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Tailoring the losses of optical systems within the frame of non-Hermitian physics has appeared very fruitful in the past few years. In particular, the description of exceptional points (EPs) with coupled resonators has become widespread. The on-chip realization of these functionalities is crucial for integrated nanophotonics but requires fine control techniques of the nanodevice properties. Here, we demonstrate pump-controlled directional emission of two coupled nanolasers that distantly interact via an integrated waveguide. This coupling scheme unusually enables both frequency and loss couplings between two cavities, which can be advantageously exploited to reach EPs by either detuning the cavities or controlling the gain of nanolasers. The system can be readily reconfigured from bidirectional to unidirectional emission by adjusting the pump power.

Purpose: The current primary hyperparathyroidism (PHPT) presents as a mild disease. We explored skeletal phenotypes in postmenopausal women affected by PHPT, focusing on fracture prevalence., Methods: PHPT women were retrospectively evaluated at four Italian centers for osteoporosis management (two centers in Milan, n = 244; Cuneo, n = 128; Pisa, n = 131). Data collected from clinical records were analyzed by hierarchical clusterization., Results: Considering the whole PHPT series [ n = 503, aged 67.0 (61.0-74.0) years], 90% had low bone mineral density (BMD) and approximately 30% reported at least one fracture. Vertebral fractures were associated with older age and lower hypophosphatemia, while women with appendicular fractures were younger with less severe hypophosphatemia. Fractures were predicted by lumbar T -score. By using a clustering approach, we identified four different skeletal phenotypes (cluster, C): C1 ( n = 53) and C2 ( n = 172) included women with lumbar and femur neck osteopenia, with low prevalence of fractures (11.3%). Osteoporotic PHPT women were grouped into C3 ( n = 142) and C4 ( n = 136); all women in C4 experienced fractures, were older, and were more frequently affected with cardiovascular diseases. In contrast, women included in C3 never experienced fractures and had a lower body mass index (BMI), though they were characterized by severe reduction in BMD at both lumbar and femur sites. Ionized and total calcium, phosphate, 25hydroxyvitamin D levels, kidney function, and stone prevalence (range, 26.4%-29.0%) were similar among clusters C1, C2, and C4, while unfractured women in C3 showed slightly higher ionized hypercalcemia, lower hypophosphatemia, and higher hypercalciuria with a trend to more frequently develop kidney stones (38.7%) than women in the remaining clusters., Conclusions: Skeletal involvement in women with PHPT presented heterogeneous phenotypes with different prevalence of fractures. Fractures were not related to PHPT severity, suggesting that other factors besides PHPT, such as age, BMI, and lumbar and femur BMD, should be considered in the evaluation of bone involvement in postmenopausal women with PHPT., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Corbetta, Gianotti, Castellano, Carrara, Raineri, Munari, Guabello, Cairoli, Chiodini, Giovanelli, Pierotti, Dinoi, Della Valentina and Cetani.)

Non-steroidal anti-inflammatory drugs (NSAIDs) are the second most widely used class of analgesics in France, after paracetamol. Some NSAIDs are available over the counter (OTC), without a prescription, on the advice of a pharmacist. NSAIDs have recently been the subject of safety alerts from France's Agence nationale de sécurité du médicament et des produits de santé (ANSM), highlighting a risk of worsening certain bacterial infections. This signal has not been confirmed by the European Medicines Agency (EMA) although a "risk of complications due to masking of symptoms of infection" has not been ruled out. These divergent messages can be confusing for healthcare professionals. This literature review, based on an analysis of nearly 200 scientific publications, considers the place of NSAIDs in the OTC management of migraine, tension headaches, postoperative analgesia, acute musculoskeletal and joint pain, dysmenorrhea, viral respiratory infections, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and their toxicity. The role of the pharmacist in dispensing NSAIDs without a prescription is also addressed. NSAIDs offer rapid and effective pain management in a context of increasingly challenging access to care. Their safety profile is reassuring and generally well established but could be strengthened by conducting an ad hoc study to rule on the safety signal issued by the ANSM definitively. Pharmacists have the knowledge and tools to ensure the safe dispensing and rational use of NSAIDs, with or without a prescription. The introduction of risk minimization measures, such as decision-support tools, could enable further progress in ensuring the safe dispensing of OTC NSAIDs., (Copyright © 2024 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Chimeric antigen receptor (CAR) T-cell therapy for multiple myeloma targeting B-cell maturation antigen (BCMA) induces high overall response rates. However, relapse still occurs and novel strategies for targeting multiple myeloma cells using CAR T-cell therapy are needed. SLAMF7 (also known as CS1) and CD38 on tumor plasma cells represent potential alternative targets for CAR T-cell therapy in multiple myeloma, but their expression on activated T cells and other hematopoietic cells raises concerns about the efficacy and safety of such treatments. Here, we used CRISPR/Cas9 deletion of the CD38 gene in T cells and developed DCAR, a double CAR system targeting CD38 and CS1 through activation and costimulation receptors, respectively. Inactivation of CD38 enhanced the anti-multiple myeloma activity of DCAR T in vitro. Edited DCAR T cells showed strong in vitro and in vivo responses specifically against target cells expressing both CD38 and CS1. Furthermore, we provide evidence that, unlike anti-CD38 CAR T-cell therapy, which elicited a rapid immune reaction against hematopoietic cells in a humanized mouse model, DCAR T cells showed no signs of toxicity. Thus, DCAR T cells could provide a safe and efficient alternative to anti-BCMA CAR T-cell therapy to treat patients with multiple myeloma., (©2024 American Association for Cancer Research.)

