Surgery after biological therapy in locally advanced NSCLC with molecular driver: feasibility and effectiveness of a new multidisciplinary approach

Introduction: Surgical outcomes after biological therapy have not been investigated yet and no information about timing, postoperative complications and survival have been recorded. Methods: This is a prospective study which compares a group of stage IIIA and IIIB NSCLC patients treated with biological therapy with patients undergoing standard induction chemotherapy. Data reported are preliminary results on the safety and effectiveness of surgery after target therapy. Results: We compared 22 patients treated with standard chemotherapy (Group 1) and 6 patients who received target therapy (Group 2). No differences were observed with an important bias due to the limited number of cases. The median time of resection was 159.8 ± 62.8 for group 1 and 201 ± 57.8 for group 2 (p=0.194). Complete resection was obtained in all Group 1-cases. Post-operative complication rate was 22% vs 16% (p=1). Pathologists reported necrosis >50% in 13% in group 1, Fibrosis >50% was presents respectively in 27% and 33% of patients (p=1). Residual vital tumor was >50% in 77% of patients undergone CT and in 66% of patients undergone TT (p=0.622). A total of 6 (31%) patients in the CT-group developed recurrence, 3 in the TT- group (64.2%), p was 0.634. No difference was observed both in terms of OS (P=0.29, Figure 3) and in term of DFS (P=0.106, Figure 4). Discussion: There is no consensus in the use of target therapy for advanced tumor in association with surgery. EGFR-tyrosine kinase inhibitors showed higher and more rapid response and our study wants to demonstrate that surgery after target therapy gives full access to the advantage of definitive local treatment. In our series, despite fibrosis, radical surgery has been achieved in all patients operated. The intraoperative blood loss, operation time, postoperative hospital stay and postoperative complication rate seems to be similar.

Contaminants of emerging concern in drinking water: assessment of the effectiveness of removal by drinking water treatments and possible risks to human health

Contaminants of emerging concern are increasingly detected in the water cycle, with endocrine-disrupting chemicals (EDCs) receiving attention due to their potential to cause adverse health effects even at low concentrations. Although the EU has recently introduced some EDCs into drinking water legislation, most drinking water treatment plants (DWTPs) are not designed to remove EDCs, making their detection and removal in DWTPs an important challenge. The aim of this doctoral project was to investigate hormones and phenolic compounds as suspected EDCs in drinking waters across the Romagna area (Italy). The main objectives were to assess the occurrence of considered contaminants in source and drinking water from three DWTPs, characterize the effectiveness of removal by different water treatment processes, and evaluate the potential biological impact on drinking water and human health. Specifically, a complementary approach of target chemical analysis and effect-based methods was adopted to explore drinking water quality, treatment efficacy, and biological potential. This study found that nonylphenol (NP) was prevalent in all samples, followed by BPA. Sporadic contamination of hormones was found only in source waters. Although the measured EDC concentrations in drinking water did not exceed threshold guideline values, the potential role of DWTPs as an additional source of EDC contamination should be considered. Significant increases in BPA and NP levels were observed during water treatment steps, which were also reflected in estrogenic and mutagenic responses in water samples after the ultrafiltration. This highlights the need to monitor water quality during various treatment processes to improve the efficiency of DWTPs. Biological assessments on finished water did not reveal any bioactivity, except for few treated water samples that exhibited estrogenic responses. Overall, the data emphasize the high quality of produced drinking water and the value of applying integrated chemical analysis and in vitro bioassays for water quality assessment.

