We introduce a dual-comb spectrometer based on erbium fiber oscillators at 250â MHz that operates in the 7.5-11.5â µm spectral range over optical bandwidths up to 9â THz with a multi-kHz acquisition rate. Over an observation bandwidth of 0.8â THz, the signal-to-noise ratio per spectral point reaches 168â Hz0.5 at an acquisition rate of 26â kHz, which allows the investigation of transient processes in the gas phase at high temporal resolution. The system also represents an attractive solution for multi-species atmospheric gas detection in open paths due to the water transparency of the spectral window, the use of thermo-electrically cooled detectors, and the out-of-loop phase correction of the interferograms.
Accreditation processes for health care professions are designed to ensure that individuals and programs in these fields meet established standards of quality and effectiveness. The accelerating pace of globalization in the health care professions has increased the need for a shared understanding of the vocabulary of evaluation, assessment, and accreditation. The psychometric principles of valid and reliable assessment are commonly accepted, but the terminology is confusing. We believe that all stakeholders - evaluators, faculty, students but also the community - will benefit from a shared language and common set of definitions. We recognize that not all readers will agree with the definitions we propose, but we hope that this guide will help to ensure clarity, consistency, transparency, and fairness, and that it will promote through the stimulation of a debate greater collaboration across national and international boundaries.
We report an approach for high-resolution spectroscopy using a widely tunable laser emitting in the molecular fingerprint region. The laser is based on difference-frequency generation (DFG) in a nonlinear orientation-patterned GaAs crystal. The signal laser, a CO2 gas laser, is operated in a kHz-pulsed mode while the pump laser, an external-cavity quantum cascade laser, is finely mode-hop-free tuned. The idler radiation covers a spectral range of â¼11.6-15â µm with a laser linewidth of â¼ 2.3 MHz. We showcase the versatility and the potential for molecular fingerprinting of the developed DFG laser source by resolving the absorption features of a mixture of several species in the long-wavelength mid-infrared. Furthermore, exploiting the wide tunability and resolution of the spectrometer, we resolve the broadband absorption spectrum of ethylene (C2H4) over â¼13-14.2 µm and quantify the self-broadening coefficients of some selected spectral lines.
We present chemical kinetics and environmental monitoring applications in the long-wavelength mid-infrared (LW-MIR) region using a new diagnostic that exploits a widely tunable light source emitting in the LW-MIR. The custom-designed laser source is based on a difference-frequency generation (DFG) process in a nonlinear orientation-patterned GaAs crystal. The pump laser, an external-cavity quantum cascade laser, is tuned in a continuous-wave (cw) mode, while the signal laser, a C O 2 gas laser, is operated in a pulsed mode with a kilohertz repetition rate. The idler wavelength can be tuned between 11.58 (863.56c m -1) and 15.00 µm (666.67c m -1) in a quasi-cw manner. We discuss the unique prospective applications offered by probing the LW-MIR region for chemical kinetics and environment-monitoring applications. We showcase the potential of the DFG laser source by some representative applications.
Resumen El ataque cerebrovascular (ACV) es la primera causa de discapacidad y la tercera causa de muerte en la Argentina y en el mundo. La etiología del stroke es isquémica en su mayoría (más del 80% de los casos), siendo las causas más frecuentes las lesiones isquémicas de pequeños vasos de tipo lacunar y las tromboembólicas debido a ateroesclerosis de grandes arterias o cardioembolia. Las secuencias utilizadas en nuestro protocolo de estudio incluyen DWI, FLAIR, angio-RM 3D-TOF, SWI y FSE-T1 (tiempo aproximado de exploración de 13 minutos). Pueden observarse diferentes hallazgos en cada una de estas secuencias que son orientativos para determinar la etiología subyacente y estimar el tiempo de evolución de la lesión. En la actualidad, la trombectomía mecánica se ha convertido en el tratamiento de elección en pacientes seleccionados con accidente cerebral isquémico agudo. La transformación hemorrágica es la complicación más temida luego de la terapia de reperfusión intraarterial. La técnica de difusión de la resonancia magnética (RM) posee una mayor sensibilidad para detectar lesiones isquémicas, permite sospechar la etiología según el patrón lesional y aporta información valiosa para la selección de los pacientes candidatos a la reperfusión arterial.
