Manifesto ShaRP LAB

ShaRP LAB (dove ShaRP sta per Sharing Religious Places) è una rete transdi- sciplinare di studiosi interessati alle dinamiche spaziali dell’interazione re- ligiosa. Riunisce antropologi, architetti, geografi, sociologi, storici dell’arte e delle religioni. Ispirati da un approccio olistico, i membri di ShaRP LAB affrontano il tema della condivisione religiosa da angolazioni e approcci metodologici diversi: dallo sguardo emico alla cornice sociale, dal metodo storico-critico a quello delle scienze sociali e delle digital humanities

Materials R&D for a timely DEMO: Key findings and recommendationsof the EU Roadmap Materials Assessment Group

The findings of the EU Fusion Programme’s ‘Materials Assessment Group’ (MAG), assessing readiness ofStructural, Plasma Facing (PF) and High Heat Flux (HHF) materials for DEMO, are discussed. These areincorporated into the EU Fusion Power Roadmap [1], with a decision to construct DEMO in the early2030s.The methodology uses project-based and systems-engineering approaches, the concept of TechnologyReadiness Levels, and considers lessons learned from Fission reactor material development. ‘Baseline’materials are identified for each DEMO role, and the DEMO mission risks analysed from the known lim-itations, or unknown properties, associated with each baseline material. R&D programmes to addressthese risks are developed. The DEMO assessed has a phase I with a ‘starter blanket’: the blanket mustwithstand @le;2 MW yr m−2fusion neutron flux (equivalent to ∼20 dpa front-wall steel damage). The base-line materials all have significant associated risks, so development of ‘Risk Mitigation Materials’ (RMM)is recommended. The R&D programme has parallel development of the baseline and RMM, up to ‘down-selection’ points to align with decisions on the DEMO blanket and divertor engineering definition. ITERlicensing experience is used to refine the issues for materials nuclear testing, and arguments are devel-oped to optimise scope of materials tests with fusion neutron (‘14 MeV’) spectra before DEMO designfinalisation. Some 14 MeV testing is still essential, and the Roadmap requires deployment of a ≥30 dpa(steels) testing capability by 2026. Programme optimisation by the pre-testing with fission neutronson isotopically- or chemically-doped steels and with ion-beams is discussed along with the minimum14 MeV testing programme, and the key role which fundamental and mission-oriented modelling canplay in orienting the research

Power Exhaust Concepts and Divertor Designs for Japanese and European DEMO Fusion Reactors

Concepts of the power exhaust and divertor design have been developed, with a high priority in the pre-conceptual design phase of the Japan-Europe Broader Approach DEMO Design Activity. A common critical issue is the large power exhaust and its fraction in the main plasma and divertor by the radiative cooling. Different exhaust concepts in the main plasma and divertor have been developed for JA and EU DEMOs. JA proposed a conventional closed divertor geometry to challenge large Psep/Rp handling of 30-35 MWm-1 in order to maintain the radiation fraction in the main plasma at the ITER-level (fradmain = Pradmain/Pheat ~0.4) and higher plasma performance. EU challenged both increasing fradmain to ~0.65 and handling the ITER-level Psep/Rp in the open divertor geometry. Power exhaust simulations have been performed by SONIC (JA) and SOLPS5.1 (EU) with corresponding Psep = 250-300 MW and 150-200 MW, respectively. Both results showed that large divertor radiation fraction (Praddiv/Psep 0.8) was required to reduce both peak qtarget ( 10MWm-2) and Te,idiv. In addition, the JA divertor performance with EU-reference Psep of 150MW showed benefit of the closed geometry to reduce the peak qtarget and Te,idiv near the separatrix, and to produce the partial detachment. Integrated designs of the water cooled divertor target, cassette and coolant pipe routing have been developed in both EU and JA, based on the tungsten (W) monoblock concept with Cu-alloy pipe. For year-long operation, DEMO-specific risks such as radiation embrittlement of Cu-interlayers and Cu-alloy cooling pipe were recognized, and both foresee higher water temperature (130-200 °C) compared to that for ITER. At the same time, several improved technologies of high heat flux components have been developed in EU, and different heat sink design, i.e. Cu-alloy cooling pipes for targets and RAFM steel ones for the baffle, dome and cassette, was proposed in JA. The two approaches provide important case-studies of the DEMO divertor, and will significantly contribute to both DEMO designs

