PoN-S : a systematic approach for applying the Physics of Notation (PoN)

Visual Modeling Languages (VMLs) are important instruments of communication between modelers and stakeholders. Thus, it is important to provide guidelines for designing VMLs. The most widespread approach for analyzing and designing concrete syntaxes for VMLs is the so-called Physics of Notation (PoN). PoN has been successfully applied in the analysis of several VMLs. However, despite its popularity, the application of PoN principles for designing VMLs has been limited. This paper presents a systematic approach for applying PoN in the design of the concrete syntax of VMLs. We propose here a design process establishing activities to be performed, their connection to PoN principles, as well as criteria for grouping PoN principles that guide this process. Moreover, we present a case study in which a visual notation for representing Ontology Pattern Languages is designed

Spontaneous and iatrogenic ovarian hyperstimulation syndrome in the absence of FSHR mutations: a case report of two unexpected cases

Background: Ovarian hyperstimulation syndrome (OHSS) is a complication of controlled ovarian hyperstimulation (COH). It is a potentially life-threatening condition that usually occurs either after human chorionic gonadotropins (hCG) administration in susceptible patients or as a result of an implanting pregnancy, regardless of whether it was achieved by natural conception or infertility treatments. Despite many years of clinical experience regarding the adoption of preventive measures and the identification of patients at high risk, the pathophysiology of OHSS is poorly understood and no reliable predictive risk factors have been identified. Cases presentation: We report about two unexpected cases of OHSS following infertility treatments, occurring after freeze-all strategy with embryo cryopreservation approaches. The first case developed spontaneous OHSS (sOHSS), despite efforts to prevent its manifestation by a segmentation approach, including frozen embryo replacement cycle. The second case developed a late form of iatrogenic OHSS (iOHSS), even though the absence of any risk factors. No mutations in the follicle-stimulating hormone (FSH) receptor (FSHR)-encoding gene were detected, suggesting that the high levels of hCG due to the twin implanting pregnancies could be the only triggering factor of OHSS outbreak. Conclusion: Freeze-all strategy with embryo cryopreservation cannot entirely prevent the development of OHSS, which may occur in its spontaneous form independently from the FSHR genotype. Although OHSS remains a rare event, all infertile patients requiring ovulation induction or controlled ovarian stimulation (COS) may be at potential risk of OHSS, either in the presence or in the absence of risk factors. We suggest closely monitoring cases of pregnancy following infertility treatments in order to provide early diagnosis and adopt the conservative management

Retrospective Cohort Study on Acute Care in Obstetrics and Gynecology. Analogies and Differences When Compared to Emergency Medicine

Introduction: the demand for urgent obstetric and gynecology care has progressively increased: in the United States approximately 1.4 million gynecologic visits are made to the emergency department (ED) annually, while almost 75% of women make at least 1 unscheduled visit during pregnancy. Moreover, research has recently focused on setting standards in unscheduled care, and developing quality indicators to improve patients’ health. Therefore, we investigated the characteristics of women with acute gynecological or pregnancy complaints using quality indicators developed for emergency medicine, to better define the needs of this population and improve care. Methods: Retrospective cohort study on ED, and Obstetrics and Gynecology (ObGyn) triage visits, at a tertiary care hospital in Italy, during 2012. Data were analyzed with population-averaged logistic regression and Poisson regression. Results: When compared to the 33,557 ED visits, the 9245 ObGyntriage referrals were more frequently associated with pregnancy (≤12 weeks’ gestation, OR: 30.7, 95%CI; 24.5 - 38.4; >12 weeks’ gestation, OR 81.2, 95%CI; 64.8 - 101.4), vaginal bleeding (OR 156.6, 95%CI; 82.7 - 294.4), diurnal (night access OR 0.87, 95% CI; 0.78 - 0.96) and weekday access (holiday access OR 0.87, 95%CI; 0.78 - 0.95), frequent users (recurrent ED visits IRR 0.87, 95%CI; 0.83 - 0.9) and lower hospital admissions (ED admission OR 1.6, 95%CI; 1.4 - 1.8). Conclusion: ObGyn triage patients differed from ED users, and were at higher risk of “crowding”. Such diversities should be considered to improve female healthcare services and allocate resources more efficiently

