Bisacylphosphane oxides as photo-latent cytotoxic agents and potential photo-latent anticancer drugs

Bisacylphosphane oxides (BAPOs) are established as photoinitiators for industrial applications. Light irradiation leads to their photolysis, producing radicals. Radical species induce oxidative stress in cells and may cause cell death. Hence, BAPOs may be suitable as photolatent cytotoxic agents, but such applications have not been investigated yet. Herein, we describe for the first time a potential use of BAPOs as drugs for photolatent therapy. We show that treatment of the breast cancer cell lines MCF-7 and MDA-MB-231 and of breast epithelial cells MCF-10A with BAPOs and UV irradiation induces apoptosis. Cells just subjected to BAPOs or UV irradiation alone are not affected. The induction of apoptosis depend on the BAPO and the irradiation dose. We proved that radicals are the active species since cells are rescued by an antioxidant. Finally, an optimized BAPO-derivative was designed which enters the cells more efficiently and thus leads to stronger effects at lower doses

AN-Type Fittings in the International Space System (ISS) Node 2 Ammonia System Technical Assessment Report

Based on an anonymous request, an NESC Assessment Team was formed to investigate potential leakage problems from the ISS Program's Node 2 Anhydrous Ammonia System AN fittings. The Team's charter was to provide the ISS Program with a path to follow, which could include testing, to ensure the ISS Program felt confident that the AN fittings' leakage would not exceed specified limits in orbit. The findings from that assessment are contained in this document

"It's all in the game" : Computerspiele zwischen Spiel und Erzählung

Mit der Etablierung des Computerspiels im System der Medien vollzieht sich heute ein ähnlich tiefer Einschnitt in der Geschichte der Medienästhetik wie mit der Etablierung des Films um 1900. Und in ähnlicher Weise provoziert das Computerspiel Stellungnahmen über den gesellschaftlichen Nutzen und Schaden digitaler Spiele. Bevor man aber weit reichende Aussagen über Chancen und Gefahren des Computerspiels formulieren kann, muss man sich zunächst vergewissern, was man in Computerspielen zu sehen, zu hören und zu verstehen bekommt und wie uns Computerspiele etwas zu sehen, zu hören und zu verstehen geben. In diesem Sinne fragen die Beiträge dieses Navigationen-Themenheftes nach der ästhetischen Immanenz des digitalen Spiel-Erlebnisses im Schnittfeld zwischen Spielformen, Erzählformen und sozial freigestellter Interaktion. Im Computerspiel können offenbar alle medialen Formen, d.h. alle nur denkbaren Bildtypen, Textsorten, Klangformen und Bewegungsmuster auftauchen, die mit den gegenwärtigen Medienbegriffen überhaupt nur identifizierbar sind. Es kommt daher auf die genaue Einzelanalyse an, auf die prägnante Beschreibung der spezifischen Gestaltungspotenziale dieses neuartigen Modus medialer Vermittlung: IT'S ALL IN THE GAME

Frailty's influence on 30-day mortality in old critically ill ICU patients: a bayesian analysis evaluating the clinical frailty scale

INTRODUCTION: Frailty is widely acknowledged as influencing health outcomes among critically ill old patients. Yet, the traditional understanding of its impact has predominantly been through frequentist statistics. We endeavored to explore this association using Bayesian statistics aiming to provide a more nuanced understanding of this multifaceted relationship. METHODS: Our analysis incorporated a cohort of 10,363 older (median age 82 years) patients from three international prospective studies, with 30-day all-cause mortality as the primary outcome. We defined frailty as Clinical Frailty Scale ≥ 5. A hierarchical Bayesian logistic regression model was employed, adjusting for covariables, using a range of priors. An international steering committee of registry members reached a consensus on a minimal clinically important difference (MCID). RESULTS: In our study, the 30-day mortality was 43%, with rates of 38% in non-frail and 51% in frail groups. Post-adjustment, the median odds ratio (OR) for frailty was 1.60 (95% CI 1.45-1.76). Frailty was invariably linked to adverse outcomes (OR > 1) with 100% probability and had a 90% chance of exceeding the minimal clinically important difference (MCID) (OR > 1.5). For the Clinical Frailty Scale (CFS) as a continuous variable, the median OR was 1.19 (1.16-1.22), with over 99% probability of the effect being more significant than 1.5 times the MCID. Frailty remained outside the region of practical equivalence (ROPE) in all analyses, underscoring its clinical importance regardless of how it is measured. CONCLUSIONS: This research demonstrates the significant impact of frailty on short-term mortality in critically ill elderly patients, particularly when the Clinical Frailty Scale (CFS) is used as a continuous measure. This approach, which views frailty as a spectrum, enables more effective, personalized care for this vulnerable group. Significantly, frailty was consistently outside the region of practical equivalence (ROPE) in our analysis, highlighting its clinical importance

