Real-world efficacy and safety of nivolumab in previously-treated metastatic renal cell carcinoma, and association between immune-related adverse events and survival: the Italian expanded access program

Background: The Italian Renal Cell Cancer Early Access Program was an expanded access program that allowed access to nivolumab, for patients (pts) with metastatic renal cell carcinoma (mRCC) prior to regulatory approval. Methods: Pts with previously treated advanced or mRCC were eligible to receive nivolumab 3 mg/kg every 2 weeks. Pts included in the analysis had received ≥1 dose of nivolumab and were monitored for drug-related adverse events (drAEs) using CTCAE v.4.0. Immune-related (ir) AEs were defined as AEs displaying a certain, likely or possible correlation with immunotherapy (cutaneous, endocrine, hepatic, gastro-intestinal and pulmonary). The association between overall survival (OS) and irAEs was assessed, and associations between variables were evaluated with a logistic regression model. Results: A total of 389 pts were enrolled between July 2015 and April 2016. Overall, the objective response rate was 23.1%. At a median follow-up of 12 months, the median progression-free survival was 4.5 months (95% CI 3.7-6.2) and the 12-month overall survival rate was 63%. Any grade and grade 3-4 drAEs were reported in 124 (32%) and 27 (7%) of pts, respectively, and there were no treatment-related deaths. Any grade irAEs occurred in 76 (20%) of patients, 8% cutaneous, 4% endocrine, 2% hepatic, 5% gastro-intestinal and 1% pulmonary. Of the 22 drAEs inducing treatment discontinuation, 10 (45%) were irAEs. Pts with drAEs had a significantly longer survival than those without drAEs (median OS 22.5 versus 16.4 months, p = 0.01). Pts with irAEs versus without irAEs had a more significant survival benefit (median OS not reached versus 16.8 months, p = 0.002), confirmed at the landmark analysis at 6 weeks. The occurrence of irAEs displayed a strong association with OS in univariable (HR 0.48, p = 0.003) and multivariable (HR 0.57, p = 0.02) analysis. Conclusions: The appearance of irAEs strongly correlates with survival benefit in a real-life population of mRCC pts treated with nivolumab

Exploring the land-use urban heat island nexus under climate change conditions using machine learning approach: A spatio-temporal analysis of remotely sensed data

Urbanization strongly correlates with land use land cover (LULC) dynamics, which further links to changes in land surface temperature (LST) & urban heat island (UHI) intensity. Each LULC type influences UHI differently with changing climate, therefore knowing this impact & connection is critical. To understand such relations, long temporal studies using remote sensing data play promising role by analysing the trend with continuity over vast area. Therefore, this study is aimed at machine learning centred spatio-temporal analysis of LST and land use indices to identify their intra-urban interaction during 1991–2021 (summer) in Imola city (specifically representing small urban environment) using Landsat-5/8 imageries. It was found that LST in 2021 increased by 38.36% from 1991, whereas average Normalised Difference Built-up Index (NDBI) increased by 43.75%, associating with increased thermal stress area evaluated using ecological evaluation index. Major LULC transformations included green area into agricultural arable-land and built-up. Finally, the modelled output shows that built-up & vegetation index have strongly impacted LST. This study, help to understand the relative impact of land-use dynamics on LST at intra-urban level specifically with respect to the small urban settings. Further assisting in designing and regenerating urban contexts with stable configuration, considering sustainability and liveable climate, for benefit of health of public and fragile population in particular

Development of a Pilot Borehole Storage System of Solar Thermal Energy: Modeling, Design, and Installation

Borehole thermal energy storage systems represent a potential solution to increase the energy efficiency of renewable energy plants, but they generally have to comply with strict regulatory frameworks, mainly due to the deliberate modification of the subsoil’s natural state. This paper presents the design, testing, and monitoring phases carried out to set up a borehole thermal energy storage (BTES) system able to exploit the excess solar heat from photovoltaic thermal (PVT) collectors. The case study is the refurbishment of a pig nursery barn, hosting up to 2500 weaners, in Northern Italy. This study aims to define a BTES suitable to develop a heating system based on renewable energy, ensuring environmental protection and long-term sustainability. The retrofitting intervention includes the installation of a dual-source heat pump (DSHP), in order to recover the solar heat stored in summer during winter. Specific constraints by the Environmental Authority were as follows: maximum storage temperature of 35 °C, authorization to intercept the shallowest aquifer at a maximum depth of 30 m, obligation of BHE grouting, and the definition of a strategy for continuous measuring and monitoring of the groundwater’s thermophysical properties. The results were used as inputs to optimize the design and installation of the integrated system with PVT, BTES, and DSHP

Relation between Morphology and Chiroptical Properties in Chiral Conducting Polymer Films: A Case Study in Chiral PEDOT