Abstract Stroke or cerebrovascular attack (CVA) is the first cause of disability and the third cause of death in Argentina and in the world. The etiology of strokes is mostly ischemic (more than 80% of cases), with the most frequent causes being lacunar-type ischemic lesions of small vessels and thromboembolic lesions due to atherosclerosis of large arteries or cardioembolism. The sequences used in our study protocol include DWI, FLAIR, angio-RM 3D-TOF, SWI, and FSE-T1 (approximate scan time of 13 minutes). Different findings can be observed in each of these sequences that are indicative to determine the underlying etiology and estimate the time of evolution of the lesion. Currently, mechanical thrombectomy has become the treatment of choice in selected patients with acute ischemic stroke. Hemorrhagic transformation is the most feared complication after intra-arterial reperfusion therapy. The diffusion magnetic resonance technique is more sensitive for detecting ischemic lesions, allows one to suspect the etiology based on the lesion pattern, and provides valuable information for the selection of patients who are candidates for arterial reperfusion.
Introduction: Erdheim-Chester Disease (ECD) is a rare form of histiocytosis, characterized by xanthogranulomatous infiltration of multiple organs by lipid-laden histiocytes. It is considered a myeloid inflammatory clonal disorder that mainly affects men with a mean age of 55 years. Methods: We present the case of a 65-year-old man who consulted our Endocrinology Unit because of polyuria and polydipsia of 4 months of evolution, diagnosing central diabetes insipidus associated with pituitary infiltration. Physical examination showed skin lesions he has had for several years, that were papules-nodules in the anterior chest and xantelasma-like in the face and neck, with biopsy compatible with non-Langerhans histiocytosis. The genetic study of the skin biopsy showed the presence of a mutation in MAP2K1, confirming the ECD. Results: The patient started treatment with interferon alfa, but the response was incomplete and associated with severe intolerance, so given the findings of the genetic study, we decided to indicate treatment with cobimetinib, a potent and selective inhibitor of MEK. After 8 months of treatment, skin lesions have disappeared, as has the pituitary infiltration, with a remarkable improvement in his quality of life. Conclusions: We present a 65-year-old patient with a rare form of histiocytosis (ECD) who in turn presented an atypical form of ECD and, where the genetic study allowed us to confirm the diagnosis and use targeted therapy with cobimetinib with outstanding results.
Introducción: La Enfermedad de Erdheim-Chester (ECD) es una rara forma de histiocitosis, caracterizada por la infiltración xantogranulomatosa de múltiples órganos por histiocitos cargados de lípidos. Se la considera un trastorno clonal inflamatorio mieloide que afecta principalmente a hombres con una edad media de 55 años. Métodos: Presentamos el caso de un hombre de 65 años que consultó a nuestro Servicio de Endocrinología por poliuria y polidipsia de 4 meses de evolución diagnosticándose diabetes insípida central asociada a infiltración hipofisaria. El paciente presentaba lesiones cutáneas pápulo-nodulares en tórax y xantelasma-símiles en cuello y cara de varios años de evolución, con biopsia compatible con histiocitosis no-Langerhans. El estudio genético de la biopsia cutánea detectó la mutación MAP2K1 confirmando la ECD. Resultados: El paciente inició tratamiento con interferón alfa con respuesta incompleta y mala tolerancia por lo que cambiamos el tratamiento a un inhibidor potente y selectivo de MEK, el cobimetinib. Tras 8 meses de tratamiento presenta desaparición de lesiones cutáneas y de la infiltración hipofisaria con notable mejoría de su calidad de vida. Conclusión: Presentamos el caso de un paciente adulto con una forma rara de histiocitosis (ECD) que a su vez presentó una forma atípica de ECD y, donde el estudio genético nos permitió confirmar el diagnóstico e introducir una terapia dirigida con cobimetinib con excelentes resultados.
Erdheim-Chester Disease , Aged , Azetidines , Biopsy , Erdheim-Chester Disease/drug therapy , Erdheim-Chester Disease/genetics , Humans , Male , Middle Aged , Mutation , Piperidines , Quality of Life
We introduce a high-sensitivity broadband stimulated Raman scattering (SRS) setup featuring wide spectral coverage (up to 500 cm-1) and high-frequency resolution (≈20 cm-1). The system combines a narrowband Stokes pulse, obtained by spectral filtering an Yb laser, with a broadband pump pulse generated by a home-built optical parametric oscillator. A single-channel lock-in amplifier connected to a single-pixel photodiode measures the stimulated Raman loss signal, whose spectrum is scanned rapidly using a galvanometric mirror after the sample. We use the in-line balanced detection approach to suppress laser fluctuations and achieve close to shot-noise-limited sensitivity. The setup is capable of measuring accurately the SRS spectra of several solvents and of obtaining hyperspectral data cubes consisting in the broadband SRS microscopy images of polymer beads test samples as well as of the distribution of different biological substances within plant cell walls.
