Smart Optode for 8-Wavelength Time-Gated Diffuse Optics

We present the most compact (4 cm3) time domain diffuse optical spectroscopy system, hosting 8 laser sources emitting at different wavelengths, a large area time-gated detector, and a time-to-digital converter. We tested the optode using standardized protocols, enlightening a high light harvesting capability and large penetration depth in detecting realistic optical inhomogeneities. We tested it also in vivo for the non-invasive assessment of blood parameters in a vascular occlusion test and for the detection of brain activation, demonstrating the optode capability to follow task-related hemodynamic changes even through a single measurement, with no need for averaging or filtering as instead needed with most available systems. The optode is thus a good candidate for next generation home-monitoring devices, thanks to its good performances, small dimension and potential low-cost

Relaxed Current Matching Requirements in Highly Luminescent Perovskite Tandem Solar Cells and Their Fundamental Efficiency Limits.

Perovskite-based tandem solar cells are of increasing interest as they approach commercialization. Here we use experimental parameters from optical spectroscopy measurements to calculate the limiting efficiency of perovskite-silicon and all-perovskite two-terminal tandems, employing currently available bandgap materials, as 42.0% and 40.8%, respectively. We show luminescence coupling between subcells (the optical transfer of photons from the high-bandgap to low-bandgap subcell) relaxes current matching when the high-bandgap subcell is a luminescent perovskite. We calculate that luminescence coupling becomes important at charge trapping rates (≤106 s-1) already being achieved in relevant halide perovskites. Luminescence coupling increases flexibility in subcell thicknesses and tolerance to different spectral conditions. For maximal benefit, the high-bandgap subcell should have the higher short-circuit current under average spectral conditions. This can be achieved by reducing the bandgap of the high-bandgap subcell, allowing wider, unstable bandgap compositions to be avoided. Lastly, we visualize luminescence coupling in an all-perovskite tandem through cross-section luminescence imaging.ARB acknowledges funding from a Winton Studentship, Oppenheimer Studentship the Engineering and Physical Sciences Research Council (EPSRC) Doctoral Training Centre in Photovoltaics (CDT-PV). ARB thanks Luis Pazos-Outón for supplying data for MAPbI3 solar cells. FL acknowledges financial support from the Alexander Von Humboldt Foundation via the Feodor Lynen program and thanks Prof. Sir R. Friend for supporting his Fellowship at the Cavendish Laboratory. Y-HC acknowledges the funding from Taiwan Cambridge Scholarship. AJ-S gratefully acknowledges a postdoctoral scholarship from the Max Planck Society. KF acknowledges a George and Lilian Schiff Studentship, Winton Studentship, the Engineering and Physical Sciences Research Council (EPSRC) studentship, Cambridge Trust Scholarship, and Robert Gardiner Scholarship. GE was funded by NREL’s LDRD program. ER acknowledges the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (HYPERION, Grant Agreement Number 756962) and the EPSRC for a DTP Part Studentship. MA-J acknowledges funding support from EPSRC through the program grant: EP/M005143/1. MA-J thanks Cambridge Materials Limited for their funding and technical support. MA acknowledges funding from the European Research Council (ERC) (grant agreement No. 756962 [HYPERION]) and the Marie Skłodowska-Curie actions (grant agreement No. 841386) under the European Union’s Horizon 2020 research and innovation programme. BVL acknowledges funding from the Max Planck Society, the Cluster of Excellence e-conversion and the Center for Nanoscience (CeNS). SDS acknowledges the Royal Society and Tata Group (UF150033) and the EPSRC (EP/R023980/1, EP/T02030X/1, EP/S030638/1). We thank Axel Palmstrom and William Nemeth at NREL for depositing some of the layers in the tandem stack

Tackling the dysregulated immune-checkpoints in classical Hodgkin lymphoma: bidirectional regulations between the microenvironment and Hodgkin/Reed-Sternberg cells

Immune evasion is considered one of the modern hallmarks of cancer and is a key element in the pathogenesis of classical Hodgkin Lymphoma (cHL). This haematological cancer achieves effective avoidance of the host’s immune system by overexpressing the PD-L1 and PD-L2 proteins on the surface of the neoplastic cells. Subversion of the PD-1/PD-L axis, however, is not the sole contributor to immune evasion in cHL, as the microenvironment nurtured by the Hodgkin/Reed-Sternberg cells is a major player in the creation of a biological niche that sustains their survival and hinders immune recognition. In this review, we will discuss the physiology of the PD-1/PD-L axis and how cHL is able to exploit a plethora of different molecular mechanisms to build an immunosuppressive microenvironment and achieve optimal immune evasion. We will then discuss the success obtained by checkpoint inhibitors (CPI) in treating cHL, both as single agents and as part of combination strategies, analysing the rationale for their combination with traditional chemotherapeutic compounds and the proposed mechanisms of resistance to CPI immunotherapy

