The main aim of the cryogenic wide-area light detectors with excellent resolution project is the development of cryogenic light detectors with large active area (~50 mm × 50 mm) and noise energy ...resolution smaller than 20-eV RMS. Such detectors will be used to discriminate the background in next generation large-mass bolometric experiments, such as cryogenic underground observatory for rare events. In this paper, we present the fabrication process of the phonon-mediated kinetic inductance detectors (KIDs). In the first part of the project, Al KIDs have been developed. Thin film Al (40 nm) were evaporated on high quality, high resistivity (>10 kΩ·cm) Si(1 0 0) wafers using a high vacuum electron beam evaporator. Detectors were patterned by direct-write Electron Beam Lithography (EBL) using positive tone resist AR-P 669.06. To improve the energy resolution of our detector, superconductors with higher kinetic inductance, such as the substoichiometric titanium nitride (TiNx), were developed. TiNx is deposited with reactive dc magnetron sputtering. Thus, the fabrication process is subtractive and consists of EBL patterning through negative tone resist AR-N 7700 and SF6 etch using a Deep Reactive Ion Etching - Inductively Coupled Plasma. Critical temperature of TiNx samples was measured using the 4-point probe geometry.
Background suppression plays a crucial role in particle physics experiments searching for rare events, such as neutrinoless double beta decay and dark matter interactions. Bolometers, that are among ...the most competitive devices in this field, would largely benefit from the development of ultrasensitive light detectors, as the combined readout of the bolometric and light signals enables the particle identification. The CALDER collaboration is developing superconducting light detectors that will match the requirements of next generation experiments: noise lower than 20 eV, large active area (>20 cm 2 ), wide temperature range of operation, high radiopurity, and ease in fabricating hundreds of channels. For this purpose, we are exploiting the excellent energy resolution and the natural multiplexed readout provided by kinetic inductance detectors (KIDs). KIDs have already demonstrated their potentiality as direct detectors of photons for different astrophysical applications. The aim of our project is to apply this technology in particle physics, using indirect detection. These devices can be operated in a phonon-mediated approach, in which KIDs are coupled to a large insulating substrates in order to increase the active surface from a few mm2 to 25 cm 2 . We have already demonstrated the feasibility of a phonon-mediated KIDs-based light detectors, using aluminium sensors. These device reached a baseline sensitivity of around 80 eV with an overall efficiency of about 20%. Currently, we are testing new materials (e.g., Ti-Al and nonstoichiometric TiN) to enhance the sensitivity and reach the goal of our project. We present our results and the physical interpretation of the device behavior. Finally, we also discuss the impact of this project on the most advanced bolometric experiments searching for neutrinoless double beta decay and dark matter.
Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is a ligand-activated transcription factor. In addition to its canonical role in lipid and glucose metabolism, PPAR-gamma controls cell ...proliferation, death, and differentiation in several tissues. Here we have examined the expression of PPAR-gamma in ovarian tumors and the cellular and molecular consequences of its activation in ovarian cancer cells. PPAR-gamma was expressed in a large number of epithelial ovarian tumors and cell lines. The PPAR-gamma ligand ciglitazone inhibited the growth and clonogenic survival of ovarian cancer cells, inducing cell cycle arrest and cell death. Growth inhibition by ciglitazone was reversed by the PPAR-gamma antagonist GW9662, indicating the involvement of PPAR-gamma-dependent mechanisms. Microarray-based gene profiling revealed complex changes in the transcriptional program of ovarian cancer cells on treatment with ciglitazone and identified multiple pathways that may contribute to PPAR-gamma ligands' antitumor activity. Genes upregulated by ciglitazone were predominantly associated with metabolic, differentiation, and tumor-suppressor pathways, whereas downregulated genes were involved in cell proliferation, cell cycle, cell organization, and steroid biosynthesis. Collectively, our data indicate that PPAR-gamma activation by selective agonists is a valid strategy for ovarian cancer therapy and prevention, and should be tested alone and in combination with other anticancer drugs.
