Two dimensional dynamical systems which admit Lie and Noether symmetries

We prove two theorems which relate the Lie point symmetries and the Noether symmetries of a dynamical system moving in a Riemannian space with the special projective group and the homothetic group of the space respectively. The theorems are applied to classify the two dimensional Newtonian dynamical systems, which admit a Lie point/Noether symmetry. Two cases are considered, the non-conservative and the conservative forces. The use of the results is demonstrated for the Kepler - Ermakov system, which in general is non-conservative and for potentials similar to the H\`enon Heiles potential. Finally it is shown that in a FRW background with no matter present, the only scalar cosmological model which is integrable is the one for which 3-space is flat and the potential function of the scalar field is exponential. It is important to note that in all applications the generators of the symmetry vectors are found by reading the appropriate entry in the relevant tables.Comment: 25 pages, 17 table

Involutive orbits of non-Noether symmetry groups

We consider set of functions on Poisson manifold related by continues one-parameter group of transformations. Class of vector fields that produce involutive families of functions is investigated and relationship between these vector fields and non-Noether symmetries of Hamiltonian dynamical systems is outlined. Theory is illustrated with sample models: modified Boussinesq system and Broer-Kaup system.Comment: LaTeX 2e, 10 pages, no figure

Iterative algorithm versus analytic solutions of the parametrically driven dissipative quantum harmonic oscillator

We consider the Brownian motion of a quantum mechanical particle in a one-dimensional parabolic potential with periodically modulated curvature under the influence of a thermal heat bath. Analytic expressions for the time-dependent position and momentum variances are compared with results of an iterative algorithm, the so-called quasiadiabatic propagator path integral algorithm (QUAPI). We obtain good agreement over an extended range of parameters for this spatially continuous quantum system. These findings indicate the reliability of the algorithm also in cases for which analytic results may not be available a priori.Comment: 15 pages including 11 figures, one reference added, minor typos correcte

Anomalies in T cell function are associated with individuals at risk of mycobacterium abscessus complex infection

The increasing global incidence and prevalence of non-tuberculous mycobacteria (NTM) infection is of growing concern. New evidence of person-to-person transmission of multidrug-resistant NTM adds to the global concern. The reason why certain individuals are at risk of NTM infections is unknown. Using high definition flow cytometry, we studied the immune profiles of two groups that are at risk of Mycobacterium abscessus complex infection and matched controls. The first group was cystic fibrosis (CF) patients and the second group was elderly individuals. CF individuals with active M. abscessus complex infection or a history of M. abscessus complex infection exhibited a unique surface T cell phenotype with a marked global deficiency in TNFa production during mitogen stimulation. Importantly, immune-based signatures were identified that appeared to predict at baseline the subset of CF individuals who were at risk of M. abscessus complex infection. In contrast, elderly individuals with M. abscessus complex infection exhibited a separate T cell phenotype underlined by the presence of exhaustion markers and dysregulation in type 1 cytokine release during mitogen stimulation. Collectively, these data suggest an association between T cell signatures and individuals at risk of M. abscessus complex infection, however, validation of these immune anomalies as robust biomarkers will require analysis on larger patient cohorts

CD161 expression defines new human γδ T cell subsets

γδ T cells are a highly versatile immune lineage involved in host defense and homeostasis, but questions remain around their heterogeneity, precise function and role during health and disease. We used multi−parametric flow cytometry, dimensionality reduction, unsupervised clustering, and self-organizing maps (SOM) to identify novel γδ T cell naïve/memory subsets chiefly defined by CD161 expression levels, a surface membrane receptor that can be activating or suppressive. We used middle-to-old age individuals given immune blockade is commonly used in this population. Whilst most Vδ1+subset cells exhibited a terminal differentiation phenotype, Vδ1− subset cells showed an early memory phenotype. Dimensionality reduction revealed eight γδ T cell clusters chiefly diverging through CD161 expression with CD4 and CD8 expression limited to specific subpopulations. Comparison of matched healthy elderly individuals to bronchiectasis patients revealed elevated Vδ1+ terminally differentiated effector memory cells in patients potentially linking this population with chronic proinflammatory disease

Gravity modelling along CROP04 seismic profile

The processing and interpretation of seismic lines, together with the analysis of surficial geological data and hydrocarbon wells data, are powerful tools for the investigation of crust structures. Nevertheless, for depths exceeding that portion of crust usually investigated for commercial purposes, only geophysical data are generally available (among the others: NVR seismic from CROP project, DSS data, magnetic data, gravity data). In this context, the possibility of comparing two independent geophysical data sets, such as data from seismic exploration (CROP Project) and gravimetric analysis (Bouguer anomalies), is of particular interest for investigations into the deeper crust portion. In the present work gravity data modelling was used to study deep crust, constraints being provided by WARR data and by reflection seismic data obtained along the CROP04 profile that crosses the Southern Apennines (Italy) from Agropoli (SW) to Barletta (NE). A preliminary interpretation has been made of the regional gravity anomaly trend in deep crust in Southern Italy; the role of this anomaly trend as an independent constraint for the geological interpretation of the CROP04 seismic line is discussed

