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BackgroundObjective symptom monitoring of patients with Amyotrophic Lateral Sclerosis (ALS) has the potential to provide an important source of information to evaluate the impact of the disease on aspects of real-world functional capacity and activities of daily living in the home setting, providing useful objective outcome measures for clinical trials. ObjectiveThis study aimed to investigate the feasibility of a novel digital platform for remote data collection of multiple symptoms—physical activity, heart rate variability (HRV), and digital speech characteristics—in 25 patients with ALS in an observational clinical trial setting to explore the impact of the devices on patients’ everyday life and to record tolerability related to the devices and study procedures over 48 weeks. MethodsIn this exploratory, noncontrolled, nondrug study, patients attended a clinical site visit every 3 months to perform activity reference tasks while wearing a sensor, to conduct digital speech tests and for conventional ALS monitoring. In addition, patients wore the sensor in their daily life for approximately 3 days every month for the duration of the study. ResultsThe amount and quality of digital speech data captured at the clinical sites were as intended, and there were no significant issues. All the home monitoring sensor data available were propagated through the system and were received as expected. However, the amount and quality of physical activity home monitoring data were lower than anticipated. A total of 3 or more days (or partial days) of data were recorded for 65% of protocol time points, with no data collected for 24% of time points. At baseline, 24 of 25 patients provided data, reduced to 13 of 18 patients at Week 48. Lower-than-expected quality HRV data were obtained, likely because of poor contact between the sensor and the skin. In total, 6 of 25 patients had mild or moderate adverse events (AEs) in the skin and subcutaneous tissue disorders category because of skin irritation caused by the electrode patch. There were no reports of serious AEs or deaths. Most patients found the sensor comfortable, with no or minimal impact on daily activities. ConclusionsThe platform can measure physical activity in patients with ALS in their home environment; patients used the equipment successfully, and it was generally well tolerated. The quantity of home monitoring physical activity data was lower than expected, although it was sufficient to allow investigation of novel physical activity end points. Good-quality in-clinic speech data were successfully captured for analysis. Future studies using objective patient monitoring approaches, combined with the most current technological advances, may be useful to elucidate novel digital biomarkers of disease progression.

BackgroundUsing smartphones to enroll, obtain consent, and gather self-reported data from patients has the potential to enhance our understanding of disease burden and quantify physiological impact in the real world. It may also be possible to harness integral smartphone sensors to facilitate remote collection of clinically relevant data. ObjectiveWe conducted the Patient Rheumatoid Arthritis Data From the Real World (PARADE) observational study using a customized ResearchKit app with a bring-your-own-device approach. Our objective was to assess the feasibility of using an entirely digital approach (social media and smartphone app) to conduct a real-world observational study of patients with rheumatoid arthritis. MethodsWe conducted this observational study using a customized ResearchKit app with a bring-your-own-device approach. To recruit patients, the PARADE app, designed to guide patients through a series of tasks, was publicized via social media platforms and made available for patients in the United States to download from the Apple App Store. We collected patient-reported data, such as medical history, rheumatoid arthritis-related medications (past and present), and a range of patient-reported outcome measures. We included in the assessment a joint-pain map and a novel objective assessment of wrist range of movement, measured by the smartphone-embedded gyroscope and accelerometer. ResultsWithin 1 month of recruitment via social media campaigns, 399 participants self-enrolled, self-consented, and provided complete demographic data. Joint pain was the most frequently reported rheumatoid arthritis symptom to bother study participants (344/393, 87.5%). Severe patient-reported wrist pain appeared to be inversely linked with the range of wrist movement measured objectively by the app. At study entry, 292 of 399 participants (73.2%) indicated a preference for participating in a mobile app–based study. The number of participants in the study declined to 45 of 399 (11.3%) at week 12. ConclusionsDespite the declining number of participants over time, the combination of social media and smartphone app with sensor integration was a feasible and cost-effective approach for the collection of patient-reported data in rheumatoid arthritis. Integral sensors within smartphones can be harnessed to provide novel end points, and the novel wrist range of movement test warrants further clinical validation.

