Measurement accuracy in silicon photonic ring resonator thermometers: identifying and mitigating intrinsic impairments.

Silicon photonic ring resonator thermometers have been shown to provide temperature measurements with a 10 mK accuracy. In this work we identify and quantify the intrinsic on-chip impairments that may limit further improvement in temperature measurement accuracy. The impairments arise from optically induced changes in the waveguide effective index, and from back-reflections and scattering at defects and interfaces inside the ring cavity and along the path between light source and detector. These impairments are characterized for 220 × 500 nm Si waveguide rings by experimental measurement in a calibrated temperature bath and by phenomenological models of ring response. At different optical power levels both positive and negative light induced resonance shifts are observed. For a ring with L = 100 µm cavity length, the self-heating induced resonance red shift can alter the temperature reading by 200 mK at 1 mW incident power, while a small blue shift is observed below 100 µW. The effect of self-heating is shown to be effectively suppressed by choosing longer ring cavities. Scattering and back-reflections often produce split and distorted resonance line shapes. Although these distortions can vary with resonance order, they are almost completely invariant with temperature for a given resonance and do not lead to measurement errors in themselves. The effect of line shape distortions can largely be mitigated by tracking only selected resonance orders with negligible shape distortion, and by measuring the resonance minimum wavelength directly, rather than attempting to fit the entire resonance line shape. The results demonstrate the temperature error due to these impairments can be limited to below the 3 mK level through appropriate design choices and measurement procedures.

Optical wavefront phase-tilt measurement using Si-photonic waveguide grating couplers.

Silicon photonic wavefront phase-tilt sensors for wavefront monitoring using surface coupling grating arrays are demonstrated. The first design employs the intrinsic angle dependence of the grating coupling efficiency to determine local wavefront tilt, with a measured sensitivity of 7 dB/°. The second design connects four gratings in an interferometric waveguide circuit to determine incident wavefront phase variation across the sensor area. In this device, one fringe spacing corresponds to 2° wavefront tilt change. These sensor elements sample a wavefront incident on the chip surface without the use of bulk optic elements, fiber arrays, or imaging arrays. Both sensor elements are less than 60 µm across and are potential unit cell sensor elements for large arrays that monitor wavefront shape across an image or pupil plane in adaptive optics systems for free-space optical communications, astronomy, and beam pointing applications.

Use of CPAP Machines in the Perioperative Setting in Ambulatory Surgical Centers.

INTRODUCTION: Obstructive sleep apnea is a common sleep-related breathing disorder that is associated with significant perioperative complications. In 2012 and 2017, Society of Ambulatory Anesthesia and Society of Anesthesia and Sleep Medicine published consensus statements for the selection of patients with OSA scheduled for ambulatory surgery. Despite these recommendations, the need for a CPAP device in the immediate postoperative period at ambulatory surgical centers remains controversial because these ambulatory patients are healthier and have fewer complications. This study aims to investigate the compliance rate with this recommendation among busy ASCs. METHODS: We created a survey to investigate if ASCs require patients to bring their CPAP devices to the facility. The survey measured compliance rates of ASCs to SAMBA's recommended guidelines of having CPAP machines available. RESULTS: The survey had a response rate of 60.9% encompassing 408,147 cases among 1946 providers. Of the facilities that responded, only 59.7% of them required their patients to bring their CPAP devices on the day of surgery. Out of the 67 facilities that responded, only 25.37% reported using a CPAP machine postoperatively within the past 2 years, with the highest CPAP usage at one facility being 20 times in that 2-year period. DISCUSSION: This would mean that 40.3% of ASCs that did respond do not have access to a CPAP device on-site and may possibly lack the proper equipment needed to handle these complications. The frequency and fatality rate associated with postoperative respiratory complications requiring a CPAP device are still inconclusive, making the need for CPAP devices during perioperative management controversial. Studies further in-depth are therefore necessary to assess postoperative complications that require the use of a CPAP device to determine the urgency of ASCs implementing SAMBA's recommendations.

[Investigating postvention best practices : The Delphi method]. / Examen des meilleures pratiques de postvention : méthode Delphi.

BACKGROUND: Postvention aims to implement services adapted to the needs of a population that may be vulnerable after suicide. While a plethora of postvention programs exist, they are generally based less on solid evidence than on the judgment of health professionals. Using the Delphi method, an Australian study obtained a consensus among experts as to which postvention actions are to be engineered in a postvention program. Since no similar study has been carried out for programs in French-speaking countries, it seemed important to reproduce the same type of study and to compare the respective results. The present study is aimed at establishing a French inventory of postvention actions and at achieving a consensus among experts as to the actions to be included in a postvention program. METHODS: A systematic review of the scientific literature (PRISMA method) and the gray literature (documentation on the WEB) made it possible to identify the different actions that have been included in various postvention programs. Using the DELPHI method, experts endeavored to assess their relevance. RESULTS: An inventory of 190 postvention actions was established and they were classified according to a sequential axis (pre-event, at the time of the event, and post-event), according to type of action (environment-centered or people-centered). The experts identified 128 actions to be included in a postvention program. CONCLUSION: Convergence was observed among the experts, as they identified the practices to be encouraged following a suicide. When comparing the results in French-speaking countries to the 548 actions selected in the Australian study, we observe similarities between the two studies regarding types of postvention actions. This study provides an update for health professionals on the most relevant practices to be included in a postvention program.

