Expanding indication of padeliporfin (WST11) vascular-targeted photodynamic therapy: results of prostate cancer Latin-American multicenter study

OBJECTIVES: To explore the proportion of patients with higher risk localized prostate cancer (PCa) that would become safely biopsy negative 12 months after non-thermal focal therapy with padeliporfin vascular-targeted photodynamic therapy (VTP). METHODS: Multicenter study in a scenario of prostate-specific antigen (PSA) ≤20ng/ml and variable PCa target volumes Gleason pattern 3 or low-volume secondary Gleason pattern 4, all patients received VTP, consisting of intravenous 4mg/kg padeliporfin activated by light-diffusing fibers in the prostate. The prostate was biopsied at baseline, months 6 and 12, PSA, patient-reported functional outcomes and quality of life (QoL) questionnaires were recorded at baseline, months 3, 6, and 12 and adverse events (AE) throughout the study. RESULTS: In the intention-to-treat population (n=81), the proportion of patients with negative biopsies at month 12 was 74% (60/81 patients; 95% CI: 63.1%,83.2%). In the per-protocol population, the proportion was 79% (58/73 patients; 95% CI: 68.4%,88.0%). Questionnaire results indicated a slight improvement in urinary function and limited deterioration in sexual function. No difference in QoL was observed over time. A total of 42/81 (52%) patients reported mild or moderate and 4 of 81 (4.9%) experienced serious AE, all resolved without sequelae. No phototoxicity, cardiovascular event, fistula or prolonged urinary incontinence, secondary cancer or death was reported. CONCLUSIONS: Results support the efficacy, safety, and QoL associated with padeliporfin focal treatment for low/intermediate risk localized PCa

Towards Electrical, Integrated Implementations of SIMPL Systems

International audienceThis paper discusses strategies for the electrical, integrated implementation of a novel security tool termed SIMPL system, which was introduced in [1]. SIMPL systems are a public key version of Physical Unclonable Functions (PUFs). Like a PUF, each SIMPL system S is physically unique and non-reproducible, and implements an individual function FS. In opposition to a PUF, every SIMPL system S possesses a publicly known numerical description D(S), which allows its digital simulation and prediction. However, any such simulation must work at a detectably lower speed than the real-time behavior of S. As argued in [1], SIMPL systems have practicality and security advantages over PUFs, Certificates of Authenticity (COAs), Physically Obfuscated Keys (POKs), and also over standard mathematical cryptotechniques. This manuscript focuses on electrical, integrated realizations of SIMPL systems, and proposes two potential candidates: SIMPL systems derived from special SRAM-architectures (so-called "skew designs" of SRAM cells), and implementations based on analog computing arrays called Cellular Non-Linear Networks (CNNs)

Current strategies for quantification of estrogens in clinical research

Estrogens and their bioactive metabolites play key roles in regulating diverse processes in health and disease. In particular, estrogens and estrogenic metabolites have shown both protective and non-protective effects on disease pathobiology, implicating the importance of this steroid pathway in disease diagnostics and monitoring. All estrogens circulate in a wide range of concentrations, which in some patient cohorts can be extremely low. However, elevated levels of estradiol are reported in disease. For example, in pulmonary arterial hypertension (PAH) elevated levels have been reported in men and postmenopausal women. Conventional immunoassay techniques have come under scrutiny, with their selectivity, accuracy and precision coming into question. Analytical methodologies such as gas and liquid chromatography coupled to single and tandem mass spectrometric approaches (GC–MS, GC–MS/MS, LC–MS and LC–MS/MS) have been developed to quantify endogenous estrogens and in some cases their bioactive metabolites in biological fluids such as urine, serum, plasma and saliva. Liquid-liquid or solid-phase extraction approaches are favoured with derivatization remaining a necessity for detection in lower volumes of sample. The limits of quantitation of individual assays vary but are commonly in the range of 0.5–5 pg/mL for estrone and estradiol, with limits for their bioactive metabolites being higher. This review provides an overview of current approaches for measurement of unconjugated estrogens in biological matrices by MS, highlighting the advances in this field and the challenges remaining for routine use in the clinical and research environment

The WEBT BL Lacertae Campaign 2001 and its extension : Optical light curves and colour analysis 1994–2002

BL Lacertae has been the target of four observing campaigns by the Whole Earth Blazar Telescope (WEBT) collaboration. In this paper we present UBVRI light curves obtained by theWEBT from 1994 to 2002, including the last, extended BL Lac 2001 campaign. A total of about 7500 optical observations performed by 31 telescopes from Japan to Mexico have been collected, to be added to the ∼15 600 observations of the BL Lac Campaign 2000. All these data allow one to follow the source optical emission behaviour with unprecedented detail. The analysis of the colour indices reveals that the flux variability can be interpreted in terms of two components: longer-term variations occurring on a fewday time scale appear as mildly-chromatic events, while a strong bluer-when-brighter chromatism characterizes very fast (intraday) flares. By decoupling the two components, we quantify the degree of chromatism inferring that longer-term flux changes imply moving along a ∼0.1 bluerwhen- brighter slope in the B − R versus R plane; a steeper slope of ∼0.4 would distinguish the shorter-term variations. This means that, when considering the long-term trend, the B-band flux level is related to the R-band one according to a power law of index ∼1.1. Doppler factor variations on a “convex” spectrum could be the mechanism accounting for both the long-term variations and their slight chromatism.Reig Torres, Pablo, [email protected]

Effect of light, food additives and heat on the stability of sorghum 3-deoxyanthocyanins in model beverages.

