Development of a coherent ultrafast transmission electron microscope based on a laser-driven cold field emission source

L'étude de la physique des systèmes à l'échelle nanométrique nécessite idéalement une résolution spatiale atomique et une résolution temporelle de l'ordre de la femtoseconde. La microscopie électronique en transmission ultra-rapide (UTEM), qui combine une résolution temporelle inférieure à la picoseconde et une résolution spatiale nanométrique, est récemment apparue comme un outil unique doté de résolutions spatio-temporelles sans précédent. Cependant, les performances des premiers UTEMs étaient limitées par la brillance des photocathodes utilisées comme source d'électrons ultra-rapide. Dans ce contexte, il a été vite réalisé que les UTEMs utilisant des sources d'électrons déclenchées par laser et basées sur des pointes métalliques comme émetteur, permettraient de dépasser cette limitation. L'objectif de cette thèse est de décrire le développement d'un microscope électronique en transmission ultra-rapide basé sur ce type de source dites " source à émission de champ froide ", pouvant fonctionner en mode continu ou ultra-rapide. L'émission d'électrons d'une nanopointe de tungstène est déclenchée par des impulsions laser femtosecondes, qui sont fortement focalisées par des composants optiques insérés proche de la cathode. La brillance mesurée est la plus grande mesurée à ce jour dans un UTEM. En associant cette nouvelle source de brillance élevée à un système d'injection/cathodoluminescence composé d'un miroir parabolique installé au-dessus du porte-échantillon, l'UTEM peut être utilisé pour réaliser des expériences TEM-pompe-sonde ultra-rapides résolues dans le temps. Les possibilités d'un tel instrument pour l'imagerie ultra-rapide, la diffraction, l'holographie électronique et la spectroscopie sont présentées. Une attention particulière a été accordée aux applications en nano-optique. La spectroscopie électronique de gain d'énergie (EEGS) permet notamment d'étudier les excitations optiques de nano-systèmes à travers les modifications du spectre d'énergie des électrons. La possibilité de synchroniser facilement les impulsions d'électrons libres ultra-courts avec l'excitation optique de l'échantillon dans les UTEM est essentielle pour l'observation d'interactions électron/photon fortement non linéaires. Ces expériences nous ont permis de caractériser les propriétés spectro-temporelles du faisceau d'électrons ultra-courts. La dernière partie propose une discussion des premières expériences d'holographie électronique hors-axe réalisées avec des impulsions électroniques ultra-rapides. En effet, la dose d'électrons dans le plan de l'échantillon étant considérablement réduite en raison du faible taux de répétition du train d'impulsions électronique, les hologrammes ultra-rapides sont obtenus dans des conditions dites " low dose " complexes. En conséquence, les paramètres expérimentaux couramment utilisés pour l'acquisition d'hologrammes avec des TEM conventionnels ne peuvent pas être directement utilisés en mode ultra-rapide. Des études expérimentales ont été réalisées pour déterminer les conditions optimales pour l'holographie électronique hors-axe ultra-rapide. L'influence de la dose, la longueur de cohérence de la source, les conditions d'illumination et les instabilités de l'instrument ont été systématiquement prises en compte.The investigation of the physics of nanoscale systems ideally requires atomic spatial resolution and femtosecond time-resolution. Ultrafast Transmission Electron Microscopy (UTEM) combining subpicosecond temporal resolution and nanometer spatial resolution has recently emerged as a unique tool with unprecedented spatio-temporal resolutions. However, the performances of the first UTEMs were limited by the brightness of the photocathodes used as ultrafast electron source. In this context, it was soon realized that UTEMs relying on laser-driven electron sources based on nanoscale emitters would overcome this limitation. The aim of this thesis is to report the development of an ultrafast Transmission Electron Microscope based on a cold field emission source, which can operate either in DC or ultrafast mode. Electron emission from a tungsten nanotip is triggered by femtosecond laser pulses, which are tightly focused by optical components integrated inside a cold-field emission source close to the cathode. The measured brightness is the largest reported so far for UTEMs. Combining this new high brightness source with an injection/Cathodoluminescence system, composed of a parabolic mirror placed above the sample holder, the UTEM can be used to perform time-resolved ultrafast pump-probe TEM experiments. The possibilities of such an instrument for ultrafast imaging, diffraction, electron holography and spectroscopy are presented. Particular attention has been paid on applications in nano-optics. In particular, Electron Energy Gain Spectroscopy (EEGS) allows to investigate the optical excitations of nanosystems in the energy domain. The ability to easily synchronize ultrashort free electron pulses with the optical excitation of the sample in UTEMs is essential for the observation of strongly nonlinear electron/photon interactions. These experiments will enable us to characterize the spectro-temporal properties of the ultrashort electron beam. Off-axis electron holography performed with ultrafast electron pulses are finally discussed. The electron dose in the specimen plane is considerably reduced due to the low repetition rate of the electron pulse train. This peculiar property of ultrafast FE-TEMs implies that ultrafast holograms are acquired in low-dose-like conditions. As a consequence, the experimental parameters commonly used for the acquisition of off-axis electron holograms with conventional TEMs cannot be directly implemented in the ultrafast mode. Experimental studies were performed to find the optimum conditions for ultrafast off-axis electron holography. Influence of the dose, the coherence length of the source, the illumination condition and the instrument instabilities have been addressed