Recent studies on exceptional points (EPs) in non-Hermitian optical systems have revealed unique traits, including unidirectional invisibility, chiral mode switching and laser self-termination. In systems featuring gain/loss components, EPs are commonly accessed below the lasing threshold, i.e., in the linear regime. In this work, we experimentally demonstrate that EP singularities in coupled semiconductor nanolasers can be accessed above the lasing threshold, where they become branch points of a nonlinear dynamical system. Contrary to the common belief that unavoidable cavity detuning impedes the formation of EPs, here we demonstrate that such detuning is necessary for compensating the carrier-induced frequency shift, hence restoring the EP. Furthermore, we find that the pump imbalance at lasing EPs varies with the total pump power, enabling their continuous tracking. This work uncovers the unstable nature of EPs above laser threshold in coupled semiconductor lasers, offering promising opportunities for the realization of self-pulsing nanolaser devices and frequency combs., (© 2023. The Author(s).)

Background: The pancreatic ductal adenocarcinoma (PDAC) microenvironment is highly fibrotic and hypoxic, with poor immune cell infiltration. Recently, we showed that nucleolin (NCL) inhibition normalizes tumour vessels and impairs PDAC growth. Methods: Immunocompetent mouse models of PDAC were treated by the pseudopeptide N6L, which selectively inhibits NCL. Tumour-infiltrating immune cells and changes in the tumour microenvironment were analysed. Results: N6L reduced the proportion of regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs) and increased tumour-infiltrated T lymphocytes (TILs) with an activated phenotype. Low-dose anti-VEGFR2 treatment normalized PDAC vessels but did not modulate the immune suppressive microenvironment. RNAseq analysis of N6L-treated PDAC tumours revealed a reduction of cancer-associated fibroblast (CAF) expansion in vivo and in vitro. Notably, N6L treatment decreased IL-6 levels both in tumour tissues and in serum. Treating mPDAC by an antibody blocking IL-6 reduced the proportion of Tregs and MDSCs and increased the amount of TILs, thus mimicking the effects of N6L. Conclusions: These results demonstrate that NCL inhibition blocks the amplification of lymphoid and myeloid immunosuppressive cells and promotes T cell activation in PDAC through a new mechanism of action dependent on the direct inhibition of the tumoral stroma.

We report on the first experimental observation of spontaneous mirror symmetry breaking (SSB) in coherently driven-dissipative coupled optical cavities. SSB is observed as the breaking of the spatial or mirror Z&#95;{2} symmetry between two symmetrically pumped and evanescently coupled photonic crystal nanocavities, and manifests itself as random intensity localization in one of the two cavities. We show that, in a system featuring repulsive boson interactions (U>0), the observation of a pure pitchfork bifurcation requires negative photon hopping energies (J<0), which we have realized in our photonic crystal molecule. SSB is observed over a wide range of the two-dimensional parameter space of driving intensity and detuning, where we also find a region that exhibits bistable symmetric behavior. Our results pave the way for the experimental study of limit cycles and deterministic chaos arising from SSB, as well as the study of nonclassical photon correlations close to SSB transitions.

Background: Smoking cessation is a major public health issue. In France, primary care physicians (PCP) are the first contact points for tobacco management. The objective of this study was to understand how PCPs are involved in the management of smoking cessation: ownership, commitment, barriers., Methods: A qualitative study was conducted using group and individual semi-structured techniques with PCPs. A thematic analysis of verbatim transcripts was performed to identify concepts and sub-concepts of interest. Saturation was evaluated retrospectively to ensure adequate sample size., Results: A sample of 35 PCPs were interviewed, 31 in four focus groups and four in individual interviews. PCPs discussed their roles in the management of tobacco smoking cessation, including the different strategies they are using (e.g., Minimal Intervention Strategy, Motivational Interviewing), the multiple barriers encountered (e.g., lack of time, patients' resistance to medical advice), the support resources and the treatment and intervention they prescribed (e.g. nicotine replacement therapy, supporting therapist)., Conclusions: This study provides a better understanding of the beliefs, attitudes, and behaviors of PCPs in managing smoking cessation. Guiding and encouraging patients toward smoking cessation remains a major objective of PCPs. While PCPs reported that progress has been made in recent years in terms of tools, technology and general awareness, they still face major barriers, some of which could be overcome by appropriate training., (© 2022. The Author(s).)

