Immunotherapy for Biliary Tract Cancer in the Era of Precision Medicine: Current Knowledge and Future Perspectives

Biliary tract cancers (BTC) represent a heterogeneous and aggressive group of tumors with dismal prognosis. For a long time, BTC has been considered an orphan disease with very limited therapeutic options. In recent years a better understanding of the complex molecular landscape of biology is rapidly changing the therapeutic armamentarium. However, while 40–50% of patients there are molecular drivers susceptible to target therapy, for the remaining population new therapeutic options represent an unsatisfied clinical need. The role of immunotherapy in the continuum of treatment of patients with BTC is still debated. Despite initial signs of antitumor-activity, single-agent immune checkpoint inhibitors (ICIs) demonstrated limited efficacy in an unselected population. Therefore, identifying the best partner to combine ICIs and predictive biomarkers represents a key challenge to optimize the efficacy of immunotherapy. This review provides a critical analysis of completed trials, with an eye on future perspectives and possible biomarkers of response.     

Habitat Suitability and Landscape Structure: A Maximum Entropy Approach in a Mediterranean Area

Species distribution models have recently become important tools in ecological research. Prediction of suitable habitats for threatened and endangered species is essential for the conservation and management of their native habitats. A landscape scale approach is relevant for biodiversity conservation since landscape planning and management are generally conducted at wide spatial scales, focusing on areas with complex landscape configuration as a consequence of human activities. The aims of this study were to test a maximum entropy approach (Maxent) to the development of a niche-based model for species of conservation interest and to relate this model to landscape structure metrics. The results obtained here showed a good predictive power of Maxent for the three target species and highlighted the importance of landscape structure analysis for the detection of patterns of habitat suitability. Moreover, this work stressed that combining classical environmental information with landscape structure in analysing habitat suitability for species of conservation interest may be used to guide conservation efforts and landscape management practices.     

Upgrading the data acquisition and control systems of the European Breeding Blanket Test Facility

The EBBTF (European Breeding Blanket Test Facility) experimental plant is a key component for the development of the breeding blankets (TBMs test blanket modules, HCLL helium cooled lithium lead and HCPB helium cooled pebble bed types) used by ITER. EBBTF is an experimental plant which provides the double breeding/cooling loops (liquid metal and gas) required for HCLL testing. EBBTF is composed of four subsystems (TBM, IELLLO integrated European lead lithium loop, HE-FUS3 helium fusion loop, version 3 and helium compressor build by ATEKO) with dedicated control systems realized with hardware/software combinations covering 15 years (1995–2010) time span. At the end of 2010 we began to upgrade the HE-FUS3 data acquisition control systems (DACS) replacing the obsolete PLC Siemens S5 with National Instruments Compact FieldPoint and LabVIEW. The control room has been completely reorganized using high resolution monitors and workstations linked with standard Ethernet interfaces. The data acquisition, control, safety and SCADA software has been completely developed in ENEA using LabVIEW. In this paper we are going to discuss the technical difficulties and the solutions that we have used to accomplish the upgrade.     

Expression pattern of CD2 locus control region containing retroviral vectors in hemopoietic cells in vitro and in vivo

OBJECTIVE: To determine whether individual surgeon experience is associated with improved short-term clinical and economic outcomes for patients with benign and malignant thyroid disease who underwent thyroid procedures in Maryland between 1991 and 1996. SUMMARY BACKGROUND DATA: There is a prevailing belief that surgeon experience affects patient outcomes in endocrine surgery, but there is a paucity of objective evidence outside of clinical series published by experienced surgeons that supports this view. METHODS: A cross-sectional analysis of all patients who underwent thyroidectomy in Maryland between 1991 and 1996 was conducted using a computerized statewide hospital discharge data base. Surgeons were categorized by volume of thyroidectomies over the 6-year study period: A (1 to 9 cases), B (10 to 29 cases), C (30 to 100 cases), and D (>100 cases). Multivariate regression was used to assess the relation between surgeon caseload and in-hospital complications, length of stay, and total hospital charges, adjusting for case mix and hospital volume. RESULTS: The highest-volume surgeons (group D) performed the greatest proportion of total thyroidectomies among the 5860 discharges, and they were more likely to operate on patients with cancer. After adjusting for case mix and hospital volume, highest-volume surgeons had the shortest length of stay (1.4 days vs. 1.7 days for groups B and C and 1.9 days for group A) and the lowest complication rate (5.1 % vs. 6.1% for groups B and C and 8.6% for group A). Length of stay and complications were more determined by surgeon experience than hospital volume, which had no consistent association with outcomes. CONCLUSIONS: Individual surgeon experience is significantly associated with complication rates and length of stay for thyroidectomy.     

