Development of a rapid LC-MS/MS method for simultaneous quantification of ten commonly used antibiotic drugs in human serum.

The use of TDM in clinical practice to monitor the plasma levels of antibiotics administered to critically ill patients is a well-established approach that allows for optimization of the patient's response to drug therapy, considering the characteristics of the drug, the clinical and physiological status of the patient and any peculiar of the pathogen that caused the clinical picture. In our laboratory, we have developed a single LC-MS/MS analysis for dosing the serum concentration of an antibacterial panel composed of eight antibacterial and two selective inhibitors. The method presented used a certified material furnished by a commercial company and was internally validated using the EMA guidelines. The results have shown high sensitivity, precision, and accuracy, a lower matrix effect combined with simple sample preparation and a time-saving procedure. We have evaluated the recovery rate and matrix effect by testing serum samples without pathological index and serum pools obtained from haemolysed, icteric, or lipemic samples. The assay has shown a recovery range between 94% and 101%.

Characterization of a flexible a-Si:H detector for in vivo dosimetry in therapeutic x-ray beams.

BACKGROUND: The increasing use of complex and high dose-rate treatments in radiation therapy necessitates advanced detectors to provide accurate dosimetry. Rather than relying on pre-treatment quality assurance (QA) measurements alone, many countries are now mandating the use of in vivo dosimetry, whereby a dosimeter is placed on the surface of the patient during treatment. Ideally, in vivo detectors should be flexible to conform to a patient's irregular surfaces. PURPOSE: This study aims to characterize a novel hydrogenated amorphous silicon (a-Si:H) radiation detector for the dosimetry of therapeutic x-ray beams. The detectors are flexible as they are fabricated directly on a flexible polyimide (Kapton) substrate. METHODS: The potential of this technology for application as a real-time flexible detector is investigated through a combined dosimetric and flexibility study. Measurements of fundamental dosimetric quantities were obtained including output factor (OF), dose rate dependence (DPP), energy dependence, percentage depth dose (PDD), and angular dependence. The response of the a-Si:H detectors investigated in this study are benchmarked directly against commercially available ionization chambers and solid-state diodes currently employed for QA practices. RESULTS: The a-Si:H detectors exhibit remarkable dose linearities in the direct detection of kV and MV therapeutic x-rays, with calibrated sensitivities ranging from (0.580 ± 0.002) pC/cGy to (19.36 ± 0.10) pC/cGy as a function of detector thickness, area, and applied bias. Regarding dosimetry, the a-Si:H detectors accurately obtained OF measurements that parallel commercially available detector solutions. The PDD response closely matched the expected profile as predicted via Geant4 simulations, a PTW Farmer ionization chamber and a PTW ROOS chamber. The most significant variation in the PDD performance was 5.67%, observed at a depth of 3 mm for detectors operated unbiased. With an external bias, the discrepancy in PDD response from reference data was confined to ± 2.92% for all depths (surface to 250 mm) in water-equivalent plastic. Very little angular dependence is displayed between irradiations at angles of 0° and 180°, with the most significant variation being a 7.71% decrease in collected charge at a 110° relative angle of incidence. Energy dependence and dose per pulse dependence are also reported, with results in agreement with the literature. Most notably, the flexibility of a-Si:H detectors was quantified for sample bending up to a radius of curvature of 7.98 mm, where the recorded photosensitivity degraded by (-4.9 ± 0.6)% of the initial device response when flat. It is essential to mention that this small bending radius is unlikely during in vivo patient dosimetry. In a more realistic scenario, with a bending radius of 15-20 mm, the variation in detector response remained within ± 4%. After substantial bending, the detector's photosensitivity when returned to a flat condition was (99.1 ± 0.5)% of the original response. CONCLUSIONS: This work successfully characterizes a flexible detector based on thin-film a-Si:H deposited on a Kapton substrate for applications in therapeutic x-ray dosimetry. The detectors exhibit dosimetric performances that parallel commercially available dosimeters, while also demonstrating excellent flexibility results.

Hydrogenated amorphous silicon high flux x-ray detectors for synchrotron microbeam radiation therapy.

