Effect of frequency compression on fricative perception between normal-hearing English and Mandarin listeners.

High-frequency speech information is susceptible to inaccurate perception in even mild to moderate forms of hearing loss. Some hearing aids employ frequency-lowering methods such as nonlinear frequency compression (NFC) to help hearing-impaired individuals access high-frequency speech information in more accessible lower-frequency regions. As such techniques cause significant spectral distortion, tests such as the S-Sh Confusion Test help optimize NFC settings to provide high-frequency audibility with the least distortion. Such tests have been traditionally based on speech contrasts pertinent to English. Here, the effects of NFC processing on fricative perception between English and Mandarin listeners are assessed. Small but significant differences in fricative discrimination were observed between the groups. The study demonstrates possible need for language-specific clinical fitting procedures for NFC.

Depth-dependent mechanical properties of the human cornea by uniaxial extension.

The purpose of this study was to investigate the depth-dependent biomechanical properties of the human corneal stroma under uniaxial tensile loading. Human stroma samples were obtained after the removal of Descemet's membrane in the course of Descemet's membrane endothelial keratoplasty (DMEK) transplantation. Uniaxial tensile tests were performed at three different depths: anterior, central, and posterior on 2 × 6 × 0.15 mm strips taken from the central DMEK graft. The measured force-displacement data were used to calculate stress-strain curves and to derive the tangent modulus. The study showed that mechanical strength decreased significantly with depth. The anterior cornea appeared to be the stiffest, with a stiffness approximately 18% higher than that of the central cornea and approximately 38% higher than that of the posterior layer. Larger variations in mechanical response were observed in the posterior group, probably due to the higher degree of alignment of the collagen fibers in the posterior sections of the cornea. This study contributes to a better understanding of the biomechanical tensile properties of the cornea, which has important implications for the development of new treatment strategies for corneal diseases. Accurate quantification of tensile strength as a function of depth is critical information that is lacking in human corneal biomechanics to develop numerical models and new treatment methods.

Efficacy of customized corneal crosslinking versus standard corneal crosslinking in patients with progressive keratoconus (C-CROSS study): study protocol for a randomized controlled trial.

BACKGROUND: Keratoconus is a degenerative disorder of the cornea leading to a protrusion and thinning with loss of visual acuity. The only treatment to halt the progression is corneal crosslinking (CXL), which uses riboflavin and UV-A light to stiffen the cornea. Recent ultra-structural examinations show that the disease is regional and does not affect the entire cornea. Treating only the affected zone with CXL could be as good as the standard CXL, that treats the entire cornea. METHODS: We set up a multicentre non-inferiority randomized controlled clinical trial comparing standard CXL (sCXL) and customized CXL (cCXL). Patients between 16 and 45 years old with progressive keratoconus were included. Progression is based on one or more of the following changes within 12 months: 1 dioptre (D) increase in keratometry (Kmax, K1, K2); or 10% decrease of corneal thickness; or 1 D increase in myopia or refractive astigmatism, requiring corneal crosslinking. DISCUSSION: The goal of this study is to evaluate whether the effectiveness of cCXL is non-inferior to sCXL in terms of flattening of the cornea and halting keratoconus progression. Treating only the affected zone could be beneficial for minimalizing the risk of damaging surrounding tissues and faster wound healing. Recent non-randomized studies suggest that a customized crosslinking protocol based on the tomography of the patient's cornea may stop the progression of keratoconus and result in flattening of the cornea. TRIAL REGISTRATION: This study was prospectively registered at ClinicalTrials.gov on August 31st, 2020, the identifier of the study is NCT04532788.

Orientation and depth dependent mechanical properties of the porcine cornea: Experiments and parameter identification.

