The influence of toxicity constraints in models of chemotherapeutic protocol escalation

The prospect of exploiting mathematical and computational models to gain insight into the influence of scheduling on cancer chemotherapeutic effectiveness is increasingly being considered. However, the question of whether such models are robust to the inclusion of additional tumour biology is relatively unexplored. In this paper, we consider a common strategy for improving protocol scheduling that has foundations in mathematical modelling, namely the concept of dose densification, whereby rest phases between drug administrations are reduced. To maintain a manageable scope in our studies, we focus on a single cell cycle phase-specific agent with uncomplicated pharmacokinetics, as motivated by 5-Fluorouracil-based adjuvant treatments of liver micrometastases. In particular, we explore predictions of the effectiveness of dose densification and other escalations of the protocol scheduling when the influence of toxicity constraints, cell cycle phase specificity and the evolution of drug resistance are all represented within the modelling. For our specific focus, we observe that the cell cycle and toxicity should not simply be neglected in modelling studies. Our explorations also reveal the prediction that dose densification is often, but not universally, effective. Furthermore, adjustments in the duration of drug administrations are predicted to be important, especially when dose densification in isolation does not yield improvements in protocol outcomes

A new technique for elucidating β\beta-decay schemes which involve daughter nuclei with very low energy excited states

A new technique of elucidating $\beta$-decay schemes of isotopes with large density of states at low excitation energies has been developed, in which a Broad Energy Germanium (BEGe) detector is used in conjunction with coaxial hyper-pure germanium detectors. The power of this technique has been demonstrated on the example of 183Hg decay. Mass-separated samples of 183Hg were produced by a deposition of the low-energy radioactive-ion beam delivered by the ISOLDE facility at CERN. The excellent energy resolution of the BEGe detector allowed $\gamma$ rays energies to be determined with a precision of a few tens of electronvolts, which was sufficient for the analysis of the Rydberg-Ritz combinations in the level scheme. The timestamped structure of the data was used for unambiguous separation of $\gamma$ rays arising from the decay of 183Hg from those due to the daughter decays

Two-neutron transfer reaction mechanisms in 12^{12}C(6^6He,4^{4}He)14^{14}C using a realistic three-body 6^{6}He model

The reaction mechanisms of the two-neutron transfer reaction $^{12}$C($^6$He,$^4$He) have been studied at 30 MeV at the TRIUMF ISAC-II facility using the SHARC charged-particle detector array. Optical potential parameters have been extracted from the analysis of the elastic scattering angular distribution. The new potential has been applied to the study of the transfer angular distribution to the 2$^+_2$ 8.32 MeV state in $^{14}$C, using a realistic 3-body $^6$He model and advanced shell model calculations for the carbon structure, allowing to calculate the relative contributions of the simultaneous and sequential two-neutron transfer. The reaction model provides a good description of the 30 MeV data set and shows that the simultaneous process is the dominant transfer mechanism. Sensitivity tests of optical potential parameters show that the final results can be considerably affected by the choice of optical potentials. A reanalysis of data measured previously at 18 MeV however, is not as well described by the same reaction model, suggesting that one needs to include higher order effects in the reaction mechanism.Comment: 9 pages, 9 figure

Production of antihydrogen at reduced magnetic field for anti-atom trapping

We have demonstrated production of antihydrogen in a 1$,$T solenoidal magnetic field. This field strength is significantly smaller than that used in the first generation experiments ATHENA (3$,$T) and ATRAP (5$,$T). The motivation for using a smaller magnetic field is to facilitate trapping of antihydrogen atoms in a neutral atom trap surrounding the production region. We report the results of measurements with the ALPHA (Antihydrogen Laser PHysics Apparatus) device, which can capture and cool antiprotons at 3$,$T, and then mix the antiprotons with positrons at 1$,$T. We infer antihydrogen production from the time structure of antiproton annihilations during mixing, using mixing with heated positrons as the null experiment, as demonstrated in ATHENA. Implications for antihydrogen trapping are discussed

