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Background and aim Near infra-red/indocyanine green imaging fluorescence (NIR/ICG) technology is showing promising results in several fields of surgical oncology. However, the clinical value of NIR/ICG technology in the surgical treatment of advanced gastric cancer (AGC) is not clearly established. Indeed, although lymphadenectomy is one of the main steps in curative-intent surgery for gastric cancer and lymph node status is the most important prognostic factor for survival, several questions have risen in literature on considering the overall number of harvested lymph nodes as the best indicator of the NIR/ICG technology clinical value. At present, no data exist regarding the ability of NIR/ICG technology to modify the surgical conduct at the moment of lymphadenectomy. Methods This is the ‘iGreenGO’ (indocyanine Green Gastric Observation) study protocol: an international, prospective, multicentre study. Study population will be a cohort of Western patients undergoing preoperative upper gastrointestinal endoscopy with submucosal peritumoral ICG injection followed by curative-intent minimally invasive gastrectomy with D2 lymphadenectomy for locally AGC. High-volume western academic and non-academic hospitals will be allowed to participate in the study. The primary endpoint will be the ‘change of the surgical conduct’ (CSC) at the moment of intraoperative NIR/ICG technology activation after completing a D2 lymphadenectomy ‘with the naked eye’. Key secondary endpoints will be the identification of preoperative clinical variables potentially associated with CSC, the number of additional LNs retrieved and pTNM stage migration using NIR/ICG technology, abdominal fluorescence location according to patient’s and tumor’s characteristics. Results The sample size was calculated by considering the estimated incidence of intraoperative change of the surgical conduct when using NIR/ICG technology. Data from the literature indirectly suggest an approximate rate of such event around 17%. A sample size of 350 patients will be necessary to obtain a measurement with an estimated precision of 4% with a confidence level of 1-alfa = 95%. Conclusion The iGreenGO study will be the first western study to investigate the intraoperative clinical role of NIR/ICG technology in surgical treatment of AGC in a large cohort of Western patients. Results from the present study can further clarify the role of the NIR/ICG technology in helping the surgeon during lymphadenectomy for AGC.

Optical communications, imaging, and biomedicine require efficient detection of infrared radiation. Growing demand pushes for the integration of such detectors on chips. It is a challenge for conventional semiconductor devices to meet these specs due to spectral limitations arising from their finite band gap, as well as material incompatibilities. Single layer graphene (SLG) is compatible with complementary metal-oxide-semiconductor (CMOS) Si technology, while its broadband (UV to THz) absorption makes the SLG/Si junction a promising platform for photodetection. Here we model the thermionic operation of SLG/Si Schottky photodetectors, considering SLG’s absorption, heat capacity, and carrier cooling dependence on temperature and carrier density. We self-consistently solve coupled rate equations involving electronic and lattice temperatures, and nonequilibrium carrier density under light illumination. We use as an example the infrared photon energy of 0.4 eV, below the threshold for direct photoemission over the Schottky barrier, to study the photothermionic response as a function of voltage bias, input power, pulse width, electronic injection, and relaxation rates. We find that device and operation parameters can be optimized to reach responsivities competitive with the state of the art for any light frequency, unlike conventional semiconductor-based devices. Our results prove that the SLG/Si junction is a broadband photodetection platform.

This commentary describes the unusual self-portrait contributed by a 26-year-old receiving treatment for relapsing medulloblastoma to a photography project undertaken by a group of patients as part of the Youth Project, a scheme dedicated to young cancer patients with the dual aim of optimizing medical aspects of their care and promoting a holistic approach to their needs. The article briefly describes how creative projects can play an important part in giving young people with cancer new ways to tell their stories and express their feelings. There is still a limited understanding of the specific needs of adolescents and young adults with cancer, and it is important to draw attention to them and to the need to devise a person-centered approach to cancer patients in this age group.

Purpose: Preclinical studies demonstrated that a DNA vaccine (pTVG-AR, MVI-118) encoding the androgen receptor ligand-binding domain (AR LBD) augmented antigen-specific CD8+ T cells, delayed prostate cancer progression and emergence of castration-resistant disease, and prolonged survival of tumor-bearing mice. This vaccine was evaluated in a multicenter phase I trial. Patients and Methods: Patients with metastatic castration-sensitive prostate cancer (mCSPC) who had recently begun androgen deprivation therapy were randomly assigned to receive pTVG-AR on one of two treatment schedules over one year, and with or without GM-CSF as a vaccine adjuvant. Patients were followed for 18 months. Primary objectives were safety and immune response. Secondary objectives included median time to PSA progression, and 18-month PSA-PFS (PPFS). Results: Forty patients were enrolled at three centers. Twenty-seven patients completed treatment and 18 months of follow-up. Eleven patients (28%) had a PSA progression event before the 18-month time point. No grade 3 or 4 adverse events were observed. Of 30 patients with samples available for immune analysis, 14 (47%) developed Th1-type immunity to the AR LBD, as determined by IFNγ and/or granzyme B ELISPOT. Persistent IFNγ immune responses were observed irrespective of GM-CSF adjuvant. Patients who developed T-cell immunity had a significantly prolonged PPFS compared with patients without immunity (HR = 0.01; 95% CI, 0.0–0.21; P = 0.003). Conclusions: pTVG-AR was safe and immunologically active in patients with mCSPC. Association between immunity and PPFS suggests that treatment may delay the time to castration resistance, consistent with preclinical findings, and will be prospectively evaluated in future trials. See related commentary by Shenderov and Antonarakis, p. 5056

