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A method in Clinical Ethics Consultation between normative theories and applied ethics
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Il sepolcreto dell’Ospedale Maggiore (Ca’ Granda) di Milano: indagini antropologiche di un singolare contesto di resti commisti
No full textRecently lots of human inhumations have been found in the burial chambers of Milan ancient hospital (Ospedale Maggiore commonly named Ca’ Granda). This institution was able to provide free medical assistance for the poorest of the city and to improve efficiency in healthcare starting from the 15th century. Actually, only people suffering from acute diseases could be admitted to this hospital. The Ca’ Granda connected the concept of charity with the therapeutic ideas, being a model for similar institutions in Italy and all over Europe.
The commingled human remains found into the burial chambers represent an extraordinary biological and historical archive remarkable for the large amount of bones (over 2.000.000 remains estimated) and the uniqueness of the context. In fact, according to the historical sources, the osteological findings refer to the deceased population from the 17th century onwards.
In order to outline the main features of this context, standard macroscopic and microscopic anthropological and paleopathological analyses have been carried out. In addition, toxicological, chemical and entomological studies have been conducted. Furthermore, taphonomic modifications have been observed.
Results allow to classify the context as a long-term usage commingled assemblage, indicative of long-term use of the same burial space through time, sometimes over hundreds years, as confirmed by the entomological study. The population seems to be heterogeneous both from sex and age, showing remains belonging to males and females of all age classes, even foetuses. Paleopathological studies reveal the presence of signs referring to lots of different diseases, such as osteoarthritis, erosive arthropathies, congenital anomalies, metabolic disorders, dental diseases. Particularly interesting are the infectious pathologies, especially the signs of syphilis, and the evidences of trauma. Results also show how important laboratory analyses may be in providing additional pieces of the complex puzzle of palaeopathological analysis.
This study represents a remarkable case of commingled human remains and highlights the importance of a multidisciplinary approach
La tutela dei minori in biomedicina: nuove sfide per l'etica clinica.
No full textClinical ethics in paediatrics may be considered as the clinical application of ethics in the field of paediatrics and its sub-specialties and there are many healthcare settings where the applications of clinical and experimental medicine in paediatrics pose ethical questions of paramount importance, and in which it is often difficult, for healthcare professionals, to make appropriate choices.
The purpose of the PhD project was to analyze the main clinical ethical issues in some areas of pediatrics that have been poorly addressed since nowadays in the literature and may therefore represent new challenges both for ethical reflection and for the contribution that clinical ethics counseling can provide for the analysis of conflicts in concrete cases. When dealing with individual situations it is important to ensure more adequate protection as possible for children involved, in order to respect the rights of children as embodied by the Convention on the rights of the child, which entered into force September 2, 1990.
Each topic has been dealt with starting from the medical ethics principles, in particular, the principle of autonomy and the characterization of the best interests of the child, both when children are placed in their familiar environment and thus are involved in definite relationships with parents, and when they are placed, more generally, in relation to society and to the needs of health promotion and protection of the common good that emerge from research.
The contribution given by clinical ethics consultation can be applied in everyday paediatric practice, facilitating conflict resolution in an atmosphere of respect and attention to the interests, rights and responsibilities of all persons involved
Development and optimization of the production process of a recombinant human protein by high-throughput techniques. Sviluppo e ottimizzazione del processo di produzione di una proteina umana ricombinante attraverso l'utilizzo di tecniche high-throughput.
No full textMost biotechnology unit operations are complex with numerous process variables, feed material and raw material attributes that play significant impact on the performance of a process. Design of Experiment (DoE)-based approach together with HTPD (High-Throughput Process Development) techniques offer a solution to this issue allowing for an efficient estimation of effects and interactions by employing a minimal number of experiments. In the first part of the PhD work the HTPD approaches combined to statistical software were adopted in order to optimize a production process of a 340 kDa therapeutic recombinant protein expressed in PER.C6 cell line. The optimization of the purification process was performed by increasing the yield and by reducing the HCPs, residual DNA and viral contamination in order to obtain a fully compliant GMP process. This was achieved by introducing an arginine washing step during the capture on AEX resin and by reducing the concentration of phosphate in elution buffer in the intermediate step on hydroxyapatite, preventing the co-elution of the protein of interest and rDNA. A decrease of rDNA was then obtained by a membrane AEX step (by flow-through mode). Finally, two viral reduction steps (by thermal inactivation and filtration) were used in order to satisfy ICH Q5A guidelines.
In the second part of the work, the DoE and HTPD technology were used as a “tool box” inside a step by step “decision tree” in order to lead the experimenter in a well defined path with the purpose of purifying and formulate any protein of interest. The protein used to test the procedure was a 13 kDa protein expressed in E. coli as inclusion bodies. The novel process allowed to obtain a pure and active preparation of the protein compliant to GMP requirements
Enzyme functionalized magnetic nanoparticles for biomedical and industrial applications. Nanoparticelle magnetiche funzionalizzate con enzimi per applicazioni biomediche ed industriali.
