A multicenter phase II trial (SAKK 36/06) of single-agent everolimus (RAD001) in patients with relapsed or refractory mantle cell lymphoma.

BACKGROUND: Mantle cell lymphoma accounts for 6% of all B-cell lymphomas and is generally incurable. It is characterized by the translocation t(11;14) leading to cyclin D1 over-expression. Cyclin D1 is downstream of the mammalian target of rapamycin threonine kinase and can be effectively blocked by mammalian target of rapamycin inhibitors. We set out to examine the single agent activity of the orally available mammalian target of rapamycin inhibitor everolimus in a prospective, multicenter trial in patients with relapsed or refractory mantle cell lymphoma (NCT00516412). DESIGN AND METHODS: Eligible patients who had received a maximum of three prior lines of chemotherapy were given everolimus 10 mg for 28 days (one cycle) for a total of six cycles or until disease progression. The primary endpoint was the best objective response. Adverse reactions, progression-free survival and molecular response were secondary endpoints. RESULTS: Thirty-six patients (35 evaluable) were enrolled and treatment was generally well tolerated with Common Terminology Criteria grade ≥ 3 adverse events (>5%) including anemia (11%), thrombocytopenia (11%) and neutropenia (8%). The overall response rate was 20% (95% CI: 8-37%) with two complete remissions and five partial responses; 49% of the patients had stable disease. At a median follow-up of 6 months, the median progression-free survival was 5.5 months (95% CI: 2.8-8.2) overall and 17.0 (6.4-23.3) months for 18 patients who received six or more cycles of treatment. Three patients achieved a lasting complete molecular response, as assessed by polymerase chain reaction analysis of peripheral blood. CONCLUSIONS: Everolimus as a single agent is well tolerated and has anti-lymphoma activity in relapsed or refractory mantle cell lymphoma. Further studies of everolimus in combination with chemotherapy or as a single agent for maintenance treatment are warranted.

Severe hypercalcemia after a single high dose of vitamin D in a patient with sarcoidosis.

LETTER TO THE EDITOR

Cation distribution and magnetization of BaFe12-2xCoxSnxO19 (x=0.9,1.28) single crystals

The distribution of Sn4+ cations within the five crystallographic sites of the magnetoplumbite (M) ‐like compound BaFe12−2xCoxSnxO19 has been analyzed using single‐crystal x‐ray‐diffraction data. The species Fe3+ and Co2+ cannot be distinguished using x rays because of their very similar atomic numbers; however, the calculation of the apparent valencies for the different sites allows an insight into the Co2+ cation segregation. The use of previous data from neutron powder diffraction allows a precise picture of the cation distribution, which indicates a pronounced site selectivity for both Sn4+ and Co2+ cations. The Sn4+ cations prefer the 4f2 sites and to a much lower extent the 12k sites, while they do not enter the octahedral 2a sites at all. Co2+ cations are distributed among tetrahedral and octahedral sites displaying a clear preference for the tetrahedral 4f1 sites. Magnetic measurements indicate that the compound still exhibits uniaxial anisotropy with the easy direction parallel to the c axis. Nevertheless, the magnetic structure shows a considerable degree of noncolinearity. A strong reduction of the magnetic anisotropy regarding that of the undoped compound is also detected.

Debris Mitigation Methods for Bridge Piers, Final Repory, June 2012

Debris accumulation on bridge piers is an on-going national problem that can obstruct the waterway openings at bridges and result in significant erosion of stream banks and scour at abutments and piers. In some cases, the accumulation of debris can adversely affect the operation of the waterway opening or cause failure of the structure. In addition, removal of debris accumulation is difficult, time consuming, and expensive for maintenance programs. This research involves a literature search of publications, products, and pier design recommendations that provide a cost effective method to mitigate debris accumulation at bridges. In addition, a nationwide survey was conducted to determine the state-of-the-practice and the results are presented within.

