Mitomycin C with continuous fluorouracil or with cisplatin in combination with radiotherapy for locally advanced anal cancer (European Organisation for Research and Treatment of Cancer phase II study 22011-40014).

PURPOSE: To assess the feasibility and activity of radio-chemotherapy with mitomycin C (MMC) and cisplatin (CDDP) in locally advanced squamous cell anal carcinoma with reference to radiotherapy (RT) combined with MMC and fluorouracil (5-FU). PATIENTS AND METHODS: Patients with measurable disease >4 cmN0 or N+ received RT (36Gy+2 week gap+23.4Gy) with either MMC/CDDP or MMC/5-FU (MMC 10mg/m(2) d1 of each sequence; 5-FU 200mg/m(2)/day c.i.v. daily; CDDP 25mg/m(2) weekly). Forty patients/arm were needed to exclude a RECIST objective response rate (ORR), 8 weeks after treatment, of <75% (Fleming 1, alpha=10%, beta=10%). RESULTS: The ORR was 79.5% (31/39) (lower bound confidence interval [CI]: 68.8%) with MMC/5-FU versus 91.9% (34/ 37) (lower bound CI: 82.8%) with MMC/CDDP. In the MMC/5-FU group, two patients (5.1%) discontinued treatment due to toxicity versus 11 (29.7%) in the MMC/CDDP group. Nine grade 3 haematological events occurred with MMC/CDDP versus none with 5-FU/MMC. The rate of other toxicities did not differ. There was no toxic death. Thirty-one patients in the MMC/5-FU arm (79.5%) and 18 in the MMC/CDDP arm (48.6%) were fully compliant with the protocol treatment (p=0.005). CONCLUSIONS: Radio-chemotherapy with MMC/CDDP seems promising as only MMC/CDDP demonstrated enough activity (RECIST ORR >75%) to be tested further in phase III trials; MMC/5-FU did not. MMC/CDDP also had an overall acceptable toxicity profile.

Evaluation des Nationalen Krebsbekämpfungsprogrammes, Phase I, 1999. Studie 2: Inventar der vorhandenen Datenquellen und Indikatoren

[Table des matières] 1. Allgemeine Schlussforschungen und Empfehlungen. 2. Einleitung. 3. Methodik. 4. Ergebnisse. 4.1. Zentrale Datenquellen : Kontinuierliche und periodische Erhabungen, Mortalitätsstatistik, Spitalstatistik, Vereinigung Schweizerischer Krebsregister, Schweizerische Gesundheitsbefragung, Trendstudie zum Konsum von Alkohol, Tabak, Medikamenten und illegalen Drogen SFA, SChülerbefragung SFA, Warenkorb BFS, Schweizer Haushalt-Panel, Traditioneller Haushaltspanel IHA-GfM, Pharmaabsatzzahlen IHA-GfM, Sonnenexposition und Sonnenschutz, Indikatoren für den Tabakkonsum in der Schweiz, Statistische Erhebungen und Schätzungen über Landwirtschaft und Ernährung, Participants' Report SIAK, Trial guide SAKK, Guidelines, Berufskrankheiten SUVA, Krebstelefon SKL. 4.2. Weitere Datenquellen : Kontinuierliche und periodische Erhebungen, Statistik der verteilten Broschüren SKL, Jahresbericht von im Bereich Krebs tätigen Institutionen, Invalidenversicherung BSV, Andere Statistiken des BSV, Konkordat der Schweizerischen Krankenversicherer, Nestlé-Studie. 4.3. Zentrale Einzelerhebungen : Frauen und Krebs, Vorstudie für eine nationale Kampagne zur Früherfassung des kolorektalen Karzinoms, Ausmass und Intensität von Krebsschmerzen in der Schweiz. 4.4. Weitere Einzelerhebungen : IUMSP : die Gesundheit Jugendlicher in der Schweiz, Stillhäufigkeit und Stilldauer in der Schweiz 1994, Kohortenstudie Alkohol- und Drogenkonsum SFA. 4.5. Abgeschlossene Erhebungen : Krebsvorsorge, MONICA-Studie und Basler Ernährungsstudie. 5. Schlussfolgerungen und Empfehlungen : Zusammenfassende Schlussfolgerungen und Empfehlungen. 6. Anhang. 6.1. Zentrale Datenquellen im Uberblick : Globalkonzept, Brustkrebsprogramm, Lungenkrebsprogramm, Hautkrebsprogramm, Darmkrebsprogramm. 6.2. Zieltabelle : formulierte Ziele des nationalen Krebsbekämpfungsprogramms. 6.3. Abkürzungen.

