Parallel reaction dedicated model with mathematic/statistic/ parameters values/ phenomenological model / experimental validation confidence levels.
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A major challenge for the ...pharmaceutical/vaccine industry is to anticipate and test/control product stability, regardless of the time/temperature profile of the product, from release to administration. Current empirical stability protocols performed to ensure product stability remain limited to the prediction of product stability in a thermal excursion (cold chain break) during their long-term storage. As recently recommended by the World Health Organization, mathematical models can be used for shelf-life and stability predictions. Therefore, various approaches have been published with good performance for simple chemical reactions. However, for biomolecules/vaccines, more complex reaction profiles require more complex models to predict their stability with a good level of confidence. This complexity constitutes a real scientific challenge because the number of model parameters increases with model complexity and need to be balanced with the limited number and quality of the available experimental data.
We have developed a dedicated method/software based on different vaccines/pharmaceutical case studies. This predictive method considers phenomenological models, five levels of model confidence assessment, predictive quality value and simulated designs of experiment to improve and define the limits within which the prediction models can be used, and to increase model/prediction confidence to the required regulatory and scientific levels. This artificial intelligence system should help to avoid any doubt of stability at time of vaccine injection.
AIM: To assess the performance of a bespoke software for automated counting of intraocular lens (IOL) glistenings in slit-lamp images.
METHODS: IOL glistenings from slit-lamp-derived digital images ...were counted manually and automatically by the bespoke software. The images of one randomly selected eye from each of 34 participants were used as a training set to determine the threshold setting that gave the best agreement between manual and automatic grading. A second set of 63 images, selected using randomised stratified sampling from 290 images, were used for software validation. The images were obtained using a previously described protocol. Software-derived automated glistenings counts were compared to manual counts produced by three ophthalmologists.
RESULTS: A threshold value of 140 was determined that minimised the total deviation in the number of glistenings for the 34 images in the training set. Using this threshold value, only slight agreement was found between automated software counts and manual expert counts for the validating set of 63 images (κ=0.104, 95%CI, 0.040-0.168). Ten images (15.9%) had glistenings counts that agreed between the software and manual counting. There were 49 images (77.8%) where the software overestimated the number of glistenings.
CONCLUSION: The low levels of agreement show between an initial release of software used to automatically count glistenings in in vivo slit-lamp images and manual counting indicates that this is a non-trivial application. Iterative improvement involving a dialogue between software developers and experienced ophthalmologists is required to optimise agreement. The results suggest that validation of software is necessary for studies involving semi-automatic evaluation of glistenings.
•We combine GIS and Differential Calculus to introduce new road effect and edge effect indices through new free software.•We evaluate the performance of these new indices to explain the abundance of ...small mammals.•Road and edge effects were more relevant to explain abundance of small mammals than forest area.•LIE and AVLIE allow for separating the road effect from the edge effect.
Roads negatively affect many vertebrate species, whereas edge effect may favor some generalist species. This study aims to: 1) present a new way to calculate "line integral effects", represented by LIE and AVLIE, through new computer software, making this concept accessible to a broad audience of researchers interested in the study of Road Ecology and Tropical Forest Ecology; and, 2) test the performance of LIE and AVLIE indices, applied to road effect (LIE_road and AVLIE_road) and to edge effect (LIE_edge and AVLIE_edge), other road effect indices and forest area, using a data set on small mammal abundance in a human modified landscape in the Brazilian Atlantic Forest. Road and edge effects were represented by new metrics: Line Integral Effect (LIE) and Average Integral Effect (AVLIE), calculated using Line Integral from Differential Calculus of Several Variables through new free software developed by the second author. LIE_road and LIE_edge measure the total sum of the effect of roads (represented by lines) and edges (polygons), respectively, in relation to the forest fragment (point). AVLIE_road and AVLIE_edge measure the average of road and edge effect, respectively, in relation to the same sampling point. We used generalized linear regression models to explore the relationships between the abundance of the two groups of small mammals (forest specialists and habitat generalists) and the independent variables representing road, edge and forest effects. For forest specialists, the best model included AVLIE_road (negatively associated with abundance) and AVLIE_edge (negatively associated), while for habitat generalists, the best model included AVLIE_road (negatively associated) and LIE_edge (positively associated). Thus, there are more small mammals where road effect is lower. Forest fragments with higher edge effect showed more habitat generalists and less forest specialists. LIE and AVLIE could be useful metrics to explore edge effect separately to road effect on wildlife in forest fragments.
The article deals with the problem of research of software solutions of efficiently layout of material within a defined space for the needs of production storages and transport. The problem relates ...to using knowledge with branches of logistics, layout, math and geometry for needs of research and for needs the creation of an expert system of materials layout as the software application. Similar systems do not occur in the market for the needs of practice. The aim of the article is to point out the principles, which is necessary to take into account in the research of an expert system of materials layout. Final implementation of the goal consists of the idea to achieve a logistic computer system design, focused on the effective use of loading areas, combined with an aesthetic, comfortable and logically moulded outlet as a possible realistic graphic illustration of the desired result. This part refers to the object-oriented programming language, mainly because of its object-oriented features, such as polymorphism, or templating. The results of the program solution show an improvement in the utilization of the loading area of the means of transport by up to 30%.