The porcine cornea is a standard animal model in ophthalmic research, making its biomechanical characterization and modeling important to develop novel treatments such as crosslinking and refractive surgeries. In this study, we present a numerical model of the porcine cornea based on experimental measurements that captures both the depth dependence and orientation dependence of the mechanical response. The mechanical parameters of the established anisotropic hyperelastic material models of Gasser, Holzapfel and Ogden (HGO) and Markert were determined using tensile tests. Corneas were cut with a femtosecond laser in the anterior (100 µm), central (350 µm), and posterior (600 µm) regions into nasal-temporal, superior-inferior, and diagonal strips of 150 µm thickness. These uniformly thick strips were tested at a low speed using a single-axis testing machine. The results showed that the corneal mechanical properties remained constant in the anterior half of the cornea regardless of orientation, but that the material softened in the posterior layer. These results are consistent with the circular orientation of collagen observed in porcine corneas using X-ray scattering. In addition, the parameters obtained for the HGO model were able to reproduce the published inflation tests, indicating that it is suitable for simulating the mechanical response of the entire cornea. Such a model constitutes the basis for in silico platforms to develop new ophthalmic treatments. In this way, researchers can match their experimental surrogate porcine model with a numerical counterpart and validate the prediction of their algorithms in a complete and accessible environment.

Corneal Biomechanics and Intraocular Pressure Following Scleral Lens Wear in Penetrating Keratoplasty and Keratoconus.

OBJECTIVE: To compare corneal biomechanics and intraocular pressure (IOP) in keratoconus and penetrating keratoplasty eyes before and after nonfenestrated scleral lens wear. METHODS: Twenty-three participants were enrolled, and 37 eyes were included in the analysis (11 penetrating keratoplasty and 26 keratoconus). A range of corneal biomechanical parameters and IOP were measured using the CORVIS ST before and after 8 hr of nonfenestrated scleral lens wear (Keracare, Acculens, Denver, CO). RESULTS: Before lens wear, penetrating keratoplasty eyes displayed significantly greater median values for central corneal thickness (97 µm thicker, P=0.02), IOP (3.89 mm Hg higher, P=0.01), and biomechanical parameter A2 length (0.48 mm longer, P=0.003) compared with keratoconic eyes. No significant changes in corneal biomechanical parameters or IOP were observed after scleral lens wear in either group (all P>0.05). CONCLUSION: Although nonfenestrated scleral contact lenses can induce a subatmospheric pressure after lens settling and compress tissue surrounding the limbus, no significant changes were detected in the corneal biomechanical parameters studied using CORVIS ST after scleral lens wear in eyes with penetrating keratoplasty and keratoconus.

The new world of philanthropy: How changing financial behavior, public policies, and COVID-19 affect nonprofit fundraising and marketing.

Evolving financial behavior, an unpredictable public policy atmosphere, and an unparalleled global pandemic have collaborated to disrupt nonprofit fundraising. The COVID-19 pandemic alone exacerbated consumer demands for nonprofit services while curtailing nonprofit organizations' ability to fundraise. Without fundraising, nonprofit organizations cannot achieve their mission or support their causes, leading to a precarious situation for societal well-being. Meanwhile, consumers are changing their financial behaviors, with younger generations often going cashless. At the same time, governments continue to change policies that affect nonprofit organizations. In keeping with the transformative consumer research movement, the present study provides a conceptual framework for the state of nonprofit fundraising amid the challenges associated with changes in financial behavior and public policy, coupled with the effects of the global pandemic. Marketing strategies for fundraising success are presented to aid nonprofits going forward and serve societal interests.

Shannon entropy and degree of polarization of a speckle pattern.

The dependence of the Shannon entropy (SE) of a speckle pattern on the degree of polarization (DoP) of the pattern is investigated both experimentally and numerically. The superposition of two uncorrelated speckle patterns with polarization diversity is utilized to control the DoP of the superposed speckle pattern, and the SE of the pattern is estimated from the determined probability density function of intensity of the pattern. The SE is observed to be increasing quadratically with the DoP of the speckle pattern. The experimental observations are supported by the numerical studies. As the change of the SE indicates a change in the randomness of the intensity distribution, the variation of the standard deviation of intensity with the DoP is also investigated. Moreover, a linear relation between the SE and the standard deviation of intensity of a speckle pattern is also established.

Polarization-based intensity correlation of a depolarized speckle pattern.

A different kind of intensity correlation, denoted as polarization-based intensity correlation (PBIC), is proposed and demonstrated to investigate the correlation between different polarizations of a depolarized speckle pattern (DSP), which has non-uniform spatial polarization distribution. It is shown both theoretically and experimentally that the range of the PBIC for any polarization of the DSP depends on the spatial average intensity of the speckles corresponding to that particular polarization. The experimentally determined nature of the change of the range of the PBIC for different polarization components, due to the variation in the average intensity, is found to be matching well with the theoretical prediction. The existence of non-zero correlation between two orthogonally polarized speckle patterns, filtered from a partially DSP, is also observed. This study may be useful in exploiting the PBIC for different applications such as speckle cryptography.

