Quantum circuit mapping for universal and scalable computing in MZI-based integrated photonics.

Linear optical quantum computing (LOQC) offers a quantum computation paradigm based on well-established and robust technology and flexible environmental conditions following DiVincenzo's criteria. Within this framework, integrated photonics can be utilized to achieve gate-based quantum computing, defining qubits by path-encoding, quantum gates through the use of Mach-Zehnder interferometers (MZIs), and measurements through single-photon detectors. In particular, universal two-qubit gates can be achieved by suitable structures of MZIs together with post-selection or heralding. The most resource-efficient choice is given by the post-selected Controlled-Z (CZ) gate. However, this implementation is characterized by a design which has a non-regular structure and cannot be cascaded. This limits the implementation of large-scale LOQC. Starting from these issues, we suggest an approach to move toward a universal and scalable LOQC on the integrated photonic platform. First of all, choosing the post-selected CZ as a universal two-qubit gate, we extend the path-encoded dual-rail qubit to a triplet of waveguides, composed of an auxiliary waveguide and the pair of waveguides corresponding to the qubit basis states. Additionally, we introduce a swap photonic network that maps the regularly-labeled structure of the new path-encoded qubits to the structure needed for the post-selected CZ. We also discuss the optical swap gate that allows the connection of non-nearest neighbor path-encoded qubits. In this way, we can deterministically exchange the locations of the qubits and execute controlled quantum gates between any path-encoded qubits. Next, by truncating the auxiliary waveguides after any post-selected CZ, we find that it is possible to cascade this optical gate when it acts on different pairs that share only one qubit. Finally, we show the Bell state and the Greenberger-Horne-Zeilinger (GHZ) state generation circuits implementing the regular structure, the cascading procedure of post-selected CZ and the optical swap.

SiN integrated photonic components in the visible to near-infrared spectral region.

Integrated photonics has emerged as one of the most promising platforms for quantum applications. The performances of quantum photonic integrated circuits (QPIC) necessitate a demanding optimization to achieve enhanced properties and tailored characteristics with more stringent requirements with respect to their classical counterparts. In this study, we report on the simulation, fabrication, and characterization of a series of fundamental components for photons manipulation in QPIC based on silicon nitride. These include crossing waveguides, multimode-interferometer-based integrated beam splitters (MMIs), asymmetric integrated Mach-Zehnder interferometers (MZIs) based on MMIs, and micro-ring resonators. Our investigation revolves primarily around the visible to near-infrared spectral region, as these integrated structures are meticulously designed and tailored for optimal operation within this wavelength range. By advancing the development of these elementary building blocks, we aim to pave the way for significant improvements in QPIC in a spectral region only little explored so far.

On the spectral response of a taiji-CROW device.

Physical systems with topological properties are robust against disorder. However, implementing them in integrated photonic devices is challenging because of the various fabrication imperfections and/or limitations that affect the spectral response of their building blocks. One such feature is strong backscattering due to the surface wall roughness of the waveguides, which can flip the propagating modes to counterpropagating modes and destroy the desired topological behavior. Here, we report a study on modeling, designing and testing an integrated photonic structure based on a sequence of two taiji microresonators coupled with a middle link microresonator (a taiji-CROW device, where CROW stands for coupled resonator optical waveguides). Our study provides design constraints to preserve the ideal operation of the structure by quantifying a minimum ratio between the coupling coefficients and the backscattering coefficients. This ratio is valuable to avoid surface roughness problems in designing topological integrated photonic devices based on arrays of microresonators.

Time delay reservoir computing with a silicon microring resonator and a fiber-based optical feedback loop.

Silicon microring resonators serve as critical components in integrated photonic neural network implementations, owing to their compact footprint, compatibility with CMOS technology, and passive nonlinear dynamics. Recent advancements have leveraged their filtering properties as weighting functions, and their nonlinear dynamics as activation functions with spiking capabilities. In this work, we investigate experimentally the linear and nonlinear dynamics of microring resonators for time delay reservoir computing, by introducing an external optical feedback loop. After effectively mitigating the impact of environmental noise on the fiber-based feedback phase dependencies, we evaluate the computational capacity of this system by assessing its performance across various benchmark tasks at a bit rate of few Mbps. We show that the additional memory provided by the optical feedback is necessary to achieve error-free operation in delayed-boolean tasks that require up to 3 bits of memory. In this case the microring was operated in the linear regime and the photodetection was the nonlinear activation function. We also show that the Santa Fe and Mackey Glass prediction tasks are solved when the microring nonlinearities are activated. Notably, our study reveals competitive outcomes even when employing only 7 virtual nodes within our photonic reservoir. Our findings illustrate the silicon microring's versatile performance in the presence of optical feedback, highlighting its ability to be tailored for various computing applications.