This study aimed to evaluate the effects of a newly developed Advanced Edge Enhancement software (AEE) (Canon Europe, Amsterdam, NL) on image quality (IQ) of Digital Radiography (DR) hand images ...focusing on rheumatoid arthritis (RA).
Fifty posterior-anterior hand images with or suspected for RA were collected. For each of the 50 images, six copies were made with each their AEE algorithm settings. A total of 330 images (30 images iterated) were evaluated using relative Visual Grading Analysis (VGA) by three observers and combined into a VGA Score (VGAS). Second, 50 images of a technical Contrast Detail Radiography Phantom (CDRAD) was produced with three different AEE software settings, each at level 1,5 and without the AEE software yielding 350 CDRAD images. All images was analysed by the CDRAD Analyser and included for an objective analysis of the AEE software.
The VGA study showed a significant difference in image quality between a standard image and images with AEE software applied. The average VGA score of the AEE software was better than the standard images (interval between 0.2 and 0.9). The AEE algorithms at level 5 scored significantly lower for noise but significantly higher for spatial resolution, sharpness and contrast in the VGA. The CDRAD images showed that all AEE algorithms had a statistically significant improvement for level 1 and deterioration for level 5 compared to the standard image.
Overall the AEE algorithm: small structure level 1 showed an improvement of all IQ criteria in the VGA and a better technical IQ.
The AEE software ought to be considered as a useful addition to the current software, possibly enabling visualisation of structures currently visible.
Two new programs have been developed for searching the Cambridge Structural Database (CSD) and visualizing database entries: ConQuest and Mercury. The former is a new search interface to the CSD, the ...latter is a high‐performance crystal‐structure visualizer with extensive facilities for exploring networks of intermolecular contacts. Particular emphasis has been placed on making the programs as intuitive as possible. Both ConQuest and Mercury run under Windows and various types of Unix, including Linux.
Purpose
To validate a next-generation sequencing (NGS)-based companion diagnostic using the MiSeqDx
®
sequencing instrument to simultaneously detect 56
RAS
mutations in DNA extracted from ...formalin-fixed paraffin-embedded metastatic colorectal cancer (mCRC) tumor samples from the PRIME study. The test’s ability to identify patients with mCRC likely to benefit from panitumumab treatment was assessed.
Methods
Samples from PRIME, which compared first-line panitumumab + FOLFOX4 with FOLFOX4, were processed according to predefined criteria using a multiplex assay that included input DNA qualification, library preparation, sequencing, and the bioinformatics reporting pipeline. NGS mutational analysis of
KRAS
and
NRAS
exons 2, 3, and 4 was performed and compared with Sanger sequencing.
Results
In 441 samples, positive percent agreement of the Extended RAS Panel with Sanger sequencing was 98.7% and negative percent agreement was 97.6%. For clinical validation (
n
= 528), progression-free survival (PFS) and overall survival (OS) were compared between patients with
RAS
mutations (
RAS
Positive) and those without (
RAS
Negative). Panitumumab + FOLFOX4 improved PFS in
RAS
Negative patients (
P
= 0.02). Quantitative interaction testing indicated the treatment effect (measured by the hazard ratio of panitumumab + FOLFOX4 versus FOLFOX4) differed for
RAS
Negative versus
RAS
Positive for PFS (
P
= 0.0038) and OS (
P
= 0.0323).
Conclusions
NGS allows for broad, rapid, highly specific analyses of genomic regions. These results support use of the Extended RAS Panel as a companion diagnostic for selecting patients for panitumumab, and utilization is consistent with recent clinical guidelines regarding mCRC
RAS
testing. Overall, approximately 13% more patients were detected with the Extended RAS Panel versus
KRAS
exon 2 alone.
Clinical trial registry identifier
NCT00364013 (ClinicalTrials.gov).
Project SMART (Strategies to Promote Small-Scale Hydro Electricity Production in Europe) from the Intelligent Energy Europe (IEE) program, in which 7 institutions from 5 European states participate, ...pointed to the important barriers for the expansion of small hydro power plants (SHP) in Europe. One of the main barriers is the lack of suitable methodology and software able to create a clear view of the SHP potential in the given territory, as well as a complete techno-economic analysis for certain locations. Worldwide, there are a certain number of software for this purpose, and will be presented in this paper. However, in practical application for concrete cases, they show certain disadvantages. For example, one software is not able to take into account all the specifics of watercourses and plants; another does not have the option of selecting all types of turbines; in others, the calculation models are based on a limited number of equations that do not describe all possible cases; in some, economic analysis is oversimplified, etc. The aim of this paper is to develop software that is more comprehensive than any existing software. A new software for the techno-economic analysis of SHP is developed using Python and will be presented in this paper. The software is very useful for experts in the field of SHP, but also much wider, for decision-makers, potential investors, and stakeholders, especially in developing countries. It will improve water resources management, disseminate opportunities to investors, and increase the interest of stakeholders to invest in SHP, resulting in their wider use. The software is tested on location for SHP in the Republic of Croatia by comparison with the results obtained by the usual classical calculation. The agreement of the results is satisfactory.
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