Choosing among techniques for quantifying single-case intervention effectiveness

If single case experimental designs are to be used to establish guidelines for evidence-based interventions in clinical and educational settings, numerical values that reflect treatment effect sizes are required. The present study compares four recently developed procedures for quantifying the magnitude of intervention effect using data with known characteristics. Monte Carlo methods were used to generate AB designs data with potential confounding variables (serial dependence, linear and curvilinear trend, and heteroscedasticity between phases) and two types of treatment effect (level and slope change). The results suggest that data features are important for choosing the appropriate procedure and, thus, inspecting the graphed data visually is a necessary initial stage. In the presence of serial dependence or a change in data variability, the Nonoverlap of All Pairs (NAP) and the Slope and Level Change (SLC) were the only techniques of the four examined that performed adequately. Introducing a data correction step in NAP renders it unaffected by linear trend, as is also the case for the Percentage of Nonoverlapping Corrected Data and SLC. The performance of these techniques indicates that professionals" judgments concerning treatment effectiveness can be readily complemented by both visual and statistical analyses. A flowchart to guide selection of techniques according to the data characteristics identified by visual inspection is provided.

Correlation of photodynamic activity and fluorescence signaling for free and pegylated mTHPC in mesothelioma xenografts

Rapport de synthèse : Introduction : Les premières applications cliniques de la thérapie photodynamique (PDT) remontent à plus d'une vingtaine d'années. Basée sur l'activation d'un médicament photosensibilisateur par une source lumineuse à une longueur d'onde spécifique, la PDT permet la destruction sélective de tissus contenant le produit actif. Ce procédé a été expérimenté dans le traitement de cancers en raison de la propriété du médicament à se concentrer dans les tumeurs tout en épargnant les structures normales contigües. Cependant, les photosensibilisateurs utilisés jusqu'à ce jour n'ont pas démontré une accumulation exclusive dans les tissus néoplasiques mais également dans les structures saines avoisinantes induisant une destruction tissulaire non sélective. Notamment, d'importantes complications ont été rapportées suite à l'utilisation de la PDT dans la cavité thoracique après la résection de mésothéliomes pleuraux, et ce malgré l'arrivée de photosensibilisateurs de secondes générations. De ce fait, plusieurs études expérimentales ont été menées afin d'améliorer la sélectivité tumorale du médicament en modulant différentes conditions de traitement et en modifiant la structure du photosensibilisateur par pégylation. Le but de cette étude expérimentale est de corréler l'activité photodynamique, la phototoxicité et la distribution du m-tetrahydroxyphenylchlorin (mTHPC) et de sa forme pégylée, le PEG-mTHPC. De ce fait, un modèle de souris nues porteur de xenogreffes de mésothéliome humain a été utilisé pour étudier les deux photosensibilisateurs. De récents travaux avec ce modèle ont montré que la mesure de la concentration tissulaire du mTHPC et de sa forme pégylée par HPLC restait limitée afin de prédire l'activité photodynamique. De ce fait, nous pensons que les mesures de fluorescence peuvent être plus appropriée. Le signalement fluorescent est mesuré dans le tissu tumoral et dans une région contrôle de la peau afin d'étudier la distribution et l'intensité des deux sensibilisateurs. Méthode : Des souris nues (cd1nu/nu mice) de 8 semaines ont été transplantées avec des fragments de mésothéliome malin humain (H-meso-1). Ces derniers ont été obtenus à partir d'une suspension cellulaire. Au moins trois passages ont été faits dans les animaux, avant que le traitement soit initié. Deux groupes de 6 souris chacun ont été utilisés pour l'injection intraveineuse par la queue du mTHPC à 0.15 mg/kg et du PEG-mTHPC à dose équimolaire. Après trois jour, la tumeur ainsi qu'une région contrôle de la cuisse ont été illuminées sur une surface d'un diamètre de 1.2 cm et pendant 133 secondes avec un laser à une longueur