Vertically tapered waveguide spot size converters fabricated via a linewidth controlled grey tone lithography for InP-based photonic integrated circuits.

We report a novel and simple fabrication process to realize vertically tapered spot size converters (SSC) on InP photonic integrated circuits. The vertical tapering was achieved via a linewidth controlled local optical dose variation, leading to a grey tone photoresist profile. The fabricated SSCs are compact, polarization insensitive and demonstrate a very high mode conversion efficiency of 95%. Integrated SSCs improved the overall loss by 5 dB giving a coupling loss as low as 1.3 dB/facet, for a lensed fibre with a mode field diameter of 3.0 µm. A good agreement was found between the fibre-to-fibre optical loss measurements and those predicted from simulations.

Molecular surveillance of hepatitis C virus genotypes identifies the emergence of a genotype 4d lineage among men in Quebec, 2001-2017.

BACKGROUND: Molecular phylogenetics are generally used to confirm hepatitis C virus (HCV) transmission events. In addition, the Laboratoire de santé publique du Québec (LSPQ) has been using molecular phylogenetics for surveillance of HCV genotyping since November 2001. OBJECTIVES: To describe the emergence of a specific lineage of HCV genotype 4d (G4d) and its characteristics using molecular phylogenetics as a surveillance tool for identifying HCV strain clustering. METHODS: The LSPQ prospectively applied Sanger sequencing and phylogenetic analysis to determine the HCV genotype on samples collected from November 2001 to December 2017. When a major G4d cluster was identified, demographic information, HIV-infection status and syphilis test results were analyzed. RESULTS: Phylogenetic analyses performed on approximately 22,000 cases identified 122 G4d cases. One major G4d cluster composed of 37 cases was singled out. Two cases were identified in 2010, 10 from 2011-2014 and 25 from 2015-2017. Cases in the cluster were concentrated in two urban health regions. Compared to the other G4d cases, cluster cases were all male (p<0.001) and more likely to be HIV-positive (adjusted risk ratio: 4.4; 95% confidence interval: 2.5-7.9). A positive syphilis test result was observed for 27 (73%) of the cluster cases. The sequences in this cluster and of four outlier cases were located on the same monophyletic lineage as G4d sequences reported in HIV-positive men who have sex with men (MSM) in Europe. CONCLUSION: Molecular phylogenetics enabled the identification and surveillance of ongoing transmission of a specific HCV G4d lineage in HIV-positive and HIV-negative men in Quebec and its cross-continental spread. This information can orient intervention strategies to avoid transmission of HCV in MSM.

VISIT-TS: A multimedia tool for population studies on tic disorders.

Population-based assessment of Tourette syndrome (TS) and other tic disorders produces a paradox. On one hand, ideally diagnosis of tic disorders requires expert observation. In fact, diagnostic criteria for TS explicitly require expert assessment of tics for a definite diagnosis. On the other hand, large-scale population surveys with expert assessment of every subject are impracticable. True, several published studies have successfully used expert assessment to find tic prevalence in a representative population (e.g. all students in a school district). However, extending these studies to larger populations is daunting. We created a multimedia tool to demonstrate tics to a lay audience, discuss their defining and common attributes, and address features that differentiate tics from other movements and vocalizations. A first version was modified to improve clarity and to include a more diverse group in terms of age and ethnicity. The result is a tool intended for epidemiological research. It may also provide additional benefits, such as more representative minority recruitment for other TS studies and increased community awareness of TS.

Rapid Quantitative Pharmacodynamic Imaging with Bayesian Estimation.

We recently described rapid quantitative pharmacodynamic imaging, a novel method for estimating sensitivity of a biological system to a drug. We tested its accuracy in simulated biological signals with varying receptor sensitivity and varying levels of random noise, and presented initial proof-of-concept data from functional MRI (fMRI) studies in primate brain. However, the initial simulation testing used a simple iterative approach to estimate pharmacokinetic-pharmacodynamic (PKPD) parameters, an approach that was computationally efficient but returned parameters only from a small, discrete set of values chosen a priori. Here we revisit the simulation testing using a Bayesian method to estimate the PKPD parameters. This improved accuracy compared to our previous method, and noise without intentional signal was never interpreted as signal. We also reanalyze the fMRI proof-of-concept data. The success with the simulated data, and with the limited fMRI data, is a necessary first step toward further testing of rapid quantitative pharmacodynamic imaging.