Objective. Microbeam radiation therapy (MRT) is an alternative emerging radiotherapy treatment modality which has demonstrated effective radioresistant tumour control while sparing surrounding healthy tissue in preclinical trials. This apparent selectivity is achieved through MRT combining ultra-high dose rates with micron-scale spatial fractionation of the delivered x-ray treatment field. Quality assurance dosimetry for MRT must therefore overcome a significant challenge, as detectors require both a high dynamic range and a high spatial resolution to perform accurately.Approach. In this work, a series of radiation hard a-Si:H diodes, with different thicknesses and carrier selective contact configurations, have been characterised for x-ray dosimetry and real-time beam monitoring applications in extremely high flux beamlines utilised for MRT at the Australian Synchrotron.Results. These devices displayed superior radiation hardness under constant high dose-rate irradiations on the order of 6000 Gy s-1, with a variation in response of 10% over a delivered dose range of approximately 600 kGy. Dose linearity of each detector to x-rays with a peak energy of 117 keV is reported, with sensitivities ranging from (2.74 ± 0.02) nC/Gy to (4.96 ± 0.02) nC/Gy. For detectors with 0.8µm thick active a-Si:H layer, their operation in an edge-on orientation allows for the reconstruction of micron-size beam profiles (microbeams). The microbeams, with a nominal full-width-half-max of 50µm and a peak-to-peak separation of 400µm, were reconstructed with extreme accuracy. The full-width-half-max was observed as 55 ± 1µm. Evaluation of the peak-to-valley dose ratio and dose-rate dependence of the devices, as well as an x-ray induced charge (XBIC) map of a single pixel is also reported.Significance. These devices based on novel a-Si:H technology possess a unique combination of accurate dosimetric performance and radiation resistance, making them an ideal candidate for x-ray dosimetry in high dose-rate environments such as FLASH and MRT.

Organs-on-chips technologies - A guide from disease models to opportunities for drug development.

Current in-vitro 2D cultures and animal models present severe limitations in recapitulating human physiopathology with striking discrepancies in estimating drug efficacy and side effects when compared to human trials. For these reasons, microphysiological systems, organ-on-chip and multiorgans microdevices attracted considerable attention as novel tools for high-throughput and high-content research to achieve an improved understanding of diseases and to accelerate the drug development process towards more precise and eventually personalized standards. This review takes the form of a guide on this fast-growing field, providing useful introduction to major themes and indications for further readings. We start analyzing Organs-on-chips (OOC) technologies for testing the major drug administration routes: (1) oral/rectal route by intestine-on-a-chip, (2) inhalation by lung-on-a-chip, (3) transdermal by skin-on-a-chip and (4) intravenous through vascularization models, considering how drugs penetrate in the bloodstream and are conveyed to their targets. Then, we focus on OOC models for (other) specific organs and diseases: (1) neurodegenerative diseases with brain models and blood brain barriers, (2) tumor models including their vascularization, organoids/spheroids, engineering and screening of antitumor drugs, (3) liver/kidney on chips and multiorgan models for gastrointestinal diseases and metabolic assessment of drugs and (4) biomechanical systems recapitulating heart, muscles and bones structures and related diseases. Successively, we discuss technologies and materials for organ on chips, analyzing (1) microfluidic tools for organs-on-chips, (2) sensor integration for real-time monitoring, (3) materials and (4) cell lines for organs on chips. (Nano)delivery approaches for therapeutics and their on chip assessment are also described. Finally, we conclude with a critical discussion on current significance/relevance, trends, limitations, challenges and future prospects in terms of revolutionary impact on biomedical research, preclinical models and drug development.

Optimization of SAW Sensors for Nanoplastics and Grapevine Virus Detection.

