FAM-MDR: a flexible family-based multifactor dimensionality reduction technique to detect epistasis using related individuals

We propose a novel multifactor dimensionality reduction method for epistasis detection in small or extended pedigrees, FAM-MDR. It combines features of the Genome-wide Rapid Association using Mixed Model And Regression approach (GRAMMAR) with Model-Based MDR (MB-MDR). We focus on continuous traits, although the method is general and can be used for outcomes of any type, including binary and censored traits. When comparing FAM-MDR with Pedigree-based Generalized MDR (PGMDR), which is a generalization of Multifactor Dimensionality Reduction (MDR) to continuous traits and related individuals, FAM-MDR was found to outperform PGMDR in terms of power, in most of the considered simulated scenarios. Additional simulations revealed that PGMDR does not appropriately deal with multiple testing and consequently gives rise to overly optimistic results. FAM-MDR adequately deals with multiple testing in epistasis screens and is in contrast rather conservative, by construction. Furthermore, simulations show that correcting for lower order (main) effects is of utmost importance when claiming epistasis. As Type 2 Diabetes Mellitus (T2DM) is a complex phenotype likely influenced by gene-gene interactions, we applied FAM-MDR to examine data on glucose area-under-the-curve (GAUC), an endophenotype of T2DM for which multiple independent genetic associations have been observed, in the Amish Family Diabetes Study (AFDS). This application reveals that FAM-MDR makes more efficient use of the available data than PGMDR and can deal with multi-generational pedigrees more easily. In conclusion, we have validated FAM-MDR and compared it to PGMDR, the current state-of-the-art MDR method for family data, using both simulations and a practical dataset. FAM-MDR is found to outperform PGMDR in that it handles the multiple testing issue more correctly, has increased power, and efficiently uses all available information.

Assessment of Nondestructive Testing Technologies for Quality Control/Quality Assurance of Asphalt Mixtures, TR-653, 2015

Asphalt pavements suffer various failures due to insufficient quality within their design lives. The American Association of State Highway and Transportation Officials (AASHTO) Mechanistic-Empirical Pavement Design Guide (MEPDG) has been proposed to improve pavement quality through quantitative performance prediction. Evaluation of the actual performance (quality) of pavements requires in situ nondestructive testing (NDT) techniques that can accurately measure the most critical, objective, and sensitive properties of pavement systems. The purpose of this study is to assess existing as well as promising new NDT technologies for quality control/quality assurance (QC/QA) of asphalt mixtures. Specifically, this study examined field measurements of density via the PaveTracker electromagnetic gage, shear-wave velocity via surface-wave testing methods, and dynamic stiffness via the Humboldt GeoGauge for five representative paving projects covering a range of mixes and traffic loads. The in situ tests were compared against laboratory measurements of core density and dynamic modulus. The in situ PaveTracker density had a low correlation with laboratory density and was not sensitive to variations in temperature or asphalt mix type. The in situ shear-wave velocity measured by surface-wave methods was most sensitive to variations in temperature and asphalt mix type. The in situ density and in situ shear-wave velocity were combined to calculate an in situ dynamic modulus, which is a performance-based quality measurement. The in situ GeoGauge stiffness measured on hot asphalt mixtures several hours after paving had a high correlation with the in situ dynamic modulus and the laboratory density, whereas the stiffness measurement of asphalt mixtures cooled with dry ice or at ambient temperature one or more days after paving had a very low correlation with the other measurements. To transform the in situ moduli from surface-wave testing into quantitative quality measurements, a QC/QA procedure was developed to first correct the in situ moduli measured at different field temperatures to the moduli at a common reference temperature based on master curves from laboratory dynamic modulus tests. The corrected in situ moduli can then be compared against the design moduli for an assessment of the actual pavement performance. A preliminary study of microelectromechanical systems- (MEMS)-based sensors for QC/QA and health monitoring of asphalt pavements was also performed.

