Femtosecond laser inscription of depressed cladding single-mode mid-infrared waveguides in sapphire

Mid-infrared optical waveguides were inscribed in sapphire with femtosecond pulses at 515 nm. We show that such pulses induce a smooth negative refractive index change allowing for the inscription of a depressed cladding waveguide by closely overlapping the corresponding type I modification traces. The resulting structure consists of a highly symmetrical, uniform, and homogeneous waveguide. The size and numerical aperture of the waveguides were tailored to achieve efficient transmission in the mid-infrared. Single mode operation at a wavelength of 2850 nm and propagation loss of <0.37  dB/cm are reported for a 33 mm long depressed cladding waveguide. Thermal annealing was performed, and the refractive index contrast was still preserved to 50% (i.e., Δ=∼2.5×10−3) up to 1400°C

Rapport du comité d'évaluation de la qualité de la recherche scientifique du CQRDA

Rapport d'évaluation de la qualité de la recherche scientifique à laquelle le CQRDA est associé, incluant une évaluation de l'exploitation des résultats des projets de recherche. Plus particulièrement, l'évaluation de la recherche scientifique devrait permettre d'illustrer la valeur des projets de recherche sur le plan scientifique ainsi que la valeur des experts et des chercheurs sollicités. Cette évaluation a porté sur les travaux couvant la période du 1er juin 2001 au 31 mai 2006

Archimedean spiral cavity ring resonators in silicon as ultra-compact optical comb filters

We present an ultra-compact comb filter using an add-drop ring resonator with an Archimedean spiral cavity. The cavity consists of two interleaved spiral branches which are connected in the center using arcs of circle of a radius that causes minimum bend loss. We describe the design procedure and examine the physical parameters governing the resonator performance. As an example, we demonstrate experimentally a comb filter with a 25 GHz channel spacing made of silicon photonic wires and only occupies an area of 80 × 90 µm2, approximately a 70 fold size reduction compared to a racetrack resonator. The filter transmission is free of spurious reflections, attesting to the smooth transition between different sections of the resonator cavity. Over a 40 channel wavelength span, the filter exhibits a quality factor Q > 35,000, extinction ratios > 10 dB, and an excellent power uniformity with variations < 0.5 dB for both the through and drop ports

Real-time cancellation of temperature induced resonance shifts in SOI wire waveguide ring resonator label-free biosensor arrays.

A comprehensive investigation of real-time temperature-induced resonance shift cancellation for silicon wire based biosensor arrays is reported for the first time. A reference resonator, protected by either a SU8 or SiO(2) cladding layer, is used to track temperature changes. The temperature dependence of resonators in aqueous solutions, pertinent to biosensing applications, is measured under steady-state conditions and the operating parameters influencing these properties are discussed. Real-time measurements show that the reference resonator resonances reflect the temperature changes without noticeable time delay, enabling effective cancellation of temperature-induced shifts. Binding between complementary IgG protein pairs is monitored over 4 orders of magnitude dynamic range down to a concentration of 20 pM, demonstrating a resolvable mass of 40 attograms. Reactions are measured over time periods as long as 3 hours with high stability, showing a scatter corresponding to a fluid refractive index fluctuation of ± 4 × 10(-6) in the baseline data. Sensor arrays with a SU8 protective cladding are easy to fabricate, while oxide cladding is found to provide superior stability for measurements involving long time scales

Use of human splenocytes in an innovative humanised mouse model for prediction of immunotherapy-induced cytokine release syndrome.

OBJECTIVES: Humanised mice have emerged as valuable models for pre-clinical testing of the safety and efficacy of immunotherapies. Given the variety of models available, selection of the most appropriate humanised mouse model is critical in study design. Here, we aimed to develop a model for predicting cytokine release syndrome (CRS) while minimising graft-versus-host disease (GvHD). METHODS: To overcome donor-induced variation, we directly compared the in vitro and in vivo immune phenotype of immunodeficient NSG mice reconstituted with human bone marrow (BM) CD34+ haematopoietic stem cells (HSCs), peripheral blood mononuclear cells (PBMCs) or spleen mononuclear cells (SPMCs) from the same human donors. SPMC engraftment in NSG-dKO mice, which lack MHC class I and II, was also evaluated as a strategy to limit GvHD. Another group of mice was engrafted with umbilical cord blood (UCB) CD34+ HSCs. Induction of CRS in vivo was investigated upon administration of the anti-CD3 monoclonal antibody OKT3. RESULTS: PBMC- and SPMC-reconstituted NSG mice showed short-term survival, with engrafted human T cells exhibiting mostly an effector memory phenotype. Survival in SPMC-reconstituted NSG-dKO mice was significantly longer. Conversely, both BM and UCB-HSC models showed longer survival, without demonstrable GvHD and a more naïve T-cell phenotype. PBMC- and SPMC-reconstituted mice, but not BM-HSC or UCB-HSC mice, experienced severe clinical signs of CRS upon administration of OKT3. CONCLUSION: PBMC- and SPMC-reconstituted NSG mice better predict OKT3-mediated CRS. The SPMC model allows generation of large experimental groups, and the use of NSG-dKO mice mitigates the limitation of early GvHD

Global profiling of alternative RNA splicing events provides insights into molecular differences between various types of hepatocellular carcinoma