Mitigating indistinguishability issues in photon pair sources by delayed-pump intermodal four wave mixing.

Large arrays of independent, pure and identical heralded single photon sources are an important resource for linear optical quantum computing protocols. In the race towards the development of increasingly ideal sources, delayed-pump intermodal four wave mixing (IFWM) in multimode waveguides has recently emerged as one of the most promising approaches. Despite this, fabrication imperfections still spoil the spectral indistinguishability of photon pairs from independent sources. Here we show that by tapering the width of the waveguide and by controlling the delay between the pump pulses, we add additional spectral tunability to the source while still inheriting all the distinctive metrics of the IFWM scheme. This feature is used to recover spectral indistinuishability in presence of fabrication errors. Under realistic tolerances on the waveguide dimensions, we predict >99.5% indistinguishability between independent sources on the same chip, and a maximum degradation of the heralded Hong-Ou-Mandel visibility <0.35%.

Microring resonators with external optical feedback for time delay reservoir computing.

Microring resonators (MRRs) are a key photonic component in integrated devices, due to their small size, low insertion losses, and passive operation. While the MRRs have been established for optical filtering in wavelength-multiplexed systems, the nonlinear properties that they can exhibit give rise to new perspectives on their use. For instance, they have been recently considered for introducing optical nonlinearity in photonic reservoir computing systems. In this work, we present a detailed numerical investigation of a silicon MRR operation, in the presence of external optical feedback, in a time delay reservoir computing scheme. We demonstrate the versatility of this compact, passive device, by exploiting different operating regimes and solving computing tasks with diverse memory requirements. We show that when large memory is required, as it occurs in the Narma 10 task, the MRR nonlinearity does not play a significant role when the photodetection nonlinearity is involved, while the contribution of the external feedback is significant. On the contrary, for computing tasks such as the Mackey-Glass and the Santa Fe chaotic timeseries prediction, the MRR and the photodetection nonlinearities contribute both to efficient computation. The presence of optical feedback improves the prediction of the Mackey-Glass timeseries while it plays a minor role in the Santa Fe timeseries case.

Tailoring Adjuvant Endocrine Therapy for Premenopausal Breast Cancer.

BACKGROUND: In the Suppression of Ovarian Function Trial (SOFT) and the Tamoxifen and Exemestane Trial (TEXT), the 5-year rates of recurrence of breast cancer were significantly lower among premenopausal women who received the aromatase inhibitor exemestane plus ovarian suppression than among those who received tamoxifen plus ovarian suppression. The addition of ovarian suppression to tamoxifen did not result in significantly lower recurrence rates than those with tamoxifen alone. Here, we report the updated results from the two trials. METHODS: Premenopausal women were randomly assigned to receive 5 years of tamoxifen, tamoxifen plus ovarian suppression, or exemestane plus ovarian suppression in SOFT and to receive tamoxifen plus ovarian suppression or exemestane plus ovarian suppression in TEXT. Randomization was stratified according to the receipt of chemotherapy. RESULTS: In SOFT, the 8-year disease-free survival rate was 78.9% with tamoxifen alone, 83.2% with tamoxifen plus ovarian suppression, and 85.9% with exemestane plus ovarian suppression (P=0.009 for tamoxifen alone vs. tamoxifen plus ovarian suppression). The 8-year rate of overall survival was 91.5% with tamoxifen alone, 93.3% with tamoxifen plus ovarian suppression, and 92.1% with exemestane plus ovarian suppression (P=0.01 for tamoxifen alone vs. tamoxifen plus ovarian suppression); among the women who remained premenopausal after chemotherapy, the rates were 85.1%, 89.4%, and 87.2%, respectively. Among the women with cancers that were negative for HER2 who received chemotherapy, the 8-year rate of distant recurrence with exemestane plus ovarian suppression was lower than the rate with tamoxifen plus ovarian suppression (by 7.0 percentage points in SOFT and by 5.0 percentage points in TEXT). Grade 3 or higher adverse events were reported in 24.6% of the tamoxifen-alone group, 31.0% of the tamoxifen-ovarian suppression group, and 32.3% of the exemestane-ovarian suppression group. CONCLUSIONS: Among premenopausal women with breast cancer, the addition of ovarian suppression to tamoxifen resulted in significantly higher 8-year rates of both disease-free and overall survival than tamoxifen alone. The use of exemestane plus ovarian suppression resulted in even higher rates of freedom from recurrence. The frequency of adverse events was higher in the two groups that received ovarian suppression than in the tamoxifen-alone group. (Funded by Pfizer and others; SOFT and TEXT ClinicalTrials.gov numbers, NCT00066690 and NCT00066703 , respectively.).

