In vitro and in vivo evaluation of sunitinib eluting beads

Background: Chemoembolization is used to treat liver malignancies. However recurrence occurs frequently, possibly because of neoangiogenesis triggered by ischemia caused by the embolic agent. In this context, the combination of an embolic agent with an anti-angiogenic drug seems appealing. This study characterizes the in vitro loading and release profile of sunitinib eluting beads of different sizes and their pharmacokinetic profile in a rabbit model. Methods: 70-150 μm and 100-300 μm drug eluting beads (DC Bead, Biocompatibles UK) were loaded by incubation in a sunitinib hydrochloride solution. Drug was quantified by spectrophotometry at 430 nm. Drug release was measured over one-week periods and normalized using an internal standard in 30% ethanol in NaCl 0.9%. New-Zealand white rabbits were used. Eight animals received 0.2 ml of 100-300 μm DC Bead loaded with 6 mg of sunitinib in the hepatic artery (group 1) and 4 animals received 6 mg of sunitinib p.o. (group 2). Half of the animals were sacrificed after 6 hours and half after24 hours. Liver enzymes were measured at 0, 6 and 24 hours in both groups. Plasmatic sunitinib concentration was determined by tandem mass spectroscopy (LC MS/MS) at 0, 1, 2, 3, 4, 5, 6 and 24 hours. At sacrifice, the livers were harvested and sunitinib concentration in liver tissue was assessed by LC MS/MS. Results: High drug loading was obtained for both microsphere bead sizes. Particle shrinking was observed with adsorption of sunitinib. Almost complete release of sunitinib was detected under physiological conditions, with very similar release for 70-150 μm and 100-300 μm (t50%=1.2 h) DC Bead. Conclusions: Sunitinib eluting beads are well tolerated by rabbits when administered in the hepatic artery. No unexpected toxicity was observed. Very high drug concentration can be obtained at the site of embolization with minimal systemic passage.

08019-011 Staff Beaver Creek Final Report

Staff and Beaver Creeks are two tributaries of the Upper Iowa River (UIR). Additional acres that drain directly into the UIR bring the size of the project area to 41,328 acres. The goal of the project is to reduce sediment loading and excess nutrients from reaching the streams which ultimately reach the UIR. Staff/Beaver Water Quality Project initially received funding as part of the FY 2005 WSPF/319 grant application cycle. Tremendous progress has been accomplished towards the original goals of the project. Due to the large number of Best Management Practices (BMPs) installed and the continued high interest for those practices, more work remains to be done. The heavy rains received in 2008 caused severe erosion and has dramatically increased interest in conservation practices. A thorough watershed assessment was completed in the fall of 2008. Data from this assessment indicates additional work is needed. The initial grant funding will be exhausted within fiscal year 2009. Therefore, the Howard Soil and Water Conservation District is seeking 3 years of funding. The District believes interest in the water quality project is at an all time high and that with an additional three years of funding, even more progress can be achieved in reducing sediment delivery and excess nutrients to these priority streams.

Assessment of Asphalt Interlayer Designed on Jointed Concrete, InTrans Project 13-475, 2014

Reflective cracking in hot mix asphalt (HMA) overlays has been a common cause of poor pavement performance in Iowa for many years. Reflective cracks commonly occur in HMA overlays when deteriorated portland cement concrete is paved over with HMA. This results in HMA pavement surfaces with poor ride quality and increased transportation maintenance costs. To delay the formation of cracks in HMA overlays, the Iowa Department of Transportation (Iowa DOT) has begun to implement a crack-relief interlayer mix design specification. The crack-relief interlayer is an asphalt-rich, highly flexible HMA that can resist cracking in high strain loading conditions. In this project, the field performance of an HMA overlay using a one inch interlayer was compared to a conventional HMA overlay without an interlayer. Both test sections were constructed on US 169 in Adel, Iowa as part of an Iowa DOT overlay project. The laboratory performance of the interlayer mix design was assessed for resistance to cracking from repeated strains by using the four-point bending beam apparatus. An HMA using a highly polymer modified binder was designed and shown to meet the laboratory performance test criteria. The field performance of the overlay with the interlayer exceeded the performance of the conventional overlay that did not have the interlayer. After one winter season, 29 percent less reflective cracking was measured in the pavement section with the interlayer than the pavement section without the interlayer. The level of cracking severity was also reduced by using the interlayer in the overlay.

