Tracking down hyper-boosted top quarks

The identification of hadronically decaying heavy states, such as vector bosons, the Higgs, or the top quark, produced with large transverse boosts has been and will continue to be a central focus of the jet physics program at the Large Hadron Collider (LHC). At a future hadron collider working at an order-of-magnitude larger energy than the LHC, these heavy states would be easily produced with transverse boosts of several TeV. At these energies, their decay products will be separated by angular scales comparable to individual calorimeter cells, making the current jet substructure identification techniques for hadronic decay modes not directly employable. In addition, at the high energy and luminosity projected at a future hadron collider, there will be numerous sources for contamination including initial- and final-state radiation, underlying event, or pile-up which must be mitigated. We propose a simple strategy to tag such "hyper-boosted" objects that defines jets with radii that scale inversely proportional to their transverse boost and combines the standard calorimetric information with charged track-based observables. By means of a fast detector simulation, we apply it to top quark identification and demonstrate that our method efficiently discriminates hadronically decaying top quarks from light QCD jets up to transverse boosts of 20 TeV. Our results open the way to tagging heavy objects with energies in the multi-TeV range at present and future hadron colliders.Comment: 19 pages + appendices, 17 figures; v2: added references, updated cross section tabl

DELPHES 3, A modular framework for fast simulation of a generic collider experiment

The version 3.0 of the DELPHES fast-simulation is presented. The goal of DELPHES is to allow the simulation of a multipurpose detector for phenomenological studies. The simulation includes a track propagation system embedded in a magnetic field, electromagnetic and hadron calorimeters, and a muon identification system. Physics objects that can be used for data analysis are then reconstructed from the simulated detector response. These include tracks and calorimeter deposits and high level objects such as isolated electrons, jets, taus, and missing energy. The new modular approach allows for greater flexibility in the design of the simulation and reconstruction sequence. New features such as the particle-flow reconstruction approach, crucial in the first years of the LHC, and pile-up simulation and mitigation, which is needed for the simulation of the LHC detectors in the near future, have also been implemented. The DELPHES framework is not meant to be used for advanced detector studies, for which more accurate tools are needed. Although some aspects of DELPHES are hadron collider specific, it is flexible enough to be adapted to the needs of electron-positron collider experiments.Comment: JHEP 1402 (2014

Clinical efficacy of minimally invasive surgical (MIS) and non-surgical (MINST) treatments of periodontal intra-bony defect. A systematic review and network meta-analysis of RCT's

Objective: The aim of this systematic review was to explore the efficacy of different minimal invasive surgical (MIS) and non-surgical (MINST) approaches for the treatment of intra-bony defect in terms of clinical attachment level (CAL) gain and periodontal pocket depth (PPD) reduction. / Methods: A detailed review protocol was designed according to PRISMA guideline. Online search was conducted on PubMed, Cochrane library and Embase. Only randomized clinical trials (RCTs) testing MIS or MINST procedure, with or without the application of a regenerative tool for the treatment of intra-bony defect, were included. Cochrane checklist for risk of bias assessment was used. Network meta-Analysis (NMAs) was used to rank the treatment efficacy. / Results: Nine RCTs accounting for 244 patients and a total of 244 defects were included. Only two studies were at low risk of bias. CAL gain for included treatment ranged from 2.58 ± 1.13 mm to 4.7 ± 2.5 mm while PPD reduction ranged from 3.19 ± 0.71 mm to 5.3 ± 1.5 mm. On the basis of the ranking curve, MINST showed the lowest probability to be the best treatment option for CAL gain. Pairwise comparisons and treatment rankings suggest superiority for regenerative approaches (CAL difference 0.78 mm, (0.14–1.41); P < 0.05) and surgical treatment elevating only the buccal or palatal flap (CAL difference: 0.95 mm, (0.33–1.57); P < 0.05). / Conclusions: Minimally invasive surgical (MIS) and non-surgical (MINST) periodontal therapy show promising results in the treatment of residual pocket with intra-bony defect. / Clinical relevance: MIS procedures represent a reliable treatment for isolated intra-bony defect

Efficacy and safety of first-line treatment strategies for anaplastic lymphoma kinase-positive non-small cell lung cancer: a Bayesian network meta-analysis.

Background: Targeted therapies have led to significant improvement in the management and prognosis of anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC). We performed a network meta-analysis of frontline treatment options of ALK-positive NSCLC to provide clinical guidance. Methods: PubMed, Embase, ClinicalTrials.gov, and international conference databases were searched to identify relevant trials from inception to June 30, 2021. Phase III randomized controlled trials (RCTs) comparing treatments for patients with ALK-positive advanced NSCLC in the first-line setting were included in a Bayesian network meta-analysis. Eligible studies reported at least one of the following clinical outcomes: progression-free survival (PFS), overall survival (OS), risk of the central nervous system (CNS) progression, adverse events (AEs) of grade (G) 3 or higher (G3 AEs), or serious AEs (SAEs). Hazard ratios (HRs) and CI for primary outcome of PFS and secondary outcome of OS and risk of CNS progression were obtained. A multivariate, consistency model, fixed-effects analysis was used in the network meta-analysis. Data on G3 AEs and SAEs were abstracted and meta-analyzed. Risk of bias (RoB) was assessed using the Cochrane Collaboration's tool. Results: Nine RCTs comprising 2,484 patients were included with seven treatments: alectinib, brigatinib, ceritinib, crizotinib, ensartinib, lorlatinib, and chemotherapy. Compared with chemotherapy, ALK-tyrosine kinase inhibitors (TKIs) significantly prolong PFS and reduced risk of CNS progression except for ceritinib. Lorlatinib appears superior at reducing risk of CNS progression. None of the ALK-TKIs have a significantly prolonged OS as compared with chemotherapy. Lorlatinib increases the risk of G3 AEs as compared with alectinib (odds ratio 4.26 [95% CrI 1.22 to 15.53]), while alectinib caused the fewest G3 AEs. Conclusions: Lorlatinib is associated with the highest PFS benefit and lowest risk of CNS progression benefits for patients with advanced ALK-positive NSCLC, compared with other first-line treatments, but with higher toxicity. The implementation of a newer generation of ALK-TKIs in the first-line treatment of ALK-positive NSCLC into current clinical practice is evolving rapidly

