Effects of different sweet preloads on incretin hormone secretion, gastric emptying, and postprandial glycemia in healthy humans.

Science.gov (United States)

Wu, Tongzhi; Zhao, Beiyi R; Bound, Michelle J; Checklin, Helen L; Bellon, Max; Little, Tanya J; Young, Richard L; Jones, Karen L; Horowitz, Michael; Rayner, Christopher K

2012-01-01

Macronutrient "preloads" can stimulate glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), slow gastric emptying, and reduce postprandial glycemic excursions. After sweet preloads, these effects may be signaled by sodium-glucose cotransporter-1 (SGLT1), sweet taste receptors, or both. We determined the effects of 4 sweet preloads on GIP and GLP-1 release, gastric emptying, and postprandial glycemia. Ten healthy subjects were studied on 4 separate occasions each. A preload drink containing 40 g glucose, 40 g tagatose/isomalt mixture (TIM), 40 g 3-O-methylglucose (3OMG; a nonmetabolized substrate of SGLT1), or 60 mg sucralose was consumed 15 min before a (13)C-octanoic acid-labeled mashed potato meal. Blood glucose, plasma total GLP-1 and GIP, serum insulin, and gastric emptying were determined. Both glucose and 3OMG stimulated GLP-1 and GIP release in advance of the meal (each P < 0.05), whereas TIM and sucralose did not. The overall postprandial GLP-1 response was greater after glucose, 3OMG, and TIM than after sucralose (P < 0.05), albeit later after TIM than the other preloads. The blood glucose and insulin responses in the first 30 min after the meal were greatest after glucose (each P < 0.05). Gastric emptying was slower after both 3OMG and TIM than after sucralose (each P < 0.05). In healthy humans, SGLT1 substrates stimulate GLP-1 and GIP and slow gastric emptying, regardless of whether they are metabolized, whereas the artificial sweetener sucralose does not. Poorly absorbed sweet tastants (TIM), which probably expose a greater length of gut to nutrients, result in delayed GLP-1 secretion but not in delayed GIP release. These observations have the potential to optimize the use of preloads for glycemic control. This trial was registered at www.actr.org.au as ACTRN12611000775910.

Efficient preloading of the ventricles by a properly timed atrial contraction underlies stroke work improvement in the acute response to cardiac resynchronization therapy

Science.gov (United States)

Hu, Yuxuan; Gurev, Viatcheslav; Constantino, Jason; Trayanova, Natalia

2013-01-01

Background The acute response to cardiac resynchronization therapy (CRT) has been shown to be due to three mechanisms: resynchronization of ventricular contraction, efficient preloading of the ventricles by a properly timed atrial contraction, and mitral regurgitation reduction. However, the contribution of each of the three mechanisms to the acute response of CRT, specifically stroke work improvement, has not been quantified. Objective The goal of this study was to use an MRI-based anatomically accurate 3D model of failing canine ventricular electromechanics to quantify the contribution of each of the three mechanisms to stroke work improvement and identify the predominant mechanisms. Methods An MRI-based electromechanical model of the failing canine ventricles assembled previously by our group was further developed and modified. Three different protocols were used to dissect the contribution of each of the three mechanisms to stroke work improvement. Results Resynchronization of ventricular contraction did not lead to significant stroke work improvement. Efficient preloading of the ventricles by a properly timed atrial contraction was the predominant mechanism underlying stroke work improvement. Stroke work improvement peaked at an intermediate AV delay, as it allowed ventricular filling by atrial contraction to occur at a low diastolic LV pressure but also provided adequate time for ventricular filling before ventricular contraction. Diminution of mitral regurgitation by CRT led to stroke work worsening instead of improvement. Conclusion Efficient preloading of the ventricles by a properly timed atrial contraction is responsible for significant stroke work improvement in the acute CRT response. PMID:23928177

Probabilistic analysis of preload in the abutment screw of a dental implant complex.

Science.gov (United States)

Guda, Teja; Ross, Thomas A; Lang, Lisa A; Millwater, Harry R

2008-09-01

Screw loosening is a problem for a percentage of implants. A probabilistic analysis to determine the cumulative probability distribution of the preload, the probability of obtaining an optimal preload, and the probabilistic sensitivities identifying important variables is lacking. The purpose of this study was to examine the inherent variability of material properties, surface interactions, and applied torque in an implant system to determine the probability of obtaining desired preload values and to identify the significant variables that affect the preload. Using software programs, an abutment screw was subjected to a tightening torque and the preload was determined from finite element (FE) analysis. The FE model was integrated with probabilistic analysis software. Two probabilistic analysis methods (advanced mean value and Monte Carlo sampling) were applied to determine the cumulative distribution function (CDF) of preload. The coefficient of friction, elastic moduli, Poisson's ratios, and applied torque were modeled as random variables and defined by probability distributions. Separate probability distributions were determined for the coefficient of friction in well-lubricated and dry environments. The probabilistic analyses were performed and the cumulative distribution of preload was determined for each environment. A distinct difference was seen between the preload probability distributions generated in a dry environment (normal distribution, mean (SD): 347 (61.9) N) compared to a well-lubricated environment (normal distribution, mean (SD): 616 (92.2) N). The probability of obtaining a preload value within the target range was approximately 54% for the well-lubricated environment and only 0.02% for the dry environment. The preload is predominately affected by the applied torque and coefficient of friction between the screw threads and implant bore at lower and middle values of the preload CDF, and by the applied torque and the elastic modulus of the abutment

Ball Nut Preload Diagnosis of the Hollow Ball Screw through Support Vector Machine

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Yi-Cheng Huang

2018-01-01

Full Text Available This paper studies the diagnostic results of hollow ball screws with different ball nut preload through the support vector machine (SVM process. The method is testified by considering the use of ball screw pretension and different ball nut preload. SVM was used to discriminate the hollow ball screw preload status through the vibration signals and servo motor current signals. Maximum dynamic preloads of 2%, 4%, and 6% ball screws were predesigned, manufactured, and conducted experimentally. Signal patterns with different preload features are separatedby SVM. The irregularity development of the ball screw driving motion current and rolling balls vibration of the ball screw can be discriminated via SVM based on complexity perception. The experimental results successfully show that the prognostic status of ball nut preload can be envisaged by the proposed methodology. The smart reasoning for the health of the ball screw is available based on classification of SVM. This diagnostic method satisfies the purposes of prognostic effectiveness on knowing the ball nut preload status

Ultrasonic extensometer measures bolt preload

Science.gov (United States)

Daniels, C. M., Jr.

1978-01-01

Extensometer using ultrasonic pulse reflections to measure elongations in tightened belts and studs is much more accurate than conventional torque wrenches in application of specified preload to bolts and other threaded fasteners.

Improving sensitivity of the polyurethane/CNT laminate strain sensor by controlled mechanical preload

International Nuclear Information System (INIS)

Slobodian, Petr; Olejnik, Robert; Matyas, Jiri; Babar, Dipak Gorakh

2016-01-01

This article describes strain detection potential of polyurethane/CNT layered composite and further possible enhance of its sensitivity to strain, expressed by value of gauge factor, GF, employing its controlled mechanical preload. In course of its fabrication a non-woven polyurethane membrane made by electro spinning was used as filtering membrane for CNT aqueous dispersion. Final CNT polyurethane laminate composite is prepared by compression molding. Produced polyurethane/CNT composite laminate is electrically conductive and high elastic. Its elongation leads to change of its macroscopic electrical resistance. Changes in resistance are further reversible, reproducible and can monitor deformation in real time. Gauge factor reaches very high values around 8 for strain reaching 3.5% comparing with conventional metallic strain gauges. Finally, controlled mechanical preload significantly increases value of GF. For example for value of 8.1% of preload value of GF reaches 23.3 for strain 3.5%. (paper)

Evaluation of satiety sensations and food intake after different preloads.

Science.gov (United States)

Porrini, M; Crovetti, R; Testolin, G; Silva, S

1995-08-01

The reproducibility of three questions, related to fullness, satiety and desire to eat, rated on an unmarked triangle was verified. In four sessions 12 volunteers ate pasta with tomato sauce (520 kcal) and were asked to rate the sensations felt. There was no difference in rating scores of the replications so the proposed questionnaire provides a stable measure of sensations related to satiety. Subsequently three satiety conditions were studied. Two foods, one rich in carbohydrate, pasta (baked macaroni) and the other in protein, polpette (meatballs), were used as loads at two calorie levels and as preload before an "ad libitum" meal. All the three questions proved useful in discriminating between the different satiety conditions. The food intake underlines the specificity of satiety: subjects, after eating a preload which previously had satiated them, ate other foods in different amounts depending on the kind of preload eaten. Food intake was significantly higher after the pasta preload, furthermore "fullness" and "satiety" ratings were significantly highest after the meatball preload, suggesting that in our experimental conditions, meatballs were more satiating than pasta. In conclusion, this study highlights the validity of using several quite different questions to study hunger and satiety, together with the actual food intake.

Protein-Enriched Liquid Preloads Varying in Macronutrient Content Modulate Appetite and Appetite-Regulating Hormones in Healthy Adults.

Science.gov (United States)

Dougkas, Anestis; Östman, Elin

2016-03-01

Dietary protein is considered the most satiating macronutrient, yet there is little evidence on whether the effects observed are attributable to the protein or to the concomitant manipulation of carbohydrates and fat. The aim was to examine the effect of consumption of preloads varying in macronutrient content on appetite, energy intake, and biomarkers of satiety. Using a randomized, within-subjects, 2-level factorial design, 36 adults [mean ± SD age: 27 ± 5 y; body mass index (in kg/m(2)): 24.3 ± 1.6) received a breakfast consisting of 1 of 7 isovolumetric (670 mL) and isoenergetic (2100 kJ) liquid preloads matched for energy density and sensory properties but with different macronutrient composition (levels: 9%, 24%, or 40% of energy from protein combined with a carbohydrate-to-fat ratio of 0.4, 2, or 3.6, respectively). Appetite ratings and blood samples were collected and assessed at baseline and every 30 and 60 min, respectively, until a lunch test meal, which participants consumed ad libitum, was served 3.5 h after breakfast. Prospective consumption was 12% lower after intake of the high-protein (40%)/3.6 carbohydrate:fat preload than after intake of the low-protein (9%)/0.4 carbohydrate:fat preload (P = 0.02) solely because of the increased protein, irrespective of the manipulation of the other macronutrients. Most appetite ratings tended to be suppressed (13%) with increasing protein content of the preloads (P appetite than did carbohydrates and fat. Modulating the nutritional profile of a meal by replacing fat with protein can influence appetite in healthy adults. This trial was registered at www.clinicaltrials.gov as NCT01849302. © 2016 American Society for Nutrition.

Laboratory model study of newly deposited dredger fills using improved multiple-vacuum preloading technique

Directory of Open Access Journals (Sweden)

Jingjin Liu

2017-10-01

Full Text Available Problems continue to be encountered concerning the traditional vacuum preloading method in field during the treatment of newly deposited dredger fills. In this paper, an improved multiple-vacuum preloading method was developed to consolidate newly dredger fills that are hydraulically placed in seawater for land reclamation in Lingang Industrial Zone of Tianjin City, China. With this multiple-vacuum preloading method, the newly deposited dredger fills could be treated effectively by adopting a novel moisture separator and a rapid improvement technique without sand cushion. A series of model tests was conducted in the laboratory for comparing the results from the multiple-vacuum preloading method and the traditional one. Ten piezometers and settlement plates were installed to measure the variations in excess pore water pressures and moisture content, and vane shear strength was measured at different positions. The testing results indicate that water discharge–time curves obtained by the traditional vacuum preloading method can be divided into three phases: rapid growth phase, slow growth phase, and steady phase. According to the process of fluid flow concentrated along tiny ripples and building of larger channels inside soils during the whole vacuum loading process, the fluctuations of pore water pressure during each loading step are divided into three phases: steady phase, rapid dissipation phase, and slow dissipation phase. An optimal loading pattern which could have a best treatment effect was proposed for calculating the water discharge and pore water pressure of soil using the improved multiple-vacuum preloading method. For the newly deposited dredger fills at Lingang Industrial Zone of Tianjin City, the best loading step was 20 kPa and the loading of 40–50 kPa produced the highest drainage consolidation. The measured moisture content and vane shear strength were discussed in terms of the effect of reinforcement, both of which indicate

Comparison of colloid (polygeline) over crystalloid (lactated ringer) preloading in preventing hypotension in patients undergoing caesarean-section under spinal anaesthesia

International Nuclear Information System (INIS)

Boota, M.; Haq, I.

2012-01-01

Objective: To assess efficacy of colloid (Polygeline) over crystalloid (Lactated Ringer) preloading in preventing hypotension in patients undergoing caesarean-section under spinal anaesthesia. Study design: Randomized control trial. Settings: The study was conducted in department of Anesthesiology and Intensive care Combined Military Hospital Peshawar over a period of 6 months from 01 March 2007 to 31 August 2007. Material and Methods: One hundred patients fulfilling the inclusion criteria were selected for study and divided into two groups of 50 each. Group A was given 500 ml Polygeline as preloading solution while group B received 1 liter of Ringer's Lactate as preloading solution just before administration of spinal anaesthesia. Heart rate and systolic blood pressure were recorded at 01 min, 05 mins, 10 mins, 15 mins, 20 mins, 30 mins and 45 mins after the performance of spinal block. Dose of ephedrine given to treat hypotension after the block was also recorded. Results: There was significant difference in terms of heart rate and systolic arterial pressure 1 and 5 minutes after block between both the groups. There was also significant difference in terms of dose of ephedrine between both the groups. Conclusion: Polygeline is more effective than Ringer's Lactate as preloading fluid in preventing hypotension for caesarean section under spinal anaesthesia. (author)

A pilot investigation to optimise methods for a future satiety preload study

OpenAIRE

Hobden, Mark R.; Guérin-Deremaux, Laetitia; Commane, Daniel M.; Rowland, Ian; Gibson, Glenn R.; Kennedy, Orla B.

2017-01-01

Background Preload studies are used to investigate the satiating effects of foods and food ingredients. However, the design of preload studies is complex, with many methodological considerations influencing appetite responses. The aim of this pilot investigation was to determine acceptability, and optimise methods, for a future satiety preload study. Specifically, we investigated the effects of altering (i) energy intake at a standardised breakfast (gender-specific or non-gender specific), an...

Soup preloads in a variety of forms reduce meal energy intake.

Science.gov (United States)

Flood, Julie E; Rolls, Barbara J

2007-11-01

Consuming soup can enhance satiety and reduce energy intake. Little is known about the influence on energy intake and satiety of varying the form of soup by altering the blending of ingredients. We tested the effects on meal intake of consuming different forms of soup as a preload: broth and vegetables served separately, chunky vegetable soup, chunky-pureed vegetable soup, or pureed vegetable soup. Normal-weight men and women (n = 60) came to the laboratory for lunch once a week for 5 weeks. Each week, one of four compulsory preloads, or no preload, was consumed prior to lunch. A test meal was consumed ad libitum 15 min after the soup was served. Results showed that consuming soup significantly reduced test meal intake and total meal energy intake (preload + test meal) compared to having no soup. When soup was consumed, subjects reduced meal energy intake by 20% (134+/-25 kcal; 561+/-105 kJ). The type of soup had no significant effect on test meal intake or total meal energy intake. Consuming a preload of low-energy-dense soup, in a variety of forms, is one strategy for moderating energy intake in adults.

Increasing preload volume with water reduces rated appetite but not food intake in healthy men even with minimum delay between preload and test meal.

Science.gov (United States)

Gray, Richard W; French, Stephen J; Robinson, Tristan M; Yeomans, Martin R

2003-02-01

The role of gastric volume in the short-term control of eating in humans remains unclear, with some studies reporting that food volume alone can reduce appetite but others finding no such effect. A recent study in our laboratory, found effects of preload volume on subjective appetite (hunger, fullness) but not intake, and found effects of preload energy on intake but not appetite. That study used an interval of 30 min between serving preloads and the test meal, and the present study attempted to maximise the effects of the volume manipulation by removing the delay between the preload and test meal. We administered four soup-based preloads varying in volume (150 and 450 ml) using water, and energy density (1.4 and 4.2 kJ/ml) using maltodextrin, producing three energy levels (209, 629, 629 and 1886 kJ; repeated measures). These were followed immediately by an unlimited hot pasta lunch, during which food weight was monitored continuously by computer. Increasing soup volume at constant energy (629 kJ) reduced appetite ratings, but not intake. In contrast, increasing soup energy at constant volume (450 ml) reduced intake, without affecting appetite. The discrepancies between our results and other reported studies suggest that volume is more influential when intakes are large, or that there may be a threshold concentration for nutrients in the GI tract before volume alone is tangibly expressed in subsequent eating.

Influence of cyclic torsional preloading on cyclic fatigue resistance of nickel - titanium instruments.

Science.gov (United States)

Pedullà, E; Lo Savio, F; Boninelli, S; Plotino, G; Grande, N M; Rapisarda, E; La Rosa, G

2015-11-01

To evaluate the effect of different torsional preloads on cyclic fatigue resistance of endodontic rotary instruments constructed from conventional nickel-titanium (NiTi), M-Wire or CM-Wire. Eighty new size 25, 0.06 taper Mtwo instruments (Sweden & Martina), size 25, 0.06 taper HyFlex CM (Coltene/Whaledent, Inc) and X2 ProTaper Next (Dentsply Maillefer) were used. The Torque and distortion angles at failure of new instruments (n = 10) were measured, and 0% (n = 10), 25%, 50% and 75% (n = 20) of the mean ultimate torsional strength as preloading condition were applied according to ISO 3630-1 for each brand. The twenty files tested for every extent of preload were subjected to 20 or 40 torsional cycles (n = 10). After torsional preloading, the number of cycles to failure was evaluated in a simulated canal with 60° angle of curvature and 5 mm of radius of curvature. Data were analysed using two-way analysis of variance. The fracture surface of each fragment was examined with a scanning electron microscope (SEM). Data were analysed by two-way analyses of variance. Preload repetitions did not influence the cyclic fatigue of the three brands; however, the 25%, 50% and 75% torsional preloading significantly reduced the fatigue resistance of all instruments tested (P 0.05). Torsional preloads reduced the cyclic fatigue resistance of conventional and treated (M-wire and CM-wire) NiTi rotary instruments except for size 25, 0.06 taper HyFlex CM instruments with a 25% of torsional preloading. © 2014 International Endodontic Journal. Published by John Wiley & Sons Ltd.

Nuclear fuel rack lateral support and preload device

International Nuclear Information System (INIS)

Knight, C.B.

1979-01-01

A lateral support device for a nuclear fuel rack is described. It is vertically positioned within a walled enclosure which provides a preload to maintain effective support. The device includes a scissors-jack which is mounted so that the drive screw is vertical. Upon rotation of the drive screw the jack expands horizontally, seating a load pad against a vertical wall. The load pad is affixed to the jack by an arm having a stack of spring washers which compress between the pad and the jack, thereby applying a selected preload

Influences of preload on the friction and wear properties of high-speed instrument angular contact ball bearings

Directory of Open Access Journals (Sweden)

Tao ZHANG

2018-03-01

Full Text Available For starved-oil or solid lubrication of high-speed instrument angular contact ball bearings, friction heating and wear are the main reasons of bearing failures. This paper presents a dynamic wear simulation model to investigate the impacts of different preload methods and the changes of preload caused by wear on bearing wear life. The integral value QV of stress and sliding velocity in the contact ellipses between a ball and the inner and outer races determines friction heating and wear. The changes of QV with the friction coefficient and the wear volume under constant-force preload and fixed-position preload are analyzed. Results show that under the same initial preload, the QV decreases with an increase of the friction coefficient for both preload methods, and the latter is slightly larger. The wear of the ball and the race is equivalent to the ball diameter reduction. The QV of constant-force preload is almost not changed with a decrease of the ball diameter, but for fixed-position preload, the value decreases firstly and then increases substantially due to insufficient preload, and slipping occurs, the ball diameter is reduced by 0.025%, while the preload is reduced by 60.33%. An estimation of the bearing wear life under different preload methods requires a consideration of the changes in the wear rate of bearing parts. Keywords: Angular contact ball bearings, Bearing life, Dynamic model, Preload methods, Wear rate

Reconfiguring the violent encounter? Preloading, security staff and breathalyser use in the night-time economy.

Science.gov (United States)

Farrimond, Hannah; Boyd, Katharine; Fleischer, Dreolin

2018-06-01

In a culture of preloading and late-night licenses, alcohol-related violence remains a persistent problem for police and public health. Understood as a ritualized 'micro-social' interaction (Collins 2009a, 2009b), entry into bars and clubs is a particular flashpoint for violence between bouncers/door staff and customers. A police-led initiative to deter excessive drunkenness and preloading using hand-held breathalysers (the #RU2Drunk scheme) was investigated from the perspective of security and bar staff using the devices. Interviews (n = 18 + 12), a focus group with security staff (n = 22) and a focus group with a security company (n = 3) were conducted in two seaside towns in the South-West of England, UK. A qualitative thematic analysis was conducted. Door staff emphasised the normality of 'determined drunkenness' and associated violence in their working lives. Breathalyser use appeared to disrupt the 'ritual' of the violent encounter by reconfiguring it into an interaction between customer and technology. This depersonalized the judgement about who was 'too drunk' to enter the venue, with the more discretionary nature of who to breathalyse hidden from customers. Other door staff found it less useful and saw it as a challenge to their authority and expertise. At a managerial level there was concern about the transfer of responsibility for policing the night time economy (NTE). There is potential to reconfigure the violent encounter for door staff using breathalyser devices. However, this is more likely to succeed where other structural limits (e.g. restrictions on late licenses) are in place, and as part of wider policy initiatives to reconfigure the alcohol-saturated NTE leisure scene. Copyright © 2018 Elsevier B.V. All rights reserved.

Simulations and Experiments on Vibration Control of Aerospace Thin-Walled Parts via Preload

Directory of Open Access Journals (Sweden)

Qiong Wu

2017-01-01

Full Text Available Thin-walled parts primarily comprise the entire piece of rough machining, and the material removal rate can surpass 95%. Numerous components with thin-walled structures are preferred in the aerospace industry for their light weight, high strength, and other advantages. In aerospace thin-walled workpiece machining processes and practical applications, they are excited by the vibration. The preload changing the modal stiffness of the part is found and this change causes continuous changes in the natural frequency. Researching on the influence of pretightening force on dynamic characteristics of thin-walled components is highly significant for controlling vibration. In this study, the typical aviation thin-walled part is the research object. Finite element numerical simulation and experimental verification are employed to analyze the dynamic characteristics of 7075 aluminum alloy thin-walled plates under different preloads for exploring the relationship between natural frequency and preload. The relationship is validated by comparative results. Both the simulation and experimental results show that the natural frequencies of plates increase following the augmentation of the preload. Thus, this research introduces the method where vibration of aerospace thin-walled parts is reduced by preload. For practical engineering application, a program showing the relationship between natural frequency and preload is written using Visual Basic language.

Analytical solutions for a single vertical drain with time-dependent vacuum combined surcharge preloading in membrane and membraneless systems

International Nuclear Information System (INIS)

Geng, X Y; Indraratna, B; Rujikiatkamjorn, C

2010-01-01

Vertical drains combined with vacuum pressure and surcharge preloading are widely used to accelerate the consolidation process of soft clay in order to decrease the pore pressure as well as to increase the effective stress. Currently there are two types of vacuum preloading systems commercially available; (a) membrane system with an airtight membrane over the drainage layer and, (b) membraneless system where a vacuum system is connected to individual drain. Their effectiveness varies from site to site depending on the type of soil treated and the characteristics of the drain-vacuum system. This study presents the analytical solutions of vertical drains with vacuum preloading for both membrane and membraneless systems. According to the field and laboratory observations, the vacuum in both of the membraneless and membrane system was assumed to be decreasing along the drain whereas in the membrane system, it was maintained at a constant level. This model was verified by using the measured settlements and excess pore pressures obtained from large-scale laboratory testing and case studies in Australia. The analytical solutions improved the accuracy of predicting the dissipation of pore water pressure and the associated settlement. The effects of the permeability of the sand blanket in a membrane system and the possible loss of vacuum were also discussed.

Dynamic preload indicators fail to predict fluid responsiveness in open-chest conditions

NARCIS (Netherlands)

de Waal, Eric E. C.; Rex, Steffen; Kruitwagen, Cas L. J. J.; Kalkman, Cor J.; Buhre, Wolfgang F.

Objective: Dynamic preload indicators like pulse pressure variation (PPV) and stroke volume variation (SVV) are increasingly being used for optimizing cardiac preload since they have been demonstrated to predict fluid responsiveness in a variety of perioperative settings. However, in open-chest

A technique for monitoring fast tuner piezoactuator preload forces for superconducting rf cavities

International Nuclear Information System (INIS)

Pischalnikov, Y.; Branlard, J.; Carcagno, R.; Chase, B.; Edwards, H.; Orris, D.; Makulski, A.; McGee, M.; Nehring, R.; Poloubotko, V.; Sylvester, C.; Fermilab

2007-01-01

The technology for mechanically compensating Lorentz Force detuning in superconducting RF cavities has already been developed at DESY. One technique is based on commercial piezoelectric actuators and was successfully demonstrated on TESLA cavities [1]. Piezo actuators for fast tuners can operate in a frequency range up to several kHz; however, it is very important to maintain a constant static force (preload) on the piezo actuator in the range of 10 to 50% of its specified blocking force. Determining the preload force during cool-down, warm-up, or re-tuning of the cavity is difficult without instrumentation, and exceeding the specified range can permanently damage the piezo stack. A technique based on strain gauge technology for superconducting magnets has been applied to fast tuners for monitoring the preload on the piezoelectric assembly. The design and testing of piezo actuator preload sensor technology is discussed. Results from measurements of preload sensors installed on the tuner of the Capture Cavity II (CCII)[2] tested at FNAL are presented. These results include measurements during cool-down, warmup, and cavity tuning along with dynamic Lorentz force compensation

A technique for monitoring fast tuner piezoactuator preload forces for superconducting rf cavities

Energy Technology Data Exchange (ETDEWEB)

Pischalnikov, Y.; Branlard, J.; Carcagno, R.; Chase, B.; Edwards, H.; Orris, D.; Makulski, A.; McGee, M.; Nehring, R.; Poloubotko, V.; Sylvester, C.; /Fermilab

2007-06-01

The technology for mechanically compensating Lorentz Force detuning in superconducting RF cavities has already been developed at DESY. One technique is based on commercial piezoelectric actuators and was successfully demonstrated on TESLA cavities [1]. Piezo actuators for fast tuners can operate in a frequency range up to several kHz; however, it is very important to maintain a constant static force (preload) on the piezo actuator in the range of 10 to 50% of its specified blocking force. Determining the preload force during cool-down, warm-up, or re-tuning of the cavity is difficult without instrumentation, and exceeding the specified range can permanently damage the piezo stack. A technique based on strain gauge technology for superconducting magnets has been applied to fast tuners for monitoring the preload on the piezoelectric assembly. The design and testing of piezo actuator preload sensor technology is discussed. Results from measurements of preload sensors installed on the tuner of the Capture Cavity II (CCII)[2] tested at FNAL are presented. These results include measurements during cool-down, warmup, and cavity tuning along with dynamic Lorentz force compensation.

Effects of Screw Configuration on the Preload Force of Implant-Abutment Screws.

Science.gov (United States)

Zipprich, Holger; Rathe, Florian; Pinz, Sören; Schlotmann, Luca; Lauer, Hans-Christoph; Ratka, Christoph

The aim of this study was to investigate the effects of tightening torque, screw head angle, and thread number on the preload force of abutment screws. The test specimens consisted of three self-manufactured components (ie, a thread sleeve serving as an implant analog, an abutment analog, and an abutment screw). The abutment screws were fabricated with metric M1.6 external threads. The thread number varied between one and seven threads. The screw head angles were produced in eight varying angles (30 to 180 degrees). A sensor unit simultaneously measured the preload force of the screw and the torsion moment inside the screw shank. The tightening of the screw with the torque wrench was performed in five steps (15 to 35 Ncm). The torque wrench was calibrated before each step. Only the tightening torque and screw head angle affected the resulting preload force of the implant-abutment connection. The thread number had no effect. There was an approximately linear correlation between tightening torque and preload force. The tightening torque and screw head angle were the only study parameters that affected the resulting preload force of the abutment screw. The results obtained from this experiment are valid only for a single torque condition. Further investigations are needed that analyze other parameters that affect preload force. Once these parameters are known, it will add value for a strong, but detachable connection between the implant and abutment. Short implants and flat-to-flat connections especially will benefit significantly from this knowledge.

Movement of unlined landfill under preloading surcharge.

Science.gov (United States)

Al-Yaqout, Anwar F; Hamoda, Mohamed F

2007-01-01

As organic solid waste is decomposed in a landfill and mass is lost due to gas and leachate formation, the landfill settles. Settlement of a landfill interferes with the rehabilitation and subsequent use of the landfill site after closure. This study examined the soil/solid waste movement at the Al-Qurain landfill in Kuwait after 15 years of closure as plans are underway for redevelopment of the landfill site that occupies about a km(2) with an average depth of 8-15m. Field experiments were conducted for 6 mo to measure soil/solid waste movement and water behavior within the landfill using two settlement plates with a level survey access, Casagrande-type piezometers, pneumatic piezometers, and magnetic probe extensometers. Previous results obtained indicated that biological decomposition of refuse continued after closure of the landfill site. The subsurface water rise enhanced the biological activities, which resulted in the production of increasing quantities of landfill gas. The refuse fill materials recorded a high movement rate under the imposed preloading as a result of an increase in the stress state. Up to 55% of the total movement was observed during the first 2 weeks of fill placement and increased to 80% within the first month of the 6-mo preloading test. Pneumatic piezometers showed an increase in water head, which is attributed to the developed pressure of gases escaping during the preloading period.

Influence of bearing pre-load coefficient on shaft vibration and pad temperature in a hydroturbine generator unit. A case study

Energy Technology Data Exchange (ETDEWEB)

Feng Fuzhou; Chu Fulei; Guo Dan; Lu Wenxiu [Tsinghua Univ., Beijing, BJ (China). Dept. of Precision Instruments

2001-07-01

From data collected by an online condition monitoring and fault diagnosis system, a higher pad temperature at the upper guide bearing in a pumped storage power generator unit installed in Guangdong province(GPSPS), China, was found. And also a relatively intensive shaft vibration occurred at the lower guide bearing. By calculating the Reynolds equation and viscosity-temperature equation of the lubricant, a curve between the pre-load coefficient and the increment of pad temperature is obtained, which shows that the larger, the pre-load coefficient, the bigger, the increment of pad temperature. For a practical unit in GPSPS, by employing Transfer matrix method and Wilson-{theta} method to analyze shaft vibration at different pre-load coefficients of the whole bearing or ''pad pair'' bearings, the results show that the larger the pre-load coefficient is, the smaller the vibration amplitude is, the shorter the time for vibration to become steady is. And an uneven pre-load coefficient of the ''pad pair'' bearings will cause shaft orbit from a circle to an ellipse whose long axes is at the direction of the ''pad pair'' with the lowest pre-load coefficient. Finally, reasons of higher pad temperature of the upper guide bearing and larger shaft vibration at the lower guide bearing are due to the inconsistent relation of bearing assembling clearance or pre-load coefficient of the upper and lower guide bearing, and also due to the too small, uneven pre-load coefficient of ''pad pair'' bearings. After a scheme for adjusting the bearing clearance is given, data measured show that the analysis and simulation methods are correct and the adjustment scheme to the assembling clearance of the upper and lower guide bearings is feasible and can be used to guide the field maintenance conveniently. (orig.)

Effect of Torsional and Fatigue Preloading on HyFlex EDM Files.

Science.gov (United States)

Shen, Ya; Tra, Charles; Hieawy, Ahmed; Wang, Zhejun; Haapasalo, Markus

2018-04-01

The purpose of this study was to evaluate the effect of a low amount of torsional preloading on the fatigue life and different degrees of cyclic fatigue on torsional failure of HyFlex EDM (EDM; Coltene-Whaledent, Allstetten, Switzerland) and HyFlex CM (CM; Coltene-Whaledent) instruments. EDM and CM files were used. The fatigue resistance was examined in a 5-mm radius and 60° single curve, and the mean number of cycles to failure (N f ) was recorded. The torque and rotation angles at failure of the instruments were measured according to ISO 3630-1. New files were precycled to 0%, 50%, and 75% of the N f , and torsional tests were then performed. Other new files were preloaded at 5%, 15%, 25%, and 50% of the mean rotation angles before the fatigue test. The fracture surfaces of the fragments were examined under a scanning electron microscope. The fatigue resistance of EDM instruments was higher than that of CM instruments (P EDM at 15% preloading (P EDM files even with 50% torsional preloading was significantly higher than unused CM files (P EDM files. Moderate precycling (50%) of EDM files increased their torsional resistance. The fractographic patterns corresponded to the pattern defined by the last stage test. A low amount (15%) of torsional preloading reduced the fatigue resistance of EDM files, whereas even extensive (75%) precyclic fatigue was not detrimental to their torsional resistance. Copyright © 2017 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

A Study of the Preload Force in Metal-Elastomer Torsion Springs

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Sikora Wojciech

2016-12-01

Full Text Available Neidhart type suspension units composed of metal-elastomer torsion springs can be a good alternative to steel helical springs in applications such as vibration absorbers or vehicle suspension systems. Assembling this type of spring requires initial preload of the elastomeric working elements, which determines their operating properties. The results of experimental tests and numerical simulations concerning the preload of elastomeric working elements in Neidhart type suspension units are presented in the paper. The performed research made it possible to propose a new calculation model for determining the preload force value acting on the elastomeric cylindrical elements applied in this type of suspension unit. The results obtained using the proposed model exhibit good convergence with FEM simulation results within the range of the tested geometrical and material properties.

Muscle fatigue and metabolic responses following three different antagonist pre-load resistance exercises

NARCIS (Netherlands)

Carregaro, Rodrigo; Cunha, Rafael; Oliveira, Carlos Gomes; Brown, Lee E.; Bottaro, Martim

2013-01-01

Purpose: Preload of antagonist muscles can be achieved by reciprocal actions (RAs) or by opposing muscle actions. However, evidence concerning neuromuscular and fatigue responses are scarce. Objective: To compare the effects of different knee flexor (KF) preload methods on knee extension (KE) vastus

A general model for preload calculation and stiffness analysis for combined angular contact ball bearings

Science.gov (United States)

Zhang, Jinhua; Fang, Bin; Hong, Jun; Wan, Shaoke; Zhu, Yongsheng

2017-12-01

The combined angular contact ball bearings are widely used in automatic, aerospace and machine tools, but few researches on the combined angular contact ball bearings have been reported. It is shown that the preload and stiffness of combined bearings are mutual influenced rather than simply the superposition of multiple single bearing, therefore the characteristic calculation of combined bearings achieved by coupling the load and deformation analysis of a single bearing. In this paper, based on the Jones quasi-static model and stiffness analytical model, a new iterative algorithm and model are proposed for the calculation of combined bearings preload and stiffness, and the dynamic effects include centrifugal force and gyroscopic moment have to be considered. It is demonstrated that the new method has general applicability, the preload factors of combined bearings are calculated according to the different design preloads, and the static and dynamic stiffness for various arrangements of combined bearings are comparatively studied and analyzed, and the influences of the design preload magnitude, axial load and rotating speed are discussed in detail. Besides, the change rule of dynamic contact angles of combined bearings with respect to the rotating speed is also discussed. The results show that bearing arrangement modes, rotating speed and design preload magnitude have a significant influence on the preload and stiffness of combined bearings. The proposed formulation provides a useful tool in dynamic analysis of the complex bearing-rotor system.

Experimental and numerical investigation on laser-assisted bending of pre-loaded metal plate

Science.gov (United States)

Nowak, Zdzisław; Nowak, Marcin; Widłaszewski, Jacek; Kurp, Piotr

2018-01-01

The laser forming technique has an important disadvantage, which is the limitation of plastic deformation generated by a single laser beam pass. To increase the plastic deformation it is possible to apply external forces in the laser forming process. In this paper, we investigate the influence of external pre-loads on the laser bending of steel plate. The pre-loads investigated generate bending towards the laser beam. The thermal, elastic-plastic analysis is performed using the commercial nonlinear finite element analysis package ABAQUS. The focus of the paper is to identify how this pattern of the pre-load influence the final bend angle of the plate.

Effects of bolt pre-loading variations on performance of GDL in a bolted PEMFC by 3-D FEM analysis

International Nuclear Information System (INIS)

Chien, Chi-Hui; Hu, Yao-Lun; Su, Ting-Hsuan; Liu, Hsuan-Ting; Wang, Chung-Ting; Yang, Ping-Feng; Lu, Ying-Xu

2016-01-01

This study numerically investigated the effects of different bolt pre-loadings on the performance of the gas diffusion layer (GDL) in a bolted proton exchange membrane fuel cell (PEMFC). Firstly, a complete three-dimensional finite element model of a PEMFC bolted by 12 bolts with a reactive area of 5 cm by 5 cm was established using the commercial software SolidWorks. Then, a pre-loading of 1 MPa to 7 MPa on each bolt was applied, increasing in increments 1 MPa, and the corresponding deformation and stress fields of each component of the fuel cell were obtained using the commercial software ANSYS 15.0/Workbench. Finally, the effects of the bolt pre-loading variations on the performance of the GDL were discussed. The results showed that the compression ratio of the GDL increased linearly with the magnitude of bolt pre-loading, and improving the performance of the GDL. However, when the pre-loading on each bolt reached 7 MPa, the compression ratio exceeded 15%, degrading the efficiency of the PEMFC. Also, by comparing the relationships between bolt pre-loading and conductivity and porosity of GDL, in order to obtain the maximum performance of GDL, an optimum value of 4 MPa for bolt preloading was recommended. - Highlights: • Effect of bolt pre-loading on deformations is more serious than that of thermal loading. • Bolt pre-loading improves compression ratio of GDL. • For obtaining a maximum performance of GDL, 4 MPa of bolt pre-loading was recommended. • Flow channel volume reduced by bolt pre-loading degrades the efficiency of PEMFC.

Assessing the impact of preload on pyrite-rich sediment and groundwater quality.

Science.gov (United States)

Karikari-Yeboah, Ohene; Addai-Mensah, Jonas

2017-02-01

Pyrite-rich sediments would, invariably, undergo redox reactions which would lead to acidic aqueous environment containing solubilized toxic metal species. When such sediments are subjected to preload, a technique employed by geotechnical engineers to improve the load-bearing capacity of highly compressible formation, transient flow of pore water, accompanied by acidity transfer, would occur as a response. Despite the concomitant environmental and socio-economic significance, to date, there has been limited interdisciplinary research on the underpinning geotechnical engineering and geo-environmental science issues for pyrite-rich sediments under preload. In this study, we investigate the effect of pyrite-rich sediment pore water transfer under preload surcharge on the receiving environment and the impact on the groundwater speciation and quality. Sediment samples were obtained at close depth intervals from boreholes established within pristine areas and those subjected to the preload application. Soil and pore water samples were subjected to solid/solution speciation, moisture contents, soil pH and the Atterberg Limits' analyses using standard analytical techniques and methods. Standpipes were also installed in the boreholes for groundwater sampling and in situ monitoring of water quality parameters. It is shown that the imposition of preload surcharge over pyritic sediment created a reducing environment rich in SO 4 2- , iron oxide minerals and organic matter. This reducing environment fostered organic carbon catabolism to generate excess pyrite and bicarbonate alkalinity, which would invariably impact adversely on soil quality and plant growth. These were accompanied by increase in pH, dissolved Al, Ca, Mg and K species beneath the surcharge.

Probability distribution of von Mises stress in the presence of pre-load.

Energy Technology Data Exchange (ETDEWEB)

Segalman, Daniel Joseph; Field, Richard V.,; Reese, Garth M.

2013-04-01

Random vibration under preload is important in multiple endeavors, including those involving launch and re-entry. There are some methods in the literature to begin to address this problem, but there is nothing that accommodates the existence of preloads and the necessity of making probabilistic statements about the stress levels likely to be encountered. An approach to achieve to this goal is presented along with several simple illustrations.

Simulation of Degraded Properties of 2D plain Woven C/SiC Composites under Preloading Oxidation Atmosphere

Science.gov (United States)

Chen, Xihui; Sun, Zhigang; Sun, Jianfen; Song, Yingdong

2017-12-01

In this paper, a numerical model which incorporates the oxidation damage model and the finite element model of 2D plain woven composites is presented for simulation of the oxidation behaviors of 2D plain woven C/SiC composite under preloading oxidation atmosphere. The equal proportional reduction method is firstly proposed to calculate the residual moduli and strength of unidirectional C/SiC composite. The multi-scale method is developed to simulate the residual elastic moduli and strength of 2D plain woven C/SiC composite. The multi-scale method is able to accurately predict the residual elastic modulus and strength of the composite. Besides, the simulated residual elastic moduli and strength of 2D plain woven C/SiC composites under preloading oxidation atmosphere show good agreements with experimental results. Furthermore, the preload, oxidation time, temperature and fiber volume fractions of the composite are investigated to show their influences upon the residual elastic modulus and strength of 2D plain woven C/SiC composites.

Dissociation of the effects of preload volume and energy content on subjective appetite and food intake.

Science.gov (United States)

Gray, Richard; French, Stephen; Robinson, Tristan; Yeomans, Martin

2002-05-01

Previous research suggests that enhancing the volume of a food preload without altering energy content can result in reduced appetite, although the limited evidence means that the conditions under which this effect will occur are not yet clear. In the present study, we used a Universal Eating Monitor (UEM) to record test meal intake constantly, in parallel with appetite ratings, following soup-based preloads that varied both in volume (150 vs. 450 ml) and energy density (1.4 vs. 4.2 kJ/ml). Healthy young men (n=20) received four different preload conditions (repeated measures) followed by unlimited hot pasta test meals (interval 30 min). They completed appetite ratings during and after each laboratory session, and food diaries for the afternoon and evening following each session. Subjective appetite after the preloads was reduced by the high-volume preloads relative to low-volume preloads, with no difference between the two at each volume level. This indicates an effect of volume, but no effect of energy. Test meal intake in the high-volume, high-energy-density condition was reduced relative to the other conditions, which did not differ from one another. This indicates an effect of total energy, but no effect of volume. The dissociation between these different measures of appetite might be explained in terms of largely cognitive influences on subjective appetite between preload and test meal, contrasted with stronger physiological influences on actual intake during the test meal. With regard to previous studies, it is argued that food volume is more influential under circumstances where gastric volume is closer to its normal limits.

Global end-diastolic volume an emerging preload marker vis-a-vis other markers - Have we reached our goal?

Directory of Open Access Journals (Sweden)

P M Kapoor

2016-01-01

Full Text Available A reliable estimation of cardiac preload is helpful in the management of severe circulatory dysfunction. The estimation of cardiac preload has evolved from nuclear angiography, pulmonary artery catheterization to echocardiography, and transpulmonary thermodilution (TPTD. Global end-diastolic volume (GEDV is the combined end-diastolic volumes of all the four cardiac chambers. GEDV has been demonstrated to be a reliable preload marker in comparison with traditionally used pulmonary artery catheter-derived pressure preload parameters. Recently, a new TPTD system called EV1000™ has been developed and introduced into the expanding field of advanced hemodynamic monitoring. GEDV has emerged as a better preload marker than its previous conventional counterparts. The advantage of it being measured by minimum invasive methods such as PiCCO™ and newly developed EV1000™ system makes it a promising bedside advanced hemodynamic parameter.

Accelerated Testing Methodology in Constant Stress-Rate Testing for Advanced Structural Ceramics: A Preloading Technique

Science.gov (United States)

Choi, Sung R.; Gyekenyesi, John P.; Huebert, Dean; Bartlett, Allen; Choi, Han-Ho

2001-01-01

Preloading technique was used as a means of an accelerated testing methodology in constant stress-rate (dynamic fatigue) testing for two different brittle materials. The theory developed previously for fatigue strength as a function of preload was further verified through extensive constant stress-rate testing for glass-ceramic and CRT glass in room temperature distilled water. The preloading technique was also used in this study to identify the prevailing failure mechanisms at elevated temperatures, particularly at lower test rates in which a series of mechanisms would be associated simultaneously with material failure, resulting in significant strength increase or decrease. Two different advanced ceramics including SiC whisker-reinforced composite silicon nitride and 96 wt% alumina were used at elevated temperatures. It was found that the preloading technique can be used as an additional tool to pinpoint the dominant failure mechanism that is associated with such a phenomenon of considerable strength increase or decrease.

Quantitative Analysis of Endothelial Cell Loss in Preloaded Descemet Membrane Endothelial Keratoplasty Grafts.

Science.gov (United States)

Wolle, Meraf A; DeMill, David L; Johnson, Lauren; Lentz, Stephen I; Woodward, Maria A; Mian, Shahzad I

2017-11-01

Availability of preloaded Descemet membrane endothelial keratoplasty (pDMEK) tissue may increase acceptance of DMEK in surgical management of endothelial disease. The goal of this study was to determine the safety of pDMEK grafts for 24 hours before surgery by analyzing endothelial cell loss (ECL) using 2 image analysis software programs. A total of 18 cadaveric corneas were prepared for DMEK using a standardized technique and loaded in a modified Jones tube injector. Nine of the corneas were injected into Calcein AM vital dye after 1 minute (controls), and the remaining 9 corneas were left preloaded for 24 hours before injection into vital dye for staining. The stained corneas were imaged using an inverted confocal microscope. ECL was then analyzed and quantified by 2 different graders using 2 image analysis software programs. The control DMEK tissue resulted in 22.0% ± 4.0% ECL compared with pDMEK tissue, which resulted in 19.2% ± 7.2% ECL (P = 0.31). Interobserver agreement was 0.93 for MetaMorph and 0.92 for Fiji. The average time required to process images with MetaMorph was 2 ± 1 minutes and with Fiji was 20 ± 10 minutes. Intraobserver agreement was 0.97 for MetaMorph and 0.93 for Fiji. Preloading DMEK tissue is safe and may provide an alternative technique for tissue distribution and surgery for DMEK. The use of MetaMorph software for quantifying ECL is a novel and accurate imaging method with increased efficiency and reproducibility compared with the previously validated Fiji.

Digital implementation of the preloaded filter pulse processor

International Nuclear Information System (INIS)

Westphal, G.P.; Cadek, G.R.; Keroe, N.; Sauter, TH.; Thorwartl, P.C.

1995-01-01

Adapting it's processing time to the respective pulse intervals, the Preloaded Filter (PLF) pulse processor offers optimum resolution together with highest possible throughput rates. The PLF algorithm could be formulated in a recursive manner which made possible it's implementation by means of a large field-programmable gate array, as a fast, pipe-lined digital processor with 10 MHz maximum throughput rate. While pre-filter digitization by an ADC with 12 bit resolution and 10M Hz sampling rate resulted in a poorer resolution than that of an analog filter, a digital PLF based on an ADC with 14 bit resolution and 10 MHz sampling rate, surpassed high-quality analog filters in resolution, throughput rate and long-term stability. (author) 6 refs.; 7 figs

Study of laser bending of a preloaded Titanium alloy sheet

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Wang Xiufeng

2014-01-01

Full Text Available Laser bending of sheet metals with preload offers some attractive characteristics/merits, comparing to laser free bending without prestressing on the metals. The study reported in this paper was focused on a Titanium alloy which finds widespread applications in aerospace manufacturing. FE simulation of laser bending with prestressing on the Titanium alloy sheet was conducted for the analysis of the bending process and experiment carried out to verify the model and the result. It was shown that the simulation result is close to that measured in the experiment. Based on the computed result, the load-displacement curve was analysed and transmission efficiency of the elastic energy defined to evaluate the bending effect. These enhanced understanding of the mechanism of laser bending with a preload. A method for the optimization on technological parameters was further proposed. Referring to the deformation targeted, the preload value was determined through the FE simulation. The result showed that, on the premise that the specimen surface can be prevented from damaging, transmission efficiency of the elastic energy could reach to the maximum value through adjusting technological parameters of the laser system and deformation accuracy of the specimen could also be improved through this approach. The work presented in this paper may find its application in the manufacture of Titanium alloy sheets with a more cost-effective and a more precise way.

Research on reinforcement effect of vacuum preloading to treatment of the soft foundation

Science.gov (United States)

Li, bin; Li, maoji

2017-12-01

vacuum preloading method is a commonly used method to reinforce soft ground at present. Monitoring during construction stage is a dynamic monitoring, which is a standard to judge the quality of construction. This paper relies on the reclamation project of Tianjin Port Industrial Zone in North China, analyzed the monitoring purposes, monitoring method and collection data. Results had shown that vacuum preloading monitoring can make an accurate evaluation of construction quality during construction. The project practice can provide reference for similar projects.

Does fasting influence preload responsiveness in ASA 1 and 2 volunteers?

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Daniel Rodrigues Alves

2017-03-01

Full Text Available Introduction: Preoperative fasting was long regarded as an important cause of fluid depletion, leading to hemodynamic instability during surgery should replenishment is not promptly instituted. Lately, this traditional point of view has been progressively challenged, and a growing number of authors now propose a more restrictive approach to fluid management, although doubt remains as to the true hemodynamic influence of preoperative fasting. Methods: We designed an observational, analytic, prospective, longitudinal study in which 31 ASA 1 and ASA 2 volunteers underwent an echocardiographic examination both before and after a fasting period of at least 6 hours (h. Data from both static and dynamic preload indices were obtained on both periods, and subsequently compared. Results: Static preload indices exhibited a markedly variable behaviour with fasting. Dynamic indices, however, were far more consistent with one another, all pointing in the same direction, i.e., evidencing no statistically significant change with the fasting period. We also analysed the reliability of dynamic indices to respond to known, intentional preload changes. Aortic velocity time integral (VTI variation with the passive leg raise manoeuvre was the only variable that proved to be sensitive enough to consistently signal the presence of preload variation. Conclusion: Fasting does not appear to cause a change in preload of conscious volunteers nor does it significantly alter their position in the Frank–Starling curve, even with longer fasting times than usually recommended. Transaortic VTI variation with the passive leg raise manoeuvre is the most robust dynamic index (of those studied to evaluate preload responsiveness in spontaneously breathing patients. Resumo: Introdução: O jejum no pré-operatório é há muito tempo considerado como uma importante causa de depleção de líquidos, levando à instabilidade hemodinâmica durante a cirurgia, caso a reposição n

Effect of cyclic torsional preloading on cyclic fatigue resistance of ProTaper Next and Mtwo nickel–titanium instruments

Directory of Open Access Journals (Sweden)

Eugenio Pedullà

2015-06-01

Conclusions: Torsional preloads reduced the cyclic fatigue resistance of M-wire and conventional (as ProTaper Next and Mtwo NiTi rotary instruments except for Mtwo with 25% or 50% of torsional preloading.

Fatigue response of a PZT multilayer actuator under high-field electric cycling with mechanical preload

Science.gov (United States)

Wang, Hong; Wereszczak, Andrew A.; Lin, Hua-Tay

2009-01-01

An electric fatigue test system was developed for evaluating the reliability of piezoelectric actuators with a mechanical loading capability. Fatigue responses of a lead zirconate titanate (PZT) multilayer actuator with a platethrough electrode configuration were studied under an electric field (1.7 times that of the coercive field of PZT material) and a concurrent mechanical preload (30.0 MPa). A total of 109 cycles was carried out. Variations in charge density and mechanical strain under the high electric field and constant mechanical loads were observed during the fatigue test. The dc and the first harmonic (at 10 Hz) dielectric and piezoelectric coefficients were subsequently characterized using fast Fourier transformation. Both the dielectric and the piezoelectric coefficients exhibited a monotonic decrease prior to 2.86×108 cycles under certain preloading conditions, and then fluctuated. Both the dielectric loss tangent and the piezoelectric loss tangent also fluctuated after a decrease. The results are interpreted and discussed with respect to domain wall activities, microdefects, and other anomalies.

[The anesthesiological procedure for correcting preloading in the surgery of acquired mitral valve defects].

Science.gov (United States)

Kiselev, V O; Shipulin, V M; Evtushenko, A V; Podoksenov, Iu K; Shishneva, E V

2000-01-01

Intraoperative correction of preload in patients with acquired valvular disease (AVD) complicated by right-ventricular failure and severe pulmonary hypertension necessitates search for pathogenetically based algorithms of anesthesiological strategy. The objective of this study was to develop a strategy of assessing and treating the preload at the stage of induction anesthesia in patients with right-ventricular failure. During surgery central hemodynamic parameters and their response to a short head-down-tilt (15-20 degrees) were evaluated in patients (n = 42) with cardiac index (CI) less than 2 l/min/m2 after induction anesthesia. The patients were divided into 2 groups with different severity of preoperative status. Group 1 (main) included 24 patients with stages II-III cardiac failure (according to N. Strazhesko and B. Vasilenko) and group 2 (control) consisted of 18 patients with stage IIA cardiac failure. Progressing preoperative cardiac failure resulted in decrease of cardiac index and failure of compensatory hemodynamic mechanisms in AVD patients. The level of right-ventricular preload, pulmonary resistance, and stroke index were lower in group 1 than in the controls; however, 8% of group 1 patients responded positively to increased preload. In the control group 50% responded favorably to head-down-tilt. Hence, comprehensive assessment of cardiac index, central hemodynamic parameters and their response to head-down tilt help individually choose the anesthesiological strategy.

Can alginate-based preloads increase weight loss beyond calorie restriction? A pilot study in obese individuals.

Science.gov (United States)

Georg Jensen, M; Kristensen, M; Astrup, A

2011-12-01

This randomized, controlled, 2-week intervention study in 24 obese subjects tested the effect on body weight loss and gastrointestinal tolerance of consuming low viscous alginate fibre-based preloads of 3% concentration (500 ml volume) three times a day as an adjuvant to a calorie-restricted diet. The pilot study showed that intake of the alginate preloads was moderately acceptable to the majority of subjects but did not produce additional body weight loss beyond calorie restriction (-1.42 ± 0.38 kg) (n=12) compared to control group (-1.56 ± 0.21 kg) (n=8). These results do not support that alginate supplementation enhance the weight loss effects of a hypo-caloric diet, but a sufficiently powered long-term study is needed to explore whether alginate could be an aid for improving weight loss during caloric-restriction. Copyright © 2011 Elsevier Ltd. All rights reserved.

Deconstructing alcohol use on a night out in England: promotions, preloading and consumption.

Science.gov (United States)

McClatchley, Kirstie; Shorter, Gillian W; Chalmers, Jenny

2014-07-01

To examine alcohol consumed during a drinking event (a single drinking occasion) by those attending public house/on-trade establishments on nights with standard pricing and nights with promotional prices. Data (n = 425) were collected in an ecological momentary assessment over eight nights in two locations (Midlands and London) on both promotional and standard (Saturday) nights. Multiple regression was used to predict event alcohol consumption by sex, age, type of night, alcohol preloading behaviour, marital and employment status, education, Alcohol Use Disorders Identification Test alcohol consumption questions separately or total AUDIT-C and social group size. Mean (UK) units consumed were 11.8 (London) and 14.4 (Midlands). In London, consumption was similar on promotional and standard nights, but in the Midlands, standard night consumption was three units higher. Preloading was reported by 30%; more common on standard nights. Regression analyses revealed being male, preloading and past-year total AUDIT-C were associated with higher event consumption. However, when AUDIT-C questions were added separately, being a standard night was associated with increased event consumption and different AUDIT-C questions were significantly associated with event consumption in each location. Event consumption reflected heavy episodic drinking and was influenced by price. Promotional night consumption either matched standard Saturday night consumption or was slightly lower. In London, there was a significant preference for drinking at least one promotional beverage on promotional nights. On standard nights, consumption was over a wider range of venues, and preloading with off-trade alcohol was more likely. © 2014 Australasian Professional Society on Alcohol and other Drugs.

Detecting Protein-Glycolipid Interactions Using CaR-ESI-MS and Model Membranes: Comparison of Pre-loaded and Passively Loaded Picodiscs

Science.gov (United States)

Li, Jun; Han, Ling; Li, Jianing; Kitova, Elena N.; Xiong, Zi Jian; Privé, Gilbert G.; Klassen, John S.

2018-04-01

Catch-and-release electrospray ionization mass spectrometry (CaR-ESI-MS), implemented using model membranes (MMs), is a promising approach for the discovery of glycolipid ligands of glycan-binding proteins (GBPs). Picodiscs (PDs), which are lipid-transporting complexes composed of the human sphingolipid activator protein saposin A and phospholipids, have proven to be useful MMs for such studies. The present work compares the use of conventional (pre-loaded) PDs with passively loaded PDs (PLPDs) for CaR-ESI-MS screening of glycolipids against cholera toxin B subunit homopentamer (CTB5). The pre-loaded PDs were prepared from a mixture of purified glycolipid and phospholipid or a mixture of lipids extracted from tissue, while the PLPDs were prepared by incubating PDs containing only phospholipid with glycolipid-containing lipid mixtures in aqueous solution. Time-dependent changes in the composition of the PLPDs produced by incubation with glycomicelles of the ganglioside GM1 were monitored using collision-induced dissociation of the gaseous PD ions and from the extent of ganglioside binding to CTB5 measured by ESI-MS. GM1 incorporation into PDs was evident within a few hours of incubation. At incubation times ≥ 10 days, GM1 binding to CTB5 was indistinguishable from that observed with pre-loaded PDs produced directly from GM1 at the same concentration. Comparison of ganglioside binding to CTB5 measured for pre-loaded PDs and PLPDs prepared from glycolipids extracted from pig and mouse brain revealed that the PLPDs allow for the detection of a greater number of ganglioside ligands. Together, the results of this study suggest PLPDs may have advantages over conventionally prepared PDs for screening glycolipids against GBPs using CaR-ESI-MS. [Figure not available: see fulltext.

Influence of activated carbon preloading by EfOM fractions from treated wastewater on adsorption of pharmaceutically active compounds.

Science.gov (United States)

Hu, Jingyi; Shang, Ran; Heijman, Bas; Rietveld, Luuk

2016-05-01

In this study, the preloading effects of different fractions of wastewater effluent organic matter (EfOM) on the adsorption of trace-level pharmaceutically active compounds (PhACs) onto granular activated carbon (GAC) were investigated. A nanofiltration (NF) membrane was employed to separate the EfOM by size, and two GACs with distinct pore structures were chosen for comparison. The results showed that preloading with EfOM substantially decreased PhAC uptake of the GACs; however, comparable PhAC adsorption capacities were achieved on GACs preloaded by feed EfOM and the NF-permeating EfOM. This indicates that: (1) the NF-rejected, larger EfOM molecules with an expectation to block the PhAC adsorption pores exerted little impact on the adsorbability of PhACs; (2) the smaller EfOM molecules present in the NF permeate contributed mainly to the decrease in PhAC uptake, mostly due to site competition. Of the two examined GACs, the wide pore-size-distributed GAC was found to be more susceptible to EfOM preloading than the microporous GAC. Furthermore, among the fourteen investigated PhACs, the negatively charged hydrophilic PhACs were generally subjected to a greater EfOM preloading impact. Copyright © 2016 Elsevier Ltd. All rights reserved.

Effects of Fat and Protein Preloads on Pouch Emptying, Intestinal Transit, Glycaemia, Gut Hormones, Glucose Absorption, Blood Pressure and Gastrointestinal Symptoms After Roux-en-Y Gastric Bypass.

Science.gov (United States)

Nguyen, Nam Q; Debreceni, Tamara L; Burgstad, Carly M; Neo, Melissa; Bellon, Max; Wishart, Judith M; Standfield, Scott; Bartholomeusz, Dylan; Rayner, Chris K; Wittert, Gary; Horowitz, Michael

2016-01-01

The aim was to determine the effects of fat and protein preloads on pouch emptying (PE), caecal arrival time (CAT), glucose absorption, blood glucose (BSL), gut hormones, haemodynamics and gastrointestinal (GI) symptoms in subjects who had undergone Roux-en-Y gastric bypass (RYGB) >12 months previously. Ten RYGB subjects were studied on three occasions, in randomised order, receiving 200-ml preloads of either water, fat (30 ml olive oil) or whey protein (55 g), 30 min before a mixed meal. PE, CAT, BSL, plasma 3-O-methyl-D-glucopyranose (3-OMG), insulin, glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide 1 (GLP-1) and glucagon, blood pressure (BP), heart rate (HR) and GI symptoms were assessed over 270 min. Although fat and protein preloads did not alter PE of either solids or liquids, the CAT of solids, but not liquids, was longer than that after the water preload (fat 68 ± 5 min and protein 71 ± 6 min vs. water 46 ± 5 min; P = 0.02). BSL elevated promptly after the meal on all days (P area under the curve (AUC(0-75 min)), 18.7 ± 18.2 vs. 107.2 ± 30.4 and 76.1 ± 19.3 mmol/L/min; P < 0.05). Compared to water preload, the protein and fat preloads were associated with greater increases in plasma insulin, GLP-1 and glucagon concentrations, a reduction in BP, and greater increases in HR, fullness, bloating and nausea. Plasma 3-OMG levels were lower after the protein than after the water and fat preloads (P < 0.001). Given its effects to attenuate post-prandial glycaemia, reduce intestinal glucose absorption and potentiate the "incretin response", without inducing more adverse post-prandial GI symptom, protein preload may prove clinically useful in RYGB patients and warrant further evaluation, particularly in those with type 2 diabetes (T2DM) and/or dumping syndrome.

Review of Bolt Preload and Torque for Assembling Threaded Fasteners in Nuclear Power Plant

International Nuclear Information System (INIS)

Lee, Yong-Sung; Lee, Jae-Gon; Kang, Yong-Chul; Shin, Ki-Jong

2007-01-01

There are numerous threaded fasteners such as bolts, studs, nuts, cap screws and anchor bolts used in nuclear power plants(NPPs). The major applications of threaded fasteners are reactor coolant pressure boundary components, their internals and supports. With the increase of commercial operation period of NPPs, the incidents caused by degradation of threaded fasteners have been occurred. A large number of reported incidents are involved in the pressure boundary and major component supports. The degradation and failure of threaded fasteners is affected by material, preload and torque value at assembly, bolting practice, etc. It is very important to select appropriate bolt preload and decide assembly torque value because torque control using a torque wrench is the most common method in a power plant to assemble a bolted flange connection. Many researches have been studied to define the proper bolt preload and desired torque value with regard to the integrity of bolted connections including pressure boundary joints by EPRI and other plant industry. But in domestic NPPs, considerably few works are done on the bolted joint assembly in spite of increasing events related with threaded faster. Therefore we investigated degradation or failure of the threaded fasteners used in NPPs, also examined the codes, standards and technical trends concerning bolt preload and assembly torque in NPPs. It is the purpose of this study to provide proper technical information for assuring integrity of the threaded fasteners

Effect of preload reduction by hemodialysis on left atrial volume and echocardiographic Doppler parameters in patients with end-stage renal disease.

Science.gov (United States)

Barberato, Silvio H; Mantilla, Diego E V; Misocami, M Arcio; Gonçalves, Simone M; Bignelli, Alexandre T; Riella, Miguel C; Pecoits-Filho, Roberto

2004-11-01

Left atrial (LA) volume has been proposed as a less preload-dependent parameter of diastolic function than Doppler mitral inflow. We hypothesize that in the absence of mitral regurgitation and atrial fibrilation, LA enlargement could be a more practical (and relatively preload-independent) method for the evaluation of left ventricular diastolic function. The aim of the present study was to determine the effects of preload reduction by hemodialysis on LA volume.

Automatic control of the preload in adaptive friction drives of chemical production machines

Science.gov (United States)

Balakin, P. D.

2017-08-01

Being based on the principle of providing the systems with adaptation property to the real parameters and operational condition, the energy effective mechanical system constructed on the base of friction gear with automated preload is offered and this allows keeping mechanical efficiency value adequate transforming drive path to in the terms of multimode operation. This is achieved by integrated control loop, operating on the basis of the laws of motion with the energy of the main power flow by changing automatically the kinematic dimension of the section and, hence, the value of preload in the friction contact. The given ratios of forces and deformations in the control loop are required at the stage of conceptual design to determine design dimensions of power transmission elements with new properties.

Implications of the center of rotation concept for the reconstruction of anterior column lordosis and axial preloads in spinal deformity surgery.

Science.gov (United States)

Koller, Heiko; Mayer, Michael; Zenner, Juliane; Resch, Herbert; Niederberger, Alfred; Fierlbeck, Johann; Hitzl, Wolfgang; Acosta, Frank L

2012-07-01

In thoracolumbar deformity surgery, anterior-only approaches are used for reconstruction of anterior column failures. It is generally advised that vertebral body replacements (VBRs) should be preloaded by compression. However, little is known regarding the impact of different techniques for generation of preloads and which surgical principle is best for restoration of lordosis. Therefore, the authors analyzed the effect of different surgical techniques to restore spinal alignment and lordosis as well as the ability to generate axial preloads on VBRs in anterior column reconstructions. The authors performed a laboratory study using 7 fresh-frozen specimens (from T-3 to S-1) to assess the ability for lordosis reconstruction of 5 techniques and their potential for increasing preloads on a modified distractable VBR in a 1-level thoracolumbar corpectomy. The testing protocol was as follows: 1) Radiographs of specimens were obtained. 2) A 1-level corpectomy was performed. 3) In alternating order, lordosis was applied using 1 of the 5 techniques. Then, preloads during insertion and after relaxation using the modified distractable VBR were assessed using a miniature load-cell incorporated in the modified distractable VBR. The modified distractable VBR was inserted into the corpectomy defect after lordosis was applied using 1) a lamina spreader; 2) the modified distractable VBR only; 3) the ArcoFix System (an angular stable plate system enabling in situ reduction); 4) a lordosizer (a customized instrument enabling reduction while replicating the intervertebral center of rotation [COR] according to the COR method); and 5) a lordosizer and top-loading screws ([LZ+TLS], distraction with the lordosizer applied on a 5.5-mm rod linked to 2 top-loading pedicle screws inserted laterally into the vertebra). Changes in the regional kyphosis angle were assessed radiographically using the Cobb method. The bone mineral density of specimens was 0.72 ± 22.6 g/cm(2). The maximum regional

Effects of polydextrose with breakfast or with a midmorning preload on food intake and other appetite-related parameters in healthy normal-weight and overweight females: An acute, randomized, double-blind, placebo-controlled, and crossover study.

Science.gov (United States)

Ibarra, Alvin; Olli, Kaisa; Pasman, Wilrike; Hendriks, Henk; Alhoniemi, Esa; Raza, Ghulam Shere; Herzig, Karl-Heinz; Tiihonen, Kirsti

2017-03-01

Polydextrose (PDX) reduces subsequent energy intake (EI) when administered at midmorning in single-blind trials of primarily normal-weight men. However, it is unclear if this effect also occurs when PDX is given at breakfast time. Furthermore, for ecological validity, it is desirable to study a female population, including those at risk for obesity. We studied the effects of PDX, served as part of a breakfast or midmorning preload, on subsequent EI and other appetite-related parameters in healthy normal-weight and overweight females. Per earlier studies, the primary outcome was defined as the difference in subsequent EI when PDX was consumed at midmorning versus placebo. Thirty-two volunteers were enrolled in this acute, double-blind, placebo-controlled, randomized, and crossover trial to examine the effects of 12.5 g of PDX, administered as part of a breakfast or midmorning preload, on subsequent EI, subjective feelings of appetite, well-being, and mood. Gastric emptying rates and the blood concentrations of glucose, insulin, cholecystokinin, ghrelin, glucagon-like peptide 1 (GLP-1), and peptide tyrosine-tyrosine were measured in the group that received PDX as part of their breakfast. There were no differences in EI between volunteers who were fed PDX and placebo. PDX intake with breakfast tended to elevate blood glucose (P = 0.06) during the postabsorptive phase, significantly lowered insulin by 15.7% (P = 0.04), and increased GLP-1 by 39.9% (P = 0.02); no other effects on blood parameters or gastric emptying rates were observed. PDX intake at midmorning reduced hunger by 31.4% during the satiation period (P = 0.02); all other subjective feelings of appetite were unaffected. Volunteers had a uniform mood profile during the study. PDX was well tolerated, causing one mild adverse event throughout the trial. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Configuration development of a hydraulic press for preloading the toroidal field coils of the Compact Ignition Tokamak

International Nuclear Information System (INIS)

Lee, V.D.

