Feasibility study to characterize the production of antineutrons in high energy pppp collisions through charge exchange interactions

Simulations to evaluate the feasibility of $\bar{n}$ identification and kinematic characterization via the hadronic charge exchange (CEX) interaction $n+\bar{n}\rightarrow p+\bar{p}$ are reported. The target neutrons are those composing the silicon nuclei of which inner tracking devices present in LHC experiments are made. Simulations of $pp$ collisions in PYTHIA were carried out at different energies to investigate $\bar{n}$ production and the expected $\bar{n}$ energy spectra. Then, two types of GEANT4 simulations were performed, placing an $\bar{n}$ point source at the ALICE primary vertex as a working example. In the first simulation, the $E_k$ was kept at an arbitrary (1 GeV) fix value to develop an $\bar{n}$ identification and kinematics reconstruction protocol. The second GEANT4 simulation used the resulting PYTHIA at $\sqrt{s_{pp}}=13$ TeV $\bar{n}$ energy spectra. In both simulations, the occurrence of CEX interactions was identified by the unique outgoing $\bar{p}$. The simplified simulation allowed to estimate a 0.11% CEX-interaction identification efficiency at $E_k = 1$ GeV. The $p$ CEX-partner identification is challenging because of the presence of silicon nucleus-fragmentation protons. Momentum correlations between the $\bar{n}$ and all possible $\bar{p}p$ pairs showed that $p$ CEX-partner identification and $\bar{n}$ kinematics reconstruction corresponds to minimal momentum-loss events. The use of ITS $dE/dx$ information is found to improve $\bar{n}$ identification and kinematic characterization in both simulations. The final protocol applied to the realistic simulation resulted in a $\bar{n}$ identification and kinematic reconstruction efficiency of 0.006%, based solely on $\bar{p}p$ pair observable. Thus, the expected rate of identified and kinematically reconstructed $\bar{n}$ should lie in the order of 100,000 per second, illustrating the feasibility of the method.Comment: 6 pages, 11 figure

The Spatial Distribution of Star Formation in the Solar Neighbourhood: Do all stars form in clusters?

We present a global study of low mass, young stellar object (YSO) surface densities in nearby (< 500 pc) star forming regions based on a comprehensive collection of Spitzer Space Telescope surveys. We show that the distribution of YSO surface densities in the solar neighbourhood is a smooth distribution, being adequately described by a lognormal function from a few to 10^3 YSOs per pc^2, with a peak at 22 stars/pc^2 and a dispersion of 0.85. We do not find evidence for multiple discrete modes of star-formation (e.g. clustered and distributed). Comparing the observed surface density distribution to previously reported surface density threshold definitions of clusters, we find that the fraction of stars in clusters is crucially dependent on the adopted definitions, ranging from 40 to 90%. However, we find that only a low fraction (< 26%) of stars are formed in dense environments where their formation/evolution (along with their circumstellar disks and/or planets) may be affected by the close proximity of their low-mass neighbours.Comment: 6 pages, 2 figures, MNRAS letters, accepte

Impact of COVID-19 on medical education: Introducinghomo digitalis

Purpose To determine how members of the Societe Internationale d'Urologie (SIU) are continuing their education in the time of COVID-19. Methods A survey was disseminated amongst SIU members worldwide by email. Results were analyzed to examine the influence of age, practice region and settings on continuing medical education (CME) of the respondents. Results In total, 2494 respondents completed the survey. Internet searching was the most common method of CME (76%; allps = 2 platforms, with approximately 10% of the respondents using up to 5 different platforms. Urologists < 40 years old were more likely to use online literature (69%), podcasts/AV media (38%), online CME courses/webinars (40%), and social media (39%). There were regional variations in the CME modality used but no significant difference in the number of methods by region. There was no significant difference in responses between urologists in academic/public hospitals or private practice. Conclusion During COVID-19, urologists have used web-based learning for their CME. Internet learning and literature were the top frequently cited learning methods. Younger urologists are more likely to use all forms of digital learning methods, while older urologists prefer fewer methods

Do All Stars in the Solar Neighbourhood Form in Clusters?

