A UK framework for the assessment and integration of different scientific evidence streams in chemical risk assessment.

Background: Few methods are available for transparently combining different evidence streams for chemical risk assessment to reach an integrated conclusion on the probability of causation. Hence, the UK Committees on Toxicity (COT) and on Carcinogenicity (COC) have reviewed current practice and developed guidance on how to achieve this in a transparent manner, using graphical visualisation.

Methods/approach: All lines of evidence, including toxicological, epidemiological, new approach methodologies, and mode of action should be considered, taking account of their strengths/weaknesses in their relative weighting towards a conclusion on the probability of causation.

Metagenomic Sequencing of Two Cultures Grown on Chemically Deconstructed Plastic Products.

We report the metagenome sequences of two microbial cultures that were grown with chemically deconstructed plastic products as their sole carbon source. These metagenomes will provide insights into the metabolic capabilities of cultures grown on deconstructed plastics and can serve as a starting point for the identification of novel plastic degradation mechanisms.

Theoretical Analyses of Multiobjective Evolutionary Algorithms on Multimodal Objectives.

Multiobjective evolutionary algorithms are successfully applied in many real-world multiobjective optimization problems. As for many other AI methods, the theoretical understanding of these algorithms is lagging far behind their success in practice. In particular, previous theory work considers mostly easy problems that are composed of unimodal objectives.

The Univariate Marginal Distribution Algorithm Copes Well with Deception and Epistasis.

In their recent work, Lehre and Nguyen (2019) show that the univariate marginal distribution algorithm (UMDA) needs time exponential in the parent populations size to optimize the DeceptiveLeadingBlocks (DLB) problem. They conclude from this result that univariate EDAs have difficulties with deception and epistasis. In this work, we show that this negative finding is caused by the choice of the parameters of the UMDA.

Evaluation of the prothrombotic potential of four-factor prothrombin complex concentrate (4F-PCC) in animal models.

Objectives: Acquired coagulopathy may be associated with bleeding risk. Approaches to restore haemostasis include administration of coagulation factor concentrates, but there are concerns regarding potential prothrombotic risk. The present study assessed the prothrombotic potential of four-factor prothrombin complex concentrate (4F-PCC) versus activated PCC (aPCC) and recombinant factor VIIa (rFVIIa), using three preclinical animal models.

Lower Bounds for Non-Elitist Evolutionary Algorithms via Negative Multiplicative Drift.

A decent number of lower bounds for non-elitist population-based evolutionary algorithms has been shown by now. Most of them are technically demanding due to the (hard to avoid) use of negative drift theorems-general results which translate an expected movement away from the target into a high hitting time. We propose a simple negative drift theorem for multiplicative drift scenarios and show that it can simplify existing analyses.

Tissue distribution of rIX-FP after intravenous application to rodents.

Background: Hemophilia B is caused by coagulation factor IX (FIX) deficiency. Recombinant fusion protein linking coagulation FIX with recombinant albumin (rIX-FP; Idelvion ) is used for replacement therapy with an extended half-life. A previous quantitative whole-body autoradiography (QWBA) study investigating the biodistribution of rIX-FP indicated equal biodistribution, but more prolonged tissue retention compared with a marketed recombinant FIX product.

Treatment of iliac atherosclerotic lesions using the balloon-expandable dynamic bare metal stent: One-year outcomes of the BIODYNAMIC single-center retrospective analysis.

Objectives: Endovascular therapy using balloon expandable stents has become the treatment standard for most iliac atherosclerotic lesions. We aimed to assess the safety and performance of the Dynamic stainless-steel balloon-expanding stent system in this location.

Methods: BIODYNAMIC is a retrospective single center study including consecutive patients with iliac lesions treated with the Dynamic stent system.

Scalable Gas Sensing, Mapping, and Path Planning via Decentralized Hilbert Maps.

This paper develops a decentralized approach to gas distribution mapping (GDM) and information-driven path planning for large-scale distributed sensing systems. Gas mapping is performed using a probabilistic representation known as a Hilbert map, which formulates the mapping problem as a multi-class classification task and uses kernel logistic regression to train a discriminative classifier online. A novel Hilbert map information fusion method is presented for rapidly merging the information from individual robot maps using limited data communication.

