Generating Airy beams through multimode fibres.

Focussing light through a multimode fibre (MMF) is the basis of holographic endoscopes, which currently enable detailed imaging of deep tissue. Achieving high fidelity and purity diffraction-limited foci has been shown to be possible, when fully controlling the amplitude, phase, and two orthogonal polarisation states of the input field. Yet, generating more complex field distributions with similar performance remains to be assessed. Here, we demonstrate the generation of Airy beams through an MMF containing in excess of 90 % of the optical power delivered by the fibre. We discuss two distinct methods for generating optical landscapes: the direct field and the Fourier domain synthesis. Moreover, we showcase the flexibility of the Fourier domain synthesis to modify the generated beam.

Interoperable workflows by exchanging grid-based data between quantum-chemical program packages.

Quantum-chemical subsystem and embedding methods require complex workflows that may involve multiple quantum-chemical program packages. Moreover, such workflows require the exchange of voluminous data that go beyond simple quantities, such as molecular structures and energies. Here, we describe our approach for addressing this interoperability challenge by exchanging electron densities and embedding potentials as grid-based data. We describe the approach that we have implemented to this end in a dedicated code, PyEmbed, currently part of a Python scripting framework. We discuss how it has facilitated the development of quantum-chemical subsystem and embedding methods and highlight several applications that have been enabled by PyEmbed, including wave-function theory (WFT) in density-functional theory (DFT) embedding schemes mixing non-relativistic and relativistic electronic structure methods, real-time time-dependent DFT-in-DFT approaches, the density-based many-body expansion, and workflows including real-space data analysis and visualization. Our approach demonstrates, in particular, the merits of exchanging (complex) grid-based data and, in general, the potential of modular software development in quantum chemistry, which hinges upon libraries that facilitate interoperability.

A Measure of Synergy Based on Union Information.

The partial information decomposition (PID) framework is concerned with decomposing the information that a set of (two or more) random variables (the sources) has about another variable (the target) into three types of information: unique, redundant, and synergistic. Classical information theory alone does not provide a unique way to decompose information in this manner and additional assumptions have to be made. One often overlooked way to achieve this decomposition is using a so-called measure of union information-which quantifies the information that is present in at least one of the sources-from which a synergy measure stems. In this paper, we introduce a new measure of union information based on adopting a communication channel perspective, compare it with existing measures, and study some of its properties. We also include a comprehensive critical review of characterizations of union information and synergy measures that have been proposed in the literature.

Phenotype of BTK-lacking myeloid cells during prolonged COVID-19 and upon convalescent plasma.

XLA patient with 7-month course of COVID-19 with persistent plasma SARS-CoV-2 load revealed a sustained non-inflammatory profile of myeloid cells in association with contained severity of disease, arguing in favor of the use of BTK inhibitors in SARS-COV-2 infection.

Core Excitations of Uranyl in Cs2UO2Cl4 from Relativistic Embedded Damped Response Time-Dependent Density Functional Theory Calculations.

X-ray spectroscopies, by their high selectivity and sensitivity to the chemical environment around the atoms probed, provide significant insights into the electronic structures of molecules and materials. Interpreting experimental results requires reliable theoretical models, accounting for environmental, relativistic, electron correlation, and orbital relaxation effects in a balanced manner. In this work, we present a protocol for the simulation of core excited spectra with damped response time-dependent density functional theory based on the Dirac-Coulomb Hamiltonian (4c-DR-TD-DFT), in which environmental effects are accounted for through the frozen density embedding (FDE) method. We showcase this approach for the uranium M4- and L3-edges and oxygen K-edge of the uranyl tetrachloride (UO2Cl42-) unit as found in a host Cs2UO2Cl4 crystal. We have found that the 4c-DR-TD-DFT simulations yield excitation spectra that very closely match the experiment for the uranium M4-edge and the oxygen K-edge, with good agreement for the broad experimental spectra for the L3-edge. By decomposing the complex polarizability in terms of its components, we have been able to correlate our results with angle-resolved spectra. We have observed that for all edges, but in particular the uranium M4-edge, an embedded model in which the chloride ligands are replaced by an embedding potential reproduces rather well the spectral profile obtained for UO2Cl42-. Our results underscore the importance of the equatorial ligands to simulating core spectra at both uranium and oxygen edges.

