Search

Abstract Recent findings suggest that Hematopoietic Stem Cells (HSC) and progenitors arise simultaneously and independently of each other already in the embryonic aorta-gonad mesonephros region, but it is still unknown how their different features are established. Here, we uncover IκBα (Nfkbia, the inhibitor of NF-κB) as a critical regulator of HSC proliferation throughout development. IκBα balances retinoic acid signaling levels together with the epigenetic silencer, PRC2, specifically in HSCs. Loss of IκBα decreases proliferation of HSC and induces a dormancy related gene expression signature instead. Also, IκBα deficient HSCs respond with superior activation to in vitro culture and in serial transplantation. At the molecular level, chromatin regions harboring binding motifs for retinoic acid signaling are hypo-methylated for the PRC2 dependent H3K27me3 mark in IκBα deficient HSCs. Overall, we show that the proliferation index in the developing HSCs is regulated by a IκBα-PRC2 axis, which controls retinoic acid signaling.

Objectives: To assess the safety and efficacy of an allogeneic adipose-derived mesenchymal stem cell preparation (MAG200) in the treatment of knee osteoarthritis over 12 months. Design: A single-centre, double-blind, ascending dose, randomised controlled trial. 40 participants with moderate knee osteoarthritis were randomised to receive a single intra-articular injection of MAG200 (dose cohorts:10, 20, 50, 100 ​× ​106 ​cells) or placebo. Primary objectives were safety and efficacy according to a compound responder analysis of minimal clinically important difference in pain (numerical pain rating scale [NPRS]) and function (Knee Injury and Osteoarthritis Outcome Score - Function in Daily Living subscale [KOOSADL]) at month 12. Secondary efficacy outcomes included changes from baseline in patient reported outcome measures and evaluation of disease-modification using quantitative MRI. Results: Treatment was well tolerated with no treatment-related serious adverse events. MAG200 cohorts reported a greater proportion of responders than placebo and demonstrated clinical and statistically significant improvement in pain and clinically relevant improvement in all KOOS subscales. MAG200 demonstrated a reproducible treatment effect over placebo, which was clinically relevant for pain in the 10 ​× ​106 dose cohort (mean difference NPRS:-2.25[95%CI:-4.47,-0.03, p ​= ​0.0468]) and for function in the 20 ​× ​106 and 100 ​× ​106 dose cohorts (mean difference KOOSADL:10.12[95%CI:-1.51,21.76, p ​= ​0.0863] and 10.81[95%CI:-1.42,23.04, p ​= ​0.0810] respectively). A trend in disease-modification was observed with improvement in total knee cartilage volume in MAG200 10, 20, and 100 ​× ​106 dose cohorts, with progression of osteoarthritis in placebo, though this was not statistically significant. No clear dose response was observed. Conclusion: This early-phase study provides supportive safety and efficacy evidence to progress MAG200 to later-stage trial development. Trial registration: ACTRN12617001095358/ACTRN12621000622808.

Abstract During the second long shutdown period of the CERN accelerator complex (LS2, 2019-2021), several upgrade activities took place at the n_TOF facility. The most important have been the replacement of the spallation target with a next generation nitrogen-cooled lead target. Additionally, a new experimental area, at a very short distance from the target assembly (the NEAR Station) was established. In this paper, the core commissioning actions of the new installations are described. The improvement in the n_TOF infrastructure was accompanied by several detector development projects. All these upgrade actions are discussed, focusing mostly on the future perspectives of the n_TOF facility. Furthermore, some indicative current and future measurements are briefly reported.

