621 research outputs found
Some Remarks on the Recent SRM Related Case-Law of the CJEU with Special Regard to the Meroni Doctrine
The study elaborates on the development of the Meroni doctrine, derived from the Meroni judgment of the Court of Justice of the European Coal and Steel Community under a different Founding Treaty framework and its applicability to the Banking Union under the current Treaty framework. To fulfil this aim, the author first elaborates on the Advocate General’s opinion and the Judgment of the Court of Justice in the Meroni case and then briefly introduces the evolution and the literature on the issue. After a short introduction of the Banking Union’s institutional order, the author introduces two cases in which issues related to the Meroni doctrine were raised before the General Court, as well as the appellate procedures before the Court of Justice in one of these cases
New strategies to address the pharmacodynamics and pharmacokinetics of tumor necrosis factor (TNF) inhibitors: A systematic analysis.
AIM:
To assess the putative link between antibody formation to adalimumab, infliximab and etanercept, circulating drug levels and clinical outcomes.
METHODS:
A literature search was conducted using Pubmed from inception to 5th March 2013 of original research articles relating to adalimumab, etanercept and infliximab that investigated the immunogenicity of each drug. Data were extracted to document the disease, anti-TNF-α agent, regimen, study design, use of concomitant immunosuppressive therapy, the relationship between drug administration and antibody assessment, the type of immunoassay and cut-off, plasma drug concentration, frequency of antibody and clinical assessments, antibody positivity rate and relationship between antibody positivity and clinical outcome. Studies were stratified by drug, disease area and whether or not concomitant immunosuppressive therapy had been given. All data were tabulated by publication and analyzed descriptively.
RESULTS:
A total of 57 original research articles were included in the analysis (infliximab n=34; adalimumab n=18; etanercept n=5). There was considerable heterogeneity in study design, methodology for anti-drug antibody detection and drug bioavailability evaluation. Consequently, it was difficult to compare the immunogenic potential of infliximab, adalimumab and etanercept, particularly because different assays with variable sensitivity and specificity were used. The timing of occurrence and the persistence of anti-drug antibodies appeared to be influenced by administration schedules and concomitant immunosuppressive therapy. Monitoring of circulating drug levels and anti-drug antibodies appears to be an emerging and cost-effective strategy for the management of the individual patient.
CONCLUSIONS:
Monitoring drug and anti-drug antibody levels appears to be a putative strategy for optimal and cost-effective intervention. However studies of consistent and homogeneous design, methodology and duration are warranted to assess the true incidence and consequences of immunogenicity
MOLECULAR CHARACTERIZATION OF STAPHYLOCOCCUS PSEUDINTERMEDIUS: RESEARCH ON VIRULENCE FACTORS, ANTIBIOTIC-RESISTANCE AND QUORUM-SENSING
Staphylococcus pseudintermedius (S. pseudintermedius) is one of the most important pathogens in small animal veterinary medicine. In the dog, it is a commensal bacterium able to cause severe diseases (mainly dermatological), which rapidly evolve to persistent and chronic infections. This pathogen is also considered a public health problem due to the rapid evolution and spread of antibiotic-resistant clones, in particular, the worldwide dissemination of Multi-Drug Resistant (MDR) strains and methicillin-resistant S. pseudintermedius (MRSP). Nowadays, its zoonotic potential is under constant investigations. The first chapter of the thesis centers the attention on the typing techniques used to study a population of S. pseudintermedius isolated from the skin of dogs and raw milk of Holstein-Fresian dairy cattle. The aims of this study were the investigation of the genetic relatedness of different S. pseudintermedius strains using three molecular typing techniques; the Ribosomal Spacers Amplification PCR (RSA-PCR), the Random Amplification of Polymorphic DNA PCR (RAPD-PCR) and the Restriction Fragment Length Polymorphism PCR (RAPD-PCR). Moreover, the dissemination of species-specific genes coding for exfoliative toxins (siet, expA, and expB), enterotoxin (seCcanine) and a bicomponent leukocidin (lukS-F) was studied to understand the virulence of the strains. The study was carried out on a final population of 40 S. pseudintermedius strains isolated from 42 clinical cases of deep canine pyoderma and from 5 samples of raw milk from Holstein-Fresian dairy cattle with intramammary infection. After the microbiological examination and phenotypic typing, 47 S. pseudintermedius strains were collected and genetically analyzed. RSA-PCR