Refinement of the diagnostic approach for the identification of children and adolescents affected by familial hypercholesterolemia: Evidence from the LIPIGEN study

Background and aims: We aimed to describe the limitations of familiar hypercholesterolemia (FH) diagnosis in childhood based on the presence of the typical features of FH, such as physical sings of cholesterol accumulation and personal or family history of premature cardiovascular disease or hypercholesterolemia, comparing their prevalence in the adult and paediatric FH population, and to illustrate how additional information can lead to a more effective diagnosis of FH at a younger age.Methods: From the Italian LIPIGEN cohort, we selected 1188 (>= 18 years) and 708 (<18 years) genetically-confirmed heterozygous FH, with no missing personal FH features. The prevalence of personal and familial FH features was compared between the two groups. For a sub-group of the paediatric cohort (N = 374), data about premature coronary heart disease (CHD) in second-degree family members were also included in the evaluation.Results: The lower prevalence of typical FH features in children/adolescents vs adults was confirmed: the prevalence of tendon xanthoma was 2.1% vs 13.1%, and arcus cornealis was present in 1.6% vs 11.2% of the cohorts, respectively. No children presented clinical history of premature CHD or cerebral/peripheral vascular disease compared to 8.8% and 5.6% of adults, respectively. The prevalence of premature CHD in first-degree relatives was significantly higher in adults compared to children/adolescents (38.9% vs 19.7%). In the sub-cohort analysis, a premature CHD event in parents was reported in 63 out of 374 subjects (16.8%), but the percentage increased to 54.0% extending the evaluation also to second-degree relatives.Conclusions: In children, the typical FH features are clearly less informative than in adults. A more thorough data collection, adding information about second-degree relatives, could improve the diagnosis of FH at younger age

Lipoprotein(a) Genotype Influences the Clinical Diagnosis of Familial Hypercholesterolemia

: Background Evidence suggests that LPA risk genotypes are a possible contributor to the clinical diagnosis of familial hypercholesterolemia (FH). This study aimed at determining the prevalence of LPA risk variants in adult individuals with FH enrolled in the Italian LIPIGEN (Lipid Transport Disorders Italian Genetic Network) study, with (FH/M+) or without (FH/M-) a causative genetic variant. Methods and Results An lp(a) [lipoprotein(a)] genetic score was calculated by summing the number risk-increasing alleles inherited at rs3798220 and rs10455872 variants. Overall, in the 4.6% of 1695 patients with clinically diagnosed FH, the phenotype was not explained by a monogenic or polygenic cause but by genotype associated with high lp(a) levels. Among 765 subjects with FH/M- and 930 subjects with FH/M+, 133 (17.4%) and 95 (10.2%) were characterized by 1 copy of either rs10455872 or rs3798220 or 2 copies of either rs10455872 or rs3798220 (lp(a) score ≥1). Subjects with FH/M- also had lower mean levels of pretreatment low-density lipoprotein cholesterol than individuals with FH/M+ (t test for difference in means between FH/M- and FH/M+ groups <0.0001); however, subjects with FH/M- and lp(a) score ≥1 had higher mean (SD) pretreatment low-density lipoprotein cholesterol levels (223.47 [50.40] mg/dL) compared with subjects with FH/M- and lp(a) score=0 (219.38 [54.54] mg/dL for), although not statistically significant. The adjustment of low-density lipoprotein cholesterol levels based on lp(a) concentration reduced from 68% to 42% the proportion of subjects with low-density lipoprotein cholesterol level ≥190 mg/dL (or from 68% to 50%, considering a more conservative formula). Conclusions Our study supports the importance of measuring lp(a) to perform the diagnosis of FH appropriately and to exclude that the observed phenotype is driven by elevated levels of lp(a) before performing the genetic test for FH

Familial hypercholesterolaemia in children and adolescents from 48 countries: a cross-sectional study

