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A space-based detector dedicated to measurements of γ-rays and charged particles has to achieve a balance between different instrumental requirements. A good angular resolution is necessary for the γ-rays, whereas an excellent geometric factor is needed for the charged particles. The tracking reference technique of γ-ray physics is based on a pair-conversion telescope made of passive material (e.g., tungsten) coupled with sensitive layers (e.g., silicon microstrip). However, this kind of detector has a limited acceptance because of the large lever arm between the active layers, needed to improve the track reconstruction capability. Moreover, the passive material can induce fragmentation of nuclei, thus worsening charge reconstruction performances. The Tracker-In-Calorimeter (TIC) project aims to solve all these drawbacks. In the TIC proposal, the silicon sensors are moved inside a highly-segmented isotropic calorimeter with a couple of external scintillators dedicated to charge reconstruction. In principle, this configuration has a good geometrical factor, and the angle of the γ-rays can be precisely reconstructed from the lateral profile of the electromagnetic shower sampled, at different depths in the calorimeter, by silicon strips. The effectiveness of this approach has been studied with Monte Carlo simulations and validated with beam test data of a small prototype.

Background: Melanoma is a serious skin cancer that has been on the rise in the United States. Some genetic component is apparent. Purpose: The purpose of this study was to identify demographic, clinical, attitudinal, and health belief factors associated with intention to obtain genetic testing for hereditary melanoma among unaffected first-degree relatives of melanoma patients at low to moderate risk for hereditary melanoma. Methods: Using contact information provided by index cases diagnosed with melanoma, 92 unaffected first-degree relatives were asked to complete questionnaires via mail. Results: The average age of respondents was 45.7 (plus or minus 12.8) years, and the majority were female (59%), currently married (80%), and Caucasian (98%). Only 11% of the sample was aware of genetic testing for hereditary melanoma prior to the survey. However, once such a test was described, 48% said they would take the test in the next six months if it were made available to them. Logistic regression analyses revealed that being married, physician recommendation, and helping family members make health care decisions were associated with intention to obtain genetic testing. Discussion: In light of these results, health education efforts for low-to-moderate-risk patients should include information about the clinical utility of genetic testing and the implications of test results for family members. Translation to Health Education Practice: As genetic testing for cancer becomes more widely available, demand for information will increase as well. Health educators will be instrumental in meeting the increased demand for such information and ensuring that those at low risk are appropriately informed and reassured. (Contains 3 tables.)

The Large Observatory For x-ray Timing (LOFT) was studied within ESA M3 Cosmic Vision framework and participated in the final downselection for a launch slot in 2022-2024. Thanks to the unprecedented combination of effective area and spectral resolution of its main instrument, LOFT will study the behaviour of matter under extreme conditions, such as the strong gravitational field in the innermost regions of accretion flows close to black holes and neutron stars, and the supranuclear densities in the interior of neutron stars. The science payload is based on a Large Area Detector (LAD, 10 m2 effective area, 2-30 keV, 240 eV spectral resolution, 1° collimated field of view) and a Wide Field Monitor (WFM, 2-50 keV, 4 steradian field of view, 1 arcmin source location accuracy, 300 eV spectral resolution). The WFM is equipped with an on-board system for bright events (e.g. GRB) localization. The trigger time and position of these events are broadcast to the ground within 30 s from discovery. In this paper we present the status of the mission at the end of its Phase A study.

Here we provide demonstration that fast fluorescence fluctuation spectroscopy is a fast and robust approach to extract information on the dynamics of molecules enclosed within subcellular nanostructures (e.g., organelles or vesicles) which are also moving in the complex cellular environment. In more detail, Raster Image Correlation Spectroscopy (RICS) performed at fast timescales (i.e., microseconds) reveals the fast motion of fluorescently labeled molecules within two exemplary dynamic subcellular nanostructures of biomedical interest, the lysosome and the insulin secretory granule (ISG). The measurement of molecular diffusion is then used to extract information on the average properties of subcellular nanostructures, such as macromolecular crowding or molecular aggregation. Concerning the lysosome, fast RICS on a fluorescent tracer allowed us to quantitatively assess the increase in organelle viscosity in the pathological condition of Krabbe disease. In the case of ISGs, fast RICS on two ISG-specific secreting peptides unveiled their differential aggregation propensity depending on intragranular concentration. Finally, a combination of fast RICS and feedback-based 3D orbital tracking was used to subtract the slow movement of subcellular nanostructures from the fast diffusion of molecules contained within them and independently validate the results. Results presented here not only demonstrate the acquired ability to address the dynamic behavior of molecules in moving, nanoscopic reference systems, but prove the relevance of this approach to advance our knowledge on cell function at the subcellular scale.

