Design of a high power production target for the Beam Dump Facility at CERN

The Beam Dump Facility (BDF) project is a proposed general-purpose facility at CERN, dedicated to beam dump and fixed target experiments. In its initial phase, the facility is foreseen to be exploited by the Search for Hidden Particles (SHiP) experiment. Physics requirements call for a pulsed 400 GeV/c proton beam as well as the highest possible number of protons on target (POT) each year of operation, in order to search for feebly interacting particles. The target/dump assembly lies at the heart of the facility, with the aim of safely absorbing the full high intensity Super Proton Synchrotron (SPS) beam, while maximizing the production of charmed and beauty mesons. High-Z materials are required for the target/dump, in order to have the shortest possible absorber and reduce muon background for the downstream experiment. The high average power deposited on target (305 kW) creates a challenge for heat removal. During the BDF facility Comprehensive Design Study (CDS), launched by CERN in 2016, extensive studies have been carried out in order to define and assess the target assembly design. These studies are described in the present contribution, which details the proposed design of the BDF production target, as well as the material selection process and the optimization of the target configuration and beam dilution. One of the specific challenges and novelty of this work is the need to consider new target materials, such as a molybdenum alloy (TZM) as core absorbing material and Ta2.5W as cladding. Thermo-structural and fluid dynamics calculations have been performed to evaluate the reliability of the target and its cooling system under beam operation. In the framework of the target comprehensive design, a preliminary mechanical design of the full target assembly has also been carried out, assessing the feasibility of the whole target system.Comment: 17 pages, 18 figure

Intramedullary melanotic schwannoma

We present a case of an intramedullary melanotic schwannoma (IMS) of the thoracic spinal cord. To our knowledge, this is the seventh reported case of an IMS of the central nervous system. Schwannomas are benign nerve sheath tumors of neural crest origin composed entirely of well differentiated Schwann cells that typically occur in peripheral nerves. Both the intramedullary location and the melanotic component of the reported lesion make it exceedingly rare. We will present our case, theories as to the origin of these tumors, clues in radiographic identification, and current clinical follow-up recommendations

Intracranial complications of sinogenic and otogenic infections in children:an ESPN survey on their occurrence in the pre-COVID and post-COVID era

Background: COVID-19 pandemic is thought to have changed the epidemiology of some pediatric neurosurgical disease: among them are the intracranial complications of sinusitis and otitis (ICSO). According to some studies on a limited number of cases, both streptococci-related sinusitis and ICSO would have increased immediately after the pandemic, although the reason is not clear yet (seasonal changes versus pandemic-related effects). The goal of the present survey of the European Society for Pediatric Neurosurgery (ESPN) was to collect a large number of cases from different European countries encompassing the pre-COVID (2017–2019), COVID (2020–2021), and post-COVID period (2022–June 2023) looking for possible epidemiological and/or clinical changes. Material and methods: An English language questionnaire was sent to ESPN members about year of the event, patient’s age and gender, presence of immune-deficit or other favoring risk factors, COVID infection, signs and symptoms at onset, site of primary infection, type of intracranial complication, identified germ, type and number of surgical operations, type and duration of medical treatment, clinical and radiological outcome, duration of the follow-up. Results: Two hundred fifty-four cases were collected by 30 centers coming from 14 different European countries. There was a statistically significant difference between the post-COVID period (129 children, 86 cases/year, 50.7% of the whole series) and the COVID (40 children, 20 cases/year, 15.7%) or the pre-COVID period (85 children, 28.3 cases/year, 33.5%). Other significant differences concerned the presence of predisposing factors/concurrent diseases (higher in the pre-COVID period) and previous COVID infection (higher in the post-COVID period). No relevant differences occurred as far as demographic, microbiological, clinical, radiological, outcome, morbidity, and mortality data were concerned. Paranasal sinuses and middle ear/mastoid were the most involved primary site of infection (71% and 27%, respectively), while extradural or subdural empyema and brain abscess were the most common ICSO (73% and 17%, respectively). Surgery was required in 95% of cases (neurosurgical and ENT procedure in 71% and 62% of cases, respectively) while antibiotics in 99% of cases. After a 12.4-month follow-up, a full clinical and radiological recovery was obtained in 85% and 84% of cases, respectively. The mortality rate was 2.7%. Conclusions: These results suggest that the occurrence of ICSO was significantly increased after the pandemic. Such an increase seems to be related to the indirect effects of the pandemic (e.g., immunity debt) rather than to a direct effect of COVID infection or to seasonal fluctuations. ICSO remain challenging diseases but the pandemic did not affect the management strategies nor their prognosis. The epidemiological change of sinusitis/otitis and ICSO should alert about the appropriate follow-up of children with sinusitis/otitis.</p

