Forecasts of cohort mortality after age 50

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Simulations of a mortality plateau in the sexual Penna model for biological ageing

The Penna model is a strategy to simulate the genetic dynamics of age-structured populations, in which the individuals genomes are represented by bit-strings. It provides a simple metaphor for the evolutionary process in terms of the mutation accumulation theory. In its original version, an individual dies due to inherited diseases when its current number of accumulated mutations, n, reaches a threshold value, T. Since the number of accumulated diseases increases with age, the probability to die is zero for very young ages (n = T). Here, instead of using a step function to determine the genetic death age, we test several other functions that may or may not slightly increase the death probability at young ages (n < T), but that decreases this probability at old ones. Our purpose is to study the oldest old effect, that is, a plateau in the mortality curves at advanced ages. Imposing certain conditions, it has been possible to obtain a clear plateau using the Penna model. However, a more realistic one appears when a modified version, that keeps the population size fixed without fluctuations, is used. We also find a relation between the birth rate, the age-structure of the population and the death probability.Comment: submitted to Phys. Rev.

Imaging oxygenation of human tumours

Tumour hypoxia represents a significant challenge to the curability of human tumours leading to treatment resistance and enhanced tumour progression. Tumour hypoxia can be detected by non-invasive and invasive techniques but the inter-relationships between these remains largely undefined. (18)F-MISO and Cu-ATSM-PET, and BOLD-MRI are the lead contenders for human application based on their non-invasive nature, ease of use and robustness, measurement of hypoxia status, validity, ability to demonstrate heterogeneity and general availability, these techniques are the primary focus of this review. We discuss where developments are required for hypoxia imaging to become clinically useful and explore potential new uses for hypoxia imaging techniques including biological conformal radiotherapy

Dimensions of global population projections: what do we know about future population trends and structures?

The total size of the world population is likely to increase from its current 7 billion to 8–10 billion by 2050. This uncertainty is because of unknown future fertility and mortality trends in different parts of the world. But the young age structure of the population and the fact that in much of Africa and Western Asia, fertility is still very high makes an increase by at least one more billion almost certain. Virtually, all the increase will happen in the developing world. For the second half of the century, population stabilization and the onset of a decline are likely. In addition to the future size of the population, its distribution by age, sex, level of educational attainment and place of residence are of specific importance for studying future food security. The paper provides a detailed discussion of different relevant dimensions in population projections and an evaluation of the methods and assumptions used in current global population projections and in particular those produced by the United Nations and by IIASA

A prospective pilot clinical trial evaluating the utility of a dynamic near-infrared imaging device for characterizing suspicious breast lesions

Introduction: Characterizing and differentiating between malignant tumors, benign tumors, and normal breast tissue is increasingly important in the patient presenting with breast problems. Near-infrared diffuse optical imaging and spectroscopy is capable of measuring multiple physiologic parameters of biological tissue systems and may have clinical applications for assessing the development and progression of neoplastic processes, including breast cancer. The currently available application of near-infrared imaging technology for the breast, however, is compromised by low spatial resolution, tissue heterogeneity, and interpatient variation. Materials and methods: We tested a dynamic near-infrared imaging schema for the characterization of suspicious breast lesions identified on diagnostic clinical ultrasound. A portable handheld near-infrared tissue imaging device (P-Scan; ViOptix Inc., Fremont, CA, USA) was utilized. An external mechanical compression force was applied to breast tissue. The tissue oxygen saturation and hemoglobin concentration were recorded simultaneously by the handheld near-infrared imaging device. Twelve categories of dynamic tissue parameters were derived based on real-time measurements of the tissue hemoglobin concentration and the oxygen saturation. Results: Fifty suspicious breast lesions were evaluated in 48 patients. Statistical analyses were carried out on 36 out of 50 datasets that satisfied our inclusion criteria. Suspicious breast lesions identified on diagnostic clinical ultrasound had lower oxygenation and higher hemoglobin concentration than the surrounding normal breast tissue. Furthermore, histopathologic-proven malignant breast tumors had a lower differential hemoglobin contrast (that is, the difference of hemoglobin concentration variability between the suspicious breast lesion and the normal breast parenchyma located remotely elsewhere within the ipsilateral breast) as compared with histopathologic-proven benign breast lesions. Conclusion: The proposed dynamic near-infrared imaging schema has the potential to differentiate benign processes from those of malignant breast tumors. Further development and refinement of the dynamic imaging device and additional subsequent clinical testing are necessary for optimizing the accuracy of detection

