Surveillance of multiple congenital anomalies; searching for new associations

\ua9 2023, The Author(s).Many human teratogens are associated with a spectrum of congenital anomalies rather than a single defect, and therefore the identification of congenital anomalies occurring together more frequently than expected may improve the detection of teratogens. Thirty-two EUROCAT congenital anomaly registries covering 6,599,765 births provided 123,566 cases with one or more major congenital anomalies (excluding chromosomal and genetic syndromes) for the birth years 2008–2016. The EUROCAT multiple congenital anomaly algorithm identified 8804 cases with two or more major congenital anomalies in different organ systems, that were not recognized as part of a syndrome or sequence. For each pair of anomalies, the odds of a case having both anomalies relative to having only one anomaly was calculated and the p value was estimated using a two-sided Fisher’s exact test. The Benjamini–Hochberg procedure adjusted p values to control the false discovery rate and pairs of anomalies with adjusted p values < 0.05 were identified. A total of 1386 combinations of two anomalies were analyzed. Out of the 31 statistically significant positive associations identified, 20 were found to be known associations or sequences already described in the literature and 11 were considered “potential new associations” by the EUROCAT Coding and Classification Committee. After a review of the literature and a detailed examination of the individual cases with the anomaly pairs, six pairs remained classified as new associations. In summary, systematically searching for congenital anomalies occurring together more frequently than expected using the EUROCAT database is worthwhile and has identified six new associations that merit further investigation

Report from the EPAA workshop: In vitro ADME in safety testing used by EPAA industry sectors

AbstractThere are now numerous in vitro and in silico ADME alternatives to in vivo assays but how do different industries incorporate them into their decision tree approaches for risk assessment, bearing in mind that the chemicals tested are intended for widely varying purposes? The extent of the use of animal tests is mainly driven by regulations or by the lack of a suitable in vitro model. Therefore, what considerations are needed for alternative models and how can they be improved so that they can be used as part of the risk assessment process? To address these issues, the European Partnership for Alternative Approaches to Animal Testing (EPAA) working group on prioritisation, promotion and implementation of the 3Rs research held a workshop in November, 2008 in Duesseldorf, Germany. Participants included different industry sectors such as pharmaceuticals, cosmetics, industrial- and agro-chemicals. This report describes the outcome of the discussions and recommendations (a) to reduce the number of animals used for determining the ADME properties of chemicals and (b) for considerations and actions regarding in vitro and in silico assays. These included: standardisation and promotion of in vitro assays so that they may become accepted by regulators; increased availability of industry in vivo kinetic data for a central database to increase the power of in silico predictions; expansion of the applicability domains of in vitro and in silico tools (which are not necessarily more applicable or even exclusive to one particular sector) and continued collaborations between regulators, academia and industry. A recommended immediate course of action was to establish an expert panel of users, developers and regulators to define the testing scope of models for different chemical classes. It was agreed by all participants that improvement and harmonization of alternative approaches is needed for all sectors and this will most effectively be achieved by stakeholders from different sectors sharing data

Surveillance of multiple congenital anomalies; searching for new associations.

Many human teratogens are associated with a spectrum of congenital anomalies rather than a single defect, and therefore the identification of congenital anomalies occurring together more frequently than expected may improve the detection of teratogens. Thirty-two EUROCAT congenital anomaly registries covering 6,599,765 births provided 123,566 cases with one or more major congenital anomalies (excluding chromosomal and genetic syndromes) for the birth years 2008-2016. The EUROCAT multiple congenital anomaly algorithm identified 8804 cases with two or more major congenital anomalies in different organ systems, that were not recognized as part of a syndrome or sequence. For each pair of anomalies, the odds of a case having both anomalies relative to having only one anomaly was calculated and the p value was estimated using a two-sided Fisher's exact test. The Benjamini-Hochberg procedure adjusted p values to control the false discovery rate and pairs of anomalies with adjusted p values < 0.05 were identified. A total of 1386 combinations of two anomalies were analyzed. Out of the 31 statistically significant positive associations identified, 20 were found to be known associations or sequences already described in the literature and 11 were considered "potential new associations" by the EUROCAT Coding and Classification Committee. After a review of the literature and a detailed examination of the individual cases with the anomaly pairs, six pairs remained classified as new associations. In summary, systematically searching for congenital anomalies occurring together more frequently than expected using the EUROCAT database is worthwhile and has identified six new associations that merit further investigation

MAGNETIC BUBBLE MEMORIES AND THEIR APPLICATIONS by

cussion which followed the original paper are included here

Design of a parallel genetic algorithm for the Internet

This paper proposes that a parallel implementa-tion of the genetic algorithm (GA) on the Internet will improve the algorithm’s performance. It is moti-vated by the possibility of aiding research into com-plex search and optimization problems that use the GA. Requirements and constraints regarding paral-lelization of the GA are identified. A parallel GA is developed for an ideal PRAM architecture and is shown to have an asymptotic running time of O(log n), an improvement over the sequential GA. A paral-lel GA is also designed for a Unix network and has an asymptotic running time comparable to the ideal sys-tem. The algorithm is a decentralized, asynchronous, and fault-tolerant design that matches characteristics of the network. The GA population is divided into colonies that are distributed among processors. Trade policies are executed for the exchange of genes.

Wavelet packet best basis search using generalized Renyi entropy

This paper introduces an approach to wavelet packet best basis searches using the generalized Renyi entropy. The approach extends work by R.R. Coifman and M.V. Wickerhauser who showed how Shannon entropy can be used as an additive cost function in the wavelet packet best basis selection (see IEEE Trans. on Inform. Theory, vol.38, no.2, p.713-18, 1992). This paper also extends the idea of an additive cost function to an arithmetic mean. These extensions allow for a redefinition of additive cost functions as arithmetic means in a way consistent with the approach of Coifman and Wickerhauser. The approach using an arithmetic mean is then extended to include the geometric mean. This extension to geometric means allows us to introduce the Renyi generalized entropy as a cost function in the best basis search. These two extensions also allow the use of incomplete probability distributions, whereas Coifman and Wickerhauser's entropy based cost function is limited to complete probability distributions