Reduction formula for cross-spectral purity of nonstationary light fields.

We examine cross-spectral purity of random, nonstationary (pulsed), scalar light fields with arbitrary spectral bandwidth. In particular, we derive a reduction formula in terms of time-integrated coherence functions, which ensures cross-spectral purity of interfering fields having identical normalized spectra. We further introduce fields that are cross-spectrally pure in either a global or local sense. Our analysis is based on an ideal field superposition realizable with all-reflective wavefront-shearing interferometers. Such devices avoid certain problems related to Young's interferometer, which is the framework customarily employed in assessing cross-spectral purity. We show that any partially coherent beam can be transformed into a locally cross-spectrally pure beam whose cross-spectral density is specular. On the other hand, lack of space-frequency (and space-time) coupling ensures cross-spectral purity in the global sense, i.e., across an entire transverse plane, regardless of the spectral bandwidth or the temporal shape of the pulses.

Efficacy and safety of Lacticaseibacillus paracasei Lpc-37® in students facing examination stress: A randomized, triple-blind, placebo-controlled clinical trial (the ChillEx study).

Lacticaseibacillus paracasei Lpc-37 (Lpc-37) has previously shown to reduce perceived stress in healthy adults. The ChillEx study investigated whether Lpc-37 reduces stress in a model of chronic examination stress in healthy students. One hundred ninety university students (18-40 y) were randomized to take 1.56 × 1010 colony-forming units of Lpc-37 or placebo (1:1) each day for 10 weeks, in a triple-blind, parallel, multicenter clinical trial consisting of six visits: two screening visits, a baseline visit, and visits at 4, 8, and 10 weeks after baseline. The primary objective was to demonstrate that Lpc-37 reduces stress, as measured by the change in state anxiety from baseline to just before the first examination, after 8 weeks using the State Trait Anxiety Inventory (STAI-state). Secondary objectives aimed to demonstrate that Lpc-37 modulates psychological stress-induced symptoms and biomarkers related to mood and sleep. An exploratory analysis of fecal microbiota composition was also conducted. There was no difference between Lpc-37 and placebo groups in the change of STAI-state score (estimate 1.03; 95% confidence interval [CI]: -1.62, 3.67; p = 0.446). None of the secondary outcomes resulted in significant results when corrected for multiplicity, but exploratory results were notable. Results showed an improvement in sleep-disturbance scores (odds ratio 0.30; 95% CI: 0.11, 0.82; p = 0.020) and reduction in duration of sleep (odds ratio 3.52; 95% CI: 1.46, 8.54; p = 0.005) on the Pittsburgh Sleep Quality Index questionnaire after 8 weeks in the Lpc-37 group compared to placebo. A reduction in Bond Lader VAS-alertness was also demonstrated in the Lpc-37 group compared to placebo (estimate -3.97; 95% CI: -7.78, -0.15; p = 0.042) just prior to the examination. Analysis of fecal microbiota found no differences between study groups for alpha and beta diversity or microbiota abundance. Adverse events were similar between groups. Vital signs, safety-related laboratory measures, and gastrointestinal parameters were stable during the trial. In conclusion, probiotic Lpc-37 was safe but had no effect on stress, mood, or anxiety in healthy university students in this model of chronic academic stress. ClinicalTrials.gov: NCT04125810.

Feasibility of neural network metamodels for emulation and sensitivity analysis of radionuclide transport models.

In this paper we compare the outputs of neural network metamodels with numerical solutions of differential equation models in modeling cesium-137 transportation in sand. Convolutional neural networks (CNNs) were trained with differential equation simulation results. Training sets of various sizes (from 5120 to 163,840) were used. First order and total order Sobol methods were applied to both models in order to test the feasibility of neural network metamodels for sensitivity analysis of a radionuclide transport model. Convolutional neural networks were found to be capable of emulating the differential equation models with high accuracy when the training set size was 40,960 or higher. Neural network metamodels also gave similar results compared with the numerical solutions of the partial differential equation model in sensitivity analysis.

Measurement of spatial coherence of light [Invited].

