Pharmacodynamic evaluation and safety assessment of treatment with antibodies to serum amyloid P component in patients with cardiac amyloidosis: an open-label Phase 2 study and an adjunctive immuno-PET imaging study

BACKGROUND: In a Phase I study treatment with the serum amyloid P component (SAP) depleter miridesap followed by monoclonal antibody to SAP (dezamizumab) showed removal of amyloid from liver, spleen and kidney in patients with systemic amyloidosis. We report results from a Phase 2 study and concurrent immuno-positron emission tomography (PET) study assessing efficacy, pharmacodynamics, pharmacokinetics, safety and cardiac uptake (of dezamizumab) following the same intervention in patients with cardiac amyloidosis. METHODS: Both were uncontrolled open-label studies. After SAP depletion with miridesap, patients received ≤ 6 monthly doses of dezamizumab in the Phase 2 trial (n = 7), ≤ 2 doses of non-radiolabelled dezamizumab plus [89Zr]Zr-dezamizumab (total mass dose of 80 mg at session 1 and 500 mg at session 2) in the immuno-PET study (n = 2). Primary endpoints of the Phase 2 study were changed from baseline to follow-up (at 8 weeks) in left ventricular mass (LVM) by cardiac magnetic resonance imaging and safety. Primary endpoint of the immuno-PET study was [89Zr]Zr-dezamizumab cardiac uptake assessed via PET. RESULTS: Dezamizumab produced no appreciable or consistent reduction in LVM nor improvement in cardiac function in the Phase 2 study. In the immuno-PET study, measurable cardiac uptake of [89Zr]Zr-dezamizumab, although seen in both patients, was moderate to low. Uptake was notably lower in the patient with higher LVM. Treatment-associated rash with cutaneous small-vessel vasculitis was observed in both studies. Abdominal large-vessel vasculitis after initial dezamizumab dosing (300 mg) occurred in the first patient with immunoglobulin light chain amyloidosis enrolled in the Phase 2 study. Symptom resolution was nearly complete within 24 h of intravenous methylprednisolone and dezamizumab discontinuation; abdominal computed tomography imaging showed vasculitis resolution by 8 weeks. CONCLUSIONS: Unlike previous observations of visceral amyloid reduction, there was no appreciable evidence of amyloid removal in patients with cardiac amyloidosis in this Phase 2 trial, potentially related to limited cardiac uptake of dezamizumab as demonstrated in the immuno-PET study. The benefit-risk assessment for dezamizumab in cardiac amyloidosis was considered unfavourable after the incidence of large-vessel vasculitis and development for this indication was terminated. Trial registration NCT03044353 (2 February 2017) and NCT03417830 (25 January 2018)

Measurements of layer thickness for diagnostics of surface

W pracy przedstawiono zagadnienia, dotyczące pomiaru grubości warstw wierzchnich, przeprowadzane z wykorzystaniem przetworników indukcyjnych. Opisano badania, dotyczące przetwornika indukcyjnego transformatorowego. Na potrzeby pomiarów wykonano przetworniki pomiarowe, dla których przeprowadzono badania ich przydatności w diagnostyce wybranych warstw wierzchnich.Questions relating to the measurement of a top layer thickness were introduced in the work. Measurements carried out with the use of inductive transducers are taken into account. Problems were illustrated by examples of possible applications in diagnostics of protective coatings in car and airplanes industry. In Chapters 2 and 3 there is shown the construction of typical inductive transducer (Fig.1) and some sources of measuring errors. Model of transformer transducers (Fig. 2 and 3) and construction of applied measuring transducer (Fig. 4) were introduced in Chapters 4 and 5. Measuring transducers for which the investigations were conducted were made on needs of measurements. In Chapter 6 there are described results of investigations (Fig. 7 and 8), relating to the inductive transformer transducer. In conclusions the utility of transformer transducers for diagnostics of chosen top layers was defined

A new method to estimate dimensions of vehicle using a single camera

The capability of a telematic vision system of estimating dimensions of vehicles is used for such tasks as vehicle classification or preselection of vehicles that violate local vehicle size limitations. Also in some European countries dimensions of heavy vehicles must obey some global regulations. Furthermore, vehicle size estimation allows us to determine the structure of traffic and can be very useful for advanced traffic flow control. Many existing Intelligent Transportation Systems consist of a large number of video cameras located in various places e.g., the ITS in Wrocław uses more than 1400 cameras. In this paper we propose a new method developed by the ArsNumerica Group and CyberTech Scientific Circle for the precise estimation of vehicle sizes using a single camera. The method does not require the entering of measurements such as the distance between lane lines or the height of the camera above the roadway. Only one vehicle’s dimensions are used for calibration. The proposed method is easy to implement and may be applied with the OpenCV library which is free both for academic and commercial use. The method is tested on real-world video streams. The obtained results are shown and analyzed in the paper