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.

Development of Quality Standards for Inclusion of High Recycled Asphalt Pavement Content in Asphalt Mixtures – Phase II, TR-658, 2015

To conserve natural resources and energy, the amount of recycled asphalt pavement has been steadily increasing in the construction of asphalt pavements. The objective of this study is to develop quality standards for inclusion of high RAP content. To determine if the higher percentage of RAP materials can be used on Iowa’s state highways, three test sections with target amounts of RAP materials of 30%, 35% and 40% by weight were constructed on Highway 6 in Iowa City. To meet Superpave mix design requirements for mixtures with high RAP contents, it was necessary to fractionate the RAP materials. Three test sections with actual RAP materials of 30.0%, 35.5% and 39.2% by weight were constructed and the average field densities from the cores were measured as 95.3%, 94.0%, and 94.3%, respectively. Field mixtures were compacted in the laboratory to evaluate moisture sensitivity using a Hamburg Wheel Tracking Device. After 20,000 passes, rut depths were less than 3mm for mixtures obtained from three test sections. The binder was extracted from the field mixtures from each test section and tested to identify the effects of RAP materials on the performance grade of the virgin binder. Based on Dynamic Shear Rheometer and Bending Beam Rheometer tests, the virgin binders (PG 64-28) from test sections with 30.0%, 35.5% and 39.2% RAP materials were stiffened to PG 76-22, PG 76-16, and PG 82-16, respectively. The Semi-Circular Bending (SCB) test was performed on laboratory compacted field mixtures with RAP amounts of 30.0%, 35.5% and 39.2% at two different temperatures of -18 and -30 °C. As the test temperature decreased, the fracture energy decreased and the stiffness increased. As the RAP amount increased, the stiffness increased and the fracture energy decreased. Finally, a condition survey of the test sections was conducted to evaluate their short-term pavement performance and the reflective transverse cracking did not increase as RAP amount was increased from 30.0% to 39.2%.

Spreading due to heterogeneity in two-phase flow

Postprint (published version)

Efficacy and safety of a phospholipid emulsion (GR270773) in Gram-negative severe sepsis: results of a phase II multicenter, randomized, placebo-controlled, dose-finding clinical trial.

OBJECTIVE: To assess the survival benefit and safety profile of low-dose (850 mg/kg) and high-dose (1350 mg/kg) phospholipid emulsion vs. placebo administered as a continuous 3-day infusion in patients with confirmed or suspected Gram-negative severe sepsis. Preclinical and ex vivo studies show that lipoproteins bind and neutralize endotoxin, and experimental animal studies demonstrate protection from septic death when lipoproteins are administered. Endotoxin neutralization correlates with the amount of phospholipid in the lipoprotein particles. DESIGN: A three-arm, randomized, blinded, placebo-controlled trial. SETTING: Conducted at 235 centers worldwide between September 2004 and April 2006. PATIENTS: A total of 1379 patients participated in the study, 598 patients received low-dose phospholipid emulsion, and 599 patients received placebo. The high-dose phospholipid emulsion arm was stopped, on the recommendation of the Independent Data Monitoring Committee, due to an increase in life-threatening serious adverse events at the fourth interim analysis and included 182 patients. MEASUREMENTS AND MAIN RESULTS: A 28-day all-cause mortality and new-onset organ failure. There was no significant treatment benefit for low- or high-dose phospholipid emulsion vs. placebo for 28-day all-cause mortality, with rates of 25.8% (p = .329), 31.3% (p = .879), and 26.9%, respectively. The rate of new-onset organ failure was not statistically different among groups at 26.3%, 31.3%, 20.4% with low- and high-dose phospholipid emulsion, and placebo, respectively (one-sided p = .992, low vs. placebo; p = .999, high vs. placebo). Of the subjects treated, 45% had microbiologically confirmed Gram-negative infections. Maximal changes in mean hemoglobin levels were reached on day 10 (-1.04 g/dL) and day 5 (-1.36 g/dL) with low- and high-dose phospholipid emulsion, respectively, and on day 14 (-0.82 g/dL) with placebo. CONCLUSIONS: Treatment with phospholipid emulsion did not reduce 28-day all-cause mortality, or reduce the onset of new organ failure in patients with suspected or confirmed Gram-negative severe sepsis.