Geosynthetic Reinforced Soil for Low-Volume Bridge Abutments, January 2012

This report presents a review of literature on geosynthetic reinforced soil (GRS) bridge abutments, and test results and analysis from two field demonstration projects (Bridge 1 and Bridge 2) conducted in Buchanan County, Iowa, to evaluate the feasibility and cost effectiveness of the use of GRS bridge abutments on low-volume roads (LVRs). The two projects included GRS abutment substructures and railroad flat car (RRFC) bridge superstructures. The construction costs varied from $43k to $49k, which was about 50 to 60% lower than the expected costs for building a conventional bridge. Settlement monitoring at both bridges indicated maximum settlements ≤1 in. and differential settlements ≤ 0.2 in transversely at each abutment, during the monitoring phase. Laboratory testing on GRS fill material, field testing, and in ground instrumentation, abutment settlement monitoring, and bridge live load (LL) testing were conducted on Bridge 2. Laboratory test results indicated that shear strength parameters and permanent deformation behavior of granular fill material improved when reinforced with geosynthetic, due to lateral restraint effect at the soilgeosynthetic interface. Bridge LL testing under static loads indicated maximum deflections close to 0.9 in and non-uniform deflections transversely across the bridge due to poor load transfer between RRFCs. The ratio of horizontal to vertical stresses in the GRS fill was low (< 0.25), indicating low lateral stress on the soil surrounding GRS fill material. Bearing capacity analysis at Bridge 2 indicated lower than recommended factor of safety (FS) values due to low ultimate reinforcement strength of the geosynthetic material used in this study and a relatively weak underlying foundation layer. Global stability analysis of the GRS abutment structure revealed a lower FS than recommended against sliding failure along the interface of the GRS fill material and the underlying weak foundation layer. Design and construction recommendations to help improve the stability and performance of the GRS abutment structures on future projects, and recommendations for future research are provided in this report.

Magnetic properties and domain-wall motion in single-crystal BaFe10.2Sn0.74Co0.66O19

The magnetic properties of BaFe12O19 and BaFe10.2Sn0.74Co0.66O19 single crystals have been investigated in the temperature range (1.8 to 320 K) with a varying field from -5 to +5 T applied parallel and perpendicular to the c axis. Low-temperature magnetic relaxation, which is ascribed to the domain-wall motion, was performed between 1.8 and 15 K. The relaxation of magnetization exhibits a linear dependence on logarithmic time. The magnetic viscosity extracted from the relaxation data, decreases linearly as temperature goes down, which may correspond to the thermal depinning of domain walls. Below 2.5 K, the viscosity begins to deviate from the linear dependence on temperature, tending to be temperature independent. The near temperature independence of viscosity suggests the existence of quantum tunneling of antiferromagnetic domain wall in this temperature range.

Evaluation of Dense Bridge Floor Concrete Using High Range Water Reducer, May 1983

The objectives of this research project are: (1) To determine the feasibility of proportioning, mixing, placing and finishing a dense portland cement concrete in a bridge floor using conventional mixing, placing and finishing equipment. (2) To determine the economics, longevity, maintenance performance and protective qualities of a dense portland cement concrete bridge floor when using a high rangewater reducing admixture. The purpose of a high range water reducing admixture is to produce a dense, high quality concrete at a low water-cement ratio witj adequate workability. A low water-cement ratio contributes greatly to increased strength. The normal 7 day strength of untreated concrete would be expected i n 3 days using a superplasticizer. A dense concrete also has the desirable properties of excellent durability and reduced permeability. It is felt that a higher quality, denser, higher strength portland cement concrete can be produced and placed, using conventional equipment, by the addition of a high range water reducing admixture. Such a dense concrete, w i t h a water/cement ratio of approximately 0.30 to 0.35, would be expected to be much less permeable and thus retard the intrusion of chloride. With care and attention given to obtaining the design cover over steel (2% inches clear), it i s hoped that protection for the design life of the structure will be obtained. Evaluation of this experimental concrete bridge floor included chloride content and delamination testing of the concrete floor five years after construction. A comparitive evaluation o f a control section o f concrete without the water reducing admixture was conducted. Other items o f comparison include workability during construction, strength, density, water-cement ratio and chloride penetration.

ZHARP: three-dimensional motion tracking from a single image plane.

Three-dimensional imaging and quantification of myocardial function are essential steps in the evaluation of cardiac disease. We propose a tagged magnetic resonance imaging methodology called zHARP that encodes and automatically tracks myocardial displacement in three dimensions. Unlike other motion encoding techniques, zHARP encodes both in-plane and through-plane motion in a single image plane without affecting the acquisition speed. Postprocessing unravels this encoding in order to directly track the 3-D displacement of every point within the image plane throughout an entire image sequence. Experimental results include a phantom validation experiment, which compares zHARP to phase contrast imaging, and an in vivo study of a normal human volunteer. Results demonstrate that the simultaneous extraction of in-plane and through-plane displacements from tagged images is feasible.