How Does Bending the Uranyl Unit Influence Its Spectroscopy and Luminescence?

Bent uranyl complexes can be formed with chloride ligands and 1,10-phenanthroline (phen) ligands bound to the equatorial and axial planes of the uranyl(VI) moiety, as revealed by the crystal structures, IR and Raman spectroscopy, and quantum-chemical calculations. With the goal of probing the influence of chloride and phenanthroline coordination enforcing the bending on the absorption and emission spectra of this complex, spin-orbit time-dependent density functional theory calculations for the bare uranyl complexes as well as for the free UO2Cl2 subunit and the UO2Cl2(phen)2 complex were performed. The emission spectra have been fully simulated by ab initio methods and compared to experimental photoluminescence spectra, recorded for the first time for UO2Cl2(phen)2. Notably, the bending of uranyl in UO2Cl2 and UO2Cl2(phen)2 triggers excitations of the uranyl bending mode, yielding a denser luminescence spectrum.

Orders between Channels and Implications for Partial Information Decomposition.

The partial information decomposition (PID) framework is concerned with decomposing the information that a set of random variables has with respect to a target variable into three types of components: redundant, synergistic, and unique. Classical information theory alone does not provide a unique way to decompose information in this manner, and additional assumptions have to be made. Recently, Kolchinsky proposed a new general axiomatic approach to obtain measures of redundant information based on choosing an order relation between information sources (equivalently, order between communication channels). In this paper, we exploit this approach to introduce three new measures of redundant information (and the resulting decompositions) based on well-known preorders between channels, contributing to the enrichment of the PID landscape. We relate the new decompositions to existing ones, study several of their properties, and provide examples illustrating their novelty. As a side result, we prove that any preorder that satisfies Kolchinsky's axioms yields a decomposition that meets the axioms originally introduced by Williams and Beer when they first proposed PID.

SARS-CoV2 pneumonia recovery is linked to expansion of innate lymphoid cells type 2 expressing CCR10.

Accelerate lung repair in SARS-CoV-2 pneumonia is essential for pandemic handling. Innate lymphoid cells (ILCs) are likely players, given their role in mucosal protection and tissue homeostasis. We studied ILC subpopulations at two time points in a cohort of patients admitted in the hospital due to SARS-CoV-2 infection. COVID-19 patients with moderate/severe respiratory failure featured profound depletion of circulating ILCs at hospital admission, in agreement with overall lymphocyte depletion. However, ILCs recovered in direct correlation with lung function improvement as measured by oxygenation index and in negative association with inflammatory and lung/endothelial damage markers like RAGE. While both ILC1 and ILC2 expanded, ILC2 showed the most striking phenotype changes, with CCR10 upregulation in strong correlation with these parameters. Overall, CCR10+ ILC2 emerge as relevant contributors to SARS-CoV-2 pneumonia recovery.

Near perfect focusing through multimode fibres.

Holographic, multimode fibre (MMF) based endoscopes envision high-quality in-vivo imaging inside previously inaccessible structures of living organisms, amongst other perspective applications. Within these instruments, a digital micro-mirror device (DMD) is deployed in order to holographically synthesise light fields which, after traversing the multimode fibre, form foci at desired positions behind the distal fibre facet. When applied in various imaging modalities, the purity and sharpness of the achieved foci are determinant for the imaging performance. Here we present diffraction-limited foci, which contain in excess of 96% of optical power delivered by the fibre which, to the best of our knowledge, represents the highest value reported to date. Further, we quantitatively study the impact of various conditions of the experimental procedure including input polarisation settings, influence of ghost diffraction orders, light modulation regimes, bias of the calibration camera and the influence of noise.

Simulating core electron binding energies of halogenated species adsorbed on ice surfaces and in solution via relativistic quantum embedding calculations.