Primary hypothyroidism commonly occurs after radiotherapy (RT), and coincides with increased circulating thyroid-stimulating hormone (TSH) levels.We tested therefore the protective effect of suppressing TSH with L-thyroxine during RT for medulloblastoma/PNET and Hodgkin lymphoma (HL) in a prospective cohort study. From1998 to 2001, a total of 37 euthyroid children with medulloblastoma/PNET plus 14 with HL, scheduled for craniospinal irradiation and mediastinum/neck radiotherapy, respectively, underwent thyroid ultrasound and free triiodothyronine (FT3), free thyroxine (FT4), and TSH evaluation at the beginning and end of craniospinal iiradiation. From 14 days before and up to the end of radiotherapy, patients were administered L-thyroxine checking every 3 days TSH to ensure a value < 0.3 μIU/mL. During follow-up, blood tests and ultrasound were repeated; primary hypothyroidism was considered an increased TSH level greater than normal range. Twenty-two/37 patients with medulloblastoma/PNET and all the 14 patients with HL were alive after a median 231 months from radiotherapy with 7/22 and 8/14 having correctly reached TSH levels < 0.3 μIU/mL and well matched for other variables. Twenty years on, hypothyroidism-free survival rates differed significantly, being 60% ± 15% and 15.6% ± 8.2% in TSH-suppressed vs. not-TSH suppressed patients, respectively (P = 0.001). These findings suggest that hypothyroidism could be durably prevented in two populations at risk of late RT sequelae, but it should be confirmed in a larger cohort.

Ultrafast and sensitive (noise equivalent power, This is the unedited authors' version of the article accepted for publication in Nanophotonics 2020 (Online ISSN: 2192-8614)

Resumen No existe un tratamiento medico curativo para el hallux valgus, pero el tratamiento precoz y especifico puede a veces mejorar la tolerabilidad. Con demasiada frecuencia se ignora la eficacia del tratamiento conservador: una revision de la literatura de 2015 senala efectos beneficiosos con reduccion del dolor y correccion de la deformacion, pero ningun estudio lo ha evaluado a largo plazo. Al ser cada paciente distinto y tener cada podologo sus propias practicas, el primer objetivo es definir lo que se desea corregir, compensar o modificar: las posibilidades tecnicas quedan a la libre eleccion del profesional de acuerdo con su paciente, sea cual sea la situacion clinica, es decir, no hay un tratamiento estandar. Este tratamiento paliativo solo es eficaz despues de una exploracion clinica completa, de indicaciones bien planteadas y de explicaciones claras de las soluciones buscadas. El primer tratamiento medico para un hallux valgus sintomatico es aconsejar una adaptacion del calzado al volumen del pie. El origen del dolor y las molestias causadas por la deformacion guiaran al profesional en su tratamiento.

Background: Bacteria in low abundance represent the majority of Earth’s biodiversity and perform vital ecological functions, but little is known about their biogeography nor the ecological processes that drive their community assembly in terrestrial ecosystems. Here, we investigated the community compositions and phylogenies of rare (relative abundance < 0.1%) and abundant (> 1%) soil bacteria along a transect containing three alpine grassland types (meadow, steppe, and desert) on the Tibetan Plateau. Results: Our results revealed similar biogeographical patterns of rare and abundant bacteria, with their community compositions and phylogenies shifting gradually along the transect. The similar patterns, however, were driven by contrasting community assembly processes, with rare subcommunity being more heavily influenced by stochasticity (72%) than abundant (57%). The composition of abundant subcommunity (80%) was better explained by local (including soil and vegetation factors), geospatial and climatic factors than that of rare subcommunity (41%), while the phylogeny of the rare one (36%) was better explained than that of the abundant one (29%). Variation partitioning analysis indicated that pure local factors consistently explained a higher proportion of the community composition than geospatial factors in both rare (12.3% and 8.7%, respectively) and abundant bacteria (18.3% and 14.1%, respectively). In contrast, the phylogeny of rare subcommunity was explained by local and geospatial factors equally (11.5% and 11.9%, respectively), while that of abundant subcommunity was more explained by geospatial (22.1%) than local factors (11.3%). Furthermore, our results revealed a tighter connection between the community phylogeny and composition in rare than in abundant bacteria. Conclusions: Our results revealed consistent biogeographical patterns of rare and abundant bacteria in grassland soils, but their assembly processes were distinct. We further demonstrated that rare subcommunity was less predictable than the abundant subcommunity by environmental and geospatial factors. Rare and abundant bacteria responded differentially to factors, which was attributed to the distinct life strategies. Our study provides novel insights into the assembly processes and biographical patterns of rare and abundant bacteria in terrestrial ecosystems.

