Real-Time Monitoring of Odour Emissions at the Fenceline of a Waste Treatment Plant by Instrumental Odour Monitoring Systems: Focus on Training Methods.

Waste treatment plants (WTPs) often generate odours that may cause nuisance to citizens living nearby. In general, people are becoming more sensitive to environmental issues, and particularly to odour pollution. Instrumental Odour Monitoring Systems (IOMSs) represent an emerging tool for continuous odour measurement and real-time identification of odour peaks, which can provide useful information about the process operation and indicate the occurrence of anomalous conditions likely to cause odour events in the surrounding territories. This paper describes the implementation of two IOMSs at the fenceline of a WTP, focusing on the definition of a specific experimental protocol and data processing procedure for dealing with the interferences of humidity and temperature affecting sensors' responses. Different approaches for data processing were compared and the optimal one was selected based on field performance testing. The humidity compensation model developed proved to be effective, bringing the IOMS classification accuracy above 95%. Also, the adoption of a class-specific regression model compared to a global regression model resulted in an odour quantification capability comparable with those of the reference method (i.e., dynamic olfactometry). Lastly, the validated models were used to process the monitoring data over a period of about one year.

Accuracy of a new electronic nose for prostate cancer diagnosis in urine samples.

OBJECTIVE: To evaluate the accuracy of a new electronic nose to recognize prostate cancer in urine samples. METHODS: A blind, prospective study on consecutive patients was designed. Overall, 174 subjects were included in the study: 88 (50.6%) in prostate cancer group, and 86 (49.4%) in control group. Electronic nose performance for prostate cancer was assessed using sensitivity and specificity. The diagnostic accuracy of electronic nose was reported as area under the receiver operating characteristic curve. RESULTS: The electronic nose in the study population reached a sensitivity 85.2% (95% confidence interval 76.1-91.9; 13 false negatives out of 88), a specificity 79.1% (95% confidence interval 69.0-87.1; 18 false positives out of 86). The accuracy of the electronic nose represented as area under the receiver operating characteristic curve 0.821 (95% confidence interval 0.764-0.879). CONCLUSIONS: The diagnostic accuracy of electronic nose for recognizing prostate cancer in urine samples is high, promising and susceptible to supplemental improvement. Additionally, further studies will be necessary to design a clinical trial to validate electronic nose application in diagnostic prostate cancer nomograms.

Early Gastric Cancer: identification of molecular markers able to distinguish submucosa-penetrating lesions with different prognosis.

BACKGROUND: Early Gastric Cancer (EGC) reaches 25% of the gastric cancers surgically treated in some areas of Northeastern Italy and is usually characterized by a good prognosis. However, among EGCs classified according to Kodama's criteria, Pen A subgroup is characterized by extensive submucosal invasion, lymph node metastases and worse prognosis, whereas Pen B subgroup by better prognosis. The aim of the study was to characterize the differences between Pen A, Pen B and locally advanced gastric cancer (T3N0) in order to identify biomarkers involved in aggressiveness and clinical outcome. METHODS: We selected 33 Pen A, 34 Pen B and 20 T3N0 tumors and performed immunohistochemistry of mucins, copy number variation analysis of a gene panel, microsatellite instability (MSI), TP53 mutation and loss of heterozygosity (LOH) analyses. RESULTS: Pen A subgroup was characterized by MUC6 overexpression (p = 0.021). Otherwise, the Pen B subgroup was significantly associated with the amplification of GATA6 gene (p = 0.002). The higher percentage of MSI tumors was observed in T3N0 group (p = 0.002), but no significant differences between EGC types were found. Finally, TP53 gene analysis showed that 32.8% of Pen tumors have a mutation in exons 5-8 and 50.0% presented LOH. Co-occurrence of TP53 mutation and LOH mainly characterized Pen A tumors (p = 0.022). CONCLUSIONS: Our analyses revealed that clinico-pathological parameters, microsatellite status and frequency of TP53 mutations do not seem to distinguish Pen subgroups. Conversely, the amplification of GATA6 was associated with Pen B, as well as the overexpression of MUC6 and the TP53mut/LOH significantly characterized Pen A.

Non-carcinogenic occupational exposure risk related to foundry emissions: focus on the workers involved in olfactometric assessments.