In this work, we report the parametric optimization of surface acoustic wave (SAW) delay lines on Lithium niobate for environmental monitoring applications. First, we show that the device performance can be improved by acting opportunely on geometrical design parameters of the interdigital transducers such as the number of finger pairs, the finger overlap length and the distance between the emitter and the receiver. Then, the best-performing configuration is employed to realize SAW sensors. As aerosol particulate matter (PM) is a major threat, we first demonstrate a capability for the detection of polystyrene particles simulating nanoparticulates/nanoplastics, and achieve a limit of detection (LOD) of 0.3 ng, beyond the present state-of-the-art. Next, the SAW sensors were used for the first time to implement diagnostic tools able to detect Grapevine leafroll-associated virus 3 (GLRaV-3), one of the most widespread viruses in wine-growing areas, outperforming electrochemical impedance sensors thanks to a five-times better LOD. These two proofs of concept demonstrate the ability of miniaturized SAW sensors for carrying out on-field monitoring campaigns and their potential to replace the presently used heavy and expensive laboratory instrumentation.

Halogen-Bonding-Mediated Radical Reactions: The Unexpected Behavior of Piperazine-Based Dithiooxamide Ligands in the Presence of Diiodine.

N,N'-Dialkylpiperazine-2,3-dithiones (R2pipdt) were recognized as a class of hexa-atomic cyclic dithiooxamide ligands with peculiar charge-transfer donor properties toward soft electron-acceptors such as noble metal cations and diiodine. The latter interaction is nowadays better described as halogen bonding. In the reaction with diiodine, R2pipdt unexpectedly provides the corresponding triiodide salts, differently from the other dithiooxamides, which instead typically achieve ligand·nI2 halogen-bonded adducts. In this paper, we report a combined experimental and theoretical study that allows elucidation of the nature of the cited products and the reasons behind the unpredictable behavior of these ligands. Specifically, low-temperature single-crystal X-ray diffraction measurements on a series of synthetically obtained R2pipdt (R = Me, iPr, Bz)/I3 salts, complemented by neutron diffraction experiments, were able to experimentally highlight the formation of [R2pipdtH]+ cations with a -S-H bond on the dithionic moiety. Differently, with R = Ph, a benzothiazolylium cation, resulting from an intramolecular condensation reaction of the ligand, is obtained. Based on density functional theory (DFT) calculations, a reasonable reaction mechanism where diiodine plays the fundamental role of promoting a halogen-bonding-mediated radical reaction has been proposed. In addition, the comparison of combined experimental and computational results with the corresponding reactions of N,N'-dialkylperhydrodiazepine-2,3-dithione (R2dazdt, a hepta-atomic cyclic dithiooxamide), which provide neutral halogen-bonded adducts, pointed out that the difference in the torsion angle of the free ligands represents the structural key factor in determining the different reactivities of the two systems.

Quality control on digital cancer registration.

Population-based cancer registration methods are subject to internationally-established rules. To ensure efficient and effective case recording, population-based cancer registries widely adopt digital processing (DP) methods. At the Veneto Tumor Registry (RTV), about 50% of all digitally-identified (putative) cases of cancer are further profiled by means of registrars' assessments (RAs). Taking these RAs for reference, the present study examines how well the registry's DP performs. A series of 1,801 (putative) incident and prevalent cancers identified using DP methods were randomly assigned to two experienced registrars (blinded to the DP output), who independently re-assessed every case. This study focuses on the concordance between the DP output and the RAs as concerns cancer status (incident versus prevalent), topography, and morphology. The RAs confirmed the cancer status emerging from DP for 1,266/1,317 incident cancers (positive predictive value [PPV] = 96.1%) and 460/472 prevalent cancers (PPV = 97.5%). This level of concordance ranks as "optimal", with a Cohen's K value of 0.91. The overall prevalence of false-positive cancer cases identified by DP was 2.9%, and was affected by the number of digital variables available. DP and the RAs were consistent in identifying cancer topography in 88.7% of cases; differences concerned different sites within the same anatomo-functional district (according to the International Agency for Research on Cancer [IARC]) in 9.6% of cases. In short, using DP for cancer case registration suffers from only trivial inconsistencies. The efficiency and reliability of digital cancer registration is influenced by the availability of good-quality clinical information, and the regular interdisciplinary monitoring of a registry's DP performance.

High-Resolution Photoemission Study of Neutron-Induced Defects in Amorphous Hydrogenated Silicon Devices.

