First evaluation of neutron induced single event effects on the CMS barrel muon electronics

Neutron irradiation tests of the currently available electronics for the CMS barrel muon detector were performed using Thermal and fast neutrons at E< 11MeV. The Single Event Upset rate on the Static RAM was measured, while upper limits are derived for events having experienced no failure. The results are used to guess the upper limits on the mean time between failures in the whole barrel muon detector

The value of source data verification in a cancer clinical trial

Background Source data verification (SDV) is a resource intensive method of quality assurance frequently used in clinical trials. There is no empirical evidence to suggest that SDV would impact on comparative treatment effect results from a clinical trial. Methods Data discrepancies and comparative treatment effects obtained following 100% SDV were compared to those based on data without SDV. Overall survival (OS) and Progression-free survival (PFS) were compared using Kaplan-Meier curves, log-rank tests and Cox models. Tumour response classifications and comparative treatment Odds Ratios (ORs) for the outcome objective response rate, and number of Serious Adverse Events (SAEs) were compared. OS estimates based on SDV data were compared against estimates obtained from centrally monitored data. Findings Data discrepancies were identified between different monitoring procedures for the majority of variables examined, with some variation in discrepancy rates. There were no systematic patterns to discrepancies and their impact was negligible on OS, the primary outcome of the trial (HR (95% CI): 1.18(0.99 to 1.41), p = 0.064 with 100% SDV; 1.18(0.99 to 1.42), p = 0.068 without SDV; 1.18(0.99 to 1.40), p = 0.073 with central monitoring). Results were similar for PFS. More extreme discrepancies were found for the subjective outcome overall objective response (OR (95% CI): 1.67(1.04 to 2.68), p = 0.03 with 100% SDV; 2.45(1.49 to 4.04), p = 0.0003 without any SDV) which was mostly due to differing CT scans. Interpretation Quality assurance methods used in clinical trials should be informed by empirical evidence. In this empirical comparison, SDV was expensive and identified random errors that made little impact on results and clinical conclusions of the trial. Central monitoring using an external data source was a more efficient approach for the primary outcome of OS. For the subjective outcome objective response, an independent blinded review committee and tracking system to monitor missing scan data could be more efficient than SDV

Doxorubicin versus doxorubicin and cisplatin in endometrial carcinoma: definitive results of a randomised study (55872) by the EORTC Gynaecological Cancer Group

Background: Combination chemotherapy yields better response rates which do not always lead to a survival advantage. The aim of this study was to investigate whether the reported differences in the efficacy and toxicity of monotherapy with doxorubicin (DOX) versus combination therapy with cisplatin (CDDP) in endometrial adenocarcinoma lead to significant advantage in favour of the combination. Patients and methods: Eligible patients had histologically-proven advanced and/or recurrent endometrial adenocarcinoma and were chemo-naïve. Treatment consisted of either DOX 60 mg/m2 alone or CDDP 50 mg/m2 added to DOX 60 mg/m2, every 4 weeks. Results: A total of 177 patients were entered and median follow-up is 7.1 years. The combination DOX-CDDP was more toxic than DOX alone. Haematological toxicity consisted mainly of white blood cell toxicity grade 3 and 4 (55% versus 30%). Non-haematological toxicity consisted mainly of grade 3 and 4 alopecia (72% versus 65%) and nausea/vomiting (36 % versus 12%). The combination DOX-CDDP provided a significantly higher response rate than single agent DOX (P <0.001). Thirty-nine patients (43%) responded on DOX-CDDP [13 complete responses (CRs) and 26 partial responses (PRs)], versus 15 patients (17%) on DOX alone (8 CR and 7 PR). The median overall survival (OS) was 9 months in the DOX-CDDP arm versus 7 months in the DOX alone arm (Wilcoxon P = 0.0654). Regression analysis showed that WHO performance status was statistically significant as a prognostic factor for survival, and stratifying for this factor, treatment effect reaches significance (hazard ratio = 1.46, 95% confidence interval 1.05-2.03, P = 0.024). Conclusions: In comparison to single agent DOX, the combination of DOX-CDDP results in higher but acceptable toxicity. The response rate produced is significantly higher, and a modest survival benefit is achieved with this combination regimen, especially in patients with a good performance statu

Efficacy and safety of rituximab with and without methotrexate in the treatment of rheumatoid arthritis patients: Results from the GISEA register.

Rituximab (RTX) is a monoclonal anti-CD20 antibody approved for the treatment of rheumatoid arthritis (RA) in association with methotrexate (MTX)

Treatment of rheumatoid arthritis with anti-TNF-alpha agents: A reappraisal

It has been found that tumour necrosis factor(TNF)-alpha plays a pivotal role in the pathogenesis of rheumatoid arthritis (RA), and the development of drugs targeting this molecule has extended the therapeutical approaches to RA patients. A number of observational studies of large patient series have also been published over the last few years, many of which have been based on national registries designed to monitor the efficacy and safety of anti-TNF agents, and allow healthcare institutions to control expenditure. Registry data can also help in identifying clinical and laboratory findings capable of predicting response. It has been suggested that the percentage of responding patients is lower in everyday clinical practice than that observed in RCTs, possibly because of patient selection, the use of a washout period before inclusion (which may artificially increase disease activity), and differences in doses, co-morbidities and adherence to therapy. A number of safety concerns have been raised since the introduction of anti-TNF agents, and they are now contraindicated in patients with advanced heart failure; however, the most widely debated current issues regard infections and neoplastic diseases. Moreover, the marketing of new and expensive biological agents has made strictly necessary to create systems capable of monitoring their safety and effectiveness in everyday practice, including the use of longitudinal observational studies. As the first published registry of anti-TNFalpha-treated patients in Italy, Lombardy Rheumatology Network (LORHEN) is already making its contribution in this directio

