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Cyclosporine A (CsA) is one of the systemic therapeutic options for moderate-to-severe psoriasis, based on its efficacy and rapidity of action. The current study investigated the response to CsA in patients with moderate-to-severe plaque psoriasis. TRANSITION was an observational, cross-sectional, multicentre study which evaluated the proportion of partial- and suboptimal-responders among patients with moderate-to-severe plaque psoriasis treated with continuous CsA for ≥12 weeks. Patients demonstrating a Psoriasis Area and Severity Index (PASI) response of ≥90, ≥75 and <90, ≥50 and <75 and <50 were defined as responders, suboptimal-responders, partial-responders, and non-responders, respectively. A total of 196 patients (mean age, 46.6 years; 62.8% males) from 14 sites in Italy were evaluated. At the study visit, the mean (SD) PASI score was 4.2(5.5) compared with 15.3(7.1) prior to the last CsA cycle. For response categories, 39.8%, 22.4%, 16.8%, and 20.9% of patients were responders, suboptimal-responders, partial-responders, and non-responders to CsA treatment. Overall, 28.6% of patients permanently discontinued treatment with CsA (lack of efficacy [10.2%], poor tolerability and voluntary discontinuation [3.6% each], and other [11.7%]). Patients were only partially satisfied with CsA treatment, reporting measurable impact on quality of life. Only 40% patients showed a satisfactory response to CsA. [ABSTRACT FROM AUTHOR]

Superconducting meanders of NbN thin films have applications as single-photon detectors with high sensitivity in the infrared region. We report here a detailed analysis of the electrical characteristics of such meanders, by studying structures where each wire of the meander is separately contacted. The effect of heating on the superconducting-normal transition of adjacent stripes is evidenced. Moreover, the analysis of the switching current distribution of each wire highlights the high-critical current uniformity achieved by our meander process. [ABSTRACT FROM AUTHOR]

There are both fundamental and practical motivations for studying whether quantum entanglement can exist in macroscopic systems. However, multiparty entanglement is generally fragile and difficult to quantify. Dicke states are multiparty entangled states where a single excitation is delocalized over many systems. Building on previous work on quantum memories for photons, we create a Dicke state in a solid by storing a single photon in a crystal that contains many large atomic ensembles with distinct resonance frequencies. The photon is re-emitted at a well-defined time due to an interference effect analogous to multi-slit diffraction. We derive a lower bound for the number of entangled ensembles based on the contrast of the interference and the single-photon character of the input, and we experimentally demonstrate entanglement between over two hundred ensembles, each containing a billion atoms. We also illustrate the fact that each individual ensemble contains further entanglement. [ABSTRACT FROM AUTHOR]

We demonstrate a 64-pixel free-space-coupled array of superconducting nanowire single photon detectors optimized for high detection efficiency in the near-infrared range. An integrated, readily scalable, multiplexed readout scheme is employed to reduce the number of readout lines to 16. The cryogenic, optical, and electronic packaging to read out the array as well as characterization measurements are discussed. [ABSTRACT FROM AUTHOR]

We present the characteristics of superconducting nanowire single photon detectors (SNSPDs) fabricated from amorphous Mo0.75Ge0.25 thin-films. Fabricated devices show a saturation of the internal detection efficiency at temperatures below 1 K, with system dark count rates below 500 cps. Operation in a closed-cycle cryocooler at 2.5 K is possible with system detection efficiencies exceeding 20% for SNSPDs which have not been optimized for high detection efficiency. Jitter is observed to vary between 69 ps at 250 mK and 187 ps at 2.5 K using room temperature amplifiers. [ABSTRACT FROM AUTHOR]

We demonstrate a scalable readout scheme for an infrared single-photon pulse-position camera consisting of WSi superconducting nanowire single-photon detectors. For an N × N array, only 2 × N wires are required to obtain the position of a detection event. As a proof-of-principle, we show results from a 2 × 2 array. [ABSTRACT FROM AUTHOR]

Single-photon detectors at near-infrared wavelengths with high system detection efficiency (>90%), low dark count rate (<1 c.p.s.), low timing jitter (<100 ps) and short reset time (<100 ns) would enable landmark experiments in a variety of fields. Although some of the existing approaches to single-photon detection fulfil one or two of the above specifications, to date, no detector has met all of the specifications simultaneously. Here, we report on a fibre-coupled single-photon detection system that uses superconducting nanowire single-photon detectors and closely approaches the ideal performance of single-photon detectors. Our detector system has a system detection efficiency (including optical coupling losses) greater than 90% in the wavelength range λ = 1,520-1,610 nm, with a device dark count rate (measured with the device shielded from any background radiation) of ∼1 c.p.s., timing jitter of ∼150 ps full-width at half-maximum (FWHM) and reset time of 40 ns. [ABSTRACT FROM AUTHOR]

