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1.
Nat Commun ; 11(1): 657, 2020 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-32005876

RESUMO

To advance microfluidic integration, we present the use of two-photon additive manufacturing to fold 2D channel layouts into compact free-form 3D fluidic circuits with nanometer precision. We demonstrate this technique by tailoring microfluidic nozzles and mixers for time-resolved structural biology at X-ray free-electron lasers (XFELs). We achieve submicron jets with speeds exceeding 160 m s-1, which allows for the use of megahertz XFEL repetition rates. By integrating an additional orifice, we implement a low consumption flow-focusing nozzle, which is validated by solving a hemoglobin structure. Also, aberration-free in operando X-ray microtomography is introduced to study efficient equivolumetric millisecond mixing in channels with 3D features integrated into the nozzle. Such devices can be printed in minutes by locally adjusting print resolution during fabrication. This technology has the potential to permit ultracompact devices and performance improvements through 3D flow optimization in all fields of microfluidic engineering.

2.
Opt Express ; 27(25): 36580-36586, 2019 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-31873433

RESUMO

Imaging biological molecules in the gas-phase requires novel sample delivery methods, which generally have to be characterized and optimized to produce high-density particle beams. A non-destructive characterization method of the transverse particle beam profile is presented. It enables the characterization of the particle beam in parallel to the collection of, for instance, x-ray-diffraction patterns. As a rather simple experimental method, it requires the generation of a small laser-light sheet using a cylindrical telescope and a microscope. The working principle of this technique was demonstrated for the characterization of the fluid-dynamic-focusing behavior of 220 nm polystyrene beads as prototypical nanoparticles. The particle flux was determined and the velocity distribution was calibrated using Mie-scattering calculations.

3.
Artigo em Inglês | MEDLINE | ID: mdl-31449035

RESUMO

Hereditary spastic paraplegias (HSP) represents a group of orphan neurodegenerative diseases with gait disturbance as the predominant clinical feature. Due to its rarity, research within this field is still limited. Aside from clinical analysis using established scales, gait analysis has been employed to enhance the understanding of the mechanisms behind the disease. However, state of the art gait analysis systems are often large, immobile and expensive. To overcome these limitations, this paper presents the first clinically relevant mobile gait analysis system for HSP patients. We propose an unsupervised model based on local cyclicity estimation and hierarchical hidden Markov models (LCE-hHMM). The system provides stride time, swing time, stance time, swing duration and cadence. These parameters are validated against a GAITRite® system and manual sensor data labelling using a cohort of 24 patients within 2 separate studies. The proposed system achieves a stride time error of -0.00 ± 0.09 s (correlation coefficient, r = 1.00) and a swing duration error of -0.67 ± 3.27 % (correlation coefficient, r = 0.93) with respect to the GAITRite® system. We show that these parameters are also correlated to the clinical spastic paraplegia rating scale (SPRS) in a similar manner to other state of the art gait analysis systems, as well as to supervised and general versions of the proposed model. Finally, we show a proof of concept for this system to be used to analyse alterations in the gait of individual patients. Thus, with further clinical studies, due to its automated approach and mobility, this system could be used to determine treatment effects in future clinical trials.

4.
Sensors (Basel) ; 19(14)2019 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-31337067

RESUMO

Mobile gait analysis systems using wearable sensors have the potential to analyze and monitor pathological gait in a finer scale than ever before. A closer look at gait in Parkinson's disease (PD) reveals that turning has its own characteristics and requires its own analysis. The goal of this paper is to present a system with on-shoe wearable sensors in order to analyze the abnormalities of turning in a standardized gait test for PD. We investigated turning abnormalities in a large cohort of 108 PD patients and 42 age-matched controls. We quantified turning through several spatio-temporal parameters. Analysis of turn-derived parameters revealed differences of turn-related gait impairment in relation to different disease stages and motor impairment. Our findings confirm and extend the results from previous studies and show the applicability of our system in turning analysis. Our system can provide insight into the turning in PD and be used as a complement for physicians' gait assessment and to monitor patients in their daily environment.


Assuntos
Algoritmos , Monitorização Fisiológica/instrumentação , Doença de Parkinson/fisiopatologia , Sapatos , Dispositivos Eletrônicos Vestíveis , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Desenho de Equipamento , Feminino , Transtornos Neurológicos da Marcha/diagnóstico , Transtornos Neurológicos da Marcha/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Monitorização Fisiológica/métodos , Monitorização Fisiológica/normas , Reprodutibilidade dos Testes , Análise Espaço-Temporal
5.
J Neuroeng Rehabil ; 16(1): 98, 2019 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-31349860

RESUMO

The original article [1] contained an error whereby Fig. 6 contained a minor shading glitch affecting its presentation. This has now been corrected.