In this work, we investigate the effects of the environment on the X-ray photoelectron spectra of hydrogen chloride and chloride ions adsorbed on ice surfaces, as well as of chloride ions in water droplets. In our approach, we combine a density functional theory (DFT) description of the ice surface with that of halogen species using the recently developed relativistic core-valence separation equation of motion coupled cluster (CVS-EOM-IP-CCSD) via the frozen density embedding formalism (FDE), to determine the K and L1,2,3 edges of chlorine. Our calculations, which incorporate temperature effects through snapshots from classical molecular dynamics simulations, are shown to reproduce experimental trends in the change of the core binding energies of Cl- upon moving from a liquid (water droplets) to an interfacial (ice quasi-liquid layer) environment. Our simulations yield water valence band binding energies in good agreement with experiment, which vary little between the droplets and the ice surface. For halide core binding energies there is an overall trend for overestimating experimental values, though good agreement between theory and experiment is found for Cl- in water droplets and on ice. For HCl on the other hand there are significant discrepancies between experimental and calculated core binding energies when we consider structural models that maintain the H-Cl bond more or less intact. An analysis of models that allow for pre-dissociated and dissociated structures suggests that experimentally observed chemical shifts in binding energies between Cl- and HCl would require that H+ (in the form of H3O+) and Cl- are separated by roughly 4-6 Å.

Assessing MP2 frozen natural orbitals in relativistic correlated electronic structure calculations.

The high computational scaling with the basis set size and the number of correlated electrons is a bottleneck limiting applications of coupled cluster algorithms, in particular for calculations based on two- or four-component relativistic Hamiltonians, which often employ uncontracted basis sets. This problem may be alleviated by replacing canonical Hartree-Fock virtual orbitals by natural orbitals (NOs). In this paper, we describe the implementation of a module for generating NOs for correlated wavefunctions and, in particular, second order Møller-Plesset perturbation frozen natural orbitals (MP2FNOs) as a component of our novel implementation of relativistic coupled cluster theory for massively parallel architectures [Pototschnig et al. J. Chem. Theory Comput. 17, 5509, (2021)]. Our implementation can manipulate complex or quaternion density matrices, thus allowing for the generation of both Kramers-restricted and Kramers-unrestricted MP2FNOs. Furthermore, NOs are re-expressed in the parent atomic orbital (AO) basis, allowing for generating coupled cluster singles and doubles NOs in the AO basis for further analysis. By investigating the truncation errors of MP2FNOs for both the correlation energy and molecular properties-electric field gradients at the nuclei, electric dipole and quadrupole moments for hydrogen halides HX (X = F-Ts), and parity-violating energy differences for H2Z2 (Z = O-Se)-we find MP2FNOs accelerate the convergence of the correlation energy in a roughly uniform manner across the Periodic Table. It is possible to obtain reliable estimates for both energies and the molecular properties considered with virtual molecular orbital spaces truncated to about half the size of the full spaces.

Reassessing the potential of TlCl for laser cooling experiments via four-component correlated electronic structure calculations.

Following the interest in the experimental realization of laser cooling for thallium fluoride (TlF), determining the potential of thallium chloride (TlCl) as a candidate for laser cooling experiments has recently received attention from a theoretical perspective [Yuan et al., J. Chem. Phys. 149, 094306 (2018)]. From these ab initio electronic structure calculations, it appeared that the cooling process, which would proceed from transitions between a3Π0 + and X1Σ0 + states, had as a potential bottleneck the long lifetime (6.04 µs) of the excited state a3Π0 +, that would make it very difficult to experimentally control the slowing zone. In this work, we revisit the electronic structure of TlCl by employing four-component Multireference Configuration Interaction (MRCI) and Polarization Propagator (PP) calculations and investigate the effect of such approaches on the computed transition dipole moments between a3Π0 + and a3Π1 excited states of TlCl and TlF (the latter serving as a benchmark between theory and experiment). Whenever possible, MRCI and PP results have been cross-validated by four-component equation of motion coupled-cluster calculations. We find from these different correlated approaches that a coherent picture emerges in which the results of TlF are extremely close to the experimental values, whereas for TlCl the four-component calculations now predict a significantly shorter lifetime (between 109 and 175 ns) for the a3Π0 + than prior estimates. As a consequence, TlCl would exhibit rather different, more favorable cooling dynamics. By numerically calculating the rate equation, we provide evidence that TlCl may have similar cooling capabilities to TlF. Our analysis also indicates the potential advantages of boosting stimulated radiation in optical cycles to improve cooling efficiency.