The scope of this work is the evaluation of the non-carcinogenic occupational risk related to foundry emissions, focusing on the category of workers involved in olfactometric assessments. Odor pollution from industrial activities such as foundries is a serious environmental concern. Sensorial techniques (e.g. dynamic olfactometry, EN13725:2003) currently represent the preferred method for odor emission characterization. During olfactometric analyses, human assessors are directly exposed to the odor at increasing concentrations, thus requiring the assessment of the associated exposure risk to guarantee workers' safety. This paper presents an investigation aiming to produce an inventory of compounds emitted from foundries together with their odor thresholds and toxicological limits (TLVs), with the final objective to propose a procedure for ensuring workers' safety during olfactometric analyses. Looking at the database resulting from this study, among the >100 compounds emitted by foundries, 8 have a maximum concentration above their TLV. Among those, ammonia, H2S, phenol, toluene and trimethylamine, produce an odor stimulus before they reach a toxic concentration, thus not representing a risk for olfactometric workers. Benzene, formaldehyde and SO2 are identified as the most critical compounds because they may reach toxic concentrations in foundry emissions, and they start being perceived by humans above their TLV. The proposed procedure entails a minimum dilution factor of 27'000 to be applied to odor samples analyzed by olfactometry, which however might result inapplicable in practical cases, thus pointing out the necessity to adopt chemical measurements to investigate specifically the concentration of the most critical compounds identified in this study.

Proposal of Odor Nuisance Index as Urban Planning Tool.

This article analyzes the state of the art of the methods and models used for the characterization of odor annoyance and it preliminary advances some proposals for the evaluation of the olfactory nuisance. The use of a sensorial technique, such as dynamic olfactometry, is proposed for the analysis of odor concentrations, odor emission rates, and odor dispersions. A simple model for the quantification of environmental odor nuisance, based on the use of FIDOL factors, that are, frequency, intensity, duration, hedonic tone, and location, is proposed.

H2S Loss through Nalophan™ Bags: Contributions of Adsorption and Diffusion.

Hydrogen-sulfide (H2S) is a molecule of small dimensions typically present in the odor emissions from different plants. The European Standard EN 13725:2003 set a maximum storage time allowed of 30 hours, during which the sampling bag has to maintain the mixture of odorants with minimal changes. This study investigates the H2S losses through Nalophan bags and it shows that nonnegligible losses of H2S can be observed. The percent H2S loss after 30 hrs with respect to the initial concentration is equal to 33% ± 3% at a relative humidity of 20% and equal to 22% ± 1% at a relative humidity of 60%. The average quantity of adsorbed H2S at 30 h is equal to 2.17 105 gH2S/gNalophan at a storage humidity of 20% and equal to 1.79 105 gH2S/gNalophan at a storage humidity of 60%. The diffusion coefficients of H2S through Nalophan, for these two humidity conditions tested, are comparable (i.e., 7.5 10-12 m2/sec at 20% humidity and 6.6 10-12 m2/sec at 60% humidity).

Assessment of the Indoor Odour Impact in a Naturally Ventilated Room.

Indoor air quality influences people's lives, potentially affecting their health and comfort. Nowadays, ventilation is the only technique commonly used for regulating indoor air quality. CO2 is the reference species considered in order to calculate the air exchange rates of indoor environments. Indeed, regarding air quality, the presence of pleasant or unpleasant odours can strongly influence the environmental comfort. In this paper, a case study of indoor air quality monitoring is reported. The indoor field tests were conducted measuring both CO2 concentration, using a photoacoustic multi-gas analyzer, and odour trends, using an electronic nose, in order to analyze and compare the information acquired. The indoor air monitoring campaign was run for a period of 20 working days into a university room. The work was focused on the determination of both CO2 and odour emission factors (OEF) emitted by the human activity and on the evaluation of the odour impact in a naturally ventilated room. The results highlighted that an air monitoring and recycling system based only on CO2 concentration and temperature measurements might be insufficient to ensure a good indoor air quality, whereas its performances could be improved by integrating the existing systems with an electronic nose for odour detection.

Right- vs. Left-Sided Metastatic Colorectal Cancer: Differences in Tumor Biology and Bevacizumab Efficacy.