revealed the presence of a unique biotype. The dendrogram obtained from RAPD-PCR disclosed two important results: i) the staphylococcal strains isolated from dogs and cows are genetically similar underlying the ability of this pathogen to colonize also dairy cattle; ii) the presence of a single cluster grouping all the S. pseudintermedius strains. Based on the presence of a specific restriction site in the phosphotransacetylase (pta) gene, RFLP-PCR confirmed the presence of 40 S. pseudintermedius and 7 non-S. pseudintermedius strains. The sequencing unveiled the effective presence of one strain of S. aureus and one of E. faecalis, 5 strains of S. schleiferi and 40 of S. pseudintermedius. All the S. pseudintermedius isolates were positive for siet gene, while expA and expB were amplified by, respectively, 10% and 17,5%. Specific enterotoxin seCcanine and leukotoxin luk-S-F were found with a prevalence of 35% and 92,5%, respectively. Therefore, the combined use of molecular typing techniques and virulence factors screening allows to better characterize S. pseudintermedius and to understand its zoonotic potential. The second chapter points out the attention to the problem of antibiotic resistance. Frequently, in Veterinary and Human medicine too, wide-spectrum antibiotics are prescribed to face with bacteria-based diseases without the microbiological examination and relative antibiotic-resistance screening. This could lead to the selection and spread of antibiotic-resistant strains. The aim of this work was to study the antibiotic-resistance profile of a large population of S. pseudintermedius strains collected in two Italian veterinary teaching hospitals, the first in Milan (Università degli Studi di Milano) and the second in Naples (Università degli Studi di Napoli “Federico II”) One-hundred sixteen and one-hundred twenty-six strains were collected in Milan and Naples, respectively. A panel of 10 different antibiotic molecules was tested with the Kirby-Bauer assay, qualitative PCR was used to describe the dissemination of mecA and tetM/K genes. The results showed a high rate of resistance for amoxicillin+clavulanate, clindamycin, tobramycin and tetracycline also confirmed by statistical significance. The prevalence of methicillin-resistant strains (MRSP) was 30% in Milan and18% in Naples also confirmed by the amplification of mecA gene. The cohort of methicillin-sensible strains in Naples (N= 103) was significantly more resistant compared to that from Milan (N= 81). In relation to the MDR population, all the MRSP in Milan and 91% in Naples are considered resistant to three or more pharmaceutical categories. These results totally agree with the recent report about the “Surveillance of antimicrobial resistance in Europe, 2017” and could be a starting point to set out a clearer use and prescription of antibiotics. The third chapter describes quorum-sensing and biofilm. It is known that bacteria are able to communicate via small peptides (Gram-positive) or lipids (Gram-negative) using a system called quorum-sensing. This complex behavior acts in response to external stimuli (e.g. cell density) and controls gene expression. Biofilm is one of the products of this communication, defined as a complex ecosystem of bacteria (sometimes also fungi and algae) enclosed in a self-produced matrix and adherent to a biotic or abiotic surface. This structure is frequently resistant to commonly used antibiotics and causes severe and more complex re-infections. The aim of the work was to describe the biofilm-forming ability of MDR and non-MDR S. pseudintermedius strains investigating the dissemination of virulence factors and antibiotic-resistance genes. A panel of 22 antibiotics was used to screen the antibiotic-resistance profiles of 73 S. pseudintermedius strains isolated from deep canine pyoderma. The biofilm-forming ability was investigated using a microtiter assay. The results clearly highlight a correlation between antibiotic-resistance and the ability to produce biofilm. All the MDR strains (N=42) are biofilm producers while 27 out of 31 non-MDR strains were able to produce biofilm. The last chapter of the thesis focused on an alternative strategy for the treatment of bacterial infections caused by Gram-positive and Gram-negative bacteria. For centuries, silver was used for its antimicrobial properties. Recently, the nanobiotechnology research area aimed to synthesize small particles (less than 100 nm) of silver metal to use as an alternative to traditional antibiotic-based therapies. The aim of this work was to synthesize silver nanoparticles using i) a Curcuma longa infusion and ii) the supernatant of E. coli. Furthermore, the antibacterial properties of synthesized nanoparticles were determined against 10 S. pseudintermedius strains and 10 Pseudomonas aeruginosa isolates by Kirby-Bauer disk diffusion assay and via Minimum Inhibitory Concentration (MIC). The anti-biofilm capacities were also investigated using an in vitro model of biofilm growth. Results showed that silver nanoparticles exert strong antibacterial activity compared to antibiotic alone and these properties are magnified when antibiotic was adjuvated with silver. Nanoparticles are also able to disrupt mature biofilm by directly linking to the cell wall of bacteria causing bacterial lysis. The use of silver nanoparticles obtained with green technology (e.g plant or organism derived molecules) is an eco-friendly alternative to classical antibiotic-based therapies and can be used to fight against both Gram-positive and Gram-negative infections
