Radiation hardness of open Fabry-Pérot microcavities.

High-finesse microcavities offer a platform for compact, high-precision sensing by employing high-reflectivity, low-loss mirrors to create effective optical path lengths that are orders of magnitude larger than the device geometry. Here, we investigate the radiation hardness of Fabry-Pérot microcavities formed from dielectric mirrors deposited on the tips of optical fibers. The microcavities are irradiated under both conventional (∼ 0.1 Gy/s) and ultrahigh (FLASH, ∼ 20 Gy/s) radiotherapy dose rates. Within our measurement sensitivity of ∼ 40 ppm loss, we observe no degradation in the mirror absorption after irradiation with over 300 Gy accumulated dose. This result highlights the excellent radiation hardness of the dielectric mirrors forming the cavities, enabling new optics-based, real-time, in-vivo, tissue-equivalent radiation dosimeters with ∼ 10 micron spatial resolution (our motivation), as well as other applications in high-radiation environments.

Sideband cavity absorption readout (SideCAR) with a robust frequency lock.

We present a simple, continuous, cavity-enhanced optical absorption measurement technique based on high-bandwidth Pound-Drever-Hall (PDH) sideband locking. The technique provides a resonant amplitude quadrature readout that can be mapped onto the cavity's internal loss rate and is naturally compatible with weak probe beams. With a proof-of-concept 5-cm-long Fabry-Perot cavity, we measure an absorption sensitivity ∼10-10cm-1/Hz from 30 kHz to 1 MHz, and a minimum value of 6.6×10-11cm-1/Hz at 100 kHz, with 38 µW collected from the cavity's circulating power.

Gene profiling reveals a contact allergy signature in most positive Amerchol L-101 patch test reactions.

BACKGROUND: Diagnosis of contact allergy (CA) to Amerchol L-101 (AL-101), a marker for lanolin allergy, is problematic. Positive patch test reactions are frequently doubtful or weakly positive and difficult to associate with clinical relevance. OBJECTIVE: To gain further insight on the allergic or irritant nature of skin reactions induced by AL-101 patch test. METHODS: We re-tested in a dose-response fashion, 10 subjects with AL-101 CA and performed comprehensive transcriptomic analysis (gene arrays, quantitative real-time polymerase chain reaction [qRT-PCR]) of samples of their skin reactions. RESULTS: Eight of the 10 CA subjects reacted positively upon re-test, whereas two did not react. Most of AL-101 positive patch tests expressed an allergy signature with strong activation of gene modules associated with adaptive immunity and downregulation of cornification pathway genes. In addition, the breadth of gene modulation correlated with the magnitude of patch test reactions and the concentration of AL-101 applied. However, we observed that some of the positive patch test reactions to AL-101 expressed no/few allergy biomarkers, suggesting the induction of an irritant skin inflammation in these samples. CONCLUSIONS: This study confirms that AL-101 is an allergen that can cause both contact allergy and contact irritation. Our results also highlight that molecular profiling might help to strengthen clinical diagnosis.

Measurement of Cortical Bone Elasticity Tensor with Resonant Ultrasound Spectroscopy.

Resonant Ultrasound Spectroscopy estimates the stiffness coefficients of a material from the free resonant frequencies of a single specimen. It is particularly suitable for complete stiffness characterization of anisotropic materials available only as small samples (typically a few mm), and it does not suffer from some limitations associated to quasi-static mechanical test and ultrasound wave velocity measurements. RUS has been used for decades on geological samples and single crystals, but was until recently not applied to mineralized tissues such as bone. The reason is the significant mechanical damping presents in these materials, which causes the resonant peaks to overlap and prevent a direct measurement of the resonant frequencies. This chapter describes the use of RUS for the elastic characterization of mineralized tissues, cortical bone in particular. All steps are described, from sample preparation and measurement setup to signal processing and data analysis, including the developments and adaptions necessary to overcome the difficulties linked to damping. Viscoelastic characterization, from the width of the resonant peaks, is also presented. Mostly technical aspects are developed in this chapter, while the data obtained from RUS on several collections of mineralized tissues specimens are presented and discussed in Chap. 13.