We demonstrate an approach to improving the detection efficiency, removing the polarization dependence, and increasing the signal-to-noise ratio of conventional superconducting nanowire single photon detectors (SNSPDs) by vertically stacking two WSi SNSPDs and electrically connecting them in parallel, forming a three-dimensional superconducting nanowire avalanche photodetector. We measure a peak system detection efficiency of 87.7% ± 0.5% and a polarization dependence of less than 2%, representing nearly an order of magnitude improvement in both system detection efficiency and reduction of polarization dependence compared to conventional SNSPDs. [ABSTRACT FROM AUTHOR]

We investigated the reset time of superconducting nanowire avalanche photodetectors (SNAPs) based on 30 nm wide nanowires. We studied the dependence of the reset time of SNAPs on the device inductance and discovered that SNAPs can provide a speed-up relative to superconducting nanowire single-photon detectors with the same area but with some limitations: (1) Reducing the series inductance of SNAPs (necessary for the avalanche formation) could result in the detectors operating in an unstable regime, (2) a trade-off exists between maximizing the bias current margin and minimizing the reset time of SNAPs, and (3) reducing the reset time of SNAPs below ∼1 ns resulted in afterpulsing. [ABSTRACT FROM AUTHOR]

We present a new photon number resolving detector (PNR), the Parallel Nanowire Detector (PND), which uses spatial multiplexing on a subwavelength scale to provide a single electrical output proportional to the photon number. The basic structure of the PND is the parallel connection of several NbN superconducting nanowires (≈100 nm wide, few nm thick), folded in a meander pattern. Electrical and optical equivalents of the device were developed in order to gain insight on its working principle. PNDs were fabricated on 3-4 nm thick NbN films grown on sapphire (substrate temperature TS = 900°C) or MgO (TS = 400°C) substrates by reactive magnetron sputtering in an Ar/N2 gas mixture. The device performance was characterized in terms of speed and sensitivity. The photoresponse shows a full width at half maximum (FWHM) as low as 660 ps. PNDs showed counting performance at 80 MHz repetition rate. Building the histograms of the photoresponse peak, no multiplication noise buildup is observable and a one-photon quantum efficiency can be estimated to be η ∼ 3% (at 700 nm wavelength and 4.2 K temperature). The PND significantly outperforms existing PNR detectors in terms of simplicity, sensitivity, speed, and multiplication noise. [ABSTRACT FROM AUTHOR]

We report on the fabrication and characterization of high performance nanowire superconducting single photon detectors (SSPD) on MgO substrates. The deposition of the superconducting material (NbN) has been performed by magnetron sputtering at 400°C. This deposition temperature is low enough to be compatible with the fabrication on traditional optical materials like GaAs. First, SSPD meanders covering a surface of 5 × 5 µm2 were characterized. We measured quantum efficiencies up to 20% at 1300 nm. Then, we used a straight 250 µm-long NbN nanowire to perform a spatially resolved measurement of the efficiency. Both efficiency dips and peaks were observed. The dips were correlated to lithographic defects, as confirmed by scanning electron microscopy. Conversely, no evidence of a lithographic origin of efficiency peaks was found. [ABSTRACT FROM AUTHOR]

We describe the design and characterization of a fiber-coupled double-channel single-photon detection system based on superconducting single-photon detectors (SSPD), and its application for quantum optics experiments on semiconductor nanostructures. When operated at 2-K temperature, the system shows 10% quantum efficiency at 1.3-mum wavelength with dark count rate below 10 counts per second and timing resolution <100 ps. The short recovery time and absence of afterpulsing leads to counting frequencies as high as 40 MHz. Moreover, the low dark count rate allows operation in continuous mode (without gating). These characteristics are very attractive-as compared to InGaAs avalanche photodiodes-for quantum optics experiments at telecommunication wavelengths. We demonstrate the use of the system in time-correlated fluorescence spectroscopy of quantum wells and in the measurement of the intensity correlation function of light emitted by semiconductor quantum dots at 1300 nm. [ABSTRACT FROM PUBLISHER]