On the modeling of thermal and free carrier nonlinearities in silicon-on-insulator microring resonators.

The temporal dynamics of integrated silicon resonators has been modeled using a set of equations coupling the internal energy, the temperature and the free carrier population. Owing to its simplicity, Newton's law of cooling is the traditional choice for describing the thermal evolution of such systems. In this work, we theoretically and experimentally prove that this can be inadequate in monolithic planar devices, leading to inaccurate predictions. A new equation that we train to reproduce the correct temperature behaviour is introduced to fix the discrepancies with the experimental results. We discuss the limitations and the range of validity of our refined model, identifying those cases where Netwon's law provides, nevertheless, accurate solutions. Our modeling describes the phenomena underlying thermal and free carrier instabilities and is a valuable tool for the engineering of photonic systems which rely on resonator dynamical states, such as all optical spiking neural networks or reservoirs for neuromorphic computing.

Influence of the bus waveguide on the linear and nonlinear response of a taiji microresonator.

We study the linear and nonlinear response of a unidirectional reflector where a nonlinear breaking of the Lorentz reciprocity is observed. The device under test consists of a racetrack microresonator, with an embedded S-shaped waveguide, coupled to an external bus waveguide (BW). This geometry of the microresonator is known as "taiji" microresonator (TJMR). Here, we show that a full description of the device needs to consider also the role of the BW, which introduces (i) Fabry-Perot oscillations (FPOs) due to reflections at its facets, and (ii) asymmetric losses, which depend on the actual position of the TJMR. At sufficiently low powers the asymmetric loss does not affect the unidirectional behavior, but the FP interference fringes can cancel the effect of the S-shaped waveguide. However, at high input power, both the asymmetric loss and the FPOs contribute to the redistribution of energy between counterpropagating modes within the TJMR. This strongly modifies the nonlinear response, giving rise to counter-intuitive features where, due to the FP effect and the asymmetric losses, the BW properties can determine the violation of the Lorentz reciprocity and, in particular, the difference between the transmittance in the two directions of excitation.

Second-harmonic generation in periodically poled silicon waveguides with lateral p-i-n junctions.

Electric-field-induced second-harmonic generation is demonstrated in silicon waveguides with reverse biased lateral p-i-n junctions. Phase matching is achieved by periodically poling the applied electric field. Two different poling configurations are compared: in the first, the p- and n-type doped regions of the junctions are on different sides of the waveguide (simple configuration), while in the second, they are alternated periodically across the waveguide sides (interdigitated configuration). Both simulations and experiments show that the generation efficiency is increased by 10 times comparing the interdigitated and simple configurations. The effective second-order susceptibility modulation obtained at a reverse bias voltage of 3.5 V is Δχeff,S(2)≃0.14pm/V for the simple configuration and Δχeff,I(2)≃0.64pm/V for the interdigitated one.

Second-harmonic generation in periodically poled silicon waveguides with lateral p-i-n junctions: publisher's note.

This publisher's note contains corrections to Opt. Lett.45, 3188 (2020)OPLEDP0146-959210.1364/OL.391988.

