space and time resolved diagnostics of the enea euv discharge produced plasma source used for metrology and other applications

A discharge-produced-plasma (DPP) source emitting in the extreme ultraviolet (EUV) spectral region is running at the ENEA Frascati Research Centre. The plasma is generated in low-pressure xenon gas and efficiently emits 100-ns duration radiation pulses in the 10–20-nm wavelength range, with an energy of $20~\text{mJ}/\text{shot}/\text{sr}$ at a 10-Hz repetition rate. The complex discharge evolution is constantly examined and controlled with electrical measurements, while a ns-gated CCD camera allowed observation of the discharge development in the visible, detection of time-resolved plasma-column pinching, and optimization of the pre-ionization timing. Accurately calibrated Zr-filtered PIN diodes are used to monitor the temporal behaviour and energy emission of the EUV pulses, while the calibration of a dosimetric film allows quantitative imaging of the emitted radiation. This comprehensive plasma diagnostics has demonstrated its effectiveness in suitably adjusting the source configuration for several applications, such as exposures of photonic materials and innovative photoresists

Tissue immune profile: a tool to predict response to neoadjuvant therapy in triple negative breast cancer

Abstract: Pathological complete response (pCR) after neoadjuvant chemotherapy (NACT) can predict better survival outcomes in patients with early triple negative breast cancer (TNBC). Tumor infiltrating lymphocytes (TILs), Programmed Death-Ligand 1 (PD-L1), and Cluster of Differentiation 73 (CD73) are immune-related biomarkers that can be evaluated in the tumor microenvironment. We investigated if the contemporary expression of these biomarkers combined in a tissue immune profile (TIP) can predict pCR better than single biomarkers in TNBC. Tumor infiltrating lymphocytes (TILs), CD73 expression by cancer cells (CC), and PD-L1 expression by immune cells (IC) were evaluated on pre-NACT biopsies. We defined TIP positive (TIP+) as the simultaneous presence of TILS ≥ 50%, PD-L1 ≥ 1%, and CD73 ≤ 40%. To consider the effects of all significant variables on the pCR, multivariate analysis was performed. Akaike information criterion (AIC) and Bayesian information criterion (BIC) were used for model selection. We retrospectively analyzed 60 biopsies from patients with TNBC who received standard NACT. Pathological complete response was achieved in 23 patients (38.0%). Twelve (20.0%) cases resulted to be TIP+. The pCR rate was significantly different between TIP+ (91.7%) and TIP− (25.0%) (p < 0.0001). Using a multivariate analysis, TIP was confirmed as an independent predictive factor of pCR (OR 49.7 (6.30–392.4), p < 0.0001). Finally, we compared the efficacy of TIP versus each single biomarker in predicting pCR by AIC and BIC. The combined immune profile is more accurate in predicting pCR (AIC 68.3; BIC 74.5) as compared to single biomarkers. The association between TIP+ and pCR can be proposed as a novel link between immune background and response to chemotherapy in TNBC, highlighting the need to consider an immunological patients’ profile rather than single biomarkers

Contact X-ray microscopy of living cells by using LiF crystal as imaging detector

In this paper, the use of lithium fluoride (LiF) as imaging radiation detector to analyse living cells by single-shot soft X-ray contact microscopy is presented. High resolved X-ray images on LiF of cyanobacterium Leptolyngbya VRUC135, two unicellular microalgae of the genus Chlamydomonas and mouse macrophage cells (line RAW 264.7) have been obtained utilizingX-ray radiation in the water window energy range from a laser plasma source. The used method is based on loading of the samples, the cell suspension, in a special holder where they are in close contactwith a LiF crystal solid-state Xray imaging detector. After exposure and sample removal, the images stored in LiF by the softX-ray contactmicroscopy technique are read by an optical microscope in fluorescence mode. The clear image of the mucilaginous sheath the structure of the filamentous Leptolyngbya and the visible nucleolus in the macrophage cells image, are noteworthiness results. The peculiarities of the used X-ray radiation and of the LiF imaging detector allow obtaining images in absorption contrast revealing the internal structures of the investigated samples at high spatial resolution. Moreover, thewidedynamicrangeof theLiF imaging detector contributes to obtain high-quality images. In particular, we demonstrate that this peculiar characteristic of LiF detector allows enhancing the contrast and reveal details even when they were obscured by a nonuniform stray light

