Individual patient data systematic review and meta-analysis of optic nerve sheath diameter ultrasonography for detecting raised intracranial pressure: protocol of the ONSD research group.

BACKGROUND: The purpose of the optic nerve sheath diameter (ONSD) research group project is to establish an individual patient-level database from high quality studies of ONSD ultrasonography for the detection of raised intracranial pressure (ICP), and to perform a systematic review and an individual patient data meta-analysis (IPDMA), which will provide a cutoff value to help physicians making decisions and encourage further research. Previous meta-analyses were able to assess the diagnostic accuracy of ONSD ultrasonography in detecting raised ICP but failed to determine a precise cutoff value. Thus, the ONSD research group was founded to synthesize data from several recent studies on the subject and to provide evidence on the diagnostic accuracy of ONSD ultrasonography in detecting raised ICP. METHODS: This IPDMA will be conducted in different phases. First, we will systematically search for eligible studies. To be eligible, studies must have compared ONSD ultrasonography to invasive intracranial devices, the current reference standard for diagnosing raised ICP. Subsequently, we will assess the quality of studies included based on the QUADAS-2 tool, and then collect and validate individual patient data. The objectives of the primary analyses will be to assess the diagnostic accuracy of ONSD ultrasonography and to determine a precise cutoff value for detecting raised ICP. Secondly, we will construct a logistic regression model to assess whether patient and study characteristics influence diagnostic accuracy. DISCUSSION: We believe that this IPD MA will provide the most reliable basis for the assessment of diagnostic accuracy of ONSD ultrasonography for detecting raised ICP and to provide a cutoff value. We also hope that the creation of the ONSD research group will encourage further study. TRIAL REGISTRATION: PROSPERO registration number: CRD42012003072.

Cost-effective experimental design to support modeling of concentration-response functions

Modeling concentration-response function became extremely popular in ecotoxicology during the last decade. Indeed, modeling allows determining the total response pattern of a given substance. However, reliable modeling is consuming in term of data, which is in contradiction with the current trend in ecotoxicology, which aims to reduce, for cost and ethical reasons, the number of data produced during an experiment. It is therefore crucial to determine experimental design in a cost-effective manner. In this paper, we propose to use the theory of locally D-optimal designs to determine the set of concentrations to be tested so that the parameters of the concentration-response function can be estimated with high precision. We illustrated this approach by determining the locally D-optimal designs to estimate the toxicity of the herbicide dinoseb on daphnids and algae. The results show that the number of concentrations to be tested is often equal to the number of parameters and often related to the their meaning, i.e. they are located close to the parameters. Furthermore, the results show that the locally D-optimal design often has the minimal number of support points and is not much sensitive to small changes in nominal values of the parameters. In order to reduce the experimental cost and the use of test organisms, especially in case of long-term studies, reliable nominal values may therefore be fixed based on prior knowledge and literature research instead of on preliminary experiments

Design, data management, and population baseline characteristics of the PERFORM magnetic resonance imaging project.

Quantitative information from magnetic resonance imaging (MRI) may substantiate clinical findings and provide additional insight into the mechanism of clinical interventions in therapeutic stroke trials. The PERFORM study is exploring the efficacy of terutroban versus aspirin for secondary prevention in patients with a history of ischemic stroke. We report on the design of an exploratory longitudinal MRI follow-up study that was performed in a subgroup of the PERFORM trial. An international multi-centre longitudinal follow-up MRI study was designed for different MR systems employing safety and efficacy readouts: new T2 lesions, new DWI lesions, whole brain volume change, hippocampal volume change, changes in tissue microstructure as depicted by mean diffusivity and fractional anisotropy, vessel patency on MR angiography, and the presence of and development of new microbleeds. A total of 1,056 patients (men and women ≥ 55 years) were included. The data analysis included 3D reformation, image registration of different contrasts, tissue segmentation, and automated lesion detection. This large international multi-centre study demonstrates how new MRI readouts can be used to provide key information on the evolution of cerebral tissue lesions and within the macrovasculature after atherothrombotic stroke in a large sample of patients.