There is evidence of a different response to treatment with regard to the primary tumor localization (right-sided or left-sided) in patients with metastatic colorectal cancer (mCRC). We analyzed the different outcomes and biomolecular characteristics in relation to tumor localization in 122 of the 370 patients with metastatic colorectal cancer enrolled onto the phase III prospective multicenter "Italian Trial in Advanced Colorectal Cancer (ITACa)", randomized to receive first-line chemotherapy (CT) or CT plus bevacizumab (CT + B). RAS and BRAF mutations; baseline expression levels of circulating vascular endothelial growth factor (VEGF), endothelial nitric oxide synthase (eNOS), cyclooxygenase-2 (COX2), ephrin type-B receptor 4 (EPHB4), hypoxia-inducible factor 1-alpha (HIF-1α), lactate dehydrogenase (LDH), and high-sensitivity C reactive protein (hs-CRP); and inflammatory indexes such as the neutrophil-to-lymphocyte ratio, platelet-lymphocyte rate and systemic immune-inflammation index were evaluated. Patients with right-sided tumors showed a longer median progression-free survival in the CT + B arm than in the CT group (12.6 vs. 9.0 months, respectively, p = 0.017). Baseline inflammatory indexes were significantly higher in left-sided tumors, whereas eNOS and EPHB4 expression was significantly higher and BRAF mutation more frequent in right-sided tumors. Our data suggest a greater efficacy of the CT + B combination in right-sided mCRC, which might be attributable to the lower inflammatory status and higher expression of pro-angiogenic factors that appear to characterize these tumors.

Sampling method for the determination of methane emissions from landfill surfaces.

The first aim of this work is the definition and the study of a suitable sampling method for the measurement of landfill gas (LFG) emissions from landfill surfaces, since, up to now, there are no codified nor universally accepted sampling methods for this specific task. The studied sampling method is based on the use of a static hood. The research work involves a preliminary theoretical study for the hood design, experimental tests for the definition of the optimal sampling procedures, and simulations of the hood fluid-dynamics for the system validation. The second aim of this study is the investigation of the correlations between LFG emissions and meteorological conditions, whose identification would be very useful in terms of effective landfill management and pollution control. This involved a wide literature study for the selection of those parameters that seem to have an influence on LFG emission, and the collection of a great number of experimental data on a target site, which led to the conclusion that atmospheric pressure and soil humidity are the parameters that mostly affect LFG emissions.

Electronic Nose Testing Procedure for the Definition of Minimum Performance Requirements for Environmental Odor Monitoring.

Despite initial enthusiasm towards electronic noses and their possible application in different fields, and quite a lot of promising results, several criticalities emerge from most published research studies, and, as a matter of fact, the diffusion of electronic noses in real-life applications is still very limited. In general, a first step towards large-scale-diffusion of an analysis method, is standardization. The aim of this paper is describing the experimental procedure adopted in order to evaluate electronic nose performances, with the final purpose of establishing minimum performance requirements, which is considered to be a first crucial step towards standardization of the specific case of electronic nose application for environmental odor monitoring at receptors. Based on the experimental results of the performance testing of a commercialized electronic nose type with respect to three criteria (i.e., response invariability to variable atmospheric conditions, instrumental detection limit, and odor classification accuracy), it was possible to hypothesize a logic that could be adopted for the definition of minimum performance requirements, according to the idea that these are technologically achievable.

Application and Uses of Electronic Noses for Clinical Diagnosis on Urine Samples: A Review.

The electronic nose is able to provide useful information through the analysis of the volatile organic compounds in body fluids, such as exhaled breath, urine and blood. This paper focuses on the review of electronic nose studies and applications in the specific field of medical diagnostics based on the analysis of the gaseous headspace of human urine, in order to provide a broad overview of the state of the art and thus enhance future developments in this field. The research in this field is rather recent and still in progress, and there are several aspects that need to be investigated more into depth, not only to develop and improve specific electronic noses for different diseases, but also with the aim to discover and analyse the connections between specific diseases and the body fluids odour. Further research is needed to improve the results obtained up to now; the development of new sensors and data processing methods should lead to greater diagnostic accuracy thus making the electronic nose an effective tool for early detection of different kinds of diseases, ranging from infections to tumours or exposure to toxic agents.