No full textIn the first part of this work two nanoparticle-enzyme (NP-enzyme) systems were designed: one for medical and one for industrial applications. The first is the NP-DAAO system that, developed for cancer therapy purpose, combines the magnetic properties of iron oxide nanoparticles (γ-Fe2O3 NPs) with those of the H2O2 generating enzyme D-amino acid oxidase (DAAO) in order to target the system near to the cancer and once there, to induce a local toxicity able to kill the surrounding tumor cells.
The second NP-enzyme system is the NP-LASPO and finds application in the industrial field. This NP-system, composed by magnetic Fe3O4 NPs conjugated to L-aspartate oxidase (LASPO), allows the resolution of a racemic mixture of D, L-aspartate offering many advantages such as the possibility to recover and reuse the system once the reaction in the bioreactor is over but also to obtain pure end-products without the enzyme contamination.
In the second part of this work is presented a preliminary study of the toxicity and influence of Cobalt, Iron, Nickel zerovalent NPs on the differentiation process of Adipose-derived Stem Cells (ASCs). A population of hASCs was isolated from human adipose tissue and characterized by flow cytometry before to proceed with the cytotoxicity test of CoNPs, FeNPs and NiNPs. Subsequently it was evaluated the possible hASCs adipogenic differentiation induced by CoNPs
Secure execution of collaborative processes
No full textSo far the number of users on the social network sites has been increasing year-on-year. In the meanwhile, the price of mobile devices drops vertically. Both events push up vigorously the quantity of social users who use mobile devices. This results in a need for collaboration among mobile social users to attain the common goals. The fact that the huge number of users goes online lifts forcefully up the number of services over the Internet. The user requirements for services then get more complex. As a consequence, responding such a complex service request needs a composition of several single services.
However, the collaboration among several participants can make the personal data disclosed to the other sides during the collaborative process. Despite the fact that all participants comply with the common protocol and agree on contributing their personal data, they do not trust adequately in each other. This leads to the requirement of preserving user privacy and securing the user data against the other sides.
In this dissertation, we investigate different collaboration and participant types. More specifically, they are centralized and decentralized models among users/services. We also concern the communication environment, e.g., mobile network, Internet, or mobile ad-hoc network. The protocols that are enforced in a mobile network environment have more rigorous constraints due to limited physical and performance resources. For preserving user privacy and data security, we study and select different rational and effective cryptography algorithms then apply them into the collaborative protocols. For more understanding, we propose several collaboration scenarios and present them in detail in the upcoming chapters. Each scenario describes a combination of different collaborative type, participant type and network environment. For each scenario, we address issues on privacy preserving and data security and propose selective solutions. In addition, we propose methods for improving network performance. The experimental results show that our proposals are efficient and effective
Edge manipulation techniques for complex networks with applications to communicability and triadic closure.
No full textComplex networks are ubiquitous in our everyday life and can be used to model a wide variety of phenomena. For this reason, they have captured the interest of researchers from a wide variety of fields. In this work, we describe how to tackle two problems that have their focus on the edges of networks.
Our first goal is to develop mathematically inferred, efficient methods based on some newly introduced edge centrality measures for the manipulation of links in a network. We want to make a small number of changes to the edges in order to tune its overall ability to exchange information according to certain goals. Specifically, we consider the problem of adding a few links in order to increase as much as possible this ability and that of selecting a given number of connections to be removed from the graph in order to penalize it as little as possible. Techniques to tackle these problems are developed for both undirected and directed networks. Concerning the directed case, we further discuss how to approximate certain quantities that are used to measure the importance of edges.
Secondly, we consider the problem of understanding the mechanism underlying triadic closure in networks and we describe how communicability distance functions play a role in this process.
Extensive numerical tests are presented to validate our approaches
Production and characterization of novel lignin-modifying enzymes from actinomycetes and heterologous expression of metagenome-source laccases. Produzione e caratterizzazione di enzimi ligninolitici in attinomiceti e espressione eterologa di laccasi da metagenoma.
No full textThe lignin is a recalcitrant aromatic biopolymer and its bio-degradation occurs by white rot fungi through the production of an enzyme array such as lignin, manganese and versatile peroxidases and laccases. The aims of this PhD project were the production and characterization of novel lignin-degrading enzymes from actinomycetes and the heterologous expression of a metagenome-sourced laccase. The classical approach of screening applied to microbial isolates led to the discovery of a novel peroxidase activity produced by Nonomuraea gerenzanensis.
This peroxidase showed features such as high alkaline pH, thermo stability and decolorization of industrial dyes that favorably compare with the ones of fungal peroxidases. A possible application for this peroxidase might be in textile and decontamination meal of environmental pollutants. The metagenome-based approach allows to overcome cultivation-dependent limitations, directly analyzing genomes’ potential in environmental samples. This approach led to the discovery of a novel bacterial laccase (MetaLacc) affiliated to phylum Acidobacteria. MetaLacc shows ability to oxide a variety of phenolic substrates in a wide range of pHs, high tolerance towards salts, increased activity in the presence of alcohols and decolorization of industrial dyes. A possible application for Metalac might be as well in the treatment industrial wastewater. Finally, N. gerenzanensis and Streptomyces coelicolor A3 (2) were analyzed to degrade wheat straw or/and lignin in a two-stage bioconversion process. The first stage is the enzymatic digestion of pre-treated wheat straw by the two selected aerobic microorganisms. A second stage of anaerobic fermentation to produce biofuels will eventually follow