UX Designers Education and Practice: Making Designer as Topic Connectors to Enhance Intrinsic Complex Values of Made in Italy Craftsmanship. E.Craft Joint Lab Case History at Luisaviaroma.com
The word “design” is associated with specific disciplines, and, in turn complex. How is it possible then to define the formation of a designer? The "x-designer" always moves from research, for example to define exactly the needs, the context, the limits where the design process starts; s/he operates technical choices, which are ergonomically, aesthetically and economically correspondent. It becomes very difficult to find a positioning for the figure of the designer that is appropriate to other declinations and specificity of the modern designer
Biofilm-forming ability and virulence factors of methicillin-resistant Staphylococcus pseudintermedius from canine pyoderma
Staphylococcus pseudintermedius (SP) has been associated with high antibiotic-resistance rates (e.g. methicillin) in European countries [1,3]. This condition could be also related to the ability to produce biofilm [2]. The aim of this study was to investigate the presence of methicillin-resistant SP strains and determine their ability to produce biofilm and some crucial virulence factors.Forty-two SP strains, previously determined as multi drug resistant (MDR) by the disk diffusion method using a panel of 17 antimicrobial agents, were selected from our collection and tested phenotypically for the minimum inhibitory concentration (MIC) of methicillin and genotypically for the presence of mecA and blaZ genes. The ability to produce biofilm was assessed phenotypically by two different assays: the Congo Red Agar plates (CRA) and the Microtitre Plate test (MtP) and genetically by the amplification of icaA and icaD genes. Three virulence factors genes coding for bicomponent leukocidin and enterotoxins (luk-I, seC, se-int) were searched.Twenty-three strains revealed a value of MIC for the methicillin greater than 128 µg/mL. The 83% were mecA-positive and 86% resulted blaZ-positive; all the strains positive for mecA were also positive for blaZ. All SP strains resulted biofilm-producers by MtP assay and classified as weakly producers (4.7%), moderate producers (47.6 %) and strongly producers (47.6 %). In contrast, only 35.7% of all strains were considered biofilm-producers by CRA method. The amplification of icaA and icaD gene occurred respectively in 66.6% and 97.6%; only one strain was negative for both genes. Almost all strains were positive for luk-I (95%), seC (74%) and se-int (84%).Our data reveal the pathogenicity potential of SP strains from dogs, suggesting that they could be considered zoonotic potential agents and confirming other previous studies [3-5]. Moreover could be observed a clear linkage between antibiotic-resistance and ability to produce biofilm
Periprosthetic Joint Infection Diagnosis: A Narrative Review
Replacement of native joints aims to restore patients’ quality of life by relieving pain and improving joint function. While periprosthetic joint infection (PJI) affects a small percentage of patients, with an estimated incidence of 1–9% following primary total joint replacement, this postoperative complication necessitates a lengthy hospitalisation, extended antibiotic treatment and further surgery. It is highlighted that establishing the correct diagnosis of periprosthetic infections is critical in order for clinicians to avoid unnecessary treatments in patients with aseptic failure. Of note, the PJI diagnosis could not purely rely upon clinical manifestations given the fact that heterogeneity in host factors (e.g., age and comorbidities), variability in infection period, difference in anatomical location of the involved joint and discrepancies in pathogenicity/virulence of the causative organisms may confound the clinical picture. Furthermore, intra-operative contamination is considered to be the main culprit that can result in early or delayed infection, with the hematogenous spread being the most prevalent mode. To elaborate, early and hematogenous infections often start suddenly, whereas chronic late infections are induced by less virulent bacteria and tend to manifest in a more quiescent manner. Last but not least, viruses and fungal microorganisms exert a role in PJI pathogenesis
