Universal angular-dispersion synthesizer.

We uncover a surprising gap in optics with regards to angular dispersion (AD). A systematic examination of pulsed optical field configurations classified according to their three lowest dispersion orders resulting from AD (the axial phase velocity, group velocity, and group-velocity dispersion) reveals that the majority of possible classes of fields have eluded optics thus far. This gap is due in part to the limited technical reach of the standard components that provide AD such as gratings and prisms, but due in part also to misconceptions regarding the set of physically admissible field configurations that can be accessed via AD. For example, it has long been thought that AD cannot yield normal group-velocity dispersion in free space. We introduce a "universal AD synthesizer": a pulsed-beam shaper that produces a wavelength-dependent propagation angle with arbitrary spectral profile, thereby enabling access to all physically admissible field configurations realizable via AD. This universal AD synthesizer is a versatile tool for preparing pulsed optical fields for dispersion cancellation, optical signal processing, and nonlinear optics.

Portable MRI to assess optic chiasm decompression after endoscopic endonasal resection of sellar and suprasellar lesions.

OBJECTIVE: Low-field portable MRI (pMRI) is a recent technological advancement with potential for broad applications. Compared with conventional MRI, pMRI is less resource-intensive with regard to operational costs and scan time. The application of pMRI in neurosurgical oncology has not been previously described. The goal of this study was to demonstrate the efficacy of pMRI in assessing optic nerve decompression after endoscopic endonasal surgery for sellar and suprasellar pathologies. METHODS: Patients who underwent endoscopic endonasal surgery for sellar and suprasellar lesions at a single institution and for whom pMRI and routine MRI were performed postoperatively were retrospectively reviewed to compare the two imaging systems. To assess the relative resolution of pMRI compared with MRI, the distance from the optic chiasm to the top of the third ventricle was measured, and the measurements were compared between paired equivalent slices on T2-weighted coronal images. The inter- and intrarater correlations were analyzed. RESULTS: Twelve patients were included in this study (10 with pituitary adenomas and 2 with craniopharyngiomas) with varying degrees of optic chiasm compression on preoperative imaging. Measurements were averaged across raters before calculating agreement between pMRI and MRI, which demonstrated significant interrater reliability (intraclass correlation coefficient [ICC] = 0.78, p < 0.01). Agreement between raters within the pMRI measurements was also significantly reliable (ICC = 0.93, p < 0.01). Finally, a linear mixed-effects model was specified to demonstrate that MRI measurement could be predicted using the pMRI measurement with the patient and rater set as random effects (pMRI ß coefficient = 0.80, p < 0.01). CONCLUSIONS: The results of this study suggest that resolution of pMRI is comparable to that of conventional MRI in assessing the optic chiasm position in relation to the third ventricle. Portable MRI sufficiently demonstrates decompression of the optic chiasm after endoscopic endonasal surgery. It can be an alternative strategy in cases in which cost, scan-time considerations, or lack of intraoperative MRI availability may preclude the ability to assess adequate optic nerve decompression after endoscopic endonasal surgery for sellar and suprasellar lesions.

Non-differentiable angular dispersion as an optical resource.

Introducing angular dispersion into a pulsed field associates each frequency with a particular angle with respect to the propagation axis. A perennial yet implicit assumption is that the propagation angle is differentiable with respect to the frequency. Recent work on space-time wave packets has shown that the existence of a frequency at which the derivative of the propagation angle does not exist-which we refer to as non-differentiable angular dispersion-allows for the optical field to exhibit unique and useful characteristics that are unattainable by endowing optical fields with conventional angular dispersion. Because these novel, to the best of our knowledge, features are retained in principle even when the specific non-differentiable frequency is not part of the selected spectrum, the question arises as to the impact of the proximity of the spectrum to this frequency. We show here that operating in the vicinity of the non-differentiable frequency is imperative to reduce the deleterious impact of (1) errors in implementing the angular-dispersion profile and (2) the spectral uncertainty intrinsic to finite-energy wave packets in any realistic system. Non-differential angular dispersion can then be viewed as a resource-quantified by a Schmidt number-that is maximized in the vicinity of the non-differentiable frequency. These results will be useful in designing novel phase-matching of nonlinear interactions in dispersive media.

Consequences of non-differentiable angular dispersion in optics: tilted pulse fronts versus space-time wave packets.