1987-01-01

The Fusion Engineering Design Center (FEDC) is part of a national design team that is developing the conceptual design of the Compact Ignition Tokamak (CIT). To achieve a compact device with the minimum major radius, a vertical preload system is being developed to react the vertical separating force normally carried by the inboard leg of the toroidal field (TF) coils. The preload system is in the form of a hydraulic press. Challenges in the design include the development of hydraulic and structural systems for very large force requirements, which could interface with the CIT machine, while allowing maximum access to the top, bottom, and radial periphery of the machine. Maximum access is necessary for maintenance, diagnostics, instrumentation, and control systems. Materials used in the design must function in the nuclear environment and in the presence of high magnetic fields. This paper presents the configuration development of the hydraulic press used to vertically preload the CIT device

Myocardial preload alters central pressure augmentation through changes in the forward wave

NARCIS (Netherlands)

van de Velde, Lennart; Eeftinck Schattenkerk, Daan W.; Venema, Pascale A. H. T.; Best, Hendrik J.; van den Bogaard, Bas; Stok, Wim J.; Westerhof, Berend E.; van den Born, Bert Jan H.

2018-01-01

Augmentation index (AIx) is often used to quantify the contribution of wave reflection to central pulse pressure. Recent studies have challenged this view by showing how contractility-induced changes in the forward pressure wave can markedly impact AIx. We hypothesized that changes in preload will

Potential Risk Analysis of Tailings Dam under Preloading Condition and Its Countermeasures

Directory of Open Access Journals (Sweden)

Shuren Wang

2015-01-01

Full Text Available It is very important for mine production safety to ensure the stability of the tailings dam. Taking a flatland tailings pond as the background, a threedimensional computational model was built based on a tailings dam under mullock heap preloading condition. Considering the current operating water level conditions, a liquid-solid coupling analysis of the model was conducted.The deformation characteristics of the tailings dam were revealed during successive preloading at the front of the dam. The safety factor and the potential slide face of the tailings dam were calculated under different conditions using the strength reduction method. The results show that the tailings dam in its current condition is basically stable, but if the mullock heap continues to be heightened, the tailings dam will become unstable. Therefore, in order to limit the height of the mullock heap, establishing a monitor and early warning mechanism are put forward to ensure mine production safety.

Q-switched oscillation in thulium-doped fiber lasers using preloaded dynamic microbending technique

Science.gov (United States)

Sakata, H.; Takahashi, N.; Ushiro, Y.

2018-01-01

We demonstrate Q-switched pulse generation in thulium-doped fiber lasers by introducing piezoelectric-driven microbend with preloaded stress. We employed a pair of corrugated chips each attached on piezoelectric actuators (PAs) to clamp the fiber in a ring laser resonator. The thulium-doped fiber is pumped by a laser diode emitting at 1.63 μm and generates the Q-switched laser pulses at around 1.9 μm by switching off the PAs. The laser pulse performance is improved by optimizing the preload and switch-off period for the PAs. The Q-switched pulses with a peak power of 2.8 W and a pulsewidth of 900 ns are observed for a launched pump power of 161 mW. We expect that the in-fiber Q-switching technique will provide efficient laser systems for environmental sensing and medical applications.

Effects of Consuming Preloads with Different Energy Density and Taste Quality on Energy Intake and Postprandial Blood Glucose.

Science.gov (United States)

Tey, Siew Ling; Salleh, Nurhazwani; Henry, Christiani Jeyakumar; Forde, Ciaran G

2018-01-31

Consumption of reduced energy dense foods and drink has the potential to reduce energy intake and postprandial blood glucose concentrations. In addition, the taste quality of a meal (e.g., sweet or savoury) may play a role in satiation and food intake. The objective of this randomised crossover study was to examine whether energy density and taste quality has an impact on energy intake and postprandial blood glucose response. Using a preload design, participants were asked to consume a sweet ("Cheng Teng") or a savoury (broth) preload soup in high energy density (HED; around 0.50 kcal/g; 250 kcal) or low energy density (LED; around 0.12 kcal/g; 50 kcal) in mid-morning and an ad libitum lunch was provided an hour after the preload. Participants recorded their food intake for the rest of the day after they left the study site. Energy compensation and postprandial blood glucose response were measured in 32 healthy lean males (mean age = 28.9 years, mean BMI = 22.1 kg/m²). There was a significant difference in ad libitum lunch intake between treatments ( p = 0.012), with higher intake in sweet LED and savoury LED compared to sweet HED and savoury HED. Energy intake at subsequent meals and total daily energy intake did not differ between the four treatments (both p ≥ 0.214). Consumption of HED preloads resulted in a larger spike in postprandial blood glucose response compared with LED preloads, irrespective of taste quality ( p < 0.001). Energy density rather than taste quality plays an important role in energy compensation and postprandial blood glucose response. This suggests that regular consumption of low energy-dense foods has the potential to reduce overall energy intake and to improve glycemic control.

Effects of Consuming Preloads with Different Energy Density and Taste Quality on Energy Intake and Postprandial Blood Glucose

Directory of Open Access Journals (Sweden)

Siew Ling Tey

2018-01-01

Full Text Available Consumption of reduced energy dense foods and drink has the potential to reduce energy intake and postprandial blood glucose concentrations. In addition, the taste quality of a meal (e.g., sweet or savoury may play a role in satiation and food intake. The objective of this randomised crossover study was to examine whether energy density and taste quality has an impact on energy intake and postprandial blood glucose response. Using a preload design, participants were asked to consume a sweet (“Cheng Teng” or a savoury (broth preload soup in high energy density (HED; around 0.50 kcal/g; 250 kcal or low energy density (LED; around 0.12 kcal/g; 50 kcal in mid-morning and an ad libitum lunch was provided an hour after the preload. Participants recorded their food intake for the rest of the day after they left the study site. Energy compensation and postprandial blood glucose response were measured in 32 healthy lean males (mean age = 28.9 years, mean BMI = 22.1 kg/m2. There was a significant difference in ad libitum lunch intake between treatments (p = 0.012, with higher intake in sweet LED and savoury LED compared to sweet HED and savoury HED. Energy intake at subsequent meals and total daily energy intake did not differ between the four treatments (both p ≥ 0.214. Consumption of HED preloads resulted in a larger spike in postprandial blood glucose response compared with LED preloads, irrespective of taste quality (p < 0.001. Energy density rather than taste quality plays an important role in energy compensation and postprandial blood glucose response. This suggests that regular consumption of low energy-dense foods has the potential to reduce overall energy intake and to improve glycemic control.

Effects of MRI Protocol Parameters, Preload Injection Dose, Fractionation Strategies, and Leakage Correction Algorithms on the Fidelity of Dynamic-Susceptibility Contrast MRI Estimates of Relative Cerebral Blood Volume in Gliomas.

Science.gov (United States)

Leu, K; Boxerman, J L; Ellingson, B M

2017-03-01

DSC perfusion MR imaging assumes that the contrast agent remains intravascular; thus, disruptions in the blood-brain barrier common in brain tumors can lead to errors in the estimation of relative CBV. Acquisition strategies, including the choice of flip angle, TE, TR, and preload dose and incubation time, along with post hoc leakage-correction algorithms, have been proposed as means for combating these leakage effects. In the current study, we used DSC-MR imaging simulations to examine the influence of these various acquisition parameters and leakage-correction strategies on the faithful estimation of CBV. DSC-MR imaging simulations were performed in 250 tumors with perfusion characteristics randomly generated from the distributions of real tumor population data, and comparison of leakage-corrected CBV was performed with a theoretic curve with no permeability. Optimal strategies were determined by protocol with the lowest mean error. The following acquisition strategies (flip angle/TE/TR and contrast dose allocation for preload and bolus) produced high CBV fidelity, as measured by the percentage difference from a hypothetic tumor with no leakage: 1) 35°/35 ms/1.5 seconds with no preload and full dose for DSC-MR imaging, 2) 35°/25 ms/1.5 seconds with ¼ dose preload and ¾ dose bolus, 3) 60°/35 ms/2.0 seconds with ½ dose preload and ½ dose bolus, and 4) 60°/35 ms/1.0 second with 1 dose preload and 1 dose bolus. Results suggest that a variety of strategies can yield similarly high fidelity in CBV estimation, namely those that balance T1- and T2*-relaxation effects due to contrast agent extravasation. © 2017 by American Journal of Neuroradiology.

Doing the counter-regulation shuffle: The importance of flexibility and hunger for predicting food consumption following a preload.

Science.gov (United States)

Broadbent, Jaclyn; Fuller-Tyszkiewicz, Matthew; Dennerstein, Michelle; Greenwood, Jesse; Hancock, Naomi; Thavapalan, Nithyyaa; White, Melissa

This study utilised the preload paradigm to evaluate whether trait-like dieting attitudes and behaviours (dietary restraint and flexibility in dieting rules) and context-specific factors (negative mood and hunger) predict food consumption among male and female participants. Following a high calorie preload, 79 participants aged 18-40 completed a deceptive taste test in which they were encouraged to eat as much of the taste test foods as desired, and this ad libitum intake was measured. Although each predictor (except negative mood) predicted consumption when tested individually, regression analyses revealed that dieting flexibility and current hunger were the strongest unique predictors of intake. Mood failed to directly predict food consumption, nor did it moderate the relationship between restraint and food intake. Collectively, findings suggest that emphasis on dietary restraint in preload studies may be misplaced, as other proximal and stable factors may better predict food consumption. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.

Influence of abutment screw preload on stress distribution in marginal bone.

Science.gov (United States)

Khraisat, Ameen

2012-01-01

Changes in an implant assembly after abutment connection might possibly cause deformation in the implant/abutment joint and even in the marginal bone. The aim of this study was to evaluate the influence of abutment screw preload through the implant collar on marginal bone stress without external load application. Models of three implant parts made of titanium (implant, abutment, and abutment screw) and cortical bone were built and positioned with computer-aided design software. Meshing and generation of boundary conditions, loads, and interactions were performed. Each part was meshed independently. The sole load applied to the model was a torque of 32 Ncm on the abutment screw about its axis of rotation. The implant collar was deformed axially after the screw was tightened (3 μm). This deformation resulted in 60 MPa of stress in the marginal bone. Moreover, pressure on the marginal bone in a radial direction was observed. It can be concluded that, without any external load application, abutment screw preload exerts stresses on the implant collar and the marginal bone. These findings should help guide the development of new implant/abutment joint designs that exert less stress on the marginal bone.

Adsorption of organic contaminants by graphene nanosheets, carbon nanotubes and granular activated carbons under natural organic matter preloading conditions.

Science.gov (United States)

Ersan, Gamze; Kaya, Yasemin; Apul, Onur G; Karanfil, Tanju

2016-09-15

The effect of NOM preloading on the adsorption of phenanthrene (PNT) and trichloroethylene (TCE) by pristine graphene nanosheets (GNS) and graphene oxide nanosheet (GO) was investigated and compared with those of a single-walled carbon nanotube (SWCNT), a multi-walled carbon nanotube (MWCNT), and two coal based granular activated carbons (GACs). PNT uptake was higher than TCE by all adsorbents on both mass and surface area bases. This was attributed to the hydrophobicity of PNT. The adsorption capacities of PNT and TCE depend on the accessibility of the organic molecules to the inner regions of the adsorbent which was influenced from the molecular size of OCs. The adsorption capacities of all adsorbents decreased as a result of NOM preloading due to site competition and/or pore/interstice blockage. However, among all adsorbents, GO was generally effected least from the NOM preloading for PNT, whereas there was not observed any trend of NOM competition with a specific adsorbent for TCE. In addition, SWCNT was generally affected most from the NOM preloading for TCE and there was not any trend for PNT. The overall results indicated that the fate and transport of organic contaminants by GNSs and CNTs type of nanoadsorbents and GACs in different natural systems will be affected by water quality parameters, characteristics of adsorbent, and properties of adsorbate. Copyright © 2016 Elsevier B.V. All rights reserved.

Local approach to brittle fracture under residual stress field. Assessment of pre-loading effect; Local approach no tekiyo ni yoru zanryu oryoku wo motsu buzai no zeisei hakai kyodo hyoka. Yokaju no eikyo no hyoka

Energy Technology Data Exchange (ETDEWEB)

Yamashita, Y.; Sakano, K.; Onozuka, M. [Ishikawajima-Harima Heavy Industries Co. Ltd., Tokyo (Japan); Minami, F. [Osaka University, Osaka (Japan)

2000-01-01

The effect of residual stresses on brittle fracture was investigated on the basis of the Local Approach. Compressive residual stress was introduced by pre-loading and the subsequent fracture test conducted with a 780 MPa class steel. Preloading apparently increased the critical load and critical CTOD at the onset of brittle fracture initiation. The Weibull stress criterion was used to evaluate the brittle fracture resistance of the pre-loaded specimen. The critical Weibull stress is a material property independent of test conditions with and without pre-loading. Using the Weibull stress criterion, the critical CTOD of the pre-loaded specimen can be predicted from test results of the specimen without pre-loading. (author)

Bilateral passive leg raising attenuates and delays tourniquet deflation-induced hypotension and tachycardia under spinal anaesthesia: a randomised controlled trial.

Science.gov (United States)

Huang, Go-Shine; Wang, Chih-Chien; Hu, Mei-Hua; Cherng, Chen-Hwan; Lee, Meei-Shyuan; Tsai, Chien-Sung; Chan, Wei-Hung; Hsieh, Xhang-Xian; Lin, Leou-Chyr

2014-01-01

The pneumatic tourniquet is frequently used in total knee arthroplasty. Tourniquet deflation may result in hypotension and tachycardia caused by the rapid shift of blood volume back to the ischaemic limb and a decrease in cardiac preload. Passive leg raising (PLR) represents a 'self-volume challenge' that can result in an increase in preload. Such a PLR-induced increase in preload was hypothesised to attenuate the decrease in preload resulting from tourniquet deflation. To evaluate the effect of PLR on hypotension and tachycardia following tourniquet deflation. A randomised controlled trial. Single medical centre. Seventy patients who underwent unilateral total knee arthroplasty were randomised into two groups: tourniquet deflation with PLR (n = 35) or without PLR (control group, n = 35). Patients in both groups were administered a single dose of plain bupivacaine for spinal anaesthesia. The pneumatic tourniquet was inflated on the thigh and the surgery was performed. The study composed of four steps: for the PLR group, step 1 - inflation of the tourniquet while the patient was supine; step 2 - the patient's legs were raised to a 45° angle; step 3 - the tourniquet was deflated while the patient's legs were still raised; and step 4 - the legs were returned to the supine position. In the control group, the same perioperative procedure was used, but PLR was not conducted. The patients' blood pressure and heart rate were measured before, during and after tourniquet deflation. After tourniquet deflation, the magnitude of the changes in blood pressure and heart rate was less in the PLR group than that in the control group. In addition, the blood pressure nadir also occurred later in the PLR group than in the controls. Bilateral PLR is a simple, reversible manoeuvre that mimics rapid fluid loading. Bilateral PLR attenuates the severity of, and delays the time to, hypotension and tachycardia following deflation of a lower limb tourniquet. ClinicalTrials.gov number

Analytical solution for vacuum preloading considering the nonlinear distribution of horizontal permeability within the smear zone.

Directory of Open Access Journals (Sweden)

Jie Peng

Full Text Available The vacuum preloading is an effective method which is widely used in ground treatment. In consolidation analysis, the soil around prefabricated vertical drain (PVD is traditionally divided into smear zone and undisturbed zone, both with constant permeability. In reality, the permeability of soil changes continuously within the smear zone. In this study, the horizontal permeability coefficient of soil within the smear zone is described by an exponential function of radial distance. A solution for vacuum preloading consolidation considers the nonlinear distribution of horizontal permeability within the smear zone is presented and compared with previous analytical results as well as a numerical solution, the results show that the presented solution correlates well with the numerical solution, and is more precise than previous analytical solution.

The effect of covert changes in energy density of preloads on subsequent ad libitum energy intake in lean and obese human subjects.

Science.gov (United States)

Durrant, M L; Royston, J P; Wloch, R T; Garrow, J S

1982-01-01

1. Covert changes in energy intake were made by giving preloads of disguised energy density three times daily to 14 obese and 6 lean subjects. 2. The preloads contained 2.51 MJ (600 kcal)/d on days 2 and 3 and either 3.77 MJ (900 kcal)/d or 1.26 MJ (300 kcal/d) on days 4 and 5 and 1.26 MJ (300 kcal)/d or 3.77 MJ (900 kcal)/d on days 6 and 7. The order of testing was alternated for each subject. 3. Subsequent energy intake at each meal (lunch, dinner and breakfast) was measured with an automated food-dispensing machine. 4. Overall the obese subjects ate significantly less from the machine, 3.28 +/- 1.89 MJ (785 +/- 452 kcal)/d, than the lean subjects, 6.03 +/- 1.26 MJ (1442 +/- 300 kcal)/d. 5. Both groups of subjects adjusted their energy intake in the right direction to counterbalance the effect of the preloads but the lean subjects changed their intake by an average of 0.74 MJ (176 kcal)/d compared with the obese subjects who changed their intake by an average of 0.29 MJ (70 kcal)/d. 6. Although the lean subjects were better at adjusting their energy intake than the obese subjects, regulation was still imprecise relative to the 2.51 MJ (600 kcal)/d difference in energy intake that was imposed. 7. There were no significant differences in hunger or appetite between subjects or test situations.

The head module of Mediator directs activation of preloaded RNAPII in vivo.

Science.gov (United States)

Lee, Sarah K; Chen, Xu; Huang, Liangqun; Stargell, Laurie A

2013-12-01

The successful synthesis of a transcript by RNA polymerase II (RNAPII) is a multistage process with distinct rate-limiting steps that can vary depending on the particular gene. A growing number of genes in a variety of organisms are regulated at steps after the recruitment of RNAPII. The best-characterized Saccharomyces cerevisiae gene regulated in this manner is CYC1. This gene has high occupancy of RNAPII under non-inducing conditions, defining it as a poised gene. Here, we find that subunits of the head module of Mediator, Med18 and Med20, and Med19 are required for activation of transcription at the CYC1 promoter in response to environmental cues. These subunits of Mediator are required at the preloaded promoter for normal levels of recruitment and activity of the general transcription factor TFIIH. Strikingly, these Mediator components are dispensable for activation by the same activator at a different gene, which lacks a preloaded polymerase in the promoter region. Based on these results and other studies, we speculate that Mediator plays an essential role in triggering an inactive polymerase at CYC1 into a productively elongating form.

Pre-meal video game playing and a glucose preload suppress food intake in normal weight boys.

Science.gov (United States)

Branton, Alyson; Akhavan, Tina; Gladanac, Branka; Pollard, Damion; Welch, Jo; Rossiter, Melissa; Bellissimo, Nick

2014-12-01

Increased food intake (FI) during television viewing has been reported in children, but it is unknown if this occurs following pre-meal video game playing (VGP). The objective was to determine the effect of pre-meal VGP for 30 min on subjective appetite and emotions, and FI in normal weight (NW) boys after a glucose or control preload. On four test mornings, NW boys (n = 19) received equally sweetened preloads of a non-caloric sucralose control or 50 g glucose in 250 mL of water, with or without VGP for 30 min. Food intake from an ad libitum pizza meal was measured immediately after. Subjective appetite was measured at 0, 15, 30, and 60 min. Subjective emotions were determined by visual analog scale at baseline and immediately before lunch. Both VGP (p = 0.023) and glucose (p aggression scores increased after VGP (p <0.05), but did not correlate with FI. However, baseline and pre-meal happiness and excitement scores were inversely associated with FI. In conclusion, both pre-meal VGP and the glucose preload suppressed FI, supporting the roles of both physiologic and environmental factors in the regulation of short-term FI in 9- to 14-year-old NW boys. Copyright © 2014 Elsevier Ltd. All rights reserved.

Study on Single-yarn Pullout Test of Ballistic Resistant Fabric under Different Preloads

Science.gov (United States)

Fang, Q. C.; Lei, Z. K.; Y Qin, F.; Li, W. K.; Bai, R. X.

2017-12-01

During bullet penetrating fabric, the pull-out force of yarn in fabric is related to the impact resistance of fabric when the yarn is pulled out from the fabric. The complex uncrimping and friction slip behavior occur during the yarn pullout process, which is critical to learn the impact resistance of fabric. Based on digital image correlation technique, the deformation behavior of Kevlar 49 fabric subjected to preload during the single-yarn pullout process was studied in this paper. The pullout force and displacement curve shows a straight rise and an oscillated decrease. In the linear rise stage, the yarn uncrimping causes a static friction effect. The maximum of the pullout force is not linearly increased with the preload. In the oscillating descending stage, the local descent of the pullout force indicates that the yarn end is gradually withdrawn from the fabric, and the local rise indicates that the yarn end moves to the next weft/warp interaction until the yarn is completely pulled out. The shear deformation of fabric corresponds to the single-yarn pullout process.

Fatigue responses of lead zirconate titanate stacks under semibipolar electric cycling with mechanical preload

Science.gov (United States)

Wang, Hong; Cooper, Thomas A.; Lin, Hua-Tay; Wereszczak, Andrew A.

2010-10-01

Lead zirconate titanate (PZT) stacks that had an interdigital internal electrode configuration were tested to more than 108 cycles. A 100 Hz semibipolar sine wave with a field range of +4.5/-0.9 kV/mm was used in cycling with a concurrently-applied 20 MPa preload. Significant reductions in piezoelectric and dielectric responses were observed during the cycling depending on the measuring condition. Extensive partial discharges were also observed. These surface events resulted in the erosion of external electrode and the exposure of internal electrodes. Sections prepared by sequential polishing technique revealed a variety of damage mechanisms including delaminations, pores, and etch grooves. The scale of damage was correlated with the degree of fatigue-induced reduction in piezoelectric and dielectric responses. The results from this study demonstrate the feasibility of using a semibipolar mode to drive a PZT stack under a mechanical preload and illustrate the potential fatigue and damages of the stack in service.

Rotordynamic Evaluation of Full Scale Rotor on Tilting Pad Bearings with 0.1 and 0.3 Preload

Directory of Open Access Journals (Sweden)

Weimin Wang

2014-01-01

Full Text Available A system identification method for rotating machinery stability evaluation is investigated based on sine sweep excitation testing with electromagnetic actuator. The traditional MIMO FRF is transformed into dFRF from real number field to complex field with a transformation matrix, eliminating the influence of forward and backward modal overlap and providing higher accuracy to identify rotor’s first forward modal parameters using the rational polynomial method. The modal parameters are acquired for stability estimation. Furthermore, two sets of bearing with preloads of 0.1 and 0.3 under both load-on-pad (LOP and load-between-pad (LBP conditions are investigated. The effects of oil inlet pressure (1.0 bar–1.75 bar and temperature (43°C–51°C on the stability of rotor are investigated in detail. Results indicate that the stability of rotor will be improved by increasing the oil inlet temperature and pressure. It is found that the rotor is more stable on bearing with 0.1 preload than that of 0.3 preload. Load-on-pad provides more damping to rotor than load-between-pad. The method and outcomes of this paper can provide both theory basis and technology foundation for improving the rotor stability of centrifugal compressors.

Color M-mode Doppler flow propagation velocity is a preload insensitive index of left ventricular relaxation: animal and human validation.

Science.gov (United States)

Garcia, M J; Smedira, N G; Greenberg, N L; Main, M; Firstenberg, M S; Odabashian, J; Thomas, J D

2000-01-01

To determine the effect of preload in color M-mode Doppler flow propagation velocity (v(p)). The interpretation of Doppler filling patterns is limited by confounding effects of left ventricular (LV) relaxation and preload. Color M-mode v(p) has been proposed as a new index of LV relaxation. We studied four dogs before and during inferior caval (IVC) occlusion at five different inotropic stages and 14 patients before and during partial cardiopulmonary bypass. Left ventricular (LV) end-diastolic volumes (LV-EDV), the time constant of isovolumic relaxation (tau), left atrial (LA) pre-A and LV end-diastolic pressures (LV-EDP) were measured. Peak velocity during early filling (E) and v(p) were extracted by digital analysis of color M-mode Doppler images. In both animals and humans, LV-EDV and LV-EDP decreased significantly from baseline to IVC occlusion (both p < 0.001). Peak early filling (E) velocity decreased in animals from 56 +/- 21 to 42 +/- 17 cm/s (p < 0.001) without change in v(p) (from 35 +/- 15 to 35 +/- 16, p = 0.99). Results were similar in humans (from 69 +/- 15 to 53 +/- 22 cm/s, p < 0.001, and 37 +/- 12 to 34 +/- 16, p = 0.30). In both species, there was a strong correlation between LV relaxation (tau) and v(p) (r = 0.78, p < 0.001, r = 0.86, p < 0.001). Our results indicate that color M-mode Doppler v(p) is not affected by preload alterations and confirms that LV relaxation is its main physiologic determinant in both animals during varying lusitropic conditions and in humans with heart disease.

An analytical solution for two-dimensional vacuum preloading combined with electro-osmosis consolidation using EKG electrodes

Science.gov (United States)

Qiu, Chenchen; Li, Yande

2017-01-01

China is a country with vast territory, but economic development and population growth have reduced the usable land resources in recent years. Therefore, reclamation by pumping and filling is carried out in eastern coastal regions of China in order to meet the needs of urbanization. However, large areas of reclaimed land need rapid drainage consolidation treatment. Based on past researches on how to improve the treatment efficiency of soft clay using vacuum preloading combined with electro-osmosis, a two-dimensional drainage plane model was proposed according to the Terzaghi and Esrig consolidation theory. However, the analytical solution using two-dimensional plane model was never involved. Current analytical solutions can’t have a thorough theoretical analysis of practical engineering and give relevant guidance. Considering the smearing effect and the rectangle arrangement pattern, an analytical solution is derived to describe the behavior of pore-water and the consolidation process by using EKG (electro-kinetic geo synthetics) materials. The functions of EKG materials include drainage, electric conduction and corrosion resistance. Comparison with test results is carried out to verify the analytical solution. It is found that the measured value is larger than the applied vacuum degree because of the stacking effect of the vacuum preloading and electro-osmosis. The trends of the mean measured value and the mean analytical value processes are comparable. Therefore, the consolidation model can accurately assess the change in pore-water pressure and the consolidation process during vacuum preloading combined with electro-osmosis. PMID:28771496

An analytical solution for two-dimensional vacuum preloading combined with electro-osmosis consolidation using EKG electrodes.

Directory of Open Access Journals (Sweden)

Yang Shen

Full Text Available China is a country with vast territory, but economic development and population growth have reduced the usable land resources in recent years. Therefore, reclamation by pumping and filling is carried out in eastern coastal regions of China in order to meet the needs of urbanization. However, large areas of reclaimed land need rapid drainage consolidation treatment. Based on past researches on how to improve the treatment efficiency of soft clay using vacuum preloading combined with electro-osmosis, a two-dimensional drainage plane model was proposed according to the Terzaghi and Esrig consolidation theory. However, the analytical solution using two-dimensional plane model was never involved. Current analytical solutions can't have a thorough theoretical analysis of practical engineering and give relevant guidance. Considering the smearing effect and the rectangle arrangement pattern, an analytical solution is derived to describe the behavior of pore-water and the consolidation process by using EKG (electro-kinetic geo synthetics materials. The functions of EKG materials include drainage, electric conduction and corrosion resistance. Comparison with test results is carried out to verify the analytical solution. It is found that the measured value is larger than the applied vacuum degree because of the stacking effect of the vacuum preloading and electro-osmosis. The trends of the mean measured value and the mean analytical value processes are comparable. Therefore, the consolidation model can accurately assess the change in pore-water pressure and the consolidation process during vacuum preloading combined with electro-osmosis.

Friction modelling of preloaded tube contact dynamics

International Nuclear Information System (INIS)

Hassan, M.A.; Rogers, R.J.

2004-01-01

Many loosely supported components are subjected to flow-induced vibration leading to localized wear. Life prediction depends on robust and accurate modelling of the nonlinear dynamics as the components interact with their supports. The output of such analysis is the component dynamic response and impact forces, including friction forces during stick-slip motions. Such results are used to determine the normal work rates, which are utilized to predict fretting wear damage. Accurate estimates of these parameters are essential. This paper presents simulations of a loosely supported fuel-channel tube subject to turbulence excitation. The effects of tube/support clearance and preload are investigated. Several friction models, including velocity-limited, spring-damper, and force-balance are utilized. A comparison of these models is carried out to investigate their accuracy. The results show good agreement with experimental work rates when a simple iterative procedure to update the friction forces is used. (authors)

Friction modelling of preloaded tube contact dynamics

International Nuclear Information System (INIS)

Hassan, M.A.; Rogers, R.J.

2005-01-01

Many loosely supported components are subjected to flow-induced vibration leading to localized wear. Life prediction depends on robust and accurate modelling of the nonlinear dynamics as the components interact with their supports. The output of such analysis is the component dynamic response and impact forces, including friction forces during stick-slip motions. Such results are used to determine the normal work rates, which are utilized to predict fretting wear damage. Accurate estimates of these parameters are essential. This paper presents simulations of a loosely supported fuel-channel tube subject to turbulence excitation. The effects of tube/support clearance and preload are investigated. Several friction models, including velocity-limited, spring-damper and force-balance are utilized. A comparison of these models is carried out to investigate their accuracy. The results show good agreement with experimental work rates when a simple iterative procedure to update the friction forces is used

L-DOPA Preloading Increases the Uptake of Borophenylalanine in C6 Glioma Rat Model: A New Strategy to Improve BNCT Efficacy

International Nuclear Information System (INIS)

Capuani, Silvia; Gili, Tommaso; Bozzali, Marco; Russo, Salvatore; Porcari, Paola; Cametti, Cesare; D'Amore, Emanuela; Colasanti, Marco; Venturini, Giorgio; Maraviglia, Bruno; Lazzarino, Giuseppe; Pastore, Francesco S.

2008-01-01

Purpose: Boron neutron capture therapy (BNCT) is a radiotherapeutic modality based on 10 B(n,α) 7 Li reaction, for the treatment of malignant gliomas. One of the main limitations for BNCT effectiveness is the insufficient intake of 10 B nuclei in the tumor cells. This work was aimed at investigating the use of L-DOPA as a putative enhancer for 10 B-drug 4-dihydroxy-borylphenylalanine (BPA) uptake in the C6-glioma model. The investigation was first performed in vitro and then extended to the animal model. Methods and Materials: BPA accumulation in C6-glioma cells was assessed using radiowave dielectric spectroscopy, with and without L-DOPA preloading. Two L-DOPA incubation times (2 and 4 hours) were investigated, and the corresponding effects on BPA accumulation were quantified. C6-glioma cells were also implanted in the brain of 32 rats, and tumor growth was monitored by magnetic resonance imaging. Rats were assigned to two experimental branches: (1) BPA administration; (2) BPA administration after pretreatment with L-DOPA. All animals were sacrificed, and assessments of BPA concentrations in tumor tissue, normal brain, and blood samples were performed using high-performance liquid chromatography. Results: L-DOPA preloading induced a massive increase of BPA concentration in C6-glioma cells only after a 4-hour incubation. In the animal model, L-DOPA pretreatment produced a significantly higher accumulation of BPA in tumor tissue but not in normal brain and blood samples. Conclusions: This study suggests the potential use of L-DOPA as enhancer for BPA accumulation in malignant gliomas eligible for BNCT. L-DOPA preloading effect is discussed in terms of membrane transport mechanisms

Effect of preload alternations on a new Doppler echocardiographic index of combined systolic and diastolic performance

DEFF Research Database (Denmark)

Møller, J E; Poulsen, S H; Egstrup, K

1999-01-01

The objective of the study was to assess the effect of preload alternations on a nongeometric Doppler index of combined systolic and diastolic myocardial performance (MPI). Doppler echocardiography was performed during Valsalva maneuver, passive leg lifting, and after sublingual administration of...

Effect of the coefficient of friction and tightening speed on the preload induced at the dental implant complex with the finite element method.

Science.gov (United States)

Bulaqi, Haddad Arabi; Mousavi Mashhadi, Mahmoud; Geramipanah, Farideh; Safari, Hamed; Paknejad, Mojgan

2015-05-01

To prevent screw loosening, a clear understanding of the factors influencing secure preload is necessary. The purpose of this study was to investigate the effect of coefficient of friction and tightening speed on screw tightening based on energy distribution method with exact geometric modeling and finite element analysis. To simulate the proper boundary conditions of the screw tightening process, the supporting bone of an implant was considered. The exact geometry of the implant complex, including the Straumann dental implant, direct crown attachment, and abutment screw were modeled with Solidworks software. Abutment screw/implant and implant/bone interfaces were designed as spiral thread helixes. The screw-tightening process was simulated with Abaqus software, and to achieve the target torque, an angular displacement was applied to the abutment screw head at different coefficients of friction and tightening speeds. The values of torque, preload, energy distribution, elastic energy, and efficiency were obtained at the target torque of 35 Ncm. Additionally, the torque distribution ratio and preload simulated values were compared to theoretically predicted values. Upon reducing the coefficient of friction and enhancing the tightening speed, the angle of turn increased at the target torque. As the angle of turn increased, the elastic energy and preload also increased. Additionally, by increasing the coefficient of friction, the frictional dissipation energy increased but the efficiency decreased, whereas the increase in tightening speed insignificantly affected efficiency. The results of this study indicate that the coefficient of friction is the most influential factor on efficiency. Increasing the tightening speed lowered the response rate to the frictional resistance, thus diminishing the coefficient of friction and slightly increasing the preload. Increasing the tightening speed has the same result as reducing the coefficient of friction. Copyright © 2015

Study on the prevention of spragging in a tilting pad journal bearing using the variation of preload

International Nuclear Information System (INIS)

Yang, Seong Heon; Park, Chul Hyun; Ha, Hyun Cheon; Kim, Chae Sil

2001-01-01

Tilting pad journal bearings have been widely used in a high speed rotating machinery, such as steam turbines and gas turbines, owing to their inherent stability characteristics. However, some peculiar fatigue failure in the babbitt metal due to spragging has been continuously occurred at the leading edge of the upper pads. The spragging is defined as the pad vibration initiated on the upper unloaded pads in tilting pad journal bearing. This paper describes both several kinds of bearing failure related with spragging and the theoretical investigation on the prevention of the spragging phenomenon using the variation of preload. Results show that positive preload(m>0.5) assures all pads remain statically loaded under all operating conditions. For the change of design parameter to prevent spragging, thermo-hydrodynamic lubrication and rotor dynamic analysis were performed to verify temperature limitation on bearing and vibration problems on rotor bearing system

Sucrose preload reduces snacking after mild mental stress in healthy participants as a function of 5-hydroxytryptamine transporter gene promoter polymorphism.

Science.gov (United States)

Markus, C Rob; Jonkman, Lisa M; Capello, Aimee; Leinders, Sacha; Hüsch, Fabian

2015-01-01

Brain serotonin (5-hydroxytryptamine, 5-HT) dysfunction is considered to promote food intake and eating-related disturbances, especially under stress or negative mood. Vulnerability for 5-HT disturbances is considered to be genetically determined, including a short (S) allele polymorphism in the serotonin transporter gene (5-HTTLPR) that is associated with lower serotonin function. Since 5-HT function may be slightly increased by carbohydrate consumption, S-allele 5-HTTLPR carriers in particular may benefit from a sugar-preload due to their enhanced 5-HT vulnerability. The aim of the current study was to investigate whether a sugar-containing preload may reduce appetite and energy intake after exposure to stress to induce negative mood, depending on genetic 5-HT vulnerability. From a population of 771 healthy young male and female genotyped college students 31 S/S carriers (8 males, 23 females) and 26 long allele (L/L) carriers (9 males, 17 females) (mean ± S.D. 22 ± 1.6 years; body mass index, BMI, 18-33 kg/m(2)) were monitored for changes in appetite and snacking behavior after stress exposure. Results revealed an increased energy intake after mild mental stress (negative mood) mainly for high-fat sweet foods, which was significantly greater in S/S carriers, and only in these genotypes this intake was significantly reduced by a sucrose-containing preload. Although alternative explanations are possible, it is suggested that S/S participants may have enhanced brain (hypothalamic) 5-HT responsiveness to food that makes them more susceptible to the beneficial satiation effects of a sucrose-preload as well as to the negative effects of mild mental stress on weight gain.

Participant verification: prevention of co-enrolment in clinical trials in South Africa.

Science.gov (United States)

Harichund, C; Haripersad, K; Ramjee, R

2013-05-15

As KwaZulu-Natal Province is the epicentre of the HIV epidemic in both South Africa (SA) and globally, it is an ideal location to conduct HIV prevention and therapeutic trials. Numerous prevention trials are currently being conducted here; the potential for participant co-enrolment may compromise the validity of these studies and is therefore of great concern. To report the development and feasibility of a digital, fingerprint-based participant identification method to prevent co-enrolment at multiple clinical trial sites. The Medical Research Council (MRC) HIV Prevention Research Unit (HPRU) developed the Biometric Co-enrolment Prevention System (BCEPS), which uses fingerprint-based biometric technology to identify participants. A trial website was used to determine the robustness and usability of the system. After successful testing, the BCEPS was piloted in July 2010 across 7 HPRU clinical research sites. The BCEPS was pre-loaded with study names and clinical trial sites, with new participant information loaded at first visit to a trial site. We successfully implemented the BCEPS at the 7 HPRU sites. Using the BCEPS, we performed real-time 'flagging' of women who were already enrolled in another study as they entered a trial at an HPRU site and, where necessary, excluded them from participation on site. This system has promise in reducing co-enrolment in clinical trials and represents a valuable tool for future implementation by all groups conducting trials. The MRC is currently co-ordinating this effort with clinical trial sites nationally.

Improvements in Cycling but Not Handcycling 10 km Time Trial Performance in Habitual Caffeine Users.

Science.gov (United States)

Graham-Paulson, Terri; Perret, Claudio; Goosey-Tolfrey, Victoria

2016-06-25

Caffeine supplementation during whole-/lower-body exercise is well-researched, yet evidence of its effect during upper-body exercise is equivocal. The current study explored the effects of caffeine on cycling/handcycling 10 km time trial (TT) performance in habitual caffeine users. Eleven recreationally trained males (mean (SD) age 24 (4) years, body mass 85.1 (14.6) kg, cycling/handcycling peak oxygen uptake ( V · peak) 42.9 (7.3)/27.6 (5.1) mL∙kg∙min(-1), 160 (168) mg/day caffeine consumption) completed two maximal incremental tests and two familiarization sessions. During four subsequent visits, participants cycled/handcycled for 30 min at 65% mode-specific V · peak (preload) followed by a 10 km TT following the ingestion of 4 mg∙kg(-1) caffeine (CAF) or placebo (PLA). Caffeine significantly improved cycling (2.0 (2.0)%; 16:35 vs. 16:56 min; p = 0.033) but not handcycling (1.8 (3.0)%; 24:10 vs. 24:36 min; p = 0.153) TT performance compared to PLA. The improvement during cycling can be attributed to the increased power output during the first and last 2 km during CAF. Higher blood lactate concentration (Bla) was reported during CAF compared to PLA (p Caffeine improved cycling but not handcycling TT performance. The lack of improvement during handcycling may be due to the smaller active muscle mass, elevated (Bla) and/or participants' training status.

Ultrasonic extensometry for determining bolt preload in heavy industry - from petrochemical to reactors

International Nuclear Information System (INIS)

Erdman, D.C.

1981-01-01

Use of ultrasonic extensometers has found wide application for bolt preload determination in airborne and aerospace applications where elongation measurement accuracy is often required to .0001 in. Experience has now been gained in heavy industry with fasteners up to 12 feet long, often on studs and bolts with relatively rough head surfaces. Here, accuracy may be reduced to .001 inch, a figure far better than available from torque wrenches. This paper describes some of these heavy industry applications

Effect of humic acid preloading on phosphate adsorption onto zirconium-modified zeolite.

Science.gov (United States)

Lin, Jianwei; Zhang, Zhe; Zhan, Yanhui

2017-05-01

A zirconium-modified zeolite (ZrMZ) was prepared, and then, humic acid (HA) was immobilized on the ZrMZ surface to prepare HA-loaded ZrMZ (HA-ZrMZ). The obtained ZrMZ and HA-ZrMZ were characterized by energy dispersive X-ray spectroscopy, elemental analyzer, N 2 adsorption/desorption isotherms, pH at the point of zero charge, and X-ray photoelectron spectroscopy. The adsorption characteristics of phosphate on ZrMZ and HA-ZrMZ were comparatively investigated in batch mode. The adsorption mechanism of phosphate on ZrMZ and HA-ZrMZ was investigated by ionic strength effect and 31 P nuclear magnetic resonance. The mechanism for phosphate adsorption onto ZrMZ was the formation of inner-sphere phosphate complexes at the solid/solution interface. The preloading of HA on ZrMZ reduced the phosphate adsorption capacity, and the more the HA loading amount, the lower the phosphate adsorption capacity. However, the preloading of HA on ZrMZ did not change the phosphate adsorption mechanism; i.e., the formation of inner-sphere phosphate surface complexes was still responsible for the adsorption of phosphate on HA-ZrMZ. The decreased phosphate adsorption capacity for ZrMZ after HA coating could be attributed to the fact that the coating of HA on ZrMZ reduced the amount of binding active sites available for phosphate adsorption, changed the adsorbent surface charges, and reduced the specific surface areas and pore volumes of ZrMZ.

Boronophenylalanine uptake in C6 glioma model is dramatically increased by L-DOPA preloading

Energy Technology Data Exchange (ETDEWEB)

Capuani, S. [CNR-INFM SOFT, Department of Physics, Sapienza University of Rome, Piazzale Aldo Moro 2, Rome (Italy); Enrico Fermi Center, Compendio Viminale, Rome (Italy)], E-mail: silvia.capuani@roma1.infn.it; Gili, T. [CNR-INFM SOFT, Department of Physics, Sapienza University of Rome, Piazzale Aldo Moro 2, Rome (Italy); Enrico Fermi Center, Compendio Viminale, Rome (Italy); Bozzali, M. [Neuroimaging Laboratory, Santa Lucia Foundation, Via Ardeatina 306, Rome (Italy); Russo, S. [Victor Horsley Department of Neurosurgery, National Hospital for Neurology and Neurosurgery, Queen Square, London (United Kingdom); Porcari, P. [CNR-INFM SOFT, Department of Physics, Sapienza University of Rome, Piazzale Aldo Moro 2, Rome (Italy); Cametti, C. [CNR-INFM SOFT, Department of Physics, Sapienza University of Rome, Piazzale Aldo Moro 2, Rome (Italy); Department of Physics, Sapienza University of Rome, Piazzale Aldo Moro 2, Rome (Italy); Muolo, M. [Department of Biological Science, University ' Rome III' , Viale G. Marconi 446, Rome (Italy); D' Amore, E. [Serv. Qual./Sicurezza Sperim. Anim., Istituto Superiore di Sanita, Rome (Italy); Maraviglia, B. [Enrico Fermi Center, Compendio Viminale, Rome (Italy); Neuroimaging Laboratory, Santa Lucia Foundation, Via Ardeatina 306, Rome (Italy); Lazzarino, G. [Laboratory of Biochemistry, Department of Chemical Sciences, University of Catania, Viale A. Doria 6, Catania (Italy); Pastore, F.S. [Department of Neuroscience, Institute of Neurosurgery, University ' Tor Vergata' , Via Montpellier 1, Rome (Italy)

2009-07-15

One of the main limitations for BNCT effectiveness is the insufficient intake of {sup 10}B nuclei within tumour cells. This work was aimed at investigating the use of L-DOPA as enhancer for boronophenylalanine (BPA) uptake in the C6 glioma model. The investigation was first performed in vitro, and then extended in vivo to the animal model. BPA accumulation in C6 glioma cells was assessed, using radiowave dielectric spectroscopy (RDS), with and without L-DOPA preloading. C6 glioma cells were also implanted in the brain of 25 rats, randomly assigned to two experimental branches: (1) intra-carotid BPA infusion; (2) intra-carotid BPA infusion after pre-treatment with L-DOPA, administrated 24 h before BPA infusion. All animals were sacrificed, and assessment of BPA concentrations in tumour tissue, normal brain, and blood samples was performed using high performance liquid chromatography (HPLC). L-DOPA preloading induced a massive increase of BPA concentration either in vitro on C6 glioma cells or in vivo in the animal model tumour. Moreover, no significant difference was found in the normal brain and blood samples between the two animal groups. This study suggests the potential use of L-DOPA as enhancer for BPA accumulation in malignant gliomas eligible for BNCT.

Boronophenylalanine uptake in C6 glioma model is dramatically increased by L-DOPA preloading

International Nuclear Information System (INIS)

Capuani, S.; Gili, T.; Bozzali, M.; Russo, S.; Porcari, P.; Cametti, C.; Muolo, M.; D'Amore, E.; Maraviglia, B.; Lazzarino, G.; Pastore, F.S.

2009-01-01

One of the main limitations for BNCT effectiveness is the insufficient intake of 10 B nuclei within tumour cells. This work was aimed at investigating the use of L-DOPA as enhancer for boronophenylalanine (BPA) uptake in the C6 glioma model. The investigation was first performed in vitro, and then extended in vivo to the animal model. BPA accumulation in C6 glioma cells was assessed, using radiowave dielectric spectroscopy (RDS), with and without L-DOPA preloading. C6 glioma cells were also implanted in the brain of 25 rats, randomly assigned to two experimental branches: (1) intra-carotid BPA infusion; (2) intra-carotid BPA infusion after pre-treatment with L-DOPA, administrated 24 h before BPA infusion. All animals were sacrificed, and assessment of BPA concentrations in tumour tissue, normal brain, and blood samples was performed using high performance liquid chromatography (HPLC). L-DOPA preloading induced a massive increase of BPA concentration either in vitro on C6 glioma cells or in vivo in the animal model tumour. Moreover, no significant difference was found in the normal brain and blood samples between the two animal groups. This study suggests the potential use of L-DOPA as enhancer for BPA accumulation in malignant gliomas eligible for BNCT.

The impact of preload reduction with head-up tilt testing on longitudinal and transverse left ventricular mechanics.

Science.gov (United States)

Schneider, Caroline; Forsythe, Lynsey; Somauroo, John; George, Keith; Oxborough, David

2018-01-03

Left ventricular (LV) function is dependent on load, intrinsic contractility and relaxation with a variable impact on specific mechanics. Strain (ε) imaging allows the assessment of cardiac function however the direct relationship between volume and strain is currently unknown. The aim of this study was to establish the impact of preload reduction through head-up tilt (HUT) testing on simultaneous left ventricular (LV) longitudinal and transverse function and their respective contribution to volume change. A focused transthoracic echocardiogram was performed on 10 healthy male participants (23 ± 3 years,) in the supine position and following 1 min and 5 min of HUT testing. Raw temporal longitudinal ε (Ls) and transverse ε (Ts) values were exported and divided into 5% increments across the cardiac cycle and corresponding LV volumes were traced at each 5% increment. This provided simultaneous LV longitudinal and transverse ε and volume-loops (deformation-volume analysis - DVA). There was a leftward- shift of the ε -volume loop from supine to 1 min and 5 min of HUT, ptransverse thickening from supine to 1min, which was further augmented at 5min (p=0.018). Preload reduction occurs within 1 minute of HUT but does not further reduce at 5 minutes. This decline is associated with a decrease in longitudinal ε and concomitant increase in transverse ε. Consequently, augmented transverse relaxation appears to be an important factor in the maintenance of LV filling in the setting of reduced preload. DVA provides information on the relative contribution of mechanics to a change in LV volume and may have a role in the assessment of clinical populations. © 2018 The authors.

Preload dependence of color M-mode Doppler flow propagation velocity in controls and in patients with left ventricular dysfunction

DEFF Research Database (Denmark)

Møller, J E; Poulsen, S H; Søndergaard, E

2000-01-01

The purpose of this study was to assess the effects of preload alterations on color M-mode flow propagation velocity (Vp) in volunteers with normal left ventricular (LV) function and in patients with depressed LV function. Color M-mode Doppler echocardiography was performed during Valsalva maneuv...

The effect of extrinsic motivation on cycle time trial performance.

Science.gov (United States)

Hulleman, Michiel; De Koning, Jos J; Hettinga, Florentina J; Foster, Carl

2007-04-01

Athletes occasionally follow pacing patterns that seem unreasonably aggressive compared with those of prerace performances, potentially because of the motivation provided by competition. This study evaluated the effect of extrinsic motivation on cyclists' time trial performance. Well-trained recreational cyclists (N=7) completed four 1500-m laboratory time trials including a practice trial, two self-paced trials, and a trial where a monetary reward was offered. Time, total power output, power output attributable to aerobic and anaerobic metabolic sources, VO2, and HR were measured. The time required for the second, third, and last (extrinsically motivated) time trials was 133.1 +/- 2.1, 134.1 +/- 3.4, and 133.6 +/- 3.0 s, respectively, and was not different (P>0.05). There were no differences for total (396 +/- 19, 397 +/- 23, and 401 +/- 17 W), aerobic (253 +/- 12, 254 +/- 10, and 246 +/- 13 W), and anaerobic (143 +/- 14, 143 +/- 21, and 155 +/- 11 W) power output. The highest VO2 was not different over consecutive time trials (3.76 +/- 0.19, 3.73 +/- 0.16, and 3.71 +/- 0.22 L x min(-1)). When ranked by performance, without reference to the extrinsic motivation (131.9 +/- 2.4, 133.4 +/- 2.4, and 135.4 +/- 2.5 s), there was a significant difference for the first 100 m and from 100 to 300 m in power output, with a larger total power (560 +/- 102, 491 +/- 82, and 493 +/- 93; and 571 +/- 94, 513 +/- 41, and 484 +/- 88 W) and power attributable to anaerobic sources (446 +/- 100, 384 +/- 80, and 324 +/- 43; and 381 +/- 87, 383 +/- 90, and 289 +/- 91 W) for the fastest trial. Extrinsic motivation did not change the time trial performance, suggesting that 1500-m performance is extremely stable and not readily changeable with simple external motivation. The results suggest that spontaneous improvement in performance for time trials of this duration is attributable to greater early power output, which is primarily attributable to anaerobic metabolic sources.

The Guidelines for Modelling the Preloading Bolts in the Structural Connection Using Finite Element Methods

OpenAIRE

Paulina Krolo; Davor Grandić; Mladen Bulić

2016-01-01

The aim of this paper is the development of the two different numerical techniques for the preloading of bolts by the finite element method using the software Abaqus Standard. Furthermore, this paper gave detailed guidelines for modelling contact, method for solving the numerical error problems such as numerical singularity error and negative eigenvalues due to rigid body motion or the problem of the extensive elongation of bolts after pretension which is occurring during the analysis. The be...

Electromechanical characterization of piezoelectric actuators subjected to a variable pre-loading force at cryogenic temperature

International Nuclear Information System (INIS)

Fouaidy, M.; Saki, M.; Hammoudi, N.; Simonet, L.

2007-01-01

A dedicated apparatus was designed and constructed for studying the electromechanical behavior of prototype piezoelectric actuators subjected to a variable pre-loading force at cryogenic temperatures. This device was successfully used for testing a piezoelectric actuator of PICMA type from PI TM , for T in the range 2 K-300 K. The dielectric properties as well as dynamic properties were measured including the actuator characteristics when used as force sensor. The corresponding data are reported and discussed. (authors)

Influence of abutment type and esthetic veneering on preload maintenance of abutment screw of implant-supported crowns.

Science.gov (United States)

Delben, Juliana Aparecida; Barão, Valentim Adelino Ricardo; Dos Santos, Paulo Henrique; Assunção, Wirley Gonçalves

2014-02-01

The effect of veneering materials on screw joint stability remains inconclusive. Thus, this study evaluated the preload maintenance of abutment screws of single crowns fabricated with different abutments and veneering materials. Sixty crowns were divided into five groups (n = 12): UCLA abutment in gold alloy with ceramic (group GC) and resin (group GR) veneering, UCLA abutment in titanium with ceramic (group TiC) and resin (group TiR) veneering, and zirconia abutment with ceramic veneering (group ZiC). Abutment screws made of gold were used with a 35 Ncm insertion torque. Detorque measurements were obtained initially and after mechanical cycling. Data were analyzed by ANOVA and Fisher's exact test at a significance level of 5%. For the initial detorque means (in Ncm), group TiC (21.4 ± 1.78) exhibited statistically lower torque maintenance than groups GC (23.9 ± 0.91), GR (24.1 ± 1.34), and TiR (23.2 ± 1.33) (p abutment type and veneering material. More irregular surfaces in the hexagon area of the castable abutments were observed. The superiority of any veneering material concerning preload maintenance was not established. © 2013 by the American College of Prosthodontists.

Age-related differences in the neural correlates of trial-to-trial variations of reaction time

Directory of Open Access Journals (Sweden)

Nancy E. Adleman

2016-06-01

Full Text Available Intra-subject variation in reaction time (ISVRT is a developmentally-important phenomenon that decreases from childhood through young adulthood in parallel with the development of executive functions and networks. Prior work has shown a significant association between trial-by-trial variations in reaction time (RT and trial-by-trial variations in brain activity as measured by the blood-oxygenated level-dependent (BOLD response in functional magnetic resonance imaging (fMRI studies. It remains unclear, however, whether such “RT-BOLD” relationships vary with age. Here, we determined whether such trial-by-trial relationships vary with age in a cross-sectional design. We observed an association between age and RT-BOLD relationships in 11 clusters located in visual/occipital regions, frontal and parietal association cortex, precentral/postcentral gyrus, and thalamus. Some of these relationships were negative, reflecting increased BOLD associated with decreased RT, manifesting around the time of stimulus presentation and positive several seconds later. Critically for present purposes, all RT-BOLD relationships increased with age. Thus, RT-BOLD relationships may reflect robust, measurable changes in the brain-behavior relationship across development.

Configuration development of a hydraulic press for preloading the toroidal field coils of the Compact Ignition Tokamak

International Nuclear Information System (INIS)

Lee, V.D.

1987-01-01

The Fusion Engineering Design Center (FEDC) is part of a national design team that is developing the conceptual design of the Compact Ignition Tokamak (CIT). To achieve a compact device with the minimum major radius, a vertical preload system is being developed to react the vertical separating force normally carried by the inboard leg of the toroidal field (TF) coils. The preload system is in the form of a hydraulic press. Challenges in the design include the development of hydraulic and structural systems for very large force requirements, which could interface with the CIT machine, while allowing maximum access to the top, bottom, and radial periphery of the machine. Maximum access is necessary for maintenance, diagnostics, instrumentation, and control systems. Materials used in the design must function in the nuclear environment and in the presence of high magnetic fields. The structural system developed is an arrangement in which the CIT device is installed in the jaws of the press. Large built-up beams above and below the CIT span the machine and deliver the vertical force to the center cylinder formed by the inboard legs of the TF coils. During the conceptual design study, the vertical force requirement has ranged between 25,000 and 52,000 t. The access requirement on top and bottom limits the width of the spanning beams. Nonmagnetic steel materials are also required because of operation in the high magnetic fields. In the hydraulic system design for the press, several options are being explored. These range from small-diameter jacks operating at very high pressure [228 MPa (33 ksi)] to large-diameter jacks operating at pressures up to 69 MPa (10 ksi). Configurations with various locations for the hydraulic cylinders have also been explored. The nuclear environment and maintenance requirements are factors that affect cylinder location. This paper presents the configuration development of the hydraulic press used to vertically preload the CIT device

Noninvasive Assessment of Preload Reserve Enhances Risk Stratification of Patients With Heart Failure With Reduced Ejection Fraction.

Science.gov (United States)

Matsumoto, Kensuke; Onishi, Akira; Yamada, Hirotsugu; Kusunose, Kenya; Suto, Makiko; Hatani, Yutaka; Matsuzoe, Hiroki; Tatsumi, Kazuhiro; Tanaka, Hidekazu; Hirata, Ken-Ichi

2018-05-01

The leg-positive pressure maneuver can safely and noninvasively apply preload stress without increase in total body fluid volume. The purpose of this study was to determine whether preload stress could be useful for risk stratification of patients with heart failure with reduced ejection fraction. For this study, 120 consecutive patients with heart failure with reduced ejection fraction were prospectively recruited. The stroke work index was estimated as product of stroke volume index and mean blood pressure, and the E/e' ratio was calculated to estimate ventricular filling pressure. The echocardiographic parameters were obtained both at rest and during leg-positive pressure stress. During the median follow-up period of 20 months, 30 patients developed adverse cardiovascular events. During preload stress, stroke work index increased significantly (from 3280±1371 to 3857±1581 mm Hg·mL/m 2 ; P <0.001) along with minimal changes in ventricular filling pressure (E/e', from 16±10 to 17±9; P <0.05) in patients without cardiovascular events. However, patients with cardiovascular events showed impairment of Frank-Starling mechanism (stroke work index, from 2863±969 to 2903±1084 mm Hg·mL/m 2 ; P =0.70) and a serious increase in E/e' ratio (from 19±11 to 25±14; P <0.001). Both the patients without contractile reserve and those without diastolic reserve exhibited worse event-free survival than the others ( P <0.001). In a Cox proportional-hazards analysis, the changes in stroke work index (hazard ratio: 0.44 per 500 mm Hg·mL/m 2 increase; P =0.001) and in E/e' (hazard ratio: 2.58 per 5-U increase; P <0.001) were predictors of cardiovascular events. Contractile reserve and diastolic reserve during leg-positive pressure stress are important determinants of cardiovascular outcomes for patients with heart failure with reduced ejection fraction. © 2018 American Heart Association, Inc.

Evaluating Protocol Lifecycle Time Intervals in HIV/AIDS Clinical Trials

Science.gov (United States)

Schouten, Jeffrey T.; Dixon, Dennis; Varghese, Suresh; Cope, Marie T.; Marci, Joe; Kagan, Jonathan M.

2014-01-01

Background Identifying efficacious interventions for the prevention and treatment of human diseases depends on the efficient development and implementation of controlled clinical trials. Essential to reducing the time and burden of completing the clinical trial lifecycle is determining which aspects take the longest, delay other stages, and may lead to better resource utilization without diminishing scientific quality, safety, or the protection of human subjects. Purpose In this study we modeled time-to-event data to explore relationships between clinical trial protocol development and implementation times, as well as identify potential correlates of prolonged development and implementation. Methods We obtained time interval and participant accrual data from 111 interventional clinical trials initiated between 2006 and 2011 by NIH’s HIV/AIDS Clinical Trials Networks. We determined the time (in days) required to complete defined phases of clinical trial protocol development and implementation. Kaplan-Meier estimates were used to assess the rates at which protocols reached specified terminal events, stratified by study purpose (therapeutic, prevention) and phase group (pilot/phase I, phase II, and phase III/ IV). We also examined several potential correlates to prolonged development and implementation intervals. Results Even though phase grouping did not determine development or implementation times of either therapeutic or prevention studies, overall we observed wide variation in protocol development times. Moreover, we detected a trend toward phase III/IV therapeutic protocols exhibiting longer developmental (median 2 ½ years) and implementation times (>3years). We also found that protocols exceeding the median number of days for completing the development interval had significantly longer implementation. Limitations The use of a relatively small set of protocols may have limited our ability to detect differences across phase groupings. Some timing effects

Effects of music on work-rate distribution during a cycling time trial.

Science.gov (United States)

Atkinson, G; Wilson, D; Eubank, M

2004-11-01

Previous research work on the ergogenic effects of music has mainly involved constant power tests to exhaustion as dependent variables. Time trials are more externally valid than constant power tests, may be more reliable and allow the distribution of self-selected work-rate to be explored. We examined whether music improved starting, finishing and/or overall power during a 10-km cycling time trial, and whether heart rate and subjective responses to this time trial were altered by music. Sixteen participants performed two 10-km time trials on a Cybex cycle ergometer with, and without, the presence of a form of dance music known as "trance" (tempo = 142 beats x min (-1), volume at ear = 87 dB). Participants also completed the Brunel music rating inventory (BMRI) after each time trial in the music condition. The mean +/- SD time to complete the time trial was 1030 +/- 79 s in the music condition compared to 1052 +/- 77 s without music (95 % CI of difference = 10 to 34 s, p = 0.001). Nevertheless, ratings of perceived exertion were consistently (0.8 units) higher throughout the time trial with music (p music-induced increases in cycling speed and heart rate were observed in the first 3 km of the time trial. After completion of the BMRI, participants rated the "tempo" and "rhythm" of the music as more motivating than the "harmony" and "melody" aspects. These results suggest that music improves cycling speed mostly in the first few minutes of a 10-km time trial. In contrast to the findings of previous research, which suggested that music lowers perceived exertion at a constant work-rate, the participants in our time trials selected higher work-rates with music, whilst at the same time perceived these work-rates as being harder than without music.

Effects of differentiated music on cycling time trial.

Science.gov (United States)

Lim, H B T; Atkinson, G; Karageorghis, C I; Eubank, M R; Eubank, M M

2009-06-01

The aim of this study was to investigate the effects of music introduced and removed during a 10-km cycling time trial with reference to Rejeski's parallel processing theory and Karageorghis, Terry and Lane's conceptual framework for the prediction of responses to asynchronous music during sub-maximal exercise. A range of performance variables, ratings of perceived exertion, positive affect, negative affect, and blood lactate were assessed. Eleven males (mean age=24.9, s=6.1 years) completed a 10-km time trial under three conditions; no music, music played initially then removed between 5-10 km, and music played between 5-10 km only. Variables of time, power, cadence, speed, RPE, blood lactate, positive and negative affect were analysed using a ConditionxDistance ANOVA. There was no significant main effect for music conditions for the performance variables, perceived exertion, blood lactate, and affect (p>0.05). Nevertheless, a significant interaction effect for ConditionxDistance was found for cycling speed, with participants cycling 1-1.25 km/h faster at the start of the music introduced time trial than in both the music removed and no music time trials (pmusic during exercise and this finding can be used to extend current theory as it does not specifically address the periodic use music. The fact that participants exercised harder when they expected music to be introduced at a later stage illustrates the behavioural influences that music can engender during self-paced exercise.

Electrochemical performance of a hybrid lithium-ion capacitor with a graphite anode preloaded from lithium bis(trifluoromethane)sulfonimide-based electrolyte

International Nuclear Information System (INIS)

Decaux, C.; Lota, G.; Raymundo-Piñero, E.; Frackowiak, E.; Béguin, F.

2012-01-01

A hybrid LiC capacitor combining a lithium-ion battery type (graphite) electrode and an electrical double-layer (activated carbon) one has been developed by preloading graphite from 2 mol L −1 lithium bis(trifluoromethane)sulfonimide (LiTFSI) organic electrolyte. The graphite intercalation compound was formed by applying ca. 10 successive charge/self-discharge pulses. The optimized hybrid device operates in the voltage range from 1.5 to 4.2 V and displays 60% higher gravimetric capacitance than an electric double-layer (EDL) capacitor using the same activated carbon for both electrodes. As a result, the energy density reaches 80 Wh kg −1 , which is four times higher than the value for the EDL capacitor with the same total mass of carbon.

Preload-based Starling-like control of rotary blood pumps: An in-vitro evaluation.

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Mahdi Mansouri

Full Text Available Due to a shortage of donor hearts, rotary left ventricular assist devices (LVADs are used to provide mechanical circulatory support. To address the preload insensitivity of the constant speed controller (CSC used in conventional LVADs, we developed a preload-based Starling-like controller (SLC. The SLC emulates the Starling law of the heart to maintain mean pump flow ([Formula: see text] with respect to mean left ventricular end diastolic pressure (PLVEDm as the feedback signal. The SLC and CSC were compared using a mock circulation loop to assess their capacity to increase cardiac output during mild exercise while avoiding ventricular suction (marked by a negative PLVEDm and maintaining circulatory stability during blood loss and severe reductions in left ventricular contractility (LVC. The root mean squared hemodynamic deviation (RMSHD metric was used to assess the clinical acceptability of each controller based on pre-defined hemodynamic limits. We also compared the in-silico results from our previously published paper with our in-vitro outcomes. In the exercise simulation, the SLC increased [Formula: see text] by 37%, compared to only 17% with the CSC. During blood loss, the SLC maintained a better safety margin against left ventricular suction with PLVEDm of 2.7 mmHg compared to -0.1 mmHg for CSC. A transition to reduced LVC resulted in decreased mean arterial pressure (MAP and [Formula: see text] with CSC, whilst the SLC maintained MAP and [Formula: see text]. The results were associated with a much lower RMSHD value with SLC (70.3% compared to CSC (225.5%, demonstrating improved capacity of the SLC to compensate for the varying cardiac demand during profound circulatory changes. In-vitro and in-silico results demonstrated similar trends to the simulated changes in patient state however the magnitude of hemodynamic changes were different, thus justifying the progression to in-vitro evaluation.

Mouth rinsing improves cycling endurance performance during Ramadan fasting in a hot humid environment.

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Che Muhamed, Ahmad Munir; Mohamed, Nazirah Gulam; Ismail, Norjana; Aziz, Abdul Rashid; Singh, Rabindarjeet

2014-04-01

This study examined the effect of mouth rinsing during endurance cycling in a hot humid environment (32 °C and 75% relative humidity) on athletes in the Ramadan fasted state. Nine trained adolescent male cyclists completed 3 trials that consisted of a carbohydrate mouth-rinse (CMR), a placebo mouth-rinse (PMR), and a no-rinse (NOR) trial during the last 2 weeks of Ramadan. Each trial consisted of a preloading cycle at 65% peak rate of oxygen consumption for 30 min followed by a 10-km time trial (TT10 km) under hot humid condition. During the CMR and PMR trials, each cyclist rinsed his mouth with 25 mL of the solution for 5 s before expectorating the solution pre-exercise, after 5, 15, and 25 min of the preloading cycle, and 15 s prior to the start of TT10 km. Time to complete the TT10 km was significantly faster in the CMR and PMR trials compared with the NOR trial (12.9 ± 1.7 and 12.6 ± 1.7 vs. 16.8 ± 1.6 min, respectively; p benefits compared with a no-rinse condition on TT10 km performance in acute Ramadan fasted subjects during endurance cycling in a heat stress environment.

Launch Lock Assemblies with Reduced Preload and Spacecraft Isolation Systems Including the Same

Science.gov (United States)

Barber, Tim Daniel (Inventor); Young, Ken (Inventor); Hindle, Timothy (Inventor)

2016-01-01

Launch lock assemblies with reduced preload are provided. The launch lock assembly comprises first and second mount pieces, a releasable clamp device, and a pair of retracting assemblies. Each retracting assembly comprises a pair of toothed members having interacting toothed surfaces. The releasable clamp device normally maintains the first and second mount pieces in clamped engagement. When the releasable clamp device is actuated, the first and second mount pieces are released from clamped engagement and one toothed member of each retracting assembly moves in an opposite direction relative to the other one toothed member of the other retracting assembly to define an axial gap on each side of the first mount piece.

