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This study investigated the impact of HFpEF on neuromuscular fatigue and peripheral hemodynamics during small muscle mass exercise not limited by cardiac output. Eight HFpEF patients (NYHA II-III, ejection-fraction: 61 ± 2%) and eight healthy controls performed dynamic knee extension exercise (80% peak workload) to task failure and maximal intermittent quadriceps contractions (8 × 15 s). Controls repeated knee extension at the same absolute intensity as HFpEF. Leg blood flow (QL) was quantified using Doppler ultrasound. Pre/postexercise changes in quadriceps twitch torque (ΔQtw; peripheral fatigue), voluntary activation (ΔVA; central fatigue), and corticospinal excitability were quantified. At the same relative intensity, HFpEF (24 ± 5 W) and controls (42 ± 6 W) had a similar time-to-task failure (â¼10 min), ΔQtw (â¼50%), and ΔVA (â¼6%). This resulted in a greater exercise-induced change in neuromuscular function per unit work in HFpEF, which was significantly correlated with a slower QL response time. Knee extension exercise at the same absolute intensity resulted in an â¼40% lower QL and greater ΔQtw and ΔVA in HFpEF than in controls. Corticospinal excitability remained unaltered during exercise in both groups. Finally, despite a similar ΔVA, ΔQtw was larger in HFpEF versus controls during isometric exercise. In conclusion, HFpEF patients are characterized by a similar development of central and peripheral fatigue as healthy controls when tested at the same relative intensity during exercise not limited by cardiac output. However, HFpEF patients have a greater susceptibility to neuromuscular fatigue during exercise at a given absolute intensity, and this impairs functional capacity. The patients' compromised QL response to exercise likely accounts, at least partly, for the patients' attenuated fatigue resistance.NEW & NOTEWORTHY The susceptibility to neuromuscular fatigue during exercise is substantially exaggerated in individuals with heart failure with a preserved ejection fraction. The faster rate of fatigue development is associated with the compromised peripheral hemodynamic response characterizing these patients during exercise. Given the role of neuromuscular fatigue as a factor limiting exercise, this impairment likely accounts for a significant portion of the exercise intolerance typical for this population.
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Tolerância ao Exercício , Insuficiência Cardíaca/fisiopatologia , Fadiga Muscular , Força Muscular , Músculo Quadríceps/irrigação sanguínea , Músculo Quadríceps/inervação , Volume Sistólico , Função Ventricular Esquerda , Idoso , Estudos de Casos e Controles , Feminino , Insuficiência Cardíaca/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Fluxo Sanguíneo Regional , Fatores de TempoRESUMO
BACKGROUND AND PURPOSE: Olfactory bulb atrophy is associated with cognitive dysfunction in Parkinson's and Alzheimer's disease, and with major depression. It has been suggested that olfactory bulb atrophy or dysfunction is therefore a marker of neurodegeneration. Multiple sclerosis (MS) is now also recognized as having a significant neurodegenerative component. Thus, the aim of this study was to investigate associations between physical and cognitive disability, depression and olfactory bulb volume in MS. METHODS: In total, 146 patients with MS (mean age 49.0 ± 10.9 years, disease duration 21.2 ± 9.3 years, median Expanded Disability Status Scale (EDSS) score 3.0 (range 0-7.5), 103 relapsing-remitting, 35 secondary progressive and eight primary progressive MS) underwent a standardized neurological examination, comprehensive neuropsychological testing and magnetic resonance imaging (MRI); data of 27 healthy people served as age- and gender-matched control subjects. The olfactory bulb was semi-automatically segmented on high-resolution three-dimensional T1-weighted MRI. RESULTS: Mean olfactory bulb volume was lower in MS patients than healthy controls (183.9 ± 40.1 vs. 209.2 ± 59.3 µl; P = 0.018 adjusted to intracranial volume). Olfactory bulb volume was similar across clinical disease subtypes and did not correlate with cognitive performance, EDSS scores or total proton density/T2 white matter lesion volume. However, in progressive MS, the mean olfactory bulb volume correlated with depression scores (Spearman's rho = -0.38, P < 0.05) confirmed using a multivariate linear regression analysis including cognitive fatigue scores. This association was not observed in relapsing-remitting MS. CONCLUSION: Olfactory bulb volume was lower in MS than in healthy controls. Olfactory bulb volume does not seem to mirror cognitive impairment in MS; however, it is associated with higher depression scores in progressive MS.