The Effectiveness of the Clean Development Mechanism – A law and economics analysis

Climate change has been acknowledged as a threat to humanity. Most scholars agree that to avert dangerous climate change and to transform economies into low-carbon societies, deep global emission reductions are required by the year 2050. Under the framework of the Kyoto Protocol, the Clean Development Mechanism (CDM) is the only market-based instrument that encourages industrialised countries to pursue emission reductions in developing countries. The CDM aims to pay the incremental finance necessary to operationalize emission reduction projects which are otherwise not financially viable. According to the objectives of the Kyoto Protocol, the CDM should finance projects that are additional to those which would have happened anyway, contribute to sustainable development in the countries hosting the projects, and be cost-effective. To enable the identification of such projects, an institutional framework has been established by the Kyoto Protocol which lays out responsibilities for public and private actors. This thesis examines whether the CDM has achieved these objectives in practice and can thus be considered an effective tool to reduce emissions. To complete this investigation, the book applies economic theory and analyses the CDM from two perspectives. The first perspective is the supply-dimension which answers the question of how, in practice, the CDM system identified additional, cost-effective, sustainable projects and, generated emission reductions. The main contribution of this book is the second perspective, the compliance-dimension, which answers the question of whether industrialised countries effectively used the CDM for compliance with their Kyoto targets. The application of the CDM in the European Union Emissions Trading Scheme (EU ETS) is used as a case-study. Where the analysis identifies inefficiencies within the supply or the compliance dimension, potential improvements of the legal framework are proposed and discussed.

Feasibility and diagnostic effectiveness of new capsule endoscopy techniques

Since its approval by FDA in 2001, capsule endoscopy revolutionized the study of small bowel. One of the main limitations of its diffusion has been the high cost. More recently, a new videocapsule system (OMOM CE) has been developed in China and obtained the CE mark. Its cost is approximately half that of other capsule systems. However, there are few studies regarding the clinical experience with this new videocapsule system and none of them has been performed in the western world. Among the limitations of capsule endoscopy, there is also one linked to the diagnostic yield. The rapid transit of the device in the proximal segments implies a high risk of false negatives; an indirect confirmation of this limit is offered by the poor ability to identify the papilla of Vater. In addition, recent studies show that in patients with obscure gastrointestinal bleeding, the negative outcome of capsule endoscopy is correlated to a significant risk of recurrence of anemia in the short term, as well as the presence of small bowel lesions documented by a second capsule endoscopy. It was recently approved the use of a new device called "CapsoCam" (CapsoVision, Inc. Saratoga) characterized by four side cameras that offer a panoramic view of 360 degrees, instead of the front to 160°. Two recent pilot studies showed comparable safety profiles and diagnostic yield with the more standardized capsule. Namely, side vision has made possible a clear visualization of the papilla in 70% of cases. The aim of our study is to evaluate the feasibility and diagnostic yield of these two new devices, which first may allow a reduction in costs. Moreover, their complementary use could lead to a recovery diagnostic in patients with false negative results in an initial investigation.

Cost-Effectiveness of Alternative Retrofit Options to Support Decision Making

How to evaluate the cost-effectiveness of repair/retrofit intervention vs. demolition/replacement and what level of shaking intensity can the chosen repairing/retrofit technique sustain are open questions affecting either the pre-earthquake prevention, the post-earthquake emergency and the reconstruction phases. The (mis)conception that the cost of retrofit interventions would increase linearly with the achieved seismic performance (%NBS) often discourages stakeholders to consider repair/retrofit options in a post-earthquake damage situation. Similarly, in a pre-earthquake phase, the minimum (by-law) level of %NBS might be targeted, leading in some cases to no-action. Furthermore, the performance measure enforcing owners to take action, the %NBS, is generally evaluated deterministically. Not directly reflecting epistemic and aleatory uncertainties, the assessment can result in misleading confidence on the expected performance. The present study aims at contributing to the delicate decision-making process of repair/retrofit vs. demolition/replacement, by developing a framework to assist stakeholders with the evaluation of the effects in terms of long-term losses and benefits of an increment in their initial investment (targeted retrofit level) and highlighting the uncertainties hidden behind a deterministic approach. For a pre-1970 case study building, different retrofit solutions are considered, targeting different levels of %NBS, and the actual probability of reaching Collapse when considering a suite of ground-motions is evaluated, providing a correlation between %NBS and Risk. Both a simplified and a probabilistic loss modelling are then undertaken to study the relationship between %NBS and expected direct and indirect losses.