Measurement of charged particle yields from therapeutic beams in view of the design of an innovative hadrontherapy dose monitor

Particle Therapy (PT) is an emerging technique, which makes use of charged particles to efficiently cure different kinds of solid tumors. The high precision in the hadrons dose deposition requires an accurate monitoring to prevent the risk of under-dosage of the cancer region or of over-dosage of healthy tissues. Monitoring techniques are currently being developed and are based on the detection of particles produced by the beam interaction into the target, in particular: charged particles, result of target and/or projectile fragmentation, prompt photons coming from nucleus de-excitation and back-to-back γ s, produced in the positron annihilation from β + emitters created in the beam interaction with the target. It has been showed that the hadron beam dose release peak can be spatially correlated with the emission pattern of these secondary particles. Here we report about secondary particles production (charged fragments and prompt γ s) performed at different beam and energies that have a particular relevance for PT applications: 12C beam of 80 MeV/u at LNS, 12C beam 220 MeV/u at GSI, and 12C, 4He, 16O beams with energy in the 50–300 MeV/u range at HIT. Finally, a project for a multimodal dose-monitor device exploiting the prompt photons and charged particles emission will be presented

Magnetic Nanoparticles for Power Absorption: optimizing size, shape and magnetic properties

We present a study on the magnetic properties of naked and silica-coated Fe3O4 nanoparticles with sizes between 5 and 110 nm. Their efficiency as heating agents was assessed through specific power absorption (SPA) measurements as a function of particle size and shape. The results show a strong dependence of the SPA with the particle size, with a maximum around 30 nm, as expected for a Neel relaxation mechanism in single-domain particles. The SiO2 shell thickness was found to play an important role in the SPA mechanism by hindering the heat outflow, thus decreasing the heating efficiency. It is concluded that a compromise between good heating efficiency and surface functionality for biomedical purposes can be attained by making the SiO2 functional coating as thin as possible.Comment: 15 pages, 7 figures, 2 table

Development and Validation of a New Prognostic System for Patients with Hepatocellular Carcinoma

BACKGROUND: Prognostic assessment in patients with hepatocellular carcinoma (HCC) remains controversial. Using the Italian Liver Cancer (ITA.LI.CA) database as a training set, we sought to develop and validate a new prognostic system for patients with HCC. METHODS AND FINDINGS: Prospective collected databases from Italy (training cohort, n = 3,628; internal validation cohort, n = 1,555) and Taiwan (external validation cohort, n = 2,651) were used to develop the ITA.LI.CA prognostic system. We first defined ITA.LI.CA stages (0, A, B1, B2, B3, C) using only tumor characteristics (largest tumor diameter, number of nodules, intra- and extrahepatic macroscopic vascular invasion, extrahepatic metastases). A parametric multivariable survival model was then used to calculate the relative prognostic value of ITA.LI.CA tumor stage, Eastern Cooperative Oncology Group (ECOG) performance status, Child-Pugh score (CPS), and alpha-fetoprotein (AFP) in predicting individual survival. Based on the model results, an ITA.LI.CA integrated prognostic score (from 0 to 13 points) was constructed, and its prognostic power compared with that of other integrated systems (BCLC, HKLC, MESIAH, CLIP, JIS). Median follow-up was 58 mo for Italian patients (interquartile range, 26-106 mo) and 39 mo for Taiwanese patients (interquartile range, 12-61 mo). The ITA.LI.CA integrated prognostic score showed optimal discrimination and calibration abilities in Italian patients. Observed median survival in the training and internal validation sets was 57 and 61 mo, respectively, in quartile 1 (ITA.LI.CA score 64 1), 43 and 38 mo in quartile 2 (ITA.LI.CA score 2-3), 23 and 23 mo in quartile 3 (ITA.LI.CA score 4-5), and 9 and 8 mo in quartile 4 (ITA.LI.CA score > 5). Observed and predicted median survival in the training and internal validation sets largely coincided. Although observed and predicted survival estimations were significantly lower (log-rank test, p < 0.001) in Italian than in Taiwanese patients, the ITA.LI.CA score maintained very high discrimination and calibration features also in the external validation cohort. The concordance index (C index) of the ITA.LI.CA score in the internal and external validation cohorts was 0.71 and 0.78, respectively. The ITA.LI.CA score's prognostic ability was significantly better (p < 0.001) than that of BCLC stage (respective C indexes of 0.64 and 0.73), CLIP score (0.68 and 0.75), JIS stage (0.67 and 0.70), MESIAH score (0.69 and 0.77), and HKLC stage (0.68 and 0.75). The main limitations of this study are its retrospective nature and the intrinsically significant differences between the Taiwanese and Italian groups. CONCLUSIONS: The ITA.LI.CA prognostic system includes both a tumor staging-stratifying patients with HCC into six main stages (0, A, B1, B2, B3, and C)-and a prognostic score-integrating ITA.LI.CA tumor staging, CPS, ECOG performance status, and AFP. The ITA.LI.CA prognostic system shows a strong ability to predict individual survival in European and Asian populations

Testing for SARS-CoV-2 (COVID-19): a systematic review and clinical guide to molecular and serological in-vitro diagnostic assays

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its associated Coronavirus disease 2019 (COVID-19) pandemic has demanded rapid upscaling of in-vitro diagnostic assays to enable mass screening and testing of high-risk groups, and simultaneous ascertainment of robust data on past SARS-CoV-2 exposure at an individual and population level. To meet the exponential demand in testing, there has been an accelerated development of both molecular and serological assays across a plethora of platforms. In the present review, we discuss the current literature on these modalities including the nucleic acid amplification tests, direct viral antigen tests and the rapidly expanding laboratory based and point of care serological tests. This suite of complementary tests will inform crucial decisions by healthcare providers and policy makers and understanding their strengths and limitations will be critical to their judicious application for the development of algorithmic approaches to treatment and public health strategies

