Tailoring CD19xCD3-DART exposure enhances T-cells to eradication of B-cell neoplasms.

Many patients with B-cell malignancies can be successfully treated, although tumor eradication is rarely achieved. T-cell-directed killing of tumor cells using engineered T-cells or bispecific antibodies is a promising approach for the treatment of hematologic malignancies. We investigated the efficacy of CD19xCD3 DART bispecific antibody in a broad panel of human primary B-cell malignancies. The CD19xCD3 DART identified 2 distinct subsets of patients, in which the neoplastic lymphocytes were eliminated with rapid or slow kinetics. Delayed responses were always overcome by a prolonged or repeated DART exposure. Both CD4 and CD8 effector cytotoxic cells were generated, and DART-mediated killing of CD4+ cells into cytotoxic effectors required the presence of CD8+ cells. Serial exposures to DART led to the exponential expansion of CD4 + and CD8 + cells and to the sequential ablation of neoplastic cells in absence of a PD-L1-mediated exhaustion. Lastly, patient-derived neoplastic B-cells (B-Acute Lymphoblast Leukemia and Diffuse Large B Cell Lymphoma) could be proficiently eradicated in a xenograft mouse model by DART-armed cytokine induced killer (CIK) cells. Collectively, patient tailored DART exposures can result in the effective elimination of CD19 positive leukemia and B-cell lymphoma and the association of bispecific antibodies with unmatched CIK cells represents an effective modality for the treatment of CD19 positive leukemia/lymphoma

Characterization of a fluvial aquifer at a range of depths and scales: the Triassic St Bees Sandstone Formation, Cumbria, UK

Fluvial sedimentary successions represent porous media that host groundwater and geothermal resources. Additionally, they overlie crystalline rocks hosting nuclear waste repositories in rift settings. The permeability characteristics of an arenaceous fluvial succession, the Triassic St Bees Sandstone Formation in England (UK), are described, from core-plug to well-test scale up to ~1 km depth. Within such lithified successions, dissolution associated with the circulation of meteoric water results in increased permeability (K~10−1–100 m/day) to depths of at least 150 m below ground level (BGL) in aquifer systems that are subject to rapid groundwater circulation. Thus, contaminant transport is likely to occur at relatively high rates. In a deeper investigation (> 150 m depth), where the aquifer has not been subjected to rapid groundwater circulation, well-test-scale hydraulic conductivity is lower, decreasing from K~10−2 m/day at 150–400 m BGL to 10−3 m/day down-dip at ~1 km BGL, where the pore fluid is hypersaline. Here, pore-scale permeability becomes progressively dominant with increasing lithostatic load. Notably, this work investigates a sandstone aquifer of fluvial origin at investigation depths consistent with highly enthalpy geothermal reservoirs (~0.7–1.1 km). At such depths, intergranular flow dominates in unfaulted areas with only minor contribution by bedding plane fractures. However, extensional faults represent preferential flow pathways, due to presence of high connective open fractures. Therefore, such faults may (1) drive nuclear waste contaminants towards the highly permeable shallow (< 150 m BGL) zone of the aquifer, and (2) influence fluid recovery in geothermal fields

Identifying associations between diabetes and acute respiratory distress syndrome in patients with acute hypoxemic respiratory failure: an analysis of the LUNG SAFE database

Background: Diabetes mellitus is a common co-existing disease in the critically ill. Diabetes mellitus may reduce the risk of acute respiratory distress syndrome (ARDS), but data from previous studies are conflicting. The objective of this study was to evaluate associations between pre-existing diabetes mellitus and ARDS in critically ill patients with acute hypoxemic respiratory failure (AHRF). Methods: An ancillary analysis of a global, multi-centre prospective observational study (LUNG SAFE) was undertaken. LUNG SAFE evaluated all patients admitted to an intensive care unit (ICU) over a 4-week period, that required mechanical ventilation and met AHRF criteria. Patients who had their AHRF fully explained by cardiac failure were excluded. Important clinical characteristics were included in a stepwise selection approach (forward and backward selection combined with a significance level of 0.05) to identify a set of independent variables associated with having ARDS at any time, developing ARDS (defined as ARDS occurring after day 2 from meeting AHRF criteria) and with hospital mortality. Furthermore, propensity score analysis was undertaken to account for the differences in baseline characteristics between patients with and without diabetes mellitus, and the association between diabetes mellitus and outcomes of interest was assessed on matched samples. Results: Of the 4107 patients with AHRF included in this study, 3022 (73.6%) patients fulfilled ARDS criteria at admission or developed ARDS during their ICU stay. Diabetes mellitus was a pre-existing co-morbidity in 913 patients (22.2% of patients with AHRF). In multivariable analysis, there was no association between diabetes mellitus and having ARDS (OR 0.93 (0.78-1.11); p = 0.39), developing ARDS late (OR 0.79 (0.54-1.15); p = 0.22), or hospital mortality in patients with ARDS (1.15 (0.93-1.42); p = 0.19). In a matched sample of patients, there was no association between diabetes mellitus and outcomes of interest. Conclusions: In a large, global observational study of patients with AHRF, no association was found between diabetes mellitus and having ARDS, developing ARDS, or outcomes from ARDS. Trial registration: NCT02010073. Registered on 12 December 2013