The electronic properties of conducting polymers are influenced by their micro- and macrostructural orders, which can be tailored by substituent modification. However, while the effect of substituents on conducting polymers is extensively investigated, chiral substituents are far less studied. Furthermore, many chiral conducting polymers have regioirregular structures, which result in polymer films with inferior properties. In this work, we apply electronic circular dichroism (ECD) spectroscopy to study the morphological changes to the chiral polymers under different polymerization conditions. For this purpose, we investigated 3,4-ethylenedioxythiophene (EDOT) derivatives having two stereogenic centers on each monomer and bearing methyl or phenyl side groups (dimethyl-EDOT and diphenyl-EDOT, respectively). Polymerizing the enantiomerically pure monomers produces regioregular and stereoregular dimethyl-PEDOT and diphenyl-PEDOT, respectively. The effect of the electrolyte and solvent on polymer film morphology was studied using scanning electron microscopy (SEM) and ECD, showing a correlation between the polymer's morphology and the chiroptical properties of its films. We found that, for diphenyl-PEDOT, the combination of perchlorate anion electrolyte and acetonitrile solvent resulted in a unique morphology characterized by significant intermolecular interactions. These interactions were clearly observable in the ECD spectra in the form of exciton couplings, whose presence was supported by TD-DFT calculations. A small enantiomeric excess was sufficient to induce very intense ECD signals, demonstrating chiral amplification in electropolymerized films

Assessment of construction and demolition waste materials for sublayers of low traffic rural roads

The need for exploiting massive amounts of natural raw materials for constructing pavements of roads as a key element for development of infrastructures in modern age, together with enormous production amounts of wastes related to civil engineering activities as biggest portion of solid waste generated all over the world, have highlighted the importance of utilizing recycled aggregates of these materials in road pavement layers. The key factor in this quest, is to evaluate load-bearing abilities of various kinds of waste aggregates. Aggregates of reclaimed asphalt, pre-stressed or normal concrete, masonry and demolition waste (CDW) exhibit different behavior under loading after compaction. The ideal situation would be to achieve the densest compacted and durable layer in order to get the highest durability, comparing to traditional road materials. In this study, aggregates from four types of recycled materials are being subjected to study for unbound and cemented pavement layers. Initial laboratory evaluations of size and composition are followed by constructing a field on a subgrade with high non-homogenous surface. Vibrating elastic modulus (Evib) for these materials were determined by Continuous Compaction Control (CCC) Oscillating Rollers. It is observed that, despite the weaknesses arisen from weak components such as masonry and elongated tiles, the stabilized distribution of the particle size can accelerate reaching to final compaction of unbound aggregates with roller passing. This process could be repeated with more or less same pattern in cemented layer, which exhibited an enhanced stiffness and uniformity in order to minimize the weak parts of non-uniform subgrade layer, and provide a high rigid pavement

Policy and political challenges for a better world: The United States and China pathways towards the 2030 Agenda

The Agenda 2030 poses critical elements regarding the transition towards a more sustainable development. This paper aims at exploring and comparing the path of sustainable development within the United States and China at the subnational level. An index of Integrated Sustainable Development is introduced to measure local sustainable development on an internationally-comparable scale. This Index is computed both at the national and subnational level and the resulting scores are compared within and across the two countries, also through the adoption of convergence and cluster analysis, allowing to answer four questions: Are the US and China moving towards a sustainable development agenda? Are the current achievements uniformly distributed within the two countries? Are states/provinces converging towards a more uniform level of sustainable development? Do the existing differences and analogies between states and provinces give rise to common clusters across the two countries? The results lead to one robust conclusion: while the US can claim a better result in the national and subnational rankings of sustainable development, China exhibits a more balanced achievement in terms of synergies across Goals and spatial distribution. Nonetheless, both countries are characterized by subnational disparities and scarce achievements of Planet-related Goals. Policy recommendations are discussed accordingly

Research model for farm building design: General structure and physiognomic characterization phase

The design of contemporary farm buildings often subordinates architectural quality and aesthetic features to economic aspects, thus leading to poor landscape consistency and compatibility.  The research presented in this paper is based on the theoretical principle that historic rural buildings, being expression of an accumulation of empirical knowledge broadly associated with high architectural quality, have remarkable potentials to contribute with useful elements to the design of contemporary buildings, and on the awareness that the design process is also necessarily and substantially determined by technological, economic and functional variables.  The paper presents the FarmBuiLD model (Farm Building Landscape Design), a research model proposed by the authors as a tool for the analysis of the architectural characteristics of both historical and contemporary rural buildings, as well as the meta-design of new construction and transformation of contemporary rural buildings.  In particular, the work focuses on the general structure of this model and a synthesis of the main results of the critical analysis of the scientific literature aimed at identifying a set of synthetic architectural parameters suitable for its implementation, through the interpretation of the main physiognomical characteristics of rural buildings.  These parameters are not meant as a tool to obtain quantitative data to be translated into design constraints automatically; on the contrary, they are mainly considered as an interpretive-analytical tool, part of a broader knowledge framework aimed at supporting, stimulating and suggesting the design choices.Keywords: Rural building design, historical-typological consistency, landscape compatibility, architectural quality, analytical and meta-design criteria, Italian rural building heritage Citation: Tassinari P, D. Torreggiani, S. Benni, and E. Dall’Ara.  Research model for farm building design: General structure and physiognomic characterization phase.  Agric Eng Int: CIGR Journal, 2010; 12(1): 47-54