The number of social contacts of mammals is positively correlated with the diversity of their gut microbes. There is some evidence that sociality also affects microbes in the respiratory tract. We tested whether the airway microbiota of cetacean species differ depending on the whales' level of sociality. We sampled the blow of blue (Balaenoptera musculus), grey (Eschrichtius robustus), humpback (Megaptera novaeangliae) and long-finned pilot whales (PWs) (Globicephala melas) and analysed the blow microbiota by barcode tag sequencing targeting the V4 region of the bacterial 16S rRNA gene. Humpback whales (HWs) show higher levels of sociality than blue (BW) and grey (GW), while PWs are the most gregarious among the four species. The blow samples of the HWs showed the highest richness and diversity. HWs were also the only species with a species-specific clustering of their microbial community composition and a relatively large number of core taxa. Therefore, we conclude that it cannot be sociality alone shaping the diversity and composition of airway microbiota. We suggest the whale species' lung volume and size of the plume of exhaled air as an additional factor impacting the transmission potential of blow microbiota from one individual whale to another.

The emerging understanding of microbial trace gas chemotrophy as a metabolic strategy to support energy and carbon acquisition for microbial survival and growth has significant implications in the search for past, and even extant, life beyond Earth. The use of trace gases, including hydrogen and carbon monoxide as substrates for microbial oxidation, potentially offers a viable strategy with which to support life on planetary bodies that possess a suitable atmospheric composition, such as Mars and Titan. Here, we discuss the current state of knowledge of this process and explore its potential in the field of astrobiological exploration.

The Beam Expander Testing X-ray facility (BEaTriX) is a unique X-ray apparatus now operated at the Istituto Nazionale di Astrofisica (INAF), Osservatorio Astronomico di Brera (OAB), in Merate, Italy. It has been specifically designed to measure the point spread function (PSF) and the effective area (EA) of the X-ray mirror modules (MMs) of the Advanced Telescope for High-ENergy Astrophysics (ATHENA), based on silicon pore optics (SPO) technology, for verification before integration into the mirror assembly. To this end, BEaTriX generates a broad, uniform, monochromatic, and collimated X-ray beam at 4.51 keV. [...] In BEaTriX, a micro-focus X-ray source with a titanium anode is placed in the focus of a paraboloidal mirror, which generates a parallel beam. A crystal monochromator selects the 4.51 keV line, which is expanded to the final size by a crystal asymmetrically cut with respect to the crystalline planes. [...] After characterization, the BEaTriX beam has the nominal dimensions of 170 mm x 60 mm, with a vertical divergence of 1.65 arcsec and a horizontal divergence varying between 2.7 and 3.45 arcsec, depending on the monochromator setting: either high collimation or high intensity. The flux per area unit varies from 10 to 50 photons/s/cm2 from one configuration to the other. The BEaTriX beam performance was tested using an SPO MM, whose entrance pupil was fully illuminated by the expanded beam, and its focus was directly imaged onto the camera. The first light test returned a PSF and an EA in full agreement with expectations. As of today, the 4.51 keV beamline of BEaTriX is operational and can characterize modular X-ray optics, measuring their PSF and EA with a typical exposure of 30 minutes. [...] We expect BEaTriX to be a crucial facility for the functional test of modular X-ray optics, such as the SPO MMs for ATHENA., Accepted on 29 June 2022 for publication in Astronomy & Astrophysics, Sect. 13, Astronomical instrumentation of Astronomy and Astrophysics. Version after language correction

The Mu2e experiment at Fermilab will search for the CLFV neutrino-less coherent conversion of a muon into an electron in the field of an aluminum nucleus. The observation of this process would be the evidence of physics beyond the Standard Model. Mu2e comprises a straw-tracker, an electromagnetic calorimeter and an external veto for cosmic rays. The calorimeter provides electron identification, a fast trigger and aids track reconstruction. It is a state-of-the-art crystal calorimeter and employs 1340 pure CsI crystals readout by UV-extended SiPM and fast electronics. The design consists of two identical annular disks positioned at the relative distance of 70 cm downstream the target.The hostile Mu2e conditions (total ionizing dose of 12 krad and a neutron fluence of 5 × 1010 n/cm2 @ 1 MeVeq (Si)/y, 1 T magnetic field and vacuum level of 10−4 Torr) posed tight constraints on the mechanical structures and materials choice. The support structure of the two crystal matrices employs two aluminum hollow rings and parts made of open-cell vacuum-compatible carbon fiber. SiPMs and front-end electronics for each crystal are assembled in one mechanical unit inserted in a machined copper holder. The units are supported by a plate made of vacuum-compatible material. The plate integrates the cooling system made of a network of copper lines flowing a low temperature fluid and placed in thermal contact with the copper holders. The DAQ is hosted in aluminum crates positioned on the lateral surface of the disks. The crates also integrate the DAQ electronics cooling system. We review the constraints on the calorimeter structures design, the development of all the structural components, including the simulations that have determined the materials and technological choices and the specifications of the cooling station, components production and quality assurance tests, the procedures for detector assembly, transportation and installation in the experimental area.