Protein families encoded by transcripts that are differentially spliced in various types of HCC. Table S2. Bioinformatical prediction of functional changes caused by some of ASEs identified. Table S3. List of tumor suppressors for which AS is dysregulated in various types of HCC. Table S4. List of oncogenes for which AS is dysregulated in various types of HCC. Table S5. List of kinases for which AS is dysregulated in various types of HCC. Table S6. List of transcription factors for which AS is dysregulated in various types of HCC. Table S7. List of genes for which AS is dysregulated in all types of HCC. Table S8. List of genes uniquely dysregulated in HBV-associated HCC. Table S9. List of genes uniquely dysregulated in HCV-associated HCC. Table S10. List of genes uniquely dysregulated in HBV&HCV-associated HCC. Table S11. List of genes uniquely dysregulated in virus-free HCC. Figure S1. Characterization of splicing mysregulation in HCC. Figure S2. Characterization of ASEs that are modified in HBV- and HCV-associated HCC. Figure S3. AS modifications in transcripts encoded by kinases and transcriptions factores in HBV- and HCV-associated HCC. Figure S4. Global profiling of ASE modifications in both HBV&HCV-associated HCC and virus-free-associated HCC. Figure S5. RNA splicing factors in HCC. Figure S6. Modifications to AS of 96 transcripts in response to knockdown of splicing factors with specific siRNAs (PDF 6675 kb

Canadian Healthcare Professionals’ Views and Attitudes toward Risk-Stratified Breast Cancer Screening

Given the controversy over the effectiveness of age-based breast cancer (BC) screening, offering risk-stratified screening to women may be a way to improve patient outcomes with detection of earlier-stage disease. While this approach seems promising, its integration requires the buy-in of many stakeholders. In this cross-sectional study, we surveyed Canadian healthcare professionals about their views and attitudes toward a risk-stratified BC screening approach. An anonymous online questionnaire was disseminated through Canadian healthcare professional associations between November 2020 and May 2021. Information collected included attitudes toward BC screening recommendations based on individual risk, comfort and perceived readiness related to the possible implementation of this approach. Close to 90% of the 593 respondents agreed with increased frequency and earlier initiation of BC screening for women at high risk. However, only 9% agreed with the idea of not offering BC screening to women at very low risk. Respondents indicated that primary care physicians and nurse practitioners should play a leading role in the risk-stratified BC screening approach. This survey identifies health services and policy enhancements that would be needed to support future implementation of a risk-stratified BC screening approach in healthcare systems in Canada and other countries

Multiparametric MRI of early tumor response to immune checkpoint blockade in metastatic melanoma

Background: Immune checkpoint inhibitors are now standard of care treatment for many cancers. Treatment failure in metastatic melanoma is often due to tumor heterogeneity, which is not easily captured by conventional CT or tumor biopsy. The aim of this prospective study was to investigate early microstructural and functional changes within melanoma metastases following immune checkpoint blockade using multiparametric MRI. Methods: Fifteen treatment-naïve metastatic melanoma patients (total 27 measurable target lesions) were imaged at baseline and following 3 and 12 weeks of treatment on immune checkpoint inhibitors using: T2-weighted imaging, diffusion kurtosis imaging, and dynamic contrast-enhanced MRI. Treatment timepoint changes in tumor cellularity, vascularity, and heterogeneity within individual metastases were evaluated and correlated to the clinical outcome in each patient based on Response Evaluation Criteria in Solid Tumors V.1.1 at 1 year. Results: Differential tumor growth kinetics in response to immune checkpoint blockade were measured in individual metastases within the same patient, demonstrating significant intertumoral heterogeneity in some patients. Early detection of tumor cell death or cell loss measured by a significant increase in the apparent diffusivity (Dapp) (p<0.05) was observed in both responding and pseudoprogressive lesions after 3 weeks of treatment. Tumor heterogeneity, as measured by apparent diffusional kurtosis (Kapp), was consistently higher in the pseudoprogressive and true progressive lesions, compared with the responding lesions throughout the first 12 weeks of treatment. These preceded tumor regression and significant tumor vascularity changes (Ktrans, ve, and vp) detected after 12 weeks of immunotherapy (p<0.05). Conclusions: Multiparametric MRI demonstrated potential for early detection of successful response to immune checkpoint inhibitors in metastatic melanoma

A collaborative model to implement flexible, accessible and efficient oncogenetic services for hereditary breast and ovarian cancer : the C-MOnGene study

Medical genetic services are facing an unprecedented demand for counseling and testing for hereditary breast and ovarian cancer (HBOC) in a context of limited resources. To help resolve this issue, a collaborative oncogenetic model was recently developed and implemented at the CHU de Québec-Université Laval; Quebec; Canada. Here, we present the protocol of the C-MOnGene (Collaborative Model in OncoGenetics) study, funded to examine the context in which the model was implemented and document the lessons that can be learned to optimize the delivery of oncogenetic services. Within three years of implementation, the model allowed researchers to double the annual number of patients seen in genetic counseling. The average number of days between genetic counseling and disclosure of test results significantly decreased. Group counseling sessions improved participants' understanding of breast cancer risk and increased knowledge of breast cancer and genetics and a large majority of them reported to be overwhelmingly satisfied with the process. These quality and performance indicators suggest this oncogenetic model offers a flexible, patient-centered and efficient genetic counseling and testing for HBOC. By identifying the critical facilitating factors and barriers, our study will provide an evidence base for organizations interested in transitioning to an oncogenetic model integrated into oncology care; including teams that are not specialized but are trained in genetics