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

Sulfur reduction in sediments of marine and evaporite environments

Transformations of sulfur in sediments of ponds ranging in salinities from that of normal seawater to those of brines saturated with sodium chloride were examined. The chemistry of the sediment and pore waters were focused on with emphasis on the fate of sulfate reduction. The effects of increasing salinity on both forms of sulfur and microbial activity were determined. A unique set of chemical profiles and sulfate-reducing activity was found for the sediments of each of the sites examined. The quantity of organic matter in the salt pond sediments was significantly greater than that occurring in the adjacent intertidal site. The total quantitative and qualitative distribution of volatile fatty acids was also greater in the salt ponds. Volatile fatty acids increased with salinity

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

Equine cheek tooth extraction: Comparison of outcomes for five extraction methods

BACKGROUND: Post-operative complications are reported for all methods of equine cheek tooth extraction but not all methods carry the same risks. An outcome comparison for commonly used methods is needed so that clinicians can make informed treatment decisions. OBJECTIVES: We conducted a side-by-side comparison of five cheek tooth extraction methods, comparing types and incidence of complications among oral extraction, tooth repulsion (three surgical approaches) and lateral buccotomy techniques. STUDY DESIGN: Retrospective clinical study using hospital medical records. METHODS: Medical records of all horses undergoing cheek tooth extraction between 1997 and 2013 were reviewed. Logistic regression was used to determine the likelihood of various post-operative complications, comparing oral extraction, tooth repulsion by maxillary and mandibular trephination or maxillary sinus bone flap, and lateral buccotomy. RESULTS: The study included 137 horses and 162 cheek teeth extractions. Oral extraction was successful in 71% of patients in which it was attempted. Oral extraction (n = 55) had the lowest incidence of complications (20%) and repulsion by sinus bone flap (n = 20) the highest (80%). Complication rates for repulsion by maxillary (n = 19) and mandibular trephination (n = 28), and extraction by lateral buccotomy (n = 15) were 42, 54 and 53%, respectively. Cheek tooth repulsion by sinus bone flap significantly increased the odds of damage to adjacent teeth, post-operative sinusitis, damage to alveolar bone, delayed alveolar granulation and orosinus fistulation. Repulsion by maxillary trephination significantly increased the odds of superficial incisional surgical site infection; and extraction by lateral buccotomy significantly increased the odds of facial nerve neuropraxia. Post-operative pyrexia was more common in all repulsion methods. MAIN LIMITATIONS: Some clinically relevant differences may have been missed due to small group numbers in several categories. CONCLUSIONS: Oral extraction was associated with fewer post-operative complications than any other methods. Standing oral extraction remains the preferred choice, and recent surgical advances promise to further improve its success rate

Managing for change: October 11, 1989

Bi-weekly newsletter of University Hospital's Change Project, provided to managers at the hospital

London governance and the politics of neighbourhood planning: a case for investigation

The Localism Act 2011 has successfully devolved planning powers to over 2,500 English communities, involving 14 million people, with over 700 ‘made’ neighbourhood plans legitimised by referendum. In London, however, there are less than one-tenth of the made plans than in the rest of England. Institutional resistance and policy choices may be implicated. Two national studies of neighbourhood planning are reviewed. The role of the local authority is found to be a crucial factor in determining progress, and issues of social deprivation and unequal access are highlighted. Theorisation is considered by reference to a range of academic studies of localism and neighbourhood planning. Distinctions made between ‘representative’ and ‘community’ localism, and objections to anti-political effects, are noted. There has been remarkably little research into borough governance and neighbourhood planning in the capital. Based upon evidence of anomalous and differentiated governance practice, a study in London is called for

‘If independence goes, the planning system goes’: New Political Governance and the English Planning Inspectorate

Radical restructuring of 'arms-length' government bodies following the 2010 UK national election signalled a change in relations between government and the civil service. This was seen as a major shift in modes of governance from 'new public management' to a more politicised mode of 'new political governance'. This paper presents an analysis of the impacts of these shifts on the English Planning Inspectorate, an executive agency central to the land-use planning system. It identifies measures by ministers to increase control over the Inspectorate that represent a shift in governance culture and a shift in the planning system itself

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