Controlling the Growth Kinetics and Optoelectronic Properties of 2D/3D Lead–Tin Perovskite Heterojunctions

Halide perovskites are emerging as valid alternatives to conventional photovoltaic active materials owing to their low cost and high device performances. This material family also shows exceptional tunability of properties by varying chemical components, crystal structure, and dimensionality, providing a unique set of building blocks for new structures. Here, highly stable self-assembled lead–tin perovskite heterostructures formed between low bandgap 3D and higher bandgap 2D components are demonstrated. A combination of surface-sensitive X-ray diffraction, spatially resolved photoluminescence, and electron microscopy measurements is used to reveal that microstructural heterojunctions form between high bandgap 2D surface crystallites and lower bandgap 3D domains. Furthermore, in situ X-ray diffraction measurements are used during film formation to show that an ammonium thiocyanate additive delays formation of the 3D component and thus provides a tunable lever to substantially increase the fraction of 2D surface crystallites. These novel heterostructures will find use in bottom cells for stable tandem photovoltaics with a surface 2D layer passivating the 3D material, or in energy transfer devices requiring controlled energy flow from localized surface crystallites to the bulk.- EPSRC Departmental Graduate Studentship - Royal Society - Polish Ministry of Science and Higher Education within the Mobilnosc Plus program (Grant no. 1603/ 2 MOB/V/2017/0). - Jardine Foundation - Cambridge Trus

feasibility and outcome of haploidentical hematopoietic stem cell transplantation with post transplant high dose cyclophosphamide for children and adolescents with hematologic malignancies an aieop gitmo retrospective multicenter study

Post-transplant high-dose cyclophosphamide (PTCy) is a novel approach to prevent graft-versus-host disease (GVHD) and rejection in patients given haploidentical hematopoietic stem cell transplantation (HSCT). Thirty-three patients with high-risk hematologic malignancies and lacking a match-related or -unrelated donor were treated with PTCy haploidentical HSCT in 5 Italian AIEOP centers. Nineteen patients had a nonmyeloablative preparative regimen (57%), and 14 patients received a full myeloablative conditioning regimen (43%). No patients received serotherapy; GVHD prophylaxis was based on PTCy (50 mg/kg on days +3 and +4) combined with mycophenolate plus tacrolimus or cyclosporine A. Neutrophil and platelet engraftment was achieved on days +17 (range, 14 to 37) and +27 (range, 16 to 71). One patient had autologous reconstitution for anti-HLA antibodies. Acute GVHD grades II to IV and III to IV and chronic GVHD developed in 22% (95% CI, 11 to 42), 3% (95% CI, 0 to 21), and 4% (95% CI, 0 to 27) of cases, respectively. The 1-year overall survival rate was 72% (95% CI, 56 to 88), progression-free survival rate was 61% (95% CI, 43 to 80), cumulative incidence of relapse was 24% (95% CI, 13 to 44), and transplant-related mortality was 9% (95% CI, 3 to 26). The univariate analysis for risk of relapse incidence showed how 3 significant variables, mother as donor (P = .02), donor gender as female (P = .04), and patient gender as female (P = .02), were significantly associated with a lower risk of relapse. Disease progression was the main cause of death. PTCy is a safe procedure also for children and adolescents who have already received several lines of chemotherapy. Among the different diseases, a trend for better 1-year rates of overall survival was obtained for nonacute leukemia patients

Microsecond Carrier Lifetimes, Controlled p-Doping, and Enhanced Air Stability in Low-Bandgap Metal Halide Perovskites.

Mixed lead-tin halide perovskites have sufficiently low bandgaps (∼1.2 eV) to be promising absorbers for perovskite-perovskite tandem solar cells. Previous reports on lead-tin perovskites have typically shown poor optoelectronic properties compared to neat lead counterparts: short photoluminescence lifetimes (<100 ns) and low photoluminescence quantum efficiencies (<1%). Here, we obtain films with carrier lifetimes exceeding 1 μs and, through addition of small quantities of zinc iodide to the precursor solutions, photoluminescence quantum efficiencies under solar illumination intensities of 2.5%. The zinc additives also substantially enhance the film stability in air, and we use cross-sectional chemical mapping to show that this enhanced stability is because of a reduction in tin-rich clusters. By fabricating field-effect transistors, we observe that the introduction of zinc results in controlled p-doping. Finally, we show that zinc additives also enhance power conversion efficiencies and the stability of solar cells. Our results demonstrate substantially improved low-bandgap perovskites for solar cells and versatile electronic applications.EPSRC (EP/M005143/1 and DTP funding) Royal Society ER

A Highly Emissive Surface Layer in Mixed-Halide Multication Perovskites.