d'onde à 652 nm (fluence 20 J/cm2, fluence rate 150 mW/cm2). Les animaux ont été ensuite sacrifiés 72 heures après l'illumination. L'étendue de la nécrose tumorale et de la région contrôle ont été déterminées en aveugle par histomorphometrie par un pathologue (HJA). La fluorescence microscopique a été évaluée dans 12 souris à une concentration de 0.15 et 0.5 mg/kg pour le mTHPC, et à doses équimolaires pour le PEG-mTHPC. Trois animaux ont été injectés avec le mTHPC à 0.15 mg/kg, 3 autres à dose équimolaire avec la forme pégylée et 6 souris avec le mTHPC à 0.5 mg/kg et à dose équimolaire. Les animaux ont été sacrifiés 72 heures après injection. L'intensité fluorescente des sensibilisateurs a été mesurée dans la tumeur et la région contrôle. Suite à cela, les coupes ont été fixées par H&E et superposées aux images fluorescentes, afin de localiser la distribution des deux photosensibilisateurs dans les différents compartiments tissulaires. Six souris transplantées n'ayant ni été injectées avec les sensibilisateurs ou illuminées ont servi de groupe contrôle. Résultats : Trois jours après l'illumination, la PDT provoque une nécrose tumorale de 10 ±5.4 mm2 pour le mTHPC à 0.15mg/kg et 5.2 ± 4.6 mm2 pour sa forme pégylée à dose équimolaire. Cependant, la nécrose tumorale induite par les deux formulations du sensibilisateur est significativement plus élevée que dans le groupe contrôle (0.33 ± 0.58 mm2) (P=0.02). Toutefois, le mTHPC pégylé provoque une photosensibilité cutanée moins importante que la forme non-pegylée. Dans les deux groupes, aucune nécrose n'a été observée dans la cuisse des animaux. Trois jours après l'injection du mTHPC et de la forme pégylée à 0.15 mg/kg, aucune activité fluorescente n'a été détectée. Cependant, à 0.5 mg/kg, la fluorescence microscopique révèle une distribution hétérogène des deux photo-sensibilisateurs dans le tissu tumoral avec une accumulation prédominante dans les régions peri-vasculaires. Les deux médicaments montrent une distribution intracellulaire homogène dans le cytoplasme et une absence de signalement dans le nucleus. La mesure de l'intensité fluorescente du mTHPC à 0.5mg/kg ne montre pas de différence significative entre le tissu tumoral et la région contrôle. Par contre, le PEG-mTHPC montre une intensité fluorescente supérieure dans le tissu tumoral que dans la peau (ratio tumeur- peau 0.94 pour le mTHPC et 1.73 pour le PEG-mTHPC). Conclusion : L'utilisation du mTHPC à 0.15mg/kg induit une nécrose tumorale similaire à celle du PEG-mTHPC à dose équimolaire. Cependant, ce dernier démontre une photo-toxicité plus atténuée de la peau. La fluorescence microscopique permet de localiser les deux sensibilisateurs dans les différents compartiments tissulaires à partir d'une dose de 0.5 mg/kg. Le PEG-mTHPC induit un signalement fluorescent supérieur dans le tissu tumoral par rapport à la peau. La mesure du signalement fluorescent a le potentiel de prédire l'activité photodynamique du mTHPC et de sa forme pégylée dans les xénogreffes de mésothéliome humain dans un modèle de souris nue.

Low Cost Techniques of Base Stabilization, HR-312, 1994

This project was initiated in 1988 to study the effectiveness of four different construction techniques for establishing a stable base on a granular surfaced roadway. After base stabilization, the roadway was then seal coated, eliminating dust problems associated with granular surfaced roads. When monies become available, the roadway can be surfaced with a more permanent structure. A 2.8 mi (4.5 km) section of the Horseshoe Road in Dubuque County was divided into four divisions for this study. This report discusses the procedures used during construction of these different divisions. Problems and possible solutions have been analyzed to better understand the capabilities of the materials and construction techniques used on the project. The project had the following results: High structural ratings and soil K factors for the BIO CAT and Consolid bases did not translate to good roadway performance; the macadam base had the best overall performance; the tensar fabric had no noticeable effect on the macadam base; and the HFE-300 performed acceptably.

Transobturator surgery for female stress incontinence: a comparative anatomical study of outside-in vs inside-out techniques.