In this paper, by means of high-resolution photoemission, soft X-ray absorption and atomic force microscopy, we investigate, for the first time, the mechanisms of damaging, induced by neutron source, and recovering (after annealing) of p-i-n detector devices based on hydrogenated amorphous silicon (a-Si:H). This investigation will be performed by mean of high-resolution photoemission, soft X-Ray absorption and atomic force microscopy. Due to dangling bonds, the amorphous silicon is a highly defective material. However, by hydrogenation it is possible to reduce the density of the defect by several orders of magnitude, using hydrogenation and this will allow its usage in radiation detector devices. The investigation of the damage induced by exposure to high energy irradiation and its microscopic origin is fundamental since the amount of defects determine the electronic properties of the a-Si:H. The comparison of the spectroscopic results on bare and irradiated samples shows an increased degree of disorder and a strong reduction of the Si-H bonds after irradiation. After annealing we observe a partial recovering of the Si-H bonds, reducing the disorder in the Si (possibly due to the lowering of the radiation-induced dangling bonds). Moreover, effects in the uppermost coating are also observed by spectroscopies.

The Encapsulation of Citicoline within Solid Lipid Nanoparticles Enhances Its Capability to Counteract the 6-Hydroxydopamine-Induced Cytotoxicity in Human Neuroblastoma SH-SY5Y Cells.

(1) Backgrond: Considering the positive effects of citicoline (CIT) in the management of some neurodegenerative diseases, the aim of this work was to develop CIT-Loaded Solid Lipid Nanoparticles (CIT-SLNs) for enhancing the therapeutic use of CIT in parkinsonian syndrome; (2) Methods: CIT-SLNs were prepared by the melt homogenization method using the self-emulsifying lipid Gelucire® 50/13 as lipid matrix. Solid-state features on CIT-SLNs were obtained with FT-IR, thermal analysis (DSC) and X-ray powder diffraction (XRPD) studies. (3) Results: CIT-SLNs showed a mean diameter of 201 nm, -2.20 mV as zeta potential and a high percentage of entrapped CIT. DSC and XRPD analyses evidenced a greater amorphous state of CIT in CIT-SLNs. On confocal microscopy, fluorescent SLNs replacing unlabeled CIT-SLNs released the dye selectively in the cytoplasm. Biological evaluation showed that pre-treatment of SH-SY5Y dopaminergic cells with CIT-SLNs (50 µM) before the addition of 40 µM 6-hydroxydopamine (6-OHDA) to mimic Parkinson's disease's degenerative pathways counteracts the cytotoxic effects induced by the neurotoxin, increasing cell viability with the consistent maintenance of both nuclear and cell morphology. In contrast, pre-treatment with CIT 50 and 60 µM or plain SLNs for 2 h followed by 6-OHDA (40 µM) did not significantly influence cell viability. (4) Conclusions: These data suggest an enhanced protection exerted by CIT-SLNs with respect to free CIT and prompt further investigation of possible molecular mechanisms that underlie this difference.

Young immigrant women and cervical cancer screening: participation and lesions detected at the first screening round.

OBJECTIVES: to evaluate if the country of origin affects participation and outcomes of cervical cancer screening. DESIGN: retrospective cohort study. SETTING AND PARTICIPANTS: all Italian and foreign women resident in the Veneto region (North-Eastern Italy) who were born between 1986 and 1992 and who had been invited for the first time through the screening programme between 2011 and 2017 were identified and included in the survey. MAIN OUTCOME MEASURES: participation to screening was calculated along with the detection of Cervical Intraepithelial Neoplasia (CIN) grade 2 or 3 and of carcinoma, by citizenship. RESULTS: 96,105 (77.5%) Italians and 27,958 (22.5%) foreign women were included. Overall, the adjusted participation was 53.3%, with large differences among the geographical study areas. The value was highest for Italian women (56.4%), while women with other citizenships showed lower attendance: 45.5% for Eastern Europe, 44.8% for Sub Saharan Africa, 40.0% for Northern Africa, 38.5% for Central and Southern America, and 36.5% for Asia. The detection of CIN2+ was higher for women from Central and Southern America (23.0‰) or from Eastern Europe (17.9‰), while it was lower for those from Italy (11.9‰), Northern Africa (7.5‰), Sub-Saharan Africa (6.6‰), and from Asia (2.5‰) (p<0.001). CONCLUSIONS: cervical screening programmes should identify and face the barriers to participation of foreign women. This is particularly important for women from geographic areas with a high prevalence of disease, such as Central and Southern America and Eastern Europe.