Documenting the Anisotropic Stiffness of Hard Tissues with Resonant Ultrasound Spectroscopy.

Recent advances in resonant ultrasound spectroscopy (RUS) leverage accurate measurements of the anisotropic stiffness of hard tissues at millimeter scale. RUS is the only available technique to date to assess the entire stiffness tensor of bone from a unique rectangular parallelepiped specimen. Accurately measured stiffness constants are required for bone mechanics models and may provide information on some fundamental aspects of hard tissues biology such as regulation of bone mass, remodeling and healing. In this chapter, we review the anisotropic stiffness data of human hard tissues measured with RUS, mostly during the last decade. Hard tissues covered here include human enamel and dentin, cortical bone from the femur and tibia of human adults, and child cortical bone tissue, accounting for 288 specimens in total. Data was collected in the literature and from previous works of our group. We performed a comparative study to depict the differences in the elastic properties of these hard tissues. Our objectives were to: (1) document the range of anisotropic stiffness constants in human hard tissues (orthotropic or transverse isotropic symmetry); and (2) provide empirical laws between mass density and anisotropic stiffness of cortical bone at different skeletal sites. Finally, we discuss the challenges and perspectives to use RUS for large collections of specimens.

Ultrasound Computed Tomography.

This chapter presents theoretical, numerical, and experimental frameworks for the use of Ultrasound Computed Tomography (USCT) for cortical bone tissue imaging. Most of the research conducted on this topic concerns adult bone, although some work presented in this chapter is specific to the study of child bone. USCT is recognized as a powerful method for soft tissue imaging. In bone imaging, the difficulties arise from the very high impedance contrast between tissues which alters the propagation of the ultrasonic waves and limits the linear inversion algorithms used. Solutions consist in optimally assessing non-linear effects in an iterative approach aiming at local linearization. When the problem can be reduced to the study of a fluid-like cavity buried in an elastic cylinder surrounded by water, the signal processing and/or compound algorithms can be added as an extension to the linear algorithms. The main limitation of these methods is the heavy experimental costs involved. We have then suggested the introduction of purely numerical non-linear full-waveform inversion algorithms. The performances and the limitations of these linear and non-linear methods applied to cortical bone tissue imaging problems are overviewed and discussed.

Identifying early pulmonary arterial hypertension biomarkers in systemic sclerosis: machine learning on proteomics from the DETECT cohort.

Pulmonary arterial hypertension (PAH) is a devastating complication of systemic sclerosis (SSc). Screening for PAH in SSc has increased detection, allowed early treatment for PAH and improved patient outcomes. Blood-based biomarkers that reliably identify SSc patients at risk of PAH, or with early disease, would significantly improve screening, potentially leading to improved survival, and provide novel mechanistic insights into early disease. The main objective of this study was to identify a proteomic biomarker signature that could discriminate SSc patients with and without PAH using a machine learning approach and to validate the findings in an external cohort.Serum samples from patients with SSc and PAH (n=77) and SSc without pulmonary hypertension (non-PH) (n=80) were randomly selected from the clinical DETECT study and underwent proteomic screening using the Myriad RBM Discovery platform consisting of 313 proteins. Samples from an independent validation SSc cohort (PAH n=22 and non-PH n=22) were obtained from the University of Sheffield (Sheffield, UK).Random forest analysis identified a novel panel of eight proteins, comprising collagen IV, endostatin, insulin-like growth factor binding protein (IGFBP)-2, IGFBP-7, matrix metallopeptidase-2, neuropilin-1, N-terminal pro-brain natriuretic peptide and RAGE (receptor for advanced glycation end products), that discriminated PAH from non-PH in SSc patients in the DETECT Discovery Cohort (average area under the receiver operating characteristic curve 0.741, 65.1% sensitivity/69.0% specificity), which was reproduced in the Sheffield Confirmatory Cohort (81.1% accuracy, 77.3% sensitivity/86.5% specificity).This novel eight-protein biomarker panel has the potential to improve early detection of PAH in SSc patients and may provide novel insights into the pathogenesis of PAH in the context of SSc.