OBJECTIVE To assess the specific risks of injury to neural and vascular structures inherent in two approaches to transobturator surgery for inserting a suburethral sling, i.e. the outside-in (standard technique) and inside-out approaches. MATERIALS AND METHODS The study comprised seven cadavers, providing 14 obturator regions. Five specimens had a tape inserted outside-in on one side, and inside-out on the other; of the remaining two cadavers, one had an inside-out tape and one an outside-in tape, bilaterally. After tape insertion, the cadavers were dissected. Particular attention was paid to the distances between the tape and the deep external pudendal vessels, and between the tape and the posterior branch of the obturator nerve. RESULTS With the inside-out technique, the safety margins were reduced, and the external pudendal vessels and the posterior branch of the obturator nerve were at greater risk of injury. CONCLUSION The two techniques are not equivalent, with a lower risk of injury to vascular and nerve structures with the outside-in technique.

Image Analysis for Evaluating Air Void Parameters of Concrete, HR-396, 1998

This research project investigated the use of image analysis to measure the air void parameters of concrete specimens produced under standard laboratory conditions. The results obtained from the image analysis technique were compared to results obtained from plastic air content tests, Danish air meter tests (also referred to as Air Void Analyzer tests), high-pressure air content tests on hardened concrete, and linear traverse tests (as per ASTM C-457). Hardened concrete specimens were sent to three different laboratories for the linear traverse tests. The samples that were circulated to the three labs consisted of specimens that needed different levels of surface preparation. The first set consisted of approximately 18 specimens that had been sectioned from a 4 in. by 4 in. by 18 in. (10 cm by 10 cm by 46 cm) beam using a saw equipped with a diamond blade. These specimens were subjected to the normal sample preparation techniques that were commonly employed by the three different labs (each lab practiced slightly different specimen preparation techniques). The second set of samples consisted of eight specimens that had been ground and polished at a single laboratory. The companion labs were only supposed to retouch the sample surfaces if they exhibited major flaws. In general, the study indicated that the image analysis test results for entrained air content exhibited good to strong correlation to the average values determined via the linear traverse technique. Specimens ground and polished in a single laboratory and then circulated to the other participating laboratories for the air content determinations exhibited the strongest correlation between the image analysis and linear traverse techniques (coefficient of determination, r-squared = 0.96, for n=8). Specimens ground and polished at each of the individual laboratories exhibited considerably more scatter (coefficient of determination, r-squared = 0.78, for n=16). The image analysis technique tended to produce low estimates of the specific surface of the voids when compared to the results from the linear traverse method. This caused the image analysis spacing factor calculations to produce larger values than those obtained from the linear traverse tests. The image analysis spacing factors were still successful at distinguishing between the frost-prone test specimens and the other (more durable) test specimens that were studied in this research project.

Correlation Studies BPR Type Roughometer vs. PCE Type Road Meter, MLR-68-2, 1968

The BPR type Roughometer has been used by the Iowa State Highway Commission since 1955 for the evaluation of the relative roughness of the various Iowa road surfaces. Since the commencement of this program, standardized information about the roughness of the various Iowa roads with respect to their type, construction, location and usage has been obtained. The Roughometer has also served to improve the economics and quality of road construction by making the roughness results of various practices available to all who are interested. In 1965, the Portland Cement Association developed a device known as the PCA Road Meter for measuring road roughness. Mounted in a regular passenger car, the Road Meter is a simple electromechanical device of durable construction which can perform consistently with extremely low maintenance. In 1967, the Iowa State Highway Commission's Laboratory constructed a P.C.A. type Road Meter in order to provide an efficient and reliable method for measuring the Present Serviceability Index for the state's highways. Another possibility was that after considerable testing the Road Meter might eventually replace the Roughometer. Some advantages of the Road Meter over the Roughometer are: (1) Road Meter tests are made by the automobile driver and one assistant without the need of traffic protection. The Roughometer has a crew of four men; two operating the roughometer and two driving safety vehicles. (2) The Road Meter is able to do more miles of testing because of its faster testing speed and the fa.ct that it is the only vehicle involved in the testing. (3) Because of the faster testing speed, the Road Meter gives a better indication of how the road actually rides to the average highway traveler. (4) The cost of operating a Road Meter is less than that of a Roughometer because of the fewer number of vehicles and men needed in testing.