Intrathecal administration of Ziconotide: does single-shot injection predict efficacy?

Introduction: Though a trial of intrathecal (IT) therapy should always be performed before implantation of a definitive intrathecal pump, there is no agreement as to how this test should be performed. Ziconotide is trialed in most of cases with continuous IT administration using implanted catheters. Unlike other intrathecal drugs, there is little experience with single bolus IT injections of ziconotide. The aim of the study is to assess the feasibility of single-shot IT trialing with ziconotide. Patients and methods: Eleven consecutive patients with chronic neuropathic intractable pain were trialed with a single IT bolus of 2.5 mcg of ziconotide. Pain and side effects are monitored for at least 72 hours after the injection. Depending on the response, a second injection is given a week later, with either the same dose (if VAS decreased ≥50% without side effects), a higher dose of 3.75 mcg (if VAS decreased <50% without side effects) or a lower dose of 1.25 mcg (if VAS decreased ≥50% but with side effects). If VAS decreased less than 50% and side effects occurred, no further injection was performed. When VAS decreased >50% without side effects after the first or the second dose, the result is confirmed by one more injection of the same dose one week later. The trial is considered positive if two successive injections provide a VAS decreased more than 50% without side effects. Results: Eleven patients (6 females and 5 males) were included. Nine patients experienced modest or no pain relief. Four of these had significant side effects (dizziness, nausea, vomiting or abdominal pain) and had no further injection. In the others 5, one patient retired from study and four received a second injection of 3.75 mcg. The trial was negative in all 5 cases because of side effects (dizziness, drowsiness, weakness, muscle cramps), the pain decreased in only 2 patients. Two patients experienced profound pain relief with an IT injection of 2.5 mcg. One patient had no side effects and the other had dizziness and drowsiness that disappeared with an injection of 1.25 mcg. Pain relief without adverse effects was confirmed with the second injection. The trial was considered positive for those two patients. Discussion and conclusion: The response rate of 18% (2/11) is consistent with the success rate of a continuous infusion trialing with an implanted catheter. Single-shot injection of ziconotide may therefore predict efficacy.

Sediment Control in Bridge Waterways, February 1990

The objective of this study was to develop guidelines for use of the Iowa Vanes technique for sediment control in bridge waterways. Iowa Vanes are small flow-training structures (foils) designed to modify the near-bed flow pattern and redistribute flow and sediment transport within the channel cross section. The structures are installed at an angleof attack of 15 - 25' with the flow, and their initial height is 0.2 - 0.5 times water depth at design stage. The vanes function by generating secondary circulation in the flow. The circulation alters magnitude and direction of the bed shear stress and causes a reduction in velocity and sediment transport in the vane controlled area. As a result, the river bed aggrades in the vane controlled area and degrades outside. This report summarizes the basic theory, describes results of laboratory and field tests, and presents the resulting design procedure. Design graphs have been developed based on the theory. The graphs are entered with basic flow variables and desired bed topography. The output is vane layout and design. The procedure is illustrated with two numerical examples prepared with data that are typical for many rivers in Iowa and the midwest. The report also discusses vane material. In most applications, the vane height will be between 30% and 50% of bankfull flow depth and the vane length will be two to three times vane height. The vanes will be placed in arrays along the bank of the river. Each array will contain two or more vanes. The vanes in an array will be spaced laterally a distance of two to three times vane height. The streamwise spacing between the arrays will be 15 to 30 times vane height, and the vane-to-bank distance will be three to four times vane height. The study also show that the first (most upstream) array in the vane system must be located a distance of at least three array spacings upstream from the bridge, and there must be at least three arrays in the system for it to be effective at and downstream from the third array.