OBJECTIVES:. First, to investigate whether the severity of acute respiratory distress syndrome (ARDS) influences ventilator-induced lung injury (VILI) risk in ventilated patients with similar mechanical power of respiratory system (MPRS). Second, to determine whether, under these circumstances, there is a relationship between transpulmonary mechanical power (MPTp) normalized to the aerated lung (specific lung mechanical power or SLMP) and VILI risk, and third, to determine whether normalizing MPRS to compliance of respiratory system (CRS) can replace SLMP to bedside. DESIGN:. Prospective cohort study. SETTING:. The study was conducted in a tertiary academic ICU. PATIENTS:. The study included 18 patients with ARDS. INTERVENTIONS:. Ventilatory settings were adjusted to achieve a similar MPRS. MEASUREMENTS AND MAIN RESULTS:. Mechanical power was normalized to CRS (specific mechanical power or SMP = MPRS/CRS), and SLMP was calculated as the ratio between MPTp and end-expiratory lung volume (SLMP = MPTp/EELV). The strain was defined as the ratio between tidal volume and EELV (strain = Vt/EELV), stress as transpulmonary pressure at the end of inspiration, and atelectrauma as the difference between expiration and inspiration in the nonaerated lung. Although patients had been ventilated with similar MPRS = 23.75 (23–24) J/min and MPTp = 11.6 (10.8–12.8) J/min, SLMP increased linearly with the fall in Pao2/Fio2 (R = –0.83, p = 0.0001). MPRS only correlated positively with VILI-associated mechanisms when normalized to aerated lung size: correlations between SLMP and stress (R = 0.9, R2 = 0.84, p = 0.00004), strain (R = 0.97, R2 = 0.94, p < 0.00001) and atelectrauma (R = 0.82, R2 = 0.70, p = 0.00002), and correlations between SMP and stress (R = 0.86, R2 = 0.75, p = 0.00001), strain (R = 0.68, R2 = 0.47, p = 0.001) and atelectrauma (R = 0.67, R2 = 0.46, p = 0.002). CONCLUSIONS:. The results suggest that normalizing mechanical power to lung-aerated size or CRS may correlate positively with stress, strain, and atelectrauma.

Background and Aims: The management of post-operative pain after surgical repair of pectus excavatum with the Ravitch procedure is challenging. Although previous studies have compared various methods of pain control in these patients, few have compared different local anesthetics. This retrospective analysis compares the use of bupivacaine to its longer-acting form, liposomal bupivacaine, in patients who had undergone pectus excavatum repair with the Ravitch method. Material and Methods: Eleven patients who received local infiltration with liposomal bupivacaine were matched to 11 patients who received local infiltration utilizing bupivacaine with epinephrine. The primary outcome was total morphine milligram equivalents per kilogram body weight (MME/kg) over the complete length of hospital stay. Secondary outcomes included total cumulative diazepam, acetaminophen, ondansetron, and NSAID dose per kilogram body weight (mg/kg) over the course of the hospital stay, chest tube drainage (ml/kg body weight), number of post-operative hours until the first bowel movement, Haller Index, patient request for magnesium hydroxide, average pain scores from post-operative day 1 to post-operative day 5, and length of hospital stay. Continuous variables were reported as medians with inter-quartile ranges, and categorical values were reported as percentages and frequencies. Results: The total MME/kg [1.7 (1.2-2.4) vs 2.9 (2.0-3.9), P = 0.007] and hydromorphone (mg/kg) [0.1 (0.0-0.2) vs 0.3 (0.1-0.4), P = 0.006] use in the liposomal bupivacaine group versus bupivacaine with epinephrine was significantly reduced over total length of hospital stay. Similarly, there was a reduction in diazepam use in the liposomal bupivacaine group versus the bupivacaine group [0.4 (0.1-0.8) vs 0.6 (0.4-0.7), P = 0.249], but this did not reach statistical significance. The total dose of ondansetron (mg/kg) was not statistically different when comparing the liposomal bupivacaine group to the bupivacaine group [0.3 (0.0-0.5) vs 0.3 (0.2-0.6), P = 0.332]. Interestingly, the total dose of acetaminophen (mg/kg) was statistically increased in the liposomal bupivacaine group compared to the bupivacaine with epinephrine group [172 (138-183) vs 74 (55-111), P = 0.007]. Additionally, the total chest tube drainage (ml/kg) was significantly reduced in the liposomal bupivacaine group [9.3 (7.5-10.6) vs 12.8 (11.3-18.5), P = 0.027]. Finally, the percentage of patients without requests for magnesium hydroxide to promote laxation was significantly higher in the liposomal bupivacaine group than in the bupivacaine group (63.6% vs 18.2%, P = 0.027). Conclusion: The use of liposomal bupivacaine for local infiltration in patients who undergo the Ravitch procedure for pectus repair offers advantages over plain bupivacaine, including reduced opioid consumption and opioid-related side effects. However, more data are needed to understand the significance of these findings.

