Background
Immunotherapy is a firmly established pillar in the treatment of cancer, alongside the traditional approaches of surgery, radiotherapy, and chemotherapy. Like every treatment, also cancer ...immunotherapy causes a diverse spectrum of side effects, collectively referred to as immune-related adverse events.
Objective
This review will examine the main forms of immunotherapy, the proposed mechanism(s) of action, and the incidence of thyroid dysfunctions.
Methods
A comprehensive MEDLINE search was performed for articles published up to March 30, 2017.
Results
Following the pioneering efforts with administration of cytokines such as IL-2 and IFN-g, which caused a broad spectrum of thyroid dysfunctions (ranging in incidence from 1 to 50%), current cancer immunotherapy strategies comprise immune checkpoint inhibitors, oncolytic viruses, adoptive T-cell transfer, and cancer vaccines. Oncolytic viruses, adoptive T-cell transfer, and cancer vaccines cause thyroid dysfunctions only rarely. In contrast, immune checkpoint blockers (such as anti-CTLA-4, anti-PD-1, anti-PD-L1) are associated with a high risk of thyroid autoimmunity. This risk is highest for anti-PD-1 and increases further when a combination of checkpoint inhibitors is used.
Conclusions
Cancer patients treated with monoclonal antibodies that block immune checkpoint inhibitors are at risk of developing thyroid dysfunctions. Their thyroid status should be assessed at baseline and periodically after initiation of the immunotherapy.
Thinned epitaxial silicon hybrid pixel sensors for the PANDA experiment Calvo, D.; De Remigis, P.; Osmic, F. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
08/2008, Letnik:
594, Številka:
1
Journal Article
Recenzirano
First prototypes of hybrid pixel assemblies using thinned epitaxial silicon pixels as the sensor element have been produced and tested as part of the ongoing programme to develop a custom pixel-based ...solution for the innermost layers of the tracking system of the PANDA experiment. Results were obtained from assemblies with three different epitaxial thicknesses of 50, 75 and 100
μm. The front-end chip for PANDA is still in development at this time and therefore the ALICE pixel front-end chips and readout chain were used. Basic detector characteristics, bump-bonding yield and tests with various radioactive sources are presented.
To sustain and extend its discovery potential, the Large Hadron Collider (LHC) will undergo a major upgrade in the coming years, referred to as High Luminosity LHC (HLLHC), aimed to increase its ...instantaneous luminosity, 5 times larger than the designed limit, and, consequently leading to high levels of radiation, with the goal to collect 10 times larger the original designed integrated luminosity. The drift tube chambers (DT) of CMS muon detector system is built to proficiently measure and trigger on muons in the harsh radiation environment expected during the HL-LHC era. Ageing studies are performed at the CERNs gamma ray irradiation facility (GIF++) by measuring the muon hit efficiency of these detectors at various LHC operation conditions. One such irradiation campaign was started in October 2017, when a spare MB2 chamber moved inside the bunker and irradiated at lower acceleration factors. Two out of twelve layers of the DT chamber were operated while being irradiated with the radioactive source and then their muon hit efficiency was calculated in coincidence with other ten layers which were kept on the standby. The chamber absorbed an integrated dose equivalent to two times the expected integrated luminosity of the HL-LHC. Investigation on the outgassing of cell materials and of the gas components used at the GIF++ are underway and strategies to mitigate the aging effects are also being developed. The effect of radiation on the performance of DT chamber and its impact on the overall muon reconstruction efficiency expected during the HL-LHC are presented.
The design of the Micro Vertex Detector for the PANDA experiment faces a number of challenging aspects. The high radiation level, the limited space and accessibility, the strict material budget ...combined with the absence of a trigger signal and thus the huge amount of data to be sent to the DAQ require innovative solutions. Hybrid silicon pixels based on epitaxial material are under study as a detector technology capable to sustain the expected radiation levels at room temperature. A reduced scale prototype for the readout ASIC in a CMOS
0.13
μ
m
technology has been designed and tested. Irradiation tests have been performed on both the detector and the readout ASIC.
This paper describes a multi-event buffering and readout ASIC used in the front-end electronics for the silicon drift detectors (SDDs) of the ALICE experiment. The ASIC, named AMBRA, provides a ...number of control functions, mainly baseline equalization, first level data compression and a four event buffering to the data read-out of the SDD. It also controls the data and configuration flow between the front-end electronics and the data acquisition circuits.