Effect of caffeine on cycling time-trial performance in the heat.

Science.gov (United States)

Pitchford, Nathan W; Fell, James W; Leveritt, Michael D; Desbrow, Ben; Shing, Cecilia M

2014-07-01

The purpose of this investigation was to determine whether a moderate dose of caffeine would improve a laboratory simulated cycling time-trial in the heat. Nine well-trained male subjects (VO2max 64.4±6.8mLmin(-1)kg(-1), peak power output 378±40W) completed one familiarisation and two experimental laboratory simulated cycling time-trials in environmental conditions of 35°C and 25% RH 90min after consuming either caffeine (3mgkg(-1) BW) or placebo, in a double blind, cross-over study. Time-trial performance was faster in the caffeine trial compared with the placebo trial (mean±SD, 3806±359s versus 4079±333s, p=0.06, 90%CI 42-500s, 86% likelihood of benefit, d=-0.79). Caffeine ingestion was associated with small to moderate increases in average heart rate (p=0.178, d=0.39), VO2 (p=0.154, d=0.45), respiratory exchange ratio (p=0.292, d=0.35) and core temperature (p=0.616, d=0.22) when compared to placebo, however, these were not statistically significant. Average RPE during the caffeine supplemented time-trial was not significantly different from placebo (p=0.41, d=-0.13). Caffeine supplementation at 3mgkg(-1) BW resulted in a worthwhile improvement in cycling time-trial performance in the heat. Double-blind cross-over study. Copyright © 2013 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

Source strength verification and quality assurance of preloaded brachytherapy needles using a CMOS flat panel detector

Energy Technology Data Exchange (ETDEWEB)

Golshan, Maryam, E-mail: maryam.golshan@bccancer.bc.ca [Department of Physics, University of British Columbia, Vancouver, British Columbia V6T1Z1, Canada and Department of Medical Physics, Vancouver Center, British Columbia Cancer Agency, Vancouver, British Columbia V5Z 4E6 (Canada); Spadinger, Ingrid [Department of Medical Physics, Vancouver Center, British Columbia Cancer Agency, Vancouver, British Columbia V5Z 4E6 (Canada); Chng, Nick [Department of Medical Physics, Center for the North, British Columbia Cancer Agency, Prince George, British Columbia V2M 7E9 (Canada)

2016-06-15

Purpose: Current methods of low dose rate brachytherapy source strength verification for sources preloaded into needles consist of either assaying a small number of seeds from a separate sample belonging to the same lot used to load the needles or performing batch assays of a subset of the preloaded seed trains. Both of these methods are cumbersome and have the limitations inherent to sampling. The purpose of this work was to investigate an alternative approach that uses an image-based, autoradiographic system capable of the rapid and complete assay of all sources without compromising sterility. Methods: The system consists of a flat panel image detector, an autoclavable needle holder, and software to analyze the detected signals. The needle holder was designed to maintain a fixed vertical spacing between the needles and the image detector, and to collimate the emissions from each seed. It also provides a sterile barrier between the needles and the imager. The image detector has a sufficiently large image capture area to allow several needles to be analyzed simultaneously.Several tests were performed to assess the accuracy and reproducibility of source strengths obtained using this system. Three different seed models (Oncura 6711 and 9011 {sup 125}I seeds, and IsoAid Advantage {sup 103}Pd seeds) were used in the evaluations. Seeds were loaded into trains with at least 1 cm spacing. Results: Using our system, it was possible to obtain linear calibration curves with coverage factor k = 1 prediction intervals of less than ±2% near the centre of their range for the three source models. The uncertainty budget calculated from a combination of type A and type B estimates of potential sources of error was somewhat larger, yielding (k = 1) combined uncertainties for individual seed readings of 6.2% for {sup 125}I 6711 seeds, 4.7% for {sup 125}I 9011 seeds, and 11.0% for Advantage {sup 103}Pd seeds. Conclusions: This study showed that a flat panel detector dosimetry system

Comparative effect of implant-abutment connections, abutment angulations, and screw lengths on preloaded abutment screw using three-dimensional finite element analysis: An in vitro study

Directory of Open Access Journals (Sweden)

Krishna Chaitanya Kanneganti

2018-01-01

Conclusions: The present study suggests selecting appropriate implant-abutment connection based on the abutment angulation, as well as preferring long screws with more number of threads for effective preload retention by the screws.

Effect of β-alanine supplementation on 20 km cycling time trial performance

Directory of Open Access Journals (Sweden)

Ruth Margaret JAMES

2014-09-01

Full Text Available The effects of β-alanine supplementation on high-intensity cycling performance and capacity have been evaluated, although the effects on longer duration cycling performance are unclear. Nineteen UK category 1 male cyclists completed four 20 km cycling time trials, two before and two after supplementation with either 6.4 g•d-1 β-alanine (n = 10; BA or a matched placebo (n = 9; P. Performance time for the 20 km time trial and 1 km split times were recorded. There was no significant effect of β-alanine supplementation on 20 km time trial performance (BA-pre 1943 ± 129 s; BA-post 1950 ± 147 s; P-pre 1989 ± 106 s; P-post 1986 ± 115 s or on the performance of each 1 km split. The effect of β-alanine on 20 km time trial performance was deemed unclear as determined by magnitude based inferences. Supplementation with 6.4 g•d-1 of β-alanine for 4 weeks did not affect 20 km cycling time trial performance in well trained male cyclists.

Persistence of long term isokinetic strength deficits in subjects with lateral ankle sprain as measured with a protocol including maximal preloading.

Science.gov (United States)

Perron, Marc; Moffet, Hélène; Nadeau, Sylvie; Hébert, Luc J; Belzile, Sylvain

2014-12-01

The assessment of muscle function is a cornerstone in the management of subjects who have sustained a lateral ankle sprain. The ankle range of motion being relatively small, the use of preloading allows to measure maximal strength throughout the whole amplitude and therefore to better characterize ankle muscles weaknesses. This study aimed to assess muscle strength of the injured and uninjured ankles in subjects with a lateral ankle sprain, to document the timeline of strength recovery, and to determine the influence of sprain grade on strength loss. Maximal torque of the periarticular muscles of the ankle in a concentric mode using a protocol with maximal preloading was tested in 32 male soldiers at 8 weeks and 6 months post-injury. The evertor muscles of the injured ankles were weaker than the uninjured ones at 8 weeks and 6 months post-injury (Pankles at 8 weeks (P=0.0014, effect size=0.52-0.58) while at 6 months, only the subjects with a grade II sprain displayed such weaknesses (Pankle sprain in very active individuals. Copyright © 2014 Elsevier Ltd. All rights reserved.

A Protein Preload Enhances the Glucose-Lowering Efficacy of Vildagliptin in Type 2 Diabetes

DEFF Research Database (Denmark)

Wu, T; Little, TL; Bound, MJ

2016-01-01

to evaluate whether a proteinpreload could improve the efficacy of the dipeptidyl peptidase-4 (DPP-4)inhibitor vildagliptin to increase incretin concentrations, slow gastric emptying,and lower postprandial glycemia in type 2 diabetes. RESEARCH DESIGN AND METHODSTwenty-two patients with type 2 diabetes treated...... with metformin were studiedon four occasions, receiving either 50 mg vildagliptin (VILD) or placebo (PLBO) onboth the evening before and the morning of each study day. The latter dose wasfollowed after 60 min by a preload drink containing either 25 gwhey protein (WHEY)or control flavoring (CTRL), and after...... intact GLP-1 and GIP, slower gastric emptying, and lowerpostprandial glycemia (P vildagliptin to slow gastric emptying, increase plasma intactincretins, and reduce postprandial...

The net effect of alternative allocation ratios on recruitment time and trial cost.

Science.gov (United States)

Vozdolska, Ralitza; Sano, Mary; Aisen, Paul; Edland, Steven D

2009-04-01

Increasing the proportion of subjects allocated to the experimental treatment in controlled clinical trials is often advocated as a method of increasing recruitment rates and improving the performance of trials. The presumption is that the higher likelihood of randomization to the experimental treatment will be perceived by potential study enrollees as an added benefit of participation and will increase recruitment rates and speed the completion of trials. However, studies with alternative allocation ratios require a larger sample size to maintain statistical power, which may result in a net increase in time required to complete recruitment and a net increase in total trial cost. To describe the potential net effect of alternative allocation ratios on recruitment time and trial cost. Models of recruitment time and trial cost were developed and used to compare trials with 1:1 allocation to trials with alternative allocation ratios under a range of per subject costs, per day costs, and enrollment rates. In regard to time required to complete recruitment, alternative allocation ratios are net beneficial if the recruitment rate improves by more than about 4% for trials with a 1.5:1 allocation ratio and 12% for trials with a 2:1 allocation ratio. More substantial improvements in recruitment rate, 13 and 47% respectively for scenarios we considered, are required for alternative allocation to be net beneficial in terms of tangible monetary cost. The cost models were developed expressly for trials comparing proportions or means across treatment groups. Using alternative allocation ratio designs to improve recruitment may or may not be time and cost-effective. Using alternative allocation for this purpose should only be considered for trial contexts where there is both clear evidence that the alternative design does improve recruitment rates and the attained time or cost efficiency justifies the added study subject burden implied by a larger sample size.

The influence of isometric preload on power expressed during bench press in strength-trained men.

Science.gov (United States)

Bartolomei, Sandro; Fukuda, David H; Hoffman, Jay R; Stout, Jeffrey R; Merni, Franco

2017-03-01

The purpose of this study was to compare the power expressed during the bench press exercise in resistance-trained men following different pre-activation conditions. Twenty-two trained men (age 24.1 ± 1.7 years, height 178.6 ± 6.1 cm, body mass 81.1 ± 10.6 kg) completed a maximal effort bench press (1-RM) test (100.0 kg ± 8.1 kg). In a subsequent assessment, each participant performed concentric bench press movements with loads of 20%, 30%, 40% and 50% of their 1-RM preceded by either a concentric contraction (CC), a low isometric preload (LIP; 70% 1-RM) or a high isometric preload (HIP; 100% 1-RM) conditions. All movements were performed in a Smith machine with a settable quick-release device. Participants performed all three conditions in randomized fashion. Results indicated that power outputs during the bench press exercise following HIP were significantly (p < 0.05) greater than CC at 20% 1-RM (+9%), 30% 1-RM (+16%) and 40% 1-RM (+14%), and LIP at 20% 1-RM (+4%), 30% 1-RM (+20%) and 40% 1-RM (+15%). No differences were found between conditions at 50% 1-RM. Area under the force-power curve with HIP was greater (p < 0.05) than with CC and LIP. In conclusion, results of this study indicate that the use of a HIP (100% 1-RM) in trained participants results in significantly greater power output during the concentric phase of a multi-joint exercise when compared to standard concentric movement.

Microrandomized trials: An experimental design for developing just-in-time adaptive interventions.

Science.gov (United States)

Klasnja, Predrag; Hekler, Eric B; Shiffman, Saul; Boruvka, Audrey; Almirall, Daniel; Tewari, Ambuj; Murphy, Susan A

2015-12-01

This article presents an experimental design, the microrandomized trial, developed to support optimization of just-in-time adaptive interventions (JITAIs). JITAIs are mHealth technologies that aim to deliver the right intervention components at the right times and locations to optimally support individuals' health behaviors. Microrandomized trials offer a way to optimize such interventions by enabling modeling of causal effects and time-varying effect moderation for individual intervention components within a JITAI. The article describes the microrandomized trial design, enumerates research questions that this experimental design can help answer, and provides an overview of the data analyses that can be used to assess the causal effects of studied intervention components and investigate time-varying moderation of those effects. Microrandomized trials enable causal modeling of proximal effects of the randomized intervention components and assessment of time-varying moderation of those effects. Microrandomized trials can help researchers understand whether their interventions are having intended effects, when and for whom they are effective, and what factors moderate the interventions' effects, enabling creation of more effective JITAIs. (PsycINFO Database Record (c) 2015 APA, all rights reserved).

Multiple linear regression to estimate time-frequency electrophysiological responses in single trials.

Science.gov (United States)

Hu, L; Zhang, Z G; Mouraux, A; Iannetti, G D

2015-05-01

Transient sensory, motor or cognitive event elicit not only phase-locked event-related potentials (ERPs) in the ongoing electroencephalogram (EEG), but also induce non-phase-locked modulations of ongoing EEG oscillations. These modulations can be detected when single-trial waveforms are analysed in the time-frequency domain, and consist in stimulus-induced decreases (event-related desynchronization, ERD) or increases (event-related synchronization, ERS) of synchrony in the activity of the underlying neuronal populations. ERD and ERS reflect changes in the parameters that control oscillations in neuronal networks and, depending on the frequency at which they occur, represent neuronal mechanisms involved in cortical activation, inhibition and binding. ERD and ERS are commonly estimated by averaging the time-frequency decomposition of single trials. However, their trial-to-trial variability that can reflect physiologically-important information is lost by across-trial averaging. Here, we aim to (1) develop novel approaches to explore single-trial parameters (including latency, frequency and magnitude) of ERP/ERD/ERS; (2) disclose the relationship between estimated single-trial parameters and other experimental factors (e.g., perceived intensity). We found that (1) stimulus-elicited ERP/ERD/ERS can be correctly separated using principal component analysis (PCA) decomposition with Varimax rotation on the single-trial time-frequency distributions; (2) time-frequency multiple linear regression with dispersion term (TF-MLRd) enhances the signal-to-noise ratio of ERP/ERD/ERS in single trials, and provides an unbiased estimation of their latency, frequency, and magnitude at single-trial level; (3) these estimates can be meaningfully correlated with each other and with other experimental factors at single-trial level (e.g., perceived stimulus intensity and ERP magnitude). The methods described in this article allow exploring fully non-phase-locked stimulus-induced cortical

Personalized Digital Interventions Showed no Impact on Risky Drinking in Young Adults: A Pilot Randomized Controlled Trial.

Science.gov (United States)

Davies, Emma L; Lonsdale, Adam J; Hennelly, Sarah E; Winstock, Adam R; Foxcroft, David R

2017-11-01

To assess the effectiveness of two personalized digital interventions (OneTooMany and Drinks Meter) compared to controls. Randomized controlled trial (AEARCTR-0,001,082). Volunteers for the study, aged 18-30, were randomly allocated to one of two interventions or one of two control groups and were followed up 4 weeks later. Primary outcomes were AUDIT-C, drinking harms and pre-loading. Drinks Meter provided participants with brief screening and advice for alcohol in addition to normative feedback, information on calories consumed and money spent. OneTooMany presented a series of socially embarrassing scenarios that may occur when drinking, and participants were scored according to if/how recently they had been experienced. The study failed to recruit and obtain sufficient follow-up data to reach a prior estimated power for detecting a difference between groups and there was no indication in the analysable sample of 402 subjects of a difference on the primary outcome measures (Drinks Meter; AUDIT-C IRR = 0.98 (0.89-1.09); Pre-loading IRR = 1.01 (0.95-1.07); Harms IRR = 0.97 (0.79-1.20); OneTooMany; AUDIT-C IRR = 0.96 (0.86-1.07); Pre-loading IRR = 0.99 (0.93-1.06); Harms IRR = 1.16 (0.94-1.43). Further research is needed on the efficacy of such instruments and their ingredients. However, recruitment and follow-up are a challenge. © The Author 2017. Medical Council on Alcohol and Oxford University Press. All rights reserved.

Thermal buckling behavior of defective CNTs under pre-load: A molecular dynamics study.

Science.gov (United States)

Mehralian, Fahimeh; Tadi Beni, Yaghoub; Kiani, Yaser

2017-05-01

Current study is concentrated on the extraordinary properties of defective carbon nanotubes (CNTs). The role of vacancy defects in thermal buckling response of precompressed CNTs is explored via molecular dynamics (MD) simulations. Defective CNTs are initially compressed at a certain ratio of their critical buckling strain and then undergo a uniform temperature rise. Comprehensive study is implemented on both armchair and zigzag CNTs with different vacancy defects including monovacancy, symmetric bivacancy and asymmetric bivacancy. The results reveal that defects have a pronounced impact on the buckling behavior of CNTs; interestingly, defective CNTs under compressive pre-load show higher resistance to thermal buckling than pristine ones. In the following, the buckling response of defective CNTs is shown to be dependent on the vacancy defects, location of defects and chirality. Copyright © 2017 Elsevier Inc. All rights reserved.

Effect of mechanical pre-loadings on corrosion resistance of chromium-electroplated steel rods in marine environment

Science.gov (United States)

Shubina Helbert, Varvara; Dhondt, Matthieu; Homette, Remi; Arbab Chirani, Shabnam; Calloch, Sylvain

2018-03-01

Providing high hardness, low friction coefficient, as well as, relatively good corrosion resistance, chromium-plated coatings (∼20 μm) are widely used for steel cylinder rods in marine environment. However, the standardized corrosion test method (ISO 9227, NSS) used to evaluate efficiency of this type of coatings does not take into account in-service mechanical loadings on cylinder rods. Nevertheless, the uniform initial network of microcracks in chromium coating is changing under mechanical loadings. Propagation of these microcracks explains premature corrosion of the steel substrate. The aim of the study was to evaluate relationship between mechanical loadings, propagation of microcracks network and corrosion resistance of chromium coatings. After monotonic pre-loading tests, it was demonstrated by microscopic observations that the microcracks propagation started at stress levels higher than the substrate yield stress (520 MPa). The microcracks become effective, i.e. they have instantly undergone through the whole coating thickness to reach the steel substrate. The density of effective microcracks increases with the total macroscopic level, i.e. the intercrack distance goes from 60 ± 5 μm at 1% of total strain to approximately 27 ± 2 μm at 10%. Electrochemical measurements have shown that the higher the plastic strain level applied during mechanical loading, the more the corrosion potential of the sample decreased until reaching the steel substrate value of approximately ‑0.65 V/SCE after 2 h of immersion. The polarization curves have also highligthed an increase in the corrosion current density with the strain level. Therefore, electrochemical measurements could be used to realize quick and comprehensive assesment of the effect of monotonic pre-loadings on corrosion properties of the chromium coating.

The impact of preload reduction with head-up tilt testing on longitudinal and transverse left ventricular mechanics: a study utilizing deformation volume analysis.

Science.gov (United States)

Schneider, Caroline; Forsythe, Lynsey; Somauroo, John; George, Keith; Oxborough, David

2018-03-01

Left ventricular (LV) function is dependent on load, intrinsic contractility and relaxation with a variable impact on specific mechanics. Strain (ε) imaging allows the assessment of cardiac function; however, the direct relationship between volume and strain is currently unknown. The aim of this study was to establish the impact of preload reduction through head-up tilt (HUT) testing on simultaneous left ventricular (LV) longitudinal and transverse function and their respective contribution to volume change. A focused transthoracic echocardiogram was performed on 10 healthy male participants (23 ± 3 years) in the supine position and following 1 min and 5 min of HUT testing. Raw temporal longitudinal ε (Ls) and transverse ε (Ts) values were exported and divided into 5% increments across the cardiac cycle and corresponding LV volumes were traced at each 5% increment. This provided simultaneous LV longitudinal and transverse ε and volume loops (deformation volume analysis - DVA). There was a leftward shift of the ε-volume loop from supine to 1 min and 5 min of HUT ( P  transverse thickening from supine to 1 min, which was further augmented at 5 min ( P  = 0.018). Preload reduction occurs within 1 min of HUT but does not further reduce at 5 min. This decline is associated with a decrease in longitudinal ε and concomitant increase in transverse ε. Consequently, augmented transverse relaxation appears to be an important factor in the maintenance of LV filling in the setting of reduced preload. DVA provides information on the relative contribution of mechanics to a change in LV volume and may have a role in the assessment of clinical populations. © 2018 The authors.

Numerical Study Of The Effects Of Preloading, Axial Loading And Concrete Shrinkage On Reinforced Concrete Elements Strengthened By Concrete Layers And Jackets

International Nuclear Information System (INIS)

Lampropoulos, A. P.; Dritsos, S. E.

2008-01-01

In this study, the technique of seismic strengthening existing reinforced concrete columns and beams using additional concrete layers and jackets is examined. The finite element method and the finite element program ATENA is used in this investigation. When a reinforced jacket or layer is being constructed around a column it is already preloaded due to existing service loads. This effect has been examined for different values of the axial load normalized to the strengthened column. The techniques of strengthening with a concrete jacket or a reinforced concrete layer on the compressive side of the column are examined. Another phenomenon that is examined in this study is the shrinkage of the new concrete of an additional layer used to strengthen an existing member. For this investigation, a simply supported beam with an additional reinforced concrete layer on the tensile side is examined. The results demonstrate that the effect of preloading is important when a reinforced concrete layer is being used with shear connectors between the old and the new reinforcement. It was also found that the shrinkage of the new concrete reduces the strength of the strengthened beam and induces an initial sliding between the old and the new concrete

Augmenting performance feedback does not affect 4 km cycling time-trials in the heat.

Science.gov (United States)

Waldron, Mark; Villerius, Vincent; Murphy, Aron

2015-01-01

We compared the effects of (1) accurate and (2) surreptitiously augmented performance feedback on power output and physiological responses to a 4000 m time-trial in the heat. Nine cyclists completed a baseline (BaseL) 4000 m time-trial in ambient temperatures of 30°C, followed by two further 4000 m time-trials at the same temperature, randomly assigning the participants to an accurate (ACC; accurate feedback of baseline) or deceived (DEC; 2% increase above baseline) feedback group. The total power output (PO) and aerobic (Paer) and anaerobic (Pan) contributions were determined at 0.4 km stages during the time-trials, alongside measurements of rectal (Trec) and skin (Tskin) temperatures. There were no differences (P > 0.05) in any of the variables between BaseL, ACC and DEC, despite increases (P 0.05) between feedback condition and time-trial stage. Providing surreptitiously augmented performance feedback to well-trained cyclists did not alter their performance or physiological responses to a 4000 m time-trial in a hot environment. The assumed influence of augmented performance feedback was nullified in the heat, perhaps reflecting a central down-regulation of exercise intensity in response to an increased body temperature.

Mental Toughness Moderates Social Loafing in Cycle Time-Trial Performance

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Haugen, Tommy; Reinboth, Michael; Hetlelid, Ken J.; Peters, Derek M.; Høigaard, Rune

2016-01-01

Purpose: The purpose of this study was to determine if mental toughness moderated the occurrence of social loafing in cycle time-trial performance. Method: Twenty-seven men (M[subscript age] = 17.7 years, SD = 0.6) completed the Sport Mental Toughness Questionnaire prior to completing a 1-min cycling trial under 2 conditions: once with individual…

Field-measured drag area is a key correlate of level cycling time trial performance

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James E. Peterman

2015-08-01

Full Text Available Drag area (Ad is a primary factor determining aerodynamic resistance during level cycling and is therefore a key determinant of level time trial performance. However, Ad has traditionally been difficult to measure. Our purpose was to determine the value of adding field-measured Ad as a correlate of level cycling time trial performance. In the field, 19 male cyclists performed a level (22.1 km time trial. Separately, field-determined Ad and rolling resistance were calculated for subjects along with projected frontal area assessed directly (AP and indirectly (Est AP. Also, a graded exercise test was performed to determine $\\dot {V}{O}_{2}$V̇O2 peak, lactate threshold (LT, and economy. $\\dot {V}{O}_{2}$V̇O2 peak ($\\mathrm{l}~\\min ^{-1}$lmin−1 and power at LT were significantly correlated to power measured during the time trial (r = 0.83 and 0.69, respectively but were not significantly correlated to performance time (r = − 0.42 and −0.45. The correlation with performance time improved significantly (p < 0.05 when these variables were normalized to Ad. Of note, Ad alone was better correlated to performance time (r = 0.85, p < 0.001 than any combination of non-normalized physiological measure. The best correlate with performance time was field-measured power output during the time trial normalized to Ad (r = − 0.92. AP only accounted for 54% of the variability in Ad. Accordingly, the correlation to performance time was significantly lower using power normalized to AP (r = − 0.75 or Est AP (r = − 0.71. In conclusion, unless normalized to Ad, level time trial performance in the field was not highly correlated to common laboratory measures. Furthermore, our field-measured Ad is easy to determine and was the single best predictor of level time trial performance.

Micro-Randomized Trials: An Experimental Design for Developing Just-in-Time Adaptive Interventions

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Klasnja, Predrag; Hekler, Eric B.; Shiffman, Saul; Boruvka, Audrey; Almirall, Daniel; Tewari, Ambuj; Murphy, Susan A.

2015-01-01

Objective This paper presents an experimental design, the micro-randomized trial, developed to support optimization of just-in-time adaptive interventions (JITAIs). JITAIs are mHealth technologies that aim to deliver the right intervention components at the right times and locations to optimally support individuals’ health behaviors. Micro-randomized trials offer a way to optimize such interventions by enabling modeling of causal effects and time-varying effect moderation for individual intervention components within a JITAI. Methods The paper describes the micro-randomized trial design, enumerates research questions that this experimental design can help answer, and provides an overview of the data analyses that can be used to assess the causal effects of studied intervention components and investigate time-varying moderation of those effects. Results Micro-randomized trials enable causal modeling of proximal effects of the randomized intervention components and assessment of time-varying moderation of those effects. Conclusions Micro-randomized trials can help researchers understand whether their interventions are having intended effects, when and for whom they are effective, and what factors moderate the interventions’ effects, enabling creation of more effective JITAIs. PMID:26651463

Effect of time of day on performance, hormonal and metabolic response during a 1000-M cycling time trial.

Directory of Open Access Journals (Sweden)

Alan Lins Fernandes

Full Text Available The aim of this study was to determine the effect of time of day on performance, pacing, and hormonal and metabolic responses during a 1000-m cycling time-trial. Nine male, recreational cyclists visited the laboratory four times. During the 1st visit the participants performed an incremental test and during the 2nd visit they performed a 1000-m cycling familiarization trial. On the 3rd and 4th visits, the participants performed a 1000-m TT at either 8 am or 6 pm, in randomized, repeated-measures, crossover design. The time to complete the time trial was lower in the evening than in the morning (88.2±8.7 versus 94.7±10.9 s, respectively, p0.05, but the norepinephrine response to the exercise was increased in the morning (+46%, p0.05. Our findings suggest that performance was improved in the evening, and it was accompanied by an improved hormonal and metabolic milieu.

Time Trials--An AP Physics Challenge Lab

Science.gov (United States)

Jones, David

2009-01-01

I have come to the conclusion that for high school physics classroom and laboratory experiences, simpler is better! In this paper I describe a very simple and effective lab experience that my AP students have thoroughly enjoyed year after year. I call this lab exercise "Time Trials." The experiment is simple in design and it is a lot of fun for…

Novel precooling strategy enhances time trial cycling in the heat.

Science.gov (United States)

Ross, Megan L R; Garvican, Laura A; Jeacocke, Nikki A; Laursen, Paul B; Abbiss, Chris R; Martin, David T; Burke, Louise M

2011-01-01

To develop and investigate the efficacy of a new precooling strategy combining external and internal techniques on the performance of a cycling time trial (TT) in a hot and humid environment. Eleven well-trained male cyclists undertook three trials of a laboratory-based cycling TT simulating the course characteristics of the Beijing Olympic Games event in a controlled hot and humid environment (32°C-35°C at 50%-60% relative humidity). The trials, separated by 3-7 d, were undertaken in a randomized crossover design and consisted of the following: 1) CON-no treatment apart from the ad libitum consumption of cold water (4°C), 2) STD COOL-whole-body immersion in cold (10°C) water for 10 min followed by wearing a cooling jacket, or 3) NEW COOL-combination of consumption of 14 g of ice slurry ("slushie") per kilogram body mass made from a commercial sports drink while applying iced towels. There was an observable effect on rectal temperature (T(rec)) before the commencement of the TT after both precooling techniques (STD COOL < NEW COOL < CON, P < 0.05), but pacing of the TT resulted in similar T(rec), HR, and RPE throughout the cycling protocol in all trials. NEW COOL was associated with a 3.0% increase in power (approximately 8 W) and a 1.3% improvement in performance time (approximately 1:06 min) compared with the CON trial, with the true likely effects ranging from a trivial to a large benefit. The effect of the STD COOL trial compared with the CON trial was "unclear." This new precooling strategy represents a practical and effective technique that could be used by athletes in preparation for endurance events undertaken in hot and humid conditions.

How many research nurses for how many clinical trials in an oncology setting? Definition of the Nursing Time Required by Clinical Trial-Assessment Tool (NTRCT-AT).

Science.gov (United States)

Milani, Alessandra; Mazzocco, Ketti; Stucchi, Sara; Magon, Giorgio; Pravettoni, Gabriella; Passoni, Claudia; Ciccarelli, Chiara; Tonali, Alessandra; Profeta, Teresa; Saiani, Luisa

2017-02-01

Few resources are available to quantify clinical trial-associated workload, needed to guide staffing and budgetary planning. The aim of the study is to describe a tool to measure clinical trials nurses' workload expressed in time spent to complete core activities. Clinical trials nurses drew up a list of nursing core activities, integrating results from literature searches with personal experience. The final 30 core activities were timed for each research nurse by an outside observer during daily practice in May and June 2014. Average times spent by nurses for each activity were calculated. The "Nursing Time Required by Clinical Trial-Assessment Tool" was created as an electronic sheet that combines the average times per specified activities and mathematic functions to return the total estimated time required by a research nurse for each specific trial. The tool was tested retrospectively on 141 clinical trials. The increasing complexity of clinical research requires structured approaches to determine workforce requirements. This study provides a tool to describe the activities of a clinical trials nurse and to estimate the associated time required to deliver individual trials. The application of the proposed tool in clinical research practice could provide a consistent structure for clinical trials nursing workload estimation internationally. © 2016 John Wiley & Sons Australia, Ltd.

Caffeinated nitric oxide-releasing lozenge improves cycling time trial performance.

Science.gov (United States)

Lee, J; Kim, H T; Solares, G J; Kim, K; Ding, Z; Ivy, J L

2015-02-01

Boosting nitric oxide production during exercise by various means has been found to improve exercise performance. We investigated the effects of a nitric oxide releasing lozenge with added caffeine (70 mg) on oxygen consumption during steady-state exercise and cycling time trial performance using a double-blinded randomized, crossover experimental design. 15 moderately trained cyclists (7 females and 8 males) were randomly assigned to ingest the caffeinated nitric oxide lozenge or placebo 5 min before exercise. Oxygen consumption and blood lactate were assessed at rest and at 50%, 65% and 75% maximal oxygen consumption. Exercise performance was assessed by time to complete a simulated 20.15 km cycling time-trial course. No significant treatment effects for oxygen consumption or blood lactate at rest or during steady-state exercise were observed. However, time-trial performance was improved by 2.1% (p<0.01) when participants consumed the nitric oxide lozenge (2,424±69 s) compared to placebo (2,476±78 s) and without a significant difference in rating of perceived exertion. These results suggest that acute supplementation with a caffeinated nitric oxide releasing lozenge may be a practical and effective means of improving aerobic exercise performance. © Georg Thieme Verlag KG Stuttgart · New York.

Fluid loading and norepinephrine infusion mask the left ventricular preload decrease induced by pleural effusion.

Science.gov (United States)

Wemmelund, Kristian Borup; Ringgård, Viktor Kromann; Vistisen, Simon Tilma; Hyldebrandt, Janus Adler; Sloth, Erik; Juhl-Olsen, Peter

2017-09-11

Pleural effusion (PLE) may lead to low blood pressure and reduced cardiac output. Low blood pressure and reduced cardiac output are often treated with fluid loading and vasopressors. This study aimed to determine the impact of fluid loading and norepinephrine infusion on physiologic determinants of cardiac function obtained by ultrasonography during PLE. In this randomised, blinded, controlled laboratory study, 30 piglets (21.9 ± 1.3 kg) had bilateral PLE (75 mL/kg) induced. Subsequently, the piglets were randomised to intervention as follows: fluid loading (80 mL/kg/h for 1.5 h, n = 12), norepinephrine infusion (0.01, 0.03, 0.05, 0.1, 0.2 and 0.3 μg/kg/min (15 min each, n = 12)) or control (n = 6). Main outcome was left ventricular preload measured as left ventricular end-diastolic area. Secondary endpoints included contractility and afterload as well as global measures of circulation. All endpoints were assessed with echocardiography and invasive pressure-flow measurements. PLE decreased left ventricular end-diastolic area, mean arterial pressure and cardiac output (p values  0.05) to baseline. Left ventricular contractility increased with norepinephrine infusion (p = 0.002), but was not affected by fluid loading (p = 0.903). Afterload increased in both active groups (p values > 0.001). Overall, inferior vena cava distensibility remained unchanged during intervention (p values ≥ 0.085). Evacuation of PLE caused numerical increases in left ventricular end-diastolic area, but only significantly so in controls (p = 0.006). PLE significantly reduced left ventricular preload. Both fluid and norepinephrine treatment reverted this effect and normalised global haemodynamic parameters. Inferior vena cava distensibility remained unchanged. The haemodynamic significance of PLE may be underestimated during fluid or norepinephrine administration, potentially masking the presence of PLE.

Predictive event modelling in multicenter clinical trials with waiting time to response.

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Anisimov, Vladimir V

2011-01-01

A new analytic statistical technique for predictive event modeling in ongoing multicenter clinical trials with waiting time to response is developed. It allows for the predictive mean and predictive bounds for the number of events to be constructed over time, accounting for the newly recruited patients and patients already at risk in the trial, and for different recruitment scenarios. For modeling patient recruitment, an advanced Poisson-gamma model is used, which accounts for the variation in recruitment over time, the variation in recruitment rates between different centers and the opening or closing of some centers in the future. A few models for event appearance allowing for 'recurrence', 'death' and 'lost-to-follow-up' events and using finite Markov chains in continuous time are considered. To predict the number of future events over time for an ongoing trial at some interim time, the parameters of the recruitment and event models are estimated using current data and then the predictive recruitment rates in each center are adjusted using individual data and Bayesian re-estimation. For a typical scenario (continue to recruit during some time interval, then stop recruitment and wait until a particular number of events happens), the closed-form expressions for the predictive mean and predictive bounds of the number of events at any future time point are derived under the assumptions of Markovian behavior of the event progression. The technique is efficiently applied to modeling different scenarios for some ongoing oncology trials. Case studies are considered. Copyright © 2011 John Wiley & Sons, Ltd.

Separation of time-based and trial-based accounts of the partial reinforcement extinction effect.

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Bouton, Mark E; Woods, Amanda M; Todd, Travis P

2014-01-01

Two appetitive conditioning experiments with rats examined time-based and trial-based accounts of the partial reinforcement extinction effect (PREE). In the PREE, the loss of responding that occurs in extinction is slower when the conditioned stimulus (CS) has been paired with a reinforcer on some of its presentations (partially reinforced) instead of every presentation (continuously reinforced). According to a time-based or "time-accumulation" view (e.g., Gallistel and Gibbon, 2000), the PREE occurs because the organism has learned in partial reinforcement to expect the reinforcer after a larger amount of time has accumulated in the CS over trials. In contrast, according to a trial-based view (e.g., Capaldi, 1967), the PREE occurs because the organism has learned in partial reinforcement to expect the reinforcer after a larger number of CS presentations. Experiment 1 used a procedure that equated partially and continuously reinforced groups on their expected times to reinforcement during conditioning. A PREE was still observed. Experiment 2 then used an extinction procedure that allowed time in the CS and the number of trials to accumulate differentially through extinction. The PREE was still evident when responding was examined as a function of expected time units to the reinforcer, but was eliminated when responding was examined as a function of expected trial units to the reinforcer. There was no evidence that the animal responded according to the ratio of time accumulated during the CS in extinction over the time in the CS expected before the reinforcer. The results thus favor a trial-based account over a time-based account of extinction and the PREE. This article is part of a Special Issue entitled: Associative and Temporal Learning. Copyright © 2013 Elsevier B.V. All rights reserved.

Timely and complete publication of economic evaluations alongside randomized controlled trials.

Science.gov (United States)

Thorn, Joanna C; Noble, Sian M; Hollingworth, William

2013-01-01

Little is known about the extent and nature of publication bias in economic evaluations. Our objective was to determine whether economic evaluations are subject to publication bias by considering whether economic data are as likely to be reported, and reported as promptly, as effectiveness data. Trials that intended to conduct an economic analysis and ended before 2008 were identified in the International Standard Randomised Controlled Trial Number (ISRCTN) register; a random sample of 100 trials was retrieved. Fifty comparator trials were randomly drawn from those not identified as intending to conduct an economic study. The trial start and end dates, estimated sample size and funder type were extracted. For trials planning economic evaluations, effectiveness and economic publications were sought; publication dates and journal impact factors were extracted. Effectiveness abstracts were assessed for whether they reached a firm conclusion that one intervention was most effective. Primary investigators were contacted about reasons for non-publication of results, or reasons for differential publication strategies for effectiveness and economic results. Trials planning an economic study were more likely to be funded by government (p = 0.01) and larger (p = 0.003) than other trials. The trials planning an economic evaluation had a mean of 6.5 (range 2.7-13.2) years since the trial end in which to publish their results. Effectiveness results were reported by 70 %, while only 43 % published economic evaluations (p economic results included the intervention being ineffective, and staffing issues. Funding source, time since trial end and length of study were not associated with a higher probability of publishing the economic evaluation. However, studies that were small or of unknown size were significantly less likely to publish economic evaluations than large studies (p journal impact factor was 1.6 points higher for effectiveness publications than for the

Metabolic Responses and Pacing Strategies during Successive Sprint Skiing Time Trials

DEFF Research Database (Denmark)

Andersson, Erik; Holmberg, Hans-Christer; Ørtenblad, Niels

2016-01-01

PURPOSE: To examine the metabolic responses and pacing strategies during the performance of successive sprint time trials (STTs) in cross-country skiing. METHODS: Ten well-trained male cross-country skiers performed four self-paced 1300-m STTs on a treadmill, each separated by 45 min of recovery...... to estimate the anaerobic energy supply. RESULTS: The individual trial-to-trial variability in STT performance time was 1.3%, where variations in O2 deficit and V˙O2 explained 69% (P 0.05) of the variation in performance. The first and last STTs were equally fast (228 ± 10 s), and ~ 1...... on the first than second course half. In addition, metabolic rates were substantially higher (~_30%) for uphill than for flat skiing, indicating that pacing was regulated to the terrain. CONCLUSIONS: The fastest STTs were characterized primarily by a greater anaerobic energy production, which also explained 69...

Between-Trial Forgetting Due to Interference and Time in Motor Adaptation.

Directory of Open Access Journals (Sweden)

Sungshin Kim

Full Text Available Learning a motor task with temporally spaced presentations or with other tasks intermixed between presentations reduces performance during training, but can enhance retention post training. These two effects are known as the spacing and contextual interference effect, respectively. Here, we aimed at testing a unifying hypothesis of the spacing and contextual interference effects in visuomotor adaptation, according to which forgetting between trials due to either spaced presentations or interference by another task will promote between-trial forgetting, which will depress performance during acquisition, but will promote retention. We first performed an experiment with three visuomotor adaptation conditions: a short inter-trial-interval (ITI condition (SHORT-ITI; a long ITI condition (LONG-ITI; and an alternating condition with two alternated opposite tasks (ALT, with the same single-task ITI as in LONG-ITI. In the SHORT-ITI condition, there was fastest increase in performance during training and largest immediate forgetting in the retention tests. In contrast, in the ALT condition, there was slowest increase in performance during training and little immediate forgetting in the retention tests. Compared to these two conditions, in the LONG-ITI, we found intermediate increase in performance during training and intermediate immediate forgetting. To account for these results, we fitted to the data six possible adaptation models with one or two time scales, and with interference in the fast, or in the slow, or in both time scales. Model comparison confirmed that two time scales and some degree of interferences in either time scale are needed to account for our experimental results. In summary, our results suggest that retention following adaptation is modulated by the degree of between-trial forgetting, which is due to time-based decay in single adaptation task and interferences in multiple adaptation tasks.

Preloading Effect on Strengthening Efficiency of RC Beams Strengthened with Non- and Pretensioned NSM Strips

Directory of Open Access Journals (Sweden)

Renata Kotynia

2018-02-01

Full Text Available The near surface mounted (NSM technique has been shown to be one of the most promising methods for upgrading reinforced concrete (RC structures. Many tests carried out on RC members strengthened in flexure with NSM fiber-reinforced polymer (FRP systems have demonstrated greater strengthening efficiency than the use of externally-bonded (EB FRP laminates. Strengthening with simultaneous pretensioning of the FRP results in improvements in the serviceability limit state (SLS conditions, including the increased cracking moment and decreased deflections. The objective of the reported experimental program, which consisted of two series of RC beams strengthened in flexure with NSM CFRP strips, was to investigate the influence of a number of parameters on the strengthening efficiency. The test program focused on an analysis of the effects of preloading on the strengthening efficiency which has been investigated very rarely despite being one of the most important parameters to be taken into account in strengthening design. Two preloading levels were considered: the beam self-weight only, which corresponded to stresses on the internal longitudinal reinforcement of 25% and 14% of the yield stress (depending on a steel reinforcement ratio, and the self-weight with the additional superimposed load, corresponding to 60% of the yield strength of the unstrengthened beam and a deflection equal to the allowable deflection at the SLS. The influence of the longitudinal steel reinforcement ratio was also considered in this study. To reflect the variability seen in existing structures, test specimens were varied by using different steel bar diameters. Finally, the impact of the composite reinforcement ratio and the number of pretensioned FRP strips was considered. Specimens were divided into two series based on their strengthening configuration: series “A” were strengthened with one pretensioned and two non-pretensioned carbon FRP (CFRP strips, while series �

Consumption of a high-fat soup preload leads to differences in short-term energy and fat intake between PROP non-taster and super-taster women.

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Shafaie, Yasmine; Hoffman, Daniel J; Tepper, Beverly J

2015-06-01

Taste blindness to the bitterness of PROP (6-n-propylthiouracil) has been used as a genetic marker for food selection and adiposity. We have shown that PROP non-taster (NT) women have higher BMIs and habitually consume more fat and energy than either medium-taster (MT) or super-taster (ST) women. These data imply that differences in dietary selection underlie the body weight differences among PROP taster groups. However, no studies investigated energy compensation in women classified by PROP status. We investigated if NTs would compensate less accurately for the calories and fat in a high-fat soup preload in a subsequent test meal compared to MTs and STs. Energy intake from a buffet meal was measured in 75 healthy non-diet-restrained, lean women 30 min after the ingestion of a high-fat soup preload (0.8 kcal/g; 55% calories from fat), calculated to represent 10% of resting energy expenditure for each subject, or the same volume of water. Subjects (n = 20-28/taster group) ate a standard breakfast followed 3 hr later by an ad-libitum buffet lunch, on two occasions. There were no differences in energy intake or macronutrient selection across taster groups after water. After soup, NTs consumed more energy than STs. Fat intake (as %-energy) was higher in NTs (46.4% ± 2.4) compared to either MTs (36.1 ± 1.9%) or STs (38.1% ± 2.3; p < 0.05). NTs overate by 11% ± 5 after the soup compared to MTs and STs who underrate by 16% ± 6 and 26% ± 10, respectively (p < 0.01). These data suggest that small discrepancies in short-term energy compensation and selection of fat after a mixed-nutrient, high-fat preload may play a role in positive energy balance and increased adiposity in women with the PROP non-taster phenotype. Copyright © 2015 Elsevier Ltd. All rights reserved.

Protocol of the Definition for the Assessment of Time-to-event Endpoints in CANcer trials (DATECAN) project: formal consensus method for the development of guidelines for standardised time-to-event endpoints' definitions in cancer clinical trials.

Science.gov (United States)

Bellera, Carine A; Pulido, Marina; Gourgou, Sophie; Collette, Laurence; Doussau, Adélaïde; Kramar, Andrew; Dabakuyo, Tienhan Sandrine; Ouali, Monia; Auperin, Anne; Filleron, Thomas; Fortpied, Catherine; Le Tourneau, Christophe; Paoletti, Xavier; Mauer, Murielle; Mathoulin-Pélissier, Simone; Bonnetain, Franck

2013-03-01

In randomised phase III cancer clinical trials, the most objectively defined and only validated time-to-event endpoint is overall survival (OS). The appearance of new types of treatments and the multiplication of lines of treatment have resulted in the use of surrogate endpoints for overall survival such as progression-free survival (PFS), or time-to-treatment failure. Their development is strongly influenced by the necessity of reducing clinical trial duration, cost and number of patients. However, while these endpoints are frequently used, they are often poorly defined and definitions can differ between trials which may limit their use as primary endpoints. Moreover, this variability of definitions can impact on the trial's results by affecting estimation of treatments' effects. The aim of the Definition for the Assessment of Time-to-event Endpoints in CANcer trials (DATECAN) project is to provide recommendations for standardised definitions of time-to-event endpoints in randomised cancer clinical trials. We will use a formal consensus methodology based on experts' opinions which will be obtained in a systematic manner. Definitions will be independently developed for several cancer sites, including pancreatic, breast, head and neck and colon cancer, as well as sarcomas and gastrointestinal stromal tumours (GISTs). The DATECAN project should lead to the elaboration of recommendations that can then be used as guidelines by researchers participating in clinical trials. This process should lead to a standardisation of the definitions of commonly used time-to-event endpoints, enabling appropriate comparisons of future trials' results. Copyright © 2012 Elsevier Ltd. All rights reserved.

Effects of preparation time and trial type probability on performance of anti- and pro-saccades.

Science.gov (United States)

Pierce, Jordan E; McDowell, Jennifer E

2016-02-01

Cognitive control optimizes responses to relevant task conditions by balancing bottom-up stimulus processing with top-down goal pursuit. It can be investigated using the ocular motor system by contrasting basic prosaccades (look toward a stimulus) with complex antisaccades (look away from a stimulus). Furthermore, the amount of time allotted between trials, the need to switch task sets, and the time allowed to prepare for an upcoming saccade all impact performance. In this study the relative probabilities of anti- and pro-saccades were manipulated across five blocks of interleaved trials, while the inter-trial interval and trial type cue duration were varied across subjects. Results indicated that inter-trial interval had no significant effect on error rates or reaction times (RTs), while a shorter trial type cue led to more antisaccade errors and faster overall RTs. Responses following a shorter cue duration also showed a stronger effect of trial type probability, with more antisaccade errors in blocks with a low antisaccade probability and slower RTs for each saccade task when its trial type was unlikely. A longer cue duration yielded fewer errors and slower RTs, with a larger switch cost for errors compared to a short cue duration. Findings demonstrated that when the trial type cue duration was shorter, visual motor responsiveness was faster and subjects relied upon the implicit trial probability context to improve performance. When the cue duration was longer, increased fixation-related activity may have delayed saccade motor preparation and slowed responses, guiding subjects to respond in a controlled manner regardless of trial type probability. Copyright © 2016 Elsevier B.V. All rights reserved.

Guidelines for time-to-event end point definitions in breast cancer trials: results of the DATECAN initiative (Definition for the Assessment of Time-to-event Endpoints in CANcer trials)†.

Science.gov (United States)

Gourgou-Bourgade, S; Cameron, D; Poortmans, P; Asselain, B; Azria, D; Cardoso, F; A'Hern, R; Bliss, J; Bogaerts, J; Bonnefoi, H; Brain, E; Cardoso, M J; Chibaudel, B; Coleman, R; Cufer, T; Dal Lago, L; Dalenc, F; De Azambuja, E; Debled, M; Delaloge, S; Filleron, T; Gligorov, J; Gutowski, M; Jacot, W; Kirkove, C; MacGrogan, G; Michiels, S; Negreiros, I; Offersen, B V; Penault Llorca, F; Pruneri, G; Roche, H; Russell, N S; Schmitt, F; Servent, V; Thürlimann, B; Untch, M; van der Hage, J A; van Tienhoven, G; Wildiers, H; Yarnold, J; Bonnetain, F; Mathoulin-Pélissier, S; Bellera, C; Dabakuyo-Yonli, T S

2015-05-01

Using surrogate end points for overall survival, such as disease-free survival, is increasingly common in randomized controlled trials. However, the definitions of several of these time-to-event (TTE) end points are imprecisely which limits interpretation and cross-trial comparisons. The estimation of treatment effects may be directly affected by the definitions of end points. The DATECAN initiative (Definition for the Assessment of Time-to-event Endpoints in CANcer trials) aims to provide recommendations for definitions of TTE end points. We report guidelines for randomized cancer clinical trials (RCTs) in breast cancer. A literature review was carried out to identify TTE end points (primary or secondary) reported in publications of randomized trials or guidelines. An international multidisciplinary panel of experts proposed recommendations for the definitions of these end points based on a validated consensus method that formalize the degree of agreement among experts. Recommended guidelines for the definitions of TTE end points commonly used in RCTs for breast cancer are provided for non-metastatic and metastatic settings. The use of standardized definitions should facilitate comparisons of trial results and improve the quality of trial design and reporting. These guidelines could be of particular interest to those involved in the design, conducting, reporting, or assessment of RCT. © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Effect of inhaled terbutaline on substrate utilization and 300-kcal time trial performance

DEFF Research Database (Denmark)

Kalsen, Anders; Hostrup, Morten; Karlsson, Sebastian

2014-01-01

. There was no difference between PLA and TER in net muscle glycogen utilization and lactate accumulation during the time trial. IMTG did not change with treatment or exercise. PDH-E1α Ser(293) and Ser(300) phosphorylation were lower (P...In a randomized double-blind crossover design, we investigated the effect of the beta2-agonist terbutaline on endurance performance and substrate utilization in nine moderately trained males (maximum oxygen uptake (VO2max): 58.9±3.1 mL min(-1) kg(-1)). Subjects performed 60 min of submaximal...... exercise (65-70% of VO2max) immediately followed by a 300-kcal time trial with inhalation of either terbutaline (TER) or placebo (PLA). Pulmonary gas exchange was measured during the submaximal exercise and muscle biopsies were collected before and after the exercise bouts. Time trial performance...

Comparative effect of implant-abutment connections, abutment angulations, and screw lengths on preloaded abutment screw using three-dimensional finite element analysis: An in vitro study

OpenAIRE

Krishna Chaitanya Kanneganti; Dileep Nag Vinnakota; Srinivas Rao Pottem; Mahesh Pulagam

2018-01-01

Purpose: The purpose of this study is to compare the effect of implant-abutment connections, abutment angulations, and screw lengths on screw loosening (SL) of preloaded abutment using three dimensional (3D) finite element analysis. Materials and Methods: 3D models of implants (conical connection with hex/trilobed connections), abutments (straight/angulated), abutment screws (short/long), and crown and bone were designed using software Parametric Technology Corporation Creo and assembled t...

The effect of extrinsic motivation on cycle time trial performance

NARCIS (Netherlands)

Hulleman, M.; de Koning, J.J.; Hettinga, F.J.; Foster, C.

2007-01-01

PURPOSE: Athletes occasionally follow pacing patterns that seem unreasonably aggressive compared with those of prerace performances, potentially because of the motivation provided by competition. This study evaluated the effect of extrinsic motivation on cyclists' time trial performance. METHODS:

Mountain time trial in handcycling : exercise intensity and predictors of race time in people with spinal cord injury

NARCIS (Netherlands)

de Groot, Sonja; Postma, Karin; van Vliet, Linda; Timmermans, Remco; Valent, L J M

Study design: Cross-sectional analyses. Objectives: To analyze exercise intensity during a mountain time trial in handcycling and to determine predictors of race time. Setting: Eight Dutch rehabilitation centers and Austrian mountain. Methods: Forty participants with spinal cord injury (SCI; high

Pacing Strategy, Muscle Fatigue, and Technique in 1500-m Speed-Skating and Cycling Time Trials.

Science.gov (United States)

Stoter, Inge K; MacIntosh, Brian R; Fletcher, Jared R; Pootz, Spencer; Zijdewind, Inge; Hettinga, Florentina J

2016-04-01

To evaluate pacing behavior and peripheral and central contributions to muscle fatigue in 1500-m speed-skating and cycling time trials when a faster or slower start is instructed. Nine speed skaters and 9 cyclists, all competing at regional or national level, performed two 1500-m time trials in their sport. Athletes were instructed to start faster than usual in 1 trial and slower in the other. Mean velocity was measured per 100 m. Blood lactate concentrations were measured. Maximal voluntary contraction (MVC), voluntary activation (VA), and potentiated twitch (PT) of the quadriceps muscles were measured to estimate central and peripheral contributions to muscle fatigue. In speed skating, knee, hip, and trunk angles were measured to evaluate technique. Cyclists showed a more explosive start than speed skaters in the fast-start time trial (cyclists performed first 300 m in 24.70 ± 1.73 s, speed skaters in 26.18 ± 0.79 s). Both trials resulted in reduced MVC (12.0% ± 14.5%), VA (2.4% ± 5.0%), and PT (25.4% ± 15.2%). Blood lactate concentrations after the time trial and the decrease in PT were greater in the fast-start than in the slow-start trial. Speed skaters showed higher trunk angles in the fast-start than in the slow-start trial, while knee angles remained similar. Despite similar instructions, behavioral adaptations in pacing differed between the 2 sports, resulting in equal central and peripheral contributions to muscle fatigue in both sports. This provides evidence for the importance of neurophysiological aspects in the regulation of pacing. It also stresses the notion that optimal pacing needs to be studied sport specifically, and coaches should be aware of this.

Effect of lactate supplementation and sodium bicarbonate on 40-km cycling time trial performance.

Science.gov (United States)

Northgraves, Matthew J; Peart, Daniel J; Jordan, Christian A; Vince, Rebecca V

2014-01-01

The use of nutritional supplements to improve sporting performance and increase training adaptations is commonplace among athletes and is an expanding market in terms of product choice and availability. The purpose of this study was to examine the effects of 2 ergogenic aids with extracellular blood buffering potential, namely sodium bicarbonate (NaHCO3) and a lactate supplement, during a 40-km cycling time trial. Seven recreationally active men (age, 22.3 ± 3.3 years; height, 182.5 ± 6.5 cm; body mass, 79.2 ± 6.3 kg) completed five 40-km cycling time trials, including a familiarization trial in a randomized, blind, double placebo-controlled design. Subjects ingested (a) 300 mg·kg-1 body mass NaHCO3 (BICARB), (b) 45 mg·kg-1 body mass sodium chloride (PL-BICARB) as the placebo for the NaHCO3 trial, (c) 1115 mg lactate (LACTATE), or (d) plain flour as the placebo for the lactate trial (PL-LACTATE) 60 minutes before exercise. There was no significant difference in performance between the 4 conditions (p > 0.05). Although NaHCO3 ingestion induced significant changes in all the acid-base variables (all p 0.05). Subjects in the LACTATE condition did have a significantly higher heart rate (p 0.05) than the other 3 conditions. Neither NaHCO3 nor lactate supplementation seem to improve 40-km cycling time trial performance. However, the potential benefits following LACTATE regarding perceived exertion require further research.

Endothelin-1 stimulates the release of preloaded [3H]D-aspartate from cultured cerebellar granule cells

International Nuclear Information System (INIS)

Lin, W.W.; Lee, C.Y.; Chuang, D.M.

1990-01-01

We have recently reported that endothelin-1 (ET) induces phosphoinositide hydrolysis in primary cultures of rat cerebellar granule cells. Here we found that ET in a dose-dependent manner (1-30 nM) stimulated the release of preloaded [ 3 H]D-aspartate from granule cells. The ET-induced aspartate release was completely blocked in the absence of extracellular Ca 2+ , but was unaffected by 1 mM Co 2+ or 1 microM dihydropyridine derivatives (nisoldipine and nimodipine). At higher concentration (10 microM) of nisoldipine and nimodipine, the release was partially inhibited. Short-term pretreatment of cells with phorbol 12,13-dibutyrate (PDBu) potentiated the ET-induced aspartate release, while long-term pretreatment with PDBu attenuated the release. Long-term exposure of cells to pertussis toxin (PTX), on the other hand, potentiated the ET-induced effects. Our results suggest that ET has a neuromodulatory function in the central nervous system

The impact of left ventricular preload reduction on cardiac pulsed doppler indices during hemodialysis and its relation to intra-dialysis hypotension: A pulsed doppler study

International Nuclear Information System (INIS)

Alarrayed, Sameer; Garadah Taysir Said; Alawdi, Abdulhai Ali

2009-01-01

Fluid status in the body plays an important role on left ventricular (LV) filling in patients with end-stage renal disease (ESRD) on regular hemodialysis (HD), and plays a role in intra-dialysis hemodynamic derangement. Fifty-two patients with ESRD on regular HD, including 34 males with a mean age of 45.5 +- 13 years (range 18-72 years), were studied. All patients underwent Echo-pulsed Doppler study before and immediately after a HD session. The Echo Doppler indices noted were: LV cavity dimension and wall thickness, LV ejection fraction (LVEF%), trans-mitral early diastolic filling velocity (E wave), atrial filling diastolic velocity (A wave), E/A ratio, Deceleration Time (DT) of E wave, Isovolumic relaxation time (IVRT), Aortic Velocity Integral (AVI) and Inferior Vena Cava Diameter (VCD) at expiration. Patients were divided into two groups according to the amount of net ultra filtrate loss after HD. Group I comprised of 25 patients with fluid loss of 2 liters. During the HD session, each patient was observed for the development of acute clinical events such as arterial hypotension (systolic BP less than 90 mmHg), chest pain and arrhythmias. There was a significant difference between the two groups in the mean values, pre- and post- HD, of reduction of E wave velocity (p < 0.01), the reduction of E/A ratio (p< 0.05), the increment in DT of E wave (p< 0.05), the reduction in AVI (p< 0.01) and the reduction of VCD (p< 0.05). There was no significant difference between the groups in the reduction of A wave velocity and the reduction of IVRT. Among the study patients, 11 (21%) developed systolic hypo-tension during HD. The pre-dialysis mean values of E/A ratio and DT of E wave in patients who developed hypotension compared to those who did not was 0.7 +- 0.2 vs 1.1 +- 0.2.1 (p< 0.001) and 246 +- 40 vs 224 +- 34 msec (p< 0.05), respectively. Our study suggests that preload reduction in patients with ESRD on regular HD is directly proportional to the reduction of left

Guidelines for time-to-event end point definitions in sarcomas and gastrointestinal stromal tumors (GIST) trials: results of the DATECAN initiative (Definition for the Assessment of Time-to-event Endpoints in CANcer trials)†.

Science.gov (United States)

Bellera, C A; Penel, N; Ouali, M; Bonvalot, S; Casali, P G; Nielsen, O S; Delannes, M; Litière, S; Bonnetain, F; Dabakuyo, T S; Benjamin, R S; Blay, J-Y; Bui, B N; Collin, F; Delaney, T F; Duffaud, F; Filleron, T; Fiore, M; Gelderblom, H; George, S; Grimer, R; Grosclaude, P; Gronchi, A; Haas, R; Hohenberger, P; Issels, R; Italiano, A; Jooste, V; Krarup-Hansen, A; Le Péchoux, C; Mussi, C; Oberlin, O; Patel, S; Piperno-Neumann, S; Raut, C; Ray-Coquard, I; Rutkowski, P; Schuetze, S; Sleijfer, S; Stoeckle, E; Van Glabbeke, M; Woll, P; Gourgou-Bourgade, S; Mathoulin-Pélissier, S

2015-05-01

The use of potential surrogate end points for overall survival, such as disease-free survival (DFS) or time-to-treatment failure (TTF) is increasingly common in randomized controlled trials (RCTs) in cancer. However, the definition of time-to-event (TTE) end points is rarely precise and lacks uniformity across trials. End point definition can impact trial results by affecting estimation of treatment effect and statistical power. The DATECAN initiative (Definition for the Assessment of Time-to-event End points in CANcer trials) aims to provide recommendations for definitions of TTE end points. We report guidelines for RCT in sarcomas and gastrointestinal stromal tumors (GIST). We first carried out a literature review to identify TTE end points (primary or secondary) reported in publications of RCT. An international multidisciplinary panel of experts proposed recommendations for the definitions of these end points. Recommendations were developed through a validated consensus method formalizing the degree of agreement among experts. Recommended guidelines for the definition of TTE end points commonly used in RCT for sarcomas and GIST are provided for adjuvant and metastatic settings, including DFS, TTF, time to progression and others. Use of standardized definitions should facilitate comparison of trials' results, and improve the quality of trial design and reporting. These guidelines could be of particular interest to research scientists involved in the design, conduct, reporting or assessment of RCT such as investigators, statisticians, reviewers, editors or regulatory authorities. © The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Sodium Phosphate Supplementation and Time Trial Performance in Female Cyclists

Directory of Open Access Journals (Sweden)

Christopher L. Buck

2014-09-01

Full Text Available This study investigated the effects of three doses of sodium phosphate (SP supplementation on cycling 500 kJ (119.5 Kcal time trial (TT performance in female cyclists. Thirteen cyclists participated in a randomised, Latin-square design study where they completed four separate trials after ingesting either a placebo, or one of three different doses (25, 50 or 75 mg·kg-1 fat free mass: FFM of trisodium phosphate dodecahydrate which was split into four equal doses a day for six days. On the day after the loading phase, the TT was performed on a cycle ergometer. Serum phosphate blood samples were taken at rest both before and after each loading protocol, while a ~21 day washout period separated each loading phase. No significant differences in TT performance were observed between any of the supplementation protocols (p = 0.73 with average completion times for the 25, 50 or 75 mg·kg-1 FFM being, 42:21 ± 07:53, 40:55 ± 07:33 and 40:38 ± 07:20 min respectively, and 40:39 ± 07:51 min for the placebo. Likewise, average and peak power output did not significantly differ between trials (p = 0.06 and p = 0.46, respectively. Consequently, 500 kJ cycling TT performance was not different in any of the supplementation protocols in female cyclists.

Precooling and Warm-Up Effects on Time Trial Cycling During Heat Stress.

Science.gov (United States)

Al-Horani, Ramzi A; Wingo, Jonathan E; Ng, Jason; Bishop, Phillip; Richardson, Mark

2018-02-01

Heat stress limits endurance exercise performance. Combining precooling and warm-up prior to endurance exercise in the heat may exploit the benefits of both strategies while avoiding the potential negative consequences of each. This study tested the hypothesis that precooling combined with warm-up improves time trial cycling performance in the heat relative to either treatment alone. Nine healthy men completed three 16.1-km time trials in 33°C after: 1) precooling (ice slurry and ice vest) alone (PREC); 2) warm-up alone (WU); or 3) PREC plus WU (COMBO). Tre was lower after PREC compared to WU throughout exercise and lower than COMBO for the first 12 km; COMBO was lower than WU for the first 4 km. Tsk during PREC was lower than COMBO and WU for the first 8 km, and lower in COMBO than WU for the first 4 km. PREC lowered pre-exercise heart rate relative to COMBO and WU (68 ± 10, 106 ± 12, 101 ± 13 bpm, respectively), but it increased similarly during exercise. Local sweat rate (SR) was lower in PREC (0.1 ± 0.1 mg · cm-2 · min-1) than COMBO (0.5 ± 0.2 mg · cm-2 · min-1) and WU (0.6 ± 0.2 mg · cm-2 · min-1) for the first 4 km. Treatments did not differentially affect performance (PREC = 31.9 ± 1.9 min, COMBO = 32.6 ± 2.7 min, WU = 33.1 ± 2.9 min). We conclude precooling alone or with warm-up mitigated thermal strain during exercise, but did not significantly improve 16.1-km cycling time trial performance.Al-horani RA, Wingo JE, Ng J, Bishop P, Richardson M. Precooling and warm-up effects on time trial cycling during heat stress. Aerosp Med Hum Perform. 2018; 89(2):87-93.

Working Memory Load Affects Processing Time in Spoken Word Recognition: Evidence from Eye-Movements

Science.gov (United States)

Hadar, Britt; Skrzypek, Joshua E.; Wingfield, Arthur; Ben-David, Boaz M.

2016-01-01

In daily life, speech perception is usually accompanied by other tasks that tap into working memory capacity. However, the role of working memory on speech processing is not clear. The goal of this study was to examine how working memory load affects the timeline for spoken word recognition in ideal listening conditions. We used the “visual world” eye-tracking paradigm. The task consisted of spoken instructions referring to one of four objects depicted on a computer monitor (e.g., “point at the candle”). Half of the trials presented a phonological competitor to the target word that either overlapped in the initial syllable (onset) or at the last syllable (offset). Eye movements captured listeners' ability to differentiate the target noun from its depicted phonological competitor (e.g., candy or sandal). We manipulated working memory load by using a digit pre-load task, where participants had to retain either one (low-load) or four (high-load) spoken digits for the duration of a spoken word recognition trial. The data show that the high-load condition delayed real-time target discrimination. Specifically, a four-digit load was sufficient to delay the point of discrimination between the spoken target word and its phonological competitor. Our results emphasize the important role working memory plays in speech perception, even when performed by young adults in ideal listening conditions. PMID:27242424

Guidelines for time-to-event end-point definitions in trials for pancreatic cancer. Results of the DATECAN initiative (Definition for the Assessment of Time-to-event End-points in CANcer trials).

Science.gov (United States)

Bonnetain, Franck; Bonsing, Bert; Conroy, Thierry; Dousseau, Adelaide; Glimelius, Bengt; Haustermans, Karin; Lacaine, François; Van Laethem, Jean Luc; Aparicio, Thomas; Aust, Daniela; Bassi, Claudio; Berger, Virginie; Chamorey, Emmanuel; Chibaudel, Benoist; Dahan, Laeticia; De Gramont, Aimery; Delpero, Jean Robert; Dervenis, Christos; Ducreux, Michel; Gal, Jocelyn; Gerber, Erich; Ghaneh, Paula; Hammel, Pascal; Hendlisz, Alain; Jooste, Valérie; Labianca, Roberto; Latouche, Aurelien; Lutz, Manfred; Macarulla, Teresa; Malka, David; Mauer, Muriel; Mitry, Emmanuel; Neoptolemos, John; Pessaux, Patrick; Sauvanet, Alain; Tabernero, Josep; Taieb, Julien; van Tienhoven, Geertjan; Gourgou-Bourgade, Sophie; Bellera, Carine; Mathoulin-Pélissier, Simone; Collette, Laurence

2014-11-01

Using potential surrogate end-points for overall survival (OS) such as Disease-Free- (DFS) or Progression-Free Survival (PFS) is increasingly common in randomised controlled trials (RCTs). However, end-points are too often imprecisely defined which largely contributes to a lack of homogeneity across trials, hampering comparison between them. The aim of the DATECAN (Definition for the Assessment of Time-to-event End-points in CANcer trials)-Pancreas project is to provide guidelines for standardised definition of time-to-event end-points in RCTs for pancreatic cancer. Time-to-event end-points currently used were identified from a literature review of pancreatic RCT trials (2006-2009). Academic research groups were contacted for participation in order to select clinicians and methodologists to participate in the pilot and scoring groups (>30 experts). A consensus was built after 2 rounds of the modified Delphi formal consensus approach with the Rand scoring methodology (range: 1-9). For pancreatic cancer, 14 time to event end-points and 25 distinct event types applied to two settings (detectable disease and/or no detectable disease) were considered relevant and included in the questionnaire sent to 52 selected experts. Thirty experts answered both scoring rounds. A total of 204 events distributed over the 14 end-points were scored. After the first round, consensus was reached for 25 items; after the second consensus was reached for 156 items; and after the face-to-face meeting for 203 items. The formal consensus approach reached the elaboration of guidelines for standardised definitions of time-to-event end-points allowing cross-comparison of RCTs in pancreatic cancer. Copyright © 2014 Elsevier Ltd. All rights reserved.

