Predictive And Prognostic Role Of Biological Markers In Neuroendocrine Neoplasia And Evaluation Of Activity And Safety Of Second Line Treatments In Neuroendocrine Carcinoma Patients

BACKGROUND Neuroendocrine neoplasia (NEN) are divided in well differentiated G1,G2 and G3 neuroendocrine tumors (NETs) and G3 neuroendocrine carcinomas (NECs). For the latter no standard therapy in second-line is available and prognosis is poor. METHODS Primary aim was to evaluate new prognostic and predictive biomarkers (WP1-3). In WP4 we explored the activity of FOLFIRI and CAPTEM as second-line in NEC patients in a multicenter non-comparative phase II trial RESULTS In WP1-2 we found that 4 of 6 GEP-NEC patients with a negative 68Ga-PET/CT had a loss of expression of RB1. In WP3 on 47 GEP-NENs patients the presence of DLL3 in 76.9% of G3 NEC correlate with RB1-loss (p<0.001), negative 68Ga-PET/CT(p=0.001) and a poor prognosis. In the WP4 we conducted a multicenter non-comparative phase II trial to explore the activity of FOLFIRI or CAPTEM in terms of DCR, PFS and OS given as second-line in NEC patients. From 06/03/2017 to 18/01/2021 53 out of 112 patients were enrolled in 17 of 23 participating centers. Median follow-up was 10.8 (range 1.4 – 38.6) months. The 3-month DCR was 39.3% in the FOLFIRI and 32.0 % in the CAPTEM arm. The 6-months PFS rate was 34.6% ( 95%CI 17.5-52.5) in FOLFIRI and 9.6% (95%CI 1.8-25.7) in CAPTEM group. In the FOLFIRI subgroup the 6-months and 12-months OS rate were 55.4% (95%CI 32.6-73.3) and 30.3% (CI 11.1-52.2) respectively. In CAPTEM arm the 6-months and 12-months OS rate were 57.2% (95%34.9-74.3) and 29.0% (95%10.0-43.3). The miRNA analysis of 20 patients compared with 20 healthy subjects shows an overexpression of miRNAs involved in staminality , neo-angiogenesis and mitochontrial anaerobic glycolysis activation. CONCLUSION WP1-3 support the hypothesis that G3NECs carrying RB1 loss is associated with a DLL3 expression highlighting a potential therapeutic opportunity. Our study unfortunately didn’t met the primary end–point but the results are promising

Design and evaluation of aerosol and liquid separation systems

Conventional chromatographic columns are packed with porous beads by the universally employed slurry-packing method. The lack of precise control of the particle size distribution, shape and position inside the column have dramatic effects on the separation efficiency. In the first part the thesis an ordered, three-dimensional, pillar-array structure was designed by a CAD software. Several columns, characterized by different fluid distributors and bed length, were produced by a stereolithographic 3D printer and compared in terms of pressure drop and height equivalent to a theroretical plate (HETP). To prevent the release of unwanted substances and to provide a surface for immobilizing a ligand, pillars were coated with one or more of the following materials: titanium dioxide, nanofibrillated cellulose (NFC) and polystyrene. The external NFC layer was functionalized with Cibacron Blue and the dynamic binding capacity of the column was measured by performing three chromatographic cycles, using bovine serum albumin (BSA) as target molecule. The second part of the thesis deals with Covid-19 pandemic related research activities. In early 2020, due to the pandemic outbreak, surgical face masks became an essential non-pharmaceutical intervention to limit the spread. To address the consequent shortage and to support the reconversion of the Italian industry, in late March 2020 a multidisciplinary group of the University of Bologna created the first Italian laboratory able to perform all the tests required for the evaluation and certification of surgical masks. More than 1200 tests were performed on about 350 prototypes, according to the standard EN 14683:2019. The results were analyzed to define the best material properties and masks composition for the production of masks with excellent efficiency. To optimize the usage of surgical masks and to reduce their environmental burden, the variation of their performance over time of usage were investigated as to determine the maximum lifetime.

