12 research outputs found

    Relationship between dynamical heterogeneities and stretched exponential relaxation

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    We identify the dynamical heterogeneities as an essential prerequisite for stretched exponential relaxation in dynamically frustrated systems. This heterogeneity takes the form of ordered domains of finite but diverging lifetime for particles in atomic or molecular systems, or spin states in magnetic materials. At the onset of the dynamical heterogeneity, the distribution of time intervals spent in such domains or traps becomes stretched exponential at long time. We rigorously show that once this is the case, the autocorrelation function of the renewal process formed by these time intervals is also stretched exponential at long time.Comment: 8 pages, 4 figures, submitted to PR

    Manifestation of the long-range interaction in processes of ionization of excited atoms in thermal and subthermal collisions

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    Specific features are considered and an analysis is performed of the influence of the long-range dipole interaction on the efficiency of ionization processes in slow collisions of excited atoms with values of the principal quantum number 3 < n < 25. It is shown that the configuration mixing, which disturbs the selectivity of initial excitation, can lead to the formation of new reaction channels. It is noted that in the case of slow collisions, for systems with a small number of degrees of freedom, the stochastic dynamics of valence electrons can have a significant effect, during a single collisional event, on the efficiency of physicochemical reactions because of the appearance of internal resonances in the excited quasi-molecule

    FOLFOXIRI or FOLFOXIRI plus bevacizumab as first-line treatment of metastatic colorectal cancer: A propensity score-adjusted analysis from two randomized clinical trials

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    Background: FOLFOXIRI plus bevacizumab is a valid option as upfront treatment for metastatic colorectal cancer (mCRC) patients. While several trials investigated the effect of combining bevacizumab with different chemotherapy regimens, including fluoropyrimidines monotherapy and oxaliplatin- or irinotecan-containing doublets, no randomized comparison assessing the impact of the addition of bevacizumab to FOLFOXIRI is available. Patients and methods: A total of 122 mCRC patients received first-line FOLFOXIRI in the phase III trial by the GONO (FOLFOXIRI group) and 252 patients received first-line FOLFOXIRI plus bevacizumab in the TRIBE trial (FOLFOXIRI plus bevacizumab group). A propensity score-adjusted method was adopted to provide an estimation of the benefit from the addition of bevacizumab to FOLFOXIRI in terms of survival and activity parameters. Results: Patients in the FOLFOXIRI group had more frequently Eastern Cooperative Oncology Group performance status of one or two, high Köhne score, metachronous and liver-limited disease, had previously received adjuvant treatments and had their primary tumors resected. The median progression-free survival (PFS) was 12.3 months in the FOLFOXIRI plus bevacizumab group compared with 10.0 months in the FOLFOXIRI group [propensity score-adjusted hazard ratio (HR) 0.74 [95% confidence interval (CI) 0.59-0.94], P = 0.013]. This association was significant also in the multivariable model (P = 0.024). The median OS was 29.8 months in the FOLFOXIRI plus bevacizumab group compared with 23.6 months in the FOLFOXIRI group [propensity score-adjusted HR: 0.72 (95% CI 0.56-0.93), P = 0.014]. At the multivariable model, the addition of bevacizumab was still associated with significantly longer OS (P = 0.030). No significant differences in RECIST response rate (RR) [65.1% versus 55.7%; propensity score-adjusted odds ratio (OR): 1.29 (95% CI 0.81-2.05), P = 0.280], early RR [62.7% versus 57.8%; OR: 1.14 (95% CI 0.68-1.93), P = 0.619] and median depth of response (42.2% versus 53.8%, P = 0.259) were reported. Conclusions: Though in the absence of a randomized comparison, the addition of bevacizumab to FOLFOXIRI provides significant benefit in PFS and OS, thus supporting the use of FOLFOXIRI plus bevacizumab as upfront treatment for mCRC patients. Trials' numbers: NCT01219920 and NCT00719797