This work aimed to evaluate the stability of sorghum 3-deoxyanthocyanins (DXA) in model beverages (pH 3.5) elaborated with crude sorghum phenolic extract, containing ascorbic acid and sulphite, under fluorescent light exposure and subjected to heat treatment. There was no significant difference in the DXA degradation during storage under light exposure (24.16%) and absence of light (20.72%). DXA degradation did not differ in the presence of ascorbic acid during storage under light exposure (23.99-25.38%) and absence of light (19.87-21.74%). The addition of sulphite caused an initial bleaching reaction, but as a reversible reaction, the anthocyanin content was higher on the last day of storage compared to the first day. There were no significant differences in total anthocyanin content of all treatments subjected to the heat treatment (80 °C for 5 and 25 min). Thus, crude DXA are very stable under light, additives and heat, and may be useful as natural food colourants

The importance of Real-Life research in Respiratory Medicine: Manifesto of the Respiratory Effectiveness Group:Endorsed by the International Primary Care Respiratory Group and the World Allergy Organization

status: publishe

Evolution of the use of corticosteroids for the treatment of hospitalised COVID-19 patients in Spain between March and November 2020: SEMI-COVID national registry

Objectives: Since the results of the RECOVERY trial, WHO recommendations about the use of corticosteroids (CTs) in COVID-19 have changed. The aim of the study is to analyse the evolutive use of CTs in Spain during the pandemic to assess the potential influence of new recommendations. Material and methods: A retrospective, descriptive, and observational study was conducted on adults hospitalised due to COVID-19 in Spain who were included in the SEMI-COVID- 19 Registry from March to November 2020. Results: CTs were used in 6053 (36.21%) of the included patients. The patients were older (mean (SD)) (69.6 (14.6) vs. 66.0 (16.8) years; p < 0.001), with hypertension (57.0% vs. 47.7%; p < 0.001), obesity (26.4% vs. 19.3%; p < 0.0001), and multimorbidity prevalence (20.6% vs. 16.1%; p < 0.001). These patients had higher values (mean (95% CI)) of C-reactive protein (CRP) (86 (32.7-160) vs. 49.3 (16-109) mg/dL; p < 0.001), ferritin (791 (393-1534) vs. 470 (236- 996) µg/dL; p < 0.001), D dimer (750 (430-1400) vs. 617 (345-1180) µg/dL; p < 0.001), and lower Sp02/Fi02 (266 (91.1) vs. 301 (101); p < 0.001). Since June 2020, there was an increment in the use of CTs (March vs. September; p < 0.001). Overall, 20% did not receive steroids, and 40% received less than 200 mg accumulated prednisone equivalent dose (APED). Severe patients are treated with higher doses. The mortality benefit was observed in patients with oxygen saturation </=90%. Conclusions: Patients with greater comorbidity, severity, and inflammatory markers were those treated with CTs. In severe patients, there is a trend towards the use of higher doses. The mortality benefit was observed in patients with oxygen saturation </=90%

Volume I. Introduction to DUNE

The preponderance of matter over antimatter in the early universe, the dynamics of the supernovae that produced the heavy elements necessary for life, and whether protons eventually decay—these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our universe, its current state, and its eventual fate. The Deep Underground Neutrino Experiment (DUNE) is an international world-class experiment dedicated to addressing these questions as it searches for leptonic charge-parity symmetry violation, stands ready to capture supernova neutrino bursts, and seeks to observe nucleon decay as a signature of a grand unified theory underlying the standard model. The DUNE far detector technical design report (TDR) describes the DUNE physics program and the technical designs of the single- and dual-phase DUNE liquid argon TPC far detector modules. This TDR is intended to justify the technical choices for the far detector that flow down from the high-level physics goals through requirements at all levels of the Project. Volume I contains an executive summary that introduces the DUNE science program, the far detector and the strategy for its modular designs, and the organization and management of the Project. The remainder of Volume I provides more detail on the science program that drives the choice of detector technologies and on the technologies themselves. It also introduces the designs for the DUNE near detector and the DUNE computing model, for which DUNE is planning design reports. Volume II of this TDR describes DUNE\u27s physics program in detail. Volume III describes the technical coordination required for the far detector design, construction, installation, and integration, and its organizational structure. Volume IV describes the single-phase far detector technology. A planned Volume V will describe the dual-phase technology