scholarly journals The Phase-1 Upgrade of the ATLAS Level-1 Endcap Muon Trigger

2018 ◽  
pp. 341-345
Author(s):  
Shunichi Akatsuka ◽  
Keyword(s):  
Phase 1 ◽  
Muon Trigger ◽  
Level 1

scholarly journals ATLAS Level-1 Endcap Muon Trigger for Run 3

2020 ◽  
Vol 245 ◽  
pp. 01002
Author(s):  
Atsushi Mizukami
Keyword(s):  
Data Transfer ◽  
Phase 1 ◽  
Hadron Collider ◽  
High Transverse Momentum ◽  
Readout System ◽  
Trigger System ◽  
Muon Trigger ◽  
Combining Data ◽  
Level 1 ◽  
High Event

The Large Hadron Collider is expected to operate with a centre-ofmass energy of 14 TeV and an instantaneous luminosity of 2.0 1034 cm−2s−1 for Run 3 scheduled from 2021 to 2024. In order to cope with the high event rate, an upgrade of the ATLAS trigger system is required. The level-1 endcap muon trigger system identifies muons with high transverse momentum by combining data from fast muon trigger detectors, called Thin Gap Chambers on the Big Wheel. Inner muon detectors (the Small Wheel and the Tile Calorimeter) coincidence was introduced to reduce fake muon contamination. In the ongoing Phase-1 upgrade the present Small Wheel is replaced with the New Small Wheel and additional Resistive Plate Chambers are installed in the inner region of the ATLAS muon spectrometer for the endcap muon trigger. Precision track information from the new detectors can be used as part of the muon trigger logic to enhance the performance significantly. The trigger processor board, Sector Logic, has been upgraded to handle the additional data from the new detectors. The new Sector Logic board has a modern FPGA to make use of Multi-Gigabit transceiver technology, which is used to receive data from the new detectors. The readout system for trigger data has also been re-designed to minimize the use of custom electronics and instead use commercial computers and network switches, by using TCP/IP for the data transfer. The new readout system uses a software-based data-handling. This paper describes the development of the level-1 endcap muon trigger and its readout system for Run 3.

The level 1 muon trigger for Run 2 of DO

1997 ◽  
Vol 44 (3) ◽  
pp. 348-353 ◽  
Author(s):  
J. Steinberg ◽  
K. Davis ◽  
D. Fein ◽  
R. Jayanti ◽  
K. Johns ◽  
...  
Keyword(s):  
Muon Trigger ◽  
Level 1

The Two-Dimensional CCSMM

2021 ◽  
pp. 32-54
Keyword(s):  
Cyber Security ◽  
Phase 1 ◽  
Maturity Model ◽  
Two Dimensional ◽  
Four Dimensions ◽  
Level 1 ◽  
Level 2

The community cyber security maturity model (CCSMM) defines four dimensions and five implementation mechanisms in describing the relative maturity of an organization or an SLTT's cybersecurity program. These are used in defining levels of maturity and the cybersecurity characteristics of an organization or SLTT at each level. In order to progress from one level to the next, a variety of activities should take place, and these are defined in terms of five different mechanisms. In between two levels are a variety of activities that should take place to help the entity to advance from one level to the next. These groups of activities describe four phases, each of which takes place between two levels. Thus, Phase 1 defines the activities that should occur for an entity to advance from Level 1 to Level 2.

PERFORMANCES OF THE ATLAS LEVEL-1 MUON TRIGGER PROCESSOR IN THE BARREL

2006 ◽  
Author(s):  
V. BOCCI ◽  
G. CHIODI ◽  
G. CIAPETTI ◽  
D. DE PEDIS ◽  
A. DI GIROLAMO ◽  
...  
Keyword(s):  
Muon Trigger ◽  
Level 1

scholarly journals ACTR-63. PHASE I DOSE ESCALATION STUDY OF PROCASPASE ACTIVATING COMPOUND-1 (PAC-1) IN COMBINATION WITH TEMOZOLOMIDE IN PATIENTS WITH RECURRENT ANAPLASTIC ASTROCYTOMA OR GLIOBLASTOMA

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi28-vi28
Author(s):  
Matthias Holdhoff ◽  
Martin Nicholas ◽  
Richard Peterson ◽  
Oana Danciu ◽  
Stefania Maraka ◽  
...  
Keyword(s):  
Dose Level ◽  
Dose Escalation ◽  
Anaplastic Astrocytoma ◽  
Caspase 3 ◽  
Phase 1 ◽  
Maximum Tolerated Dose ◽  
Pharmacokinetic Data ◽  
Dose Escalation Study ◽  
Level 1 ◽  
Level 2