Automated Recording of Bridge Inspection Data in the Pontis Format Final Report, HR-364 April 1995

A large percentage of bridges in the state of Iowa are classified as structurally or fiinctionally deficient. These bridges annually compete for a share of Iowa's limited transportation budget. To avoid an increase in the number of deficient bridges, the state of Iowa decided to implement a comprehensive Bridge Management System (BMS) and selected the Pontis BMS software as a bridge management tool. This program will be used to provide a selection of maintenance, repair, and replacement strategies for the bridge networks to achieve an efficient and possibly optimal allocation of resources. The Pontis BMS software uses a new rating system to evaluate extensive and detailed inspection data gathered for all bridge elements. To manually collect these data would be a highly time-consuming job. The objective of this work was to develop an automated-computerized methodology for an integrated data base that includes the rating conditions as defined in the Pontis program. Several of the available techniques that can be used to capture inspection data were reviewed, and the most suitable method was selected. To accomplish the objectives of this work, two userfriendly programs were developed. One program is used in the field to collect inspection data following a step-by-step procedure without the need to refer to the Pontis user's manuals. The other program is used in the office to read the inspection data and prepare input files for the Pontis BMS software. These two programs require users to have very limited knowledge of computers. On-line help screens as well as options for preparing, viewing, and printing inspection reports are also available. The developed data collection software will improve and expedite the process of conducting bridge inspections and preparing the required input files for the Pontis program. In addition, it will eliminate the need for large storage areas and will simplify retrieval of inspection data. Furthermore, the approach developed herein will facilitate transferring these captured data electronically between offices within the Iowa DOT and across the state.

Autofluorescence Study In NR2E3 p.G56R-linked Autosomal Dominant Retinitis Pigmentosa In A Single Kindred

Purpose: To date, the genotype/phenotype correlation of p.G56R-linked autosomal dominant retinitis pigmentosa (ADRP) is limited to less than 10 kindred. The purpose of this study is to report an unusual appearance of fundus autofluorescence (AF) with NR2E3 p.G56R-linked ADRP in a single kindred.Methods: Patients were enrolled among three generations in a previously unreported family. Molecular diagnosis was performed on all exons of NR2E3 and a p.G56R mutation was identified in affected family members only. Examinations included fundus photography, visual fields, optical coherence tomography, AF, near-infrared AF and ISCEV-standard electrophysiology (ERG).Results: Among 10 examined family members, 5 were affected. The youngest and oldest patients were 16 and 65 years old, respectively. Fundus examination revealed a range of retinal disorder from normal to optic nerve pallor, attenuated arterial caliber and bone spicule-like pigment deposits. In all patients, AF showed a double hyperfluorescent ring; an inner paramacular ring which extension was comparable among patients and an outer ring along the vascular arcades which extended towards periphery in older patients and became hypofluorescent. Maximal scotopic ERGs when recordable showed an increased a/b wave ratio.Conclusions: A double hyperfluorescent ring on AF is an uncommon observation and might be a specific clinical finding in NR2E3 p.G56R-linked ADRP. The consistency of that finding in all affected members of our 3-generation family confirms a previous study. Further analysis is required to determine whether AF changes are associated with particular retinal layer abnormalities.

Comprehensive Bridge Deck Deterioration Mapping of Nine Bridges by Nondestructive Evaluation Technologies Final Report, January 2011

The primary objective of this research was to demonstrate the benefits of NDT technologies for effectively detecting and characterizing deterioration in bridge decks. In particular, the objectives were to demonstrate the capabilities of ground-penetrating radar (GPR) and impact echo (IE), and to evaluate and describe the condition of nine bridge decks proposed by Iowa DOT. The first part of the report provides a detailed review of the most important deterioration processes in concrete decks, followed by a discussion of the five NDT technologies utilized in this project. In addition to GPR and IE methods, three other technologies were utilized, namely: half-cell (HC) potential, electrical resistivity (ER), and ultrasonic surface waves (USW) method. The review includes a description of the principles of operation, field implementation, data analysis, and interpretation; information regarding their advantages and limitations in bridge deck evaluations and condition monitoring are also implicitly provided.. The second part of the report provides descriptions and bridge deck evaluation results from the nine bridges. The results of the NDT surveys are described in terms of condition assessment maps and are compared with the observations obtained from the recovered cores or conducted bridge deck rehabilitation. Results from this study confirm that the used technologies can provide detailed and accurate information about a certain type of deterioration, electrochemical environment, or defect. However, they also show that a comprehensive condition assessment of bridge decks can be achieved only through a complementary use of multiple technologies at this stage,. Recommendations are provided for the optimum implementation of NDT technologies for the condition assessment and monitoring of bridge decks.