Photonic wire biosensor microarray chip and instrumentation with application to serotyping of Escherichia coli isolates.

A complete photonic wire molecular biosensor microarray chip architecture and supporting instrumentation is described. Chip layouts with 16 and 128 independent sensors have been fabricated and tested, where each sensor can provide an independent molecular binding curve. Each sensor is 50 µm in diameter, and consists of a millimeter long silicon photonic wire waveguide folded into a spiral ring resonator. An array of 128 sensors occupies a 2 × 2 mm2 area on a 6 × 9 mm2 chip. Microfluidic sample delivery channels are fabricated monolithically on the chip. The size and layout of the sensor array is fully compatible with commercial spotting tools designed to independently functionalize fluorescence based biochips. The sensor chips are interrogated using an instrument that delivers sample fluid to the chip and is capable of acquiring up to 128 optical sensor outputs simultaneously and in real time. Coupling light from the sensor chip is accomplished through arrays of sub-wavelength surface grating couplers, and the signals are collected by a fixed two-dimensional detector array. The chip and instrument are designed so that connection of the fluid delivery system and optical alignment are automated, and can be completed in a few seconds with no active user input. This microarray system is used to demonstrate a multiplexed assay for serotyping E. coli bacteria using serospecific polyclonal antibody probe molecules.

Glutathione S-transferase gene variations influence BU pharmacokinetics and outcome of hematopoietic SCT in pediatric patients.

BU is a key compound of conditioning regimens in children undergoing hematopoietic SCT (HSCT). Inter-individual differences in BU pharmacokinetics (PKs) might affect BU efficacy and toxicity. As BU is mainly metabolized by glutathione S-transferase (GST), we investigated the relationship between GSTA1, GSTM1 and GSTP1 genotypes with first-dose BU PKs, and the relationship with HSCT outcomes in 69 children receiving myeloablative conditioning regimen. GSTM1 null genotype correlated with higher BU exposure and lower clearance in patients older than 4 years (P ≤ 0.04). In accordance with the suggested functional role, GSTA1*A2 haplotype was associated with lower drug levels and higher drug clearance (P ≤ 0.03). Gene-dosage effect was also observed (P ≤ 0.007). GSTA1 haplotypes were associated with HSCT outcomes. Patients with two copies of haplotype *A2 had better event free survival (P=0.03). In contrast, homozygous individuals for haplotypes *B and *B1 had higher occurrence of veno-occlusive disease (P=0.009). GSTM1 null individuals older than 4 years had more frequently graft versus host disease (P=0.03). In conclusion, we showed that GST gene variants influence BU PK and outcomes of HSCT in children. A model for the dosage adjustment with the inclusion of genetic and non-genetic factors should be evaluated in a future prospective validation cohort.

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.

Label-free biosensor array based on silicon-on-insulator ring resonators addressed using a WDM approach.

We report a silicon-on-insulator ring resonator biosensor array with one output port, using wavelength division multiplexing as the addressing scheme. With the use of on-chip referencing for environmental drift cancellation, simultaneous monitoring of multiplexed molecular bindings is demonstrated, with a resolution of 0.3 pg/mm(2) (40 ag of total mass) for protein concentrations over 4 orders of magnitude down to 20 pM. Reactions are measured over time periods as long as 3 h with high stability.

Influence of GST gene polymorphisms on busulfan pharmacokinetics in children.

Busulfan (BU) is a key compound in conditioning myeloablative regimens for children undergoing hematopoietic stem cell transplantation (HSCT). There are wide interindividual differences in BU pharmacokinetics, which increase the risk of veno-occlusive disease, graft rejection and disease relapse. As BU is mainly metabolized by glutathione S-transferase (GST), it is hypothesized that functional polymorphisms in GST genes may explain in part the variability in BU pharmacokinetics. We analyzed polymorphisms in GSTA1 (C-69T, A-513G, G-631T, C-1142G), GSTM1 (deletion) and GSTP1 (A1578G, C2293T) genes in 28 children undergoing HSCT. All patients had individualized dosing based on pharmacokinetics after the first dose of intravenous BU. GSTM1-null individuals had higher drug exposure (P(Cmax)=0.008; P(AUC)=0.003; P(Css)=0.02) and lower clearance (P(CL)=0.001). Multivariate regression models showed that, other than the drug dose and age, the GSTM1 genotype was the best predictor of first-dose pharmacokinetic variability. GSTM1-null patients also received lower cumulative BU doses (P=0.02). No association was found between BU exposure and major GSTA1 or GSTP1 gene variants. In children, GSTM1 polymorphism seems to modify BU pharmacokinetics after intravenous drug administration.