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive and resistant cancer with no available effective therapy. We have previously demonstrated that nucleolin targeting by N6L impairs tumor growth and normalizes tumor vessels in PDAC mouse models. Here, we investigated new pathways that are regulated by nucleolin in PDAC. We found that N6L and nucleolin interact with β-catenin. We found that the Wnt/β-catenin pathway is activated in PDAC and is necessary for tumor-derived 3D growth. N6L and nucleolin loss of function induced by siRNA inhibited Wnt pathway activation by preventing β-catenin stabilization in PDAC cells. N6L also inhibited the growth and the activation of the Wnt/β-catenin pathway in vivo in mice and in 3D cultures derived from MIA PaCa2 tumors. On the other hand, nucleolin overexpression increased β-catenin stabilization. In conclusion, in this study, we identified β-catenin as a new nucleolin interactor and suggest that the Wnt/β-catenin pathway could be a new target of the nucleolin antagonist N6L in PDAC.

We theoretically and experimentally investigate type II second harmonic generation in III-V-on-insulator wire waveguides. We show that the propagation direction plays a crucial role and that longitudinal field components can be leveraged for robust and efficient conversion. We predict that the maximum theoretical conversion is larger than that of type I second harmonic generation for similar waveguide dimensions and reach an experimental conversion efficiency of 12%/W, limited by the propagation loss.

We report a new class of Optical Parametric Oscillators, based on a 20 μm -long semiconductor Photonic Crystal Cavity and operating at Telecom wavelengths. Because the confinement results from Bragg scattering, the optical cavity contains a few modes, approximately equispaced in frequency. Parametric oscillation is reached when these high Q modes are thermally tuned into a triply resonant configuration, whereas any other parametric interaction is strongly suppressed. The lowest pump power threshold is estimated to 50 - 70 μW . This source behaves as an ideal degenerate Optical Parametric Oscillator addressing the needs in the field of quantum optical circuits, paving the way to the dense integration of highly efficient nonlinear sources of squeezed light or entangled photons pairs., Competing Interests: Additional Information The authors declare no competing interests.

Two coupled nanolasers exhibit a mode switching transition, theoretically described by mode beating limit cycle oscillations. Their decay rate is vanishingly small in the thermodynamic limit, i.e., when the spontaneous emission noise tends to zero. We provide experimental statistical evidence of mesoscopic limit cycles (∼10^{3} intracavity photons). Specifically, we show that the order parameter quantifying the limit cycle amplitude can be reconstructed from the mode intensity statistics. We observe a maximum of the averaged amplitude at the mode switching, accounting for limit cycle oscillations. We finally relate this maximum to a dip of mode cross-correlations, reaching a minimum of g&#95;{ij}^{(2)}=2/3, which we show to be a mesoscopic limit. Coupled nanolasers are thus an appealing test bed for the investigation of spontaneous breaking of time translation symmetry in the presence of strong quantum fluctuations.

Objective Weibel-Palade bodies (WPBs) are endothelial cell (EC)-specific organelles formed by vWF (von Willebrand factor) polymerization and that contain the proangiogenic factor Ang-2 (angiopoietin-2). WPB exocytosis has been shown to be implicated for vascular repair and inflammatory responses. Here, we investigate the role of WPBs during angiogenesis and vessel stabilization. Approach and Results WPB density in ECs decreased at the angiogenic front of retinal vascular network during development and neovascularization compared with stable vessels. In vitro, VEGF (vascular endothelial growth factor) induced a VEGFR-2 (vascular endothelial growth factor receptor-2)-dependent exocytosis of WPBs that contain Ang-2 and consequently the secretion of vWF and Ang-2. Blocking VEGF-dependant WPB exocytosis and Ang-2 secretion promoted pericyte migration toward ECs. Pericyte migration was inhibited by adding recombinant Ang-2 or by silencing Ang-1 (angiopoietin-1) or Tie2 (angiopoietin-1 receptor) in pericytes. Consistently, in vivo anti-VEGF treatment induced accumulation of WPBs in retinal vessels because of the inhibition of WPB exocytosis and promoted the increase of pericyte coverage of retinal vessels during angiogenesis. In tumor angiogenesis, depletion of WPBs in vWF knockout tumor-bearing mice promoted an increase of tumor angiogenesis and a decrease of pericyte coverage of tumor vessels. By another approach, normalized tumor vessels had higher WPB density. Conclusions We demonstrate that WPB exocytosis and Ang-2 secretion are regulated during angiogenesis to limit pericyte coverage of remodeling vessels by disrupting Ang-1/Tie2 autocrine signaling in pericytes.