A new generation magnetic spectrometer in space will open the opportunity to investigate the frontiers in direct high-energy cosmic ray measurements and to precisely measure the amount of the rare antimatter component in cosmic rays beyond the reach of current missions. We propose the concept for an Antimatter Large Acceptance Detector In Orbit (ALADInO), designed to take over the legacy of direct measurements of cosmic rays in space performed by PAMELA and AMS-02. ALADInO features technological solutions conceived to overcome the current limitations of magnetic spectrometers in space with a layout that provides an acceptance larger than 10 m2 sr. A superconducting magnet coupled to precision tracking and time-of-flight systems can provide the required matter–antimatter separation capabilities and rigidity measurement resolution with a Maximum Detectable Rigidity better than 20 TV. The inner 3D-imaging deep calorimeter, designed to maximize the isotropic acceptance of particles, allows for the measurement of cosmic rays up to PeV energies with accurate energy resolution to precisely measure features in the cosmic ray spectra. The operations of ALADInO in the Sun–Earth L2 Lagrangian point for at least 5 years would enable unique revolutionary observations with groundbreaking discovery potentials in the field of astroparticle physics by precision measurements of electrons, positrons, and antiprotons up to 10 TeV and of nuclear cosmic rays up to PeV energies, and by the possible unambiguous detection and measurement of low-energy antideuteron and antihelium components in cosmic rays.

This study aimed to determine if dietary modifications using a nutritional regimen could prevent or reduce the incidence of cancer therapy-induced diarrhea in patients with metastatic colorectal cancer and to evaluate the relationship of Vitamin D blood levels with diarrhea severity. Patients with metastatic colorectal cancer were enrolled. A Mediterranean diet, containing some special limitations aiming to reduce the risk of diarrhea, was administered before and during the entire chemotherapy program. Enrolled patients numbering 60/137 (44%) had diarrhea during chemotherapy. Adherence to the diet was high in 36 (26.3%) patients, medium in 94 (68.6%), and low in 7 (5.1%). Mean adherence to the diet was significantly lower in patients who experienced diarrhea with maximum grade 2–3 compared to those who had no diarrhea or grade 1 diarrhea (score = 5.4 ± 1.9 vs. 7.1 ± 1.5, p < 0.001). Patients with higher adherence to the diet had a lower risk of grade 2–3 diarrhea (odds ratio: 0.5 (95% CI: 0.3–0.7, p < 0.001)). In addition, patients who completed a higher number of chemotherapy cycles had an increased risk of grade 2–3 diarrhea (odds ratio: 1.2 (95% CI: 1.0–1.5, p = 0.02)). Of note, a lower level of Vitamin D correlated with an increased risk of G2-G3 diarrhea (p = 0.03). A diet based on vegetables with a controlled fiber content, Mediterranean Modified Healthy Diet (MMHD), is useful to control the incidence of cancer therapy-induced diarrhea.

In the last decade, cardiologists and oncologists have provided clinical and experimental evidence that cancer, and not only chemotherapeutic agents, can cause detrimental effects on heart structure and function, a consequence that has serious clinical implications for patient management. In parallel, the intriguing idea that heart failure (HF) may be an oncogenic condition has also received growing attention. A number of epidemiological and clinical studies have reported that patients with HF have a higher risk of developing cancer. Chronic low-grade systemic inflammation has been proposed as a major pathophysiological process linking the failing heart to the multi-step process of carcinogenesis. According to this view, pro-inflammatory mediators secreted by the damaged heart generate a favorable milieu that promotes tumor development and accelerates malignant transformation. HF-associated inflammation synergizes with tumor-associated inflammation, so that over time it is no longer possible to distinguish the effects of one or the other. Experimental studies have just begun to search for the molecular effectors of this process, with the ultimate goal that of identifying mechanisms suitable for anti-cancer target therapy to reduce the risk of incident cancer in patients already affected by HF. In this review we critically discuss strengths and limitations of clinical and experimental studies that support a causal relationship between HF and cancer, and focus on HF-associated inflammation, cardiokines and their endocrine functions linking one and the other disease.