The growth of newly formed vessels, or neoangiogenesis, represents an important step in both physiological and pathological situations: in particular, tumour growth and metastasis require ...angiogenesis. Microvessel count (MC), which represents a measure of tumour angiogenesis, has been associated with metastatic spread in cutaneous, mammary, prostatic, head and neck, and early-stage lung cancer. In this study, the role of tumour angiogenesis as a prognostic indicator was examined in 253 primary non-small lung cancer (NSCLC) patients. Microvessels were counted by highlighting endothelial cells with anti-Factor VIII monoclonal antibody (Mab) in methacarn-fixed tumour samples. In univariat analysis, MC (P< 0.000001), sex (P=0.0036), histotype (P < 0.014), tumour status (P <0.007), and vessel invasion (P < 0.019) were significantly related to hilar and/or mediastinal nodal involvement. However, in the stepwise logistic regression analysis, MC (P<0.000003) retained the most important influence on nodal metastasis. The overall survival analysis calculated by the Kaplan-Meier method revealed that tumours with high MC ( > 25 vessels/field) were significantly associated with increased death risk (log-rank test P = 0.00067; Cox's test P = 0.00046; Gehan's Wilcoxon test P = 0.00108). In 94 patients, the development of metastatic disease during follow-up was significantly related to MC. Indeed, patients who developed metastasis during follow-up showed a higher MC, either as a dichotomous (P = 0.01) or as a continuous (P = 0.003) variable, than patients who had developed no metastasis at the time of the analysis. Moreover, in the stepwise logistic regression analysis, MC retained the most important influence on distant metastases.
CUPID-0 is the first large array of scintillating Zn 82 Se cryogenic calorimeters (bolometers) implementing particle identification for the search of the neutrinoless double beta decay (0 ν β β ). ...The detector consists of 24 enriched Zn 82 Se bolometers for a total 82 Se mass of 5.28 kg and it has been taking data in the underground LNGS (Italy) since March 2017. In this article we show how the dual read-out provides a powerful tool for the α particles rejection. The simultaneous use of the heat and light information allows us to reduce the background down to (3.2 − 1.1 + 1.3 )×10 − 3 counts/(keV kg year), an unprecedented level for cryogenic calorimeters. In a total exposure of 5.46 kg year Zn 82 Se we set the most stringent limit on the 0 ν β β decay 82 Se half-life T 1 / 2 0 ν > 4.0 × 10 24 year at 90% C.I.
Abstract 4102
several approaches have been used in AML and MDS patients (pts) in Complete Remission (CR) to detect Minimal Residual Disease (MRD) and predict the risk of relapse. The Wilms’ tumor ...gene 1 (WT1) is over-expressed in > 80% of AML and advanced MDS, making this molecule an ideal marker for MRD monitoring. We analyzed WT1 quantitative expression in pts at high risk of relapse who received an Allogeneic Hematopoietic Stem Cell Transplantation (allo-HSCT) at our Institute.
to analyze WT1 based MRD monitoring as a predictive marker of relapse in AML/MDS pts after allo-HSCT.
in this retrospective study we included 54 pts with high-risk disease (50 AML and 4 MDS) who underwent allo-HSCT (10 MRD, 13 MUD, 28 MMRD, 3 CB), mostly after a myeloablative treosulfan-based (51/54 pts) conditioning between November 2007 and January 2011. In all pts (54/54) WT1 was over-expressed in the presence of active disease. Post-transplant disease evaluations, including WT1 quantification, were performed monthly for the first six months, every three months until one year and then every six months. WT1 transcript levels were quantified in Bone Marrow (BM) by RQ-PCR, with TaqMan technology on RNA from mononucleated cells. The housekeeping gene ABL was used as control gene, with WT1 level being normalized to 10^4 copies of ABL per sample. The cut-off value for WT1 positivity in BM samples was 250 copies/10^4 copies of ABL.