Ruthenium supported on new TiO2–ZrO2 systems as catalysts for the partial oxidation of methane

The partial oxidation of methane is studied at 673–873 K over new Ru-based catalysts supported on TiO₂–ZrO₂ with different TiO₂ content. Supports were prepared by a sol–gel method, and RuCl₃ and RuNO(NO₃)₃ were used as ruthenium precursors to prepare the catalysts (1–2 wt% Ru). The effect of the reaction temperature on the catalytic behavior is analyzed, along with the support composition and the Ru precursor used.     

The assessment of the damage probability of storage tanks in domino events triggered by fire

An approach aimed to the quantitative assessment of the risk caused by escalation scenarios triggered by fire was developed. Simplified models for the estimation of the vessel time to failure (ttf) with respect to the radiation intensity on the vessel shell were obtained using a multi-level approach to the analysis of vessel wall failure under different fire conditions. Each vessel “time to failure” calculated by this approach for the specific fire scenario of concern was compared to a reference time required for effective mitigation actions and related to the escalation probability. The failure probability of each vessel was correlated to the probability of scenarios involving multiple vessel failure as a consequence of the primary fire, thus allowing a comprehensive assessment of domino scenarios triggered by fire. The application of the methodology to the analysis of several case-studies allowed the estimation of the quantitative contribution of escalation events triggered by fire to the overall individual and societal risk indexes.     

The quantitative assessment of domino effects caused by overpressure. Part I. Probit models

Accidents caused by domino effect are among the more severe that took place in the chemical and process industry. However, a well established and widely accepted methodology for the quantitative assessment of domino accidents contribution to industrial risk is still missing. Hence, available data on damage to process equipment caused by blast waves were revised in the framework of quantitative risk analysis, aiming at the quantitative assessment of domino effects caused by overpressure. Specific probit models were derived for several categories of process equipment and were compared to other literature approaches for the prediction of probability of damage of equipment loaded by overpressure. The results evidence the importance of using equipment-specific models for the probability of damage and equipment-specific damage threshold values, rather than general equipment correlation, which may lead to errors up to 500%.     

Forensic analysis of poly(ethylene terephthalate) fibers by infrared spectroscopy

Poly(ethylene terephthalate) (PET) is one of the most commonly employed polymers in the textile industry. Its relevance as a source of evidence in the reconstruction of criminal cases is nevertheless very limited because the properties and morphologies of fibers from different producers tend to be very similar. By integrating bands, obtained on single fibers by infrared (IR) microscopy, associated with trans and gauche conformation and to the O-H end-groups of the molecules, a method is proposed that can discriminate otherwise similar PET fibers. The absorbancies at 1370 and at 846 cm(-1) relative, respectively, to the gauche and trans conformation, were measured and ratioed. The end-group content was evaluated by ratioing the absorbancies of the signals at 3440 and at 874 cm(-1). Relative standard deviation (R. S. D.) was 1% for repetitive analyses on the same location of the same single fiber. Precision was reduced if the ratios were measured along the length of a single fiber (R. S. D. = 3%) and even further when different fibers of the same sample were examined (R. S. D. varied from 2 to 10%). This simple method can greatly enhance the evidential value of PET fibers by subclassifying them, thus helping the Court to better assess their significance.