Engineering Study for Reducing Sign Vandalism Final Report Highway Research Advisory Board Projec HR 246, June 1992

Sign vandalism has traditionally been a vexing problem for Iowa counties. The extent of the cost and incidence of these acts have never been fully ascertained, but a 1990 survey indicated that they cost Iowa counties more than 1.5 million dollars annually. In 1990, the Iowa Legislature recognized the seriousness of the problem and strengthened the existing sign vandalism law by increasing the penalty for illegal possession of a traffic control device from a simple to a serious misdemeanor. However, the courts must be willing to prosecute vandals to the magnitude provided in the Iowa Code. An educational campaign begun in 1987 involving over 200 Iowa school districts to educate students on the seriousness of the problem evidently did not have the effect of dramatically reducing the overall cost of sign vandalism in Iowa. This study sought to define the scope of the problem and possibly offer some effective countermeasures to combat sign vandalism and theft in Iowa.

MEPDG Work Plan Task No. 5: Characterization of Unbound Materials (Soils/Aggregates) for Mechanistic-Empirical Pavement Design Guide, 2009

The resilient modulus (MR) input parameters in the Mechanistic-Empirical Pavement Design Guide (MEPDG) program have a significant effect on the projected pavement performance. The MEPDG program uses three different levels of inputs depending on the desired level of accuracy. The primary objective of this research was to develop a laboratory testing program utilizing the Iowa DOT servo-hydraulic machine system for evaluating typical Iowa unbound materials and to establish a database of input values for MEPDG analysis. This was achieved by carrying out a detailed laboratory testing program designed in accordance with the AASHTO T307 resilient modulus test protocol using common Iowa unbound materials. The program included laboratory tests to characterize basic physical properties of the unbound materials, specimen preparation and repeated load triaxial tests to determine the resilient modulus. The MEPDG resilient modulus input parameter library for Iowa typical unbound pavement materials was established from the repeated load triaxial MR test results. This library includes the non-linear, stress-dependent resilient modulus model coefficients values for level 1 analysis, the unbound material properties values correlated to resilient modulus for level 2 analysis, and the typical resilient modulus values for level 3 analysis. The resilient modulus input parameters library can be utilized when designing low volume roads in the absence of any basic soil testing. Based on the results of this study, the use of level 2 analysis for MEPDG resilient modulus input is recommended since the repeated load triaxial test for level 1 analysis is complicated, time consuming, expensive, and requires sophisticated equipment and skilled operators.

How single-trial electrical neuroimaging contributes to multisensory research.

This study details a method to statistically determine, on a millisecond scale and for individual subjects, those brain areas whose activity differs between experimental conditions, using single-trial scalp-recorded EEG data. To do this, we non-invasively estimated local field potentials (LFPs) using the ELECTRA distributed inverse solution and applied non-parametric statistical tests at each brain voxel and for each time point. This yields a spatio-temporal activation pattern of differential brain responses. The method is illustrated here in the analysis of auditory-somatosensory (AS) multisensory interactions in four subjects. Differential multisensory responses were temporally and spatially consistent across individuals, with onset at approximately 50 ms and superposition within areas of the posterior superior temporal cortex that have traditionally been considered auditory in their function. The close agreement of these results with previous investigations of AS multisensory interactions suggests that the present approach constitutes a reliable method for studying multisensory processing with the temporal and spatial resolution required to elucidate several existing questions in this field. In particular, the present analyses permit a more direct comparison between human and animal studies of multisensory interactions and can be extended to examine correlation between electrophysiological phenomena and behavior.