We present a global study of low mass, young stellar object (YSO) surface densities (Sigma) in nearby (< 500 pc) star forming regions based on a comprehensive collection of Spitzer Space Telescope surveys. We show that the distribution of YSO surface densities is a smooth distribution, being adequately described by a lognormal function from a few to 10^3 YSOs per pc^2, with a peak at ~22 stars pc^-2. The observed lognormal Sigma is consistent with predictions of hierarchically structured star-formation at scales below 10 pc, arising from the molecular cloud structures. We do not find evidence for multiple discrete modes of star-formation (e.g. clustered and distributed). Comparing the observed Sigma distribution to previous Sigma threshold definitions of clusters show that they are arbitrary. We find that only a low fraction (< 26$) of stars are formed in dense environments where their formation/evolution (along with their circumstellar disks and/or planets) may be affected by the close proximity of their low-mass neighbours.Comment: 7 Pages, 2 Figures, JENAM conference (Lisbon

Identification of Cis-Acting Promoter Elements in Cold- and Dehydration-Induced Transcriptional Pathways in Arabidopsis, Rice, and Soybean

The genomes of three plants, Arabidopsis (Arabidopsis thaliana), rice (Oryza sativa), and soybean (Glycine max), have been sequenced, and their many genes and promoters have been predicted. In Arabidopsis, cis-acting promoter elements involved in cold- and dehydration-responsive gene expression have been extensively analysed; however, the characteristics of such cis-acting promoter sequences in cold- and dehydration-inducible genes of rice and soybean remain to be clarified. In this study, we performed microarray analyses using the three species, and compared characteristics of identified cold- and dehydration-inducible genes. Transcription profiles of the cold- and dehydration-responsive genes were similar among these three species, showing representative upregulated (dehydrin/LEA) and downregulated (photosynthesis-related) genes. All (46 = 4096) hexamer sequences in the promoters of the three species were investigated, revealing the frequency of conserved sequences in cold- and dehydration-inducible promoters. A core sequence of the abscisic acid-responsive element (ABRE) was the most conserved in dehydration-inducible promoters of all three species, suggesting that transcriptional regulation for dehydration-inducible genes is similar among these three species, with the ABRE-dependent transcriptional pathway. In contrast, for cold-inducible promoters, the conserved hexamer sequences were diversified among these three species, suggesting the existence of diverse transcriptional regulatory pathways for cold-inducible genes among the species

Preclinical and randomized phase I studies of plitidepsin in adults hospitalized with COVID-19

Plitidepsin, a marine-derived cyclic-peptide, inhibits SARS-CoV-2 replication at nanomolar concentrations by targeting the host protein eukaryotic translation elongation factor 1A. Here, we show that plitidepsin distributes preferentially to lung over plasma, with similar potency against across several SARS-CoV-2 variants in preclinical studies. Simultaneously, in this randomized, parallel, open-label, proof-of-concept study (NCT04382066) conducted in 10 Spanish hospitals between May and November 2020, 46 adult hospitalized patients with confirmed SARS-CoV-2 infection received either 1.5 mg (n = 15), 2.0 mg (n = 16), or 2.5 mg (n = 15) plitidepsin once daily for 3 d. The primary objective was safety; viral load kinetics, mortality, need for increased respiratory support, and dose selection were secondary end points. One patient withdrew consent before starting procedures; 45 initiated treatment; one withdrew because of hypersensitivity. Two Grade 3 treatment-related adverse events were observed (hypersensitivity and diarrhea). Treatment-related adverse events affecting more than 5% of patients were nausea (42.2%), vomiting (15.6%), and diarrhea (6.7%). Mean viral load reductions from baseline were 1.35, 2.35, 3.25, and 3.85 log10 at days 4, 7, 15, and 31. Nonmechanical invasive ventilation was required in 8 of 44 evaluable patients (16.0%); six patients required intensive care support (13.6%), and three patients (6.7%) died (COVID-19-related). Plitidepsin has a favorable safety profile in patients with COVID-19

