Influence of patient and tumor characteristics on early therapy persistence with letrozole in postmenopausal women with early breast cancer: results of the prospective Evaluate-TM study with 3941 patients.

Background: Patients' compliance and persistence with endocrine treatment has a significant effect on the prognosis in early breast cancer (EBC). The purpose of this analysis was to identify possible reasons for non-persistence, defined as premature cessation of therapy, on the basis of patient and tumor characteristics in individuals receiving adjuvant treatment with letrozole. Patients and methods: The EvAluate-TM study is a prospective, multicenter, noninterventional study in which treatment with the aromatase inhibitor letrozole was evaluated in postmenopausal women with hormone receptor-positive EBC in the early therapy phase. Treatment persistence was evaluated at two pre-specified study visits after 6 and 12 months. As a measure of early therapy persistence the time from the start to the end of treatment (TTEOT) was analyzed. Cox regression analyses were carried out to identify patient characteristics and tumor characteristics predicting TTEOT. Results: Out of the total population of 3941 patients with EBC, 540 (13.7%) events involving treatment cessation unrelated to disease progression were observed. This was due to drug-related toxicity in the majority of cases (73.5%). Persistence rates were 92.2%, 86.9%, and 86.3% after 6, 12, and 15 months, respectively. The main factors influencing premature treatment discontinuation were older age [hazard ratio (HR) 1.02/year], comorbidities (HR 1.06 per comorbidity), low body mass index, and lower tumor grade (HR 0.85 per grade unit). Conclusion: These results support the view that older, multimorbid patients with low tumor grade and low body mass index are at the greatest risk for treatment discontinuation and might benefit from compliance and support programs.

Optical Sensing of Microbial Life on Surfaces.

The label-free detection of microbial cells attached to a surface is an active field of research. The field is driven by the need to understand and control the growth of biofilms in a number of applications, including basic research in natural environments, industrial facilities, and clinical devices, to name a few. Despite significant progress in the ability to monitor the growth of biofilms and related living cells, the sensitivity and selectivity of such sensors are still a challenge. We believe that among the many different technologies available for monitoring biofilm growth, optical techniques are the most promising, as they afford direct imaging and offer high sensitivity and specificity. Furthermore, as each technique offers different insights into the biofilm growth mechanism, our analysis allows us to provide an overview of the biological processes at play. In addition, we use a set of key parameters to compare state-of-the-art techniques in the field, including a critical assessment of each method, to identify the most promising types of sensors. We highlight the challenges that need to be overcome to improve the characteristics of current biofilm sensor technologies and indicate where further developments are required. In addition, we provide guidelines for selecting a suitable sensor for detecting microbial cells on a surface.

Hydrogen induced optically-active defects in silicon photonic nanocavities.

We demonstrate intense room temperature photoluminescence (PL) from optically active hydrogen- related defects incorporated into crystalline silicon. Hydrogen was incorporated into the device layer of a silicon on insulator (SOI) wafer by two methods: hydrogen plasma treatment and ion implantation. The room temperature PL spectra show two broad PL bands centered at 1300 and 1500 nm wavelengths: the first one relates to implanted defects while the other band mainly relates to the plasma treatment. Structural characterization reveals the presence of nanometric platelets and bubbles and we attribute different features of the emission spectrum to the presence of these different kind of defects. The emission is further enhanced by introducing defects into photonic crystal (PhC) nanocavities. Transmission electron microscopy analyses revealed that the isotropicity of plasma treatment causes the formation of a higher defects density around the whole cavity compared to the ion implantation technique, while ion implantation creates a lower density of defects embedded in the Si layer, resulting in a higher PL enhancement. These results further increase the understanding of the nature of optically active hydrogen defects and their relation with the observed photoluminescence, which will ultimately lead to the development of intense and tunable crystalline silicon light sources at room temperature.

Insights into Enchondroma, Enchondromatosis and the risk of secondary Chondrosarcoma. Review of the literature with an emphasis on the clinical behaviour, radiology, malignant transformation and the follow up.

The Enchondroma is a common, benign, cartilage forming tumour. They usually occur as a single, asymptomatic lesion. Occasionally patients present with multiple enchondromas which is generally defined as enchondromatosis. This entity encompasses several different subtypes including Ollier disease and Maffucci syndrome (enchondromatosis associated with soft tissue haemangiomas) as the most commons. Some of them have a complicated clinical course when malignant transformation occurs. This malignant progression is a well known fact especially in enchondromatosis, but up to now there is still a lack of recommendations concerning the follow up. The aim of this article is to review the clinical and imaging features of patients with solitary enchondroma and enchondromatosis focusing on the development of secondary chondrosarcoma and the follow up.

