Effects of Sex, Age, and Season on Plasma Steroids in Free-ranging Texas Horned Lizards (Phrynosoma cornutum)

The Texas horned lizard (Phrynosoma cornutum) is protected in several states due to its apparently declining numbers; information on its physiology is therefore of interest from both comparative endocrine and applied perspectives. We collected blood samples from free-ranging P. cornutum in Oklahoma from April to September 2005, spanning their complete active period. We determined plasma concentrations of the steroids, progesterone (P), testosterone (T), and corticosterone (CORT) by radioimmunoassay following chromatographic separation and 17β-estradiol (E2) by direct radioimmunoassay. T concentrations in breeding males were significantly higher than in non-breeding males. P showed no significant seasonal variation within either sex. CORT was significantly higher during the egg-laying season compared to breeding and non-breeding seasons for adult females and it was marginally higher in breeding than in non-breeding males (P = 0.055). CORT concentrations also significantly increased with handling in non-breeding males and egg-laying females. Perhaps most surprisingly, there were no significant sex differences in plasma concentrations of P and E2. Furthermore, with respect to seasonal differences, plasma E2 concentrations were significantly higher in breeding females than in egg-laying or non-breeding females, and they were significantly higher in breeding than in non-breeding males. During the non-breeding season, yearling males exhibited higher E2 concentrations than adult males; no other differences between the steroid concentrations of yearlings and adults were detected. In comparison to other vertebrates, the seasonal steroid profile of P. cornutum exhibited both expected and unexpected patterns, and our results illustrate the value of collecting such baseline data as a springboard for appropriate questions for future research

A phase I pharmacokinetic and safety study of cabazitaxel in adult cancer patients with normal and impaired renal function

$\textbf{PURPOSE}$ Limited data are available on cabazitaxel pharmacokinetics in patients with renal impairment. This open-label, multicenter study assessed cabazitaxel in patients with advanced solid tumors and normal or impaired renal function. $\textbf{METHODS}$ Cohorts A (normal renal function: creatinine clearance [CrCL] >80 mL/min/1.73 m$^{2}$), B (moderate renal impairment: CrCL 30 to <50 mL/min/1.73 m$^{2}$) and C (severe impairment: CrCL <30 mL/min/1.73 m(2)) received cabazitaxel 25 mg/m$^{2}$ (A, B) or 20 mg/m(2) (C, could be escalated to 25 mg/m$^{2}$), once every 3 weeks. Pharmacokinetic parameters and cabazitaxel unbound fraction (F$_{U}$) were assessed using linear regression and mixed models. Geometric mean (GM) and GM ratios (GMRs) were determined using mean CrCL intervals (moderate and severe renal impairment: 40 and 15 mL/min/1.73 m$^{2}$) versus a control (90 mL/min/1.73 m$^{2}$). $\textbf{RESULTS}$ Overall, 25 patients received cabazitaxel (median cycles: 3 [range 1-20]; Cohort A: 5 [2-13]; Cohort B: 3 [1-15]; and Cohort C: 5 [1-20]), of which 24 were eligible for pharmacokinetic analysis (eight in each cohort). For moderate and severe renal impairment versus normal renal function, GMR estimates were: clearance normalized to body surface area (CL/BSA) 0.95 (90% CI 0.80-1.13) and 0.89 (0.61-1.32); area under the curve normalized to dose (AUC/dose) 1.06 (0.88-1.27) and 1.14 (0.76-1.71); and F U 0.99 (0.94-1.04) and 0.97 (0.87-1.09), respectively. Estimated slopes of linear regression of log parameters versus log CrCL (renal impairment) were: CL/BSA 0.06 (-0.15 to 0.28); AUC/dose -0.07 (-0.30 to 0.16); and F U 0.02 (-0.05 to 0.08). Cabazitaxel safety profile was consistent with previous reports. $\textbf{CONCLUSIONS}$ Renal impairment had no clinically meaningful effect on cabazitaxel pharmacokinetics.This study was supported by Sanofi. Javier Garcia-Corbacho acknowledges clinical fellowship support from SEOM. Experimental Cancer Medicine Centre (ECMC) and NIHR Biomedical Research Centre (BRC) funding is also acknowledged for the Cambridge Cancer Centre