Evaluating Roadway Subsurface Drainage Practices - Phase II, TR-662, 2015

Well-performing subsurface drainage systems form an important aspect of pavement design by the Iowa Department of Transportation (DOT). The recently completed Iowa Highway Research Board (IHRB) project TR-643 provided extensive insights into Iowa subsurface drainage practices and pavement subdrain outlet performance. However, the project TR-643 (Phase I) forensic testing and evaluation were carried out in a drought year and during the fall season in 2012. Based on the findings of IHRB Project TR-643, the Iowa DOT requested an expanded Phase II study to address several additional research needs: evaluate the seasonal variation effects (dry fall 2012 versus wet spring/summer 2013, etc.) on subdrain outlet condition and performance; investigate the characteristics of tufa formation in Iowa subdrain outlets; investigate the condition of composite pavement subdrain outlets; examine the effect of resurfacing/widening/rehabilitation on subdrain outlets (e.g., the effects of patching on subdrain outlet performance); and identify a suitable drain outlet protection mechanism (like a headwall) and design for Iowa subdrain outlets based on a review of practices adopted by nearby states. A detailed forensic test plan was developed and executed for inspecting the Iowa pavement subdrains in pursuit of fulfilling the Phase II study objectives. The observed outlets with blockage and the associated surface distresses in newly constructed jointed plain concrete pavements (JPCPs) were slightly higher during summer 2013 compared to fall 2012. However, these differences are not significant. Less tufa formation due to the recycled portland cement concrete (RPCC) base was observed with (a) the use of plastic outlet pipe without the gate screen–type rodent guard and (b) the use of blended RPCC and virgin aggregate materials. In hot-mix asphalt (HMA) over JPCP, moisture-related distress types (e.g., reflection cracking) were observed more near blocked drainage outlet locations than near “no blockage” outlet locations. This finding indicates that compromised drainage outlet performance could accelerate the development of moisture-related distresses in Iowa composite pavement systems. ****** Note: This report follows on work report in "Evaluating Roadway Subsurface Drainage Practices, 2013" http://publications.iowa.gov/14902/ Note: This record contains links to the 210 page full report as well as the 3 page tech transfer summary. The summary is NOT deposited separately.

Preoperative hyperfractionated accelerated radiotherapy (HART) and concomitant CPT-11 in locally advanced rectal carcinoma: a phase I study.

