The relation between normative rituals/routines and obsessive-compulsive symptoms at a young age:A systematic review

Objective One of the most challenging issues in the pediatric obsessive–compulsive (OC) disorder field is to differentiate pathological OC symptoms from the phenotypically similar normative rituals/routines that characterize normal childhood development. Given their similarities, it can be questioned whether both constructs reflect two qualitatively distinct behavioral expressions of different etiological factors or rather reflect two diverse manifestations of one single continuum (cfr. the continuity hypothesis). Method This paper aims to improve our understanding of the relation between normative childhood rituals/routines and OC symptoms in two ways. First, the continuity hypothesis was investigated by systematically reviewing current evidence on this association, using various databases (Web of Science Core Collection, MEDLINE/PubMed, and SciELO Citation Index) from 1950 until February 1, 2019 (registration number: CRD42019121293). Second, based on this systematic review, an integrative conceptual model was developed describing this relation from different perspectives on sources of influence. Results The literature search initially revealed 2122 hits, with 114 full-texts being assessed for eligibility. After applying several selection criteria, 18 studies were included in the review. The results generally support the continuity hypothesis and reveal important etiological factors at different levels of behavioral analysis, including the phenotypic (anxiety), neurobiological and genetic level. Also age and the presence of other disorders appeared to be important factors in evaluating the level of normality. Conclusion We provide a conceptual framework to inform future research aimed at improving the understanding of the relationship between normative rituals/routines and pathological OC symptoms. Conceptual implications are discussed and clinical recommendations are given to improve early identification and differentiation

QuantUM: Quantitative Safety Analysis of UML Models

When developing a safety-critical system it is essential to obtain an assessment of different design alternatives. In particular, an early safety assessment of the architectural design of a system is desirable. In spite of the plethora of available formal quantitative analysis methods it is still difficult for software and system architects to integrate these techniques into their every day work. This is mainly due to the lack of methods that can be directly applied to architecture level models, for instance given as UML diagrams. Also, it is necessary that the description methods used do not require a profound knowledge of formal methods. Our approach bridges this gap and improves the integration of quantitative safety analysis methods into the development process. All inputs of the analysis are specified at the level of a UML model. This model is then automatically translated into the analysis model, and the results of the analysis are consequently represented on the level of the UML model. Thus the analysis model and the formal methods used during the analysis are hidden from the user. We illustrate the usefulness of our approach using an industrial strength case study.Comment: In Proceedings QAPL 2011, arXiv:1107.074

A non-local method for robustness analysis of floating point programs

Robustness is a standard correctness property which intuitively means that if the input to the program changes less than a fixed small amount then the output changes only slightly. This notion is useful in the analysis of rounding error for floating point programs because it helps to establish bounds on output errors introduced by both measurement errors and by floating point computation. Compositional methods often do not work since key constructs---like the conditional and the while-loop---are not robust. We propose a method for proving the robustness of a while-loop. This method is non-local in the sense that instead of breaking the analysis down to single lines of code, it checks certain global properties of its structure. We show the applicability of our method on two standard algorithms: the CORDIC computation of the cosine and Dijkstra's shortest path algorithm.Comment: QAPL - Tenth Workshop on Quantitative Aspects of Programming Languages (2012

Lipid droplet degradation by autophagy connects mitochondria metabolism to Prox1-driven expression of lymphatic genes and lymphangiogenesis.

Autophagy has vasculoprotective roles, but whether and how it regulates lymphatic endothelial cells (LEC) homeostasis and lymphangiogenesis is unknown. Here, we show that genetic deficiency of autophagy in LEC impairs responses to VEGF-C and injury-driven corneal lymphangiogenesis. Autophagy loss in LEC compromises the expression of main effectors of LEC identity, like VEGFR3, affects mitochondrial dynamics and causes an accumulation of lipid droplets (LDs) in vitro and in vivo. When lipophagy is impaired, mitochondrial ATP production, fatty acid oxidation, acetyl-CoA/CoA ratio and expression of lymphangiogenic PROX1 target genes are dwindled. Enforcing mitochondria fusion by silencing dynamin-related-protein 1 (DRP1) in autophagy-deficient LEC fails to restore LDs turnover and lymphatic gene expression, whereas supplementing the fatty acid precursor acetate rescues VEGFR3 levels and signaling, and lymphangiogenesis in LEC-Atg5-/- mice. Our findings reveal that lipophagy in LEC by supporting FAO, preserves a mitochondrial-PROX1 gene expression circuit that safeguards LEC responsiveness to lymphangiogenic mediators and lymphangiogenesis.We thank K. Rillaerts, J. Souffreau, and A. Bouche, for expert technical support and Dr. A. Luttun and Dr. A. Zijsen for sharing tools and advices. P.A. is supported by grants from the Flemish Research Foundation (FWO-Vlaanderen; G076617N, G049817N, G070115N), the EOS MetaNiche consortium N degrees 40007532, Stichting tegen Kanker (FAF-F/2018/1252) and the iBOF/21/053 ATLANTIS consortium with G.B. D.H. is the recipient of an FWO Doctoral Fellowship from the Flemish Research Foundation (FWO-Vlaanderen, 1186019N), Belgium. M.B. is supported by the `Fonds voor Wetenschappelijk Onderzoek' (FWO). K.J. is the recipient of an FWO Postdoctoral Fellowship from the Flemish Research Foundation (FWO-Vlaanderen). P.C. is supported by Methusalem funding by the Flemish government, and by an ERC Advanced Research Grant (EU-ERC269073).S