Unique molecular signatures typify skin inflammation induced by chemical allergens and irritants.

BACKGROUND: Skin exposure to chemicals may induce an inflammatory disease known as contact dermatitis (CD). Distinguishing the allergic and irritant forms of CD often proves challenging in the clinic. METHODS: To characterize the molecular signatures of chemical-induced skin inflammation, we conducted a comprehensive transcriptomic analysis on the skin lesions of 47 patients with positive patch tests to reference contact allergens and nonallergenic irritants. RESULTS: A clear segregation was observed between allergen- and irritant-induced gene profiles. Distinct modules pertaining to the epidermal compartment, metabolism, and proliferation were induced by both contact allergens and irritants; whereas only contact allergens prompted strong activation of adaptive immunity, notably of cytotoxic T-cell responses. Our results also confirmed that: (a) unique pathways characterize allergen- and irritant-induced dermatitis; (b) the intensity of the clinical reaction correlates with the magnitude of immune activation. Finally, using a machine-learning approach, we identified and validated several minimal combinations of biomarkers to distinguish contact allergy from irritation. CONCLUSION: These results highlight the value of molecular profiling of chemical-induced skin inflammation for improving the diagnosis of allergic versus irritant contact dermatitis.

Comparison of Photo-optical Transcutaneous Oxygen Tension Measurement with Electro-chemical Transcutaneous Oxygen Tension Measurement in Patients with Arterial Claudication.

PURPOSE: Photo-optical TCpO2 (pTCpO2) has been proposed as a new method to determine the partial oxygen pressure of the lower extremity in patients with peripheral arterial disease. It is aimed to determine the level of agreement between pTCpO2 and the traditional electro-chemical transcutaneous oxygen tension measurement (eTCpO2). METHODS: Eighteen patients with intermittent claudication underwent simultaneous ankle-brachial index measurement, toe-pressure, pTCpO2 and eTCpO2 tests. Oxygen tension levels were measured on anterior chest and calf prior in rest (T0), during induced ischemia (T1) and after blood flow restoration (T2). TCpO2 agreement was assessed according to the principles of Bland and Altman. RESULTS: Absolute average TCpO2 values differed between eTCpO2 and pTCpO2 for calf in T2 (38,1 mmHg (σ 14,4) vs. 49,8 (σ 22.3) with P = 0.35). The Bland-Altman plots demonstrated eTCpO2 and pTCpO2 bias of 3,7 mmHg (σ 18,8), 11,6 mmHg (σ 17,6) and 6,7 mmHg (σ 23,5) for T0, T1 and T2 for the calf. CONCLUSION: pTCpO2 is in agreement with eTCpO2 in measuring pO2 levels of the lower extremity in rest and during induced ischemia in patients with vascular claudication. The large variability between eTCpO2 and pTCpO2 should be accounted for, while pTCpO2 values have a tendency to demonstrate higher values in comparison to eTCpO2.

Low-Level Light Therapy Downregulates Scalp Inflammatory Biomarkers in Men With Androgenetic Alopecia and Boosts Minoxidil 2% to Bring a Sustainable Hair Regrowth Activity.