Development of Non-Petroleum Based Binders for Use in Flexible Pavements, TR-594, 2010

Most bituminous adhesives or binders that are used for pavement materials are derived primarily from fossil fuels. With petroleum oil reserves becoming depleted and the drive to establish a bio-based economy, there is a push to produce binders from alternative sources, particularly from biorenewable resources. However, until now, no research has studied the applicability of utilizing bio-oils as a bitumen replacement (100% replacement) in the pavement industry. The main objective of this research was to test various properties of bio-oils in order to determine the applicability of using bio-oils as binders in the pavement industry. The overall conclusions about the applicability of using bio-oils as bio-binders in the pavement industry can be summarized as follows: 1. Bio-oils cannot be used as bio-binders/pavement materials without any heat pre-treatment/upgrading procedure. 2. Current testing standards and specifications, especially Superpave procedures, should be modified to comply with the properties of bio-binders. 3. The temperature range of the viscous behavior for bio-oils may be lower than that of bitumen binders by about 30°–40° C. 4. The rheological properties of the unmodified bio-binders vary in comparison to bitumen binders, but the rheological properties of these modified bio-binders change significantly upon adding polymer modifiers. 5. The high-temperature performance grade for the developed bio-binders may not vary significantly from that of the bitumen binders, but the low-temperature performance grade may vary significantly

Subject-based steroid profiling and the determination of novel biomarkers for DHT and DHEA misuse in sports.

Doping with natural steroids can be detected by evaluating the urinary concentrations and ratios of several endogenous steroids. Since these biomarkers of steroid doping are known to present large inter-individual variations, monitoring of individual steroid profiles over time allows switching from population-based towards subject-based reference ranges for improved detection. In an Athlete Biological Passport (ABP), biomarkers data are collated throughout the athlete's sporting career and individual thresholds defined adaptively. For now, this approach has been validated on a limited number of markers of steroid doping, such as the testosterone (T) over epitestosterone (E) ratio to detect T misuse in athletes. Additional markers are required for other endogenous steroids like dihydrotestosterone (DHT) and dehydroepiandrosterone (DHEA). By combining comprehensive steroid profiles composed of 24 steroid concentrations with Bayesian inference techniques for longitudinal profiling, a selection was made for the detection of DHT and DHEA misuse. The biomarkers found were rated according to relative response, parameter stability, discriminative power, and maximal detection time. This analysis revealed DHT/E, DHT/5β-androstane-3α,17β-diol and 5α-androstane-3α,17β-diol/5β-androstane-3α,17β-diol as best biomarkers for DHT administration and DHEA/E, 16α-hydroxydehydroepiandrosterone/E, 7β-hydroxydehydroepiandrosterone/E and 5β-androstane-3α,17β-diol/5α-androstane-3α,17β-diol for DHEA. The selected biomarkers were found suitable for individual referencing. A drastic overall increase in sensitivity was obtained.The use of multiple markers as formalized in an Athlete Steroidal Passport (ASP) can provide firm evidence of doping with endogenous steroids. Copyright © 2010 John Wiley & Sons, Ltd.

A general theory of rank testing

This paper develops an approach to rank testing that nests all existing rank tests andsimplifies their asymptotics. The approach is based on the fact that implicit in every ranktest there are estimators of the null spaces of the matrix in question. The approach yieldsmany new insights about the behavior of rank testing statistics under the null as well as localand global alternatives in both the standard and the cointegration setting. The approach alsosuggests many new rank tests based on alternative estimates of the null spaces as well as thenew fixed-b theory. A brief Monte Carlo study illustrates the results.

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.

Awareness of HIV Testing Guidelines Is Low among Swiss Emergency Doctors: A Survey of Five Teaching Hospitals in French-Speaking Switzerland.

BACKGROUND: In Switzerland, 30% of HIV-infected individuals are diagnosed late. To optimize HIV testing, the Swiss Federal Office of Public Health (FOPH) updated 'Provider Induced Counseling and Testing' (PICT) recommendations in 2010. These permit doctors to test patients if HIV infection is suspected, without explicit consent or pre-test counseling; patients should nonetheless be informed that testing will be performed. We examined awareness of these updated recommendations among emergency department (ED) doctors. METHODS: We conducted a questionnaire-based survey among 167 ED doctors at five teaching hospitals in French-Speaking Switzerland between 1(st) May and 31(st) July 2011. For 25 clinical scenarios, participants had to state whether HIV testing was indicated or whether patient consent or pre-test counseling was required. We asked how many HIV tests participants had requested in the previous month, and whether they were aware of the FOPH testing recommendations. RESULTS: 144/167 doctors (88%) returned the questionnaire. Median postgraduate experience was 6.5 years (interquartile range [IQR] 3; 12). Mean percentage of correct answers was 59 ± 11%, senior doctors scoring higher (P=0.001). Lowest-scoring questions pertained to acute HIV infection and scenarios where patient consent was not required. Median number of test requests was 1 (IQR 0-2, range 0-10). Only 26/144 (18%) of participants were aware of the updated FOPH recommendations. Those aware had higher scores (P=0.001) but did not perform more HIV tests. CONCLUSIONS: Swiss ED doctors are not aware of the national HIV testing recommendations and rarely perform HIV tests. Improved recommendation dissemination and adherence is required if ED doctors are to contribute to earlier HIV diagnoses.