On making web accessibility more accessible: strategy and tools for social good

The world currently faces a paradox in terms of accessibility for people with disabilities. While digital technologies hold immense potential to improve their quality of life, the majority of web content still exhibits critical accessibility issues. This PhD thesis addresses this challenge by proposing two interconnected research branches. The first introduces a groundbreaking approach to improving web accessibility by rethinking how it is approached, making it more accessible itself. It involves the development of: 1. AX, a declarative framework of web components that enforces the generation of accessible markup by means of static analysis. 2. An innovative accessibility testing and evaluation methodology, which communicates test results by exploiting concepts that developers are already familiar with (visual rendering and mouse operability) to convey the accessibility of a page. This methodology is implemented through the SAHARIAN browser extension. 3. A11A, a categorized and structured collection of curated accessibility resources aimed at facilitating their intended audiences discover and use them. The second branch focuses on unleashing the full potential of digital technologies to improve accessibility in the physical world. The thesis proposes the SCAMP methodology to make scientific artifacts accessible to blind, visually impaired individuals, and the general public. It enhances the natural characteristics of objects, making them more accessible through interactive, multimodal, and multisensory experiences. Additionally, the prototype of \gls{a11yvt}, a system supporting accessible virtual tours, is presented. It provides blind and visually impaired individuals with features necessary to explore unfamiliar indoor environments, while maintaining universal design principles that makes it suitable for usage by the general public. The thesis extensively discusses the theoretical foundations, design, development, and unique characteristics of these innovative tools. Usability tests with the intended target audiences demonstrate the effectiveness of the proposed artifacts, suggesting their potential to significantly improve the current state of accessibility.

Comparison of different solutions for the hybridization of a motorcycle engine for Formula Student applications and evaluation of the effectiveness on the simulated lap time

Following the latest environmental concerns, the importance of minimising the detrimental effect of emissions of terrestrial vehicles has become a major goal for the whole automotive field. The key to achieve an emission-free long term future is the electrification of vehicle fleets; this huge step cannot be taken without intermediate technologies. In this context, hybrid vehicles are fundamental to reach this goal. Specifically, mild hybrid vehicles represent a trade-off between cost and emissions that could act now as a bridge towards electrification. Like the industry, also student engineering competitions are likely to take the same route: Combustion vehicles may well turn into hybrid vehicles. For this reason, a preliminary design overview is necessary to pinpoint the key performance indicators for the prototypes of the future.

Neural Machine Translation in the Field of Law. Analysis and Evaluation against Human Reference of NMT Raw Outputs of an Atto Costitutivo of S.r.l. from Italian into German.

Artificial Intelligence (AI) is gaining ever more ground in every sphere of human life, to the point that it is now even used to pass sentences in courts. The use of AI in the field of Law is however deemed quite controversial, as it could provide more objectivity yet entail an abuse of power as well, given that bias in algorithms behind AI may cause lack of accuracy. As a product of AI, machine translation is being increasingly used in the field of Law too in order to translate laws, judgements, contracts, etc. between different languages and different legal systems. In the legal setting of Company Law, accuracy of the content and suitability of terminology play a crucial role within a translation task, as any addition or omission of content or mistranslation of terms could entail legal consequences for companies. The purpose of the present study is to first assess which neural machine translation system between DeepL and ModernMT produces a more suitable translation from Italian into German of the atto costitutivo of an Italian s.r.l. in terms of accuracy of the content and correctness of terminology, and then to assess which translation proves to be closer to a human reference translation. In order to achieve the above-mentioned aims, two human and automatic evaluations are carried out based on the MQM taxonomy and the BLEU metric. Results of both evaluations show an overall better performance delivered by ModernMT in terms of content accuracy, suitability of terminology, and closeness to a human translation. As emerged from the MQM-based evaluation, its accuracy and terminology errors account for just 8.43% (as opposed to DeepL’s 9.22%), while it obtains an overall BLEU score of 29.14 (against DeepL’s 27.02). The overall performances however show that machines still face barriers in overcoming semantic complexity, tackling polysemy, and choosing domain-specific terminology, which suggests that the discrepancy with human translation may still be remarkable.

Proof of Location through a Blockchain Agnostic Smart Contract Language: Design and Evaluation over Algorand and Ethereum

Le applicazioni che offrono servizi sulla base della posizione degli utenti sono sempre più utilizzate, a partire dal navigatore fino ad arrivare ai sistemi di trasporto intelligenti (ITS) i quali permetteranno ai veicoli di comunicare tra loro. Alcune di questi servizi permettono perfino di ottenere qualche incentivo se l'utente visita o passa per determinate zone. Per esempio un negozio potrebbe offrire dei coupon alle persone che si trovano nei paraggi. Tuttavia, la posizione degli utenti è facilmente falsificabile, ed in quest'ultima tipologia di servizi, essi potrebbero ottenere gli incentivi in modo illecito, raggirando il sistema. Diviene quindi necessario implementare un'architettura in grado di impedire alle persone di falsificare la loro posizione. A tal fine, numerosi lavori sono stati proposti, i quali delegherebbero la realizzazione di "prove di luogo" a dei server centralizzati oppure collocherebbero degli access point in grado di rilasciare prove o certificati a quegli utenti che si trovano vicino. In questo lavoro di tesi abbiamo ideato un'architettura diversa da quelle dei lavori correlati, cercando di utilizzare le funzionalità offerte dalla tecnologia blockchain e dalla memorizzazione distribuita. In questo modo è stato possibile progettare una soluzione che fosse decentralizzata e trasparente, assicurando l'immutabilità dei dati mediante l'utilizzo della blockchain. Inoltre, verrà dettagliato un'idea di caso d'uso da realizzare utilizzando l'architettura da noi proposta, andando ad evidenziare i vantaggi che, potenzialmente, si potrebbero trarre da essa. Infine, abbiamo implementato parte del sistema in questione, misurando i tempi ed i costi richiesti dalle transazioni su alcune delle blockchain disponibili al giorno d'oggi, utilizzando le infrastrutture messe a disposizione da Ethereum, Polygon e Algorand.