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Disfunção Cognitiva/fisiopatologia , Depressão/fisiopatologia , Esclerose Múltipla/patologia , Esclerose Múltipla/fisiopatologia , Bulbo Olfatório/patologia , Adulto , Atrofia/patologia , Disfunção Cognitiva/etiologia , Depressão/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/complicações , Esclerose Múltipla Recidivante-Remitente/complicações , Esclerose Múltipla Recidivante-Remitente/patologia , Esclerose Múltipla Recidivante-Remitente/fisiopatologiaRESUMO
We investigated the role of exercise intensity and associated central motor drive in determining corticomotoneuronal excitability. Ten participants performed a series of nonfatiguing (3 s) isometric single-leg knee extensions (ISO; 10-100% of maximal voluntary contractions, MVC) and cycling bouts (30-160% peak aerobic capacity, W peak). At various exercise intensities, electrical potentials were evoked in the vastus lateralis (VL) and rectus femoris (RF) via transcranial magnetic stimulation (motor-evoked potentials, MEP), and electrical stimulation of both the cervicomedullary junction (cervicomedullary evoked potentials, CMEP) and the femoral nerve (maximal M-waves, M max). Whereas M max remained unchanged in both muscles (P > 0.40), voluntary electromyographic activity (EMG) increased in an exercise intensity-dependent manner for ISO and cycling exercise in VL and RF (both P < 0.001). During ISO exercise, MEPs and CMEPs progressively increased in VL and RF until a plateau was reached at â¼ 75% MVC; further increases in contraction intensity did not cause additional changes (P > 0.35). During cycling exercise, VL-MEPs and CMEPs progressively increased by â¼ 65% until a plateau was reached at W peak. In contrast, RF MEPs and CMEPs progressively increased by â¼ 110% throughout the tested cycling intensities without the occurrence of a plateau. Furthermore, alterations in EMG below the plateau influenced corticomotoneuronal excitability similarly between exercise modalities. In both exercise modalities, the MEP-to-CMEP ratio did not change with exercise intensity (P > 0.22). In conclusion, increases in exercise intensity and EMG facilitates the corticomotoneuronal pathway similarly in isometric knee extension and locomotor exercise until a plateau occurs at a submaximal exercise intensity. This facilitation appears to be primarily mediated by increases in excitability of the motoneuron pool.
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Exercício Físico , Contração Isométrica , Atividade Motora , Córtex Motor/fisiologia , Neurônios Motores/fisiologia , Tratos Piramidais/fisiologia , Músculo Quadríceps/inervação , Adulto , Ciclismo , Estimulação Elétrica/métodos , Eletromiografia , Potencial Evocado Motor , Nervo Femoral/fisiologia , Humanos , Joelho , Masculino , Fatores de Tempo , Estimulação Magnética TranscranianaRESUMO
In this paper we show the suitability of a miniaturized tunable diode laser spectroscopy (TDLS)-based carbon-monoxide (CO) sensor for fire detection applications. The sensor utilizes a vertical-cavity surface-emitting laser (VCSEL) and inherent calibration scheme with reference gas filled in the photodetector housing. The fire-detection experiments are carried out under realistic conditions as described in the European standard EN54. The CO generation of all class C fires (according to EN54) could be well resolved. The cross-sensitivity to other substances was found to be very low: the maximum CO false response from cigarette smoke, hairspray and general aerosols reaches a low value of a few µL/L and only if the substance is directly applied into the sensor gas inlet. Therefore this sensor overcomes the disadvantage of high false alarm rate given by smoke detectors and is also in small size which is suitable for household and industrial applications. Hence, the VCSEL-based TDLS sensor is shown to have sufficient performance for fire-detection. It has advantages such as capability for fail-safe operation and, low cross-sensitivities as compared to existing point fire detector technology which is presently limited by these factors.