Targeted anticancer therapies demand discovery of new cellular targets to be exploited for the delivery of toxic molecules and drugs. In this perspective, in the last few years, nucleolin has been identified as an interesting surface marker to be used for the therapy of glioblastoma. In this study, we investigated whether a synthetic antagonist of cell-surface nucleolin known as N6L, previously reported to decrease both tumor growth and tumor angiogenesis in several cancer cell lines, including glioblastoma cells, as well as endothelial cells proliferation, could be exploited to deliver a protein toxin (saporin) to glioblastoma cells. The pseudopeptide N6L cross-linked to saporin-S6 induced internalization of the toxin inside glioblastoma cancer cells. Our results in vitro demonstrated the effectiveness of this conjugate in inducing cell death, with an ID 50 four orders of magnitude lower than that observed for free N6L. Furthermore, the preliminary in vivo study demonstrated efficiency in reducing the tumor mass in an orthotopic mouse model of glioblastoma., (© 2017 Wiley Periodicals, Inc.)

NPM1 is a multifunctional nucleolar protein implicated in several processes such as ribosome maturation and export, DNA damage response and apoptotic response to stress stimuli. The NPM1 gene is involved in human tumorigenesis and is found mutated in one third of acute myeloid leukemia patients, leading to the aberrant cytoplasmic localization of NPM1. Recent studies indicated that the N6L multivalent pseudopeptide, a synthetic ligand of cell-surface nucleolin, is also able to bind NPM1 with high affinity. N6L inhibits cell growth with different mechanisms and represents a good candidate as a novel anticancer drug for a number of malignancies of different histological origin. In this study we investigated whether N6L treatment could drive antitumor effect in acute myeloid leukemia cell lines. We found that N6L binds NPM1 at the N-terminal domain, co-localizes with cytoplasmic, mutated NPM1, and interferes with its protein-protein associations. N6L toxicity appears to be p53 dependent but interestingly, the leukemic cell line harbouring the mutated form of NPM1 is more resistant to treatment, suggesting that NPM1 cytoplasmic delocalization confers protection from p53 activation. Moreover, we show that N6L sensitizes AML cells to doxorubicin and cytarabine treatment. These studies suggest that N6L may be a promising option in combination therapies for acute myeloid leukemia treatment., (Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.)

Wedge prisms shifting the visual field laterally create a mismatch between the straight ahead position signalled by vision and that encoded by extraretinal and head-on-trunk proprioceptive information. Short-term adaptation to left-deviating prisms in normal subjects results in a visuomotor attentional bias towards the right-hand side (aftereffect). Prismatic adaptation (PA) is usually induced through a training consisting in repeated ballistic movements of the dominant arm towards visual targets, while participants are wearing prismatic goggles. The present study demonstrates that an original oculomotor PA procedure with leftward deviating prisms-without pointing movements and only consisting in repeated gaze shifts towards visual targets-can induce a rightward bias in normal subjects as assessed by visual straight ahead and line bisection tasks (Experiments 1 and 2). We show that oculomotor PA induces a bias in line bisection similar to that reported after visuomotor PA (Experiment 2). We suggest that a conflict between retinal, extraretinal and proprioceptive information about the straight ahead location causes the observed effects. In follow-up experiments 3, 4, and 5, we demonstrate that neither eye deviation without prisms nor shift of the visual field without eye deviation induces PA biases. We propose that an optimal integration model of visual and proprioceptive inputs can best account for the observed results.

Heat dissipation is improved in nonlinear III-V photonic crystal waveguides owing to the hybrid III-V/Silicon integration platform, allowing efficient four-wave mixing in the continuous-wave regime. A conversion efficiency of -17.6  dB is demonstrated with a pump power level below 100 mW in a dispersion-engineered waveguide with a flat group index of 28 over a 10 nm bandwidth.

We investigate the basic mechanism of nonlinear mode competition in two semiconductor-coupled nanocavities operating in the laser regime. For this, we study energy transfer between bonding (in-phase) and anti-bonding (out-of-phase) modes of the system formed by two strongly coupled photonic crystal nanolasers. We experimentally observe mode switching from the blue-detuned to the red-detuned mode as the pump power is increased. A semi-classical description in terms of mean-field equations allows us to explain this phenomenon as stimulated scattering due to carrier population oscillations in the cavities at the mode splitting frequency. We predict such asymmetrical mode interaction to be universal in arrays of optically coupled semiconductor micro and nanocavities.

