Ulam method for the Chirikov standard map

We introduce a generalized Ulam method and apply it to symplectic dynamical maps with a divided phase space. Our extensive numerical studies based on the Arnoldi method show that the Ulam approximant of the Perron-Frobenius operator on a chaotic component converges to a continuous limit. Typically, in this regime the spectrum of relaxation modes is characterized by a power law decay for small relaxation rates. Our numerical data show that the exponent of this decay is approximately equal to the exponent of Poincar\'e recurrences in such systems. The eigenmodes show links with trajectories sticking around stability islands.Comment: 13 pages, 13 figures, high resolution figures available at: http://www.quantware.ups-tlse.fr/QWLIB/ulammethod/ minor corrections in text and fig. 12 and revised discussio

The nuclear energy density functional formalism

The present document focuses on the theoretical foundations of the nuclear energy density functional (EDF) method. As such, it does not aim at reviewing the status of the field, at covering all possible ramifications of the approach or at presenting recent achievements and applications. The objective is to provide a modern account of the nuclear EDF formalism that is at variance with traditional presentations that rely, at one point or another, on a {\it Hamiltonian-based} picture. The latter is not general enough to encompass what the nuclear EDF method represents as of today. Specifically, the traditional Hamiltonian-based picture does not allow one to grasp the difficulties associated with the fact that currently available parametrizations of the energy kernel $E[g',g]$ at play in the method do not derive from a genuine Hamilton operator, would the latter be effective. The method is formulated from the outset through the most general multi-reference, i.e. beyond mean-field, implementation such that the single-reference, i.e. "mean-field", derives as a particular case. As such, a key point of the presentation provided here is to demonstrate that the multi-reference EDF method can indeed be formulated in a {\it mathematically} meaningful fashion even if $E[g',g]$ does {\it not} derive from a genuine Hamilton operator. In particular, the restoration of symmetries can be entirely formulated without making {\it any} reference to a projected state, i.e. within a genuine EDF framework. However, and as is illustrated in the present document, a mathematically meaningful formulation does not guarantee that the formalism is sound from a {\it physical} standpoint. The price at which the latter can be enforced as well in the future is eventually alluded to.Comment: 64 pages, 8 figures, submitted to Euroschool Lecture Notes in Physics Vol.IV, Christoph Scheidenberger and Marek Pfutzner editor

Global Geographic Distribution and Host Range of Fusarium circinatum, the Causal Agent of Pine Pitch Canker

Fusarium circinatum, the causal agent of pine pitch canker (PPC), is currently one of the most important threats of Pinus spp. globally. This pathogen is known in many pine-growing regions, including natural and planted forests, and can affect all life stages of trees, from emerging seedlings to mature trees. Despite the importance of PPC, the global distribution of F. circinatum is poorly documented, and this problem is also true of the hosts within countries that are affected. The aim of this study was to review the global distribution of F. circinatum, with a particular focus on Europe. We considered (1) the current and historical pathogen records, both positive and negative, based on confirmed reports from Europe and globally; (2) the genetic diversity and population structure of the pathogen; (3) the current distribution of PPC in Europe, comparing published models of predicted disease distribution; and (4) host susceptibility by reviewing literature and generating a comprehensive list of known hosts for the fungus. These data were collated from 41 countries and used to compile a specially constructed geo-database. A review of 6297 observation records showed that F. circinatum and the symptoms it causes on conifers occurred in 14 countries, including four in Europe, and is absent in 28 countries. Field observations and experimental data from 138 host species revealed 106 susceptible host species including 85 Pinus species, 6 non-pine tree species and 15 grass and herb species. Our data confirm that susceptibility to F. circinatum varies between different host species, tree ages and environmental characteristics. Knowledge on the geographic distribution, host range and the relative susceptibility of different hosts is essential for disease management, mitigation and containment strategies. The findings reported in this review will support countries that are currently free of F. circinatum in implementing effective procedures and restrictions and prevent further spread of the pathogen

Real-world outcomes of ipilimumab plus nivolumab combination therapy in a nationwide cohort of advanced melanoma patients in the Netherlands

Background: In phase III trials, ipilimumab plus nivolumab combination therapy is highly efficacious for advanced melanoma, despite many treatment-related grade 3-4 adverse events (AEs). Here, we report real-world safety and survival outcomes of ipilimumab plus nivolumab for advanced melanoma.Methods: Patients with advanced melanoma who received first-line ipilimumab plus nivolumab between 1-1-2015 and 30-6-2021 were selected from the Dutch Melanoma Treatment Registry. We evaluated response status at 3, 6, 12,18, and 24 months. OS and PFS were estimated with the Kaplan-Meier method. Separate analyses were performed for patients with or without brain metastases and for patients who met the inclusion criteria of the Checkmate-067 trial.Results: In total, 709 patients received first-line ipilimumab plus nivolumab. Three hundred sixty (50.7%) patients experienced grade 3-4 AEs with 211 of them (58.6%) patients requiring hospital admission. Median treatment duration was 42 days (IQR = 31-139). At 24-months, disease control was achieved in 37% of patients. Median PFS since the start of treatment was 6.6 months (95%CI: 5.3-8.7), and median OS was 28.7 months (95%CI: 20.7-42.2). CheckMate-067 trial-like patients had a 4-year OS of 50% (95%CI: 43-59). Among patients with no, asymptomatic or symptomatic brain metastases, the 4-year OS probabilities were 48% (95%CI: 41-55), 45% (95%CI: 35-57), and 36% (95%CI: 27-48).Conclusion: Ipilimumab plus nivolumab can achieve long-term survival in advanced melanoma patients in a real-world setting, including patients not represented in the CheckMate-067 trial. However, the proportion of patients with disease control in the real-world is lower compared to clinical trials.Experimentele farmacotherapi

