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

Substandard Housing and the Cost of Providing Housing-Related Services

Designed as a comparative undertaking by the National League of Cities (NLC) , this study is officially entitled National Research Agenda Project No. 5: Substandard Housing and the Cost of Providing Housing-Related Services. A similar study was carried out by the urban observatories in Denver and Nashville. According to the study scope of services, the NLC was interested in the cost of a wide variety of local government activities ... required to support and service urban housing, and how these costs are affected by housing quality, housing location, age and type of structures. ... It was also suggested that attention be given to examining variations in the type and level of services provided on the basis of such factors as housing ownership . . . and according to the demographic characteristics of the occupants. In addition, consideration will be given to identifying, insofar as possible, special costs related to substandard housing and to estimating their magnitude. More specifically, the following tasks were identified in the scope of study services: 1) Develop indicators of standardness and substandardness; 2) Identify typical housing areas of essentially uniform characteristics; 3) Determine the cost of providing housing-related services, and; 4) Develop current and five-year projections of the cost of providing housing-related services if all housing were standard

Carry My Back to Old Virginny / words by James A. Bland

Cover: drawing of an African American family sitting in the courtyard, a man playing Banjo, a woman dancing with a child; Publisher: Oliver Ditson Company (Boston)https://egrove.olemiss.edu/sharris_b/1074/thumbnail.jp

When it\u27s Cotton Pickin\u27 Time in Tennessee / music by James A. Brennan; words by Jack Caddigan

Cover: drawing of idyllic farm scene, where African Americans smile as they pick cotton; Publisher: Daly Music Publisher (Boston)https://egrove.olemiss.edu/sharris_c/1142/thumbnail.jp