Design of a plasma discharge circuit for particle wakefield acceleration

Plasma wakefield acceleration is the most promising acceleration technique known nowadays, able to provide very high accelerating fields (10–100 GV m 1), enabling acceleration of electrons to GeV energy in few centimetres. However, the quality of the electron bunches accelerated with this technique is still not comparable with that of conventional accelerators; radiofrequency-based accelerators, in fact, are limited in the accelerating field (10–100 MV m 1) requiring therefore kilometric distances to reach the GeV energies, but can provide very bright electron bunches. Combining high brightness electron bunches from conventional accelerators and high accelerating fields reachable with plasmas could be a good compromise allowing to further accelerate high brightness electron bunches coming from LINAC while preserving electron beam quality. Following the idea of plasma wave resonant excitation driven by a train of short bunches, we have started to study the requirements in terms of plasma for SPARC-LAB [1,2]. In particular, here we focus on the ionization process; we show a simplified model to study the evolution of plasma induced by discharge, very useful to design the discharge circuit able to fully ionize the gas and bring the plasma at the needed temperature and density

Lithium fluoride coloration by laser-plasma soft x-rays: A promising tool for X-ray microscopy and photonics

A new imaging detector for EUV or soft-X-ray radiation based on optically stimulated luminescence (OSL) of lithium fluoride (LiF) films or crystals is presented. The first micro-radiography images of biological samples and of meshes obtained on LiF using a laser-plasma source or an X-ray laser are shown, and (up to now) a resolution better than one micron is demonstrated. The dependence of the coloration density vs the deposited X-ray dose is considered and the advantages of this new diagnostic technique for both coherent and non-coherent EUV sources, compared with CCDs detectors, photographic films and photoresists are discussed. This new detector is extremely suitable for laser plasmas and for X-ray lasers sources

The agnostic role of site of metastasis in predicting outcomes in cancer patients treated with immunotherapy

Immune checkpoint inhibitors have revolutionized treatment and outcome of melanoma and many other solid malignancies including non-small cell lung cancer (NSCLC) and renal cell carcinoma (RCC). Unfortunately, only a minority of patients have a long-term benefit, while the remaining demonstrate primary or acquired resistance. Recently, it has been demonstrated that the prevalence of programmed death-ligand 1 (PD-L1) and tumor-infiltrating lymphocytes (TILs) varies based on the anatomical site of metastases. In particular, liver seems to have more immunosuppressive microenvironment while both the presence of lymph nodal disease and lung metastases seem to have the highest prevalence of PD-L1 and TILs. The aim of the present study is to investigate the possible role of site of metastases as a predictive factor for response or resistance to immunotherapy in several types of cancer. In this multicenter retrospective study, we enrolled patients with metastatic NSCLC, melanoma, RCC, urothelial, merkel carcinoma, and colon cancer who received immunotherapy from April 2015 to August 2019. Major clinicopathological parameters were retrieved and correlated with patients' survival outcomes in order to assess their prognostic value and build a useful tool to assist in the decision-making process. A total of 291 patients were included in this study. One hundred eighty-seven (64%) patients were male and 104 (36%) female. The tumor histology was squamous NSCLC in 56 (19%) patients, non-squamous NSCLC in 99 (34%) patients, melanoma in 101 (35%) patients, RCC in 28 (10%) patients, and other tumors in the remaining 7 (2%) patients. The number of metastatic sites was 1 in 103 patients (35%), 2 in 104 patients (36%) and 3 in 84 patients (29%). Out of 183 valuable patients, the entity of response was complete response (CR), partial response (PR), stable disease (SD), and progression disease (PD) in 15, 53, 31, and 79 patients, respectively. Using an univariate analysis (UVA), tumor burden (p = 0.0004), the presence of liver (p = 0.0009), bone (p = 0.0016), brain metastases (p < 0.0001), the other metastatic sites (p = 0.0375), the number of metastatic sites (p = 0.0039), the histology (p = 0.0034), the upfront use of immunotherapy (p = 0.0032), and Eastern Cooperative Oncology Group (ECOG) Perfomance status (PS) ≥ 1 (p < 0.0001) were significantly associated with poor overall survival (OS). Using a multivariate analysis (MVA) the presence of liver (p = 0.0105) and brain (p = 0.0026) metastases, the NSCLC diagnosis (p < 0.0001) and the ECOG PS (p < 0.0001) resulted as significant prognostic factors of survival. Regarding the progression free survival (PFS), using a UVA of the tumor burden (p = 0.0004), bone (p = 0.0098) and brain (p = 0.0038) metastases, the presence of other metastatic sites (p = 0.0063), the number of metastatic sites (p = 0.0007), the histology (p = 0.0007), the use of immunotherapy as first line (p = 0.0031), and the ECOG PS ≥ 1 (p ≤ 0.0001) were associated with a lower PFS rate. Using an MVA, the presence of brain (p = 0.0088) and liver metastases (p = 0.024) and the ECOG PS (p < 0.0001) resulted as predictors of poor PFS. Our study suggests that the site of metastases could have a role as prognostic and predictive factor in patients treated with immunotherapy. Indeed, regardless of the histology, the presence of liver and brain metastases was associated with a shorter PFS and OS, but these results must be confirmed in further studies. In this context, a deep characterization of microenvironment could be crucial to prepare patients through novel strategies with combination or sequential immunotherapy in order to improve treatment response