Abstract BACKGROUND Procaspase activating compound -1 (PAC-1) is a small molecule that catalyzes conversion of procaspase-3 to caspase-3 which induces apoptosis in cancer cells. Glioblastoma (GBM) is among the tumors with high concentrations of procaspase-3 and low levels of caspase-3. PAC-1 crosses the blood brain barrier and has been shown to synergize with temozolomide (TMZ) in canine malignant glioma and meningioma that arise spontaneously. METHODS This is a multicenter phase 1 dose-escalation study to assess the maximum tolerated dose (MTD) of PAC-1 administered days 1–21 in combination with TMZ days 8–12 at a dose of 150 mg/m2 of each 28 day cycle in subjects with recurrent anaplastic astrocytoma (AA) or GBM. A modified Fibonacci 3 + 3 design is used with up to 4 dose levels of PAC-1 (375, 500, 625 and 750 mg/day). Neurologic toxicity, including cognitive function, is closely monitored throughout the trial. INTERIM DATA: A total of 14 subjects have been enrolled to-date. Of these, 7 at dose level 1, PAC-1 375 mg/day (6 GBM, 1 AA; median age 58y, range 25–75) and 7 at dose level 2, PAC-1 500 mg/day (5 GBM, 2 AA; median age 51y, range 35–60). Best responses to-date were 2 subjects with a partial response and 2 with stable disease. Grade 3 (hepatotoxicity) and 4 (cerebral edema) was reported as possibly related to PAC-1 in 1 patient at dose level 1. The median number of cycles received was 4 (range, 1–12+) at dose level 1 and 2 (range, 1–3) at dose level 2. Enrollment to dose level 2 has been completed and data analysis is ongoing. Updated response and toxicity as well as pharmacokinetic data will be presented.

scholarly journals Heart Rate Kinetics Response of Pre-Pubertal Children during the Yo-Yo Intermittent Endurance Test—Level 1

Sports ◽  
2019 ◽  
Vol 7 (3) ◽  
pp. 65 ◽  
Author(s):  
João Brito ◽  
Luís Fernandes ◽  
António Rebelo ◽  
Peter Krustrup ◽  
Gustavo Silva ◽  
...  
Keyword(s):  
Heart Rate ◽  
Body Weight ◽  
Physical Fitness ◽  
Inflection Point ◽  
Phase 1 ◽  
Second Phase ◽  
Endurance Test ◽  
School Sports ◽  
Level 1 ◽  
Test Level

This study analyzed heart rate (HR) kinetics during the Yo-Yo Intermittent Endurance Test—level 1 (Yo-Yo IE1) in children. At the middle of the school year, 107 boys (7–10 years old) performed the Yo-Yo IE1. Individual HR curves during the Yo-Yo IE1 were analyzed to detect an inflection point between an initial phase of fast rise in HR, and a second phase in which the rise of HR is slower. The 7th shuttle of the test was established as the inflection point. Engagement with extra-school sports practice was identified. Percentile groups (P1, P2 and P3) were created for body weight and physical fitness data composite (PFcomposite). Differences were found between the slopes of P1 and P3 on phase 1 for body weight (12.5 ± 2.7 vs. 13.7 ± 2.0 bpm/shuttle; p = 0.033; d = 0.50) and PFcomposite (14.2 ± 2.5 vs. 12.5 ± 2.0 bpm/shuttle; p = 0.015; d = 0.75). Time spent >95% of peak HR was longer for the children engaged with extra-school sports practice (335 ± 158 vs. 234 ± 124 s; p < 0.001; d = 0.71); differences were also detected for PFcomposite (P1, P2 and P3: 172 ± 92, 270 ± 109, and 360 ± 157 s, respectively; p < 0.05; d = 0.66–1.46). This study indicates that physical fitness and body weight influence HR kinetics during the Yo-Yo IE1 in pre-pubertal boys.