New perspectives in the use of ink evidence in forensic science: Part III: Operational applications and evaluation.

The research reported in this series of article aimed at (1) automating the search of questioned ink specimens in ink reference collections and (2) at evaluating the strength of ink evidence in a transparent and balanced manner. These aims require that ink samples are analysed in an accurate and reproducible way and that they are compared in an objective and automated way. This latter requirement is due to the large number of comparisons that are necessary in both scenarios. A research programme was designed to (a) develop a standard methodology for analysing ink samples in a reproducible way, (b) comparing automatically and objectively ink samples and (c) evaluate the proposed methodology in forensic contexts. This report focuses on the last of the three stages of the research programme. The calibration and acquisition process and the mathematical comparison algorithms were described in previous papers [C. Neumann, P. Margot, New perspectives in the use of ink evidence in forensic science-Part I: Development of a quality assurance process for forensic ink analysis by HPTLC, Forensic Sci. Int. 185 (2009) 29-37; C. Neumann, P. Margot, New perspectives in the use of ink evidence in forensic science-Part II: Development and testing of mathematical algorithms for the automatic comparison of ink samples analysed by HPTLC, Forensic Sci. Int. 185 (2009) 38-50]. In this paper, the benefits and challenges of the proposed concepts are tested in two forensic contexts: (1) ink identification and (2) ink evidential value assessment. The results show that different algorithms are better suited for different tasks. This research shows that it is possible to build digital ink libraries using the most commonly used ink analytical technique, i.e. high-performance thin layer chromatography, despite its reputation of lacking reproducibility. More importantly, it is possible to assign evidential value to ink evidence in a transparent way using a probabilistic model. It is therefore possible to move away from the traditional subjective approach, which is entirely based on experts' opinion, and which is usually not very informative. While there is room for the improvement, this report demonstrates the significant gains obtained over the traditional subjective approach for the search of ink specimens in ink databases, and the interpretation of their evidential value.

Hydraulic Cement Grout Testing, MLR-89-14, 1990

Currently, hydraulic cement grouts are approved for Iowa Department of Transportation projects on the basis of a pullout test. However, other properties of the grouts should be evaluated. Therefore, this research was initiated to develop criteria to better evaluate hydraulic cement grouts. Fourteen grouts were tested for compressive strength, time of set, durability, consistency and shrinkage. Tested grouts all yielded compressive strengths higher than 3000 psi at 7 days and durability factors were well above 70. Time of set and consistency was adequate. The testing showed most grouts tested shrank, even though tested grouts were labeled non-shrink grouts. For many applications of grouts such as setting in anchor bolts and as a filler, minor shrinkage is not a problem. However, for some critical applications, shrinkage cannot be tolerated. The proposed Instructional Memorandum will identify those grouts which do not excessively shrink or expand in the tests used. Based on test results, criteria for evaluation of hydraulic cement grouts have been recommended. Evaluation consists of tests for compressive strength, time of set, durability, consistency, shrinkage and pullout test.

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).

Field Testing of Railroad Flatcar Bridges Volume I: Single Spans, TR-498, 2007

Based on the conclusions of IHRB Project TR-444, Demonstration Project Using Railroad Flat Car Bridges for Low Volume Road Bridges, additional research on the use of RRFC bridges was undertaken. This portion of the project investigated the following: (1) Different design and rating procedures; (2) Additional single span configurations plus multiple span configurations; (3) Different mechanisms for connecting adjacent RRFCs and the resulting lateral load distribution factors; (4) Sheet pile abutments; and (5) Behavior RRFCs that had been strengthened so that they could be used on existing abutments. A total of eight RRFC bridges were tested (five single span bridges, two two-span bridges, and one three-span bridge). Based on the results of this study a simplified design and rating procedure has been developed for the economical replacement bridge alternative. In Volume 1, this volume, the results from the testing of four single span RRFC bridges are presented, while in Volume 2 the results from the testing of the strengthened single span bridge plus the three multiple span bridges are presented.

