Combining Decision Procedures for Sorted Theories

Abstract. The Nelson-Oppen combination method combines decision procedures for theories satisfying certain conditions into a decision pro-cedure for their union. While the method is known to be correct in the setting of unsorted first-order logic, some current implementations of it appear in tools that use a sorted input language. So far, however, there have been no theoretical results on the correctness of the method in a sorted setting, nor is it obvious that the method in fact lifts as is to logics with sorts. To bridge this gap between the existing theoretical results and the current implementations, we extend the Nelson-Oppen method to (order-)sorted logic and prove it correct under conditions sim-ilar to the original ones. From a theoretical point of view, the extension is relevant because it provides a rigorous foundation for the application of the method in a sorted setting. From a practical point of view, the extension has the considerable added benefits that in a sorted setting the method’s preconditions become easier to satisfy in practice, and the method’s nondeterminism is generally reduced.

Global network analysis in Schizosaccharomyces pombe reveals three distinct consequences of the common 1-kb deletion causing juvenile CLN3 disease

Juvenile CLN3 disease is a recessively inherited paediatric neurodegenerative disorder, with most patients homozygous for a 1-kb intragenic deletion in CLN3. The btn1 gene is the Schizosaccharomyces pombe orthologue of CLN3. Here, we have extended the use of synthetic genetic array (SGA) analyses to delineate functional signatures for two different disease-causing mutations in addition to complete deletion of btn1. We show that genetic-interaction signatures can differ for mutations in the same gene, which helps to dissect their distinct functional effects. The mutation equivalent to the minor transcript arising from the 1-kb deletion (btn1102–208del) shows a distinct interaction pattern. Taken together, our results imply that the minor 1-kb deletion transcript has three consequences for CLN3: to both lose and retain some inherent functions and to acquire abnormal characteristics. This has particular implications for the therapeutic development of juvenile CLN3 disease. In addition, this proof of concept could be applied to conserved genes for other mendelian disorders or any gene of interest, aiding in the dissection of their functional domains, unpacking the global consequences of disease pathogenesis, and clarifying genotype–phenotype correlations. In doing so, this detail will enhance the goals of personalised medicine to improve treatment outcomes and reduce adverse events

The Biological Relevance of NHERF1 Protein in Gynecological Tumors

Gynecological cancer management remains challenging and a better understanding of molecular mechanisms that lead to carcinogenesis and development of these diseases is needed to improve the therapeutic approaches. The Na+/H+ exchanger regulatory factor 1 (NHERF1) is a scaffold protein that contains modular protein-interaction domains able to interact with molecules with an impact on carcinogenesis and cancer progression. During recent years, its involvement in gynecological cancers has been explored, suggesting that NHERF1 could be a potential biomarker for the development of new targeted therapies suitable to the management of these tumors. This comprehensive review provides an update on the recent study on NHERF1 activity and its pathological role in cervical and ovarian cancer, as well as on its probable involvement in the therapeutic landscape of these cancer types

Eradication of isolated para-aortic nodal recurrence in a patient with an advanced high grade sorous ovarian carcinoma: our experience and review of literature

Abstract: We report a case report regarding the eradication of isolated lymph-nodal para-aortic recurrence in the aortic region down the left renal vein (LRV) in a patient treated two years earlier in another hospital for a FIGO stage IC2 high-grade serous ovarian carcinoma with a video showing the para-aortic space after eradication of the metastatic tissue. A 66 year-old woman was admitted 24 months after the initial surgical procedure for an increased Ca 125 level and CT scan that revealed a 3 cm para-aortic infrarenal lymph-nodal recurrence that was confirmed by PET/CT scan. A secondary cytoreductive surgery (SCS) with a para-aortic lymph-nodal dissection of the tissue down the LRV and radical omentectomy were performed: during the cytoreduction, the right hemicolon was mobilized. The anterior surface of the inferior vena cava (IVC), aorta and LRV were exposed. The metastatic lymph nodes were detected in the para-ortic space down the proximal part of the LRV and eradicated; an en bloc infrarenal lymph-node dissection from the aortocaval region was performed. The operative time during the surgical procedure was 212 min with a blood loss of 120 mL. No intra- and postoperative complications, including ureteral or vascular injury or renal dysfunction, occurred. At histological examination, three dissected lymph nodes were positive for metastasis, and the patient was discharged five days after laparotomy without side effects and underwent chemotherapy 3 weeks later; after a follow-up of 42 months, no recurrence was detected. In conclusion, secondary debulking surgery can be considered a safe and effective therapeutic option for the management of recurrences, although long-term follow-ups are necessary to evaluate the overall oncologic outcomes of this procedure