Pachychoroid disease spectrum: review article.

PURPOSE: The aim of this article is to do a comprehensive literature review about the current understandings of the pachychoroid disease spectrum, describing its multimodal imaging analysis, pathophysiology, differential diagnosis, and current types of management. METHODS: This comprehensive literature review was performed based on a search on the PubMed database, of relevant pachychoroid published papers according to our current knowledge. DISCUSSION: The pachychoroid disease spectrum, according to some authors, includes the following: pachychoroid pigment epitheliopathy (PPE), central serous chorioretinopathy (CSC), pachychoroid neovasculopathy (PNV), polypoidal choroidal vasculopathy (PCV)/aneurysmal type 1 neovascularization (AT1), and more recently focal choroidal excavation (FCE) and peripapillary pachychoroid syndrome (PPS). Each one of these entities will be described and discussed in this article. CONCLUSION: Significant advances in multimodal imaging have enabled a better understanding of the typical choroidal changes in pachychoroid disease spectrum. The clinical knowledge and managing options about this disease significantly increased in the last years. However, it is still unclear why some eyes with typical pachychoroid disease phenotype show no evidence of RPE damage and subretinal fluid (uncomplicated pachychoroid) while others present progressive tissue damage, neovascularization, and atrophy.

Paulo Freire: Review of "The Pedagogy of the Oppressed" : 1st Edition, Penguin Random House UK, London, 2017.

Book review of "The Pedagogy of the Oppressed" by Paulo Freire.

Monitoring of the Forgotten Immune System during Critical Illness-A Narrative Review.

Immune organ failure is frequent in critical illness independent of its cause and has been acknowledged for a long time. Most patients admitted to the ICU, whether featuring infection, trauma, or other tissue injury, have high levels of alarmins expression in tissues or systemically which then activate innate and adaptive responses. Although necessary, this response is frequently maladaptive and leads to organ dysfunction. In addition, the counter-response aiming to restore homeostasis and repair injury can also be detrimental and contribute to persistent chronic illness. Despite intensive research on this topic in the last 40 years, the immune system is not routinely monitored in critical care units. In this narrative review we will first discuss the inflammatory response after acute illness and the players of maladaptive response, focusing on neutrophils, monocytes, and T cells. We will then go through commonly used biomarkers, like C-reactive protein, procalcitonin and pancreatic stone protein (PSP) and what they monitor. Next, we will discuss the strengths and limitations of flow cytometry and related techniques as an essential tool for more in-depth immune monitoring and end with a presentation of the most promising cell associated markers, namely HLA-DR expression on monocytes, neutrophil expression of CD64 and PD-1 expression on T cells. In sum, immune monitoring critically ill patients is a forgotten and missing piece in the monitoring capacity of intensive care units. New technology, including bed-side equipment and in deep cell phenotyping using emerging multiplexing techniques will likely allow the definition of endotypes and a more personalized care in the future.

Lactoferrin affects rhinovirus B-14 entry into H1-HeLa cells.

Lactoferrin is part of the innate immune system, with antiviral activity against numerous DNA and RNA viruses. Rhinoviruses, the leading cause of the common cold, are associated with exacerbation of respiratory illnesses such as asthma. Here, we explored the effect of bovine lactoferrin (BLf) on RV-B14 infectivity. Using different assays, we show that the effect of BLf is strongest during adhesion of the virus to the cell and entry. Tracking the internalisation of BLf and virus revealed a degree of colocalisation, although their interaction was only confirmed in vitro using empty viral particles, indicating a possible additional influence of BLf on other infection steps.

Electronic spectra of ytterbium fluoride from relativistic electronic structure calculations.