Ammonia diffusion through Nalophan double bags: effect of concentration gradient reduction.

The ammonia loss through Nalophan bags has been studied. The losses observed for storage conditions and times as allowed by the reference standard for dynamic olfactometry (EN 13725:2003) indicate that odour concentration values due to the presence of small molecules may be significantly underestimated if samples are not analysed immediately after sampling. A diffusion model was used in order to study diffusion through the bag. The study discusses the effect of concentration gradient (ΔC) across the polymeric membrane of the analyte. The ΔC was controlled by using a setup bag called "double bags." Experimental data show a reduction of ammonia percentage losses due to the effect of the external multibarrier. The expedient of the double bag loaded with the same gas mixture allows a reduced diffusion of ammonia into the inner bag. Comparing the inner bag losses with those of the single bag stored in the same conditions (T, P, u) and with equal geometrical characteristics (S/V, z), it was observed that the inner bag of the double bag displays a 16% loss while the single bag displays a 37% loss. Acting on the ΔC it is possible to achieve a gross reduction of 57% in the ammonia leakage due to diffusion.

Electronic noses for environmental monitoring applications.

Electronic nose applications in environmental monitoring are nowadays of great interest, because of the instruments' proven capability of recognizing and discriminating between a variety of different gases and odors using just a small number of sensors. Such applications in the environmental field include analysis of parameters relating to environmental quality, process control, and verification of efficiency of odor control systems. This article reviews the findings of recent scientific studies in this field, with particular focus on the abovementioned applications. In general, these studies prove that electronic noses are mostly suitable for the different applications reported, especially if the instruments are specifically developed and fine-tuned. As a general rule, literature studies also discuss the critical aspects connected with the different possible uses, as well as research regarding the development of effective solutions. However, currently the main limit to the diffusion of electronic noses as environmental monitoring tools is their complexity and the lack of specific regulation for their standardization, as their use entails a large number of degrees of freedom, regarding for instance the training and the data processing procedures.

Gene mutation analysis in EGFR wild type NSCLC responsive to erlotinib: are there features to guide patient selection?

Tyrosine kinase inhibitors (TKIs) are very efficacious in non-small-cell lung cancer (NSCLC) patients harboring activating Epidermal Growth Factor Receptor (EGFR) mutations. However, about 10% of EGFR wild type (wt) patients respond to TKI, with unknown molecular mechanisms of sensitivity. We considered a case series of 34 EGFR wt NSCLC patients responsive to erlotinib after at least one line of therapy. Responsive patients were matched with an equal number of non-responsive EGFR wt patients. A panel of 26 genes, for a total of 214 somatic mutations, was analyzed by MassARRAY® System (Sequenom, San Diego, CA, USA). A 15% KRAS mutation was observed in both groups, with a prevalence of G12C in non-responders (80% vs. 40% in responders). NOTCH1, p53 and EGFR-resistance-related mutations were found more frequently in non-responders, whereas EGFR-sensitizing mutations and alterations in genes involved in proliferation pathways were more frequent in responders. In conclusion, our findings indicate that p53, NOTCH1 and exon 20 EGFR mutations seem to be related to TKI resistance. KRAS mutations do not appear to influence the TKI response, although G12C mutation is more frequent in non-responders. Finally, the use of highly sensitive methodologies could lead to the identification of under-represented EGFR mutations potentially associated with TKI sensitivity.

The need for electronic noses for environmental odour exposure assessment.

This paper focuses on the opportunities for using electronic noses for odour exposure assessment purposes, especially in cases where dispersion modelling is not applicable. Such cases include, for instance, those sources where a detailed characterisation and quantification of the odour emissions for every hour of the simulation time domain is particularly difficult, due to the nature of the source or to the variability of the emissions over time. In such situations, it is useful to determine odour exposure directly at receptors instead. This paper critically discusses the state of the art of electronic nose technology as far as its application to the determination of odour exposure at receptors is concerned. One example of electronic nose application to the monitoring of odours from an Italian municipal solid waste (MSW) landfill is reported, in order to discuss the instrument's potential and limits. The monitoring results are represented by the number of measures that are classified in a specific olfactory class; this information allows the odour exposure at each monitoring site in terms of odour detection frequency to be determined. Besides a quantification of the odour episodes, electronic noses allowed the identification of the landfill gas as the monitored landfill major odour source.