Correlation of the Roughometer to the High-Speed Laser Profiler, MLR-97-7, 1997

The Iowa Department of Transportation has been using the Bureau of Public Roads (BPR) Roughometer as part of its detour analysis process for more than 20 years. Advances in technology have made the BPR Roughometer obsolete for ride quality testing. High-speed profilers that can collect the profile of the road at highway speeds are the standard ride instruments for determining ride quality on pavements. The objective of the project was to develop a correlation between the BPR Roughometer and the high-speed laser South Dakota type Profiler (SD Profiler). Nineteen pavement sections were chosen to represent the range of types and conditions for detours. Three computer simulation models were tested on the profiler profiles. The first model is the International Ride Index (IRI) which is considered the standard index for reporting ride quality in the United States. The second model is the Ride Number (RN) developed by the University of Michigan Transportation Research Institute and the third model used is a quarter-car simulation of the BPR Roughometer (ASTM E-1170) which should match the speed and range of roadway features experienced by Iowa's BPR Roughometer Unit. The BPR Roughometer quarter-car model provided the best overall correlation with Iowa's BPR Roughometer.

Correlation of Locally-Based Performance of Asphalts with their Physicochemical Parameters, Task 1 Report, HR-298, 1988

This is the first report of 6 tasks to be performed in an effort to establish locally-based quality and performance criteria for asphalts, and ultimately to develop performance-related specifications based on simple physicochemical methods. Three of the most promising chemical methods (high performance liquid chromatography (HPLC), thermal analysis, and X-ray diffraction were selected to analyze 4 different types of samples. The results will indicate the fundamental asphalt property variables that directly affect the field performance in Iowa. The details of the materials and procedures employed are described, and the results of the tests are presented.

Service Correlation of the Traffic Simulator, HR-100, 1967

A study was undertaken by the Bituminous Research Laboratory of the Engineering Research Institute at Iowa State University, under the sponsorship of the Iowa Highway Research Board, project HR 100, to ascertain the effects of a number of characteristics and properties of asphaltic concrete mixes upon the service behavior of the mixes as evaluated by the Traffic Simulator and by field observations. The study included: Investigations of the relations, of gradation, fraction and resistance to wear of aggregates; of stability, cohesion, per cent voids and asphalt content: of a number of laboratory and field mixes to service behavior as indicated by the Traffic Simulator under various test conditions. Based upon the results of the tests and the relationships noted, tentative criteria for the Traffic Simulator test were devised, subject to verification by observations and measurements of field service behavior of the mixes.

Advanced MRI unravels the nature of tissue alterations in early multiple sclerosis.

INTRODUCTION: In patients with multiple sclerosis (MS), conventional magnetic resonance imaging (MRI) provides only limited insights into the nature of brain damage with modest clinic-radiological correlation. In this study, we applied recent advances in MRI techniques to study brain microstructural alterations in early relapsing-remitting MS (RRMS) patients with minor deficits. Further, we investigated the potential use of advanced MRI to predict functional performances in these patients. METHODS: Brain relaxometry (T1, T2, T2*) and magnetization transfer MRI were performed at 3T in 36 RRMS patients and 18 healthy controls (HC). Multicontrast analysis was used to assess for microstructural alterations in normal-appearing (NA) tissue and lesions. A generalized linear model was computed to predict clinical performance in patients using multicontrast MRI data, conventional MRI measures as well as demographic and behavioral data as covariates. RESULTS: Quantitative T2 and T2* relaxometry were significantly increased in temporal normal-appearing white matter (NAWM) of patients compared to HC, indicating subtle microedema (P = 0.03 and 0.004). Furthermore, significant T1 and magnetization transfer ratio (MTR) variations in lesions (mean T1 z-score: 4.42 and mean MTR z-score: -4.09) suggested substantial tissue loss. Combinations of multicontrast and conventional MRI data significantly predicted cognitive fatigue (P = 0.01, Adj-R (2) = 0.4), attention (P = 0.0005, Adj-R (2) = 0.6), and disability (P = 0.03, Adj-R (2) = 0.4). CONCLUSION: Advanced MRI techniques at 3T, unraveled the nature of brain tissue damage in early MS and substantially improved clinical-radiological correlations in patients with minor deficits, as compared to conventional measures of disease.