We investigate the operation of WSi superconducting nanowire single-photon detectors (SNSPDs) at 2.5 K, a temperature which is ~70% of the superconducting transition temperature (TC) of 3.4 K. We demonstrate saturation of the system detection efficiency at 78±2% at a wavelength of 1310 nm, with a jitter of 191 ps. We find that the jitter at 2.5K is limited by the noise of the readout and can be improved through the use of cryogenic amplifiers. Operation of SNSPDs with high efficiency at temperatures very close to TC appears to be a unique property of amorphous WSi. [ABSTRACT FROM AUTHOR]

We demonstrate efficient nanowire superconducting single photon detectors (SSPDs) based on NbN thin films grown on GaAs. NbN films ranging from 3 to 5 nm in thickness have been deposited by dc magnetron sputtering on GaAs substrates at 350 °C. These films show superconducting properties comparable to similar films grown on sapphire and MgO. In order to demonstrate the potential for monolithic integration, SSPDs were fabricated and measured on GaAs/AlAs Bragg mirrors, showing a clear cavity enhancement, with a peak quantum efficiency of 18.3% at λ=1300 nm and T=4.2 K. [ABSTRACT FROM AUTHOR]

The authors report fiber-coupled superconducting single-photon detectors with specifications that exceed those of avalanche photodiodes, operating at telecommunication wavelength, in sensitivity, temporal resolution, and repetition frequency. The improved performance is demonstrated by measuring the intensity correlation function g(2)(τ) of single-photon states at 1300 nm produced by single semiconductor quantum dots. [ABSTRACT FROM AUTHOR]

We experimentally studied the dynamics of optically excited hotspots in current-carrying WSi superconducting nanowires as a function of bias current, bath temperature, and excitation wavelength. We observed that the hotspot relaxation time depends on bias current, temperature, and wavelength. We explained this effect with a model based on quasiparticle recombination, which provides insight into the quasiparticle dynamics of superconductors. [ABSTRACT FROM AUTHOR]

We investigated the timing jitter of superconducting nanowire avalanche photodetectors (SNAPs, also referred to as cascade-switching superconducting single-photon detectors) based on 30-nm-wide nanowires. At bias currents (IB) near the switching current, SNAPs showed sub-35-ps FWHM Gaussian jitter similar to standard 100-nm-wide superconducting nanowire single-photon detectors. At lower values of IB, the instrument response function (IRF) of the detectors became wider, more asymmetric, and shifted to longer time delays. We could reproduce the experimentally observed IRF time-shift in simulations based on an electrothermal model and explain the effect with a simple physical picture. [ABSTRACT FROM AUTHOR]

A correction to the article "Single photon experiments at telecom wavelengths using nanowire superconducting detectors," that was published on February 23, 2010 is presented.

Because of their universal nature, Fano fluctuations are expected to influence the response of superconducting-nanowire single-photon detectors (SNSPDs). We predict that photon counting rate (PCR) as a function of bias current (IB) in SNSPDs is described by an integral over a transverse coordinate-dependent complementary error function. Fano fluctuations in the amount of energy deposited into the electronic system contribute to the finite width of this error function ΔIB. The local response of an SNSPD can also affect this width: the location of the initial photon absorption site across the width of the wire can impact the probability of vortex-antivortex unbinding and vortex entry from the edges. In narrow-nanowire SNSPDs, the local responses are uniform, and Fano fluctuations dominate ΔIB. We demonstrate good agreement between theory and experiments for a series of bath temperatures and photon energies in narrow-wire WSi SNSPDs. In a wide-nanowire device, the strong local dependence will introduce a finite width to the PCR curve, but with sharp cusps. We show how Fano fluctuations can smooth these features to produce theoretical curves that better match experimental data. We also show that the time-resolved hotspot relaxation curves predicted by Fano fluctuations match the previously measured Lorentzian shapes (except for their tails) over the entire range of bias currents investigated experimentally. [ABSTRACT FROM AUTHOR]

We propose and experimentally realize a novel versatile protocol that allows the quantum state engineering of heralded optical coherent-state superpositions. This scheme relies on a two-mode squeezed state, linear mixing, and a n-photon detection. It is optimally using expensive non-Gaussian resources to build up only the key non-Gaussian part of the targeted state. In the experimental case of a two-photon detection based on high-efficiency superconducting nanowire single-photon detectors, the freely propagating state exhibits a 67% fidelity with a squeezed even coherent-state superposition with a size ∣α∣²=3. The demonstrated procedure and the achieved rate will facilitate the use of such superpositions in subsequent protocols, including fundamental tests and optical hybrid quantum information implementations. [ABSTRACT FROM AUTHOR]