Enhanced 1.54 µm emission in Y-Er disilicate thin films on silicon photonic crystal cavities.

We introduce an Y-Er disilicate thin film deposited on top of a silicon photonic crystal cavity as a gain medium for active silicon photonic devices. Using photoluminescence analysis, we demonstrate that Er luminescence at 1.54 µm is enhanced by coupling with the cavity modes, and that the directionality of the Er optical emission can be controlled through far-field optimization of the cavity. We determine the maximum excitation power that can be coupled into the cavity to be 12 mW, which is limited by free carrier absorption and thermal heating. At maximum excitation, we observe that nearly 30% of the Er population is in the excited state, as estimated from the direct measurement of the emitted power. Finally, using time-resolved photoluminescence measurements, we determine a value of 2.3 for the Purcell factor of the system at room temperature. These results indicate that overcoating a silicon photonic nanostructure with an Er-rich dielectric layer is a promising method for achieving light emission at 1.54 µm wavelength on a silicon platform.

Bidirectional multiplexing of heralded single photons from a silicon chip.

We demonstrate integrated spatial multiplexing of heralded single photons generated from a single 96 µm long silicon photonic crystal waveguide in a bidirectional pump configuration. By using a low-loss fiber-coupled opto-ceramic switch, the multiplexing technique enhances the brightness of the single photon source by 51.2±4.0% while maintaining the coincidence-to-accidental ratio. Compared with the demonstration of multiplexing two individual sources, the bidirectional pump scheme represents a twofold reduction in the footprint of nonlinear devices for future large-scale integration of on-chip single photon sources. The 51.2±4.0% gain will make any quantum operation requiring n photons 1.5(n) times faster.

Ultracompact all-optical XOR logic gate in a slow-light silicon photonic crystal waveguide.

We demonstrate an ultracompact, chip-based, all-optical exclusive-OR (XOR) logic gate via slow-light enhanced four-wave mixing (FWM) in a silicon photonic crystal waveguide (PhCWG). We achieve error-free operation (<10⁻9) for 40 Gbit/s differential phase-shift keying (DPSK) signals with a 2.8 dB power penalty. Slowing the light to vg = c/32 enables a FWM conversion efficiency, η, of -30 dB for a 396 µm device. The nonlinear FWM process is enhanced by 20 dB compared to a relatively fast mode of vg = c/5. The XOR operation requires ≈ 41 mW, corresponding to a switching energy of 1 pJ/bit. We compare the slow-light PhCWG device performance with experimentally demonstrated XOR DPSK logic gates in other platforms and discuss scaling the device operation to higher bit-rates. The ultracompact structure suggests the potential for device integration.

Mode structure of coupled L3 photonic crystal cavities.

We investigate the energy splitting, quality factor and polarization of the fundamental modes of coupled L3 photonic crystal cavities. Four different geometries are evaluated theoretically, before experimentally investigating coupling in a direction at 30◦ to the line of the cavities. In this geometry, a smooth variation of the energy splitting with the cavity separation is predicted and observed, together with significant differences between the polarizations of the bonding and anti-bonding states. The controlled splitting of the coupled states is potentially useful for applications that require simultaneous resonant enhancement of two transitions.

Optical chromatography using a photonic crystal fiber with on-chip fluorescence excitation.

We describe the realization of integrated optical chromatography, in conjunction with on-chip fluorescence excitation, in a monolithically fabricated poly-dimethylsiloxane (PDMS) microfluidic chip. The unique endlessly-single-mode guiding property of the Photonic Crystal Fiber (PCF) facilitates simultaneous on-chip delivery of beams to perform optical sorting in conjunction with fluorescence excitation. We use soft lithography to define the chip and insert the specially capped PCF into it through a predefined fiber channel that is intrinsically aligned with the sorting channel. We compare the performance of the system to a standard ray optics model and use the system to demonstrate both size-driven and refractive index-driven separations of colloids. Finally we demonstrate a new technique of enhanced optofluidic separation of biological particles, by sorting of human kidney embryonic cells (HEK-293), internally tagged with fluorescing microspheres through phagocytocis, from those without microspheres and the separation purity is monitored using fluorescence imaging.

