Preventative ibandronate treatment has the most beneficial effect on the microstructure of bone in experimental tumor osteolysis

We investigated the effect of ibandronate on three-dimensional (3-D) microstructure and bone mass in experimentally induced tumor osteolysis. Walker carcinosarcoma cells were implanted into the left femur of female rats that received 26-day ibandronate pretreatment followed by continued therapy or ibandronate posttreatment only. A tumor-only group received isotonic saline. At endpoint, excised femurs were scanned using microcomputed tomography (μCT) to assess bone volume density, bone mineral content, trabecular number/thickness, and separation for cortical plus trabecular bone or trabecular bone alone. Compared with the nonimplanted right femur, bone volume and surface density and trabecular number and thickness were reduced in the distal left femur following tumor cell implantation. μCT analysis revealed greater cortical and trabecular bone mineral content in the preventative and interventional (pre-post tumor) ibandronate group, and the interventional (post-tumor) ibandronate group, versus the tumor-only group. Bone volume density was significantly higher in pre-post and post-tumor groups compared to the tumor-only group. After preventative and interventional ibandronate, bone volume density and trabecular thickness were 13% and 60% greater, respectively, than in the post-tumor treatment group. 3-D μCT images confirmed microstructural changes. We conclude that combined interventional and preventative ibandronate preserves bone strength and integrity more than intervention alon

The ATLAS Level-1 muon topological trigger information for run 2 of the LHC

For run 2 of the LHC, the ATLAS Level-1 trigger system will include topological information on trigger objects in order to cope with the increased trigger rates. The existing Muon-to-Central-Trigger- Processor interface (MUCTPI) has been modified in order to provide coarse-grained topological information on muon candidates. A MUCTPI- to-Level-1-Topological-Processor interface (MuCTPiToTopo) has been developed to receive the electrical information and to send it optically to the Level-1 Topological Processor (L1TOPO). This poster will describe the different modules mentioned above and present results of functionality and connection tests performed

An A2A adenosine receptor agonist, ATL313, reduces inflammation and improves survival in murine sepsis models

<p>Abstract</p> <p>Background</p> <p>The pathophysiology of sepsis is due in part to early systemic inflammation. Here we describe molecular and cellular responses, as well as survival, in A_2Aadenosine receptor (AR) agonist treated and untreated animals during experimental sepsis.</p> <p>Methods</p> <p>Sepsis was induced in mice by intraperitoneal inoculation of live bacteria (<it>Escherichia coli </it>or <it>Staphylococcus aureus</it>) or lipopolysaccharide (LPS). Mice inoculated with live bacteria were treated with an A_2AAR agonist (ATL313) or phosphate buffered saline (PBS), with or without the addition of a dose of ceftriaxone. LPS inoculated mice were treated with ATL313 or PBS. Serum cytokines and chemokines were measured sequentially at 1, 2, 4, 8, and 24 hours after LPS was administered. In survival studies, mice were followed until death or for 7 days.</p> <p>Results</p> <p>There was a significant survival benefit in mice infected with live <it>E. coli </it>(100% vs. 20%, <it>p </it>= 0.013) or <it>S. aureus </it>(60% vs. 20%, <it>p </it>= 0.02) when treated with ATL313 in conjunction with an antibiotic versus antibiotic alone. ATL313 also improved survival from endotoxic shock when compared to PBS treatment (90% vs. 40%, <it>p </it>= 0.005). The serum concentrations of TNF-α, MIP-1α, MCP-1, IFN-γ, and IL-17 were decreased by ATL313 after LPS injection (<it>p </it>< 0.05). Additionally, ATL313 increased the concentration of IL-10 under the same conditions (<it>p </it>< 0.05). Circulating white blood cell concentrations were higher in ATL313 treated animals (<it>p </it>< 0.01).</p> <p>Conclusion</p> <p>Further studies are warranted to determine the clinical utility of ATL313 as a novel treatment for sepsis.</p

Bisphosphonate nephrotoxicity

Bisphosphonates are valuable agents for the treatment of post-menopausal osteoporosis (PMO), hypercalcemia of malignancy, and osteolytic bone metastases. Oral bisphosphonates are used mainly to treat PMO and are not associated with significant nephrotoxicity. In contrast, nephrotoxicity is a significant potential limiting factor to the use of intravenous (IV) bisphosphonates, and the nephrotoxicity is both dose-dependent and infusion time-dependent. The two main IV bisphosphonates available to treat hypercalcemia of malignancy and osteolytic bone disease in the United States are zoledronate and pamidronate. Patterns of nephrotoxicity described with these agents include toxic acute tubular necrosis and collapsing focal segmental glomerulosclerosis, respectively. With both of these agents, severe nephrotoxicity can be largely avoided by stringent adherence to guidelines for monitoring serum creatinine prior to each treatment, temporarily withholding therapy in the setting of renal insufficiency, and adjusting doses in patients with pre-existing chronic kidney disease. In patients with PMO, zoledronate and pamidronate are associated with significantly less nephrotoxicity, which undoubtedly relates to the lower doses and longer dosing intervals employed for this indication. Ibandronate is approved in the US for treatment of PMO and in Europe for treatment of PMO and malignancy-associated bone disease. Available data suggest that ibandronate has a safe renal profile without evidence of nephrotoxicity, even in patients with abnormal baseline kidney function

Production Test Rig for the ATLAS Level-1 Calorimeter Trigger Digital Processors

The Level-1 Calorimeter Trigger is a digital pipelined system, reducing the 40 MHz bunch-crossing rate down to 75 kHz. It consists of a Preprocessor, a Cluster Processor (CP), and a Jet/Energy-sum Processor (JEP). The CP and JEP receive digitised trigger-tower data from the Preprocessor and produce electron/photon, tau, and jet trigger multiplicities, total and missing transverse energies, and Region-of-Interest (RoI) information. Data are read out to the data acquisition (DAQ) system to monitor the trigger by using readout driver modules (ROD). A dedicated backplane has been designed to cope with the demanding requirements of the CP and JEP sub-systems. A number of pre-production boards were manufactured in order to fully populate a crate and test the robustness of the design on a large scale. Dedicated test modules to emulate digitised calorimeter signals have been used. All modules, cables and backplanes on test are final versions for use at the LHC. This test rig represents up to one third of the Level-1 digital processor system. Real-time data between modules were processed and time-slice readout data was transferred to the ROD at a trigger rate up to 100 kHz. Intensive testing consisted of checking the readout data by comparing to hardware simulations of the trigger. Domains of validity of the boards were also measured and dedicated stressful data patterns were used to check the reliability of the system. Tests results have been successful and the Level-1 calorimeter trigger system is proceeding to full production