Operation and performance of the CMS silicon strip tracker with proton-proton collisions at the CERN LHC

Salient aspects of the commissioning, calibration, and performance of the CMS silicon strip tracker are discussed, drawing on experience during operation with proton-proton collisions delivered by the CERN LHC. The data were obtained with a variety of luminosities. The operating temperature of the strip tracker was changed several times during this period and results are shown as a function of temperature in several cases. Details of the system performance are presented, including occupancy, signal-to-noise ratio, Lorentz angle, and single-hit spatial resolution. Saturation effects in the APV25 readout chip preamplifier observed during early Run 2 are presented, showing the effect on various observables and the subsequent remedy. Studies of radiation effects on the strip tracker are presented both for the optical readout links and the silicon sensors. The observed effects are compared to simulation, where available, and they generally agree well with expectations

Discovery of BLU-945, a Reversible, Potent, and Wild-Type-Sparing Next-Generation EGFR Mutant Inhibitor for Treatment-Resistant Non-Small-Cell Lung Cancer

While epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have changed the treatment landscape for EGFR mutant (L858R and ex19del)-driven non-small-cell lung cancer (NSCLC), most patients will eventually develop resistance to TKIs. In the case of first- and second-generation TKIs, up to 60% of patients will develop an EGFR T790M mutation, while third-generation irreversible TKIs, like osimertinib, lead to C797S as the primary on-target resistance mutation. The development of reversible inhibitors of these resistance mutants is often hampered by poor selectivity against wild-type EGFR, resulting in potentially dose-limiting toxicities and a sub-optimal profile for use in combinations. BLU-945 (compound 30) is a potent, reversible, wild-type-sparing inhibitor of EGFR+/T790M and EGFR+/​T790M/​C797S resistance mutants that maintains activity against the sensitizing mutations, especially L858R. Pre-clinical efficacy and safety studies supported progression of BLU-945 into clinical studies, and it is currently in phase 1/2 clinical trials for treatment-resistant EGFR-driven NSCLC

Discovery of BLU-945, a Reversible, Potent, and Wild-Type-Sparing Next-Generation EGFR Mutant Inhibitor for Treatment-Resistant Non-Small-Cell Lung Cancer

While epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have changed the treatment landscape for EGFR mutant (L858R and ex19del)-driven non-small-cell lung cancer (NSCLC), most patients will eventually develop resistance to TKIs. In the case of first- and second-generation TKIs, up to 60% of patients will develop an EGFR T790M mutation, while third-generation irreversible TKIs, like osimertinib, lead to C797S as the primary on-target resistance mutation. The development of reversible inhibitors of these resistance mutants is often hampered by poor selectivity against wild-type EGFR, resulting in potentially dose-limiting toxicities and a sub-optimal profile for use in combinations. BLU-945 (compound 30) is a potent, reversible, wild-type-sparing inhibitor of EGFR+/T790M and EGFR+/​T790M/​C797S resistance mutants that maintains activity against the sensitizing mutations, especially L858R. Pre-clinical efficacy and safety studies supported progression of BLU-945 into clinical studies, and it is currently in phase 1/2 clinical trials for treatment-resistant EGFR-driven NSCLC

Measurement of the fractional radiation length of a pixel module for the CMS Phase-2 upgrade via the multiple scattering of positrons

International audienceHigh-luminosity particle collider experiments such as the ones planned at the High-Luminosity Large Hadron Collider require ever-greater vertexing precision of the tracking detectors, necessitating also reductions in the material budget of the detectors. Traditionally, the fractional radiation length ($x/X_0$) of detectors is either estimated using known properties of the constituent materials, or measured in dedicated runs of the final detector. In this paper, we present a method of direct measurement of the material budget of a CMS prototype module designed for the Phase-2 upgrade of the CMS detector using a 40-65 MeV positron beam. A total of 630 million events were collected at the Paul Scherrer Institut PiE1 experimental area using a three-plane telescope consisting of the prototype module as the central plane, surrounded by two MALTA monolithic pixel detectors. Fractional radiation lengths were extracted from scattering angle distributions using the Highland approximation for multiple scattering. A statistical technique recovered runs suffering from trigger desynchronisation, and several corrections were introduced to compensate for local inefficiencies related to geometric and beam shape constraints. An overall average $x/X_0$ of (0.84 $\pm$ 0.10)% across the surveyed regions was measured, which is compatible with an empirical estimate of 0.825% computed from known material properties. Higher-granularity maps of the fractional radiation length were produced for both rectangular regions and regions of uniform material composition. The results bode well for the CMS Phase-2 upgrade modules, which will play a key role in the minimisation of the material budget of the upgraded detector