Background: GOLFIG is a chemo-immunotherapy regimen established in preclinical models that combines gemcitabine + FOLFOX (fluoropyrimidine backbone coupled to oxaliplatin) poly-chemotherapy with low-dose s. c. recombinant interleukin-2 (rIL-2) and granulocyte-macrophage colony stimulating factor (GM-CSF). Promising antitumor effects in metastatic colorectal cancer (mCRC) patients were obtained in previous phase II and III trials. Here we report the results of 15 years of follow-up.Methods: This is a multi-institutional retrospective analysis including 179 mCRC patients receiving GOLFIG regimen between June 2002 and June 2018. Sixty-two of them received the treatment as frontline (enrolled in the GOLFIG-2 phase III trial) and 117 as second/third line (49 enrolled in the GOLFIG-1 phase II trial and 68 as compassionate use). One hundred twelve patients showed a primary left side and 67 a primary right side; K/N-ras mutational status was available in 74 cases, and an activating mutation was detected in 33. Kaplan–Meier and Cox regression analyses were carried out to relate PFS and OS with different parameters.Results: Overall, we recorded a mean PFS and OS of 15.28 (95% CI: 10.36–20.20) and 24.6 (95% CI: 19.07–30.14) months, respectively, with 14 patients surviving free of progression for 10 years. This regimen, in our updated survey of the GOLFIG-2 trial, confirmed superiority over FOLFOX in terms of PFS (hazard ratio (HR) = 0.58, p = 0.006) with a trend to a longer OS (HR = 0.69, P = 0.06) in the first line. Our analysis also confirmed significant antitumor activity in pre-treated patients, reporting a mean PFS and OS of 12.55 (95% CI: 7.19–17.9) and 20.28 (95% CI: 14.4–26.13) months, respectively. Immune-related adverse events (irAEs) were recorded in 24% of the cases and were related to a longer survival (HR = 0.36; P = 0.0001). Finally, patients' outcome was not correlated to sex, sidedness, and MT-K/N-ras.Conclusions: The GOLFIG regimen is a reliable underestimated therapeutic option in pre-treated mCRC patients and offers a strong rationale to design further trials.

An immune checkpoint blockade with mAbs to PD-1 and PD-L1 is an expanding therapeutic option for mNSCLC patients. This treatment strategy is based on the use of mAbs able to restore the anti-tumor activity of intratumoral T cells inhibited by PD-1 binding to PD-L1/2 on tumor and inflammatory cells. It has been speculated that a chronic status of systemic inflammation as well as the immunosenescence physiologically occurring in elderly patients may affect the efficacy of the treatment and the occurrence of irAEs. We performed a multi-institutional retrospective study aimed at evaluating the effects of these mAbs (nivolumab or atezolizumab) in 117 mNSCLC patients younger (90 cases) and older (27 cases) than 75 years in correlation with multiple inflammatory parameters (NLR, CRP, ESR, LDH and PCT). No differences were observed when the cohorts were compared in terms of the frequency of PFS, OS, inflammatory markers and immune-related adverse events (irAEs). Similarly, the occurrence of irAEs was strictly correlated with a prolonged OS survival in both groups. On the contrary, a negative correlation between the high baseline levels of inflammatory markers and OS could be demonstrated in the younger cohort only. Overall, PD-1/PD-L1-blocking mAbs were equally effective in young and elderly mNSCLC patients; however, the detrimental influence of a systemic inflammation at the baseline was only observed in young patients, suggesting different aging-related inflammation immunoregulative effects.