Cyclosporine Modulation of Multidrug Resistance in Combination with Pravastatin, Mitoxantrone, and Etoposide for Adult Patients with Relapsed/Refractory Acute Myeloid Leukemia (AML): A Phase 1/2 Study

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4343-4343
Author(s):  
Tara L Chen ◽  
Elihu H. Estey ◽  
Megan Othus ◽  
Kelda M. Gardner ◽  
Lauren Markle ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Multidrug Resistance ◽  
Dose Level ◽  
Phase 1 ◽  
Kidney Injury ◽  
Adult Patients ◽  
Hematologic Toxicity ◽  
Heavily Pretreated ◽  
Level 1 ◽  
Level 2

Abstract Abstract 4343 Background: Outcomes in relapsed/refractory AML are dismal. Given the high prevalence of multidrug resistance (MDR), many clinical studies have tested whether MDR reversal agents such as cyclosporine (CSA) could increase the efficacy of conventional chemotherapeutics but results have been inconsistent. More recently, HMG-CoA reductase inhibitors (e.g. pravastatin) have been investigated after demonstration that cholesterol synthesis inhibition can restore chemosensitivity of AML cells in vitro. As studies further suggested the HMG-CoA inhibitors could downregulate MDR function, we attempted to improve the efficacy of mitoxantrone and etoposide in patients with relapsed/persistent AML by combining CSA and pravastatin in a single-arm, open-label phase 1/2 trial. Patients and Methods: Adult patients with relapsed/refractory non-APL AML and a treatment-related mortality score of <9.2 (Walter et al. J Clin Oncol 2011) were eligible if they had an ECOG performance status (PS) ≤3 and adequate organ function. Prior hematopoietic cell transplantation (HCT) was permissible if relapse occurred >180 days post-HCT. Planned treatment included induction and consolidation therapy with pravastatin, CSA, and increasing doses of mitoxantrone and etoposide. All patients received pravastatin 320mg PO every 6 hours on days 1–10. The starting dose level (level 1) used etoposide 60mg/m2/day and mitoxantrone 5mg/m2/day via continuous infusion on days 5–9. CSA started 6 hours before the first doses of mitoxantrone/etoposide; after loading with 6mg/kg over 2 hours and 4mg/kg over 6 hours, CSA was infused at 18mg/kg/day on days 5–9. CSA levels were monitored on Day 6 and 8 to maintain levels <2,400ng/mL (by LCMS-MS). At dose level 2, identical doses of pravastatin and CSA were combined with etoposide (80mg/m2/day) and mitoxantrone (6mg/m2/day). Dose-limiting toxicities (DLTs) were defined as: 1) any Grade 3 non-hematologic toxicity lasting >48 hours except of febrile neutropenia (FN), infection, or hyperbilirubinemia; and 2) any Grade ≥4 non-hematologic toxicity except FN/infection, constitutional symptoms if recovery to Grade ≤2 within 14 days, and hyperbilirubinemia. An “adaptive” Bayesian phase 1–2 design that monitored both toxicity and response was used. The maximal acceptable rate of toxicity was 30%, the minimum acceptable rate of efficacy 20% (historical rate of 15% in this population), stopping when posterior probability >90%. A maximum of 45 patients would be treated in cohorts of 3. Results: Between October 2010 and February 2012, 10 patients (median age 52 [range 40–58] years) were treated, including 4 patients (all at dose level 1) who received therapy off protocol. Two patients had secondary AML, and 6 had complex cytogenetics. PS was 1 (7 patients) or 2 (3 patients). Average TRM score was 4.32 for on-study patients. All patients had received at least 2 prior regimens, and 7 received 3 prior therapies. One patient had undergone HCT. The average CSA level on Day 6 was 1,366.3ng/mL (range 713–2,082ng/mL) and 1,199.8ng/mL on Day 8 (range 526–1,593ng/mL). Efficacy (CR or CRi)/DLTs for on-study patients were: level 1 (n=3): 0/1 (grade 4 acute kidney injury); level 2 (n=3): 0/2 (grade 4 acute kidney injury; sepsis/multiorgan failure). Among the 7 patients treated at level 1, other toxicities included septic shock (n=1), FN (4), mucositis (2), and decreased left ventricular ejection fraction (1). One off-study patient achieved CR after 1 course and received 1 cycle of consolidation with pravastatin, etoposide, and mitoxantrone but experienced CNS relapse after CR duration of only 46 days. Based on the results of the on-study patients, the statistical monitoring mandated early study closure for lack of efficacy & excessive toxicity. Conclusion: In the targeted, heavily pretreated patient population, the study regimen was excessively toxic and failed to achieve acceptable efficacy. Further clinical testing, if any, should be limited to less heavily pretreated, otherwise “fit” patients with AML. This trial was registered at ClinicalTrials.gov as NCT01342887. Disclosures: No relevant conflicts of interest to declare.

