Acceptability to patients, carers and clinicians of an mHealth platform for the management of Parkinson's disease (PD_Manager): study protocol for a pilot randomised controlled trial.

BACKGROUND: Parkinson's disease is a degenerative neurological condition causing multiple motor and non-motor symptoms that have a serious adverse effect on quality of life. Management is problematic due to the variable and fluctuating nature of symptoms, often hourly and daily. The PD_Manager mHealth platform aims to provide a continuous feed of data on symptoms to improve clinical understanding of the status of any individual patient and inform care planning. The objectives of this trial are to (1) assess patient (and family carer) perspectives of PD_Manager regarding comfort, acceptability and ease of use; (2) assess clinician views about the utility of the data generated by PD_Manager for clinical decision making and the acceptability of the system in clinical practice. METHODS/DESIGN: This trial is an unblinded, parallel, two-group, randomised controlled pilot study. A total of 200 persons with Parkinson's disease (Hoehn and Yahr stage 3, experiencing motor fluctuations at least 2 h per day), with primary family carers, in three countries (110 Rome, 50 Venice, Italy; 20 each in Ioannina, Greece and Surrey, England) will be recruited. Following informed consent, baseline information will be gathered, including the following: age, gender, education, attitudes to technology (patient and carer); time since Parkinson's diagnosis, symptom status and comorbidities (patient only). Randomisation will assign participants (1:1 in each country), to PD_Manager vs control, stratifying by age (1 ≤ 70 : 1 > 70) and gender (60% M: 40% F). The PD_Manager system captures continuous data on motor symptoms, sleep, activity, speech quality and emotional state using wearable devices (wristband, insoles) and a smartphone (with apps) for storing and transmitting the information. Control group participants will be asked to keep a symptom diary covering the same elements as PD_Manager records. After a minimum of two weeks, each participant will attend a consultation with a specialist doctor for review of the data gathered (by either means), and changes to management will be initiated as indicated. Patients, carers and clinicians will be asked for feedback on the acceptability and utility of the data collection methods. The PD_Manager intervention, compared to a symptom diary, will be evaluated in a cost-consequences framework. DISCUSSION: Information gathered will inform further development of the PD_Manager system and a larger effectiveness trial. TRIAL REGISTRATION: ISRCTN Registry, ISRCTN17396879 . Registered on 15 March 2017

Electrospray deposition of physical unclonable functions for drug anti-counterfeiting

Abstract In recent years, pharmaceutical counterfeiting has become an increasingly dangerous situation. A patient who unknowingly consumes a counterfeit drug is at a serious health risk. To address this problem, a low-cost and robust approach for authentication that can be administered at the point-of-care is required. Our proposed solution uses Optical Physical Unclonable Functions (PUFs); patterns formed by a stochastic process that can be used for authentication. We create edible PUFs (ePUFs) using electrospray deposition, which utilizes strong electric fields to atomize a liquid suspension into a plume of micro-scale droplets that are delivered to the target. The ePUFs are electrospray-deposited from an edible ink directly onto the surface of the drug tablets. The process parameters (flow rate, translation speed, and suspension concentration) govern the characteristics of the ePUF to provide highly stochastic patterns. To evaluate our approach, 200 ePUFs were deposited onto tablets at various conditions, followed by imaging and storage of the patterns in a database. For ePUF authentication, a machine vision approach was created using the open source SIFT pattern matching algorithm. Using optimized pattern-matching constraints, our algorithm was shown to be 100% successful in authenticating the cellphone images of the ePUFs to the database. Additionally, the algorithm was found to be robust against changes in illumination and orientation of the cellphone images

Interfacial Targeting of Sessile Droplets Using Electrospray

We report on the use of electrospray atomization to deliver nanoparticles and surfactant directly to the surface of sessile droplets. The particles delivered to the target droplet remained adsorbed at its interface since they arrived solvent-free. Upon complete evaporation, the interface of the target drop was mapped to the underlying substrate, forming a nanoparticle deposit. The use of electrospray permitted the exploration of the interfacial particle transport and the role of surfactants in governing particle motion and deposit structure. When no surfactant was present in the sprayed solution, there was no observable convection of the interfacial particles. When Tween 80, a high-molecular-weight surfactant, was added to the sprayed solution, the surface flow was similarly suppressed. Only when small surfactants (e.g., sodium dodecyl sulfate) were present in the sprayed solution was Marangoni flow, directed toward the droplet apex, induced at the interface. This flow drove the interfacial particles to the apex of the target droplet, creating a particle-dense region at the center of the final deposit. We found that small surfactants were capable of desorbing from the interface at a sufficiently high rate relative to the evaporation time scale of the target droplet. Once inside the drop, the desorbed surfactant was convected to the contact line where it accumulated, inducing a surface tension gradient and a solutal Marangoni flow. Numerical modeling using the lattice Boltzmann–Brownian dynamics method confirmed this mechanism of particle transport and its relationship to deposit structure. The use of sacrificial targets combined with electrospray may provide a unique capability for building colloidal monolayers with organized structure in a scalable way

Structure, dynamics and immunogenicity of a catalytically inactive CXC chemokine-degrading protease SpyCEP from Streptococcus pyogene