Rapid Replacement of Bridge Deck Expansion Joints Study – Phase I, RB33-013, 2014

Bridge deck expansion joints are used to allow for movement of the bridge deck due to thermal expansion, dynamics loading, and other factors. More recently, expansion joints have also been utilized to prevent the passage of winter de-icing chemicals and other corrosives applied to bridge decks from penetrating and damaging substructure components of the bridge. Expansion joints are often one of the first components of a bridge deck to fail and repairing or replacing expansion joints are essential to extending the life of any bridge. In the Phase I study, the research team focused on the current means and methods of repairing and replacing bridge deck expansion joints. Research team members visited with Iowa Department of Transportation (DOT) Bridge Crew Leaders to document methods of maintaining and repairing bridge deck expansion joints. Active joint replacement projects around Iowa were observed to document the means of replacing expansion joints that were beyond repair, as well as, to identify bottlenecks in the construction process that could be modified to decrease the length of expansion joint replacement projects. After maintenance and replacement strategies had been identified, a workshop was held at the Iowa State Institute for Transportation to develop ideas to better maintain and replace expansion joints. Maintenance strategies were included in the discussion as a way to extend the useful life of a joint, thus decreasing the number of joints replaced in a year and reducing the traffic disruptions.

Implantació d'un sistema SCADA en una cèl·lula flexible de fabricació

La Universitat de Vic disposa, entre altres equips, d’una cèl·lula flexible de fabricació, del fabricant Festo, que simula un procés de formació de palets amb els productes que es disposen en un magatzem intermedi. Aquesta cèl·lula està composta de quatre estacions de muntatge diferenciades (càrrega de palets, càrrega de plaques, magatzem intermedi i transport). Cada una disposa d'un PLC SIEMENS S7-300 per la seva automatització, i tots aquests es troben interconnectats amb una xarxa industrial Profibus. L'objectiu d'aquest projecte és implantar el sistema SCADA Vijeo Citect pel control i supervisió de l'estació magatzem d'aquesta cèl·lula flexible de fabricació, establint també un intercanvi de dades entre l'SCADA i el Microsoft Access, per poder ser utilitzat per la docència. Aquest projecte s'ha desenvolupat en cinc fases diferents: 1. La primera fase s'ha dedicat a l'automatització pròpiament de l'estació magatzem a partir de l'autòmat programable Siemens S7-300 i complint amb les necessitats plantejades. 2. En la segona fase s'ha programat i establert la comunicació per l'intercanvi de dades (lectura i escriptura) entre el sistema SCADA Vijeo Citect i la base de dades de Microsoft Access. 3. En la tercera fase s'ha elaborat i programat l'entorn gràfic de supervisió i control del procés a partir del sistema SCADA Vijeo Citect. 4. En la quarta fase s'ha instal·lat un OPC Server en el PC i s'ha establert la comunicació entre el PLC i el sistema SCADA. 5. Finalment s'ha anat revisant i depurant les diferents programacions i comunicacions per tal de que el sistema funcioni com a un conjunt.

A regulatory role for the cohesin loader NIPBL in nonhomologous end joining during immunoglobulin class switch recombination.

DNA double strand breaks (DSBs) are mainly repaired via homologous recombination (HR) or nonhomologous end joining (NHEJ). These breaks pose severe threats to genome integrity but can also be necessary intermediates of normal cellular processes such as immunoglobulin class switch recombination (CSR). During CSR, DSBs are produced in the G1 phase of the cell cycle and are repaired by the classical NHEJ machinery. By studying B lymphocytes derived from patients with Cornelia de Lange Syndrome, we observed a strong correlation between heterozygous loss-of-function mutations in the gene encoding the cohesin loading protein NIPBL and a shift toward the use of an alternative, microhomology-based end joining during CSR. Furthermore, the early recruitment of 53BP1 to DSBs was reduced in the NIPBL-deficient patient cells. Association of NIPBL deficiency and impaired NHEJ was also observed in a plasmid-based end-joining assay and a yeast model system. Our results suggest that NIPBL plays an important and evolutionarily conserved role in NHEJ, in addition to its canonical function in sister chromatid cohesion and its recently suggested function in HR.