Follow-up Study to Evaluate the Long-term Safety and Efficacy of Darvadstrocel (Mesenchymal Stem Cell Treatment) in Patients With Perianal Fistulizing Crohn’s Disease: ADMIRE-CD phase 3 randomized controlled trial

BACKGROUND: Darvadstrocel is an expanded allogeneic adipose-derived mesenchymal stem cell therapy for the treatment of complex perianal fistulas in patients with Crohn’s disease. Safety and efficacy outcomes from the clinical trial known as “Adipose derived mesenchymal stem cells for induction of remission in perianal fistulizing Crohn’s disease,” or ADMIRE-CD (NCT01541579), from up to 52 weeks posttreatment were previously reported. Here, the outcomes from an extended 104-week follow-up are reported. OBJECTIVE: The goal of this study was to assess the long-term safety and efficacy of darvadstrocel at 2 years post-treatment in patients with Crohn’s disease and complex perianal fistulas. DESIGN: This was a phase 3 double-blind randomized controlled study (ADMIRE-CD) in patients with perianal fistulizing Crohn’s disease. SETTINGS: This study extension was conducted in multiple hospitals across 7 European countries and Israel. PATIENTS: Forty patients entered the extended follow-up period: 25 patients in the darvadstrocel treatment group and 15 in the control group. INTERVENTIONS: Darvadstrocel or saline solution (control group) was administered once, locally, after fistula tract curettage and internal opening closure (with previous seton placement). All patients were permitted to continue ongoing medical treatments for fistulas. MAIN OUTCOME MEASURES: Treatment-emergent serious adverse events were recorded through week 104. Clinical remission, defined as closure of all treated external openings that were draining at baseline despite gentle finger compression, was assessed at week 104. RESULTS: Of 40 patients, 37 completed the extended follow-up. Through week 104, 7 treatment-emergent serious adverse events were reported, of which 4 occurred between weeks 52 and 104. At week 104, clinical remission was reported in 14/25 (56%) patients in the darvadstrocel group and 6/15 (40%) patients in the control group. LIMITATIONS: Limitations include the small number of patients who entered the extended follow-up period, and no imaging examinations were performed at the 104-week time point. CONCLUSIONS: Darvadstrocel was well tolerated and clinical remission after treatment with darvadstrocel may be sustained for up to 104 weeks in patients with perianal fistulizing Crohn’s disease

Physics at a 100 TeV pp collider: Higgs and EW symmetry breaking studies

This report summarises the physics opportunities for the study of Higgs bosons and the dynamics of electroweak symmetry breaking at the 100 TeV pp collider.Comment: 187 pages, 94 figures. Chapter 2 of the "Physics at the FCC-hh" Repor

Computing the External Magnetic Scalar Potential due to an Unbalanced Six-Pole Permanent Magnet Motor

The accurate computation of the external magnetic field from a permanent magnet motor is accomplished by first computing its magnetic scalar potential. In order to find a solution which is valid for any arbitrary point external to the motor, a number of proven methods have been employed. Firstly, A finite element model is developed which helps generate magnetic scalar potential values valid for points close to and outside the motor. Secondly, charge simulation is employed which generates an equivalent magnetic charge matrix. Finally, an equivalent multipole expansion is developed through the application of a toroidal harmonic expansion. This expansion yields the harmonic components of the external magnetic scalar potential which can be used to compute the magnetic field at any point outside the motor

JAK3/STAT5/6 Pathway Alterations Are Associated with Immune Deviation in CD8+ T Cells in Renal Cell Carcinoma Patients

To investigate the molecular mechanisms underlying altered T cell response in renal cell carcinoma (RCC) patients, we compared autologous and allogeneic CD8+ T cell responses against RCC line from RCC patients and their HLA-matched donors, using mixed lymphocyte/tumor cell cultures (MLTCs). In addition, we analyzed the expression of molecules associated with cell cycle regulation. Autologous MLTC responder CD8+ T cells showed cytotoxic activity against RCC cell lines; however the analysis of the distribution of CD8+ T-cell subsets revealed that allogenic counterparts mediate superior antitumor efficacy. In RCC patients, a decreased proliferative response to tumor, associated with defects in JAK3/STAT5/6 expression that led to increased p27KIP1 expression and alterations in the cell cycle, was observed. These data define a molecular pathway involved in cell cycle regulation that is associated with the dysfunction of tumor-specific CD8+ effector cells. If validated, this may define a therapeutic target in the setting of patients with RCC