Music benefits on postoperative distress and pain in pediatric day care surgery

Postoperative effect of music listening has not been established in pediatric age. Response on postoperative distress and pain in pediatric day care surgery has been evaluated. Forty-two children were enrolled. Patients were randomly assigned to the music-group (music intervention during awakening period) or the non-music group (standard postoperative care). Slow and fast classical music and pauses were recorded and played via ambient speakers. Heart rate, blood pressure, oxygen saturation, glucose and cortisol levels, faces pain scale and Face, Legs, Activity, Cry, Consolability (FLACC) Pain Scale were considered as indicators of response to stress and pain experience. Music during awakening induced lower increase of systolic and diastolic blood pressure levels. The non-music group showed progressive increasing values of glycemia; in music-group the curve of glycemia presented a plateau pattern (P<0.001). Positive impact on reactions to pain was noted using the FLACC scale. Music improves cardiovascular parameters, stress-induced hyperglycemia. Amelioration on pain perception is more evident in older children. Positive effects seems to be achieved by the alternation of fast, slow rhythms and pauses even in pediatric age

Design, modeling, synthesis and biological activity evaluation of camptothecin linked platinum anticancer agents

The design, modeling, synthesis and biological activity evaluation of two hybrid agents formed by 7-oxyiminomethylcamptothecin derivatives and diaminedichloro-platinum (II) complex are reported. The compounds showed growth inhibitory activity against a panel of human tumor cell lines, including sublines resistant to topotecan and platinum compounds. The derivatives were active in all the tested cell lines, and compound 1b, the most active one, was able to overcome cisplatin resistance in the osteosarcoma U2OS/Pt cell line. Platinum-containing camptothecins produced platinum-DNA adducts and topoisomerase I-mediated DNA damage with cleavage pattern and persistence similar to SN38, the active principle of irinotecan. Compound 1b exhibited an appreciable antitumor activity in vivo against human H460 tumor xenograft, comparable to that of irinotecan at lower well-tolerated dose levels and superior to cisplatin. The results support the interpretation that the diaminedichloro-platinum (II) complex conjugated via an oxyiminomethyl linker at the 7-position of the camptothecin resulted in a new class of effective antitumor compounds

Structural Brain MR Imaging Changes Associated with Obsessive-Compulsive Disorder in Patients with Multiple Sclerosis

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Time matters in multiple sclerosis: can early treatment and long-term follow-up ensure everyone benefits from the latest advances in multiple sclerosis?

[Excerpt] Introduction The management of multiple sclerosis (MS) has been a neurology success story for the past 25 years. Advances in understanding of the disease mechanisms and the dynamic nature of the disease have brought around 12 disease-modifying therapies (DMTs) to market in many countries.[...]This study was funded by F Hoffmann-La Roche.info:eu-repo/semantics/publishedVersio

Quantifier-Free Interpolation of a Theory of Arrays

The use of interpolants in model checking is becoming an enabling technology to allow fast and robust verification of hardware and software. The application of encodings based on the theory of arrays, however, is limited by the impossibility of deriving quantifier- free interpolants in general. In this paper, we show that it is possible to obtain quantifier-free interpolants for a Skolemized version of the extensional theory of arrays. We prove this in two ways: (1) non-constructively, by using the model theoretic notion of amalgamation, which is known to be equivalent to admit quantifier-free interpolation for universal theories; and (2) constructively, by designing an interpolating procedure, based on solving equations between array updates. (Interestingly, rewriting techniques are used in the key steps of the solver and its proof of correctness.) To the best of our knowledge, this is the first successful attempt of computing quantifier- free interpolants for a variant of the theory of arrays with extensionality