We propose and experimentally demonstrate a novel approach to a heralded single-photon source based on spectral multiplexing (SMUX) and feed-forward-based spectral manipulation of photons created by means of spontaneous parametric down-conversion in a periodically poled LiNbO3 crystal. As a proof of principle, we show that our three-mode SMUX increases the heralded single-photon rate compared to that of the individual modes without compromising the quality of the emitted single photons. We project that by adding further modes, our approach can lead to a deterministic single-photon source. [ABSTRACT FROM AUTHOR]

We report on a free-space-coupled superconducting nanowire single-photon detector array developed for NASA's Deep Space Optical Communications project (DSOC). The array serves as the downlink detector for DSOC's primary ground receiver terminal located at Palomar Observatory's 200-inch Hale Telescope. The 64-pixel WSi array comprises four quadrants of 16 co-wound pixels covering a 320-µm diameter active area and embedded in an optical stack. The detector system also includes cryogenic optics for filtering and focusing the downlink signal and electronics for biasing the array and amplifying the output pulses. The detector system exhibits a peak system detection efficiency of 76% at 1550 nm, a background-limited false count rate as low as 3.7 kcps across the array, a timing jitter less than 120 ps FWHM, and a maximum count rate of ∼1 Gcps.

Introduction: The rapid development of software tools to assist systematic reviewers has led to varying degrees of adoption and selection among researchers. However, the actual usage patterns of these tools, their preferred features, and the criteria for selecting the most suitable tools remain unclear., Methods: To understand these aspects, we collected 175 responses from researchers across different continents., Results: In terms of handsearching, despite new tools developed, our findings reveal that manual handsearching remains prevalent among more than half of the participants. Databases are the most popular tools for citation searching, followed by citation management tools and spreadsheets. This reliance on citation management tools and spreadsheets is concerning as they are not specifically designed for systematic reviews. The primary factors influencing tool selection are the research environment and ease of use. Barriers stopping researchers from adopting alternative tools include limited awareness, challenges in learning new tools, and the financial costs associated with acquiring licenses. Moreover, researchers located in Europe show greater familiarity with a wider range of tools compared to their North American counterparts., Discussion: This preregistered study contributes valuable insights into the tool usage patterns of education researchers, emphasizing the importance of promoting awareness and facilitating the broader adoption of existing tools., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhang, Pellegrini, Marsili and Neitzel.)

We present ATLAS, a 512 × 512 single-photon avalanche diode (SPAD) array with embedded autocorrelation computation, implemented in 3D-stacked CMOS technology, suitable for single-photon correlation spectroscopy applications, including diffuse correlation spectroscopy (DCS). The shared per-macropixel SRAM architecture provides a 128 × 128 macropixel resolution, with parallel autocorrelation computation, with a minimum autocorrelation lag-time of 1 µs. We demonstrate the direct, on-chip computation of the autocorrelation function of the sensor, and its capability to resolve changes in decorrelation times typical of body tissue in real time, at long source-detector separations similar to those achieved by the current leading optical modalities for cerebral blood flow monitoring. Finally, we demonstrate the suitability for in-vivo measurements through cuff-occlusion and forehead cardiac signal measurements., Competing Interests: Robert Henderson and Neil Finlayson are co-founders of Singular Photonics, a company producing SPAD cameras for a variety of applications., (© 2024 The Author(s).)

