Anti-Methadone monoclonal antibody, clone D62H64

The Compact Muon Solenoid (CMS) detector at the European Council for Nuclear Research (CERN) Large Hadron Collider (LHC) is undergoing an extensive Phase II upgrade program to prepare for the challenging conditions of the high-luminosity LHC (HL-LHC). In particular, a new timing layer will measure minimum ionizing particles (MIPs) with a time resolution of similar to 30-40 ps and hermetic coverage up to a pseudorapidity of vertical bar eta vertical bar =3 . The precision time information from this detector will reduce the effects of the high levels of pileup expected at the HL-LHC and will bring new and unique capabilities to the CMS detector. This MIP Timing Detector (MTD) will consist of a central barrel timing layer (BTL) based on L(Y)SO:Ce crystals read out with silicon photomultipliers (SiPMs) and two end-caps instrumented with radiation-tolerant low-gain avalanche detectors (LGADs). With the goal of maximizing the detector performance within the stringent constraints of space, cost, and channel count, the BTL exploits elongated crystal bars, each read out with two SiPMs. This unusual geometry enables the instrumentation of large surfaces while minimizing the active area of the photodetectors and thus noise and power consumption. This article presents a summary of the research and development studies carried out to optimize this crystal-based technology and key beam test results in which the target time resolution of 30 ps has been achieved.

Background Breast cancer patients with early-stage disease are increasingly administered neoadjuvant chemotherapy (NAC) to downstage their tumors prior to surgery. In this setting, approximately 31% of patients fail to respond to therapy. This demonstrates the need for techniques capable of providing personalized feedback about treatment response at the earliest stages of therapy to identify patients likely to benefit from changing treatment. Diffuse optical spectroscopic imaging (DOSI) has emerged as a promising functional imaging technique for NAC monitoring. DOSI uses non-ionizing near-infrared light to provide non-invasive measures of absolute concentrations of tissue chromophores such as oxyhemoglobin. In 2011, we reported a new DOSI prognostic marker, oxyhemoglobin flare: a transient increase in oxyhemoglobin capable of discriminating NAC responders within the first day of treatment. In this follow-up study, DOSI was used to confirm the presence of the flare as well as to investigate whether DOSI markers of NAC response are regimen dependent. Methods This dual-center study examined 54 breast tumors receiving NAC measured with DOSI before therapy and the first week following chemotherapy administration. Patients were treated with either a standard of care maximum tolerated dose (MTD) regimen or an investigational metronomic (MET) regimen. Changes in tumor chromophores were tracked throughout the first week and compared to pathologic response and treatment regimen at specific days utilizing generalized estimating equations (GEE). Results Within patients receiving MTD therapy, the oxyhemoglobin flare was confirmed as a prognostic DOSI marker for response appearing as soon as day 1 with post hoc GEE analysis demonstrating a difference of 48.77% between responders and non-responders (p < 0.0001). Flare was not observed in patients receiving MET therapy. Within all responding patients, the specific treatment was a significant predictor of day 1 changes in oxyhemoglobin, showing a difference of 39.45% (p = 0.0010) between patients receiving MTD and MET regimens. Conclusions DOSI optical biomarkers are differentially sensitive to MTD and MET regimens at early timepoints suggesting the specific treatment regimen should be considered in future DOSI studies. Additionally, DOSI may help to identify regimen-specific responses in a more personalized manner, potentially providing critical feedback necessary to implement adaptive changes to the treatment strategy.