Intracranial complications of sinogenic and otogenic infections in children:an ESPN survey on their occurrence in the pre-COVID and post-COVID era

Background: COVID-19 pandemic is thought to have changed the epidemiology of some pediatric neurosurgical disease: among them are the intracranial complications of sinusitis and otitis (ICSO). According to some studies on a limited number of cases, both streptococci-related sinusitis and ICSO would have increased immediately after the pandemic, although the reason is not clear yet (seasonal changes versus pandemic-related effects). The goal of the present survey of the European Society for Pediatric Neurosurgery (ESPN) was to collect a large number of cases from different European countries encompassing the pre-COVID (2017–2019), COVID (2020–2021), and post-COVID period (2022–June 2023) looking for possible epidemiological and/or clinical changes. Material and methods: An English language questionnaire was sent to ESPN members about year of the event, patient’s age and gender, presence of immune-deficit or other favoring risk factors, COVID infection, signs and symptoms at onset, site of primary infection, type of intracranial complication, identified germ, type and number of surgical operations, type and duration of medical treatment, clinical and radiological outcome, duration of the follow-up. Results: Two hundred fifty-four cases were collected by 30 centers coming from 14 different European countries. There was a statistically significant difference between the post-COVID period (129 children, 86 cases/year, 50.7% of the whole series) and the COVID (40 children, 20 cases/year, 15.7%) or the pre-COVID period (85 children, 28.3 cases/year, 33.5%). Other significant differences concerned the presence of predisposing factors/concurrent diseases (higher in the pre-COVID period) and previous COVID infection (higher in the post-COVID period). No relevant differences occurred as far as demographic, microbiological, clinical, radiological, outcome, morbidity, and mortality data were concerned. Paranasal sinuses and middle ear/mastoid were the most involved primary site of infection (71% and 27%, respectively), while extradural or subdural empyema and brain abscess were the most common ICSO (73% and 17%, respectively). Surgery was required in 95% of cases (neurosurgical and ENT procedure in 71% and 62% of cases, respectively) while antibiotics in 99% of cases. After a 12.4-month follow-up, a full clinical and radiological recovery was obtained in 85% and 84% of cases, respectively. The mortality rate was 2.7%. Conclusions: These results suggest that the occurrence of ICSO was significantly increased after the pandemic. Such an increase seems to be related to the indirect effects of the pandemic (e.g., immunity debt) rather than to a direct effect of COVID infection or to seasonal fluctuations. ICSO remain challenging diseases but the pandemic did not affect the management strategies nor their prognosis. The epidemiological change of sinusitis/otitis and ICSO should alert about the appropriate follow-up of children with sinusitis/otitis.</p

T Cells Enhance Stem-Like Properties and Conditional Malignancy in Gliomas

Small populations of highly tumorigenic stem-like cells (cancer stem cells; CSCs) can exist within, and uniquely regenerate cancers including malignant brain tumors (gliomas). Many aspects of glioma CSCs (GSCs), however, have been characterized in non-physiological settings.We found gene expression similarity superiorly defined glioma "stemness", and revealed that GSC similarity increased with lower tumor grade. Using this method, we examined stemness in human grade IV gliomas (GBM) before and after dendritic cell (DC) vaccine therapy. This was followed by gene expression, phenotypic and functional analysis of murine GL26 tumors recovered from nude, wild-type, or DC-vaccinated host brains.GSC similarity was specifically increased in post-vaccine GBMs, and correlated best to vaccine-altered gene expression and endogenous anti-tumor T cell activity. GL26 analysis confirmed immune alterations, specific acquisition of stem cell markers, specifically enhanced sensitivity to anti-stem drug (cyclopamine), and enhanced tumorigenicity in wild-type hosts, in tumors in proportion to anti-tumor T cell activity. Nevertheless, vaccine-exposed GL26 cells were no more tumorigenic than parental GL26 in T cell-deficient hosts, though they otherwise appeared similar to GSCs enriched by chemotherapy. Finally, vaccine-exposed GBM and GL26 exhibited relatively homogeneous expression of genes expressed in progenitor cells and/or differentiation.T cell activity represents an inducible physiological process capable of proportionally enriching GSCs in human and mouse gliomas. Stem-like gliomas enriched by strong T cell activity, however, may differ from other GSCs in that their stem-like properties may be disassociated from increased tumor malignancy and heterogeneity under specific host immune conditions