The effect of music on 10-km cycle time-trial performance.

Science.gov (United States)

Hagen, Jana; Foster, Carl; Rodríguez-Marroyo, Jose; de Koning, Jos J; Mikat, Richard P; Hendrix, Charles R; Porcari, John P

2013-01-01

Music is widely used as an ergogenic aid in sport, but there is little evidence of its effectiveness during closed-loop athletic events. In order to determine the effectiveness of music as an ergogenic aid, well-trained and task-habituated cyclists performed 10-km cycle time trials either while listening to self-selected motivational music or with auditory input blocked. There were no statistically significant differences in performance time or physiological or psychological markers related to music (time-trial duration17.75 ± 2.10 vs 17.81 ± 2.06 min, mean power output 222 ± 66 vs 220 ± 65 W, peak heart rate184 ± 9 vs 183 ± 8 beats/min, peak blood lactate12.1 ± 2.6 vs 11.9 ± 2.1 mmol/L, and final rating of perceived exertion 8.4 ± 1.5 vs 8.5 ± 1.6). It is concluded that during exercise at competitive intensity, there is no meaningful effect of music on either performance or physiology.

Mouth Rinsing with Maltodextrin Solutions Fails to Improve Time Trial Endurance Cycling Performance in Recreational Athletes

Directory of Open Access Journals (Sweden)

Tuğba Nilay Kulaksız

2016-05-01

Full Text Available The carbohydrate (CHO concentration of a mouth rinsing solution might influence the CHO sensing receptors in the mouth, with consequent activation of brain regions involved in reward, motivation and regulation of motor activity. The purpose of the present study was to examine the effects of maltodextrin mouth rinsing with different concentrations (3%, 6% and 12% after an overnight fast on a 20 km cycling time trial performance. Nine recreationally active, healthy males (age: 24 ± 2 years; V ˙ O 2 m a x : 47 ± 5 mL·kg−1·min−1 participated in this study. A double-blind, placebo-controlled randomized study was conducted. Participants mouth-rinsed every 2.5 km for 5 s. Maltodextrin mouth rinse with concentrations of 3%, 6% or 12% did not change time to complete the time trial and power output compared to placebo (p > 0.05. Time trial completion times were 40.2 ± 4.0, 40.1 ± 3.9, 40.1 ± 4.4, and 39.3 ± 4.2 min and power output 205 ± 22, 206 ± 25, 210 ± 24, and 205 ± 23 W for placebo, 3%, 6%, and 12% maltodextrin conditions, respectively. Heart rate, lactate, glucose, and rating of perceived exertion did not differ between trials (p > 0.05. In conclusion, mouth rinsing with different maltodextrin concentrations after an overnight fast did not affect the physiological responses and performance during a 20 km cycling time trial in recreationally active males.

Trial function method and exact solutions to the generalized nonlinear Schrödinger equation with time-dependent coefficient

International Nuclear Information System (INIS)

Cao Rui; Zhang Jian

2013-01-01

In this paper, the trial function method is extended to study the generalized nonlinear Schrödinger equation with time-dependent coefficients. On the basis of a generalized traveling wave transformation and a trial function, we investigate the exact envelope traveling wave solutions of the generalized nonlinear Schrödinger equation with time-dependent coefficients. Taking advantage of solutions to trial function, we successfully obtain exact solutions for the generalized nonlinear Schrödinger equation with time-dependent coefficients under constraint conditions. (general)

Real-time enrollment dashboard for multisite clinical trials

Directory of Open Access Journals (Sweden)

William A. Mattingly

2015-10-01

Conclusion: We have designed and implemented a visualization dashboard for managing multi-site clinical trial enrollment in two community acquired pneumonia studies. Information dashboards are useful for clinical trial management. They can be used in a standalone trial or can be included into a larger management system.

The effects of loading on the preload and dimensions of the abutment screw for a 3-unit cantilever-fixed prosthesis design.

Science.gov (United States)

Setia, Gaurav; Yousef, Hoda; Ehrenberg, David; Luke, Allyn; Weiner, Saul

2013-08-01

The purpose of this study was to use an in vitro model system to compare the effects on the screw torque and screw dimensions within 2 commercially available implant systems from occlusal loading on a cantilevered-fixed partial denture. Cantilevered implant-supported 3-unit prostheses with 2 premolar abutments and 1 premolar pontic (7.3 mm in length) were made on resin casts containing 2 implant analogs for 2 implant systems: BioLok Silhouette Tapered Implant System (Birmingham, AL) and Zimmer Tapered Screw-Vent Implant System (Carlsbad, CA) with 10 samples in each group. Each sample was loaded with either of 2 protocols: (1) a load of 50 N on the cantilevered pontic unit and (2) a loading of 150 N on all 3 units. The outcome measures were (1) changes in residual torque of the abutment screws and (2) changes in screw dimension. The BioLok Silhouette Tapered Implant group demonstrated slight but statistically significant torque loss 18.8% to 28.5% in both abutment screws for both protocols, P ≤ 0.05, without any changes in screw dimension. In the Zimmer Tapered Screw-Vent Implant group, there was a significant elongation of the abutment screws and a markedly significant 44.4%, (P ≤ 0.01) loss in torque in the mesial screw and a 28.5%, (P ≤ 0.05) loss in torque in the distal screw when the cantilever alone was loaded. Differences in screw design influence the maintenance of preload and distortion of the shank. The influence of the interface design, namely an internal hex of 1 mm versus an external hex did not influence the preload. Cantilevered prostheses can cause loss of torque and dimensional changes in abutment screws.

Physiological Correlations with Short, Medium, and Long Cycling Time-Trial Performance

Science.gov (United States)

Borszcz, Fernando K.; Tramontin, Artur F.; de Souza, Kristopher M.; Carminatti, Lorival J.; Costa, Vitor P.

2018-01-01

Purpose: Several studies have demonstrated that physiological variables predict cycling endurance performance. However, it is still unclear whether the predictors will change over different performance durations. The aim of this study was to assess the correlations between physiological variables and cycling time trials with different durations.…

Comparative effect of implant-abutment connections, abutment angulations, and screw lengths on preloaded abutment screw using three-dimensional finite element analysis: An in vitro study.

Science.gov (United States)

Kanneganti, Krishna Chaitanya; Vinnakota, Dileep Nag; Pottem, Srinivas Rao; Pulagam, Mahesh

2018-01-01

The purpose of this study is to compare the effect of implant-abutment connections, abutment angulations, and screw lengths on screw loosening (SL) of preloaded abutment using three dimensional (3D) finite element analysis. 3D models of implants (conical connection with hex/trilobed connections), abutments (straight/angulated), abutment screws (short/long), and crown and bone were designed using software Parametric Technology Corporation Creo and assembled to form 8 simulations. After discretization, the contact stresses developed for 150 N vertical and 100 N oblique load applications were analyzed, using ABAQUS. By assessing damage initiation and shortest fatigue load on screw threads, the SL for 2.5, 5, and 10 lakh cyclic loads were estimated, using fe-safe program. The obtained values were compared for influence of connection design, abutment angulation, and screw length. In straight abutment models, conical connection showed more damage (14.3%-72.3%) when compared to trilobe (10.1%-65.73%) at 2.5, 5, and 10 lakh cycles for both vertical and oblique loads, whereas in angulated abutments, trilobe (16.1%-76.9%) demonstrated more damage compared to conical (13.5%-70%). Irrespective of the connection type and abutment angulation, short screws showed more percentage of damage compared to long screws. The present study suggests selecting appropriate implant-abutment connection based on the abutment angulation, as well as preferring long screws with more number of threads for effective preload retention by the screws.

Endothelin-1 stimulates the release of preloaded ( sup 3 H)D-aspartate from cultured cerebellar granule cells

Energy Technology Data Exchange (ETDEWEB)

Lin, W.W.; Lee, C.Y.; Chuang, D.M. (NIMH Neuroscience Center, Washington, DC (USA))

1990-03-16

We have recently reported that endothelin-1 (ET) induces phosphoinositide hydrolysis in primary cultures of rat cerebellar granule cells. Here we found that ET in a dose-dependent manner (1-30 nM) stimulated the release of preloaded ({sup 3}H)D-aspartate from granule cells. The ET-induced aspartate release was completely blocked in the absence of extracellular Ca{sup 2+}, but was unaffected by 1 mM Co{sup 2+} or 1 microM dihydropyridine derivatives (nisoldipine and nimodipine). At higher concentration (10 microM) of nisoldipine and nimodipine, the release was partially inhibited. Short-term pretreatment of cells with phorbol 12,13-dibutyrate (PDBu) potentiated the ET-induced aspartate release, while long-term pretreatment with PDBu attenuated the release. Long-term exposure of cells to pertussis toxin (PTX), on the other hand, potentiated the ET-induced effects. Our results suggest that ET has a neuromodulatory function in the central nervous system.

Comparison of inter-trial recovery times for the determination of critical power and W' in cycling.

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Karsten, Bettina; Hopker, James; Jobson, Simon A; Baker, Jonathan; Petrigna, Luca; Klose, Andreas; Beedie, Christopher

2017-07-01

Critical Power (CP) and W' are often determined using multi-day testing protocols. To investigate this cumbersome testing method, the purpose of this study was to compare the differences between the conventional use of a 24-h inter-trial recovery time with those of 3 h and 30 min for the determination of CP and W'. 9 moderately trained cyclists performed an incremental test to exhaustion to establish the power output associated with the maximum oxygen uptake (p[Formula: see text] max ), and 3 protocols requiring time-to-exhaustion trials at a constant work-rate performed at 80%, 100% and 105% of p[Formula: see text] max. Design: Protocol A utilised 24-h inter-trial recovery (CP 24 /W' 24 ), protocol B utilised 3-h inter-trial recovery (CP 3 /W' 3 ), and protocol C used 30-min inter-trial recovery period (CP 0.5 /W' 0.5 ). CP and W' were calculated using the inverse time (1/t) versus power (P) relation (P = W'(1/t) + CP). 95% Limits of Agreement between protocol A and B were -9 to 15 W; -7.4 to 7.8 kJ (CP/W') and between protocol A and protocol C they were -27 to 22 W; -7.2 to 15.1 kJ (CP/W'). Compared to criterion protocol A, the average prediction error of protocol B was 2.5% (CP) and 25.6% (W'), whilst for protocol C it was 3.7% (CP) and 32.9% (W'). 3-h and 30-min inter-trial recovery time protocols provide valid methods of determining CP but not W' in cycling.

Intragastric preloads of l-tryptophan reduce ingestive behavior via oxytocinergic neural mechanisms in male mice.

Science.gov (United States)

Gartner, Sarah N; Aidney, Fraser; Klockars, Anica; Prosser, Colin; Carpenter, Elizabeth A; Isgrove, Kiriana; Levine, Allen S; Olszewski, Pawel K

2018-06-01

Human and laboratory animal studies suggest that dietary supplementation of a free essential amino acid, l-tryptophan (TRP), reduces food intake. It is unclear whether an acute gastric preload of TRP decreases consumption and whether central mechanisms underlie TRP-driven hypophagia. We examined the effect of TRP administered via intragastric gavage on energy- and palatability-induced feeding in mice. We sought to identify central mechanisms through which TRP suppresses appetite. Effects of TRP on consumption of energy-dense and energy-dilute tastants were established in mice stimulated to eat by energy deprivation or palatability. A conditioned taste aversion (CTA) paradigm was used to assess whether hypophagia is unrelated to sickness. c-Fos immunohistochemistry was employed to detect TRP-induced activation of feeding-related brain sites and of oxytocin (OT) neurons, a crucial component of satiety circuits. Also, expression of OT mRNA was assessed with real-time PCR. The functional importance of OT in mediating TRP-driven hypophagia was substantiated by showing the ability of OT receptor blockade to abolish TRP-induced decrease in feeding. TRP reduced intake of energy-dense standard chow in deprived animals and energy-dense palatable chow in sated mice. Anorexigenic doses of TRP did not cause a CTA. TRP failed to affect intake of palatable yet calorie-dilute or noncaloric solutions (10% sucrose, 4.1% Intralipid or 0.1% saccharin) even for TRP doses that decreased water intake in thirsty mice. Fos analysis revealed that TRP increases activation of several key feeding-related brain areas, especially in the brain stem and hypothalamus. TRP activated hypothalamic OT neurons and increased OT mRNA levels, whereas pretreatment with an OT antagonist abolished TRP-driven hypophagia. We conclude that intragastric TRP decreases food and water intake, and TRP-induced hypophagia is partially mediated via central circuits that encompass OT. Copyright © 2018 Elsevier Ltd. All

Real-Time Enrollment Dashboard For Multisite Clinical Trials.

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Mattingly, William A; Kelley, Robert R; Wiemken, Timothy L; Chariker, Julia H; Peyrani, Paula; Guinn, Brian E; Binford, Laura E; Buckner, Kimberley; Ramirez, Julio

2015-10-30

Achieving patient recruitment goals are critical for the successful completion of a clinical trial. We designed and developed a web-based dashboard for assisting in the management of clinical trial screening and enrollment. We use the dashboard to assist in the management of two observational studies of community-acquired pneumonia. Clinical research associates and managers using the dashboard were surveyed to determine its effectiveness as compared with traditional direct communication. The dashboard has been in use since it was first introduced in May of 2014. Of the 23 staff responding to the survey, 77% felt that it was easier or much easier to use the dashboard for communication than to use direct communication. We have designed and implemented a visualization dashboard for managing multi-site clinical trial enrollment in two community acquired pneumonia studies. Information dashboards are a useful tool for clinical trial management. They can be used as a standalone trial information tool or included into a larger management system.

Timing of insertion of levonorgestrel-releasing intrauterine system : a randomised controlled trial

NARCIS (Netherlands)

van der Heijden, Pahh; Geomini, Pmaj; Herman, M C; Veersema, S; Bongers, M Y

OBJECTIVE: The objective was to assess whether patient-perceived pain during the insertion of the levonorgestrel-releasing intrauterine system (LNG-IUS) depends on the timing during the menstrual cycle. DESIGN: A stratified two-armed non-inferiority randomised controlled trial. SETTING: Large

Ketone Diester Ingestion Impairs Time-Trial Performance in Professional Cyclists

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Jill J. Leckey

2017-10-01

Full Text Available We investigated the effect of pre- “race” ingestion of a 1,3-butanediol acetoacetate diester on blood ketone concentration, substrate metabolism and performance of a cycling time trial (TT in professional cyclists. In a randomized cross-over design, 10 elite male cyclists completed a ~31 km laboratory-based TT on a cycling ergometer programmed to simulate the 2017 World Road Cycling Championships course. Cyclists consumed a standardized meal [2 g/kg body mass (BM carbohydrate (CHO] the evening prior to a trial day and a CHO breakfast (2 g/kg BM CHO with 200 mg caffeine on the morning of a trial day. Cyclists were randomized to consume either the ketone diester (2 × 250 mg/kg or a placebo drink, followed immediately by 200 mL diet cola, given ~ 30 min before and immediately prior to commencing a 20 min incremental warm-up. Blood samples were collected prior to and during the warm-up, pre- and post- TT and at regular intervals after the TT. Urine samples were collected pre- and post- warm-up, immediately post TT and 60 min post TT. Pre-exercise ingestion of the diester resulted in a 2 ± 1% impairment in TT performance that was associated with gut discomfort and higher perception of effort. Serum β-hydroxybutyrate, serum acetoacetate, and urine ketone concentrations increased from rest following ketone ingestion and were higher than placebo throughout the trial. Ketone ingestion induces hyperketonemia in elite professional cyclists when in a carbohydrate fed state, and impairs performance of a cycling TT lasting ~50 min.

Mental Toughness Moderates Social Loafing in Cycle Time-Trial Performance.

Science.gov (United States)

Haugen, Tommy; Reinboth, Michael; Hetlelid, Ken J; Peters, Derek M; Høigaard, Rune

2016-09-01

The purpose of this study was to determine if mental toughness moderated the occurrence of social loafing in cycle time-trial performance. Twenty-seven men (Mage = 17.7 years, SD = 0.6) completed the Sport Mental Toughness Questionnaire prior to completing a 1-min cycling trial under 2 conditions: once with individual performance identified, and once in a group with individual performance not identified. Using a median split of the mental toughness index, participants were divided into high and low mental toughness groups. Cycling distance was compared using a 2 (trial) × 2 (high-low mental toughness) analysis of variance. We hypothesized that mentally tough participants would perform equally well under both conditions (i.e., no indication of social loafing) compared with low mentally tough participants, who would perform less well when their individual performance was not identifiable (i.e., demonstrating the anticipated social loafing effect). The high mental toughness group demonstrated consistent performance across both conditions, while the low mental toughness group reduced their effort in the non-individually identifiable team condition. The results confirm that (a) clearly identifying individual effort/performance is an important situational variable that may impact team performance and (b) higher perceived mental toughness has the ability to negate the tendency to loaf.

The effect of time trial cycling position on physiological and aerodynamic variables.

Science.gov (United States)

Fintelman, D M; Sterling, M; Hemida, H; Li, F-X

2015-01-01

To reduce aerodynamic resistance cyclists lower their torso angle, concurrently reducing Peak Power Output (PPO). However, realistic torso angle changes in the range used by time trial cyclists have not yet been examined. Therefore the aim of this study was to investigate the effect of torso angle on physiological parameters and frontal area in different commonly used time trial positions. Nineteen well-trained male cyclists performed incremental tests on a cycle ergometer at five different torso angles: their preferred torso angle and at 0, 8, 16 and 24°. Oxygen uptake, carbon dioxide expiration, minute ventilation, gross efficiency, PPO, heart rate, cadence and frontal area were recorded. The frontal area provides an estimate of the aerodynamic drag. Overall, results showed that lower torso angles attenuated performance. Maximal values of all variables, attained in the incremental test, decreased with lower torso angles (P aerodynamic drag and physiological functioning.

Likelihood of Null Effects of Large NHLBI Clinical Trials Has Increased over Time.

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Robert M Kaplan

Full Text Available We explore whether the number of null results in large National Heart Lung, and Blood Institute (NHLBI funded trials has increased over time.We identified all large NHLBI supported RCTs between 1970 and 2012 evaluating drugs or dietary supplements for the treatment or prevention of cardiovascular disease. Trials were included if direct costs >$500,000/year, participants were adult humans, and the primary outcome was cardiovascular risk, disease or death. The 55 trials meeting these criteria were coded for whether they were published prior to or after the year 2000, whether they registered in clinicaltrials.gov prior to publication, used active or placebo comparator, and whether or not the trial had industry co-sponsorship. We tabulated whether the study reported a positive, negative, or null result on the primary outcome variable and for total mortality.17 of 30 studies (57% published prior to 2000 showed a significant benefit of intervention on the primary outcome in comparison to only 2 among the 25 (8% trials published after 2000 (χ2=12.2,df= 1, p=0.0005. There has been no change in the proportion of trials that compared treatment to placebo versus active comparator. Industry co-sponsorship was unrelated to the probability of reporting a significant benefit. Pre-registration in clinical trials.gov was strongly associated with the trend toward null findings.The number NHLBI trials reporting positive results declined after the year 2000. Prospective declaration of outcomes in RCTs, and the adoption of transparent reporting standards, as required by clinicaltrials.gov, may have contributed to the trend toward null findings.

Screen-time Weight-loss Intervention Targeting Children at Home (SWITCH: A randomized controlled trial study protocol

Directory of Open Access Journals (Sweden)

Tsai Midi

2011-06-01

Full Text Available Abstract Background Approximately one third of New Zealand children and young people are overweight or obese. A similar proportion (33% do not meet recommendations for physical activity, and 70% do not meet recommendations for screen time. Increased time being sedentary is positively associated with being overweight. There are few family-based interventions aimed at reducing sedentary behavior in children. The aim of this trial is to determine the effects of a 24 week home-based, family oriented intervention to reduce sedentary screen time on children's body composition, sedentary behavior, physical activity, and diet. Methods/Design The study design is a pragmatic two-arm parallel randomized controlled trial. Two hundred and seventy overweight children aged 9-12 years and primary caregivers are being recruited. Participants are randomized to intervention (family-based screen time intervention or control (no change. At the end of the study, the control group is offered the intervention content. Data collection is undertaken at baseline and 24 weeks. The primary trial outcome is child body mass index (BMI and standardized body mass index (zBMI. Secondary outcomes are change from baseline to 24 weeks in child percentage body fat; waist circumference; self-reported average daily time spent in physical and sedentary activities; dietary intake; and enjoyment of physical activity and sedentary behavior. Secondary outcomes for the primary caregiver include change in BMI and self-reported physical activity. Discussion This study provides an excellent example of a theory-based, pragmatic, community-based trial targeting sedentary behavior in overweight children. The study has been specifically designed to allow for estimation of the consistency of effects on body composition for Māori (indigenous, Pacific and non-Māori/non-Pacific ethnic groups. If effective, this intervention is imminently scalable and could be integrated within existing weight

Competitor presence reduces internal attentional focus and improves 16.1km cycling time trial performance.

Science.gov (United States)

Williams, Emily L; Jones, Hollie S; Andy Sparks, S; Marchant, David C; Midgley, Adrian W; Mc Naughton, Lars R

2015-07-01

Whilst the presence of a competitor has been found to improve performance, the mechanisms influencing the change in selected work rates during direct competition have been suggested but not specifically assessed. The aim was to investigate the physiological and psychological influences of a visual avatar competitor during a 16.1-km cycling time trial performance, using trained, competitive cyclists. Randomised cross-over design. Fifteen male cyclists completed four 16.1km cycling time trials on a cycle ergometer, performing two with a visual display of themselves as a simulated avatar (FAM and SELF), one with no visual display (DO), and one with themselves and an opponent as simulated avatars (COMP). Participants were informed the competitive avatar was a similar ability cyclist but it was actually a representation of their fastest previous performance. Increased performance times were evident during COMP (27.8±2.0min) compared to SELF (28.7±1.9min) and DO (28.4±2.3min). Greater power output, speed and heart rate were apparent during COMP trial than SELF (pperformance. Competitive cyclists performed significantly faster during a 16.1-km competitive trial than when performing maximally, without a competitor. The improvement in performance was elicited due to a greater external distraction, deterring perceived exertion. Copyright © 2014 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

Effects of average uncertainty and trial-type frequency on choice response time: A hierarchical extension of Hick/Hyman Law.

Science.gov (United States)

Mordkoff, J Toby

2017-12-01

Hick/Hyman Law is the linear relationship between average uncertainty and mean response time across entire blocks of trials. While unequal trial-type frequencies within blocks can be used to manipulate average uncertainty, the current version of the law does not apply to or account for the differences in mean response time across the different trial types contained in a block. Other simple predictors of the effects of trial-type frequency also fail to produce satisfactory fits. In an attempt to resolve this limitation, the present work takes a hierarchical approach, first fitting the block-level data using average uncertainty (i.e., Hick/Hyman Law is given priority), then fitting the remaining trial-level differences using various versions of trial-type frequency. The model that employed the relative probability of occurrence as the second-layer predictor produced very strong fits, thereby extending Hick/Hyman Law to the level of trial types within blocks. The advantages and implications of this hierarchical model are briefly discussed.

Analysis of time to event outcomes in randomized controlled trials by generalized additive models.

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Christos Argyropoulos

Full Text Available Randomized Controlled Trials almost invariably utilize the hazard ratio calculated with a Cox proportional hazard model as a treatment efficacy measure. Despite the widespread adoption of HRs, these provide a limited understanding of the treatment effect and may even provide a biased estimate when the assumption of proportional hazards in the Cox model is not verified by the trial data. Additional treatment effect measures on the survival probability or the time scale may be used to supplement HRs but a framework for the simultaneous generation of these measures is lacking.By splitting follow-up time at the nodes of a Gauss Lobatto numerical quadrature rule, techniques for Poisson Generalized Additive Models (PGAM can be adopted for flexible hazard modeling. Straightforward simulation post-estimation transforms PGAM estimates for the log hazard into estimates of the survival function. These in turn were used to calculate relative and absolute risks or even differences in restricted mean survival time between treatment arms. We illustrate our approach with extensive simulations and in two trials: IPASS (in which the proportionality of hazards was violated and HEMO a long duration study conducted under evolving standards of care on a heterogeneous patient population.PGAM can generate estimates of the survival function and the hazard ratio that are essentially identical to those obtained by Kaplan Meier curve analysis and the Cox model. PGAMs can simultaneously provide multiple measures of treatment efficacy after a single data pass. Furthermore, supported unadjusted (overall treatment effect but also subgroup and adjusted analyses, while incorporating multiple time scales and accounting for non-proportional hazards in survival data.By augmenting the HR conventionally reported, PGAMs have the potential to support the inferential goals of multiple stakeholders involved in the evaluation and appraisal of clinical trial results under proportional and

Effects of whey protein and its two major protein components on satiety and food intake in normal-weight women.

Science.gov (United States)

Chungchunlam, Sylvia M S; Henare, Sharon J; Ganesh, Siva; Moughan, Paul J

2017-06-01

Protein is the most satiating macronutrient and is source dependent, with whey protein thought to be particularly satiating. The purported satiating effect of whey protein may be due to the unique mixture of proteins in whey or to the major constituent individual proteins (β-lactoglobulin and α-lactalbumin). The objective of the study was to compare the effects of isoenergetic (~2100kJ, ~500kcal) preload meals enriched (~50g protein) with either whey protein isolate (WP), β-lactoglobulin (BL) isolate or α-lactalbumin (AL) isolate, on food intake at an ad libitum test meal 120min later and subjective ratings of appetite (hunger, desire to eat, prospective food consumption and fullness) using visual analogue scales (VAS). Twenty adult normal-weight women (mean age 24.2±0.8years; mean BMI 22.7±0.4kg/m 2 ) participated in the study which used a single-blind completely randomised block design, where each subject consumed each of the three preload meals. Energy intake at the ad libitum test meal and total energy intakes (preload+test meal) did not differ between the three preload meals (p>0.05). There were no significant differences observed for the VAS scores and net incremental area under the curve (net iAUC) during the 120min following consumption of the three preload meals for subjective ratings of appetite (p>0.05). The findings show that the satiating effect of whey protein was similar to that of BL or AL individually and suggest that the major whey protein components BL and AL do not mediate the satiating effect of whey protein. The present human trial was registered with the Australian New Zealand Clinical Trials Registry (www.anzctr.org.au) as ACTRN12615000344594. Copyright © 2017 Elsevier Inc. All rights reserved.

The Role of Time-Limited Trials in Dialysis Decision Making in Critically Ill Patients.

Science.gov (United States)

Scherer, Jennifer S; Holley, Jean L

2016-02-05

Technologic advances, such as continuous RRT, provide lifesaving therapy for many patients. AKI in the critically ill patient, a fatal diagnosis in the past, is now often a survivable condition. Dialysis decision making for the critically ill patient with AKI is complex. What was once a question solely of survival now is nuanced by an individual's definition of quality of life, personal values, and short- and long-term prognoses. Clinical evaluation of AKI in the critically ill is multifaceted. Treatment decision making requires consideration of the natural evolution of the patient's AKI within the context of the global prognosis. Situations are often marked by prognostic uncertainty and clinical unknowns. In the face of these uncertainties, establishment of patient-directed therapies is imperative. A time-limited trial of continuous RRT in this setting is often appropriate but difficult to execute. Using patient preferences as a clinical guide, a proper time-limited trial requires assessment of prognosis, elicitation of patient values, strong communication skills, clear documentation, and often, appropriate integration of palliative care services. A well conducted time-limited trial can avoid interprofessional conflict and provide support for the patient, family, and staff. Copyright © 2016 by the American Society of Nephrology.

Effect of sucrose and safflower oil preloads on short term appetite and food intake of young men.

Science.gov (United States)

Woodend, D M; Anderson, G H

2001-12-01

The effects of carbohydrate and fat on satiety have been examined primarily through meal composition studies. The purpose of this study was to compare the effects of pure sucrose and safflower oil, isovolumetric beverage preloads, on appetite (measured every 15 minutes by visual analogue scales) and food intake 60 minutes later. Young men consumed 0, 418, 836 and 1254 kJ of sucrose in the first two experiments and these same doses of safflower oil in the third. Finally, the largest doses of sucrose and safflower oil were compared. Sucrose, but not safflower oil, suppressed average appetite compared with control. In experiment 2, food intake was reduced (psafflower oil significantly suppressed food intake by 480 kJ in the third experiment. When the 1254 kJ doses were compared directly, sucrose suppressed food intake by 653 kJ compared with control where as safflower oil did not. It is concluded that, in the short-term, sucrose produces a dose dependent reduction in appetite and food intake that is greater than that produced by safflower oil.

Analysis of classical time-trial performance and technique-specific physiological determinants in elite female cross-country skiers

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Øyvind Sandbakk

2016-08-01

Full Text Available The present study investigated the contribution of performance on uphill, flat, and downhill sections to overall performance in an international 10-km classical time-trial in elite female cross-country skiers, as well as the relationships between performance on snow and laboratory-measured physiological variables in the double poling (DP and diagonal (DIA techniques. Ten elite female cross-country skiers were continuously measured by a global positioning system device during an international 10-km cross-country skiing time-trial in the classical technique. One month prior to the race, all skiers performed a 5-min submaximal and 3-min self-paced performance test while roller skiing on a treadmill, both in the DP and DIA techniques. The time spent on uphill (r=0.98 and flat (r=0.91 sections of the race correlated most strongly with the overall 10-km performance (both p<0.05. Approximately 56% of the racing time was spent uphill, and stepwise multiple regression revealed that uphill time explained 95.5% of the variance in overall performance (p<0.001. Distance covered during the 3-min roller-skiing test and body-mass normalized peak oxygen uptake (VO2peak in both techniques showed the strongest correlations with overall time-trial performance (r=0.66-0.78, with DP capacity tending to have greatest impact on the flat and DIA capacity on uphill terrain (all p<0.05. Our present findings reveal that the time spent uphill most strongly determine classical time-trial performance, and that the major portion of the performance differences among elite female cross-country skiers can be explained by variations in technique-specific aerobic power.

The N-of-1 Clinical Trial: A Timely Research Opportunity in Homeopathy.

Science.gov (United States)

Ulbrich-Zürni, Susanne; Teut, Michael; Roll, Stephanie; Mathie, Robert T

2018-02-01

 The randomised controlled trial (RCT) is considered the 'gold standard' for establishing treatment efficacy or effectiveness of an intervention, but its data do not infer response in an individual patient. Individualised clinical care, a fundamental principle in complementary and alternative medicine (CAM), including homeopathy, seems well disposed in principle to being researched by single-patient (N-of-1) study design. Guidelines for reporting N-of-1 trials have recently been developed.  To overview the current status in the literature of the N-of-1 method and its application in medicine, including CAM. To consider whether the N-of-1 trial design offers an opportunity for novel research in homeopathy. N-OF-1 TRIAL DESIGN:  The N-of-1 trial applies the principles of the conventional crossover, blinded, RCT design. The treatment under study and the comparator are repeated in a randomised order, and with suitable washout time, over a defined period. N-of-1 design is constrained for use in chronic stable conditions, and for interventions that have quick onset and cessation of effect, with modest or negligible carryover. Outcome data can be aggregated and interpreted for the individual subject; they can also be pooled with data from several similar N-of-1 trials, enabling more generalisable conclusions. THE N-OF-1 TRIAL IN CAM: The typical individualisation of patient care can be accommodated in N-of-1 study design if the patient and the specific therapeutic intervention are selected within the constraints of the method. Application of the N-of-1 method in CAM has been advocated but has been mainly limited, in practice, to a small number of studies in herbal and traditional Chinese medicine. THE N-OF-1 TRIAL IN HOMEOPATHY:  Individualised homeopathy can be accommodated for investigation within the same methodological constraints; less in-depth homeopathic approaches to prescribing are also amendable to investigation using the N-of-1 method. No such studies

Reward magnitude, but not time of day, influences the trial-spacing effect in autoshaping with rats.

Science.gov (United States)

Thomas, B; Huneycutt, D; Papini, M R

1998-12-01

The arousal hypothesis of the trial-spacing effect suggests that spaced-trial training increases emotional arousal and thus invigorates Pavlovian behavior, relative to massed-trial conditions. Emotional arousal was manipulated by varying reinforcer magnitude during training (either one or five food pellets/trial, across groups). In addition, autoshaping training was administered either in the morning (0900 h) or in the evening (1700 h). Rats were housed in an enclosed colony room and exposed to a regular light:dark cycle (light from 0700 to 1900 h). Available evidence indicates that reinforcer magnitude and time of day are related to arousal levels. As expected, a larger reinforcer magnitude led to a highly significant trial spacing effect. Evening training led to a higher response rate than morning training, but the trial-spacing effect was equally strong whether training was administered in the morning or in the evening. These results provide partial support for the arousal hypothesis and are discussed in the context of research on schedule-induced behavior.

Introducing a Third Timed Up & Go Test Trial Improves Performances of Hospitalized and Community-Dwelling Older Individuals

DEFF Research Database (Denmark)

Bloch, Mette Linding; R. Jønsson, Line R. Jønsson; T. Kristensen, Morten

2017-01-01

in hospitalized and community-dwelling older individuals. Methods: Eighty-two participants (50 from a geriatric hospital unit and 32 from an outpatient geriatric center; 52 women, 30 men) with a mean (SD) age of 83.6 (7.9) years were included in this cross-sectional study. All participants (except one from...... the hospital unit) performed 3 TUG trials, as fast as safely possible on the same day, and separated by up to 1-minute pauses. A rollator (4-wheeled rolling walker) was used as a standardized walking aid in the geriatric hospital unit, whereas participants used their normal walking aid (if any......) in the outpatient geriatric center. Results and Discussion: The fastest trial was trial 3 for 47 (57%), trial 2 for 25 (31%), and trial 1 for 10 (12%). Repeated-measures analyses of variance with Bonferroni corrections showed that TUG times improved from trial 1 to trial 3 (P

Computed tomography to estimate cardiac preload and extravascular lung water. A retrospective analysis in critically ill patients

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Schmid Roland M

2011-05-01

Full Text Available Abstract Background In critically ill patients intravascular volume status and pulmonary edema need to be quantified as soon as possible. Many critically ill patients undergo a computed tomography (CT-scan of the thorax after admission to the intensive care unit (ICU. This study investigates whether CT-based estimation of cardiac preload and pulmonary hydration can accurately assess volume status and can contribute to an early estimation of hemodynamics. Methods Thirty medical ICU patients. Global end-diastolic volume index (GEDVI and extravascular lung water index (EVLWI were assessed using transpulmonary thermodilution (TPTD serving as reference method (with established GEDVI/EVLWI normal values. Central venous pressure (CVP was determined. CT-based estimation of GEDVI/EVLWI/CVP by two different radiologists (R1, R2 without analyzing software. Primary endpoint: predictive capabilities of CT-based estimation of GEDVI/EVLWI/CVP compared to TPTD and measured CVP. Secondary endpoint: interobserver correlation and agreement between R1 and R2. Results Accuracy of CT-estimation of GEDVI ( 800 mL/m2 was 33%(R1/27%(R2. For R1 and R2 sensitivity for diagnosis of low GEDVI (2 was 0% (specificity 100%. Sensitivity for prediction of elevated GEDVI (> 800 mL/m2 was 86%(R1/57%(R2 with a specificity of 57%(R1/39%(R2 (positive predictive value 38%(R1/22%(R2; negative predictive value 93%(R1/75%(R2. Estimated CT-GEDVI and TPTD-GEDVI were significantly different showing an overestimation of GEDVI by the radiologists (R1: mean difference ± standard error (SE: 191 ± 30 mL/m2, p 2, p 10 mL/kg was 30% for R1 and 40% for R2. CT-EVLWI and TPTD-EVLWI were significantly different (R1: mean difference ± SE: 3.3 ± 1.2 mL/kg, p = 0.013; R2: mean difference ± SE: 2.8 ± 1.1 mL/kg, p = 0.021. Again ccc was low with -0.02 (R1; 95% CI: -0.20 to +0.13, BCF = 0.44 and +0.14 (R2; 95% CI: -0.05 to +0.32, BCF = 0.53. GEDVI, EVLWI and CVP estimations of R1 and R2 showed a poor

A sense of urgency: Evaluating the link between clinical trial development time and the accrual performance of cancer therapy evaluation program (NCI-CTEP) sponsored studies.

Science.gov (United States)

Cheng, Steven K; Dietrich, Mary S; Dilts, David M

2010-11-15

Postactivation barriers to oncology clinical trial accruals are well documented; however, potential barriers prior to trial opening are not. We investigate one such barrier: trial development time. National Cancer Institute Cancer Therapy Evaluation Program (CTEP)-sponsored trials for all therapeutic, nonpediatric phase I, I/II, II, and III studies activated between 2000 and 2004 were investigated for an 8-year period (n = 419). Successful trials were those achieving 100% of minimum accrual goal. Time to open a study was the calendar time from initial CTEP submission to trial activation. Multivariate logistic regression analysis was used to calculate unadjusted and adjusted odds ratios (OR), controlling for study phase and size of expected accruals. Among the CTEP-approved oncology trials, 37.9% (n = 221) failed to attain the minimum accrual goals, with 70.8% (n = 14) of phase III trials resulting in poor accrual. A total of 16,474 patients (42.5% of accruals) accrued to those studies were unable to achieve the projected minimum accrual goal. Trials requiring less than 12 months of development were significantly more likely to achieve accrual goals (OR, 2.15; 95% confidence interval, 1.29-3.57, P = 0.003) than trials with the median development times of 12 to 18 months. Trials requiring a development time of greater than 24 months were significantly less likely to achieve accrual goals (OR, 0.40; 95% confidence interval, 0.20-0.78; P = 0.011) than trials with the median development time. A large percentage of oncology clinical trials do not achieve minimum projected accruals. Trial development time appears to be one important predictor of the likelihood of successfully achieving the minimum accrual goals. ©2010 AACR.

Time Trials Versus Time-to-Exhaustion Tests: Effects on Critical Power, W', and Oxygen-Uptake Kinetics.

Science.gov (United States)

Karsten, Bettina; Baker, Jonathan; Naclerio, Fernando; Klose, Andreas; Bianco, Antonino; Nimmerichter, Alfred

2018-02-01

To investigate single-day time-to-exhaustion (TTE) and time-trial (TT) -based laboratory tests values of critical power (CP), W prime (W'), and respective oxygen-uptake-kinetic responses. Twelve cyclists performed a maximal ramp test followed by 3 TTE and 3 TT efforts interspersed by 60 min recovery between efforts. Oxygen uptake ( V ˙ O 2 ) was measured during all trials. The mean response time was calculated as a description of the overall [Formula: see text]-kinetic response from the onset to 2 min of exercise. TTE-determined CP was 279 ± 52 W, and TT-determined CP was 276 ± 50 W (P = .237). Values of W' were 14.3 ± 3.4 kJ (TTE W') and 16.5 ± 4.2 kJ (TT W') (P = .028). While a high level of agreement (-12 to 17 W) and a low prediction error of 2.7% were established for CP, for W' limits of agreements were markedly lower (-8 to 3.7 kJ), with a prediction error of 18.8%. The mean standard error for TTE CP values was significantly higher than that for TT CP values (2.4% ± 1.9% vs 1.2% ± 0.7% W). The standard errors for TTE W' and TT W' were 11.2% ± 8.1% and 5.6% ± 3.6%, respectively. The [Formula: see text] response was significantly faster during TT (~22 s) than TTE (~28 s). The TT protocol with a 60-min recovery period offers a valid, time-saving, and less error-filled alternative to conventional and more recent testing methods. Results, however, cannot be transferred to W'.

The behavior of an opponent alters pacing decisions in 4-km cycling time trials.

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Konings, Marco J; Schoenmakers, Patrick P J M; Walker, Andrew J; Hettinga, Florentina J

2016-05-01

The present study aimed to explore how athletes respond to different behaviors of their opponents. Twelve moderately to highly physically active participants with at least two years of cycling experience completed four 4-km time trials on a Velotron cycle ergometer. After a familiarization time trial (FAM), participants performed three experimental time trials in randomized order with no opponent (NO), a virtual opponent who started slower and finished faster compared to FAM (OP-SLOWFAST), or a virtual opponent who started faster and finished slower compared to FAM (OP-FASTSLOW). Repeated-measures ANOVAs (Ppower output, velocity and RPE. OP-SLOWFAST and OP-FASTSLOW were completed faster compared to NO (385.5±27.5, 385.0±28.6, and 390.6±29.3s, respectively). An interaction effect for condition×distance (F=3.944, Ppower outputs by the participants in the initial 750m compared to a slower starting opponent. The present study is the first to show that the behavior of an opponent affects pacing-related decisions in laboratory-controlled conditions. Our findings support the recently proposed interdependence of perception and action, and emphasize the interaction with the environment as an important determinant for an athlete's pacing decisions, especially during the initial stages of a race. Copyright © 2016 Elsevier Inc. All rights reserved.

The Effect of 400 µg Inhaled Salbutamol on 3 km Time Trial Performance in a Low Humidity Environment

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John Molphy, John W. Dickinson, Neil J. Chester, Mike Loosemore, Gregory Whyte

2017-12-01

Full Text Available The Objectives of the study were to investigate whether 400 µg inhaled salbutamol influences 3 km running time-trial performance and lung function in eucapnic voluntary hyperpnoea positive (EVH+ve and negative (EVH-ve individuals. Fourteen male participants (22.4 ± 1.6yrs; 76.4 ± 8.7kg; 1.80 ± 0.07 m; (7 EVH+ve; 7 EVH-ve were recruited following written informed consent. All participants undertook an EVH challenge to identify either EVH+ve (↓FEV1>10% or EVH-ve (↓FEV110% from baseline in FEV1 following any time-trial. Administration of 400µg inhaled salbutamol does not improve 3 km time-trial performance in either mild EVH+ve or EVH–ve individuals despite significantly increased HR and FEV1.

Evaluating the optimal timing of surgical antimicrobial prophylaxis: study protocol for a randomized controlled trial.

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Mujagic, Edin; Zwimpfer, Tibor; Marti, Walter R; Zwahlen, Marcel; Hoffmann, Henry; Kindler, Christoph; Fux, Christoph; Misteli, Heidi; Iselin, Lukas; Lugli, Andrea Kopp; Nebiker, Christian A; von Holzen, Urs; Vinzens, Fabrizio; von Strauss, Marco; Reck, Stefan; Kraljević, Marko; Widmer, Andreas F; Oertli, Daniel; Rosenthal, Rachel; Weber, Walter P

2014-05-24

Surgical site infections are the most common hospital-acquired infections among surgical patients. The administration of surgical antimicrobial prophylaxis reduces the risk of surgical site infections . The optimal timing of this procedure is still a matter of debate. While most studies suggest that it should be given as close to the incision time as possible, others conclude that this may be too late for optimal prevention of surgical site infections. A large observational study suggests that surgical antimicrobial prophylaxis should be administered 74 to 30 minutes before surgery. The aim of this article is to report the design and protocol of a randomized controlled trial investigating the optimal timing of surgical antimicrobial prophylaxis. In this bi-center randomized controlled trial conducted at two tertiary referral centers in Switzerland, we plan to include 5,000 patients undergoing general, oncologic, vascular and orthopedic trauma procedures. Patients are randomized in a 1:1 ratio into two groups: one receiving surgical antimicrobial prophylaxis in the anesthesia room (75 to 30 minutes before incision) and the other receiving surgical antimicrobial prophylaxis in the operating room (less than 30 minutes before incision). We expect a significantly lower rate of surgical site infections with surgical antimicrobial prophylaxis administered more than 30 minutes before the scheduled incision. The primary outcome is the occurrence of surgical site infections during a 30-day follow-up period (one year with an implant in place). When assuming a 5% surgical site infection risk with administration of surgical antimicrobial prophylaxis in the operating room, the planned sample size has an 80% power to detect a relative risk reduction for surgical site infections of 33% when administering surgical antimicrobial prophylaxis in the anesthesia room (with a two-sided type I error of 5%). We expect the study to be completed within three years. The results of this

Soil settlement analysis in soft soil by using preloading system and prefabricated vertical draining runway of Kualanamu Airport

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Roesyanto; Iskandar, R.; Silalahi, S. A.; Fadliansyah

2018-02-01

The method of soil improvement, using the combination of prefabricated vertical drain (PVD) and preloading, was used to accelerate the process of consolidation and the consolidation settlement in the runway of Kualanamu International Airport, which was constructed on the soft soil sediment like silty clay. In this research, the investigated area was the runway of Kualanamu International Airport zone I which had 11 meter-thickness of soft soil. Geotechnic instruments surveyed was settlement plate. Monitoring was done toward the behavior of landfill such as basic soil settlement. The result were compared with the analysis of finite element method of full scale in Mohr-Coulomb model by verifying the vertical drain of asymmetric unit cell and equivalent plane strain unit cell condition. The results of the research showed that there were an interesting behavior between the data in field observation and finite element of Mohr-Coulomb model. It was also found that the result of soil settlement of finite element method of Mohr-Coulomb model was closed to the result of settlement plate monitoring.

Short-term effects of a low glycemic index carob-containing snack on energy intake, satiety, and glycemic response in normal-weight, healthy adults: Results from two randomized trials.

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Papakonstantinou, Emilia; Orfanakos, Nickolaos; Farajian, Paul; Kapetanakou, Anastasia E; Makariti, Ifigenia P; Grivokostopoulos, Nikolaos; Ha, Marie-Ann; Skandamis, Panagiotis N

2017-10-01

The potential positive health effects of carob-containing snacks are largely unknown. Therefore, the aims of these studies were to determine the glycemic index (GI) of a carob snack compared with chocolate cookie containing equal amounts of available carbohydrates and to compare the effects of a carob versus chocolate cookie preload consumed as snack before a meal on (a) short-term satiety response measured by subsequent ad libitum meal intake, (b) subjective satiety as assessed by visual analog scales and (c) postprandial glycemic response. Ten healthy, normal-weight volunteers participated in GI investigation. Then, 50 healthy, normal-weight individuals consumed, crossover, in random order, the preloads as snack, with 1-wk washout period. Ad libitum meal (lunch and dessert) was offered. Capillary blood glucose samples were collected at baseline, 2 h after breakfast, just before preload consumption, 2 h after preload, 3 h after preload, just before meal (lunch and dessert), 1 h after meal, and 2 h after meal consumption. The carob snack was a low GI food, whereas the chocolate cookie was a high GI food (40 versus 78, respectively, on glucose scale). Consumption of the carob preload decreased the glycemic response to a following meal and to the individual's feelings of hunger, desire to eat, preoccupation with food, and thirst between snack and meal, as assessed with the use of visual analog scales. Subsequently, participants consumed less amounts of food (g) and had lower total energy intake at mealtimes. The carob snack led to increased satiety, lower energy intake at meal, and decreased postmeal glycemic response possibly due to its low GI value. Identifying foods that promote satiety and decrease glycemic response without increasing the overall energy intake may offer advantages to body weight and glycemic control. Copyright © 2017 Elsevier Inc. All rights reserved.

Participatory workplace interventions can reduce sedentary time for office workers--a randomised controlled trial.

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Sharon Parry

Full Text Available BACKGROUND: Occupational sedentary behaviour is an important contributor to overall sedentary risk. There is limited evidence for effective workplace interventions to reduce occupational sedentary time and increase light activity during work hours. The purpose of the study was to determine if participatory workplace interventions could reduce total sedentary time, sustained sedentary time (bouts >30 minutes, increase the frequency of breaks in sedentary time and promote light intensity activity and moderate/vigorous activity (MVPA during work hours. METHODS: A randomised controlled trial (ANZCTR NUMBER: ACTN12612000743864 was conducted using clerical, call centre and data processing workers (n = 62, aged 25-59 years in 3 large government organisations in Perth, Australia. Three groups developed interventions with a participatory approach: 'Active office' (n = 19, 'Active Workstation' and promotion of incidental office activity; 'Traditional physical activity' (n = 14, pedometer challenge to increase activity between productive work time and 'Office ergonomics' (n = 29, computer workstation design and breaking up computer tasks. Accelerometer (ActiGraph GT3X, 7 days determined sedentary time, sustained sedentary time, breaks in sedentary time, light intensity activity and MVPA on work days and during work hours were measured before and following a 12 week intervention period. RESULTS: For all participants there was a significant reduction in sedentary time on work days (-1.6%, p = 0.006 and during work hours (-1.7%, p = 0.014 and a significant increase in number of breaks/sedentary hour on work days (0.64, p = 0.005 and during work hours (0.72, p = 0.015; there was a concurrent significant increase in light activity during work hours (1.5%, p = 0.012 and MVPA on work days (0.6%, p = 0.012. CONCLUSIONS: This study explored novel ways to modify work practices to reduce occupational sedentary behaviour

Prevention of post-spinal hypotension using crystalloid, colloid and ephedrine with three different combinations: A double blind randomized study

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Mitra Jabalameli

2012-01-01

Full Text Available Background: The benefit of prophylactic combination therapy using crystalloid and colloid preload with ephedrine has not been cleared to prevent maternal hypotension after spinal anesthesia at cesarean delivery. This study evaluated the efficacy of three combinational methods to prevent hypotension following spinal anesthesia. Materials and Methods: In this prospective double blind trial, 150 candidates of elective cesarean delivery under spinal anesthesia were randomly allocated to three treatment groups; 1---Ringer′s Lactate (RL solution (15 ml/kg plus Hemaxel (7 ml/kg preload, 2---RL solution (15 ml/kg preload plus ephedrine (15 mg, IV, bolus, 3---Hemaxel (7 ml/kg preload plus ephedrine (15 mg, IV, bolus. Maternal hemodynamic changes during 60 min after spinal injection, nausea/vomiting, and neonatal condition were compared among the groups. Results: The cumulative incidence of hypotension was 44%, 40%, and 46% in groups 1 to 3, respectively. There were not significant differences in supplementary ephedrine requirement among groups which received or among groups which did not receive prophylactic ephedrine. Groups were not different in the incidence of hypertension and nausea or vomiting. There were no significant differences among groups in Apgar scores at 1 or 5 min and umbilical artery PH. Conclusion: Combination of preventive methods decreased the occurrence of hypotension following spinal anesthesia to an acceptable level. Overall, the most effective method was a combination of crystalloid preload with ephedrine.

Is Time of the Essence? The Impact of Time of Hospital Presentation in Acute Heart Failure: Insights From ASCEND-HF Trial.

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Cerbin, Lukasz P; Ambrosy, Andrew P; Greene, Stephen J; Armstrong, Paul W; Butler, Javed; Coles, Adrian; DeVore, Adam D; Ezekowitz, Justin A; Hernandez, Adrian F; Metra, Marco; Starling, Randall C; Tang, Wilson; Teerlink, John R; Voors, Adriaan A; Wu, Angie; O'Connor, Christopher M; Mentz, Robert J

2018-04-01

As the largest acute heart failure (AHF) trial conducted to date, the global ASCEND-HF (Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure) trial database presented an opportunity to systematically describe the relationship among time of hospital presentation, clinical profile, inpatient management, and outcomes among patients admitted with AHF. Time of hospital presentation has been shown to impact outcomes among patients hospitalized with many conditions. However, the association among time of presentation and patient characteristics, management, and clinical outcomes among patients hospitalized with AHF has not been well characterized. A post hoc analysis of the ASCEND-HF trial was performed, which enrolled 7,141 patients hospitalized for AHF. Patients were divided based on when they presented to the hospital; regular hours were defined as 9 am to 5 pm, Monday through Friday, and off hours were defined as 5 pm to 9 am, Monday through Friday and weekends. Clinical characteristics and outcomes were compared by time of presentation. Overall, 3,298 patients (46%) presented during off hours. Off-hour patients were more likely to have orthopnea (80% vs. 74%, respectively) and rales (56% vs. 49%, respectively) than regular-hour patients. Off-hour patients were more likely to receive intravenous (IV) nitroglycerin (18% vs. 11%, respectively) and IV loop diuretics (92% vs. 86%, respectively) as initial therapy and reported greater relief from dyspnea at 24 h (odds ratio [OR]: 1.14; 95% confidence interval [CI]: 1.04 to 1.24; p = 0.01) than regular-hour patients. After adjustment, off-hour presentation was associated with significantly lower 30-day mortality (OR: 0.74; 95% CI: 0.57 to 0.96; p = 0.03) and 180-day mortality (hazard ratio [HR]: 0.82; 95% CI: 0.72 to 0.94; p = 0.01) but similar 30-day rehospitalization rates (p = 0.40). In this AHF trial, patients admitted during off hours exhibited a distinct clinical profile

Managing clinical trials

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Kenyon Sara

2010-07-01

Full Text Available Abstract Managing clinical trials, of whatever size and complexity, requires efficient trial management. Trials fail because tried and tested systems handed down through apprenticeships have not been documented, evaluated or published to guide new trialists starting out in this important field. For the past three decades, trialists have invented and reinvented the trial management wheel. We suggest that to improve the successful, timely delivery of important clinical trials for patient benefit, it is time to produce standard trial management guidelines and develop robust methods of evaluation.

Effects of partial reinforcement and time between reinforced trials on terminal response rate in pigeon autoshaping.

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Gottlieb, Daniel A

2006-03-01

Partial reinforcement often leads to asymptotically higher rates of responding and number of trials with a response than does continuous reinforcement in pigeon autoshaping. However, comparisons typically involve a partial reinforcement schedule that differs from the continuous reinforcement schedule in both time between reinforced trials and probability of reinforcement. Two experiments examined the relative contributions of these two manipulations to asymptotic response rate. Results suggest that the greater responding previously seen with partial reinforcement is primarily due to differential probability of reinforcement and not differential time between reinforced trials. Further, once established, differences in responding are resistant to a change in stimulus and contingency. Secondary response theories of autoshaped responding (theories that posit additional response-augmenting or response-attenuating mechanisms specific to partial or continuous reinforcement) cannot fully accommodate the current body of data. It is suggested that researchers who study pigeon autoshaping train animals on a common task prior to training them under different conditions.

An audit strategy for time-to-event outcomes measured with error: application to five randomized controlled trials in oncology.

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Dodd, Lori E; Korn, Edward L; Freidlin, Boris; Gu, Wenjuan; Abrams, Jeffrey S; Bushnell, William D; Canetta, Renzo; Doroshow, James H; Gray, Robert J; Sridhara, Rajeshwari

2013-10-01

Measurement error in time-to-event end points complicates interpretation of treatment effects in clinical trials. Non-differential measurement error is unlikely to produce large bias [1]. When error depends on treatment arm, bias is of greater concern. Blinded-independent central review (BICR) of all images from a trial is commonly undertaken to mitigate differential measurement-error bias that may be present in hazard ratios (HRs) based on local evaluations. Similar BICR and local evaluation HRs may provide reassurance about the treatment effect, but BICR adds considerable time and expense to trials. We describe a BICR audit strategy [2] and apply it to five randomized controlled trials to evaluate its use and to provide practical guidelines. The strategy requires BICR on a subset of study subjects, rather than a complete-case BICR, and makes use of an auxiliary-variable estimator. When the effect size is relatively large, the method provides a substantial reduction in the size of the BICRs. In a trial with 722 participants and a HR of 0.48, an average audit of 28% of the data was needed and always confirmed the treatment effect as assessed by local evaluations. More moderate effect sizes and/or smaller trial sizes required larger proportions of audited images, ranging from 57% to 100% for HRs ranging from 0.55 to 0.77 and sample sizes between 209 and 737. The method is developed for a simple random sample of study subjects. In studies with low event rates, more efficient estimation may result from sampling individuals with events at a higher rate. The proposed strategy can greatly decrease the costs and time associated with BICR, by reducing the number of images undergoing review. The savings will depend on the underlying treatment effect and trial size, with larger treatment effects and larger trials requiring smaller proportions of audited data.

Clinical Trials

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Full Text Available ... at the smallest dose and for the shortest time possible. Clinical trials, like the two described above, ... in a clinical trial, find out ahead of time about costs and coverage. You should learn about ...

Clinical Trials

Medline Plus

Full Text Available ... clinical trials. If you're thinking about taking part in a clinical trial, find out ahead of time about costs and coverage. You should learn about the risks and benefits of any clinical trial before you agree to take part in the trial. Talk with your doctor about ...

A clinical trial design using the concept of proportional time using the generalized gamma ratio distribution.

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Phadnis, Milind A; Wetmore, James B; Mayo, Matthew S

2017-11-20

Traditional methods of sample size and power calculations in clinical trials with a time-to-event end point are based on the logrank test (and its variations), Cox proportional hazards (PH) assumption, or comparison of means of 2 exponential distributions. Of these, sample size calculation based on PH assumption is likely the most common and allows adjusting for the effect of one or more covariates. However, when designing a trial, there are situations when the assumption of PH may not be appropriate. Additionally, when it is known that there is a rapid decline in the survival curve for a control group, such as from previously conducted observational studies, a design based on the PH assumption may confer only a minor statistical improvement for the treatment group that is neither clinically nor practically meaningful. For such scenarios, a clinical trial design that focuses on improvement in patient longevity is proposed, based on the concept of proportional time using the generalized gamma ratio distribution. Simulations are conducted to evaluate the performance of the proportional time method and to identify the situations in which such a design will be beneficial as compared to the standard design using a PH assumption, piecewise exponential hazards assumption, and specific cases of a cure rate model. A practical example in which hemorrhagic stroke patients are randomized to 1 of 2 arms in a putative clinical trial demonstrates the usefulness of this approach by drastically reducing the number of patients needed for study enrollment. Copyright © 2017 John Wiley & Sons, Ltd.

A flexible and coherent test/estimation procedure based on restricted mean survival times for censored time-to-event data in randomized clinical trials.

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Horiguchi, Miki; Cronin, Angel M; Takeuchi, Masahiro; Uno, Hajime

2018-04-22

In randomized clinical trials where time-to-event is the primary outcome, almost routinely, the logrank test is prespecified as the primary test and the hazard ratio is used to quantify treatment effect. If the ratio of 2 hazard functions is not constant, the logrank test is not optimal and the interpretation of hazard ratio is not obvious. When such a nonproportional hazards case is expected at the design stage, the conventional practice is to prespecify another member of weighted logrank tests, eg, Peto-Prentice-Wilcoxon test. Alternatively, one may specify a robust test as the primary test, which can capture various patterns of difference between 2 event time distributions. However, most of those tests do not have companion procedures to quantify the treatment difference, and investigators have fallen back on reporting treatment effect estimates not associated with the primary test. Such incoherence in the "test/estimation" procedure may potentially mislead clinicians/patients who have to balance risk-benefit for treatment decision. To address this, we propose a flexible and coherent test/estimation procedure based on restricted mean survival time, where the truncation time τ is selected data dependently. The proposed procedure is composed of a prespecified test and an estimation of corresponding robust and interpretable quantitative treatment effect. The utility of the new procedure is demonstrated by numerical studies based on 2 randomized cancer clinical trials; the test is dramatically more powerful than the logrank, Wilcoxon tests, and the restricted mean survival time-based test with a fixed τ, for the patterns of difference seen in these cancer clinical trials. Copyright © 2018 John Wiley & Sons, Ltd.

Clinical Trials

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Full Text Available ... and treatments that work best. How Clinical Trials Work If you take part in a clinical trial, ... from a study at any time, for any reason. Also, during the trial, you have the right ...

Sensitivity of adaptive enrichment trial designs to accrual rates, time to outcome measurement, and prognostic variables

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Tianchen Qian

2017-12-01

Full Text Available Adaptive enrichment designs involve rules for restricting enrollment to a subset of the population during the course of an ongoing trial. This can be used to target those who benefit from the experimental treatment. Trial characteristics such as the accrual rate and the prognostic value of baseline variables are typically unknown when a trial is being planned; these values are typically assumed based on information available before the trial starts. Because of the added complexity in adaptive enrichment designs compared to standard designs, it may be of special concern how sensitive the trial performance is to deviations from assumptions. Through simulation studies, we evaluate the sensitivity of Type I error, power, expected sample size, and trial duration to different design characteristics. Our simulation distributions mimic features of data from the Alzheimer's Disease Neuroimaging Initiative cohort study, and involve two subpopulations based on a genetic marker. We investigate the impact of the following design characteristics: the accrual rate, the time from enrollment to measurement of a short-term outcome and the primary outcome, and the prognostic value of baseline variables and short-term outcomes. To leverage prognostic information in baseline variables and short-term outcomes, we use a semiparametric, locally efficient estimator, and investigate its strengths and limitations compared to standard estimators. We apply information-based monitoring, and evaluate how accurately information can be estimated in an ongoing trial.

RARtool: A MATLAB Software Package for Designing Response-Adaptive Randomized Clinical Trials with Time-to-Event Outcomes.

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Ryeznik, Yevgen; Sverdlov, Oleksandr; Wong, Weng Kee

2015-08-01

Response-adaptive randomization designs are becoming increasingly popular in clinical trial practice. In this paper, we present RARtool , a user interface software developed in MATLAB for designing response-adaptive randomized comparative clinical trials with censored time-to-event outcomes. The RARtool software can compute different types of optimal treatment allocation designs, and it can simulate response-adaptive randomization procedures targeting selected optimal allocations. Through simulations, an investigator can assess design characteristics under a variety of experimental scenarios and select the best procedure for practical implementation. We illustrate the utility of our RARtool software by redesigning a survival trial from the literature.

Effects of dietary nitrate, caffeine, and their combination on 20-km cycling time trial performance.

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Glaister, Mark; Pattison, John R; Muniz-Pumares, Daniel; Patterson, Stephen D; Foley, Paul

2015-01-01

The aim of this study was to examine the acute supplementation effects of dietary nitrate, caffeine, and their combination on 20-km cycling time trial performance. Using a randomized, counterbalanced, double-blind Latin-square design, 14 competitive female cyclists (age: 31 ± 7 years; height: 1.69 ± 0.07 m; body mass: 61.6 ± 6.0 kg) completed four 20-km time trials on a racing bicycle fitted to a turbo trainer. Approximately 2.5 hours before each trial, subjects consumed a 70-ml dose of concentrated beetroot juice containing either 0.45 g of dietary nitrate or with the nitrate content removed (placebo). One hour before each trial, subjects consumed a capsule containing either 5 mg·kg of caffeine or maltodextrin (placebo). There was a significant effect of supplementation on power output (p = 0.001), with post hoc tests revealing higher power outputs in caffeine (205 ± 21 W) vs. nitrate (194 ± 22 W) and placebo (194 ± 25 W) trials only. Caffeine-induced improvements in power output corresponded with significantly higher measures of heart rate (caffeine: 166 ± 12 b·min vs. placebo: 159 ± 15 b·min; p = 0.02), blood lactate (caffeine: 6.54 ± 2.40 mmol·L vs. placebo: 4.50 ± 2.11 mmol·L; p caffeine: 0.95 ± 0.04 vs. placebo: 0.91 ± 0.05; p = 0.03). There were no effects (p ≥ 0.05) of supplementation on cycling cadence, rating of perceived exertion, (Equation is included in full-text article.), or integrated electromyographic activity. The results of this study support the well-established beneficial effects of caffeine supplementation on endurance performance. In contrast, acute supplementation with dietary nitrate seems to have no effect on endurance performance and adds nothing to the benefits afforded by caffeine supplementation.

The fastest of three trials is recommended for Timed Up & Go testing of functional mobility in an outpatient geriatric setting

DEFF Research Database (Denmark)

Bloch, Mette Linding

trials are needed to produce the best performance. Purpose: To examine if the fastest of three timed TUG trials producesbetter (faster) results than the recording of the second trial in elderly people when following an outpatient geriatric rehabilitation programme. Material and Methods: A total of 32...... to 5.5 seconds in difference between the two recordings. Subjects using walking aids (n=10) were the oldest (P=0.057, mean age of 87.7 versus 81.5 years), and performed worse (P=0.033, 26.3 versus 17.3seconds) when using the best of the three TUG trials. Also, this score was significantly correlated...... elderly people (20 women), at a mean (SD) age of 83.4 (8.6) years were included. All subjects performed three timed TUG trials as fast as safely possible with their normal walking aid (if using). In addition, 30 of the 32 subjects performed the Chair Stand Test (CST) (number of sit to stands in 30 seconds...

Just-in-time information improved decision-making in primary care: a randomized controlled trial.

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Jessie McGowan

Full Text Available BACKGROUND: The "Just-in-time Information" (JIT librarian consultation service was designed to provide rapid information to answer primary care clinical questions during patient hours. This study evaluated whether information provided by librarians to answer clinical questions positively impacted time, decision-making, cost savings and satisfaction. METHODS AND FINDING: A randomized controlled trial (RCT was conducted between October 2005 and April 2006. A total of 1,889 questions were sent to the service by 88 participants. The object of the randomization was a clinical question. Each participant had clinical questions randomly allocated to both intervention (librarian information and control (no librarian information groups. Participants were trained to send clinical questions via a hand-held device. The impact of the information provided by the service (or not provided by the service, additional resources and time required for both groups was assessed using a survey sent 24 hours after a question was submitted. The average time for JIT librarians to respond to all questions was 13.68 minutes/question (95% CI, 13.38 to 13.98. The average time for participants to respond their control questions was 20.29 minutes/question (95% CI, 18.72 to 21.86. Using an impact assessment scale rating cognitive impact, participants rated 62.9% of information provided to intervention group questions as having a highly positive cognitive impact. They rated 14.8% of their own answers to control question as having a highly positive cognitive impact, 44.9% has having a negative cognitive impact, and 24.8% with no cognitive impact at all. In an exit survey measuring satisfaction, 86% (62/72 responses of participants scored the service as having a positive impact on care and 72% (52/72 indicated that they would use the service frequently if it were continued. CONCLUSIONS: In this study, providing timely information to clinical questions had a highly positive impact on

Time regained: when people stop a physical activity program, how does their time use change? A randomised controlled trial.

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Sjaan Gomersall

Full Text Available The aim of this study was to investigate how previously inactive adults who had participated in a structured, partly supervised 6-week exercise program restructured their time budgets when the program ended. Using a randomised controlled trial design, 129 previously inactive adults were recruited and randomly allocated to one of three groups: a Moderate or Extensive six-week physical activity intervention (150 and 300 additional minutes of exercise per week, respectively or a Control group. Additional physical activity was accumulated through both group and individual exercise sessions with a wide range of activities. Use of time and time spent in energy expenditure zones was measured using a computerised 24-h self-report recall instrument, the Multimedia Activity Recall for Children and Adults, and accelerometry at baseline, mid- and end-program and at 3- and 6-months follow up. At final follow up, all significant changes in time use domains had returned to within 20 minutes of baseline levels (Physical Activity 1-2 min/d, Active Transport 3-9 min/d, Self-Care 0-2 min/d, Television/Videogames 13-18 min/d in the Moderate and Extensive group, relative to Controls, respectively, p > 0.05. Similarly, all significant changes in time spent in the moderate energy expenditure zone had returned to within 1-3 min/d baseline levels (p > 0.05, however time spent in vigorous physical activity according to accelerometry estimates remained elevated, although the changes were small in magnitude (1 min/d in the Moderate and Extensive groups, relative to Controls, p = 0.01. The results of this study demonstrate strong recidivist patterns in physical activity, but also in other aspects of time use. In designing and determining the effectiveness of exercise interventions, future studies would benefit from considering the whole profile of time use, rather than focusing on individual activities,Australian New Zealand Clinical Trials Registry ACTRN12610000248066.