Developing a 3D City Digital Twin: Enhancing Walkability through a Green Pedestrian Network (GPN) in the City of Imola, Italy

Predominantly, dense historical cities face insufficient pedestrian-level greenery in the urban spaces. The lack of greenery impacts the human thermal comfort on the walking paths, which contributes to a considerable reduction in pedestrian flow rate. This study aims at developing a model to assess pedestrian-level thermal comfort in city environments and then evaluate the feasibility of creating a green pedestrian network (GPN). Imola, as a historical city in Italy with a compact urban pattern, is selected as the case study of this paper. To accomplish this, a three-dimensional digital twin at city scale is developed for the recognition of real-time shade patterns and for designing a GPN in this city. The 3D model of the proposed digital twin is developed in the Rhinoceros platform, and the physiological equivalence temperature (PET) is simulated through EnergyPlus, Honeybee, and Ladybug components in grasshopper. This study provides the city with a digital twin that is capable of examining pedestrian-level thermal comfort for designing a GPN based on real-time PET in the compact urban morphology of Imola. The PET model indicates that during the hottest hour of the 25th of June, pedestrians in open spaces can experience 3  C more than on narrow shaded streets. The results are validated based on in situ datasets that prove the reliability of the developed digital twin for the GPN. It provides urban planners and policy makers with a precise and useful methodology for simulating the effects of pedestrian-level urban greenery on human thermal comfort and also guarantees the functionality of policies in different urban settings

Side effects of analgesia may significantly reduce quality of life in symptomatic multiple myeloma: a cross-sectional prevalence study

Background Pain is a common symptom in patients with multiple myeloma (MM). Many patients are dependent on analgesics and in particular opioids, but there is limited information on the impact of these drugs and their side effects on health-related quality of life (HRQoL). Method In a cross-sectional study, semi-structured interviews were performed in 21 patients attending the hospital with symptomatic MM on pain medications. HRQoL was measured using items 29 and 30 of the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30. Results Patients were able to recall a median of two (range 0–4) analgesics. They spontaneously identified a median of two (range 1–5) side effects attributable to their analgesic medications. Patients’ assessment of HRQoL based on the EORTC QLQ-C30 questions 29/30 was mean 48.3 (95 % CI; 38.7–57.9) out of 100. Patients’ assessment of their HRQoL in the hypothetical situation, in which they would not experience any side effects from analgesics, was significantly higher: 62.6 (53.5–71.7) (t test, p=0.001). Conclusion This study provides, for the first time, evidence that side effects of analgesics are common in symptomatic MM and may result in a statistically and clinically significant reduction of self-reported HRQoL

A comparison of energy and thermal performance of rooftop greenhouses and green roofs in Mediterranean climate: A hygrothermal assessment in WuFi

In urban areas, a considerable proportion of energy demand is allocated to buildings. Since rooftops constitute one-fourth of all urban surfaces, an increasing amount of attention is paid to achieving the most efficient shapes and component designs compatible with every climate and urban context, for rooftops of varying sizes. In this study, three types of rooftop technologies, namely insulated, green roof, and rooftop greenhouse, are evaluated for energy and thermal performance using computer simulations. Water surface exposure, absorption, and intrusion are the three important factors in the calculation of hygrothermal models that impact energy consumption and building envelope performance; however, a few studies are specifically focused on providing realistic results in multi-dimensional hygrothermal models and the assessment of the impact of moisture in roofing solutions. This paper aims at evaluating the performance of three different roofing technologies through a two-dimensional hygrothermal simulation in software WUFI. To accomplish this, a precise localized microclimate model of a complex urban context on the scale of a neighborhood was employed to evaluate the cooling and heating loads of the buildings, the impact of the water content in the green roof on the thermal behavior of the roof surface, and the feasibility of designing a building with nearly zero cooling needs. A two-story building in the city center of Bologna, Italy is modelled. Simulation results have shown that during the cooling period, the performance of the designed rooftop greenhouse is the most effective by 50% reduction in cooling loads. Besides, the impact of moisture in green roofs has been detected as a negative factor for thermal and energy performance of the building in the Mediterranean climate. The results ultimately highlighted the capability of passively-designed rooftop greenhouses to create a building with nearly zero cooling needs