Phase 1 Dose-Escalation Study of 90yttrium-Labeled Anti-CD22 Epratuzumab Tetraxetan in Adults with Refractory/Relapsed CD22+ B-Cell Acute Lymphoblastic Leukemia (B-ALL)

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3708-3708
Author(s):  
Patrice Chevallier ◽  
Thomas Eugene ◽  
Nelly Robillard ◽  
Françoise Isnard ◽  
Franck E Nicolini ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Phase 1 ◽  
Whole Body ◽  
Organ Distribution ◽  
Hematologic Toxicity ◽  
Level 3 ◽  
Level 1 ◽  
Level 2

Abstract Background: Prognosis of relapsed/refractory acute lymphoblastic leukemia (ALL) in adults is dismal. CD22 is highly expressed in patients with B-ALL. Epratuzumab (hLL2) is a humanized monoclonal antibody targeting CD22 surface antigen. We performed a standard 3+3 phase 1 study to assess the feasibility, tolerability, and efficacy of a 90yttrium-labeled anti-CD22 epratuzumab tetraxetan (90Y-DOTA-hLL2) radioimmunotherapy (RIT) in adults with refractory/relapsed CD22+ B-ALL. Methods: After premedication with corticosteroid, 90Y-DOTA-hLL2 was administered twice on days 1 and 8 (+2), successively at 2.5 (level 1), 5.0 (level 2), 7.5 (level 3), and 10.0 (level 4) mCi/m². The first two patients also received 4 infusions of DOTA-hLL2 360 mg/m²/day before the RIT. This “cold phase” was terminated after observing no efficacy and full saturation of the CD22 target on the leukemic cells. Minimal residual disease (MRD) was assessed either by flow cytometry or by RQ-PCR for BCR-ABL1 analyses in Philadelphia chromosome positive (Ph+) B-ALL patients. Dose-limiting toxicity (DLT) was defined as any non-reversible grade >3 non-hematological toxicity or grade 4 pancytopenia with hypocellular bone marrow lasting for >6 weeks. Maximum tolerated dose (MTD) was defined as the dose level at which 2 of 3 or 2 of 6 patients experienced a DLT. Dosimetry, organ distribution and elimination of the radiotracer were studied between the two RIT infusions in all but one patient, using whole-body scintigraphy recorded after 111Indium-epratuzumab tetraxetan injection and blood pharmacokinetics. Patients were evaluated for response between 4 and 6 weeks following the first infusion of RIT. Findings: Between October 2011 and June 2014, 20 patients were enrolled. Three patients were not considered for analyses because of disease progression (n=2) or persistent non-blastic pancytopenia (n=1) before RIT. Overall, 17 cases were treated (5 at level 1 including 2 previously treated with the cold phase, 3 at level 2, 3 at level 3, and 6 at level 4). There were 10 males and 7 females with a median age of 62 years (range: 27-77). Two patients had primary refractory B-ALL; 10, 3 and 2 were in first, second or third relapse, respectively. Median percentage of blasts in the bone marrow was 75%. Karyotypes were as follows: Ph+ B-ALL n=6, complex n=3, MLL rearrangement n=1, hyperdiploidy n=1, hypodiploidy n=1, near-triploidy n=1, del4q (+ikaros mutation) n=1, normal (but ikaros mutation) n=1, and unknown n=2. Four patients were previously allotransplanted. Median interval between diagnosis and RIT was 16.5 months. Five patients presented immediate infusion reactions (3 grade 1, 1 grade 2 and 1 grade 3 in a patient with a previous history of severe allergic reactions) after the first RIT infusion, but received the second infusions without toxicities. All examined patients showed expected uptake of the radiotracer on potential disease sites (blood, spleen, liver, and bone marrow). No response was seen at levels 1 and 3. One molecular complete response was documented at level 2 (54-year old woman in third relapse of Ph+ B-ALL). At level 4, 2 patients achieved complete remissions (1 Ph+ ALL and 1 Ph- ALL), while all 6 cases presented with grade 4 hematologic toxicity. One DLT was documented at level 4 (non-blastic pancytopenia lasting 8 weeks), but MTD was not reached. Two patients in response received a second RIT cycle. Currently, only one non-responder is alive, while 2 of 3 responders are alive. One relapsed at 1 year and died of progression (level 2), while the two remaining are in persistent CR at 6 months post RIT, with low positive MRD. Interpretation: 90Y-DOTA-hLL2 RIT is well-tolerated and induced complete remissions even in heavily pre-treated CD22+ relapsed/refractory B-ALL patients, thus appearing to be a promising targeted therapy for CD22+ B-ALL. We recommend the dose of 10 mCi/m² given twice, one week apart/cycle, for phase 2 studies. The trial is registered at http://clinicaltrials.gov/ct no.NCT01354457. Funding: Immunomedics, Inc. Disclosures Goldenberg: immunomedics: Employment. Wegener:immunomedics: Employment.

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