A luminosity monitor for the Large Hadron Collider

The LHC luminosity will reach 1034 cm-2s-1 but special runs at 1028 cm-2 s-1 are foreseen. Thus a luminosity monitor must have a dynamic range of six orders of magnitude. A good tolerance to radiation is also required. A detector using both ionisation and secondary emission techniques has been studied in this context. Its design is based on monitors used previously at the CERN PS and SPS machines. Special attention was devoted to minimize leakage currents. Linearity in both Secondary Emission Counter (SEC) and Ionisation Chamber (IC) modes has been tested from ~104 incident particles to ~108 incident particles. SEC is linear above ~3 x 106 incident particles while IC is linear over the full studied range. However, because of the radiation environment at the LHC, the SEC mode is much preferred at high intensity. A solution actually foreseen is to switch from IC to SEC mode when the incident current on the monitor is ~10-13 A corresponding to an LHC luminosity of ~1031 cm-2 s-1

A luminosity monitor for LHC

The Large Hadron Collider (LHC) under construction at CERN will give high luminosities to experiments covering six orders of magnitude from of 1028 cm-2s-1 to 1034 cm-2s-1. A new approach is needed to measure the LHC luminosity. This work reports the study of a LHC luminosity monitor based on the concept of Secondary Emission Chamber (SEC). The main request for such a detector is to cover the six orders of magnitude of the LHC luminosity range. Its precision is expected to be of the order of 2 %. The TOTEM collaboration proposes to calibrate the monitor at low luminosity. The construction of the detector based on the previous SECs developed years ago at CERN is presented. The performances of the new prototype are determined for incident currents between ~10-12 A and 10-13 A. The tests lead to conclude that at the LHC the SEC will be able to measure luminosity with a precision of 3 % within 1 s for luminosity above 1031 cm-2s-1. A conversion of the SEC into an Ionisation Chamber (IC) is proposed to cover the LHC low luminosity region. It is achieved by filling the SEC with argon at atmospheric pressure. The IC response is found to be linear with the foreseen precision over the full experimental range of intensity corresponding to currents between 10-15 A and 10-12 A. The linear continuity between the responses of the monitor in the SEC and the IC modes is observed. We propose to use, at the LHC, the detector in the IC mode at low luminosity and in the SEC mode at high luminosity with a switch in mode at a luminosity of ~ 1031 cm-2s-1

Impact of Baricitinib on Patients’ Quality of Life after One Year of Treatment for Atopic Dermatitis in Real-World Practice: Results of the Observatory of Chronic Inflammatory Skin Diseases Registry

The efficacy and safety of baricitinib for treatment of atopic dermatitis have been demonstrated in clinical trials; however, very few real-life studies have been published to date. The Observatory of Chronic Inflammatory Skin Diseases (OMCCI) registry was initiated to prospectively determine the long-term impairment caused by chronic inflammatory dermatoses on patients’ lives. The study included 88 patients starting baricitinib for treatment of atopic dermatitis. Clinical evaluation and patient-reported outcomes were recorded at baseline and after 6 and 12 months. After 6 months and 1 year of follow-up, 65 and 47 patients, respectively, were still being treated with baricitinib. Treatment failure was the main reason for discontinuation. Only 1 patient stopped baricitinib because of a side-effect. After 1 year of follow-up, the mean Eczema Area and Severity Index score decreased significantly from 20.7 to 6.4; the percentage of patients with severe atopic dermatitis decreased from 42.9% to 6.5% and a significant improvement in most patient-reported outcomes was noted. There was no difference in terms of efficacy whether or not patients were previously treated with dupilumab. The results remained stable after 6 and 12 months of treatment, which suggests a sustained efficacy of the treatment in patients who initially responded well

Real-world study of the efficacy and safety of belantamab mafodotin (GSK2857916) in relapsed or refractory multiple myeloma based on data from the nominative ATU in France: the IFM 2020-04 study

