Plasma concentrations of the enantiomers of methadone and therapeutic response in methadone maintenance treatment

Methadone is a 50:50 mixture of two enantiomers and (R)-methadone accounts for the majority of its opioid effect. The aim of this study was to determine whether a blood concentration of (R)-methadone can be associated with therapeutic response in addict patients in methadone maintenance treatment. Trough plasma concentrations of (R)-, (S)- and (R,S)-methadone were measured in 180 patients in maintenance treatment. Therapeutic response was defined by the absence of illicit opiate or cocaine in urine samples collected during a 2-month period prior to blood sampling. A large interindividual variability of (R)-methadone concentration-to-dose-to-weight ratios was found (mean, S.D., median, range: 112, 54, 100, 19-316 ng x kg/ml x mg). With regard to the consumption of illicit opiate (but not of cocaine), a therapeutic response was associated with (R)- (at 250 ng/ml) and (R,S)-methadone (at 400 ng/ml) but not with (S)-methadone concentrations. A higher specificity was calculated for (R)- than for (R,S)-methadone, as the number of non-responders above this threshold divided by the total number of non-responders was higher for (R,S)-methadone (19%) than for (R)-methadone (7%). The results support the use of therapeutic drug monitoring of (R)-methadone in cases of continued intake of illicit opiates. Due to the variability of methadone concentration-to-dose-to-weight ratios, theoretical doses of racemic methadone could be as small as 55 mg/day and as large as 921 mg/day to produce a plasma (R)-methadone concentration of 250 ng/ml in a 70-kg patient. This demonstrates the importance of individualizing methadone treatment.

Appropriate maintenance treatment for Crohn's disease: results of a multidisciplinary international expert panel - EPACT II

Introduction: Biological. therapy has dramatically changed management of Crohn's disease (CD). New data have confirmed the benefit and relative long-term safety of anti-TNF alpha inhibition as part of a regular scheduled administration programme. The EPACT appropriateness criteria for maintenance treatment after medically-induced remission (MIR) or surgically-induced remission (SIR) of CD thus required updating. Methods: A multidisciplinary international expert panel (EPACT II, Geneva, Switzerland) discussed and anonymously rated detailed, explicit clinical indications based on evidence in the literature and personal expertise. Median ratings (on a 9-point scale) were stratified into three assessment categories: appropriate (7-9), uncertain (4-6 and/or disagreement) and inappropriate (1-3). Experts ranked appropriate medication according to their own clinical practice, without any consideration of cost. Results: Three hundred and ninety-two specific indications for maintenance treatment of CD were rated (200 for MIR and 192 for SIR). Azathioprine, methotrexate and/or anti-TNF alpha antibodies were considered appropriate in 42 indications, corresponding to 68% of all appropriate interventions (97% of MIR and 39% of SIR). The remaining appropriate interventions consisted of mesalazine and a "wait-and-see" strategy. Factors that influenced the panel's voting were patient characteristics and outcome of previous treatment. Results favour use of anti-TNF alpha agents after failure of any immunosuppressive therapy, while earlier primary use remains controversial. Conclusion: Detailed explicit appropriateness criteria (EPACT) have been updated for maintenance treatment of CD. New expert recommendations for use of the classic immunosuppressors as well as anti-TNF alpha agents are now freely available online (www.epact.ch). The validity of these criteria should now be tested by prospective evaluation. (C) 2009 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

Automated Traffic/Truck Weight Monitoring Equipment (Weigh-in-Motion), HR-282, 1988

This report documents work undertaken in the demonstration of a low-cost Automatic Weight and Classification System (AWACS). An AWACS procurement specification and details of the results of the project are also included. The intent of the project is to support and encourage transferring research knowledge to state and local agencies and manufacturers through field demonstrations. Presently available, Weigh-in-Motion and Classification Systems are typically too expensive to permit the wide deployment necessary to obtain representative vehicle data. Piezo electric technology has been used in the United Kingdom and Europe and is believed to be the basic element in a low-cost AWACS. Low-cost systems have been installed at two sites, one in Portland Cement Concrete (PCC) pavement in Iowa and the other in Asphaltic Cement Concrete (ACC) pavement in Minnesota to provide experience with both types of pavement. The systems provide axle weights, gross vehicle weight, axle spacing, vehicle classification, vehicle speed, vehicle count, and time of arrival. In addition, system self-calibration and a method to predict contact tire pressure is included in the system design. The study has shown that in the PCC pavement, the AWACS is capable of meeting the needs of state and federal highway agencies, producing accuracies comparable to many current commercial WIM devices. This is being achieved at a procurement cost of substantially less than currently available equipment. In the ACC pavement the accuracies were less than those observed in the PCC pavement which is concluded to result from a low pavement rigidity at this site. Further work is needed to assess the AWACS performance at a range of sites in ACC pavements.