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Frequency combs have made optical metrology accessible to hundreds of laboratories worldwide and they have set new benchmarks in multi-species trace gas sensing for environmental, industrial and medical applications. However, current comb spectrometers privilege either frequency precision and sensitivity through interposition of a cw probe laser with limited tuning range, or spectral coverage and measurement time using the comb itself as an ultra-broadband probe. We overcome this restriction by introducing a comb-locked frequency-swept optical synthesizer that allows a continuous-wave laser to be swept in seconds over spectral ranges of several terahertz while remaining phase locked to an underlying frequency comb. This offers a unique degree of versatility, as the synthesizer can be either repeatedly scanned over a single absorption line to achieve ultimate precision and sensitivity, or swept in seconds over an entire rovibrational band to capture multiple species. The spectrometer enables us to determine line center frequencies with an absolute uncertainty of 30 kHz and at the same time to collect absorption spectra over more than 3 THz with state-of-the-art sensitivity of a few 10-10 cm-1. Beyond precision broadband spectroscopy, the proposed synthesizer is an extremely promising tool to force a breakthrough in terahertz metrology and coherent laser ranging.
We study the frequency noise and the referencing to a near-infrared frequency comb of a widely tunable external-cavity quantum-cascade-laser that shows a relatively narrow free-running emission linewidth of 1.7 MHz. The frequency locking of the laser to the comb further narrows its linewidth to 690 kHz and enables sub-Doppler spectroscopy on an N2O transition of the ν1 band near 7.7 µm with sub-MHz resolution and absolute frequency calibration. The combined uncertainty on the measured transition center is estimated to be less than 50 kHz.
Los ataques cerebrovasculares (ACV), representan un problema mayor en salud y son una causa importante de discapacidad en todo el mundo. La estenosis u oclusión carotídea aterosclerótica causa alrededor del 20% de las isquemias cerebrovasculares.¹ Los ACV en los enfermos con estenosis carotídea se producen, en la mayoría de los casos, por la aparición de embolismos distales de trombo formado en la placa, oclusión trombótica aguda debido a rotura de la placa, o bien secundarios a las alteraciones hemodinámicas atribuibles a la estenosis, la cual produce disminución de la perfusión cerebral por el hipoflujo, en casos de estenosis críticas o suboclusivas. El tratamiento de la patología carotídea ha evolucionado de forma considerable a lo largo de los últimos años. Existen dos tratamientos invasivos para la estenosis carotídea significativa, que consisten en el abordaje quirúrgico con endarterectomía o tratamiento por vía percutánea con angioplastia y colocación de stent. En nuestra institución se realizaron, en el periodo comprendido entre marzo de 2013 y junio de 2017, aproximadamente 100 angioplastias carotídeas con colocación de stent. Todas fueron valoradas con ecografía Doppler color (EDC) al mes, a los seis meses y al año (en casos no complicados). En esta revisión bibliográfica es nuestra intención desarrollar las indicaciones, aplicaciones, hallazgos normales y patológicos en el examen de EDC en la evaluación de un paciente con stent carotídeo.
Acute stroke represents a major problem in health and is a major cause of disability worldwide. Atherosclerotic carotid stenosis or occlusion causes around 20% of cerebrovascular ischemias.¹ Stroke in patients with carotid stenosis occurs, in most cases, due to embolisms of thrombus formed in the plaque, acute thrombotic occlusion due to rupture of the plaque, or secondary to hemodynamic alterations, attributable to stenosis, which produces decreased cerebral perfusion by low flow, in cases of critical or sub occlusive stenosis. The treatment of carotid disease has evolved considerably over recent years. There are two invasive treatments for significant carotid stenosis, which consist of the surgical approach with endarterectomy or percutaneous treatment with angioplasty and stenting. In our institution, in the period between March 2013 and June 2017, ~100 carotid angioplasties with stent placement were performed. All were assessed with color Doppler ultrasound (DUS) at month, six months and one year (in non complicated cases). In this literature review it is our intention to develop the indications, applications, normal and pathological findings in the DUS examination in the evaluation of a patient with carotid stent.