Nonlinear Dynamics Modeling and Analysis of Torsional Spring-Loaded Antibacklash Gear with Time-Varying Meshing Stiffness and Friction

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Zheng Yang

2013-01-01

Full Text Available Torsional spring-loaded antibacklash gear which can improve the transmission precision is widely used in many precision transmission fields. It is very important to investigate the dynamic characteristics of antibacklash gear. In the paper, applied force analysis is completed in detail. Then, defining the starting point of double-gear meshing as initial position, according to the meshing characteristic of antibacklash gear, single- or double-tooth meshing states of two gear pairs and the transformation relationship at any moment are determined. Based on this, a nonlinear model of antibacklash gear with time-varying friction and meshing stiffness is proposed. The influences of friction and variations of torsional spring stiffness, damping ratio and preload on dynamic transmission error (DTE are analyzed by numerical calculation and simulation, and the results show that antibacklash gear can increase the composite meshing stiffness; when the torsional spring stiffness is large enough, the oscillating components of the DTE (ODTE and the RMS of the DTE (RDTE trend to be a constant value; the variations of ODTE and RDTE are not significant, unless preload exceeds a certain value.

Accelerated Testing Methodology for the Determination of Slow Crack Growth of Advanced Ceramics

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Choi, Sung R.; Salem, Jonathan A.; Gyekenyesi, John P.

1997-01-01

Constant stress-rate (dynamic fatigue) testing has been used for several decades to characterize slow crack growth behavior of glass and ceramics at both ambient and elevated temperatures. The advantage of constant stress-rate testing over other methods lies in its simplicity: Strengths are measured in a routine manner at four or more stress rates by applying a constant crosshead speed or constant loading rate. The slow crack growth parameters (n and A) required for design can be estimated from a relationship between strength and stress rate. With the proper use of preloading in constant stress-rate testing, an appreciable saving of test time can be achieved. If a preload corresponding to 50 % of the strength is applied to the specimen prior to testing, 50 % of the test time can be saved as long as the strength remains unchanged regardless of the applied preload. In fact, it has been a common, empirical practice in strength testing of ceramics or optical fibers to apply some preloading (less then 40%). The purpose of this work is to study the effect of preloading on the strength to lay a theoretical foundation on such an empirical practice. For this purpose, analytical and numerical solutions of strength as a function of preloading were developed. To verify the solution, constant stress-rate testing using glass and alumina at room temperature and alumina silicon nitride, and silicon carbide at elevated temperatures was conducted in a range of preloadings from O to 90 %.

No differences in satiety or energy intake after high-fructose corn syrup, sucrose, or milk preloads.

Science.gov (United States)

Soenen, Stijn; Westerterp-Plantenga, Margriet S

2007-12-01

It is unclear whether energy-containing drinks, especially those sweetened with high-fructose corn syrup (HFCS), promote positive energy balance and thereby play a role in the development of obesity. The objective was to examine the satiating effects of HFCS and sucrose in comparison with milk and a diet drink. The effects of four 800-mL drinks [corrected] containing no energy or 1.5 MJ from sucrose, HFCS, or milk on satiety were assessed, first in 15 men and 15 women with a mean (+/-SD) body mass index (BMI; in kg/m(2)) of 22.1 +/- 1.9 according to visual analogue scales (VAS) and blood variables and second in 20 men and 20 women (BMI: 22.4 +/- 2.1) according to ingestion of a standardized ad libitum meal (granola cereal + yogurt, 10.1 kJ/g). Fifty minutes after consumption of the 1.5-MJ preload drinks containing sucrose, HFCS, or milk, 170%-mm VAS changes in satiety were observed. Glucagon-like peptide 1 (GLP-1) (P glucose, GLP-1, and ghrelin concentrations. Changes in appetite VAS ratings were a function of changes in GLP-1, ghrelin, insulin, and glucose concentrations. Energy balance consequences of HFCS-sweetened soft drinks are not different from those of other isoenergetic drinks, eg, a sucrose-drink or milk.

Features of calculation of reasonable time of the trial in civil cases in the context of the practice of the European court of human rights

Directory of Open Access Journals (Sweden)

Т. Цувіна

2015-11-01

Full Text Available Problem setting. European Convention of Human Rights (ECHR guarantees right to a fair trial within a reasonable time for everyone (par. 1 art. 6 ECHR. Reasonable time of the trial is an element of the right to a fair trial. One of the main directions for development of civil procedure in Ukraine is the implementation of international standards of fair trial, in particular standards of reasonable time of the trial. Recent research and publications analyses. Foreign and Ukrainian scientists such as Komarov V. V., Neshataeva T. M., Sakara N. U. and others in their works paid attention to different aspects of problems connected with the right to a fair trial within a reasonable time, but a comprehensive study devoted to a features of calculation of reasonable time of the trial taking into account the practice of the ECHR on this issue wasn’t conducted. Paper objective. Main objective of the article is to study decisions of the ECHR concerning the interpretation of Par. 1, Art. 6 ECHR and analyze features of calculation of reasonable time of the trial to make recommendations on implementation of such national level. Paper main body. As a rule, according to a practice of ECHR reasonable time of civil proceedings begins on the date on which the case is referred to a judicial authority. Thus ECHR can take as the starting point the date of a preliminary application to an administrative authority, especially when this is a prerequisite for commencement of proceedings. The end of reasonable time of the trial connected with the moment when the court decision become final or its execution. Conclusions of the research. Calculation of reasonable time of the trial in civil cases in circumstances when an application to the court was preceded by a seeking for protection from the authorities and public servants of executive power has features. In such situations a calculation of reasonable time of the trial doesn’t begin from the moment of seeking for

How many trials are needed to achieve performance stability of the Timed Up & Go test in patients with hip fracture?

DEFF Research Database (Denmark)

Kristensen, Morten T; Ekdahl, Charlotte; Kehlet, Henrik

2010-01-01

To examine the number of trials needed to achieve performance stability of the Timed Up & Go (TUG) test using a standardized walking aid in patients with hip fracture who are allowed full weight bearing (FWB).......To examine the number of trials needed to achieve performance stability of the Timed Up & Go (TUG) test using a standardized walking aid in patients with hip fracture who are allowed full weight bearing (FWB)....

Rejection Positivity Predicts Trial-to-Trial Reaction Times in an Auditory Selective Attention Task: A Computational Analysis of Inhibitory Control

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Sufen eChen

2014-08-01

Full Text Available A series of computer simulations using variants of a formal model of attention (Melara & Algom, 2003 probed the role of rejection positivity (RP, a slow-wave electroencephalographic (EEG component, in the inhibitory control of distraction. Behavioral and EEG data were recorded as participants performed auditory selective attention tasks. Simulations that modulated processes of distractor inhibition accounted well for reaction-time (RT performance, whereas those that modulated target excitation did not. A model that incorporated RP from actual EEG recordings in estimating distractor inhibition was superior in predicting changes in RT as a function of distractor salience across conditions. A model that additionally incorporated momentary fluctuations in EEG as the source of trial-to-trial variation in performance precisely predicted individual RTs within each condition. The results lend support to the linking proposition that RP controls the speed of responding to targets through the inhibitory control of distractors.

Timing of birth for women with a twin pregnancy at term: a randomised controlled trial

Directory of Open Access Journals (Sweden)

Haslam Ross R

2010-10-01

Full Text Available Abstract Background There is a well recognized risk of complications for both women and infants of a twin pregnancy, increasing beyond 37 weeks gestation. Preterm birth prior to 37 weeks gestation is a recognized complication of a twin pregnancy, however, up to 50% of twins will be born after this time. The aims of this randomised trial are to assess whether elective birth at 37 weeks gestation compared with standard care in women with a twin pregnancy affects the risk of perinatal death, and serious infant complications. Methods/Design Design: Multicentred randomised trial. Inclusion Criteria: women with a twin pregnancy at 366 weeks or more without contraindication to continuation of pregnancy. Trial Entry & Randomisation: Following written informed consent, eligible women will be randomised from 36+6 weeks gestation. The randomisation schedule uses balanced variable blocks, with stratification for centre of birth and planned mode of birth. Women will be randomised to either elective birth or standard care. Treatment Schedules: Women allocated to the elective birth group will be planned for elective birth from 37 weeks gestation. Where the plan is for vaginal birth, this will involve induction of labour. Where the plan is for caesarean birth, this will involve elective caesarean section. For women allocated to standard care, birth will be planned for 38 weeks gestation or later. Where the plan is for vaginal birth, this will involve either awaiting the spontaneous onset of labour, or induction of labour if required. Where the plan is for caesarean birth, this will involve elective caesarean section (after 38 and as close to 39 weeks as possible. Primary Study Outcome: A composite of perinatal mortality or serious neonatal morbidity. Sample Size: 460 women with a twin pregnancy to show a reduction in the composite outcome from 16.3% to 6.7% with adjustment for the clustering of twin infants within mothers (p = 0.05, 80% power. Discussion This

Clinical trial optimization: Monte Carlo simulation Markov model for planning clinical trials recruitment.

Science.gov (United States)

Abbas, Ismail; Rovira, Joan; Casanovas, Josep

2007-05-01

The patient recruitment process of clinical trials is an essential element which needs to be designed properly. In this paper we describe different simulation models under continuous and discrete time assumptions for the design of recruitment in clinical trials. The results of hypothetical examples of clinical trial recruitments are presented. The recruitment time is calculated and the number of recruited patients is quantified for a given time and probability of recruitment. The expected delay and the effective recruitment durations are estimated using both continuous and discrete time modeling. The proposed type of Monte Carlo simulation Markov models will enable optimization of the recruitment process and the estimation and the calibration of its parameters to aid the proposed clinical trials. A continuous time simulation may minimize the duration of the recruitment and, consequently, the total duration of the trial.

The effects of Red Bull energy drink compared with caffeine on cycling time-trial performance.

Science.gov (United States)

Quinlivan, Alannah; Irwin, Christopher; Grant, Gary D; Anoopkumar-Dukie, Sheilandra; Skinner, Tina; Leveritt, Michael; Desbrow, Ben

2015-10-01

This study investigated the ergogenic effects of a commercial energy drink (Red Bull) or an equivalent dose of anhydrous caffeine in comparison with a noncaffeinated control beverage on cycling performance. Eleven trained male cyclists (31.7 ± 5.9 y 82.3 ± 6.1 kg, VO2max = 60.3 ± 7.8 mL · kg-1 · min-1) participated in a double-blind, placebo-controlled, crossover-design study involving 3 experimental conditions. Participants were randomly administered Red Bull (9.4 mL/kg body mass [BM] containing 3 mg/kg BM caffeine), anhydrous caffeine (3 mg/kg BM given in capsule form), or a placebo 90 min before commencing a time trial equivalent to 1 h cycling at 75% peak power output. Carbohydrate and fluid volumes were matched across all trials. Performance improved by 109 ± 153 s (2.8%, P = .039) after Red Bull compared with placebo and by 120 ± 172 s (3.1%, P = .043) after caffeine compared with placebo. No significant difference (P > .05) in performance time was detected between Red Bull and caffeine treatments. There was no significant difference (P > .05) in mean heart rate or rating of perceived exertion among the 3 treatments. This study demonstrated that a moderate dose of caffeine consumed as either Red Bull or in anhydrous form enhanced cycling time-trial performance. The ergogenic benefits of Red Bull energy drink are therefore most likely due to the effects of caffeine, with the other ingredients not likely to offer additional benefit.

Comparative analysis of international standards for the fatigue testing of posterior spinal fixation systems: the importance of preload in ISO 12189.

Science.gov (United States)

La Barbera, Luigi; Ottardi, Claudia; Villa, Tomaso

2015-10-01

compared with the previous model where the precompression was not considered. Neglecting the initial preload due to the assembly of the overall construct according to ISO 12189 standard could lead to an overestimation of the stress on the rods up to 50%. To correctly describe the state of stress on the posterior spinal fixator, tested according to the ISO procedure, it is important to take into account the initial preload due to the assembly of the overall construct. Copyright © 2015 Elsevier Inc. All rights reserved.

Sensitivity Analysis of Per-Protocol Time-to-Event Treatment Efficacy in Randomized Clinical Trials

Science.gov (United States)

Gilbert, Peter B.; Shepherd, Bryan E.; Hudgens, Michael G.

2013-01-01

Summary Assessing per-protocol treatment effcacy on a time-to-event endpoint is a common objective of randomized clinical trials. The typical analysis uses the same method employed for the intention-to-treat analysis (e.g., standard survival analysis) applied to the subgroup meeting protocol adherence criteria. However, due to potential post-randomization selection bias, this analysis may mislead about treatment efficacy. Moreover, while there is extensive literature on methods for assessing causal treatment effects in compliers, these methods do not apply to a common class of trials where a) the primary objective compares survival curves, b) it is inconceivable to assign participants to be adherent and event-free before adherence is measured, and c) the exclusion restriction assumption fails to hold. HIV vaccine efficacy trials including the recent RV144 trial exemplify this class, because many primary endpoints (e.g., HIV infections) occur before adherence is measured, and nonadherent subjects who receive some of the planned immunizations may be partially protected. Therefore, we develop methods for assessing per-protocol treatment efficacy for this problem class, considering three causal estimands of interest. Because these estimands are not identifiable from the observable data, we develop nonparametric bounds and semiparametric sensitivity analysis methods that yield estimated ignorance and uncertainty intervals. The methods are applied to RV144. PMID:24187408

A multi-dataset time-reversal approach to clinical trial placebo response and the relationship to natural variability in epilepsy.

Science.gov (United States)

Goldenholz, Daniel M; Strashny, Alex; Cook, Mark; Moss, Robert; Theodore, William H

2017-12-01

Clinical epilepsy drug trials have been measuring increasingly high placebo response rates, up to 40%. This study was designed to examine the relationship between the natural variability in epilepsy, and the placebo response seen in trials. We tested the hypothesis that 'reversing' trial direction, with the baseline period as the treatment observation phase, would reveal effects of natural variability. Clinical trial simulations were run with time running forward and in reverse. Data sources were: SeizureTracker.com (patient reported diaries), a randomized sham-controlled TMS trial, and chronically implanted intracranial EEG electrodes. Outcomes were 50%-responder rates (RR50) and median percentage change (MPC). The RR50 results showed evidence that temporal reversal does not prevent large responder rates across datasets. The MPC results negative in the TMS dataset, and positive in the other two. Typical RR50s of clinical trials can be reproduced using the natural variability of epilepsy as a substrate across multiple datasets. Therefore, the placebo response in epilepsy clinical trials may be attributable almost entirely to this variability, rather than the "placebo effect". Published by Elsevier Ltd.

Do Electrochemiluminescence Assays Improve Prediction of Time to Type 1 Diabetes in Autoantibody-Positive TrialNet Subjects?

OpenAIRE

Fouts, Alexandra; Pyle, Laura; Yu, Liping; Miao, Dongmei; Michels, Aaron; Krischer, Jeffrey; Sosenko, Jay; Gottlieb, Peter; Steck, Andrea K.

2016-01-01

OBJECTIVE To explore whether electrochemiluminescence (ECL) assays can help improve prediction of time to type 1 diabetes in the TrialNet autoantibody-positive population. RESEARCH DESIGN AND METHODS TrialNet subjects who were positive for one or more autoantibodies (microinsulin autoantibody, GAD65 autoantibody [GADA], IA-2A, and ZnT8A) with available ECL-insulin autoantibody (IAA) and ECL-GADA data at their initial visit were analyzed; after a median follow-up of 24 months, 177 of these 1,2...

Planetary Load Sharing in Three-Point Mounted Wind Turbine Gearboxes: A Design and Test Comparison

Energy Technology Data Exchange (ETDEWEB)

Keller, Jonathan [National Renewable Energy Lab. (NREL), Golden, CO (United States); Guo, Yi [National Renewable Energy Lab. (NREL), Golden, CO (United States); Zhang, Zhiwei [Romax InSight, Nottingham, (United Kingdom); Lucas, Doug [The Timken Company, Jackson Township, OH (United States)

2017-04-06

This work compares the planetary load-sharing characteristics of wind turbine gearboxes supported by cylindrical roller bearings (CRBs) and preloaded tapered roller bearings (TRBs) when subjected to rotor moments. Planetary bearing loads were measured in field-representative dynamometer tests and compared to loads predicted by finite-element models. Preloaded TRBs significantly improved load sharing. In pure torque conditions, the upwind planet bearing load in the gearbox with preloaded TRBs was only 14% more than the assumed load compared to 47% more for the gearbox with CRBs. Consequently, the predicted fatigue life of the complete set of planetary bearings for the gearbox with preloaded TRBs is 3.5 times greater than that of the gearbox with CRBs.

Pacing Strategy, Muscle Fatigue and Technique in 1500m Speed Skating and Cycling Time-Trials

NARCIS (Netherlands)

Stoter, Inge K; MacIntosh, Brian R; Fletcher, Jared R; Pootz, Spencer; Zijdewind, Inge; Hettinga, Florentina J

2016-01-01

PURPOSE: To evaluate pacing behavior and peripheral and central contributions to muscle fatigue in 1500m speed skating and cycling time-trials, when a faster or slower start is instructed. METHODS: Nine speed skaters and nine cyclists, all competing at regional or national level, performed two 1500m

Surrogate marker analysis in cancer clinical trials through time-to-event mediation techniques.

Science.gov (United States)

Vandenberghe, Sjouke; Duchateau, Luc; Slaets, Leen; Bogaerts, Jan; Vansteelandt, Stijn

2017-01-01

The meta-analytic approach is the gold standard for validation of surrogate markers, but has the drawback of requiring data from several trials. We refine modern mediation analysis techniques for time-to-event endpoints and apply them to investigate whether pathological complete response can be used as a surrogate marker for disease-free survival in the EORTC 10994/BIG 1-00 randomised phase 3 trial in which locally advanced breast cancer patients were randomised to either taxane or anthracycline based neoadjuvant chemotherapy. In the mediation analysis, the treatment effect is decomposed into an indirect effect via pathological complete response and the remaining direct effect. It shows that only 4.2% of the treatment effect on disease-free survival after five years is mediated by the treatment effect on pathological complete response. There is thus no evidence from our analysis that pathological complete response is a valuable surrogate marker to evaluate the effect of taxane versus anthracycline based chemotherapies on progression free survival of locally advanced breast cancer patients. The proposed analysis strategy is broadly applicable to mediation analyses of time-to-event endpoints, is easy to apply and outperforms existing strategies in terms of precision as well as robustness against model misspecification.

Accelerated Testing Methodology Developed for Determining the Slow Crack Growth of Advanced Ceramics

Science.gov (United States)

Choi, Sung R.; Gyekenyesi, John P.

1998-01-01

Constant stress-rate ("dynamic fatigue") testing has been used for several decades to characterize the slow crack growth behavior of glass and structural ceramics at both ambient and elevated temperatures. The advantage of such testing over other methods lies in its simplicity: strengths are measured in a routine manner at four or more stress rates by applying a constant displacement or loading rate. The slow crack growth parameters required for component design can be estimated from a relationship between strength and stress rate. With the proper use of preloading in constant stress-rate testing, test time can be reduced appreciably. If a preload corresponding to 50 percent of the strength is applied to the specimen prior to testing, 50 percent of the test time can be saved as long as the applied preload does not change the strength. In fact, it has been a common, empirical practice in the strength testing of ceramics or optical fibers to apply some preloading (<40 percent). The purpose of this work at the NASA Lewis Research Center is to study the effect of preloading on measured strength in order to add a theoretical foundation to the empirical practice.

The Power of Low Back Pain Trials: A Systematic Review of Power, Sample Size, and Reporting of Sample Size Calculations Over Time, in Trials Published Between 1980 and 2012.

Science.gov (United States)

Froud, Robert; Rajendran, Dévan; Patel, Shilpa; Bright, Philip; Bjørkli, Tom; Eldridge, Sandra; Buchbinder, Rachelle; Underwood, Martin

2017-06-01

A systematic review of nonspecific low back pain trials published between 1980 and 2012. To explore what proportion of trials have been powered to detect different bands of effect size; whether there is evidence that sample size in low back pain trials has been increasing; what proportion of trial reports include a sample size calculation; and whether likelihood of reporting sample size calculations has increased. Clinical trials should have a sample size sufficient to detect a minimally important difference for a given power and type I error rate. An underpowered trial is one within which probability of type II error is too high. Meta-analyses do not mitigate underpowered trials. Reviewers independently abstracted data on sample size at point of analysis, whether a sample size calculation was reported, and year of publication. Descriptive analyses were used to explore ability to detect effect sizes, and regression analyses to explore the relationship between sample size, or reporting sample size calculations, and time. We included 383 trials. One-third were powered to detect a standardized mean difference of less than 0.5, and 5% were powered to detect less than 0.3. The average sample size was 153 people, which increased only slightly (∼4 people/yr) from 1980 to 2000, and declined slightly (∼4.5 people/yr) from 2005 to 2011 (P pain trials and the reporting of sample size calculations may need to be increased. It may be justifiable to power a trial to detect only large effects in the case of novel interventions. 3.

Participatory workplace interventions can reduce sedentary time for office workers--a randomised controlled trial.

Science.gov (United States)

Parry, Sharon; Straker, Leon; Gilson, Nicholas D; Smith, Anne J

2013-01-01

Occupational sedentary behaviour is an important contributor to overall sedentary risk. There is limited evidence for effective workplace interventions to reduce occupational sedentary time and increase light activity during work hours. The purpose of the study was to determine if participatory workplace interventions could reduce total sedentary time, sustained sedentary time (bouts >30 minutes), increase the frequency of breaks in sedentary time and promote light intensity activity and moderate/vigorous activity (MVPA) during work hours. A randomised controlled trial (ANZCTR NUMBER: ACTN12612000743864) was conducted using clerical, call centre and data processing workers (n = 62, aged 25-59 years) in 3 large government organisations in Perth, Australia. Three groups developed interventions with a participatory approach: 'Active office' (n = 19), 'Active Workstation' and promotion of incidental office activity; 'Traditional physical activity' (n = 14), pedometer challenge to increase activity between productive work time and 'Office ergonomics' (n = 29), computer workstation design and breaking up computer tasks. Accelerometer (ActiGraph GT3X, 7 days) determined sedentary time, sustained sedentary time, breaks in sedentary time, light intensity activity and MVPA on work days and during work hours were measured before and following a 12 week intervention period. For all participants there was a significant reduction in sedentary time on work days (-1.6%, p = 0.006) and during work hours (-1.7%, p = 0.014) and a significant increase in number of breaks/sedentary hour on work days (0.64, p = 0.005) and during work hours (0.72, p = 0.015); there was a concurrent significant increase in light activity during work hours (1.5%, p = 0.012) and MVPA on work days (0.6%, p = 0.012). This study explored novel ways to modify work practices to reduce occupational sedentary behaviour. Participatory workplace interventions can reduce

Sodium bicarbonate improves 4 km time trial cycling performance when individualised to time to peak blood bicarbonate in trained male cyclists.

Science.gov (United States)

Gough, Lewis A; Deb, Sanjoy K; Sparks, S Andy; McNaughton, Lars R

2018-08-01

The aim of this study was to investigate the effects of sodium bicarbonate (NaHCO 3 ) on 4 km cycling time trial (TT) performance when individualised to a predetermined time to peak blood bicarbonate (HCO 3 - ). Eleven male trained cyclists volunteered for this study (height 1.82 ± 0.80 m, body mass (BM) 86.4 ± 12.9 kg, age 32 ± 9 years, peak power output (PPO) 382 ± 22 W). Two trials were initially conducted to identify time to peak HCO 3 - following both 0.2 g . kg -1 BM (SBC2) and 0.3 g . kg -1 BM (SBC3) NaHCO 3 . Thereafter, on three separate occasions using a randomised, double-blind, crossover design, participants completed a 4 km TT following ingestion of either SBC2, SBC3, or a taste-matched placebo (PLA) containing 0.07 g . kg -1 BM sodium chloride (NaCl) at the predetermined individual time to peak HCO 3 - . Both SBC2 (-8.3 ± 3.5 s; p < 0.001, d = 0.64) and SBC3 (-8.6 ± 5.4 s; p = 0.003, d = 0.66) reduced the time to complete the 4 km TT, with no difference between SBC conditions (mean difference = 0.2 ± 0.2 s; p = 0.87, d = 0.02). These findings suggest trained cyclists may benefit from individualising NaHCO 3 ingestion to time to peak HCO 3 - to enhance 4 km TT performance.

Changes in clinical trials methodology over time: a systematic review of six decades of research in psychopharmacology.

Science.gov (United States)

Brunoni, André R; Tadini, Laura; Fregni, Felipe

2010-03-03

There have been many changes in clinical trials methodology since the introduction of lithium and the beginning of the modern era of psychopharmacology in 1949. The nature and importance of these changes have not been fully addressed to date. As methodological flaws in trials can lead to false-negative or false-positive results, the objective of our study was to evaluate the impact of methodological changes in psychopharmacology clinical research over the past 60 years. We performed a systematic review from 1949 to 2009 on MEDLINE and Web of Science electronic databases, and a hand search of high impact journals on studies of seven major drugs (chlorpromazine, clozapine, risperidone, lithium, fluoxetine and lamotrigine). All controlled studies published 100 months after the first trial were included. Ninety-one studies met our inclusion criteria. We analyzed the major changes in abstract reporting, study design, participants' assessment and enrollment, methodology and statistical analysis. Our results showed that the methodology of psychiatric clinical trials changed substantially, with quality gains in abstract reporting, results reporting, and statistical methodology. Recent trials use more informed consent, periods of washout, intention-to-treat approach and parametric tests. Placebo use remains high and unchanged over time. Clinical trial quality of psychopharmacological studies has changed significantly in most of the aspects we analyzed. There was significant improvement in quality reporting and internal validity. These changes have increased study efficiency; however, there is room for improvement in some aspects such as rating scales, diagnostic criteria and better trial reporting. Therefore, despite the advancements observed, there are still several areas that can be improved in psychopharmacology clinical trials.

Changes in clinical trials methodology over time: a systematic review of six decades of research in psychopharmacology.

Directory of Open Access Journals (Sweden)

André R Brunoni

2010-03-01

Full Text Available There have been many changes in clinical trials methodology since the introduction of lithium and the beginning of the modern era of psychopharmacology in 1949. The nature and importance of these changes have not been fully addressed to date. As methodological flaws in trials can lead to false-negative or false-positive results, the objective of our study was to evaluate the impact of methodological changes in psychopharmacology clinical research over the past 60 years.We performed a systematic review from 1949 to 2009 on MEDLINE and Web of Science electronic databases, and a hand search of high impact journals on studies of seven major drugs (chlorpromazine, clozapine, risperidone, lithium, fluoxetine and lamotrigine. All controlled studies published 100 months after the first trial were included. Ninety-one studies met our inclusion criteria. We analyzed the major changes in abstract reporting, study design, participants' assessment and enrollment, methodology and statistical analysis. Our results showed that the methodology of psychiatric clinical trials changed substantially, with quality gains in abstract reporting, results reporting, and statistical methodology. Recent trials use more informed consent, periods of washout, intention-to-treat approach and parametric tests. Placebo use remains high and unchanged over time.Clinical trial quality of psychopharmacological studies has changed significantly in most of the aspects we analyzed. There was significant improvement in quality reporting and internal validity. These changes have increased study efficiency; however, there is room for improvement in some aspects such as rating scales, diagnostic criteria and better trial reporting. Therefore, despite the advancements observed, there are still several areas that can be improved in psychopharmacology clinical trials.

The central role of vascular extracellular matrix and basement membrane remodeling in metabolic syndrome and type 2 diabetes: the matrix preloaded

Directory of Open Access Journals (Sweden)

Tyagi Suresh C

2005-06-01

Full Text Available Abstract The vascular endothelial basement membrane and extra cellular matrix is a compilation of different macromolecules organized by physical entanglements, opposing ionic charges, chemical covalent bonding, and cross-linking into a biomechanically active polymer. These matrices provide a gel-like form and scaffolding structure with regional tensile strength provided by collagens, elasticity by elastins, adhesiveness by structural glycoproteins, compressibility by proteoglycans – hyaluronans, and communicability by a family of integrins, which exchanges information between cells and between cells and the extracellular matrix of vascular tissues. Each component of the extracellular matrix and specifically the capillary basement membrane possesses unique structural properties and interactions with one another, which determine the separate and combined roles in the multiple diabetic complications or diabetic opathies. Metabolic syndrome, prediabetes, type 2 diabetes mellitus, and their parallel companion (atheroscleropathy are associated with multiple metabolic toxicities and chronic injurious stimuli. The adaptable quality of a matrix or form genetically preloaded with the necessary information to communicate and respond to an ever-changing environment, which supports the interstitium, capillary and arterial vessel wall is individually examined.

Rationale and study design for a randomised controlled trial to reduce sedentary time in adults at risk of type 2 diabetes mellitus: project stand (Sedentary Time ANd diabetes

Directory of Open Access Journals (Sweden)

Wilmot Emma G

2011-12-01

Full Text Available Abstract Background The rising prevalence of Type 2 Diabetes Mellitus (T2DM is a major public health problem. There is an urgent need for effective lifestyle interventions to prevent the development of T2DM. Sedentary behaviour (sitting time has recently been identified as a risk factor for diabetes, often independent of the time spent in moderate-to-vigorous physical activity. Project STAND (Sedentary Time ANd Diabetes is a study which aims to reduce sedentary behaviour in younger adults at high risk of T2DM. Methods/Design A reduction in sedentary time is targeted using theory driven group structured education. The STAND programme is subject to piloting and process evaluation in line with the MRC framework for complex interventions. Participants are encouraged to self-monitor and self-regulate their behaviour. The intervention is being assessed in a randomised controlled trial with 12 month follow up. Inclusion criteria are a aged 18-40 years with a BMI in the obese range; b 18-40 years with a BMI in the overweight range plus an additional risk factor for T2DM. Participants are randomised to the intervention (n = 89 or control (n = 89 arm. The primary outcome is a reduction in sedentary behaviour at 12 months as measured by an accelerometer (count Conclusions This is the first UK trial to address sedentary behaviour change in a population of younger adults at risk of T2DM. The results will provide a platform for the development of a range of future multidisciplinary interventions in this rapidly expanding high-risk population. Trial registration Current controlled trials ISRCTN08434554, MRC project 91409.

Clinical Trials

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Ad-libitum drinking and performance during a 40-km cycling time trial in the heat

NARCIS (Netherlands)

Berkulo, M.A.R.; Bol, S.; Levels, K.; Lamberts, R.P.; Daanen, H.A.M.; Noakes, T.D.

2015-01-01

The aim of this study was to investigate if drinking ad-libitum can counteract potential negative effects of a hypohydrated start caused by fluid restriction during a 40-km time trial (TT) in the heat. Twelve trained males performed one 40-km cycling TT euhydrated (EU: no water during the TT) and

Ad-libitum drinking and performance during a 40-km cycling time trial in the heat

NARCIS (Netherlands)

Berkulo, M.A.R.; Bol, S.; Levels, K.; Lamberts, R.P.; Daanen, H.A.M.; Noakes, T.D.

2016-01-01

The aim of this study was to investigate if drinking ad-libitum can counteract potential negative effects of a hypohydrated start caused by fluid restriction during a 40-km time trial (TT) in the heat. Twelve trained males performed one 40-km cycling TT euhydrated (EU: no water during the TT) and

Do Electrochemiluminescence Assays Improve Prediction of Time to Type 1 Diabetes in Autoantibody-Positive TrialNet Subjects?

Science.gov (United States)

Fouts, Alexandra; Pyle, Laura; Yu, Liping; Miao, Dongmei; Michels, Aaron; Krischer, Jeffrey; Sosenko, Jay; Gottlieb, Peter; Steck, Andrea K

2016-10-01

To explore whether electrochemiluminescence (ECL) assays can help improve prediction of time to type 1 diabetes in the TrialNet autoantibody-positive population. TrialNet subjects who were positive for one or more autoantibodies (microinsulin autoantibody, GAD65 autoantibody [GADA], IA-2A, and ZnT8A) with available ECL-insulin autoantibody (IAA) and ECL-GADA data at their initial visit were analyzed; after a median follow-up of 24 months, 177 of these 1,287 subjects developed diabetes. Univariate analyses showed that autoantibodies by radioimmunoassays (RIAs), ECL-IAA, ECL-GADA, age, sex, number of positive autoantibodies, presence of HLA DR3/4-DQ8 genotype, HbA1c, and oral glucose tolerance test (OGTT) measurements were all significantly associated with progression to diabetes. Subjects who were ECL positive had a risk of progression to diabetes within 6 years of 58% compared with 5% for the ECL-negative subjects (P < 0.0001). Multivariate Cox proportional hazards models were compared, with the base model including age, sex, OGTT measurements, and number of positive autoantibodies by RIAs. The model with positivity for ECL-GADA and/or ECL-IAA was the best, and factors that remained significantly associated with time to diabetes were area under the curve (AUC) C-peptide, fasting C-peptide, AUC glucose, number of positive autoantibodies by RIAs, and ECL positivity. Adding ECL to the Diabetes Prevention Trial risk score (DPTRS) improved the receiver operating characteristic curves with AUC of 0.83 (P < 0.0001). ECL assays improved the ability to predict time to diabetes in these autoantibody-positive relatives at risk for developing diabetes. These findings might be helpful in the design and eligibility criteria for prevention trials in the future. © 2016 by the American Diabetes Association.

Evaluation of the Efficacy and Color Stability of Two Different At-Home Bleaching Systems on Teeth of Different Shades: A Randomized Controlled Clinical Trial.

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Aka, Betül; Celik, Esra Uzer

2017-09-01

This randomized controlled clinical trial compared the bleaching efficacy of two different at-home bleaching systems on teeth of different shades and their color stability after a 6-month follow-up. Ninety-two patients (777 teeth) were randomly divided into three groups: (a) negative control, (b) patients treated with a custom-made tray containing 10% carbamide peroxide (10% CP/PF) (Opalescence PF), and (c) patients treated with a pre-loaded tray containing 6% hydrogen peroxide (6% HP/Go) (Opalescence Go). Teeth in all groups were divided into three sub-groups according to the VITA Classic Shade Guide: light (A1-C1), medium dark (C2-B3), and dark (A3.5-C4). Bleaching systems were performed in accordance with manufacturers' instructions for 14 days. The color values were measured at the baseline, 10 days and 14 days of bleaching, 2 weeks, and 6 months after bleaching. Three-way ANOVA and Mann-Whitney U tests were used for statistical analysis (α = 0.05). Irrespective of original shade, both bleaching groups showed significantly higher ΔE* values than the control groups, and the ΔE* values were significantly higher in the 10% CP/PF groups than those in the 6% HP/Go groups (p bleaching systems, the dark teeth showed higher ΔE* values than the light teeth (p bleaching agents produced a bleaching effect, but 10% CP/PF was more effective. A pre-loaded tray system may be used for dental bleaching, but it is still less effective than conventional a 10% carbamide peroxide system, irrespective of the initial shade. (J Esthet Restor Dent 29:325-338, 2017). © 2017 Wiley Periodicals, Inc.

Recovery from a cycling time trial is enhanced with carbohydrate-protein supplementation vs. isoenergetic carbohydrate supplementation

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Lemon Peter WR

2008-12-01

Full Text Available Abstract Background In this study we assessed whether a liquid carbohydrate-protein (C+P supplement (0.8 g/kg C; 0.4 g/kg P ingested early during recovery from a cycling time trial could enhance a subsequent 60 min effort on the same day vs. an isoenergetic liquid carbohydrate (CHO supplement (1.2 g/kg. Methods Two hours after a standardized breakfast, 15 trained male cyclists completed a time trial in which they cycled as far as they could in 60 min (AMex using a Computrainer indoor trainer. Following AMex, subjects ingested either C+P, or CHO at 10, 60 and 120 min, followed by a standardized meal at 4 h post exercise. At 6 h post AMex subjects repeated the time trial (PMex. Results There was a significant reduction in performance for both groups in PMex versus AMex. However, performance and power decreases between PMex and AMex were significantly greater (p ≤ 0.05 with CHO (-1.05 ± 0.44 km and -16.50 ± 6.74 W vs C+P (-0.30 ± 0.50 km and -3.86 ± 6.47 W. Fat oxidation estimated from RER values was significantly greater (p ≤ 0.05 in the C+P vs CHO during the PMex, despite a higher average workload in the C+P group. Conclusion Under these experimental conditions, liquid C+P ingestion immediately after exercise increases fat oxidation, increases recovery, and improves subsequent same day, 60 min efforts relative to isoenergetic CHO ingestion.

Clinicians? and womens? experiences of two consent pathways in a trial of timing of clamping at very preterm birth: a qualitative study

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Ayers, Susan; Sawyer, Alex; Chhoa, Celine; Pushpa-Rajah, Angela; Duley, Lelia

2015-01-01

Background\\ud Recruitment to trials when birth is imminent requires offering consent at a difficult and stressful time, often with limited time. The Cord Pilot Trial assessed timing of cord clamping at very preterm birth. To ensure high risk women were not excluded we developed a two stage oral assent pathway, for use when birth was imminent. A third of women were recruited using this pathway. The aim of this study was to explore clinicians’ and women’s’ experiences of the two consent pathway...

Findings of the Chronic Obstructive Pulmonary Disease-Sitting and Exacerbations Trial (COPD-SEAT) in Reducing Sedentary Time Using Wearable and Mobile Technologies With Educational Support: Randomized Controlled Feasibility Trial.

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Orme, Mark W; Weedon, Amie E; Saukko, Paula M; Esliger, Dale W; Morgan, Mike D; Steiner, Michael C; Downey, John W; Sherar, Lauren B; Singh, Sally J

2018-04-11

Targeting sedentary time post exacerbation may be more relevant than targeting structured exercise for individuals with chronic obstructive pulmonary disease. Focusing interventions on sitting less and moving more after an exacerbation may act as a stepping stone to increase uptake to pulmonary rehabilitation. The aim of this paper was to conduct a randomized trial examining trial feasibility and the acceptability of an education and self-monitoring intervention using wearable technology to reduce sedentary behavior for individuals with chronic obstructive pulmonary disease admitted to hospital for an acute exacerbation. Participants were recruited and randomized in hospital into 3 groups, with the intervention lasting 2 weeks post discharge. The Education group received verbal and written information about reducing their time in sedentary behavior, sitting face-to-face with a study researcher. The Education+Feedback group received the same education component along with real-time feedback on their sitting time, stand-ups, and steps at home through a waist-worn inclinometer linked to an app. Patients were shown how to use the technology by the same study researcher. The inclinometer also provided vibration prompts to encourage movement at patient-defined intervals of time. Patients and health care professionals involved in chronic obstructive pulmonary disease exacerbation care were interviewed to investigate trial feasibility and acceptability of trial design and methods. Main quantitative outcomes of trial feasibility were eligibility, uptake, and retention, and for acceptability, were behavioral responses to the vibration prompts. In total, 111 patients were approached with 33 patients recruited (11 Control, 10 Education, and 12 Education+Feedback). Retention at 2-week follow-up was 52% (17/33; n=6 for Control, n=3 for Education, and n=8 for Education+Feedback). No study-related adverse events occurred. Collectively, patients responded to 106 out of 325

Phase II trial of a syllable-timed speech treatment for school-age children who stutter.

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Andrews, Cheryl; O'Brian, Sue; Onslow, Mark; Packman, Ann; Menzies, Ross; Lowe, Robyn

2016-06-01

A recent clinical trial (Andrews et al., 2012) showed Syllable Timed Speech (STS) to be a potentially useful treatment agent for the reduction of stuttering for school-age children. The present trial investigated a modified version of this program that incorporated parent verbal contingencies. Participants were 22 stuttering children aged 6-11 years. Treatment involved training the children and their parents to use STS in conversation. Parents were also taught to use verbal contingencies in response to their child's stuttered and stutter-free speech and to praise their child's use of STS. Outcome assessments were conducted pre-treatment, at the completion of Stage 1 of the program and 6 months and 12 months after Stage 1 completion. Outcomes are reported for the 19 children who completed Stage 1 of the program. The group mean percent stuttering reduction was 77% from pre-treatment to 12 months post-treatment, and 82% with the two least responsive participants removed. There was considerable variation in response to the treatment. Eleven of the children showed reduced avoidance of speaking situations and 18 were more satisfied with their fluency post-treatment. However, there was some suggestion that stuttering control was not sufficient to fully eliminate situation avoidance for the children. The results of this trial are sufficiently encouraging to warrant further clinical trials of the method. Copyright © 2016 Elsevier Inc. All rights reserved.

Compliance to the prescribed dose and overall treatment time in five randomized clinical trials of altered fractionation in radiotherapy for head-and-neck carcinomas

International Nuclear Information System (INIS)

Khalil, Azza A.; Bentzen, Soeren M.; Bernier, Jacques; Saunders, Michele I.; Horiot, Jean-Claude; Bogaert, Walter van den; Cummings, Bernard J.; Dische, Stanley

2003-01-01

Purpose: To investigate compliance to the prescribed dose-fractionation schedule in five randomized controlled trials of altered fractionation in radiotherapy for head-and-neck carcinoma. Methods and Materials: Individual patient data from 2566 patients participating in the European Organization for Research and Treatment of Cancer (EORTC) 22791, EORTC 22811, EORTC 22851, Princess Margaret Hospital (PMH), and continuous hyperfractionated accelerated radiotherapy (CHART) head-and-neck trials were merged in the fractionation IMPACT (Intergroup Merger of Patient data from Altered or Conventional Treatment schedules) study database. The ideal treatment time was defined as the minimum time required to deliver a prescribed schedule. Compliance to the prescribed overall treatment time was quantified as the difference between the actual and the ideal overall time. An overall measure of compliance in an individual patient, the total dose lost (TDL), was calculated as the dose lost due to prolongation of therapy (assuming a D prolif of 0.64 Gy/day) plus the difference between the prescribed and the actual dose given. Results: The time in excess of the ideal ranged up to 97 days (average 3.9 days), and 25% of the patients had delays of 6 days or more. World Health Organization (WHO) performance status and nodal stage had a significant effect on TDL. TDL was significantly higher in the conventional than in the altered arm of the EORTC 22851 and CHART trials. In the PMH trial, TDL was significantly higher in the hyperfractionation than in the conventional arm. Centers participating in the three EORTC trials varied significantly in their compliance. There was a significant improvement in compliance in patients treated more recently. Conclusions: Even in randomized controlled trials, compliance to the prescribed radiation therapy schedule may be relatively poor, especially after conventional fractionation. This affects the interpretation of the outcome of these trials

Clinical Trial Participation and Time to Treatment Among Adolescents and Young Adults With Cancer: Does Age at Diagnosis or Insurance Make a Difference?

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Parsons, Helen M.; Harlan, Linda C.; Seibel, Nita L.; Stevens, Jennifer L.; Keegan, Theresa H.M.

2011-01-01

Purpose Because adolescent and young adult (AYA) patients with cancer have experienced variable improvement in survival over the past two decades, enhancing the quality and timeliness of cancer care in this population has emerged as a priority area. To identify current trends in AYA care, we examined patterns of clinical trial participation, time to treatment, and provider characteristics in a population-based sample of AYA patients with cancer. Methods Using the National Cancer Institute Patterns of Care Study, we used multivariate logistic regression to evaluate demographic and provider characteristics associated with clinical trial enrollment and time to treatment among 1,358 AYA patients with cancer (age 15 to 39 years) identified through the Surveillance, Epidemiology, and End Results Program. Results In our study, 14% of patients age 15 to 39 years had enrolled onto a clinical trial; participation varied by type of cancer, with the highest participation in those diagnosed with acute lymphoblastic leukemia (37%) and sarcoma (32%). Multivariate analyses demonstrated that uninsured, older patients and those treated by nonpediatric oncologists were less likely to enroll onto clinical trials. Median time from pathologic confirmation to first treatment was 3 days, but this varied by race/ethnicity and cancer site. In multivariate analyses, advanced cancer stage and outpatient treatment alone were associated with longer time from pathologic confirmation to treatment. Conclusion Our study identified factors associated with low clinical trial participation in AYA patients with cancer. These findings support the continued need to improve access to clinical trials and innovative treatments for this population, which may ultimately translate into improved survival. PMID:21931022

"You can save time if…"-A qualitative study on internal factors slowing down clinical trials in Sub-Saharan Africa.

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Nerina Vischer

Full Text Available The costs, complexity, legal requirements and number of amendments associated with clinical trials are rising constantly, which negatively affects the efficient conduct of trials. In Sub-Saharan Africa, this situation is exacerbated by capacity and funding limitations, which further increase the workload of clinical trialists. At the same time, trials are critically important for improving public health in these settings. The aim of this study was to identify the internal factors that slow down clinical trials in Sub-Saharan Africa. Here, factors are limited to those that exclusively relate to clinical trial teams and sponsors. These factors may be influenced independently of external conditions and may significantly increase trial efficiency if addressed by the respective teams.We conducted sixty key informant interviews with clinical trial staff working in different positions in two clinical research centres in Kenya, Ghana, Burkina Faso and Senegal. The study covered English- and French-speaking, and Eastern and Western parts of Sub-Saharan Africa. We performed thematic analysis of the interview transcripts.We found various internal factors associated with slowing down clinical trials; these were summarised into two broad themes, "planning" and "site organisation". These themes were consistently mentioned across positions and countries. "Planning" factors related to budget feasibility, clear project ideas, realistic deadlines, understanding of trial processes, adaptation to the local context and involvement of site staff in planning. "Site organisation" factors covered staff turnover, employment conditions, career paths, workload, delegation and management.We found that internal factors slowing down clinical trials are of high importance to trial staff. Our data suggest that adequate and coherent planning, careful assessment of the setting, clear task allocation and management capacity strengthening may help to overcome the identified

Randomised Controlled Trial to determine the appropriate time to initiate peritoneal dialysis after insertion of catheter to minimise complications (Timely PD study

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Fassett Robert G

2010-06-01

Full Text Available Abstract Background The most appropriate time to initiate dialysis after surgical insertion of Tenckhoff catheters is not clear in the literature. There is the possibility of peritoneal dialysis (PD complications such as leakage and infection if dialysis is started too soon after insertion. However, much morbidity and expense could be saved by reducing dependency on haemodialysis (HD by earlier initiation of PD post catheter insertion. Previous studies are observational and mostly compare immediate with delayed use. The primary objective is to determine the safest and shortest time interval between surgical placement of a Tenckhoff catheter and starting PD. Methods/Design This is a randomised controlled trial of patients who will start PD after insertion of Tenckhoff catheter at Royal Brisbane and Women's Hospital (RBWH or Rockhampton Base Hospital (RBH who meet the inclusion criteria. Patients will be stratified by site and diabetic status. The patients will be randomised to one of three treatment groups. Group 1 will start PD one week after Tenckhoff catheter insertion, group 2 at two weeks and group 3 at four weeks. Nurses and physicians will be blinded to the randomised allocation. The primary end point is the complication rate (leaks and infection after initiation of PD. Discussion The study will determine the most appropriate time to initiate PD after placement of a Tenckhoff catheter. Trial Registration ACTRN12610000076077

Despite law, fewer than one in eight completed studies of drugs and biologics are reported on time on ClinicalTrials.gov.

Science.gov (United States)

Law, Michael R; Kawasumi, Yuko; Morgan, Steven G

2011-12-01

Clinical trial registries are public databases created to prospectively document the methods and measures of prescription drug studies and retrospectively collect a summary of results. In 2007 the US government began requiring that researchers register certain studies and report the results on ClinicalTrials.gov, a public database of federally and privately supported trials conducted in the United States and abroad. We found that although the mandate briefly increased trial registrations, 39 percent of trials were still registered late after the mandate's deadline, and only 12 percent of completed studies reported results within a year, as required by the mandate. This result is important because there is evidence of selective reporting even among registered trials. Furthermore, we found that trials funded by industry were more than three times as likely to report results than were trials funded by the National Institutes of Health. Thus, additional enforcement may be required to ensure disclosure of all trial results, leading to a better understanding of drug safety and efficacy. Congress should also reconsider the three-year delay in reporting results for products that have been approved by the Food and Drug Administration and are in use by patients.

Impact of adaptation algorithm, timing, and stopping boundaries on the performance of Bayesian response adaptive randomization in confirmative trials with a binary endpoint.

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Jiang, Yunyun; Zhao, Wenle; Durkalski-Mauldin, Valerie

2017-11-01

Despite the concerns of time trend in subject profiles, the use of Bayesian response adaptive randomization (BRAR) in large multicenter phase 3 confirmative trials has been reported in recent years, motivated by the potential benefits in subject ethics and/or trial efficiency. However three issues remain unclear to investigators: 1) among several BRAR algorithms, how to choose one for the specific trial setting; 2) when to start and how frequently to update the allocation ratio; and 3) how to choose the interim analyses stopping boundaries to preserve the type 1 error. In this paper, three commonly used BRAR algorithms are evaluated based on type 1 error, power, sample size, the proportion of subjects assigned to the better performing arm, and the total number of failures, under two specific trial settings and different allocation ratio update timing and frequencies. Simulation studies show that for two-arm superiority trials, none of the three BRAR algorithms has predominant benefits in both patient ethics and trial efficiency when compared to fixed equal allocation design. For a specific trial aiming to identify the best or the worst among three treatments, a properly selected BRAR algorithm and its implementation parameters are able to gain ethical and efficiency benefits simultaneously. Although the simulation results come from a specific trial setting, the methods described in this paper are generally applicable to other trials. Copyright © 2017 Elsevier Inc. All rights reserved.

Real-Time Predictions of Reservoir Size and Rebound Time during Antiretroviral Therapy Interruption Trials for HIV.

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Alison L Hill

2016-04-01

Full Text Available Monitoring the efficacy of novel reservoir-reducing treatments for HIV is challenging. The limited ability to sample and quantify latent infection means that supervised antiretroviral therapy (ART interruption studies are generally required. Here we introduce a set of mathematical and statistical modeling tools to aid in the design and interpretation of ART-interruption trials. We show how the likely size of the remaining reservoir can be updated in real-time as patients continue off treatment, by combining the output of laboratory assays with insights from models of reservoir dynamics and rebound. We design an optimal schedule for viral load sampling during interruption, whereby the frequency of follow-up can be decreased as patients continue off ART without rebound. While this scheme can minimize costs when the chance of rebound between visits is low, we find that the reservoir will be almost completely reseeded before rebound is detected unless sampling occurs at least every two weeks and the most sensitive viral load assays are used. We use simulated data to predict the clinical trial size needed to estimate treatment effects in the face of highly variable patient outcomes and imperfect reservoir assays. Our findings suggest that large numbers of patients-between 40 and 150-will be necessary to reliably estimate the reservoir-reducing potential of a new therapy and to compare this across interventions. As an example, we apply these methods to the two "Boston patients", recipients of allogeneic hematopoietic stem cell transplants who experienced large reductions in latent infection and underwent ART-interruption. We argue that the timing of viral rebound was not particularly surprising given the information available before treatment cessation. Additionally, we show how other clinical data can be used to estimate the relative contribution that remaining HIV+ cells in the recipient versus newly infected cells from the donor made to the

The Reproducibility of 4-km Time Trial (TT) Performance Following Individualised Sodium Bicarbonate Supplementation: a Randomised Controlled Trial in Trained Cyclists.

Science.gov (United States)

Gough, Lewis Anthony; Deb, Sanjoy Kumar; Sparks, Andy; McNaughton, Lars Robert

2017-09-21

Individual time to peak blood bicarbonate (HCO 3 - ) has demonstrated good to excellent reproducibility following ingestion of both 0.2 g kg -1 body mass (BM) and 0.3 g kg -1 BM sodium bicarbonate (NaHCO 3 ), but the consistency of the time trial (TT) performance response using such an individualised NaHCO 3 ingestion strategy remains unknown. This study therefore evaluated the reproducibility of 4-km TT performance following NaHCO 3 ingestion individualised to time to peak blood bicarbonate. Eleven trained male cyclists completed five randomised treatments with prior ingestion of 0.2 g kg -1 (SBC2) or 0.3 g kg -1 BM (SBC3) NaHCO 3 , on two separate occasions each, or a control trial entailing no supplementation. Participants completed a 4-km cycling TT on a Velotron ergometer where time to complete, power and speed were measured, whilst acid-base blood parameters were also recorded (pH and blood bicarbonate concentration HCO 3 - ) and lactate [La - ]. Alkalosis was achieved prior to exercise in both SBC2 and SBC3, as pH and HCO 3 - were greater compared to baseline (p  0.05). The reproducibility of the mean absolute change from baseline to peak in HCO 3 - was good in SBC2 (r = 0.68) and excellent in SBC3 (r = 0.78). The performance responses following both SBC2 and SBC3 displayed excellent reproducibility (r range = 0.97 to 0.99). Results demonstrate excellent reproducibility of exercise performance following individualised NaHCO 3 ingestion, which is due to the high reproducibility of blood acid-base variables with repeat administration of NaHCO 3 . Using a time to peak HCO 3 - strategy seems to cause no dose-dependent effects on performance for exercise of this duration and intensity; therefore, athletes may consider smaller doses of NaHCO 3 to mitigate gastrointestinal (GI) discomfort.

Effect of task familiarisation on distribution of energy during a 2000 m cycling time trial.

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Corbett, J; Barwood, M J; Parkhouse, K

2009-10-01

To investigate the effect of task familiarisation on the spontaneous pattern of energy expenditure during a series of 2000 m cycling time trials (TTs). Nine trained males completed three 2000 m TTs on a Velotron cycling ergometer. To examine pacing strategy, the data were assigned to 250 m "bins," with the pattern of aerobic and anaerobic energy expenditure calculated from total work accomplished and gas-exchange data. There were no significant differences between trials in performance times (191.4 (SD 4.3), 189.4 (4.6), 190.1 (5.6) s), total aerobic (58.3 (2.7), 58.4 (3.1), 58.0 (3.4) kJ) and total anaerobic energy expenditure (16.4 (3.3), 17.3 (2.8), 16.5 (3.1) kJ). Pacing strategy in the second and third TT differed from the first TT in that a lower power output was adopted during the first 500 m, enabling a higher power output during the final 750 m of the TT. This adjustment in the pattern of energy expenditure was mediated by an alteration in the pattern of anaerobic energy expenditure, which paralleled changes in total energy expenditure. Furthermore, participants retained an anaerobic energy "reserve" enabling an end-spurt during the second and third trials. Small modifications to the pacing strategy are made following a single bout of exercise, primarily by altering the rate of anaerobic energy expenditure. This may have served to prevent critical metabolic disturbances. The alteration in pacing strategy following the first exercise bout is compatible with a complex intelligent regulatory system.

Case Study: Dose Response of Caffeine on 20-km Handcycling Time Trial Performance in a Paratriathlete.

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Graham-Paulson, Terri; Perret, Claudio; Goosey-Tolfrey, Victoria

2018-05-03

Caffeine's (CAF) ability to influence upper-body exercise endurance performance may be related to an individual's training status. This case study therefore aimed to investigate the ergogenic effects of CAF dose on 20-km time trial (TT) performance of an elite male paratriathlete (wheelchair user; age = 46 years, body mass = 76.9 kg, body fat = 25.4%, and handcycling [Formula: see text]). The athlete completed four 20-km handcycling TTs on a Cyclus II ergometer under controlled laboratory conditions following the ingestion of 2, 4, and 6 mg/kg CAF or placebo (PLA). Blood lactate concentration, power output, arousal, and ratings of perceived exertion were recorded. Ingestion of 2, 4, and 6 mg/kg CAF resulted in a 2%, 1.5%, and 2.7% faster TT compared with PLA (37:40 min:s). The participant's blood lactate concentration increased throughout all trials and was greater during CAF compared with PLA. There were no obvious differences in ratings of perceived exertion between trials despite different performance times. Baseline arousal scores differed between PLA and 4 mg/kg CAF (1 = low), and 2 and 6 mg/kg CAF (3 = moderate). Arousal increased at each time point following the ingestion of 4 and 6 mg/kg CAF. The largest CAF dose resulted in a positive pacing strategy, which, when combined with an end spurt, resulted in the fastest TT. CAF improved 20-km TT performance of an elite male paratriathlete, which may be related to greater arousal and an increased power output for a given rating of perceived exertion.

Time to institutional review board approval with local versus central review in a multicenter pragmatic trial.

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Neuman, Mark D; Gaskins, Lakisha J; Ziolek, Tracy

2018-02-01

Central institutional review board (IRB) review will be required for National Institutes of Health-funded multisite human subjects research as of January 2018, with similar requirements extending to most US multisite human research in 2020. Nonetheless, little is known regarding the relative efficiency of central versus local IRB review for multicenter studies. We compared the amount of time required for central versus local IRB review and approval for sites in one ongoing multicenter randomized trial. The REGAIN Trial (Regional versus General Anesthesia for Promoting Independence after Hip Fracture; clinicaltrials.gov number: NCT02507505) is an ongoing randomized trial comparing standard-care spinal anesthesia to standard-care general anesthesia for patients undergoing hip fracture surgery. After approval of the protocol by the sponsor IRB, each participating US site opted either to submit the protocol for local IRB review or to designate the sponsor IRB as the IRB of record (i.e. central IRB) via an authorization agreement after a limited local review. For each US REGAIN site approved through 18 April 2017, we assessed (1) the time in calendar days from protocol receipt to IRB submission, (2) the time in calendar days from IRB submission to IRB approval, and (3) the total time in calendar days from protocol receipt to IRB approval (i.e. time from protocol receipt to IRB submission plus time from IRB submission to IRB approval). The main study protocol was submitted to the sponsor IRB on 25 May 2015 and approved on 8 July 2015 (44 days). Out of 34 sites, 9 received initial approval from the central (sponsor) IRB; 25 sought initial approval via local review. The median time from protocol receipt to IRB submission was 39 days for sites approved by the central IRB (interquartile range: 35-134) versus 58 days for sites approved via local review (interquartile range: 41-105; p = 0.711). The median time from IRB submission to IRB approval for sites approved by

The Reliability and Validity of a Four-Minute Running Time-Trial in Assessing V˙O2max and Performance

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Kerry McGawley

2017-05-01

Full Text Available Introduction: Traditional graded-exercise tests to volitional exhaustion (GXTs are limited by the need to establish starting workloads, stage durations, and step increments. Short-duration time-trials (TTs may be easier to implement and more ecologically valid in terms of real-world athletic events. The purpose of the current study was to assess the reliability and validity of maximal oxygen uptake (V˙O2max and performance measured during a traditional GXT (STEP and a four-minute running time-trial (RunTT.Methods: Ten recreational runners (age: 32 ± 7 years; body mass: 69 ± 10 kg completed five STEP tests with a verification phase (VER and five self-paced RunTTs on a treadmill. The order of the STEP/VER and RunTT trials was alternated and counter-balanced. Performance was measured as time to exhaustion (TTE for STEP and VER and distance covered for RunTT.Results: The coefficient of variation (CV for V˙O2max was similar between STEP, VER, and RunTT (1.9 ± 1.0, 2.2 ± 1.1, and 1.8 ± 0.8%, respectively, but varied for performance between the three types of test (4.5 ± 1.9, 9.7 ± 3.5, and 1.8 ± 0.7% for STEP, VER, and RunTT, respectively. Bland-Altman limits of agreement (bias ± 95% showed V˙O2max to be 1.6 ± 3.6 mL·kg−1·min−1 higher for STEP vs. RunTT. Peak HR was also significantly higher during STEP compared with RunTT (P = 0.019.Conclusion: A four-minute running time-trial appears to provide more reliable performance data in comparison to an incremental test to exhaustion, but may underestimate V˙O2max.

Post-oral sugar detection rapidly and chemospecifically modulates taste-guided behavior

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Spector, Alan C.

2016-01-01

Several recent studies have shown that post-oral sugar sensing rapidly stimulates ingestion. Here, we explored the specificity with which early-phase post-oral sugar sensing influenced ingestive motivation. In experiment 1, rats were trained to associate the consumption of 0.3 M sucrose with injections of LiCl (3.0 meq/kg ip, conditioned taste aversion) or given equivalent exposures to the stimuli, but in an unpaired fashion. Then, all rats were subjected to two brief-access tests to assess appetitive and consummatory responses to the taste properties of sucrose (0.01–1.0 M), 0.12 M NaCl, and dH2O (in 10-s trials in randomized blocks). Intraduodenal infusions of either 0.3 M sucrose or equiosmolar 0.15 M NaCl (3.0 ml) were administered, beginning just before each test. For unpaired rats, intraduodenal sucrose specifically enhanced licking for 0.03–1.0 M sucrose, with no effect on trial initiation, relative to intraduodenal NaCl. Rats with an aversion to sucrose suppressed licking responses to sucrose in a concentration-dependent manner, as expected, but the intraduodenal sucrose preload did not appear to further influence licking responses; instead, intraduodenal sucrose attenuated trial initiation. Using a serial taste reactivity (TR) paradigm, however, experiment 2 demonstrated that intraduodenal sucrose preloads suppressed ingestive oromotor responses to intraorally delivered sucrose in rats with a sucrose aversion. Finally, experiment 3 showed that intraduodenal sucrose preloads enhanced preferential licking to some representative tastants tested (sucrose, Polycose, and Intralipid), but not others (NaCl, quinine). Together, the results suggest that the early phase-reinforcing efficacy of post-oral sugar is dependent on the sensory and motivational properties of the ingesta. PMID:27511277

An intervention to preschool children for reducing screen time: a randomized controlled trial.

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Yilmaz, G; Demirli Caylan, N; Karacan, C D

2015-05-01

Screen time, defined as time spent watching television, DVDs, or videos or playing computer or video games, has been related to serious health consequences in children, such as impaired language acquisition, violent behaviour, tobacco smoking and obesity. Our aim was to determine if a simple intervention aimed at preschool-aged children, applied at the health maintenance visits, in the primary care setting, would be effective in reducing screen time. We used a two group randomized controlled trial design. Two- to 6-year-old children and their parents were randomly assigned to receive an intervention to reduce their screen time, BMI and parental report of aggressive behaviour. At the end of the intervention we made home visits at 2, 6 and 9 months and the parents completed questionnaire. Parents in the intervention group reported less screen time and less aggressive behaviour than those in the control group but there were no differences in BMI z scores. This study shows that a preschool-based intervention can lead to reductions in young children's television/video viewing. © 2014 John Wiley & Sons Ltd.

Screen-time Weight-loss Intervention Targeting Children at Home (SWITCH): A randomized controlled trial study protocol

OpenAIRE

Tsai Midi; Jiang Yannan; Epstein Leonard; Foley Louise; Mhurchu Cliona; Maddison Ralph; Dewes Ofa; Heke Ihirangi

2011-01-01

Abstract Background Approximately one third of New Zealand children and young people are overweight or obese. A similar proportion (33%) do not meet recommendations for physical activity, and 70% do not meet recommendations for screen time. Increased time being sedentary is positively associated with being overweight. There are few family-based interventions aimed at reducing sedentary behavior in children. The aim of this trial is to determine the effects of a 24 week home-based, family orie...

Full Scale Model Test of Consolidation Acceleration on Soft Soil deposition with Combination of Timber Pile and PVD (Hybrid Pile)

OpenAIRE

Sandyutama, Y.; Samang, L.; Imran, A. M.; Harianto4, T.

2015-01-01

This research aims to analyze the effect of composite pile-PVD (hybrid pile) as the reinforcement in embankment on soft soil by the means of numerical simulation and Full-Scale Trial Embankment. The first phase cunducted by numerical analysis and obtained 6-8 meters hybrid pile length effective. Full-Scale trial embankment. was installed hybrid pile of 6 m and preloading of 4,50 height. Full-scale tests were performed to investigate the performances of Hybrid pile reinforcement. This research...

Phase II Trials for Heterogeneous Patient Populations with a Time-to-Event Endpoint.

Science.gov (United States)

Jung, Sin-Ho

2017-07-01

In this paper, we consider a single-arm phase II trial with a time-to-event end-point. We assume that the study population has multiple subpopulations with different prognosis, but the study treatment is expected to be similarly efficacious across the subpopulations. We review a stratified one-sample log-rank test and present its sample size calculation method under some practical design settings. Our sample size method requires specification of the prevalence of subpopulations. We observe that the power of the resulting sample size is not very sensitive to misspecification of the prevalence.

Publication status of contemporary oncology randomised controlled trials worldwide.

Science.gov (United States)

Chen, Yu-Pei; Liu, Xu; Lv, Jia-Wei; Li, Wen-Fei; Zhang, Yuan; Guo, Ying; Lin, Ai-Hua; Sun, Ying; Mao, Yan-Ping; Ma, Jun

2016-10-01

Little is known about the extent of selective publication in contemporary oncology randomised controlled trials (RCTs) worldwide. This study aimed to evaluate the rates of publication and timely publication (within 24 months) for contemporary oncology RCTs from all over the world. We also investigated the trial characteristics associated with publication and timely publication. We identified all phase III oncology RCTs registered on ClinicalTrials.gov with a primary completion date between January 2008 and December 2012. We searched PubMed and EMBASE to identify publications. The final search date was 31 December 2015. Our primary outcome measure was the time to publication from the primary completion date to the date of primary publication in a peer-reviewed journal. We identified 598 completed oncology RCTs; overall, 398 (66.6%) had been published. For published trials, the median time to publication was 25 months (interquartile range, 16-37 months). Only 192 trials (32.1%) were published within 24 months. Timely publication was independently associated with trials completed late in 2012. Trials conducted in Asia and other regions were less likely to have timely publication, but trials conducted in different locations were all equally likely to be published. Industry- and NIH-funded trials were equally likely to be published timely or at any time after trial completion. Among 391 published trials with clear primary outcomes, there was a trend for timely publication of positive trials compared with negative trials. Despite the ethical obligations and societal expectations of disclosing findings promptly, oncology RCTs performed poorly. Copyright © 2016 Elsevier Ltd. All rights reserved.

Impact of sodium citrate ingestion during recovery after dehydrating exercise on rehydration and subsequent 40-km cycling time-trial performance in the heat.

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Suvi, Silva; Mooses, Martin; Timpmann, Saima; Medijainen, Luule; Narõškina, Daria; Unt, Eve; Ööpik, Vahur

2018-01-11

The purpose of this study was to assess the impact of sodium citrate (CIT) ingestion (600 mg·kg -1 ) during recovery from dehydrating cycling exercise (DE) on subsequent 40-km cycling performance in a warm environment (32 °C). Twenty male nonheat-acclimated endurance athletes exercised in the heat until 4% body mass (BM) loss occurred. After 16 h recovery with consumption of water ad libitum and prescribed diet (evening meal 20 kcal·kg -1 , breakfast 12 kcal·kg -1 ) supplemented in a double-blind, randomized, crossover manner with CIT or placebo (PLC), they performed 40-km time-trial (TT) on a cycle ergometer in a warm environment. During recovery greater increases in BM and plasma volume (PV) concomitant with greater water intake and retention occurred in the CIT trial compared with the PLC trial (p 0.05) in sweat loss, PV decrement, ratings of perceived exertion, or TT time (CIT 68.10 ± 3.28 min, PLC 68.11 ± 2.87 min). At the end of TT blood lactate concentration was higher (7.58 ± 2.44 mmol·L -1 vs 5.58 ± 1.32 mmol·L -1 ; p = 0.0002) and rectal temperature lower (39.54 ± 0.50 °C vs 39.65 ± 0.52 °C; p = 0.033) in the CIT trial than in the PLC trial. Compared with pre-DE time point, PV had decreased to a lower level in the PLC trial than in the CIT trial (p = 0.0001). In conclusion, CIT enhances rehydration after exercise-induced dehydration but has no impact on subsequent 40-km cycling TT performance in a warm uncompensable environment.

