Belimumab promotes negative selection of activated autoreactive B cells in systemic lupus erythematosus patients.

Belimumab has therapeutic benefit in active systemic lupus erythematosus (SLE), especially in patients with high-titer anti-dsDNA antibodies. We asked whether the profound B cell loss in belimumab-treated SLE patients is accompanied by shifts in the immunoglobulin repertoire. We enrolled 15 patients who had been continuously treated with belimumab for more than 7 years, 17 matched controls, and 5 patients who were studied before and after drug initiation. VH genes of sort-purified mature B cells and plasmablasts were subjected to next-generation sequencing. We found that B cell-activating factor (BAFF) regulates the transitional B cell checkpoint, with conservation of transitional 1 (T1) cells and approximately 90% loss of T3 and naive B cells after chronic belimumab treatment. Class-switched memory B cells, B1 B cells, and plasmablasts were also substantially depleted. Next-generation sequencing revealed no redistribution of VH, DH, or JH family usage and no effect of belimumab on representation of the autoreactive VH4-34 gene or CDR3 composition in unmutated IgM sequences, suggesting a minimal effect on selection of the naive B cell repertoire. Interestingly, a significantly greater loss of VH4-34 was observed among mutated IgM and plasmablast sequences in chronic belimumab-treated subjects than in controls, suggesting that belimumab promotes negative selection of activated autoreactive B cells

The tumour volume influence on tumour recurrence and progression-free survival in the case of atypical meningiomas: Our experience on a series of 81 cases

Objective: The objective of our study was to evaluate a possible relation between the volume of atypical meningiomas (AMs) and the risk of tumour recurrence, as well as progression-free survival (PFS). Material and methods: We evaluated 81 patients diagnosed with AMs (WHO grade II meningioma) who have undergone surgery at the "Prof. Dr. N. Oblu" Emergency Clinical Hospital Iasi between January 1, 2010, and December 31, 2019. The recorded data were demographic and imagistic (MRI, contrast-enhanced T1WI). We calculated the tumour volume prior to the surgery and evaluated the tumour recurrence using MRI at 12, 24, 36, 48 and 60 months after the surgery. Results: 50.6% of patients had meningioma volume < 26.4 cm3. Women had larger tumour volumes than men (52.6%). Patients of age ? 60 years old, had tumour volumes ? 26.4 cm3 in 58.5% of cases and meningiomas with volumes ? 26.4 cm3 recurred earlier (p=0.010). Also, patients who had tumour volumes ? 26.4 cm3, had a shorter PFS (40.976 months), compared to patients with tumour volumes < 26.4 cm3, who had better PFS (53.4 months). Conclusions: the tumour volume of AMs ? 26.4 cm3 represents a negative prognostic factor for both early tumour recurrence and reduced PFS

ReaderBench Learns Dutch: Building a Comprehensive Automated Essay Scoring System for Dutch Language

Automated Essay Scoring has gained a wider applicability and usage with the integration of advanced Natural Language Processing techniques which enabled in-depth analyses of discourse in order capture the specificities of written texts. In this paper, we introduce a novel Automatic Essay Scoring method for Dutch language, built within the Readerbench framework, which encompasses a wide range of textual complexity indices, as well as an automated segmentation approach. Our method was evaluated on a corpus of 173 technical reports automatically split into sections and subsections, thus forming a hierarchical structure on which textual complexity indices were subsequently applied. The stepwise regression model explained 30.5% of the variance in students’ scores, while a Discriminant Function Analysis predicted with substantial accuracy (75.1%) whether they are high or low performance students.This study is part of the RAGE project. The RAGE project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 644187. This publication reflects only the author's view. The European Commission is not responsible for any use that may be made of the information it contains

