Detailed derivation of the generalized Snell-Descartes laws from Fermat's principle.

Beginning with Fermat's principle, we provide a detailed derivation of the generalized laws of refraction and reflection for a geometry realizing a metasurface. We first solve the Euler-Lagrange equations for a light ray propagating across the metasurface. The ray-path equation is found analytically, and the results are supported by numerical calculations. We get generalized laws of refraction and reflection that have three main features: (i) They are relevant in gradient-index optics and in geometrical optics; (ii) A collection of rays emerges from the metasurface as a result of multiple reflections inside the metasurface; and (iii) The laws, although derived from Fermat's principle, differ from previously published results.

Effect of Rocuronium vs Succinylcholine on Endotracheal Intubation Success Rate Among Patients Undergoing Out-of-Hospital Rapid Sequence Intubation: A Randomized Clinical Trial.

Importance: Rocuronium and succinylcholine are often used for rapid sequence intubation, although the comparative efficacy of these paralytic agents for achieving successful intubation in an emergency setting has not been evaluated in clinical trials. Succinylcholine use has been associated with several adverse events not reported with rocuronium. Objective: To assess the noninferiority of rocuronium vs succinylcholine for tracheal intubation in out-of-hospital emergency situations. Design, Setting and Participants: Multicenter, single-blind, noninferiority randomized clinical trial comparing rocuronium (1.2 mg/kg) with succinylcholine (1 mg/kg) for rapid sequence intubation in 1248 adult patients needing out-of-hospital tracheal intubation. Enrollment occurred from January 2014 to August 2016 in 17 French out-of-hospital emergency medical units. The date of final follow-up was August 31, 2016. Interventions: Patients were randomly assigned to undergo tracheal intubation facilitated by rocuronium (n = 624) or succinylcholine (n = 624). Main Outcomes and Measures: The primary outcome was the intubation success rate on first attempt. A noninferiority margin of 7% was chosen. A per-protocol analysis was prespecified as the primary analysis. Results: Among 1248 patients who were randomized (mean age, 56 years; 501 [40.1%] women), 1230 (98.6%) completed the trial and 1226 (98.2%) were included in the per-protocol analysis. The number of patients with successful first-attempt intubation was 455 of 610 (74.6%) in the rocuronium group vs 489 of 616 (79.4%) in the succinylcholine group, with a between-group difference of -4.8% (1-sided 97.5% CI, -9% to ∞), which did not meet criteria for noninferiority. The most common intubation-related adverse events were hypoxemia (55 of 610 patients [9.0%]) and hypotension (39 of 610 patients [6.4%]) in the rocuronium group and hypoxemia (61 of 616 [9.9%]) and hypotension (62 of 616 patients [10.1%]) in the succinylcholine group. Conclusions and Relevance: Among patients undergoing endotracheal intubation in an out-of-hospital emergency setting, rocuronium, compared with succinylcholine, failed to demonstrate noninferiority with regard to first-attempt intubation success rate. Trial Registration: ClinicalTrials.gov Identifier: NCT02000674.

Ketamine Compared With Morphine for Out-of-Hospital Analgesia for Patients With Traumatic Pain: A Randomized Clinical Trial.

