Lead plant 15N natural abundance for measuring its biological nitrogen fixation potential.

Leadplant (Amorpha canescens Pursh) is a prairie legume naturally occurring in the pastures of Nebraska Sand Hills area, as well as most of pasturelands of Central USA. Samples of Leadplant growing in two different paddocks of the University of Nebraska Bartha Brother's Ranch were collected at random and mixed to provide six replications per paddock, in early spring and late summer. In parallel, samples of six different non-legume species (or replications of a given species) growing in the same area were collected. The paddocks differ only by their rate of pasture utilization in the last few years. All samples were analyzed for their N content and natural abundance of the isotope 15N (d15N). The15N dilution technique was applied to evaluate the amount of N in Leadplant derived from biological N fixation, being assumed that the averaged d15N content of the non-legumes represents the basal soil N isotopic composition, and any dilution on that would be caused by N obtained from the atmosphe, with d15N equals to zero. Leadplant samples were significantly (p<0.001) more enriched in total N than the non-legumes (total average of 2.09% compared to 1.37%). They were also significantly (p<0.001) more depleted in d15N (total average of -2.049 compared to -4.294). Averaged N in Leadplant derived from biological N fixation varied from 39% to 46% and from 51% to 66% in the first and second paddocks in early spring and late summer, respectively. These results confirms the importance of this legume for the maintenance of natural and introduced pastures.Paper 61713. Online

Visual Fixations Duration as an Indicator of Skill Level in eSports

Using highly interactive systems like computer games requires a lot of visual activity and eye movements. Eye movements are best characterized by visual fixation - periods of time when the eyes stay relatively still over an object. We analyzed the distributions of fixation duration of professional athletes, amateur and newbie players. We show that the analysis of fixation durations can be used to deduce the skill level in computer game players. Highly skilled gaming performance is characterized by more variability in fixation durations and by bimodal fixation duration distributions suggesting the presence of two fixation types in high skill gamers. These fixation types were identified as ambient (automatic spatial processing) and focal (conscious visual processing). The analysis of computer gamers' skill level via the analysis of fixation durations may be used in developing adaptive interfaces and in interface design.Comment: 10 pages, 3 figure

A phase i pharmacokinetic study of the vascular disrupting agent ombrabulin (AVE8062) and docetaxel in advanced solid tumours

Background: The vascular disrupting agent ombrabulin shows synergy with docetaxel in vivo. Recommended phase II doses were determined in a dose escalation study in advanced solid tumours. Methods: Ombrabulin (30-min infusion, day 1) followed by docetaxel (1-h infusion, day 2) every 3 weeks was explored. Ombrabulin was escalated from 11.5 to 42 mg m -2 with 75 mg m -2 docetaxel, then from 30 to 35 mg m -2 with 100 mg m -2 docetaxel. Recommended phase II dose cohorts were expanded. Results: Fifty-eight patients were treated. Recommended phase II doses were 35 mg m -2 ombrabulin with 75 mg m -2 docetaxel (35/75 mg m -2; 13 patients) and 30 mg m -2 ombrabulin with 100 mg m -2 docetaxel (30/100 mg m -2; 16 patients). Dose-limiting toxicities were grade 3 fatigue (two patients; 42/75, 35/100), grade 3 neutropaenic infection (25/75), grade 3 headache (42/75), grade 4 febrile neutropaenia (30/100), and grade 3 thrombosis (35/100). Toxicities were consistent with each agent; mild nausea/vomiting, asthaenia/fatigue, alopecia, and anaemia were common, as were neutropaenia and leukopaenia. Diarrhoea, nail disorders and neurological symptoms were frequent at 100 mg m -2 docetaxel. Pharmacokinetic analyses did not show any relevant drug interactions. Ten patients had partial responses (seven at 30 mg m -2 ombrabulin), eight lasting >3 months. Conclusions: Sequential administration of ombrabulin with 75 or 100 mg m -2 docetaxel every 3 weeks is feasible

Fluorescent Risedronate Analogues Reveal Bisphosphonate Uptake by Bone Marrow Monocytes and Localization Around Osteocytes In Vivo

Bisphosphonates are effective antiresorptive agents owing to their bone-targeting property and ability to inhibit osteoclasts. It remains unclear, however, whether any non-osteoclast cells are directly affected by these drugs in vivo. Two fluorescent risedronate analogues, carboxyfluorescein-labeled risedronate (FAM-RIS) and Alexa Fluor 647–labeled risedronate (AF647-RIS), were used to address this question. Twenty-four hours after injection into 3-month-old mice, fluorescent risedronate analogues were bound to bone surfaces. More detailed analysis revealed labeling of vascular channel walls within cortical bone. Furthermore, fluorescent risedronate analogues were present in osteocytic lacunae in close proximity to vascular channels and localized to the lacunae of newly embedded osteocytes close to the bone surface. Following injection into newborn rabbits, intracellular uptake of fluorescently labeled risedronate was detected in osteoclasts, and the active analogue FAM-RIS caused accumulation of unprenylated Rap1A in these cells. In addition, CD14high bone marrow monocytes showed relatively high levels of uptake of fluorescently labeled risedronate, which correlated with selective accumulation of unprenylated Rap1A in CD14+ cells, as well as osteoclasts, following treatment with risedronate in vivo. Similar results were obtained when either rabbit or human bone marrow cells were treated with fluorescent risedronate analogues in vitro. These findings suggest that the capacity of different cell types to endocytose bisphosphonate is a major determinant for the degree of cellular drug uptake in vitro as well as in vivo. In conclusion, this study shows that in addition to bone-resorbing osteoclasts, bisphosphonates may exert direct effects on bone marrow monocytes in vivo. © 2010 American Society for Bone and Mineral Researc

Algorithm for the use of biochemical markers of bone turnover in the diagnosis, assessment and follow-up of treatment for osteoporosis

Introduction Increased biochemical bone turnover markers (BTMs) measured in serum are associated with bone loss, increased fracture risk and poor treatment adherence, but their role in clinical practice is presently unclear. The aim of this consensus group report is to provide guidance to clinicians on how to use BTMs in patient evaluation in postmenopausal osteoporosis, in fracture risk prediction and in the monitoring of treatment efficacy and adherence to osteoporosis medication. Methods A working group with clinical scientists and osteoporosis specialists was invited by the Scientific Advisory Board of European Society on Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO). Results Serum bone formation marker PINP and resorption marker βCTX-I are the preferred markers for evaluating bone turnover in the clinical setting due to their specificity to bone, performance in clinical studies, wide use and relatively low analytical variability. BTMs cannot be used to diagnose osteoporosis because of low sensitivity and specificity, but can be of value in patient evaluation where high values may indicate the need to investigate some causes of secondary osteoporosis. Assessing serum levels of βCTX-I and PINP can improve fracture prediction slightly, with a gradient of risk of about 1.2 per SD increase in the bone marker in addition to clinical risk factors and bone mineral density. For an individual patient, BTMs are not useful in projecting bone loss or treatment efficacy, but it is recommended that serum PINP and βCTX-I be used to monitor adherence to oral bisphosphonate treatment. Suppression of the BTMs greater than the least significant change or to levels in the lower half of the reference interval in young and healthy premenopausal women is closely related to treatment adherence. Conclusion In conclusion, the currently available evidence indicates that the principal clinical utility of BTMs is for monitoring oral bisphosphonate therapy