Adolescents and young adults with cancer have substantially different clinical and psychological needs compared to those of pediatric patients and of older adult patients. We describe the development of an Italian national project dedicated to adolescents and young adults with cancer.

Group-IV colour centres in diamond are a promising light-matter interface for quantum networking devices. We demonstrate multiaxis coherent control of the SnV spin-qubit via an all-optical stimulated Raman drive between the ground and excited states.

Infants (12 months) with rhabdomyosarcoma have historically had poorer outcome than the older age groups. We present outcomes for infants and young children aged 12-36 months with localised rhabdomyosarcoma with a particular emphasis on infants.All children less than 36 months of age enrolled on the EpSSG RMS 2005 study for localised disease are included. Treatment comprised chemotherapy, local surgery and/or radiation therapy adapted to risk group and age. Main outcome measures were event free survival (EFS) and overall survival (OS).Outcome data were available for 485/490 patients aged less than 36 months, 110 were infants. Infants received chemotherapy according to the risk group with no toxic deaths. Radiotherapy was delivered to 33.6% of infants and 63.5% of 12-36 months old, with respectively 41.7% and 22.2% receiving brachytherapy. Radical surgery was performed in 62% of infants and 57.1% of 12-36 months old. Median follow up for patients who are alive (n = 393) was 72.7 months (range 6.9-158.2). Five-year OS for infants was 88.4% (95%CI 80.3-93.2), which is significantly better than the OS in 12-36 months old patients of 78.0% (95%CI 73.2-82.0; p = 0.0204). Five-year EFS for infants was 72.5% (95%CI 62.8-80.0) compared with 66.1% (95%CI 61.0-70.7; p = 0.2663) for 12-36 months old.Infants treated on RMS 2005 achieved excellent EFS and OS. The EpSSG RMS 2005 chemotherapy regimen, combined with an increase in the application of adequate local therapy, improvements in imaging and supportive care and potentially favourable patients' characteristics may have contributed to these results.

Resistive switching (RS) devices are metal/insulator/metal (MIM) cells that can change their electrical resistance when electrical stimuli are applied between the electrodes, and they can be used to store and compute data. Planar crossbar arrays of RS devices can offer a high integration density (10

This article describes a creative project undertaken by a group of adolescent and young adult patients with cancer as part of the Milan’s Youth Project, a scheme dedicated to young patients with cancer with the dual aim of optimizing medical aspects of their care and promoting a holistic approach to their needs. The project was based on audio recordings and focused on the theme of “the journey,” such as a holiday or an adventure, or as a metaphor of the cancer experience. The podcast installments were published on the main streaming platforms. Talking about their disease and how they feel is of importance for young patients to process their feelings surrounding the cancer experience and to find the inner resources they need to facilitate coping.

Background: The lack of internationally recognized guidelines for very rare tumors, such as juvenile granulosa cell tumors (JGCTs), which are nonepithelial, unusual ovarian tumors, is a challenge for pediatric oncologists, especially in developing countries with limited resources and experience in treating rare tumors. Methods: We report clinical data of 2 girls with JGCTs treated at the Pediatric Cancer and Blood Disorders Center of Armenia with the assistance of the EXPeRT (European Cooperative Study Group for Pediatric Rare Tumors) international cooperation panel. Case presentation: Two girls (16 and 15 years old) with JGCTs of the ovaries, stage Ic, underwent surgery and, with consultation through an online advisory board ( http://vrt.cineca.it/ ), received 4 cycles of chemotherapy according to the PEI regimen (cisplatin, etoposide, ifosfamide). Conclusion: Very rare tumors, especially in advanced stages, have limited data and a low survival rate. International collaboration with the EXPeRT group is beneficial for physicians with limited experience and facilitates research in pediatric oncology.

