A Study of the Efficiency of Small Models in the Projection of Regional Populations

The work described in this paper arose out of an ongoing research project, carried out at IIASA and the Centre for Environmental Studies, London, which aims at a more complete understanding of the dynamics of population movements and regional economic growth. This general study has two main themes. One deals substantively with interurban migration within a system of post-industrial cities, and aims to recast migration from the traditional economic push-pull theory into a more dynamic multicausal theory in which job turnover in the local labour market plays an important part. The second theme is methodological and describes a structured research strategy for the dynamic analysis of complex systems. The study argues that, while it is important to recognize the usefulness of simple models at the early stages of an enquiry, those same simple models should be improved by hypothesis testing during the course of the work; the study argues further that a hierarchy of models of national settlement systems should be developed at varying levels of approximation. At the simplest level, one should be able to perform calculations on the back of an envelope that describe the broad qualitative directions of change in a way that is of interest to policy makers in the short term. In policy analysis, as in everything else, one has to begin in order to begin. But it is equally important to recognize the need for change when the inadequacy of the simpler methods has been demonstrated. Thus policy analysis becomes an iterative, structured learning process. Within this general context, this paper aims to illustrate and test some simple models for calculating differential rates of population change which require little data or time to construct, but which may be useful in preliminary explorations of policy. The paper focuses on the regional population distributions of France; a companion paper by David Gleave entitled "The Utility and Compatibility of Simple Migration Models" considers the application of similar methods in the UK, Italy, the Federal Republic of Germany and France

Epistaxis or epiphora as a sign for extension of a conjunctival melanoma. A series of six patients with nasolacrimal recurrence

Purpose To characterise malignant conjunctival melanomas with extension and recurrence in the nasolacrimal system. Methods Localisation of the primary tumour and recurrences of 210 conjunctival melanomas treated in The Netherlands were reviewed for orbital and nasal tumours (1978-2008). Based of these cases and literature data, characteristics for nasolacrimal system extension and metastasis were reviewed. Results Six patients (3%) showed a recurrence of the primary conjunctival melanoma in the nasolacrimal system. Two of the six primary tumours were limbal tumours; the other four were diffuse tumours involving the fornix. In all six patients, the primary conjunctival melanomas were associated with primary acquired melanosis. During the follow-up period (11.6 +/- 3 years, range 3.4-28.5 years, median 8.7 years) two patients developed metastases and died. Conclusions Patients should be advised to contact their treating ophthalmologist in the case of symptoms of epiphora, nose obstructions and epistaxis, especially non-bulbar and diffuse cases associated with primary acquired melanosis.Ophthalmic researc

[Multidrug resistance in uveal melanoma].

International audienceIn spite of important progress in the local treatment of uveal melanoma, the most frequent primitive intraocular tumor, 15%-30% of patients still die because of tumor metastasis. This tumor is characterized by constitutive chemoresistance, thwarting any attempt to control it using the usual chemotherapy protocols. The chemoresistance of uveal melanoma is mainly due to the typical multidrug resistance phenotype (MDR), which is linked to overexpression of membrane proteins that actively extrude anticancer drugs from the cell. Typical MDR is particularly complex in this tumor since several chemoresistance-related proteins are simultaneously produced. The negative prognostic significance of the overexpression of P-glycoprotein, the main representative among the typical MDR-related proteins, was shown in uveal melanoma. The atypical MDR phenotype, which refers to other chemoresistance mechanisms such as resistance to apoptosis also contributes to the chemoresistance of uveal melanoma. Thanks to the recent progress in molecular biology, the chemosensitization strategies of gene therapy approaches, which aim at weakening the pathological activity of MDR genes in cancer cells, are currently on the rise. This approach will disrupt current therapeutic strategies and necessarily improve and standardize the methods used to characterize the chemoresistance profile of this cancer. Indeed, we will have to know the genes to be targeted for each melanoma in order to induce cell chemosensitivity

[Toward monosomy 3 as the main prognosis factor of uveal melanoma: current cytogenetic data].

International audienceUveal melanoma is the most frequent intraocular cancer. The recent development of new technologies such as microsatellite analysis and comparative genomic hybridization have elucidated both the cytogenetics and the natural history of this disease. Fifty to 60% of uveal melanomas are linked to monosomy 3, which appears as an early and determinant event in tumor progression. Tumors with this anomaly have a very poor prognosis. Recent work suggests that this category of uveal melanomas represents a distinct pathological entity from that associated with normal disomy 3. Chromosome 6 aberrations probably make up a second entry point into the process of carcinogenesis, while gains in 8q seem to appear later in the natural history of uveal melanoma because of their higher frequency in larger tumors. Progress in genome analysis has identified regions in chromosomes 3, 6, and 8 as those most probably involved in tumorigenesis. It is to be hoped that this will soon lead to the discovery of the genes responsible