Conventional diffractive and dispersive devices introduce angular dispersion (AD) into pulsed optical fields, thus producing so-called 'tilted pulse fronts'. Naturally, it is always assumed that the functional form of the wavelength-dependent propagation angle[s] associated with AD is differentiable with respect to wavelength. Recent developments in the study of space-time wave packets - pulsed beams in which the spatial and temporal degrees of freedom are inextricably intertwined - have pointed to the existence of non-differentiable AD: field configurations in which the propagation angle does not possess a derivative at some wavelength. Here we investigate the consequences of introducing non-differentiable AD into a pulsed field and show that it is the crucial ingredient required to realize group velocities that deviate from c (the speed of light in vacuum) along the propagation axis in free space. In contrast, the on-axis group velocity for conventional pulsed fields in free space is always equal to c. Furthermore, we show that non-differentiable AD is needed for realizing anomalous or normal group-velocity dispersion along the propagation axis, while simultaneously suppressing all higher-order dispersion terms. We experimentally verify these and several other consequences of non-differentiable AD using a pulsed-beam shaper capable of introducing AD with arbitrary spectral profile. Non-differentiable AD is not an exotic phenomenon, but is rather an accessible, robust, and versatile resource for sculpting pulsed optical fields.

Arbitrarily accelerating space-time wave packets.

All known realizations of optical wave packets that accelerate along their propagation axis, such as Airy wave packets in dispersive media or wave-front-modulated X-waves, exhibit a constant acceleration; that is, the group velocity varies linearly with propagation. Here we synthesize space-time wave packets that travel in free space with arbitrary axial acceleration profiles, including group velocities that change with integer or fractional exponents of the distance. Furthermore, we realize a composite acceleration profile: the wave packet accelerates from an initial to a terminal group velocity, before decelerating back to the initial value. These never-before-seen optical-acceleration phenomena are produced using the same experimental arrangement that precisely sculpts the wave packet's spatio-temporal spectral structure.

Use of droxidopa for blood pressure augmentation after acute spinal cord injury: case reports.

Hypotension secondary to autonomic dysfunction is a common complication of acute spinal cord injury (SCI) that may worsen neurologic outcomes. Midodrine, an enteral α-1 agonist, is often used to facilitate weaning intravenous (IV) vasopressors, but its use can be limited by reflex bradycardia. Alternative enteral agents to facilitate this wean in the acute post-SCI setting have not been described. We aim to describe novel application of droxidopa, an enteral precursor of norepinephrine that is approved to treat neurogenic orthostatic hypotension, in the acute post-SCI setting. Droxidopa may be an alternative enteral therapy for those intolerant of midodrine due to reflex bradycardia. We describe two patients suffering traumatic cervical SCI who were successfully weaned off IV vasopressors with droxidopa after failing with midodrine. The first patient was a 64-year-old male who underwent C3-6 laminectomies and fusion after a ten-foot fall resulting in quadriparesis. Post-operatively, the addition of midodrine in an attempt to wean off IV vasopressors resulted in significant reflexive bradycardia. Treatment with droxidopa facilitated rapidly weaning IV vasopressors and transfer to a lower level of care within 72 hours of treatment initiation. The second patient was a 73-year-old male who underwent C3-5 laminectomies and fusion for a traumatic hyperflexion injury causing paraplegia. The addition of midodrine resulted in severe bradycardia, prompting consideration of pacemaker placement. However, with the addition of droxidopa, this was avoided, and the patient was weaned off IV vasopressors on dual oral therapy with midodrine and droxidopa. Droxidopa may be a viable enteral therapy to treat hypotension in patients after acute SCI who are otherwise not tolerating midodrine in order to wean off IV vasopressors. This strategy may avoid pacemaker placement and facilitate shorter stays in the intensive care unit, particularly for patients who are stable but require continued intensive care unit admission for IV vasopressors, which can be cost ineffective and human resource depleting.

Realizing normal group-velocity dispersion in free space via angular dispersion.

It has long been thought that normal group-velocity dispersion (GVD) cannot be produced in free space via angular dispersion. Indeed, conventional diffractive or dispersive components such as gratings or prisms produce only anomalous GVD. We identify the conditions that must be fulfilled by the angular dispersion introduced into a plane-wave pulse to yield normal GVD. We then utilize a pulsed-beam shaper capable of introducing arbitrary angular-dispersion profiles to symmetrically produce normal and anomalous GVD in free space, which are realized here on the same footing for the first time, to our knowledge.

Space-time vector light sheets.