Processes of ‘hummocky moraine’ formation in the Gaick, Scotland: insights into the ice-marginal dynamics of a Younger Dryas plateau icefield

Younger Dryas ice-marginal (‘hummocky’) moraines in Scotland represent valuable terrestrial archives that can be used to obtain important information on ice-marginal dynamics and glacier thermal regimes during a period of rapid climatic change. In this paper, we present detailed sedimentological studies of Younger Dryas ice-marginal moraines in the Gaick, central Scotland, the former site of a spatially restricted plateau icefield. Exposures demonstrate that moraines in the Gaick represent terrestrial ice-contact fans, with evidence of proglacial and subglacial glaciotectonization, as reported elsewhere in Scotland. The exposures also reveal the influence of local hydrogeological conditions, with pressurization of the groundwater system leading to the formation of hydrofracture fills within some moraines. Clast shape analysis shows that all the moraines contain debris consistent with transport in the subglacial traction zone. The sedimentological data, and the planform arrangement of the moraines as nested arcs or chevrons, indicate that retreat of the Younger Dryas Gaick Icefield outlets was incremental and oscillatory. This evidence strongly suggests a mainly temperate thermal regime and short glacier response times, but with narrow cold-ice zones near the margins facilitating the elevation of basal debris to the glacier surface. Analogous glaciodynamic regimes occur at modern ice-cap and plateau icefield outlets in Iceland and Norway, although there are significant differences in the nature of ice-marginal deposition. The glaciodynamic signature recorded by moraines in the Gaick has allowed us to shed new light on the ice-marginal dynamics and thermal regime of one of the most easterly Younger Dryas icefields in Scotland

Constructing female entrepreneurship policy in the UK : is the US a relevant benchmark?

Successive UK governments have introduced a range of policy initiatives designed to encourage more women to start new firms. Underpinning these policies has been an explicit ambition for the UK to achieve similar participation rates as those in the US where it is widely reported that women own nearly half the stock of businesses. The data underlying these objectives are critically evaluated and it is argued that the definitions and measures of female enterprise used in the UK and the US restrict meaningful comparisons between the two. It is suggested that the expansion of female entrepreneurship in the US is historically and culturally specific to that country. UK policy goals should reflect the national socioeconomic context, while drawing upon good practice examples from a range of other countries. The paper concludes by discussing the economic and social viability of encouraging more women in the UK to enter self-employment without fully recognising the intensely competitive sectors in which they are often located

A psychoanalytic concept illustrated: Will, must, may, can — revisiting the survival function of primitive omnipotence

The author explores the linear thread connecting the theory of Freud and Klein, in terms of the central significance of the duality of the life and death instinct and the capacity of the ego to tolerate contact with internal and external reality. Theoretical questions raised by later authors, informed by clinical work with children who have suffered deprivation and trauma in infancy, are then considered. Theoretical ideas are illustrated with reference to observational material of a little boy who suffered deprivation and trauma in infancy. He was first observed in the middle of his first year of life while he was living in foster care, and then later at the age of two years and three months, when he had been living with his adoptive parents for more than a year

The TRIUMF nuclear structure program and TIGRESS

The isotope separator and accelerator (ISAC) facility located at the TRIUMF laboratory in Vancouver, Canada, is one of the world\u27s most advanced isotope separator on-line-type radioactive ion beam facilities. An extensive γ-ray spectroscopy programme at ISAC is centred around two major research facilities: (i) the 8π γ-ray spectrometer for β-delayed γ-ray spectroscopy experiments with the low-energy beams from ISAC-I, and (ii) the next generation TRIUMF-ISAC gamma-ray escape suppressed spectrometer (TIGRESS) for in-beam experiments with the accelerated radioactive-ion beams. An overview of these facilities and recent results from the diverse programme of nuclear structure and fundamental interaction studies they support is presented. © 2007 Elsevier B.V. All rights reserved