Strategy for large???scale monolithic Perovskite/Silicon tandem solar cell: A review of recent progress

For any solar cell technology to reach the final mass-production/commercialization stage, it must meet all technological, economic, and social criteria such as high efficiency, large-area scalability, long-term stability, price competitiveness, and environmental friendliness of constituent materials. Until now, various solar cell technologies have been proposed and investigated, but only crystalline silicon, CdTe, and CIGS technologies have overcome the threshold of mass-production/commercialization. Recently, a perovskite/silicon (PVK/Si) tandem solar cell technology with high efficiency of 29.1% has been reported, which exceeds the theoretical limit of single-junction solar cells as well as the efficiency of stand-alone silicon or perovskite solar cells. The International Technology Roadmap for Photovoltaics (ITRPV) predicts that silicon-based tandem solar cells will account for about 5% market share in 2029 and among various candidates, the combination of silicon and perovskite is the most likely scenario. Here, we classify and review the PVK/Si tandem solar cell technology in terms of homo- and hetero-junction silicon solar cells, the doping type of the bottom silicon cell, and the corresponding so-called normal and inverted structure of the top perovskite cell, along with mechanical and monolithic tandemization schemes. In particular, we review and discuss the recent advances in manufacturing top perovskite cells using solution and vacuum deposition technology for large-area scalability and specific issues of recombination layers and top transparent electrodes for large-area PVK/Si tandem solar cells, which are indispensable for the final commercialization of tandem solar cells

Solid state perovskite solar modules by vacuum-vapor assisted sequential deposition on Nd:YVO 4 laser patterned rutile TiO 2 nanorods

The past few years have witnessed remarkable progress in solution-processed methylammonium lead halide (CH 3 NH 3 PbX 3 , X = halide) perovskite solar cells (PSCs) with reported photoconversion efficiency (η) exceeding 20% in laboratory-scale devices and reaching up to 13% in their large area perovskite solar modules (PSMs). These devices mostly employ mesoporous TiO 2 nanoparticles (NPs) as an electron transport layer (ETL) which provides a scaffold on which the perovskite semiconductor can grow. However, limitations exist which are due to trap-limited electron transport and non-complete pore filling. Herein, we have employed TiO 2 nanorods (NRs), a material offering a two-fold higher electronic mobility and higher pore-filing compared to their particle analogues, as an ETL. A crucial issue in NRs' patterning over substrates is resolved by using precise Nd:YVO 4 laser ablation, and a champion device with η ∼ 8.1% is reported via a simple and low cost vacuum-vapor assisted sequential processing (V-VASP) of a CH 3 NH 3 PbI 3 film. Our experiments showed a successful demonstration of NRs-based PSMs via the V-VASP technique which can be applied to fabricate large area modules with a pin-hole free, smooth and dense perovskite layer which is required to build high efficiency devices

Representações sociais do medicamento genérico por consumidores residentes em Natal, Rio Grande do Norte, Brasil Social representations of generic drugs by consumers from Natal, Rio Grande do Norte, Brazil

O trabalho objetivou determinar os núcleos central e periférico das representações sociais do medicamento genérico por consumidores, estabelecendo mecanismos que poderão ser utilizados no aprimoramento da política desse tipo de medicamento no Brasil. A pesquisa foi realizada no período de abril de 2002 a fevereiro de 2003, na Cidade do Natal, Rio Grande do Norte, com quatrocentos consumidores. O teste utilizado foi o de associação de palavras, e o estímulo indutor, as palavras medicamento genérico. Foi solicitada a evocação de três palavras, de acordo com a estratégia de acesso ao Núcleo Central de Vergès. A análise dos dados foi realizada com o auxílio do programa EVOC 2000 e da análise de conteúdo preconizada por Bardin. Os resultados demonstraram que o núcleo central era composto pelas categorias preço, qualidade e equivalência farmacêutica, e o sistema periférico, representado pelas categorias opção, eficácia, governo, benefício social e acessibilidade.<br>This paper aimed to determine the central and peripheral roles of consumers' social representations concerning generic drugs, establishing mechanisms that could be used to improve policies for this type of medication in Brazil. The research was done from April 2002 to February 2003 in the city of Natal, Rio Grande do Norte, with 400 consumers. The study employed the word association test with the words "generic drug" as the inductive stimulus. Evocation of three words was requested, according to the access strategy to Vergès' Central Nucleus. Data analysis used the EVOC 2000 software and the content analysis proposed by Bardin. The results demonstrated that the central nucleus consisted of the categories price, quality, and pharmaceutical equivalence, while the peripheral system was represented by the categories option, effectiveness, government, social benefit, and accessibility