Microorganisms are key to sustaining core ecosystem processes across terrestrial Antarctica but they are rarely considered in conservation frameworks. Whilst greater advocacy has been made towards the inclusion of microbial data in this context, there is still a need for better tools to quantify multispecies responses to environmental change. Here, we extend the scope of Gradient Forest modelling beyond macroorganisms and small datasets to the comprehensive polar soil microbiome encompassing >17, 000 sequence variants for bacteria, micro-eukarya and archaea throughout the hyperarid Vestfold Hills of Eastern Antarctica. Quantification of microbial diversity against 79 physiochemical variables revealed that whilst rank-order importance differed, predictors were broadly consistent between domains, with greatest sharing occurring between bacteria and micro-eukarya. Moisture was identified as the most robust predictor for shaping the regional soil microbiome, with highest compositional turnover or “splits” occurring within the 10 – 12 % moisture content range. Often the most responsive taxa were rarer lineages of bacteria and micro-eukarya with phototrophic and nutrient-cycling capacities such as Cyanobacteria (up to 61.81 % predictive capacity), Chlorophyta (62.17 %) and Ochrophyta (57.81 %). These taxa groups are thus at greater risk of biodiversity loss or gain to projected climate trajectories, which will inevitably disturb current ecosystem dynamics. Better understanding of these threshold tipping points will positively aid conservation efforts across Eastern Antarctica. Furthermore, the successful implementation of an improved Gradient Forest model also presents an exciting opportunity to broaden its use on microbial systems globally.

Background: A standardised approach to treatment of paediatric non-rhabdomyosarcoma soft tissue sarcomas (NRSTS), which account for about 4% of childhood cancers, is still lacking. We report the results of the NRSTS 2005 protocol developed specifically by the European Pediatric Soft Tissue Sarcoma Study Group (EpSSG) to determine a risk-adapted multimodal standard of care for this group of tumours. Methods: The EpSSG NRSTS 2005 study included two prospective, non-randomised, historically controlled trials (one on localised adult-type NRSTS and the other on localised synovial sarcoma) done at 100 academic centres and hospitals in 14 countries. Patients younger than 21 years with a pathologically proven diagnosis of synovial sarcoma or an adult-type NRSTS, no evidence of metastatic disease, no previous treatment other than primary surgery, and diagnostic specimens available for pathological review were included. Patients were stratified by surgical stage, tumour size, nodal involvement, tumour grade (for adult-type NRSTS), and tumour site (for synovial sarcoma). Patients were then divided into four treatment groups: surgery alone, adjuvant radiotherapy, adjuvant chemotherapy (with or without radiotherapy), or neoadjuvant chemotherapy (with or without radiotherapy). The main chemotherapy regimen was ifosfamide (3·0 g/m2 intravenously per day for 3 days) plus doxorubicin (37·5 mg/m2 intravenously per day for 2 days); only ifosfamide (3·0 g/m2 intravenously per day for 2 days) was given concomitantly with radiotherapy (delivered with three-dimensional conformal external beam technique, using conventional fractionation [1·8 daily fractions, 5 days per week] at a dose of 50·4 Gy or 54·0 Gy, to a maximum of 59·4 Gy). The number of chemotherapy cycles ranged from three to seven depending on the stage of the disease. The primary outcomes were event-free survival and overall survival. This study has been completed, and is registered under EudraCT, 2005-001139-31. Findings: Between May 31, 2005, and Dec 31, 2016, 1321 patients were enrolled, of whom 569 (206 with synovial sarcoma and 363 with adult-type NRSTS), with a median age of 12·6 years (IQR 8·2–14·9), were included in this analysis. With a median follow-up of 80·0 months (IQR 54·3–111·3) for the 467 patients alive, 5-year event-free survival was 73·7% (95% CI 69·7–77·2) and 5-year overall survival was 83·8% (95% CI 80·3–86·7). 5-year event-free survival was 91·4% (95% CI 87·0–94·4) and 5-year overall survival was 98·1% (95% CI 95·0–99·3) in the surgery alone group (n=250); 75·5% (46·9–90·1) and 88·2% (60·6–96·9) in the adjuvant radiotherapy group (n=17); 65·6% (54·8–74·5) and 75·8% (65·3–83·5) in the adjuvant chemotherapy group (n=93); and 56·4% (49·3–63·0) and 70·4% (63·3–76·4) in the neoadjuvant chemotherapy group (n=209). Reported severe adverse events included one case of generalised seizures (probably related to ifosfamide) and six cases of secondary tumours. Interpretation: Findings from the EpSSG NRSTS 2005 study help to define the risk-adapted standard of care for this patient population. Adjuvant treatment can be safely omitted in the low-risk population (classified here as the surgery alone group). Improving the outcome for patients with high-risk, initially resected adult-type NRSTS and those with initially unresectable disease remains a major clinical challenge. Funding: Fondazione Città della Speranza.

This brief report describes the SARS‐CoV‐2 vaccination program at our pediatric oncology unit. Adopting Italian regulations, patients treated for cancer within the previous 6 months were offered vaccination with the Pfizer‐BioNtech vaccine if aged ≥16 years, and with the Pfizer‐BioNtech or Moderna vaccine if aged ≥18 years. From March 24 to April 28, 2021, 80/89 adolescent and young adult patients enrolled were vaccinated, while nine refused the vaccine due to fear of side effects, disbelief regarding the pandemic, or lack of trust in the scientific community. The refusal rate in our cohort was lower than in the Italian general population.