Certolizumab Pegol Treatment in Patients with Axial-Spondyloarthritis-Associated Acute Anterior Uveitis: a Narrative Review

Background: Acute anterior uveitis (AAU) affects up to 40% of patients with axial spondyloarthritis (axSpA). An effective treatment for patients with axSpA that reduces the risk of AAU flares while also targeting axial symptoms is therefore highly desirable. Tumor necrosis factor inhibitors (TNFis) have been shown effective for treatment of axSpA and AAU occurrence, with guidelines conditionally recommending treating patients with axSpA and associated AAU with TNFi monoclonal antibodies. To date, most available data on the impact of TNFis on AAU in axSpA are from observational, open-label studies without parallel comparator arms. However, there is a growing body of evidence describing the impact of the TNFi certolizumab pegol (CZP) on the incidence of axSpA-associated AAU. Objective: Our objective was to collate data pertaining to the impact of CZP in axSpA-associated AAU in patients across the full axSpA spectrum. Methods: Data were obtained from four industry-supported phase 3 and 4 clinical trials (C-VIEW, C-axSpAnd, C-OPTIMISE, and RAPID-axSpA). To supplement these data, a targeted literature review was performed through searches of MEDLINE, Embase, and reference lists. Results: Available data from 1467 patients from the C-VIEW, C-axSpAnd, C-OPTIMISE, and RAPID-axSpA trials show CZP to be effective in AAU in patients across the full axSpA spectrum, reducing AAU flares when compared with placebo or pretreatment period. No differences in AAU outcomes were reported when stratified by axSpA subgroup age or sex. The targeted literature review identified six further studies of CZP in spondyloarthritis-associated AAU, only one of which was specific to axSpA. Conclusion: CZP was effective in reducing AAU incidence in clinical trials with patients with axSpA. The targeted literature review, however, highlighted that there remains a paucity of data beyond these trials. Data from comparative studies would further enhance the body of evidence on the effects of CZP in patients with axSpA who develop AAU. Graphical abstract: [Figure not available: see fulltext.

Prothymosin alpha: a ubiquitous polypeptide with potential use in cancer diagnosis and therapy

The thymus is a central lymphoid organ with crucial role in generating T cells and maintaining homeostasis of the immune system. More than 30 peptides, initially referred to as “thymic hormones,” are produced by this gland. Although the majority of them have not been proven to be thymus-speciWc, thymic peptides comprise an eVective group of regulators, mediating important immune functions. Thymosin fraction Wve (TFV) was the Wrst thymic extract shown to stimulate lymphocyte proliferation and diVerentiation. Subsequent fractionation of TFV led to the isolation and characterization of a series of immunoactive peptides/polypeptides, members of the thymosin family. Extensive research on prothymosin (proT) and thymosin 1 (T1) showed that they are of clinical signiWcance and potential medical use. They may serve as molecular markers for cancer prognosis and/or as therapeutic agents for treating immunodeWciencies, autoimmune diseases and malignancies. Although the molecular mechanisms underlying their eVect are yet not fully elucidated proT and T1 could be considered as candidates for cancer immunotherapy. In this review, we will focus in principle on the eventual clinical utility of proT, both as a tumor biomarker and in triggering anticancer immune responses. Considering the experience acquired via the use of T1 to treat cancer patients, we will also discuss potential approaches for the future introduction of proT into the clinical setting

Databases of L-shell X-ray intensity ratios for various elements after photon excitation

We gratefully acknowledge the support of the DGRSDT, Ministry of Higher Education and Scientific Research, Algeria . This work was done with the support of Mohamed El Bachir El Ibrahimi University , under project (PRFU) N o : B00L02UN340120230004 . This work was also supported by the Fundação para a Ciência e Tecnologia (FCT), Portugal through contract UID/FIS/04559/2020 (LIBPhys). S.C. warmly acknowledges the financial support of Lancaster University, and A.F. gratefully acknowledges the support of the Joint Research Centre of the European Commission. Publisher Copyright: © 2024 Elsevier Inc.In this study, a comprehensive dataset of X-ray emission intensity ratios has been compiled, including ILβ/ILα, ILγ/ILα, ILl/ILα, ILγ/ILβ, ILl/ILγ, ILl/ILβ, ILγ5/ILα, ILγ44′/ILα, ILη/ILα, and ILγ1/ILα, extracted from literature spanning the years 1971 to 2023, and encompassing 83 research papers. Over this timeframe, a total of 2600 values were collected, comprising some 678 values for ILβ/ILα, 696 values for ILγ/ILα, 617 values for ILl/ILα, along with 132, 132, 89, 60, 70, 71, and 55 data points for ILγ/ILβ,ILl/ILγ, ILl/ILβ, ILγ5/ILα, ILγ44′/ILα, ILη/ILα, and ILγ1/ILα, respectively. The reported values are presented with precision up to three to four decimal places, accompanied by their associated uncertainties. Additionally, the tables include calculated weighted averages (ILi/ILj)W, uncertainty values (εISD, εESD), combined standard deviations (zISD, zESD), and average z-scores (z¯ISD,z¯ESD) for these intensity ratios. The data encompasses elements ranging from 39Y to 94Pu when excited by photon bombardment. The assessment of how these experimental data values are distributed according to atomic number indicates extensive coverage across most elements. However, a few isolated instances were identified where either no data or fewer than two data values were available.publishersversionpublishe