Report and Specification for Transportation Program Management System, HR-394, 1997

TPMS is proposed as a distributed, PC-based system for automating two processes required for road improvements in Iowa: a) the annual preparation, submission, and approval of road improvement programs. b) the ongoing process of developing plans and obtaining approval for projects to be let for bids.

An Evaluation of the Second Generation Consolidation Monitoring Device, HR-1013, 1984

The objective was to evaluate the usefulness, accuracy, precision, and reproducibility of the second generation CMD for PC concrete under production conditions.

Development of Concepts for Pavement Management, MLR-79-04, 1979

Sufficient evidence was not discovered in this brief search to alter the general opinion that the Serviceability (Present Serviceability Index-PSI) - Performance Concepts developed by the AASHO Road Test provides the optimum engineering basis for pavement management. Use of these concepts in Iowa has the additional advantage in that we have a reasonable quantity of historical data over a period of time on the change in pavement condition as measured by PSI's. Some additional benefits would be the ability to better assess our needs with respect to those being recommended to Congress by AASHTO Committees. These concepts have been the basis used for developing policies on dimensions and weight of vehicles and highway needs which the AASHTO Transport Committees have recommended to the United States House Committee on Ways and Means. The first recommendation based on these concepts was made in the mid 1960's. Iowa's participation in the evaluation for this recommendation was under the direction of our present Director of Transportation, Mr. Raymond Kassel. PSI Indexes had to be derived from subjective surface ratings at that time. The most recent recommendation to Congress was made in November of 1977. Based on the rationale expressed above, a pilot study of the major part of the rural interstate system was conducted. The Objective of the study was to measure pavement performance through the use of the Present Serviceability Index (PSI) - Pavement Performance concepts as developed by the AASHO Road Test and to explore the usefulness of this type of data as a pavement management tool. Projects in the vicinity of the major urban centers were not included in this study due to the extra time that would be required to isolate accurate traffic data in these areas. Projects consisting of asphalt surface courses on crushed stone base sections were not included.

Investigation of Video Crack and Patch Surveying for Pavement Management, MLR-92-01, 1992

The Iowa DOT has been using the AASHTO Present Serviceability Index (PSI) rating procedure since 1968 to rate the condition of pavement sections. A ride factor and a cracking and patching factor make up the PSI value. Crack and patch surveys have been done by sending crews out to measure and record the distress. Advances in video equipment and computers make it practical to videotape roads and do the crack and patch measurements in the office. The objective of the study was to determine the feasibility of converting the crack and patch survey operation to a video recording system with manual post processing. The summary and conclusions are as follows: Video crack and patch surveying is a feasible alternative to the current crack and patch procedure. The cost per mile should be about 25 percent less than the current procedure. More importantly, the risk of accidents is reduced by getting the people and vehicles off the roadway and shoulder. Another benefit is the elimination of the negative public perceptions of the survey crew on the shoulder.

Thin Maintenance Surfaces for Municipalities, TR-507, 2007

As streets age, officials must deal with rehabilitating and reconstructing these pavements to maintain a safe and comfortable ride. In light of nationwide budget shortfalls, cost-effective methods of extending pavement service life must be developed or the overall condition of street systems will continue to fall. Thin maintenance surfaces (TMSs) are a set of cost-effective preventive maintenance surfacing techniques that can be used to extend the life of bituminous pavement—pavement built with hot mix asphalt, hot mix asphalt overlays of portland cement concrete pavements, built-up seal coat (chip seal), stabilized materials, or a combination of these. While previous phases of TMS research have provided information about the uses of thin maintenance surfaces in rural settings, urban areas have different road maintenance challenges that should be considered separately. This research provides city street officials with suggestions for TMS techniques that street departments can easily test and include into their current programs. This research project facilitated the construction of TMS test sections in Cedar Rapids, Council Bluffs, and West Des Moines (all urban settings in Iowa). Test section sites and surfaces were selected to suit the needs of municipalities and were applied to roads with an array of various distresses and maintenance needs. Condition surveys of each test section were performed before construction, after construction, and after the first winter to record the amount and severity of existing distress and calculate the pavement condition index. Because conditions of the test sections varied greatly, determining which surface was most successful by comparing case studies was not feasible. However, some general conclusions can be made from this research. TMSs are suitable preventive maintenance techniques for a municipal street department’s program for preserving existing pavements. Careful attention should be paid to proper planning, quality control during construction, aggregate and binder selection, and aggregate embedment in order to support successful TMS application.

