A parametric framework for reversible pi-calculi

This paper presents a study of causality in a reversible, concurrent setting. There exist various notions of causality inπ-calculus, which differ in the treatment of parallel extrusions of the same name. Hence, by using a parametric way of bookkeeping the order and the dependencies among extruders it is possible to map different causal semantics into the same framework. Starting from this simple observation, we present a uniform framework forreversibleπ-calculi that is parametric with respect to a data structure that stores information about the extrusion of a name. Different data structures yield different approaches to the parallel extrusion problem. We map three well-known causal semantics into our framework. We prove causal-consistency for the three instances of our framework. Furthermore, we prove a causal correspondence between the appropriate instances of the framework and the Boreale-Sangiorgi semantics and an operational correspondence with the reversibleπ-calculus causal semantics

Endoscopic retrograde cholangiopancreatography, lights and shadows: Handle with care

The role of endoscopic retrograde cholangiopancreatography (ERCP) has dramatically changed in the last years, mainly into that of a therapeutic procedure. The treatment of benign biliary disease, like "difficult" choledocolithiasis, with endoscopic papillary large balloon dilation combined with endoscopic sphinterotomy has proven an effective and safe technique. Moreover, safety in ERCP has improved as well, with the prevention of post-ERCP pancreatitis and patient-to-patient transmission of infections. The advent of self-expandable metal stenting has radically changed the management of biliopancreatic malignant strictures, while the role for therapy of benign strictures is still controversial. In addition, cholangioscopy (though the direct visualization of the biliopancreatic ductal system) has allowed for characterization of indeterminate biliary strictures and facilitated rescue therapy of large biliary stones deemed removable. Encouraging data from tissue ablation techniques, such as photodynamic therapy and radiofrequency ablation, need to be confirmed by large sample size clinical controlled trials. On the other hand, we have no drug-coated stents yet available to implant and evidence for the use of biodegradable stents is still weak. The competency and privileging of ERCP and endoscopic ultrasonography have been analyzed longer but the switch between the two procedures, at the same time, is becoming ordinary; as such, the endoscopist interested in this field should undergo parallel edification through training plans. Finally, the American Society for Gastrointestinal Endoscopy's statement on non-anesthesiologist administration of propofol for gastrointestinal endoscopy is not actually endorsed by the European Society of Anaesthesiology, having many medical-legal implications in some European countries

NaDES as a green technological approach for the solubility improvement of BCS class II APIs: An insight into the molecular interactions

Recently, Natural Deep Eutectic Solvents (NaDES) have emerged as potential solvents for boosting drug bioavailability. In this work, the mechanism of solubility enhancement of some APIs belonging to BCS class II (tolbutamide, nimesulide, domperidone and cinnarizine) in these eutectic bio-solvents was investigated in order to get deeper insights into the molecular interactions between the NaDES components and the selected drugs. Different NaDES formulations based on choline chloride, proline, solid organic acids (citric, tartaric and malic acid), sugars (glucose and xylitol) and water were prepared by mild heating (70 °C). Characterization of unloaded NaDES (pH, Karl Fisher titration, viscosity and FTIR analysis) indicated that the type of Hydrogen Bond Acceptor (HBA) and Hydrogen Bond Donor (HBD), their molar ratio as well as water amount strongly affect the extent of H-bonding interactions. Hard gelatin capsules filled with NaDES maintained their integrity until 6 months, proving that all water molecules participate in H-bond network. APIs' solubility enhancement was significant in all NaDES with respect to buffer solutions (pH 1.2 and 6.8). Analysing NaDES having Choline as HBA, it was found that the solubility of smaller molecules increased using larger HBD, while higher molecular weight APIs can be better inserted into the network formed by smaller HBD. NOE experiments demonstrated the formation of a robust supramolecular structure among the protons of choline, those of organic acid and water. In addition, 1D ROESY spectra revealed for the first time the crucial role of choline (methyl groups) in establishing hydrophobic interactions with the relative aliphatic or aromatic portion of the drugs. These data suggest the complex structure of the API-NaDES supramolecular assembly and underline that drug solubility is dependent on a balance network of H-bonds and hydrophobic interactions as well. Understanding the type of interactions between the API and NaDES is essential for their use as effective solubilisation aid

Type Reconstruction for the Linear π-Calculus with Composite and Equi-Recursive Types

We extend the linear π-calculus with composite and equi-recursive types in a way that enables the sharing of data containing linear values, provided that there is no overlapping access on such values. We show that the extended type system admits a complete type reconstruction algorithm and, as a by-product, we solve the problem of reconstruction for equi-recursive session types

Escherichia coli redox mutants as microbial cell factories for the synthesis of reduced biochemicals

Bioprocesses conducted under conditions with restricted O2 supply are increasingly exploited for the synthesis of reduced biochemicals using different biocatalysts. The model facultative aerobe Escherichia coli, the microbial cell factory par excellence, has elaborate sensing and signal transduction mechanisms that respond to the availability of electron acceptors and alternative carbon sources in the surrounding environment. In particular, the ArcBA and CreBC two-component signal transduction systems are largely responsible for the metabolic regulation of redox control in response to O2 availability and carbon source utilization, respectively. Significant advances in the understanding of the biochemical, genetic, and physiological duties of these regulatory systems have been achieved in recent years. This situation allowed to rationally-design novel engineering approaches that ensure optimal carbon and energy flows within central metabolism, as well as to manipulate redox homeostasis, in order to optimize the production of industrially-relevant metabolites. In particular, metabolic flux analysis provided new clues to understand the metabolic regulation mediated by the ArcBA and CreBC systems. Genetic manipulation of these regulators proved useful for designing microbial cells factories tailored for the synthesis of reduced biochemicals with added value, such as poly(3-hydroxybutyrate), under conditions with restricted O2 supply. This network-wide strategy is in contrast with traditional metabolic engineering approaches, that entail direct modification of the pathway(s) at stake, and opens new avenues for the targeted modulation of central catabolic pathways at the transcriptional level