Background: Approximately 450 000 children are born with familial hypercholesterolaemia worldwide every year, yet only 2·1% of adults with familial hypercholesterolaemia were diagnosed before age 18 years via current diagnostic approaches, which are derived from observations in adults. We aimed to characterise children and adolescents with heterozygous familial hypercholesterolaemia (HeFH) and understand current approaches to the identification and management of familial hypercholesterolaemia to inform future public health strategies. Methods: For this cross-sectional study, we assessed children and adolescents younger than 18 years with a clinical or genetic diagnosis of HeFH at the time of entry into the Familial Hypercholesterolaemia Studies Collaboration (FHSC) registry between Oct 1, 2015, and Jan 31, 2021. Data in the registry were collected from 55 regional or national registries in 48 countries. Diagnoses relying on self-reported history of familial hypercholesterolaemia and suspected secondary hypercholesterolaemia were excluded from the registry; people with untreated LDL cholesterol (LDL-C) of at least 13·0 mmol/L were excluded from this study. Data were assessed overall and by WHO region, World Bank country income status, age, diagnostic criteria, and index-case status. The main outcome of this study was to assess current identification and management of children and adolescents with familial hypercholesterolaemia. Findings: Of 63 093 individuals in the FHSC registry, 11 848 (18·8%) were children or adolescents younger than 18 years with HeFH and were included in this study; 5756 (50·2%) of 11 476 included individuals were female and 5720 (49·8%) were male. Sex data were missing for 372 (3·1%) of 11 848 individuals. Median age at registry entry was 9·6 years (IQR 5·8-13·2). 10 099 (89·9%) of 11 235 included individuals had a final genetically confirmed diagnosis of familial hypercholesterolaemia and 1136 (10·1%) had a clinical diagnosis. Genetically confirmed diagnosis data or clinical diagnosis data were missing for 613 (5·2%) of 11 848 individuals. Genetic diagnosis was more common in children and adolescents from high-income countries (9427 [92·4%] of 10 202) than in children and adolescents from non-high-income countries (199 [48·0%] of 415). 3414 (31·6%) of 10 804 children or adolescents were index cases. Familial-hypercholesterolaemia-related physical signs, cardiovascular risk factors, and cardiovascular disease were uncommon, but were more common in non-high-income countries. 7557 (72·4%) of 10 428 included children or adolescents were not taking lipid-lowering medication (LLM) and had a median LDL-C of 5·00 mmol/L (IQR 4·05-6·08). Compared with genetic diagnosis, the use of unadapted clinical criteria intended for use in adults and reliant on more extreme phenotypes could result in 50-75% of children and adolescents with familial hypercholesterolaemia not being identified. Interpretation: Clinical characteristics observed in adults with familial hypercholesterolaemia are uncommon in children and adolescents with familial hypercholesterolaemia, hence detection in this age group relies on measurement of LDL-C and genetic confirmation. Where genetic testing is unavailable, increased availability and use of LDL-C measurements in the first few years of life could help reduce the current gap between prevalence and detection, enabling increased use of combination LLM to reach recommended LDL-C targets early in life

Genetic determinants of telomere length and risk of pancreatic cancer: A PANDoRA study

Telomere deregulation is a hallmark of cancer. Telomere length measured in lymphocytes (LTL) has been shown to be a risk marker for several cancers. For pancreatic ductal adenocarcinoma (PDAC) consensus is lacking whether risk is associated with long or short telomeres. Mendelian randomization approaches have shown that a score built from SNPs associated with LTL could be used as a robust risk marker. We explored this approach in a large scale study within the PANcreatic Disease ReseArch (PANDoRA) consortium. We analyzed 10 SNPs (ZNF676-rs409627, TERT-rs2736100, CTC1-rs3027234, DHX35-rs6028466, PXK-rs6772228, NAF1-rs7675998, ZNF208-rs8105767, OBFC1-rs9420907, ACYP2-rs11125529 and TERC-rs10936599) alone and combined in a LTL genetic score (“teloscore”, which explains 2.2% of the telomere variability) in relation to PDAC risk in 2,374 cases and 4,326 controls. We identified several associations with PDAC risk, among which the strongest were with the TERT-rs2736100 SNP (OR = 1.54; 95%CI 1.35–1.76; p = 1.54 × 10−10) and a novel one with the NAF1-rs7675998 SNP (OR = 0.80; 95%CI 0.73–0.88; p = 1.87 × 10−6, ptrend = 3.27 × 10−7). The association of short LTL, measured by the teloscore, with PDAC risk reached genome-wide significance (p = 2.98 × 10−9 for highest vs. lowest quintile; p = 1.82 × 10−10 as a continuous variable). In conclusion, we present a novel genome-wide candidate SNP for PDAC risk (TERT-rs2736100), a completely new signal (NAF1-rs7675998) approaching genome-wide significance and we report a strong association between the teloscore and risk of pancreatic cancer, suggesting that telomeres are a potential risk factor for pancreatic cancer