Game laboratory studies

Prof. Dr. Jens Schröter ist Herausgeber der Reihe und die Herausgeber der einzelnen Hefte sind renommierte Wissenschaftler und -innen aus dem In- und Ausland.Um die Analyse von Computerspielen aus produktionsästhetischer Perspektive zu erproben, lehnt sich der vorliegende Band an die Akteur-Netzwerk-Theorie (ANT) an. Mit ihr geht es ihm um die Frage nach den Aktanten des Game Design – etwa: Welche Hard- und Softwarekomponenten kommen wann und wofür zum Einsatz; wie und mittels welcher Medien notieren Level-Designer ihre Ideen, und wie werden die Aufzeichnungen später von Programmierern implementiert; und welche Rolle spielt eigentlich eine Action-Figur auf dem Schreibtisch eines Textur-Artists

Relationship between the Clinical Frailty Scale and short-term mortality in patients ≥ 80 years old acutely admitted to the ICU: a prospective cohort study.

BACKGROUND: The Clinical Frailty Scale (CFS) is frequently used to measure frailty in critically ill adults. There is wide variation in the approach to analysing the relationship between the CFS score and mortality after admission to the ICU. This study aimed to evaluate the influence of modelling approach on the association between the CFS score and short-term mortality and quantify the prognostic value of frailty in this context. METHODS: We analysed data from two multicentre prospective cohort studies which enrolled intensive care unit patients ≥ 80 years old in 26 countries. The primary outcome was mortality within 30-days from admission to the ICU. Logistic regression models for both ICU and 30-day mortality included the CFS score as either a categorical, continuous or dichotomous variable and were adjusted for patient's age, sex, reason for admission to the ICU, and admission Sequential Organ Failure Assessment score. RESULTS: The median age in the sample of 7487 consecutive patients was 84 years (IQR 81-87). The highest fraction of new prognostic information from frailty in the context of 30-day mortality was observed when the CFS score was treated as either a categorical variable using all original levels of frailty or a nonlinear continuous variable and was equal to 9% using these modelling approaches (p < 0.001). The relationship between the CFS score and mortality was nonlinear (p < 0.01). CONCLUSION: Knowledge about a patient's frailty status adds a substantial amount of new prognostic information at the moment of admission to the ICU. Arbitrary simplification of the CFS score into fewer groups than originally intended leads to a loss of information and should be avoided. Trial registration NCT03134807 (VIP1), NCT03370692 (VIP2)

The handbook for standardized field and laboratory measurements in terrestrial climate change experiments and observational studies (ClimEx)

1. Climate change is a world‐wide threat to biodiversity and ecosystem structure, functioning and services. To understand the underlying drivers and mechanisms, and to predict the consequences for nature and people, we urgently need better understanding of the direction and magnitude of climate change impacts across the soil–plant–atmosphere continuum. An increasing number of climate change studies are creating new opportunities for meaningful and high‐quality generalizations and improved process understanding. However, significant challenges exist related to data availability and/or compatibility across studies, compromising opportunities for data re‐use, synthesis and upscaling. Many of these challenges relate to a lack of an established ‘best practice’ for measuring key impacts and responses. This restrains our current understanding of complex processes and mechanisms in terrestrial ecosystems related to climate change. 2. To overcome these challenges, we collected best‐practice methods emerging from major ecological research networks and experiments, as synthesized by 115 experts from across a wide range of scientific disciplines. Our handbook contains guidance on the selection of response variables for different purposes, protocols for standardized measurements of 66 such response variables and advice on data management. Specifically, we recommend a minimum subset of variables that should be collected in all climate change studies to allow data re‐use and synthesis, and give guidance on additional variables critical for different types of synthesis and upscaling. The goal of this community effort is to facilitate awareness of the importance and broader application of standardized methods to promote data re‐use, availability, compatibility and transparency. We envision improved research practices that will increase returns on investments in individual research projects, facilitate second‐order research outputs and create opportunities for collaboration across scientific communities. Ultimately, this should significantly improve the quality and impact of the science, which is required to fulfil society's needs in a changing world