Rituximab vs mycophenolate and vs cyclophosphamide pulses for induction therapy of active lupus nephritis: A clinical observational study

Objective. We report the first comparison between rituximab (RTX) and either MMF or CYC pulses in the treatment of active LN. Methods. Fifty-four patients with active LN received three methylprednisolone pulses for 3 consecutive days followed by oral prednisone and RTX 1 g at days 3 and 18 (17 patients) or MMF 2-2.5 g/day (17 patients) or six CYC pulses (0.5 g every fortnight) (20 patients). At 4 months MMF, AZA or ciclosporin were associated to prednisone as a consolidation/maintenance therapy in all groups. The outcomes of the three groups were compared at 3 and 12 months. Results. Patients in the RTX group were older, had a longer duration of SLE and LN, had more renal flares, had higher activity and had higher chronicity indexes at renal biopsy than the other two groups. Four patients in each group had acute renal dysfunction and 3c50% had nephrotic syndrome. At 3 months, proteinuria was reduced by 50% in 58.8% of patients on RTX, in 64.7% on MMF and in 63.1% on CYC. At 12 months, complete remission was present in 70.6% of patients on RTX, in 52.9% on MMF, and in 65% on CYC. Partial remission was reached in 29.4% on RTX, 41.2% on MMF, and 25% on CYC. Conclusion. RTX seems to be at least as effective as MMF and CYC pulses in inducing remission. Considering that patients treated with RTX had more negative renal prognostic factors, this drug should be considered a viable alternative for the treatment of active LN

Effectiveness and safety of vedolizumab in a matched cohort of elderly and nonelderly patients with inflammatory bowel disease: the IG-IBD LIVE study

Vedolizumab registration trials were the first to include elderly patients with moderate-to-severe ulcerative colitis (UC) or Crohn's disease (CD), but few real-life data have been reported in this population. Aims: We investigated the effectiveness and safety of vedolizumab in matched cohorts of elderly and nonelderly UC and CD patients. Methods: The Long-term Italian Vedolizumab Effectiveness (LIVE) study is a retrospective-prospective study including UC and CD patients who started vedolizumab from April 2016 to June 2017. Elderly patients (≥65 years) were matched clinically 1:2 to nonelderly patients (18-64 years); the 2 groups were followed until drug discontinuation or June 2019. Results: The study included 198 elderly (108 UC, 90 CD) and 396 matched nonelderly patients (205 UC, 191 CD). Nonelderly UC patients had a significantly higher persistence on vedolizumab compared to elderly patients (67.6% vs. 51.4%, p = 0.02). No significant difference in effectiveness was observed between elderly and nonelderly CD patients (59.4% vs. 52.4%, p = 0.32). Age ≥65 years was associated with lower persistence in UC; for CD, previous exposure to anti-TNF-α agents, Charlson comorbidity index >2 and moderate-to-severe clinical activity at baseline were associated with lower persistence. There were recorded 130 adverse events, with comparable rates between the two groups. A Charlson comorbidity index >2 was associated with an increased risk of adverse events. Conclusion: Vedolizumab can be considered a safe option in elderly IBD patients. Its effectiveness in elderly UC patients may be reduced, while no age-dependent effect on effectiveness was observed in CD

Continuos clinical remission with biologics in Ulcerative Colitis: the A.U.R.O.R.A. comparative study

Comparative trials among biological drugs for the treatment of ulcerative colitis (UC) provided conflicting results. After patent expire of infliximab originator, adalimumab, infliximab biosimilar, golimumab and vedolizumab have been approved in Italy.We compared the efficacy of these four biologics in UC according to the concept of continuous clinical remission (CCR)

Understanding recovery in the context of lived experience of personality disorders: a collaborative, qualitative research study

Background Concepts of recovery increasingly inform the development and delivery of mental health services internationally. In the UK recent policy advocates the application of recovery concepts to the treatment of personality disorders. However diagnosis and understanding of personality disorders remains contested, challenging any assumption that mainstream recovery thinking can be directly translated into personality disorders services. Methods In a qualitative interview-based study understandings of recovery were explored in extended, in-depth interviews with six people purposively sampled from a specialist personality disorders’ service in the UK. An interpretive, collaborative approach to research was adopted in which university-, clinical- and service user (consumer) researchers were jointly involved in carrying out interviews and analysing interview data. Results Findings suggested that recovery cannot be conceptualised separately from an understanding of the lived experience of personality disorders. This experience was characterised by a complexity of ambiguous, interrelating and conflicting feelings, thoughts and actions as individuals tried to cope with tensions between internally and externally experienced worlds. Our analysis was suggestive of a process of recovering or, for some, discovering a sense of self that can safely coexist in both worlds. Conclusions We conclude that key facilitators of recovery – positive personal relationships and wider social interaction – are also where the core vulnerabilities of individuals with lived experience of personaility disorders can lie. There is a role for personality disorders services in providing a safe space in which to develop positive relationships. Through discursive practice within the research team understandings of recovery were co-produced that responded to the lived experience of personality disorders and were of applied relevance to practitioners