Polydopamine-Coated Magnetic Iron Oxide Nanoparticles: From Design to Applications.

Magnetic iron oxide nanoparticles have been extensively investigated due to their applications in various fields such as biomedicine, sensing, and environmental remediation. However, they need to be coated with a suitable material in order to make them biocompatible and to add new functionalities on their surface. This review is intended to give a comprehensive overview of recent advantages and applications of iron oxide nanoparticles coated by polydopamine film. The synthesis method of magnetic nanoparticles, their functionalization with bioinspired materials and (in particular) with polydopamine are discussed. Finally, some interesting applications of polydopamine-coated magnetic iron oxide nanoparticles will be pointed out.

Miniaturized Sensors for Detection of Ethanol in Water Based on Electrical Impedance Spectroscopy and Resonant Perturbation Method-A Comparative Study.

The development of highly sensitive, portable and low-cost sensors for the evaluation of ethanol content in liquid is particularly important in several monitoring processes, from the food industry to the pharmaceutical industry. In this respect, we report the optimization of two sensing approaches based on electrical impedance spectroscopy (EIS) and complementary double split ring resonators (CDSRRs) for the detection of ethanol in water. Miniaturized EIS sensors were realized with interdigitated electrodes, and the ethanol sensing was carried out in liquid solutions without any functionalization of the electrodes. Impedance fitting analysis, with an equivalent circuit over a frequency range from 100 Hz to 1 MHz, was performed to estimate the electric parameters, which allowed us to evaluate the amount of ethanol in water solutions. On the other hand, complementary double split ring resonators (CDSRRs) were optimized by adjusting the device geometry to achieve higher quality factors while operating at a low fundamental frequency despite the small size (useful for compact electronic packaging). Both sensors were found to be efficient for the detection of low amounts of ethanol in water, even in the presence of salts. In particular, EIS sensors proved to be effective in performing a broadband evaluation of ethanol concentration and are convenient when low cost is the priority. On the other end, the employment of split ring resonators allowed us to achieve a very low limit of detection of 0.2 v/v%, and provides specific advantages in the case of known environments where they can enable fast real-time single-frequency measurements.

Detection of Ampelovirus and Nepovirus by Lab-on-a-Chip: A Promising Alternative to ELISA Test for Large Scale Health Screening of Grapevine.

The Ampelovirus Grapevine leafroll-associated virus 3 (GLRaV-3) and the Nepovirus Grapevine fanleaf virus (GFLV) are pathogens reported in many grapevine-growing areas all over the world, main causal agents of grapevine leafroll disease and grapevine fanleaf disease, respectively. Prevention of virus spread thanks to rapid diagnosis of infected plants is a key factor for control of both diseases. Although serological (e.g., enzyme-linked immunosorbent assay-ELISA test) and molecular methods are available to reveal the presence of the viruses, they turn out to be quite expensive, time-consuming and laborious, especially for large-scale health screening. Here we report the optimization of a lab-on-a-chip (LOC) for GLRaV-3 and GFLV detection, based on an electrochemical transduction and a microfluidic multichamber design for measurements in quadruplicate and simultaneous detection of both targets. The LOC detect GLRaV-3 and GFLV at dilution factors more than 15 times higher than ELISA, providing a higher sensitivity in the detection of both viruses. Furthermore, the platform offers several advantages as easy-to-use, rapid-test, portability and low costs, favoring its potential application for large-scale monitoring programs. Compared to other grapevine virus biosensors, our sensing platform is the first one to provide a dose-dependent calibration curve combined with a microfluidic module for sample analysis and a portable electronics providing an operator-independent read-out scheme.

Non-compliance with colonoscopy after a positive faecal immunochemical test doubles the risk of dying from colorectal cancer.