Background: Primary care physicians (PCPs) play a key role regarding vaccination in France. The aims of the present study were to define the scoring rules and to assess the measurement properties of the 'Determinants of Intentions to Vaccinate' (DIVA © ) questionnaire that aims to assess PCPs' attitudes and beliefs toward vaccination., Methods: The DIVA questionnaire was derived from a literature review and PCPs focus groups. Scoring and early validation of the DIVA questionnaire were determined during a cross-sectional study conducted in France. During the study, PCPs had to complete the DIVA questionnaire for any of the six vaccine-preventable diseases (VPDs) to which they were randomly assigned (measles, pertussis, pneumococcus infection, seasonal influenza, human papillomavirus -HPV- infection and tetanus). Descriptive analyses of items and the analysis of the grouping of items into domains were conducted. Internal consistency reliability and construct validity was assessed according to each VPD., Results: The DIVA questionnaire was completed by 1,069 PCPs and was well accepted. The 'Commitment of the PCP to the vaccination approach' score showed very good internal consistency reliability (Cronbach's alpha >0.70 overall and for each VPD). The construct validity of the DIVA questionnaire was confirmed., Conclusions: The DIVA questionnaire is a valid and reliable measure of PCPs' attitudes and beliefs toward vaccination.

We report on a photonic crystal (PhC) nanolaser based on the heterogeneous integration of a III-V PhC nanocavity on SOI, configured to operate as a Set-Reset Flip-Flop (SR-FF). The active layer is a nanobeam cavity made of a 650 nm × 285 nm InP-based wire waveguide evanescently coupled to 500 nm × 220 nm SOI wire waveguides, demonstrating a record-low footprint of only 6.2 μm2. Injection locking enables optical bistability allowing for memory operation with only 6.4 fJ/bit switching energies and <50 ps response times. Bit-level SR-FF memory operation was evaluated at 5 Gb/s with PRBS-resembling data patterns, revealing error free operation with a negative power penalty.

High-quality (Q) factor indium phosphide (InP)-based 1D photonic crystal nanobeam cavities are fabricated on silicon on insulator waveguides. Through the optimization of the fabrication process, the intrinsic Q factor of these fully encapsulated nanocavities is demonstrated to attain values higher than 100,000. Experimental and numerical investigations are carried out on the impact, on the Q factor, of the strength of the evanescent wave coupling between the cavity and the waveguide. We reveal that this coupling can result in a modification of the electromagnetic field distribution in the resonant mode, which gives rise up to a factor 4 reduction in the intrinsic Q factor for the structures under study.

Objectives: Vaccination is an effective way to reduce morbidity and mortality related to infectious diseases. In France, primary care physicians are the main administrators of vaccines. Our objective was to conduct an exploratory qualitative study with primary care physicians to identify determinants of their commitment to vaccination., Methods: A qualitative research study was conducted with 36 primary care physicians from different geographical regions in France. Six focus group discussions, following a semi-structured interview guide, were held. Qualitative analysis based on coding of the transcribed discussions was performed to identify the factors influencing primary care physicians’ attitudes toward vaccination. These factors were then organized into themes. Saturation was also evaluated., Results: Diphtheria, tetanus, poliomyelitis, measles, mumps, rubella, hepatitis B, tuberculosis, pneumococcal infections, meningococcus, human papillomavirus, rotavirus, pertussis, varicella and flu vaccinations were all discussed in each focus group. Saturation was reached from the fourth focus group. Forty identified determinants were divided into six themes: vaccine characteristics, disease characteristics, primary care physicians’ past experience, practical aspects, expected benefits and primary care physician-patient relationship., Conclusions: This study identified the behavioural and organizational determinants influencing primary care physicians’ attitudes toward vaccination. These attitudes and determinants varied according to diseases and vaccines. The identified determinants and themes were used as a basis for the development of a questionnaire evaluating the Determinant of Vaccination Intentions (DIVA) of primary care physicians.

Optomechanical systems, in which the vibrations of a mechanical resonator are coupled to an electromagnetic radiation, have permitted the investigation of a wealth of novel physical effects. To fully exploit these phenomena in realistic circuits and to achieve different functionalities on a single chip, the integration of optomechanical resonators is mandatory. Here, we propose a novel approach to heterogeneously integrate arrays of two-dimensional photonic crystal defect cavities on top of silicon-on-insulator waveguides. The optomechanical response of these devices is investigated and evidences an optomechanical coupling involving both dispersive and dissipative mechanisms. By controlling the optical coupling between the waveguide and the photonic crystal, we were able to vary and understand the relative strength of these couplings. This scalable platform allows for an unprecedented control on the optomechanical coupling mechanisms, with a potential benefit in cooling experiments, and for the development of multi-element optomechanical circuits in the framework of optomechanically-driven signal-processing applications.

Detrimental surface recombination of carriers in InP-based photonic crystal nanobeams containing quantum wells is reduced by employing chemical treatment followed by silica encapsulation. Carrier lifetime is shown to recover to 2.63ns close to the bulk value. This enables us to obtain optically pumped room-temperature continuous-wave nanolasers at 1.55µm integrated onto Silicon on insulator waveguide platform with a threshold of 8µW.