PURPOSE: Patients with locally advanced rectal carcinoma are at risk for both local recurrence and distant metastases. We demonstrated the efficacy of preoperative hyperfractionated accelerated radiotherapy (HART). In this Phase I trial, we aimed at introducing chemotherapy early in the treatment course with both intrinsic antitumor activity and a radiosensitizer effect. METHODS AND MATERIALS: Twenty-eight patients (19 males; median age 63, range 28-75) with advanced rectal carcinoma (cT3: 24; cT4: 4; cN+: 12; M1: 5) were enrolled, including 8 patients treated at the maximally tolerated dose. Escalating doses of CPT-11 (30-105 mg/m(2)/week) were given on Days 1, 8, and 15, and concomitant HART (41.6 Gy, 1.6 Gy bid x 13 days) started on Day 8. Surgery was to be performed within 1 week after the end of radiochemotherapy. RESULTS: Twenty-six patients completed all preoperative radiochemotherapy as scheduled; all patients underwent surgery. Dose-limiting toxicity was diarrhea Grade 3 occurring at dose level 6 (105 mg/m(2)). Hematotoxicity was mild, with only 1 patient experiencing Grade 3 neutropenia. Postoperative complications (30 days) occurred in 7 patients, with an anastomotic leak rate of 22%. CONCLUSIONS: The recommended Phase II dose of CPT-11 in this setting is 90 mg/m(2)/week. Further Phase II exploration at this dose is warranted.

Effects of Cement on Moisture Migration in Concrete, Phase A, Laboratory Study of Moisture Migration in Hardened Cement Paste, HR-141, 1972

The Columbus Laboratories of Battelle Memorial Institute is currently conducting a study of the effect of cement on moisture migration in concrete as related to the problem of D-cracking of portland cement concrete pavements. The study began on December 31, 1970, and is planned as a 3-year program. The work plan, approved by the policy committee of the members of the Iowa, Kansas, and Missouri highway departments and the Federal Highway Administration, is composed of four parts. The first phase (A) of the investigation concerned the movement of moisture into and from hardened cement pastes and the dimensional changes accompanying the moisture changes. Small slab specimens of hardened neat cement pastes were prepared from 32 different cements which were prepared at the same water/cement ratio and hydrated to the same maturity factor.

Development of a Conductometric Test for Frost Resistance of Concrete, HR-272, Phase II, 1986

The purpose of this report is to describe the major research activities during the period of February 1, 1985 - October 30, 1986 for the Iowa Highway Research Board under the research contract entitled "Development of a Conductometric Test for Frost Resistance of Concrete." The objective of this research, as stated in the project proposal, is to develop a test method which can be reasonably rapidly performed in the laboratory and in the field to predict the behavior of concrete subjected to the action of alternate freezing and thawing with a high degree of certainty. In the work plan of the proposal it was stated that the early part of the first year would be devoted to construction of testing equipment and preparation of specimens and the remainder of the year would be devoted to the testing of specimens. It was also stated that the second and third years would be devoted to performance and refinements of tests, data analysis, preparation of suggested specifications, and performance of tests covering variables which need to be studied such as types of aggregates, fly ash replacements and other admixtures. The objective of this report is to describe the progress made during the first 20 months of this project and assess the significance of the results obtained thus far and the expected significance of the results obtainable during the third year of the project.

Design Methodology for Corrugated Metal Pipe Tiedowns, HR-332, Phase 1, 1993

Questionnaires were sent to transportation agencies in all 50 states in the U.S., to Puerto Rico, and all provinces in Canada asking about their experiences with uplift problems of - corrugated metal pipe (CMP). Responses were received from 52 agencies who reported 9 failures within the last 5 years. Some agencies also provided design standards for tiedowns to resist uplift. There was a wide variety in restraining forces used; for example for a pipe 6 feet in diameter, the resisting force ranged from 10 kips to 66 kips. These responses verified the earlier conclusion based on responses from Iowa county engineers that a potential uplift danger exists.when end restraint is not provided for CMP and that existing designs have an unclear theoretical or experimental basis. In an effort to develop more rational design standards, the longitudinal stiffness of three CMP ranging from 4 to 8 feet in diameter were measured in the laboratory. Because only three tests were conducted, a theoretical model to evaluate the stiffness of pipes of a variety of gages and corrugation geometries was also developed. The experimental results indicated a "stiffness" EI in the range of 9.11 x 10^5 k-in^2 to 34.43 x 10^5 k-in^2 for the three pipes with the larger diameter pipes having greater stiffness. The theoretical model developed conservatively estimates these stiffnesses.

