Efficient computation of hashes

The sequential computation of hashes at the core of many distributed storage systems and found, for example, in grid services can hinder efficiency in service quality and even pose security challenges that can only be addressed by the use of parallel hash tree modes. The main contributions of this paper are, first, the identification of several efficiency and security challenges posed by the use of sequential hash computation based on the Merkle-Damgard engine. In addition, alternatives for the parallel computation of hash trees are discussed, and a prototype for a new parallel implementation of the Keccak function, the SHA-3 winner, is introduced

Spray congealing: An emerging technology to prepare solid dispersions with enhanced oral bioavailability of poorly water soluble drugs

The low and variable oral bioavailability of poorly water soluble drugs remains a major concern for the pharmaceutical industry. Spray congealing is an emerging technology for the production of solid dispersion to enhance the bioavailability of poorly soluble drugs by using low-melting hydrophilic excipients. The main advantages are the absence of solvents and the possibility to obtain spherical free-flowing microparticles (MPs) by a relatively inexpensive, simple, and one-step process. This review aims to fully describe the composition, structure, physico-chemical properties, and characterization techniques of spray congealed-formulations. Moreover, the influence of these properties on the MPs performance in terms of solubility and dissolution enhancement are examined. Following, an overview of the different spray congealed systems developed to increase the oral drug bioavailability is provided, with a focus on the mechanisms underpinning the bioavailability enhancement. Finally, this work gives specific insights on the main factors to be considered for the rational formulation, manufacturing, and characterization of spray congealed solid dispersions

The Simplification of Public Administration: A Managerial Perspective

The paper addresses the issue of complexity in the administrative processes of public institutions: in particular, accounting routines and processes are examined. Back-office activities, although having a mere supporting role in the delivery of public services, absorb a relevant part of the resources of public institutions. The aim of the paper is to analyse the factors that contribute to the enhancement of complexity of these activities. The paper is based on an in-depth analysis of two Italian public organisations: a university and an ASP (agency for services to persons). Italy is an interesting context since simplification policies have been adopted in the country at central government level and in specific sectors of public administration, however, at the institutional level, simplification initiatives depend on the initiative of the single organisation. The cases described in this paper show that complexity stems from the need for inspectory controls (which is typical of the law) as well as from the volume of information requested (which is typical of management studies) for different stakeholders and at different, yet correlated, levels. The paper suggests that public management scholars have the opportunity and the burden of a contribution in this field

Tailoring the release of drugs having different water solubility by hybrid polymer-lipid microparticles with a biphasic structure

The aim of this study is to investigate the potential of hybrid polymer-lipid microparticles with a biphasic structure (b-MPs) as drug delivery system. Hybrid b-MPs of Compritol & REG;888 ATO as main lipid constituent of the shell and polyethylene glycol 400 as core material were produced by an innovative solvent-free approach based on spray congealing. To assess the suitability of hybrid b-MPs to encapsulate various types of APIs, three model drugs (fluconazole, tolbutamide and nimesulide) with extremely different water solubility were loaded into the polymeric core. The hybrid systems were characterized in terms of particle size, morphology and physical state. Various techniques (e.g. optical, Confocal Raman and Scanning Electron Microscopy) were used to investigate the influence of the drugs on different aspects of the b-MPs, including external and internal morphology, properties at the lipid/polymer interface and drug distribution. Hybrid b-MPs were suitable for the encapsulation of all drugs (encapsulation efficiency > 90 %) regardless the drug hydrophobic/hydrophilic properties. Finally, the drug release behaviors from hybrid b-MPs were studied and compared with traditional solid lipid MPs (consisting of only the lipid carrier). Due to the combination of lipid and polymeric materials, hybrid b-MPs showed a wide array of release profiles that depends on their composition, the type of loaded drug, the drug loading amount and location, providing a versatile platform and allowing the formulators to finely balance the release performance of drugs intended for oral administration. Overall, the study demonstrates that hybrid, solvent-free b-MPs produced by spray congealing are an extremely versatile delivery platform able to efficiently encapsulate and release very different types of drug compounds

Glutathione-loaded solid lipid microparticles as innovative delivery system for oral antioxidant therapy

The present study aimed to develop a novel formulation containing glutathione (GSH) as an oral antioxidant therapy for the treatment of oxidative stress-related intestinal diseases. To this purpose, solid lipid microparticles (SLMs) with Dynasan 114 and a mixture of Dynasan 114 and Dynasan 118 were produced by spray congealing technology. The obtained SLMs had main particle sizes ranging from 250 to 355 µm, suitable for oral administration. GSH was efficiently loaded into the SLMs at 5% or 20% w/w and the encapsulation process did not modify its chemico-physical properties, as demonstrated by FT-IR, DSC and HSM analysis. Moreover, in vitro release studies using biorelevant media showed that Dynasan 114-based SLMs could efficiently release GSH in various intestinal fluids, while 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay demonstrated the good radical scavenging activity of this formulation. Dynasan 114-based SLMs exhibited an excellent biocompatibility on intestinal HT-29 cells at concentrations up to 2000 µg/mL. SLMs containing GSH alone or together with another antioxidant agent (catalase) were effective in reducing intracellular reactive oxygen species (ROS) levels. Overall, this study indicated that spray congealed SLMs are a promising oral drug delivery system for the encapsulation of one or more biological antioxidant agents for local intestinal treatment

The interpretation of the solutions of the Wheeler De Witt equation

We extract transition amplitudes among matter constituents of the universe from the solutions of the Wheeler De Witt equation. The physical interpretation of these solutions is then reached by an analysis of the properties of the transition amplitudes. The interpretation so obtained is based on the current carried by these solutions and confirms ideas put forward by Vilenkin.Comment: 11 pages, latex, no figure

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

Monitor, anticipate, respond, and learn: developing and interpreting a multilayer social network of resilience abilities

Resilient performance is influenced by social interactions of several types, which may be analysed as layers of interwoven networks. The combination of these layers gives rise to a “network of networks”, also known as a multilayer network. This study presents an approach to develop and interpret multilayer networks in light of resilience engineering. Layers correspond to the four abilities of resilient systems: monitor, anticipate, respond, and learn. The proposal is applied in a 34-bed intensive care unit. To map relationships between actors in each layer, a questionnaire was devised and answered by 133 staff members, including doctors, nurses, nurse technicians, and allied health professionals. Two multilayer networks were developed: one considering that actors are 100% available and reliable (work-as-imagined) and another considering suboptimal availability and reliability (work-as-done). The multilayer networks were analysed through actor-centred (Katz centrality, degree deviation, and neighbourhood centrality) and layer-centred metrics (inter-layer correlation, and assortativity correlation). Strengths and weaknesses of social interactions at the ICU are discussed based on the adopted metrics