Background: Type 2 diabetes mellitus (T2DM) is a worldwide socioeconomic burden, and is accompanied by a variety of metabolic disorders, as well as nerve dysfunction referred to as diabetic neuropathy (DN). Despite a tremendous body of research, the pathogenesis of DN remains largely elusive. Currently, two schools of thought exist regarding the pathogenesis of diabetic neuropathy: a) mitochondrial-induced toxicity, and b) microvascular damage. Both mechanisms signify DN as an intractable disease and, as a consequence, therapeutic approaches treat symptoms with limited efficacy and risk of side effects., Objective: Here, we propose that the human body exclusively employs mechanisms of adaptation to protect itself during an adverse event. For this purpose, two control systems are defined, namely the autonomic and the neural control systems. The autonomic control system responds via inflammatory and immune responses, while the neural control system regulates neural signaling, via plastic adaptation. Both systems are proposed to regulate a network of temporal and causative connections which unravel the complex nature of diabetic complications., Results: A significant result of this approach infers that both systems make DN reversible, thus opening the door to novel therapeutic applications., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Cerebral blood flow (CBF) is crucial for brain health. Speckle contrast optical spectroscopy (SCOS) is a technique that has been recently developed to measure CBF, but the use of SCOS to measure human brain function at large source-detector separations with comparable or greater sensitivity to cerebral rather than extracerebral blood flow has not been demonstrated. We describe a fiber-based SCOS system capable of measuring human brain activation induced CBF changes at 33 mm source detector separations using CMOS detectors. The system implements a pulsing strategy to improve the photon flux and uses a data processing pipeline to improve measurement accuracy. We show that SCOS outperforms the current leading optical modality for measuring CBF, i.e. diffuse correlation spectroscopy (DCS), achieving more than 10x SNR improvement at a similar financial cost. Fiber-based SCOS provides an alternative approach to functional neuroimaging for cognitive neuroscience and health science applications., (© 2023. Springer Nature Limited.)

Significance: Diffuse correlation spectroscopy (DCS) is an indispensable tool for quantifying cerebral blood flow noninvasively by measuring the autocorrelation function (ACF) of the diffused light. Recently, a multispeckle DCS approach was proposed to scale up the sensitivity with the number of independent speckle measurements, leveraging the rapid development of single-photon avalanche diode (SPAD) cameras. However, the extremely high data rate from advanced SPAD cameras is beyond the data transfer rate commonly available and requires specialized high-performance computation to calculate large number of autocorrelators (ACs) for real-time measurements., Aim: We aim to demonstrate a data compression scheme in the readout field-programmable gate array (FPGA) of a large-pixel-count SPAD camera. On-FPGA, data compression should democratize SPAD cameras and streamline system integration for multispeckle DCS., Approach: We present a 192 × 128 SPAD array with 128 linear ACs embedded on an FPGA to calculate 12,288 ACFs in real time., Results: We achieved a signal-to-noise ratio (SNR) gain of 110 over a single-pixel DCS system and more than threefold increase in SNR with respect to the state-of-the-art multispeckle DCS., Conclusions: The FPGA-embedded autocorrelation algorithm offers a scalable data compression method to large SPAD array, which can improve the sensitivity and usability of multispeckle DCS instruments., (© 2023 The Authors.)

Non-invasive continuous blood pressure monitoring remains elusive. There has been extensive research using the photoplethysmographic (PPG) waveform for blood pressure estimation, but improvements in accuracy are still needed before clinical use. Here we explored the use of an emerging technique, speckle contrast optical spectroscopy (SCOS), for blood pressure estimation. SCOS provides measurements of both blood volume changes (PPG) and blood flow index (BFi) changes during the cardiac cycle, and thus provides a richer set of parameters compared to traditional PPG. SCOS measurements were taken on the finger and wrists of 13 subjects. We investigated the correlations between features extracted from both the PPG and BFi waveforms with blood pressure. Features from the BFi waveforms were more significantly correlated with blood pressure than PPG features ( R  = - 0.55, p  = 1.1 × 10 -4 for the top BFi feature versus R  = - 0.53, p  = 8.4 × 10 -4 for the top PPG feature). Importantly, we also found that features combining BFi and PPG data were highly correlated with changes in blood pressure ( R  = - 0.59, p  = 1.7 × 10 -4 ). These results suggest that the incorporation of BFi measurements should be further explored as a means to improve blood pressure estimation using non-invasive optical techniques., Competing Interests: DB: Meta Platforms Inc. (F), DR: Meta Platforms Inc (F)., (© 2023 Optica Publishing Group under the terms of the Optica Open Access Publishing Agreement.)

Diffuse correlation spectroscopy (DCS) is a promising noninvasive technique for monitoring cerebral blood flow and measuring cortex functional activation tasks. Taking multiple parallel measurements has been shown to increase sensitivity, but is not easily scalable with discrete optical detectors. Here we show that with a large 500 × 500 SPAD array and an advanced FPGA design, we achieve an SNR gain of almost 500 over single-pixel mDCS performance. The system can also be reconfigured to sacrifice SNR to decrease correlation bin width, with 400 ns resolution being demonstrated over 8000 pixels., Competing Interests: MAW: Meta Platforms Inc. (F), EJS: Meta Platforms Inc. (E), PM: Meta Platforms Inc. (F), FM: Meta Platforms Inc. (E), EC: Fasttree3D SA (I,S) and PI Imaging Technology SA (I, S), CB: PI Imaging Technology SA (I, S)., (© 2023 Optica Publishing Group under the terms of the Optica Open Access Publishing Agreement.)