A key issue in the fabrication of Terfenol-D 2-2 composites with internal magnetic field biasing is the selection of appropriate constituent materials to obtain high magnetostriction while keeping optimum magnetomechanical properties. The fabrication process is costly and time consuming and, therefore, numerical methods to predict their properties are useful. In this paper, finite element analysis (FEA) of the magnetostriction of such composites has been carried out using the commercial package ABAQUS. It has been shown that composites fabricated using [Nd.sub.2][Fe.sub.14]B for the permanent magnetic material layers possess the highest internal fields within the Terfenol-D layers, although the overall strain of these composites is limited to approximately 800 x 10-6 due to the high elastic modulus of [Nd.sub.2][Fe.sub.14]B. Simulations showed that the strain can be enhanced by choosing a different material with a lower elastic modulus for the permanent magnetic layer even though the internal field is lower. The simulations showed that the strain can increase by 12% if the [Nd.sub.2][Fe.sub.14]B layer is substituted by Sm[Co.sub.5]; by 23% if it is substituted by [Sm.sub.2][Co.sub.17]; and by 35% if it is substituted by Alnico. Index Terms--Composites, finite element method, magnetostriction, multilayers, Terfenol-D.

Nanocrystalline ZnO films with strong (0002) texture and fine grains were deposited onto ultra-nanocrystalline diamond (UNCD) layers on silicon using high target utilization sputtering technology. The unique characteristic of this sputtering technique allows room temperature growth of smooth ZnO films with a low roughness and low stress at high growth rates. Surface acoustic wave (SAW) devices were fabricated on ZnO/UNCD structure and exhibited good transmission signals with a low insertion loss and a strong side-lobe suppression for the Rayleigh mode SAW. Based on the optimization of the layered structure of the SAW device, a good performance with a coupling coefficient of 5.2% has been realized, promising for improving the microfluidic efficiency in droplet transportation comparing with that of the ZnO/Si SAW device. An optimized temperature coefficient of frequency of −23.4 ppm °C−1 was obtained for the SAW devices with the 2.72 µm-thick ZnO and 1.1 µm-thick UNCD film. Significant thermal effect due to the acoustic heating has been redcued which is related to the temperature stability of the ZnO/UNCD SAW device. [ABSTRACT FROM AUTHOR]

Thin-film electronics in its myriad forms has underpinned much of the technological innovation in the fields of displays, sensors, and energy conversion over the past four decades. This technology also forms the basis of flexible electronics. Here we review the current status of flexible electronics and attempt to predict the future promise of these pervading technologies in healthcare, environmental monitoring, displays and human–machine interactivity, energy conversion, management and storage, and communication and wireless networks. [ABSTRACT FROM PUBLISHER]

There has been an explosion of research into the physical and chemical properties of carbon-based nanomaterials, since the discovery of carbon nanotubes (CNTs) by Iijima in 1991. Carbon nanomaterials offer unique advantages in several areas, like high surface-volume ratio, high electrical conductivity, chemical stability and strong mechanical strength, and are thus frequently being incorporated into sensing elements. Carbon nanomaterial-based sensors generally have higher sensitivities and a lower detection limit than conventional ones. In this review, a brief history of glucose biosensors is firstly presented. The carbon nanotube and grapheme-based biosensors, are introduced in Sections 3 and 4, respectively, which cover synthesis methods, up-to-date sensing approaches and nonenzymatic hybrid sensors. Finally, we briefly outline the current status and future direction for carbon nanomaterials to be used in the sensing area. [ABSTRACT FROM AUTHOR]

