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

On The Origin Of The Mass-Metallicity Relation For GRB Host Galaxies

We investigate the nature of the mass-metallicity (M-Z) relation for long gamma-ray burst (LGRB) host galaxies. Recent studies suggest that the M-Z relation for local LGRB host galaxies may be systematically offset towards lower metallicities relative to the M-Z relation defined by the general star forming galaxy (SDSS) population. The nature of this offset is consistent with suggestions that low metallicity environments may be required to produce high mass progenitors, although the detection of several GRBs in high-mass, high-metallicity galaxies challenges the notion of a strict metallicity cut-off for host galaxies that are capable of producing GRBs. We show that the nature of this reported offset may be explained by a recently proposed anti-correlation between the star formation rate (SFR) and the metallicity of star forming galaxies. If low metallicity galaxies produce more stars than their equally massive, high-metallicity counterparts, then transient events that closely trace the SFR in a galaxy would be more likely to be found in these low metallicity, low mass galaxies. Therefore, the offset between the GRB and SDSS defined M-Z relations may be the result of the different methods used to select their respective galaxy populations, with GRBs being biased towards low metallicity, high SFR, galaxies. We predict that such an offset should not be expected of transient events that do not closely follow the star formation history of their host galaxies, such as short duration GRBs and SN Ia, but should be evident in core collapse SNe found through upcoming untargeted surveys.Comment: 6 pages, 4 figures, submitted to ApJ

Evaluation of Weight Change During Carboplatin Therapy in Dogs With Appendicular Osteosarcoma.

BackgroundThe prevalence of cancer cachexia in veterinary medicine has not been studied widely, and as of yet, no definitive diagnostic criteria effectively assess this syndrome in veterinary patients.Objectives(1) To determine the patterns of weight change in dogs with appendicular osteosarcoma treated with amputation and single-agent carboplatin during the course of adjuvant chemotherapy; and (2) to determine whether postoperative weight change is a negative prognostic indicator for survival time in dogs with osteosarcoma.AnimalsEighty-eight dogs diagnosed with appendicular osteosarcoma. Animals were accrued from 3 veterinary teaching hospitals.MethodsRetrospective, multi-institutional study. Dogs diagnosed with appendicular osteosarcoma and treated with limb amputation followed by a minimum of 4 doses of single-agent carboplatin were included. Data analyzed in each patient included signalment, tumor site, preoperative serum alkaline phosphatase activity (ALP), and body weight (kg) at each carboplatin treatment.ResultsA slight increase in weight occurred over the course of chemotherapy, but this change was not statistically significant. Weight change did not have a significant effect on survival. Institution, patient sex, and serum ALP activity did not have a significant effect on survival.Conclusions and clinical importanceWeight change was not a prognostic factor in these dogs, and weight loss alone may not be a suitable method of determining cancer cachexia in dogs with appendicular osteosarcoma

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