Psoriasis is a common chronic skin disease characterized by a worldwide distribution and a natural tendency towards progression. According to the many clinical forms, the extension of the disease and the many comorbidities, almost the 20% of the patients require a systemic treatment. Biologics have greatly changed the ongoing of psoriasis and the quality of life of psoriasis patients. After the anti-TNF-alpha, which were the first biologics in use for psoriasis, the improvement in knowledge of the pathogenetic mechanisms underlying the disease has led to the development of a series of more specific therapies for psoriasis. This "second generation" of biologics includes the interleukin (IL)-12/23 inhibitor ustekinumab, IL-17 inhibitors (secukinumab and ixekizumab), the IL-17 receptor A (IL-17RA) antagonist brodalumab, and the IL-23 inhibitors guselkumab, risankizumab and tildrakizumab. This study represents an update of the Tuscany consensus focused on the use of new drugs, such as anti-IL-17 and anti-IL-23 in moderate-to-severe psoriasis and their correct place in therapy according to specific clinical requests and in full respect of the current financial restrictions.

We introduce a dynamic speckle model (DSM) to simulate the temporal evolution of fully developed speckle patterns arising from the interference of scattered light reemitted from dynamic tissue. Using this numerical tool, the performance of laser speckle contrast imaging (LSCI) or speckle contrast optical spectroscopy (SCOS) systems which quantify tissue dynamics using the spatial contrast of the speckle patterns with a certain camera exposure time is evaluated. We have investigated noise sources arising from the fundamental speckle statistics due to the finite sampling of the speckle patterns as well as those induced by experimental measurement conditions including shot noise, camera dark and read noise, and calibrated the parameters of an analytical noise model initially developed in the fundamental or shot noise regime that quantifies the performance of SCOS systems using the number of independent observables (NIO). Our analysis is particularly focused on the low photon flux regime relevant for human brain measurements, where the impact of shot noise and camera read noise can become significant. Our numerical model is also validated experimentally using a novel fiber based SCOS (fb-SCOS) system for a dynamic sample. We have found that the signal-to-noise ratio (SNR) of fb-SCOS measurements plateaus at a camera exposure time, which marks the regime where shot and fundamental noise dominates over camera read noise. For a fixed total measurement time, there exists an optimized camera exposure time if temporal averaging is utilized to improve SNR. For a certain camera exposure time, photon flux value, and camera noise properties, there exists an optimized speckle-to-pixel size ratio (s/p) at which SNR is maximized. Our work provides the design principles for any LSCI or SCOS systems given the detected photon flux and properties of the instruments, which will guide the experimental development of a high-quality, low-cost fb-SCOS system that monitors human brain blood flow and functions., Competing Interests: Dr. Boas consulted with Meta Platforms Inc. on topics related to speckle contrast optical spectroscopy and diffuse correlation spectroscopy that ultimately led to the ideas presented in this paper. Dr. Boas’s interests were reviewed and are managed by Boston University in accordance with their conflict of interest policies., (© 2022 Optica Publishing Group under the terms of the Optica Open Access Publishing Agreement.)

Atopic dermatitis (AD) is a common inflammatory skin disease often associated with a significant impairment in the quality of life of affected patients. The Italian Society of Dermatology and Venereology (SIDeMaST) planned a national information campaign, providing direct access to 27 dermatologic centers dedicated to the management of AD. The aim of this study aimed was to outline critical aspects related to AD in the general population. Overall, 643 adult subjects were included in this study, and in 44.2% (284/643) of cases, a diagnosis of AD was confirmed, whereas about 55% of subjects were affected by other pruritic cutaneous diseases. Higher intensity of pruritus and sleep disturbance, as well as an increased interference in sport, work, and social confidence was reported in the AD group compared to the non-AD group. In the AD subgroup, the mean duration of disease was of 15.3 years, with a mean eczema area and severity index (EASI) score of 11.2, and investigator global assessment (IGA) score of 1.9 and an itch numeric rating scale (NRS) of 6.9. Almost 32% of patients were untreated, either with topical or systemic agents, whereas 44.3% used routine topical compounds (topical corticosteroids and calcineurin inhibitors), and only 7.0% of patients were systemically treated. Only 2.8% of patients reported complete satisfaction with the treatment received for AD to date. This study reveals a profound unmet need in AD, showing a poorly managed and undertreated patient population despite a high reported burden of disease. This suggests the usefulness of information campaigns with the goal of improving patient awareness regarding AD and facilitating early diagnosis and access to dedicated healthcare institutions., Competing Interests: The authors declare no conflict of interest related to this study.