The most frequently used experimental techniques for measuring the spatial coherence properties of classical light fields in the space-frequency and space-time domains are reviewed and compared, with some attention to polarization effects. In addition to Young's classical two-pinhole experiment and several of its variations, we discuss methods that allow the determination of spatial coherence at higher data acquisition rates and also permit the characterization of lower-intensity light fields. These advantages are offered, in particular, by interferometric schemes that employ only beam splitters and reflective elements, and thereby also facilitate spatial coherence measurements of broadband fields.

On the inclusion of forest exposure pathways into a stylized lake-farm scenario in a geological repository safety analysis.

Geological disposal of radioactive waste has been recognized as the 'reference solution' to ensure the safety required for the present and future society and environment. To study the possible exposure pathways from groundwater to humans, radioactive transport modelling is used. One of the ecosystems that may play a significant role when assessing the dose conversion factor (i.e. the dose resulting from a nominal release of 1 Bq/year of each radionuclide) for humans is forest. In this paper we have developed a model of a lake-farm system with a forest component. The biosphere system used in this study represents a typical agricultural scenario in Finland, amended with a typical forest. A lake is assumed to form due to post-glacial land uplift. The main features of this future lake have been obtained from our probabilistic shoreline displacement model. Both deterministic calculations and sensitivity analysis were carried out to simulate the model. The deterministic simulation demonstrates the behaviour of the studied radionuclides (36Cl, 135Cs, 129I, 237Np, 90Sr, 99Tc and 238U) and the proportions of different exposure pathways to humans. Particularly for 135Cs and 129I, forest pathways make a notable contribution to the dose conversion factor. The sensitivity analysis was done using two methods: EFAST and Sobol'. With both methods, the parameters related to the farm contribute the most to the variance of the dose conversion factor for humans. The study demonstrates that the exposure pathways related to forest products may make a considerable contribution to the dose conversion factor in a lake-farm-forest system. It is also confirmed that an advanced sensitivity analysis for a radionuclide transport and dose assessment model on such a landscape scale is feasible even with moderate computational efforts.

Pulse modulation by Bloch surface wave excitation.

Considering dielectric multilayers with N identical bilayers and an additional terminating layer, we address the effect of Bloch surface wave excitation on the temporal characteristics of short optical pulses. When such a resonant excitation occurs within the spectrum of the incident pulse, the reflected pulse splits into leading and trailing parts, the latter having an exponentially decaying tail. The role of the number of bilayers and the level of absorption in the multilayer stack is illustrated.

Azimuthally periodic and radially quasi-periodic Bessel-correlated fields.

We introduce a class of partially coherent sources, which are capable of producing beams with radially quasi-periodic and azimuthally fully periodic intensity profiles. The physical properties of the source, as well as the propagation of the intensity distribution and the complex degree of spatial coherence of the ensuing beams are investigated and interpreted. It is shown that the shape and symmetry of the intensity and the degree of spatial coherence are generally adjustable and modulated by the parameters related to the beam source. Moreover, the periodic changes of intensity arise from the discontinuity of the phase. The results provide a method for synthesizing fields with peculiar periodic intensity distributions in polar coordinates.

Pulse shaping by spectral-domain polarization gratings.

We consider the spectral-domain counterparts of spatial-domain polarization gratings and study their effect on the temporal evolution of femtosecond-scale light pulses. These devices divide an incident light pulse to several orders via spectral polarization modulation, permitting pulse splitting and shaping with controlled time-domain polarization dynamics.

Propagation of Bessel-correlated specular and antispecular beams.

We address the specular properties of Bessel-correlated fields, generated by illuminating a tilted rotating plane-parallel glass plate with a coherent Gaussian beam and passing the output beam though a mirror-based wavefront folding interferometer. This device allows us to produce beams whose specular properties are preserved in propagation. In the far zone, the specular nature of these partially coherent fields is shown to produce intensity-profile oscillations in the sub-diffraction-limit scale. The analytical results at various propagation distances are verified experimentally by using another wavefront-folding interferometer for coherence measurements.