Innovative tools are urgently needed to accelerate the evaluation and subsequent approval of novel treatments that may slow, halt, or reverse the relentless progression of Parkinson disease (PD). Therapies that intervene early in the disease continuum are a priority for the many candidates in the drug development pipeline. There is a paucity of sensitive and objective, yet clinically interpretable, measures that can capture meaningful aspects of the disease. This poses a major challenge for the development of new therapies and is compounded by the considerable heterogeneity in clinical manifestations across patients and the fluctuating nature of many signs and symptoms of PD. Digital health technologies (DHT), such as smartphone applications, wearable sensors, and digital diaries, have the potential to address many of these gaps by enabling the objective, remote, and frequent measurement of PD signs and symptoms in natural living environments. The current climate of the COVID-19 pandemic creates a heightened sense of urgency for effective implementation of such strategies. In order for these technologies to be adopted in drug development studies, a regulatory-aligned consensus on best practices in implementing appropriate technologies, including the collection, processing, and interpretation of digital sensor data, is required. A growing number of collaborative initiatives are being launched to identify effective ways to advance the use of DHT in PD clinical trials. The Critical Path for Parkinson's Consortium of the Critical Path Institute is highlighted as a case example where stakeholders collectively engaged regulatory agencies on the effective use of DHT in PD clinical trials. Global regulatory agencies, including the US Food and Drug Administration and the European Medicines Agency, are encouraging the efficiencies of data-driven engagements through multistakeholder consortia. To this end, we review how the advancement of DHT can be most effectively achieved by aligning knowledge, expertise, and data sharing in ways that maximize efficiencies., Competing Interests: Critical Path Institute staff (D. Stephenson, V. Aggarawal, R. Bhatnagar, K. Romero, J. Burton, S. Sadar, and M. Minchick) and R. Badawy, L. Bain, J.M. Cedarbaum, D.T. Dexter, M. Frasier, D. Hill Michael, and P. Lawton have no conflict of interests to declare. R. Alexander, N. Zach, and R. Rubens are full-time employees of Takeda. A.V. Dowling is an employee of Takeda Pharmaceuticals and also serves on the Strategic Advisory Board of the DiMe Society. B.R. Bloem currently serves as associate editor for the Journal of Parkinson Disease, serves on the editorial board of Practical Neurology and Digital Biomarkers, has received honoraria from serving on the scientific advisory board for AbbVie, Biogen, UCB, and Walk with Path, has received fees for speaking at conferences from AbbVie, Zambon, Roche, GE Healthcare, and Bial, and has received research support from The Netherlands Organisation for Scientific Research, the Michael J. Fox Foundation, UCB, AbbVie, the Stichting Parkinson-Fonds, the Hersenstichting Nederland, the Parkinson Foundation, Verily Life Sciences, Horizon 2020, Topsector Life Sciences and Health, and the Parkinson Vereniging. B. Boroojerdi and E. Sengoku are employed by UCB. J. Cosman was a full-time employee of Biogen, Inc., and is currently a full-time employee of AbbVie, Inc. M. Dockendorf, S.J. Lee, and N. Mehrotra are employees of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc. (Kenilworth, NJ, USA), and may own stock/stock options in Merck & Co., Inc. E.R. Dorsey has received honoraria for speaking at American Academy of Neurology courses, the American Neurological Association, and the University of Michigan. E.R. Dorsey received compensation for consulting services from: 23andMe; Abbott; AbbVie; American Well; Biogen; BrainNeuroBio; Clintrex; Curasen Therapeutics; DeciBio; Denali Therapeutics; GlaxoSmithKline; Grand Rounds; Karger; Lundbeck; MC10; MedAvante; Medical-Legal Services; Mednick Associates; the National Institute of Neurological Disorders and Stroke; the Olson Research Group; Optio; Origent Data Sciences, Inc.; Otsuka, Prilenia; Putnam Associates; Roche; Sanofi; Shire; Spark; Sunovion Pharma; Teva; Theravance; UCB; and Voyager Therapeutics. E.R. Dorsey also received research support from AbbVie, Acadia Pharmaceuticals, AMC Health, Biosensics, the Burroughs Wellcome Fund, the Davis Phinney Foundation, Duke University, the FDA, GlaxoSmithKline, the Greater Rochester Health Foundation, the Huntington Study Group, the Michael J. Fox Foundation, the National Institutes of Health/National Institute