    Atividade antifúngica dos óleos essenciais de sassafrás (Ocotea odorifera Vell.) e alecrim (Rosmarinus officinalis L.) sobre o gênero Candida Antifungal activity of Brazilian sassafras (Ocotea odorifera Vell.) and rosemary (Rosmarinus officinalis L.) essential oils against the genus Candida

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    Este estudo objetivou avaliar, in vitro, a atividade antifúngica dos óleos essenciais de Ocotea odorifera (Vellozo) Rohwer (Sassafrás) e Rosmarinus officinalis L. (Alecrim) sobre cepas de Candida albicans e C. tropicalis, envolvidas com infecções da cavidade oral. Para tanto, 16 cepas de Candida de origem clínica e de referência foram utilizadas para determinação da concentração inibitória mínima (CIM), utilizando a técnica da microdiluição. Miconazol e nistatina foram utilizados como controles positivos. Observou-se discreta atividade antifúngica de ambos os óleos, com CIM de 2,5 mg mL-1 para sassafrás e CIM de 5 mg mL-1 para alecrim em 68% e 81% das cepas avaliadas, respectivamente. Todas as cepas de Candida mostraram-se sensíveis ao miconazol e nistatina. A partir dos resultados obtidos, foi possível concluir que os óleos essenciais de O. odorifera Vell. e R. officinalis L. apresentam fraca atividade sobre cepas de C. albicans e C. tropicalis envolvidas em infecções da cavidade oral.<br>This study aimed to evaluate the in vitro antifungal activity of essential oils from Ocotea odorifera Vell. (Brazilian sassafras) and Rosmarinus officinalis L. (rosemary) against Candida albicans and C. tropicalis strains, both involved in oral cavity infections. Thus, 16 Candida strains from clinical origin and standards were used to determine the minimum inhibitory concentration (MIC), using the microdilution technique. Miconazole and nystatin were used as positive controls. A slight antifungal activity was observed for both oils, with 2.5 mg mL-1 MIC for Brazilian sassafras and 5 mg mL-1 MIC for rosemary in 68 and 81% strains, respectively. All Candida strains were sensitive to miconazole and nystatin. In conclusion, essential oils from O. odorifera Vell. and R. officinalis L. had weak activity against C. albicans and C. tropicalis strains involved in oral cavity infections

    Continuity of Genetic Risk for Aggressive Behavior Across the Life-Course

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    We test whether genetic influences that explain individual differences in aggression in early life also explain individual differences across the life-course. In two cohorts from The Netherlands (N = 13,471) and Australia (N = 5628), polygenic scores (PGSs) were computed based on a genome-wide meta-analysis of childhood/adolescence aggression. In a novel analytic approach, we ran a mixed effects model for each age (Netherlands: 12–70 years, Australia: 16–73 years), with observations at the focus age weighted as 1, and decaying weights for ages further away. We call this approach a ‘rolling weights’ model. In The Netherlands, the estimated effect of the PGS was relatively similar from age 12 to age 41, and decreased from age 41–70. In Australia, there was a peak in the effect of the PGS around age 40 years. These results are a first indication from a molecular genetics perspective that genetic influences on aggressive behavior that are expressed in childhood continue to play a role later in life

    Hypothesis-driven genome-wide association studies provide novel insights into genetics of reading disabilities.