It is challenging for conventional top-down lithography to fabricate reproducible devices very close to atomic dimensions, whereas identical molecules and very similar nanoparticles can be made bottom-up in large quantities, and can be self-assembled on surfaces. The challenge is to fabricate electrical contacts to many such small objects at the same time, so that nanocrystals and molecules can be incorporated into conventional integrated circuits. Here, we report a scalable method for contacting a self-assembled monolayer of nanoparticles with a single layer of graphene. This produces single-electron effects, in the form of a Coulomb staircase, with a yield of 87 ± 13% in device areas ranging from, The integration of nano-molecules into microelectronic circuitry is challenging. Here, the authors provide a scalable method for contacting a self-assembled monolayer of nanoparticles with a single layer of graphene that produces single-electron effects, in the form of a Coulomb staircase, with a yield of at least 70%.

Background Children with progressive (PD) or relapsed disease (RD) of pleuropulmonary blastoma (PPB) type II/III are known to have a very poor outcome. Methods A retrospective review of children registered in national and European databases and trials (2000-2018) with diagnosis of PPB type II/III and PD or RD was performed. Results A total of 35 patients with PPB were analysed: patients with PD (n = 9) and RD (n = 26). Patients experienced PD at the median age of 3.9 years [range, 0.5-17.8] despite surgery, chemotherapy (CHT, n = 9) and radiotherapy (RT, n = 1) with a median time to progression of 0.58 years [range, 0.02-1.27] from diagnosis. All of them died. Patients suffered from RD at the median age of 4.3 years [1.7-15.1], median delay to relapse 1.03 years [range, 0.03-2.95]. RD occurred locally (n = 12), combined (n = 1) and in metastatic sites (n = 13): central nervous system (n = 11) and unspecified site (n = 2). Patients were treated with salvage CHT (n = 20), surgery (n = 10) ± RT (n = 10). After a median follow-up of 4.2 years [range, 2.1-14.6], a second complete remission (CR) was achieved in nine out of 26 patients. Patients were alive in the second CR (n = 6), in the third CR (n = 1), in partial remission (n = 2) and lost of follow-up (n = 1). Five-year event-free survival (EFS) and overall survival (OS) for patients with RD were both 37% (±19, CI 95%). Local therapy (surgery, RT) had a favourable impact on OS (p = 0.03 and 0.02, respectively). Conclusions Cure of patients with RD of PPB type II/III with multimodal treatment is possible but rare. Progressive PPB is fatal and patients need new treatment options.

PROCEDURE The survival of children with rhabdomyosarcoma (RMS) has gradually improved as a result of the adoption of multidisciplinary treatments. Dedicated skills and facilities are indispensable and more readily available at reference centers. In this study, we examined the role of centers' experience (based on the number of patients treated) in their management of patients with RMS. METHODS We analyzed 342 patients with localized RMS enrolled in the European RMS 2005 protocol from October 2005 to December 2016 at 31 Italian centers that are part of the Soft Tissue Sarcoma Committee (STSC). We grouped the centers by the number of patients each one enrolled (Group 1: >40; Group 2: 10; and Group 3

Interlayer excitons in layered materials constitute a novel platform to study many-body phenomena arising from long-range interactions between quantum particles. Long-lived excitons are required to achieve high particle densities, to mediate thermalisation, and to allow for spatially and temporally correlated phases. Additionally, the ability to confine them in periodic arrays is key to building a solid-state analogue to atoms in optical lattices. Here, we demonstrate interlayer excitons with lifetime approaching 0.2 ms in a layered-material heterostructure made from WS2 and WSe2 monolayers. We show that interlayer excitons can be localised in an array using a nano-patterned substrate. These confined excitons exhibit microsecond-lifetime, enhanced emission rate, and optical selection rules inherited from the host material. The combination of a permanent dipole, deterministic spatial confinement and long lifetime places interlayer excitons in a regime that satisfies one of the requirements for simulating quantum Ising models in optically resolvable lattices. Excitons are quasiparticles consisting of an electron-hole pair and can be used to study many-body phenomenon. Here, the authors demonstrate on-demand quantum confinement of long-lived interlayer excitons in WS2/WSe2 heterostructures deposited on nanopatterned substrates.