BACKGROUND: The risk of colorectal cancer (CRC) among subjects with a positive faecal immunochemical test (FIT) who do not undergo a colonoscopy is unknown. We estimated whether non-compliance with colonoscopy after a positive FIT is associated with increased CRC incidence and mortality. METHODS: The FIT-based CRC screening programme in the Veneto region (Italy) invited persons aged 50 to 69 years with a positive FIT (>20 µg Hb/g faeces) for diagnostic colonoscopy at an endoscopic referral centre. In this retrospective cohort study, we compared the 10-year cumulative CRC incidence and mortality among FIT positives who completed a diagnostic colonoscopy within the programme (compliers) and those who did not (non-compliers), using the Kaplan-Meier estimator and Cox-Aalen models. RESULTS: Some 88 013 patients who were FIT positive complied with colonoscopy (males: 56.1%; aged 50-59 years: 49.1%) while 23 410 did not (males: 54.6%; aged 50-59 years: 44.9%).The 10-year cumulative incidence of CRC was 44.7 per 1000 (95% CI, 43.1 to 46.3) among colonoscopy compliers and 54.3 per 1000 (95% CI, 49.9 to 58.7) in non-compliers, while the cumulative mortality for CRC was 6.8 per 1000 (95% CI, 5.9 to 7.6) and 16.0 per 1000 (95% CI, 13.1 to 18.9), respectively. The risk of dying of CRC among non-compliers was 103% higher than among compliers (adjusted HR, 2.03; 95% CI, 1.68 to 2.44). CONCLUSION: The excess risk of CRC death among those not completing colonoscopy after a positive faecal occult blood test should prompt screening programmes to adopt effective interventions to increase compliance in this high-risk population.

Validation of a Lab-on-Chip Assay for Measuring Sorafenib Effectiveness on HCC Cell Proliferation.

Hepatocellular carcinoma (HCC) is a highly lethal cancer, and although a few drugs are available for treatment, therapeutic effectiveness is still unsatisfactory. New drugs are urgently needed for hepatocellular carcinoma (HCC) patients. In this context, reliable preclinical assays are of paramount importance to screen the effectiveness of new drugs and, in particular, measure their effects on HCC cell proliferation. However, cell proliferation measurement is a time-consuming and operator-dependent procedure. The aim of this study was to validate an engineered miniaturized on-chip platform for real-time, non-destructive cell proliferation assays and drug screening. The effectiveness of Sorafenib, the first-line drug mainly used for patients with advanced HCC, was tested in parallel, comparing the gold standard 96-well-plate assay and our new lab-on-chip platform. Results from the lab-on-chip are consistent in intra-assay replicates and comparable to the output of standard crystal violet proliferation assays for assessing Sorafenib effectiveness on HCC cell proliferation. The miniaturized platform presents several advantages in terms of lesser reagents consumption, operator time, and costs, as well as overcoming a number of technical and operator-dependent pitfalls. Moreover, the number of cells required is lower, a relevant issue when primary cell cultures are used. In conclusion, the availability of inexpensive on-chip assays can speed up drug development, especially by using patient-derived samples to take into account disease heterogeneity and patient-specific characteristics.

Stereoselective synthesis of 2-spirocyclopropyl-indolin-3-ones through cyclopropanation of aza-aurones with tosylhydrazones.

A simple and efficient approach for the synthesis of 2-spirocyclopropyl-indolin-3-ones is herein described. The method involves a diasteroselective cyclopropanation of aza-aurones with tosylhydrazones, selected as versatile carbene sources, and represents a remarkable synthetic alternative to get access to this class of C2-spiropseudoindoxyl scaffolds. The reactions proceed in the presence of a base and catalytic amounts of benzyl triethylammonium chloride and well-tolerate a broad range of substituents on both aza-aurones and tosylhydrazones to afford a series of C2-spirocyclopropanated derivatives in high yields. In addition, selected functional group transformations of the final products were explored demonstrating the synthetic potential of these indole-based derivatives.

Interval colorectal cancers after negative faecal immunochemical test in a 13-year screening programme.