Modulation of coherence-polarization property of speckles using a birefringent scatterer.

The change of the spatial coherence-polarization (CP) property of a speckle pattern due to the modulation of birefringence in a scattering medium is investigated experimentally. The birefringence is introduced to the scattering medium by attaching layers of overhead projector (OHP) sheets to it. It is shown that the spatial polarization distribution can be tuned from a uniformly polarized case to a randomly polarized case by increasing the number of OHP sheets. The change of the spatial CP property with the number of OHP sheets is investigated from the study of the spatial degree of coherence and the degree of polarization, and these variations are further confirmed from the probability density function of the intensity of the speckle pattern and from the measurement of the generalized Stokes parameters. The effect of the change of the number of OHP sheets on the visibility of the intensity correlation function and the quality of the object retrieved through the scattering medium are also investigated.

Effect of MRI acquisition acceleration via compressed sensing and parallel imaging on brain volumetry.

OBJECTIVES: To investigate the effect of compressed SENSE (CS), an acceleration technique combining parallel imaging and compressed sensing, on potential bias and precision of brain volumetry and evaluate it in the context of normative brain volumetry. MATERIALS AND METHODS: In total, 171 scans from scan-rescan experiments on three healthy subjects were analyzed. Each subject received 3D-T1-weighted brain MRI scans at increasing degrees of acceleration (CS-factor = 1/4/8/12/16/20/32). Single-scan acquisition times ranged from 00:41 min (CS-factor = 32) to 21:52 min (CS-factor = 1). Brain segmentation and volumetry was performed using two different software tools: md.brain, a proprietary software based on voxel-based morphometry, and FreeSurfer, an open-source software based on surface-based morphometry. Four sub-volumes were analyzed: brain parenchyma (BP), total gray matter, total white matter, and cerebrospinal fluid (CSF). Coefficient of variation (CoV) of the repeated measurements as a measure of intra-subject reliability was calculated. Intraclass correlation coefficient (ICC) with regard to increasing CS-factor was calculated as another measure of reliability. Noise-to-contrast ratio as a measure of image quality was calculated for each dataset to analyze the association between acceleration factor, noise and volumetric brain measurements. RESULTS: For all sub-volumes, there is a systematic bias proportional to the CS-factor which is dependent on the utilized software and subvolume. Measured volumes deviated significantly from the reference standard (CS-factor = 1), e.g. ranging from 1 to 13% for BP. The CS-induced systematic bias is driven by increased image noise. Except for CSF, reliability of brain volumetry remains high, demonstrated by low CoV (< 1% for CS-factor up to 20) and good to excellent ICC for CS-factor up to 12. CONCLUSION: CS-acceleration has a systematic biasing effect on volumetric brain measurements.

Comparison of waveform-derived corneal stiffness and stress-strain extensometry-derived corneal stiffness using different cross-linking irradiances: an experimental study with air-puff applanation of ex vivo porcine eyes.

PURPOSE: To assess corneal stiffening of standard (S-CXL) and accelerated (A-CXL) cross-linking protocols by dynamic corneal response parameters and corneal bending stiffness (Kc[mean/linear]) derived from Corvis (CVS) Scheimpflug-based tonometry. These investigations were validated by corneal tensile stiffness (K[ts]), derived from stress-strain extensometry in ex vivo porcine eyes. METHODS: Seventy-two fresh-enucleated and de-epithelized porcine eyes were soaked in 0.1% riboflavin solution including 10% dextran for 10 min. The eyes were separated into four groups: controls (n = 18), S-CXL (intensity in mW/cm2*time in min; 3*30) (n = 18), A-CXL (9*10) (n = 18), and A-CXL (18*5) (n = 18), respectively. CXL was performed using CCL Vario. CVS measurements were performed on all eyes. Subsequently, corneal strips were extracted by a double-bladed scalpel and used for stress-strain measurements. K[ts] was calculated from a force-displacement curve. Mean corneal stiffness (Kc[mean]) and constant corneal stiffness (Kc[linear]) were calculated from raw CVS data. RESULTS: In CVS, biomechanical effects of cross-linking were shown to have a significantly decreased deflection amplitude as well as integrated radius, an increased IOP, and SP A1 (P < 0.05). Kc[mean]/Kc[linear] were significantly increased after CXL (P < 0.05). In the range from 2 to 6% strain, K[ts] was significantly higher in S-CXL (3*30) compared to A-CXL (9*10), A-CXL (18*5), and controls (P < 0.05). At 8% to 10% strain, all protocols induced a higher stiffness than controls (P < 0.05). CONCLUSION: Several CVS parameters and Kc[mean] as well as Kc[linear] verify corneal stiffening effect after CXL on porcine eyes. S-CXL seems to have a higher tendency of stiffening than A-CXL protocols have, which was demonstrated by Scheimpflug-based tonometry and stress-strain extensometry.