Adjuvant nivolumab for stage III/IV melanoma: Evaluation of safety outcomes and association with recurrence-free survival

Background Several therapeutic options are now available in the adjuvant melanoma setting, mandating an understanding of their benefit €'risk profiles in order to make informed treatment decisions. Herein we characterize adjuvant nivolumab select (immune-related) treatment-related adverse events (TRAEs) and evaluate possible associations between safety and recurrence-free survival (RFS) in the phase III CheckMate 238 trial. Methods Patients with resected stage IIIB-C or IV melanoma received nivolumab 3 mg/kg every 2 weeks (n=452) or ipilimumab 10 mg/kg every 3 weeks for four doses and then every 12 weeks (n=453) for up to 1 year or until disease recurrence, unacceptable toxicity, or consent withdrawal. First-occurrence and all-occurrence select TRAEs were analyzed within discrete time intervals: from 0 to 3 months of treatment, from >3-12 months of treatment, and from the last dose (regardless of early or per-protocol treatment discontinuation) to 100 days after the last dose. Possible associations between select TRAEs and RFS were investigated post randomization in 3-month landmark analyses and in Cox model analyses (including a time-varying covariate of select TRAE), within and between treatment groups. Results From the first nivolumab dose to 100 days after the last dose, first-occurrence select TRAEs were reported in 67.7% (306/452) of patients. First-occurrence select TRAEs were reported most frequently from 0 to 3 months (48.0%), during which the most common were pruritus (15.5%) and diarrhea (15.3%). Most select TRAEs resolved within 6 months. There was no clear association between the occurrence (or not) of select TRAEs and RFS by landmark analysis or by Cox model analysis within treatment arms or comparing nivolumab to the ipilimumab comparator arm. Conclusion Results of this safety analysis of nivolumab in adjuvant melanoma were consistent with its established safety profile. In the discrete time intervals evaluated, most first-occurrence TRAEs occurred early during treatment and resolved. No association between RFS and select TRAEs was evident. Trial registration number NCT02388906

Safety & efficacy of lifileucel (LN-144) tumor infiltrating lymphocyte therapy in metastatic melanoma patients after progression on multiple therapies – independent review committee data update

Treatment options are limited for patients with advanced melanoma who have progressed on checkpoint inhibitors and targeted therapies such as BRAF/MEK inhibitors (if BRAF-V600E mutated). Adoptive cell therapy utilizing tumor-infiltrating lymphocytes (TIL) has shown antitumor efficacy with durable responses in heavily pretreated melanoma patients. Safety and efficacy of lifileucel, a centrally manufactured cryopreserved autologous TIL therapy assessed by both investigator and an independent review committee (IRC), are presented

Impact of Sequencing Targeted Therapies With High-dose Interleukin-2 Immunotherapy: An Analysis of Outcome and Survival of Patients With Metastatic Renal Cell Carcinoma From an On-going Observational IL-2 Clinical Trial: PROCLAIM

BACKGROUND: This analysis describes the outcome for patients who received targeted therapy (TT) prior to or following high-dose interleukin-2 (HD IL-2). PATIENTS AND METHODS: Patients with renal cell carcinoma (n = 352) receiving HD IL-2 were enrolled in Proleukin RESULTS: Overall, there were 4% complete response (CR), 13% partial response (PR), 39% stable disease (SD), and 43% progressive disease (PD) with HD IL-2. The median overall survival (mOS) was not reached in patients with CR, PR, or SD, and was 15.5 months in patients with PD (median follow-up, 21 months). Sixty-one patients had prior TT before HD IL-2 with an overall response rate (ORR) to HD IL-2 of 19% (1 CR, 9 PR) and an mOS of 22.1 months. One hundred forty-nine patients received TT only after HD IL-2 with an mOS of 35.5 months. One hundred forty-two patients had no TT before or after HD IL-2, and mOS was not reached. The mOS was 8.5 months in PD patients who received HD IL-2 without follow-on TT and 29.7 months in PD patients who received follow-on TT after HD IL-2. CONCLUSIONS: HD IL-2 as sole front-line therapy, in the absence of added TT, shows extended clinical benefit (CR, PR, and SD). Patients with PD after HD IL-2 appear to benefit from follow-on TT. Patients who progressed on TT and received follow-on HD IL-2 experienced major clinical benefit. HD IL-2 therapy should be considered in eligible patients