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Several Applications for tunable laser diodes have strict constraints in terms of overall power consumption. Furthermore, the implementation in harsh environments with large temperature fluctuations is necessary. Due to the constraint in power consumption, the application of active cooling might not be an option. For this reason we investigate the temperature characteristics of an electrically pumped MEMS-VCSEL with wide continuous wavelength tuning. For the first time, a mode hop free single mode (side mode suppression ratio (SMSR) > 40dB) tuning range of 45nm at 70°C is demonstrated with a MEMS-VCSEL. An increase of the tuning range from 85nm at 20°C to 92nm at 40°C is measured and explained. In contrast to fixed wavelength VCSEL, the investigated device shows a negative temperature induced wavelength shift of -4.5nmK(-1), which is caused by the MEMS-mirror. At 1560nm, the fibre-coupled optical output power is above 0.6mW over the entire temperature range between 20°C to 70°C and shows a maximum of > 3mW at 20°C.
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INTRODUCTION: In this study, we used surface electromyography (EMG) electrodes in order to measure and compare activity in the neck, back and thigh muscles of soldiers wearing two different types of body armour. A secondary objective was to analyse shoulder and hip ranges of motion using inertial motion sensors. METHODS: Fourteen male soldiers were instructed to march 6 km on a treadmill while wearing different types of body armour. All participants wore shorts and a T-shirt and the same size vest regardless of their body size. We measured back and thigh muscle activity as well as shoulder and hip ranges of motion at regular intervals during the march. RESULTS: Over the course of a 6 km march, muscle activity was already increased to 1.3 to 2.0 times after putting on the vest and increased by up to 13 times during the march with equipment. The new vest with hip belt required higher levels of muscle activity. CONCLUSIONS: Body armour with hip belt placed higher levels of stress on back and neck muscles during a 6 km march than without. There was no major difference between the two types of body armour in terms of thigh muscle activity. TRIAL REGISTRATION NUMBER: DRKS00016005.
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We generate a 105.7-Gb/s signal by directly modulating a 1.5-µm VCSEL with a 33.35-Gbaud 3-level signal and polarization multiplexing. By using digital coherent detection, we successfully transmit the 105.7-Gb/s line rate (88.10 Gb/s net bit rate) signal over 960-km standard single-mode-fiber (SSMF) at a 20% hard-decision forward-error correction (FEC) threshold, which is at bit-error ratio (BER) of 1.5 x 10(-2)
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Algoritmos , Tecnologia de Fibra Óptica/instrumentação , Processamento de Sinais Assistido por Computador/instrumentação , Telecomunicações/instrumentação , Desenho de Equipamento , Análise de Falha de EquipamentoRESUMO
BACKGROUND: Non-communicating syringomyelia (NCS) has occasionally been described in case reports and small case series as an incidental finding of spinal cord (SC) pathology in patients with multiple sclerosis (MS), but only little is known on the clinical course and progression of NCS, and in more general terms on the prognosis of patients with MS and NCS. METHODS: Nine patients with MS with known NCS at baseline and a control group of 18 age-, sex- and disease course-matched patients with MS without NCS were recruited for a follow-up visit after 6 years. All 27 patients underwent clinical examination and brain magnetic resonance imaging (MRI), and 8/9 patients with NCS were additionally studied with MRI of the SC. MRI data were analysed for changes in length and maximal cross-sectional area of the NCS, lesion volumes of the brain and cord as well as for volumetric metrics of the whole brain (using SIENAX), the cerebellum and medulla oblongata (using ECCET). RESULTS: NCS did not significantly change in size when corrected for multiple comparisons. The clinical data (annual relapse rate, EDSS and disease duration) and MRI metrics (T2 and T1 lesion load; whole brain, cerebellar and medulla oblongata volumes as well as their percentage volume change per year) did not significantly differ between patients with MS with or without NCS. CONCLUSION: The stable findings regarding size and shape of the syrinx and lack of distinguishing MRI and clinical features support the assumption that NCS is not defining a prognostically or pathogenetically distinct subgroup of patients with MS.