The laser-hybrid accelerator for radiobiological applications

The `Laser-hybrid Accelerator for Radiobiological Applications', LhARA, is conceived as a novel, uniquely-flexible facility dedicated to the study of radiobiology. The technologies demonstrated in LhARA, which have wide application, will be developed to allow particle-beam therapy to be delivered in a completely new regime, combining a variety of ion species in a single treatment fraction and exploiting ultra-high dose rates. LhARA will be a hybrid accelerator system in which laser interactions drive the creation of a large flux of protons or light ions that are captured using a plasma (Gabor) lens and formed into a beam. The laser-driven source allows protons and ions to be captured at energies significantly above those that pertain in conventional facilities, thus evading the current space-charge limit on the instantaneous dose rate that can be delivered. The laser-hybrid approach, therefore, will allow the vast ``terra incognita'' of the radiobiology that determines the response of tissue to ionising radiation to be studied with protons and light ions using a wide variety of time structures, spectral distributions, and spatial configurations at instantaneous dose rates up to and significantly beyond the ultra-high dose-rate `FLASH' regime. It is proposed that LhARA be developed in two stages. In the first stage, a programme of in vitro radiobiology will be served with proton beams with energies between 10MeV and 15MeV. In stage two, the beam will be accelerated using a fixed-field accelerator (FFA). This will allow experiments to be carried out in vitro and in vivo with proton beam energies of up to 127MeV. In addition, ion beams with energies up to 33.4MeV per nucleon will be available for in vitro and in vivo experiments. This paper presents the conceptual design for LhARA and the R&D programme by which the LhARA consortium seeks to establish the facility

Charge transport and trapping in Cs-doped poly(dialkoxy-p-phenylene vinylene) light-emitting diodes

Al/Cs/MDMO-PPV/ITO (where MDMO-PPV stands for poly[2-methoxy-5-(3'-7'-dimethyloctyloxy)-1,4phenylene vinylene] and ITO is indium tin oxide) light-emitting diode (LED) structures, made by physical vapor deposition of Cs on the emissive polymer layer, have been characterized by electroluminescence, current-voltage, and admittance spectroscopy. Deposition of Cs is found to improve the balance between electron and hole currents, enhancing the external electroluminescence efficiency from 0.01 cd A-1 for the bare Al cathode to a maximum of 1.3 cd A-1 for a Cs coverage of only 1.5×1014 atoms/cm2. By combining I-V and admittance spectra with model calculations, in which Cs diffusion profiles are explicitly taken into account, this effect could be attributed to a potential drop at the cathode interface due to a Cs-induced electron donor level 0.61 eV below the lowest unoccupied molecular orbital. In addition, the admittance spectra in the hole-dominated regime are shown to result from space-charge-limited conduction combined with charge relaxation in trap levels. This description allows us to directly determine the carrier mobility, even in the presence of traps. In contrast to recent literature, we demonstrate that there is no need to include dispersive transport in the description of the carrier mobility to explain the excess capacitance that is typically observed in admittance spectra of p-conjugated materials

A large topographic feature on the surface of the trans-Neptunian object (307261) 2002 MS4_4 measured from stellar occultations

This work aims at constraining the size, shape, and geometric albedo of the dwarf planet candidate 2002 MS4 through the analysis of nine stellar occultation events. Using multichord detection, we also studied the object's topography by analyzing the obtained limb and the residuals between observed chords and the best-fitted ellipse. We predicted and organized the observational campaigns of nine stellar occultations by 2002 MS4 between 2019 and 2022, resulting in two single-chord events, four double-chord detections, and three events with three to up to sixty-one positive chords. Using 13 selected chords from the 8 August 2020 event, we determined the global elliptical limb of 2002 MS4. The best-fitted ellipse, combined with the object's rotational information from the literature, constrains the object's size, shape, and albedo. Additionally, we developed a new method to characterize topography features on the object's limb. The global limb has a semi-major axis of 412 $\pm$ 10 km, a semi-minor axis of 385 $\pm$ 17 km, and the position angle of the minor axis is 121 $^\circ$ $\pm$ 16$^\circ$. From this instantaneous limb, we obtained 2002 MS4's geometric albedo and the projected area-equivalent diameter. Significant deviations from the fitted ellipse in the northernmost limb are detected from multiple sites highlighting three distinct topographic features: one 11 km depth depression followed by a 25$^{+4}_{-5}$ km height elevation next to a crater-like depression with an extension of 322 $\pm$ 39 km and 45.1 $\pm$ 1.5 km deep. Our results present an object that is $\approx$138 km smaller in diameter than derived from thermal data, possibly indicating the presence of a so-far unknown satellite. However, within the error bars, the geometric albedo in the V-band agrees with the results published in the literature, even with the radiometric-derived albedo

