5-Fluorouracil degradation rate as a predictive biomarker of toxicity in breast cancer patients treated with capecitabine

Capecitabine is an oral prodrug of 5-fluorouracil with a relevant role in the treatment of breast cancer. Severe and unexpected toxicities related to capecitabine are not rare, and the identification of biomarkers is challenging. We evaluate the relationship between dihydropyrimidine dehydrogenase, thymidylate synthase enhancer region and methylenetetrahydrofolate reductase polymorphisms, 5-fluorouracil degradation rate and the onset of G3–4 toxicities in breast cancer patients. Genetic polymorphisms and the 5-fluorouracil degradation rate of breast cancer patients treated with capecitabine were retrospectively studied. Genetic markers and the 5-fluorouracil degradation rate were correlated with the reported toxicities. Thirty-seven patients with a median age of 58 years old treated with capecitabine for stages II–IV breast cancer were included in this study. Overall, 34 (91.9%) patients suffered from at least an episode of any grade toxicity while nine patients had G3–4 toxicity. Homozygous methylenetetrahydrofolate reductase 677TT was found to be significantly related to haematological toxicity (OR = 6.5 [95% IC 1.1–37.5], P = 0.04). Three patients had a degradation rate less than 0.86 ng/mL/106 cells/min and three patients greater than 2.1 ng/mL/106 cells/min. At a univariate logistic regression analysis, an altered value of 5-fluorouracil degradation rate (values < 0.86 or >2.10 ng/mL/106 cells/min) increased the risk of G3–4 adverse events (OR = 10.40 [95% IC: 1.48–7.99], P = 0.02). A multivariate logistic regression analysis, adjusted for age, comorbidity and CAPE-regimen, confirmed the role of 5-fluorouracil degradation rate as a predictor of G3–4 toxicity occurrence (OR = 10.9 [95% IC 1.2–96.2], P = 0.03). The pre-treatment evaluation of 5-fluorouracil degradation rate allows to identify breast cancer patients at high risk for severe 5-FU toxicity

Strong Correlations in Actinide Redox Reactions

Reduction-oxidation (redox) reactions of the redox couples An(VI)/An(V), An(V)/An(IV), and An(IV)/An(III), where An is an element in the family of early actinides (U, Np, and Pu), as well as Am(VI)/Am(V) and Am(V)/Am(III), are modeled by combining density functional theory with a generalized Anderson impurity model that accounts for the strong correlations between the 5f electrons. Diagonalization of the Anderson impurity model yields improved estimates for the redox potentials and the propensity of the actinide complexes to disproportionate.Comment: 17 pages, 10 figure, 3 tables. Corrections and clarifications; this version has been accepted for publication in The Journal of Chemical Physic

The symptom of low mood in the prodromal stage of mild cognitive impairment and dementia: a cohort study of a community dwelling elderly population

OBJECTIVE: To investigate the symptom of low mood as a predictor of mild cognitive impairment (MCI) and its progression to dementia, taking into account: (i) MCI severity, (ii) time of assessment and (iii) interaction with other factors. METHODS: 764 cognitively healthy elderly subjects living in the community, from the Kungsholmen Project. Participants were assessed by direct interview to detect low mood. Subjects were then followed for 6 years to identify those who developed MCI. People with incident MCI were followed for a further 3 years to assess progression to dementia. RESULTS: People with low mood at baseline had a 2.7-fold (95% CI 1.9 to 3.7) increased risk of developing MCI at follow-up. The association was stronger for amnestic MCI (aMCI: HR 5.8; 95% CI 3.1 to 10.9) compared with global cognitive impairment (other cognitive impairment no dementia, oCIND: HR 2.2; 95% CI 1.5 to 3.3). ApoE-ε4 interacted with low mood in a synergistic fashion, increasing the risk of aMCI, while no interaction with psychiatric, vascular, frailty related or psychosocial factors was observed. Low mood at baseline, as opposed to low mood co-occurring with MCI, was associated with a 5.3-fold (95% CI 1.2 to 23.3) increased risk of progression to dementia in aMCI. In contrast, no association was found in oCIND. CONCLUSION: Low mood was more strongly associated with aMCI than with global cognitive impairment. Progression towards dementia was predicted only by low mood manifest in the prodromal stage of MCI. These findings indicate that low mood is particularly prominent in the very early stages of cognitive decline