Belantamab mafodotin (BM) is an anti-BCMA antibody-drug conjugate (GSK2857916) that represents an alternative option in multiple myeloma. We sought to assess the efficacy and safety of BM in a real-world setting in patients who benefited from an early access program. We conducted an observational, retrospective, multicenter study. Eligibility criteria were treatment of relapsed or refractory multiple myeloma (RRMM) in monotherapy in adult patients who have received at least three lines of therapy previously, including at least one immunomodulatory agent (IMiD), a proteasome inhibitor (PI) and an anti-CD38 monoclonal antibody, and whose disease progressed during the last treatment period. The primary endpoint of the study is to assess the overall survival (OS). Between November 2019 and December 2020, 106 patients were treated with BM; 97 were eligible for the efficacy evaluation and 104 for safety. The median age was 66 (range, 37–82) years. High-risk cytogenetics were identified in 40.9% of patients. Fifty-five (56.7%) patients were triple-class refractory and 11 (11.3%) were penta-class refractory. The median number of prior lines of treatment was five (range, 3–12). The median number of BM cycles administered was three (range, 1–22). The overall response rate at best response was 38.1% (37/97). The median OS was 9.3 months (95% confidence interval [CI]: 5.9-15.3), and median progression-free survival was 3.5 months (95% CI: 1.9-4.7). The median duration of response was 9 months (range, 4.65-10.4). Treatment was delayed for 55 (52.9%) patients including 36.5% for treatment-related toxicity. Ophthalmic adverse events, mainly grade ≤2, were the most common toxicity (48%). The occurrence of keratopathy was 37.5%. Overall, our data are concordant with the results from DREAMM-2 in terms of efficacy and safety on a non-biased population

Safety Concern between Autologous Fat Graft, Mesenchymal Stem Cell and Osteosarcoma Recurrence

Background: Osteosarcoma is the most common malignant primary bone tumour in young adult treated by neo adjuvant chemotherapy, surgical tumor removal and adjuvant multidrug chemotherapy. For correction of soft tissue defect consecutive to surgery and/or tumor treatment, autologous fat graft has been proposed in plastic and reconstructive surgery. Principal Findings: We report here a case of a late local recurrence of osteosarcoma which occurred 13 years after the initial pathology and 18 months after a lipofilling procedure. Because such recurrence was highly unexpected, we investigated the possible relationship of tumor growth with fat injections and with mesenchymal stem/stromal cell like cells which are largely found in fatty tissue. Results obtained in osteosarcoma pre-clinical models show that fat grafts or progenitor cells promoted tumor growth. Significance: These observations and results raise the question of whether autologous fat grafting is a safe reconstructive procedure in a known post neoplasic context

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

A luminosity monitor for LHC: [notes of a thesis]

LHC luminosity will reach 10/sup 34/ cm/sup -2/ s/sup -1/ but special runs at 10/sup 28/ cm/sup -2/ s/sup -1/ are foreseen. Thus a luminosity monitor must have a dynamic range of six orders of magnitude. A good tolerance to radiation is also required. A detector using both ionisation and secondary emission techniques has been studied in this context. Its design is based on monitors used previously at the CERN PS and SPS. Special attention was devoted to minimise leakage currents. Linearity in both Secondary Emission Counter (SEC) and Ionisation Chamber (IC) modes has been tested from ~10/sup 4/ incident particles to ~10/sup 8/ incident particles. SEC is linear above ~5.10/sup 6/ incident particles while IC is linear over the full studied range. However, because of the radiation environment at LHC, the SEC mode is much preferred at high intensity. A solution actually foreseen is to switch from IC to SEC mode when the intensity is around 5.10/sup 6/ incident particles per second corresponding to an LHC luminosity of 6.10/sup 30/ cm/sup -2/ s/sup -1/. (12 refs)

Assessment of the requirements for the thermoluminescent dosimeters (LTD) during LHC Operation

The CERN TLD (Thermo-Luminescent Dosimetry) service of the radiation protection group provides since many years TLD monitoring of the environmental doses and of the doses around the accelerators and in the experimental areas. TLDs will be installed in the LHC experimental areas to measure the absorbed doses during LHC operation in specific locations close to technical equipment. The total amount of TLDs required by the experiments is presently estimated at about 1600. This note describes the material presently available in the TLD laboratory and the procedure employed for the TLD reading, the additional requirements (in terms of manpower and material) that will be demanded to extend TLD monitoring to the LHC experimental areas, and compares the option of maintaining the service at CERN or outsourcing it

Configuration Management Best Practices

Configuration management (CM) is used for the configuration of complex systems in many fields, such as IT, aeronautics, shipbuilding, space systems, nuclear power plants, etc. and is indispensable for the long-term operation of any large facility. In the Engineering Department, configuration management consists of managing the technical description and layout of the accelerators and transfer lines (and their various components), as well as managing all the modifications made during their evolution over time. It is about all the processes that ensure the conformity of the accelerators with the requirements of their operation, throughout their life cycle. The aim is to provide a clear and coherent representation of the CERN main technical facilities at a given point in time. This paper will present, the best practices that constitute the configuration management of accelerators and transfer lines in the EN-ACE group