Influência de fatores ambientais na distribuição de famílias de insetos aquáticos em rios no sul do Brasil

Os rios neotropicais sofrem os efeitos das ações humanas. Medidas conservacionistas, pela escassez de estudos na região e do conhecimento límnico, baseiam-se em dados referentes a outras regiões, sendo muitas vezes ineficazes pela inobservância das diferenças nas respostas das comunidades aquáticas às variáveis ambientais em escalas distintas. Este estudo teve como objetivos: conhecer a riqueza de insetos aquáticos em uma bacia neotropical; verificar qual a influência das variáveis ambientais na distribuição das famílias de insetos aquáticos em quatro tributários dessa bacia e observar se o padrão de distribuição das famílias de insetos aquáticos varia entre as ordens dos rios ou entre microbacias, de acordo com a influência de variáveis ambientais e espaciais. Foi encontrado um total de 9.135 indivíduos distribuídos em 26 famílias de macroinvertebrados. A estrutura das comunidades foi distinta entre as microbacias. As famílias de insetos aquáticos foram influenciadas pelas variáveis ambientais e espaciais diferentes em cada microbacia

First-line BRAF/MEK inhibitors versus anti-PD-1 monotherapy in BRAFV600-mutant advanced melanoma patients: a propensity-matched survival analysis

Background: Anti-PD-1 antibodies and BRAF/MEK inhibitors are the two main groups of systemic therapy in the treatment of BRAFV600-mutant advanced melanoma. Until now, data are inconclusive on which therapy to use as first-line treatment. The aim of this study was to use propensity score matching to compare first-line anti-PD-1 monotherapy vs. BRAF/MEK inhibitors in advanced BRAFV600-mutant melanoma patients. Methods: We selected patients diagnosed between 2014 and 2017 with advanced melanoma and a known BRAFV600-mutation treated with first-line BRAF/MEK inhibitors or anti-PD-1 antibodies, registered in the Dutch Melanoma Treatment Registry. Patients were matched based on their propensity scores using the nearest neighbour and the optimal matching method. Results: Between 2014 and 2017, a total of 330 and 254 advanced melanoma patients received BRAF/MEK inhibitors and anti-PD-1 monotherapy as first-line systemic therapy. In the matched cohort, patients receiving anti-PD-1 antibodies as a first-line treatment had a higher median and 2-year overall survival compared to patients treated with first-line BRAF/MEK inhibitors, 42.3 months (95% CI: 37.3-NE) vs. 19.8 months (95% CI: 16.7–24.3) and 85.4% (95% CI: 58.1–73.6) vs. 41.7% (95% CI: 34.2–51.0). Conclusions: Our data suggest that in the matched BRAFV600-mutant advanced melanoma patients, anti-PD-1 monotherapy is the preferred first-line treatment in patients with relatively favourable patient and tumour characteristics

Curvature-bias corrections using a pseudomass method

Momentum measurements for very high momentum charged particles, such as muons from electroweak vector boson decays, are particularly susceptible to charge-dependent curvature biases that arise from misalignments of tracking detectors. Low momentum charged particles used in alignment procedures have limited sensitivity to coherent displacements of such detectors, and therefore are unable to fully constrain these misalignments to the precision necessary for studies of electroweak physics. Additional approaches are therefore required to understand and correct for these effects. In this paper the curvature biases present at the LHCb detector are studied using the pseudomass method in proton-proton collision data recorded at centre of mass energy √s = 13 TeV during 2016, 2017 and 2018. The biases are determined using Z → μ+μ- decays in intervals defined by the data-taking period, magnet polarity and muon direction. Correcting for these biases, which are typically at the 10-4 GeV-1 level, improves the Z → μ+μ- mass resolution by roughly 18% and eliminates several pathological trends in the kinematic-dependence of the mean dimuon invariant mass

Geographic origin of the Y Chromosomes in “old” inbred strains of mice

Six distinct Y Chromosomes (Chr) were identified among 39 standard inbred strains of mice with five probes that identified Y Chr-specific restriction fragments on Southern blots. Three Y Chr types, distributed among 31 strains, were of Asian Mus musculus origin. The remaining three Y Chr types, distributed among eight strains, were of M. domesticus origin. The Asian source of the M. musculus Y Chr was confirmed by determining the DNA sequence of 221 bp from an open reading frame within the Sry (sex determining region Y) gene (Gubbay et al., Nature 346 245–250, 1990) in three inbred strains (C57BL/6J, AKR/J, and SWR/J) and comparing the sequence to the homologous sequences derived from wild caught European and Asian M. musculus males. These data indicate that a minimum of six male mice contributed to the formation of the old inbred strains.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46993/1/335_2004_Article_BF00292153.pd

Measurement of the CKM angle γ in the B0→DK *0 channel using self-conjugate D→ KS0h+ h- decays

A model-independent study of CP violation in B-0 -> DK (*0) decays is presented using data corresponding to an integrated luminosity of 9 fb(-1) collected by the LHCb experiment at centre-of-mass energies of v s = 7, 8 and 13TeV. The CKM angle. is determined by examining the distributions of signal decays in phase-space bins of the self-conjugate D. K(S)(0)h(+) h(-) decays, where h = p, K. Observables related to CP violation are measured and the angle. is determined to be. = (49+22 -19).. Measurements of the amplitude ratio and strong-phase difference between the favoured and suppressed B-0 decays are also presented

The nuclear collective motion

Current developments in nuclear structure are discussed from a theoretical perspective. First, the progress in theoretical modeling of nuclei is reviewed. This is followed by the discussion of nuclear time scales, nuclear collective modes, and nuclear deformations. Some perspectives on nuclear structure research far from stability are given. Finally, interdisciplinary aspects of the nuclear many-body problem are outlined