BACKGROUND AND OBJECTIVES: Low-level light therapies using visible to infrared light are known to activate several cellular functions, such as adenosine triphosphate and nitric oxide synthesis. However, few clinical observations report its biological consequences for skin and scalp homeostasis. Since scalp inflammation was recognized as a potential physiological obstacle to the efficacy of the reference hair regrowth drug Minoxidil in vivo and since perifollicular inflammation is the hallmark of about 50%-70% follicular units in androgenetic alopecia, we decided to investigate whether the anti-inflammatory activity of LLLT/GentleWaves® device were assigned to L'Oréal by Light BioScience L.L.C., Virginia Beach, VA (US) could enhance hair regrowth activity of Minoxidil. STUDY DESIGN/MATERIALS AND METHODS: We conducted a first experimental clinical study on 64 men with androgenetic alopecia using LLLT/GentleWaves®, 590-nm predominant wavelength 70 seconds, specifically pulsed once per day, for 3 days, and we performed a whole-genome analysis of treated scalp biopsies. In a second clinical study, including 135 alopecic volunteers, we evaluated the hair regrowth activity in response to the upgraded LLLT/GentleWaves® device and Minoxidil. RESULTS: In the first clinical study, whole-genome analysis of treated scalp biopsies showed downregulation of scalp inflammatory biomarkers, such as AP1/FOSB messenger RNA (mRNA) and mir21, together with the disappearance of CD69 mRNA, specific to scalp-infiltrating T cells of about 50% of the studied volunteers prior to the LLLT/GentleWaves® treatment. In the second clinical study, we observed that LLLT/GentleWaves® was able to boost the hair regrowth activity of a Minoxidil 2% lotion to the extent of the highest concentration (5%) in terms of efficacy, number of responders, and perceived performance. CONCLUSIONS: Altogether, these observations suggest the potential benefit of LLLT/GentleWaves® as a noninvasive adjunctive technology for skin and scalp conditions, where a mild perifollicular inflammation is involved. Lasers Surg. Med. 2021. Copyright © 2021 Wiley Periodicals LLC.

Ultrafast imaging of cell elasticity with optical microelastography.

Elasticity is a fundamental cellular property that is related to the anatomy, functionality, and pathological state of cells and tissues. However, current techniques based on cell deformation, atomic force microscopy, or Brillouin scattering are rather slow and do not always accurately represent cell elasticity. Here, we have developed an alternative technique by applying shear wave elastography to the micrometer scale. Elastic waves were mechanically induced in live mammalian oocytes using a vibrating micropipette. These audible frequency waves were observed optically at 200,000 frames per second and tracked with an optical flow algorithm. Whole-cell elasticity was then mapped using an elastography method inspired by the seismology field. Using this approach we show that the elasticity of mouse oocytes is decreased when the oocyte cytoskeleton is disrupted with cytochalasin B. The technique is fast (less than 1 ms for data acquisition), precise (spatial resolution of a few micrometers), able to map internal cell structures, and robust and thus represents a tractable option for interrogating biomechanical properties of diverse cell types.

Ultrasonic Imaging of High-contrasted Objects Based on Full-waveform Inversion: Limits under Fluid Modeling.

Quantitative ultrasound techniques have been previously used to evaluate biological hard tissues, characterized by a large acoustic impedance contrast. Here, we are interested in the imaging of experimental data from different test-targets with high acoustic impedance contrast, using the Full Waveform Inversion (FWI) method to solve the inverse problem. This method is based on high-resolution numerical modeling of the forward problem of interaction between waves and medium, considering the full time series. To reduce the complexity of the numerical implementation, the model considers a fluid medium. Therefore, the aim is to evaluate the precision of the reconstruction under this assumption for materials with a different level of attenuation of shear waves, to study the limits of this hypothesis. Images of the sound speed obtained using the experimental data are presented, and the precision of the reconstruction is evaluated. Future work should include viscoelastic materials.

Monitored wet-etch removal of individual dielectric layers from high-finesse Bragg mirrors.

It is prohibitively expensive to deposit customized dielectric coatings on individual optics. One solution is to batch-coat many optics with extra dielectric layers, then remove layers from individual optics as needed. Here we present a low-cost, single-step, monitored wet etch technique for reliably removing individual SiO2 and Ta2O5 dielectric layers, in this case from a high-reflectivity fiber mirror. By immersing in acid and monitoring off-band reflected light, we show it is straightforward to iteratively (or continuously) remove six bilayers. At each stage, we characterize the coating performance with a Fabry-Pérot cavity, observing the expected stepwise decrease in finesse from 92,000 ± 3,000 to 3, 950 ± 50, finding no evidence of added optical losses. The etch also removes the fiber's sidewall coating after a single bilayer, and, after six bilayers, confines the remaining coating to a 60-µm-diameter pedestal at the center of the fiber tip. Vapor etching above the solution produces a tapered "pool cue" cladding profile, reducing the fiber diameter (nominally 125 µm) to 95 µm at an angle of ∼0.3° near the tip. Finally, we note that the data generated by this technique provides a sensitive estimate of the layers' optical depths. This technique could be readily adapted to free-space optics and other coatings.