Design Methodology for Corrugated Metal Pipe Tiedowns, HR-362, Phase II, 1995

This investigation is the final phase of a three part study whose overall objectives were to determine if a restraining force is required to prevent inlet uplift failures in corrugated metal pipe (CMP) installations, and to develop a procedure for calculating the required force when restraint is required. In the initial phase of the study (HR-306), the extent of the uplift problem in Iowa was determined and the forces acting on a CMP were quantified. In the second phase of the study (HR- 332), laboratory and field tests were conducted. Laboratory tests measured the longitudinal stiffness ofCMP and a full scale field test on a 3.05 m (10 ft) diameter CMP with 0.612 m (2 ft) of cover determined the soil-structure interaction in response to uplift forces. Reported herein are the tasks that were completed in the final phase of the study. In this phase, a buried 2.44 m (8 ft) CMP was tested with and without end-restraint and with various configurations of soil at the inlet end of the pipe. A total of four different soil configurations were tested; in all tests the soil cover was constant at 0.61 m (2 ft). Data from these tests were used to verify the finite element analysis model (FEA) that was developed in this phase of the research. Both experiments and analyses indicate that the primary soil contribution to uplift resistance occurs in the foreslope and that depth of soil cover does not affect the required tiedown force. Using the FEA, design charts were developed with which engineers can determine for a given situation if restraint force is required to prevent an uplift failure. If an engineer determines restraint is needed, the design charts provide the magnitude of the required force. The design charts are applicable to six gages of CMP for four flow conditions and two types of soil.

Investigation of Plastic Pipes for Highway Applications, HR-373A, Phase II, 1997

It is generally accepted that high density polyethylene pipe (HDPE) performs well under live loads with shallow cover, provided the backfill is well compacted. Although industry standards require carefully compacted backfill, poor inspection and/or faulty construction may result in soils that provide inadequate restraint at the springlines of the pipes thereby causing failure. The objectives of this study were: 1) to experimentally define a lower limit of compaction under which the pipes perform satisfactorily, 2) to quantify the increase in soil support as compaction effort increases, 3) to evaluate pipe response for loads applied near the ends of the buried pipes, 4) to determine minimum depths of cover for a variety of pipes and soil conditions by analytically expanding the experimental results through the use of the finite element program CANDE. The test procedures used here are conservative especially for low-density fills loaded to high contact stresses. The failures observed in these tests were the combined effect of soil bearing capacity at the soil surface and localized wall bending of the pipes. Under a pavement system, the pipes' performance would be expected to be considerably better. With those caveats, the following conclusions are drawn from this study. Glacial till compacted to 50% and 80% provides insufficient support; pipe failureoccurs at surface contact stresses lower than those induced by highway trucks. On the other hand, sand backfill compacted to more than 110 pcf (17.3 kN/m3) is satisfactory. The failure mode for all pipes with all backfills is localized wall bending. At moderate tire pressures, i.e. contact stresses, deflections are reduced significantly when backfill density is increased from about 50 pcf (7.9 kN/m^3) to 90 pcf (14.1 kN/m^3). Above that unit weight, little improvement in the soil-pipe system is observed. Although pipe stiffness may vary as much as 16%, analyses show that backfill density is more important than pipe stiffness in controlling both deflections at low pipe stresses and at the ultimate capacity of the soil-pipe system. The rate of increase in ultimate strength of the system increases nearly linearly with increasing backfill density. When loads equivalent to moderate tire pressures are applied near the ends of the pipes, pipe deflections are slighly higher than when loaded at the center. Except for low density glacial till, the deflections near the ends are not excessive and the pipes perform satisfactorily. For contact stresses near the upper limit of truck tire pressures and when loaded near the end, pipes fail with localized wall bending. For flowable fill backfill, the ultimate capacity of the pipes is nearly doubled and at the upper limit of highway truck tire pressures, deflections are negligible. All pipe specimens tested at ambient laboratory room temperatures satisfied AASHTO minimum pipe stiffness requirements at 5% deflection. However, nearly all specimens tested at elevated pipe surface temperatures, approximately 122°F (50°C), failed to meet these requirements. Some HDPE pipe installations may not meet AASHTO minimum pipe stiffness requirements when installed in the summer months (i.e. if pipe surface temperatures are allowed to attain temperatures similar to those tested here). Heating of any portion of the pipe circumference reduced the load carrying capacity of specimens. The minimum soil cover depths, determined from the CANOE analysis, are controlled by the 5% deflection criterion. The minimum soil cover height is 12 in. (305 mm). Pipes with the poor silt and clay backfills with less than 85% compaction require a minimum soil cover height of 24 in. (610 mm). For the sand at 80% compaction, the A36 HDPE pipe with the lowest moment of inertia requires a minimum of 24 in. (610 mm) soil cover. The C48 HDPE pipe with the largest moment of inertia and all other pipes require a 12 in. (305 mm) minimum soil cover.

