Search

IMPORTANCE: Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) is a severe hypersensitivity reaction. Identifying a culprit drug is critical for patient care, yet identification is based on clinical judgment. Data are limited on the accuracy in or approach to identifying a culprit drug. OBJECTIVE: To evaluate patient allergy list outcomes, current approaches in identifying culprit drugs, and potential methods of improving culprit drug identification. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study spanned 18 years (January 2000 to July 2018), was conducted at Brigham and Women’s Hospital and Massachusetts General Hospital (Boston), and included patients with clinically and histologically confirmed cases of SJS/TEN overlap and TEN. MAIN OUTCOMES AND MEASURES: This study descriptively analyzed potential culprits to SJS/TEN, patients’ allergy lists, and currently used approaches that led to those lists. It then tested the theoretical contribution of incorporating various parameters to allergy list outcomes. RESULTS: Of 48 patients (29 women [60.4%]; 4 Asian [8.3%], 6 Black [12.5%], 5 Hispanic [10.4%], and 25 White [52.1%] individuals; median age, 40 years [range, 1-82 years]), the mean (SD) number of drugs taken per patient at disease onset was 6.5 (4.7). Physicians labeled 17 patients as allergic to a single culprit drug. Comparatively, 104 drugs were added to allergy lists across all patients. Physicians’ approaches relied largely on heuristic identification of high-notoriety drugs and the timing of drug exposure. Use of a vetted database for drug risk improved sensitivity. Algorithm for Drug Causality for Epidermal Necrolysis scoring was discordant in 28 cases, labeling an additional 9 drugs missed by physicians and clearing 43 drugs labeled as allergens by physicians. Human leukocyte antigen testing could have potentially affected 20 cases. Consideration of infection as a culprit was limited. CONCLUSIONS AND RELEVANCE: The results of this cohort study suggest that currently used approaches to identify culprit drugs in SJS/TEN are associated with overlabeling patients allergic to likely nonculprit drugs and less commonly missed possible culprit drugs. Incorporation of a systematized unbiased approach could potentially improve culprit drug identification, although ultimately a diagnostic test is necessary.

When dysregulated, skin fibrosis can lead to a multitude of pathologies. We provide a framework for understanding the wide clinical spectrum, mechanisms, and management of cutaneous fibrosis encompassing a variety of matrix disorders, fibrohistiocytic neoplasms, injury-induced scarring, and autoimmune scleroses. Underlying such entities are common mechanistic pathways that leverage morphogenic signaling, immune activation, and mechanotransduction to modulate fibroblast function. In light of the limited array of available treatments for cutaneous fibrosis, scientific insights have opened new therapeutic and investigative avenues for conditions that still lack effective interventions.

A method to measure the refractive index of an optically flat, regularly shaped slab of glass using speckle correlation-based techniques is reported. The intensity of the diffraction field of the diffuser is captured by a CCD both with and without the glass present. As the position of the peak correlation coefficient is quantitatively related to the change in optical path length arising due to the presence of the glass, the refractive index of the glass can be evaluated by cross-correlating the two captured images. The theoretical correlation function that describes the effects of such an optical path length change is discussed, and the resulting speckle decorrelation function derived. Two glass samples are measured to demonstrate the accuracy and robustness of the proposed technique.

Typical methods of automatic estimation of focusing in digital holography calculate every single reconstructed frame to get a critical function and then ascertain the focal plane by finding the extreme value of that function. Here, we propose a digital holographic autofocusing method that computes the focused distance using the first longitudinal difference of the magnitude of the reconstructed image. We demonstrate the proposed method with both numerical simulations and optical experiments of amplitude-contrast and phase-contrast objects. The results suggest that the proposed method performs better than other existing methods, in terms of applicability and computation efficiency, with potential applications in industrial and biomedical inspections where automatic focus tracking is necessary.

Light field reconstruction from images captured by focal plane sweeping can achieve high lateral resolution comparable to the modern camera sensor. This is impossible for the conventional micro-lenslet-based light field capture systems. However, the severe defocus noise and the low depth resolution limit its applications. In this paper, we analyze the defocus noise in the focal-plane-sweeping-based light field reconstruction technique, and propose a method to reduce the defocus noise. Both numerical and experimental results verify the proposed method.

Imaging the propagation of light in time and space is crucial in optics, notably for the study of complex media. We demonstrate the passive measurement of time-dependent Green’s functions between every point at the surface of a strongly scattering medium by means of low coherence interferometry. The experimental access to this Green’s matrix is essential since it contains all the information about the complex trajectories of light within the medium. In particular, the spatio-temporal spreading of the diffusive halo and the coherent backscattering effect can be locally investigated in the vicinity of each point acting as a virtual source. On the one hand, this approach allows quantitative imaging of the diffusion constant in the scattering medium with a spatial resolution of the order of a few transport mean-free paths. On the other hand, our approach is able to reveal and quantify the anisotropy of light diffusion, which can be of great interest for optical characterization purposes. This study opens important perspectives both in optical diffuse tomography with potential applications to biomedical imaging and in fundamental physics for the experimental investigation of Anderson localization.

Speckle suppression in a two-diffuser system is examined. An analytical expression for the speckle space–time correlation function is derived, so that the speckle suppression mechanism can be investigated statistically. The grain size of the speckle field illuminating the second diffuser has a major impact on the speckle contrast after temporal averaging. It is shown that, when both the diffusers are rotating, the one with the lower rotating speed determines the period of the speckle correlation function. The coherent length of the averaged speckle intensity is shown to equal the mean speckle size of the individual speckle pattern before averaging. Numerical and experimental results are presented to verify our analysis in the context of speckle reduction.