Hypoxia increases the metastatic ability of breast cancer cells via upregulation of CXCR4

<p>Abstract</p> <p>Background</p> <p>Chemokine SDF1α and its unique receptor CXCR4 have been implicated in organ-specific metastases of many cancers including breast cancer. Hypoxia is a common feature of solid tumors and is associated with their malignant phenotype. We hypothesized that hypoxia would upregulate CXCR4 expression and lead to increased chemotactic responsiveness to its specific ligand SDF1α.</p> <p>Methods</p> <p>Three breast cancer cell lines MDA-MB-231, MCF7 and 4T1 were subjected to 48 hrs of hypoxia or normoxia. Cell surface receptor expression was evaluated using flow cytometry. An extracellular matrix invasion assay and microporous migration assay was used to assess chemotactic response and metastatic ability.</p> <p>Results</p> <p>CXCR4 surface expression was significantly increased in the two human breast cancer cell lines, MDA-MB-231 and MCF7, following exposure to hypoxia. This upregulation of CXCR4 cell surface expression corresponded to a significant increase in migration and invasion in response to SDF1-α <it>in vitro</it>. The increase in metastatic potential of both the normoxic and the hypoxic treated breast cancer cell lines was attenuated by neutralization of CXCR4 with a CXCR4 neutralizing mAb, MAB172 or a CXCR4 antagonist, AMD3100, showing the relationship between CXCR4 overexpression and increased chemotactic responsiveness.</p> <p>Conclusions</p> <p>CXCR4 expression can be modulated by the tissue microenvironment such as hypoxia. Upregulation of CXCR4 is associated with increased migratory and invasive potential and this effect can be abrogated by CXCR4 inhibition. Chemokine receptor CXCR4 is a potential therapeutic target in the adjuvant treatment of breast cancer.</p

Cancer cells that survive radiation therapy acquire HIF-1 activity and translocate towards tumour blood vessels

Tumour recurrence frequently occurs after radiotherapy, but the characteristics, intratumoural localization and post-irradiation behaviour of radioresistant cancer cells remain largely unknown. Here we develop a sophisticated strategy to track the post-irradiation fate of the cells, which exist in perinecrotic regions at the time of radiation. Although the perinecrotic tumour cells are originally hypoxia-inducible factor 1 (HIF-1)-negative, they acquire HIF-1 activity after surviving radiation, which triggers their translocation towards tumour blood vessels. HIF-1 inhibitors suppress the translocation and decrease the incidence of post-irradiation tumour recurrence. For the first time, our data unveil the HIF-1-dependent cellular dynamics during post-irradiation tumour recurrence and provide a rational basis for targeting HIF-1 after radiation therapy

Polarisation Patterns and Vectorial Defects in Type II Optical Parametric Oscillators

Previous studies of lasers and nonlinear resonators have revealed that the polarisation degree of freedom allows for the formation of polarisation patterns and novel localized structures, such as vectorial defects. Type II optical parametric oscillators are characterised by the fact that the down-converted beams are emitted in orthogonal polarisations. In this paper we show the results of the study of pattern and defect formation and dynamics in a Type II degenerate optical parametric oscillator for which the pump field is not resonated in the cavity. We find that traveling waves are the predominant solutions and that the defects are vectorial dislocations which appear at the boundaries of the regions where traveling waves of different phase or wave-vector orientation are formed. A dislocation is defined by two topological charges, one associated with the phase and another with the wave-vector orientation. We also show how to stabilize a single defect in a realistic experimental situation. The effects of phase mismatch of nonlinear interaction are finally considered.Comment: 38 pages, including 15 figures, LATeX. Related material, including movies, can be obtained from http://www.imedea.uib.es/Nonlinear/research_topics/OPO