Over 18 million disease cases and half a million deaths worldwide are estimated to be caused annually by Group A Streptococcus. A vaccine to prevent GAS disease is urgently needed. SpyCEP (Streptococcus pyogenes Cell-Envelope Proteinase) is a surface-exposed serine protease that inactivates chemokines, impairing neutrophil recruitment and bacterial clearance, and has shown promising immunogenicity in preclinical models. Although SpyCEP structure has been partially characterized, a more complete and higher resolution understanding of its antigenic features would be desirable prior to large scale manufacturing. To address these gaps and facilitate development of this globally important vaccine, we performed immunogenicity studies with a safety-engineered SpyCEP mutant, and comprehensively characterized its structure by combining X-ray crystallography, NMR spectroscopy and molecular dynamics simulations. We found that the catalytically-inactive SpyCEP antigen conferred protection similar to wild-type SpyCEP in a mouse infection model. Further, a new higher-resolution crystal structure of the inactive SpyCEP mutant provided new insights into this large chemokine protease comprising nine domains derived from two non-covalently linked fragments. NMR spectroscopy and molecular simulation analyses revealed conformational flexibility that is likely important for optimal substrate recognition and overall function. These combined immunogenicity and structural data demonstrate that the full-length SpyCEP inactive mutant is a strong candidate human vaccine antigen. These findings show how a multi-disciplinary study was used to overcome obstacles in the development of a GAS vaccine, an approach applicable to other future vaccine programs. Moreover, the information provided may also facilitate the structure-based discovery of small-molecule therapeutics targeting SpyCEP protease inhibition

Investigation of lung nodule detectability in low-dose 320-slice computed tomography

Low-dose imaging protocols in chest CT are important in the screening and surveillance of suspicious and indeterminate lung nodules. Techniques that maintain nodule detectability yet permit dose reduction, particularly for large body habitus, were investigated. The objective of this study was to determine the extent to which radiation dose can be minimized while maintaining diagnostic performance through knowledgeable selection of reconstruction techniques. A 320-slice volumetric CT scanner (Aquilion ONE™, Toshiba Medical Systems) was used to scan an anthropomorphic phantom at doses ranging from ∼0.1 mGy up to that typical of low-dose CT (LDCT, ∼5 mGy) and diagnostic CT (∼10 mGy). Radiation dose was measured via Farmer chamber and MOSFET dosimetry. The phantom presented simulated nodules of varying size and contrast within a heterogeneous background, and chest thickness was varied through addition of tissue-equivalent bolus about the chest. Detectability of a small solid lung nodule (3.2 mm diameter, −37 HU, typically the smallest nodule of clinical significance in screening and surveillance) was evaluated as a function of dose, patient size, reconstruction filter, and slice thickness by means of nine-alternative forced-choice (9AFC) observer tests to quantify nodule detectability. For a given reconstruction filter, nodule detectability decreased sharply below a threshold dose level due to increased image noise, especially for large body size. However, nodule detectability could be maintained at lower doses through knowledgeable selection of (smoother) reconstruction filters. For large body habitus, optimal filter selection reduced the dose required for nodule detection by up to a factor of ∼3 (from ∼3.3 mGy for sharp filters to ∼1.0 mGy for the optimal filter). The results indicate that radiation dose can be reduced below the current low-dose (5 mGy) and ultralow-dose (1 mGy) levels with knowledgeable selection of reconstruction parameters. Image noise, not spatial resolution, was found to be the limiting factor in detection of small lung nodules. Therefore, the use of smoother reconstruction filters may permit lower-dose protocols without trade-off in diagnostic performance

Full transient response of Taylor cones to a step change in electric field

We studied experimentally the complete transient response of Taylor cones subject to a step change in external electric field with the goal of finding optimal conditions to reduce the overall response time and achieve the highest possible switching bandwidth. The transient behavior of electrified menisci is of interest for many applications that would benefit from active control of on/off switching of the electrospray, such as femtoliter droplet-on-demand or novel fuel injectors in next generation internal combustion engines. We first investigated the transient behavior of ethanol, a typical solvent for droplet-on-demand. We then expanded the study to fuels such as JP-8 and E-30 biogas, a biofuel with 30% ethanol (vol.). The system response is a multi-stage process that can last from ~100 μs to ~100 ms. Potential bottleneck stages include liquid accumulation, meniscus oscillation, and cone relaxation, depending on the experimental conditions. A typical full response time is ~1 ms, and the shortest transient process observed is ~400 μs. For a given liquid, nozzle outer diameter (OD) and applied voltage are the two most important parameters to influence the full response time. Onset or near-onset voltage for the establishment of the cone jet often leads to a large number of oscillation cycles and should be avoided. Changes in conductivity and viscosity by less than a factor of 10 have negligible effects on the transient process. Using JP-8 or E-30 biogas, 90 μm OD nozzle with extractor, and flow rate of 0.4 mL/h, we can routinely achieve bandwidth of 1 kHz, corresponding to a full response time of 1 ms, after which quasi-monodispersed droplets of ~10 μm are generated. Adaptation of an inviscid model of a charged oscillating droplet to the oscillating meniscus satisfactorily explains several key phenomena observed in our experiments, such as the full response time and the overshoot of the meniscus height. © 2011 Springer-Verlag