Humans , Carotid Stenosis/diagnostic imaging , Ultrasonography, Doppler, Color/methods , Stents , Carotid Stenosis/drug therapy , Angioplasty , Stroke/complications
The transfer of phase coherence from an ultrastable master laser to a distributed feedback diode laser, using an optical comb as a transfer oscillator, is obtained via a new scheme allowing continuous scanning across the whole tuning range of the slave laser together with absolute frequency determination. This is accomplished without phase lock loops, through a robust high-bandwidth feed-forward control acting directly on the slave laser output radiation. The correction is obtained by means of a dual-parallel Mach-Zehnder interferometer used as an optical single-sideband modulator. Coherence transfer across a master-slave frequency gap of 14 THz yields an â¼10 kHz linewidth providing high injection efficiency of an optical cavity with finesse 250 000. This allows demonstrating a cavity ring-down absorption spectrum of low-pressure ambient air over a 300 GHz spectral window.
BACKGROUND: Optic pathway gliomas (OPGs) are present in 20% of children with neurofibromatosis 1 (NF1) but are less frequently observed in adults. Our goal was to determine the natural history of OPGs in children and adults with NF1. RESULTS: We analyzed the features of OPGs and other intracranial lesions on 1775 head MRI scans of 562 unselected adults and children with NF1 collected between 2003 and 2015. 52 (9.3%) of 562 patients in this study had an OPG diagnosed on their MRI. The median age at first scan with an OPG present was 12.7 years. Of the 52 OPG patients, the intraorbital optic nerves were affected in 29 patients (56%), the prechiasmatic optic nerves were affected in 32 patients (62%), the optic chiasm was affected in 17 patients (33%) and the optic radiations were affected in 19 patients (37%). 29 patients had two or more areas affected. One patient had a newly-appearing OPG, and 1 patient showed progression. The rate of progression over 5 years was 2.4% (95% CI: 0.4% to 16%). Four patients showed partial regression of their OPGs, but we observed no case of complete regression during this study. The rate of regression over 5 years was 8.9% (95% confidence intervals: 2.8% to 26%). We found the presence of UBOs and the presence of OPGs in individual patients to be highly associated (p = 0.0061). CONCLUSION: OPGs are more common in older adults with NF1 than previously thought. The occurrences of unidentified bright objects (UBOs) and asymptomatic OPGs are associated with each other. This suggests the possibility that OPGs that remain asymptomatic may differ pathogenically from those that become symptomatic.
Magnetic Resonance Imaging/methods , Neurofibromatosis 1/pathology , Optic Nerve Glioma/pathology , Adolescent , Adult , Child , Child, Preschool , Cohort Studies , Female , Humans , Infant , Infant, Newborn , Male , Young Adult
We apply a feed-forward frequency control scheme to establish a phase-coherent link from an optical frequency comb to a distributed feedback (DFB) diode laser: This allows us to exploit the full laser tuning range (up to 1 THz) with the linewidth and frequency accuracy of the comb modes. The approach relies on the combination of an RF single-sideband modulator (SSM) and of an electro-optical SSM, providing a correction bandwidth in excess of 10 MHz and a comb-referenced RF-driven agile tuning over several GHz. As a demonstration, we obtain a 0.3 THz cavity ring-down scan of the low-pressure methane absorption spectrum. The spectral resolution is 100 kHz, limited by the self-referenced comb, starting from a DFB diode linewidth of 3 MHz. To illustrate the spectral resolution, we obtain saturation dips for the 2ν3 R(6) methane multiplet at µbar pressure. Repeated measurements of the Lamb-dip positions provide a statistical uncertainty in the kHz range.
We report for the first time the frequency locking of an extended-cavity quantum-cascade-laser (EC-QCL) to a near-infrared frequency comb. The locked laser source is exploited to carry out molecular spectroscopy around 7.8 µm with a line-centre frequency combined uncertainty of ~63 kHz. The strength of the approach, in view of an accurate retrieval of line centre frequencies over a spectral range as large as 100 cm-1, is demonstrated on the P(40), P(18) and R(31) lines of the fundamental rovibrational band of N2O covering the centre and edges of the P and R branches. The spectrometer has the potential to be straightforwardly extended to other spectral ranges, till 12 µm, which is the current wavelength limit for commercial cw EC-QCLs.