Constructability in the Bridge Design Process, HR-320, 1991

In the United States many bridge structures have been designed without consideration for their unique construction problems. Many problems could have been avoided if construction knowledge and experience was utilized in the design process. A systematic process is needed to create and capture construction knowledge for use in the design process. This study was conducted to develop a system to capture construction considerations from field people and incorporate it into a knowledge-base for use by the bridge designers. This report presents the results of this study. As a part of this study a microcomputer-based constructability system has been developed. The system is a user-friendly microcomputer database which codifies construction knowledge, provides easy access to specifications, and provides simple design computation checks for the designer. A structure for the final database was developed and used in the prototype system. A process for collecting, developing and maintaining the database is presented and explained. The study involved a constructability survey, interviews with designers and constructors, and visits to construction sites to collect constuctability concepts. The report describes the development of the constructability system and addresses the future needs for the Iowa Department of Transportation to make the system operational. A user's manual for the system is included along with the report.

Stream Stabilization in Western Iowa: Structure Evaluation and Design Manual, HR-385, 1998

Stream degradation is the action of deepening the stream bed and widening the banks due to the increasing velocity of water flow. Degradation is pervasive in channeled streams found within the deep to moderately deep loess regions of the central United States. Of all the streams, however, the most severe and widespread entrenchment occurs in western Iowa streams that are tributaries to the Missouri River. In September 1995 the Iowa Department of Transportation awarded a grant to Golden Hills Resource Conservation and Development, Inc. The purpose of the grant, HR-385 "Stream Stabilization in Western Iowa: Structure Evaluation and Design Manual", was to provide an assessment of the effectiveness and costs of various stabilization structures in controlling erosion on channeled streams. A review of literature, a survey of professionals, field observations and an analysis of the data recorded on fifty-two selected structures led to the conclusions presented in the project's publication, Design Manual, Streambed Degradation and Streambank Widening in Western Iowa. Technical standards and specifications for the design and construction of stream channel stabilization structures are included in the manual. Additional information on non-structural measures, monitoring and evaluation of structures, various permit requirements and further resources are also included. Findings of the research project and use and applications of the Design Manual were presented at two workshops in the Loess Hills region. Participants in these workshops included county engineers, private contractors, state and federal agency personnel, elected officials and others. The Design Manual continues to be available through Golden Hills Resource Conservation and Development.

Design, conduct, and analyses of Breast International Group (BIG) 1-98: a randomized, double-blind, phase-III study comparing letrozole and tamoxifen as adjuvant endocrine therapy for postmenopausal women with receptor-positive, early breast cancer.

BACKGROUND: Aromatase inhibitors provide superior disease control when compared with tamoxifen as adjuvant therapy for postmenopausal women with endocrine-responsive early breast cancer. PURPOSE: To present the design, history, and analytic challenges of the Breast International Group (BIG) 1-98 trial: an international, multicenter, randomized, double-blind, phase-III study comparing the aromatase inhibitor letrozole with tamoxifen in this clinical setting. METHODS: From 1998-2003, BIG 1-98 enrolled 8028 women to receive monotherapy with either tamoxifen or letrozole for 5 years, or sequential therapy of 2 years of one agent followed by 3 years of the other. Randomization to one of four treatment groups permitted two complementary analyses to be conducted several years apart. The first, reported in 2005, provided a head-to-head comparison of letrozole versus tamoxifen. Statistical power was increased by an enriched design, which included patients who were assigned sequential treatments until the time of the treatment switch. The second, reported in late 2008, used a conditional landmark approach to test the hypothesis that switching endocrine agents at approximately 2 years from randomization for patients who are disease-free is superior to continuing with the original agent. RESULTS: The 2005 analysis showed the superiority of letrozole compared with tamoxifen. The patients who were assigned tamoxifen alone were unblinded and offered the opportunity to switch to letrozole. Results from other trials increased the clinical relevance about whether or not to start treatment with letrozole or tamoxifen, and analysis plans were expanded to evaluate sequential versus single-agent strategies from randomization. LIMITATIONS: Due to the unblinding of patients assigned tamoxifen alone, analysis of updated data will require ascertainment of the influence of selective crossover from tamoxifen to letrozole. CONCLUSIONS: BIG 1-98 is an example of an enriched design, involving complementary analyses addressing different questions several years apart, and subject to evolving analytic plans influenced by new data that emerge over time.

