The changing face of cancer therapeutics improved : outcome and decreased toxicity with Molecular Targeted Drugs

The treatment of patients with cancer has largely involved the administration of cytotoxic drugs with narrow therapeutic indices, with little selectivity for cancer cells over normal proliferating cells. The primary exception to this has been the successful administration of hormonal manipulation to treat breast and prostate malignancies. The development of hormonal manipulation arose from the observation by Sir George Beatson that breast carcinomas improved after bilateral oophorectomy. This led to the use of Tamoxifen and more recently aromatase inhibitors and oestrogen receptor antagonists. These targeted therapeutics are characterised by their ability to induce selective tumour cell death and achieve patient benefit with low toxicity, and have had a significant impact on the outcome of patients with early and advanced oestrogen receptor positive breast cancer. Further advances in the understanding of tumour cell biology, the sequencing of the human genome, and the characterisation of the molecular differences between malignant and normal cells have, over the past two decades, resulted in the identification of a large number of critically important molecular targets. As with the identification of the importance of oestrogens and the oestrogen receptor, this has accelerated the development of molecularly targeted therapeutics and is rapidly revolutionising cancer medicine (Table 1). This brief review will describe some of the most important advances achieved and will attempt to predict what future cancer therapeutics will entail.peer-reviewe

Riesz external field problems on the hypersphere and optimal point separation

We consider the minimal energy problem on the unit sphere $\mathbb{S}^d$ in the Euclidean space $\mathbb{R}^{d+1}$ in the presence of an external field $Q$, where the energy arises from the Riesz potential $1/r^s$ (where $r$ is the Euclidean distance and $s$ is the Riesz parameter) or the logarithmic potential $\log(1/r)$. Characterization theorems of Frostman-type for the associated extremal measure, previously obtained by the last two authors, are extended to the range $d-2 \leq s < d - 1.$ The proof uses a maximum principle for measures supported on $\mathbb{S}^d$. When $Q$ is the Riesz $s$-potential of a signed measure and $d-2 \leq s <d$, our results lead to explicit point-separation estimates for $(Q,s)$-Fekete points, which are $n$-point configurations minimizing the Riesz $s$-energy on $\mathbb{S}^d$ with external field $Q$. In the hyper-singular case $s > d$, the short-range pair-interaction enforces well-separation even in the presence of more general external fields. As a further application, we determine the extremal and signed equilibria when the external field is due to a negative point charge outside a positively charged isolated sphere. Moreover, we provide a rigorous analysis of the three point external field problem and numerical results for the four point problem.Comment: 35 pages, 4 figure

An Electrostatics Problem on the Sphere Arising from a Nearby Point Charge

For a positively charged insulated d-dimensional sphere we investigate how the distribution of this charge is affected by proximity to a nearby positive or negative point charge when the system is governed by a Riesz s-potential 1/r^s, s>0, where r denotes Euclidean distance between point charges. Of particular interest are those distances from the point charge to the sphere for which the equilibrium charge distribution is no longer supported on the whole of the sphere (i.e. spherical caps of negative charge appear). Arising from this problem attributed to A. A. Gonchar are sequences of polynomials of a complex variable that have some fascinating properties regarding their zeros.Comment: 44 pages, 9 figure

Theory of strong localization effects of light in disordered loss or gain media

We present a systematical theory for the interplay of strong localization effects and absorption or gain of classical waves in 3-dimensional, disordered dielectrics. The theory is based on the selfconsistent Cooperon resummation, implementing the effects of energy conservation and its absorptive or emissive corrections by an exact, generalized Ward identity. Substantial renormalizations are found, depending on whether the absorption/gain occurs in the scatterers or in the background medium. We find a finite, gain-induced correlation volume which may be significantly smaller than the scale set by the scattering mean free path, even if there are no truly localized modes. Possible consequences for coherent feedback in random lasers as well as the possibility of oscillatory in time behavior induced by sufficiently strong gain are discussed.Comment: Published versio

Inter-sectoral Water Use in South Africa: Efficiency Versus Equity

While water supply sources are dwindling in South Africa, the demand for the scarce water resource is increasing. This situation requires a switch from supply to demand management of water in the country. The study updates the 1999 social accounting matrix for South Africa, using the Trade and Industrial Policy Strategies (TIPS) time series data, STATSA's 2001 census report and 2000 water accounts, the 2002 national income accounts, published by the South African Reserve Bank (SARB) and the Water Resource Management Strategy (WRMS) registration data. Using the updated SAM, the contribution of water to economic development in South Africa is estimated through the traditional SAM multiplier analysis. The paper then investigates the impact of reallocating water among the production sectors, on the basis of economic efficiency, on output growth, factor remuneration and households' income generation. The computational and simulation results show that, though agriculture is among the sectors that have the least marginal value of water, water reallocation based on marginal values will reduce the incomes of the poorest households, and put at stake the livelihoods of the most vulnerable population. Scenario analyses suggest that this effect will be minimal if marginal productivity consideration for inter-sectoral water reallocation is reduced to 30%, while intra-sectoral water reallocation on the basis of efficiency is currently viewed as the most viable option.SAM multipliers, output growth, factor remuneration, income generation, efficiency, equity, R20, Resource /Energy Economics and Policy, C67, D57, L60, Q25,