of Neurological Disorders and Stroke, the National Science Foundation, Nuredis Pharmaceuticals, the Patient-Centered Outcomes Research Institute, Pfizer, Prana Biotechnology, Raptor Pharmaceuticals, Roche, Safra Foundation, Teva Pharmaceuticals, and the University of California, Irvine; has provided editorial services for Karger Publications; and has ownership interests with Blackfynn (data integration company) and Grand Rounds (second opinion service). L.J.W. Evers has received research support from the Michael J. Fox Foundation, UCB, the Stichting Parkinson Fonds, The Netherlands Organisation for Scientific Research, and Topsector Life Sciences and Health. L. Garcia-Gancedo is a full-time employee of GSK. J.C. Goldsack is a part-time employee of HealthMode, Inc. J. Hitchcock is an employee of Hitchcock Regulatory Consulting, Inc., and has consulted for: Acumen Pharmaceuticals; Axon Advisors LLC; the Critical Path Institute; the Gerson Lehrman Group; H. Lundbeck A/S; the High Lantern Group LLC; Regenera Pharma LTD; UCB Biopharma SPRL; Vaccinex, Inc.; and Washington University. She is retired from Eli Lilly and Company and holds Lilly shares. M.T. Hu serves as a consultant for Biogen and Roche Advisory Boards and for CuraSen Therapeutics, Inc. Prof. Hu has received funding and support from Parkinson's UK, Oxford NIHR BRC, the University of Oxford, NIHR, the Michael J Fox Foundation, H2020 European Union, GE Healthcare, and the PSP Association. M. Lindemann is a consultant for F. Hoffmann-La Roche through Inovigate. M.J. Meinders has received research support from the Michael J. Fox Foundation, UCB, the Stichting Parkinson Fonds, Horizon 2020, and Topsector Life Sciences and Health. L. Oliva and K. Fisher are employees of Biogen. G. Roussos acknowledges funding from the Michael J. Fox Foundation and is a joint patent holder for UK patent GB2433856 (which is not related to healthcare). J. Scheeren was formerly employed by Bayer AG-Pharmaceuticals and as of 2019 is the president and CEO of C-Path. Dr. J. Scheeren is also currently an adjunct professor of regulatory sciences at Peking University in Beijing, China, the chair of the fellows for the Drug Information Association (DIA), a member of the advisory board for the Centre of Regulatory Excellence (CoRE), a special advisor to the scientific advisory council of the Centre for Innovation in Regulatory Science (CIRS), a lecturer at Yale University, and a foreign corresponding member of the French Académie Nationale de Pharmacie. T. Simuni, MD, has served as a consultant for Acadia, AbbVie, Accorda, Adamas, Allergan, Amneal, Aptinyx, Denali, General Electric (GE), Kyowa, Neuroderm, Neurocrine, Sanofi, Sinopia, Sunovion, Roche, Takeda, Voyager, US World Meds, the Parkinson's Foundation, and the Michael J. Fox Foundation for Parkinson research. Dr. T. Simuni has served as a speaker and received an honorarium from Acadia and Adamas, is on the scientific advisory board for Neuroderm and Sanofi, and has received research funding from the NINDS, the Parkinson's Foundation, MJFF, Biogen, Roche, Neuroderm, Sanofi, Sun Pharma, AbbVie, IMPAX, and Prevail. G. Stebbins is an employee of Rush University. Dr. G. Stebbins has consulting and advisory board membership with honoraria for: Acadia Pharmaceuticals; Adamas Pharmaceuticals, Inc.; Biogen, Inc.; Ceregene, Inc.; CHDI Management, Inc.; the Cleveland Clinic Foundation; Ingenix Pharmaceutical Services (i3 Research); MedGenesis Therapeutix, Inc.; Neurocrine Biosciences, Inc.; Pfizer, Inc.; Tools-4-Patients; Ultragenyx, Inc.; and the Sunshine Care Foundation. He has received grants from and done research for: the National Institutes of Health, the Department of Defense, the Michael J. Fox Foundation for Parkinson's Research, the Dystonia Coalition, CHDI, the Cleveland Clinic Foundation, the International Parkinson and Movement Disorder Society, and CBD Solutions, and has received honoraria from: the International Parkinson and Movement Disorder Society, the American Academy of Neurology, the Michael J. Fox Foundation for Parkinson's Research, the FDA, the National Institutes of Health, and the Alzheimer's Association. K.I. Taylor is a full-time employee and shareholder of F. Hoffmann-La Roche Ltd. B. Yang is a full-time employee at Lundbeck A/S., (Copyright © 2020 by S. Karger AG, Basel.)