Local Agency Pavement Marking Plan, TR-551, 2010

The proposed Federal Highway Administration (FHWA) amendments to the Manual of Uniform Traffic Control Devices (MUTCD) will change the way local agencies manage their pavement markings and places a focus on pavement marking quality and management methods. This research effort demonstrates how a pavement marking maintenance method could be developed and used at the local agency level. The report addresses the common problems faced by agencies in achieving good pavement marking quality and provides recommendations specific towards these problems in terms of assessing pavement marking needs, selecting pavement marking materials, contracting out pavement marking services, measuring and monitoring performance, and in developing management tools to visualize pavement marking needs in a GIS format. The research includes five case studies, three counties and two cities, where retroreflectivity was measured over a spring and fall season and then mapped to evaluate pavement marking performance and needs. The research also includes over 35 field demonstrations (installation and monitoring) of both longitudinal and transverse durable markings in a variety of local agency settings all within an intense snow plow state.

Performance Evaluation of Concrete Pavement Granular Subbase - Pavement Surface Condition Evaluation, TR-554, 2008

This research project covered a wide range of activities that allowed researchers to understand the relationship between stability, pavement distress, and recycled portland cement concrete (RPCC) subbase aggregate materials. Detailed laboratory and field tests, including pavement distress surveys, were conducted at 26 sites in Iowa. Findings show that specific gravities of RPCC are lower than those of crushed limestone. RPCC aggregate material varies from poorly or well-graded sand to gravel. A modified Micro-Deval test procedure showed that abrasion losses of virgin aggregate materials were within the maximum Micro-Deval abrasion loss of 30% recommended by ASTM D6028-06. Micro-Deval abrasion loss of RPCC aggregate materials, however, was much higher than that of virgin materials and exceeded 30% loss. Modulus of elasticity of RPCC subbase materials is high but variable. RPCC subbase layers normally have low permeability. The pavement surfaces for both virgin and RPCC subbase across Iowa were evaluated to fulfill the objectives of this study related to field evaluation. Visual distress surveys were conducted to gather the detailed current pavement condition information including the type, extent, and severity of the pavement distresses. The historical pavement condition information for the surveyed field sections was extracted from the Iowa DOT's Pavement Management Information System (PMIS). The current surface condition of existing field pavements with RPCC subbase was compared with the virgin aggregate subbase sections using two different approaches. The changes in pavement condition indices (PCI and IRI) with time for both types of pavements (subbases) were compared.

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.

Field Instrumentation, Testing, and Long-Term Monitoring of High-Mast Lighting Tower No. 1 at the I-35/US 18 Interchange Near Clear Lake in the State of Iowa Phase 3, TR-562, 2009

The current study was initiated to quantify the stresses induced in critical details on the reinforcing jacket and the tower itself through the use of field instrumentation, load testing, and long-term monitoring. Strain gages were installed on the both the tower and the reinforcing jacket. Additional strain gages were installed on two anchor rods. Tests were conducted with and without the reinforcing jacket installed. Data were collected from all strain gages during static load testing and were used to study the stress distribution of the tower caused by known loads, both with and without the reinforcing jacket. The tower was tested dynamically by first applying a static load, and then quickly releasing the load causing the tower to vibrate freely. Furthermore, the tower was monitored over a period of over 1 year to obtain stress range histograms at the critical details to be used for a fatigue evaluation. Also during the long-term monitoring, triggered time-history data were recorded to study the wind loading phenomena that excite the tower.

