The Importance of Being Constrained: Dealing with Infeasible Solutions in Differential Evolution and Beyond.

We argue that results produced by a heuristic optimisation algorithm cannot be considered reproducible unless the algorithm fully specifies what should be done with solutions generated outside the domain, even in the case of simple bound constraints. Currently, in the field of heuristic optimisation, such specification is rarely mentioned or investigated due to the assumed triviality or insignificance of this question. Here, we demonstrate that, at least in algorithms based on Differential Evolution, this choice induces notably different behaviours in terms of performance, disruptiveness, and population diversity. This is shown theoretically (where possible) for standard Differential Evolution in the absence of selection pressure and experimentally for the standard and state-of-the-art Differential Evolution variants, on a special test function and the BBOB benchmarking suite, respectively. Moreover, we demonstrate that the importance of this choice quickly grows with problem dimensionality. Differential Evolution is not at all special in this regard-there is no reason to presume that other heuristic optimisers are not equally affected by the aforementioned algorithmic choice. Thus, we urge the heuristic optimisation community to formalise and adopt the idea of a new algorithmic component in heuristic optimisers, which we refer to as the strategy of dealing with infeasible solutions. This component needs to be consistently: (a) specified in algorithmic descriptions to guarantee reproducibility of results, (b) studied to better understand its impact on an algorithm's performance in a wider sense (i.e., convergence time, robustness, etc.), and (c) included in the (automatic) design of algorithms. All of these should be done even for problems with bound constraints.

Genome-Wide Association Studies for Milk Somatic Cell Score in Romanian Dairy Cattle.

Mastitis is one of the most frequently encountered diseases in dairy cattle, negatively affecting animal welfare and milk production. For this reason, contributions to understanding its genomic architecture are of great interest. Genome-wide association studies (GWAS) have identified multiple loci associated with somatic cell score (SCS) and mastitis in cattle. However, most of the studies have been conducted in different parts of the world on various breeds, and none of the investigations have studied the genetic architecture of mastitis in Romanian dairy cattle breeds up to this point in time. In this study, we report the first GWAS for SCS in dairy cattle breeds from Romania. For GWAS, we used an Axiom Bovine v3 SNP-chip (>63,000 Single Nucleotide Polymorphism -SNPs) and 33,330 records from 690 cows belonging to Romanian Spotted (RS) and Romanian Brown (RB) cattle. The results found one SNP significantly associated with SCS in the RS breed and 40 suggestive SNPs with -log10 (p) from 4 to 4.9 for RS and from 4 to 5.4 in RB. From these, 14 markers were located near 12 known genes (AKAP8, CLHC1, MEGF10, SATB2, GATA6, SPATA6, COL12A1, EPS8, LUZP2, RAMAC, IL12A and ANKRD55) in RB cattle, 3 markers were close to ZDHHC19, DAPK1 and MMP7 genes, while one SNP overlapped the HERC3 gene in RS cattle. Four genes (HERC3, LUZP2, AKAP8 and MEGF10) associated with SCS in this study were previously reported in different studies. The most significant SNP (rs110749552) associated with SCS was located within the HERC3 gene. In both breeds, the SNPs and position of association signals were distinct among the three parities, denoting that mastitis is controlled by different genes that are dependent according to parity. The current results contribute to an expansion in the body of knowledge regarding the proportion of genetic variability explained by SNPs for SCS in dairy cattle.

Modeling the development of the post-natal mouse thymus in the absence of bone marrow progenitors.

Many mathematical models have been published with the purpose of explaining aspects of T-cell development in the thymus. In this manuscript we adapted a four-compartment model of the thymus and used a range of mathematical approaches with the aim of explaining the dynamics of the four main thymocyte populations in the mouse thymus, from the emergence of the first fetal thymocyte until the death of the animal. At various pre-natal and post-natal stages we investigated experimentally the number and composition of thymocytes populations, their apoptosis and proliferation, along with data from literature, to create and validate the model. In our model the proliferation processes are characterized by decreasing proliferation rates, which allows us to model the natural involution of the thymus. The best results were obtained when different sets of parameters were used for the fetal and post-natal periods, suggesting that birth may induce a discontinuity in the modeled processes. Our model is able to model the development of both pre-natal and post-natal thymocyte populations. Also, our findings showed that the post-natal thymus is able to develop in the absence of the daily input of bone marrow progenitors, providing more evidence to support the autonomous development of the post-natal thymus.

Insights into the mechanisms of thymus involution and regeneration by modeling the glucocorticoid-induced perturbation of thymocyte populations dynamics.

T-cells develop in the thymus and based on CD4 and CD8 expressions there are four main thymocyte populations in a normal mouse thymus. Currently, there are several mathematical models that describe the dynamics of thymocyte populations in a normal thymus, but only a few of them model the transient perturbation of their homeostasis. Our aim is to model the perturbation in the dynamics of each thymocyte population which is induced by the administration of a glucocorticoid, i.e. dexamethasone. The proposed approach relies on extending a four compartment thymus model based on differential equations by adding perturbation terms either globally (at the level of each equation) or locally (at the level of proliferation, death, and transfer rates). By fitting the perturbed model with experimental data on mice thymi collected before and after the administration of dexamethasone, it was possible to estimate the relevant parameters using a population-based stochastic search method. The fitted model is further used to conduct a quantitative analysis on the differentiated impact of dexamethasone on each T-cell population and on proliferation, death, and transfer processes. The obtained quantitative information on the perturbation could be used to explore and modify the flow of thymocytes between thymus compartments in order to elucidate the mechanisms of thymus involution and its subsequent regeneration. Since glucocorticoids are raised in many pathological situations, such a model could be useful in evaluating the impact of diseases on thymocyte dynamics in the thymus.

Exploratory analysis of medical coding practices: the relevance of reported data quality in obstetrics-gynaecology.

We aimed at identifying a suitable data analysis approach to investigate potential patterns in the current medical coding in obstetrics and perinatal care. We processed the data reported for 2006 in DRG files from three Romanian university clinics of obstetrics-gynaecology and found substantial differences in the coding practices. Based on the evidence we found with a poor usage of the coding instruments, we concluded that using objective methods and quantifiable measures in analyzing the medical coding could help putting things into the right perspective and bring support for the need for formal education of medical record administrators and coders where such programmes do not exist, e.g. in Romania.