Importance: Pain is a common out-of-hospital symptom among patients, and opioids are often prescribed. Research suggests that overprescribing for acute traumatic pain is still prevalent, even when limits restricting opioid prescriptions have been implemented. Ketamine hydrochloride is an alternative to opioids in adults with out-of-hospital traumatic pain. Objective: To assess the noninferiority of intravenous ketamine compared with intravenous morphine sulfate to provide pain relief in adults with out-of-hospital traumatic pain. Design, Setting, and Participants: The Intravenous Subdissociative-Dose Ketamine Versus Morphine for Prehospital Analgesia (KETAMORPH) study was a multicenter, single-blind, noninferiority randomized clinical trial comparing ketamine hydrochloride (20 mg, followed by 10 mg every 5 minutes) with morphine sulfate (2 or 3 mg every 5 minutes) in adult patients with out-of-hospital trauma and a verbal pain score equal to or greater than 5. Enrollment occurred from November 23, 2017, to November 26, 2022, in 11 French out-of-hospital emergency medical units. Interventions: Patients were randomly assigned to ketamine (n = 128) or morphine (n = 123). Main Outcomes and Measures: The primary outcome was the between-group difference in mean change in verbal rating scale pain scores measured from the time before administration of the study drug to 30 minutes later. A noninferiority margin of 1.3 was chosen. Results: A total of 251 patients were randomized (median age, 51 [IQR, 34-69] years; 111 women [44.9%] and 140 men [55.1%] among the 247 with data available) and were included in the intention-to-treat population. The mean pain score change was -3.7 (95% CI, -4.2 to -3.2) in the ketamine group compared with -3.8 (95% CI, -4.2 to -3.4) in the morphine group. The difference in mean pain score change was 0.1 (95% CI, -0.7 to 0.9) points. There were no clinically meaningful differences for vital signs between the 2 groups. The intravenous morphine group had 19 of 113 (16.8% [95% CI, 10.4%-25.0%]) adverse effects reported (most commonly nausea [12 of 113 (10.6%)]) compared with 49 of 120 (40.8% [95% CI, 32.0%-49.6%]) in the ketamine group (most commonly emergence phenomenon [24 of 120 (20.0%)]). No adverse events required intervention. Conclusions and Relevance: In the KETAMORPH study of patients with out-of-hospital traumatic pain, the use of intravenous ketamine compared with morphine showed noninferiority for pain reduction. In the ongoing opioid crisis, ketamine administered alone is an alternative to opioids in adults with out-of-hospital traumatic pain. Trial Registration: ClinicalTrials.gov Identifier: NCT03236805.

Properties of dentin, enamel and their junction, studied with Brillouin scattering and compared to Raman microscopy.

OBJECTIVE: Dentin, enamel and the transition zone, called the dentin-enamel junction (DEJ), have an organization and properties that play a critical role in tooth resilience and in stopping the propagation of cracks. Understanding their chemical and micro-biomechanical properties is then of foremost importance. The aim of this study is to apply Brillouin microscopy on a complex biological structure, that is, the DEJ, and to compare these results with those obtained with Raman microscopy. DESIGN: Both techniques allow noncontact measurements at the microscopic scale. Brillouin microscopy is based on the interaction between acoustic phonons and laser photons and gives a relation between the frequency shift of the scattered light and the stiffness of the sample. Raman spectra contain peaks related to specific chemical bonds. RESULTS: Comparison of the Brillouin and Raman cartographies reveals correlations between mechanical and chemical properties. Indeed, the shapes of the phosphate content and stiffness curves are similar. The two spectroscopies give compatible values for the mean distance between two tubules, i.e., 4-6 µm. Moreover, for the first time, the daily cross striations of enamel could be studied, indicating a relationship between the variation in the phosphate concentration and the variation in the rigidity within the enamel prisms. CONCLUSIONS: We demonstrate here the possibility of using Brillouin scattering microscopy to both study complex biological materials such as the enamel-dentin junction and visualize secondary structures. Correlations between the chemical composition and mechanical properties could help in better understanding the tissue histology.

Compact antenna for efficient and unidirectional launching and decoupling of surface plasmons.

Controlling the launching efficiencies and the directionality of surface plasmon polaritons (SPPs) and their decoupling to freely propagating light is a major goal for the development of plasmonic devices and systems. Here, we report on the design and experimental observation of a highly efficient unidirectional surface plasmon launcher composed of eleven subwavelength grooves, each with a distinct depth and width. Our observations show that, under normal illumination by a focused Gaussian beam, unidirectional SPP launching with an efficiency of at least 52% is achieved experimentally with a compact device of total length smaller than 8 µm. Reciprocally, we report that the same device can efficiently convert SPPs into a highly directive light beam emanating perpendicularly to the sample.

Comment on the paper "Improving Poor Man's Kramers-Kronig analysis and Kramers-Kronig constrained variational analysis".

The title paper [Spectrochim. Acta A213 (2019): 391-396] reports an improvement of the "Poor Man's Kramers-Kronig analysis" and of the "Kramers-Kronig constrained variational analysis" thanks to an ad hoc modification of some analytical formulas existing in the literature. This ad hoc modification is not based on mathematical grounds. In this comment we show that no ad hoc modification is required but a correction of the analytical formula used by the authors of the title paper [Spectrochim. Acta A213 (2019): 391-396].

InAs quantum dot in a needlelike tapered InP nanowire: a telecom band single photon source monolithically grown on silicon.