Ammonia diffusion through Nalophan™ bags.

The aim of the work is to verify the diffusion rate of ammonia through the Nalophan™ film that constitutes the sampling bag, considering storage times ranging from 1 to 26 h. The ammonia decay over time was evaluated using gas-chromatography for the quantification of ammonia concentration inside the bag. The research assesses the roles of both of ammonia and water concentration gradients at the polymeric film interface on the diffusion process. The results show that both the ammonia concentration gradient and, in a less pronounced way, the water concentration gradient are the main 'engines' of ammonia diffusion. Double bags seem to represent a simple solution for preventing ammonia losses during storage. Another interesting result concerns the role of the bag surface on the ammonia diffusion rate: the higher the surface/volume (S/V) ratio, the higher the ammonia diffusion rate through the polymeric film.

Electronic nose for odor monitoring at a landfill fenceline: Training and validation of a model for real-time odor concentration measurement.

In recent years, electronic noses, or more generally Instrumental Odor Monitoring Systems (IOMS), have aroused increasing interest in the field of environmental monitoring. One of the most interesting applications of these instruments is the real-time estimation of the odor concentration at plant fencelines to continuously monitor odor emissions and identify anomalous conditions. In this type of application, it is possible to setting a "warning" threshold, enabling the continuous check of proper functioning of the plant and sudden intervention in case of malfunctions, preventing, at the same time, the risk of odor events at the receptors. For this purpose, it is necessary to provide a continuous, fast and reliable measurement of the odor concentration, which is nowadays one of the main challenges of this technology. In this context, this work proposes the development of a quantification model for quantifying odors detected at the fenceline of a landfill characterized by very different odor fingerprints. A double-step quantification model, firstly identifying the different odor classes to which the ambient air monitored at the fenceline by the IOMS belong to, and then developing different specific PLS regression models for each of the odor classes identified, was developed. The results of the proposed quantification model were compared to the ones obtained developing a "global" quantification model, which implements the regression on the globality of the training set, without differentiating between the odor classes. Then, they were further evaluated by comparison with the odor events detected at the sensitive receptor by another electronic nose. Moreover, the combined evaluation of the odor events at the plant fenceline and the receptor, respectively, together with the meteorological data highlighted the need of identifying variable warning thresholds for the odor concentrations at the fenceline according to effectively account for meteorological conditions and produce an output that is more correlated with the probability that an odor is perceived outside of the plant.

Prostate cancer risk stratification via eNose urine odor analysis: a preliminary report.

Introduction: Prostate cancer (PCa) is known for its highly diverse clinical behavior, ranging from low-risk, slow-growing tumors to aggressive and life-threatening forms. To avoid over-treatment of low-risk PCa patients, it would be very important prior to any therapeutic intervention to appropriately classify subjects based on tumor aggressiveness. Unfortunately, there is currently no reliable test available for this purpose. The aim of the present study was to evaluate the ability of risk stratification of PCa subjects using an electronic nose (eNose) detecting PCa-specific volatile organic compounds (VOCs) in urine samples. Methods: The study involved 120 participants who underwent diagnostic prostate biopsy followed by robot assisted radical prostatectomy (RARP). PCa risk was categorized as low, intermediate, or high based on the D'Amico risk classification and the pathological grade (PG) assessed after RARP. The eNose's ability to categorize subjects for PCa risk stratification was evaluated based on accuracy and recall metrics. Results: The study population comprised 120 participants. When comparing eNose predictions with PG an accuracy of 79.2% (95%CI 70.8 - 86%) was found, while an accuracy of 74.2% (95%CI 65.4 - 81.7%) was found when compared to D'Amico risk classification system. Additionally, if compared low- versus -intermediate-/high-risk PCa, the eNose achieved an accuracy of 87.5% (95%CI 80.2-92.8%) based on PG or 90.8% (95%CI 84.2-95.3%) based on D'Amico risk classification. However, when using low-/-intermediate versus -high-risk PCa for PG, the accuracy was found to be 91.7% (95%CI 85.2-95.9%). Finally, an accuracy of 80.8% (95%CI72.6-87.4%) was found when compared with D'Amico risk classification. Discussion: The findings of this study indicate that eNose may represent a valid alternative not only for early and non-invasive diagnosis of PCa, but also to categorize patients based on tumor aggressiveness. Further studies including a wider sample population will be necessary to confirm the potential clinical impact of this new technology.

