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

TangiBoard: a toolkit to reduce the implementation burden of tangible user interfaces in education

The use of Tangible User Interfaces (TUI) as an educational technology has gained sustained interest over the years with common agreement on its innate ability to engage and intrigue students in active-learning pedagogies. Whilst encouraging results have been obtained in research, the widespread adoption of TUI architectures is still hindered by a myriad of implementation burdens imposed by current toolkits. To this end, this paper presents an innovative TUI toolkit: TangiBoard, which enables the deployment of an interactive TUI system using low-cost, and presently available educational technology. Apart from curtailing setup costs and technical expertise required for adopting TUI systems, the toolkit provides an application framework to facilitate system calibration and development integration with GUI applications. This is enabled by a robust computer vision application that tracks a contributed passive marker set providing a range of tangible interactions to TUI frameworks. The effectiveness of this toolkit was evaluated by computer systems developers with respect to alternate toolkits for TUI design. Open-source versions of the TangiBoard toolkit together with marker sets are provided online through research licens

Designing a marker set for vertical tangible user interfaces

Tangible User Interfaces (TUI)s extend the domain of reality-based human-computer interaction by providing users the ability to manipulate digital data using physical objects which embody representational significance. Whilst various advancements have been registered over the past years through the development and availability of TUI toolkits, these have mostly converged towards the deployment of tabletop TUI architectures. In this context, markers used in current toolkits can only be placed underneath the tangible objects to provide recognition. Albeit being effective in various literature studies, the limitations and challenges of deploying tabletop architectures have significantly hindered the proliferation of TUI technology due to the limited audience reach such systems can provide. Furthermore, available marker sets restrict the placement and use of tangible objects since if placed on top of the tangible object, the marker will interfere with the shape and texture of the object limiting the effect the TUI has on the end-user. To this end, this paper proposes the design and development of an innovative tangible marker set specifically designed towards the development of vertical TUIs. The proposed marker set design was optimized through a genetic algorithms to ensure robustness in scale invariance, the capability of being successfully detected with distances of up to 3.5 meters and a true occlusion resistance of up to 25%, where the marker is recognized and not tracked. Open-source versions of the marker set are provided through research license on www.geoffslab.com/tangiboard_marker_set

The Removal of Artificially Generated Polarization in SHARP Maps

We characterize the problem of artificial polarization for the Submillimeter High Angular Resolution Polarimeter (SHARP) through the use of simulated data and observations made at the Caltech Submillimeter Observatory (CSO). These erroneous, artificial polarization signals are introduced into the data through misalignments in the bolometer sub-arrays plus pointing drifts present during the data-taking procedure. An algorithm is outlined here to address this problem and correct for it, provided that one can measure the degree of the sub-array misalignments and telescope pointing drifts. Tests involving simulated sources of Gaussian intensity profile indicate that the level of introduced artificial polarization is highly dependent upon the angular size of the source. Despite this, the correction algorithm is effective at removing up to 60% of the artificial polarization during these tests. The analysis of Jupiter data taken in January 2006 and February 2007 indicates a mean polarization of 1.44%+/-0.04% and 0.95%+/-0.09%, respectively. The application of the correction algorithm yields mean reductions in the polarization of approximately 0.15% and 0.03% for the 2006 and 2007 data sets, respectively.Comment: 19 pages, 7 figure

The field theoretic derivation of the contact value theorem in planar geometries and its modification by the Casimir effect

The contact value theorem for Coulomb gases in planar or film-like geometries is derived using a Hamiltonian field theoretic representation of the system. The case where the film is enclosed by a material of different dielectric constant to that of the film is shown to contain an additional Casimir-like term which is generated by fluctuations of the electric potential about its mean-field value.Comment: Link between Sine-Gordon and Coulomb gas pressures via subtraction of self interaction terms included. Discussion of results within Debye-Huckel approximation included. Added reference