The Flexural Fatigue Strength of Prestressed Steel I-Beams, HR-73, 1962

The purpose of this investigation was to study the flexural fatigue strength of two prestressed steel I-beams which had previously been fabricated in connection with a jointly sponsored project under the auspices of the Iowa State Highway Commission. The beams were prestressed by deflecting them under the action of a concentrated load at the center of a simple span, then welding unstressed high strength steel plates to the top and bottom flanges to retain a predetermined amount of prestress. The beams were rolled sections of A36 steel and the plates were USS "T-1" steel. Each of the two test specimens were subjected to an identical repeated loading until a fatigue failure occurred. The loading was designed to produce stresses equivalent to those which would have occurred in a simulated bridge and amounted to 84 percent of a standard H-15 live load including impact. One of the beams sustained 2,469,100 repetitions of load to failure and the other sustained 2,756,100 cycles. Following the fatigue tests, an experimental study was made to determine the state of stress that had been retained in the prestressed steel beams. This information, upon which the calculated stresses of the test could be superimposed, provided a method of correlating the fatigue strength of the beams with the fatigue information available on the two steels involved.

Live Load Deflections in a Prestressed Steel Beam Bridge, HR-74, 1963

This report describes the measurement of dynamic (live load) deflections in a 240' x 30' three span continuous prestressed steel bridge, skewed 30 degrees. The design assumptions and prestressing procedure are described briefly, and the instrumentation and loading are discussed. The actual deflections are presented in tabular form, and the deflections due to the design live load are calculated. The maximum deflections are presented as a ratio of the span length, and the further use of prestressed steel beams is recommended.

Intravitreal ranibizumab for AMD : the individual rhythm of OCT guided retreatment intervals

Purpose: We intended to determine whether the need for retreatmentwith intravitreal ranibizumab follows an individual rhythm in patientswith exudative AMD. Setting: Prospective mono-centre cohort study.Methods: Prospective study. 48 patients with exudative AMD. 3 loadingdoses of ranibizumab, followed by a 12 months PRN regimen guided byearly exudative signs on SD-OCT. An intensified follow-up allowed todetect recurrences early.Results:Mean VA improved by 6.4 letters at month 3 and by 13.1 letters atmonth 12, with a mean of 8.0 injections (range 0-12) during the maintenancephase. The intra-individual variance of the intervals was relativelysmall and ranged within 20% of themean interval in 91% of patients.Thefirst interval was within 1 week of the mean interval in 84% of patients.The retreatment criteria were stable in 89% of patients.Conclusion: The relative stability of the intra-individual intervalsmay allowsimplifying the care for AMDpatients.Theremay be a predictive role for thefirst interval after the loading phase. The functional results of this PRNregimenwith early retreatmentwere excellent. Financial disclosure:None.

Design of Piles for Integral Abutment Bridges, HR-252, 1984

More and more, integral abutment bridges are being used in place of the more traditional bridge designs with expansion releases. In this study, states which use integral abutment bridges were surveyed to determine their current practice in the design of these structures. To study piles in integral abutment bridges, a finite element program for the soil-pile system was developed (1) with materially and geometrically nonlinear, two and three dimensional beam elements and (2) with a nonlinear, Winkler soil model with vertical, horizontal, and pile tip springs. The model was verified by comparison to several analytical and experimental examples. A simplified design model for analyzing piles in integral abutment bridges is also presented. This model grew from previous analytical models and observations of pile behavior. The design model correctly describes the essential behavioral characteristics of the pile and conservatively predicts the vertical load-carrying capacity. Analytical examples are presented to illustrate the effects of lateral displacements on the ultimate load capacity of a pile. These examples include friction and end-bearing piles; steel, concrete, and timber piles; and bending about the weak, strong, and 45° axes for H piles. The effects of cyclic loading are shown for skewed and nonskewed bridges. The results show that the capacity of friction piles is not significantly affected by lateral displacements, but the capacity of end-bearing piles is reduced. Further results show that the longitudinal expansion of the bridge can introduce a vertical preload on the pile.