We report an investigation of the low-lying excited states of the YbF molecule-a candidate molecule for experimental measurements of the electron electric dipole moment-with 2-component based multi-reference configuration interaction (MRCI), equation of motion coupled cluster (EOM-CCSD) and the extrapolated intermediate Hamiltonian Fock-space coupled cluster (XIHFS-CCSD). Specifically, we address the question of the nature of these low-lying states in terms of configurations containing filled or partially-filled Yb 4f shells. We show that while it does not appear possible to carry out calculations with both kinds of configurations contained in the same active space, reliable information can be extracted from different sectors of Fock space-that is, by performing electron attachment and detachment IHFS-CCSD and EOM-CCSD calculation on the closed-shell YbF+ and YbF- species, respectively. From these calculations we predict Ω = 1/2, 3/2 states, arising from the 4f13σ26s, 4f145d1/6p1, and 4f135d1σ16s configurations to be able to interact as they appear in the same energy range around the ground-state equilibrium geometry. As these states are generated from different sectors of Fock space, they are almost orthogonal and provide complementary descriptions of parts of the excited state manifold. To obtain a comprehensive picture, we introduce a simple adiabatization model to extract energies of interacting Ω = 1/2, 3/2 states that can be compared to experimental observations.

Chronic hepatitis C treatment in HIV co-infection in Portugal: Results from a cohort OF 2133 patients presented by GEPCOI (Portuguese Coinfection Study Group).

Direct-acting antiviral drugs (DAAs) have recently changed the paradigm of hepatitis C therapy, significantly improving treatment response rates, patient life expectancy and quality of life. In Portugal, sofosbuvir (SOF) and SOF/ledipasvir (SOF/LDV) were fully reimbursed by the National Health System since early 2015 and generalized use of interferon-free DAA based regimens became current practice. During 2016, the remaining DAAs were sequentially added and covered by the same health access policy. The Portuguese Study Group of Hepatitis and HIV Co-infection (GEPCOI) collected data from 15 clinical centres in Portugal, pertaining to the HCV treatment experience with DAA regimens. A cohort of 2133 patients was analysed, representing one of the largest DAA treated HCV/HIV co-infected individuals. The global sustained virologic response (SVR) achieved was 95% in this real-life cohort setting. Linear regression analysis showed significant differences in treatment response rates when using SOF plus ribavirin (RBV) combination in genotype 2 or 3 infected individuals (P < .002) and in those with liver cirrhosis (P < .002). These findings corroborate that early treatment is mandatory in HIV/HCV co-infected patients, as response rates may be negatively influenced by higher fibrosis stages and suboptimal DAA regimens. The current national Portuguese health policy should continue to promote wider treatment access and individualized therapy strategies, aiming at the elimination of HCV infection in this high-risk co-infected population.

Brolucizumab: Evolution through Preclinical and Clinical Studies and the Implications for the Management of Neovascular Age-Related Macular Degeneration.

Improving or maintaining visual acuity is the main goal for the treatment of neovascular age-related macular degeneration (nAMD). Current nAMD standard of care dictates frequent intravitreal (IVT) anti-vascular endothelial growth factor (VEGF) injections, which places a substantial burden on patients, caregivers, and physicians. Brolucizumab, a newly developed anti-VEGF molecule for nAMD treatment, has demonstrated longer durability and improvement in visual and anatomic outcomes in clinical studies in a q12-week regimen, indicating its potential to reduce treatment burden as an important therapeutic tool in nAMD management. This review focuses on the development of brolucizumab and the preclinical and clinical studies evaluating its efficacy, tolerability, and safety. Brolucizumab (also known as "RTH258" and "ESBA1008") is a humanized, single-chain variable fragment (scFv) antibody with a molecular mass of approximately 26 kDa that inhibits VEGF-A. Preclinical studies show that brolucizumab readily penetrates the retina to reach the retinal pigment epithelium (RPE)/choroid with minimal subsequent systemic exposure. The safety, tolerability, and efficacy of a single IVT brolucizumab administration in patients with treatment-naïve nAMD were first demonstrated in the SEE Phase 1/2 study. The OSPREY Phase 2 study showed brolucizumab to be as efficacious as aflibercept in a q8-week regimen with regard to best-corrected visual acuity (BCVA) and brolucizumab achieving greater fluid resolution. Brolucizumab-treated patients in the OSPREY study were subsequently challenged with a q12-week dosing interval, and the outcomes provided key information for the study design and end points of the Phase 3 studies. In the HAWK and HARRIER Phase 3 studies, after 3 monthly loading injections, brolucizumab treatment regimen (q12-week or q8-week) was guided by individual disease activity assessment using functional and anatomic parameters (central subfield thickness [CST], intraretinal fluid [IRF], or subretinal fluid [SRF]) versus aflibercept (q8-week). Fewer brolucizumab 6-mg treated eyes had disease activity versus aflibercept, and anatomic outcome results at weeks 16 and 48 demonstrate brolucizumab as a potent drying agent. Moreover, of patients treated with 6 mg brolucizumab, 55.6% and 51.0% maintained a q12-week dosing interval immediately after the loading phase until week 48 in HAWK and HARRIER, respectively. These Phase 3 studies demonstrated that the brolucizumab q12-week regimen maintains efficacy and safety while reducing treatment burden associated with regular IVT injections for patients with nAMD.