Correction to: Two years later: Is the SARS-CoV-2 pandemic still having an impact on emergency surgery? An international cross-sectional survey among WSES members

Background: The SARS-CoV-2 pandemic is still ongoing and a major challenge for health care services worldwide. In the first WSES COVID-19 emergency surgery survey, a strong negative impact on emergency surgery (ES) had been described already early in the pandemic situation. However, the knowledge is limited about current effects of the pandemic on patient flow through emergency rooms, daily routine and decision making in ES as well as their changes over time during the last two pandemic years. This second WSES COVID-19 emergency surgery survey investigates the impact of the SARS-CoV-2 pandemic on ES during the course of the pandemic. Methods: A web survey had been distributed to medical specialists in ES during a four-week period from January 2022, investigating the impact of the pandemic on patients and septic diseases both requiring ES, structural problems due to the pandemic and time-to-intervention in ES routine. Results: 367 collaborators from 59 countries responded to the survey. The majority indicated that the pandemic still significantly impacts on treatment and outcome of surgical emergency patients (83.1% and 78.5%, respectively). As reasons, the collaborators reported decreased case load in ES (44.7%), but patients presenting with more prolonged and severe diseases, especially concerning perforated appendicitis (62.1%) and diverticulitis (57.5%). Otherwise, approximately 50% of the participants still observe a delay in time-to-intervention in ES compared with the situation before the pandemic. Relevant causes leading to enlarged time-to-intervention in ES during the pandemic are persistent problems with in-hospital logistics, lacks in medical staff as well as operating room and intensive care capacities during the pandemic. This leads not only to the need for triage or transferring of ES patients to other hospitals, reported by 64.0% and 48.8% of the collaborators, respectively, but also to paradigm shifts in treatment modalities to non-operative approaches reported by 67.3% of the participants, especially in uncomplicated appendicitis, cholecystitis and multiple-recurrent diverticulitis. Conclusions: The SARS-CoV-2 pandemic still significantly impacts on care and outcome of patients in ES. Well-known problems with in-hospital logistics are not sufficiently resolved by now; however, medical staff shortages and reduced capacities have been dramatically aggravated over last two pandemic years

Monitoring quality and coverage of harm reduction services for people who use drugs: a consensus study.

BACKGROUND AND AIMS: Despite advances in our knowledge of effective services for people who use drugs over the last decades globally, coverage remains poor in most countries, while quality is often unknown. This paper aims to discuss the historical development of successful epidemiological indicators and to present a framework for extending them with additional indicators of coverage and quality of harm reduction services, for monitoring and evaluation at international, national or subnational levels. The ultimate aim is to improve these services in order to reduce health and social problems among people who use drugs, such as human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infection, crime and legal problems, overdose (death) and other morbidity and mortality. METHODS AND RESULTS: The framework was developed collaboratively using consensus methods involving nominal group meetings, review of existing quality standards, repeated email commenting rounds and qualitative analysis of opinions/experiences from a broad range of professionals/experts, including members of civil society and organisations representing people who use drugs. Twelve priority candidate indicators are proposed for opioid agonist therapy (OAT), needle and syringe programmes (NSP) and generic cross-cutting aspects of harm reduction (and potentially other drug) services. Under the specific OAT indicators, priority indicators included 'coverage', 'waiting list time', 'dosage' and 'availability in prisons'. For the specific NSP indicators, the priority indicators included 'coverage', 'number of needles/syringes distributed/collected', 'provision of other drug use paraphernalia' and 'availability in prisons'. Among the generic or cross-cutting indicators the priority indicators were 'infectious diseases counselling and care', 'take away naloxone', 'information on safe use/sex' and 'condoms'. We discuss conditions for the successful development of the suggested indicators and constraints (e.g. funding, ideology). We propose conducting a pilot study to test the feasibility and applicability of the proposed indicators before their scaling up and routine implementation, to evaluate their effectiveness in comparing service coverage and quality across countries. CONCLUSIONS: The establishment of an improved set of validated and internationally agreed upon best practice indicators for monitoring harm reduction service will provide a structural basis for public health and epidemiological studies and support evidence and human rights-based health policies, services and interventions