Propuesta para incorporar evaluación y pruebas de usabilidad dentro de un proceso de desarrollo de software

Usability is critical to consider an interactive software system successful. Usability testing and evaluation during product development have gained wide acceptance as a strategy to improve product quality. Early introduction of usability perspectives in a product is very important in order to provide a clear visibility of the quality aspects not only for the developers, but also for the testing users as well. However, usability evaluation and testing are not commonly taken into consideration as an essential element of the software development process. Then, this paper exposes a proposal to introduce usability evaluation and testing within a software development through reuse of software artifacts. Additionally, it suggests the introduction of an auditor within the classification of actors for usability tests. It also proposes an improvement of checklists used for heuristics evaluation, adding quantitative and qualitative aspects to them

Research recommendations for selected IARC-classified agents.

OBJECTIVES: There are some common occupational agents and exposure circumstances where evidence of carcinogenicity is substantial but not yet conclusive for humans. The objectives are to identify research gaps and needs for twenty agents prioritized for review based on evidence of widespread human exposures and potential carcinogenicity in animals or humans. DATA SOURCES: A systematic review was conducted of new data published since the most recent pertinent IARC monograph meeting. DATA EXTRACTION: Reviewers were charged with identifying data gaps and general and specific approaches to address them, focusing on research that would be important in resolving classification uncertainties. An expert meeting brought reviewers together to discuss each agent and the identified data gaps and approaches. DATA SYNTHESIS: Several overarching issues were identified that pertained to multiple agents; these included the importance of recognizing that carcinogenic agents can act through multiple toxicity pathways and mechanisms, including epigenetic mechanisms, oxidative stress and immuno- and hormonal modulation. CONCLUSIONS: Studies in occupational populations provide important opportunities to understand the mechanisms through which exogenous agents cause cancer and intervene to prevent human exposure and/or prevent or detect cancer among those already exposed. Scientific developments are likely to increase the challenges and complexities of carcinogen testing and evaluation in the future, and epidemiologic studies will be particularly critical to inform carcinogen classification and risk assessment processes.[Authors]

Evauation of Recycled Asphalt Concrete Pavements: Final Report for Kossuth County, Iowa, HR-1888, February 1980

After some success with a small asphalt pavement recycling project in 1975, Kossuth County, Iowa programmed a much larger undertaking during the 1976 construction season. The work performed in 1975 indicated that a quality product could be produced with some modifications to conventional equipment. As anticipated , the major problem encountered was the excessive air pollution created during the heating and mixing process. As part of its 1976 road program, Kossuth County developed plans for recycling sixteen miles of existing asphalt pavements using the "hot mix" recycling process. One project, ten miles in length, was selected by the Federal Highway Authority as part of "Demonstration Project No. 39, Recycling Asphalt Pavements." The FHWA provided a $29,500 grant t o the project to be used for project testing and evaluation. Cooperation and input into the work proposed for 1976 was received from many sources. The people and organizations contributing were the Federal Highway Authority, the Iowa Department of Environmental Quality, the Federal Environmental Protection Agency, several contractors, and personnel from the Kossuth County Engineer's Office.

Final report on the Portable Weather Station, March 2012

This station was required to have air temperature, relative humidity, wind speed and direction, and pavement temperature sensors of similar quality to the traditional RWIS sensors, have an integrated solar powered battery system, and be trailer-mounted for ease of transport. The station was tested by the Iowa DOT for basic reliability and sensor performance for a month and a half in Ames, Iowa before being moved to near Osceola, Iowa in early February 2010 for further field testing and evaluation. DOT field maintenance staff was able to successfully set up the station with minimal instruction and found the station to be relatively intuitive in its installation. Air temperature, wind speed, and wind direction observations from the station were compared to a nearby RWIS station and had good agreement. Pavement temperature readings were compared to sites within 40 miles of the station, and the readings correlated. The station has had good reliability.