Grating Theory Approach to Optics of Nanocomposites.

Nanocomposites, i.e., materials comprising nano-sized entities embedded in a host matrix, can have tailored optical properties with applications in diverse fields such as photovoltaics, bio-sensing, and nonlinear optics. Effective medium approaches such as Maxwell-Garnett and Bruggemann theories, which are conventionally used for modeling the optical properties of nanocomposites, have limitations in terms of the shapes, volume fill fractions, sizes, and types of the nanoentities embedded in the host medium. We demonstrate that grating theory, in particular the Fourier Eigenmode Method, offers a viable alternative. The proposed technique based on grating theory presents nanocomposites as periodic structures composed of unit-cells containing a large and random collection of nanoentities. This approach allows us to include the effects of the finite wavelength of light and calculate the nanocomposite characteristics regardless of the morphology and volume fill fraction of the nano-inclusions. We demonstrate the performance of our approach by calculating the birefringence of porous silicon, linear absorption spectra of silver nanospheres arranged on a glass substrate, and nonlinear absorption spectra for a layer of silver nanorods embedded in a host polymer material having Kerr-type nonlinearity. The developed approach can also be applied to quasi-periodic structures with deterministic randomness or metasurfaces containing a large collection of elements with random arrangements inside their unit cells.

Coherence Switching with Metamaterials.

We demonstrate, theoretically, how the insertion of an enhanced epsilon-near-zero (EENZ) mirror in a laser cavity grants exceptional control over the coherence properties of the emitted light beam. By exploiting the peculiar sensitivity to polarization of EENZ materials, we achieve superior control over the spatial coherence of the emitted laser light, which can be switched at will between nearly incoherent and fully coherent, solely by means of polarization optics. Our EENZ cavity design is expected to be an efficient, compact, reconfigurable, and easily scalable source of light for illumination and speckle contrast imaging, as well as any other application that benefits from controlled spatial coherence.

Correlated and uncorrelated parts of scalar fields in two-beam optical interferometry.

We show that in the interference of two partially correlated scalar light beams, the fields can be divided into parts that are mutually completely correlated (coherent) and parts that are fully uncorrelated with the correlated parts and with each other. Such correlated and uncorrelated parts cannot, in general, be unambiguously specified, but with a certain additional constraint, the partition becomes unique and can be determined. We demonstrate experimentally that the uncorrelated contribution can be physically isolated with the help of a spatial unitary transformation, such as a nonabsorbing beam splitter. Our findings constitute foundational results on optical two-beam interferometry.

Hydroxychloroquine in the treatment of adult patients with Covid-19 infection in a primary care setting (LIBERTY): A structured summary of a study protocol for a randomised controlled trial.