Realizing single photon sources emitting in the telecom band on silicon substrates is essential to reach complementary-metal-oxide-semiconductor (CMOS) compatible devices that secure communications over long distances. In this work, we propose the monolithic growth of needlelike tapered InAs/InP quantum dot-nanowires (QD-NWs) on silicon substrates with a small taper angle and a nanowire diameter tailored to support a single mode waveguide. Such a NW geometry is obtained by a controlled balance over axial and radial growths during the gold-catalyzed growth of the NWs by molecular beam epitaxy. This allows us to investigate the impact of the taper angle on the emission properties of a single InAs/InP QD-NW. At room temperature, a Gaussian far-field emission profile in the telecom O-band with a beam divergence angle θ = 30° is demonstrated using a single InAs QD embedded in a 2° tapered InP NW. Moreover, single photon emission is observed at cryogenic temperature for an off-resonant excitation and the best result, g2(0) = 0.05, is obtained for a 7° tapered NW. This all-encompassing study paves the way for the monolithic growth on silicon of an efficient single photon source in the telecom band based on InAs/InP QD-NWs.

Clinical application of targeted next-generation sequencing for colorectal cancer patients: a multicentric Belgian experience.

International guidelines made RAS (KRAS and NRAS) status a prerequisite for the use of anti-EGFR agents for metastatic colorectal cancer (CRC) patients. Daily, new data emerges on the theranostic and prognostic role of molecular biomarkers; this is a strong incentive for a validated, sensitive, and broadly available molecular screening test. Next-generation sequencing (NGS) has begun to supplant other technologies for genomic profiling. We report here our 2 years of clinical practice using NGS results to guide therapeutic decisions. The Ion Torrent AmpliSeq colon/lung cancer panel, which allows mutation detection in 22 cancer-related genes, was prospectively used in clinical practice (BELAC ISO 15189 accredited method). The DNA of 741 formalin-fixed paraffin-embedded CRC tissues, including primary tumors and metastasis, was obtained from 14 different Belgian institutions and subjected to targeted NGS. Of the tumors tested, 98% (727) were successfully sequenced and 89% (650) harbored at least one mutation. KRAS, BRAF and NRAS mutations were found in 335 (46%), 78 (11%) and 32 (4%) samples, respectively. These mutation frequencies were consistent with those reported in public databases. Moreover, mutations and amplifications in potentially actionable genes were identified in 464 samples (64%), including mutations in PIK3CA (14%), ERBB2 (0.4%), AKT1 (0.6%), and MAP2K1 (0.1%), as well as amplifications of ERBB2 (0.3%) and EGFR (0.3%). The median turnaround time between reception of the sample in the laboratory and report release was 8 calendar days. Overall, the AmpliSeq colon/lung cancer panel was successfully applied in daily practice and provided reliable clinically relevant information for CRC patients.

Trisomy 19 ependymoma, a newly recognized genetico-histological association, including clear cell ependymoma.

Ependymal tumors constitute a clinicopathologically heterogeneous group of brain tumors. They vary in regard to their age at first symptom, localization, morphology and prognosis. Genetic data also suggests heterogeneity. We define a newly recognized subset of ependymal tumors, the trisomy 19 ependymoma. Histologically, they are compact lesions characterized by a rich branched capillary network amongst which tumoral cells are regularly distributed. When containing clear cells they are called clear cell ependymoma. Most trisomy 19 ependymomas are supratentorial WHO grade III tumors of the young. Genetically, they are associated with trisomy 19, and frequently with a deletion of 13q21.31-31.2, three copies of 11q13.3-13.4, and/or deletions on chromosome 9. These altered chromosomal regions are indicative of genes and pathways involved in trisomy 19 ependymoma tumorigenesis. Recognition of this genetico-histological entity allows better understanding and dissection of ependymal tumors.

The quantum-optics Hamiltonian in the Multipolar gauge.