Impact of Metformin Use and Diabetic Status During Adjuvant Fluoropyrimidine-Oxaliplatin Chemotherapy on the Outcome of Patients with Resected Colon Cancer: A TOSCA Study Subanalysis.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is associated with increased risk of colon cancer (CC), whereas metformin use seems to be protective. However, the impact of metformin use on the risk of death or disease recurrence after radical surgery for CC remains uncertain. MATERIALS AND METHODS: This is a substudy conducted in patients with high-risk stage II or stage III CC randomized in the TOSCA trial, which compared 3 versus 6 months of fluoropyrimidine-oxaliplatin adjuvant chemotherapy. Objective of the study was to investigate the impact of metformin exposure during adjuvant chemotherapy on overall survival (OS) and relapse-free survival (RFS). We also evaluated the impact of T2DM or metformin dosage on clinical outcomes. RESULTS: Out of 3,759 patients enrolled in the TOSCA trial, 133 patients with diabetes (9.2%) and 1,319 without diabetes (90.8%) were recruited in this study. After excluding 13 patients with diabetes without information on metformin exposure, 76 patients with T2DM (63.3%) were defined as metformin users and 44 (36.7%) as metformin nonusers. After a median follow-up of 60.4 months, 26 (21.7%) patients relapsed and 16 (13.3%) died. Metformin use was neither associated with OS (adjusted hazard ratio [HR], 1.51; 95% confidence interval [CI], 0.48-4.77; p = .4781) nor with RFS (HR, 1.56; 95% CI, 0.69-3.54; p = .2881). Similarly, we found no association between T2DM or metformin dosage and OS or RFS. CONCLUSIONS: Metformin use and T2DM did not impact on OS or RFS in patients with resected CC treated with adjuvant fluoropyrimidine-oxaliplatin chemotherapy. Larger studies and longer follow-up are required to clarify the potential efficacy of metformin in improving the prognosis of patients with CC. IMPLICATIONS FOR PRACTICE: The role of the antidiabetic drug metformin in colon cancer prevention and treatment is highly debated. While low-dose metformin reduced the incidence of colorectal adenomas in two prospective studies, its effect in patients with already established colon cancer remains unclear. In this study, the potential impact of metformin on the survival of resected colon cancer patients who received adjuvant chemotherapy was investigated in the context of the TOSCA study. We did not find any association between metformin use or dosages and patient survival. Prospective studies are required to draw definitive conclusions about metformin impact on colon cancer recurrence and survival.

Tuning the strain-induced resonance shift in silicon racetrack resonators by their orientation.

In this work, we analyze the role of strain on a set of silicon racetrack resonators presenting different orientations with respect to the applied strain. The strain induces a variation of the resonance wavelength, caused by the photoelastic variation of the material refractive index as well as by the mechanical deformation of the device. In particular, the mechanical deformation alters both the resonator perimeter and the waveguide cross-section. Finite element simulations taking into account all these effects are presented, providing good agreement with experimental results. By studying the role of the resonator orientation we identify interesting features, such as the tuning of the resonance shift from negative to positive values and the possibility of realizing strain insensitive devices.

Eribulin across multiple lines of chemotherapy: a retrospective study on quality of life and efficacy in metastatic breast cancer patients.

This study evaluates efficacy, tolerability and health-related quality of life of eribulin in patients with metastatic breast cancer. Predictive and/or prognostic factors of outcome were also analyzed. Among 44 women receiving eribulin mesylate, one patient had a complete response, 22.7% a partial response and 25% a stable disease. Median overall survival and median progression-free survival were 11.8 and 4.5 months, respectively. Treatment was well tolerated; the most frequent adverse events were neutropenia (52%), leukopenia (50%), fatigue (38%) and alopecia (40%). No significant reductions of health-related quality of life parameters were observed. Disease control during previous chemotherapy lines was related with better outcome with eribulin. In conclusion, eribulin treatment should be considered in a multiple chemotherapy lines strategy in metastatic breast cancer.

The Relationships between HER2 Overexpression and DCIS Characteristics.