A pH-sensitive luminal His-cluster promotes interaction of PAM with V-ATPase along the secretory and endocytic pathways of peptidergic cells.

The biosynthetic and endocytic pathways of secretory cells are characterized by progressive luminal acidification, a process which is crucial for posttranslational modifications and membrane trafficking. This progressive fall in luminal pH is mainly achieved by the vacuolar-type-H+ ATPase (V-ATPase). V-ATPases are large, evolutionarily ancient rotary proton pumps that consist of a peripheral V1 complex, which hydrolyzes ATP, and an integral membrane V0 complex, which transports protons from the cytosol into the lumen. Upon sensing the desired luminal pH, V-ATPase activity is regulated by reversible dissociation of the complex into its V1 and V0 components. Molecular details of how intraluminal pH is sensed and transmitted to the cytosol are not fully understood. Peptidylglycine α-amidating mono-oxygenase (PAM; EC 1.14.17.3), a secretory pathway membrane enzyme which shares similar topology with two V-ATPase accessory proteins (Ac45 and prorenin receptor), has a pH-sensitive luminal linker region. Immunofluorescence and sucrose gradient analysis of peptidergic cells (AtT-20) identified distinct subcellular compartments exhibiting spatial co-occurrence of PAM and V-ATPase. In vitro binding assays demonstrated direct binding of the cytosolic domain of PAM to V1H. Blue native PAGE identified heterogeneous high-molecular weight complexes of PAM and V-ATPase. A PAM-1 mutant (PAM-1/H3A) with altered pH sensitivity had diminished ability to form high-molecular weight complexes. In addition, V-ATPase assembly status was altered in PAM-1/H3A expressing cells. Our analysis of the secretory and endocytic pathways of peptidergic cells supports the hypothesis that PAM serves as a luminal pH-sensor, regulating V-ATPase action by altering its assembly status.

Bayesian QuickNAT: Model uncertainty in deep whole-brain segmentation for structure-wise quality control.

We introduce Bayesian QuickNAT for the automated quality control of whole-brain segmentation on MRI T1 scans. Next to the Bayesian fully convolutional neural network, we also present inherent measures of segmentation uncertainty that allow for quality control per brain structure. For estimating model uncertainty, we follow a Bayesian approach, wherein, Monte Carlo (MC) samples from the posterior distribution are generated by keeping the dropout layers active at test time. Entropy over the MC samples provides a voxel-wise model uncertainty map, whereas expectation over the MC predictions provides the final segmentation. Next to voxel-wise uncertainty, we introduce four metrics to quantify structure-wise uncertainty in segmentation for quality control. We report experiments on four out-of-sample datasets comprising of diverse age range, pathology and imaging artifacts. The proposed structure-wise uncertainty metrics are highly correlated with the Dice score estimated with manual annotation and therefore present an inherent measure of segmentation quality. In particular, the intersection over union over all the MC samples is a suitable proxy for the Dice score. In addition to quality control at scan-level, we propose to incorporate the structure-wise uncertainty as a measure of confidence to do reliable group analysis on large data repositories. We envisage that the introduced uncertainty metrics would help assess the fidelity of automated deep learning based segmentation methods for large-scale population studies, as they enable automated quality control and group analyses in processing large data repositories.

QuickNAT: A fully convolutional network for quick and accurate segmentation of neuroanatomy.

