145 research outputs found
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
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
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
Relationship between impaired apoptosis of lymphocytes and distribution of dendritic cells in peripheral blood and synovial fluid of children with juvenile idiopathic arthritis
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
TELO-SCOPE study: a randomised, double-blind, placebo-controlled, phase 2 trial of danazol for short telomere related pulmonary fibrosis
Introduction: Recent discoveries have identified shortened telomeres and related mutations in people with pulmonary fibrosis (PF). There is evidence to suggest that androgens, including danazol, may be effective in lengthening telomeres in peripheral blood cells. This study aims to assess the safety and efficacy of danazol in adults and children with PF associated with telomere shortening.Methods and analysis: A multi-centre, double-blind, placebo-controlled, randomised trial of danazol will be conducted in subjects aged >5 years with PF associated with age-adjusted telomere length ≤10th centile measured by flow fluorescence in situ hybridisation; or in children, a diagnosis of dyskeratosis congenita. Adult participants will receive danazol 800 mg daily in two divided doses or identical placebo capsules orally for 12 months, in addition to standard of care (including pirfenidone or nintedanib). Paediatric participants will receive danazol 2 mg/kg/day orally in two divided doses or identical placebo for 6 months. If no side effects are encountered, the dose will be escalated to 4 mg/kg/day (maximum 800 mg daily) orally in two divided doses for a further 6 months. The primary outcome is change in absolute telomere length in base pairs, measured using the telomere shortest length assay (TeSLA), at 12 months in the intention to treat population
The immune checkpoint CD96 defines a distinct lymphocyte phenotype and is highly expressed on tumor-infiltrating T cells
CD96 has recently been shown to be a potent immune checkpoint molecule in
mice, but a similar role in humans is not known. In this study, we provide a
detailed map of CD96 expression across human lymphocyte lineages, the
kinetics of CD96 regulation on T-cell activation and co-expression with other
conventional and emerging immune checkpoint molecules. We show that
CD96 is predominantly expressed by T cells and has a unique lymphocyte
expression profile. CD96
high
T cells exhibited distinct effector functions on
activation. Of note, CD96 expression was highly correlated with T-cell markers
in primary and metastatic human tumors and was elevated on antigen-
experienced T cells and tumor-infiltrating lymphocytes. Collectively, these data
demonstrate that CD96 may be a promising immune checkpoint to enhance
T-cell function against human cancer and infectious diseas
Noncutaneous malignant melanoma: a prognostic model from a retrospective multicenter study
Abstract Background We performed multicenter study to define clinical characteristics of noncutaneous melanomas and to establish prognostic factors patients who received curative resection. Methods Of the 141 patients who were diagnosed of non-cutaneous melanoma at 4 institutions in Korea between June 1992 and May 2005, 129 (91.5%) satisfied the selection criteria. Results Of the 129 noncutaneous melanoma patients, 14 patients had ocular melanoma and 115 patients had mucosal melanoma. For mucosal melanoma, anorectum was the most common anatomic site (n = 39, 30.2%) which was followed by nasal cavity (n = 30, 23.3%), genitourinary (n = 21, 16.3%), oral cavity (n = 14, 10.9%), upper gastrointestinal tract (n = 6, 4.7%) and maxillary sinus (n = 5, 3.9%) in the order of frequency. With the median 64.5 (range 4.3-213.0) months follow-up, the median overall survival were 24.4 months (95% CI 13.2-35.5) for all patients, and 34.6 (95% CI 24.5-44.7) months for curatively resected mucosal melanoma patients. Adverse prognostic factors of survival for 87 curatively resected mucosal melanoma patients were complete resection (R1 resection margin), and age > 50 years. For 14 ocular melanoma, Survival outcome was much better than mucosal melanoma with 73.3% of 2 year OS and 51.2 months of median OS (P = .04). Conclusion Prognosis differed according to primary sites of noncutaneous melanoma. Based on our study, noncutaneous melanoma patients should be treated differently to improve survival outcome.Peer Reviewe
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