Planar photonic crystal cavities with far-field optimization for high coupling efficiency and quality factor.

Different types of planar photonic crystal cavities aimed at optimizing the far-field emission pattern are designed and experimentally assessed by resonant scattering measurements. We systematically investigate the interplay between achieving the highest possible quality (Q) factor and maximizing the in- and out-coupling efficiency into a narrow emission cone. Cavities operate at telecommunications wavelengths, i.e. around approximately 1.55 microm, and are realized in silicon membranes. A strong modification of the far-field emission pattern, and therefore a substantial increase of the coupling efficiency in the vertical direction, is obtained by properly modifying the holes around L3, L5 and L7 type PhC cavities, as we predict theoretically and show experimentally. An optimal compromise yielding simultaneously a high Q-factor and a large coupling to the fundamental cavity mode is found for a L7-type cavity with a measured Q congruent with 62000, whose resonant scattering efficiency is improved by about two orders of magnitude with respect to the unmodified structure. These results are especially useful for prospective applications in light emitting devices, such as nano-lasers or single-photon sources, in which vertical in- and out-coupling of the electromagnetic field is necessarily required.

Statistical fluctuations of transmission in slow light photonic-crystal waveguides.

We report statistical fluctuations for the transmissions of a series of photonic-crystal waveguides (PhCWs) that are supposedly identical and that only differ because of statistical structural fabrication-induced imperfections. For practical PhCW lengths offering tolerable -3dB attenuation with moderate group indices (n(g) approximately 60), the transmission spectra contains very narrow peaks (Q approximately 20,000) that vary from one waveguide to another. The physical origin of the peaks is explained by calculating the actual electromagnetic-field pattern inside the waveguide. The peaks that are observed in an intermediate regime between the ballistic and localization transports are responsible for a smearing of the local density of states, for a rapid broadening of the probability density function of the transmission, and bring a severe constraint on the effective use of slow light for on-chip optical information processing. The experimental results are quantitatively supported by theoretical results obtained with a coupled-Bloch-mode approach that takes into account multiple scattering and localization effects.

Loss engineered slow light waveguides.

Slow light devices such as photonic crystal waveguides (PhCW) and coupled resonator optical waveguides (CROW) have much promise for optical signal processing applications and a number of successful demonstrations underpinning this promise have already been made. Most of these applications are limited by propagation losses, especially for higher group indices. These losses are caused by technological imperfections ("extrinsic loss") that cause scattering of light from the waveguide mode. The relationship between this loss and the group velocity is complex and until now has not been fully understood. Here, we present a comprehensive explanation of the extrinsic loss mechanisms in PhC waveguides and address some misconceptions surrounding loss and slow light that have arisen in recent years. We develop a theoretical model that accurately describes the loss spectra of PhC waveguides. One of the key insights of the model is that the entire hole contributes coherently to the scattering process, in contrast to previous models that added up the scattering from short sections incoherently. As a result, we have already realised waveguides with significantly lower losses than comparable photonic crystal waveguides as well as achieving propagation losses, in units of loss per unit time (dB/ns) that are even lower than those of state-of-the-art coupled resonator optical waveguides based on silicon photonic wires. The model will enable more advanced designs with further loss reduction within existing technological constraints.

Four-wave mixing in slow light engineered silicon photonic crystal waveguides.

We experimentally investigate four-wave mixing (FWM) in short (80 µm) dispersion-engineered slow light silicon photonic crystal waveguides. The pump, probe and idler signals all lie in a 14 nm wide low dispersion region with a near-constant group velocity of c/30. We measure an instantaneous conversion efficiency of up to -9dB between the idler and the continuous-wave probe, with 1W peak pump power and 6 nm pump-probe detuning. This conversion efficiency is found to be considerably higher (>10 × ) than that of a Si nanowire with a group velocity ten times larger. In addition, we estimate the FWM bandwidth to be at least that of the flat band slow light window. These results, supported by numerical simulations, emphasize the importance of engineering the dispersion of PhC waveguides to exploit the slow light enhancement of FWM efficiency, even for short device lengths.

Optical signal processing on a silicon chip at 640Gb/s using slow-light.