Whole brain segmentation from structural magnetic resonance imaging (MRI) is a prerequisite for most morphological analyses, but is computationally intense and can therefore delay the availability of image markers after scan acquisition. We introduce QuickNAT, a fully convolutional, densely connected neural network that segments a MRI brain scan in 20 s. To enable training of the complex network with millions of learnable parameters using limited annotated data, we propose to first pre-train on auxiliary labels created from existing segmentation software. Subsequently, the pre-trained model is fine-tuned on manual labels to rectify errors in auxiliary labels. With this learning strategy, we are able to use large neuroimaging repositories without manual annotations for training. In an extensive set of evaluations on eight datasets that cover a wide age range, pathology, and different scanners, we demonstrate that QuickNAT achieves superior segmentation accuracy and reliability in comparison to state-of-the-art methods, while being orders of magnitude faster. The speed up facilitates processing of large data repositories and supports translation of imaging biomarkers by making them available within seconds for fast clinical decision making.

Effect of the average number of reference speckles in speckle imaging using off-axis speckle holography.

The propagation of a coherent beam of light through a random scattering medium results in the generation of a speckle pattern. Although the intensity distribution of the speckle pattern is random in nature, the information of the object hidden behind a scattering medium is scrambled into it. The scrambled object information can be retrieved using the off-axis speckle holographic technique, where the object retrieval is made from a recorded interferogram, formed by the superposition of the object speckles and a tilted reference speckle pattern. In the present paper, the effect of the average number of reference speckles on the signal-to-noise ratio of the retrieved object is investigated in two different random domains of the reference speckles, which are defined from the study of the Shannon entropy of the reference speckle patterns. The observed results can be useful in tuning the visibility and sharpness of the object, retrieved by employing the off-axis speckle holographic technique.

Metal Nanoparticle-Decorated Silicon Nanowire Arrays on Silicon Substrate and their Applications.

Herein, we report an efficient method to produce silver (Ag) nanoparticle-decorated silicon (Si) nanowire (NW) arrays on a pyramidal Si (P-Si) substrate by using a pure chemical method and rapid thermal annealing in different atmospheres. A metal-assisted chemical etching technique was used to produce vertical Si NW arrays on pyramidal Si. The etching was observed to be heavily dependent on the substrate type. On planar Si (100), the etching was observed to occur in a uniform manner. However, the etching rate was observed to increase from the top to the base of the Si pyramid. The Si NWs produced from P-Si have zig-zag sidewalls as observed from high-resolution transmission electron microscopy images. However, for the same oxidant concentration, Si NWs produced from planar Si (100) consist of straight and amorphous sidewalls. Local variation of oxidant concentration is responsible for the formation of different sidewalls. The substrates are both surface-enhanced Raman scattering (SERS) active and hydrophobic. The hydrophobicity is due to the dual scale of roughness contributed to by both pyramidal and NW structures. Finite-difference time-domain simulation shows that the gap between two Ag spheres and also the gap between Si NWs and Ag spheres contributed to SERS enhancement.

Controlled modulation of depolarization in laser speckle.

A new technique based on superposition of two speckle patterns is proposed and demonstrated for controlled modulation of the spatial polarization distribution of the resultant speckle. It is theoretically and experimentally demonstrated that controlled modulation of the spatial polarization distribution of laser speckle can be achieved by proper choice of the polarization states as well as the average spatial intensity of the constituent speckles. It is shown that the proposed technique is useful to generate different speckle patterns with sinusoidal variation in their degree of polarization, which can be tuned from zero to unity. This technique can find application in sensing, biomedical studies, and in determining the rotation of an electric field vector after passing through a scattering medium.

Generation of Aspherical Optical Lenses via Arrested Spreading and Pinching of a Cross-Linkable Liquid.

Aspherical optical lenses with spatially varying curvature are desired for capturing high quality, aberration free images in numerous optical applications. Conventionally such lenses are prepared by multistep top-down processes which are expensive, time-consuming, and prone to high failure rate. In this context, an alternate method is presented here based on arrested spreading of a sessile drop of a transparent, cross-linkable polymeric liquid on a solid substrate heated to an elevated temperature. Whereas surface tension driven flow tends to render it spherical, rapid cross-linking arrests such flow so that nonequilibrium aspherical shapes are attained. It is possible to tune also the initial state of the drop via delayed pinching of a liquid cylinder which precedes its release on the substrate. This method has led to the generation of a wide variety of optical lenses, ranging from spherical plano convex to superspherical solid immersion to exotic lenses not achieved via conventional methods.