Significance: Diffuse correlation spectroscopy (DCS) is an optical technique that measures blood flow non-invasively and continuously. The time-domain (TD) variant of DCS, namely, TD-DCS has demonstrated a potential to improve brain depth sensitivity and to distinguish superficial from deeper blood flow by utilizing pulsed laser sources and a gating strategy to select photons with different pathlengths within the scattering tissue using a single source-detector separation. A quantitative tool to predict the performance of TD-DCS that can be compared with traditional continuous wave DCS (CW-DCS) currently does not exist but is crucial to provide guidance for the continued development and application of these DCS systems., Aims: We aim to establish a model to simulate TD-DCS measurements from first principles, which enables analysis of the impact of measurement noise that can be utilized to quantify the performance for any particular TD-DCS system and measurement geometry., Approach: We have integrated the Monte Carlo simulation describing photon scattering in biological tissue with the wave model that calculates the speckle intensity fluctuations due to tissue dynamics to simulate TD-DCS measurements from first principles., Results: Our model is capable of simulating photon counts received at the detector as a function of time for both CW-DCS and TD-DCS measurements. The effects of the laser coherence, instrument response function, detector gate delay, gate width, intrinsic noise arising from speckle statistics, and shot noise are incorporated in the model. We have demonstrated the ability of our model to simulate TD-DCS measurements under different conditions, and the use of our model to compare the performance of TD-DCS and CW-DCS under a few typical measurement conditions., Conclusion: We have established a Monte Carlo-Wave model that is capable of simulating CW-DCS and TD-DCS measurements from first principles. In our exploration of the parameter space, we could not find realistic measurement conditions under which TD-DCS outperformed CW-DCS. However, the parameter space for the optimization of the contrast to noise ratio of TD-DCS is large and complex, so our results do not imply that TD-DCS cannot indeed outperform CW-DCS under different conditions. We made our code available publicly for others in the field to find use cases favorable to TD-DCS. TD-DCS also provides a promising way to measure deep brain tissue dynamics using a short source-detector separation, which will benefit the development of technologies including high density DCS systems and image reconstruction using a limited number of source-detector pairs.

Significance : Diffuse correlation spectroscopy (DCS) measures cerebral blood flow non-invasively. Variations in blood flow can be used to detect neuronal activities, but its peak has a latency of a few seconds, which is slow for real-time monitoring. Neuronal cells also deform during activation, which, in principle, can be utilized to detect neuronal activity on fast timescales (within 100 ms) using DCS. Aims : We aim to characterize DCS signal variation quantified as the change of the decay time of the speckle intensity autocorrelation function during neuronal activation on both fast (within 100 ms) and slow (100 ms to seconds) timescales. Approach : We extensively modeled the variations in the DCS signal that are expected to arise from neuronal activation using Monte Carlo simulations, including the impacts of neuronal cell motion, vessel wall dilation, and blood flow changes. Results : We found that neuronal cell motion induces a DCS signal variation of ∼ 10 - 5 . We also estimated the contrast and number of channels required to detect hemodynamic signals at different time delays. Conclusions : From this extensive analysis, we do not expect to detect neuronal cell motion using DCS in the near future based on current technology trends. However, multi-channel DCS will be able to detect hemodynamic response with sub-second latency, which is interesting for brain-computer interfaces., (© 2021 The Authors.)

Functional near-infrared spectroscopy (fNIRS) measures human brain function noninvasively. The optical response to oxy- and deoxy-hemoglobin concentration variations during brain activation is wavelength dependent because of the differing spectral shapes of the extinction coefficients of the two hemoglobin species. Choosing the optimal wavelength in fNIRS measurements is crucial to improving the performance of the technique. Here we report on a framework to estimate the spectral response to neural activation in a pre-defined local region. We found that the wavelength that exhibits the largest fractional change in the detected fluence with respect to the baseline value is around 830 nm.