Serial Coronary Imaging of Early Atherosclerosis Development in Fast-Food-Fed Diabetic and Nondiabetic Swine

Patients with diabetes mellitus (DM) are at increased risk for atherosclerosis-related events compared to non-DM (NDM) patients. With an expected worldwide epidemic of DM, early detection of anatomic and functional coronary atherosclerotic changes is gaining attention. To improve our understanding of early atherosclerosis development, we studied a swine model that gradually developed coronary atherosclerosis. Interestingly, optical coherence tomography, near-infrared spectroscopy (NIRS), vascular function, and histology demonstrated no differences between development of early atherosclerosis in fast-food-fed (FF) DM swine and that in FF-NDM swine. Coronary computed tomography angiography did not detect early atherosclerosis, but optical coherence tomography and near-infrared spectroscopy demonstrated coronary atherosclerosis development in FF-DM and FF-NDM swine

Time trends in diagnostic testing for primary ciliary dyskinesia in Europe

status: publishe

Anti-Epithelial Cell Adhesion Molecule Antibodies and the Detection of Circulating Normal-Like Breast Tumor Cells

Identification of specific subtypes of circulating tumor cells in peripheral blood of cancer patients can provide information about the biology of metastasis and improve patient management. However, to be effective, the method used to identify circulating tumor cells must detect all tumor cell types. We investigated whether the five subtypes of human breast cancer cells that have been defined by global gene expression profiling—normal-like, basal, HER2-positive, and luminal A and B—were identified by CellSearch, a US Food and Drug Administration–approved test that uses antibodies against the cell surface–expressed epithelial cell adhesion molecule (EpCAM) to isolate circulating tumor cells. We used global gene expression profiling to determine the subtypes of a well-defined panel of 34 human breast cancer cell lines (15 luminal, nine normal-like, five basal-like, and five Her2-positive). We mixed 50-150 cells from 10 of these cell lines with 7.5 mL of blood from a single healthy human donor, and the mixtures were subjected to the CellSearch test to isolate the breast cancer cells. We found that the CellSearch isolation method, which uses EpCAM on the surface of circulating tumor cells for cell isolation, did not recognize, in particular, normal-like breast cancer cells, which in general have aggressive features. New tests that include antibodies that specifically recognize normal-like breast tumor cells but not cells of hematopoietic origin are needed

Nematode-based indices in soil ecology: Application, utility, and future directions

14 Pág.The health and functioning of soil ecosystems are the foundation of sustainable food production and land management. Of key importance in achieving sustainability, is the frequent measurement of soil health, and indices based on the community structure of nematodes are amongst the most widely used toolsets by soil ecologists. Thirty years after the development of the Maturity Index, we aimed to evaluate the application, utility, and future directions of nematode-based indices (NBIs). This review focused on NBIs that are calculated using the coloniser-persister classification of nematodes. Data from 672 empirical studies in terrestrial environments revealed that the NBIs presented a dissimilar usage trend. The Channel Index and Metabolic Footprints showed the strongest increase in application rates over time, thus indicating a greater interest in studying decomposition pathways and ecosystem functioning, respectively. Furthermore, nematode-based indices were mostly applied in agricultural systems associated with herbaceous crops and in studies investigating, for example, soil nutrient enrichment following manure and/or inorganic fertilizer application. We further provide a framework for selecting a focus-orientated subset of NBIs for testing hypotheses based on the underlying ecological mechanisms. Also, we highlight important considerations, including the unexpected behaviour of some nematode taxa, in the interpretation of NBIs. The improvement of NBIs relies on advancing our understanding of the autecology of nematodes. Finally, we deliver insight into the further development of NBIs considering recent methodological advancements. We highlight that NBIs have been and might become increasingly important in providing valuable information on soil ecosystem health and functioning, especially considering the urgent need for more sustainable land use.The contribution of JHS was funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) — :— Project no. 420414676: “The self-regulatory potential of agro-ecosystems: Using nematodes as indicators for legume disease suppressive soils”.Peer reviewe