The actions for the preservation of cultural heritage must work on the identity and specificity of the places, paying the utmost attention to the context relationships. The analysis of these elements is fundamental to the recognition of the intrinsic “value” of the building, of the cultural, architectural, and landscape type and of the “value relations” that the building holds with the surrounding context of the social and economic but, above all, cultural and identity type. The methodological approaches defined by the ICOMOS Document of Madrid–New Delhi recognize the identification of the cultural value as a fundamental passage for the promotion of the 20th-century heritage. The contribution analyzes the design process developed by applying the ICOMOS methodology for the preservation of the cultural value of a building complex in Pozzuoli dating back to the early 1900s. The evolutionary history of the different volumes and the configuration of the “modern ruins” give rise to prospective relationships with the local reality that today assume a stronger identity value than that connected to the original project. The different construction techniques used and the state of conservation of the buildings lead to the identifying of different elements of value and, consequently, to the elaborating different design choices.

Hydropower (HP) is a key source of renewable energy, but also poses significant environmental challenges, including habitat fragmentation, hydropeaking and perturbations of flow and sediment regime. This study analyzed how Italian companies managing HP plants, and registered to the European Eco-Management and Audit Scheme (EMAS) in 2022, evaluated their sustainability and publicly disclosed related data. The analysis was based on the environmental statements (ESs) of 206 hydropower plants (29% of Italian HP production in 2019). The applied methodology involved an inventory of the plants and their categorization about technical features and the reporting of technical, environmental, and social aspects. The results of the analysis revealed that the companies rarely described the environmental state of the site, even less frequently adopting quantitative indicators. “Soil contamination”, “biodiversity”, “waste production”, “risk of environmental accidents”, “water pollution and flow management”, and “noise emissions” were the aspects considered most significant. No correlation was found among the significance of an aspect, the number of indicators used to describe the associated impacts, and the number of objectives set for reducing those impacts. “Biodiversity” was mostly described through irrelevant indicators (i.e., total site area) and 76% of the allocated budget was assigned to technical aspects without a clear connection with any environmental improvement. In particular, the specific impacts on the aquatic ecosystems were scarcely reported, mitigation measures were rarely mentioned and with few details. In conclusion, the results of the study highlight the need for specific guidelines, directed to the HP sector, for effectively reporting the environmental performances and the effectiveness of the adopted Environmental Management Systems, while providing valuable information to policymakers and researchers.

The neutron Time-of-Flight (TOF) research facility at CERN, n_TOF, has been a pioneering platform for neutron cross-section measurements since its inception in 2001. It boasts three distinct experimental areas, each tailored to address a specific range of neutron energies. This paper delves into the intricacies of the n_TOF facility, including its recent upgrade during the Long Shutdown 2 (LS2) at CERN. Additionally, it highlights the key characteristics of the detectors employed for capture and fission cross-section measurements, paving the way for future research endeavors.

Chromium is a very relevant element regarding criticality safety in nuclear reactors because of its presence in stainless steel, an important structural material. Currently, there are serious discrepancies between the different evaluations regarding the neutron capture cross sections of 50Cr and 53Cr, most probably related to the difficulty of reducing and then estimating the very large neutron scattering effects on the shape of the resonances. In this context, there is a recent entry in the Nuclear Energy Agency (NEA) High Priority Request List (HPRL) to measure these reactions between 1 and 100 keV with an accuracy of 8-10%. In response to this request, we have performed a time-of-flight experiment at CERN n_TOF (Switzerland) and a complementary activation experimenton 50Crat30and90keVatCNAHiSPANoS(Spain).Theexperiments are presented herein, together with a discussion on the quality of the preliminary data and the results to be expected.