Feasibility Study for an Engineering Concept in a Stainless-Steel Copper Divertor Plate Protected by Tungsten-5% Rhenium Alloy or Graphite

THE PRESENT PROPOSAL OF THE NEW DIVERTOR PANEL CONCEPT MAY BE CONSIDERED AS AN EVOLUTION OF THE PREVIOUS STUDIES CARRIED OUT AT JRC-ISPRA, AND IT IS INTENDED TO BE A GLOBAL PROPOSAL ABLE TO SATISFY THE REQUIREMENTS OF THE TECHNOLOGICAL FEASIBILITY, THE ENGINEERING DESIGN, THE RELIABILITY AND THE ACCEPTANCE FROM SAFETY AND LICENSING AUTHORITIES. THE MATERIALS CONSIDERED IN THIS STUDY ARE STAINLESS-STEEL (AISI 316) FOR THE COOLING TUBES, PURE COPPER FOR THE HEAT SINK, TUNGSTEN-5% RHENIUM ALLOY OR GRAPHITE FOR THE PROTECTIVE ARMOUR. THE COOLING OF THE PANEL IS ACHIEVED BY PRESSURIZED WATER CIRCULATING IN U-TUBES. A PRELIMINARY THERMOHYDRAULIC ANALYSIS HAS BEEN CARRIED OUT IN ORDER, TO EVALUATE A SET OF REFERENCE PARAMETERS SUCH AS OPTIMUM COOLANT VELO- CITY, MAXIMUM OUTLET WATER TEMPERATURE, CONVECTIVE HEAT EXCHANGE COEFFICIENT, AND THE EXPECTED PRESSURE DROPS IN THE CHANNELS. THE THERMAL AND THE MECHANI- CAL CALCULATIONS HAVE BEEN PERFORMED BY USING THE FINITE ELEMENT TECHNIQUE AND ASSUMING THE ASME CODE AS A GUIDE FOR THE DESIGN. SEVERAL GEOMETRIC AND MATE-ASRIAL RELATED EFFECTS HAVE BEEN TAKEN INTO ACCOUNT WITH PARTICULAR REFERENCE TO RIAL RELATED EFFECTS HAVE BEEN TAKEN INTO ACCOUNT WITH PARTICULAR REFERENCE TOTHE HEAT TRANSFER PERFORMANCE OF THE COMPONENT AND THE CONSEQUENT TEMPERATURE AND STRESS DISTRIBUTIONS. THE RESULTS OF THESE PRELIMINARY ELASTIC CALCULA- TIONS HAVE SHOWN THE ENGINEERING FEASIBILITY OF THE DIVERTOR FOR LOADING CONDITIONS SIMILAR TO THOSE OF NET DOUBLE NULL ASSUMED AS REFERENCE MAINFRAME.NA-NOT AVAILABL

Influence of a high magnetic field to the design of EU DEMO

The limitation considered in the definition of DEMO in 2016 to not exceed the magnetic field strength foreseen in the ITER machine is reviewed here. At the time, a Nb3Sn superconductor operated in a magnetic field, Bmax, no greater than 13T was considered to rely on existing and mature technology. This limitation is no longer seen as a boundary here, recognizing that the first model coil with Rare Earth Yttrium Barium Copper Oxid (REBCO) superconductor was recently operated at a field of &gt;20T. DEMO must have a burning plasma which, at a higher magnetic field, is reached in a significantly smaller plasma volume. Accordingly, a system code study was carried out to size the DEMO machine by varying the magnetic field. The outcome confirmed previous observations that the magnetic field strength is linearly dependent on the plasma aspect ratio, A, when we target a minimum machine size. It was notable that in a machine with a high A, the increased Bmax raises the plasma performance but does not allow for reducing its size. The reduced plasma elongation of plasmas with high aspect ratio is a caveat as it reduces the gain in plasma performance achieved in the high field. Furthermore, the higher magnetic field at high A challenges the engineering of the magnets and associated structures, and substantially increases the heat loads on the divertor. This article assesses the engineering feasibility assessment of large DEMO coils operated at high field, also considering advanced i.e., non-ITER like, mechanical concepts. No advanced coil concepts appeared suitable for a large device like DEMO. Consequently, DEMO design points with lower Bmax and lower A were investigated. This resulted in the identification of a maximum magnetic field of approximately 11–12 T to ensure the engineering feasibility of the DEMO TF coils.</div