OBJECTIVES: The primary objective of this study is to evaluate the therapeutic potential of hydroxychloroquine (HCQ) in the treatment of adult patients with PCR-confirmed Covid-19 infection in a primary open-care setting, as compared to placebo. The study hypothesis is that treatment with HCQ will reduce the risk of hospitalization because of Covid-19 infection, and the sample size estimate of the study is based on the need to test this hypothesis. The secondary objectives of the study are: to evaluate the safety and tolerability of HCQ in the treatment of adult patients with PCR-confirmed Covid-19 infection in a primary open-care setting, as compared to placebo; to collect experience of the use of HCQ in the treatment of Covid-19 infection in outpatients, in order to be able to identify patient characteristics that predict specific treatment responses (favourable or unfavourable); this objective will also be addressed by post-hoc subgroup analysis of the study results and by meta-analysis of pooled patient data from other clinical trials of HCQ in outpatients; and to evaluate the impact of Covid-19 infection and its treatment on the mental health and well-being of the study participants. In addition, if the data allow, the study has the following exploratory objectives: to evaluate the extent and duration of SARS-CoV-2 viral shedding by PCR testing of nasopharyngeal swab samples in study subjects treated with HCQ, as compared to placebo; to evaluate the extent and time course of SARS-CoV-2 virus-specific antibody responses in serum of study subjects treated with HCQ, as compared to placebo; to evaluate other possible biomarker changes in blood in study subjects treated with HCQ, as compared to placebo; to explore the possible effects of genetic variation in drug metabolizing enzymes on HCQ-related outcomes in the study population; to explore the associations of HCQ-related outcome variables with other patient characteristics, e.g. HLA haplotypes, HCQ concentrations, demographic variables, disease history and concomitant medications. TRIAL DESIGN: This is a phase 2, placebo-controlled, double-blind, randomized, parallel-group treatment trial comparing HCQ with placebo in outpatients with Covid-19 infection. Participants will be randomized in a 1:1 ratio to the two treatment arms. PARTICIPANTS: Main inclusion criteria: 1. Males and females >40 years of age, or 18-40 years of age with one or both of the following: i. diabetes mellitus (type 1 or type 2); ii. BMI > 35 kg/m2; 2. Valid independent informed consent obtained; 3. Symptoms typical of Covid-19 infection, according to criteria specified in the study protocol. The onset of symptoms must be within 5 days of enrolment; 4. Positive SARS-CoV-2 PCR test result of a nasopharyngeal swab sample. Main exclusion criteria: 1. Suspected severe or moderately severe pneumonia, presenting with any of the following: respiratory rate > 26 breaths/min; significant respiratory distress; or SpO2 ≤94% on room air; 2. Requiring treatment in the hospital, according to the treating physician's judgement; 3. Any contraindication to treatment with HCQ; 4. Pregnancy or lactation. The trial will be conducted at seven study sites in a primary public health care setting in the region of Satakunta, Finland. INTERVENTION AND COMPARATOR: Participants will be randomized to receive either HCQ capsules at 300 mg twice a day for one day and then 200 mg twice a day for 6 days, or placebo capsules for 7 days. MAIN OUTCOMES: The primary endpoint of the study is the number of hospitalizations due to Covid-19 infection within four weeks of entry into the study. The secondary endpoints of the study include the following: duration and severity of Covid-19-related symptoms, as reported by daily self-assessments; number of Intensive Care Unit treatment episodes due to Covid-19 infection within four weeks of entry into the study; number of deaths due to Covid-19 infection within four weeks of entry into the study; number of treatment-related adverse events (AEs) and serious AEs (SAEs); all-cause hospitalizations and mortality within six months of entry into the study; and self-assessed symptoms of anxiety, as assessed with repeated administration of the Generalized Anxiety Disorder 7-item scale (GAD-7). The exploratory endpoints of the study include the following: extent and duration of SARS-CoV-2 viral shedding and virus-specific antibody responses in serum; and possible other blood biomarker changes. RANDOMISATION: Eligible study participants are randomly allocated into two treatment arms (1:1 ratio). The randomization list has been generated using Viedoc™ (Viedoc Technologies AB, Uppsala, Sweden) that is used as an electronic data capture system for this study. BLINDING (MASKING): The participants and all study personnel remain blinded to the treatment allocation by having both IMPs packed in identical containers. Masking of the treatments was performed by re-formulation of the IMPs so that the HCQ capsules and the placebo capsules have identical appearance. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): 600 participants are to be randomised with 300 in each arm. TRIAL STATUS: Protocol version 2, dated 14 July 2020; recruitment is expected to start in December, 2020, and to be completed in June, 2021. TRIAL REGISTRATION: EudraCT 2020-002038-33 , registered 26 June 2020 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). The protocol has been redacted to conform with privacy regulations by deleting the names and contact information of individuals mentioned in the protocol but not listed as authors in this communication. In the interest of expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Genuine-field modeling of partially coherent X-ray imaging systems.

A genuine representation of the cross-spectral density function as a superposition of mutually uncorrelated, spatially localized modes is applied to model the propagation of spatially partially coherent light beams in X-ray optical systems. Numerical illustrations based on mode propagation with VirtualLab software are presented for imaging systems with ideal and non-ideal grazing-incidence mirrors.

Mirror-based scanning wavefront-folding interferometer for coherence measurements.