The experimental setup of the new measurement of 239Pu fission and capture cross-section in the n_TOF time-of-flight facility at CERN is presented. The measurement aims to address the needs and demands of nuclear data users. The experiment incorporates an innovative fast Fission Fragment Detector and the n_TOF Total Absorption Calorimeter, enabling the implementation of the fission tagging technique. Preliminary results exhibit the robust performance of the detector systems, along with the high quality of the new 239Pu samples. These samples were exclusively produced for this measurement by the European Commission’s Joint Research Centre in Geel.

Previous research has demonstrated that speakers changephonetic forms in response to variability in their immediatelinguistic milieu, such that they converge with an interlocutor.While much is known about the impact of social dynamics onthis process, the impact of individual variability in cognitionand perception is less well-explored. The present study seeksto examine the impact of these individual differences onphonetic convergence during a naturalistic conversation,comparing convergence in autism spectrum disorder (ASD)and typical development. Results showed a small effect oftemporal convergence within typically developing dyads,compared with evidence of divergence within ASD dyads.While preliminary, this pattern of results suggests that socialmotivation may play a more important role in phoneticconvergence than sensory accounts (such as self-monitoring).

The reliability of turbine engines depends significantly on the environment experienced during flight. Air humidity, corrosive contaminant substances, and high operating temperatures are among the attributes that affect engine lifespans. The specifics of the environment that affect materials are not always known, and damage is often evaluated by time-consuming manual inspection. This study innovates by demonstrating that machine learning approaches can identify the environmental conditions that degrade jet engine metallic materials. We used the state-of-the-art pre-trained neural network models to assess images of damaged nickel-based superalloy samples to identify the environment temperature, the exposure time, and the deposited amounts of salt contaminants. These parameters are predicted by training the model with a database of approximately 3,600 sample images tested in laboratory conditions. A novel tree classification process results in excellent predictive power for classifying the type of environment experienced by nickel-based superalloys.

In the frame of Radon rEal time monitoring System and Proactive Indoor Remediation (RESPIRE), a LIFE 2016 project funded by the European Commission, the contribution of building materials of volcanic origin to indoor radon concentration was investigated. First, total gamma radiation and related outdoor dose rates of geological materials in the Caprarola area (Central Italy) were measured to define main sources of radiation. Second, 222Rn and 220Rn exhalation rates of these rocks used as building materials were measured using an accumulation chamber connected in a closed loop with a RAD7 radon monitor. Among others, the very porous “Tufo di Gallese” ignimbrite provided the highest values. This material was then used to construct a scale model room of 62 cm × 50 cm × 35 cm (inner length × width × height, respectively) to assess experimental radon and thoron activity concentration at equilibrium and study the effects of climatic conditions and different coatings on radon levels. A first test was carried out at ambient temperature to determine experimental 222Rn and 220Rn equilibrium activities in the model room, not covered with plaster or other coating materials. Experimental 222Rn equilibrium was recorded in just two days demonstrating that the room “breaths”, exchanging air with the outdoor environment. This determines a dilution of indoor radon concentration. Other experiments showed that inner covers (such as plasterboard and different kinds of paints) partially influence 222Rn but entirely cut the short-lived 220Rn. Finally, decreases in ambient temperature reduce radon exhalation from building material and, in turn, indoor activity concentration.

Capture and total cross section measurements for 94,95,96Mo have been performed at the neutron time-of-flight facilities, n_TOF at CERN and GELINA at JRC-Geel. The measurements were performed using isotopically enriched samples with an enrichment above 95% for each of the 94,95,96Mo isotopes. The capture measurements were performed at n_TOF using C6D6 detectors and a new sTED detector. The transmission measurements were performed at a 10 m station of GELINA using a 6Li glass neutron detector. Preliminary results of these measurements are presented.

The neutron time-of-flight facility n_TOF is characterised by its high instantaneous neutron intensity, high-resolution and broad neutron energy spectra, specially conceived for neutron-induced reaction cross section measurements. Two Time-Of-Flight (TOF) experimental areas are available at the facility: experimental area 1 (EAR1), located at the end of the 185 m horizontal flight path from the spallation target, and experimental area 2 (EAR2), placed at 20 m from the target in the vertical direction. The neutron fluence in EAR2 is ˜ 300 times more intense than in EAR1 in the relevant time-of-flight window. EAR2 was designed to carry out challenging cross-section measurements with low mass samples (approximately 1 mg), reactions with small cross-sections or/and highly radioactive samples. The high instantaneous fluence of EAR2 results in high counting rates that challenge the existing capture systems. Therefore, the sTED detector has been designed to mitigate these effects. In 2021, a dedicated campaign was done validating the performance of the detector up to at least 300 keV neutron energy. After this campaign, the detector has been used to perform various capture cross section measurements at n_TOF EAR2.