Evaluating Roadway Subsurface Drainage Practices - Phase II, TR-662, 2015

Well-performing subsurface drainage systems form an important aspect of pavement design by the Iowa Department of Transportation (DOT). The recently completed Iowa Highway Research Board (IHRB) project TR-643 provided extensive insights into Iowa subsurface drainage practices and pavement subdrain outlet performance. However, the project TR-643 (Phase I) forensic testing and evaluation were carried out in a drought year and during the fall season in 2012. Based on the findings of IHRB Project TR-643, the Iowa DOT requested an expanded Phase II study to address several additional research needs: evaluate the seasonal variation effects (dry fall 2012 versus wet spring/summer 2013, etc.) on subdrain outlet condition and performance; investigate the characteristics of tufa formation in Iowa subdrain outlets; investigate the condition of composite pavement subdrain outlets; examine the effect of resurfacing/widening/rehabilitation on subdrain outlets (e.g., the effects of patching on subdrain outlet performance); and identify a suitable drain outlet protection mechanism (like a headwall) and design for Iowa subdrain outlets based on a review of practices adopted by nearby states. A detailed forensic test plan was developed and executed for inspecting the Iowa pavement subdrains in pursuit of fulfilling the Phase II study objectives. The observed outlets with blockage and the associated surface distresses in newly constructed jointed plain concrete pavements (JPCPs) were slightly higher during summer 2013 compared to fall 2012. However, these differences are not significant. Less tufa formation due to the recycled portland cement concrete (RPCC) base was observed with (a) the use of plastic outlet pipe without the gate screen–type rodent guard and (b) the use of blended RPCC and virgin aggregate materials. In hot-mix asphalt (HMA) over JPCP, moisture-related distress types (e.g., reflection cracking) were observed more near blocked drainage outlet locations than near “no blockage” outlet locations. This finding indicates that compromised drainage outlet performance could accelerate the development of moisture-related distresses in Iowa composite pavement systems. ****** Note: This report follows on work report in "Evaluating Roadway Subsurface Drainage Practices, 2013" http://publications.iowa.gov/14902/ Note: This record contains links to the 210 page full report as well as the 3 page tech transfer summary. The summary is NOT deposited separately.

Laboratory Investigation of Grouted Coupler Connection Details for ABC Bridge Projects, RB07-013, 2015

With an ever increasing desire to utilize accelerated bridge construction (ABC) techniques, it is becoming critical that bridge designers and contractors have confidence in typical details. The Keg Creek Bridge on US 6 in Iowa was a recent ABC example that utilized connection details that had been utilized elsewhere. The connection details used between the drilled shaft and pier column and between the pier column and the pier cap were details needing evaluation. These connection details utilized grouted couplers that have been tested by others with mixed results—some indicating quality performance and others indicating questionable performance. There was a need to test these couplers to gain an understanding of their performance in likely Iowa details and to understand how their performance might be impacted by different construction processes. The objective of the work was to perform laboratory testing and evaluation of the grouted coupler connection details utilized on precast concrete elements for the Keg Creek Bridge. The Bridge Engineering Center (BEC), with the assistance of the Iowa Department of Transportation (DOT) Office of Bridges and Structures, developed specimens representative of the Keg Creek Bridge connections for testing under static and fatigue loads in the structures laboratory. The specimens were also evaluated for their ability to resist the intrusion of water and chlorides. Evaluation of their performance was made through comparisons with design assumptions and previous research, as well as the physical performance of the coupled connections.

Use of niche models in invasive species risk assessments.

Risk maps summarizing landscape suitability of novel areas for invading species can be valuable tools for preventing species' invasions or controlling their spread, but methods employed for development of such maps remain variable and unstandardized. We discuss several considerations in development of such models, including types of distributional information that should be used, the nature of explanatory variables that should be incorporated, and caveats regarding model testing and evaluation. We highlight that, in the case of invasive species, such distributional predictions should aim to derive the best hypothesis of the potential distribution of the species by using (1) all distributional information available, including information from both the native range and other invaded regions; (2) predictors linked as directly as is feasible to the physiological requirements of the species; and (3) modelling procedures that carefully avoid overfitting to the training data. Finally, model testing and evaluation should focus on well-predicted presences, and less on efficient prediction of absences; a k-fold regional cross-validation test is discussed.

Assessment of Water Quality along the Coastal Areas of Kerala: A Study of the Tsunami Impact on Groundwater

Everywhere, on the coastal belt it is proved without doubt that the pristine ground water quality was severely deteriorated after the 26 December 2004 Indian Ocean Tsunami. But how far is more relevant, as it is decided by the so-called pre-tsunamic situation of the region. In water quality studies it is this reference finger print which earmarks regional ground water chemistry based on which the monthly variability could rationally be interpreted. This Ph D thesis comprises the testing and evaluation of the facts: whether there is any significant difference in the water quality parameters under study between stations and between months in Tsunami Affected Dug Wells (TADW). Whether the selected water quality parameters vary significantly from BIS and WHO standards. Whether the water quality index (WQI) differ significantly between Tsunami Affected Dug Wells (TADW) and Bore Wells (BW). Whether there is any significant difference in the water quality parameters during December 2005 and December 2008. Is there any significant change in the Water Quality Parameters before 2001 and after tsunami (2005) in TADW.