Rare Driver Mutations in Advanced, Oncogene-Addicted Non-Small Cell Lung Cancer: A North Italian, Real-World, Registry Experience.

The real-world, retrospective, NEROnE registry investigated the impact of next-generation sequencing (NGS) in advanced non-small-cell lung cancer (NSCLC) patients (pts) at three oncology units in the north of Italy between January 2020 and December 2022. We focused on the clinical characterization and outcomes of NSCLC with rare molecular alterations: EGFR exon 20 insertion, non-activating EGFR mutations, BRAF V600E and non-V600, ROS1 and RET rearrangements, MET, ErbB2, and FGFR mutations. Overall, these represented 6.4% (62/970) of the pts analysed with NGS in the daily practice. The most heavily represented rare alterations were ROS1 rearrangement (15 pts-24%) and MET exon 14 skipping mutation (11 pts-18%). No associations were found with the demographic and clinical features. Forty-nine pts received targeted therapies, of which 38.8% were first- and 9.8% were second-line. The remaining pts received chemotherapy and/or immunotherapy. In terms of the clinical outcomes, although not statistically significant, a tendency toward shorter OS was seen when therapies other than specific targeted therapies were used (HR: 1.84, 95% CI: 0.79-4.33, p = 0.158). The pts with co-mutations (19.4%) seemed to receive an advantage from the front-line chemotherapy-based regimen. Finally, an NLR score (a well-known inflammatory index) ≥ 4 seemed to be related to shorter OS among the pts treated with immunotherapy alone or in combination with chemotherapy (HR: 2.83, 95% CI: 1.08-7.40, p = 0.033). Prospective evaluations need to be performed to clarify whether these indexes may help to identify patients with oncogene-addicted NSCLC who could benefit from immunotherapy.

Non-Small Cell Lung Cancer Testing on Reference Specimens: An Italian Multicenter Experience.

INTRODUCTION: Biomarker testing is mandatory for the clinical management of patients with advanced non-small cell lung cancer (NSCLC). Myriads of technical platforms are now available for biomarker analysis with differences in terms of multiplexing capability, analytical sensitivity, and turnaround time (TAT). We evaluated the technical performance of the diagnostic workflows of 24 representative Italian institutions performing molecular tests on a series of artificial reference specimens built to mimic routine diagnostic samples. METHODS: Sample sets of eight slides from cell blocks of artificial reference specimens harboring exon 19 EGFR (epidermal growth factor receptor) p.E746_AT50del, exon 2 KRAS (Kirsten rat sarcoma viral oncogene homologue) p.G12C, ROS1 (c-ros oncogene 1)-unknown gene fusion, and MET (MET proto-oncogene, receptor tyrosine kinase) Δ exon 14 skipping were distributed to each participating institution. Two independent cell block specimens were validated by the University of Naples Federico II before shipment. Methodological and molecular data from reference specimens were annotated. RESULTS: Overall, a median DNA concentration of 3.3 ng/µL (range 0.1-10.0 ng/µL) and 13.4 ng/µL (range 2.0-45.8 ng/µL) were obtained with automated and manual technical procedures, respectively. RNA concentrations of 5.7 ng/µL (range 0.2-11.9 ng/µL) and 9.3 ng/µL (range 0.5-18.0 ng/µL) were also detected. KRAS exon 2 p.G12C, EGFR exon 19 p.E736_A750del hotspot mutations, and ROS1 aberrant transcripts were identified in all tested cases, whereas 15 out of 16 (93.7%) centers detected MET exon 14 skipping mutation. CONCLUSIONS: Optimized technical workflows are crucial in the decision-making strategy of patients with NSCLC. Artificial reference specimens enable optimization of diagnostic workflows for predictive molecular analysis in routine clinical practice.