We demonstrate the generation of an octave-spanning supercontinuum in InGaP membrane waveguides on a silicon substrate pumped by a 1550-nm femtosecond source. The broadband nature of the supercontinuum in these dispersion-engineered high-index-contrast waveguides is enabled by dispersive wave generation on both sides of the pump as well as by the low nonlinear losses inherent to the material. We also measure the coherence properties of the output spectra close to the pump wavelength and find that the supercontinuum is highly coherent at least in this wavelength range.

We propose high index contrast InGaP photonic wires as a platform for the integration of nonlinear optical functions in the telecom wavelength window. We characterize the linear and nonlinear properties of these waveguide structures. Waveguides with a linear loss of 12 dB/cm and which are coupled to a single mode fiber through gratings with a -7.5 dB coupling loss are realized. From four wave mixing experiments, we extract the real part of the nonlinear parameter γ to be 475 ± 50 W(-1)m(-1) and from nonlinear transmission measurements we infer the absence of two-photon absorption and measure a three-photon absorption coefficient of (2.5 ± 0.5) x 10(-2) cm(3)GW(-2).

Thermal properties of InP-based quantum well photonic crystal nanobeam lasers heterogeneously integrated on silicon on insulator waveguides are studied. We show both numerically and experimentally the reduction of the thermal resistance of the III-V cavities by adjusting the composition of the layer which bonds the III-V materials to the silicon wafer and by adding an over-cladding on top of the cavities. Using a bonding layer made of benzocyclobutene and SiO(2) and an over-cladding of MgF(2), we found a decrease by a factor higher than 35 compared to air-suspended photonic crystal nanobeam cavities. Such optimized structures are demonstrated to operate under continuous wave pumping for several 10's of minutes despite the adverse effect of non-radiative surface recombination of carriers.

Photonic crystal cavity-based switching is studied both theoretically and experimentally in order to identify the best configuration to maximize "wavelength conversion" efficiency. In particular, it is shown that an enhanced contrast can be reached when the probe is blueshifted with respect to the resonance. The use of an InP/SOI hybrid photonic crystal nanocavity is reported for the first time for all-optical error-free "wavelength conversion" at 20  Gbit/s with a nonreturn to zero on-off keying signal.

We present the experimental demonstration of a novel class of hybrid III-V-on-silicon microlasers. We show that by coupling a silicon cavity to a III-V waveguide, the interaction between the propagating mode in the III-V waveguide and the cavity mode in the silicon resonator results in high, narrowband reflection back into the III-V waveguide, forming a so-called resonant mirror. By combining two such mirrors and providing optical gain in the III-V wire between these two mirrors, laser operation can be realized. This optically pumped device measures 55 by 2 μm, requires microwatt-level threshold pump power, and shows single-mode laser emission with a side-mode suppression ratio of up to 39 dB.

We present a coupler design allowing normally-incident light coupling from free-space into a monomode photonic crystal waveguide operating in the slow-light regime. Numerical three-dimensional calculations show that extraction efficiencies as high as 80% can be achieved for very large group indices up to 100. We demonstrate experimentally the device feasibility by coupling and extracting light from a photonic crystal waveguide over a large group-index range (from 10 to 60). The measurements are in good agreement with theoretical predictions. We also study numerically the impact of various geometrical parameters on the coupler performances.

Ring-down temporal measurements of silicon-on-insulator wire racetrack resonators are performed with 150 fs input pulses using a parametric process in a nonlinear crystal to gate and amplify the weak output pulses. We measure the cavity round trip time and the quality factor of these all-pass filters and find excellent agreement with continuous wave spectroscopic measurements as well as with an analytic model built using numerical solutions for the fully vectorial waveguide modes.

We report a high lasing wavelength uniformity of optically pumped InP-based microdisk lasers processed with electron-beam lithography, heterogeneously integrated with adhesive bonding on silicon-on-insulator (SOI) waveguide circuits and evanescently coupled to an underlying waveguide. We study the continuous wave laser emission coupling out of the SOI via a grating coupler etched at one side of the waveguide, and demonstrate a standard deviation in lasing wavelength of nominally identical devices on the same chip lower than 500 pm. The deviation in the diameter of the microdisks as low as a few nanometers makes all-optical signal processing applications requiring cascadability possible.

We start from a 2D photonic crystal nanocavity with moderate Q-factor and dynamically increase it by two order of magnitude by the joint action of coherent population oscillations and nonlinear refractive index.

Slow light induced by coherent population oscillations and cavity dispersive nonlinear response are combined achieving 2 orders of magnitude enhancement of the group delay and an equivalent decreasing of the spectral linewidth of a L3 two-dimensional photonic crystal nanocavity.