The NEAR Station is a new experimental area developed at the n_TOF Facility at CERN. The activation station of NEAR underwent a characterization of the beam following the installation of the new n_TOF Spallation Target. The commissioning of the neutron beam comprises a set of simulations made with the FLUKA code and experimental verification. The experimental determination of the neutron spectrum was made using activation techniques with three separate set-ups. Two set-ups were based on the Multi-foil Activation technique (MAM-1 and MAM-2), and the third set-up relied on the process of neutron moderation and activation of a single material (ANTILoPE). The three set-ups are presented. Also the present plans and future perspectives of the activation station of NEAR are discussed.

The n_TOF facility hosts CERN’s pulsed neutron source, comprising two beam lines of different flight paths and one activation station. It is based on a proton beam delivered by the PS accelerator impinging on a lead spallation target. During Long Shutdown 2 (LS2) at CERN (2019-2021), a major upgrade of the spallation target was carried out in order to optimize the performances of the neutron beam. Therefore, the characteristics of n_TOF two experimental areas were investigated in detail. In this work, the focus is on the second experimental area (EAR2), located 20 m above the spallation target. Preliminary results of the neutron energy distribution and beam line energy resolution are presented, compared to previous experimental campaigns and Monte Carlo simulations with the FLUKA code. Moreover, preliminary results of the spatial beam profile measurements are shown.

Several international agencies recommend the study of new routes and new facilities for producing radioisotopes with application to nuclear medicine. 177Lu is a versatile radioisotope used for therapy and diagnosis (theranostics) of cancer with good success in neuroendocrine tumours that is being studied to be applied to a wider range of tumours. 177Lu is produced in few nuclear reactors mainly by the neutron capture on 176Lu. However, it could be produced at high-intensity celeratorbased neutron facilities. The energy of the neutrons in accelerator-based neutron facilities is higher than in thermal reactors.Thus, experimental data on the 176Yb(n,γ) cross-section in the eV and keV region are mandatory to calculate accurately the production of 177Yb, which beta decays to 177Lu. At present, there are not experimental data available from thermal to 3 keV of the 176Yb(n,γ) cross-section. In addition, there is no data in the resolved resonance region (RRR). This contribution shows the first results of the 176Yb capture measurement performed at the n_TOF facility at CERN.

The increasing worldwide interest in Lead-cooled Fast Reactors (LFRs) substantiates the need to validate the analytical codes and methods used to support their design. For neutronic analyses, this is chiefly reflected in assessing the impact of nuclear data uncertainties on the integral and local parameters resulting from such analyses. The aim of refining nuclear data moves continuous efforts for more accurate measurements, be them differential or integral, for which adequate facilities are required. The availability at the ENEA's Casaccia research center of a fast source reactor – RSV TAPIRO – provides a unique opportunity to perform new integral experiments in support of fast reactors, including LFRs, owing to the well-characterized neutron spectrum of the thermal column. A series of experiments has been envisaged, dealing with the use of Lead in a reactor. The experiments concern the propagation of neutrons through blocks of materials representing relevant elements of a reactor core, and ranging from pure Lead to mixtures reproducing portions of the reflector and shield in LFRs. The paper is focused on the feasibility study of some of these experiments in which Lead and mixture blocks are inserted in the so-called thermal column of the RSV TAPIRO reactor and irradiated by the neutron flux emerging from the Copper reflector surrounding the reactor core.