The scattering of coherent monochromatic light at an optically rough surface, such as a diffuser, produces a speckle field, which is usually described by reference to its statistical properties. For example, the real and imaginary parts of a fully developed speckle field can be modeled as a random circular Gaussian process. When such a speckle field is used to illuminate a second diffuser, the statistics of the resulting doubly scattered field are in general no longer Gaussian, but rather follow a K distribution. In this paper we determine the space–time correlation function of such a doubly scattered speckle field that has been imaged by a single lens system. A space–time correlation function is derived that contains four separate terms; similar to the Gaussian case it contains an average DC term and a fluctuating AC term. However, in addition there are two terms that are related to contributions from each of the diffusers independently. We examine how our space–time correlation function varies as the diffusers are rotated at different speeds and as the point spread function of the imaging system is changed. A series of numerical simulations are used to confirm different aspects of the theoretical analysis. We then finish with a discussion of our results and some potential applications, including controlling spatial coherence and speckle reduction.

Speckle fields are formed when quasi-monochromatic light is scattered by an optically rough surface. These fields are usually described by reference to their first and second order statistical properties. In this paper we review and extend some of these fundamental properties and propose a novel technique for estimating the refractive index of a smooth sample. Theoretical and experimental results are presented. Separately, we also report on a preliminary experiment to determine some characteristics of speckle fields formed in free space by a rotating compound diffuser. Some initial measurements are made where we examine how the speckle intensity pattern in the output plane changes as a function of the relative rotation angle.

The statistical properties of speckles in paraxial optical systems depend on the system parameters. In particular, the speckle orientation and the lateral dependence (x and y) of the longitudinal speckle size can vary significantly. For example, the off-axis longitudinal correlation length remains equal to the on-axis size for speckles in a Fourier transform system, while it decreases dramatically as the observation position moves off axis in a Fresnel system. In this paper, we review the speckle correlation function in general linear canonical transform (LCT) systems, clearly demonstrating that speckle properties can be controlled by introducing different optical components, i.e., lenses and sections of free space. Using a series of numerical simulations, we examine how the correlation function changes for some typical LCT systems. The integrating effect of the camera pixel and the impact this has on the measured first- and second-order statistics of the speckle intensities is also examined theoretically. A series of experimental results are then presented to confirm several of these predictions. First, the effect the pixel size has on the measured first-order speckle statistics is demonstrated, and second, the orientation of speckles in a Fourier transform system is measured, showing that the speckles lie parallel to the optical axis.

When monochromatic light is scattered from an optically rough surface a complicated three-dimensional (3D) field is generated. These fields are often described by reference to the 3D volume (extent) of their speckles, leading to the definition of lateral (x,y) and longitudinal speckle sizes (z). For reasons of mathematical simplicity the longitudinal speckle size is often derived by examining the decorrelation of the speckle field for a single point lying on axis, i.e., x=y=0, and this size is generally assumed to be representative for other speckles that lie further off-axis. Some recent theoretical results, however, indicate that in fact longitudinal speckle size gets smaller as the observation position moves to off-axis spatial locations. In this paper (Part I), we review the physical argument leading to this conclusion and support this analysis with a series of robust numerical simulations. We discuss, in some detail, computational issues that arise when simulating the propagation of speckle fields numerically, showing that the spectral method is not a suitable propagation algorithm when the autocorrelation of the scattering surface is assumed to be delta correlated. In Part II [J. Opt. Soc. Am. A28, 1904 (2011)] of this paper, experimental results are provided that exhibit the predicted variation of longitudinal speckle size as a function of position in x and y. The results are not only of theoretical interest but have practical implications, and in Part II a method for locating the optical system axis is proposed and experimentally demonstrated.

In Part I [J. Opt. Soc. Am. A28, 1896 (2011) of this paper, the physical model for fully developed speckle is examined based on two critical assumptions. (i) It is assumed that in the object plane, the speckle field is delta correlated, and (ii) it is assumed that the speckle field in the observation plane can be described as a Gaussian random process. A satisfactory simulation technique, based on the assumption that spatial averaging can be used to replace ensemble averaging, is also presented. In this part a detailed experimental investigation of the three-dimensional speckle properties is performed using spatial averaging. The results provide solid verification for the predictions presented in Part I. The results are not only of theoretical interest but have practical implications. Techniques for locating and aligning the optical system axis with the camera center, and for measuring out-of-plane displacement, are demonstrated.

Access to the spatial derivatives of an optical wave field can be used to enhance edge detection, focusing, and holographic imaging. It was recently shown that, by using digital holographic techniques, the Laplacian of an object field can be extracted. Here it is demonstrated that equivalent results can be found using two holograms captured at either two distances or with two appropriately related wavelengths. Experimental and numerical results confirming the theoretical analyses are presented. The proposed two-wavelength-based system requires no mechanical repositioning of the object and is shown to provide superior performance.

Quasi-monochromatic light reflected from an optically rough surface produces a complicated 3D speckle field. This speckle field is often described using a correlation function from which the 3D speckle properties can be examined. The derivation of the correlation function is based on a physical model where several critical assumptions about the input and output fields in the model are made. However, experimental works verifying this correlation function are rare and sometimes produce inconsistent results. In this paper, we examine some practical issues encountered when experimentally measuring this correlation function, including: The realization of the ensemble average between speckle fields at two point positions; and, The pixel integrating effect of the recording camera and the implications this has for the statistics of the measured speckle field. Following verification of the correlation function and examining the speckle decorrelation properties in 3D space, two practical applications are proposed, one is the aligning of the system optical axis with the camera center and the other is the measurement of the out-of-plane displacement of an object surface. Simulation and experimental results that support our analysis are presented.