BACKGROUND Since the advent of high-throughput sequencing technologies, organised germline screening, independent of the personal and family cancer history, has been frequently proposed. Since ethnic and geographic populations significantly differ in their mutation spectra and prevalence, one critical prerequisite would be the knowledge of the expected carrier frequencies. OBJECTIVE For the first time, in a retrospective non-cancer related cohort from a single Swiss genetic centre, we systematically assessed the prevalence of secondary findings in 19 genes (BRCA1/2 plus 17 non-BRCA genes) previously designated by the US National Comprehensive Cancer Network (NCCN) for hereditary breast and ovarian cancer (HBOC) germline testing. DESIGN A total of 400 individuals without a cancer diagnosis undergoing whole-exome sequencing (WES) analysis for neurodevelopmental disorders (NDDs) from 2015 to 2017 at IMG Zurich were included after quality assessment. Among these, 180 were unaffected parental couples, 27 unaffected parental singles and 13 NDD index patients (mean age 43 years). The majority of the cohort was of Caucasian ethnicity (n = 336, 84.0%) and of Northwest European ancestry (n = 202, 50.5%), for 70 of whom (42.5%) an autochthonous Swiss descent was assumed. For WES filtering of rare, potentially actionable secondary variants in HBOC genes, an overall minor allele frequency (MAF) below 0.65% was used as cut-off. Each rare variant was manually evaluated according to the recommended ACGM-AMP standards, with some adaptations including “hypomorphic” as an additional distinct pathogenicity class. RESULTS Overall, 526 rare secondary variants (339 different variants) were encountered, with the BRCA1/2 genes accounting for 27.2% of the total variant yield. If stratified for variant pathogenicity, for BRCA1/2, three pathogenic variants were found in three females of Italian ancestry (carrier frequency of 0.8%). In the non-BRCA genes, five carriers of (likely) pathogenic variants (1.3%) were identified, with two Swiss individuals harbouring the same CHEK2 Arg160Gly variant known to be recurrent among Caucasians. Hence, the overall carrier rate added up to 2.0%. Additionally, seven various hypomorphic HBOC predisposing alleles were detected in 22 individuals (5.5%). CONCLUSION We provide the first evidence of a high prevalence of HBOC-related cancer susceptibility in the heterogeneous Swiss general population and relevant subpopulations, particularly in individuals of Italian descent. These pioneering data may substantiate population-based HBOC screening in Switzerland.

The quality of coffee is linked to the aroma created by the chemical reactions that occur during the roasting process. While it is generally thought that roasted coffee is a stable product with a relatively long shelf-life, little information is available on the evolution (kinetic) of the volatile organic compounds (VOCs) in the days immediately following the process. The aim of this study is to determine the evolution of VOCs released by coffee beans, on samples of Coffea arabica (three different origins) and Coffea canephora (1 single origin), by using a Proton Transfer Reaction Time-of-Flight Mass Spectrometer (PTR-ToF-MS) 24 hours after roasting, and for the next 9 days. Results confirmed the differences already highlighted in previous studies between the VOCs spectra of the two species. There were also significant differences in the intensity of emissions for the different origins of Coffea arabica, with the highest VOCs amount over time always detected in the Honduras Arabica samples. The involved detected protonated ions were grouped into three classes: compounds (ppbv) present with decreasing quantity ; weakly increasing; almost constant trend; or always increasing. A complex dynamic emerged for the different protonated ions over time, which not only affects the mass spectra of the different species but also influences the configuration of the mass spectra of the different geographical zones of production.

Poplar and willow demonstrate great potential for the phytoextraction of trace elements (TEs) from soils. In most cases, these species are managed as short-rotation coppice, producing high woody biomass yields, which could provide a valuable contribution toward reducing greenhouse gas emissions in the atmosphere. In the current study, we compared the TE extraction and CO2 sequestration rates in a four-year field trial in Southern Italy of two arboreal species (willow and poplar). The results show that, once established in the study area, willow extracted more Cd and Cu and less Pb than poplar. The two species demonstrated the same average Ni and Zn extraction rates. Greater biomass yields in poplar suggest that this species was able to fix greater amounts of CO2 (28.7 Mg ha−1 yr−1) than willow (24.9 Mg ha−1 yr−1). We argue that the choice of the species to be used in phytoextraction should first be made considering the TE-specific affinity and phytoextraction rates. For TEs whose extraction rates were the same (i.e., Ni and Zn), poplar is to be preferred because of its ability to fix greater amounts of CO2 than willow.