Remarks on 2+1 Self-dual Chern-Simons Gravity

We study 2+1 Chern-Simons gravity at the classical action level. In particular we rederive the linear combinations of the ``standard'' and ``exotic'' Einstein actions, from the (anti) self-duality of the ``internal'' Lorentzian indices. The relation to a genuine four-dimensional (anti)self-dual topological theory greatly facilitates the analysis and its relation to hyperbolic three-dimensional geometry. Finally a non-abelian vector field ``dual'' action is also obtained.Comment: 16+1 pages, LaTeX file, no figures, clarifications and comments added, typos corrected and one reference adde

New insight into the identity of italian grapevine varieties: The case study of calabrian germplasm

Calabria is a region located in Southern Italy and it is characterized by a long tradition of viticulture practices and favorable pedoclimatic conditions for grapevine cultivation. Nevertheless, less than 2% of cultivated land is dedicated to grapevine growing in Calabria. The characterization of local grapevine accessions is crucial to valorize the local and peculiar Italian products and boost the Calabrian winemaking sector. With this purpose, we performed a deep characterization of two widespread Calabrian grapevine varieties—Magliocco Dolce and Brettio Nero, of which very little is known. In particular, a genetic and morphological analysis, a berry physico-chemical and polyphenolic compositions assessment, and oenological evaluation of monovarietal wines were carried out. Our results allowed us to demonstrate that Magliocco Dolce and Brettio Nero are unique and distinct varieties with peculiar morphological and chemical characteristics and show the suitability of these two varieties in high-quality wine production. Moreover, the obtained molecular profiles will be useful for authentication and traceability purposes

Class I Integrons and SXT Elements in El Tor Strains Isolated before and after 1992 Vibrio cholerae O139 Outbreak, Calcutta, India

We examined the distribution of class I integrons and SXT elements in Vibrio cholerae O1 El Tor strains, isolated in Calcutta, India, before and after the V. cholerae O139 outbreak in 1992. Class I integrons, with aadA1 gene cassette, were detected primarily in the pre-O139 strains; the SXT element was found mainly in the post-O139 strains

Sphingosine-1 phosphate induces cAMP/PKA-independent phosphorylation of the cAMP response element-binding protein (CREB) in granulosa cells

Background and aims: Sphingosine-1 phosphate (S1P) is a lysosphingolipid present in the ovarian follicular fluid. The role of the lysosphingolipid in gonads of the female is widely unclear. At nanomolar concentrations, S1P binds and activates five specific G protein-coupled receptors (GPCRs), known as S1P1-5, modulating different signaling pathways. S1P1 and S1P3 are highly expressed in human primary granulosa lutein cells (hGLC), as well as in the immortalized human primary granulosa cell line hGL5. In this study, we evaluated the signaling cascade activated by S1P and its synthetic analogues in hGLC and hGL5 cells, exploring the biological relevance of S1PR-stimulation in this context. METHODS AND RESULTS. hGLC and hGL5 cells were treated with a fixed dose (0.1 \u3bcM) of S1P, or by S1P1- and S1P3-specific agonists SEW2871 and CYM5541. In granulosa cells, S1P and, at a lesser extent, SEW2871 and CYM5541, potently induced CREB phosphorylation. No cAMP production was detected and pCREB activation occurred even in the presence of the PKA inhibitor H-89. Moreover, S1P-dependent CREB phosphorylation was dampened by the mitogen-activate protein kinase (MEK) inhibitor U0126 and by the L-type Ca2+ channel blocker verapamil. The complete inhibition of CREB phosphorylation occurred by blocking either S1P2 or S1P3 with the specific receptor antagonists JTE-013 and TY52156, or under PLC/PI3K depletion. S1P-dependent CREB phosphorylation induced FOXO1 and the EGF-like epiregulin-encoding gene (EREG), confirming the exclusive role of gonadotropins and interleukins in this process, but did not affect steroidogenesis. However, S1P or agonists did not modulate granulosa cell viability and proliferation in our conditions. Conclusions: This study demonstrates for the first time that S1P may induce a cAMP-independent activation of pCREB in granulosa cells, although this is not sufficient to induce intracellular steroidogenic signals and progesterone synthesis. S1P-induced FOXO1 and EREG gene expression suggests that the activation of S1P\u2013S1PR axis may cooperate with gonadotropins in modulating follicle development