Antigen-Induced but Not Innate Memory CD8 T Cells Express NKG2D and Are Recruited to the Lung Parenchyma upon Viral Infection.

The pool of memory-phenotype CD8 T cells is composed of Ag-induced (AI) and cytokine-induced innate (IN) cells. IN cells have been described as having properties similar to those of AI memory cells. However, we found that pathogen-induced AI memory cells can be distinguished in mice from naturally generated IN memory cells by surface expression of NKG2D. Using this marker, we described the increased functionalities of AI and IN memory CD8 T cells compared with naive cells, as shown by comprehensive analysis of cytokine secretion and gene expression. However, AI differed from IN memory CD8 T cells by their capacity to migrate to the lung parenchyma upon inflammation or infection, a process dependent on their expression of ITGA1/CD49a and ITGA4/CD49d integrins.

Flexure-tuned membrane-at-the-edge optomechanical system.

We introduce a passively-aligned, flexure-tuned cavity optomechanical system in which a membrane is positioned microns from one end mirror of a Fabry-Perot optical cavity. By displacing the membrane through gentle flexure of its silicon supporting frame (i.e., to ∼80 m radius of curvature (ROC)), we gain access to the full range of available optomechanical couplings, finding also that the optical spectrum exhibits none of the abrupt discontinuities normally found in "membrane-in-the-middle" (MIM) systems. More aggressive flexure (3 m ROC) enables >15 µm membrane travel, milliradian tilt tuning, and a wavelength-scale (1.64 ± 0.78 µm) membrane-mirror separation. We also provide a complete set of analytical expressions for this system's leading-order dispersive and dissipative optomechanical couplings. Notably, this system can potentially generate orders of magnitude larger linear dissipative or quadratic dispersive strong coupling parameters than is possible with a MIM system. Additionally, it can generate the same purely quadratic dispersive coupling as a MIM system, but with significantly suppressed linear dissipative back-action (and force noise).

Prevalence of Convergence Insufficiency-Type Symptomatology in Parkinson's Disease.

BACKGROUND: Individuals with Parkinson's disease (PD) often present with visual symptoms (e.g., difficulty in reading, double vision) that can also be found in convergence insufficiency (CI). Our objective was to estimate the prevalence of CI-type visual symptomatology in individuals with PD, in comparison with controls. METHODS: Participants ≥50 years with (n=300) and without (n=300) PD were recruited. They were administered the Convergence Insufficiency Symptom Survey (CISS-15) over the phone. A score of ≥21 on the CISS-15, considered positive for CI-type symptomatology, served as the cutoff. Data from individuals (n=87 with, n=94 without PD) who were approached but who reported having a known oculovisual condition were analysed separately. Student's t test and chi-square at the 0.05 level were employed for statistical significance. RESULTS: A total of 29.3% of participants with versus 7.3% without PD presented with a score of ≥21 on the CISS-15 (p=0.001). Of the participants having a known oculovisual condition, 39.1% with versus 19.1% without PD presented with a score of ≥21 on the CISS-15 (p=0.01). CONCLUSIONS: The prevalence of CI-type visual symptoms is higher in individuals with versus without PD whether or not they have a coexisting oculovisual condition. These results suggest that PD per se places individuals with the disease at greater risk of visual symptomatology. These results further underline the importance of providing regular eye exams for individuals with PD.

Social disparities in children's exposure to secondhand smoke in privately owned vehicles.