We introduce the space-time (ST) vector light sheet. This unique one-dimensional ST wave packet is characterized by classical entanglement (CE), a correlation between at least two non-separable intrinsic degrees-of-freedom (DoFs), which in this case are the spatiotemporal DoFs in parallel with the spatial-polarization DoFs. We experimentally confirm that the ST vector light sheet maintains the intrinsic features of the uniformly polarized ST light sheet, such as near-diffraction-free propagation and self-healing, while also maintaining the intrinsic polarization structure of common vector beams, such as those that are radially polarized and azimuthally polarized. We also show that the vector beam structure of the ST vector light sheet is maintained in the subluminal and superluminal regimes.

Temporal Talbot effect in free space.

The temporal Talbot effect refers to the periodic revivals of a pulse train propagating in a dispersive medium and is a temporal analog of the spatial Talbot effect with group-velocity dispersion in time replacing diffraction in space. Because of typically large temporal Talbot lengths, this effect has been observed to date in only single-mode fibers, rather than with freely propagating fields in bulk dispersive media. Here we demonstrate for the first time, to the best of our knowledge, the temporal Talbot effect in free space by employing dispersive space-time wave packets, whose spatiotemporal structure induces group-velocity dispersion of controllable magnitude and sign in free space.

MicroRNAs as biomarkers of atrophic scarring in acne: a cross-sectional analysis of 41 patients.

BACKGROUND: Acne is the commonest inflammatory dermatosis seen worldwide. Atrophic acne scarring is a frequent complication, which can arise from acne of any severity. Micro (mi)RNAs are noncoding RNA molecules of 19-25 nucleotides that function as post-transcriptomic mediators of gene expression. They have demonstrated differential expression in various pathologies, such as eczema and psoriasis, allowing for a unique miRNA 'signature' profile to be established for different disease states. AIM: To establish a miRNA signature for acne, and acne-associated atrophic scarring and to identify if a pattern of circulating miRNA is evident in patients who are prone to scarring. METHODS: In total, 41 participants were consecutively recruited to this study. Circulating miRNA was quantified from plasma samples in all 41 patients, while in 8 patients, and in a further validation cohort of 9 patients, whole miRNAome was undertaken from tissue specimens, which included lesional, normal and where present, scarred skin. RESULTS: Three miRNAs, miR-223, miR-21 and miR-150, were statistically significantly overexpressed in acne lesions, and notably, in clinically uninvolved skin in participants prone to scarring. In this subgroup, we also found statistically significantly elevated levels of circulating miRNA-21 and miRNA-150. CONCLUSION: The presence of elevated levels of these specific miRNAs in the serum of patients with acne raises the potential of a blood test to identify those at risk of scarring, allowing for earlier intervention with effective therapy.

Space-time wave packets violate the universal relationship between angular dispersion and pulse-front tilt.

Introducing angular dispersion into a pulsed field tilts the pulse front with respect to the phase front. There exists between the angular dispersion and pulse-front tilt a universal relationship that is device-independent, and also independent of the pulse shape and bandwidth. We show here that this relationship is violated by propagation-invariant space-time (ST) wave packets, which are pulsed beams endowed with precise spatiotemporal structure corresponding to a particular form of angular dispersion. We demonstrate theoretically and experimentally that ST wave packets represent, to the best of our knowledge, the first example in optics of non-differentiable angular dispersion, resulting in pulse-front tilt that depends on the square-root of the pulse bandwidth.

Topical preparations for the treatment of mild-to-moderate acne vulgaris: systematic review and network meta-analysis.

BACKGROUND: Acne is very common and can have a substantial impact on wellbeing. Guidelines suggest first-line management with topical treatments, but there is little evidence regarding which treatments are most effective. OBJECTIVES: To identify the most effective and best tolerated topical treatments for acne using network meta-analysis. METHODS: CENTRAL, MEDLINE, Embase and World Health Organization Trials Registry were searched from inception to June 2020 for randomized trials that included participants with mild/moderate acne. Primary outcomes were self-reported improvement in acne, and trial withdrawal. Secondary outcomes included change in lesion counts, Investigator's Global Assessment, change in quality of life and total number of adverse events. Network meta-analysis was undertaken using a frequentist approach. Risk of bias was assessed using the Cochrane Risk of Bias Tool and confidence in evidence was assessed using CINeMA. RESULTS: A total of 81 papers were included, reporting 40 trials with a total of 18 089 participants. Patient Global Assessment of Improvement was reported in 11 trials. Based on the pooled network estimates, compared with vehicle, benzoyl peroxide (BPO) was effective (35% vs. 26%) for improving self-reported acne. The combinations of BPO with adapalene (54% vs. 35%) or with clindamycin (49% vs. 35%) were ranked more effective than BPO alone. The withdrawal of participants from the trial was reported in 35 trials. The number of patients withdrawing owing to adverse events was low for all treatments. Rates of withdrawal were slightly higher for BPO with adapalene (2·5%) or clindamycin (2·7%) than BPO (1·6%) or adapalene alone (1·0%). Overall confidence in the evidence was low. CONCLUSIONS: Adapalene in combination with BPO may be the most effective treatment for acne but with a slightly higher incidence of withdrawal than monotherapy. Inconsistent reporting of trial results precluded firmer conclusions.