We carried out an investigation on rabies virus-like particles (RV-VLPs) expressed in HEK293 cells using serum free medium. These RV-VLPs were formulated with two different adjuvants in order to analyse the enhancement of the triggered immune response and its stability. In experiments in mice, RV-VLPs showed an enhanced humoral immune response when injected with adjuvant, in contrast to the obtained for the RV-VLPs without adjuvant addition. Besides, higher titers of neutralizing antibodies were induced when RV-VLPs were formulated with LipoSap® in comparison with the obtained with Alhydrogel®. At the same time, the positive effect of this adjuvant in vaccine's potency and stability was demonstrated, showing that LipoSap® significantly increases the value obtained in NIH efficiency test for rabies vaccine, and proving that this value is maintained after 15 months storage at 4 °C. Further, we showed that RV-VLPs induces an immune response based on neutralizing antibodies when cat, dogs and bovines were vaccinated with only one dose of RV-VLPs. These results demonstrated that this vaccine candidate could be applied for the prevention of rabies in pets as well as for the control of paralytic rabies in cattle., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Significance: Cerebral blood flow is an important biomarker of brain health and function as it regulates the delivery of oxygen and substrates to tissue and the removal of metabolic waste products. Moreover, blood flow changes in specific areas of the brain are correlated with neuronal activity in those areas. Diffuse correlation spectroscopy (DCS) is a promising noninvasive optical technique for monitoring cerebral blood flow and for measuring cortex functional activation tasks. However, the current state-of-the-art DCS adoption is hindered by a trade-off between sensitivity to the cortex and signal-to-noise ratio (SNR). Aim: We aim to develop a scalable method that increases the sensitivity of DCS instruments. Approach: We report on a multispeckle DCS (mDCS) approach that is based on a 1024-pixel single-photon avalanche diode (SPAD) camera. Our approach is scalable to > 100,000 independent speckle measurements since large-pixel-count SPAD cameras are becoming available, owing to the investments in LiDAR technology for automotive and augmented reality applications. Results: We demonstrated a 32-fold increase in SNR with respect to traditional single-speckle DCS. Conclusion: A mDCS system that is based on a SPAD camera serves as a scalable method toward high-sensitivity DCS measurements, thus enabling both high sensitivity to the cortex and high SNR., (© The Authors. Published by SPIE under a Creative Commons Attribution 4.0 Unported License. Distribution or reproduction of this work in whole or in part requires full attribution of the original publication, including its DOI.)

Atopic dermatitis (AD) is an inflammatory disease with a chronic-relapsing course that is intensely itchy. A correct diagnosis of AD in adults and consequently appropriate clinical therapeutic management is a critical issue for extreme clinical expression heterogeneity and various grades of disease severity. In order to ensure high levels of care and standardization of clinical therapeutic management of Adult AD, the decision was taken to create an AD Tuscan Consensus Group (the Group), to work on and validate a consensus based regional clinical-therapeutic management model. The aims of the Group were to find agreement on the criteria for diagnosis, scoring of severity, multidisciplinary approach and treatment of adult atopic dermatitis and to create an easier way for patients to access specialized dermatology outpatient services and importantly to reduce waiting lists and costs related to the management of AD. The Tuscan Consensus Group adopted a simplified Delphi method, in three principal steps: 1) literature metanalysis and critical review of patient's clinical experience to identify the main areas considered questionable or uncertain; 2) discussion of those areas requiring consensus and statement definition through four different sub-committees (diagnosis, severity evaluation, scoring and comorbidities); 3) a consensus based simplified process with final approval of each statement by plenary vote with approval >80% of the participants. The Group here presents and discusses the consensus based recommendation statements on adult atopic dermatitis.

Rabies is a neglected disease with an estimated annual mortality of 55,000 human deaths, affecting mainly low-income countries. Over 95% of these cases result from virus transmission through the bite of infected dogs and for this reason there is a real need for a cheap and effective rabies veterinary vaccine to be used in mass vaccination campaigns. In this work, we describe the establishment of a simple platform for the production of a virus-like particles based rabies vaccine using mammalian cells and roller bottles as culture system. Adherent cells were cultured during more than 15 days and VLPs were continuously produced and secreted to the culture supernatant. Immunogenicity and protective efficacy of VLPs were tested through rabies virus neutralizing antibody test and NIH potency test. These viral particles induced high titer of long lasting neutralizing antibodies and protected mice against active virus challenge. Therefore, this development represents a promising platform for the production of a new generation and virus-free rabies vaccine candidate for veterinary applications., (Copyright © 2019 Elsevier Ltd. All rights reserved.)