Validation of Design Recommendations for Integral Abutment Piles, HR-292, 1989

Since integral abutment bridges decrease the initial and maintenance costs of bridges, they provide an attractive alternative for bridge designers. The objective of this project is to develop rational and experimentally verified design recommendations for these bridges. Field testing consisted of instrumenting two bridges in Iowa to monitor air and bridge temperatures, bridge displacements, and pile strains. Core samples were also collected to determine coefficients of thermal expansion for the two bridges. Design values for the coefficient of thermal expansion of concrete are recommended, as well as revised temperature ranges for the deck and girders of steel and concrete bridges. A girder extension model is developed to predict the longitudinal bridge displacements caused by changing bridge temperatures. Abutment rotations and passive soil pressures behind the abutment were neglected. The model is subdivided into segments that have uniform temperatures, coefficients of expansion, and moduli of elasticity. Weak axis pile strains were predicted using a fixed-head model. The pile is idealized as an equivalent cantilever with a length determined by the surrounding soil conditions and pile properties. Both the girder extension model and the fixed-head model are conservative for design purposes. A longitudinal frame model is developed to account for abutment rotations. The frame model better predicts both the longitudinal displacement and weak axis pile strains than do the simpler models. A lateral frame model is presented to predict the lateral motion of skewed bridges and the associated strong axis pile strains. Full passive soil pressure is assumed on the abutment face. Two alternatives for the pile design are presented. Alternative One is the more conservative and includes thermally induced stresses. Alternative Two neglects thermally induced stresses but allows for the partial formation of plastic hinges (inelastic redistribution of forces). Ductility criteria are presented for this alternative. Both alternatives are illustrated in a design example.

History and Design of Iowa's Highway Maintenance and Weighing Facilities, 2003

In June 2001, the Iowa Department of Transportation announced the imminent closure and disposal of selected highway maintenance facilities as part of cost-cutting measures mandated by the Iowa legislature, an action that was to be completed by July 31, 2001. The DOT recognized that some of these facilities might be "historical sites," which in the Iowa Code are defined as any district, site, building or structure listed on the National Register of Historic Places or identified as eligible for listing in the National Register by the State Historic Preservation Office. Section 303 of the Code requires state agencies to "enter into an agreement with the Department of Cultural Affairs [in which the SHPO is located] to ensure the proper management, maintenance and development of historical sites." The DOT saw this disposal action as an opportunity to compile information about its highway maintenance facilities that could be employed in development of a management program for historic highway maintenance facilities in the future. Subsequently, the DOT authorized a similar study of highway weigh stations.

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.

Blended Cement Patching Research, MLR-04-01, 2005

With the recent introduction of blended cements, many ready mix producers are using them as their sole source of cement. Iowa DOT specifications currently do not allow blended cements in patching due to their assumed slower strength gain. Patching specifications require opening at 5 hours on 2-lane or 10 hours on 4-lane pavement. This research will investigate early strength of concrete cast with ordinary Type I/II Portland cements and Type I(SM) blended Portland cements.

Design Guide for Improved Quality of Roadway Subgrades and Subbases, TR-525, 2008

The performance of a pavement depends on the quality of its subgrade and subbase layers; these foundational layers play a key role in mitigating the effects of climate and the stresses generated by traffic. Therefore, building a stable subgrade and a properly drained subbase is vital for constructing an effective and long lasting pavement system. This manual has been developed to help Iowa highway engineers improve the design, construction, and testing of a pavement system’s subgrade and subbase layers, thereby extending pavement life. The manual synthesizes current and previous research conducted in Iowa and other states into a practical geotechnical design guide [proposed as Chapter 6 of the Statewide Urban Design and Specifications (SUDAS) Design Manual] and construction specifications (proposed as Section 2010 of the SUDAS Standard Specifications) for subgrades and subbases. Topics covered include the important characteristics of Iowa soils, the key parameters and field properties of optimum foundations, embankment construction, geotechnical treatments, drainage systems, and field testing tools, among others.