Is Cutibacterium (previously Propionibacterium) acnes a potential pathogenic factor in the aetiology of the skin disease progressive macular hypomelanosis?

Progressive macular hypomelanosis (PMH) is a skin condition that normally causes symmetrically distributed hypopigmented macules on the front and back of the trunk, but rarely the face. To date, the pathophysiology of the condition is not well understood, but a role for the anaerobic skin bacterium Cutibacterium (previously Propionibacterium) acnes in the development of the disease has been proposed due to its sole presence within lesional, but not normal peri-lesional, skin. The success of antimicrobials in the treatment of PMH also provides circumstantial evidence that this association may be causal, although this is still to be proven. More recent culture and metagenomic typing studies indicate that strains of C. acnes subsp. elongatum (type III) may be important in the aetiology of the condition, which would help to explain why PMH does not normally affect the face since such strains are rarely present there, and why no association between this condition and acne vulgaris is found; acne appears to primarily involve type IA1 strains from C. acnes subsp. acnes (type I). In this review, we summarize current knowledge on the relationship between C. acnes and PMH, and re-examine previous challenges to the view that the bacterium plays a role in the condition against the backdrop of newly emerged data.

Reviewing the global burden of acne: how could we improve care to reduce the burden?

Acne (also known as acne vulgaris) remains the most common inflammatory dermatosis treated worldwide, as estimated by global skin disease prevalence studies. Latest reports suggest that the prevalence may be increasing in adolescents and adults, particularly female adults. The concept of 'burden of skin disease' is multidimensional and can be difficult to quantify in light of different healthcare systems across the globe. In acne, the resulting burden may vary according to patient demographics, access to treatments and duration of the disease. The visible nature of acne, symptoms and sequelae all contribute physically and psychosocially to the overall burden of disease, as do the costs required for management. Acne typically presents in adolescence at a time of significant transition. Profound effects on functional status have been demonstrated, along with a strong impact on interpersonal relationships, social functioning and mental health. The high prevalence of acne also presents an economic burden for society. The widespread and prolonged use of antibiotics introduces a potential added burden through resulting antimicrobial resistance. A James Lind Alliance Acne Priority Setting Partnership has identified numerous areas to inform future research, which would help to improve acne management and reduce the burden. The lack of standardized assessments is a major issue in acne trials and challenges the ability to compare treatments and perform meta-analyses. This paper reviews the current literature on burden of acne, identifies areas of treatment uncertainties and summarizes the work of the Acne Core Outcome Research Network as a means of supporting a reduction in the burden of disease.

Veiled Talbot Effect.

A freely propagating optical field having a periodic transverse spatial profile undergoes periodic axial revivals-a well-known phenomenon known as the Talbot effect or self-imaging. We show here that introducing tight spatiotemporal spectral correlations into an ultrafast pulsed optical field with a periodic transverse spatial profile eliminates all axial dynamics in physical space, while revealing a novel veiled Talbot effect that can be observed only when carrying out time-resolved measurements. Indeed, "time diffraction" is observed, whereupon the temporal profile of the field envelope at a fixed axial plane corresponds to a segment of the spatial propagation profile of a monochromatic field sharing the initial spatial profile and observed at the same axial plane. Time averaging, which is intrinsic to observing the intensity, altogether veils this effect.

Assessing effectiveness in acne clinical trials: steps towards a core outcome measure set.

BACKGROUND: Acne ranks second to dermatitis in terms of global burden of skin disease. As such, it is essential that data on treatment efficacy are generated in a way that maximizes the opportunity for comparison among treatments. Interest in developing core outcome sets for use in clinical trials to standardize data collection in skin disease is surging. OBJECTIVES: The goal of this review is to provide an update on the efforts underway, challenges encountered and future directions in the development of an acne core outcome measure set for use in clinical trials. METHODS: The activities of the Acne Core Outcomes Research Network (ACORN) are presented in the context of currently acceptable methodologies for core outcome set development. CONCLUSIONS: Emphasis is placed on following a rigorous methodology, involving patients and recognizing a role for emerging technologies.