Fermion Superfluids of Non-Zero Orbital Angular Momentum near Resonance

We study the pairing of Fermi gases near the scattering resonance of the $\ell\neq 0$ partial wave. Using a model potential which reproduces the actual two-body low energy scattering amplitude, we have obtained an analytic solution of the gap equation. We show that the ground state of $\ell=1$ and $\ell=3$ superfluid are orbital ferromagnets with pairing wavefunctions $Y_{11}$ and $Y_{32}$ respectively. For $\ell=2$, there is a degeneracy between $Y_{22}$ and a "cyclic state". Dipole energy will orient the angular momentum axis. The gap function can be determined by the angular dependence of the momentum distribution of the fermions.Comment: 4 pages, 1 figur

Neutrino Spin Flavor Precession and Leptogenesis

We argue that \Delta L=2 neutrino spin flavor precession, induced by the primordial magnetic fields, could have a significant impact on the leptogenesis process that accounts for the baryon asymmetry of the universe. Although the extra galactic magnetic fields is extremely weak at present time (about 10^{-9} Gauss), the primordial magnetic filed at the electroweak scale could be quite strong (of order 10^{17} Gauss). Therefore, at this scale, the effects of the spin flavor precession are not negligible. We show that the lepton asymmetry may be reduced by 50% due to the spin flavor precession. In addition, the leptogenesis will have different feature from the standard scenario of leptogenesis, where the lepton asymmetry continues to oscillate even after the electroweak phase transition.Comment: 5 pages, one figure. References adde

Local trace formulae and scaling asymptotics in Toeplitz quantization

A trace formula for Toeplitz operators was proved by Boutet de Monvel and Guillemin in the setting of general Toeplitz structures. Here we give a local version of this result for a class of Toeplitz operators related to continuous groups of symmetries on quantizable compact symplectic manifolds. The local trace formula involves certain scaling asymptotics along the clean fixed locus of the Hamiltonian flow of the symbol, reminiscent of the scaling asymptotics of the equivariant components of the Szeg\"o kernel along the diagonal

Scaling asymptotics for quantized Hamiltonian flows

In recent years, the near diagonal asymptotics of the equivariant components of the Szeg\"{o} kernel of a positive line bundle on a compact symplectic manifold have been studied extensively by many authors. As a natural generalization of this theme, here we consider the local scaling asymptotics of the Toeplitz quantization of a Hamiltonian symplectomorphism, and specifically how they concentrate on the graph of the underlying classical map

Instability statistics and mixing rates

We claim that looking at probability distributions of \emph{finite time} largest Lyapunov exponents, and more precisely studying their large deviation properties, yields an extremely powerful technique to get quantitative estimates of polynomial decay rates of time correlations and Poincar\'e recurrences in the -quite delicate- case of dynamical systems with weak chaotic properties.Comment: 5 pages, 5 figure

Vacuum Breakdown near a Black Hole Charged by Hypercritical Accretion

We consider a black hole accreting spherically from the surrounding medium. If accretion produces a luminosity close to the Eddington limit the hole acquires a net charge so that electrons and ions can fall with the same velocity. The condition for the electrostatic field to be large enough to break the vacuum near the hole horizon translates into an upper limit for the hole mass, $M\sim 6.6\times 10^{20} {\rm g}.$ The astrophysical conditions under which this phaenomenon can take place are rather extreme, but in principle they could be met by a mini black hole residing at the center of a star.Comment: 6 pages, accepted for publication in the Astrophysical Journa

Galaxy Orientations in the Coma Cluster

We have examined the orientations of early-type galaxies in the Coma cluster to see whether the well-established tendency for brightest cluster galaxies to share the same major axis orientation as their host cluster also extends to the rest of the galaxy population. We find no evidence of any preferential orientations of galaxies within Coma or its surroundings. The implications of this result for theories of the formation of clusters and galaxies (particularly the first-ranked members) are discussed.Comment: Accepted for publication in the Astrophysical Journal Letters. 4 pages, 4 figure