Investigation of High Performance Concrete Pavement, MLR-05-01, 2006

The Iowa DOT has been using blended cements in ternary mixes since 1999. Use of these supplementary cementitious materials gives concrete with higher strengths and much lower permeability. Use of these materials has been incorporated for use in High Performance Concrete (HPC) decks to achieve lower permeability and thus long term performance. Since we have been using these materials in paving, it would be informative to determine what concrete pavement properties are enhanced as related to high performance concrete. The air void system was excellent at a spacing factor of 0.0047 in (0.120 mm). AVA spacing factor results are much higher than the hardened air void analysis. Although only 3 samples were tested between the image analysis air content and the RapidAir457, there is pretty good agreement between those test methods. Air void analysis indicates that excessive vibration was not required to place the concrete. Vibration was well within the specification limits with an average of 6683 vpm’s with a standard deviation of 461. Overall ride of the project was very good. The average smoothness for the project was 2.1 in/mile (33.8 mm/km). The International Roughness Index (IRI) was 81 in/mi (1.29 m/km). The compressive strength was 6260 psi (43.2 MPa) at 28 days and 6830 (47.1 MPa) at 56 days. The modulus of rupture by third point loading (MOR-TPL) tested at 28 days was 660 psi (4.55 MPa). The AASHTO T277 rapid chloride permeability results at 28 days using the Virginia cure method correlate fairly well with the 56 and 90 day results with standard curing. The Virginia cure method 28 day results were 2475 coulombs and the standard cure 56 and 90 day test results were 2180 and 2118, respectively.

Evaluation of PCC Specification Changes Impact on Durability: 1992 - 1997 Core Study, MLR-98-06, 2005

In 1990, early distress had shown up on US 20 in Hamilton/Webster counties, three years after paving. Since that time, over a dozen more projects, constructed between 1984 and 1994, have been found to exhibit similar early distress. Several changes to the concrete and Portland cement specifications occurred in 1994 and 1996. This study was undertaken to investigate in place concrete pavements before and after specification changes were implemented. The objective of this research is to evaluate the impact of Portland cement and concrete specification changes made in 1994 and 1996 on PCC durability. Cores were obtained in 1998 and 2003 from projects constructed in 1992, before specification changes, and 1997 after specification changes. The following is a brief summary of the conclusions: 1. The pavements in the study constructed under the new specifications are performing much better after 5 years of service than the pavements constructed under the old specifications. 2. According to ISU, micro-cracking is evident in all concrete that has been in service, due to thermal stresses and loading stresses. Also, the low vacuum SEM will desiccate the concrete enough to cause micro-cracking. The SEM should not be used as a tool to indicate micro-cracking. 3. Use of Type II cement (C3A <8%) and a 3.0% SO3 limit does not completely eliminate ettringite infilling in air voids, as indicated in the bottom of the 1997 cores. 4. In areas of high moisture (bottom of the core), infilling is present in most of the 1997 cores. 5. Low air content and high spacing factor in the top of 1992 cores apparently causes F/T cycling cracking and then increased moisture paths from cracking causes infilling. 6. Use of ground granulated blast furnace slag (GGBFS) and fly ash reduces ettringite infilling either by diluting the aluminate (C3A) or lowering permeability, which slows ingress of moisture. 7. The specification changes that made the biggest impact on pavement durability are the limits on vibration and increase in air content in September 1994. 8. Investigations of cores from pavements placed in 2002 and 2003 indicate improved air contents and spacing factors. In-place air content and spacing factors should be monitored to determine if appropriate air void parameters are being met.