Graphene is ideally suited for optoelectronics. It offers absorption at telecom wavelengths, high-frequency operation and CMOS-compatibility. We show how high speed optoelectronic mixing can be achieved with high frequency (~20 GHz bandwidth) graphene field effect transistors (GFETs). These devices mix an electrical signal injected into the GFET gate and a modulated optical signal onto a single layer graphene (SLG) channel. The photodetection mechanism and the resulting photocurrent sign depend on the SLG Fermi level (E

Background: Postoperative hypocalcemia is a frequent complication after thyroid surgery. Hypoparathyroidism may develop as transient (TtHP), with normalization within six months from surgery, or permanent (PtHP) if the patient requires replacement therapy. The present study analyzes rates and factors associated with the development of TtHP or PtHP following thyroid surgery in a pediatric population. Procedure: A retrospective multicenter study analyzing 363 patients was carried out. We recorded gender, age, tumor size, type of surgery, lymph node dissection, histology. Calcium levels were acquired daily for 72 hours after discharge. Subsequent sample collection was customized on the patient’s hypocalcemia severity. Results: We analyzed 363 patients aged ≤18 years (mean age 14.2 years) who underwent thyroid surgery clustered into age groups (≤15 or >15). Patients mean follow-up was 5.8 years (1-11yrs). At histology 310 (85%) were papillary carcinoma, 32 (9%) were follicular carcinoma, 6 (2%) presented diffuse sclerosing variant of papillary thyroid carcinoma whilst 15 (4%) had familial medullary carcinoma. TtHP developed in 36 (9,9%), PtHP in 20 (5.5%) cases. TtHP was more frequent in younger patients (p=0,009). Both PtHP and TtHP were increased in case of larger tumors (≥2 cm) (p=0,001). All TtHP and PtHP were in TT group. PtHP rate was increased if lymph node dissection was carried out (p

The diffusion of lithium ions decoupled from a solid polymer electrolyte matrix is the key for high-energy electrochemical devices with the safety needed for commercial use. This Letter reports how the ion mobility in a single-phase hybrid polyelectrolyte (SPHP) matrix can be tuned by changing an inorganic coordinating atom from silicon (Si) to germanium (Ge). Nuclear Magnetic Resonance (NMR) results show that the lithium ion activation barrier in the polyelectrolyte with Si can be modulated from 0.26 eV to the unprecedented value of 0.12 eV in the polyelectrolyte with Ge. Density functional theory is used to show that the electronic structures of both polymers are very different, although their chemical structures are very similar, except for the coordinating atom. This simple chemical substitution route will certainly increase the interest in these polymers for applications in electrochemical devices.

Hydrocarbon polar metabolites are gaining interest from industry and the remediation community due to their ubiquity and uncertainty around their toxicity. In this study, we used headspace-gas chromatography/mass spectrometry (HS-GC/MS) to characterize polar metabolites present in elutriates derived from uncontaminated, freshly hydrocarbon contaminated and partially remediated Antarctic soils. Elutriates represent the bioavailable fraction and may be used as a proxy for leachate runoff in environmental risk assessments. Control and contaminated soil elutriates were analysed for the presence of 12 aldehydes and two ketones, which cover a broad spectrum of metabolites, ranging from nC2 – nC12 carbon chain length. A total of nine aldehydes were detected in the soil elutriates. Types of aldehydes present in uncontaminated and hydrocarbon contaminated elutriates were similar. Among the polar metabolites measured in elutriates, acetaldehyde was most abundant in partially remediated soils. Microtox assays were used to determine the potential toxicity of elutriates. In addition, three aldehydes that were present at the highest concentrations in the contaminated and partially remediated soil elutriates (acetaldehyde, octanal and undecanal) were tested as single compounds. Contaminated soil elutriates tested were found to be toxic, with partially remediated elutriates less toxic than freshly contaminated elutriates. None of the three aldehydes tested separately were toxic at levels at which they were measured in elutriates. We infer that high levels of acetaldehyde in partially remediated soil due to hydrocarbon degradation highlight the potential of this metabolite as a useful chemical marker for hydrocarbon degradation under certain conditions. Microtox was sensitive to metabolites and provided a useful initial screening tool for elutriates.

We report high room-temperature mobility in single layer graphene grown by Chemical Vapor Deposition (CVD) after wet transfer on SiO$_2$ and hexagonal boron nitride (hBN) encapsulation. By removing contaminations trapped at the interfaces between single-crystal graphene and hBN, we achieve mobilities up to$\sim70000cm^2 V^{-1} s^{-1}$ at room temperature and$\sim120000cm^2 V^{-1} s^{-1}$ at 9K. These are over twice those of previous wet transferred graphene and comparable to samples prepared by dry transfer. We also investigate the combined approach of thermal annealing and encapsulation in polycrystalline graphene, achieving room temperature mobilities$\sim30000 cm^2 V^{-1} s^{-1}$. These results show that, with appropriate encapsulation and cleaning, room temperature mobilities well above $10000cm^2 V^{-1} s^{-1}$ can be obtained in samples grown by CVD and transferred using a conventional, easily scalable PMMA-based wet approach.