Lymphoscintigraphy with peritumoral injection versus lymphoscintigraphy with subdermal periareolar injection of technetium-labeled human albumin to identify sentinel lymph nodes in breast cancer patients

Background: Preoperative lymphoscintigraphy is without doubt a valid method for the detection of the sentinel lymph node (SLN). There has been considerable debate regarding the optimal site for the introduction of the tracer; various sites include peritumoral (PT), periareolar (PA), subdermal, and intradermal injection Purpose: To evaluate retrospectively the lymphoscintigraphic identification rate of peritumoral (PT) injection versus subdermal periareolar (PA) injection in the detection of SLNs in breast cancer. Material and Methods: Between October 2002 and December 2011, a cohort of 906 consecutive patients with biopsy proven breast cancer underwent 914 SLN biopsy procedures. A total of 339 procedures (Group A) were performed using a peritumoral (PT) deep injection of radiotracer while 575 procedures (Group B) adopted a subdermal periareolar PA injection of radiotracer towards the upper outer quadrant, regardless of the site of the carcinoma. All the patients underwent synchronous excision of the breast cancer and SLN biopsy. Results: SLNs were identified in the lymphoscintigram in 308/339 cases (90.85%) of Group A (PT injection) and in 537/ 575 cases (93.39%) of Group B (PA injection). Furthermore, in 2/339 patients (0.58%) of Group A, internal mammary lymph nodes were found at lymphoscintigraphy, whereas no internal mammary sentinel nodes were found in the Group B patients. The intraoperative identification rate of axillary SLNs was 99.41% (337 of 339) in the Group A patients and 99.65% (573 of 575) in the Group B patients. There was no significant difference in the two groups between the incidence of the number of SLNs detected and the incidence of identification of positive SLNs. Conclusion: PT versus PA injection of radiotracer showed comparable success rates for axillary SLN identification, and can be considered a rapid and reliable method

TAO Conceptual Design Report: A Precision Measurement of the Reactor Antineutrino Spectrum with Sub-percent Energy Resolution

The Taishan Antineutrino Observatory (TAO, also known as JUNO-TAO) is a satellite experiment of the Jiangmen Underground Neutrino Observatory (JUNO). A ton-level liquid scintillator detector will be placed at about 30 m from a core of the Taishan Nuclear Power Plant. The reactor antineutrino spectrum will be measured with sub-percent energy resolution, to provide a reference spectrum for future reactor neutrino experiments, and to provide a benchmark measurement to test nuclear databases. A spherical acrylic vessel containing 2.8 ton gadolinium-doped liquid scintillator will be viewed by 10 m^2 Silicon Photomultipliers (SiPMs) of >50% photon detection efficiency with almost full coverage. The photoelectron yield is about 4500 per MeV, an order higher than any existing large-scale liquid scintillator detectors. The detector operates at -50 degree C to lower the dark noise of SiPMs to an acceptable level. The detector will measure about 2000 reactor antineutrinos per day, and is designed to be well shielded from cosmogenic backgrounds and ambient radioactivities to have about 10% background-to-signal ratio. The experiment is expected to start operation in 2022

Tolerability and efficacy of vortioxetine versus SSRIs in elderly with major depression. Study protocol of the VESPA study: a pragmatic, multicentre, open-label, parallel-group, superiority, randomized trial

Depression is a highly prevalent condition in the elderly, with a vast impact on quality of life, life expectancy, and medical outcomes. Selective serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed agents in this condition and, although generally safe, tolerability issues cannot be overlooked. Vortioxetine is an antidepressant with a novel mechanism of action. Based on studies to date, it may have a promising tolerability profile in the elderly, as it does not adversely affect psychomotor or cognitive performance and does not alter cardiovascular and endocrine parameters. The present study aims to assess the tolerability profile of vortioxetine in comparison with the SSRIs considered as a single group in elderly participants with depression. The rate of participants withdrawing from treatment due to adverse events after 6 months of follow up will be the primary outcome