The aim of this study was to demonstrate the correlation between human epidermal growth factor receptor 2 (HER2) overexpression and some poor prognosis factors in patients affected by ductal carcinoma in situ (DCIS). We evaluated 48 cases of DCIS, divided into two groups according to HER2 amplification status. Nuclear grade and "cancerization of lobules" were determined within primary DCIS and Ki67, estrogen receptor (ER), PR, and HER2 expression was established using immunohistochemistry. The histopathological variables in HER2-positive and in HER2-negative patients were compared to determine the recurrence risk. We also considered the median age at the time of surgery according to HER2 status. There were 11 recurrences (23%), 6 DCIS (55%), and 5 invasive cancer (45%). In an 8-year-long median follow-up, we hypothesized high risk of recurrence in HER2-positive DCIS. Patients with HER2-positive DCIS were younger than HER2-negative ones (p = 0.002). HER2-positive DCIS was also related to histopathological predictors of recurrence such as high nuclear grade (p < 0.001), high Ki67 expression (p = 0.003), low ER and PgR levels (p < 0.001), and the presence of "cancerization of lobules" (p < 0.049). Our trial suggests that HER2 amplification in primary DCIS is identified more frequently in younger patients and hypothesizes high risk of recurrence in HER2-positive DCIS related to histopathological predictors of overall relapse as high nuclear grade, high Ki67 expression, low ER and PgR levels, and the presence of "cancerization of lobules." In HER2-positive DCIS, other variables of recurrence risk are compared to HER2-negative lesions, without statistical significance. Our results show that HER2 testing might suggest clinicians the optimal treatment of patients with DCIS.

High-Dose Chemotherapy and Autologous Hematopoietic Stem Cell Transplantation as Adjuvant Treatment in High-Risk Breast Cancer: Data from the European Group for Blood and Marrow Transplantation Registry.

The aim of this retrospective study was to assess toxicity and efficacy of adjuvant high-dose chemotherapy (HDC) and autologous hematopoietic stem cell transplantation (AHSCT) in 583 high-risk breast cancer (BC) patients (>3 positive nodes) who were transplanted between 1995 and 2005 in Europe. All patients received surgery before transplant, and 55 patients (9.5%) received neoadjuvant treatment before surgery. Median age was 47.1 years, 57.3% of patients were premenopausal at treatment, 56.5% had endocrine-responsive tumors, 19.5% had a human epidermal growth factor receptor 2 (HER2)-negative tumor, and 72.4% had ≥10 positive lymph nodes at surgery. Seventy-nine percent received a single HDC procedure. Overall transplant-related mortality was 1.9%, at .9% between 2001 and 2005, whereas secondary tumor-related mortality was .9%. With a median follow-up of 120 months, overall survival and disease-free survival rates at 5 and 10 years in the whole population were 75% and 64% and 58% and 44%, respectively. Subgroup analysis demonstrated that rates of overall survival were significantly better in patients with endocrine-responsive tumors, <10 positive lymph nodes, and smaller tumor size. HER2 status did not affect survival probability. Adjuvant HDC with AHSCT has a low mortality rate and provides impressive long-term survival rates in patients with high-risk BC. Our results suggest that this treatment modality should be considered in selected high-risk BC patients and further investigated in clinical trials.

Patient-reported outcomes with adjuvant exemestane versus tamoxifen in premenopausal women with early breast cancer undergoing ovarian suppression (TEXT and SOFT): a combined analysis of two phase 3 randomised trials.

BACKGROUND: The combined efficacy analysis of the TEXT and SOFT trials showed a significant disease-free survival benefit with exemestane plus ovarian function suppression (OFS) compared with tamoxifen plus OFS. We present patient-reported outcomes from these trials. METHODS: Between Nov 7, 2003, and April 7, 2011, 4717 premenopausal women with hormone-receptor positive breast cancer were enrolled in TEXT or SOFT to receive unmasked adjuvant treatment with 5 years of exemestane plus OFS or tamoxifen plus OFS. Gonadotropin-releasing hormone analogue triptorelin, bilateral oophorectomy, or bilateral ovarian irradiation were used to achieve OFS. Chemotherapy use was optional. Randomisation with permuted blocks was done with the International Breast Cancer Study Group's internet-based system and was stratified by chemotherapy use and status of lymph nodes. Patients completed a quality of life (QoL) form comprising several global and symptom indicators at baseline, every 6 months for 24 months, and then every year during years 3 to 6. Differences in the change of QoL from baseline between the two treatments were tested at 6 months, 24 months, and 60 months with mixed-models for repeated measures for each trial with and without chemotherapy and overall. The analysis was by intention to treat. At the time of analysis, the median follow-up was 5·7 years (IQR 3·7-6·9); treatment and follow-up of patients continue. The trials are registered with ClinicalTrials.gov, as NCT00066703 (TEXT) and NCT00066690 (SOFT). FINDINGS: Patients on tamoxifen plus OFS were more affected by hot flushes and sweats over 5 years than were those on exemestane plus OFS, although these symptoms improved. Patients on exemestane plus OFS reported more vaginal dryness, greater loss of sexual interest, and difficulties becoming aroused than did patients on tamoxifen plus OFS; these differences persisted over time. An increase in bone or joint pain was more pronounced, particularly in the short term, in patients on exemestane plus OFS than patients on tamoxifen plus OFS. Changes in global QoL indicators from baseline were small and similar between treatments over the 5 years. INTERPRETATION: Overall, from a QoL perspective, there is no strong indication to favour either exemestane plus OFS or tamoxifen plus OFS. The distinct effects of the two treatments on the burden of endocrine symptoms need to be addressed with patients individually. FUNDING: Pfizer, International Breast Cancer Study Group, and US National Cancer Institute.