We demonstrate a modification to the traditional prism-based wavefront-folding interferometer that allows the measurement of spatial and temporal coherence, free of distortions and diffraction caused by the prism corners. In our modified system, the two prisms of the conventional system are replaced with six mirrors. The whole system is mounted on a linear XY-translation stage, with an additional linear stage in the horizontal arm. This system enables rapid and exact measurement of the full four-dimensional degree of coherence, even for relatively weak signals. The capabilities of our system are demonstrated by measuring the spatial coherence of two inhomogeneous and non-Schell model light sources with distinct characteristics.

Temporal coherence and polarization modulation of pulse trains by resonance gratings.

We analyze the effects of subwavelength-period resonance gratings on temporally partially coherent optical plane-wave pulse trains. The interaction of the grating with pulses is simulated with the Fourier modal method and finite-difference time-domain method whose performances are compared. Both TE and TM linearly polarized Gaussian Schell-model pulse trains are examined, and partial temporal coherence is modeled with the identical elementary-pulse method. The polarization-dependent response of the grating is seen to lead to significant variations in the average intensity, polarization properties, and degree of temporal coherence of the reflected (and transmitted) pulse trains when the coherence time and polarization state of the incident field are altered. As an important example, we demonstrate that a fully polarized incident pulse train can become partially polarized in grating reflection. The results find use in tailoring of random electromagnetic pulse trains.

Large-angle beaming from asymmetric nanoslit-corrugation structures.

The beaming effect in single apertures surrounded by periodic corrugations and the manipulation of beaming directions from such structures has gained considerable attention since discovery. Different materials and structural profiles have been studied in this context but directional beaming at angles larger than 45° has not been achieved. We design and demonstrate nanoslits in a gold film flanked by corrugations, which give rise to beaming angles ranging from 45° to 60°. While the previous designs are based on achieving constructive interference at the aimed beaming angle, our approach complements such constructive interference with destructive interference at 0° and, as a result, enhances the directional beaming effect at angles larger than 45°. The structures are fabricated by electron beam lithography with two consecutive lift-off processes. The experimental far-field intensity distributions agree well with the designs.

Temporal coherence modulation of pulsed, scalar light with a Fabry-Pérot interferometer.

We analyze the effect of a high-finesse Fabry-Pérot interferometer on the temporal coherence properties of scalar optical plane-wave pulse trains. We focus on the cases of single-peak and double-peak transmissions of Gaussian Schell-model (GSM) and supercontinuum (SC) pulses. For the GSM light, we show how the characteristics of the average intensity and temporal degree of coherence of the transmitted pulses depend on the coherence parameters of the incident field. Regarding the SC light, the output is found to depend specifically on the location of the transmission peak(s) within the average spectrum. The results demonstrate that a Fabry-Pérot etalon can act as a simple passive element for tailoring the temporal (and spectral) coherence properties of optical pulse trains.

Imaging-quality 3D-printed centimeter-scale lens.

Three-dimensional (3D) printing of imaging-quality optics has been challenging due to the tight tolerances on surface shape and roughness. We report on manufacturing such optics with Print optical Technology, which is based on modified ink-jet printing. We demonstrate for the first time a 3D-printed singlet lens with a surface profile deviation of ±500 nm within a 12-mm aperture diameter. Its RMS surface roughness is below 1 nm without surface polishing. The printed lens exhibits an imaging resolution of some 140 lp mm -1 at 100-mm focal length in the visible region.

Scanning wavefront folding interferometers.

We present modified scanning-type wavefront folding interferometers (WFIs), which allow spatial coherence measurements of non-uniformly correlated fields, where the degree of coherence is a function of two absolute spatial coordinates instead of coordinate separation only (Schell model). As an alternative to conventional prism-based WFI implementations, we introduce a scheme based on reflections by three mirrors. This setup allows us to avoid obstructions due to prism corners, and it is remarkably robust to polarization effects. Experimental results on measurement of fields that do not obey the Schell model are provided with the three-mirror WFI, and the results are compared to those obtained with a Young's interferometer realized using a digital micromirror device.