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Esclerose Múltipla/complicações , Siringomielia/complicações , Siringomielia/patologia , Idoso , Progressão da Doença , Feminino , Seguimentos , História do Século XVI , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND AND PURPOSE: Fully automatic quantification methods of spinal cord compartments are needed to study pathologic changes of the spinal cord GM and WM in MS in vivo. We propose a novel method for automatic spinal cord compartment segmentation (SCORE) in patients with MS. MATERIALS AND METHODS: The cervical spinal cords of 24 patients with MS and 24 sex- and age-matched healthy controls were scanned on a 3T MR imaging system, including an averaged magnetization inversion recovery acquisition sequence. Three experienced raters manually segmented the spinal cord GM and WM, anterior and posterior horns, gray commissure, and MS lesions. Subsequently, manual segmentations were used to train neural segmentation networks of spinal cord compartments with multidimensional gated recurrent units in a 3-fold cross-validation fashion. Total intracranial volumes were quantified using FreeSurfer. RESULTS: The intra- and intersession reproducibility of SCORE was high in all spinal cord compartments (eg, mean relative SD of GM and WM: ≤ 3.50% and ≤1.47%, respectively) and was better than manual segmentations (all P < .001). The accuracy of SCORE compared with manual segmentations was excellent, both in healthy controls and in patients with MS (Dice similarity coefficients of GM and WM: ≥ 0.84 and ≥0.92, respectively). Patients with MS had lower total WM areas (P < .05), and total anterior horn areas (P < .01 respectively), as measured with SCORE. CONCLUSIONS: We demonstrate a novel, reliable quantification method for spinal cord tissue segmentation in healthy controls and patients with MS and other neurologic disorders affecting the spinal cord. Patients with MS have reduced areas in specific spinal cord tissue compartments, which may be used as MS biomarkers.
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Esclerose Múltipla , Humanos , Esclerose Múltipla/complicações , Esclerose Múltipla/diagnóstico por imagem , Esclerose Múltipla/patologia , Reprodutibilidade dos Testes , Medula Espinal/diagnóstico por imagem , Medula Espinal/patologia , Substância Cinzenta/patologia , Imageamento por Ressonância Magnética/métodosRESUMO
The exact role of arousal in central and peripheral hemodynamic responses to passive limb movement in humans is unclear but has been proposed as a potential contributor. Thus, we used a human model with no lower limb afferent feedback to determine the role of arousal on the hemodynamic response to passive leg movement. In nine people with a spinal cord injury, we compared central and peripheral hemodynamic and ventilatory responses to one-leg passive knee extension with and without visual feedback (M+VF and M-VF, respectively) as well as in a third trial with no movement or visual feedback but the perception of movement (F). Ventilation (Ve), heart rate, stroke volume, cardiac output, mean arterial pressure, and leg blood flow (LBF) were evaluated during the three protocols. Ve increased rapidly from baseline in M+VF (55 ± 11%), M-VF (63 ± 13%), and F (48 ± 12%) trials. Central hemodynamics (heart rate, stroke volume, cardiac output, and mean arterial pressure) were unchanged in all trials. LBF increased from baseline by 126 ± 18 ml/min in the M+VF protocol and 109 ± 23 ml/min in the M-VF protocol but was unchanged in the F protocol. Therefore, with the use of model that is devoid of afferent feedback from the legs, the results of this study reveal that, although arousal is invoked by passive movement or the thought of passive movement, as evidenced by the increase in Ve, there is no central or peripheral hemodynamic impact of this increased neural activity. Additionally, this study revealed that a central hemodynamic response is not an obligatory component of movement-induced LBF.