Abstract
Background
The neutrophil-lymphocyte ratio (NLR), derived from the complete blood count, independently predicts atherosclerotic events and is a potential biomarker for residual inflammatory ...risk. A previous study showed that interleukin (IL)-1β inhibition reduces the NLR, but whether inhibition with IL-6, a cytokine downstream of IL-1, also lowers the NLR is unknown.
Purpose
To evaluate whether ziltivekimab, a monoclonal antibody targeting the IL-6 ligand, dose-dependently lowers the NLR compared to placebo.
Methods
The phase II RESCUE trial randomized 264 patients with moderate to severe chronic kidney disease (CKD) and high-sensitivity CRP (hsCRP) >2mg/L in a 1:1:1:1 ratio to placebo or ziltivekimab 7.5 mg, 15 mg, and 30 mg subcutaneously once every four weeks. As previously reported, the trial met its primary endpoint as demonstrated by hsCRP reductions of 4% in the placebo group as compared to 77%, 88%, and 92% at 12 weeks in the ziltivekimab 7.5, 15, and 30 mg groups, respectively. Using RESCUE trial data, we further evaluated the percent change from baseline in the NLR at 12 weeks and sought evidence of correlation between any observed changes in the NLR with changes in other measured biomarkers.
Results
Ziltivekimab dose-dependently reduced the NLR starting at week one and sustained through week 12 (Table). The median change in the NLR at 12 weeks, the primary pre-specified endpoint, was −13.5% in the 7.5 mg group, −14.3% in the 15 mg group, and −22.4% in the 30 mg group compared to 1.56% in the placebo group. The estimated treatment difference was −14.6% (p=0.004), −15.3% (p=0.004), and −23.6% (p<0.0001) in the ziltivekimab 7.5, 15, and 30 mg groups respectively. These changes were driven largely by reductions in the absolute neutrophil count with minimal change in lymphocyte count. The change in NLR with ziltivekimab correlated modestly with the changes in hsCRP (R=0.26, p=0.0006), fibrinogen (R=0.18, p=0.02), and haptoglobin (R=0.17, p=0.03), but not serum amyloid A, ApoA1, ApoB, ApoB/ApoA ratio, or traditional risk markers.
Conclusions
IL-6 inhibition with ziltivekimab lowers the NLR. The ongoing ZEUS cardiovascular (CV) outcomes trial will assess whether ziltivekimab can reduce CV event rates among individuals with stage 3 to 4 CKD, known atherosclerotic disease, and elevated hsCRP. If ziltivekimab reduces CV risk, it would provide further evidence for critical inter-relationships between bone marrow function and atherothrombosis.
Funding Acknowledgement
Type of funding sources: Private company. Main funding source(s): Novo Nordisk
Summary
Vitiligo is a common skin disease characterized by depigmented maculae resulting from a reduction of the number and function of melanocytes. Many studies suggest that vitiligo might be an ...autoimmune disease. Vitiligo has been frequently described in association with other autoimmune diseases. Among the diseases described in association with vitiligo are the so‐called autoimmune polyglandular syndromes (APS). Vitiligo can be present in all types of APS but the most frequent association appears to be in APS‐3. APS‐3 was defined as the association between autoimmune thyroiditis and another autoimmune disease. Here we report one patient with thyroiditis, vitiligo and autoimmune gastritis (APS‐3B + C), one patient with chronic autoimmune thyroiditis, vitiligo and alopecia (APS‐3C), and one case of a young patient with type 1 diabetes mellitus and vitiligo (APS‐4), according to the newest classification. We stress the importance of a thorough assessment for autoimmune diseases in selected patients with vitiligo.
The silicon pixel detector of the PANDA experiment is characterized by both high track density and the absence of a hardware trigger signal, thus leading to a huge amount of data to be acquired and ...transmitted to the DAQ. In order to cope with such challenging requirements, an ASIC based custom solution for the electronic readout has been chosen. The ASIC, named ToPiX, will provide the time position of each hit and a measure of the charge released with the Time over Threshold (ToT) technique. A reduced scale prototype in a CMOS 0.13μm technology has been designed and tested. The prototype includes four columns made of 128 pixel cells, four columns of 32 cells and the end of column readout with a 32 cells deep FIFO for each double column. Each cell embeds a charge amplifier with constant current feedback capacitor discharge, a comparator with per cell adjustable threshold, 12-bits leading and trailing edge register for time and ToT measurement and an 8 bits configuration register. All the readout logic has been SEU-hardened by design using either Hamming encoding or triple modular redundancy. The chip has been tested both electrically via a test pulse input and connected to a detector in a beam test.
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