Toll-Like Receptor 9 Is Required for Opioid-Induced Microglia Apoptosis

Opioids have been widely applied in clinics as one of the most potent pain relievers for centuries, but their abuse has deleterious physiological effects beyond addiction. However, the underlying mechanism by which microglia in response to opioids remains largely unknown. Here we show that morphine induces the expression of Toll-like receptor 9 (TLR9), a key mediator of innate immunity and inflammation. Interestingly, TLR9 deficiency significantly inhibited morphine-induced apoptosis in microglia. Similar results were obtained when endogenous TLR9 expression was suppressed by the TLR9 inhibitor CpGODN. Inhibition of p38 MAPK by its specific inhibitor SB203580 attenuated morphine-induced microglia apoptosis in wild type microglia. Morphine caused a dramatic decrease in Bcl-2 level but increase in Bax level in wild type microglia, but not in TLR9 deficient microglia. In addition, morphine treatment failed to induce an increased levels of phosphorylated p38 MAPK and MAP kinase kinase 3/6 (MKK3/6), the upstream MAPK kinase of p38 MAPK, in either TLR9 deficient or µ-opioid receptor (µOR) deficient primary microglia, suggesting an involvement of MAPK and µOR in morphine-mediated TLR9 signaling. Moreover, morphine-induced TLR9 expression and microglia apoptosis appears to require μOR. Collectively, these results reveal that opioids prime microglia to undergo apoptosis through TLR9 and µOR as well. Taken together, our data suggest that inhibition of TLR9 and/or blockage of µOR is capable of preventing opioid-induced brain damage

Rate and duration of hospitalisation for acute pulmonary embolism in the real-world clinical practice of different countries : Analysis from the RIETE registry

publishersversionPeer reviewe

How do 66 European institutional review boards approve one protocol for an international prospective observational study on traumatic brain injury? Experiences from the CENTER-TBI study

Background The European Union (EU) aims to optimize patient protection and efficiency of health-care research by harmonizing procedures across Member States. Nonetheless, further improvements are required to increase multicenter research efficiency. We investigated IRB procedures in a large prospective European multicenter study on traumatic brain injury (TBI), aiming to inform and stimulate initiatives to improve efficiency. Methods We reviewed relevant documents regarding IRB submission and IRB approval from European neurotrauma centers participating in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI). Documents included detailed information on IRB procedures and the duration from IRB submission until approval(s). They were translated and analyzed to determine the level of harmonization of IRB procedures within Europe. Results From 18 countries, 66 centers provided the requested documents. The primary IRB review was conducted centrally (N = 11, 61%) or locally (N = 7, 39%) and primary IRB approval was obtained after one (N = 8, 44%), two (N = 6, 33%) or three (N = 4, 23%) review rounds with a median duration of respectively 50 and 98 days until primary IRB approval. Additional IRB approval was required in 55% of countries and could increase duration to 535 days. Total duration from submission until required IRB approval was obtained was 114 days (IQR 75-224) and appeared to be shorter after submission to local IRBs compared to central IRBs (50 vs. 138 days, p = 0.0074). Conclusion We found variation in IRB procedures between and within European countries. There were differences in submission and approval requirements, number of review rounds and total duration. Research collaborations could benefit from the implementation of more uniform legislation and regulation while acknowledging local cultural habits and moral values between countries.Peer reviewe

Diminishing benefits of urban living for children and adolescents’ growth and development

Optimal growth and development in childhood and adolescence is crucial for lifelong health and well-being1–6. Here we used data from 2,325 population-based studies, with measurements of height and weight from 71 million participants, to report the height and body-mass index (BMI) of children and adolescents aged 5–19 years on the basis of rural and urban place of residence in 200 countries and territories from 1990 to 2020. In 1990, children and adolescents residing in cities were taller than their rural counterparts in all but a few high-income&nbsp;countries. By 2020, the urban height advantage became smaller in most countries, and in many high-income western countries it reversed into a small urban-based disadvantage. The exception was for boys in most countries in sub-Saharan Africa and in some countries in Oceania, south Asia and the region of central Asia, Middle East and north Africa. In these countries, successive cohorts of boys from rural places either did not gain height or possibly became shorter, and hence fell further behind their urban peers. The difference between the age-standardized mean BMI of children in urban and rural areas was &lt;1.1 kg m–2 in the vast majority of&nbsp;countries. Within this small range, BMI increased slightly more in cities than in rural areas, except in south Asia, sub-Saharan Africa and some countries in central and eastern Europe. Our results show that in much of the world, the growth and developmental advantages of living in cities have diminished in the twenty-first century, whereas in much of sub-Saharan Africa they have amplified