Investigation of High Density Polyethylene Pipe for Highway Applications, HR-373, Phase 1, 1996

In the past, culvert pipes were made only of corrugated metal or reinforced concrete. In recent years, several manufacturers have made pipe of lightweight plastic - for example, high density polyethylene (HDPE) - which is considered to be viscoelastic in its structural behavior. It appears that there are several highway applications in which HDPE pipe would be an economically favorable alternative. However, the newness of plastic pipe requires the evaluation of its performance, integrity, and durability; A review of the Iowa Department of Transportation Standard Specifications for Highway and Bridge Construction reveals limited information on the use of plastic pipe for state projects. The objective of this study was to review and evaluate the use of HDPE pipe in roadway applications. Structural performance, soil-structure interaction, and the sensitivity of the pipe to installation was investigated. Comprehensive computerized literature searches were undertaken to define the state-of-the-art in the design and use of HDPE pipe in highway applications. A questionnaire was developed and sent to all Iowa county engineers to learn of their use of HDPE pipe. Responses indicated that the majority of county engineers were aware of the product but were not confident in its ability to perform as well as conventional materials. Counties currently using HDPE pipe in general only use it in driveway crossings. Originally, we intended to survey states as to their usage of HDPE pipe. However, a few weeks after initiation of the project, it was learned that the Tennessee DOT was in the process of making a similar survey of state DOT's. Results of the Tennessee survey of states have been obtained and included in this report. In an effort to develop more confidence in the pipe's performance parameters, this research included laboratory tests to determine the ring and flexural stiffness of HDPE pipe provided by various manufacturers. Parallel plate tests verified all specimens were in compliance with ASTM specifications. Flexural testing revealed that pipe profile had a significant effect on the longitudinal stiffness and that strength could not be accurately predicted on the basis of diameter alone. Realizing that the soil around a buried HDPE pipe contributes to the pipe stiffness, the research team completed a limited series of tests on buried 3 ft-diameter HDPE pipe. The tests simulated the effects of truck wheel loads above the pipe and were conducted with two feet of cover. These tests indicated that the type and quality of backfill significantly influences the performance of HDPE pipe. The tests revealed that the soil envelope does significantly affect the performance of HDPE pipe in situ, and after a certain point, no additional strength is realized by increasing the quality of the backfill.

The Use of Remote Sensing Techniques Compared to Traditional Archaeological Phase II Testing Methods: A Cost-Benefit Analysis, HR-524, 1986

Remote sensing was utilized in the Phase II Cultural Resources Investigation for this project in lieu of extensive excavations. The purpose of the present report is to compare the costs and benefits of the use of remote sensing to the hypothetical use of traditional excavation methods for this project. Estimates for this hypothetical situation are based on the project archaeologist's considerable past experience in conducting similar investigations. Only that part of the Phase II investigation involving field investigations is addressed in this report. Costs for literature review, laboratory analysis, report preparation, etc., are not included. The project manager proposed the use of this technique for the fol lowing logistic, safety and budgetary reasons.