Neutron-induced cross sections represent the main nuclear input to models of stellar and Big-Bang nucleosynthesis. While (n,γ) reactions are relevant for the formation of elements heavier than iron, (n,p) and (n,α) reactions can play an important role in specific cases. The time-of-flight method is routinely used at n_TOF to experimentally determine the cross section data. In addition, recent upgrades of the facility will allow the use of activation techniques as well, possibly opening the way to a systematic study of neutron interaction with radioactive isotopes. In the last 20 years n_TOF has provided a large amount of experimental data for Nuclear Astrophysics. Our plan is to carry on challenging measurements and produce nuclear data in the next decades as well.

Background: Meditation is gaining recognition as a tool to impact health and well-being. Samyama is an 8-day intensive residential meditation experience conducted by Isha Foundation requiring several months of extensive preparation and vegan diet. The health effects of Samyama have not been previously studied. The objective was to assess physical and emotional well-being before and after Samyama participation by evaluating psychological surveys and objective health biomarkers.Methods: This was an observational study of 632 adults before and after the Isha Samyama retreat. All participants were invited to complete surveys. Controls included household significant others. Surveys were completed at baseline (T1), just before Samyama (T2), immediately after Samyama (T3), and 3 months later (T4) to assess anxiety, depression, mindfulness, joy, vitality, and resilience through validated psychometric scales. Voluntary blood sampling for biomarker analysis was done to assess hemoglobin (Hb), HbA1c, lipid profile, and C-reactive protein (CRP). Primary outcomes were changes in psychometric scores, body weight, and blood biomarkers.Results: Depression and anxiety scores decreased from T1 to T3, with the effect most pronounced in participants with baseline depression or anxiety. Scores at T4 remained below baseline for those with pre-existing depression or anxiety. Vitality, resilience, joy, and mindfulness increased from T1 to T3 (sustained at T4). Body weight decreased by 3% from T1 to T3. Triglycerides (TG) were lower from T2 to T3. Participants had lower HbA1c and HDL at T2, and lower CRP at all timepoints compared with controls.Conclusions: Participation in the Isha Samyama program led to multiple benefits. The 2-month preparation reduced anxiety, and participants maintained lower anxiety levels at 3 months post-retreat. Physical health improved over the course of the program as evidenced by weight loss and improved HbA1C and lipid profile. Practices associated with the Samyama preparation phase and the retreat may serve as an effective way to improve physical and mental health. Future studies may examine their use as an alternative therapy in patients with depression and/or anxiety.Clinical Trial Registration:www.ClinicalTrials.gov, Identifier: 1801728792. Registered retrospectively on 4/17/2020.

The literature proposes many software metrics for evaluating the source code non-functional properties, such as its complexity and maintainability. The literature also proposes several tools to compute those properties on source codes developed with many different software languages. However, the Rust language emergence has not been paired by the community’s effort in developing parsers and tools able to compute metrics for the Rust source code. Also, metrics tools often fall short in providing immediate means of comparing maintainability metrics between different algorithms or coding languages. We hence introduce rust-code-analysis, a Rust library that allows the extraction of a set of eleven maintainability metrics for ten different languages, including Rust. rust-code-analysis, through the Abstract Syntax Tree (AST) of a source file, allows the inspection of the code structure, analyzing source code metrics at different levels of granularity, and finding code syntax errors before compiling time. The tool also offers a command-line interface that allows exporting the results in different formats. The possibility of analyzing source codes written in different programming languages enables simple and systematic comparisons between the metrics produced from different empirical and large-scale analysis sources.

The neutron capture cross section of 154Gd was measured from 1 eV to 300 keV in the experimental area located 185 m from the CERN n_TOF neutron spallation source, using a metallic sample of gadolinium, enriched to 67% in 154Gd. The capture measurement, performed with four C6D6 scintillation detectors, has been complemented by a transmission measurement performed at the GELINA time-of-flight facility (JRC-Geel), thus minimising the uncertainty related to sample composition. An accurate Maxwellian averaged capture cross section (MACS) was deduced over the temperature range of interest for s process nucleosynthesis modelling. We report a value of 880(50) mb for the MACS at kT=30 keV, significantly lower compared to values available in literature. The new adopted 154Gd(n,γ) cross section reduces the discrepancy between observed and calculated solar s-only isotopic abundances predicted by s-process nucleosynthesis models. Keywords: s process, 154Gd, Neutron time of flight, n_TOF