Efficacy of night-time compression for breast cancer related lymphedema (LYNC): protocol for a multi-centre, randomized controlled efficacy trial

International Nuclear Information System (INIS)

McNeely, Margaret L.; Campbell, Kristin L.; Webster, Marc; Kuusk, Urve; Tracey, Karen; Mackey, John

2016-01-01

Lymphedema is a prevalent long-term effect of breast cancer treatment that is associated with reduced quality of life. More recent observational data suggest that the addition of night-time compression to day-time use of a compression garment results in better long-term control of arm lymphedema. The primary objectives of the randomized controlled phase of the trial are to determine the efficacy of night-time compression on arm lymphedema volume maintenance and quality of life in breast cancer survivors who have completed intensive reduction treatment for their lymphedema. The study will be a parallel 3-arm, multi-centre randomized fast-track trial. A total of 120 women with breast cancer related lymphedema will be recruited from 3 centres in Canada and randomized to group 1: Day-time compression garment alone or Group 2: Day-time compression garment + night-time compression bandaging or Group 3: Day-time compression garment + use of a night-time compression system garment. The duration of the primary intervention period will be 12 weeks. The follow-up period after the intervention (weeks 13 to 24) will follow a longitudinal observational design. The primary outcome variables: differences from baseline to week 12 in arm volume and quality of life (Lymphoedema Functioning, Disability and Health Questionnaire: Lymph-ICF). Secondary outcomes include bioimpedance analysis, sleep disturbance and self-efficacy. All measurements are standardized and will be performed prior to randomization, and at weeks 6, 12, 18 and 24. The use of night-time compression as a self-management strategy for chronic breast cancer related lymphedema is seen as an innovative approach to improve long-term control over the condition. This trial aims to advance the knowledge on self-management strategies for lymphedema

A randomised controlled trial of sensory awareness training and additional motor practice for learning scalpel skills in podiatry students.

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Causby, Ryan S; McDonnell, Michelle N; Reed, Lloyd; Hillier, Susan L

2016-12-05

The process of using a scalpel, like all other motor activities, is dependent upon the successful integration of afferent (sensory), cognitive and efferent (motor) processes. During learning of these skills, even if motor practice is carefully monitored there is still an inherent risk involved. It is also possible that this strategy could reinforce high levels of anxiety experienced by the student and affect student self-efficacy, causing detrimental effects on motor learning. An alternative training strategy could be through targeting sensory rather than motor processes. Second year podiatry students who were about to commence learning scalpel skills were recruited. Participants were randomly allocated into sensory awareness training (Sensory), additional motor practice (Motor) or usual teaching only (Control) groups. Participants were then evaluated on psychological measures (Intrinsic Motivation Inventory) and dexterity measures (Purdue Pegboard, Grooved Pegboard Test and a grip-lift task). A total of 44 participants were included in the study. There were no baseline differences or significant differences between the three groups over time on the Perceived Competence, Effort/ Importance or Pressure/ Tension, psychological measures. All groups showed a significant increase in Perceived Competence over time (F 1,41  = 13.796, p = 0.001). Only one variable for the grip-lift task (Preload Duration for the non-dominant hand) showed a significant difference over time between the groups (F 2,41  = 3.280, p = 0.038), specifically, Motor and Control groups. The use of sensory awareness training, or additional motor practice did not provide a more effective alternative compared with usual teaching. Further research may be warranted using more engaged training, provision of supervision and greater participant numbers. Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12616001428459 . Registered 13 th October 2016. Registered Retrospectively.

Crack sizing by the time-of-flight diffraction method, in the light of recent international round-robin trials, (UKAEA, DDT and PISC II)

International Nuclear Information System (INIS)

Curtis, G.J.

1987-01-01

In 1980-81, Harwell developed a mini-computer controlled multi-probe defect detection and sizing system based on the ultrasonic time-of-flight/diffraction principle introduced by Silk. This system proved to be capable of fully automatic data collection from the PWR girth-weld simulation Plates 1 and 2 in the Defect Detection Trials of 1981-82. The speed of collection and subsequent analysis was such that a report on the defects found could be filed within 48 hours. The mode of operation adopted simulated minimum time of access to the defects, and was intended to define that dimension of a defect which has greatest significance, i.e. the through-thickness dimension. In 1984, for the PISC II Trial, the approach adopted changed to emphasize the three-dimensional location and sizing capabilities of the time-of-flight/diffraction method. Data collection and analysis became highly interactive and the mode of operation simulated NDE at the manufacturing stage of a pressure vessel. The purpose of this paper is to indicate the defect through-thickness sizing capability of TOFD achieved in the 1981-82 Defect Detection Trials and the defect mapping capability achieved in the 1984 PISC II Trial

UK Dermatology Clinical Trials Network's STOP GAP trial (a multicentre trial of prednisolone versus ciclosporin for pyoderma gangrenosum): protocol for a randomised controlled trial.

Science.gov (United States)

Craig, Fiona F; Thomas, Kim S; Mitchell, Eleanor J; Williams, Hywel C; Norrie, John; Mason, James M; Ormerod, Anthony D

2012-04-28

Pyoderma gangrenosum (PG) is a rare inflammatory skin disorder characterised by painful and rapidly progressing skin ulceration. PG can be extremely difficult to treat and patients often require systemic immunosuppression. Recurrent lesions of PG are common, but the relative rarity of this condition means that there is a lack of published evidence regarding its treatment. A systematic review published in 2005 found no randomised controlled trials (RCTs) relating to the treatment of PG. Since this time, one small RCT has been published comparing infliximab to placebo, but none of the commonly used systemic treatments for PG have been formally assessed. The UK Dermatology Clinical Trials Network's STOP GAP Trial has been designed to address this lack of trial evidence. The objective is to assess whether oral ciclosporin is more effective than oral prednisolone for the treatment of PG. The trial design is a two-arm, observer-blind, parallel-group, randomised controlled trial comparing ciclosporin (4 mg/kg/day) to prednisolone (0.75 mg/kg/day). A total of 140 participants are to be recruited over a period of 4 years, from up to 50 hospitals in the UK and Eire. Primary outcome of velocity of healing at 6 weeks is assessed blinded to treatment allocation (using digital images of the ulcers). Secondary outcomes include: (i) time to healing; (ii) global assessment of improvement; (iii) PG inflammation assessment scale score; (iv) self-reported pain; (v) health-related quality of life; (vi) time to recurrence; (vii) treatment failures; (viii) adverse reactions to study medications; and (ix) cost effectiveness/utility. Patients with a clinical diagnosis of PG (excluding granulomatous PG); measurable ulceration (that is, not pustular PG); and patients aged over 18 years old who are able to give informed consent are included in the trial. Randomisation is by computer generated code using permuted blocks of randomly varying size, stratified by lesion size, and

No appetite efficacy of a commercial structured lipid emulsion in minimally processed drinks.

Science.gov (United States)

Smit, H J; Keenan, E; Kovacs, E M R; Wiseman, S A; Mela, D J; Rogers, P J

2012-09-01

Fabuless (Olibra) is a commercially structured lipid emulsion, claimed to be a food ingredient that is effective for food intake and appetite reduction. The present study assessed its efficacy in a yoghurt-based mini-drink undergoing low or minimal food manufacturing (thermal and shear) processes. Study 1: Twenty-four healthy volunteers (16 female, 8 male; age: 18-47 years; body mass index (BMI): 17-28 kg m(-2)) took part in a randomised, placebo-controlled, double-blind parallel crossover trial. Consumption of a minimally processed 'preload' mini-drink (containing two different doses of Fabuless or a control fat) at 2 h after breakfast was followed by appetite and mood ratings, and food intake measured in ad libitum meals at 3 and 7 h post consumption of the preload. Study 2: As Study 1 (16 female, 8 male; age: 20-54 years; BMI: 21-30 kg m(-2)). A chilled, virtually unprocessed, preload breakfast mini-drink (containing minimally processed Fabuless or a control fat) was provided 5 min after a standardised breakfast, followed by appetite and mood ratings, and food intake measured in ad libitum meals at 4 and 8 h post consumption of the preload. The structured lipid emulsion tested had no significant effect on the primary measures of food intake or appetite. Even when exposed to minimal food-manufacturing conditions, Fabuless showed no efficacy on measures of appetite and food intake.

Just-in-time information improved decision-making in primary care: a randomized controlled trial.

Science.gov (United States)

McGowan, Jessie; Hogg, William; Campbell, Craig; Rowan, Margo

2008-01-01

The "Just-in-time Information" (JIT) librarian consultation service was designed to provide rapid information to answer primary care clinical questions during patient hours. This study evaluated whether information provided by librarians to answer clinical questions positively impacted time, decision-making, cost savings and satisfaction. A randomized controlled trial (RCT) was conducted between October 2005 and April 2006. A total of 1,889 questions were sent to the service by 88 participants. The object of the randomization was a clinical question. Each participant had clinical questions randomly allocated to both intervention (librarian information) and control (no librarian information) groups. Participants were trained to send clinical questions via a hand-held device. The impact of the information provided by the service (or not provided by the service), additional resources and time required for both groups was assessed using a survey sent 24 hours after a question was submitted. The average time for JIT librarians to respond to all questions was 13.68 minutes/question (95% CI, 13.38 to 13.98). The average time for participants to respond their control questions was 20.29 minutes/question (95% CI, 18.72 to 21.86). Using an impact assessment scale rating cognitive impact, participants rated 62.9% of information provided to intervention group questions as having a highly positive cognitive impact. They rated 14.8% of their own answers to control question as having a highly positive cognitive impact, 44.9% has having a negative cognitive impact, and 24.8% with no cognitive impact at all. In an exit survey measuring satisfaction, 86% (62/72 responses) of participants scored the service as having a positive impact on care and 72% (52/72) indicated that they would use the service frequently if it were continued. In this study, providing timely information to clinical questions had a highly positive impact on decision-making and a high approval rating from

A Randomized Trial of Time-Limited Antiretroviral Therapy in Acute/Early HIV Infection.

Directory of Open Access Journals (Sweden)

Joseph B Margolick

Full Text Available It has been proposed that initiation of antiretroviral treatment (ART very soon after establishment of HIV infection may be beneficial by improving host control of HIV replication and delaying disease progression.People with documented HIV infection of less than 12 months' duration in Baltimore MD and seven Canadian sites were randomized to either a observation and deferred ART, or b immediate treatment with ART for 12 months. All subjects not receiving ART were followed quarterly and permanent ART was initiated according to contemporaneous treatment guidelines. The endpoint of the trial was total ART-free time from study entry until initiation of permanent ART.One hundred thirteen people were randomized, 56 to the observation arm and 57 to the immediate treatment arm. Twenty-three had acute (<2 months infection and 90 early (2-12 months infection. Of those randomized to the immediate treatment arm, 37 completed 12 months of ART according to protocol, 9 declined to stop ART after 12 months, and 11 were nonadherent to the protocol or lost to follow-up. Comparing those in the observation arm to either those who completed 12 months of ART or all 56 who were randomized to immediate ART, there was no significant difference between the arms in treatment-free interval after study entry, which was about 18 months in both arms.This study did not find a benefit from administration of a brief, time-limited (12-month course of ART in acute or early HIV infection.ClinicalTrials.gov NCT00106171.

"Watching time tick by…": Decision making for Duchenne muscular dystrophy trials.

Science.gov (United States)

Peay, Holly L; Scharff, Hadar; Tibben, Aad; Wilfond, Benjamin; Bowie, Janice; Johnson, Joanna; Nagaraju, Kanneboyina; Escolar, Diana; Piacentino, Jonathan; Biesecker, Barbara B

2016-01-01

This interview study explored clinicians' perspectives and parents' decision making about children's participation in Duchenne muscular dystrophy (DMD) clinical trials. Data from semi-structured interviews conducted with clinicians and parents in U.S. or Canada were assessed using thematic analysis. Eleven clinicians involved in ten trials and fifteen parents involved in six trials were interviewed. Parents described benefit-risk assessments using information from advocacy, peers, professionals, and sponsors. Strong influence was attributed to the progressive nature of DMD. Most expected direct benefit. Few considered the possibility of trial failure. Most made decisions to participate before the informed consent (IC) process, but none-the-less perceived informed choice with little to lose for potential gain. Clinicians described more influence on parental decisions than attributed by parents. Clinicians felt responsible to facilitate IC while maintaining hope. Both clinicians and parents reported criticisms about the IC process and regulatory barriers. The majority of parents described undertaking benefit-risk assessments that led to informed choices that offered psychological and potential disease benefits. Parents' high expectations influenced their decisions while also reflecting optimism. Clinicians felt challenged in balancing parents' expectations and likely outcomes. Prognosis-related pressures coupled with decision making prior to IC suggest an obligation to ensure educational materials are understandable and accurate, and to consider an expanded notion of IC timeframes. Anticipatory guidance about potential trial failure might facilitate parents' deliberations while aiding clinicians in moderating overly-optimistic motivations. Regulators and industry should appreciate special challenges in progressive disorders, where doing nothing was equated with doing harm. Copyright © 2015 Elsevier Inc. All rights reserved.

Influence of ballistic bench press on upper body power output in professional rugby players.

Science.gov (United States)

West, Daniel J; Cunningham, Daniel J; Crewther, Blair T; Cook, Christian J; Kilduff, Liam P

2013-08-01

The use of heavy resistance exercise provides an effective preload stimulus for inducing postactivation potentiation (PAP) and increasing peak power output (PPO). However, this approach has limited application in many sporting situations (e.g., incorporation in a precompetition warm-up); and therefore, more practical strategies for inducing PAP need to be investigated. The aim of the present study was to compare the PPO changes after performing a preload stimulus of either a ballistic exercise or a traditional heavy resistance exercise. Twenty professional rugby union players completed 3 testing sessions, each separated by 48 hours. On the first occasion, subjects underwent a 3 repetition maximum (3RM)-bench press testing session. On the next 2 occasions, subjects performed a ballistic bench throw at baseline (30% of 1RM), followed by a preload stimulus of either heavy resistance training (HRT) (heavy bench press: 3 sets of 3 repetitions at 87% 1RM) or BBP (3 sets of 3 repetitions at 30% on 1RM) followed by ballistic bench throw after 8 minutes recovery. The trials were randomized and counterbalanced. Both preload stimuli protocols increased PPO compared with baseline (BBP baseline 892 ± 108 vs. 8 minutes 924 ± 119 W, p < 0.001; HRT baseline 893 ± 104 vs. 8 minutes 931 ± 116 W; p < 0.001). There were no conditional differences between PPO at 8 minutes (p = 0.141); moreover, the change in PPO from baseline was also similar between conditions (BBP Δ + 33 ± 18; HRT Δ + 38 ± 21 W; p = 0.112). In conclusion, a ballistic exercise provided an effective method of inducing PAP and increasing upper-body PPO; moreover, this elicited similar increases in PPO as a traditional heavy resistance exercise preloading stimulus.

An Exponential Tilt Mixture Model for Time-to-Event Data to Evaluate Treatment Effect Heterogeneity in Randomized Clinical Trials.

Science.gov (United States)

Wang, Chi; Tan, Zhiqiang; Louis, Thomas A

2014-01-01

Evaluating the effect of a treatment on a time-to-event outcome is the focus of many randomized clinical trials. It is often observed that the treatment effect is heterogeneous, where only a subgroup of the patients may respond to the treatment due to some unknown mechanism such as genetic polymorphism. In this paper, we propose a semiparametric exponential tilt mixture model to estimate the proportion of patients who respond to the treatment and to assess the treatment effect. Our model is a natural extension of parametric mixture models to a semiparametric setting with a time-to-event outcome. We propose a nonparametric maximum likelihood estimation approach for inference and establish related asymptotic properties. Our method is illustrated by a randomized clinical trial on biodegradable polymer-delivered chemotherapy for malignant gliomas patients.

Muscle inactivity and activity patterns after sedentary time--targeted randomized controlled trial.

Science.gov (United States)

Pesola, Arto J; Laukkanen, Arto; Haakana, Piia; Havu, Marko; Sääkslahti, Arja; Sipilä, Sarianna; Finni, Taija

2014-11-01

Interventions targeting sedentary time are needed. We used detailed EMG recordings to study the short-term effectiveness of simple sedentary time-targeted tailored counseling on the total physical activity spectrum. This cluster randomized controlled trial was conducted between 2011 and 2013 (InPact, ISRCTN28668090), and short-term effectiveness of counseling is reported in the present study. A total of 133 office workers volunteered to participate, from which muscle activity data were analyzed from 48 (intervention, n = 24; control, n = 24). After a lecture, face-to-face tailored counseling was used to set contractually binding goals regarding breaking up sitting periods and increasing family based physical activity. Primary outcome measures were assessed 11.8 ± 1.1 h before and a maximum of 2 wk after counseling including quadriceps and hamstring muscle inactivity time, sum of the five longest muscle inactivity periods, and light muscle activity time during work, commute, and leisure time. Compared with those in the controls, counseling decreased the intervention group's muscle inactivity time by 32.6 ± 71.8 min from 69.1% ± 8.5% to 64.6% ± 10.9% (whole day, P work, P activity time increased by 20.6 ± 52.6 min, from 22.2% ± 7.9% to 25.0% ± 9.7% (whole day, P work, P work time, average EMG amplitude (percentage of EMG during maximal voluntary isometric contraction (MVC) (%EMG MVC)) increased from 1.6% ± 0.9% to 1.8% ± 1.0% (P activity. During work time, average EMG amplitude increased by 13%, reaching an average of 1.8% of EMG MVC. If maintained, this observed short-term effect may have health-benefiting consequences.

External data required timely response by the Trial Steering-Data Monitoring Committee for the NALoxone InVEstigation (N-ALIVE pilot trial

Directory of Open Access Journals (Sweden)

Sheila M. Bird

2017-03-01

Full Text Available The prison-based N-ALIVE pilot trial had undertaken to notify the Research Ethics Committee and participants if we had reason to believe that the N-ALIVE pilot trial would not proceed to the main trial. In this paper, we describe how external data for the third year of before/after evaluation from Scotland's National Naloxone Programme, a related public health policy, were anticipated by eliciting prior opinion about the Scottish results in the month prior to their release as official statistics. We summarise how deliberations by the N-ALIVE Trial Steering-Data Monitoring Committee (TS-DMC on N-ALIVE's own interim data, together with those on naloxone-on-release (NOR from Scotland, led to the decision to cease randomization in the N-ALIVE pilot trial and recommend to local Principal Investigators that NOR be offered to already-randomized prisoners who had not yet been released.

UK Dermatology Clinical Trials Network’s STOP GAP trial (a multicentre trial of prednisolone versus ciclosporin for pyoderma gangrenosum: protocol for a randomised controlled trial

Directory of Open Access Journals (Sweden)

Craig Fiona F

2012-04-01

Full Text Available Abstract Background Pyoderma gangrenosum (PG is a rare inflammatory skin disorder characterised by painful and rapidly progressing skin ulceration. PG can be extremely difficult to treat and patients often require systemic immunosuppression. Recurrent lesions of PG are common, but the relative rarity of this condition means that there is a lack of published evidence regarding its treatment. A systematic review published in 2005 found no randomised controlled trials (RCTs relating to the treatment of PG. Since this time, one small RCT has been published comparing infliximab to placebo, but none of the commonly used systemic treatments for PG have been formally assessed. The UK Dermatology Clinical Trials Network’s STOP GAP Trial has been designed to address this lack of trial evidence. Methods The objective is to assess whether oral ciclosporin is more effective than oral prednisolone for the treatment of PG. The trial design is a two-arm, observer-blind, parallel-group, randomised controlled trial comparing ciclosporin (4 mg/kg/day to prednisolone (0.75 mg/kg/day. A total of 140 participants are to be recruited over a period of 4 years, from up to 50 hospitals in the UK and Eire. Primary outcome of velocity of healing at 6 weeks is assessed blinded to treatment allocation (using digital images of the ulcers. Secondary outcomes include: (i time to healing; (ii global assessment of improvement; (iii PG inflammation assessment scale score; (iv self-reported pain; (v health-related quality of life; (vi time to recurrence; (vii treatment failures; (viii adverse reactions to study medications; and (ix cost effectiveness/utility. Patients with a clinical diagnosis of PG (excluding granulomatous PG; measurable ulceration (that is, not pustular PG; and patients aged over 18 years old who are able to give informed consent are included in the trial. Randomisation is by computer generated code using permuted blocks of randomly varying size

Positive outcomes influence the rate and time to publication, but not the impact factor of publications of clinical trial results.

Directory of Open Access Journals (Sweden)

Pilar Suñé

Full Text Available OBJECTIVES: Publication bias may affect the validity of evidence based medical decisions. The aim of this study is to assess whether research outcomes affect the dissemination of clinical trial findings, in terms of rate, time to publication, and impact factor of journal publications. METHODS AND FINDINGS: All drug-evaluating clinical trials submitted to and approved by a general hospital ethics committee between 1997 and 2004 were prospectively followed to analyze their fate and publication. Published articles were identified by searching Pubmed and other electronic databases. Clinical study final reports submitted to the ethics committee, final reports synopses available online and meeting abstracts were also considered as sources of study results. Study outcomes were classified as positive (when statistical significance favoring experimental drug was achieved, negative (when no statistical significance was achieved or it favored control drug and descriptive (for non-controlled studies. Time to publication was defined as time from study closure to publication. A survival analysis was performed using a Cox regression model to analyze time to publication. Journal impact factors of identified publications were recorded. Publication rate was 48·4% (380/785. Study results were identified for 68·9% of all completed clinical trials (541/785. Publication rate was 84·9% (180/212 for studies with results classified as positive and 68·9% (128/186 for studies with results classified as negative (p<0·001. Median time to publication was 2·09 years (IC95 1·61-2·56 for studies with results classified as positive and 3·21 years (IC95 2·69-3·70 for studies with results classified as negative (hazard ratio 1·99 (IC95 1·55-2·55. No differences were found in publication impact factor between positive (median 6·308, interquartile range: 3·141-28·409 and negative result studies (median 8·266, interquartile range: 4·135-17·157. CONCLUSIONS

Single and combined effects of beetroot juice and caffeine supplementation on cycling time trial performance.

Science.gov (United States)

Lane, Stephen C; Hawley, John A; Desbrow, Ben; Jones, Andrew M; Blackwell, James R; Ross, Megan L; Zemski, Adam J; Burke, Louise M

2014-09-01

Both caffeine and beetroot juice have ergogenic effects on endurance cycling performance. We investigated whether there is an additive effect of these supplements on the performance of a cycling time trial (TT) simulating the 2012 London Olympic Games course. Twelve male and 12 female competitive cyclists each completed 4 experimental trials in a double-blind Latin square design. Trials were undertaken with a caffeinated gum (CAFF) (3 mg·kg(-1) body mass (BM), 40 min prior to the TT), concentrated beetroot juice supplementation (BJ) (8.4 mmol of nitrate (NO3(-)), 2 h prior to the TT), caffeine plus beetroot juice (CAFF+BJ), or a control (CONT). Subjects completed the TT (females: 29.35 km; males: 43.83 km) on a laboratory cycle ergometer under conditions of best practice nutrition: following a carbohydrate-rich pre-event meal, with the ingestion of a carbohydrate-electrolyte drink and regular oral carbohydrate contact during the TT. Compared with CONT, power output was significantly enhanced after CAFF+BJ and CAFF (3.0% and 3.9%, respectively, p caffeine (-0.9%, p = 0.4 compared with CAFF). We conclude that caffeine (3 mg·kg(-1) BM) administered in the form of a caffeinated gum increased cycling TT performance lasting ∼50-60 min by ∼3%-4% in both males and females. Beetroot juice supplementation was not ergogenic under the conditions of this study.

Measuring Time to Biochemical Failure in the TROG 96.01 Trial: When Should the Clock Start Ticking?

International Nuclear Information System (INIS)

Denham, James W.; Steigler, Allison; Kumar, Mahesh; Lamb, David S.; Joseph, David; Spry, Nigel A.; Tai, Keen-Hun; Atkinson, Chris; Turner, Sandra FRANZCR; Greer, Peter B.; Gleeson, Paul S.; D'Este, Catherine

2009-01-01

Purpose: We sought to determine whether short-term neoadjuvant androgen deprivation (STAD) duration influences the optimal time point from which Phoenix fail (time to biochemical failure; TTBF) should be measured. Methods and Materials: In the Trans-Tasman Radiation Oncology Group 96.01 trial, men with locally advanced prostate cancer were randomized to 3 or 6 months STAD before and during prostatic irradiation (XRT) or to XRT alone. The prognostic value of TTBF measured from the end of radiation (ERT) and randomization were compared using Cox models. Results: Between 1996 and 2000, 802 eligible patients were randomized. In 436 men with Phoenix failure, TTBF measured from randomization was a powerful predictor of prostate cancer-specific survival and marginally more accurate than TTBF measured from ERT in Cox models. Insufficient data were available to confirm that TTBF measured from testosterone recovery may also be a suitable option. Conclusions: TTBF measured from randomization (commencement of therapy) performed well in this trial dataset and will be a convenient option if this finding holds in other datasets that include long-term androgen deprivation data.

Cycling Time Trial Performance 4 Hours After Glycogen-Lowering Exercise Is Similarly Enhanced by Recovery Nondairy Chocolate Beverages Versus Chocolate Milk.

Science.gov (United States)

Upshaw, Adam U; Wong, Tiffany S; Bandegan, Arash; Lemon, Peter W

2016-02-01

Postexercise chocolate milk ingestion has been shown to enhance both glycogen resynthesis and subsequent exercise performance. To assess whether nondairy chocolate beverage ingestion post-glycogen-lowering exercise can enhance 20-km cycling time trial performance 4 hr later, eight healthy trained male cyclists (21.8 ± 2.3y, VO2max = 61.2 ± 1.4 ml·kg-1·min-1; M ± SD) completed a series of intense cycling intervals designed to lower muscle glycogen (Jentjens & Jeukendrup, 2003) followed by 4 hr of recovery and a subsequent 20-km cycling time trial. During the first 2 hr of recovery, participants ingested chocolate dairy milk (DAIRYCHOC), chocolate soy beverage (SOYCHOC), chocolate hemp beverage (HEMPCHOC), low-fat dairy milk (MILK), or a low-energy artificially sweetened, flavored beverage (PLACEBO) at 30-min intervals in a double-blind, counterbalanced repeated-measures design. All drinks, except the PLACEBO (247 kJ) were isoenergetic (2,107 kJ), and all chocolate-flavored drinks provided 1-g CHO·kg body mass-1·h-1. Fluid intake across treatments was equalized (2,262 ± 148 ml) by ingesting appropriate quantities of water based on drink intake. The CHO:PRO ratio was 4:1, 1.5:1, 4:1, and 6:1 for DAIRYCHOC, MILK, SOYCHOC, and HEMPCHOC, respectively. One-way analysis of variance with repeated measures showed time trial performance (DAIRYCHOC = 34.58 ± 2.5 min, SOYCHOC = 34.83 ± 2.2 min, HEMPCHOC = 34.88 ± 1.1 min, MILK = 34.47 ± 1.7 min) was enhanced similarly vs PLACEBO (37.85 ± 2.1) for all treatments (p = .019) These data suggest that postexercise macronutrient and total energy intake are more important for same-day 20-km cycling time trial performance after glycogen-lowering exercise than protein type or protein-to-carbohydrate ratio.

Predicting treatment effect from surrogate endpoints and historical trials: an extrapolation involving probabilities of a binary outcome or survival to a specific time.

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Baker, Stuart G; Sargent, Daniel J; Buyse, Marc; Burzykowski, Tomasz

2012-03-01

Using multiple historical trials with surrogate and true endpoints, we consider various models to predict the effect of treatment on a true endpoint in a target trial in which only a surrogate endpoint is observed. This predicted result is computed using (1) a prediction model (mixture, linear, or principal stratification) estimated from historical trials and the surrogate endpoint of the target trial and (2) a random extrapolation error estimated from successively leaving out each trial among the historical trials. The method applies to either binary outcomes or survival to a particular time that is computed from censored survival data. We compute a 95% confidence interval for the predicted result and validate its coverage using simulation. To summarize the additional uncertainty from using a predicted instead of true result for the estimated treatment effect, we compute its multiplier of standard error. Software is available for download. © 2011, The International Biometric Society No claim to original US government works.

Optimal timing of an invasive strategy in patients with non-ST-elevation acute coronary syndrome: a meta-analysis of randomised trials.

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Jobs, Alexander; Mehta, Shamir R; Montalescot, Gilles; Vicaut, Eric; Van't Hof, Arnoud W J; Badings, Erik A; Neumann, Franz-Josef; Kastrati, Adnan; Sciahbasi, Alessandro; Reuter, Paul-Georges; Lapostolle, Frédéric; Milosevic, Aleksandra; Stankovic, Goran; Milasinovic, Dejan; Vonthein, Reinhard; Desch, Steffen; Thiele, Holger

2017-08-19

A routine invasive strategy is recommended for patients with non-ST-elevation acute coronary syndromes (NSTE-ACS). However, optimal timing of invasive strategy is less clearly defined. Individual clinical trials were underpowered to detect a mortality benefit; we therefore did a meta-analysis to assess the effect of timing on mortality. We identified randomised controlled trials comparing an early versus a delayed invasive strategy in patients presenting with NSTE-ACS by searching MEDLINE, Cochrane Central Register of Controlled Trials, and Embase. We included trials that reported all-cause mortality at least 30 days after in-hospital randomisation and for which the trial investigators agreed to collaborate (ie, providing individual patient data or standardised tabulated data). We pooled hazard ratios (HRs) using random-effects models. This meta-analysis is registered at PROSPERO (CRD42015018988). We included eight trials (n=5324 patients) with a median follow-up of 180 days (IQR 180-360). Overall, there was no significant mortality reduction in the early invasive group compared with the delayed invasive group HR 0·81, 95% CI 0·64-1·03; p=0·0879). In pre-specified analyses of high-risk patients, we found lower mortality with an early invasive strategy in patients with elevated cardiac biomarkers at baseline (HR 0·761, 95% CI 0·581-0·996), diabetes (0·67, 0·45-0·99), a GRACE risk score more than 140 (0·70, 0·52-0·95), and aged 75 years older (0·65, 0·46-0·93), although tests for interaction were inconclusive. An early invasive strategy does not reduce mortality compared with a delayed invasive strategy in all patients with NSTE-ACS. However, an early invasive strategy might reduce mortality in high-risk patients. None. Copyright © 2017 Elsevier Ltd. All rights reserved.

Successful recruitment to trials: findings from the SCIMITAR+ Trial.

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Peckham, Emily; Arundel, Catherine; Bailey, Della; Callen, Tracy; Cusack, Christina; Crosland, Suzanne; Foster, Penny; Herlihy, Hannah; Hope, James; Ker, Suzy; McCloud, Tayla; Romain-Hooper, Crystal-Bella; Stribling, Alison; Phiri, Peter; Tait, Ellen; Gilbody, Simon

2018-01-19

Randomised controlled trials (RCT) can struggle to recruit to target on time. This is especially the case with hard to reach populations such as those with severe mental ill health. The SCIMITAR+ trial, a trial of a bespoke smoking cessation intervention for people with severe mental ill health achieved their recruitment ahead of time and target. This article reports strategies that helped us to achieve this with the aim of aiding others recruiting from similar populations. SCIMITAR+ is a multi-centre pragmatic two-arm parallel-group RCT, which aimed to recruit 400 participants with severe mental ill health who smoke and would like to cut down or quit. The study recruited primarily in secondary care through community mental health teams and psychiatrists with a smaller number of participants recruited through primary care. Recruitment opened in October 2015 and closed in December 2016, by which point 526 participants had been recruited. We gathered information from recruiting sites on strategies which led to the successful recruitment in SCIMITAR+ and in this article present our approach to trial management along with the strategies employed by the recruiting sites. Alongside having a dedicated trial manager and trial management team, we identified three main themes that led to successful recruitment. These were: clinicians with a positive attitude to research; researchers and clinicians working together; and the use of NHS targets. The overriding theme was the importance of relationships between both the researchers and the recruiting clinicians and the recruiting clinicians and the participants. This study makes a significant contribution to the limited evidence base of real-world cases of successful recruitment to RCTs and offers practical guidance to those planning and conducting trials. Building positive relationships between clinicians, researchers and participants is crucial to successful recruitment.

Single and Combined Effects of Beetroot Crystals and Sodium Bicarbonate on 4-km Cycling Time Trial Performance.

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Callahan, Marcus J; Parr, Evelyn B; Hawley, John A; Burke, Louise M

2017-06-01

When ingested alone, beetroot juice and sodium bicarbonate are ergogenic for high-intensity exercise performance. This study sought to determine the independent and combined effects of these supplements. Eight endurance trained (VO 2 max 65 mL·kg·min -1 ) male cyclists completed four × 4-km time trials (TT) in a doubleblind Latin square design supplementing with beetroot crystals (BC) for 3 days (15 g·day -1 + 15 g 1 h before TT, containing 300 mg nitrate per 15 g), bicarbonate (Bi 0.3 g·kg -1 body mass [BM] in 5 doses every 15 min from 2.5 h before TT); BC+Bi or placebo (PLA). Subjects completed TTs on a Velotron cycle ergometer under standardized laboratory conditions. Plasma nitrite concentrations were significantly elevated only in the BC+Bi trial before the TT (1520 ± 786 nmol·L -1 ) compared with baseline (665 ± 535 nmol·L -1 , p = .02) and the Bi and PLA conditions (Bi: 593 ± 203 nmol·L -1 , p .05). Blood bicarbonate concentrations were increased in the BC+Bi and Bi trials before the TT (BC+Bi: 30.9 ± 2.8 mmol·L -1 ; Bi: 31.7 ± 1.1 mmol·L -1 ). There were no differences in mean power output (386-394 W) or the time taken to complete the TT (335.8-338.1 s) between any conditions. Under the conditions of this study, supplementation was not ergogenic for 4-km TT performance.

Barriers towards the publication of academic drug trials. Follow-up of trials approved by the Danish Medicines Agency.

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Berendt, Louise; Petersen, Lene Grejs; Bach, Karin Friis; Poulsen, Henrik Enghusen; Dalhoff, Kim

2017-01-01

To characterize and quantify barriers towards the publication of academic drug trials. We identified academic drug trials approved during a 3-year period (2004-2007) by the Danish Medicines Agency. We conducted a survey among the trial sponsors to describe the rates of initiation, completion, and publication, and the reasons for the failure to reach each of these milestones. Information on size and methodological characteristics of the trials was extracted from the EudraCT database, a prospective register of all approved clinical drug trials submitted to European medicines agencies since 2004. A total of 181 academic drug trials were eligible for inclusion, 139 of which participated in our survey (response rate: 77%). Follow-up time ranged from 5.1 to 7.9 years. Most trials were randomized controlled trials (73%, 95% CI 65-81%). Initiation and completion rates were 92% (95% CI: 88-97%) and 93% (95% CI: 89-97%) respectively. The publication rate of completed trials was 73% (95% CI: 62-79%). RCTs were published faster than non-RCTs (quartile time to publication 2.9 vs. 3.1 years, p = 0.0412). Many academic drug trials are left unpublished. Main barriers towards publication were related to the process from completion to publication. Hence, there is much to gain by facilitating the process from analysis to publication. Research institutions and funders should actively influence this process, e.g. by requiring the publication of trial results within a given time after completion.

Effects of short-term isokinetic training with reciprocal knee extensors agonist and antagonist muscle actions : A controlled and randomized trial

NARCIS (Netherlands)

Cunha, Rafael; Carregaro, Rodrigo L.; Martorelli, André; Vieira, Amilton; Oliveira, Ana B.; Bottaro, Martim

Background: Previous studies have shown that preloading an antagonist muscle may increase the acute agonist neuromuscular performance. In addition, studies have suggested that very short-term resistance exercise (RE) programs may also be useful to increase strength and muscular performance.

A good time to leave?: the sunk time effect in pigeons.

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Magalhães, Paula; White, K Geoffrey

2014-06-01

Persistence in a losing course of action due to prior investments of time, known as the sunk time effect, has seldom been studied in nonhuman animals. On every trial in the present study, pigeons were required to choose between two response keys. Responses on one key produced food after a short fixed interval (FI) of time on some trials, or on other trials, no food (Extinction) after a longer time. FI and Extinction trials were not differently signaled, were equiprobable, and alternated randomly. Responses on a second Escape key allowed the pigeon to terminate the current trial and start a new one. The optimal behavior was for pigeons to peck the escape key once the duration equivalent to the short FI had elapsed without reward. Durations of the short FI and the longer Extinction schedules were varied over conditions. In some conditions, the pigeons suboptimally responded through the Extinction interval, thus committing the sunk time effect. The absolute duration of the short FI had no effect on the choice between persisting and escaping. Instead, the ratio of FI and Extinction durations determined the likelihood of persistence during extinction. Copyright © 2014 Elsevier B.V. All rights reserved.

The effect of carbohydrate mouth rinse on performance, biochemical and psychophysiological variables during a cycling time trial: a crossover randomized trial.

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Ferreira, Amanda M J; Farias-Junior, Luiz F; Mota, Thaynan A A; Elsangedy, Hassan M; Marcadenti, Aline; Lemos, Telma M A M; Okano, Alexandre H; Fayh, Ana P T

2018-01-01

The hypothesis of the central effect of carbohydrate mouth rinse (CMR) on performance improvement in a fed state has not been established, and its psychophysiological responses have not yet been described. The aim of this study was to evaluate the effect of CMR in athletes fed state on performance, biochemical and psychophysiological responses compared to ad libitum water intake. Eleven trained male cyclists completed a randomized, crossover trial, which consisted of a 30 km cycle ergometer at self-selected intensity and in a fed state. Subjects were under random influence of the following interventions: CMR with a 6% unflavored maltodextrin solution; mouth rinsing with a placebo solution (PMR); drinking "ad libitum" (DAL). The time for completion of the test (min), heart rate (bpm) and power (watts), rating of perceived exertion (RPE), affective response, blood glucose (mg/dL) and lactate (mmol/DL), were evaluated before, during and immediately after the test, while insulin (uIL/mL), cortisol (μg/dL) and creatine kinase (U/L) levels were measured before, immediately after the test and 30 min after the test. Time for completion of the 30 km trial did not differ significantly among CMR, PMR and DAL interventions (means = 54.5 ± 2.9, 54.7 ± 2.9 and 54.5 ± 2.5 min, respectively; p  = 0.82). RPE and affective response were higher in DAL intervention ( p  creatine kinase responses showed no significant difference among interventions. In a fed state, CMR has not caused metabolic changes, and it has not improved physical performance compared to ad libitum water intake, but demonstrated a possible central effect. ReBec registration number: RBR-4vpwkg. Available in http://www.ensaiosclinicos.gov.br/rg/?q=RBR-4vpwkg.

Interventions to reduce postpartum stress in first-time mothers: a randomized-controlled trial.

Science.gov (United States)

Osman, Hibah; Saliba, Matilda; Chaaya, Monique; Naasan, Georges

2014-10-15

The postpartum period can be a challenging time particularly for first-time mothers. This study aimed to assess two different interventions designed to reduce stress in the postpartum among first-time mothers. Healthy first-time mothers with healthy newborns were recruited from hospitals in Beirut, Lebanon after delivery. The two interventions were a 20-minute film addressing common stressors in the postpartum period and a 24-hour telephone support hotline. Participants were randomized to one of four study arms to receive either the postpartum support film, the hotline service, both interventions, or a music CD (control). Participants were interviewed at eight to twelve weeks postpartum for assessment of levels of stress as measured by the Cohen Perceived Stress Scale (PSS-10). Of the 632 eligible women, 552 (88%) agreed to participate in the study. Of those, 452 (82%) completed the study. Mean PSS-10 scores of mothers who received the film alone (15.76) or the film with the hotline service (15.86) were significantly lower than that of the control group (18.93) (p-value film and the 24-hour telephone hotline service reduced stress in the postpartum period in first-time mothers. These simple interventions can be easily implemented and could have an important impact on the mental wellbeing of new mothers. The trial was registered with clinicaltrials.gov (identifier # NCT00857051) on March 5, 2009.

Pancreatitis of biliary origin, optimal timing of cholecystectomy (PONCHO trial: study protocol for a randomized controlled trial

Directory of Open Access Journals (Sweden)

Bouwense Stefan A

2012-11-01

Full Text Available Abstract Background After an initial attack of biliary pancreatitis, cholecystectomy minimizes the risk of recurrent biliary pancreatitis and other gallstone-related complications. Guidelines advocate performing cholecystectomy within 2 to 4 weeks after discharge for mild biliary pancreatitis. During this waiting period, the patient is at risk of recurrent biliary events. In current clinical practice, surgeons usually postpone cholecystectomy for 6 weeks due to a perceived risk of a more difficult dissection in the early days following pancreatitis and for logistical reasons. We hypothesize that early laparoscopic cholecystectomy minimizes the risk of recurrent biliary pancreatitis or other complications of gallstone disease in patients with mild biliary pancreatitis without increasing the difficulty of dissection and the surgical complication rate compared with interval laparoscopic cholecystectomy. Methods/Design PONCHO is a randomized controlled, parallel-group, assessor-blinded, superiority multicenter trial. Patients are randomly allocated to undergo early laparoscopic cholecystectomy, within 72 hours after randomization, or interval laparoscopic cholecystectomy, 25 to 30 days after randomization. During a 30-month period, 266 patients will be enrolled from 18 hospitals of the Dutch Pancreatitis Study Group. The primary endpoint is a composite endpoint of mortality and acute re-admissions for biliary events (that is, recurrent biliary pancreatitis, acute cholecystitis, symptomatic/obstructive choledocholithiasis requiring endoscopic retrograde cholangiopancreaticography including cholangitis (with/without endoscopic sphincterotomy, and uncomplicated biliary colics occurring within 6 months following randomization. Secondary endpoints include the individual endpoints of the composite endpoint, surgical and other complications, technical difficulty of cholecystectomy and costs. Discussion The PONCHO trial is designed to show that early

Screen-Time Weight-loss Intervention Targeting Children at Home (SWITCH): a randomized controlled trial.

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Maddison, Ralph; Marsh, Samantha; Foley, Louise; Epstein, Leonard H; Olds, Timothy; Dewes, Ofa; Heke, Ihirangi; Carter, Karen; Jiang, Yannan; Mhurchu, Cliona Ni

2014-09-10

Screen-based activities, such as watching television (TV), playing video games, and using computers, are common sedentary behaviors among young people and have been linked with increased energy intake and overweight. Previous home-based sedentary behaviour interventions have been limited by focusing primarily on the child, small sample sizes, and short follow-up periods. The SWITCH (Screen-Time Weight-loss Intervention Targeting Children at Home) study aimed to determine the effect of a home-based, family-delivered intervention to reduce screen-based sedentary behaviour on body composition, sedentary behaviour, physical activity, and diet over 24 weeks in overweight and obese children. A two-arm, parallel, randomized controlled trial was conducted. Children and their primary caregiver living in Auckland, New Zealand were recruited via schools, community centres, and word of mouth. The intervention, delivered over 20 weeks, consisted of a face-to-face meeting with the parent/caregiver and the child to deliver intervention content, which focused on training and educating them to use a wide range of strategies designed to reduce their child's screen time. Families were given Time Machine TV monitoring devices to assist with allocating screen time, activity packages to promote alternative activities, online support via a website, and monthly newsletters. Control participants were given the intervention material on completion of follow-up. The primary outcome was change in children's BMI z-score from baseline to 24 weeks. Children (n = 251) aged 9-12 years and their primary caregiver were randomized to receive the SWITCH intervention (n = 127) or no intervention (controls; n = 124). There was no significant difference in change of zBMI between the intervention and control groups, although a favorable trend was observed (-0.016; 95% CI: -0.084, 0.051; p = 0.64). There were also no significant differences on secondary outcomes, except for a trend towards

Evolution of poor reporting and inadequate methods over time in 20 920 randomised controlled trials included in Cochrane reviews: research on research study.

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Dechartres, Agnes; Trinquart, Ludovic; Atal, Ignacio; Moher, David; Dickersin, Kay; Boutron, Isabelle; Perrodeau, Elodie; Altman, Douglas G; Ravaud, Philippe

2017-06-08

Objective  To examine how poor reporting and inadequate methods for key methodological features in randomised controlled trials (RCTs) have changed over the past three decades. Design  Mapping of trials included in Cochrane reviews. Data sources  Data from RCTs included in all Cochrane reviews published between March 2011 and September 2014 reporting an evaluation of the Cochrane risk of bias items: sequence generation, allocation concealment, blinding, and incomplete outcome data. Data extraction  For each RCT, we extracted consensus on risk of bias made by the review authors and identified the primary reference to extract publication year and journal. We matched journal names with Journal Citation Reports to get 2014 impact factors. Main outcomes measures  We considered the proportions of trials rated by review authors at unclear and high risk of bias as surrogates for poor reporting and inadequate methods, respectively. Results  We analysed 20 920 RCTs (from 2001 reviews) published in 3136 journals. The proportion of trials with unclear risk of bias was 48.7% for sequence generation and 57.5% for allocation concealment; the proportion of those with high risk of bias was 4.0% and 7.2%, respectively. For blinding and incomplete outcome data, 30.6% and 24.7% of trials were at unclear risk and 33.1% and 17.1% were at high risk, respectively. Higher journal impact factor was associated with a lower proportion of trials at unclear or high risk of bias. The proportion of trials at unclear risk of bias decreased over time, especially for sequence generation, which fell from 69.1% in 1986-1990 to 31.2% in 2011-14 and for allocation concealment (70.1% to 44.6%). After excluding trials at unclear risk of bias, use of inadequate methods also decreased over time: from 14.8% to 4.6% for sequence generation and from 32.7% to 11.6% for allocation concealment. Conclusions  Poor reporting and inadequate methods have decreased over time, especially for sequence generation

A Smart Washer for Bolt Looseness Monitoring Based on Piezoelectric Active Sensing Method

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Heyue Yin

2016-10-01

Full Text Available Piezoceramic based active sensing methods have been researched to monitor preload on bolt connections. However, there is a saturation problem involved with this type of method. The transmitted energy is sometimes saturated before the maximum preload which is due to it coming into contact with flat surfaces. When it comes to flat contact surfaces, the true contact area will easily saturate with the preload. The design of a new type of bolt looseness monitoring sensor, a smart washer, is to mitigate the saturation problem. The smart washer is composed of two annular disks with contact surfaces that are machined into convex and concave respectively, to eliminate the complete flat contact surfaces and to reduce the saturation effect. One piezoelectric patch is bonded on the non-contact surface of each annular disk. These two mating annular disks form a smart washer. One of the two piezoelectric patches serves as an actuator to generate an ultrasonic wave that propagates through the contact surface; the other one serves as a sensor to detect the propagated waves. The wave energy propagated through the contact surface is proportional to the true contact area which is determined by the bolt preload. The time reversal method is used to extract the peak of the focused signal as the index of the transmission wave energy; then, the relationship between the signal peak and bolt preload is obtained. Experimental results show that the focused signal peak value changes with the bolt preload and presents an approximate linear relationship when the saturation problem is experienced. The proposed smart washer can monitor the full range of the rated preload.

A scientific nutrition strategy improves time trial performance by ≈6% when compared with a self-chosen nutrition strategy in trained cyclists: a randomized cross-over study.

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Hottenrott, Kuno; Hass, Erik; Kraus, Manon; Neumann, Georg; Steiner, Martin; Knechtle, Beat

2012-08-01

We investigated whether an athlete's self-chosen nutrition strategy (A), compared with a scientifically determined one (S), led to an improved endurance performance in a laboratory time trial after an endurance exercise. S consisted of about 1000 mL·h(-1) fluid, in portions of 250 mL every 15 min, 0.5 g sodium·L(-1), 60 g glucose·h(-1), 30 g fructose·h(-1), and 5 mg caffeine·kg body mass(-1). Eighteen endurance-trained cyclists (16 male; 2 female) were tested using a randomized crossover-design at intervals of 2 weeks, following either A or S. After a warm-up, a maximal oxygen uptake test was performed. Following a 30-min break, a 2.5-h endurance exercise on a bicycle ergometer was carried out at 70% maximal oxygen uptake. After 5 min of rest, a time trial of 64.37 km (40 miles) was completed. The ingested nutrition was recorded every 15 min. In S, the athletes completed the time trial faster (128 vs. 136 min; p ≤ 0.001) and with a significantly higher power output (212 vs. 184 W; p ≤ 0.001). The intake of fluid, energy (carbohydrate-, mono-, and disaccharide), and sodium was significantly higher in S compared with A (p ≤ 0.001) during the endurance exercise. In the time trial, only sodium intake was significantly higher in S (p ≤ 0.001). We concluded that a time trial performance after a 2.5-h endurance exercise in a laboratory setting was significantly improved following a scientific nutrition strategy.

Massed Trials versus Trials Embedded into Game Play: Child Outcomes and Preference

Science.gov (United States)

Ledford, Jennifer R.; Chazin, Kate T.; Harbin, Emilee R.; Ward, Sarah E.

2017-01-01

Limited data are available regarding how response prompting procedures should be used in early childhood settings. The purpose of this study was to compare the efficiency of progressive time delay instruction presented via two trial arrangements: massed and embedded. During massed trial sessions, a short instructional session was conducted,…

Does Fidelity of Implementation Account for Changes in Teacher-Child Interactions in a Randomized Controlled Trial of Banking Time?

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LoCasale-Crouch, Jennifer; Williford, Amanda; Whittaker, Jessica; DeCoster, Jamie; Alamos, Pilar

2018-01-01

This study examined fidelity of implementation in a randomized trial of Banking Time, a classroom-based intervention intended to improve children's behavior, specifically for those at risk for developing externalizing behavior problems, through improving the quality of teacher-child interactions. The study sample comes from a randomized controlled…

End points for adjuvant therapy trials: has the time come to accept disease-free survival as a surrogate end point for overall survival?

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Gill, Sharlene; Sargent, Daniel

2006-06-01

The intent of adjuvant therapy is to eradicate micro-metastatic residual disease following curative resection with the goal of preventing or delaying recurrence. The time-honored standard for demonstrating efficacy of new adjuvant therapies is an improvement in overall survival (OS). This typically requires phase III trials of large sample size with lengthy follow-up. With the intent of reducing the cost and time of completing such trials, there is considerable interest in developing alternative or surrogate end points. A surrogate end point may be employed as a substitute to directly assess the effects of an intervention on an already accepted clinical end point such as mortality. When used judiciously, surrogate end points can accelerate the evaluation of new therapies, resulting in the more timely dissemination of effective therapies to patients. The current review provides a perspective on the suitability and validity of disease-free survival (DFS) as an alternative end point for OS. Criteria for establishing surrogacy and the advantages and limitations associated with the use of DFS as a primary end point in adjuvant clinical trials and as the basis for approval of new adjuvant therapies are discussed.

Using sit-stand workstations to decrease sedentary time in office workers: a randomized crossover trial.

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Dutta, Nirjhar; Koepp, Gabriel A; Stovitz, Steven D; Levine, James A; Pereira, Mark A

2014-06-25

This study was conducted to determine whether installation of sit-stand desks (SSDs) could lead to decreased sitting time during the workday among sedentary office workers. A randomized cross-over trial was conducted from January to April, 2012 at a business in Minneapolis. 28 (nine men, 26 full-time) sedentary office workers took part in a 4 week intervention period which included the use of SSDs to gradually replace 50% of sitting time with standing during the workday. Physical activity was the primary outcome. Mood, energy level, fatigue, appetite, dietary intake, and productivity were explored as secondary outcomes. The intervention reduced sitting time at work by 21% (95% CI 18%-25%) and sedentary time by 4.8 min/work-hr (95% CI 4.1-5.4 min/work-hr). For a 40 h work-week, this translates into replacement of 8 h of sitting time with standing and sedentary time being reduced by 3.2 h. Activity level during non-work hours did not change. The intervention also increased overall sense of well-being, energy, decreased fatigue, had no impact on productivity, and reduced appetite and dietary intake. The workstations were popular with the participants. The SSD intervention was successful in increasing work-time activity level, without changing activity level during non-work hours.

Sample size for comparing negative binomial rates in noninferiority and equivalence trials with unequal follow-up times.

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Tang, Yongqiang

2017-05-25

We derive the sample size formulae for comparing two negative binomial rates based on both the relative and absolute rate difference metrics in noninferiority and equivalence trials with unequal follow-up times, and establish an approximate relationship between the sample sizes required for the treatment comparison based on the two treatment effect metrics. The proposed method allows the dispersion parameter to vary by treatment groups. The accuracy of these methods is assessed by simulations. It is demonstrated that ignoring the between-subject variation in the follow-up time by setting the follow-up time for all individuals to be the mean follow-up time may greatly underestimate the required size, resulting in underpowered studies. Methods are provided for back-calculating the dispersion parameter based on the published summary results.

Cross-Over Clinical Trials?

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Latif Gachkar

2017-01-01

Full Text Available Abstract Cross-Over Clinical Trials in comparison with Parallel groups clinical trials have some advantages such as control of confounding variables, small sample size, and short time to implement the research project. But this type of research has few essential limitations that discusses in this monogram.

Impact of carbohydrate mouth rinsing on time to exhaustion during Ramadan: A randomized controlled trial in Jordanian men.

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Bataineh, Mo'ath F; Al-Nawaiseh, Ali M; Abu Altaieb, Mohammad H; Bellar, David M; Hindawi, Omar S; Judge, Lawrence W

2018-04-01

Mouth rinsing using a carbohydrate (CHO) solution has been suggested to improve physical performance in fasting participants. This study examined the effects of CHO mouth rinsing during Ramadan fasting on running time to exhaustion and on peak treadmill speed (V peak ). In a counterbalanced crossover design, 18 sub-elite male runners (Age: 21 ± 2 years, Weight: 68.1 ± 5.7 kg, VO 2max : 55.4 ± 4.8 ml/kg/min) who observed Ramadan completed a familiarization trial and three experimental trials. The three trials included rinsing and expectorating a 25 mL bolus of either a 7.5% sucrose solution (CHO), a flavour and taste matched placebo solution (PLA) for 10 s, or no rinse (CON). The treatments were performed prior to an incremental treadmill test to exhaustion. Three-day dietary and exercise records were obtained on two occasions and analysed. Anthropometric characteristics were obtained and recorded for all participants. A main effect for mouth rinse on peak velocity (V peak ) (CHO: 17.6 ± 1.5 km/h; PLA: 17.1 ± 1.4 km/h; CON: 16.7 ± 1.2 km/h; P  .05). Energy availability from dietary analysis, body weight, and fat-free mass did not change during the last two weeks of Ramadan (P > .05). This study concludes that carbohydrate mouth rinsing improves running time to exhaustion and peak treadmill speed under Ramadan fasting conditions.

Early diastolic time intervals during hypertensive pregnancy.

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Spinelli, L; Ferro, G; Nappi, C; Farace, M J; Talarico, G; Cinquegrana, G; Condorelli, M

1987-10-01

Early diastolic time intervals have been assessed by means of the echopolycardiographic method in 17 pregnant women who developed hypertension during pregnancy (HP) and in 14 normal pregnant women (N). Systolic time intervals (STI), stroke volume (SV), ejection fraction (EF), and mean velocity of myocardial fiber shortening (VCF) were also evaluated. Recordings were performed in the left lateral decubitus (LLD) and then in the supine decubitus (SD). In LLD, isovolumic relaxation period (IRP) was prolonged in the hypertensive pregnant women compared with normal pregnant women (HP 51 +/- 12.5 ms, N 32.4 +/- 15 ms p less than 0.05), whereas time of the mitral valve maximum opening (DE) was not different in the groups. There was no difference in SV, EF, and mean VCF, whereas STI showed only a significant (p less than 0.05) lengthening of pre-ejection period (PEP) in HP. When the subjects shifted from the left lateral to the supine decubitus position, left ventricular ejection time index (LVETi) and SV decreased significantly (p less than 0.05) in both normotensive hypertensive pregnant women. IRP and PEP lengthened significantly (p less than 0.05) only in normals, whereas they were unchanged in HP. DE time did not vary in either group. In conclusion, hypertension superimposed on pregnancy induces lengthening of IRP, as well as of PEP, and minimizes the effects of the postural changes in preload on the above-mentioned time intervals.

Differential Globalization of Industry- and Non-Industry-Sponsored Clinical Trials.

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Atal, Ignacio; Trinquart, Ludovic; Porcher, Raphaël; Ravaud, Philippe

2015-01-01

Mapping the international landscape of clinical trials may inform global health research governance, but no large-scale data are available. Industry or non-industry sponsorship may have a major influence in this mapping. We aimed to map the global landscape of industry- and non-industry-sponsored clinical trials and its evolution over time. We analyzed clinical trials initiated between 2006 and 2013 and registered in the WHO International Clinical Trials Registry Platform (ICTRP). We mapped single-country and international trials by World Bank's income groups and by sponsorship (industry- vs. non- industry), including its evolution over time from 2006 to 2012. We identified clusters of countries that collaborated significantly more than expected in industry- and non-industry-sponsored international trials. 119,679 clinical trials conducted in 177 countries were analysed. The median number of trials per million inhabitants in high-income countries was 100 times that in low-income countries (116.0 vs. 1.1). Industry sponsors were involved in three times more trials per million inhabitants than non-industry sponsors in high-income countries (75.0 vs. 24.5) and in ten times fewer trials in low- income countries (0.08 vs. 1.08). Among industry- and non-industry-sponsored trials, 30.3% and 3.2% were international, respectively. In the industry-sponsored network of collaboration, Eastern European and South American countries collaborated more than expected; in the non-industry-sponsored network, collaboration among Scandinavian countries was overrepresented. Industry-sponsored international trials became more inter-continental with time between 2006 and 2012 (from 54.8% to 67.3%) as compared with non-industry-sponsored trials (from 42.4% to 37.2%). Based on trials registered in the WHO ICTRP we documented a substantial gap between the globalization of industry- and non-industry-sponsored clinical research. Only 3% of academic trials but 30% of industry trials are

Differential Globalization of Industry- and Non-Industry–Sponsored Clinical Trials

Science.gov (United States)

Atal, Ignacio; Trinquart, Ludovic; Porcher, Raphaël; Ravaud, Philippe

2015-01-01

Background Mapping the international landscape of clinical trials may inform global health research governance, but no large-scale data are available. Industry or non-industry sponsorship may have a major influence in this mapping. We aimed to map the global landscape of industry- and non-industry–sponsored clinical trials and its evolution over time. Methods We analyzed clinical trials initiated between 2006 and 2013 and registered in the WHO International Clinical Trials Registry Platform (ICTRP). We mapped single-country and international trials by World Bank's income groups and by sponsorship (industry- vs. non- industry), including its evolution over time from 2006 to 2012. We identified clusters of countries that collaborated significantly more than expected in industry- and non-industry–sponsored international trials. Results 119,679 clinical trials conducted in 177 countries were analysed. The median number of trials per million inhabitants in high-income countries was 100 times that in low-income countries (116.0 vs. 1.1). Industry sponsors were involved in three times more trials per million inhabitants than non-industry sponsors in high-income countries (75.0 vs. 24.5) and in ten times fewer trials in low- income countries (0.08 vs. 1.08). Among industry- and non-industry–sponsored trials, 30.3% and 3.2% were international, respectively. In the industry-sponsored network of collaboration, Eastern European and South American countries collaborated more than expected; in the non-industry–sponsored network, collaboration among Scandinavian countries was overrepresented. Industry-sponsored international trials became more inter-continental with time between 2006 and 2012 (from 54.8% to 67.3%) as compared with non-industry–sponsored trials (from 42.4% to 37.2%). Conclusions Based on trials registered in the WHO ICTRP we documented a substantial gap between the globalization of industry- and non-industry–sponsored clinical research. Only 3% of

Peer-mentoring for first-time mothers from areas of socio-economic disadvantage: A qualitative study within a randomised controlled trial

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Halliday Henry L

2008-02-01

Full Text Available Abstract Background Non-professional involvement in delivering health and social care support in areas of socio-economic deprivation is considered important in attempting to reduce health inequalities. However, trials of peer mentoring programmes have yielded inconsistent evidence of benefit: difficulties in implementation have contributed to uncertainty regarding their efficacy. We aimed to explore difficulties encountered in conducting a randomised controlled trial of a peer-mentoring programme for first-time mothers in socially disadvantaged areas, in order to provide information relevant to future research and practice. This paper describes the experiences of lay-workers, women and health professionals involved in the trial. Methods Thematic analysis of semi-structured interviews with women (n = 11 who were offered peer mentor support, lay-workers (n = 11 who provided mentoring and midwives (n = 2 who supervised the programme, which provided support, from first hospital antenatal visit to one year postnatal. Planned frequency of contact was two-weekly (telephone or home visit but was tailored to individuals' needs. Results Despite lay-workers living in the same locality, they experienced difficulty initiating contact with women and this affected their morale adversely. Despite researchers' attempts to ensure that the role of the mentor was understood clearly it appeared that this was not achieved for all participants. Mentors attempted to develop peer-mentor relationships by offering friendship and sharing personal experiences, which was appreciated by women. Mentors reported difficulties developing relationships with those who lacked interest in the programme. External influences, including family and friends, could prevent or facilitate mentoring. Time constraints in reconciling flexible mentoring arrangements with demands of other commitments posed major personal difficulties for lay-workers. Conclusion Difficulties in initiating contact

The effects of the Bowen technique on hamstring flexibility over time: a randomised controlled trial.

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Marr, Michelle; Baker, Julian; Lambon, Nicky; Perry, Jo

2011-07-01

The hamstring muscles are regularly implicated in recurrent injuries, movement dysfunction and low back pain. Links between limited flexibility and development of neuromusculoskeletal symptoms are frequently reported. The Bowen Technique is used to treat many conditions including lack of flexibility. The study set out to investigate the effect of the Bowen Technique on hamstring flexibility over time. An assessor-blind, prospective, randomised controlled trial was performed on 120 asymptomatic volunteers. Participants were randomly allocated into a control group or Bowen group. Three flexibility measurements occurred over one week, using an active knee extension test. The intervention group received a single Bowen treatment. A repeated measures univariate analysis of variance, across both groups for the three time periods, revealed significant within-subject and between-subject differences for the Bowen group. Continuing increases in flexibility levels were observed over one week. No significant change over time was noted for the control group. Copyright © 2010 Elsevier Ltd. All rights reserved.

A Randomized Controlled Trial Evaluation of "Time to Read", a Volunteer Tutoring Program for 8- to 9-Year-Olds

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Miller, Sarah; Connolly, Paul

2013-01-01

Tutoring is commonly employed to prevent early reading failure, and evidence suggests that it can have a positive effect. This article presents findings from a large-scale ("n" = 734) randomized controlled trial evaluation of the effect of "Time to Read"--a volunteer tutoring program aimed at children aged 8 to 9 years--on…

Understanding inhibitory mechanisms of lumbar spinal manipulation using H-reflex and F-wave responses: a methodological approach.

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Dishman, J Donald; Weber, Kenneth A; Corbin, Roger L; Burke, Jeanmarie R

2012-09-30

The purpose of this research was to characterize unique neurophysiologic events following a high velocity, low amplitude (HVLA) spinal manipulation (SM) procedure. Descriptive time series analysis techniques of time plots, outlier detection and autocorrelation functions were applied to time series of tibial nerve H-reflexes that were evoked at 10-s intervals from 100 s before the event until 100 s after three distinct events L5-S1 HVLA SM, or a L5-S1 joint pre-loading procedure, or the control condition. Sixty-six subjects were randomly assigned to three procedures, i.e., 22 time series per group. If the detection of outliers and correlograms revealed a pattern of non-randomness that was only time-locked to a single, specific event in the normalized time series, then an experimental effect would be inferred beyond the inherent variability of H-reflex responses. Tibial nerve F-wave responses were included to determine if any new information about central nervous function following a HVLA SM procedure could be ascertained. Time series analyses of H(max)/M(max) ratios, pre-post L5-S1 HVLA SM, substantiated the hypothesis that the specific aspects of the manipulative thrust lead to a greater attenuation of the H(max)/M(max) ratio as compared to the non-specific aspects related to the postural perturbation and joint pre-loading. The attenuation of the H(max)/M(max) ratio following the HVLA SM procedure was reliable and may hold promise as a translational tool to measure the consistency and accuracy of protocol implementation involving SM in clinical trials research. F-wave responses were not sensitive to mechanical perturbations of the lumbar spine. Copyright © 2012 Elsevier B.V. All rights reserved.

[Doppler echocardiographic investigation of left ventricular diastolic function in preterm infants with and without a patent ductus arteriosus].

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Schmitz, L; Stiller, B; Koehne, P; Koch, H; Lange, P E

2004-01-01

We studied the influence of preload augmentation on Doppler-derived left ventricular diastolic function parameters in infants with a birth weight ductus arteriosus a complete echocardiographic study including Doppler investigations of the mitral inflow signals and analysis of diastolic time intervals was performed. Neonates with an open duct had a lower median gestational age (27.1 vs. 29, Pductus peak early filling velocity (41.2 vs. 30.4 cm, Pventricular diastolic failure in extremely low birth weight infants in the presence of a preload challenge. The coincidence of higher peak velocities with a shortened isovolumic relaxation time is very likely a result of left atrial pressure elevation. Preload mismatch has to be considered in preterm infants with a persistent ductus arteriosus. The results of this study can be helpful to find the indication for PDA-closure and to adjust volume replacement therapy, and catecholamine medication to a level appropriate for the individual cardiac performance.

Measurement error, time lag, unmeasured confounding: Considerations for longitudinal estimation of the effect of a mediator in randomised clinical trials.

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Goldsmith, K A; Chalder, T; White, P D; Sharpe, M; Pickles, A

2018-06-01

Clinical trials are expensive and time-consuming and so should also be used to study how treatments work, allowing for the evaluation of theoretical treatment models and refinement and improvement of treatments. These treatment processes can be studied using mediation analysis. Randomised treatment makes some of the assumptions of mediation models plausible, but the mediator-outcome relationship could remain subject to bias. In addition, mediation is assumed to be a temporally ordered longitudinal process, but estimation in most mediation studies to date has been cross-sectional and unable to explore this assumption. This study used longitudinal structural equation modelling of mediator and outcome measurements from the PACE trial of rehabilitative treatments for chronic fatigue syndrome (ISRCTN 54285094) to address these issues. In particular, autoregressive and simplex models were used to study measurement error in the mediator, different time lags in the mediator-outcome relationship, unmeasured confounding of the mediator and outcome, and the assumption of a constant mediator-outcome relationship over time. Results showed that allowing for measurement error and unmeasured confounding were important. Contemporaneous rather than lagged mediator-outcome effects were more consistent with the data, possibly due to the wide spacing of measurements. Assuming a constant mediator-outcome relationship over time increased precision.

Aerodynamic study of time-trial helmets in cycling racing using CFD analysis.

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Beaumont, F; Taiar, R; Polidori, G; Trenchard, H; Grappe, F

2018-01-23

The aerodynamic drag of three different time-trial cycling helmets was analyzed numerically for two different cyclist head positions. Computational Fluid Dynamics (CFD) methods were used to investigate the detailed airflow patterns around the cyclist for a constant velocity of 15 m/s without wind. The CFD simulations have focused on the aerodynamic drag effects in terms of wall shear stress maps and pressure coefficient distributions on the cyclist/helmet system. For a given head position, the helmet shape, by itself, obtained a weak effect on a cyclist's aerodynamic performance (CFD results have also shown that both helmet shape and head position significantly influence drag forces, pressure and wall shear stress distributions on the whole cyclist's body due to the change in the near-wake behavior and in location of corresponding separation and attachment areas around the cyclist. Copyright © 2017 Elsevier Ltd. All rights reserved.