RED4MART: Reverse Engineering for Manufacturing Digital Archive to Enhance Advanced Craftsmanship Know-How and High-End Manufacturing Values
Craftsmanship is in demand more than ever and we can see its rising appeal within modern society. The storytelling of tangible and intangible aspects of a crafted object is what crafts are about in today’s western societies. The maker understands the need for his craft to have a valid purchase potential. Why is a crafted object worse paying for and what is the story engraved into it? This last paradigm brings a new aspect of crafts and reinforces the fact that crafts are valuable goods not only in the production process but also through the message and story it carries. Italian manufacture of home furnishings consists of a system of SMES that have undergone profound transformations in various aspects, particularly in the progressive juxtaposition of innovative technologies to traditional craft processes, developing examples of advanced craftsmanship. This transformation occurred as a result of the emergence of the need to optimize processes and production methods to improve time to market, to a market that is increasingly fluid and demanding. The design research of department DIDA of University of Florence for the company Savio Firmino and for the company Baldi is then inserted in this context
Artifact-Driven Business Process Monitoring - A Novel Approach to Transparently Monitor Business Processes, Supported by Methods, Tools, and Real-World Applications
This book proposes a novel technique, named artifact-driven process monitoring, by which multi-party processes, involving non-automated activities, can be continuously and autonomously monitored. This technique exploits the Internet of Things (IoT) paradigm to make the physical objects, participating in a process, smart. Being equipped with sensors, a computing device, and a communication interface, such smart objects can then become self-aware of their own conditions and of the process they participate in, and exchange this information with the other smart objects and the involved organizations. To allow organizations to reuse preexisting process models, a method to instruct smart objects given Business Process Model and Notation (BPMN) collaboration diagrams is also presented. The work constitutes a revised version of the PhD dissertation written by the author at the PhD School of Information Engineering of Politecnico di Milano, Italy. In 2019, the PhD dissertation won the “CAiSE PhD award”, granted to outstanding PhD theses in the field of Information Systems Engineering
Should we increase instruction time in low achieving schools? Evidence from Southern Italy
AbstractThis paper investigates the short term effects of a large scale intervention, funded by the European Social Fund, which provides additional instruction time to selected classes of lower secondary schools in Southern Italy. Selection is addressed using institutional rules that regulate class formation: first year students are divided into groups distinguished by letters, they remain in the same group across grades at the school, and the composition of teachers assigned to groups is stable over time. Using a difference-in-differences strategy, we consider consecutive cohorts of first year students enrolled in the same group. We compare participating groups to non-participating groups within the same school, as well as to groups in non-participating schools. We find that the intervention raised scores in mathematics for students from the least advantaged backgrounds. We also find that targeting the best students with extra activities in language comes at the cost of lowering performance in mathematics. We go beyond average effects, finding that the positive effect for mathematics is driven by larger effects for the best students
Fostering collaboration between start-ups and students for mutually beneficial inspiring learning
This two-voiced paper is the result of a student-teacher interaction in which the teacher simply paves the floor for a student’s narrative and commentary, from their perspective, of an innovative projectbased studio experience. By partnering with an incubation and start-up program for social innovators in Milan, university faculty considered how to design a studio to stimulate both students and innovators in their different educational and personal trajectories by organising "pairs of teams" with the same design goal(s), conscientious of social innovation, environmental sustainability within a circular economy, and striving for radical solutions. The team for which this student-author is sharing their experience in this paper has been paired with the start-up team “NoLo Ricicla - ilVespaio”, whose innovation idea was based on the question “How could a system of plastic packaging recovery, production and distribution of recycled artefacts be organised on a neighbourhood scale in the neighbourhood of NoLo?
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