We demonstrate optical performance monitoring of in-band optical signal to noise ratio (OSNR) and residual dispersion, at bit rates of 40Gb/s, 160Gb/s and 640Gb/s, using slow-light enhanced optical third harmonic generation (THG) in a compact (80microm) dispersion engineered 2D silicon photonic crystal waveguide. We show that there is no intrinsic degradation in the enhancement of the signal processing at 640Gb/s relative to that at 40Gb/s, and that this device should operate well above 1Tb/s. This work represents a record 16-fold increase in processing speed for a silicon device, and opens the door for slow light to play a key role in ultra-high bandwidth telecommunications systems.

Copper-phthalocyanine based metal-organic interfaces: the effect of fluorination, the substrate, and its symmetry.

Metal-organic interfaces based on copper-phthalocyanine monolayers are studied in dependence of the metal substrate (Au versus Cu), of its symmetry [hexagonal (111) surfaces versus fourfold (100) surfaces], as well as of the donor or acceptor semiconducting character associated with the nonfluorinated or perfluorinated molecules, respectively. Comparison of the properties of these systematically varied metal-organic interfaces provides new insight into the effect of each of the previously mentioned parameters on the molecule-substrate interactions.

High-speed modulation of a compact silicon ring resonator based on a reverse-biased pn diode.

High speed modulation based on a compact silicon ring resonator operating in depletion mode is demonstrated. The device exhibits an electrical small signal bandwidth of 19 GHz. The device is therefore a candidate for highly compact, wide bandwidth modulators for a variety of applications.

Optical filter with very large stopband (approximately 300 nm) based on a photonic-crystal vertical-directional coupler.

We have designed, fabricated, and demonstrated a vertical directional coupler based on the coupling between a polymer waveguide and a W1 photonic crystal waveguide. The filters have a bandwidth of approximately 2 nm within a stopband of Delta lambda approximately 300 nm and an on-chip insertion loss of 1 dB. This is the first (to our knowledge) demonstration of a filter with such a large stopband that overcomes the bandwidth limitation of existing filters.

Photonic crystal laser with mode selective mirrors.

The mini-stopband (MSB) of a W3 line-defect photonic crystal waveguide is used as a mirror for a GaAs based quantum-dot laser. Single mode, continuous-wave lasing is demonstrated for broad area lasers up to a current of 125 mA (2.7 x laser threshold), which demonstrates the high degree of mode selectivity of the MSB mirror. FDTD calculations indicate that optimisation of the mirror interface could lead to a further fourfold increase in reflectivity resulting in significantly reduced thresholds.

Silica-embedded silicon photonic crystal waveguides.

We report on the fabrication and characterization of silicon photonic crystal waveguides completely embedded in silica. These waveguides offer a robust alternative to air-membranes and are fully compatible with monolithic integration. Despite the reduced refractive index contrast compared to the air-membranes, these waveguides offer a considerable operating range of approximately 10 nm in the 1550 nm window. While the reduced index contrast weakens the perturbations due to surface roughness, we measure losses of 35 +/- 3dB/cm compared to 12 +/- 3 dB/cm for nominally identical air-membranes. Numerical analysis reveals that the difference in loss results from the different mode distribution and group index of the respective waveguide modes. Radius disorder is used as a fitting parameter in the numerical simulations with the best fits found for disorder levels of 1.4 - 1.7 nm RMS, which attest to the high quality of our structures.

Optical deflection and sorting of microparticles in a near-field optical geometry.

Near-field optical micromanipulation permits new possibilities for controlled motion of trapped objects. In this work, we report an original geometry for optically deflecting and sorting micro-objects employing a total internal reflection microscope system. A small beam of laser light is delivered off-axis through a total internal reflection objective which creates an elongated evanescent illumination of light at a glass/water interface. Asymmetrical gradient and scattering forces from this light field are seen to deflect and sort polystyrene microparticles within a fluid flow. The speed of the deflected objects is dependent upon their intrinsic properties. We present a finite element method to calculate the optical forces for the evanescent waves. The numerical simulations are in good qualitative agreement with the experimental observations and elucidate features of the particle trajectory. In the size range of 1 microm to 5 microm in diameter, polystyrene spheres were found to be guided on average 2.9 +/- 0.7 faster than silica spheres. The velocity increased by 3.0 +/- 0.5 microms(-1) per microm increase in diameter for polystyrene spheres and 0.7 +/- 0.2 microms(-1) per microm for silica. We employ this size dependence for performing passive optical sorting within a microfluidic chip and is demonstrated in the accompanying video.