Using Sit-Stand Workstations to Decrease Sedentary Time in Office Workers: A Randomized Crossover Trial

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Nirjhar Dutta

2014-06-01

Full Text Available Objective: This study was conducted to determine whether installation of sit-stand desks (SSDs could lead to decreased sitting time during the workday among sedentary office workers. Methods: A randomized cross-over trial was conducted from January to April, 2012 at a business in Minneapolis. 28 (nine men, 26 full-time sedentary office workers took part in a 4 week intervention period which included the use of SSDs to gradually replace 50% of sitting time with standing during the workday. Physical activity was the primary outcome. Mood, energy level, fatigue, appetite, dietary intake, and productivity were explored as secondary outcomes. Results: The intervention reduced sitting time at work by 21% (95% CI 18%–25% and sedentary time by 4.8 min/work-hr (95% CI 4.1–5.4 min/work-hr. For a 40 h work-week, this translates into replacement of 8 h of sitting time with standing and sedentary time being reduced by 3.2 h. Activity level during non-work hours did not change. The intervention also increased overall sense of well-being, energy, decreased fatigue, had no impact on productivity, and reduced appetite and dietary intake. The workstations were popular with the participants. Conclusion: The SSD intervention was successful in increasing work-time activity level, without changing activity level during non-work hours.

Time flies faster under time pressure.

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Rattat, Anne-Claire; Matha, Pauline; Cegarra, Julien

2018-04-01

We examined the effects of time pressure on duration estimation in a verbal estimation task and a production task. In both temporal tasks, participants had to solve mazes in two conditions of time pressure (with or without), and with three different target durations (30 s, 60 s, and 90 s). In each trial of the verbal estimation task, participants had to estimate in conventional time units (minutes and seconds) the amount of time that had elapsed since they started to solve the maze. In the production task, they had to press a key while solving the maze when they thought that the trial's duration had reached a target value. Results showed that in both tasks, durations were judged longer with time pressure than without it. However, this temporal overestimation under time pressure did not increase with the length of the target duration. These results are discussed within the framework of scalar expectancy theory. Copyright © 2018 Elsevier B.V. All rights reserved.

Implicit and explicit timing in oculomotor control.

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Ilhame Ameqrane

Full Text Available The passage of time can be estimated either explicitly, e.g. before leaving home in the morning, or implicitly, e.g. when catching a flying ball. In the present study, the latency of saccadic eye movements was used to evaluate differences between implicit and explicit timing. Humans were required to make a saccade between a central and a peripheral position on a computer screen. The delay between the extinction of a central target and the appearance of an eccentric target was the independent variable that could take one out of four different values (400, 900, 1400 or 1900 ms. In target trials, the delay period lasted for one of the four durations randomly. At the end of the delay, a saccade was initiated by the appearance of an eccentric target. Cue&target trials were similar to target trials but the duration of the delay was visually cued. In probe trials, the duration of the upcoming delay was cued, but there was no eccentric target and subjects had to internally generate a saccade at the estimated end of the delay. In target and cue&target trials, the mean and variance of latency distributions decreased as delay duration increased. In cue&target trials latencies were shorter. In probe trials, the variance increased with increasing delay duration and scalar variability was observed. The major differences in saccadic latency distributions were observed between visually-guided (target and cue&target trials and internally-generated saccades (probe trials. In target and cue&target trials the timing of the response was implicit. In probe trials, the timing of the response was internally-generated and explicitly based on the duration of the visual cue. Scalar timing was observed only during probe trials. This study supports the hypothesis that there is no ubiquitous timing system in the brain but independent timing processes active depending on task demands.

Midwives conducting perineal repair: The Danish Suture Trial

DEFF Research Database (Denmark)

Kindberg, Sara

2007-01-01

Midwives conducting perineal repair: The Danish Suture Trial.     Background Suture techniques and materials for repair of 2nd degree perineal lacerations and episiotomies have been tested in several clinical trials. Danish midwives and obstetricians have developed a new, simple and time-efficien......Midwives conducting perineal repair: The Danish Suture Trial.     Background Suture techniques and materials for repair of 2nd degree perineal lacerations and episiotomies have been tested in several clinical trials. Danish midwives and obstetricians have developed a new, simple and time...

Clinical trials in dentistry in India: Analysis from trial registry.

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Gowri, S; Kannan, Sridharan

2017-01-01

Evidence-based practice requires clinical trials to be performed. In India, if any clinical trial has to be performed, it has to be registered with clinical trial registry of India. Studies have shown that the report of clinical trials is poor in dentistry. Hence, the present study has been conducted to assess the type and trends of clinical trials being undertaken in dentistry in India over a span of 6 years. All the clinical trials which were registered with the Central Trial Registry of India (CTRI) (www.ctri.nic.in) from January 1, 2007 to March 3, 2014 were evaluated using the keyword "dental." Following information were collected for each of the clinical trials obtained from the search; number of centres (single center/multicentric), type of the institution undertaking the research (government/private/combined), study (observational/interventional), study design (randomized/single blinded/double-blinded), type of health condition, type of participants (healthy/patients), sponsors (academia/commercial), phase of clinical trial (Phase 1/2/3/4), publication details (published/not published), whether it was a postgraduate thesis or not and prospective or retrospective registration of clinical trials, methodological quality (method of randomization, allocation concealment). Descriptive statistics was used for analysis of various categories. Trend analysis was done to assess the changes over a period of time. The search yielded a total of 84 trials of which majority of them were single centered. Considering the study design more than half of the registered clinical trials were double-blinded (47/84 [56%]). With regard to the place of conducting a trial, most of the trials were planned to be performed in private hospitals (56/84 [66.7%]). Most (79/84, 94.1%) of the clinical trials were interventional while only 5/84 (5.9%) were observational. Majority (65/84, 77.4%) of the registered clinical trials were recruiting patients while the rest were being done in healthy

Trial of real-time locating and messaging system with Bluetooth low energy.

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Arisaka, Naoya; Mamorita, Noritaka; Isonaka, Risa; Kawakami, Tadashi; Takeuchi, Akihiro

2016-09-14

Hospital real-time location systems (RTLS) are increasing efficiency and reducing operational costs, but room access tags are necessary. We developed three iPhone 5 applications for an RTLS and communications using Bluetooth low energy (BLE). The applications were: Peripheral device tags, Central beacons, and a Monitor. A Peripheral communicated with a Central using BLE. The Central communicated with a Monitor using sockets on TCP/IP (Transmission Control Protocol/Internet Protocol) via a WLAN (wireless local area network). To determine a BLE threshold level for the received signal strength indicator (RSSI), relationships between signal strength and distance were measured in our laboratory and on the terrace. The BLE RSSI threshold was set at -70 dB, about 10 m. While an individual with a Peripheral moved around in a concrete building, the Peripheral was captured in a few 10-sec units at about 10 m from a Central. The Central and Monitor showed and saved the approach events, location, and Peripheral's nickname sequentially in real time. Remote Centrals also interactively communicate with Peripherals by intermediating through Monitors that found the nickname in the event database. Trial applications using BLE on iPhones worked well for patient tracking, and messaging in indoor environments.

Analysis of Factors Affecting Successful Clinical Trial Enrollment in the Context of Three Prospective, Randomized, Controlled Trials

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Logan, Jennifer K.; Tang, Chad; Liao, Zhongxing [Department of Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas (United States); Lee, J. Jack [Department of Biostatistics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas (United States); Heymach, John V. [Department of Thoracic/Head and Neck Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas (United States); Swisher, Stephen G. [Department of Surgical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas (United States); Welsh, James W. [Department of Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas (United States); Zhang, Jianjun [Department of Thoracic/Head and Neck Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas (United States); Lin, Steven H. [Department of Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas (United States); Gomez, Daniel R., E-mail: dgomez@mdanderson.org [Department of Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas (United States)

2017-03-15

Purpose: Challenges can arise when attempting to maximize patient enrollment in clinical trials. There have been limited studies focusing on the barriers to enrollment and the efficacy of alternative study design to improve accrual. We analyzed barriers to clinical trial enrollment, particularly the influence of timing, in context of three prospective, randomized oncology trials where one arm was considered more aggressive than the other. Methods and Materials: From June 2011 to March 2015, patients who were enrolled on 3 prospective institutional protocols (an oligometastatic non-small cell lung cancer [NSCLC] trial and 2 proton vs intensity modulated radiation therapy trials in NSCLC and esophageal cancer) were screened for protocol eligibility. Eligible candidates were approached about trial participation, and patient characteristics (age, sex, T/N categorization) were recorded along with details surrounding trial presentation (appointment number). Fisher's exact test, Student's t tests, and multivariate analysis were performed to assess differences between enrolled and refusal patients. Results: A total of 309 eligible patients were approached about trial enrollment. The enrollment success rate during this time span was 52% (n=160 patients). Enrolled patients were more likely to be presented trial information at an earlier appointment (oligometastatic protocol: 5 vs 3 appointments [P<.001]; NSCLC protocol: 4 vs 3 appointments [P=.0018]; esophageal protocol: 3 vs 2 appointments [P=.0086]). No other factors or patient characteristics significantly affected enrollment success rate. Conclusion: Improvement in enrollment rates for randomized control trials is possible, even in difficult accrual settings. Earlier presentation of trial information to patients is the most influential factor for success and may help overcome accrual barriers without compromising trial design.

Analysis of Factors Affecting Successful Clinical Trial Enrollment in the Context of Three Prospective, Randomized, Controlled Trials

International Nuclear Information System (INIS)

Logan, Jennifer K.; Tang, Chad; Liao, Zhongxing; Lee, J. Jack; Heymach, John V.; Swisher, Stephen G.; Welsh, James W.; Zhang, Jianjun; Lin, Steven H.; Gomez, Daniel R.

2017-01-01

Purpose: Challenges can arise when attempting to maximize patient enrollment in clinical trials. There have been limited studies focusing on the barriers to enrollment and the efficacy of alternative study design to improve accrual. We analyzed barriers to clinical trial enrollment, particularly the influence of timing, in context of three prospective, randomized oncology trials where one arm was considered more aggressive than the other. Methods and Materials: From June 2011 to March 2015, patients who were enrolled on 3 prospective institutional protocols (an oligometastatic non-small cell lung cancer [NSCLC] trial and 2 proton vs intensity modulated radiation therapy trials in NSCLC and esophageal cancer) were screened for protocol eligibility. Eligible candidates were approached about trial participation, and patient characteristics (age, sex, T/N categorization) were recorded along with details surrounding trial presentation (appointment number). Fisher's exact test, Student's t tests, and multivariate analysis were performed to assess differences between enrolled and refusal patients. Results: A total of 309 eligible patients were approached about trial enrollment. The enrollment success rate during this time span was 52% (n=160 patients). Enrolled patients were more likely to be presented trial information at an earlier appointment (oligometastatic protocol: 5 vs 3 appointments [P<.001]; NSCLC protocol: 4 vs 3 appointments [P=.0018]; esophageal protocol: 3 vs 2 appointments [P=.0086]). No other factors or patient characteristics significantly affected enrollment success rate. Conclusion: Improvement in enrollment rates for randomized control trials is possible, even in difficult accrual settings. Earlier presentation of trial information to patients is the most influential factor for success and may help overcome accrual barriers without compromising trial design.

The role of treatment timing and mode of stimulation in the treatment of primary dysmenorrhea with acupuncture: An exploratory randomised controlled trial

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Dahlen, Hannah G.; Zhu, Xiaoshu; Farquhar, Cindy; Smith, Caroline A.

2017-01-01

Objectives We examined the effect of changing treatment timing and the use of manual, electro acupuncture on the symptoms of primary dysmenorrhea. Methods A randomised controlled trial was performed with four arms, low frequency manual acupuncture (LF-MA), high frequency manual acupuncture (HF-MA), low frequency electro acupuncture (LF-EA) and high frequency electro acupuncture (HF-EA). A manualised trial protocol was used to allow differentiation and individualized treatment over three months. A total of 74 women were randomly assigned to one of the four groups (LF-MA n = 19, HF-MA n = 18, LF-EA n = 18, HF-EA n = 19). Twelve treatments were performed over three menstrual cycles, either once per week (LF groups) or three times in the week prior to menses (HF groups). All groups received a treatment in the first 48 hours of menses. The primary outcome was the reduction in peak menstrual pain at 12 months from trial entry. Results During the treatment period and nine month follow-up all groups showed statistically significant (p 0.05). Health related quality of life increased significantly in six domains in groups having high frequency of treatment compared to two domains in low frequency groups. Manual acupuncture groups required less analgesic medication than electro-acupuncture groups (p = 0.02). HF-MA was most effective in reducing secondary menstrual symptoms compared to both–EA groups (p<0.05). Conclusion Acupuncture treatment reduced menstrual pain intensity and duration after three months of treatment and this was sustained for up to one year after trial entry. The effect of changing mode of stimulation or frequency of treatment on menstrual pain was not significant. This may be due to a lack of power. The role of acupuncture stimulation on menstrual pain needs to be investigated in appropriately powered randomised controlled trials. PMID:28700680

The role of treatment timing and mode of stimulation in the treatment of primary dysmenorrhea with acupuncture: An exploratory randomised controlled trial.

Directory of Open Access Journals (Sweden)

Mike Armour

Full Text Available We examined the effect of changing treatment timing and the use of manual, electro acupuncture on the symptoms of primary dysmenorrhea.A randomised controlled trial was performed with four arms, low frequency manual acupuncture (LF-MA, high frequency manual acupuncture (HF-MA, low frequency electro acupuncture (LF-EA and high frequency electro acupuncture (HF-EA. A manualised trial protocol was used to allow differentiation and individualized treatment over three months. A total of 74 women were randomly assigned to one of the four groups (LF-MA n = 19, HF-MA n = 18, LF-EA n = 18, HF-EA n = 19. Twelve treatments were performed over three menstrual cycles, either once per week (LF groups or three times in the week prior to menses (HF groups. All groups received a treatment in the first 48 hours of menses. The primary outcome was the reduction in peak menstrual pain at 12 months from trial entry.During the treatment period and nine month follow-up all groups showed statistically significant (p 0.05. Health related quality of life increased significantly in six domains in groups having high frequency of treatment compared to two domains in low frequency groups. Manual acupuncture groups required less analgesic medication than electro-acupuncture groups (p = 0.02. HF-MA was most effective in reducing secondary menstrual symptoms compared to both-EA groups (p<0.05.Acupuncture treatment reduced menstrual pain intensity and duration after three months of treatment and this was sustained for up to one year after trial entry. The effect of changing mode of stimulation or frequency of treatment on menstrual pain was not significant. This may be due to a lack of power. The role of acupuncture stimulation on menstrual pain needs to be investigated in appropriately powered randomised controlled trials.

The role of treatment timing and mode of stimulation in the treatment of primary dysmenorrhea with acupuncture: An exploratory randomised controlled trial.

Science.gov (United States)

Armour, Mike; Dahlen, Hannah G; Zhu, Xiaoshu; Farquhar, Cindy; Smith, Caroline A

2017-01-01

We examined the effect of changing treatment timing and the use of manual, electro acupuncture on the symptoms of primary dysmenorrhea. A randomised controlled trial was performed with four arms, low frequency manual acupuncture (LF-MA), high frequency manual acupuncture (HF-MA), low frequency electro acupuncture (LF-EA) and high frequency electro acupuncture (HF-EA). A manualised trial protocol was used to allow differentiation and individualized treatment over three months. A total of 74 women were randomly assigned to one of the four groups (LF-MA n = 19, HF-MA n = 18, LF-EA n = 18, HF-EA n = 19). Twelve treatments were performed over three menstrual cycles, either once per week (LF groups) or three times in the week prior to menses (HF groups). All groups received a treatment in the first 48 hours of menses. The primary outcome was the reduction in peak menstrual pain at 12 months from trial entry. During the treatment period and nine month follow-up all groups showed statistically significant (p 0.05). Health related quality of life increased significantly in six domains in groups having high frequency of treatment compared to two domains in low frequency groups. Manual acupuncture groups required less analgesic medication than electro-acupuncture groups (p = 0.02). HF-MA was most effective in reducing secondary menstrual symptoms compared to both-EA groups (p<0.05). Acupuncture treatment reduced menstrual pain intensity and duration after three months of treatment and this was sustained for up to one year after trial entry. The effect of changing mode of stimulation or frequency of treatment on menstrual pain was not significant. This may be due to a lack of power. The role of acupuncture stimulation on menstrual pain needs to be investigated in appropriately powered randomised controlled trials.

Ring trial 2016 for Bluetongue virus detection by real-time RT-PCR in France.

Science.gov (United States)

Sailleau, Corinne; Viarouge, Cyril; Breard, Emmanuel; Vitour, Damien; Zientara, Stephan

2017-05-01

Since the unexpected emergence of BTV-8 in Northern Europe and the incursion of BTV-8 and 1 in France in 2006-2007, molecular diagnosis has considerably evolved. Several real-time RT-PCR (rtRT-PCR) methods have been developed and published, and are currently being used in many countries across Europe for BTV detection and typing. In France, the national reference laboratory (NRL) for orbiviruses develops and validates 'ready-to-use' kits with private companies for viral RNA detection. The regional laboratories network that was set up to deal with a heavy demand for analyses has used these available kits. From 2007, ring tests were organized to monitor the performance of the French laboratories. This study presents the results of 63 regional laboratories in the ring trial organized in 2016. Blood samples were sent to the laboratories. Participants were asked to use the rtRT-PCR methods in place in their laboratory, for detection of all BTV serotypes and specifically BTV-8. The French regional laboratories are able to detect and genotype BTV in affected animals. Despite the use of several methods (i.e. RNA extraction and different commercial rtRT-PCRs), the network is homogeneous. The ring trial demonstrated that the French regional veterinary laboratories have reliable and robust BTV diagnostic tools for BTV genome detection.

Time to Angiographic Reperfusion and Clinical Outcome after Acute Ischemic Stroke in the Interventional Management of Stroke Phase III (IMS III) Trial: A Validation Study

Science.gov (United States)

Khatri, Pooja; Yeatts, Sharon D.; Mazighi, Mikael; Broderick, Joseph P.; Liebeskind, David S.; Demchuk, Andrew M.; Amarenco, Pierre; Carrozzella, Janice; Spilker, Judith; Foster, Lydia D.; Goyal, Mayank; Hill, Michael D.; Palesch, Yuko Y.; Jauch, Edward C.; Haley, E. Clarke; Vagal, Achala; Tomsick, Thomas A.

2014-01-01

BACKGROUND The IMS III Trial did not demonstrate clinical benefit of the endovascular approach compared to IV rt-PA alone for moderate or severe ischemic strokes (NIHSS≥8) enrolled within three hours of stroke onset. Late reperfusion of tissue that is no longer salvageable may be one explanation, as suggested by prior exploratory studies showing an association between time to reperfusion and good clinical outcome. We sought to validate this relationship in the large-scale IMS III trial, and consider its implications for future endovascular trials. METHODS The analysis consisted of the endovascular cohort with proximal arterial occlusions in the anterior circulation that achieved angiographic reperfusion (TICI 2–3) during the endovascular procedure (within 7 hours from the onset of symptoms). Logistic regression was used to model good clinical outcome (90-day modified Rankin 0–2) as a function of the time to reperfusion, and prespecified variables were considered for adjustment. FINDINGS Among 240 proximal vessel occlusions, angiographic reperfusion (TICI 2–3) was achieved in 182 (76%). Mean time to reperfusion was 325 minutes (range 180–418 minutes). Longer time for reperfusion was associated with a decreased likelihood of good clinical outcome (RR [95% CI] for every 30 minute delay: unadjusted 0·85 [0·77–0·94]; adjusted 0·88 [0·80–0·98]). INTERPRETATION We confirm that delay in time to angiographic reperfusion leads to a decreased likelihood of good clinical outcome. Achieving rapid reperfusion may be critical for the successes of future acute endovascular trials. FUNDING: NIH/NINDS (study sponsor), Genentech Inc. (study drug - intra-arterial t-PA), EKOS Corp. (device), Concentric Inc. (device), Cordis Neurovascular, Inc. (device), and Boehringer Ingelheim (European Investigator Meeting support). PMID:24784550

Clinical Trials

Medline Plus

Full Text Available ... Masking, or "blinding," helps avoid bias. For this reason, researchers also may not be told which treatments ... from a study at any time, for any reason. Also, during the trial, you have the right ...

A randomised controlled trial of time limited CBT informed psychological therapy for anxiety in bipolar disorder.

Science.gov (United States)

Jones, Steven; McGrath, Elly; Hampshire, Kay; Owen, Rebecca; Riste, Lisa; Roberts, Chris; Davies, Linda; Mayes, Debbie

2013-02-15

Anxiety comorbidity is common in bipolar disorder and is associated with worse treatment outcomes, greater risk of self harm, suicide and substance misuse. To date however there have been no psychological interventions specifically designed to address this problem. The primary objective of this trial is to establish the acceptability and feasibility of a new integrated intervention for anxiety in bipolar disorder designed in collaboration with individuals with personal experience of both problems. Single blind randomised controlled trials to assess the feasibility and acceptability of a time limited CBT informed psychological intervention for anxiety in bipolar disorder (AIBD) compared with treatment as usual. Participants will be recruited from across the North West of England from specialist mental health services and through primary care and self referral. The primary outcome of the study is the feasibility and acceptability of AIBD assessed by recruitment to target and retention to follow-up, as well as absence of untoward incidents associated with AIBD. We will also estimate the effect size of the impact of the intervention on anxiety and mood outcomes, as well as calculate preliminary estimates of cost-effectiveness and investigate potential mechanisms for this (stigma, self appraisal and stability of social rhythms). This is the first trial of an integrated intervention for anxiety in bipolar disorder. It is of interest to researchers involved in the development of new therapies for bipolar disorder as well as indicating the wider potential for evaluating approaches to the treatment of comorbidity in severe mental illness.

Multiattribute selection of acute stroke imaging software platform for Extending the Time for Thrombolysis in Emergency Neurological Deficits (EXTEND) clinical trial.

Science.gov (United States)

Churilov, Leonid; Liu, Daniel; Ma, Henry; Christensen, Soren; Nagakane, Yoshinari; Campbell, Bruce; Parsons, Mark W; Levi, Christopher R; Davis, Stephen M; Donnan, Geoffrey A

2013-04-01

The appropriateness of a software platform for rapid MRI assessment of the amount of salvageable brain tissue after stroke is critical for both the validity of the Extending the Time for Thrombolysis in Emergency Neurological Deficits (EXTEND) Clinical Trial of stroke thrombolysis beyond 4.5 hours and for stroke patient care outcomes. The objective of this research is to develop and implement a methodology for selecting the acute stroke imaging software platform most appropriate for the setting of a multi-centre clinical trial. A multi-disciplinary decision making panel formulated the set of preferentially independent evaluation attributes. Alternative Multi-Attribute Value Measurement methods were used to identify the best imaging software platform followed by sensitivity analysis to ensure the validity and robustness of the proposed solution. Four alternative imaging software platforms were identified. RApid processing of PerfusIon and Diffusion (RAPID) software was selected as the most appropriate for the needs of the EXTEND trial. A theoretically grounded generic multi-attribute selection methodology for imaging software was developed and implemented. The developed methodology assured both a high quality decision outcome and a rational and transparent decision process. This development contributes to stroke literature in the area of comprehensive evaluation of MRI clinical software. At the time of evaluation, RAPID software presented the most appropriate imaging software platform for use in the EXTEND clinical trial. The proposed multi-attribute imaging software evaluation methodology is based on sound theoretical foundations of multiple criteria decision analysis and can be successfully used for choosing the most appropriate imaging software while ensuring both robust decision process and outcomes. © 2012 The Authors. International Journal of Stroke © 2012 World Stroke Organization.

Sick building syndrome (SBS) and exposure to water-damaged buildings: time series study, clinical trial and mechanisms.

Science.gov (United States)

Shoemaker, Ritchie C; House, Dennis E

2006-01-01

Occupants of water-damaged buildings (WDBs) with evidence of microbial amplification often describe a syndrome involving multiple organ systems, commonly referred to as "sick building syndrome" (SBS), following chronic exposure to the indoor air. Studies have demonstrated that the indoor air of WDBs often contains a complex mixture of fungi, mycotoxins, bacteria, endotoxins, antigens, lipopolysaccharides, and biologically produced volatile compounds. A case-series study with medical assessments at five time points was conducted to characterize the syndrome after a double-blinded, placebo-controlled clinical trial conducted among a group of study participants investigated the efficacy of cholestyramine (CSM) therapy. The general hypothesis of the time series study was that chronic exposure to the indoor air of WDBs is associated with SBS. Consecutive clinical patients were screened for diagnosis of SBS using criteria of exposure potential, symptoms involving at least five organ systems, and the absence of confounding factors. Twenty-eight cases signed voluntary consent forms for participation in the time-series study and provided samples of microbial contaminants from water-damaged areas in the buildings they occupied. Twenty-six participants with a group-mean duration of illness of 11 months completed examinations at all five study time points. Thirteen of those participants also agreed to complete a double-blinded, placebo-controlled clinical trial. Data from Time Point 1 indicated a group-mean of 23 out of 37 symptoms evaluated; and visual contrast sensitivity (VCS), an indicator of neurological function, was abnormally low in all participants. Measurements of matrix metalloproteinase 9 (MMP9), leptin, alpha melanocyte stimulating hormone (MSH), vascular endothelial growth factor (VEGF), immunoglobulin E (IgE), and pulmonary function were abnormal in 22, 13, 25, 14, 1, and 7 participants, respectively. Following 2 weeks of CSM therapy to enhance toxin elimination

Effect of a novel two-desk sit-to-stand workplace (ACTIVE OFFICE on sitting time, performance and physiological parameters: protocol for a randomized control trial

Directory of Open Access Journals (Sweden)

Bernhard Schwartz

2016-07-01

Full Text Available Abstract Background Prolonged sitting is ubiquitous in modern society and linked to several diseases. Height-adjustable desks are being used to decrease worksite based sitting time (ST. Single-desk sit-to-stand workplaces exhibit small ST reduction potential and short-term loss in performance. The aim of this paper is to report the study design and methodology of an ACTIVE OFFICE trial. Design The study was a 1-year three-arm, randomized controlled trial in 18 healthy Austrian office workers. Allocation was done via a regional health insurance, with data collection during Jan 2014 – March 2015. Participants were allocated to either an intervention or control group. Intervention group subjects were provided with traditional or two-desk sit-to-stand workstations in either the first or the second half of the study, while control subjects did not experience any changes during the whole study duration. Sitting time and physical activity (IPAQ-long, cognitive performance (text editing task, Stroop-test, d2R test of attention, workload perception (NASA-TLX and physiological parameters (salivary cortisol, heartrate variability and body weight were measured pre- and post-intervention (23 weeks after baseline for intervention and control periods. Postural changes and sitting/standing time (software logger were recorded at the workplace for the whole intervention period. Discussion This study evaluates the effects of a novel two-desk sit-to-stand workplace on sitting time, physical parameters and work performance of healthy office based workers. If the intervention proves effective, it has a great potential to be implemented in regular workplaces to reduce diseases related to prolonged sitting. Trial registration ClinicalTrials.gov Identifier: NCT02825303 , July 2016 (retrospectively registered.

Effects of stevia, aspartame, and sucrose on food intake, satiety, and postprandial glucose and insulin levels

Science.gov (United States)

Anton, Stephen D.; Martin, Corby K.; Han, Hongmei; Coulon, Sandra; Cefalu, William T.; Geiselman, Paula; Williamson, Donald A.

2010-01-01

Consumption of sugar-sweetened beverages may be one of the dietary causes of metabolic disorders, such as obesity. Therefore, substituting sugar with low-calorie sweeteners may be an efficacious weight management strategy. We tested the effect of preloads containing stevia, aspartame, or sucrose on food intake, satiety, and postprandial glucose and insulin levels. Design: 19 healthy lean (BMI = 20.0 – 24.9) and 12 obese (BMI = 30.0 – 39.9) individuals 18 to 50 years old completed three separate food test days during which they received preloads containing stevia (290 kcal), aspartame (290 kcal), or sucrose (493 kcal) before the lunch and dinner meal. The preload order was balanced, and food intake (kcal) was directly calculated. Hunger and satiety levels were reported before and after meals, and every hour throughout the afternoon. Participants provided blood samples immediately before and 20 minutes after the lunch preload. Despite the caloric difference in preloads (290 vs. 493 kcals), participants did not compensate by eating more at their lunch and dinner meals when they consumed stevia and aspartame versus sucrose in preloads (mean differences in food intake over entire day between sucrose and stevia = 301 kcal, p Stevia preloads significantly lowered postprandial glucose levels compared to sucrose preloads (p stevia and aspartame preloads, participants did not compensate by eating more at either their lunch or dinner meal and reported similar levels of satiety compared to when they consumed the higher calorie sucrose preload. PMID:20303371

Evaluation of a "Just-in-Time" Nurse Consultation on Bone Health: A Pilot Randomized Controlled Trial.

Science.gov (United States)

Roblin, Douglas W; Zelman, David; Plummer, Sally; Robinson, Brandi E; Lou, Yiyue; Edmonds, Stephanie W; Wolinsky, Fredric D; Saag, Kenneth G; Cram, Peter

2017-01-01

Evidence is inconclusive whether a nurse consultation can improve osteoporosis-related patient outcomes. To evaluate whether a nurse consultation immediately after dual-energy x-ray absorptiometry (DXA) produced better osteoporosis-related outcomes than a simple intervention to activate adults in good bone health practices or usual care. Pilot randomized controlled trial, conducted within the larger Patient Activation After DXA Result Notification (PAADRN) trial (NCT01507662). After DXA, consenting adults age 50 years or older were randomly assigned to 3 groups: nurse consultation, PAADRN intervention (mailed letter with individualized fracture risk and an educational brochure), or usual care (control). Nurse consultation included reviewing DXA results, counseling on bone health, and ordering needed follow-up tests or physician referrals. Change from baseline to 52 weeks in participant-reported osteoporosis-related pharmacotherapy, lifestyle, activation and self-efficacy, and osteoporosis care satisfaction. Nurse consultation participants (n = 104) reported 52-week improvements in strengthening and weight-bearing exercise (p = 0.09), calcium intake (p Just-in-time" nurse consultation yielded a few improvements over 52 weeks in osteoporosis-related outcomes; however, most changes were not different from those obtained through the lower-cost PAADRN intervention or usual care.

Re-Engineering Alzheimer Clinical Trials: Global Alzheimer's Platform Network.

Science.gov (United States)

Cummings, J; Aisen, P; Barton, R; Bork, J; Doody, R; Dwyer, J; Egan, J C; Feldman, H; Lappin, D; Truyen, L; Salloway, S; Sperling, R; Vradenburg, G

2016-06-01

Alzheimer's disease (AD) drug development is costly, time-consuming, and inefficient. Trial site functions, trial design, and patient recruitment for trials all require improvement. The Global Alzheimer Platform (GAP) was initiated in response to these challenges. Four GAP work streams evolved in the US to address different trial challenges: 1) registry-to-cohort web-based recruitment; 2) clinical trial site activation and site network construction (GAP-NET); 3) adaptive proof-of-concept clinical trial design; and 4) finance and fund raising. GAP-NET proposes to establish a standardized network of continuously funded trial sites that are highly qualified to perform trials (with established clinical, biomarker, imaging capability; certified raters; sophisticated management system. GAP-NET will conduct trials for academic and biopharma industry partners using standardized instrument versions and administration. Collaboration with the Innovative Medicines Initiative (IMI) European Prevention of Alzheimer's Disease (EPAD) program, the Canadian Consortium on Neurodegeneration in Aging (CCNA) and other similar international initiatives will allow conduct of global trials. GAP-NET aims to increase trial efficiency and quality, decrease trial redundancy, accelerate cohort development and trial recruitment, and decrease trial costs. The value proposition for sites includes stable funding and uniform training and trial execution; the value to trial sponsors is decreased trial costs, reduced time to execute trials, and enhanced data quality. The value for patients and society is the more rapid availability of new treatments for AD.

Clinical Trial Decisions in Difficult Circumstances: Parental Consent Under Time Pressure

NARCIS (Netherlands)

Jansen-van der Weide, Marijke C.; Caldwell, Patrina H. Y.; Young, Bridget; de Vries, Martine C.; Willems, Dick L.; van't Hoff, William; Woolfall, Kerry; van der Lee, Johanna H.; Offringa, Martin

2015-01-01

Treatments and interventions used to care for children in emergencies should be based on strong evidence. Well-designed clinical trials investigating these interventions for children are therefore indispensable. Parental informed consent is a key ethical requirement for the enrollment of children in

Barriers towards the publication of academic drug trials. Follow-up of trials approved by the Danish Medicines Agency

DEFF Research Database (Denmark)

Berendt, Louise; Petersen, Lene Grejs; Bach, Karin Friis

2017-01-01

OBJECTIVE: To characterize and quantify barriers towards the publication of academic drug trials. STUDY DESIGN: We identified academic drug trials approved during a 3-year period (2004-2007) by the Danish Medicines Agency. We conducted a survey among the trial sponsors to describe the rates...... of initiation, completion, and publication, and the reasons for the failure to reach each of these milestones. Information on size and methodological characteristics of the trials was extracted from the EudraCT database, a prospective register of all approved clinical drug trials submitted to European medicines...... agencies since 2004. RESULTS: A total of 181 academic drug trials were eligible for inclusion, 139 of which participated in our survey (response rate: 77%). Follow-up time ranged from 5.1 to 7.9 years. Most trials were randomized controlled trials (73%, 95% CI 65-81%). Initiation and completion rates were...

Dependent Interviewing and Sub-Optimal Responding

Directory of Open Access Journals (Sweden)

Johannes Eggs

2015-02-01

Full Text Available With proactive dependent interviewing (PDI respondents are reminded of the answer they gave in the previous interview, before being asked about their current status. PDI is used in panel surveys to assist respondent recall and reduce spurious changes in responses over time. PDI may however provide scope for new errors if respondents falsely accept the previous information as still being an accurate description of their current situation. In this paper we use data from the German Labour Market and Social Security panel study, in which an error was made with the preload data for a PDI question about receipt of welfare benefit. The survey data were linked to individual administrative records on receipt of welfare benefit. A large proportion of respondents accepted the false preload. This behaviour seems mainly driven by the difficulty of the response task: respondents with a more complex history of receipt according to the records were more likely to confirm the false preload. Personality also seemed related to the probability of confirming. Predictors of satisficing, indicators of satisficing on other items in the survey, and characteristics of the survey and interviewer were not predictive of confirming the false preload.

Ongoing EEG phase as a trial-by-trial predictor of perceptual and attentional variability

Directory of Open Access Journals (Sweden)

Rufin eVanRullen

2011-04-01

Full Text Available Even in well-controlled laboratory environments, apparently identical repetitions of an experimental trial can give rise to highly variable perceptual outcomes and behavioral responses. This variability is generally discarded as a reflection of intrinsic noise in neuronal systems. However, part of this variability may be accounted for by trial-by-trial fluctuations of the phase of ongoing oscillations at the moment of stimulus presentation. For example, the phase of an EEG oscillation reflecting the rapid waxing and waning of sustained attention can predict the perception of a subsequent visual stimulus at threshold. Similar ongoing periodicities account for a portion of the trial-by-trial variability of visual reaction times. We review the available experimental evidence linking ongoing EEG phase to perceptual and attentional variability, and the corresponding methodology. We propose future tests of this relation, and discuss the theoretical implications for understanding the neuronal dynamics of sensory perception.

Are reports of randomized controlled trials improving over time? A systematic review of 284 articles published in high-impact general and specialized medical journals.

Science.gov (United States)

To, Matthew J; Jones, Jennifer; Emara, Mohamed; Jadad, Alejandro R

2013-01-01

Inadequate reporting undermines findings of randomized controlled trials (RCTs). This study assessed and compared articles published in high-impact general medical and specialized journals. Reports of RCTs published in high-impact general and specialized medical journals were identified through a search of MEDLINE from January to March of 1995, 2000, 2005, and 2010. Articles that provided original data on adult patients diagnosed with chronic conditions were included in the study. Data on trial characteristics, reporting of allocation concealment, quality score, and the presence of a trial flow diagram were extracted independently by two reviewers, and discrepancies were resolved by consensus or independent adjudication. Descriptive statistics were used for quantitative variables. Comparisons between general medical and specialized journals, and trends over time were performed using Chi-square tests. Reports of 284 trials were analyzed. There was a significantly higher proportion of RCTs published with adequate reporting of allocation concealment (p = 0.003), presentation of a trial flow diagram (pgeneral medical journals had higher quality scores than those in specialized journals (p = 0.001), reported adequate allocation concealment more often (p = 0.013), and presented a trial flow diagram more often (pjournals over the last fifteen years. These improvements are likely attributed to concerted international efforts to improve reporting quality such as CONSORT. There is still much room for improvement, especially among specialized journals.

Inferring Trial-to-Trial Excitatory and Inhibitory Synaptic Inputs from Membrane Potential using Gaussian Mixture Kalman Filtering

Directory of Open Access Journals (Sweden)

Milad eLankarany

2013-09-01

Full Text Available Time-varying excitatory and inhibitory synaptic inputs govern activity of neurons and process information in the brain. The importance of trial-to-trial fluctuations of synaptic inputs has recently been investigated in neuroscience. Such fluctuations are ignored in the most conventional techniques because they are removed when trials are averaged during linear regression techniques. Here, we propose a novel recursive algorithm based on Gaussian mixture Kalman filtering for estimating time-varying excitatory and inhibitory synaptic inputs from single trials of noisy membrane potential in current clamp recordings. The Kalman filtering is followed by an expectation maximization algorithm to infer the statistical parameters (time-varying mean and variance of the synaptic inputs in a non-parametric manner. As our proposed algorithm is repeated recursively, the inferred parameters of the mixtures are used to initiate the next iteration. Unlike other recent algorithms, our algorithm does not assume an a priori distribution from which the synaptic inputs are generated. Instead, the algorithm recursively estimates such a distribution by fitting a Gaussian mixture model. The performance of the proposed algorithms is compared to a previously proposed PF-based algorithm (Paninski et al., 2012 with several illustrative examples, assuming that the distribution of synaptic input is unknown. If noise is small, the performance of our algorithms is similar to that of the previous one. However, if noise is large, they can significantly outperform the previous proposal. These promising results suggest that our algorithm is a robust and efficient technique for estimating time varying excitatory and inhibitory synaptic conductances from single trials of membrane potential recordings.

Assessment of time to clinical response, a proxy for discharge readiness, among hospitalized patients with community-acquired pneumonia who received either ceftaroline fosamil or ceftriaxone in two phase III FOCUS trials.

Science.gov (United States)

Lodise, Thomas P; Anzueto, Antonio R; Weber, David J; Shorr, Andrew F; Yang, Min; Smith, Alexander; Zhao, Qi; Huang, Xingyue; File, Thomas M

2015-02-01

The primary driver of health care costs for patients with community-acquired pneumonia (CAP) is the hospital length of stay (LOS). Unfortunately, hospital LOS comparisons are difficult to make from phase III CAP trials because of their structured designs and prespecified treatment durations. However, an opportunity still exists to draw inferences about potential LOS differences between treatments through the use of surrogates for hospital discharge. The intent of this study was to quantify the time to a clinical response, a proxy for the time to discharge readiness, among hospitalized CAP patients who received either ceftaroline or ceftriaxone in two phase III CAP FOCUS clinical trials. On the basis of the Infectious Diseases Society of America and American Thoracic Society CAP management guidelines and recent FDA guidance documents for community-acquired bacterial pneumonia, a post hoc adjudication algorithm was constructed a priori to compare the time to a clinical response, a proxy for the time to discharge readiness, between patients who received ceftaroline or ceftriaxone. Overall, 1,116 patients (ceftaroline, n=562; ceftriaxone, n=554) from the pooled FOCUS trials met the selection criteria for this analysis. Kaplan-Meier analyses showed that ceftaroline was associated with a shorter time, measured in days, to meeting the clinical response criteria (P=0.03). Of the patients on ceftaroline, 61.0, 76.1, and 83.6% achieved a clinical response by days 3, 4, and 5, compared to 54.3, 69.8, and 79.3% of the ceftriaxone-treated patients. In the Cox regression, ceftaroline was associated with a shorter time to a clinical response (HR, 1.16, P=0.02). The methodology employed here provides a framework to draw comparative effectiveness inferences from phase III CAP efficacy trials. (The FOCUS trials whose data were analyzed in this study have been registered at ClinicalTrials.gov under registration no. NCT00621504 and NCT00509106.). Copyright © 2015, American Society

Time management in radiation oncology: evaluation of time, attendance of medical staff, and resources during radiotherapy for prostate cancer: the DEGRO-QUIRO trial.

Science.gov (United States)

Keilholz, L; Willner, J; Thiel, H-J; Zamboglou, N; Sack, H; Popp, W

2014-01-01

In order to evaluate resource requirements, the German Society of Radiation Oncology (DEGRO) recorded the times needed for core procedures in the radio-oncological treatment of various cancer types within the scope of its QUIRO trial. The present study investigated the personnel and infrastructural resources required in radiotherapy of prostate cancer. The investigation was carried out in the setting of definitive radiotherapy of prostate cancer patients between July and October 2008 at two radiotherapy centers, both with well-trained staff and modern technical facilities at their disposal. Personnel attendance times and room occupancy times required for core procedures (modules) were each measured prospectively by two independently trained observers using time measurements differentiated on the basis of professional group (physician, physicist, and technician), 3D conformal (3D-cRT), and intensity-modulated radiotherapy (IMRT). Total time requirements of 983 min for 3D-cRT and 1485 min for step-and-shoot IMRT were measured for the technician (in terms of professional group) in all modules recorded and over the entire course of radiotherapy for prostate cancer (72-76 Gy). Times needed for the medical specialist/physician were 255 min (3D-cRT) and 271 min (IMRT), times of the physicist were 181 min (3D-cRT) and 213 min (IMRT). The difference in time was significant, although variations in time spans occurred primarily as a result of various problems during patient treatment. This investigation has permitted, for the first time, a realistic estimation of average personnel and infrastructural requirements for core procedures in quality-assured definitive radiotherapy of prostate cancer. The increased time needed for IMRT applies to the step-and-shoot procedure with verification measurements for each irradiation planning.

Effects of stevia, aspartame, and sucrose on food intake, satiety, and postprandial glucose and insulin levels.

Science.gov (United States)

Anton, Stephen D; Martin, Corby K; Han, Hongmei; Coulon, Sandra; Cefalu, William T; Geiselman, Paula; Williamson, Donald A

2010-08-01

Consumption of sugar-sweetened beverages may be one of the dietary causes of metabolic disorders, such as obesity. Therefore, substituting sugar with low calorie sweeteners may be an efficacious weight management strategy. We tested the effect of preloads containing stevia, aspartame, or sucrose on food intake, satiety, and postprandial glucose and insulin levels. 19 healthy lean (BMI=20.0-24.9) and 12 obese (BMI=30.0-39.9) individuals 18-50 years old completed three separate food test days during which they received preloads containing stevia (290kcal), aspartame (290kcal), or sucrose (493kcal) before the lunch and dinner meal. The preload order was balanced, and food intake (kcal) was directly calculated. Hunger and satiety levels were reported before and after meals, and every hour throughout the afternoon. Participants provided blood samples immediately before and 20min after the lunch preload. Despite the caloric difference in preloads (290kcal vs. 493kcal), participants did not compensate by eating more at their lunch and dinner meals when they consumed stevia and aspartame versus sucrose in preloads (mean differences in food intake over entire day between sucrose and stevia=301kcal, paspartame=330kcal, paspartame and sucrose preloads (paspartame preloads, participants did not compensate by eating more at either their lunch or dinner meal and reported similar levels of satiety compared to when they consumed the higher calorie sucrose preload. Published by Elsevier Ltd.

Context-dependent incremental timing cells in the primate hippocampus.

Science.gov (United States)

Sakon, John J; Naya, Yuji; Wirth, Sylvia; Suzuki, Wendy A

2014-12-23

We examined timing-related signals in primate hippocampal cells as animals performed an object-place (OP) associative learning task. We found hippocampal cells with firing rates that incrementally increased or decreased across the memory delay interval of the task, which we refer to as incremental timing cells (ITCs). Three distinct categories of ITCs were identified. Agnostic ITCs did not distinguish between different trial types. The remaining two categories of cells signaled time and trial context together: One category of cells tracked time depending on the behavioral action required for a correct response (i.e., early vs. late release), whereas the other category of cells tracked time only for those trials cued with a specific OP combination. The context-sensitive ITCs were observed more often during sessions where behavioral learning was observed and exhibited reduced incremental firing on incorrect trials. Thus, single primate hippocampal cells signal information about trial timing, which can be linked with trial type/context in a learning-dependent manner.

Analysis of influence of different pressure and different depth of pvd on soft foundation treatment

Science.gov (United States)

Li, Bin; Wang, XueKui

2018-02-01

According to the depth of plastic vertical drainage (pvd), the arrangement mode and the loading mode to analyze the influence of Vacuum preloading near the existing road. An arrangement mode of vacuum preloading to reduce the impact was put forward. The combination of different depth of pvd and loading modes are used to analyze the effect of vacuum preloading treatment and its influence range. The calculations show that the deformation and the influence distance are smaller by using the 40kPa vacuum loading and 41kPa surcharge load preloading. Reducing the depth of the pvd and vacuum combined surcharge preloading can weaken the influence to the existing highway.

Clinical Trials

Medline Plus

Full Text Available ... As a result, the U.S. Food and Drug Administration now recommends never using HT to prevent heart disease. When HT is used for menopausal symptoms, it should be taken only at the smallest dose and for the shortest time possible. Clinical trials, like the two described above, ...

Can emergency medicine research benefit from adaptive design clinical trials?

Science.gov (United States)

Flight, Laura; Julious, Steven A; Goodacre, Steve

2017-04-01

Adaptive design clinical trials use preplanned interim analyses to determine whether studies should be stopped or modified before recruitment is complete. Emergency medicine trials are well suited to these designs as many have a short time to primary outcome relative to the length of recruitment. We hypothesised that the majority of published emergency medicine trials have the potential to use a simple adaptive trial design. We reviewed clinical trials published in three emergency medicine journals between January 2003 and December 2013. We determined the proportion that used an adaptive design as well as the proportion that could have used a simple adaptive design based on the time to primary outcome and length of recruitment. Only 19 of 188 trials included in the review were considered to have used an adaptive trial design. A total of 154/165 trials that were fixed in design had the potential to use an adaptive design. Currently, there seems to be limited uptake in the use of adaptive trial designs in emergency medicine despite their potential benefits to save time and resources. Failing to take advantage of adaptive designs could be costly to patients and research. It is recommended that where practical and logistical considerations allow, adaptive designs should be used for all emergency medicine clinical trials. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Perceived barriers to pediatrician and family practitioner participation in pediatric clinical trials: Findings from the Clinical Trials Transformation Initiative

Directory of Open Access Journals (Sweden)

Rachel G. Greenberg

2018-03-01

Of the 136 providers surveyed, 52/136 (38% had previously referred a pediatric patient to a trial, and only 17/136 (12% had ever been an investigator for a pediatric trial. Lack of awareness of existing pediatric trials was a major barrier to patient referral by providers, in addition to consideration of trial risks, distance to the site, and time needed to discuss trial participation with parents. Overall, providers perceived greater challenges related to parental concerns and parent or child logistical barriers than study implementation and ethics or regulatory barriers as barriers to their practice serving as a trial site. Providers who had previously been an investigator for a pediatric trial were less likely to be concerned with potential barriers than non-investigators. Understanding the barriers that limit pediatric providers from collaboration or inhibit their participation is key to designing effective interventions to optimize pediatric trial participation.

A school-based intervention program in promoting leisure-time physical activity: trial protocol.

Science.gov (United States)

Kawabata, Masato; Chua, Khai Leng; Chatzisarantis, Nikos L D

2018-04-02

willingness to engage in leisure-time PA were compared with the other activity (e.g., doing homework, shopping). This study will provide the evidence on the effectiveness of a cost-effective school-based intervention on reducing BMI of overweight students through promoting sustained participation in leisure-time PA. It will also address methodological issues on the gaps between objective and subjective measures of PA. This trial is registered with the ISRCTN registry (ISRCTN73786157, 26/10/2017, retrospectively registered).

Warm pre-stressing, preliminary experiments

International Nuclear Information System (INIS)

Hedner, G.

1984-09-01

The beneficial effect of warm pre-stressing, WPS, on apparent fracture thoughness at low temperature is well established. Tests are usually performed with constant load during the cooling part of the load cycle. In practice load variations may occur during this part. The present paper reports a preliminary study of the influence of superimposed fatigue loads. It is found that if crack propagation occurs during cooling+fatigue loading, then the maximum load during the fatigue load cycle is the preload to be used for WPS consideration. A few tests were preformed to study the effect of preload reversal. Tensile preload was followed by a compressive load and after unloading the specimens were cooled and fractured. It was found that for the high preload level used in the tests, the beneficial effect of the tensile preload could be totally annihilated by the compressive preload. (author)

The Infant Feeding Activity and Nutrition Trial (INFANT an early intervention to prevent childhood obesity: Cluster-randomised controlled trial

Directory of Open Access Journals (Sweden)

Campbell Karen

2008-03-01

Full Text Available Abstract Background Multiple factors combine to support a compelling case for interventions that target the development of obesity-promoting behaviours (poor diet, low physical activity and high sedentary behaviour from their inception. These factors include the rapidly increasing prevalence of fatness throughout childhood, the instigation of obesity-promoting behaviours in infancy, and the tracking of these behaviours from childhood through to adolescence and adulthood. The Infant Feeding Activity and Nutrition Trial (INFANT aims to determine the effectiveness of an early childhood obesity prevention intervention delivered to first-time parents. The intervention, conducted with parents over the infant's first 18 months of life, will use existing social networks (first-time parent's groups and an anticipatory guidance framework focusing on parenting skills which support the development of positive diet and physical activity behaviours, and reduced sedentary behaviours in infancy. Methods/Design This cluster-randomised controlled trial, with first-time parent groups as the unit of randomisation, will be conducted with a sample of 600 first-time parents and their newborn children who attend the first-time parents' group at Maternal and Child Health Centres. Using a two-stage sampling process, local government areas in Victoria, Australia will be randomly selected at the first stage. At the second stage, a proportional sample of first-time parent groups within selected local government areas will be randomly selected and invited to participate. Informed consent will be obtained and groups will then be randomly allocated to the intervention or control group. Discussion The early years hold promise as a time in which obesity prevention may be most effective. To our knowledge this will be the first randomised trial internationally to demonstrate whether an early health promotion program delivered to first-time parents in their existing social groups

SARCOPENIA: DESIGNING PHASE IIB TRIALS

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CHUMLEA, WM.C.; CESARI, M.; EVANS, W.J.; FERRUCCI, L.; FIELDING, R.A.; PAHOR, M.; STUDENSKI, S.; VELLAS, B.

2012-01-01

Sarcopenia is the age-related involuntary loss of skeletal muscle mass and functionality that can lead to the development of disability, frailty and increased health care costs. The development of interventions aimed at preventing and/or treating sarcopenia is complex, requiring the adoption of assumptions and standards that are not well established scientifically or clinically. A number of investigators and clinicians (both from academia and industry) met in Rome (Italy) in 2009 to develop a consensus definition of sarcopenia. Subsequently, in Albuquerque (New Mexico, USA) in 2010, the same group met again to consider the complex issues necessary for designing Phase II clinical trials for sarcopenia. Current clinical trial data indicate that fat-free mass (FFM) parameters are responsive to physical activity/nutritional treatment modalities over short time periods, but pharmacological trials of sarcopenia have yet to show significant efficacy. In order to conduct a clinical trial within a reasonable time frame, groups that model or display accelerated aging and loss of FFM are necessary. Few studies have used acceptable designs for testing treatment effects, sample sizes or primary outcomes that could provide interpretable findings or effects across studies. Dual energy x ray absorptiometry (DXA) is the measure of choice for assessing FFM, but sufficient time is needed for changes to be detected accurately and reliably. A tool set that would allow clinical, basic and epidemiological research on sarcopenia to advance rapidly toward diagnosis and treatment phases should be those reflecting function and strength. PMID:21623466

Payload Launch Lock Mechanism

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Young, Ken (Inventor); Hindle, Timothy (Inventor)

2014-01-01

A payload launch lock mechanism includes a base, a preload clamp, a fastener, and a shape memory alloy (SMA) actuator. The preload clamp is configured to releasibly restrain a payload. The fastener extends, along an axis, through the preload clamp and into the base, and supplies a force to the preload clamp sufficient to restrain the payload. The SMA actuator is disposed between the base and the clamp. The SMA actuator is adapted to receive electrical current and is configured, upon receipt of the electrical current, to supply a force that causes the fastener to elongate without fracturing. The preload clamp, in response to the fastener elongation, either rotates or pivots to thereby release the payload.

Do pregnant women prefer timing of elective cesarean section prior to versus after 39 weeks of gestation? Secondary analyses from a randomized controlled trial.

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Glavind, J; Henriksen, T B; Kindberg, S F; Uldbjerg, N

2014-11-01

To evaluate women's preferences for timing of elective cesarean section (ECS) scheduled prior to versus after 39 completed weeks. Secondary analyses from a randomized controlled open-label trial were conducted at seven Danish tertiary hospitals from March 2009 to June 2011 with inclusion of singleton pregnant women with a healthy fetus. The women were allocated by a computerized telephone system to ECS scheduled at 38(+3) weeks or 39(+3) weeks of gestation. Dissatisfaction with timing of ECS and preferred timing of the procedure in a proposed future ECS delivery were evaluated. Data analyses were done by intention-to-treat, using logistic regression. A total of 1196 women (94%) completed an online questionnaire at follow-up eight weeks postpartum. In the 38 weeks group, 61 (10%) women 601 were dissatisfied with the timing of their ECS, whereas in the 39 weeks group 157 (26%) of 595 were dissatisfied (adjOR 3.18, 95% CI 2.30; 4.40). The proportion of women who preferred the same timing in a future ECS were 272 (45%) in the 38 weeks group compared to 232 (39%) in the 39(+3) weeks group (adjOR 0.75, 95% CI 0.60; 0.95). The women in this trial preferred ECS scheduled prior to 39 weeks of gestation.

Cross-system evaluation of clinical trial search engines.

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Jiang, Silis Y; Weng, Chunhua

2014-01-01

Clinical trials are fundamental to the advancement of medicine but constantly face recruitment difficulties. Various clinical trial search engines have been designed to help health consumers identify trials for which they may be eligible. Unfortunately, knowledge of the usefulness and usability of their designs remains scarce. In this study, we used mixed methods, including time-motion analysis, think-aloud protocol, and survey, to evaluate five popular clinical trial search engines with 11 users. Differences in user preferences and time spent on each system were observed and correlated with user characteristics. In general, searching for applicable trials using these systems is a cognitively demanding task. Our results show that user perceptions of these systems are multifactorial. The survey indicated eTACTS being the generally preferred system, but this finding did not persist among all mixed methods. This study confirms the value of mixed-methods for a comprehensive system evaluation. Future system designers must be aware that different users groups expect different functionalities.

It is time to revise the international Good Clinical Practices guidelines: recommendations from non-commercial North-South collaborative trials.

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Ravinetto, Raffaella; Tinto, Halidou; Diro, Ermias; Okebe, Joseph; Mahendradhata, Yodi; Rijal, Suman; Gotuzzo, Eduardo; Lutumba, Pascal; Nahum, Alain; De Nys, Katelijne; Casteels, Minne; Boelaert, Marleen

2016-01-01

The Good Clinical Practices (GCP) codes of the WHO and the International Conference of Harmonization set international standards for clinical research. But critics argue that they were written without consideration for the challenges faced in low and middle income countries (LMICs). Based on our field experience in LMICs, we developed a non-exhaustive set of recommendations for the improvement of GCP. These cover 3 domains: ethical, legal and operational, and 8 specific issues: the double ethical review of 'externally sponsored' trials; the informed consent procedure in minors and in illiterate people; post-trial access to newly-developed products for the trial communities; the role of communities as key research actors; the definition of sponsor; and the guidance for contractual agreements, laboratory quality management systems, and quality assurance of investigational medicinal products. Issues not covered in our analysis include among others biobanking, standard of care, and study designs. The international GCP codes de facto guide national legislators and funding agencies, so the current shortcomings may weaken the regulatory oversight of international research. In addition, activities neglected by GCP are less likely to be implemented or funded. If GCP are meant to serve the interests of global society, a comprehensive revision is needed. The revised guidelines should be strongly rooted in ethics, sensitive to different sociocultural perspectives, and allow consideration for trial-specific and context-specific challenges. This can be only achieved if all stakeholders, including researchers, sponsors, regulators, ethical reviewers and patients' representatives from LMICs, as well as non-commercial researchers and sponsors from affluent countries, are transparently involved in the revision process. We hope that our limited analysis would foster advocacy for a broad and inclusive revision of the international GCP codes, to make them at the same time 'global

The Effect of Ringer versus Haemaccel Preload on Incidence of Postoperative Nausea and Vomiting

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Mansour Ghafourifard

2015-06-01

Full Text Available ABSTRACT Introduction: Postoperative nausea and vomiting (PONV is the most common and unpleasant postoperative complication. There is much controversy on preoperative fluid therapy. The aim of this study was to examine the effect of crystalloid fluid (Ringer solution versus colloid (Haemaccel solution on the incidence of postoperative nausea and vomiting in patients receiving spinal anesthesia. Methods: In this double-blinded clinical trial, 46 patients were selected according to the inclusion and exclusion criteria. Patients were randomly allocated to one of two groups. The crystalloid group received Ringer solution at a volume of 7 ml/kg and colloid group received 7ml/kg of 3% Modified Gelatin (Haemaccel as a preoperative intravenous bolus. We used a Verbal Rating Scale (VRS for assessing the nausea and vomiting occurrence. Data were analyzed using SPSS software ver.13 and x2 test and independent t-test. Results: The result showed that the incidence of PONV was less frequent in both Ringer and Haemaccel groups, but the incidence of vomiting and the intensity of nausea was not significantly different in any time point after anesthesia. Conclusion: We conclude that preoperative fluid administration decreases the incidence of PONV, and both Crystalloids (Ringer and colloids (haemaccel solution were found to be equivalent in prevention of PONV. Therefore using of either Ringer or haemaccel solution is recommended for prevention of PONV.

The Effect of Ringer versus Haemaccel Preload on Incidence of Postoperative Nausea and Vomiting.

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Ghafourifard, Mansour; Zirak, Mohammad; Broojerdi, Mohammad Hossein; Bayendor, Ali; Moradi, Abolfaz

2015-06-01

Postoperative nausea and vomiting (PONV) is the most common and unpleasant postoperative complication. There is much controversy on preoperative fluid therapy. The aim of this study was to examine the effect of crystalloid fluid (Ringer solution) versus colloid (Haemaccel solution) on the incidence of postoperative nausea and vomiting in patients receiving spinal anesthesia. In this double-blinded clinical trial, 46 patients were selected according to the inclusion and exclusion criteria. Patients were randomly allocated to one of two groups. The crystalloid group received Ringer solution at a volume of 7 ml/kg and colloid group received 7ml/kg of 3% Modified Gelatin (Haemaccel) as a preoperative intravenous bolus. We used a Verbal Rating Scale (VRS) for assessing the nausea and vomiting occurrence. Data were analyzed using SPSS software ver.13 and χ(2) test and independent t-test. The result showed that the incidence of PONV was less frequent in both Ringer and Haemaccel groups, but the incidence of vomiting and the intensity of nausea was not significantly different in any time point after anesthesia. We conclude that preoperative fluid administration decreases the incidence of PONV, and both Crystalloids (Ringer) and colloids (haemaccel) solution were found to be equivalent in prevention of PONV. Therefore using of either Ringer or haemaccel solution is recommended for prevention of PONV.

New approaches to trials in glomerulonephritis.

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Craig, Jonathan C; Tong, Allison; Strippoli, Giovanni F M

2017-01-01

Randomized controlled trials are required to reliably identify interventions to improve the outcomes for people with glomerulonephritis (GN). Unfortunately, although easier, observational studies are inherently unreliable even though the findings of both study designs agree most of the time. Currently there are ∼790 trials in GN, but suboptimal design and reporting, together with small sample sizes, mean that they may not be reliable for decision making. If the history is somewhat bleak, the future looks bright, with recent initiatives to improve the quality, size and relevance of clinical trials in nephrology, including greater patient engagement, trial networks, core outcome sets, registry-based trials and adaptive designs. Given the current state of the evidence informing the care of people with GN, disruptive technologies and pervasive culture change is required to ensure that the potential of trials to improve the health of people with this complex condition is to be realized. © The Author 2017. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

The SyBil-AA real-time fMRI neurofeedback study: protocol of a single-blind randomized controlled trial in alcohol use disorder.

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Gerchen, Martin Fungisai; Kirsch, Martina; Bahs, Nathalie; Halli, Patrick; Gerhardt, Sarah; Schäfer, Axel; Sommer, Wolfgang H; Kiefer, Falk; Kirsch, Peter

2018-01-17

Alcohol Use Disorder is a highly prevalent mental disorder which puts a severe burden on individuals, families, and society. The treatment of Alcohol Use Disorder is challenging and novel and innovative treatment approaches are needed to expand treatment options. A promising neuroscience-based intervention method that allows targeting cortical as well as subcortical brain processes is real-time functional magnetic resonance imaging neurofeedback. However, the efficacy of this technique as an add-on treatment of Alcohol Use Disorder in a clinical setting is hitherto unclear and will be assessed in the Systems Biology of Alcohol Addiction (SyBil-AA) neurofeedback study. N = 100 patients with Alcohol Use Disorder will be randomized to 5 parallel groups in a single-blind fashion and receive real-time functional magnetic resonance imaging neurofeedback while they are presented pictures of alcoholic beverages. The groups will either downregulate the ventral striatum, upregulate the right inferior frontal gyrus, negatively modulate the connectivity between these regions, upregulate, or downregulate the auditory cortex as a control region. After receiving 3 sessions of neurofeedback training within a maximum of 2 weeks, participants will be followed up monthly for a period of 3 months and relapse rates will be assessed as the primary outcome measure. The results of this study will provide insights into the efficacy of real-time functional magnetic resonance imaging neurofeedback training in the treatment of Alcohol Use Disorder as well as in the involved brain systems. This might help to identify predictors of successful neurofeedback treatment which could potentially be useful in developing personalized treatment approaches. The study was retrospectively registered in the German Clinical Trials Register (trial identifier: DRKS00010253 ; WHO Universal Trial Number (UTN): U1111-1181-4218) on May 10th, 2016.

Parents' perceived obstacles to pediatric clinical trial participation: Findings from the clinical trials transformation initiative.

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Greenberg, Rachel G; Gamel, Breck; Bloom, Diane; Bradley, John; Jafri, Hasan S; Hinton, Denise; Nambiar, Sumathi; Wheeler, Chris; Tiernan, Rosemary; Smith, P Brian; Roberts, Jamie; Benjamin, Daniel K

2018-03-01

Enrollment of children into pediatric clinical trials remains challenging. More effective strategies to improve recruitment of children into trials are needed. This study used in-depth qualitative interviews with parents who were approached to enroll their children in a clinical trial in order to gain an understanding of the barriers to pediatric clinical trial participation. Twenty-four parents whose children had been offered the opportunity to participate in a clinical trial were interviewed: 19 whose children had participated in at least 1 clinical trial and 5 who had declined participation in any trial. Each study aspect, from the initial explanation of the study to the end of the study, can affect the willingness of parents to consent to the proposed study and future studies. Establishing trust, appropriate timing, a transparent discussion of risks and benefits oriented to the layperson, and providing motivation for children to participate were key factors that impacted parents' decisions. In order for clinical trial accrual to be successful, parents' priorities and considerations must be a central focus, beginning with initial trial design. The recommendations from the parents who participated in this study can be used to support budget allocations that ensure adequate training of study staff and improved staffing on nights and weekends. Studies of parent responses in outpatient settings and additional inpatient settings will provide valuable information on the consent process from the child's and parent's perspectives. Further studies are needed to explore whether implementation of such strategies will result in improved recruitment for pediatric clinical trials.

Problems of university-based scientists associated with clinical trials.

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Remington, R D

1979-05-01

University faculty members who participate in clinical trials face a number of difficulties in connection with this association. Publication opportunities are often limited, and individual scholarship is difficult to express and evaluate within the context of a cooperative trial. Merit increases, promotion, and the award of tenure will usually require evidence of scholarly achievement outside the trial setting. For this reason, it seems inadvisable to recommend that a young investigator devote a major portion of his scholarly and research time to such an activity. A possible exception may be a full-time appointment for 1 to 2 years. Nonetheless, cooperative clinical trials are an important investigative tool and they should continue to be associated with academic centers. If appropriate administrative arrangements can be made, it should be possible to solve the academic problems of the young investigator associated with such trials.

Critical concepts in adaptive clinical trials

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Park JJH

2018-03-01

Full Text Available Jay JH Park,1 Kristian Thorlund,2,3 Edward J Mills2,3 1Department of Medicine, University of British Columbia, Vancouver, BC, Canada; 2Department of Health Research Methods, Evidence, and Impact (HEI, McMaster University, Hamilton, ON, Canada; 3The Bill and Melinda Gates Foundation, Seattle, WA, USA Abstract: Adaptive clinical trials are an innovative trial design aimed at reducing resources, decreasing time to completion and number of patients exposed to inferior interventions, and improving the likelihood of detecting treatment effects. The last decade has seen an increasing use of adaptive designs, particularly in drug development. They frequently differ importantly from conventional clinical trials as they allow modifications to key trial design components during the trial, as data is being collected, using preplanned decision rules. Adaptive designs have increased likelihood of complexity and also potential bias, so it is important to understand the common types of adaptive designs. Many clinicians and investigators may be unfamiliar with the design considerations for adaptive designs. Given their complexities, adaptive trials require an understanding of design features and sources of bias. Herein, we introduce some common adaptive design elements and biases and specifically address response adaptive randomization, sample size reassessment, Bayesian methods for adaptive trials, seamless trials, and adaptive enrichment using real examples. Keywords: adaptive designs, response adaptive randomization, sample size reassessment, Bayesian adaptive trials, seamless trials, adaptive enrichment

Timing of Radiation Therapy and Chemotherapy After Breast-Conserving Surgery for Node-Positive Breast Cancer: Long-Term Results From International Breast Cancer Study Group Trials VI and VII

International Nuclear Information System (INIS)

Karlsson, Per; Cole, Bernard F.; Price, Karen N.; Gelber, Richard D.; Coates, Alan S.; Goldhirsch, Aron; Castiglione, Monica; Colleoni, Marco; Gruber, Günther

2016-01-01

Purpose: To update the previous report from 2 randomized clinical trials, now with a median follow-up of 16 years, to analyze the effect of radiation therapy timing on local failure and disease-free survival. Patients and Methods: From July 1986 to April 1993, International Breast Cancer Study Group trial VI randomly assigned 1475 pre-/perimenopausal women with node-positive breast cancer to receive 3 or 6 cycles of initial chemotherapy (CT). International Breast Cancer Study Group trial VII randomly assigned 1212 postmenopausal women with node-positive breast cancer to receive tamoxifen for 5 years, or tamoxifen for 5 years with 3 early cycles of initial CT. For patients who received breast-conserving surgery (BCS), radiation therapy (RT) was delayed until initial CT was completed; 4 or 7 months after BCS for trial VI and 2 or 4 months for trial VII. We compared RT timing groups among 433 patients on trial VI and 285 patients on trial VII who received BCS plus RT. Endpoints were local failure, regional/distant failure, and disease-free survival (DFS). Results: Among pre-/perimenopausal patients there were no significant differences in disease-related outcomes. The 15-year DFS was 48.2% in the group allocated 3 months initial CT and 44.9% in the group allocated 6 months initial CT (hazard ratio [HR] 1.12; 95% confidence interval [CI] 0.87-1.45). Among postmenopausal patients, the 15-year DFS was 46.1% in the no-initial-CT group and 43.3% in the group allocated 3 months initial CT (HR 1.11; 95% CI 0.82-1.51). Corresponding HRs for local failures were 0.94 (95% CI 0.61-1.46) in trial VI and 1.51 (95% CI 0.77-2.97) in trial VII. For regional/distant failures, the respective HRs were 1.15 (95% CI 0.80-1.63) and 1.08 (95% CI 0.69-1.68). Conclusions: This study confirms that, after more than 15 years of follow-up, it is reasonable to delay radiation therapy until after the completion of standard CT.