We report on far-field measurements of L3 photonic crystal (PhC) cavities with high quality beaming. This is achieved by means of the so-called "band folding" technique, in which a modulation of the radius of specific holes surrounding the cavity is introduced. Far-field patterns are measured from photoluminescence of quantum wells embedded in the PhC. A very good agreement between experimental results and simulated radiation patterns has been found. Laser effect is demonstrated in the beaming cavity with a threshold comparable to the regular one. In addition, free-space input coupling to this cavity has been achieved. In order to fully analyze the coupling efficiency, we generalize the approach developed in S. Fan, et al., [J. Opt. Soc. Am. A 20, 569 (2003)], relaxing the hypothesis of mirror symmetry. The obtained coupling efficiencies are about 15% with quality factors (Q) exceeding 10(4). These results further validate the "folding" technique on L3 cavities for nanocavity realization with efficient free-space coupling and high Q factors.

Drug prescription in general practice is present in 78 to 83% of consultations; practitioners must give to their patient clear loyal and appropriate information about the undesirable side effects of the medicines prescribed. The object of the EICLAT study was to give some light on the feasibility to respect this obligation. To that effect the study evaluates, for a normal prescription activity, the average number of potential undesirable side effects (USE) in relation with the number of lines of different medicines prescribed in each doctor's prescription. A total of 8,382 doctor's prescriptions, generating 34,427 lines of prescriptions given by 175 general practitioners, were analysed. Amongst these prescriptions, 11% included only one line, 55% from 2 to 4 lines and 34% 5 lines or more. The average doctor's prescription was of 4 lines of medicines generating 407 potential USE, of which 194 were different (the same undesirable effect may be present twice or more in the same doctor's prescription), and 293 frequent or serious potential USE, of which 166 were different. The patent medicines with a major or important added medical value (AMV), present in 7,840 doctor's prescriptions for a total of 24,127 lines exposed the patient, in the average, to 151 frequent or serious USE different. The patent medicines with an insufficient AMV, present in 2,292 prescriptions for a total of 3,887 lines, exposed the patient to 37 frequent and/or serious potential USE. Supposing that the information provided by the legal authority is sufficiently adequate, precise and exhaustive, the volume of information that must be given to the patient is not compatible with the present conditions of exercise of the profession.

In this Letter, we experimentally demonstrate the enhancement of the inhomogeneous second harmonic conversion in the opaque region of a GaAs cavity with efficiencies of the order of 0.1% at 612 nm, using 3 ps pump pulses having peak intensities of the order of 10 MW/cm(2). We show that the conversion efficiency of the inhomogeneous, phase-locked second harmonic component is a quadratic function of the cavity factor Q., (© 2011 Optical Society of America)

Heterogeneous integration of III-V compound semiconductors on Silicon on Insulator is one the key technology for next-generation on-chip optical interconnects. In this context, the use of photonic crystals lasers represents a disruptive solution in terms of footprint, activation energy and ultrafast response. In this work, we propose and fabricate very compact laser sources integrated with a passive silicon waveguide circuitry. Using a subjacent Silicon-On-Insulator waveguide, the emitted light from a photonic crystal based cavity laser is efficiently captured. We study experimentally the evanescent wave coupling responsible for the funneling of the emitted light into the silicon waveguide mode as a function of the hybrid structure parameters, showing that 90% of coupling efficiency is possible., (© 2011 Optical Society of America)

Objective: Based on patient's declarations, evaluate if the media coverage of the pandemic flu (H1N1) has lead to an overconsumption of primary care. Identify the opinions of the general practionners (GP) concerning this media coverage and the health crisis., Methods: A prospective study, based on an electronic questionnaire, was conducted during the main period of the pandemic flu. Each GP was invited to include one patient who presented fever since less than 2 days, associated to two of four following clinical signs: cough, headache, coat throat and ache., Results: 730 questionnaires were fully completed and analyzed. 96 patients (12,9%) have declared to the GP an overconsumption, and two thirds of them because of their concern about the swine flu and a quarter because the social control. This concern was noted by 80% of the GP from the beginning of the flu 77% of the GP have considered the media coverage of the flu alarming, while 69% of them have declared to feel serene concerning the pandemic. No statistic link has been noticed between the GP opinions and the overconsumption of their patients., Discussion: Media coverage of the swine flu and the state organization of the crisis have lead to an overconsumption estimated to 13%. Many efforts must be done in the future to reassure patients about flu and its vaccination.

We investigate the nonlinear response of photonic crystal waveguides with suppressed two-photon absorption. A moderate decrease of the group velocity (approximately c/6 to c/15, a factor of 2.5) results in a dramatic (x 30) enhancement of three-photon absorption well beyond the expected scaling, proportional, variant 1/v3g. This non-trivial scaling of the effective nonlinear coefficients results from pulse compression, which further enhances the optical field beyond that of purely slow-group velocity interactions. These observations are enabled in mm-long slow-light photonic crystal waveguides owing to the strong anomalous group-velocity dispersion and positive chirp. Our numerical physical model matches measurements remarkably.