Susceptibility-weighted magnetic resonance imaging of cerebrovascular sequelae after radiotherapy for pediatric brain tumors.

Background And Purpose: Due to sensitive neuroimaging techniques, cerebrovascular complications such as cerebral microbleeds (CMB) and cerebral cavernous malformations (CCM) are increasingly recognized as considerable late effects after treatment for pediatric brain tumor. The aim of this study was to analyze CMB in a cohort of patients after cranial irradiation therapy for medulloblastoma or other pediatric brain tumors using susceptibility-weighted magnetic resonance imaging (SWI).

Materials And Methods: Forty former pediatric brain tumor patients were enrolled in this prospective cross-sectional study and examined by cranial MRI including SWI sequences.

Posterior Inferior Cerebellar Infarct in a Younger Adult Male with Vertigo and Ataxia.

Vertigo is a common complaint in patients who present to the emergency department. It can be a manifestation originating from several different disease processes. Although most patients with vertigo, especially younger patients, will have a benign disorder, up to 3% of such patients will have a cerebellar infarct.

A randomized, multi-center, prospective study comparing best medical treatment versus best medical treatment plus renal artery stenting in patients with hemodynamically relevant atherosclerotic renal artery stenosis (RADAR) - one-year results of a pre-maturely terminated study.

Background: The indications for conservative "best medical treatment" (BMT) versus additional renal artery stenting are a matter of ongoing debate. The RADAR study aimed to evaluate the impact of percutaneous renal artery stenting on the impaired renal function in patients with hemodynamically significant atherosclerotic renal artery stenosis (RAS).

Methods: RADAR is an international, prospective, randomized (1:1) controlled study comparing BMT alone versus BMT plus renal artery stenting in patients with duplex sonographic hemodynamically relevant RAS.

Credentialing in interventional therapy in Europe - comparison of curricula including endovascular therapy of arterial diseases.

The prevalence of peripheral artery disease (PAD) is continuously increasing. In addition, the treatment of PAD has changed substantially over the last decades. Novel treatment modalities and diagnostic tools were developed and endovascular therapy was established as a first-line therapy.

Investigation of the genotoxic potential of the marine biotoxins azaspiracid 1-3.

Azaspiracids (AZAs) are the most recently discovered group of biotoxins and are the cause of azaspiracid shellfish poisoning (AZP) in humans. To date over thirty analogues have been identified. However, toxicological studies of AZAs are limited due to the lack of availability of toxins and toxin standards.

Quantitative analysis of mucosal oxygenation using ex vivo imaging of healthy and inflamed mammalian colon tissue.

Colonic inflammation is associated with decreased tissue oxygenation, significantly affecting gut homeostasis. However, the crosstalk between O consumption and supply in the inflamed tissue are not fully understood. Using a murine model of colitis, we analysed O in freshly prepared samples of healthy and inflamed colon tissue.

The Unrestricted Black-Box Complexity of Jump Functions.

We analyze the unrestricted black-box complexity of the Jump function classes for different jump sizes. For upper bounds, we present three algorithms for small, medium, and extreme jump sizes. We prove a matrix lower bound theorem which is capable of giving better lower bounds than the classic information theory approach.

Four-factor prothrombin complex concentrate reverses apixaban-associated bleeding in a rabbit model of acute hemorrhage.

Background: Apixaban is a direct factor Xa inhibitor approved for the treatment and prevention of thromboembolic disease. There is a lack of data regarding its reversal in cases of acute bleeding or prior to emergency surgery that needs addressing.

Objectives: This study assessed whether a four-factor prothrombin complex concentrate (4F-PCC; Beriplex(®) /Kcentra(®) , CSL Behring) can effectively reverse apixaban-associated bleeding in an in vivo rabbit model and evaluated the correlations between in vivo hemostasis and in vitro coagulation parameters.

Unbiased Black-Box Complexities of Jump Functions.