Silicon photonic wire biosensor array for multiplexed real-time and label-free molecular detection.

We demonstrate a silicon photonic wire waveguide biosensor array chip for the simultaneous monitoring of different molecular binding reactions. The chip is compatible with automated commercial spotting tools and contains a monolithically integrated microfluidic channel for sample delivery. Each array sensor element is a 1.8-mm-long spiral waveguide folded within a 130 microm diameter spot and is incorporated in a balanced Mach-Zehnder interferometer with a near temperature independent response. The sensors are arranged in a 400 microm spacing grid pattern and are addressed through cascaded 1x2 optical power splitters using light from a single input fiber. We demonstrate the real-time monitoring of antibody-antigen reactions using complementary and mismatched immunoglobulin G receptor-analyte pairs and bovine serum albumin. The measured level of detection for each sensor element corresponds to a surface coverage of less than 0.3 pg/mm(2).

The soul's wisdom: stories of living and dying.

Cancer can lead to spiritual transformation, which can be seen as a form of alchemy. During this process, patients, family members, and even professional caregivers can find themselves having spiritual experiences that go beyond any they had previously encountered. This paper provides qualitative descriptions of the "Field" or "Soul Wisdom" experienced by patients and caregivers.

Cross-cultural adaptation and validation of the Questionnaire for Pruritus Assessment for use in the French Canadian burn survivor population.

BACKGROUND: Severe pruritus after burn continues to be a clinical challenge. To address this challenge, thorough documentation of burn survivors' itch experience is required. A "Questionnaire for Pruritus Assessment" has been developed to capture the sensory and affective experiences associated with itch as well as its functional and quality of life implications, but to evaluate the Quebec burn survivor population, a Canadian French version is required. Thus, the purpose of this study was to generate a Canadian French cross-cultural adaptation of the questionnaire suitable for the burn survivor population. METHODS: Cross-cultural adaptation followed six steps: forward translation into Canadian French, back translations into English, resolution between the two versions, synthesis of the Canadian French versions, revision by a committee of experts, and testing of the pre-final version. RESULTS: The adaptation process resolved issues surrounding translation, content validity, burn survivor-specific modifications, and format, resulting in a Canadian French pre-final version that was pilot-tested among 32 burn survivors. Content validity of the Canadian French version was assessed by a committee of experts and the participants. The results showed good item completion and adequate distribution of scores without a ceiling or floor effect. CONCLUSIONS: This study resulted in a Canadian French version of the "Questionnaire for Pruritus Assessment" that can confidently be compared to other investigations utilizing the same tool. The adapted questionnaire also provides a valuable data collection means, enabling more thorough documentation of the burn survivor itch experience.

Results of an unrelated transplant search strategy using partially HLA-mismatched cord blood as an immediate alternative to HLA-matched bone marrow.

Cord blood (CB) is an alternative to other sources of stem cells for transplantation. However, the impact of including CB in the initial strategy of unrelated graft search in a cohort of patients has been the object of limited analysis. Here, we report the results of such a strategy in 91 consecutive children. Absence of mismatch was required for adult donors, and up to two mismatches were allowed for CB grafts, with a nucleated cell dose over 2.5 x 10(7) cells/kg. A graft was found for 84 of the 85 children who remained available for a 3-month search. In all, 64 patients were transplanted, 36 with CB and 28 with bone marrow (BM). Primary graft failure, acute grade II-IV and extensive chronic graft-versus-host disease occurred in five, five and zero CB, and in three, one and two BM patients, respectively. The 3-year survival was 59% in CB and 57% in BM patients. Accepting CB as a source of stem cells offers a graft to almost every child in need of an unrelated transplantation, with a probability of survival similar to that of unrelated BM transplantation.

Intravenous busulfan for allogeneic hematopoietic stem cell transplantation in infants: clinical and pharmacokinetic results.

SUMMARY: High-dose busulfan is an important component of myeloablative regimens. Variable drug exposure may occur following oral administration. Therefore, the use of intravenous busulfan has been advocated. Previous work has suggested a cumulative dosage of 16 mg/kg for haematopoietic transplantation in children less than 3 years of age, but only limited data are available in infants. Pharmacokinetics of intravenous busulfan administered at the suggested dosage were studied in 14 infants (median age 4.7 months). Busulfan plasma concentrations were measured by either GC-MS or HPLC-UV. In seven patients, the dose was decreased to target an area- under- the- curve of 600-1300 micromol min. The median total dose given was 13.8 mg/kg. All patients engrafted. Severe veno-occlusive disease occurred in one patient. Our study demonstrates that a cumulative dosage of 16 mg/kg is associated with higher exposure than expected in infants. We suggest an initial dose of 0.8 mg/kg followed by pharmacokinetically guided dose adjustment.