Some aspects of Intelligent Transport System auditing

Nowadays, in urbanized areas one of the most important matters is to determine a priori the time of driving from one zone of the city to another at various times of the day. The problem of travel time prediction is crucial in Intelligent Transportation Systems. The solution to this problem is a foundation of any route guidance system that will redirect drivers to their target destination via routes that have a lighter traffic load and thus higher travel velocity. In this paper is present a concept of a statistical methodology, developed by the ArsNumerica Group, that enables a quantity audit a travel time prediction algorithm. The methodology assumes that we are given database records of vehicles recognized by their unique identifier as well as duration times for which the messages with the predicted travel time are displayed VMS. the second aspect of ITS auditing considered in this paper is a placement of video cameras to measure vehicle stream velocity. Inappropriate camera location results in the fact that the stream velocity measured by them has a low usefulness for travel time prediction

Detection of vehicles moving in wrong direction

In this paper we describe a method for detecting situations where a vehicle moves along a highway in the wrong direction. The first step of the algorithm is to build a pattern using Gaussian mixture model based on the optical flow calculated with the Lucas-Kanade method. The second stage concerns the detection of objects as a potential road hazard. The optical flow calculated on-line during the second stage is compared with the traffic pattern used in the first stage. Then the difference in movement direction is detected using predefined thresholds

Intelligent Transport System auditing using road traffic micro-simulation

ITS systems have been deployed for last one and a half decades. Their aim is to increase a traffic flow rate in a road network of an urbanized area, to improve the comfort of driving as well as to decrease the pollution. A lot of commercial software are is available to simulate road traffic in urbanized areas. Some of them are suitable to perform traffic simulations of intelligent transportation systems via traffic modeling. A process of traffic modeling exploiting numerical simulations for an urban area where an ITS is deployed requires provision of digital maps, traffic demand amongst city zones, traffic signalization micro-programs being executed in the environment that can imitate a dynamic behavior of traffic lights at intersections in the ITS. In this paper an execution environment, developed by the Ars Numerica Group, that launches a road traffic micro-simulation is used to audit a performance of intersections’ signalization micro-programs on one of the main arteries in the city of Wrocław (Poland)

Multithreaded enhancements of the Dijkstra algorithm for route optimization in urban networks

In this paper, we present a case study, showing step by step, how to speed up Dijkstra’s method by parallelizing its computation and using different data structures. We compare basic algorithm with its bidirectional version and investigate two-and-multi-thread implementations based on Fibonacci heaps and regular priority queues. Experimental results obtained for artificially generated graphs as well as real-world road network data are presented and described

Interaction effects between weather and space use on harvesting effort and patterns in red deer

Most cervid populations in Europe and North America are managed through selective harvesting, often with age- and sex-specific quotas, with a large influence on the population growth rate. Less well understood is how prevailing weather affects harvesting selectivity and off-take indirectly through changes in individual animal and hunter behavior. The behavior and movement patterns of hunters and their prey are expected to be influenced by weather conditions. Furthermore, habitat characteristics like habitat openness are also known to affect movement patterns and harvesting vulnerability, but how much such processes affect harvest composition has not been quantified. We use harvest data from red deer (Cervus elaphus) to investigate how weather and habitat characteristics affect behavioral decisions of red deer and their hunters throughout the hunting season. More specifically, we look at how sex and age class, temperature, precipitation, moon phase, and day of week affect the probability of being harvested on farmland (open habitat), hunter effort, and the overall harvest numbers. Moon phase and day of week were the strongest predictors of hunter effort and harvest numbers, with higher effort during full moon and weekends, and higher numbers during full moon. In general, the effect of fall weather conditions and habitat characteristics on harvest effort and numbers varied through the season. Yearlings showed the highest variation in the probability of being harvested on farmland through the season, but there was no effect of sex. Our study is among the first to highlight that weather may affect harvesting patterns and off-take indirectly through animal and hunter behavior, but the interaction effects of weather and space use on hunter behavior are complicated, and seem less important than hunter preference and quotas in determining hunter selection and harvest off-take. The consideration of hunter behavior is therefore key when forming management rules for sustainable harvesting