We analyze the unbiased black-box complexities of jump functions with small, medium, and large sizes of the fitness plateau surrounding the optimal solution. Among other results, we show that when the jump size is (1/2 - ε), that is, when only a small constant fraction of the fitness values is visible, then the unbiased black-box complexities for arities 3 and higher are of the same order as those for the simple OneMax function. Even for the extreme jump function, in which all but the two fitness values n/2 and n are blanked out, polynomial time mutation-based (i.

Correlation of coagulation markers and 4F-PCC-mediated reversal of rivaroxaban in a rabbit model of acute bleeding.

Introduction: Rivaroxaban is an oral, selective direct factor Xa inhibitor approved for several indications in patients at risk of thrombotic events. One limitation of its clinical use is the lack of data pertaining to its reversal in situations where urgent response is critical (e.g.

Effective reversal of edoxaban-associated bleeding with four-factor prothrombin complex concentrate in a rabbit model of acute hemorrhage.

Background: Edoxaban is an oral, selective direct factor Xa inhibitor approved in Japan for venous thromboembolism prevention after orthopedic surgery. Data are lacking regarding reversal strategies for edoxaban; this study assessed whether four-factor prothrombin complex concentrate (Beriplex/Kcentra; CSL Behring GmbH, Marburg, Germany) can effectively reverse its effects on hemostasis using a previously described rabbit model.

Methods: The study comprised assessments of thrombin generation in vitro, pharmacokinetic parameters, and edoxaban reversal in vivo.

Thrombotic safety of prothrombin complex concentrate (Beriplex P/N) for dabigatran reversal in a rabbit model.

Introduction: In vivo animal data have shown prothrombin complex concentrate (PCC) to be effective in preventing bleeding induced by excessive plasma levels of the direct thrombin inhibitor dabigatran. This animal model study was designed to determine the risk of thrombosis associated with administration of a PCC (Beriplex P/N) to reverse dabigatran-induced bleeding.

Materials And Methods: Anesthetized rabbits were treated with initial 0, 75, 200 or 450 μg kg(-1) dabigatran boluses followed by continuous infusions to maintain elevated plasma dabigatran levels.

Assessing estrogenic chemicals in anchovy and mussel samples from Karachi, Pakistan with the yeast estrogen screen bioassay.

Endocrine disrupting chemicals (EDCs) are introduced into the aquatic environment through industrial and municipal effluents along with urban and agricultural runoffs. Exposure of aquatic organisms to EDCs may lead to hormonal disruption and adverse health effects. The goals of our study were: to collect anchovy and mussel samples from the coastal region of Karachi, to use the yeast estrogen screen (YES) bioassay in estimating xeno-estrogen content in these samples, and to investigate if the bioassay could be used to quantify known amounts of 17β-estradiol (E2) injected into cod and salmon fillets.

Reversal of dabigatran anticoagulation by prothrombin complex concentrate (Beriplex P/N) in a rabbit model.

Background: One limitation of the direct thrombin inhibitor dabigatran is the lack of specific antidotes that allow acute bleeding events to be managed or urgent interventional procedures performed. Prothrombin complex concentrates (PCCs) have served as a standard treatment for the reversal of coumarin anticoagulation.

Objectives: This study was designed to determine in an animal model whether a PCC (Beriplex P/N) can effectively reverse the effects of dabigatran.

Mutation rate matters even when optimizing monotonic functions.

Extending previous analyses on function classes like linear functions, we analyze how the simple (1+1) evolutionary algorithm optimizes pseudo-Boolean functions that are strictly monotonic. These functions have the property that whenever only 0-bits are changed to 1, then the objective value strictly increases. Contrary to what one would expect, not all of these functions are easy to optimize.

Tight analysis of the (1+1)-EA for the single source shortest path problem.

We conduct a rigorous analysis of the (1+1) evolutionary algorithm for the single source shortest path problem proposed by Scharnow, Tinnefeld, and Wegener (The analyses of evolutionary algorithms on sorting and shortest paths problems, 2004, Journal of Mathematical Modelling and Algorithms, 3(4):349-366). We prove that with high probability, the optimization time is O(n2 max{ℓ, log(n)}), where ℓ is the smallest integer such that any vertex can be reached from the source via a shortest path having at most ℓ edges. This bound is tight.