OBJECTIVE: To assess faecal immunochemical test sensitivity for cancer in a very large population-based cohort followed up for six rounds with biennial faecal immunochemical test repetition. METHODS: This study is based on interval colorectal cancers diagnosed in a cohort of subjects aged 50-69 undergoing repeated faecal immunochemical test screening (six rounds) from 2002 to 2015. Test sensitivity was calculated using both the Proportional Interval Cancer Rate and the Interval Cancer Proportion method. RESULTS: Among 441,647 faecal immunochemical tests (123,347 individuals), 150 interval colorectal cancers were detected after a negative faecal immunochemical test. Interval colorectal cancer incidence rate was 1.87 per 10,000 person-years (95%CI: 1.60-2.20), and it was higher during the second interval year (rate ratio: 1.78; 95%CI: 1.28-2.47), for proximal locations (rate ratio: 3.00; 95%CI: 1.92-4.68), and among 60-71 year old subjects (rate ratio: 2.37; 95%CI: 1.61-3.50). The Proportional Interval Cancer Rate was 13.1%, with an overall faecal immunochemical test sensitivity of 86.9% (95%CI: 84.7-89.0). Sensitivity was lowest at the first round (81.5%; 95%CI: 75.6-86.2), and increased to 91.9% (95%CI: 83.9-96.5) for subsequent rounds. Applying the Interval Cancer Proportion method, sensitivity was 83.9% (95%CI: 81.3-86.2), and it was highest at the first round (89.0%; 95%CI: 85.7-91.6), ranging between 73% and 83.1% at subsequent rounds. CONCLUSIONS: A faecal immunochemical test sensitivity for cancer higher than 80% resulted in a low incidence of interval colorectal cancers, representing an accurate estimate of one of the major limits of screening programmes. Due to intrinsic biases, the Proportional Interval Cancer Rate and the Interval Cancer Proportion methods generated different trends in faecal immunochemical test sensitivity by screening round.

Advances in the Development of Innovative Sensor Platforms for Field Analysis.

Sustainable growth, environmental preservation, and improvement of life quality are strategic fields of worldwide interest and cornerstones of international policies. Humanity health and prosperity are closely related to our present choices on sustainable development. The main sources of pollution concern industry, including mining, chemical companies, and refineries, wastewater treatment; and consumers themselves. In order to guide and evaluate the effects of environmental policies, diffuse monitoring campaigns and detailed (big) data analyses are needed. In this respect, the development and availability of innovative sensor platforms for field analysis and remote sensing are of crucial relevance. In this review, we provide an overview of the area, analyzing the major needs, available technologies, novel approaches, and perspectives. Among environmental pollutants that threaten the biosphere, we focus on inorganic and organic contaminants, which affect air and water quality. We describe the technologies for their assessment in the environment and then draw some conclusions and mention future perspectives opened by the integration of sensing technologies with robotics and the Internet of Things. Without the ambition to be exhaustive in such a rapidly growing field, this review is intended as a support for researchers and stakeholders looking for current, state-of-the-art, and key enabling technologies for environmental monitoring.

Synthesis of Cyclohepta[b]indoles by (4 + 3) Cycloaddition of 2-Vinylindoles or 4H-Furo[3,2-b]indoles with Oxyallyl Cations.

The synthesis of cyclohepta[b]indole derivatives through the dearomative (4 + 3) cycloaddition reaction of 2-vinylindoles or 4H-furo[3,2-b]indoles with in situ generated oxyallyl cations is reported. Oxyallyl cations are generated from α-bromoketones in the presence of a base and a perfluorinated solvent. Cyclohepta[b]indole scaffolds are obtained under mild reaction conditions, in the absence of expensive catalysts, starting from simple reagents, in good to excellent yields and with complete diasteroselectivity. Preliminary expansion of the scope to 3-vinylindoles and to aza-oxyallyl cations is reported.

Gold-Catalyzed Cascade Reactions of 4 H-Furo[3,2- b]indoles with Allenamides: Synthesis of Indolin-3-one Derivatives.

Merging the ability of cationic gold(I) catalysts to activate unsaturated π-systems with the electrophiles-driven ring-opening reactions of furans, we describe a new approach to synthesize 2-spiroindolin-3-ones from 4 H-furo[3,2- b]indoles. The reaction occurs through a cascade sequence involving addition of a gold-activated allene to the furan moiety of the starting furoindole followed by a ring-opening/ring-closing event affording 2-spirocyclopentane-1,2-dihydro-3 H-indolin-3-ones in moderate to good yields.