Development of Bridge Load Testing Process for Load Evaluation, TR-445, 2003

Recent reports indicate that of the over 25,000 bridges in Iowa, slightly over 7,000 (29%) are either structurally deficient or functionally obsolete. While many of these bridges may be strengthened or rehabilitated, some simply need to be replaced. Before implementing one of these options, one should consider performing a diagnostic load test on the structure to more accurately assess its load carrying capacity. Frequently, diagnostic load tests reveal strength and serviceability characteristics that exceed the predicted codified parameters. Usually, codified parameters are very conservative in predicting lateral load distribution characteristics and the influence of other structural attributes. As a result, the predicted rating factors are typically conservative. In cases where theoretical calculations show a structural deficiency, it may be very beneficial to apply a "tool" that utilizes a more accurate theoretical model which incorporates field-test data. At a minimum, this approach results in more accurate load ratings and many times results in increased rating factors. Bridge Diagnostics, Inc. (BDI) developed hardware and software that are specially designed for performing bridge ratings based on data obtained from physical testing. To evaluate the BDI system, the research team performed diagnostic load tests on seven "typical" bridge structures: three steel-girder bridges with concrete decks, two concrete slab bridges, and two steel-girder bridges with timber decks. In addition, a steel-girder bridge with a concrete deck previously tested and modeled by BDI was investigated for model verification purposes. The tests were performed by attaching strain transducers on the bridges at critical locations to measure strains resulting from truck loading positioned at various locations on the bridge. The field test results were used to develop and validate analytical rating models. Based on the experimental and analytical results, it was determined that bridge tests could be conducted relatively easy, that accurate models could be generated with the BDI software, and that the load ratings, in general, were greater than the ratings, obtained using the codified LFD Method (according to AASHTO Standard Specifications for Highway Bridges).

Laboratory Performance Evaluation of CIR-Emulsion and its Comparison Against CIR-Foam Test Results from Phase 2, TR-474, 2009

Currently, no standard mix design procedure is available for CIR-emulsion in Iowa. The CIR-foam mix design process developed during the previous phase is applied for CIR-emulsion mixtures with varying emulsified asphalt contents. Dynamic modulus test, dynamic creep test, static creep test and raveling test were conducted to evaluate the short- and long-term performance of CIR-emulsion mixtures at various testing temperatures and loading conditions. A potential benefit of this research is a better understanding of CIR-emulsion material properties in comparison with those of CIR-foam material that would allow for the selection of the most appropriate CIR technology and the type and amount of the optimum stabilization material. Dynamic modulus, flow number and flow time of CIR-emulsion mixtures using CSS- 1h were generally higher than those of HFMS-2p. Flow number and flow time of CIR-emulsion using RAP materials from Story County was higher than those from Clayton County. Flow number and flow time of CIR-emulsion with 0.5% emulsified asphalt was higher than CIR-emulsion with 1.0% or 1.5%. Raveling loss of CIR-emulsion with 1.5% emulsified was significantly less than those with 0.5% and 1.0%. Test results in terms of dynamic modulus, flow number, flow time and raveling loss of CIR-foam mixtures are generally better than those of CIR-emulsion mixtures. Given the limited RAP sources used for this study, it is recommended that the CIR-emulsion mix design procedure should be validated against several RAP sources and emulsion types.

Feasibility Investigation of Segmentally Precast Bridge Piers for Accelerated Construction, TR-556, 2009

An innovative structural system for pier columns was investigated through a series of laboratory experiments. The columns and connections examined were comprised of precast concrete segments to accelerate construction. In addition some of the columns employed unbonded post-tensioning to self-center the columns when subjected to lateral loads and structural fuses to control large lateral deflections, dissipate energy, and expedite repair in the event of a catastrophic loading event. Six cantilever columns with varying component materials and connection details were subjected to a regimen of vertical dead loads and cyclic, quasi-static lateral loads. One column was designed as a control column to represent the behavior of a conventional reinforced concrete column and provide a basis for comparison with the remaining five jointed columns designed with the proposed structural system. After sustaining significant damage, the self-centering, jointed columns were repaired by replacing the structural fuses and retested to failure to investigate the effectiveness of the repair. The experiments identified both effective and unsatisfactory details for the jointed system. Two of the jointed columns demonstrated equivalent lateral strength, greater lateral stiffness, and greater lateral deformation capacity than the control column. The self-centering capability of the jointed columns was clearly demonstrated as well, and the repair technique proved effective as demonstrated by nearly identical pre and post repair behavior. The authors believe the proposed system to be a feasible alternative to conventional pier systems and recommend further development of details.