Rare germline variants in DNA repair genes and the angiogenesis pathway predispose prostate cancer patients to develop metastatic disease

Background Prostate cancer (PrCa) demonstrates a heterogeneous clinical presentation ranging from largely indolent to lethal. We sought to identify a signature of rare inherited variants that distinguishes between these two extreme phenotypes. Methods We sequenced germline whole exomes from 139 aggressive (metastatic, age of diagnosis < 60) and 141 non-aggressive (low clinical grade, age of diagnosis ≥60) PrCa cases. We conducted rare variant association analyses at gene and gene set levels using SKAT and Bayesian risk index techniques. GO term enrichment analysis was performed for genes with the highest differential burden of rare disruptive variants. Results Protein truncating variants (PTVs) in specific DNA repair genes were significantly overrepresented among patients with the aggressive phenotype, with BRCA2, ATM and NBN the most frequently mutated genes. Differential burden of rare variants was identified between metastatic and non-aggressive cases for several genes implicated in angiogenesis, conferring both deleterious and protective effects. Conclusions Inherited PTVs in several DNA repair genes distinguish aggressive from non-aggressive PrCa cases. Furthermore, inherited variants in genes with roles in angiogenesis may be potential predictors for risk of metastases. If validated in a larger dataset, these findings have potential for future clinical application

Random-phase approximation and its applications in computational chemistry and materials science

The random-phase approximation (RPA) as an approach for computing the electronic correlation energy is reviewed. After a brief account of its basic concept and historical development, the paper is devoted to the theoretical formulations of RPA, and its applications to realistic systems. With several illustrating applications, we discuss the implications of RPA for computational chemistry and materials science. The computational cost of RPA is also addressed which is critical for its widespread use in future applications. In addition, current correction schemes going beyond RPA and directions of further development will be discussed.Comment: 25 pages, 11 figures, published online in J. Mater. Sci. (2012

Systematic identification of abundant A-to-I editing sites in the human transcriptome

RNA editing by members of the double-stranded RNA-specific ADAR family leads to site-specific conversion of adenosine to inosine (A-to-I) in precursor messenger RNAs. Editing by ADARs is believed to occur in all metazoa, and is essential for mammalian development. Currently, only a limited number of human ADAR substrates are known, while indirect evidence suggests a substantial fraction of all pre-mRNAs being affected. Here we describe a computational search for ADAR editing sites in the human transcriptome, using millions of available expressed sequences. 12,723 A-to-I editing sites were mapped in 1,637 different genes, with an estimated accuracy of 95%, raising the number of known editing sites by two orders of magnitude. We experimentally validated our method by verifying the occurrence of editing in 26 novel substrates. A-to-I editing in humans primarily occurs in non-coding regions of the RNA, typically in Alu repeats. Analysis of the large set of editing sites indicates the role of editing in controlling dsRNA stability.Comment: Pre-print version. See http://dx.doi.org/10.1038/nbt996 for a reprin

Prospective study of patients with persistent symptoms of dengue in Brazil

Dengue is an arboviral infection clinically recognized as an acute and self-limited disease. Persistence of dengue symptoms is known, but it has been little studied. The aim of this study was to characterize persistent symptoms in 113 patients with dengue followed up clinically and by laboratory testing at a tertiary hospital. Symptoms that persisted for more than 14 days were observed in 61 (54.0%) patients, and six (6.2%) of them had symptoms for 6 months or more. The persistent symptoms identified were myalgia, weakness, hair loss, memory loss, reduced resistance to physical effort, headache, reasoning problems, arthralgia, sleepiness- and emotional lability. The progression to persistent symptoms was significantly associated with hospitalization, older age, more severe disease, the presence of bleeding and comorbidities upon univariate analysis. Upon multivariate analysis, the presence of persistent symptoms continued to be significantly associated only with increased age and dengue with warning signs. The platelet count during the acute phase of the disease was significantly lower in the group with persistent symptoms. In conclusion, the frequency of progression to persistent symptoms in dengue is relevant in patients seen at a tertiary hospital and the persistence of symptoms is more common in patients with dengue with warning signs

Ecology, growth and management of black locust (Robinia pseudoacacia L.), a non‑native species integrated into European forests

Black locust (Robinia pseudoacacia L.), a species native to the eastern North America, was introduced to Europe probably in 1601 and currently extends over 2.3 × 106 ha. It has become naturalized in all sub-Mediterranean and temperate regions rivaling Populus spp. as the second most planted broadleaved tree species worldwide after Eucalyptus spp. This wide-spreading planting is because black locust is an important multipurpose species, producing wood, fodder, and a source of honey as well as bio-oil and biomass. It is also important for carbon sequestration, soil stabilization and re-vegetation of landfills, mining areas and wastelands, in biotherapy and landscaping. In Europe, black locust is drought tolerant so grows in areas with annual precipitation as low as 500–550 mm. It tolerates dry, nutrient poor soils but grows best on deep, nutrient-rich, well-drained soils. It is a fast-growing tree and the height, diameter and volume growth peak before the age of 20. It mostly regenerates vegetatively by root suckers under a simple coppice system, which is considered the most cost-effective management system. It also regenerates, but less frequently, by stool sprouts. Its early silviculture in production forests includes release cutting to promote root suckers rather than stool shoots, and cleaning-respacing to remove low-quality stems, reduce the number of shoots per stool, and adjust spacing between root suckers. In addition, early, moderate and frequent thinning as well as limited pruning are carried out focusing on crop trees. The species is regarded as invasive in several European countries and its range here is expected to expand under predicted climate changes