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Nível de Alerta , Hemodinâmica , Extremidade Inferior/irrigação sanguínea , Extremidade Inferior/inervação , Movimento , Traumatismos da Medula Espinal/fisiopatologia , Traumatismos da Medula Espinal/psicologia , Adulto , Vias Aferentes/fisiopatologia , Análise de Variância , Velocidade do Fluxo Sanguíneo , Pressão Sanguínea , Retroalimentação Sensorial , Feminino , Frequência Cardíaca , Humanos , Masculino , Pessoa de Meia-Idade , Percepção , Ventilação Pulmonar , Fluxo Sanguíneo Regional , Volume Sistólico , Fatores de Tempo , UtahRESUMO
We demonstrate a self-starting Kerr-lens mode-locked (KLM) Yb:YAG thin-disk oscillator operating in the regime of positive intracavity group-delay dispersion (GDD). It delivers 1.7 ps pulses at an average power of 17 W and a repetition rate of 40 MHz. Dispersive mirrors compress the pulses to a duration of 190 fs (assuming sech2 shape; Fourier limit: 150 fs) at an average power level of 11 W. To our knowledge, this is the first KLM thin-disk oscillator with positive GDD. Output powers of up to 30 W were achieved with an increased output coupler transmission and intracavity GDD. We demonstrate increase of the pulse energy with increasing positive intracavity GDD, limited by difficulties in initiating mode-locking.
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BACKGROUND: The ability to predict the course of multiple sclerosis (MS) is highly desirable but lacking. OBJECTIVE: To test whether the MS Severity Scale (MSSS) and global neuronal viability, assessed through the quantification of the whole-brain N-acetylaspartate concentration (WBNAA), concur or complement the assessment of individual patients' disease course. METHODS: The MSSS and average WBNAA loss rate (ΔWBNAA, extrapolated based on one current measurement and the assumption that at disease onset neural sparing was similar to healthy controls, obtained with proton magnetic resonance (MR) spectroscopy and magnetic resonance imaging (MRI)) from 61 patients with MS (18 male and 43 female) with long disease duration (15 years or more) were retrospectively examined. Some 27 patients exhibited a 'benign' disease course, characterized by an Expanded Disability Status Scale score (EDSS) of 3.0 or less, and 34 were 'non-benign': EDSS score higher than 3.0. RESULTS: The two cohorts were indistinguishable in age and disease duration. Benign patients' EDSS and MSSS (2.1 ± 0.7, 1.15 ± 0.60) were significantly lower than non-benign (4.6 ± 1.0, 3.6 ± 1.2; both p < 10(-4)). Their respective average ΔWBNAA, 0.10 ± 0.16 and 0.11 ± 0.12 mM/year, however, were not significantly different (p > 0.7). While MSSS is both sensitive to (92.6%) and specific for (97.0%) benign MS, ΔWBNAA is only sensitive (92.6%) but not specific (2.9%). CONCLUSION: Since the WBNAA loss rate is similar in both phenotypes, the only difference between them is their clinical classification, characterized by MSSS and EDSS. This may indicate that 'benign' MS probably reflects fortuitous sparing of clinically eloquent brain regions and better utilization of brain plasticity.
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Ácido Aspártico/análogos & derivados , Biomarcadores/análise , Encéfalo/metabolismo , Esclerose Múltipla/metabolismo , Índice de Gravidade de Doença , Ácido Aspártico/análise , Encéfalo/patologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Espectroscopia de Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/patologia , Estudos Retrospectivos , Sensibilidade e EspecificidadeRESUMO
OBJECTIVES: Virtual reality (VR) opens a variety of therapeutic options to improve symptom burden in patients with advanced disease. Until to date, only few studies have evaluated the use of VR therapy in the context of palliative care. This case series aims to evaluate the feasibility and acceptability of VR therapy in a population of palliative care patients. METHODS: In this single-site case series, we report on six palliative care patients undergoing VR therapy. The VR therapy consisted of a one-time session ranging between 20 to 60â minutes depending on the patient's needs and the content chosen for the VR sessions. A semi-structured survey was conducted and the Edmonton Symptom Assessment System (ESAS) and the Distress Thermometer were performed pre- and post-intervention. RESULTS: Overall, VR therapy was well accepted by all patients. Five out of six patients reported having appreciated VR therapy. There were individual differences of perceived effects using VR therapy. The semi-structured survey revealed that some patients felt a temporary detachment from their body and that patients were able to experience the VR session as a break from omnipresent worries and the hospital environment ("I completely forgot where I am"). There was a considerable reduction in the total ESAS score post-treatment (T0 ESASTot = 27.2; T1 ESASTot = 18.8) and a slightly reduction in distress (T0 DTTot = 4.4; T1 DTTot = 3.8). However, two patients were more tired after the intervention.Significance of Results: Our preliminary results demonstrate that VR therapy is acceptable, feasible and safe for use within a palliative care population and appears to be a viable treatment option. Clinical trials are both warranted and necessary to confirm any therapeutic effects of VR therapy, as is the need to tailor VR systems better for use in palliative care settings.