Measurement of the cosmic ray spectrum above 4×10184{\times}10^{18} eV using inclined events detected with the Pierre Auger Observatory

A measurement of the cosmic-ray spectrum for energies exceeding $4{\times}10^{18}$ eV is presented, which is based on the analysis of showers with zenith angles greater than $60^{\circ}$ detected with the Pierre Auger Observatory between 1 January 2004 and 31 December 2013. The measured spectrum confirms a flux suppression at the highest energies. Above $5.3{\times}10^{18}$ eV, the "ankle", the flux can be described by a power law $E^{-\gamma}$ with index $\gamma=2.70 \pm 0.02 \,\text{(stat)} \pm 0.1\,\text{(sys)}$ followed by a smooth suppression region. For the energy ($E_\text{s}$) at which the spectral flux has fallen to one-half of its extrapolated value in the absence of suppression, we find $E_\text{s}=(5.12\pm0.25\,\text{(stat)}^{+1.0}_{-1.2}\,\text{(sys)}){\times}10^{19}$ eV.Comment: Replaced with published version. Added journal reference and DO

Energy Estimation of Cosmic Rays with the Engineering Radio Array of the Pierre Auger Observatory

The Auger Engineering Radio Array (AERA) is part of the Pierre Auger Observatory and is used to detect the radio emission of cosmic-ray air showers. These observations are compared to the data of the surface detector stations of the Observatory, which provide well-calibrated information on the cosmic-ray energies and arrival directions. The response of the radio stations in the 30 to 80 MHz regime has been thoroughly calibrated to enable the reconstruction of the incoming electric field. For the latter, the energy deposit per area is determined from the radio pulses at each observer position and is interpolated using a two-dimensional function that takes into account signal asymmetries due to interference between the geomagnetic and charge-excess emission components. The spatial integral over the signal distribution gives a direct measurement of the energy transferred from the primary cosmic ray into radio emission in the AERA frequency range. We measure 15.8 MeV of radiation energy for a 1 EeV air shower arriving perpendicularly to the geomagnetic field. This radiation energy -- corrected for geometrical effects -- is used as a cosmic-ray energy estimator. Performing an absolute energy calibration against the surface-detector information, we observe that this radio-energy estimator scales quadratically with the cosmic-ray energy as expected for coherent emission. We find an energy resolution of the radio reconstruction of 22% for the data set and 17% for a high-quality subset containing only events with at least five radio stations with signal.Comment: Replaced with published version. Added journal reference and DO

Measurement of the Radiation Energy in the Radio Signal of Extensive Air Showers as a Universal Estimator of Cosmic-Ray Energy

We measure the energy emitted by extensive air showers in the form of radio emission in the frequency range from 30 to 80 MHz. Exploiting the accurate energy scale of the Pierre Auger Observatory, we obtain a radiation energy of 15.8 \pm 0.7 (stat) \pm 6.7 (sys) MeV for cosmic rays with an energy of 1 EeV arriving perpendicularly to a geomagnetic field of 0.24 G, scaling quadratically with the cosmic-ray energy. A comparison with predictions from state-of-the-art first-principle calculations shows agreement with our measurement. The radiation energy provides direct access to the calorimetric energy in the electromagnetic cascade of extensive air showers. Comparison with our result thus allows the direct calibration of any cosmic-ray radio detector against the well-established energy scale of the Pierre Auger Observatory.Comment: Replaced with published version. Added journal reference and DOI. Supplemental material in the ancillary file

Association between preoperative evaluation with lung ultrasound and outcome in frail elderly patients undergoing orthopedic surgery for hip fractures: study protocol for an Italian multicenter observational prospective study (LUSHIP)

Hip fracture is one of the most common orthopedic causes of hospital admission in frail elderly patients. Hip fracture fixation in this class of patients is considered a high-risk procedure. Preoperative physical examination, plasma natriuretic peptide levels (BNP, Pro-BNP), and cardiovascular scoring systems (ASA-PS, RCRI, NSQIP-MICA) have all been demonstrated to underestimate the risk of postoperative complications. We designed a prospective multicenter observational study to assess whether preoperative lung ultrasound examination can predict better postoperative events thanks to the additional information they provide in the form of "indirect" and "direct" cardiac and pulmonary lung ultrasound signs