Field Testing of Railroad Flatcar Bridges Volume II: Multiple Spans, TR-498, 2007

Based on the conclusions of IHRB Project TR-444, Demonstration Project Using Railroad Flat Car Bridges for Low Volume Road Bridges, additional research on the use of RRFC bridges was undertaken. This portion of the project investigated the following: (1) Different design and rating procedures; (2) Additional single span configurations plus multiple span configurations; (3) Different mechanisms for connecting adjacent RRFCs and the resulting lateral load distribution factors; (4) Sheet pile abutments; and (5) Behavior RRFCs that had been strengthened so that they could be used on existing abutments. A total of eight RRFC bridges were tested (five single span bridges, two two-span bridges, and one three-span bridge). Based on the results of this study a simplified design and rating procedure has been developed for the economical replacement bridge alternative. In Volume 1, the results from the testing of four single span RRFC bridges are presented, while in Volume 2,this volume, the results from the testing of the strengthened single span bridge plus the three multiple span bridges are presented.

Design, Construction, and Field Testing of an Ultra High Performance Concrete Pi-Girder Bridge, TR-574, 2011

Among the variety of road users and vehicle types that travel on U.S. public roadways, slow moving vehicles (SMVs) present unique safety and operations issues. SMVs include vehicles that do not maintain a constant speed of 25 mph, such as large farm equipment, construction vehicles, or horse-drawn buggies. Though the number of crashes involving SMVs is relatively small, SMV crashes tend to be severe. Additionally, SMVs can be encountered regularly on non-Interstate/non-expressway public roadways, but motorists may not be accustomed to these vehicles. This project was designed to improve transportation safety for SMVs on Iowa’s public roadway system. This report includes a literature review that shows various SMV statistics and laws across the United States, a crash study based on three years of Iowa SMV crash data, and recommendations from the SMV community.

Field Testing of Abrasive Delivery Systems in Winter Maintenance, TR-458, 2009

The key goals in winter maintenance operations are preserving the safety and mobility of the traveling public. To do this, it is in general necessary to try to increase the friction of the road surface above the typical friction levels found on a snow or ice covered roadway. Because of prior work on the performance of abrasives (discussed in greater detail in chapter 2) a key concern when using abrasives has become how to ensure the greatest increase in pavement friction when using abrasives for the longest period of time. There are a number of ways in which the usage of abrasives can be optimized, and these methods are discussed and compared in this report. In addition, results of an Iowa DOT test of zero-velocity spreaders are presented. Additionally in this study the results of field studies conducted in Johnson County Iowa on the road surface friction of pavements treated with abrasive applications using different modes of delivery are presented. The experiments were not able to determine any significant difference in material placement performance between a standard delivery system and a chute based delivery system. The report makes a number of recommendations based upon the reviews and the experiments.

Field Instrumentation, Testing, and Long-Term Monitoring of High-Mast Lighting Towers in the State of Iowa, TR-518, 2006

As a result of the collapse of a 140 foot high-mast lighting tower in Sioux City, Iowa in November of 2003, a thorough investigation into the behavior and design of these tall, yet relatively flexible structures was undertaken. Extensive work regarding the root cause of this failure was carried out by Robert Dexter of The University of Minnesota. Furthermore, a statewide inspection of all the high-mast towers in Iowa revealed fatigue cracks and loose anchor bolts on other existing structures. The current study was proposed to examine the static and dynamic behavior of a variety of towers in the State of Iowa utilizing field testing, specifically long-term monitoring and load testing. This report presents the results and conclusions from this project. The field work for this project was divided into two phases. Phase 1 of the project was conducted in October 2004 and focused on the dynamic properties of ten different towers in Clear Lake, Ames, and Des Moines, Iowa. Of those ten, two were also instrumented to obtain stress distributions at various details and were included in a 12 month long-term monitoring study. Phase 2 of this investigation was conducted in May of 2005, in Sioux City, Iowa, and focused on determining the static and dynamic behavior of a tower similar to the one that collapsed in November 2003. Identical tests were performed on a similar tower which was retrofitted with a more substantial replacement bottom section in order to assess the effect of the retrofit. A third tower with different details was dynamically load tested to determine its dynamic characteristics, similar to the Phase 1 testing. Based on the dynamic load tests, the modal frequencies of the towers fall within the same range. Also, the damping ratios are significantly lower in the higher modes than the values suggested in the AASHTO and CAN/CSA specifications. The comparatively higher damping ratios in the first mode may be due to aerodynamic damping. These low damping ratios in combination with poor fatigue details contribute to the accumulation of a large number of damage-causing cycles. As predicted, the stresses in the original Sioux City tower are much greater than the stresses in the retrofitted towers at Sioux City. Additionally, it was found that poor installation practices which often lead to loose anchor bolts and out-of-level leveling nuts can cause high localized stresses in the towers, which can accelerate fatigue damage.