The bioaccumulation testing strategy for nanomaterials: correlations with particle properties and a meta-analysis of in vitro fish alternatives to in vivo fish tests

This meta-analysis identifies linkages between the tiers in the bioaccumulation testing strategy.

A Modular Digital Twinning Framework for Safety Assurance of Collaborative Robotics

Digital twins offer a unique opportunity to design, test, deploy, monitor, and control real-world robotic processes. In this paper we present a novel, modular digital twinning framework developed for the investigation of safety within collaborative robotic manufacturing processes. The modular architecture supports scalable representations of user-defined cyber-physical environments, and tools for safety analysis and control. This versatile research tool facilitates the creation of mixed environments of Digital Models, Digital Shadows, and Digital Twins, whilst standardising communication and physical system representation across different hardware platforms. The framework is demonstrated as applied to an industrial case-study focused on the safety assurance of a collaborative robotic manufacturing process. We describe the creation of a digital twin scenario, consisting of individual digital twins of entities in the manufacturing case study, and the application of a synthesised safety controller from our wider work. We show how the framework is able to provide adequate evidence to virtually assess safety claims made against the safety controller using a supporting validation module and testing strategy. The implementation, evidence and safety investigation is presented and discussed, raising exciting possibilities for the use of digital twins in robotic safety assurance.

Prenatal Diagnosis of Aortic Coarctation: Prediction Algorithm according to Gestational Age

<b><i>Objectives:</i></b> The aim of the study was first to quantify the diagnostic accuracy of predictive anatomical factors of aortic coarctation (CoA) and second to design a postnatal CoA probability algorithm according to gestational age (GA) in prenatal period. <b><i>Methods:</i></b> Global and according to GA diagnostic performance of cardiac anatomical variables using the ROC curve were evaluated in a retrospective cohort of fetuses with suspicion of CoA (2004–2020). A serial testing strategy to predict postnatal CoA by fetal echocardiography was designed. <b><i>Results:</i></b> 114 fetuses were included. Isthmus-to-ductal (I/D) ratio provided the best discrimination between healthy fetuses and those with CoA (AUC 0.91, 95% CI: 0.86–0.96, I/D &#x3c; 0.74 sensitivity 96.3%, I/D &#x3c; 0.6, specificity 92.5%) with good classification capacity in both the second and third trimesters of gestation. Isthmus <i>z</i>-score and pulmonary/aortic valve ratio increased accuracy in fetuses &#x3e;28 and tricuspid/mitral valve ratio (TV/MV) in fetuses ≤28 weeks. Study of I/D plus TV/MV ratio in fetuses ≤28 and I/D ratio plus isthmus <i>z</i>-scores in fetuses &#x3e;28 weeks allowed to correctly classify 91.8% of fetuses as high or low probability of postnatal CoA. <b><i>Conclusions:</i></b> Diagnostic discrimination of anatomic predictive factors for CoA varies according to GA. Specific algorithms according to GA increase accuracy in CoA’s prenatal prediction.

Clinical and Economic Impact of ‘ROS1-Testing’ Strategy Compared to a ‘No- ROS1-Testing’ Strategy in Advanced NSCLC in Spain

Background: Detection of the ROS1 rearrangement is mandatory in patients with advanced or metastatic non-small cell lung cancer (NSCLC) to allow targeted therapy with specific inhibitors. However, in Spanish clinical practice ROS1 determination is not yet fully widespread. The aim of this study is to determine the clinical and economic impact of sequentially testing ROS1 in addition to EGFR and ALK in Spain.Methods: A joint model (decision-tree and Markov model) was developed to determine the cost-effectiveness of testing ROS1 strategy versus a no-ROS1 testing strategy in Spain. Distribution of ROS1 techniques, rates of testing, positivity, and invalidity of biomarkers included in the analysis (EGFR, ALK, ROS1 and PD-L1) were based on expert opinion and Lungpath real-world database. Treatment allocation depending on the molecular testing results was defined by expert opinion. For each treatment, a 3-states Markov model was developed, where progression free survival (PFS) and overall survival (OS) curves were parameterized using exponential extrapolations to model transition of patients among health states. Only medical direct costs were included (€ 2021). A lifetime horizon was considered and a discount rate of 3% was applied for both costs and effects. Both deterministic and probabilistic sensitivity analyses were performed to address uncertainty.Results: A target population of 8,755 patients with advanced NSCLC (non-squamous or never smokers squamous) entered the model. Over a lifetime horizon, the ROS1 testing scenario produced additional 157.5 life years and 121.3 quality-adjusted life years (QALYs) compared with no-ROS1 testing scenario. Total direct costs were increased up to € 2,244,737 for ROS1 testing scenario. The incremental cost-utility ratio (ICUR) was 18,514 €/QALY. Robustness of the base-case results were confirmed by the sensitivity analysis.Conclusions: Our study shows that ROS1 testing in addition to EGFR and ALK is a cost-effective strategy compared to no-ROS1 testing, and it generates more than 120 QALYs in Spain over a lifetime horizon. Despite the low prevalence of ROS1 rearrangements in NSCLC patients, the clinical and economic consequences of ROS1 testing should encourage centers to test all advanced or metastatic NSCLC (non-squamous and never-smoker squamous) patients.

A network-based group testing strategy for colleges

Group testing has recently become a matter of vital importance for efficiently and rapidly identifying the spread of Covid-19. In particular, we focus on college towns due to their density, observability, and significance for school reopenings. We propose a novel group testing strategy which requires only local information about the underlying transmission network. By using cellphone data from over 190,000 agents, we construct a mobility network and run extensive data-driven simulations to evaluate the efficacy of four different testing strategies. Our results demonstrate that our group testing method is more effective than three other baseline strategies for reducing disease spread with fewer tests.

Case Studies of Two Classical Imprinting Growth Disorders: Silver–Russell and Beckwith–Wiedemann Syndromes

The genetic influences on human growth are being increasingly deciphered. Silver–Russell and Beckwith–Wiedemann syndromes (SRS; BWS) are two relatively common genetic syndromes with under- and overgrowth-related issues being the reason for referral. Aberration in genomic imprinting is the underlying genetic pathomechanism behind these syndromes. Herein, we described a series of children with these two growth disorders and give an orientation to the reader of the concept of imprinting as well as the genetic testing strategy and counseling to be offered in these syndromes.

Assessment of the National Test Strategy on the Development of the COVID-19 Pandemic in Denmark

During the COVID-19 pandemic, Denmark has pursued a mass testing strategy culminating in the testing of 12.167 individuals per 100,000 inhabitants per day during the spring of 2021. The strategy included free access to COVID-19 testing, and since 2021, compulsory documentation for negative tests or vaccination has been required for access to workplace, educational institutions, restaurants, and many other places. Testing and subsequent isolation if testing was positive were voluntary. The present study provides an analysis of whether testing frequency in Denmark showed any correlation to hospitalizations throughout the relevant stages of the pandemic. Mass testing was found not to correlate significantly with the number of hospitalizations during the pandemic. Interestingly, during the highest level of testing in spring 2021 the fraction of positive tests increased slightly; thus, the Danish mass testing strategy, at its best, failed to reduce the prevalence of COVID-19. Furthermore, the relationship between positives in antigen testing and in rt-PCR testing indicated that many patients were not tested early in their infection when the risk of transmission was at the highest. In conclusion, the Danish mass testing strategy for COVID-19 does not appear to have a detectable correlation to the number of hospitalizations due to COVID-19.