Apomictic grasses predominate among tropical forages, and specific breeding techniques are needed for their genetic improvement. The objectives were to: 1- generate hybrids by crossing tetraploid sexual and apomictic Paspalum simplex genotypes, 2- develop a technique based on molecular markers for early identification of apomictic hybrids, and 3- determine the relationship between mode of reproduction and performance of hybrids. Crosses were made between two induced sexual and seven apomictic tetraploid plants. Identification of apomictic hybrids during seedling stage was performed using a marker linked to apomixis, and by flow cytometric seed analysis (FCSA). Hybrids were evaluated under field conditions for plant diameter and height, initial regrowth, and seasonal regrowth during two consecutive growing seasons. Sexual tetraploid plants used as female parents behaved as allogamous since 95% of the progeny had male-specific markers. The ratio between apomictic and sexual hybrids differed among crosses from 1:8.7 and 1:0.6 among crosses, with a mean of 1:2.4. There was a 96% coincidence between the use of the apomixis?linked marker and FCSA. A technique based on the use of an early DNA isolation and the amplification of a molecular marker linked to apomixis was developed. We found no overall difference between apomictic and sexual hybrids for the evaluated traits, except for fall regrowth in the first year, for which apomictic hybrids were superior. Generation of large tetraploid hybrid progenies is possible in P. simplex. Segregation for mode of reproduction depends on parents involved. Agronomic performance is not related to reproductive mode among tetraploid hybrids. Fil: Brugnoli, Elsa Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Botánica del Nordeste. Universidad Nacional del Nordeste. Facultad de Ciencias Agrarias. Instituto de Botánica del Nordeste; Argentina Fil: Martínez, Eric Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Botánica del Nordeste. Universidad Nacional del Nordeste. Facultad de Ciencias Agrarias. Instituto de Botánica del Nordeste; Argentina Fil: Ferrari Usandizaga, Silvana Consuelo. Instituto Nacional de Tecnología Agropecuaria; Argentina Fil: Zilli, Alex Leonel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Botánica del Nordeste. Universidad Nacional del Nordeste. Facultad de Ciencias Agrarias. Instituto de Botánica del Nordeste; Argentina Fil: Urbani, Mario Hugo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Botánica del Nordeste. Universidad Nacional del Nordeste. Facultad de Ciencias Agrarias. Instituto de Botánica del Nordeste; Argentina Fil: Acuña, Carlos Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Botánica del Nordeste. Universidad Nacional del Nordeste. Facultad de Ciencias Agrarias. Instituto de Botánica del Nordeste; Argentina

We report for the first time the efficiency and safety of a 49-month compassionate use of the microsomal transfer protein inhibitor lomitapide in a child with homozygous familial hypercholesterolemia. On average, 20 mg of lomitapide caused a 37% reduction in low-density lipoprotein cholesterol levels on top of ezetimibe and atorvastatin. The drug was well tolerated with no changes in liver enzymes and occurrence of steatosis on hepatic ultrasound. The patient presented adequate growth and sexual maturation. Nonetheless, there was progression in either subclinical atherosclerotic carotid or aortic valve diseases. Further studies are necessary to test the impact and safety of lomitapide in children with homozygous familial hypercholesterolemia.

Purpose: This study assesses the action of panobinostat, a histone deacetylase inhibitor (HDACI), in restoring sensitivity to bicalutamide in a castration-resistant prostate cancer (CRPC) model and the efficacy and safety of the panobinostat/bicalutamide combination in CRPC patients resistant to second-line antiandrogen therapy (2ndLAARx). Patients and Methods: The CWR22PC xenograft and isogenic cell line were tested for drug interactions on tumor cell growth and on the androgen receptor (AR), AR-splice variant7, and AR targets. A phase I trial had a 3 × 3 panobinostat dose-escalation design. The phase II study randomized 55 patients to panobinostat 40 mg (A arm) or 20 mg (B arm) triweekly ×2 weeks with bicalutamide 50 mg/day in 3-week cycles. The primary endpoint was to determine the percentage of radiographic progression-free (rPF) patients at 36 weeks versus historic high-dose bicalutamide. Results: In the model, panobinostat/bicalutamide demonstrated synergistic antitumor effect while reducing AR activity. The dose-limiting toxicity was not reached. The probabilities of remaining rPF were 47.5% in the A arm and 38.5% in the B arm, exceeding the protocol-specified threshold of 35%. The A arm but not the B arm exceeded expectations for times (medians) to rP (33.9 and 10 weeks), and from PSA progression to rP (24 and 5.9 weeks). A arm/B arm events included: adverse events (AE), 62%/19%; treatment stopped for AEs, 27.5%/11.5%; dose reduction required, 41%/4%. The principal A-arm grade ≥ 3 AEs were thrombocytopenia (31%) and fatigue (14%). Conclusions: The 40 mg panobinostat/bicalutamide regimen increased rPF survival in CRPC patients resistant to 2ndLAARx. Panobinostat toxicity was tolerable with dose reductions. Epigenetic HDACI therapy reduces AR-mediated resistance to bicalutamide in CRPC models with clinical benefit in patients. The combination merits validation using a second-generation antiandrogen.