at transplant 38 pts (70%) were in CR, 12 pts (22%) had refractory disease, in 4 pts (8%) BM was not evaluable and no leukemic blasts were detectable in the peripheral blood. Median follow up (FU) after allo-HSCT was of 18 months (range: 4–42). At day 30 after transplant hematologic and cytogenetic CR and full donor chimerism (STR) were documented in all 54 pts, with a median BM WT1 value of 118/10e4 ABL (range: 0–10118). 23/54 pts (43%) relapsed at a median time of 180 days after allo-HSCT (range: 60–780). Correlation of post-transplant clinical outcome and WT1 expression levels identified: 1) 24 pts in continuous CR until last FU and BM WT1 levels persistently negative; 2) 13 pts who relapsed and showed an increase of BM WT1 levels above 250 at a median time of 40 days (range: 20–80) before hematological relapse and lose of full donor chimerism; 3) 9 pts who relapsed with WT1 increase concomitant with hematological relapse. These pts missed one or more of planned disease evaluations before relapse; 4) 1 patient who relapsed without documentation of WT1 increase; 5) 7 pts who maintained the CR but showed a transient increase of BM WT1 above 250 at one or two consecutive point of FU with normalization at subsequent evaluations. In 3 of these 7 pts concomitant GvHD was documented and in 4 pts ongoing immunosuppression was discontinued shortly after WT1 data had been obtained.
WT1 expression levels in BM are effective in predicting AML/MDS relapse after allo-HSCT thus anticipating the appearance of leukemic blasts and of host chimerism. Our data prompt the use of WT1 based MRD monitoring for tailoring ‘pre-emptive’ therapeutic approaches based on exploitation of donor immunity and its putative Graft-versus-Leukemia effect. In several patents the time occurring between WT1 MRD positive results and the clinical recurrence of the disease was relatively short, thus in order to detect disease relapse in time for therapeutic intervention we suggest a monthly monitoring of WT1 levels at least for the first year after allo-HSCT.
No relevant conflicts of interest to declare.
To assess the presence and pattern of incidental interstitial lung alterations suspicious of COVID-19 on fluorine-18-fluorodeoxyglucose positron emission tomography (PET)/computed tomography (CT) (
...FFDG PET/CT) in asymptomatic oncological patients during the period of active COVID-19 in a country with high prevalence of the virus.
This is a multi-center retrospective observational study involving 59 Italian centers. We retrospectively reviewed the prevalence of interstitial pneumonia detected during the COVID period (between March 16 and 27, 2020) and compared to a pre-COVID period (January-February 2020) and a control time (in 2019). The diagnosis of interstitial pneumonia was done considering lung alterations of CT of PET.
Overall,
FFDG PET/CT was performed on 4008 patients in the COVID period, 19,267 in the pre-COVID period, and 5513 in the control period. The rate of interstitial pneumonia suspicious for COVID-19 was significantly higher during the COVID period (7.1%) compared with that found in the pre-COVID (5.35%) and control periods (5.15%) (p < 0.001). Instead, no significant difference among pre-COVID and control periods was present. The prevalence of interstitial pneumonia detected at PET/CT was directly associated with geographic virus diffusion, with the higher rate in Northern Italy. Among 284 interstitial pneumonia detected during COVID period, 169 (59%) were FDG-avid (average SUVmax of 4.1).
A significant increase of interstitial pneumonia incidentally detected with
FFDG PET/CT has been demonstrated during the COVID-19 pandemic. A majority of interstitial pneumonia were FDG-avid. Our results underlined the importance of paying attention to incidental CT findings of pneumonia detected at PET/CT, and these reports might help to recognize early COVID-19 cases guiding the subsequent management.
The project deals with the environmental problem of water consumption. The aim of this work is to experiment the recycling of dishwasher wastewater through its reuse in growing edible vegetables or ...ornamental plants; this can also accomplish the valorization of nutrients present in the wastewater. This new process allows to ensure washing functions coupled with vegetables production and to affect users’ environmental awareness and habits, following a user-centered system design approach to understand the users and involve them actively in the system development. The presented work is also aimed to experiment a multidisciplinary approach in order to face environmental problems.
Abstract 4583
the outcome of pts older than 65 with AML is dismal because of the unfavourable characteristics of the disease and the frequent co-morbidities. Intensive chemotherapeutic programs, with ...or without haematopoietic stem cells transplantation (HSCT), are not usually offered to these pts since they are considered too toxic. If treated with intensive therapeutic programs these pts show initial complete remission (CR) rates around 45% to 55% and 2 years survival of 10–20%. Since 2001 in our institution we have systematically screened AML elderly patients older than 65 yrs for comorbidites and offered to “fit” AML elderly pts an intensive approach aimed at curing the disease. In this single-center retrospective study we describe the outcome of this court of pts.
to evaluate toxicity and survival after intensive treatments in an homogeneous court of AML pts older than 65.