Mixed-halide lead perovskites have attracted significant attention in the field of photovoltaics and other optoelectronic applications due to their promising bandgap tunability and device performance. Here, the changes in photoluminescence and photoconductance of solution-processed triple-cation mixed-halide (Cs0.06 MA0.15 FA0.79 )Pb(Br0.4 I0.6 )3 perovskite films (MA: methylammonium, FA: formamidinium) are studied under solar-equivalent illumination. It is found that the illumination leads to localized surface sites of iodide-rich perovskite intermixed with passivating PbI2 material. Time- and spectrally resolved photoluminescence measurements reveal that photoexcited charges efficiently transfer to the passivated iodide-rich perovskite surface layer, leading to high local carrier densities on these sites. The carriers on this surface layer therefore recombine with a high radiative efficiency, with the photoluminescence quantum efficiency of the film under solar excitation densities increasing from 3% to over 45%. At higher excitation densities, nonradiative Auger recombination starts to dominate due to the extremely high concentration of charges on the surface layer. This work reveals new insight into phase segregation of mixed-halide mixed-cation perovskites, as well as routes to highly luminescent films by controlling charge density and transfer in novel device structures

Intra-and extra-hospitalization monitoring of vital signs. Two sides of the same coin. Perspectives from Lims and Greenline study operators

Background: In recent years, due to the epidemiological transition, the burden of very complex patients in hospital wards has increased. Telemedicine usage appears to be a potential high-impact factor in helping with patient management, allowing hospital personnel to assess conditions in out-of-hospital scenarios. Methods: To investigate the management of chronic patients during both hospitalization for disease and discharge, randomized studies (LIMS and Greenline-HT) are ongoing in the Internal Medicine Unit at ASL Roma 6 Castelli Hospital. The study endpoints are clinical outcomes (from a patient’s perspective). In this perspective paper, the main findings of these studies, from the operators’ point of view, are reported. Operator opinions were collected from structured and unstructured surveys conducted among the staff involved, and their main themes are reported in a narrative manner. Results: Telemonitoring appears to be linked to a reduction in side-events and side-effects, which represent some of most commons risk factors for re-hospitalization and for delayed discharge during hospitalization. The main perceived advantages are increased patient safety and the quick response in case of emergency. The main disadvantages are believed to be related to low patient compliance and an infrastructural lack of optimization. Conclusions: The evidence of wireless monitoring studies, combined with the analysis of activity data, suggests the need for a model of patient management that envisages an increase in the territory of structures capable of offering patients subacute care (the possibility of antibiotic treatments, blood transfusions, infusion support, and pain therapy) for the timely management of chronic patients in the terminal phase, for which treatment in acute wards must be guaranteed only for a limited time for the management of the acute phase of their diseases

Protein kinase CK2α is overexpressed in classical hodgkin lymphoma, regulates key signaling pathways, PD-L1 and may represent a new target for therapy

IntroductionIn classical Hodgkin lymphoma (cHL), the survival of neoplastic cells is mediated by the activation of NF-κB, JAK/STAT and PI3K/Akt signaling pathways. CK2 is a highly conserved serine/threonine kinase, consisting of two catalytic (α) and two regulatory (β) subunits, which is involved in several cellular processes and both subunits were found overexpressed in solid tumors and hematologic malignancies.Methods and resultsBiochemical analyses and in vitro assays showed an impaired expression of CK2 subunits in cHL, with CK2α being overexpressed and a decreased expression of CK2β compared to normal B lymphocytes. Mechanistically, CK2β was found to be ubiquitinated in all HL cell lines and consequently degraded by the proteasome pathway. Furthermore, at basal condition STAT3, NF-kB and AKT are phosphorylated in CK2-related targets, resulting in constitutive pathways activation. The inhibition of CK2 with CX-4945/silmitasertib triggered the de-phosphorylation of NF-κB-S529, STAT3-S727, AKT-S129 and -S473, leading to cHL cell lines apoptosis. Moreover, CX-4945/silmitasertib was able to decrease the expression of the immuno-checkpoint CD274/PD-L1 but not of CD30, and to synergize with monomethyl auristatin E (MMAE), the microtubule inhibitor of brentuximab vedotin.ConclusionsOur data point out a pivotal role of CK2 in the survival and the activation of key signaling pathways in cHL. The skewed expression between CK2α and CK2β has never been reported in other lymphomas and might be specific for cHL. The effects of CK2 inhibition on PD-L1 expression and the synergistic combination of CX-4945/silmitasertib with MMAE pinpoints CK2 as a high-impact target for the development of new therapies for cH