Timing of Radiation Therapy and Chemotherapy After Breast-Conserving Surgery for Node-Positive Breast Cancer: Long-Term Results From International Breast Cancer Study Group Trials VI and VII

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Karlsson, Per, E-mail: per.karlsson@oncology.gu.se [Department of Oncology, Institute of Clinical Sciences, Sahgrenska Academy, University of Gothenburg, Sahlgrenska University Hospital, Gothenburg (Sweden); Cole, Bernard F. [Department of Mathematics and Statistics, University of Vermont, Burlington, Vermont (United States); Price, Karen N. [International Breast Cancer Study Group Statistical Center, Frontier Science and Technology Research Foundation, Boston, Massachusetts (United States); Gelber, Richard D. [International Breast Cancer Study Group Statistical Center, Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Frontier Science and Technology Research Foundation, Harvard T. F. Chan School of Public Health, Boston, Massachusetts (United States); Coates, Alan S. [International Breast Cancer Study Group and University of Sydney, Sydney (Australia); Goldhirsch, Aron [Senior Consultant Breast Cancer, European Institute of Oncology and International Breast Cancer Study Group, Milan (Italy); Castiglione, Monica [International Breast Cancer Study Group, Bern (Switzerland); Colleoni, Marco [Division of Medical Senology, European Institute of Oncology and International Breast Cancer Study Group, Milan (Italy); Gruber, Günther [Institute of Radiotherapy, Klinik Hirslanden, Zürich (Switzerland)

2016-10-01

Purpose: To update the previous report from 2 randomized clinical trials, now with a median follow-up of 16 years, to analyze the effect of radiation therapy timing on local failure and disease-free survival. Patients and Methods: From July 1986 to April 1993, International Breast Cancer Study Group trial VI randomly assigned 1475 pre-/perimenopausal women with node-positive breast cancer to receive 3 or 6 cycles of initial chemotherapy (CT). International Breast Cancer Study Group trial VII randomly assigned 1212 postmenopausal women with node-positive breast cancer to receive tamoxifen for 5 years, or tamoxifen for 5 years with 3 early cycles of initial CT. For patients who received breast-conserving surgery (BCS), radiation therapy (RT) was delayed until initial CT was completed; 4 or 7 months after BCS for trial VI and 2 or 4 months for trial VII. We compared RT timing groups among 433 patients on trial VI and 285 patients on trial VII who received BCS plus RT. Endpoints were local failure, regional/distant failure, and disease-free survival (DFS). Results: Among pre-/perimenopausal patients there were no significant differences in disease-related outcomes. The 15-year DFS was 48.2% in the group allocated 3 months initial CT and 44.9% in the group allocated 6 months initial CT (hazard ratio [HR] 1.12; 95% confidence interval [CI] 0.87-1.45). Among postmenopausal patients, the 15-year DFS was 46.1% in the no-initial-CT group and 43.3% in the group allocated 3 months initial CT (HR 1.11; 95% CI 0.82-1.51). Corresponding HRs for local failures were 0.94 (95% CI 0.61-1.46) in trial VI and 1.51 (95% CI 0.77-2.97) in trial VII. For regional/distant failures, the respective HRs were 1.15 (95% CI 0.80-1.63) and 1.08 (95% CI 0.69-1.68). Conclusions: This study confirms that, after more than 15 years of follow-up, it is reasonable to delay radiation therapy until after the completion of standard CT.

The relationship between weight loss and time and risk preference parameters: a randomized controlled trial.

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Takada, Akemi; Nakamura, Ryota; Furukawa, Masakazu; Takahashi, Yoshimitsu; Nishimura, Shuzo; Kosugi, Shinji

2011-07-01

This study aimed to assess the effectiveness of intervention (specifically, intervention by telephone and mails, known as 'tele-care') relative to self-help as a weight-loss method. The question of whether there is a correlation between changes in two preference parameters--time discounting (i.e. impatience) and risk aversion--and the level of commitment was examined. The study, spanning a period of 24 weeks in 2006-2007, comprised 118 participants, each of whom was randomly assigned to either the tele-care or the self-help group. A public-health nurse provided support through telephone and mail communications to the tele-care group, aiming to reduce their calorie intake and increase exercise via this intervention. There was a significant decrease in the body weight of the participants of the tele-care group from the baseline; however, there were no significant differences in the weight loss, median time discounting or risk aversion between the two groups. The subsequent analysis for weight loss with changes in time and risk parameters revealed a significant difference in the weight loss in the time-discounting-loss and risk-aversion-gain groups. From the results of the multiple regression analysis, the time discounting was noted to be associated with age, initial BMI and marital status among men, and risk aversion was associated with age and job status among women. There is a possibility that a decrease in time discounting and increase in risk aversion might correlate with the weight loss or effectiveness of commitment in this trial. This study suggests that time discounting and risk aversion may be useful in anti-obesity efforts, since they are accurate criteria of behavioural patterns associated with weight problems. © Cambridge University Press, 2011

OARSI Clinical Trials Recommendations: Soluble biomarker assessments in clinical trials in osteoarthritis.

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Kraus, V B; Blanco, F J; Englund, M; Henrotin, Y; Lohmander, L S; Losina, E; Önnerfjord, P; Persiani, S

2015-05-01

The objective of this work was to describe requirements for inclusion of soluble biomarkers in osteoarthritis (OA) clinical trials and progress toward OA-related biomarker qualification. The Guidelines for Biomarkers Working Group, representing experts in the field of OA biomarker research from both academia and industry, convened to discuss issues related to soluble biomarkers and to make recommendations for their use in OA clinical trials based on current knowledge and anticipated benefits. This document summarizes current guidance on use of biomarkers in OA clinical trials and their utility at five stages, including preclinical development and phase I to phase IV trials. As demonstrated by this summary, biomarkers can provide value at all stages of therapeutics development. When resources permit, we recommend collection of biospecimens in all OA clinical trials for a wide variety of reasons but in particular, to determine whether biomarkers are useful in identifying those individuals most likely to receive clinically important benefits from an intervention; and to determine whether biomarkers are useful for identifying individuals at earlier stages of OA in order to institute treatment at a time more amenable to disease modification. Copyright © 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

First external quality assurance program for bloodstream Real-Time PCR monitoring of treatment response in clinical trials of Chagas disease.

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Juan C Ramírez

Full Text Available Real-Time PCR (qPCR testing is recommended as both a diagnostic and outcome measurement of etiological treatment in clinical practice and clinical trials of Chagas disease (CD, but no external quality assurance (EQA program provides performance assessment of the assays in use. We implemented an EQA system to evaluate the performance of molecular biology laboratories involved in qPCR based follow-up in clinical trials of CD. An EQA program was devised for three clinical trials of CD: the E1224 (NCT01489228, a pro-drug of ravuconazole; the Sampling Study (NCT01678599, that used benznidazole, both conducted in Bolivia; and the CHAGASAZOL (NCT01162967, that tested posaconazole, conducted in Spain. Four proficiency testing panels containing negative controls and seronegative blood samples spiked with 1, 10 and 100 parasite equivalents (par. eq./mL of four Trypanosoma cruzi stocks, were sent from the Core Lab in Argentina to the participating laboratories located in Bolivia and Spain. Panels were analyzed simultaneously, blinded to sample allocation, at 4-month intervals. In addition, 302 random blood samples from both trials carried out in Bolivia were sent to Core Lab for retesting analysis. The analysis of proficiency testing panels gave 100% of accordance (within laboratory agreement and concordance (between laboratory agreement for all T. cruzi stocks at 100 par. eq./mL; whereas their values ranged from 71 to 100% and from 62 to 100% at 1 and 10 par. eq./mL, respectively, depending on the T. cruzi stock. The results obtained after twelve months of preparation confirmed the stability of blood samples in guanidine-EDTA buffer. No significant differences were found between qPCR results from Bolivian laboratory and Core Lab for retested clinical samples. This EQA program for qPCR analysis of CD patient samples may significantly contribute to ensuring the quality of laboratory data generated in clinical trials and molecular diagnostics laboratories of

A Randomised Controlled Trial to Reduce Sedentary Time in Young Adults at Risk of Type 2 Diabetes Mellitus: Project STAND (Sedentary Time ANd Diabetes.

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Stuart J H Biddle

Full Text Available Type 2 diabetes mellitus (T2DM, a serious and prevalent chronic disease, is traditionally associated with older age. However, due to the rising rates of obesity and sedentary lifestyles, it is increasingly being diagnosed in the younger population. Sedentary (sitting behaviour has been shown to be associated with greater risk of cardio-metabolic health outcomes, including T2DM. Little is known about effective interventions to reduce sedentary behaviour in younger adults at risk of T2DM. We aimed to investigate, through a randomised controlled trial (RCT design, whether a group-based structured education workshop focused on sitting reduction, with self-monitoring, reduced sitting time.Adults aged 18-40 years who were either overweight (with an additional risk factor for T2DM or obese were recruited for the Sedentary Time ANd Diabetes (STAND RCT. The intervention programme comprised of a 3-hour group-based structured education workshop, use of a self-monitoring tool, and follow-up motivational phone call. Data were collected at three time points: baseline, 3 and 12 months after baseline. The primary outcome measure was accelerometer-assessed sedentary behaviour after 12 months. Secondary outcomes included other objective (activPAL and self-reported measures of sedentary behaviour and physical activity, and biochemical, anthropometric, and psycho-social variables.187 individuals (69% female; mean age 33 years; mean BMI 35 kg/m2 were randomised to intervention and control groups. 12 month data, when analysed using intention-to-treat analysis (ITT and per-protocol analyses, showed no significant difference in the primary outcome variable, nor in the majority of the secondary outcome measures.A structured education intervention designed to reduce sitting in young adults at risk of T2DM was not successful in changing behaviour at 12 months. Lack of change may be due to the brief nature of such an intervention and lack of focus on environmental change

School-based intervention on healthy behaviour among Ecuadorian adolescents: effect of a cluster-randomized controlled trial on screen-time.

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Andrade, Susana; Verloigne, Maïté; Cardon, Greet; Kolsteren, Patrick; Ochoa-Avilés, Angelica; Verstraeten, Roosmarijn; Donoso, Silvana; Lachat, Carl

2015-09-22

Effective interventions on screen-time behaviours (television, video games and computer time) are needed to prevent non-communicable diseases in low- and middle-income countries. The present manuscript investigates the effect of a school-based health promotion intervention on screen-time behaviour among 12- to 15-year-old adolescents. We report the effect of the trial on screen-time after two stages of implementation. We performed a cluster-randomised pair matched trial in urban schools in Cuenca-Ecuador. Participants were adolescents of grade eight and nine (mean age 12.8 ± 0.8 years, n = 1370, control group n = 684) from 20 schools (control group n = 10). The intervention included an individual and environmental component tailored to the local context and resources. The first intervention stage focused on diet, physical activity and screen-time behaviour, while the second stage focused only on diet and physical activity. Screen-time behaviours, primary outcome, were assessed at baseline, after the first (18 months) and second stage (28 months). Mixed linear models were used to analyse the data. After the first stage (data from n = 1224 adolescents; control group n = 608), the intervention group had a lower increase in TV-time on a week day (β = -15.7 min; P = 0.003) and weekend day (β = -18.9 min; P = 0.005), in total screen-time on a weekday (β = -25.9 min; P = 0.03) and in the proportion of adolescents that did not meet the screen-time recommendation (β = -4 percentage point; P = 0.01), compared to the control group. After the second stage (data from n = 1078 adolescents; control group n = 531), the TV-time on a weekday (β = 13.1 min; P = 0.02), and total screen-time on a weekday (β = 21.4 min; P = 0.03) increased more in adolescents from the intervention group. No adverse effects were reported. A multicomponent school-based intervention was only able to mitigate the increase

A randomized trial comparing part-time patching with observation for children 3 to 10 years of age with intermittent exotropia.

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Cotter, Susan A; Mohney, Brian G; Chandler, Danielle L; Holmes, Jonathan M; Repka, Michael X; Melia, Michele; Wallace, David K; Beck, Roy W; Birch, Eileen E; Kraker, Raymond T; Tamkins, Susanna M; Miller, Aaron M; Sala, Nicholas A; Glaser, Stephen R

2014-12-01

To determine the effectiveness of prescribed part-time patching for treatment of intermittent exotropia (IXT) in children. Multicenter, randomized clinical trial. Three hundred fifty-eight children 3 to part-time patching group (difference, 5.4%; lower limit of 1-sided exact 95% confidence interval, 2.0%; P = 0.004, 1-sided hypothesis test). Deterioration of previously untreated childhood IXT over a 6-month period is uncommon with or without patching treatment. Although there is a slightly lower deterioration rate with patching, both management approaches are reasonable for treating children 3 to 10 years of age with IXT. Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Haemoglobin mass and running time trial performance after recombinant human erythropoietin administration in trained men.

Directory of Open Access Journals (Sweden)

Jérôme Durussel

Full Text Available UNLABELLED: Recombinant human erythropoietin (rHuEpo increases haemoglobin mass (Hb(mass and maximal oxygen uptake (v O(2 max. PURPOSE: This study defined the time course of changes in Hb(mass, v O(2 max as well as running time trial performance following 4 weeks of rHuEpo administration to determine whether the laboratory observations would translate into actual improvements in running performance in the field. METHODS: 19 trained men received rHuEpo injections of 50 IU•kg(-1 body mass every two days for 4 weeks. Hb(mass was determined weekly using the optimized carbon monoxide rebreathing method until 4 weeks after administration. v O(2 max and 3,000 m time trial performance were measured pre, post administration and at the end of the study. RESULTS: Relative to baseline, running performance significantly improved by ∼6% after administration (10:30±1:07 min:sec vs. 11:08±1:15 min:sec, p<0.001 and remained significantly enhanced by ∼3% 4 weeks after administration (10:46±1:13 min:sec, p<0.001, while v O(2 max was also significantly increased post administration (60.7±5.8 mL•min(-1•kg(-1 vs. 56.0±6.2 mL•min(-1•kg(-1, p<0.001 and remained significantly increased 4 weeks after rHuEpo (58.0±5.6 mL•min(-1•kg(-1, p = 0.021. Hb(mass was significantly increased at the end of administration compared to baseline (15.2±1.5 g•kg(-1 vs. 12.7±1.2 g•kg(-1, p<0.001. The rate of decrease in Hb(mass toward baseline values post rHuEpo was similar to that of the increase during administration (-0.53 g•kg(-1•wk(-1, 95% confidence interval (CI (-0.68, -0.38 vs. 0.54 g•kg(-1•wk(-1, CI (0.46, 0.63 but Hb(mass was still significantly elevated 4 weeks after administration compared to baseline (13.7±1.1 g•kg(-1, p<0.001. CONCLUSION: Running performance was improved following 4 weeks of rHuEpo and remained elevated 4 weeks after administration compared to baseline. These field performance effects coincided with r

Unexpected perturbations training improves balance control and voluntary stepping times in older adults - a double blind randomized control trial.

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Kurz, Ilan; Gimmon, Yoav; Shapiro, Amir; Debi, Ronen; Snir, Yoram; Melzer, Itshak

2016-03-04

Falls are common among elderly, most of them occur while slipping or tripping during walking. We aimed to explore whether a training program that incorporates unexpected loss of balance during walking able to improve risk factors for falls. In a double-blind randomized controlled trial 53 community dwelling older adults (age 80.1±5.6 years), were recruited and randomly allocated to an intervention group (n = 27) or a control group (n = 26). The intervention group received 24 training sessions over 3 months that included unexpected perturbation of balance exercises during treadmill walking. The control group performed treadmill walking with no perturbations. The primary outcome measures were the voluntary step execution times, traditional postural sway parameters and Stabilogram-Diffusion Analysis. The secondary outcome measures were the fall efficacy Scale (FES), self-reported late life function (LLFDI), and Performance-Oriented Mobility Assessment (POMA). Compared to control, participation in intervention program that includes unexpected loss of balance during walking led to faster Voluntary Step Execution Times under single (p = 0.002; effect size [ES] =0.75) and dual task (p = 0.003; [ES] = 0.89) conditions; intervention group subjects showed improvement in Short-term Effective diffusion coefficients in the mediolateral direction of the Stabilogram-Diffusion Analysis under eyes closed conditions (p = 0.012, [ES] = 0.92). Compared to control there were no significant changes in FES, LLFDI, and POMA. An intervention program that includes unexpected loss of balance during walking can improve voluntary stepping times and balance control, both previously reported as risk factors for falls. This however, did not transferred to a change self-reported function and FES. ClinicalTrials.gov NCT01439451 .

Pediatric Clinical Trials Conducted in South Korea from 2006 to 2015: An Analysis of the South Korean Clinical Research Information Service, US ClinicalTrials.gov and European Clinical Trials Registries.

Science.gov (United States)

Choi, Sheung-Nyoung; Lee, Ji-Hyun; Song, In-Kyung; Kim, Eun-Hee; Kim, Jin-Tae; Kim, Hee-Soo

2017-12-01

The status of pediatric clinical trials performed in South Korea in the last decade, including clinical trials of drugs with unapproved indications for children, has not been previously examined. The aim was to provide information regarding the current state of pediatric clinical trials and create a basis for future trials performed in South Korea by reviewing three databases of clinical trials registrations. We searched for pediatric clinical studies (participants South Korea between 2006 and 2015 registered on the Clinical Research Information Service (CRIS), ClinicalTrials.gov, and the European Clinical Trials Registry (EuCTR). Additionally, we reviewed whether unapproved indications were involved in each trial by comparing the trials with a list of authorized trials provided by the Ministry of Food and Drug Safety (MFDS). The primary and secondary outcomes were to determine the change in number of pediatric clinical trials with unapproved indications over time and to assess the status of unauthorized pediatric clinical trials from the MFDS and the publication of articles after these clinical trials, respectively. We identified 342 clinical studies registered in the CRIS (n = 81), ClinicalTrials.gov (n = 225), and EuCTR (n = 36), of which 306 were reviewed after excluding duplicate registrations. Among them, 181 studies were interventional trials dealing with drugs and biological agents, of which 129 (71.3%) involved unapproved drugs. Of these 129 trials, 107 (82.9%) were authorized by the MFDS. Pediatric clinical trials in South Korea aiming to establish the safety and efficacy of drugs in children are increasing; however, non-MFDS-authorized studies remain an issue.

Design of Phase II Non-inferiority Trials.

Science.gov (United States)

Jung, Sin-Ho

2017-09-01

With the development of inexpensive treatment regimens and less invasive surgical procedures, we are confronted with non-inferiority study objectives. A non-inferiority phase III trial requires a roughly four times larger sample size than that of a similar standard superiority trial. Because of the large required sample size, we often face feasibility issues to open a non-inferiority trial. Furthermore, due to lack of phase II non-inferiority trial design methods, we do not have an opportunity to investigate the efficacy of the experimental therapy through a phase II trial. As a result, we often fail to open a non-inferiority phase III trial and a large number of non-inferiority clinical questions still remain unanswered. In this paper, we want to develop some designs for non-inferiority randomized phase II trials with feasible sample sizes. At first, we review a design method for non-inferiority phase III trials. Subsequently, we propose three different designs for non-inferiority phase II trials that can be used under different settings. Each method is demonstrated with examples. Each of the proposed design methods is shown to require a reasonable sample size for non-inferiority phase II trials. The three different non-inferiority phase II trial designs are used under different settings, but require similar sample sizes that are typical for phase II trials.

Women's experiences of participating in the early external cephalic version 2 trial.

Science.gov (United States)

Murray-Davis, Beth; Marion, Anya; Malott, Anne; Reitsma, Angela; Hutton, Eileen K

2012-03-01

The international, multicenter External Cephalic Version 2 (ECV2) Trial compared early external cephalic version at 34(0/7) to 35(6/7) weeks with that at greater than 37 weeks. A total of 1,543 women were randomized from 68 centers in 21 countries. The goal of this component of the trial was to understand women's views about participation in a research trial and timing of external cephalic version. A postpartum questionnaire was completed containing a 5-point Likert scale examining contact and availability of staff, choice of timing of external cephalic version, preference of randomization, convenience of participating, and overall satisfaction. Participants also completed two open-ended questions related to timing of external cephalic version and satisfaction with the trial. Descriptive statistics and content analysis were used to analyze data. A total of 1,458 women completed the questionnaire, of whom 86 percent said "yes"-they would participate in the trial again. Themes influencing decisions about participating were perceptions of the external cephalic version experience, preferred mode of delivery, preferred timing of external cephalic version, and perceptions of the effectiveness of external cephalic version and of the trial environment. Many participants preferred the early timing of the procedure offered through the trial because of perceived advantages of a smaller baby being easier to turn and the opportunity for repeat procedures. Women were positive about their participation in the trial. Early external cephalic version was preferred over the traditional timing as it was perceived to afford both physiologic and practical advantages. © 2012, Copyright the Authors. Journal compilation © 2012, Wiley Periodicals, Inc.

The Eichmann Trial on East German Television

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Judith Keilbach

2014-06-01

Full Text Available The trial against Adolf Eichmann was one of the first transnational media events on television. Its world-wide coverage required transnational cooperation. Using East German television reports about the trial this article argues that although the event transcended national borders it maintained at the same time ideological boundaries.

Central coordination as an alternative for local coordination in a multicenter randomized controlled trial: the FAITH trial experience

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Zielinski Stephanie M

2012-01-01

Full Text Available Abstract Background Surgeons in the Netherlands, Canada and the US participate in the FAITH trial (Fixation using Alternative Implants for the Treatment of Hip fractures. Dutch sites are managed and visited by a financed central trial coordinator, whereas most Canadian and US sites have local study coordinators and receive per patient payment. This study was aimed to assess how these different trial management strategies affected trial performance. Methods Details related to obtaining ethics approval, time to trial start-up, inclusion, and percentage completed follow-ups were collected for each trial site and compared. Pre-trial screening data were compared with actual inclusion rates. Results Median trial start-up ranged from 41 days (P25-P75 10-139 in the Netherlands to 232 days (P25-P75 98-423 in Canada (p = 0.027. The inclusion rate was highest in the Netherlands; median 1.03 patients (P25-P75 0.43-2.21 per site per month, representing 34.4% of the total eligible population. It was lowest in Canada; 0.14 inclusions (P25-P75 0.00-0.28, representing 3.9% of eligible patients (p Conclusions In this trial, a central financed trial coordinator to manage all trial related tasks in participating sites resulted in better trial progression and a similar follow-up. It is therefore a suitable alternative for appointing these tasks to local research assistants. The central coordinator approach can enable smaller regional hospitals to participate in multicenter randomized controlled trials. Circumstances such as available budget, sample size, and geographical area should however be taken into account when choosing a management strategy. Trial Registration ClinicalTrials.gov: NCT00761813

Sustainable development of a GCP-compliant clinical trials platform in Africa: the malaria clinical trials alliance perspective.

Science.gov (United States)

Ogutu, Bernhards R; Baiden, Rita; Diallo, Diadier; Smith, Peter G; Binka, Fred N

2010-04-20

The Malaria Clinical Trials Alliance (MCTA), a programme of INDEPTH network of demographic surveillance centres, was launched in 2006 with two broad objectives: to facilitate the timely development of a network of centres in Africa with the capacity to conduct clinical trials of malaria vaccines and drugs under conditions of good clinical practice (GCP); and to support, strengthen and mentor the centres in the network to facilitate their progression towards self-sustaining clinical research centres. Sixteen research centres in 10 African malaria-endemic countries were selected that were already working with the Malaria Vaccine Initiative (MVI) or the Medicines for Malaria Venture (MMV). All centres were visited to assess their requirements for research capacity development through infrastructure strengthening and training. Support provided by MCTA included: laboratory and facility refurbishment; workshops on GCP, malaria diagnosis, strategic management and media training; and training to support staff to undertake accreditation examinations of the Association of Clinical Research Professionals (ACRP). Short attachments to other network centres were also supported to facilitate sharing practices within the Alliance. MCTA also played a key role in the creation of the African Media & Malaria Research Network (AMMREN), which aims to promote interaction between researchers and the media for appropriate publicity and media reporting of research and developments on malaria, including drug and vaccine trials. In three years, MCTA strengthened 13 centres to perform GCP-compliant drug and vaccine trials, including 11 centres that form the backbone of a large phase III malaria vaccine trial. MCTA activities have demonstrated that centres can be brought up to GCP compliance on this time scale, but the costs are substantial and there is a need for further support of other centres to meet the growing demand for clinical trial capacity. The MCTA experience also indicates that

Effect of electronic time monitors on children's television watching: pilot trial of a home-based intervention.

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Ni Mhurchu, Cliona; Roberts, Vaughan; Maddison, Ralph; Dorey, Enid; Jiang, Yannan; Jull, Andrew; Tin Tin, Sandar

2009-11-01

This pilot study evaluated the feasibility (recruitment, retention, and acceptability) and preliminary efficacy of a six-week home-based electronic time monitor intervention on New Zealand children's television watching in 2008. Twenty-nine children aged 9 to 12 years who watched more than 20 h of television per week (62% male, mean age 10.4 years) were randomised to either the intervention or the control group. The intervention group received an electronic TV time monitor for 6 weeks and advice to restrict TV watching to 1 h per day or less. The control group was given verbal advice to restrict TV watching. Participant retention at 6 weeks was 93%. Semi-structured interviews with intervention families confirmed moderate acceptability of TV time monitors and several perceived benefits including better awareness of household TV viewing and improved time planning. Drawbacks reported included disruption to parents' TV watching and increased sibling conflict. Time spent watching television decreased by 4.2 h (mean change [SD]: -254 [536] min) per week in the intervention group compared with no change in the control group (-3 [241] min), but the difference between groups was not statistically significant, p=0.77. Both groups reported decreases in energy intake from snacks and total screen time and increases in physical activity measured by pedometer and between-group differences were not statistically significant. Electronic TV time monitors are feasible to use for home-based TV watching interventions although acceptability varies between families. Preliminary findings from this pilot suggest that such devices have potential to decrease children's TV watching but a larger trial is needed to confirm effectiveness. Future research should be family-orientated; take account of other screen time activities; and employ TV time monitors as just one of a range of strategies to decrease sedentary behaviour.

Future vision for the quality assurance of oncology clinical trials

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Thomas eFitzGerald, MD

2013-03-01

Full Text Available The National Cancer Institute clinical cooperative groups have been instrumental over the past 50 years in developing clinical trials and evidence based process improvements for clinical oncology patient care. The cooperative groups are undergoing a transformation process as we further integrate molecular biology into personalized patient care and move to incorporate international partners in clinical trials. To support this vision, data acquisition and data management informatics tools must become both nimble and robust to support transformational research at an enterprise level. Information, including imaging, pathology, molecular biology, radiation oncology, surgery, systemic therapy and patient outcome data needs to be integrated into the clinical trial charter using adaptive clinical trial mechanisms for design of the trial. This information needs to be made available to investigators using digital processes for real time data analysis. Future clinical trials will need to be designed and completed in a timely manner facilitated by nimble informatics processes for data management. This paper discusses both past experience and future vision for clinical trials as we move to develop data management and quality assurance processes to meet the needs of the modern trial.

Publication and non-publication of drug trial results: a 10-year cohort of trials in Norwegian general practice.

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Brænd, Anja Maria; Straand, Jørund; Jakobsen, Rune Bruhn; Klovning, Atle

2016-04-11

Previously, we identified a 10-year cohort of protocols from applications to the Norwegian Medicines Agency 1998-2007, consisting of 196 drug trials in general practice. The aim of this study was to examine whether trial results were published and whether trial funding and conflicts of interest were reported. Cohort study of trials with systematic searches for published results. Clinical drug trials in Norwegian general practice. We performed systematic literature searches of MEDLINE, Embase and CENTRAL to identify publications originating from each trial using characteristics such as test drug, comparator and patient groups as search terms. When no publication was identified, we contacted trial sponsors for information regarding trial completion and reference to any publications. We determined the frequency of publication of trial results and trial characteristics associated with publication of results. Of the 196 trials, 5 were never started. Of the remaining 191 trials, 71% had results published in a journal, 11% had results publicly available elsewhere and 18% of trials had no results available. Publication was more common among trials with an active comparator drug (χ(2) test, p=0.040), with a larger number of patients (total sample size≥median, p=0.010) and with a longer trial period (duration≥median, p=0.025). Trial funding was reported in 85% of publications and increased over time, as did reporting of conflicts of interest among authors. Among the 134 main journal articles from the trials, 60% presented statistically significant results for the investigational drug, and the conclusion of the article was favourable towards the test drug in 78% of papers. We did not identify any journal publication of results for 29% of the general practice drug trials. Trials with an active comparator, larger and longer trials were more likely to be published. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a

The Effect of Medium Chain Triglycerides on Time to Nutritional Ketosis and Symptoms of Keto-Induction in Healthy Adults: A Randomised Controlled Clinical Trial

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Cliff J. d C. Harvey

2018-01-01

Full Text Available Medium chain triglycerides (MCTs are ketogenic and might reduce adverse effects of keto-induction and improve time to ketosis and the tolerability of very low carbohydrate diets. This study investigates whether MCT supplementation improves time to nutritional ketosis (NK, mood, and symptoms of keto-induction. We compared changes in beta-hydroxybutyrate (BOHB, blood glucose, symptoms of keto-induction, and mood disturbance, in 28 healthy adults prescribed a ketogenic diet, randomised to receive either 30 ml of MCT, or sunflower oil as a control, three times per day, for 20 days. The primary outcome measured was the achievement of NK (≥0.5 mmol·L−1 BOHB. Participants also completed a daily Profile of Mood States and keto-induction symptom questionnaire. MCT resulted in higher BOHB at all time points and faster time to NK, a result that failed to reach significance. Symptoms of keto-induction resulted from both diets, with a greater magnitude in the control group, except for abdominal pain, which occurred with greater frequency and severity in the MCT-supplemented diet. There was a possibly beneficial effect on symptoms by MCT, but the effect on mood was unclear. Based on these results, MCTs increase BOHB compared with LCT and reduce symptoms of keto-induction. It is unclear whether MCTs significantly improve mood or time to NK. The trial was registered by the Australia New Zealand Clinical Trial Registry ACTRN12616001099415.

Timing of urinary catheter removal after uncomplicated total abdominal hysterectomy: a prospective randomized trial.

Science.gov (United States)

Ahmed, Magdy R; Sayed Ahmed, Waleed A; Atwa, Khaled A; Metwally, Lobna

2014-05-01

To assess whether immediate (0h), intermediate (after 6h) or delayed (after 24h) removal of an indwelling urinary catheter after uncomplicated abdominal hysterectomy can affect the rate of re-catheterization due to urinary retention, rate of urinary tract infection, ambulation time and length of hospital stay. Prospective randomized controlled trial conducted at Suez Canal University Hospital, Egypt. Two hundred and twenty-one women underwent total abdominal hysterectomy for benign gynecological diseases and were randomly allocated into three groups. Women in group A (73 patients) had their urinary catheter removed immediately after surgery. Group B (81 patients) had the catheter removed 6h post-operatively while in group C (67 patients) the catheter was removed after 24h. The main outcome measures were the frequency of urinary retention, urinary tract infections, ambulation time and length of hospital stay. There was a significantly higher number of urinary retention episodes requiring re-catheterization in the immediate removal group compared to the intermediate and delayed removal groups (16.4% versus 2.5% and 0% respectively). Delayed urinary catheter removal was associated with a higher incidence of urinary tract infections (15%), delayed ambulation time (10.3h) and longer hospital stay (5.6 days) compared to the early (1.4%, 4.1h and 3.2 days respectively) and intermediate (3.7%, 6.8h and 3.4 days respectively) removal groups. Removal of the urinary catheter 6h postoperatively appears to be more advantageous than early or late removal in cases of uncomplicated total abdominal hysterectomy. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Activating clinical trials: a process improvement approach.

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Martinez, Diego A; Tsalatsanis, Athanasios; Yalcin, Ali; Zayas-Castro, José L; Djulbegovic, Benjamin

2016-02-24

The administrative process associated with clinical trial activation has been criticized as costly, complex, and time-consuming. Prior research has concentrated on identifying administrative barriers and proposing various solutions to reduce activation time, and consequently associated costs. Here, we expand on previous research by incorporating social network analysis and discrete-event simulation to support process improvement decision-making. We searched for all operational data associated with the administrative process of activating industry-sponsored clinical trials at the Office of Clinical Research of the University of South Florida in Tampa, Florida. We limited the search to those trials initiated and activated between July 2011 and June 2012. We described the process using value stream mapping, studied the interactions of the various process participants using social network analysis, and modeled potential process modifications using discrete-event simulation. The administrative process comprised 5 sub-processes, 30 activities, 11 decision points, 5 loops, and 8 participants. The mean activation time was 76.6 days. Rate-limiting sub-processes were those of contract and budget development. Key participants during contract and budget development were the Office of Clinical Research, sponsors, and the principal investigator. Simulation results indicate that slight increments on the number of trials, arriving to the Office of Clinical Research, would increase activation time by 11 %. Also, incrementing the efficiency of contract and budget development would reduce the activation time by 28 %. Finally, better synchronization between contract and budget development would reduce time spent on batching documentation; however, no improvements would be attained in total activation time. The presented process improvement analytic framework not only identifies administrative barriers, but also helps to devise and evaluate potential improvement scenarios. The strength

Marketing and clinical trials: a case study.

Science.gov (United States)

Francis, David; Roberts, Ian; Elbourne, Diana R; Shakur, Haleema; Knight, Rosemary C; Garcia, Jo; Snowdon, Claire; Entwistle, Vikki A; McDonald, Alison M; Grant, Adrian M; Campbell, Marion K

2007-11-20

Publicly funded clinical trials require a substantial commitment of time and money. To ensure that sufficient numbers of patients are recruited it is essential that they address important questions in a rigorous manner and are managed well, adopting effective marketing strategies. Using methods of analysis drawn from management studies, this paper presents a structured assessment framework or reference model, derived from a case analysis of the MRC's CRASH trial, of 12 factors that may affect the success of the marketing and sales activities associated with clinical trials. The case study demonstrates that trials need various categories of people to buy in - hence, to be successful, trialists must embrace marketing strategies to some extent. The performance of future clinical trials could be enhanced if trialists routinely considered these factors.

Inter-Trial Gait Variability Reduction Using Continous Curve Registration

National Research Council Canada - National Science Library

Sadeghi, H

2001-01-01

Timing in peak gait values shifts slightly between gait trials. When gait data are averaged, some of the standard deviation can be associated to this inter-trial variability unless normalization is carried out beforehand...

Clustering in surgical trials - database of intracluster correlations

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Cook Jonathan A

2012-01-01

Full Text Available Abstract Background Randomised trials evaluation of surgical interventions are often designed and analysed as if the outcome of individual patients is independent of the surgeon providing the intervention. There is reason to expect outcomes for patients treated by the same surgeon tend to be more similar than those under the care of another surgeon due to previous experience, individual practice, training, and infrastructure. Such a phenomenon is referred to as the clustering effect and potentially impacts on the design and analysis adopted and thereby the required sample size. The aim of this work was to inform trial design by quantifying clustering effects (at both centre and surgeon level for various outcomes using a database of surgical trials. Methods Intracluster correlation coefficients (ICCs were calculated for outcomes from a set of 10 multicentre surgical trials for a range of outcomes and different time points for clustering at both the centre and surgeon level. Results ICCs were calculated for 198 outcomes across the 10 trials at both centre and surgeon cluster levels. The number of cases varied from 138 to 1370 across the trials. The median (range average cluster size was 32 (9 to 51 and 6 (3 to 30 for centre and surgeon levels respectively. ICC estimates varied substantially between outcome type though uncertainty around individual ICC estimates was substantial, which was reflected in generally wide confidence intervals. Conclusions This database of surgical trials provides trialists with valuable information on how to design surgical trials. Our data suggests clustering of outcome is more of an issue than has been previously acknowledged. We anticipate that over time the addition of ICCs from further surgical trial datasets to our database will further inform the design of surgical trials.

Kinematics and load-sharing of an anterior thoracolumbar spinal reconstruction construct with PEEK rods: An in vitro biomechanical study.

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Zhou, Ruozhou; Huang, Zhiping; Liu, Xiang; Tong, Jie; Ji, Wei; Liu, Sheting; Zhu, Qingan

2016-12-01

Polyetheretherketone rod constructs provide adequate spinal stability. Kinematics and load sharing of anterior thoracolumbar reconstruction with polyetheretherketone rods under preload remains unknown. Eight human cadaveric specimens (T11-L3) were subjected to a pure moment of 5.0Nm in flexion-extension, lateral bending and axial rotation, and flexion-extension with a compressive preload of 300N. An anterior reconstruction of L1 corpectomy was conducted with a surrogate bone graft and anterior rod constructs (polyetheretherketone or titanium rods). An axial load-cell was built in the surrogate bone graft to measure the compressive force in the graft. Range of motion, neutral zone and compressive force in the graft were compared between constructs. The polyetheretherketone rod construct resulted in more motion than the titanium rod construct, particularly in extension (P=0.011) and axial rotation (P=0.001), but less motion than the intact in all directions except in axial rotation. There was no difference in range of motion or neutral zone between constructs in flexion-extension under preload. The polyetheretherketone rod construct kept the graft compressed 52N which was similar to the titanium rod construct (63N), but allowed the graft compressed more under the preload (203N vs. 123N, P=0.003). The compressive forces fluctuated in flexion-extension without preload, but increased in flexion and decreased in extension under preload. The polyetheretherketone rod construct allowed more motion compared to the titanium rod construct, but provided stability in flexion and lateral bending without preload, and flexion and extension under preload. The anterior graft shared higher load under preload, particularly for the polyetheretherketone rod construct. The results of this study suggest that rigidity of rods in the anterior reconstruction affects kinematic behavior and load sharing. Copyright © 2016 Elsevier Ltd. All rights reserved.

Analysis of Workflow and Time to Treatment and the Effects on Outcome in Endovascular Treatment of Acute Ischemic Stroke: Results from the SWIFT PRIME Randomized Controlled Trial.

Science.gov (United States)

Goyal, Mayank; Jadhav, Ashutosh P; Bonafe, Alain; Diener, Hans; Mendes Pereira, Vitor; Levy, Elad; Baxter, Blaise; Jovin, Tudor; Jahan, Reza; Menon, Bijoy K; Saver, Jeffrey L

2016-06-01

Purpose To study the relationship between functional independence and time to reperfusion in the Solitaire with the Intention for Thrombectomy as Primary Endovascular Treatment for Acute Ischemic Stroke (SWIFT PRIME) trial in patients with disabling acute ischemic stroke who underwent endovascular therapy plus intravenous tissue plasminogen activator (tPA) administration versus tPA administration alone and to investigate variables that affect time spent during discrete steps. Materials and Methods Data were analyzed from the SWIFT PRIME trial, a global, multicenter, prospective study in which outcomes were compared in patients treated with intravenous tPA alone or in combination with the Solitaire device (Covidien, Irvine, Calif). Between December 2012 and November 2014, 196 patients were enrolled. The relation between time from (a) symptom onset to reperfusion and (b) imaging to reperfusion and clinical outcome was analyzed, along with patient and health system characteristics that affect discrete steps in patient workflow. Multivariable logistic regression was used to assess relationships between time and outcome; negative binomial regression was used to evaluate effects on workflow. The institutional review board at each site approved the trial. Patients provided written informed consent, or, at select sites, there was an exception from having to acquire explicit informed consent in emergency circumstances. Results In the stent retriever arm of the study, symptom onset to reperfusion time of 150 minutes led to 91% estimated probability of functional independence, which decreased by 10% over the next hour and by 20% with every subsequent hour of delay. Time from arrival at the emergency department to arterial access was 90 minutes (interquartile range, 69-120 minutes), and time to reperfusion was 129 minutes (interquartile range, 108-169 minutes). Patients who initially arrived at a referring facility had longer symptom onset to groin puncture times compared with

Reporting bias in completed epilepsy intervention trials: A cross-sectional analysis.

Science.gov (United States)

Rayi, Appaji; Thompson, Stephanie; Gloss, David; Malhotra, Konark

2018-03-30

To explore the evidence of reporting bias among completed epilepsy intervention trials (EITs) and compliance of applicable EITs to Food and Drug Administration Amendments Act (FDAAA). We included consecutive EITs registered as completed on ClinicalTrials.gov from 2008 to 2015. Descriptive data was collected including study type, study phase, funding source, primary completion date, and result reporting date. Time to result reporting was analyzed using Kaplan-Meier estimates for two time periods (2008-2011 and 2012-2015). PubMed, Web of Science, and Google scholar databases were manually searched for publication details. Overall, 95/126 EITs (75%) reported, while remaining 31/126 (25%) did not report their results. Time to reporting was significantly lower for trials completed during 2012-2015 (16.5 months; 95% CI: 13.60-19.40; p = .002; Cohen's d = 0.68) as compared to the trials completed during 2008-2011 (25.9 months; 95% CI: 21.56-30.22). 72/126 trials were conducted in at least one U.S. center. 56/72 (78%) of the trials met the FDAAA criteria, while only 19/56 (34%) reported within the mandated one-year time frame. The lack of reporting of nearly one-quarter of completed epilepsy intervention trials suggests existence of reporting bias. As such, it should be considered an important criterion for determining risk of bias in epilepsy systematic reviews. Copyright © 2018 Elsevier B.V. All rights reserved.

Perceived barriers to pediatrician and family practitioner participation in pediatric clinical trials: Findings from the Clinical Trials Transformation Initiative.

Science.gov (United States)

Greenberg, Rachel G; Corneli, Amy; Bradley, John; Farley, John; Jafri, Hasan S; Lin, Li; Nambiar, Sumathi; Noel, Gary J; Wheeler, Chris; Tiernan, Rosemary; Smith, P Brian; Roberts, Jamie; Benjamin, Daniel K

2018-03-01

Despite legislation to stimulate pediatric drug development through clinical trials, enrolling children in trials continues to be challenging. Non-investigator (those who have never served as a clinical trial investigator) providers are essential to recruitment of pediatric patients, but little is known regarding the specific barriers that limit pediatric providers from participating in and referring their patients to clinical trials. We conducted an online survey of pediatric providers from a wide variety of practice types across the United States to evaluate their attitudes and awareness of pediatric clinical trials. Using a 4-point Likert scale, providers described their perception of potential barriers to their practice serving as a site for pediatric clinical trials. Of the 136 providers surveyed, 52/136 (38%) had previously referred a pediatric patient to a trial, and only 17/136 (12%) had ever been an investigator for a pediatric trial. Lack of awareness of existing pediatric trials was a major barrier to patient referral by providers, in addition to consideration of trial risks, distance to the site, and time needed to discuss trial participation with parents. Overall, providers perceived greater challenges related to parental concerns and parent or child logistical barriers than study implementation and ethics or regulatory barriers as barriers to their practice serving as a trial site. Providers who had previously been an investigator for a pediatric trial were less likely to be concerned with potential barriers than non-investigators. Understanding the barriers that limit pediatric providers from collaboration or inhibit their participation is key to designing effective interventions to optimize pediatric trial participation.

Clinical Trials

Medline Plus

Full Text Available ... Trial Protocol Each clinical trial has a master plan called a protocol (PRO-to-kol). This plan explains how the trial will work. The trial ... clinical trial; and detailed information about the treatment plan. Eligibility Criteria A clinical trial's protocol describes what ...

Trial-to-trial dynamics of selective long-term-memory retrieval with continuously changing retrieval targets.

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Kizilirmak, Jasmin M; Rösler, Frank; Khader, Patrick H

2014-10-01

How do we control the successive retrieval of behaviorally relevant information from long-term memory (LTM) without being distracted by other potential retrieval targets associated to the same retrieval cues? Here, we approach this question by investigating the nature of trial-by-trial dynamics of selective LTM retrieval, i.e., in how far retrieval in one trial has detrimental or facilitatory effects on selective retrieval in the following trial. Participants first learned associations between retrieval cues and targets, with one cue always being linked to three targets, forming small associative networks. In successive trials, participants had to access either the same or a different target belonging to either the same or a different cue. We found that retrieval times were faster for targets that had already been relevant in the previous trial, with this facilitatory effect being substantially weaker when the associative network changed in which the targets were embedded. Moreover, staying within the same network still had a facilitatory effect even if the target changed, which became evident in a relatively higher memory performance in comparison to a network change. Furthermore, event-related brain potentials (ERPs) showed topographically and temporally dissociable correlates of these effects, suggesting that they result from combined influences of distinct processes that aid memory retrieval when relevant and irrelevant targets change their status from trial to trial. Taken together, the present study provides insight into the different processing stages of memory retrieval when fast switches between retrieval targets are required. Copyright © 2014 Elsevier Inc. All rights reserved.

Behavioral insights and business taxation: Evidence from two randomized controlled trials

OpenAIRE

Biddle, Nicholas; Fels, Katja; Sinning, Mathias

2017-01-01

This paper presents the findings of two Randomized Controlled Trials (RCTs) that were conducted in collaboration with the Australian Taxation Office (ATO). The first trial tests the effect of changes to letters (timing, social norms, color, and provision of information about charitable donations) on response rates of businesses, the timing of payments and the amount of tax debt payments. The second trial consists of two parts. The first part aims to raise awareness of the relevance of tax deb...

Evaluation of the UP4FUN intervention: a cluster randomized trial to reduce and break up sitting time in European 10-12-year-old children.

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Frøydis N Vik

Full Text Available The UP4FUN intervention is a family-involved school-based intervention aiming at reducing and breaking up sitting time at home (with special emphasis on screen time, and breaking up sitting time in school among 10-12 year olds in Europe. The purpose of the present paper was to evaluate its short term effects.A total of 3147 pupils from Belgium, Germany, Greece, Hungary and Norway participated in a school-randomized controlled trial. The intervention included 1-2 school lessons per week for a period of six weeks, along with assignments for the children and their parents. Screen time and breaking up sitting time were registered by self-report and total sedentary time and breaking up sitting time by accelerometry. The effect of the intervention on these behaviors was evaluated by multilevel regression analyses. All analyses were adjusted for baseline values and gender. Significance level was p≤0.01. No significant intervention effects were observed, neither for self-reported TV/DVD or computer/game console time, nor for accelerometer-assessed total sedentary time and number of breaks in sitting time. The intervention group, however, reported more positive attitudes towards (β = 0.25 (95% CI 0.11, 0.38 and preferences/liking for (β = 0.20 (95% CI 0.08, 0.32 breaking up sitting time than the control group.No significant intervention effect on self-reported screen time or accelerometer-assessed sedentary time or breaks in sitting time was observed, but positive effects on beliefs regarding breaking up sitting time were found in favor of the intervention group. Overall, these results do not warrant wider dissemination of the present UP4FUN intervention.International Standard Randomized Controlled Trial Number Registry ISRCTN34562078.

Return to work after early part-time sick leave due to musculoskeletal disorders: a randomized controlled trial.

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Viikari-Juntura, Eira; Kausto, Johanna; Shiri, Rahman; Kaila-Kangas, Leena; Takala, Esa-Pekka; Karppinen, Jaro; Miranda, Helena; Luukkonen, Ritva; Martimo, Kari-Pekka

2012-03-01

The purpose of this study was to assess the effects of early part-time sick leave on return to work (RTW) and sickness absence among patients with musculoskeletal disorders. A randomized controlled trial was conducted in six occupational health units of medium- and large-size enterprises. Patients aged 18-60 years with musculoskeletal disorders (N=63) unable to perform their regular work were randomly allocated to part- or full-time sick leave. In the former group, workload was reduced by restricting work time by about a half. Remaining work tasks were modified when necessary, as specified in a "fit note" from the physician. The main outcomes were time to return to regular work activities and sickness absence during 12-month follow-up. Time to RTW sustained for ≥4 weeks was shorter in the intervention group (median 12 versus 20 days, P=0.10). Hazard ratio of RTW adjusted for age was 1.60 [95% confidence interval (95% CI) 0.98-2.63] and 1.76 (95% CI 1.21-2.56) after further adjustment for pain interference with sleep and previous sickness absence at baseline. Total sickness absence during the 12-month follow-up was about 20% lower in the intervention than the control group. Compliance with the intervention was high with no discontinuations of part-time sick leave due to musculoskeletal reasons. Early part-time sick leave may provide a faster and more sustainable return to regular duties than full-time sick leave among patients with musculoskeletal disorders. This is the first study to show that work participation can be safely increased with early part-time sick leave.

Clinical efficacy, onset time and safety of bright light therapy in acute bipolar depression as an adjunctive therapy: A randomized controlled trial.

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Zhou, Tian-Hang; Dang, Wei-Min; Ma, Yan-Tao; Hu, Chang-Qing; Wang, Ning; Zhang, Guo-Yi; Wang, Gang; Shi, Chuan; Zhang, Hua; Guo, Bin; Zhou, Shu-Zhe; Feng, Lei; Geng, Shu-Xia; Tong, Yu-Zhen; Tang, Guan-Wen; He, Zhong-Kai; Zhen, Long; Yu, Xin

2018-02-01

Bright light therapy (BLT) is an effective treatment for seasonal affective disorder and non- seasonal depression. The efficacy of BLT in treating patients with bipolar disorder is still unknown. The aim of this study is to examine the efficacy, onset time and clinical safety of BLT in treating patients with acute bipolar depression as an adjunctive therapy (trial registration at ClinicalTrials.gov: NCT02009371). This was a multi-center, single blind, randomized clinical trial. Seventy-four participants were randomized in one of two treatment conditions: BLT and control (dim red light therapy, dRLT). Sixty-three participants completed the study (33 BLT, 30 dRLT). Light therapy lasted for two weeks, one hour every morning. All participants were required to complete several scales assessments at baseline, and at the end of weeks 1 and 2. The primary outcome measures were the clinical efficacy of BLT which was assessed by the reduction rate of HAMD-17 scores, and the onset time of BLT which was assessed by the reduction rate of QIDS-SR16 scores. The secondary outcome measures were rates of switch into hypomania or mania and adverse events. 1) Clinical efficacy: BLT showed a greater ameliorative effect on bipolar depression than the control, with response rates of 78.19% vs. 43.33% respectively (p < 0.01). 2) Onset day: Median onset day was 4.33 days in BLT group. 3) BLT-emergent hypomania: No participants experienced symptoms of hypomania. 4) Side effects: No serious adverse events were reported. BLT can be considered as an effective and safe adjunctive treatment for patients with acute bipolar depression. Copyright © 2017 Elsevier B.V. All rights reserved.

Mobile electronic versus paper case report forms in clinical trials: a randomized controlled trial.

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Fleischmann, Robert; Decker, Anne-Marie; Kraft, Antje; Mai, Knut; Schmidt, Sein

2017-12-01

Regulations, study design complexity and amounts of collected and shared data in clinical trials render efficient data handling procedures inevitable. Recent research suggests that electronic data capture can be key in this context but evidence is insufficient. This randomized controlled parallel group study tested the hypothesis that time efficiency is superior when electronic (eCRF) instead of paper case report forms (pCRF) are used for data collection. We additionally investigated predictors of time saving effects and data integrity. This study was conducted on top of a clinical weight loss trial performed at a clinical research facility over six months. All study nurses and patients participating in the clinical trial were eligible to participate and randomly allocated to enter cross-sectional data obtained during routine visits either through pCRF or eCRF. A balanced randomization list was generated before enrolment commenced. 90 and 30 records were gathered for the time that 27 patients and 2 study nurses required to report 2025 and 2037 field values, respectively. The primary hypothesis, that eCRF use is faster than pCRF use, was tested by a two-tailed t-test. Analysis of variance and covariance were used to evaluate predictors of entry performance. Data integrity was evaluated by descriptive statistics. All randomized patients were included in the study (eCRF group n = 13, pCRF group n = 14). eCRF, as compared to pCRF, data collection was associated with significant time savings  across all conditions (8.29 ± 5.15 min vs. 10.54 ± 6.98 min, p = .047). This effect was not defined by participant type, i.e. patients or study nurses (F (1,112)  = .15, p = .699), CRF length (F (2,112)  = .49, p = .609) or patient age (Beta = .09, p = .534). Additional 5.16 ± 2.83 min per CRF were saved with eCRFs due to data transcription redundancy when patients answered questionnaires directly in eCRFs. Data integrity was

A web-based clinical trial management system for a sham-controlled multicenter clinical trial in depression.

Science.gov (United States)

Durkalski, Valerie; Wenle Zhao; Dillon, Catherine; Kim, Jaemyung

2010-04-01

Clinical trial investigators and sponsors invest vast amounts of resources and energy into conducting trials and often face daily challenges with data management, project management, and data quality control. Rather than waiting months for study progress reports, investigators need the ability to use real-time data for the coordination and management of study activities across all study team members including site investigators, oversight committees, data and safety monitoring boards, and medical safety monitors. Web-based data management systems are beginning to meet this need but what distinguishes one system from the other are user needs/requirements and cost. To illustrate the development and implementation of a web-based data and project management system for a multicenter clinical trial designed to test the superiority of repeated transcranial magnetic stimulation versus sham for the treatment of patients with major depression. The authors discuss the reasons for not using a commercially available system for this study and describe the approach to developing their own web-based system for the OPT-TMS study. Timelines, effort, system architecture, and lessons learned are shared with the hope that this information will direct clinical trial researchers and software developers towards more efficient, user-friendly systems. The developers use a combination of generic and custom application code to allow for the flexibility to adapt the system to the needs of the study. Features of the system include: central participant registration and randomization; secure data entry at the site; participant progress/study calendar; safety data reporting; device accounting; monitor verification; and user-configurable generic reports and built-in customized reports. Hard coding was more time-efficient to address project-specific issues compared with the effort of creating a generic code application. As a consequence of this strategy, the required maintenance of the system is

Time to improve and recover from depressive symptoms and interpersonal problems in a clinical trial.

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Lopes, Rodrigo T; Gonçalves, Miguel M; Fassnacht, Daniel; Machado, Paulo P P; Sousa, Inês

2015-01-01

Results from an earlier clinical trial comparing narrative therapy with cognitive-behavioural therapy (Lopes et al., 2013) suggested that narrative therapy is efficacious for depression. However, there were significant differences in symptom reduction on the Beck Depression Inventory-II, favouring cognitive-behavioural therapy, if dropouts were included in the analysis, suggesting that time to recovery or improvement would differ in both treatments. Contrarily, results showed that treatment assignment was not a predictor for differential effect. Using a survival analytic approach, it was found that four sessions were necessary for 50% improvement and 16 sessions for 50% recovery. Additionally, depressive symptoms changes occurred significantly faster than interpersonal changes, again regardless of treatment assignment. These results support previous findings of the dose-response literature and of the phase model of change, with the advantage of being specific to psychotherapy with depressive clients. Copyright © 2013 John Wiley & Sons, Ltd.

Structured functional assessments in general practice increased the use of part-time sick leave: a cluster randomised controlled trial.

Science.gov (United States)

Osterås, Nina; Gulbrandsen, Pål; Kann, Inger Cathrine; Brage, Søren

2010-03-01

A method for structured functional assessments of persons with long-term sick leave was implemented in a cluster randomised controlled trial in general practice. The aim was to analyse intervention effects on general practitioner (GP) sick-listing practice and patient sick leave. 57 GPs were randomly assigned to an intervention or a control group. The intervention group GPs learned the method at a 1-day workshop including teamwork and role-playing. The control group GPs were requested to assess functional ability as usual during the 8 months intervention period in 2005. Outcome measures included duration of patient sick leave episodes, GP prescription of part-time sick leave, active sick leave, and vocational rehabilitation. This data was extracted from a national register. The GPs in the intervention group prescribed part-time sick leave more often (p part-time and less active sick leave compared to the control group GPs. As a result, more intervention GP patients returned to part-time work compared to control GP patients. No intervention effect was seen on duration of patient sick leave episodes or on prescription of vocational rehabilitation.

Marketing and clinical trials: a case study

Directory of Open Access Journals (Sweden)

Entwistle Vikki A

2007-11-01

Full Text Available Abstract Background Publicly funded clinical trials require a substantial commitment of time and money. To ensure that sufficient numbers of patients are recruited it is essential that they address important questions in a rigorous manner and are managed well, adopting effective marketing strategies. Methods Using methods of analysis drawn from management studies, this paper presents a structured assessment framework or reference model, derived from a case analysis of the MRC's CRASH trial, of 12 factors that may affect the success of the marketing and sales activities associated with clinical trials. Results The case study demonstrates that trials need various categories of people to buy in – hence, to be successful, trialists must embrace marketing strategies to some extent. Conclusion The performance of future clinical trials could be enhanced if trialists routinely considered these factors.

Multiple treatment comparisons in epilepsy monotherapy trials

Directory of Open Access Journals (Sweden)

Chadwick David W

2007-11-01

Full Text Available Abstract Background The choice of antiepileptic drug for an individual should be based upon the highest quality evidence regarding potential benefits and harms of the available treatments. Systematic reviews and meta-analysis of randomised controlled trials should be a major source of evidence supporting this decision making process. We summarise all available individual patient data evidence from randomised controlled trials that compared at least two out of eight antiepileptic drugs given as monotherapy. Methods Multiple treatment comparisons from epilepsy monotherapy trials were synthesized in a single stratified Cox regression model adjusted for treatment by epilepsy type interactions and making use of direct and indirect evidence. Primary outcomes were time to treatment failure and time to 12 month remission from seizures. A secondary outcome was time to first seizure. Results Individual patient data for 6418 patients from 20 randomised trials comparing eight antiepileptic drugs were synthesized. For partial onset seizures (4628 (72% patients, lamotrigine, carbamazepine and oxcarbazepine provide the best combination of seizure control and treatment failure. Lamotrigine is clinically superior to all other drugs for treatment failure but estimates suggest a disadvantage compared to carbamazepine for time to 12 month remission [Hazard Ratio (95% Confidence Interval = 0.87(0.73 to 1.04] and time to first seizure [1.29(1.13 to 1.48]. Phenobarbitone may delay time to first seizure [0.77(0.61 to 0.96] but at the expense of increased treatment failure [1.60(1.22 to 2.10]. For generalized onset tonic clonic seizures (1790 (28% patients estimates suggest valproate or phenytoin may provide the best combination of seizure control and treatment failure but some uncertainty remains about the relative effectiveness of other drugs. Conclusion For patients with partial onset seizures, results favour carbamazepine, oxcarbazepine and lamotrigine. For

A Mobile Device App to Reduce Medication Errors and Time to Drug Delivery During Pediatric Cardiopulmonary Resuscitation: Study Protocol of a Multicenter Randomized Controlled Crossover Trial.

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Siebert, Johan N; Ehrler, Frederic; Lovis, Christian; Combescure, Christophe; Haddad, Kevin; Gervaix, Alain; Manzano, Sergio

2017-08-22

During pediatric cardiopulmonary resuscitation (CPR), vasoactive drug preparation for continuous infusions is complex and time-consuming. The need for individual specific weight-based drug dose calculation and preparation places children at higher risk than adults for medication errors. Following an evidence-based and ergonomic driven approach, we developed a mobile device app called Pediatric Accurate Medication in Emergency Situations (PedAMINES), intended to guide caregivers step-by-step from preparation to delivery of drugs requiring continuous infusion. In a prior single center randomized controlled trial, medication errors were reduced from 70% to 0% by using PedAMINES when compared with conventional preparation methods. The purpose of this study is to determine whether the use of PedAMINES in both university and smaller hospitals reduces medication dosage errors (primary outcome), time to drug preparation (TDP), and time to drug delivery (TDD) (secondary outcomes) during pediatric CPR when compared with conventional preparation methods. This is a multicenter, prospective, randomized controlled crossover trial with 2 parallel groups comparing PedAMINES with a conventional and internationally used drug infusion rate table in the preparation of continuous drug infusion. The evaluation setting uses a simulation-based pediatric CPR cardiac arrest scenario with a high-fidelity manikin. The study involving 120 certified nurses (sample size) will take place in the resuscitation rooms of 3 tertiary pediatric emergency departments and 3 smaller hospitals. After epinephrine-induced return of spontaneous circulation, nurses will be asked to prepare a continuous infusion of dopamine using either PedAMINES (intervention group) or the infusion table (control group) and then prepare a continuous infusion of norepinephrine by crossing the procedure. The primary outcome is the medication dosage error rate. The secondary outcome is the time in seconds elapsed since the oral

Processes for Quality Improvements in Radiation Oncology Clinical Trials

International Nuclear Information System (INIS)

FitzGerald, T.J.; Urie, Marcia; Ulin, Kenneth; Laurie, Fran; Yorty, Jeffrey C.; Hanusik, Richard; Kessel, Sandy; Jodoin, Maryann Bishop; Osagie, Gani; Cicchetti, M. Giulia; Pieters, Richard; McCarten, Kathleen; Rosen, Nancy

2008-01-01

Quality assurance in radiotherapy (RT) has been an integral aspect of cooperative group clinical trials since 1970. In early clinical trials, data acquisition was nonuniform and inconsistent and computational models for radiation dose calculation varied significantly. Process improvements developed for data acquisition, credentialing, and data management have provided the necessary infrastructure for uniform data. With continued improvement in the technology and delivery of RT, evaluation processes for target definition, RT planning, and execution undergo constant review. As we move to multimodality image-based definitions of target volumes for protocols, future clinical trials will require near real-time image analysis and feedback to field investigators. The ability of quality assurance centers to meet these real-time challenges with robust electronic interaction platforms for imaging acquisition, review, archiving, and quantitative review of volumetric RT plans will be the primary challenge for future successful clinical trials

Slimming starters. Intake of a diet-congruent food reduces meal intake in active dieters.

Science.gov (United States)

Buckland, Nicola J; Finlayson, Graham; Hetherington, Marion M

2013-12-01

Dietary restraint is known to break down in the face of tempting foods. Previous research suggests exposure to cues associated with slimming such as images or odours act as prompts to restrict intake of a tempting snack in dieters. The effects of consuming diet-congruent foods on subsequent intake of a meal have not yet been investigated. Thus, using a repeated measures design 26 female participants (dieters or non-dieters) consumed a diet-congruent (100 kcal salad), hedonic (100 kcal garlic bread) or neutral (0 kcal water) preload. A lexical decision task measured the salience of diet and hedonic thoughts and participants were then offered pizza as a main meal. Appetite sensations were measured throughout the study. Compared to the hedonic and neutral preload, a diet-congruent preload reduced dieters' entire meal intake by 21%. In contrast, non-dieters consumed 9% more in the hedonic preload condition compared to the neutral preload, yet showed no differences between the diet-congruent and other conditions. Salad lowered participants desire to eat and increased fullness compared to garlic bread and water preloads. Dieters were also less hungry after the salad compared to the garlic bread and water preloads. Consuming a diet-congruent first course may prompt lower intake at a meal, in part due to facilitating resolve to refrain from overeating a tempting second course. Copyright © 2013. Published by Elsevier Ltd.

Are You Sure? Confidence about the Satiating Capacity of a Food Affects Subsequent Food Intake.

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Schiöth, Helgi B; Ferriday, Danielle; Davies, Sarah R; Benedict, Christian; Elmståhl, Helena; Brunstrom, Jeffrey M; Hogenkamp, Pleunie S

2015-06-24

Expectations about a food's satiating capacity predict self-selected portion size, food intake and food choice. However, two individuals might have a similar expectation, but one might be extremely confident while the other might be guessing. It is unclear whether confidence about an expectation affects adjustments in energy intake at a subsequent meal. In a randomized cross-over design, 24 subjects participated in three separate breakfast sessions, and were served a low-energy-dense preload (53 kcal/100 g), a high-energy-dense preload (94 kcal/100 g), or no preload. Subjects received ambiguous information about the preload's satiating capacity and rated how confident they were about their expected satiation before consuming the preload in its entirety. They were served an ad libitum test meal 30 min later. Confidence ratings were negatively associated with energy compensation after consuming the high-energy-dense preload (r = -0.61; p = 0.001). The same relationship was evident after consuming the low-energy-dense preload, but only after controlling for dietary restraint, hunger prior to, and liking of the test meal (p = 0.03). Our results suggest that confidence modifies short-term controls of food intake by affecting energy compensation. These results merit consideration because imprecise caloric compensation has been identified as a potential risk factor for a positive energy balance and weight gain.

Beetroot Juice Improves On-Water 500 M Time-Trial Performance, and Laboratory-Based Paddling Economy in National and International-Level Kayak Athletes.

Science.gov (United States)

Peeling, Peter; Cox, Gregory R; Bullock, Nicola; Burke, Louise M

2015-06-01

We assessed the ingestion of a beetroot juice supplement (BR) on 4-min laboratory-based kayak performance in national level male (n = 6) athletes (Study A), and on 500 m on-water kayak time-trial (TT) performance in international level female (n = 5) athletes (Study B). In Study A, participants completed three laboratory-based sessions on a kayak ergometer, including a 7 × 4 min step test, and two 4 min maximal effort performance trials. Two and a half hours before the warm-up of each 4 min performance trial, athletes received either a 70 ml BR shot containing ~4.8 mmol of nitrate, or a placebo equivalent (BRPLA). The distance covered over the 4 min TT was not different between conditions; however, the average VO2 over the 4 min period was significantly lower in BR (p = .04), resulting in an improved exercise economy (p = .05). In Study B, participants completed two field-based 500 m TTs, separated by 4 days. Two hours before each trial, athletes received either two 70 ml BR shots containing ~9.6 mmol of nitrate, or a placebo equivalent (BRPLA). BR supplementation significantly enhanced TT performance by 1.7% (p = .01). Our results show that in national-level male kayak athletes, commercially available BR shots (70 ml) containing ~4.8 mmol of nitrate improved exercise economy during laboratory-based tasks predominantly reliant on the aerobic energy system. Furthermore, greater volumes of BR (140 ml; ~9.6 mmol nitrate) provided to international-level female kayak athletes resulted in enhancements to TT performance in the field.

Longitudinal Impact of a Family Critical Time Intervention on Children in High-Risk Families Experiencing Homelessness: A Randomized Trial.

Science.gov (United States)

Shinn, Marybeth; Samuels, Judith; Fischer, Sean N; Thompkins, Amanda; Fowler, Patrick J

2015-12-01