from 10/2001 to 3/2011 we treated 60 pts older than 65, median age 70 (66–77), 30 pts ≤70 yrs (median 68, 66–70), and 30 pts >70 (median 73, 71–77). Among AML pts older than 65 years old we considered eligible for intensive chemotherapy those with PS (ECOG) ≤ 2, renal, hepatic and cardiac function parameters within normal ranges. All pts signed informed consent for intensive chemotherapy. Diagnosis (WHO): 33 AML with MDS related changes, 4 AML with minimal differentiation, 6 AML w/o maturation, 8 AML with maturation, 5 AMML, 1 erythrolaeukemia, 1 AML with mutated NPM1, 2 t-AML. Cytogenetics: 43 intermediate risk (33 with normal karytotype), 10 high risk (7 complex, 3 with Monosomal Karyotype), 2 good risk, 5 not evaluable. Induction with one or two of the following chemo cycles was administered to each patient: FLAG-IDA (fludarabine + cytarabine + idarubicin) or 3–7 (cytarabine + daunorubicin, idarubicin or mitoxantrone), high-dose cytarabine (HiDAC). Post-remission treatment: chemotherapy (CHT) 1 patient, HiDAC 12 pts, autologous transplantation (AUTO) 14 pts, allogeneic transplantation (ALLO) 2 pts.
overall induction related mortality was 18.3%, 7% in pts ≤70 yrs, 30% in 30 pts >70 p=0.041, CR rate was 57% (34 pts), 73% in pts ≤70 yrs, 40% in pts >70 p=0.018. Relapse rate was 73.5% (25 pts), 68% pts ≤70 yrs, 83% in pts >70. Median OS was 386 days, 2 and 5 yrs OS was 38 and 19%, respectively, median DFS was 397 days and 2 yrs DFS was 22%. In pts ≤70 and >70 yrs, median OS and DFS were 574 and 313, 397 and 425 days, respectively, p=ns, 2 and 5 yrs OS was 41% and 27%, 30% and 8%, 2 yrs DFS 27% and 17%, respectively, p=ns. OS of pts who obtained the CR after induction: median 1155 and 790 days for pts ≤70 and >70 yrs, respectively, p=ns, 2 yrs OS 51% and 58%, respectively, p=ns.
our data suggest that prolonged survival can be achieved in elderly AML who are fit to receive intensive chemotherapy. Data on mortality and remission induction are very promising in pts 66–70 yrs old, whereas early death is an important cause of treatment failure in older pts (>70), together with disease relapse. However, also older pts, with a median age of 73, who obtain the CR can reach a survival plateau at 2 yrs. Overall, these results i) indicate that selection of elderly AML pts for treatment assignment should be refined by the development of new tools for oncologic-geriatric assessment rather than by PS and vital organ function evaluation ii) prompt to design of prospective trials addressing the role of intensive regimens and transplantation programs in “fit” elderly AML pts.
No relevant conflicts of interest to declare.
Peroxisome proliferator-activated receptor-δ (PPAR-δ) is a ligand-activated transcription factor. In addition to its canonical role in lipid, glucose metabolism, PPAR-δ controls cell proliferation, ...death, differentiation in several tissues. Here we have examined the expression of PPAR-δ in ovarian tumors, the cellular, molecular consequences of its activation in ovarian cancer cells. PPAR-δ was expressed in a large number of epithelial ovarian tumors, cell lines. The PPAR-δ lig, ciglitazone inhibited the growth, clonogenic survival of ovarian cancer cells, inducing cell cycle arrest, cell death. Growth inhibition by ciglitazone was reversed by the PPAR-δ antagonist GW9662, indicating the involvement of PPAR-δ- dependent mechanisms. Microarray-based gene profiling revealed complex changes in the transcriptional program of ovarian cancer cells on treatment with ciglitazone, identified multiple pathways that may contribute to PPAR-δ ligands' antitumor activity. Genes upregulated by ciglitazone were predominantly associated with metabolic, differentiation, tumorsuppressor pathways, whereas downregulated genes were involved in cell proliferation, cell cycle, cell organization, steroid biosynthesis. Collectively, our data indicate that PPAR-δ activation by selective agonists is a valid strategy for ovarian cancer therapy, prevention, should be tested alone, in combination with other anticancer drugs.
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