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    Reading Disability (RD) is often characterized by difficulties in the phonology of the language. While the molecular mechanisms underlying it are largely undetermined, loci are being revealed by genome-wide association studies (GWAS). In a previous GWAS for word reading (Price, 2020), we observed that top single-nucleotide polymorphisms (SNPs) were located near to or in genes involved in neuronal migration/axon guidance (NM/AG) or loci implicated in autism spectrum disorder (ASD). A prominent theory of RD etiology posits that it involves disturbed neuronal migration, while potential links between RD-ASD have not been extensively investigated. To improve power to identify associated loci, we up-weighted variants involved in NM/AG or ASD, separately, and performed a new Hypothesis-Driven (HD)–GWAS. The approach was applied to a Toronto RD sample and a meta-analysis of the GenLang Consortium. For the Toronto sample (n = 624), no SNPs reached significance; however, by gene-set analysis, the joint contribution of ASD-related genes passed the threshold (p~1.45 × 10–2, threshold = 2.5 × 10–2). For the GenLang Cohort (n = 26,558), SNPs in DOCK7 and CDH4 showed significant association for the NM/AG hypothesis (sFDR q = 1.02 × 10–2). To make the GenLang dataset more similar to Toronto, we repeated the analysis restricting to samples selected for reading/language deficits (n = 4152). In this GenLang selected subset, we found significant association for a locus intergenic between BTG3-C21orf91 for both hypotheses (sFDR q &lt; 9.00 × 10–4). This study contributes candidate loci to the genetics of word reading. Data also suggest that, although different variants may be involved, alleles implicated in ASD risk may be found in the same genes as those implicated in word reading. This finding is limited to the Toronto sample suggesting that ascertainment influences genetic associations

    Genome-wide analyses of individual differences in quantitatively assessed reading- and language-related skills in up to 34,000 people.

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    The use of spoken and written language is a fundamental human capacity. Individual differences in reading- and language-related skills are influenced by genetic variation, with twin-based heritability estimates of 30 to 80% depending on the trait. The genetic architecture is complex, heterogeneous, and multifactorial, but investigations of contributions of single-nucleotide polymorphisms (SNPs) were thus far underpowered. We present a multicohort genome-wide association study (GWAS) of five traits assessed individually using psychometric measures (word reading, nonword reading, spelling, phoneme awareness, and nonword repetition) in samples of 13,633 to 33,959 participants aged 5 to 26 y. We identified genome-wide significant association with word reading (rs11208009, P = 1.098 × 10-8) at a locus that has not been associated with intelligence or educational attainment. All five reading-/language-related traits showed robust SNP heritability, accounting for 13 to 26% of trait variability. Genomic structural equation modeling revealed a shared genetic factor explaining most of the variation in word/nonword reading, spelling, and phoneme awareness, which only partially overlapped with genetic variation contributing to nonword repetition, intelligence, and educational attainment. A multivariate GWAS of word/nonword reading, spelling, and phoneme awareness maximized power for follow-up investigation. Genetic correlation analysis with neuroimaging traits identified an association with the surface area of the banks of the left superior temporal sulcus, a brain region linked to the processing of spoken and written language. Heritability was enriched for genomic elements regulating gene expression in the fetal brain and in chromosomal regions that are depleted of Neanderthal variants. Together, these results provide avenues for deciphering the biological underpinnings of uniquely human traits

    Conceptual design of the AGATA 2<math display="inline" id="d1e396" altimg="si24.svg"><mi>π</mi></math> array at LNL

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    International audienceThe Advanced GAmma Tracking Array (AGATA) has been installed at Laboratori Nazionali di Legnaro (LNL), Italy. In this installation, AGATA will consist, at the beginning, of 13 AGATA triple clusters (ATCs) with an angular coverage of 1π, and progressively the number of ATCs will increase up to a 2π angular coverage. This setup will exploit both stable and radioactive ion beams delivered by the Tandem–PIAVE-ALPI accelerator complex and the SPES facility. The new implementation of AGATA at LNL will be used in two different configurations, firstly one coupled to the PRISMA large-acceptance magnetic spectrometer and lately a second one at Zero Degrees, along the beam line. These two configurations will allow us to cover a broad physics program, using different reaction mechanisms, such as Coulomb excitation, fusion-evaporation, transfer and fission at energies close to the Coulomb barrier. These setups have been designed to be coupled with a large variety of complementary detectors such as charged particle detectors, neutron detectors, heavy-ion detectors, high-energy γ-ray arrays, cryogenic and gasjet targets and the plunger device for lifetime measurements. We present in this paper the conceptual design, characteristics and performance figures of this implementation of AGATA at LNL
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