INTRODUCTION: Secondhand smoke (SHS) can quickly attain high concentrations in cars, posing health risks to passengers and especially to children. This paper assesses whether there are social disparities in children's exposure to SHS in privately owned vehicles. METHODS: On weekday mornings and afternoons from September to November 2011, trained observers were stationed at 100 selected street intersections in Montreal, Canada. For each car transporting at least one passenger aged 0-15 years travelling through the intersection, observers recorded the estimated age of the youngest child in the car, whether any occupant was smoking and the licence plate number of the car. Licence plate numbers were linked to an area material deprivation index based on the postal code of the neighbourhood in which the car was registered. RESULTS: Smoking was observed in 0.7% of 20 922 cars transporting children. There was an apparent dose-response in the association between area material deprivation level and children's exposure to SHS in cars. Children travelling in cars registered in the most disadvantaged areas of Montreal were more likely to be exposed to SHS than children travelling in cars registered in the most advantaged areas (unadjusted OR=3.46, 95% CI 1.99 to 6.01). CONCLUSIONS: This study revealed social disparities in children's exposure to SHS in privately owned vehicles.

Visual impairment in older institutionalised Canadian seniors with dementia.

PURPOSE: To estimate the prevalence of visual impairment (VI) in a sub-population of Canadian long-term care facilities, i.e. residents affected by dementia. METHODS: This study was conducted in the long-term care facility units at the Institut universitaire de gériatrie de Montréal. All residents ≥65 years old (y.o.), having a clinical diagnosis of dementia, and able to understand French or English, were eligible for participation in the study. All residents participating in the study received a complete eye exam by an experienced optometrist. For the purpose of the study, VI was defined as a distance visual acuity (VA) <6/12 (0.30 logMAR, 20/40) in the better seeing eye. RESULTS: One hundred and fifty residents, 68-102 y.o. took part into the study. All participants had a diagnosis of dementia recorded in their clinical chart. VI was present in 37.3% (95% CI: 29.1-46.1%) (n = 50) of residents in whom monocular VA could be measured. Ocular refraction for their better seeing eye improved the VA to ≥6/12 (0.30 logMAR, 20/40) in 40% (n = 20) of those 50 residents. When VI remained after refraction, it was due in order of frequency to cataract, age-related macular degeneration, and primary open angle glaucoma. CONCLUSIONS: Our data showed that an appreciable proportion (37.3%) of older residents with dementia also have VI, and that VI can be corrected in many by updating their refraction. Others could potentially be helped through cataract surgery. It is therefore important to offer regular eye care services to those residents, knowing that many are not able to express their visual needs.

Forward and inverse viscoelastic wave scattering by irregular inclusions for shear wave elastography.

Inversion methods in shear wave elastography use simplifying assumptions to recover the mechanical properties of soft tissues. Consequently, these methods suffer from artifacts when applied to media containing strong stiffness contrasts, and do not provide a map of the viscosity. In this work, the shear wave field recorded inside and around an inclusion was used to estimate the viscoelastic properties of the inclusion and surrounding medium, based on an inverse problem approach assuming local homogeneity of both media. An efficient semi-analytical method was developed to model the scattering of an elastic wave by an irregular inclusion, based on a decomposition of the field by Bessel functions and on a decomposition of the boundaries as Fourier series. This model was validated against finite element modeling. Shear waves were experimentally induced by acoustic radiation force in soft tissue phantoms containing stiff and soft inclusions, and the displacement field was imaged at a high frame rate using plane wave imaging. A nonlinear least-squares algorithm compared the model to the experimental data and adjusted the geometrical and mechanical parameters. The estimated shear storage and loss moduli were in good agreement with reference measurements, as well as the estimated inclusion shape. This approach provides an accurate estimation of geometry and viscoelastic properties for a single inclusion in a homogeneous background in the context of radiation force elastography.

Precision resonance tuning and design of SiN photonic crystal reflectors.

Photonic crystal reflector (PCR) membranes exhibit a resonantly enhanced normal-incidence reflectivity. Many applications require this resonance to occur at a specific wavelength, however, imposing geometrical tolerances that are not reliably achieved with standard nanolithography. Here we finely tune the resonant wavelength of a freestanding Si3N4 PCR membrane with iterative hydrofluoric acid etches, achieving a 57 nm thin crystal with a resonant wavelength 0.15 nm (0.04 linewidths) away from our target (1550 nm). This thin crystal exhibits a broader, shallower transmission dip than its simulated response to plane waves, and we identify two causes related to beam collimation. Finally, we present a series of simulations and general design considerations for realizing robust, high-reflectivity resonances.