DNA methylation in glioblastoma: impact on gene expression and clinical outcome

International audienceBACKGROUND: Changes in promoter DNA methylation pattern of genes involved in key biological pathways have been reported in glioblastoma. Genome-wide assessments of DNA methylation levels are now required to decipher the epigenetic events involved in the aggressive phenotype of glioblastoma, and to guide new treatment strategies. RESULTS: We performed a whole-genome integrative analysis of methylation and gene expression profiles in 40 newly diagnosed glioblastoma patients. We also screened for associations between the level of methylation of CpG sites and overall survival in a cohort of 50 patients uniformly treated by surgery, radiotherapy and chemotherapy with concomitant and adjuvant temozolomide (STUPP protocol). The methylation analysis identified 616 CpG sites differentially methylated between glioblastoma and control brain, a quarter of which was differentially expressed in a concordant way. Thirteen of the genes with concordant CpG sites displayed an inverse correlation between promoter methylation and expression level in glioblastomas: B3GNT5, FABP7, ZNF217, BST2, OAS1, SLC13A5, GSTM5, ME1, UBXD3, TSPYL5, FAAH, C7orf13, and C3orf14. Survival analysis identified six CpG sites associated with overall survival. SOX10 promoter methylation status (two CpG sites) stratified patients similarly to MGMT status, but with a higher Area Under the Curve (0.78 vs. 0.71, p-value < 5e-04). The methylation status of the FNDC3B, TBX3, DGKI, and FSD1 promoters identified patients with MGMT-methylated tumors that did not respond to STUPP treatment (p-value < 1e-04). CONCLUSIONS: This study provides the first genome-wide integrative analysis of DNA methylation and gene expression profiles obtained from the same GBM cohort. We also present a methylome-based survival analysis for one of the largest uniformly treated GBM cohort ever studied, for more than 27,000 CpG sites. We have identified genes whose expression may be tightly regulated by epigenetic mechanisms and markers that may guide treatment decisions

Reducing blood loss in pediatric craniosynostosis surgery by use of tranexamic acid

International audienceIntroduction - Craniosysnostosis surgical corrections are routine procedures in the pediatric neurosurgical field. However, these procedures result in significant blood loss. Tranexamic acid (TXA) is an antifibrinolytic drug, which has demonstrated a significant reduction in perioperative blood loss in many pediatric surgical procedures such as cardiac surgery and scoliosis surgery. We conducted a systematic review to evaluate protocols of TXA use in pediatric craniosynostosis procedures and its effect on intraoperative blood loss and transfusions.Material and methods - A comprehensive literature review of the National Library of Medicine (PubMed) database was performed to identify relevant studies. We included any clinical study reporting on blood loss or blood transfusion for pediatric craniosynostosis surgery with intraoperative use of tranexamic acid, with the following limits: publication date from inception to May 2019; reports in English.Results - Thirteen studies were eligible for our review. Of the 13 studies, 4 were prospective, randomised, double-blind controlled trials, 9 were retrospective studies, tailored as a "before-after" studies, comparing blood loss and transfusion without/with TXA. TXA significantly decreases the number and volume of packed red blood cell transfusions and the rate of transfusion in children undergoing craniosynostosis surgery. Significantly fewer fresh frozen plasma transfusions were required in the TXA groups in 2 randomised studies. Length of stay in hospital was significantly lower with the use of TXA in three studies. Advantages of TXA administration also include an excellent patient tolerance of side effects, ease of administration and low cost.Conclusion - TXA significantly reduces blood loss and the need for transfusions in children undergoing craniosynostosis surgery. TXA administration should be a routine part of strategy to reduce blood loss and limit transfusions in these procedures

Facteurs pronostiques des médulloblastomes de l’adulte : revue de la littérature et perspectives [Prognostic factors of adult medulloblastomas: A review of the literature and perspectives]

National audienceAdult medulloblastoma is a rare disease. Characteristics which are different from those of the pediatric population have been reported in recent years: a more frequent localization in the cerebellar hemispheres, higher proportion of the desmoplastic subtype, lower incidence of metastatic spread and delayed recurrences. It is probable that these differences are a consequence of specific cytogenetic and molecular characteristics distinguishing the two populations. A number of prognostic factors have been described in the adult population such as age, gender, histopathology, residual disease after surgery, M stage. However, the increased presence of activating mutations in the Sonic Hedgehog cell pathway, and to a lesser degree in the Wingless pathway, may explain the clinical discrepancies. Also, differences in the cytogenetic profile such as the loss of 10q and gain of 17q seem to play a critical role in the prognosis of these patients. It is obvious that knowledge of oncogene amplifications and cytogenetic markers is the key to the future management of medulloblastomas. Molecular inhibitors targeting cell signaling pathways that are activated in medulloblastoma will play an increasing role in future trials