Charge Fluctuations on Membrane Surfaces in Water

We generalize the predictions for attractions between over-all neutral surfaces induced by charge fluctuations/correlations to non-uniform systems that include dielectric discontinuities, as is the case for mixed charged lipid membranes in an aqueous solution. We show that the induced interactions depend in a non-trivial way on the dielectric constants of membrane and water and show different scaling with distance depending on these properties. The generality of the calculations also allows us to predict under which dielectric conditions the interaction will change sign and become repulsive

Comparison of minimally invasive parathyroidectomy under local anaesthesia and minimally invasive video-assisted parathyroidectomy for primary hyperparathyroidism: A cost analysis

Background: Primary hyperparathyroidism (PHPT) origins from a solitary adenoma in 70-95% of cases. Moreover, the advances in methods for localizing an abnormal parathyroid gland made minimally invasive techniques more prominent. This study presents a micro-cost analysis of two parathyroidectomy techniques. Patients and methods: 72 consecutive patients who underwent minimally invasive parathyroidectomy, video-assisted (MIVAP, group A, 52 patients) or "open" under local anaesthesia (OMIP, group B, 20 patients) for PHPT were reviewed. Operating room, consumable, anaesthesia, maintenance costs, equipment depreciation and surgeons/anaesthesiologists fees were evaluated. The patient's satisfaction and the rate of conversion to conventional parathyroidectomy were investigated. T-Student's, Kolmogorov-Smirnov tests and Odds Ratio were used for statistical analysis. Results: 1 patient of the group A and 2 of the group B were excluded from the cost analysis because of the conversion to the conventional technique. Concerning the remnant patients, the overall average costs were: for Operative Room, 1186,69 \u20ac for the MIVAP group (51 patients) and 836,11 \u20ac for the OMIP group (p<0,001); for the Team, 122,93 \u20ac (group A) and 90,02 \u20ac (group B) (p<0,001); the other operative costs were 1388,32 \u20ac (group A) and 928,23 \u20ac (group B) (p<0,001). The patient's satisfaction was very strongly in favour of the group B (Odds Ratio 20,5 with a 95% confidence interval). Conclusions: MIVAP is more expensive compared to the "open" parathyroidectomy under local anaesthesia due to the costs of general anaesthesia and the longer operative time. Moreover, the patients generally prefer the local anaesthesia. Nevertheless, the rate of conversion to the conventional parathyroidectomy was relevant in the group of the local anaesthesia compared to the MIVAP, since the latter allows a four-gland exploration

DNA-condensation, redissolution and mesocrystals induced by tetravalent counterions

The distance-resolved effective interaction potential between two parallel DNA molecules is calculated by computer simulations with explicit tetravalent counterions and monovalent salt. Adding counterions first yields an attractive minimum in the potential at short distances which then disappears in favor of a shallower minimum at larger separations. The resulting phase diagram includes a DNA-condensation and redissolution transition and a stable mesocrystal with an intermediate lattice constant for high counterion concentration.Comment: 4 pages, 4 figure

Consequences of anisotropy in electrical charge storage: application to the characterization by the mirror method of TiO2 rutile

This article is devoted first to anisotropic distributions of stored electric charges in isotropic materials, second to charge trapping and induced electrostatic potential in anisotropic dielectrics. On the one hand, we examine the case of anisotropic trapped charge distributions in linear homogeneous isotropic (LHI) insulators, obtained after an electron irradiation in a scanning electron microscope. This injection leads to the formation of a mirror image

Charge-Fluctuation-Induced Non-analytic Bending Rigidity

In this Letter, we consider a neutral system of mobile positive and negative charges confined on the surface of curved films. This may be an appropriate model for: i) a highly charged membrane whose counterions are confined to a sheath near its surface; ii) a membrane composed of an equimolar mixture of anionic and cationic surfactants in aqueous solution. We find that the charge fluctuations contribute a non-analytic term to the bending rigidity that varies logarithmically with the radius of curvature. This may lead to spontaneous vesicle formation, which is indeed observed in similar systems.Comment: Revtex, 9 pages, no figures, submitted to PR