A male patient with acromegaly and breast cancer: treating acromegaly to control tumor progression.

BACKGROUND: Acromegaly is a rare disease associated with an increased risk of developing cancer. CASE PRESENTATION: We report the case of a 72-year-old man who was diagnosed with acromegaly (IGF-1 770 ng/ml) and breast cancer. Four years before he suffered from a colon-rectal cancer. Pituitary surgery and octreotide-LAR treatment failed to control acromegaly. Normalization of IGF-1 (97 ng/ml) was obtained with pegvisomant therapy. Four years after breast cancer surgery, 2 pulmonary metastases were detected at chest CT. The patient was started on anastrozole, but, contrary to medical advice, he stopped pegvisomant treatment (IGF-I 453 ng/ml). Four months later, chest CT revealed an increase in size of the metastatic lesion of the left lung. The patient was shifted from anastrozole to tamoxifen and was restarted on pegvisomant, with normalization of serum IGF-1 levels (90 ng/ml). Four months later, a reduction in size of the metastatic lesion of the left lung was detected by CT. Subsequent CT scans throughout a 24-month follow-up showed a further reduction in size and then a stabilization of the metastasis. CONCLUSIONS: This is the first report of a male patient with acromegaly and breast cancer. The clinical course of breast cancer was closely related to the metabolic control of acromegaly. The rapid progression of metastatic lesion was temporally related to stopping pegvisomant treatment and paralleled a rise in serum IGF-1 levels. Normalization of IGF-1 after re-starting pegvisomant impressively reduced the progression of metastatic breast lesions. Control of acromegaly is mandatory in acromegalic patients with cancer.

Design and Optimization of SiON Ring Resonator-Based Biosensors for Aflatoxin M1 Detection.

In this article, we designed and studied silicon oxynitride (SiON) microring-based photonic structures for biosensing applications. We designed waveguides, directional couplers, and racetrack resonators in order to measure refractive index changes smaller than 10-6 refractive index units (RIU). We tested various samples with different SiON refractive indexes as well as the waveguide dimensions for selecting the sensor with the best performance. Propagation losses and bending losses have been measured on test structures, along with a complete characterization of the resonator's performances. Sensitivities and limit of detection (LOD) were also measured using glucose-water solutions and compared with expected results from simulations. Finally, we functionalized the resonator and performed sensing experiments with Aflatoxin M1 (AFM1). We were able to detect the binding of aflatoxin for concentrations as low as 12.5 nm. The results open up the path for designing cost-effective biosensors for a fast and reliable sensitive analysis of AFM1 in milk.

Role of edge inclination in an optical microdisk resonator for label-free sensing.

In this paper, we report on the measurement and modeling of enhanced optical refractometric sensors based on whispering gallery modes. The devices under test are optical microresonators made of silicon nitride on silicon oxide, which differ in their sidewall inclination angle. In our approach, these microresonators are vertically coupled to a buried waveguide with the aim of creating integrated and cost-effective devices. Device modeling shows that the optimization of the device is a delicate balance of the resonance quality factor and evanescent field overlap with the surrounding environment to analyze. By numerical simulations, we show that the microdisk thickness is critical to yield a high figure of merit for the sensor and that edge inclination should be kept as high as possible. We also show that bulk-sensing figures of merit as high as 1600 RIU(-1) (refractive index unit) are feasible.