Wireless Sensor Networks for Infrastructure Monitoring, TR-611, 2010

A good system of preventive bridge maintenance enhances the ability of engineers to manage and monitor bridge conditions, and take proper action at the right time. Traditionally infrastructure inspection is performed via infrequent periodical visual inspection in the field. Wireless sensor technology provides an alternative cost-effective approach for constant monitoring of infrastructures. Scientific data-acquisition systems make reliable structural measurements, even in inaccessible and harsh environments by using wireless sensors. With advances in sensor technology and availability of low cost integrated circuits, a wireless monitoring sensor network has been considered to be the new generation technology for structural health monitoring. The main goal of this project was to implement a wireless sensor network for monitoring the behavior and integrity of highway bridges. At the core of the system is a low-cost, low power wireless strain sensor node whose hardware design is optimized for structural monitoring applications. The key components of the systems are the control unit, sensors, software and communication capability. The extensive information developed for each of these areas has been used to design the system. The performance and reliability of the proposed wireless monitoring system is validated on a 34 feet span composite beam in slab bridge in Black Hawk County, Iowa. The micro strain data is successfully extracted from output-only response collected by the wireless monitoring system. The energy efficiency of the system was investigated to estimate the battery lifetime of the wireless sensor nodes. This report also documents system design, the method used for data acquisition, and system validation and field testing. Recommendations on further implementation of wireless sensor networks for long term monitoring are provided.

Wind Loads on Dynamic Message Cabinets and Behavior of Supporting Trusses, TR-612, 2013

Large Dynamic Message Signs (DMSs) have been increasingly used on freeways, expressways and major arterials to better manage the traffic flow by providing accurate and timely information to drivers. Overhead truss structures are typically employed to support those DMSs allowing them to provide wider display to more lanes. In recent years, there is increasing evidence that the truss structures supporting these large and heavy signs are subjected to much more complex loadings than are typically accounted for in the codified design procedures. Consequently, some of these structures have required frequent inspections, retrofitting, and even premature replacement. Two manufacturing processes are primarily utilized on truss structures - welding and bolting. Recently, cracks at welding toes were reported for the structures employed in some states. Extremely large loads (e.g., due to high winds) could cause brittle fractures, and cyclic vibration (e.g., due to diurnal variation in temperature or due to oscillations in the wind force induced by vortex shedding behind the DMS) may lead to fatigue damage, as these are two major failures for the metallic material. Wind and strain resulting from temperature changes are the main loads that affect the structures during their lifetime. The American Association of State Highway and Transportation Officials (AASHTO) Specification defines the limit loads in dead load, wind load, ice load, and fatigue design for natural wind gust and truck-induced gust. The objectives of this study are to investigate wind and thermal effects in the bridge type overhead DMS truss structures and improve the current design specifications (e.g., for thermal design). In order to accomplish the objective, it is necessary to study structural behavior and detailed strain-stress of the truss structures caused by wind load on the DMS cabinet and thermal load on the truss supporting the DMS cabinet. The study is divided into two parts. The Computational Fluid Dynamics (CFD) component and part of the structural analysis component of the study were conducted at the University of Iowa while the field study and related structural analysis computations were conducted at the Iowa State University. The CFD simulations were used to determine the air-induced forces (wind loads) on the DMS cabinets and the finite element analysis was used to determine the response of the supporting trusses to these pressure forces. The field observation portion consisted of short-term monitoring of several DMS Cabinet/Trusses and long-term monitoring of one DMS Cabinet/Truss. The short-term monitoring was a single (or two) day event in which several message sign panel/trusses were tested. The long-term monitoring field study extended over several months. Analysis of the data focused on trying to identify important behaviors under both ambient and truck induced winds and the effect of daily temperature changes. Results of the CFD investigation, field experiments and structural analysis of the wind induced forces on the DMS cabinets and their effect on the supporting trusses showed that the passage of trucks cannot be responsible for the problems observed to develop at trusses supporting DMS cabinets. Rather the data pointed toward the important effect of the thermal load induced by cyclic (diurnal) variations of the temperature. Thermal influence is not discussed in the specification, either in limit load or fatigue design. Although the frequency of the thermal load is low, results showed that when temperature range is large the restress range would be significant to the structure, especially near welding areas where stress concentrations may occur. Moreover stress amplitude and range are the primary parameters for brittle fracture and fatigue life estimation. Long-term field monitoring of one of the overhead truss structures in Iowa was used as the research baseline to estimate the effects of diurnal temperature changes to fatigue damage. The evaluation of the collected data is an important approach for understanding the structural behavior and for the advancement of future code provisions. Finite element modeling was developed to estimate the strain and stress magnitudes, which were compared with the field monitoring data. Fatigue life of the truss structures was also estimated based on AASHTO specifications and the numerical modeling. The main conclusion of the study is that thermal induced fatigue damage of the truss structures supporting DMS cabinets is likely a significant contributing cause for the cracks observed to develop at such structures. Other probable causes for fatigue damage not investigated in this study are the cyclic oscillations of the total wind load associated with the vortex shedding behind the DMS cabinet at high wind conditions and fabrication tolerances and induced stresses due to fitting of tube to tube connections.