Managing uncertainty: a review of food system scenario analysis and modelling

Complex socio-ecological systems like the food system are unpredictable, especially to long-term horizons such as 2050. In order to manage this uncertainty, scenario analysis has been used in conjunction with food system models to explore plausible future outcomes. Food system scenarios use a diversity of scenario types and modelling approaches determined by the purpose of the exercise and by technical, methodological and epistemological constraints. Our case studies do not suggest Malthusian futures for a projected global population of 9 billion in 2050; but international trade will be a crucial determinant of outcomes; and the concept of sustainability across the dimensions of the food system has been inadequately explored so far. The impact of scenario analysis at a global scale could be strengthened with participatory processes involving key actors at other geographical scales. Food system models are valuable in managing existing knowledge on system behaviour and ensuring the credibility of qualitative stories but they are limited by current datasets for global crop production and trade, land use and hydrology. Climate change is likely to challenge the adaptive capacity of agricultural production and there are important knowledge gaps for modelling research to address

The Lantern Vol. 50, No. 2, Spring 1984

• The Storm • Je ne sais pas • The Ghetious Blastious • An Empty Cradle • The Playing Hands • Battle Hymn • A Limerick • Parting Thoughts • The River • Miss You • De la Tristeza • Two So Special • Time of the Unicorn • The Absence • Thru The Breeze • Is the World Really a Round Ball? • Brother • To Michael • Gravity • Refuge • Der Witwer • Plastic Flowers Never Die • Book on the Shelfhttps://digitalcommons.ursinus.edu/lantern/1124/thumbnail.jp

Internal Jugular Vein Cross-Sectional Area and Cerebrospinal Fluid Pulsatility in the Aqueduct of Sylvius: A Comparative Study between Healthy Subjects and Multiple Sclerosis Patients

Objectives Constricted cerebral venous outflow has been linked with increased cerebrospinal fluid (CSF) pulsatility in the aqueduct of Sylvius in multiple sclerosis (MS) patients and healthy individuals. This study investigates the relationship between CSF pulsatility and internal jugular vein (IJV) cross-sectional area (CSA) in these two groups, something previously unknown. Methods 65 relapsing-remitting MS patients (50.8% female; mean age = 43.8 years) and 74 healthy controls (HCs) (54.1% female; mean age = 43.9 years) were investigated. CSF flow quantification was performed on cine phase-contrast MRI, while IJV-CSA was calculated using magnetic resonance venography. Statistical analysis involved correlation, and partial least squares correlation analysis (PLSCA). Results PLSCA revealed a significant difference (p<0.001; effect size = 1.072) between MS patients and HCs in the positive relationship between CSF pulsatility and IJV-CSA at C5-T1, something not detected at C2-C4. Controlling for age and cardiovascular risk factors, statistical trends were identified in HCs between: increased net positive CSF flow (NPF) and increased IJV-CSA at C5-C6 (left: r = 0.374, p = 0.016; right: r = 0.364, p = 0.019) and C4 (left: r = 0.361, p = 0.020); and increased net negative CSF flow and increased left IJV-CSA at C5-C6 (r = -0.348, p = 0.026) and C4 (r = -0.324, p = 0.039), whereas in MS patients a trend was only identified between increased NPF and increased left IJV-CSA at C5-C6 (r = 0.351, p = 0.021). Overall, correlations were weaker in MS patients (p = 0.015). Conclusions In healthy adults, increased CSF pulsatility is associated with increased IJV-CSA in the lower cervix (independent of age and cardiovascular risk factors), suggesting a biomechanical link between the two. This relationship is altered in MS patients