We present a multimodal non-linear optical (NLO) laser-scanning microscope, based on a compact fiber-format excitation laser and integrating coherent anti-Stokes Raman scattering (CARS), stimulated Raman scattering (SRS) and two-photon-excitation fluorescence (TPEF) on a single platform. We demonstrate its capabilities in simultaneously acquiring CARS and SRS images of a blend of 6-µm poly(methyl methacrylate) beads and 3-µm polystyrene beads. We then apply it to visualize cell walls and chloroplast of an unprocessed fresh leaf of Elodea aquatic plant via SRS and TPEF modalities, respectively. The presented NLO microscope, developed in house using off-the-shelf components, offers full accessibility to the optical path and ensures its easy re-configurability and flexibility.
We report on a Yb-pumped optical parametric oscillator (OPO) that delivers 30 fs pulses with spectral coverage from 680 to 910 nm and an average output power of up to 1.1 W. The resulting peak power is â¼0.5 MW, which is, to the best of our knowledge, the highest ever demonstrated in a femtosecond OPO. The intensity noise remains at a level of 0.2% rms, and rapid wavelength tuning is obtained by simply scanning the resonator length. The performances of the OPO are promising for a variety of applications in nonlinear microscopy and ultrafast spectroscopy.
We propose a novel approach to cavity-ring-down-spectroscopy (CRDS) in which spectra acquired with a frequency-agile rapid-scanning (FARS) scheme, i.e., with a laser sideband stepped across the modes of a high-finesse cavity, are interleaved with one another by a sub-millisecond readjustment of the cavity length. This brings to time acquisitions below 20 s for few-GHz-wide spectra composed of a very high number of spectral points, typically 3200. Thanks to the signal-to-noise ratio easily in excess of 10 000, each FARS-CRDS spectrum is shown to be sufficient to determine the line-centre frequency of a Doppler broadened line with a precision of 2 parts over 1011, thus very close to that of sub-Doppler regimes and in a few-seconds time scale. The referencing of the probe laser to a frequency comb provides absolute accuracy and long-term reproducibility to the spectrometer and makes it a powerful tool for precision spectroscopy and line-shape analysis. The experimental approach is discussed in detail together with experimental precision and accuracy tests on the (30 012) â (00 001) P12e line of CO2 at â¼1.57 µm.
We introduce a novel configuration for stimulated Raman scattering (SRS) microscopy, called In-line Balanced Detection (IBD), which employs a birefringent plate to generate a time-delayed polarization-multiplexed collinear replica of the probe, acting as a reference. Probe and reference cross the sample at the same position, thus maintaining their balance during image acquisition. IBD can be implemented in any conventional SRS setup, by adding a few simple elements, bringing its sensitivity close to the shot-noise limit even with a noisy laser. We tested IBD with a fiber-format laser system and observed signal-to-noise ratio improvement by up to 30 dB.
BACKGROUND: Non-optic gliomas occur in 5% of children with NF1, but little is known about these tumours in adults. We aimed to investigate progression, spontaneous regression and the natural history of non-optic gliomas in adults and compare these findings to the results found in children. RESULTS: One thousand seven hundred twenty-two brain MRI scans of 562 unselected individuals with NF1 were collected at the NF outpatient department of the University Hospital Hamburg-Eppendorf between 2003 and 2015. The number of scans per patient ranged from one to 12; patients were followed for a median of 3.7 years. We identified 24 patients (4.3%) with non-optic gliomas. Median age at first scan with glioma was 21.2 years, much higher than in previous publications. Only seven of the 24 non-optic glioma patients were symptomatic. Five of 24 patients had multiple non-optic gliomas. Four individuals developed a new tumour, and 4 cases showed progression. The risk of new tumour development was 0.19% (95% confidence interval 0.06% to 0.52%) per patient year of follow-up for patients over 10 years. The rate of progressing non-optic gliomas per patient year of follow-up in the first 5 years after tumour diagnosis was 4.7% (95% confidence interval 1.5% to 12%). CONCLUSIONS: Non-optic gliomas are twice as common in an unselected cohort of NF1 patients as previously reported. This is likely due to increased frequency of diagnosis of asymptomatic tumours when routine MRIs are performed and a higher prevalence in older individuals.
Central Nervous System Neoplasms/complications , Glioma/complications , Neurofibromatoses/complications , Adolescent , Adult , Child , Female , Humans , Male , Middle Aged , Young Adult