Spontaneous 24-h GHRELIN secretion pattern in fasting subjects : maintenance of a meal-related pattern

RESUME OBJECTIF: Outre la stimulation de la sécrétion d'hormone de croissance, la ghréline cause une prise pondérale par augmentation de l'assimilation d'aliments et réduction de la consommation lipidique. Il a été décrit que les taux de ghréline augmentent durant la phase pré-prandiale et diminuent juste après un repas, ceci suggérant qu'elle puisse jouer un rôle d'initiateur de la prise du repas. Cependant, la sécrétion de ghréline chez des sujets à jeun n'a pas encore été étudiée en détail. DESSIN: Les profils de sécrétion de ghréline pendant 24 heures ont été étudiés chez six sujets volontaires sains (3 femmes, 3 hommes; 25.5 ans; BMI 22.8 kg/m2) et comparés aux profils plasmatiques de l'hormone de croissance, de l'insuline et du glucose. METHODE: Des échantillons sanguins ont été prélevés toutes les 20 minutes pendant 24 heures et les taux de ghréline ont été mesurés par radio-immuno essai, utilisant un anticorps polyclonal de lapin. Le profil circadien de la sécrétion de ghréline (cluster analysis) a été évalué. RESULTATS: Une augmentation puis une diminution spontanée des taux de ghréline ont été observées aux moments où les sujets auraient habituellement mangé. La ghréline a été sécrétée de façon pulsatile avec approximativement 8 pics par 24 heures. Une diminution générale des taux de ghréline a également été observée durant la période d'étude. Aucune corrélation n'a pu être observée entre les taux de ghréline, d'homione de croissance, d'insuline et de glucose. CONCLUSIONS: Cette étude montre que pendant une période de jeûne les taux de ghréline suivent un profil similaire à ceux décrits chez des sujets mangeant 3 fois par jour. Durant le jeûne, l'hormone de croissance, l'insuline et le glucose ne semblent pas être impliqués dans la régulation de la sécrétion de ghréline. En outre, nous avons observé que la sécrétion de ghréline est pulsatile. La variation des taux de ghréline, indépendamment des repas, chez des sujets à jeun, renforce les observations préalables selon lesquelles le système nerveux central est primairement impliqué dans la régulation de la prise alimentaire. ABSTRACT: OBJECTIVE: Ghrelin stimulates GH release and causes weight gain through increased food intake and reduced fat utiIization. Ghrelin levels were shown to rise in the preprandial period and decrease shortly after meal consumption, suggesting a role as a possible meal initiator. However, ghrelin secretion in fasting subjects has not yet been studied in detail. DESIGN: 24-h ghrelin profiles were studied in six healthy volunteers (three females; 25.5 years; body mass index 22.8 kg/m2) and compared with GH, insulin and glucose levels. METHODS: Blood samples were taken every 20 min during a 24-h fasting period and total ghrelin levels were measured by RIA using a polyclonal rabbit antibody. The circadian pattern of ghrelin secretion and pulsatility (Cluster analysis) were evaluated. RESULTS: An increase and spontaneous decrease in ghrelin were seen at the timepoints of customary meals. Ghrelin was secreted in a pulsatile manner with approximately 8 peaks/24 h. An overall decrease in ghrelin levels was observed during the study period. There was no correlation of ghrelin with GH, insulin or blood glucose levels. CONCLUSIONS: This pilot study indicates that fasting ghrelin profiles display a circadian pattern similar to that described in people eating three times per day. In a fasting condition. GH, insulin and glucose do not appear to be involved in ghrelin regulation. In addition, we round that ghrelin is secreted in a pulsatile pattern. The variation in ghrelin independently of meals in fasting subjects supports previous observations that it is the brain that is primarily involved in the regulation of meal initiation.