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This paper discusses several performance-related aspects of electrically-pumped GaSb-based buried tunnel junction VCSELs with an emission wavelength of 2.6 µm based on theoretical and experimental results. These results allow a deeper insight into the internal device physics, such as radial diffusion of carriers, maximum continuous-wave operating temperature, diffraction loss, internal temperature, gain and loss parameters, internal quantum efficiency of the active region etc. These parameters can be taken into account while designing mid-infrared lasers which leads to an improved device performance. A simple thermal model of the devices based on the two-dimensional (2-D) finite element method using the material data from the literature is also presented. In addition, an application-based result utilizing these lasers for the measurement of absolute water vapor concentration by wavelength modulation spectroscopy (WMS) method are also described, hinting that devices are well-suited for the targeted sensing applications.
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For the first time a vertical-cavity surface-emitting laser (VCSEL) with a single-mode wavelength-tuning over 102 nm in the range of 1550 nm is demonstrated. The fiber-coupled optical output power has a maximum of 3.5 mW and is > 2 mW over the entire tuning range. The sidemode suppression ratios are > 45 dB. The wavelength tuning is achieved with the micro-electro mechanical actuation of a mirror membrane fabricated with surface micro-machining for on-wafer mass production. The mirror membrane consists of low cost dielectric materials (SiOx/SiNy) deposited with low temperature (< 100°C) Plasma Enhanced Chemical Vapor Deposition (PECVD).
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We demonstrate a power-scalable Kerr-lens mode-locked Yb:YAG thin-disk oscillator. It delivers 200 fs pulses at an average power of 17 W and a repetition rate of 40 MHz. At an increased (180 W) pump power level, the laser produces 270 fs 1.1 µJ pulses at an average power of 45 W (optical-to-optical efficiency of 25%). Semiconductor-saturable-absorber-mirror-assisted Kerr-lens mode locking (KLM) and pure KLM with a hard aperture show similar performance. To our knowledge, these are the shortest pulses achieved from a mode-locked Yb:YAG disk oscillator and this is the first demonstration of a Kerr-lens mode-locked thin-disk laser.
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BACKGROUND AND PURPOSE: Currently, accurate and reproducible spinal cord GM segmentation remains challenging and a noninvasive broadly accepted reference standard for spinal cord GM measurements is still a matter of ongoing discussion. Our aim was to assess the reproducibility and accuracy of cervical spinal cord GM and WM cross-sectional area measurements using averaged magnetization inversion recovery acquisitions images and a fully-automatic postprocessing segmentation algorithm. MATERIALS AND METHODS: The cervical spinal cord of 24 healthy subjects (14 women; mean age, 40 ± 11 years) was scanned in a test-retest fashion on a 3T MR imaging system. Twelve axial averaged magnetization inversion recovery acquisitions slices were acquired over a 48-mm cord segment. GM and WM were both manually segmented by 2 experienced readers and compared with an automatic variational segmentation algorithm with a shape prior modified for 3D data with a slice similarity prior. Precision and accuracy of the automatic method were evaluated using coefficients of variation and Dice similarity coefficients. RESULTS: The mean GM area was 17.20 ± 2.28 mm2 and the mean WM area was 72.71 ± 7.55 mm2 using the automatic method. Reproducibility was high for both methods, while being better for the automatic approach (all mean automatic coefficients of variation, ≤4.77%; all differences, P < .001). The accuracy of the automatic method compared with the manual reference standard was excellent (mean Dice similarity coefficients: 0.86 ± 0.04 for GM and 0.90 ± 0.03 for WM). The automatic approach demonstrated similar coefficients of variation between intra- and intersession reproducibility as well as among all acquired spinal cord slices. CONCLUSIONS: Our novel approach including the averaged magnetization inversion recovery acquisitions sequence and a fully-automated postprocessing segmentation algorithm demonstrated an accurate and reproducible spinal cord GM and WM segmentation. This pipeline is promising for both the exploration of longitudinal structural GM changes and application in clinical settings in disorders affecting the spinal cord.
