Genomic imbalances detected by comparative genomic hybridization are prognostic markers in invasive ductal breast carcinomas

AIMS: The aim of this work is the study of the prognostic significance of the chromosomal aberrations described in a series of invasive ductal breast carcinomas. METHODS AND RESULTS: We analysed by comparative genomic hybridization a group of 70 formalin-fixed paraffin-embedded invasive ductal breast carcinomas. Aberrations showed a frequency similar to previous studies using frozen tumours. Interestingly, we identified gains involving 6q16-q24 more frequently than in other series. We analysed the association among the chromosomal imbalances, 11 histopathological factors, relapse rate and overall survival of patients. Associations showed 16q losses as a potential marker of good prognosis, as they were more frequent in node-negative (P=0.025) and in oestrogen-positive tumours (P < 0.001). Furthermore, 100% of bcl-2+ tumours presented this aberration compared with 29.3% in bcl-2- (P=0.014). 1q, 11q, 17q and 20q gains were associated with poor prognosis: 95% of cases with 1q gains were bigger than 20 mm (P=0.041). Tumours with 1q and 11q gains showed a higher relapse rate (P=0.063; P=0.066). Within the good prognosis group of lymph node-negative patients, 17q and 20q gains identify a subgroup with increased relapse rate (P=0.039). CONCLUSIONS: Chromosomal imbalances, together with histopathological factors, may help to predict outcome in breast cancer patients

Analytical results for coupled map lattices with long-range interactions

We obtain exact analytical results for lattices of maps with couplings that decay with distance as $r^{-\alpha}$. We analyze the effect of the coupling range on the system dynamics through the Lyapunov spectrum. For lattices whose elements are piecewise linear maps, we get an algebraic expression for the Lyapunov spectrum. When the local dynamics is given by a nonlinear map, the Lyapunov spectrum for a completely synchronized state is analytically obtained. The critical lines characterizing the synchronization transition are determined from the expression for the largest transversal Lyapunov exponent. In particular, it is shown that in the thermodynamical limit, such transition is only possible for sufficiently long-range interactions, namely, for $\alpha\le alpha_c<d$, where $d$ is the lattice dimension.Comment: 4 pages, 2 figures, corrections included. Phys. Rev. E 68, 045202(R) (2003); correction in pres

The global burden of cancer attributable to risk factors, 2010–19: a systematic analysis for the Global Burden of Disease Study 2019

BACKGROUND: Understanding the magnitude of cancer burden attributable to potentially modifiable risk factors is crucial for development of effective prevention and mitigation strategies. We analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 to inform cancer control planning efforts globally. METHODS: The GBD 2019 comparative risk assessment framework was used to estimate cancer burden attributable to behavioural, environmental and occupational, and metabolic risk factors. A total of 82 risk–outcome pairs were included on the basis of the World Cancer Research Fund criteria. Estimated cancer deaths and disability-adjusted life-years (DALYs) in 2019 and change in these measures between 2010 and 2019 are presented. FINDINGS: Globally, in 2019, the risk factors included in this analysis accounted for 4·45 million (95% uncertainty interval 4·01–4·94) deaths and 105 million (95·0–116) DALYs for both sexes combined, representing 44·4% (41·3–48·4) of all cancer deaths and 42·0% (39·1–45·6) of all DALYs. There were 2·88 million (2·60–3·18) risk-attributable cancer deaths in males (50·6% [47·8–54·1] of all male cancer deaths) and 1·58 million (1·36–1·84) risk-attributable cancer deaths in females (36·3% [32·5–41·3] of all female cancer deaths). The leading risk factors at the most detailed level globally for risk-attributable cancer deaths and DALYs in 2019 for both sexes combined were smoking, followed by alcohol use and high BMI. Risk-attributable cancer burden varied by world region and Socio-demographic Index (SDI), with smoking, unsafe sex, and alcohol use being the three leading risk factors for risk-attributable cancer DALYs in low SDI locations in 2019, whereas DALYs in high SDI locations mirrored the top three global risk factor rankings. From 2010 to 2019, global risk-attributable cancer deaths increased by 20·4% (12·6–28·4) and DALYs by 16·8% (8·8–25·0), with the greatest percentage increase in metabolic risks (34·7% [27·9–42·8] and 33·3% [25·8–42·0]). INTERPRETATION: The leading risk factors contributing to global cancer burden in 2019 were behavioural, whereas metabolic risk factors saw the largest increases between 2010 and 2019. Reducing exposure to these modifiable risk factors would decrease cancer mortality and DALY rates worldwide, and policies should be tailored appropriately to local cancer risk factor burden

