower-swinging arm was correlated inversely with the change in arm swing asymmetry (R = −0.73824, p = 0.0011). Conclusions: This study provides quantitative evidence that reduced arm swing and symmetry in PD can be modulated by dopaminergic replacement. The lack of modulations of bilateral arm coordination suggests that additional neurotransmitters may also be involved in arm swing changes in PD. Further studies are warranted to investigate the longitudinal trajectory of arm swing dynamics throughout PD progression. Show more
Keywords: Arm swing, dopamine, Parkinson's disease, locomotion, asymmetry, gait
DOI: 10.3233/JPD-140447
Citation: Journal of Parkinson's Disease, vol. 5, no. 1, pp. 141-150, 2015
Authors: Brown, Gregory | Du, Guangwei | Farace, Elana | Lewis, Mechelle M. | Eslinger, Paul J. | McInerney, James | Kong, Lan | Li, Runze | Huang, Xuemei | De Jesus, Sol
Article Type: Research Article
Keywords: Parkinson’s disease, deep brain stimulation, MRI, R2*, neuropsychiatric outcomes
DOI: 10.3233/JPD-212833
Citation: Journal of Parkinson's Disease, vol. 12, no. 3, pp. 851-863, 2022
Authors: Brown, Gregory L. | Camacci, Mona L. | Kim, Sean D. | Grillo, Stephanie | Nguyen, James V. | Brown, Douglas A. | Ullah, Sarah P. | Lewis, Mechelle M. | Du, Guangwei | Kong, Lan | Sundstrom, Jeffrey M. | Huang, Xuemei | Bowie, Esther M.
Article Type: Research Article
Abstract: Background: Parkinson’s disease (PD) is marked clinically by motor symptoms and pathologically by Lewy bodies and dopamine neuron loss in the substantia nigra pars compacta (SNc). Higher iron accumulation, assessed by susceptibility MRI, also is observed as PD progresses. Recently, evidence has suggested that PD affects the retina. Objective: To better understand retinal alterations in PD and their association to clinical and SNc iron-related imaging metrics. Methods: Ten PD and 12 control participants (2 eyes each) from an ongoing PD imaging biomarker study underwent enhanced depth imaging optical coherence tomography evaluation. Choroidal (vascular) thickness and nerve layers were measured in …4 subregions [superior, temporal, inferior, and nasal] and at 3 foveal distances (1, 1.5, and 3 mm). These metrics were compared between PD and control groups. For significantly different metrics, their associations with clinical [levodopa equivalent daily dosage (LEDD), motor and visuospatial function] and SNc susceptibility MRI metrics [R2* and quantitative susceptibility mapping (QSM)] were explored. Results: Compared to control participants, PD participants had a thicker choroid (p = 0.005), but no changes in nerve layers. Higher mean choroidal thickness was associated with lower LEDD (p < 0.01) and better visuospatial function (p < 0.05). Subregion analyses revealed higher choroidal thickness correlated with lower LEDD and better motor and visuospatial measures. Higher mean choroidal thickness also was associated with lower nigral iron MRI (p < 0.05). Conclusion: A small cohort of PD research participants displayed higher choroidal thickness that was related to better clinical performance and less nigral pathology. These intriguing findings warrant further investigation. Show more
Keywords: Choroid, optical coherence tomography, Parkinson’s disease, retina, susceptibility MRI, visuospatial function
DOI: 10.3233/JPD-212676
Citation: Journal of Parkinson's Disease, vol. 11, no. 4, pp. 1857-1868, 2021
Authors: Huang, Xuemei | Lewis, Mechelle M. | Van Scoy, Lauren Jodi | De Jesus, Sol | Eslinger, Paul J. | Arnold, Amy C. | Miller, Amanda J. | Fernandez-Mendoza, Julio | Snyder, Bethany | Harrington, William | Kong, Lan | Wang, Xi | Sun, Dongxiao | Delnomdedieu, Marielle | Duvvuri, Sridhar | Mahoney, Susan E. | Gray, David L. | Mailman, Richard B.
Article Type: Research Article
Abstract: Background: Current drug treatments have little efficacy in advanced-to-end-stage Parkinson’s disease (advPD), yet there are no reports of interventional trials in advPD. D1 dopamine agonists have the potential to provide benefit. Objective: To determine the feasibility and safety of the selective D1 /D5 dopamine partial agonist PF 06412562 in advPD. Methods: A two-week, randomized, double blind, crossover phase Ib study in advPD patients compared standard-of-care (SoC) carbidopa/levodopa with PF 06412562. Each week, there was a Day 1 baseline evaluation with overnight levodopa washout, then treatment on Days 2 and 3 with either SoC or PF-06412562 (split dose 25 + 20 mg), followed by …discharge on Day 4. Primary endpoints were safety and tolerability. Secondary endpoints were global clinical impression of change (GCI-C) rated by clinicians and caregivers. Results: Eight advPD patients and their caregivers consented to participate and six were randomized (average disease duration: 22 y). None withdrew voluntarily. One participant with baseline Day 1 dehydration, pre-renal kidney injury, and autonomic dysfunction experienced symptomatic and serious hypotension after receiving PF-06412562 in Week 1 and was discontinued from the study. All other adverse events were rated mild (PF-06412562: n = 1, SoC: n = 0), moderate (PF-06412562: n = 1, SoC: n = 1), or severe but non-serious (PF-06412562: n = 3, SoC: n = 2). No clinically meaningful laboratory changes were observed. Among the five participants who completed the study, GCI-C favored PF-06412562 in two per clinicians’ and four participants per caregivers’ rating. Conclusion: PF-06412562 was tolerated in advPD patients. This study provides the feasibility for future safety and efficacy studies in this population with unmet needs. Show more
Keywords: D1 dopamine receptor, dopamine D1 agonists, advanced Parkinson’s disease, levodopa, safety, feasibilityTrial Registration#: ClinicalTrials.gov:NCT03665454
DOI: 10.3233/JPD-202188
Citation: Journal of Parkinson's Disease, vol. 10, no. 4, pp. 1515-1527, 2020