Quince is characterized as a fragrant fruit which, unlike other pomes (apple, pear), is not used for fresh consumption due to its astringency and compactness, but only in its processed form (jams, jelly, distillery products, and nutraceutical compounds). As a consequence, there is little knowledge currently available concerning the characteristics of the fruit, and in particular its aromatic and chemotaxonomic patterns. In this work, carpometric, chemometric and spectrophotometric measurements were performed on quince fruits. VOCs emitted by different tissues or parts of the fruit were studied to describe its aromatic profile. The study was carried out on the fruits of an old, well-known cultivar (‘Gigante di Wranja’, commonly called ‘Wranja’) and a new Tuscan accession. Intact, halved and solely pulp (cubed) samples were evaluated for each individual fruit. Data obtained from VOC analysis through Proton Transfer Reaction Time-of-Flight Mass Spectrometer (PTR-ToF-MS) were evaluated by multivariate statistical analysis. The spectra obtained from the intact fruit samples showed a higher amount of masses corresponding to terpenes or terpenoid compounds, which fundamentally characterize the aroma of this type of fruit; these substances were found to be much less present in the VOCs emitted by the pulp, where high values of masses linked to the maturation processes were instead found.

Virgin olive oils (VOOs) are characterized by peculiar flavors appreciated by the consumers all over the world. Their organoleptic characteristics depend on the aromatic properties of the fruits of the different cultivars, which will originate the final products. VOCs spectra of fifteen certified Italian olive cultivars of the University of Florence Germplasm collection, chosen as their different geographical origin, diffusion, and product purpose, were acquired using a Proton Transfer Reaction Time-of-Flight Mass Spectrometer (PTR-ToF-MS). The VOCs analyses highlighted a great variability among the fifteen cultivars, mostly due to compounds (C6 and C5) deriving from polyunsaturated fatty acids through the LOX pathway. The early identification in the olive fruit of these compounds which are considered among the major contributors to the positive VOOs attributes, would be useful to produce high quality olive oils, and get useful information to individuate the best parents for the genetic improvement.

In this work the emission of volatile organic compounds (VOCs) upon the heating process of an extra virgin olive oil (EVOO) and a high oleic sunflower oil (SFO) was evaluated in real time by spectrometry. Two tests were carried out, in the first VOCs emitted from both kinds of oil were measured at room temperatures (not heated, NH) and at 180°C; in the second test, VOCs emission for selected masses were monitored under increasing temperatures over time: at room temperature not heated oils (NH), 60, 90, 120, 150, and 180°C, respectively. The spectra were acquired using a Proton Transfer Reaction Time of Flight Mass Spectrometer (PTR-ToF-MS). The total VOCs emission increased at 180°C, determined both by the rise of the amount of compounds present in the NH samples and by the formation of new masses generated by oxidative chemical reaction from triglycerides and fatty acids. From the set of results it is evident that a good control of the temperatures can be useful in reducing the quantities of masses potentially harmful to health in human food.

High-grade gliomas (HGGs) are the most frequently diagnosed primary brain tumors. Even though it has been demonstrated that combined surgical therapy, chemotherapy, and radiotherapy improve survival, HGGs still harbor a very poor prognosis and limited overall survival. Differently from other types of primary neoplasm, HGG manifests also as a neurological disease. According to this, palliative care of HGG patients represents a peculiar challenge for healthcare providers and caregivers since it has to be directed to both general and neurological cancer symptoms. In this way, the end-of-life (EOL) phase of HGG patients appears to be like a journey through medical issues, progressive neurological deterioration, and psychological, social, and affective concerns. EOL is intended as the time prior to death when symptoms increase and antitumoral therapy is no longer effective. In this phase, palliative care is intended as an integrated support aimed to reduce the symptoms burden and improve the Quality Of Life (QOL). Palliative care is represented by medical, physical, psychological, spiritual, and social interventions which are primarily aimed to sustain patients’ functions during the disease time, while maintaining an acceptable quality of life and ensuring a dignified death. Since HGGs represent also a family concern, due to the profound emotional and relational issues that the progression of the disease poses, palliative care may also relieve the distress of the caregivers and increase the satisfaction of patients’ relatives. We present the results of a literature review addressed to enlighten and classify the best medical, psychological, rehabilitative, and social interventions that are addressed both to patients and to their caregivers, which are currently adopted as palliative care during the EOL phase of HGG patients in order to orientate the best medical practice in HGG management.