6.
J Neuroeng Rehabil ; 16(1): 77, 2019 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-31242915

RESUMO

BACKGROUND: Gait symptoms and balance impairment are characteristic indicators for the progression in Parkinson's disease (PD). Current gait assessments mostly focus on straight strides with assumed constant velocity, while acceleration/deceleration and turning strides are often ignored. This is either due to the set up of typical clinical assessments or technical limitations in capture volume. Wearable inertial measurement units are a promising and unobtrusive technology to overcome these limitations. Other gait phases such as initiation, termination, transitioning (between straight walking and turning) and turning might be relevant as well for the evaluation of gait and balance impairments in PD. METHOD: In a cohort of 119 PD patients, we applied unsupervised algorithms to find different gait clusters which potentially include the clinically relevant information from distinct gait phases in the standardized 4x10 m gait test. To clinically validate our approach, we determined the discriminative power in each gait cluster to classify between impaired and unimpaired PD patients and compared it to baseline (analyzing all straight strides). RESULTS: As a main result, analyzing only one of the gait clusters constant, non-constant or turning led in each case to a better classification performance in comparison to the baseline (increase of area under the curve (AUC) up to 19% relative to baseline). Furthermore, gait parameters (for turning, constant and non-constant gait) that best predict motor impairment in PD were identified. CONCLUSIONS: We conclude that a more detailed analysis in terms of different gait clusters of standardized gait tests such as the 4x10 m walk may give more insights about the clinically relevant motor impairment in PD patients.

7.
Conf Proc IEEE Eng Med Biol Soc ; 2018: 5430-5433, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-30441565

RESUMO

Gait analysis provides a quantitative method to assess disease progression or intervention effect on gait disorders. While mobile gait analysis enables continuous monitoring in free living conditions, state of the art gait analysis for diseases such as hereditary spastic paraplegia (HSP) is currently limited to motion capture systems which are large and expensive. The challenge with HSP is its heterogeneous nature and rarity, leading to a wide range of ages, severity and gait patterns as well as small patient numbers. We propose a sensor-based mobile solution, based on a personalised hierarchical hidden Markov Model (hHMM) to extract spatio-temporal gait parameters. This personalised hHMM achieves a mean absolute error of 0.04 s ± 0.03 s for stride time estimation with respect to a GAITRite® reference system. We use the successful extraction of initial ground contact to explore the limits of the double integration method for such heterogeneous diseases. While our personalised model compensates for the heterogeneity of the disease, it would require a new model per patient. We observed that the general model was sufficient for some of the less severely affected patients.


Assuntos
Análise da Marcha , Cadeias de Markov , Paraplegia Espástica Hereditária/diagnóstico , Progressão da Doença , Marcha , Humanos
8.
IUCrJ ; 5(Pt 5): 574-584, 2018 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-30224961

RESUMO

Liquid microjets are a common means of delivering protein crystals to the focus of X-ray free-electron lasers (FELs) for serial femtosecond crystallography measurements. The high X-ray intensity in the focus initiates an explosion of the microjet and sample. With the advent of X-ray FELs with megahertz rates, the typical velocities of these jets must be increased significantly in order to replenish the damaged material in time for the subsequent measurement with the next X-ray pulse. This work reports the results of a megahertz serial diffraction experiment at the FLASH FEL facility using 4.3 nm radiation. The operation of gas-dynamic nozzles that produce liquid microjets with velocities greater than 80 m s-1 was demonstrated. Furthermore, this article provides optical images of X-ray-induced explosions together with Bragg diffraction from protein microcrystals exposed to trains of X-ray pulses repeating at rates of up to 4.5 MHz. The results indicate the feasibility for megahertz serial crystallography measurements with hard X-rays and give guidance for the design of such experiments.

9.
J Appl Crystallogr ; 51(Pt 1): 133-139, 2018 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-29507547

RESUMO

High-resolution Bragg diffraction from aerosolized single granulovirus nanocrystals using an X-ray free-electron laser is demonstrated. The outer dimensions of the in-vacuum aerosol injector components are identical to conventional liquid-microjet nozzles used in serial diffraction experiments, which allows the injector to be utilized with standard mountings. As compared with liquid-jet injection, the X-ray scattering background is reduced by several orders of magnitude by the use of helium carrier gas rather than liquid. Such reduction is required for diffraction measurements of small macromolecular nanocrystals and single particles. High particle speeds are achieved, making the approach suitable for use at upcoming high-repetition-rate facilities.

10.
J Synchrotron Radiat ; 24(Pt 6): 1296-1298, 2017 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-29091073

RESUMO

The success of diffraction experiments from weakly scattering samples strongly depends on achieving an optimal signal-to-noise ratio. This is particularly important in single-particle imaging experiments where diffraction signals are typically very weak and the experiments are often accompanied by significant background scattering. A simple way to tremendously reduce background scattering by placing an aperture downstream of the sample has been developed and its application in a single-particle X-ray imaging experiment at FLASH is demonstrated. Using the concept of a post-sample aperture it was possible to reduce the background scattering levels by two orders of magnitude.

11.
Sensors (Basel) ; 17(9)2017 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-28832511

RESUMO

Mobile gait analysis systems based on inertial sensing on the shoe are applied in a wide range of applications. Especially for medical applications, they can give new insights into motor impairment in, e.g., neurodegenerative disease and help objectify patient assessment. One key component in these systems is the reconstruction of the foot trajectories from inertial data. In literature, various methods for this task have been proposed. However, performance is evaluated on a variety of datasets due to the lack of large, generally accepted benchmark datasets. This hinders a fair comparison of methods. In this work, we implement three orientation estimation and three double integration schemes for use in a foot trajectory estimation pipeline. All methods are drawn from literature and evaluated against a marker-based motion capture reference. We provide a fair comparison on the same dataset consisting of 735 strides from 16 healthy subjects. As a result, the implemented methods are ranked and we identify the most suitable processing pipeline for foot trajectory estimation in the context of mobile gait analysis.


Assuntos
Marcha , Benchmarking , , Humanos
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