A new medical record proposal to the prognostic risk assessment for mronj in oncologic patients: “Sapienza head and neck unit” proposal

Medication-related osteonecrosis of the jaw (MRONJ) is an adverse event associated with antiresorptive and antiangiogenic drugs. The use of these drugs in the treatment of cancer patients with bone metastasis is necessary and standardized in the literature. A multidisciplinary approach for the patient’s management is strongly recommended. Therefore, it should be necessary to integrate the path of these subjects with a dedicated dental screening in order to first assess the individual risk of developing a MRONJ, and then to plan dental treatments and oral hygiene sessions, and finally to schedule a follow-up to intercept and treat early osteonecrosis. The aim of this manuscript is to propose a new simple medical report to evaluate patients affected by metastatic bone cancer in order to reduce the risk of developing MRONJ

x ray imaging of bio medical samples using laser plasma based x ray sources and lif detector

This contribution to ECPD2019 is dedicated to the memory of Anatoly Faenov. During a period of approximately thirteen years 1994–2006, Anatoly and his wife Tatiana Pikuz (simply "Tania" for friends), accepting the frequent invitations of the National Institute for Nuclear Physics (INFN) and of the Italian National Agency for New Technologies, Energy and Sustainable Economic Development (ENEA), cooperated with many Italian research laboratories dedicated to EUV and soft X-ray generation, spread in different towns (L'Aquila, Frascati, Milano, Padova, Pisa, Roma, etc.). In spite of the fact that they could stay in Italy only about one or two months per year, their activity was so intense that more than 50 peer- reviewed publications were generated from their experimental and theoretical work (just considering only the results obtained at L'Aquila and Tor Vergata—Rome Universities and at the ENEA Research Center of Frascati), without mentioning the cultural atmosphere that they stimulated in the field of Science and Humanity. The numerous experimental spectra obtained at ENEA by means of their spherically bent mica spectrometers, together with the corresponding theoretical simulations performed in Moscow, allowed to study the changing role of different excitations mechanisms for various plasma conditions, and to characterize at best the ENEA laser-plasma source for different applications: polychromatic and monochromatic micro-radiography of dried biological samples at 1 keV, soft X-ray contact microscopy (SXCM) of living cells in the water-window spectral region, spectroscopy of hollow atoms, etc. In this memorial paper, the main results of biological samples imaging on lithium fluoride (LiF) detectors, obtained with the ENEA and Tor Vergata University laser-plasma sources, are presented. In particular, the improvement of the micro-radiography and of the SXCM techniques obtained after moving from photoresist detectors and photographic films to lithium fluoride (LiF) detectors are discussed, for both dried and wet biological samples