Safety and efficacy of non-steroidal anti-inflammatory drugs to reduce ileus after colorectal surgery

Background Ileus is common after elective colorectal surgery, and is associated with increased adverse events and prolonged hospital stay. The aim was to assess the role of non-steroidal anti-inflammatory drugs (NSAIDs) for reducing ileus after surgery. Methods A prospective multicentre cohort study was delivered by an international, student- and trainee-led collaborative group. Adult patients undergoing elective colorectal resection between January and April 2018 were included. The primary outcome was time to gastrointestinal recovery, measured using a composite measure of bowel function and tolerance to oral intake. The impact of NSAIDs was explored using Cox regression analyses, including the results of a centre-specific survey of compliance to enhanced recovery principles. Secondary safety outcomes included anastomotic leak rate and acute kidney injury. Results A total of 4164 patients were included, with a median age of 68 (i.q.r. 57-75) years (54 center dot 9 per cent men). Some 1153 (27 center dot 7 per cent) received NSAIDs on postoperative days 1-3, of whom 1061 (92 center dot 0 per cent) received non-selective cyclo-oxygenase inhibitors. After adjustment for baseline differences, the mean time to gastrointestinal recovery did not differ significantly between patients who received NSAIDs and those who did not (4 center dot 6 versus 4 center dot 8 days; hazard ratio 1 center dot 04, 95 per cent c.i. 0 center dot 96 to 1 center dot 12; P = 0 center dot 360). There were no significant differences in anastomotic leak rate (5 center dot 4 versus 4 center dot 6 per cent; P = 0 center dot 349) or acute kidney injury (14 center dot 3 versus 13 center dot 8 per cent; P = 0 center dot 666) between the groups. Significantly fewer patients receiving NSAIDs required strong opioid analgesia (35 center dot 3 versus 56 center dot 7 per cent; P < 0 center dot 001). Conclusion NSAIDs did not reduce the time for gastrointestinal recovery after colorectal surgery, but they were safe and associated with reduced postoperative opioid requirement

Safety and efficacy of non-steroidal anti-inflammatory drugs to reduce ileus after colorectal surgery

Background: Ileus is common after elective colorectal surgery, and is associated with increased adverse events and prolonged hospital stay. The aim was to assess the role of non-steroidal anti-inflammatory drugs (NSAIDs) for reducing ileus after surgery. Methods: A prospective multicentre cohort study was delivered by an international, student- and trainee-led collaborative group. Adult patients undergoing elective colorectal resection between January and April 2018 were included. The primary outcome was time to gastrointestinal recovery, measured using a composite measure of bowel function and tolerance to oral intake. The impact of NSAIDs was explored using Cox regression analyses, including the results of a centre-specific survey of compliance to enhanced recovery principles. Secondary safety outcomes included anastomotic leak rate and acute kidney injury. Results: A total of 4164 patients were included, with a median age of 68 (i.q.r. 57\u201375) years (54\ub79 per cent men). Some 1153 (27\ub77 per cent) received NSAIDs on postoperative days 1\u20133, of whom 1061 (92\ub70 per cent) received non-selective cyclo-oxygenase inhibitors. After adjustment for baseline differences, the mean time to gastrointestinal recovery did not differ significantly between patients who received NSAIDs and those who did not (4\ub76 versus 4\ub78 days; hazard ratio 1\ub704, 95 per cent c.i. 0\ub796 to 1\ub712; P = 0\ub7360). There were no significant differences in anastomotic leak rate (5\ub74 versus 4\ub76 per cent; P = 0\ub7349) or acute kidney injury (14\ub73 versus 13\ub78 per cent; P = 0\ub7666) between the groups. Significantly fewer patients receiving NSAIDs required strong opioid analgesia (35\ub73 versus 56\ub77 per cent; P < 0\ub7001). Conclusion: NSAIDs did not reduce the time for gastrointestinal recovery after colorectal surgery, but they were safe and associated with reduced postoperative opioid requirement