Dynamics of oscillator chains

The Fermi\u2013Pasta\u2013Ulam (FPU) nonlinear oscillator chain has proved to be a seminal system for investigating problems in nonlinear dynamics. First proposed as a nonlinear system to elucidate the foundations of statistical mechanics, the initial lack of confirmation of the researchers expectations eventually led to a number of profound insights into the behavior of high-dimensional nonlinear systems. The initial numerical studies, proposed to demonstrate that energy placed in a single mode of the linearized chain would approach equipartition through nonlinear interactions, surprisingly showed recurrences. Although subsequent work showed that the origin of the recurrences is nonlinear resonance, the question of lack of equipartition remained. The attempt to understand the regularity bore fruit in a profound development in nonlinear dynamics: the birth of soliton theory. A parallel development, related to numerical observations that, at higher energies, equipartition among modes could be approached, was the understanding that the transition with increasing energy is due to resonance overlap. Further numerical investigations showed that time-scales were also important, with a transition between faster and slower evolution. This was explained in terms of mode overlap at higher energy and resonance overlap at lower energy. Numerical limitations to observing a very slow approach to equipartition and the problem of connecting high-dimensional Hamiltonian systems to lower dimensional studies of Arnold diffusion, which indicate transitions from exponentially slow diffusion along resonances to power-law diffusion across resonances, have been considered. Most of the work, both numerical and theoretical, started from low frequency (long wavelength) initial conditions. Coincident with developments to understand equipartition was another program to connect a statistical phenomenon to nonlinear dynamics, that of understanding classical heat conduction. The numerical studies were quite different, involving the excitation of a boundary oscillator with chaotic motion, rather than the excitation of the entire chain with regular motion. Although energy transitions are still important, the inability to reproduce exactly the law of classical heat conduction led to concern for the generiticity of the FPU chain and exploration of other force laws. Important concepts of unequal masses, and \u201canti-integrability,\u201d i.e. isolation of some oscillators, were considered, as well as separated optical and acoustic modes that could only communicate through very weak interactions. The importance of chains that do not allow nonlinear wave propagation in producing the Fourier heat conduction law is now recognized. A more recent development has been the exploration of energy placed on the FPU or related oscillator chains in high-frequency (short wavelength) modes and the existence of isolated structures (breathers). Breathers are found as solutions to partial differential equations, analogous to solitons at lower frequency. On oscillator chains, such as the FPU, energy initially in a single high-frequency mode is found, at higher energies, to self-organize in oscillator space to form compact structures. These structures are \u201cchaotic breathers,\u201d i.e. not completely stable, and disintegrate on longer time-scales. With the significant progress in understanding this evolution, we now have a rather complete picture of the nonlinear dynamics of the FPU and related oscillator chains, and their relation to a wide range of concepts in nonlinear dynamics. This chapter\u2019s purpose is to explicate these many concepts. After a historical perspective the basic chaos theory background is reviewed. Types of oscillators, numerical methods, and some analytical results are considered. Numerical results of studies of equipartition, both from low-frequency and high-frequency modes, are presented, together with numerical studies of heat conduction. These numerical studies are related to analytical calculations and estimates of energy transitions and time-scales to equipartition