This retrospective study of diabetic patients undergoing non-cardiac surgery has identified that a greater number of patients are at risk of cardiac complications and death in the perioperative period than had previously been suggested. As well as insulin-dependent diabetic patients and patients with elevated creatinine (> 178 micromol/l) as previously found, our study suggests that non-insulin-dependent diabetic patients and patients with creatinine > 120 micromol/l are also at increased risk of cardiac complications and death following non-cardiac surgery. This increases by a factor of six those diabetic patients at risk of perioperative complications from non-cardiac surgery and also increases the number of patients with renal failure similarly at risk. The study confirms similar risks of cardiac complications and death to other recently published data and suggests ongoing comparisons will contribute to quality assurance activities in anaesthesia and surgery.

Band-edge photonic crystal lasers were fabricated and their temporal characteristics were minutely analyzed using a high resolution up-conversion system. The InGaAs/InP photonic crystal laser operates at room temperature at 1.55 microm with turn on time ranging from 17ps to 30ps.

Objective: The importance of prevention is increasingly recognised in most developed countries. General practitioners (GPs) have got a key role to play in this domain in primary care. But, the research evidence still concludes that GPs' preventive activities remain most of the time insufficient. The aim of our study was to contribute to this debate in adopting a more broad view of prevention-related activities to better understand the GPs practice in this matter. Our study was undertaken to measure the part of prevention-related activity hidden in each of the morbid conditions (MC) seen by the doctors daily., Methods: We carried out a cross-sectional study in a sample of 75 French GPs in the south suburb of Paris. We dropped the usual pre-established and limited list of specific preventive care activities to replace it with a list of 100 most common morbid conditions seen by the GPs in daily practice. The GPs were asked for each selected MC to rate on a five-item Likert scale the amount of primary and secondary prevention they generally offer during a patient visit., Results: All MC confounded, secondary prevention reached an average score of 3.2 (inter-quartile interval 2.82-3.58). The intensity of primary prevention was somewhat lower, but far from being negligible. Its average score was 2.3 (inter-quartile interval of 1.86-2.73). If more than 50% of the GPs declare a low intensity of primary prevention activity or even no primary prevention activity at all in nearly 3/4 of the MC encountered in their daily practice, they also declare that they carry out a considerable amount of primary prevention or in some cases spend the entire patient visit to primary prevention for MC covering more than 25% of their daily activity. Also, even if a majority of GPs did not give clear-cut scores for secondary prevention for 2/3 of the MC, they declare a considerable amount of it for the remaining 1/3 which covers more than 25% of their activity., Conclusion: Our study was useful to offer a more realistic view of the real place of the prevention-related activities in the GPs daily primary care practice even if we assess neither the appropriateness nor the quality of these activities.

We report on the continuous-wave operation of a band edge laser at room temperature near 1.55 mum in an InGaAs/InP photonic crystal. A flat dispersion band-edge photonic mode is used for surface normal operation. The photonic crystal slab is integrated onto a Silicon chip by means of Au/In bonding technology, which combines two advantages, efficient heat sinking and broad band reflectivity.

We report on reflection modulation results near 1.55 mum in InP-based two-dimensional photonic crystals. The fabrication technology uses a polymeric bonding technique to integrate the InP thin-slab onto a Silicon wafer. Reflectivity modulation greater than 90% is obtained by pumping at 810 nm with optical excitation densities of 15 muJ/cm(2). The resulting optical broadband modulation is based on the saturation of absorption of InGaAs quantum wells at a photonic mode frequency tunable by lithography.

We experimentally demonstrate excitability in a semiconductor two-dimensional photonic crystal. Excitability is a nonlinear dynamical mechanism underlying pulselike responses to small perturbations in systems possessing one stable state. We show that a band-edge photonic crystal resonator exhibits class II excitability, resulting from the nonlinear coupling between the high-Q optical mode, the charge-carrier density, and the fast (sub-micros) thermal dynamics. In this context, the critical slowing down of the electro-optical dynamics close to the excitable threshold can delay the optical response by an amount comparable to the duration of the output pulse (5 ns). The latter results from a short thermal dynamical excursion along a high local intensity manifold of the phase space.

We address, both experimentally and theoretically, phase and amplitude dynamics of the electromagnetic field in a two-dimensional photonic crystal when femtosecond pulses are injected. We demonstrate that the usual adiabatic approximation underlying the dynamics of field and carriers in a semiconductor resonator is no longer valid, since in general the photon lifetime cannot be neglected with respect to the carrier recombination lifetime. Parameter regions where adiabaticity is broken are shown, and the ubiquity of the observed dynamical scenario in the new generation of active photonic microresonators is predicted.