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Algoritmos , Substância Cinzenta/anatomia & histologia , Processamento de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Neuroimagem/métodos , Medula Espinal/anatomia & histologia , Adulto , Feminino , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Valores de Referência , Reprodutibilidade dos TestesRESUMO
BACKGROUND: There is limited evidence about the optimal length of washout when switching from natalizumab to fingolimod. OBJECTIVE: To study if a washout period of 4 weeks is associated with less disease activity compared to 8 weeks. METHODS: 25 patients with Relapsing Remitting Multiple Sclerosis were included in an open label, prospective study with a follow-up of 108 weeks. The primary endpoint (PE) was defined as "time to first relapse or MRI disease activity up to week 56". In addition, a recurrent event analysis (REA) was performed up to week 108. RESULTS: The PE was not met (HR 0.67, 95% CI [0.22,1.97], pâ¯=â¯0.462). Number of relapses before stopping natalizumab was positively associated with the hazard of relapse (HR 3.91, pâ¯=â¯0.0117, 95% CI [1.36, 11.28]). The REA showed a reduction of the hazard to develop a relapse by 77% (HR 0.23, 95% CI [0.08, 0.69], pâ¯=â¯0.00854) in favor of the cohort with 4 weeks washout. CONCLUSIONS: Our study suggests that switching from natalizumab to fingolimod with a shorter washout of 4 weeks might reduce the risk of disease reactivation after switching.
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Substituição de Medicamentos/métodos , Cloridrato de Fingolimode/uso terapêutico , Fatores Imunológicos/uso terapêutico , Esclerose Múltipla/tratamento farmacológico , Natalizumab/uso terapêutico , Adulto , Encéfalo/diagnóstico por imagem , Encéfalo/efeitos dos fármacos , Avaliação da Deficiência , Feminino , Seguimentos , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/diagnóstico por imagem , Proibitinas , Estatísticas não Paramétricas , Fatores de Tempo , Adulto JovemRESUMO
GaInAsSb/GaSb based quantum well vertical cavity surface emitting lasers (VCSELs) operating in mid-infrared spectral range between 2 and 3 micrometres are of great importance for low cost gas monitoring applications. This paper discusses the efficiency and temperature sensitivity of the VCSELs emitting at 2.6 µm and the processes that must be controlled to provide temperature stable operation. We show that non-radiative Auger recombination dominates the threshold current and limits the device performance at room temperature. Critically, we demonstrate that the combined influence of non-radiative recombination and gain peak-cavity mode de-tuning determines the overall temperature sensitivity of the VCSELs. The results show that improved temperature stable operation around room temperature can only be achieved with a larger gain peak-cavity mode de-tuning, offsetting the significant effect of increasing non-radiative recombination with increasing temperature, a physical effect which must be accounted for in mid-infrared VCSEL design.
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It was found that autoxidative degradation is responsible for the inactivation of the unstable Microcystis toxin HBP-Tx. The purified toxin was similar in its properties to the "fast-death-factor" in Microcystis, described as a cyclic peptide in the literature. The apparent presence of an entirely different toxin was simulated by the partially inactivated HBP-Tx. A number of associated fluorescent compounds were identified as the non-toxic degradation products of the toxin. As a consequence, as established method for the detection of other algal toxins was applied. This chemical assay, which uses fluorescent measurement of the oxidized toxin in the cyanobacterium Aphanizomenon flos-aquae, was applicable for HBP-Tx after the removal of interfering degradation products of the toxin. The results obtained with Microcystis toxin HBP-Tx do not confirm suggestions concerning the structure of the "fast-death-factor".