This article deals with the fundamental problem of light-matter interaction in the quantum theory. Although it is described through the vector potential in quantum electrodynamics, it is believed by some that a hamiltonian involving only the electric and the magnetic fields is preferable. In the literature this hamiltonian is known as the Power-Zienau-Woolley hamiltonian. We question its validity and show that it is not equivalent to the minimal-coupling hamiltonian. In this article, we show that these two hamiltonians are not connected through a gauge transformation. We find that the gauge is not fixed in the Power-Zienau-Woolley hamiltonian. The interaction term is written in one gauge whereas the rest of the hamiltonian is written in another gauge. The Power-Zienau-Woolley hamiltonian and the minimal-coupling one are related through a unitary transformation that does not fulfill the gauge fixing constraints. Consequently, they predict different physical results. In this letter, we provide the correct quantum theory in the multipolar gauge with a hamiltonian involving only the physical fields.

Anti-coalescence of bosons on a lossy beam splitter.

Two-boson interference, a fundamentally quantum effect, has been extensively studied with photons through the Hong-Ou-Mandel effect and observed with guided plasmons. Using two freely propagating surface plasmon polaritons (SPPs) interfering on a lossy beam splitter, we show that the presence of loss enables us to modify the reflection and transmission factors of the beam splitter, thus revealing quantum interference paths that do not exist in a lossless configuration. We investigate the two-plasmon interference on beam splitters with different sets of reflection and transmission factors. Through coincidence-detection measurements, we observe either coalescence or anti-coalescence of SPPs. The results show that losses can be viewed as a degree of freedom to control quantum processes.

Small cell tumors of the thyroid gland: a review.

The small cell group of thyroid tumors that includes lymphoma, poorly differentiated carcinoma, medullary carcinoma, secondary neoplasms, as well as tumors with uncertain histogenesis, remains as a valid diagnostic cul-de-sac due to its heterogeneous constitution. The existence of small cell thyroid tumors with EWSR1-FLI1 rearrangement together with neuroendocrine and/or carcinomatous differentiation raises not only differential diagnostic problems but also a very interesting therapeutic dilemma. This review explores the classification of small cell tumors of the thyroid taking into account the immunophenotype and molecular profile of such tumors.

C-cell-derived calcitonin-free neuroendocrine carcinoma of the thyroid: the diagnostic importance of CGRP immunoreactivity.

In the thyroid, primary neuroendocrine tumors encompass medullary thyroid carcinoma (MTC) and, rarely, other tumors such as paragangliomas. MTCs are derived from C-cells and express calcitonin and neuroendocrine markers. Besides classic MTC, some reports have documented thyroid neuroendocrine tumors, which show no calcitonin expression and raise difficult diagnostic problems. A 76-year-old man presented with a mass in the left thyroid with neither serological calcitonin elevation nor familial history. A thorough clinico-laboratorial study did not disclose any other mass elsewhere. A left hemithyroidectomy was performed, and the histological examination revealed a neuroendocrine carcinoma resembling a paraganglioma-like MTC displaying unequivocal signs of vascular invasion. Immunohistochemically, the tumor cells showed reactivity for chromogranin A, synaptophysin, thyroid transcription factor-1 (TTF-1), paired box gene 8 (PAX8), cytokeratins (AE1/AE3 and CK8/18), and calcitonin gene-related peptide (CGRP) and negativity for calcitonin, carcinoembryonic antigen, TTF-2, thyroperoxidase, and thyroglobulin. In situ hybridization showed that the tumor cells lacked expression for calcitonin and thyroglobulin mRNA. Genetic analysis did not disclose any RET mutation. A diagnosis of C-cell-derived primary neuroendocrine carcinoma of the thyroid without calcitonin expression was made, and the patient remains free of metastasis or recurrence 18 months after surgery.

Nodular sclerosing Hodgkin's disease mimicking Riedel's invasive fibrous thyroiditis.

Riedel's thyroiditis appears in the form of a hard cervical mass with rapid onset, and it is associated with extensive fibrosis that compresses nearby structures, such as the trachea and supra-aortic vessels; its diagnosis is essentially histopathological. Although its histological characteristics have been well established, there are some diagnostic pitfalls. We report here the case of a 37-year-old woman, with clinical and histopathological data suggesting Riedel's disease. Fibrosis regressed after treatment with corticosteroids, relieving the compressed airways. However, in contrast with the latest knowledge on this disease, the IgG4 serum levels were consistently normal, and positron emission tomography in search of extensive fibrosis revealed an abnormal metabolic activity of the bone marrow. The final diagnosis revised by the histopathologist was that of nodular sclerosing Hodgkin's lymphoma. This case allows us to review the diagnostic approach when facing a thyroid mass with extremely rapid evolution.