Assessment of skinfold thickness equations in estimating body composition in children with inflammatory bowel

Introduction: Growth is a central process in paediatrics. Weight and height evaluation are therefore routine exams for every child but in some situation, particularly inflammatory bowel disease (IBD), a wider evaluation of nutritional status needs to be performed. The assessment of body composition is essential in order to maintain acceptable growth using the following techniques: Dual-energy X-ray absorptiometry (DEXA), bio-impedance-analysis (BIA) and anthropometric measurements (skinfold thickness skin), the latter being most easily available and most cost effective. Objectives: To assess the accuracy of skinfold equations in estimating percentage body fat (%BF) in children with inflammatory bowel disease (IBD), compared with assessment of body fat dual energy X-ray absorptiometry (DEXA). Methods: Twenty-one patients (11 females, 10 males; mean age: 14.3 years, range 12 - 16 years) with IBD (Crohn's disease n = 15, ulcerative colitis n = 6)). Estimated%BF was computed using 6 established equations based on the triceps, biceps, subscapular and suprailiac skinfolds (Deurenberg, Weststrate, Slaughter, Durnin & Rahaman, Johnston, Brook) and compared to DEXA. Concordance analysis was performed using Lin's concordance correlation and the Bland-Altman limits of agreement method. Results: Durnin & Rahaman's equation shows a higher Lin's concordance coefficient with a small difference amongst raw values for skinfolds and DEXA compared to the other equations. Correlation coefficient between mean and difference is close to zero with a non-significant Bradley-Blackwood test. Conclusion: Body composition in paediatric IBD patients using the Durnin & Rahaman skinfold-equation adequately reflects values obtained by DEXA.

Transmission electron microscopy in cell biology: sample preparation techniques and image information

Transmission electron microscopy is a proven technique in the field of cell biology and a very useful tool in biomedical research. Innovation and improvements in equipment together with the introduction of new technology have allowed us to improve our knowledge of biological tissues, to visualizestructures better and both to identify and to locate molecules. Of all the types ofmicroscopy exploited to date, electron microscopy is the one with the mostadvantageous resolution limit and therefore it is a very efficient technique fordeciphering the cell architecture and relating it to function. This chapter aims toprovide an overview of the most important techniques that we can apply to abiological sample, tissue or cells, to observe it with an electron microscope, fromthe most conventional to the latest generation. Processes and concepts aredefined, and the advantages and disadvantages of each technique are assessedalong with the image and information that we can obtain by using each one ofthem.

The use of uniaxial accelerometry for the assessment of physical-activity-related energy expenditure: a validation study against whole-body indirect calorimetry.

Assessing the total energy expenditure (TEE) and the levels of physical activity in free-living conditions with non-invasive techniques remains a challenge. The purpose of the present study was to investigate the accuracy of a new uniaxial accelerometer for assessing TEE and physical-activity-related energy expenditure (PAEE) over a 24 h period in a respiratory chamber, and to establish activity levels based on the accelerometry ranges corresponding to the operationally defined metabolic equivalent (MET) categories. In study 1, measurement of the 24 h energy expenditure of seventy-nine Japanese subjects (40 (SD 12) years old) was performed in a large respiratory chamber. During the measurements, the subjects wore a uniaxial accelerometer (Lifecorder; Suzuken Co. Ltd, Nagoya, Japan) on their belt. Two moderate walking exercises of 30 min each were performed on a horizontal treadmill. In study 2, ten male subjects walked at six different speeds and ran at three different speeds on a treadmill for 4 min, with the same accelerometer. O2 consumption was measured during the last minute of each stage and was expressed in MET. The measured TEE was 8447 (SD 1337) kJ/d. The accelerometer significantly underestimated TEE and PAEE (91.9 (SD 5.4) and 92.7 (SD 17.8) % chamber value respectively); however, there was a significant correlation between the two values (r 0.928 and 0.564 respectively; P<0.001). There was a strong correlation between the activity levels and the measured MET while walking (r(2) 0.93; P<0.001). Although TEE and PAEE were systematically underestimated during the 24 h period, the accelerometer assessed energy expenditure well during both the exercise period and the non-structured activities. Individual calibration factors may help to improve the accuracy of TEE estimation, but the average calibration factor for the group is probably sufficient for epidemiological research. This method is also important for assessing the diurnal profile of physical activity.