HAWK and HARRIER: Phase 3, Multicenter, Randomized, Double-Masked Trials of Brolucizumab for Neovascular Age-Related Macular Degeneration.

PURPOSE: Two similarly designed phase 3 trials (HAWK and HARRIER) compared brolucizumab, a single-chain antibody fragment that inhibits vascular endothelial growth factor-A, with aflibercept to treat neovascular age-related macular degeneration (nAMD). DESIGN: Double-masked, multicenter, active-controlled, randomized trials. PARTICIPANTS: Patients (N = 1817) with untreated, active choroidal neovascularization due to age-related macular degeneration in the study eye. INTERVENTION: Patients were randomized to intravitreal brolucizumab 3 mg (HAWK only) or 6 mg or aflibercept 2 mg. After loading with 3 monthly injections, brolucizumab-treated eyes received an injection every 12 weeks (q12w) and were interval adjusted to every 8 weeks (q8w) if disease activity was present; aflibercept-treated eyes received q8w dosing. MAIN OUTCOME MEASURES: The primary hypothesis was noninferiority in mean best-corrected visual acuity (BCVA) change from baseline to Week 48 (margin: 4 letters). Other key end points included the percentage of patients who maintained q12w dosing through Week 48 and anatomic outcomes. RESULTS: At Week 48, each brolucizumab arm demonstrated noninferiority to aflibercept in BCVA change from baseline (least squares [LS] mean, +6.6 [6 mg] and +6.1 [3 mg] letters with brolucizumab vs. +6.8 letters with aflibercept [HAWK]; +6.9 [brolucizumab 6 mg] vs. +7.6 [aflibercept] letters [HARRIER]; P < 0.001 for each comparison). Greater than 50% of brolucizumab 6 mg-treated eyes were maintained on q12w dosing through Week 48 (56% [HAWK] and 51% [HARRIER]). At Week 16, after identical treatment exposure, fewer brolucizumab 6 mg-treated eyes had disease activity versus aflibercept in HAWK (24.0% vs. 34.5%; P = 0.001) and HARRIER (22.7% vs. 32.2%; P = 0.002). Greater central subfield thickness reductions from baseline to Week 48 were observed with brolucizumab 6 mg versus aflibercept in HAWK (LS mean -172.8 µm vs. -143.7 µm; P = 0.001) and HARRIER (LS mean -193.8 µm vs. -143.9 µm; P < 0.001). Anatomic retinal fluid outcomes favored brolucizumab over aflibercept. Overall, adverse event rates were generally similar with brolucizumab and aflibercept. CONCLUSIONS: Brolucizumab was noninferior to aflibercept in visual function at Week 48, and >50% of brolucizumab 6 mg-treated eyes were maintained on q12w dosing interval through Week 48. Anatomic outcomes favored brolucizumab over aflibercept. Overall safety with brolucizumab was similar to aflibercept (ClinicalTrials.gov; NCT02307682, NCT02434328).